Frontiers of Medicine 2017 年第 1 期（ Vol.11,No.1 ）已经出版，共 16 篇文章，汇聚了心血管疾病、胃肠道疾病、血液病、中医药学等领域的诸多研究成果。 您可以点击下面文章列表中的链接，浏览内容；也欢迎您将链接转发给同道或推荐给所在机构图书馆及资料室，让更多人了解期刊上的好文章。 到目前为止， Frontiers of Medicine 已被 SCI 、 MEDLINE/PubMed 、 SCOPUS 、 EMBASE 、中国科技核心期刊、 CSCD （中国科学引文数据库）核心库等收录。 欢迎访问投审稿平台 http://mc.manuscriptcentral.com/fmd ，让您的优秀成果更快发表。 您可以点击 这里 ，查看期刊最新一期目录；也可以点击下面的文章列表链接，查看每篇文章的全文或摘要信息。 REVIEWTranslational initiatives in thrombolytic therapy DOI: 10.1007/s11684-017-0497-8Melvin E. KlegermanAbstract: Once thrombi have formed as part of the pathology defining myocardial infarction, ischemic stroke, peripheral arterial disease, deep venous thrombosis or other embolic disorders, the only clinically meaningful thrombolytic agents available for reversing the thrombogenic process are various plasminogen activators. These agents are enzymes that reverse fibrin polymerization underlying the coagulation process by converting endogenous plasminogen to plasmin, which cleaves the fibrin network to form increasingly smaller protein fragments, a process known as fibrinolysis. For the most part, the major clinically used thrombolytics, tissue plasminogen activator, urokinase and streptokinase, as well as the experimentally investigated agent staphylokinase, are the products of recombinant DNA technology, which permits molecular optimization of clinical efficacy. In all cases of molecular optimization and targeting, however, the primary challenge of thrombolytic therapy remains hemorrhagic side effects, which are especially devastating when they occur intracerebrally. Currently, the best strategy to ameliorate this adverse effect is nanoparticulate encapsulation or complexation, and many strategies of this sort are being actively pursued. This review summarizes the variety of targeted and untargeted thrombolytic formulations that have been investigated in preclinical studies. Full text PDFCite this article: Melvin E. Klegerman. Translational initiatives in thrombolytic therapy . Frontiers of Medicine, 2017. 11(1): 1-19 Detection of digestive malignancies and post-gastrectomy complications via gastrointestinal fluid examination DOI: 10.1007/s11684-016-0493-4Lei Huang,Aman XuAbstract: To date, gastric carcinoma (GC) is one of the common and fatal digestive malignancies worldwide. The prognosis of GC is not always satisfactory because of late diagnosis. Scholars are keen on discovering novel accurate and economical biomarkers in body liquids for GC screening to detect and evaluate the lesion before the results of imaging techniques are obtained. While traditional serum assays have limited sensitivity and specificity, gastrointestinal juice may provide relevant specific biomarkers because of its close contact with the tumor. Herein, the current progress in the relationship between gastrointestinal fluid analyses and GC is systematically and comprehensively reviewed. The detection of gastric juice pH, fluorescence spectrum, cytology, Helicobacter pylori-associated markers, nitrosamines, conventional tumor markers, amino acids, proteomics, microRNAs, long noncoding RNAs, protein-coding genes, vitamin C, etc., and combination tests of different category markers could provide important diagnostic and prognostic clues for gastrointestinal diseases. Particularly, early GC may be efficiently screened using gastric juice. Gastrointestinal fluid examination could also predict the adverse effects of postgastrectomy, such as pancreatic leakage, fistula, and abscess. Gastric fluid markers should be further studied to reveal the early predicators of malignancy and complications. The methods for obtaining the samples of gastrointestinal juice with minimum incision should also be comprehensively investigated. Full text PDFCite this article: Lei Huang,Aman Xu. Detection of digestive malignancies and post-gastrectomy complications via gastrointestinal fluid examination . Frontiers of Medicine, 2017. 11(1): 20-31 Innovative development path of ethnomedicines: the interpretation of the path DOI: 10.1007/s11684-016-0495-2Zhaoyun Zhu,Dehuan Fu,Yali Gui,Tao Cui,Jingkun Wang,Ting Wang,Zhizhong Yang,Yanfei Niu,Zhennan She,Li WangAbstract: One of the primary purposes of the innovative development of ethnomedicines is to use their excellent safety and significant efficacy to serve a broader population. To achieve this purpose, modern scientific and technological means should be referenced, and relevant national laws and regulations as well as technical guides should be strictly followed to develop standards and to perform systemic research in producing ethnomedicines. Finally, ethnomedicines, which are applied to a limited extent in ethnic areas, can be transformed into safe, effective, and quality-controllable medical products to relieve the pain of more patients. The innovative development path of ethnomedicines includes the following three primary stages: resource study, standardized development research, and industrialization of the achievements and efforts for internationalization. The implementation of this path is always guaranteed by the research and development platform and the talent team. This article is based on the accumulation of long-term practice and is combined with the relevant disciplines, laws and regulations, and technical guidance from the research and development of ethnomedicines. The intention is to perform an in-depth analysis and explanation of the major research thinking, methods, contents, and technical paths involved in all stages of the innovative development path of ethnomedicines to provide useful references for the development of proper ethnomedicine use. Full text PDFCite this article: Zhaoyun Zhu,Dehuan Fu,Yali Gui,Tao Cui,Jingkun Wang,Ting Wang,Zhizhong Yang,Yanfei Niu,Zhennan She,Li Wang. Innovative development path of ethnomedicines: the interpretation of the path . Frontiers of Medicine, 2017. 11(1): 32-47 Arthrogryposis multiplex congenita: classification, diagnosis, perioperative care, and anesthesia DOI: 10.1007/s11684-017-0500-4Lulu Ma,Xuerong YuAbstract: Arthrogryposis multiplex congenita (AMC) is a rare disorder characterized by non-progressive, multiple contractures. In addition to affected extremities, patients may also present microstomia, decreased temporomandibular joint mobility. Although the etiology of AMC is unclear, any factor that decreases fetal movement is responsible for AMC. Thus, accurate diagnosis and classification are crucial to the appropriate treatment of AMC. The development of ultrasound technology has enabled prenatal diagnosis. Very early treatment is favorable, and multidisciplinary treatment is necessary to improve the function of AMC patients. Most patients require surgery to release contracture and reconstruct joints. However, perioperative care is challenging, and difficult airway is the first concern of anesthesiologists. Postoperative pulmonary complications are common and regional anesthesia is recommended for postoperative analgesia. This review on AMC is intended for anesthesiologists. Thus, we discuss the treatment and perioperative management of patients undergoing surgery, as well as the diagnosis and classification of AMC. Full text PDFCite this article: Lulu Ma,Xuerong Yu. Arthrogryposis multiplex congenita: classification, diagnosis, perioperative care, and anesthesia . Frontiers of Medicine, 2017. 11(1): 48-52 RESEARCH ARTICLEPoor adherence to P2Y12 antagonists increased cardiovascular risks in Chinese PCI-treated patients DOI: 10.1007/s11684-017-0502-2Yang Sun,Chenze Li,Lina Zhang,Dong Hu,Xudong Zhang,Ting Yu,Min Tao,Dao Wen Wang,Xiaoqing ShenAbstract: Low adherence to secondary prevention medications (ATM) of patients after acute coronary syndrome (ACS) is associated with poor clinical outcomes. However, literature provides limited data on assessment of ATM and risks associated with poor in Chinese patients with ACS. In the current work, ATM was assessed in consecutively recruited patients with ACS in Tongji Hospital from November 5, 2013 to December 31, 2014. A total of 2126 patients were classified under low adherence (proportion of days covered (PDC)50%) and high adherence (PDC50%) groups based on their performance after discharge. All patients were followed up at the 1st, 6th, and 12th month of discharge while recording ATM and major adverse cardiac events (MACE). Bivariate logistic regression was used to identify the factors associated with ATM. Cox regression was used to analyze the association between ATM and MACE within one year after discharge. Results showed that coronary artery bypass grafting (CABG) alone had significantly lower proportion of high adherence to P2Y12 antagonists (83.0% vs. 90.7%, P0.01) than patients treated with percutaneous coronary intervention (PCI) only. Moreover, in patients undergoing PCI, high adherence to P2Y12 antagonists decreased the risk of MACE (hazard ratio=0.172, 95% confidence interval: 0.039–0.763; P=0.021). In conclusion, PCI-treated patients are more prone to remaining adherent to medications than CABG-treated patients. High adherence to P2Y12 antagonists was associated with lower risk of MACE. Full text PDFCite this article: Yang Sun,Chenze Li,Lina Zhang,Dong Hu,Xudong Zhang,Ting Yu,Min Tao,Dao Wen Wang,Xiaoqing Shen. Poor adherence to P2Y12 antagonists increased cardiovascular risks in Chinese PCI-treated patients . Frontiers of Medicine, 2017. 11(1): 53-61 Aortic aneurysm and chronic disseminated intravascular coagulation: a retrospective study of 235 patients DOI: 10.1007/s11684-017-0498-7Yun Zhang,Chen Li,Min Shen,Bao Liu,Xuejun Zeng,Ti ShenAbstract: Chronic disseminated intravascular coagulation (DIC) is a rare but devastating complication of aortic aneurysm (AA). This study investigated the clinical manifestations, laboratory findings, and treatment of patients with AA-associated chronic DIC (AA-DIC) and explored the mechanisms, duration, and therapeutic response of AA-DIC. We retrospectively reviewed the medical records of 235 AA patients admitted at the Peking Union Medical College Hospital between September 2009 and January 2015. The patients were classified as those with DIC (AA-DIC) and those without DIC (non-DIC). The AA-DIC group showed a significantly higher proportion of female patients and a significantly longer AA disease course than the non-DIC group did. The AA-DIC patients presented mural thrombi, dissecting aneurysms, a family history of AA, and diabetes significantly more frequently than the non-DIC patients did. Furthermore, multiple regression analyses revealed that sex, mural thrombus, aneurysm type, diabetes, and stent surgery are possible independent risk factors for AA-DIC patients. Fifty-two (22.1%) patients presented AA-DIC. Among these patients, 43 had non-typical DIC and 9 had typical DIC; the mortality rate of the latter was 22.2%. The mean age of the patients with typical DIC was significantly higher than of that of patients with non-typical DIC. The non-typical DIC patients also presented abnormal coagulation disorders of varying degrees. Furthermore, heparin or low-molecular-weight heparin improved the clinical symptoms and laboratory parameters in patients with AA and typical DIC. Thus, chronic DIC should be considered in patients with AA. Full text PDFCite this article: Yun Zhang,Chen Li,Min Shen,Bao Liu,Xuejun Zeng,Ti Shen. Aortic aneurysm and chronic disseminated intravascular coagulation: a retrospective study of 235 patients . Frontiers of Medicine, 2017. 11(1): 62-67 Improved control of hypertension following laparoscopic fundoplication for gastroesophageal reflux disease DOI: 10.1007/s11684-016-0490-7Zhiwei Hu,Meiping Chen,Jimin Wu,Qing Song,Chao Yan,Xing Du,Zhonggao WangAbstract: This study aims to determine whether successful laparoscopic fundoplication for gastroesophageal reflux disease (GERD) can improve the control of hypertension. We conducted an observational study of GERD patients with hypertension. The esophageal and gastroesophageal symptoms of these patients were successfully treated with laparoscopic fundoplication, as measured by the reduced GERD symptoms and proton pump inhibitor consumption. A hypertension control scale was used to classify the use of antihypertensive medications and the quality of blood pressure control before and after anti-reflux surgery. Wilcoxon signed-ranks test was used for the statistical analyses. Seventy GERD patients were included in the analysis and followed up for a mean period of 3.5±1.4 years. Prior to surgery, all participating patients were taking at least one class of antihypertensive medication, and 56 patients (80%) had intermittently high blood pressure. After surgery, the mean number of antihypertensive medication classes per patient was significantly reduced from 1.61±0.77 pre-procedure to 1.27±0.88 post-procedure (P??0.001). The blood pressure of 48 of the 56 cases (86%) with preoperative intermittent high blood pressure returned to normal post procedure. A total of 50 patients (71%) recorded improvements on the hypertension control scale, with the overall mean score decreasing from 3.1±1.0 pre-procedure to 1.4±1.0 post-procedure (P??0.001). Therefore, successful laparoscopic fundoplication may result in better blood pressure control in some hypertensive GERD patients. This result suggests a possible connection between gastroesophageal reflux and hypertension. Full text PDFCite this article: Zhiwei Hu,Meiping Chen,Jimin Wu,Qing Song,Chao Yan,Xing Du,Zhonggao Wang. Improved control of hypertension following laparoscopic fundoplication for gastroesophageal reflux disease . Frontiers of Medicine, 2017. 11(1): 68-73 Changes in lncRNAs and related genes in β-thalassemia minor and β-thalassemia major DOI: 10.1007/s11684-017-0503-1Jing Ma,Fei Liu,Xin Du,Duan Ma,Likuan XiongAbstract: β-thalassemia is caused by β-globin gene mutations. However, heterogeneous phenotypes were found in individuals with same genotype, and still undescribed mechanism underlies such variation. We collected blood samples from 30 β-thalassemia major, 30 β-thalassemia minor patients, and 30 matched normal controls. Human lncRNA Array v2.0 (8 × 60 K, Arraystar) was used to detect changes in long non-coding RNAs (lncRNAs) and mRNAs in three samples each from β-thalassemia major, β-thalassemia minor, and control groups. Compared with normal controls, 1424 and 2045 lncRNAs were up- and downregulated, respectively, in β-thalassemia major patients, whereas 623 and 349 lncRNAs were up- and downregulated, respectively, in β-thalassemia minor patients. Compared with β-thalassemia minor group, 1367 and 2356 lncRNAs were up- and downregulated, respectively, in β-thalassemia major group. We selected five lncRNAs that displayed altered expressions (DQ583499, X-inactive specific transcript (Xist), lincRNA-TPM1, MRFS16P, and lincRNA-RUNX2-2) and confirmed their expression levels in all samples using real-time polymerase chain reaction. Based on coding-non-coding gene co-expression network and gene ontology biological process analyses, several signaling pathways were associated with three common organ systems exhibiting β-thalassemia phenotypes: hematologic, skeletal, and hepatic systems. This study implicates that abnormal expression levels of lncRNAs and mRNA in β-thalassemia cases may be correlated with its various clinical phenotypes. Full text PDFCite this article: Jing Ma,Fei Liu,Xin Du,Duan Ma,Likuan Xiong. Changes in lncRNAs and related genes in β-thalassemia minor and β-thalassemia major . Frontiers of Medicine, 2017. 11(1): 74-86 Regulatory mechanism and functional analysis of S100A9 in acute promyelocytic leukemia cells DOI: 10.1007/s11684-016-0469-4Yonglan Zhu,Fang Zhang,Shanzhen Zhang,Wanglong Deng,Huiyong Fan,Haiwei Wang,Ji ZhangAbstract: S100A9, a calcium-binding protein, participates in the inflammatory process and development of various tumors, thus attracting much attention in the field of cancer biology. This study aimed to investigate the regulatory mechanism of S100A9 and its function involvement in APL. We used real-time quantitative PCR to determine whether PML/RARα affects the expression of S100A9 in NB4 and PR9 cells upon ATRA treatment. ChIP-based PCR and dual-luciferase reporter assay system were used to detect how PML/RARα and PU.1 regulate S100A9 promoter activity. CCK-8 assay and flow cytometry were employed to observe the viability and apoptosis of NB4 cells when S100A9 was overexpressed. Results showed that S100A9 was an ATRA-responsive gene, and PML/RARα was necessary for the ATRA-induced expression of S100A9 in APL cells. In addition, PU.1 could bind to the promoter of S100A9, especially when treated with ATRA in NB4 cells, and promote its activity. More importantly, overexpression of S100A9 induced the apoptosis of NB4 cells and inhibited cell growth. Collectively, our data indicated that PML/RARα and PU.1 were necessary for the ATRA-induced expression of S100A9 in APL cells. Furthermore, S100A9 promoted apoptosis in APL cells and affected cell growth. Full text PDFCite this article: Yonglan Zhu,Fang Zhang,Shanzhen Zhang,Wanglong Deng,Huiyong Fan,Haiwei Wang,Ji Zhang. Regulatory mechanism and functional analysis of S100A9 in acute promyelocytic leukemia cells . Frontiers of Medicine, 2017. 11(1): 87-96 iTRAQ-based quantitative proteomic analysis on differentially expressed proteins of rat mandibular condylar cartilage induced by reducing dietary loading DOI: 10.1007/s11684-016-0496-1Liting Jiang,Yinyin Xie,Li Wei,Qi Zhou,Ning Li,Xinquan Jiang,Yiming GaoAbstract: As muscle activity during growth is considerably important for mandible quality and morphology, reducing dietary loading directly influences the development and metabolic activity of mandibular condylar cartilage (MCC). However, an overall investigation of changes in the protein composition of MCC has not been fully described in literature. To study the protein expression and putative signaling in vivo, we evaluated the structural changes of MCC and differentially expressed proteins induced by reducing functional loading in rat MCC at developmental stages. Isobaric tag for relative and absolute quantitation-based 2D nano-high performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization time-of-flight/ time-of-flight (MALDI-TOF/TOF) technologies were used. Global protein profiling, KEGG and PANTHER pathways, and functional categories were analyzed. Consequently, histological and tartrate-resistant acid phosphatase staining indicated the altered histological structure of condylar cartilage and increased bone remodeling activity in hard-diet group. A total of 805 differentially expressed proteins were then identified. GO analysis revealed a significant number of proteins involved in the metabolic process, cellular process, biological regulation, localization, developmental process, and response to stimulus. KEGG pathway analysis also suggested that these proteins participated in various signaling pathways, including calcium signaling pathway, gap junction, ErbB signaling pathway, and mitogen-activated protein kinase signaling pathway. Collagen types I and II were further validated by immunohistochemical staining and Western blot analysis. Taken together, the present study provides an insight into the molecular mechanism of regulating condylar growth and remodeling induced by reducing dietary loading at the protein level. Full text PDFCite this article: Liting Jiang,Yinyin Xie,Li Wei,Qi Zhou,Ning Li,Xinquan Jiang,Yiming Gao. iTRAQ-based quantitative proteomic analysis on differentially expressed proteins of rat mandibular condylar cartilage induced by reducing dietary loading . Frontiers of Medicine, 2017. 11(1): 97-109 Association of periodontal disease with glycemic control in patients with type 2 diabetes in Indian population DOI: 10.1007/s11684-016-0484-5Palka Kaur Khanuja,Satish Chander Narula,Rajesh Rajput,Rajinder Kumar Sharma,Shikha TewariAbstract: This study aims to investigate the link between glycated hemoglobin and diabetic complications with chronic periodontitis. A total of 207 patients with type 2 diabetes and chronic periodontitis (CP) were divided according to tertiles of mean PISA (periodontal inflamed surface area) scores as low, middle and high PISA groups. Simultaneously a group of 67 periodontally healthy individuals (PH) was recruited. Periodontal examinations, including full-mouth assessment of probing depths (PPD), bleeding on probing, clinical attachment level and plaque scores were determined. Blood analyses were carried out for glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2 h post parandial glucose (PPG). Individuals in PH group had significantly better glycemic control than CP group. Upon one-way analysis of variance, subjects with increased PISA had significantly higher HbA1c levels, retinopathy and nephropathy (P0.05). After controlling for age, gender, body mass index (BMI), socioeconomic status (SES), family history of diabetes and periodontitis, duration of diabetes, the mean PISA in mm2, PPD 4--6 mm (%) and PPD≥7 mm (%) emerged as significant predictors for elevated HbA1c in regression model (P0.05). Logistic regression analysis revealed that PISA was associated with higher risk of having retinopathy and neuropathy (odds ratio). In our study, the association between glycemic control and diabetic complications with periodontitis was observed. Full text PDFCite this article: Palka Kaur Khanuja,Satish Chander Narula,Rajesh Rajput,Rajinder Kumar Sharma,Shikha Tewari. Association of periodontal disease with glycemic control in patients with type 2 diabetes in Indian population . Frontiers of Medicine, 2017. 11(1): 110-119 Cotransfecting norepinephrine transporter and vesicular monoamine transporter 2 genes for increased retention of metaiodobenzylguanidine labeled with iodine 131 in malignant hepatocarcinoma cells DOI: 10.1007/s11684-017-0501-3Yanlin Zhao,Xiao Zhong,Xiaohong Ou,Huawei Cai,Xiaoai Wu,Rui HuangAbstract: Norepinephrine transporter (NET) transfection leads to significant uptake of iodine-131-labeled metaiodobenzylguanidine (131I-MIBG) in non-neuroendocrine tumors. However, the use of 131I-MIBG is limited by its short retention time in target cells. To prolong the retention of 131I-MIBG in target cells, we infected hepatocarcinoma (HepG2) cells with Lentivirus-encoding human NET and vesicular monoamine transporter 2 (VMAT2) genes to obtain NET-expressing, NET-VMAT2-coexpressing, and negative-control cell lines. We evaluated the uptake and efflux of 131I-MIBG both in vitro and in vivo in mice bearing transfected tumors. NET-expressing and NET-VMAT2-coexpressing cells respectively showed 2.24 and 2.22 times higher 131I-MIBG uptake than controls. Two hours after removal of 131I-MIBG-containing medium, 25.4% efflux was observed in NET-VMAT2-coexpressing cells and 38.6% in NET-expressing cells. In vivo experiments were performed in nude mice bearing transfected tumors; results revealed that NET-VMAT2-coexpressing tumors had longer 131I-MIBG retention time than NET-expressing tumors. Meanwhile, NET-VMAT2-coexpressing and NET-expressing tumors displayed 0.54% and 0.19%, respectively, of the injected dose per gram of tissue 24 h after 131I-MIBG administration. Cotransfection of HepG2 cells with NET and VMAT2 resulted in increased 131I-MIBG uptake and retention. However, the degree of increase was insufficient to be therapeutically effective in target cells. Full text PDFCite this article: Yanlin Zhao,Xiao Zhong,Xiaohong Ou,Huawei Cai,Xiaoai Wu,Rui Huang. Cotransfecting norepinephrine transporter and vesicular monoamine transporter 2 genes for increased retention of metaiodobenzylguanidine labeled with iodine 131 in malignant hepatocarcinoma cells . Frontiers of Medicine, 2017. 11(1): 120-128 A comparative study of electroacupuncture at Zhongliao (BL33) and other acupoints for overactive bladder symptoms DOI: 10.1007/s11684-016-0491-6Likun Yang,Yang Wang,Qian Mo,Zhishun LiuAbstract: Electroacupuncture (EA) at Zhongliao (BL33) can improve the symptoms of overactive bladder (OAB), such as urinary frequency, urgency, and incontinence. However, its performance compared with other acupoints remains unclear. This study investigated the effects of EA at BL33 with deep needling on rats with OAB by detecting urodynamics in eight groups: no intervention group, D-BL33 group (deep needling at BL33), S-BL33 group (shallow needling at BL33), non-acupoint group (needling at the non-acupoint next to BL33), Weizhong (BL40) group, Sanyinjiao (SP6) group, Tongtian (BL7) group, and Hegu (LI4) group. Results revealed that EA at BL33 with deep needling, BL40, and SP6 prolonged the intercontraction interval (ICI) of rats with OAB (P=0.001, P=0.005, P=0.046, respectively, post-treatment vs. post-modeling). Furthermore, the change in ICI from post-modeling in the D-BL33 group was significantly greater than those of the no intervention and other EA groups (all P0.01). Significantly shortened vesical micturition time (VMT) and elevated maximum detrusor pressure (MDP) were also observed in the D-BL33 group (P=0.017 and P=0.024, respectively, post-treatment vs. post-modeling). However, no statistically significant differences in the changes of VMT and MDP from post-modeling were observed between D-BL33 and the other EA groups. In conclusion, EA at BL33 with deep needling may inhibit acetic-acid-induced OAB more effectively. Full text PDFCite this article: Likun Yang,Yang Wang,Qian Mo,Zhishun Liu. A comparative study of electroacupuncture at Zhongliao (BL33) and other acupoints for overactive bladder symptoms . Frontiers of Medicine, 2017. 11(1): 129-136 Effects of different doses of cadmium on secondary metabolites and gene expression in Artemisia annua L. DOI: 10.1007/s11684-016-0486-3Liangyun Zhou,Guang Yang,Haifeng Sun,Jinfu Tang,Jian Yang,Yizhan Wang,Thomas Avery Garran,Lanping GuoAbstract: This study aims to elucidate the underlying molecular mechanisms of artemisinin accumulation induced by cadmium (Cd). The effects of different Cd concentrations (0, 20, 60, and 120 μmol/L) on the biosynthesis of Artemisia annua L. were examined. Intermediate and end products were quantified by HPLC-ESI-MS/MS analysis. The expression of key biosynthesis enzymes was also determined by qRT-PCR. The results showed that the application of treatment with 60 and 120 μmol/L Cd for 3 days significantly improved the biosynthesis of artemisinic acid, arteannuin B, and artemisinin. The concentrations of artemisinic acid, arteannuin B, and artemisinin in the 120 μmol/L Cd-treated group were 2.26, 102.08, and 33.63 times higher than those in the control group, respectively. The concentrations of arteannuin B and artemisinin in 60 μmol/L Cd-treated leaves were 61.10 and 26.40 times higher than those in the control group, respectively. The relative expression levels of HMGR, FPS, ADS, CYP71AV1, DBR2, ALDH1, and DXR were up-regulated in the 120 μmol/L Cd-treated group because of increased contents of artemisinic metabolites after 3 days of treatment. Hence, appropriate doses of Cd can increase the concentrations of artemisinic metabolites at a certain time point by up-regulating the relative expression levels of key enzyme genes involved in artemisinin biosynthesis. Full text PDFCite this article: Liangyun Zhou,Guang Yang,Haifeng Sun,Jinfu Tang,Jian Yang,Yizhan Wang,Thomas Avery Garran,Lanping Guo. Effects of different doses of cadmium on secondary metabolites and gene expression in Artemisia annua L. . Frontiers of Medicine, 2017. 11(1): 137-146 Study of blood exposure-related mental health illness among clinical nurses DOI: 10.1007/s11684-016-0481-8Xiaojia Xiong,Min Li,Yongliang Jiang,Xindeng Tong,Yanzhong PengAbstract: Nurses are subjected to high amount of stress in the medical setting, and work-related stress often leads to mental problems. This study aims to investigate the mental health status of nurses exposed to blood through needlestick injuries. A total of 302 nurses working in the hospital of Guangdong, China, participated in this study. Out of the 302 nurses, 140 did not experience any needlestick injuries during the previous week, whereas 162 nurses experienced needlestick injuries. The General Health Questionnaire (GHQ)-28 Standardized Questionnaire, which uses physical, anxiety, social function, and depression subscales, was used in this study. No significant difference between nurses exposed to blood and nurses not exposed to blood was found in terms of gender, age, length of employment, and civil status (P0.05). Results from the GHQ-28 Standardized Questionnaire showed that 75.9% (123/162) of nurses exposed to blood were suspected to suffer from mental disorders, whereas 40% (56/140) of nurses not exposed to blood were suspected to suffer from mental disorders. The mean mental health scores of nurses exposed to blood and those not exposed were 8.73±7.32 and 5.69±5.70, respectively. From these results, we can conclude that blood exposure from needlestick injuries leads to higher prevalence of depression, anxiety, and stress symptoms in nurses. This finding highlights the importance of providing efficient, adequate, and appropriate support services after nurses are exposed to blood from needlestick injuries. Full text PDFCite this article: Xiaojia Xiong,Min Li,Yongliang Jiang,Xindeng Tong,Yanzhong Peng. Study of blood exposure-related mental health illness among clinical nurses . Frontiers of Medicine, 2017. 11(1): 147-151 LETTER TO FRONTIERS OF MEDICINEHolistic integrative medicine: toward a new era of medical advancement DOI: 10.1007/s11684-017-0499-6Daiming FanAbstract: Medicine has encountered unprecedented problems associated with changes in nature, society, and environment, as well as with new human quests for survival, longevity, and health. In the meantime, the development of medicine is facing challenges that resulted from the over-division and specialization of disciplines and the fragmentation of medical knowledge. To construct a new medical system that is more suitable for human health and disease treatment, holistic integrative medicine (HIM), which regards the human body as a holistic entity, organically integrates the most advanced knowledge and theories in each medical field and the most effective practices in various clinical specialties to revise and adjust on the basis of social, environmental, and psychological conditions. HIM is the inevitable and necessary direction for the future development of medicine. In this article, we illustrated the connotation of HIM, the differences between HIM and other medical conceptions, and the practice of HIM in recent years. Full text PDFCite this article: Daiming Fan. Holistic integrative medicine: toward a new era of medical advancement . Frontiers of Medicine, 2017. 11(1): 152-159 Do you want to publish your article in this journal? 欢迎订阅 邮发代号 80-967 ；或联系高等教育出版社 010-58556485 customercenter@pub.hep.cn 在线浏览 http://journal.hep.com.cn/fmd http://hep.calis.edu.cn/ 谢谢您的关注！ Frontiers of Medicine Website: http://journal.hep.com.cn/fmd or http://www.springer.com/medicine/journal/11684 Frontiers of Medicine 由中国工程院、高等教育出版社和上海交通大学医学院附属瑞金医院联合主办，由高等教育出版社出版、德国 Springer 公司海外发行，为中国工程院院刊。主编为中国工程院院士、上海交通大学医学院附属瑞金医院上海血液学研究所陈赛娟教授，中国工程院院士、哈尔滨医科大学杨宝峰教授和中国科学院院士、华中科技大学同济医学院附属同济医院外科学系陈孝平教授。本刊为英文医学综合性学术期刊，报道领域包括临床医学、基础医学、转化医学、流行病学、中医药学、公共卫生、医疗卫生政策等，文章类型分 Editorial( 社论 ) ， News Views ( 新闻视点 ) ， Reviews( 综述 ) ， Mini-reviews （短篇综述 ) ， ResearchArticles ( 原创性研究论文 ) ， Case Report ( 病例报告 ) ， Commentary （评论）， Letter to Frontiers of Medicine （通讯报道），等等。
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我国中药治疗“甲流”效果获国际认可（附原文） 发布时间： 2011-08-23 | 作者：周婷玉 http://www.stdaily.com 2011年08月23日 ■医卫动态 国际权威医学期刊《内科学年鉴》16日发表我国学者的临床研究结果。这一研究显示，中药汤剂可有效缓解甲型H1N1流感引起的发热症状，其效果与达菲相仿或有更加优效趋势。 记者18日从首都医科大学附属北京朝阳医院——北京呼吸疾病研究所获悉，这一关于奥司他韦（达菲）和传统中药汤剂（麻杏石甘汤和银翘散加减方）治疗甲型H1N1流感（简称甲流）的临床研究是由该所及卫生部北京医院王辰教授领衔、由国内11家医院组成的课题组共同完成。 这一研究在《内科学年鉴》的发表，标志着国际权威医学刊物对我国中医药学研究的认可。研究以科学的方法向世界展示了中医药在人类应对新发呼吸道传染病和突发公共卫生事件中的作用，是中医药研究走向世界进程中具有标识性的重要事件。文章发表后受到国际广泛关注，包括美国卫生部网站在内的3万多个国际主流网站对相关报道进行了转载。 研究采用规范、严格的现代循证医学研究方法，将410例确诊为轻症甲流的成年患者随机分为4组：对照组、达菲组、中药组（应用麻杏石甘汤和银翘散加减方汤剂）、达菲加中药组。结果发现，对照组的发热持续时间为26小时，达菲组的发热时间为20小时，中药组的发热时间只有16小时，达菲加中药汤剂患者的发热时间为15小时。统计分析显示，三个用药组的发热时间均显著短于对照组，中药汤剂可以显著降低甲流发热持续时间。 因为麻杏石甘汤和银翘散加减方中有炙麻黄，含有麻黄碱成分，而一些国家对含有麻黄碱的药物是禁用的。针对西方学者对麻黄毒副作用的担心，课题组解释，方剂中麻黄的使用剂量很小，完全在中医药典的安全剂量范围内。而且，研究观察的205例使用该方剂的患者中未见较大剂量麻黄所引起的心率加快、血压高等副作用，安全性好。 据介绍，2009年秋天，为应对甲流疫情，有关中西医专家提出应当迅速组织评价、验证传统中医药对于甲流的预防与治疗效果，以在达菲储量不足或病毒对达菲出现耐药的情况下提供有效的防治药物。经中西医专家联合讨论，决定采用我国传统上用于“热病”治疗的麻杏石甘汤和银翘散的加减方作为统一处方，所含12味中药均采用同一产地、同一批号的饮片。汤剂制作过程采用严格的标准操作程序，确保中药饮片煎制后其成分固定。经严密筹备，课题组启动了此项在以现代科学方法验证中医药有效性、寻找应对突发呼吸道传染病疫情方面具有极为重要意义的研究。 《内科学年鉴》创刊于1927年，是美国内科医师学院的官方杂志，为世界权威医学杂志，被公认为国际内科学领域“第一刊”。 （新华社） （文·周婷玉） 本篇文章来源于 科技网|www.stdaily.com 原文链接： http://www.stdaily.com/kjrb/content/2011-08/23/content_339704.htm 原文如下（ http://www.annals.org/content/155/4/217.full ）： Original Research Oseltamivir Compared With the Chinese Traditional Therapy Maxingshigan–Yinqiaosan in the Treatment of H1N1 Influenza A Randomized Trial Chen Wang , MD, PhD ; Bin Cao , MD ; Qing-Quan Liu , MD ; Zhi-Qiang Zou , MD ; Zong-An Liang , MD ; Li Gu , MD ; Jian-Ping Dong , MD ; Li-Rong Liang , MD ; Xing-Wang Li , MD ; Ke Hu , MD ; Xue-Song He , MD ; Yan-Hua Sun , MD ; Yu An , MD ; Ting Yang , MD ; Zhi-Xin Cao , MD ; Yan-Mei Guo , MD ; Xian-Min Wen , MD ; Yu-Guang Wang , MD ; Ya-Ling Liu , MD ; and Liang-Duo Jiang , MD + Author Affiliations From Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, and Beijing Hospital, Ministry of Health, Beijing; Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing; Yantai Infectious Disease Hospital, Shandong; Chengdu Infectious Disease Hospital, Sichuan; Beijing Haidian Hospital, Beijing; Beijing Ditan Hospital, Institute of Infectious Diseases, Capital Medical University, Beijing; Renmin Hospital of Wuhan University; Changxindian Hospital of Fengtai District of Beijing, Beijing; Second Hospital of Chaoyang District of Beijing, Beijing; Second Hospital of Beijing, Beijing; and West China Medical School, West China Hospital, Sichuan University, Sichuan, China. Next Section Abstract Background: Observational studies from Asia suggest that maxingshigan–yinqiaosan may be effective in the treatment of acute H1N1 influenza. Objective: To compare the efficacy and safety of oseltamivir and maxingshigan–yinqiaosan in treating uncomplicated H1N1 influenza. Design: Prospective, nonblinded, randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00935194 ) Setting: Eleven hospitals from 4 provinces in China. Patients: 410 young adults aged 15 to 59 years with laboratory-confirmed H1N1 influenza. Intervention: Oseltamivir, 75 mg twice daily; maxingshigan–yinqiaosan decoction (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae), 200 mL 4 times daily; oseltamivir plus maxingshigan–yinqiaosan; or no intervention (control). Interventions and control were given for 5 days. Measurements: Primary outcome was time to fever resolution. Secondary outcomes included symptom scores and viral shedding determined by using real-time reverse transcriptase polymerase chain reaction. Results: Significant reductions in the estimated median time to fever resolution compared with the control group (26.0 hours ) were seen with oseltamivir (34% ; P 0.001), maxingshigan–yinqiaosan (37% ; P 0.001), and oseltamivir plus maxingshigan–yinqiaosan (47% ; P 0.001). Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P = 0.05) with oseltamivir plus maxingshigan–yinqiaosan compared with oseltamivir. The interventions and control did not differ in terms of decrease in symptom scores ( P = 0.38). Two patients who received maxingshigan–yinqiaosan reported nausea and vomiting. Limitations: Participants were young and had mild H1N1 influenza virus infection. Missing viral data precluded definitive conclusions about viral shedding. Conclusion: Oseltamivir and maxingshigan–yinqiaosan, alone and in combination, reduced time to fever resolution in patients with H1N1 influenza virus infection. These data suggest that maxingshigan–yinqiaosan may be used as an alternative treatment of H1N1 influenza virus infection. Primary Funding Source: Beijing Science and Technology Project and Beijing Nova Program. Editors' Notes Context Some speculate that the herbal therapy maxingshigan–yinqiaosan could serve as an alternative therapy to antivirals. Contribution In this randomized trial that compared maxingshigan–yinqiaosan with oseltamivir alone, oseltamivir plusmaxingshigan–yinqiaosan, and no treatment in mildly ill patients with confirmed H1N1 influenza, fever resolved sooner in all 3 therapeutic groups than in the group that received no treatment. Caution Ephedra is an ingredient of maxingshigan–yinqiaosan; it is legally unavailable in settings in which ephedra is banned. The study could not determine whether the observed effects of maxingshigan–yinqiaosan were due to antipyretic or antiviral effects. Implication Among patients with mild H1N1 infection, maxingshigan–yinqiaosan speeds fever resolution similarly to oseltamavir. —The Editors In April 2009, cases of human infection with H1N1 influenza A virus were identified in the United States (1) and Mexico (2) and spread rapidly to other regions of the world (3) , resulting in the first influenza pandemic since 1968. As of March 2010, almost all countries had reported cases, and more than 17700 deaths among laboratory-confirmed cases had been reported to the World Health Organization (4) . Influenza A pandemic is typically characterized by abrupt onset of fever, nonproductive cough, sore throat, headache, and myalgia. The illness is usually self-limited, with relief of symptoms within 5 to 7 days (5) . Nevertheless, it is an important disease owing to its ease of communicability and the possibility of severe complications (6, 7) . The antiviral agent oseltamivir was widely used during the H1N1 influenza A pandemic, as recommended by the World Health Organization (8) . Observational studies of hospitalized patients with pandemic H1N1 influenza A infection have suggested that treatment with oseltamivir may reduce severity of and mortality from the disease (9) . However, no direct comparative evidence on the role of oseltamivir in the current novel H1N1 influenza A pandemic has been reported. Isolates of pandemic H1N1 influenza A virus with resistance to oseltamivir have been detected (10) . In resource-limited settings, such as rural areas of China, where the supply of oseltamivir was often insufficient, traditional Chinese medicine (TCM) was used as an alternative therapy. Traditional Chinese medicine has been used to treat seasonal influenza for thousands of years (11) . In a recent meta-analysis of 31 randomized clinical trials including 5514 cases of influenza (12) , the authors concluded that TCM had significantly increased clinical efficacy compared with placebo or no intervention (93.46% vs. 79.03%, respectively; odds ratio, 3.99 ; P 0.001), and no serious adverse effects were reported. Modern pharmacologic studies demonstrated that some TCM formulas had antiviral and immunomodulating effects (13, 14) . During the early days of the 2009 H1N1 influenza A pandemic, the popular herbal formula maxingshigan–yinqiaosan was used widely by TCM practitioners to reduce symptoms. We sought to compare the efficacy and safety of oseltamivir, TCM, and no treatment in adults and adolescents with uncomplicated 2009 H1N1 influenza A virus infection. Persons with mild illness who do not have high-risk conditions do not usually require testing or treatment, and the decision about whether to initiate antiviral therapy is individualized on the basis of the clinician's judgment and on what is known about the benefits of therapy. Therefore, it was ethically possible for us to include a control group that received no intervention. Previous Section Next Section Methods Study Design We conducted a prospective, randomized, controlled, nonblinded, multicenter trial during the H1N1 influenza A epidemic between July and November 2009 at 11 medical sites in 4 provinces in China. The institutional review board of Beijing Chao-Yang Hospital reviewed and approved the protocol and consent forms before the start of the study. All participants signed written informed consent forms before enrollment. Patient Enrollment Patients aged 15 to 70 years who presented within 72 hours of onset of H1N1 influenza A symptoms were enrolled. All patients were admitted to hospitals, where they could be quarantined and observed. Patients who fulfilled all of the following criteria were included: documented body temperature 37.5°C or greater, 1 or more respiratory symptoms (cough, sore throat, or rhinorrhea), and a positive result for H1N1 influenza A virus on real-time reverse transcriptase polymerase chain reaction (RT-PCR). Women were required to have a negative urine pregnancy test before drug administration. Patients were excluded if they had received influenza vaccination in the 12 months before the start of the study; had active, clinically significant chronic illness or HIV disease; were receiving systemic steroids or other immunosuppressants; had taken Chinese medicinal herbs or antivirals; or had new infiltrate of the lungs on chest radiography. Drug Administration The TCM formula that we used in our study was maxingshigan–yinqiaosan, which is composed of 12 herbs: zhimahuang (honey-fried Herba Ephedrae), 6 g; zhimu (Rhizoma Anemarrhenae), 10 g; qinghao (Herba Artemisiae Annuae), 15 g; shigao (Gypsum Fibrosum), 30 g; yinhua (Flos Lonicerae Japonicae), 15 g; huangqin (Radix Scutellariae), 15 g; chaoxingren (stir-baked Semen Armeniacae Amarum), 15 g; lianqiao (Fructus Forsythiae), 15 g; bohe (Fructus Forsythiae), 6 g; zhebeimu (Bulbus Fritillariae Thunbergii), 10 g; niubangzi (Fructus Arctii Tosum), 15 g; and gancao (Radix Et Rhizoma Glycyrrhizae), 10 g. Appendix Table 1 lists the names of these herbs in Chinese and English. View this table: In this window In a new window Appendix Table 1. Chinese Simplified Script and Traditional Script and English Translations of Traditional Chinese Medicines Mentioned in This Article The criteria for the quality of the herbs we used were in accordance with the 2005 Chinese pharmacopoeia (15) . All herbs were distributed to the 11 study sites from the same source. Before the start of the trial, the herbs were tested for heavy metals, microbial contamination, and residual pesticides; all results met safety standards in China. Laboratory personnel were blinded to the identity of the herbs. At each study site, a trained technician prepared the decoction according to a standardized procedure; each unit of formula yielded 800 mL of decoction. Oseltamivir was given as capsules, and the TCM intervention was given as a decoction. Placebo capsules were not used; the control group received no intervention. After agreeing to participate, signing the informed consent form, and completing the baseline visit, all patients were randomly assigned to 1 of the 3 active treatment groups or the control group by using random-number tables with a block size of 8 (SPSS software, version 13.0 ). Randomization was stratified by the 4 study centers, located in Beijing, Yantai, Chengdu, and Wuhan. These centers were selected to ensure broad geographic spread and representation of H1N1 influenza A epidemic areas in mainland China. A statistician who was not involved in data collection or analysis produced the randomization list. A coordinator at each site who was blinded to the participants' characteristics assigned the participants to treatment by telephoning a contact at the study coordinating center in Beijing Chao-Yang hospital. The contact was not involved in the number generation and recruitment process. Participants were then randomly allocated to the control group or one of the intervention groups: oral oseltamivir, 75 mg daily for 5 days; maxingshigan–yinqiaosan decoction, 200 mL orally 4 times daily for 5 days; or oseltamivir plus maxingshigan–yinqiaosan. All participants were hospitalized so that they could be quarantined and closely observed and were followed until discharge. Adherence to therapy was assessed by nurses who were blinded to the study. On the basis of the attending physician's judgment, participants were allowed to use acetaminophen if their body temperature was greater than 39°C. Likewise, the need for antibiotics was determined by the attending physicians. The use of acetaminophen or antibiotics was recorded on the case record form. Assessment During hospitalization, nurses who were blinded to the study used a mercury thermometer to measure participants' body temperature daily at 2 a.m. to 6 a.m., 6 a.m. to 10 a.m., 10 a.m. to 2 p.m., 2 p.m. to 6 p.m., 6 p.m. to 10 p.m., and 10 p.m. to 2 a.m. The presence and severity of influenza symptoms (cough, sore throat, rhinorrhea, headache, and fatigue) and drug-associated side effects were also recorded daily. Symptom scores (0 = absent, 1 = mild, 2 = moderate, and 3 = severe) were recorded and compared with baseline scores until 5 days after treatment in all groups. The primary efficacy end point was time from randomization to fever resolution (body temperature ≤37°C for ≥24 hours). Secondary outcomes were the proportion of patients who became afebrile (body temperature ≤37°C for ≥24 hours); improvement in symptom scores during the study period; side effects associated with the interventions; and incidence of secondary complications of influenza, such as otitis, bronchitis, sinusitis, and pneumonia. Throat swab specimens were collected from all participants and sent to local branches of the Chinese Center for Disease Control and Prevention for H1N1 influenza A RNA testing by using the protocol from the U.S. Centers for Disease Control and Prevention (16) . Serial real-time RT-PCR for viral RNA titers was performed daily from enrollment until discharge. Statistical Analysis We set the sample size to provide adequate power to detect differences of 12 hours or more in time to fever resolution. Clinical analysis of initial cases of 2009 H1N1 influenza in China demonstrated that the median duration of fever was 3 days (interquartile range, 2 to 4 days) (5) . Randomized, controlled studies have shown that oseltamivir reduced duration of illness of patients with influenza by 25% to 32% (17, 18) . On this basis, the difference of at least 12 hours is accepted in the routine clinical practice of treating 2009 H1N1 influenza. Therefore, 100 patients per study group provided 80% power to detect a significant difference of 12 hours or more in time to fever resolution, assuming an SD of 30 and a 2-sided α value of 0.05 for the primary outcome comparisons. All patients who were randomly assigned were included in all efficacy analyses, and patients were analyzed according to their treatment assignment. Means (SDs) or medians (interquartile ranges) were calculated to summarize continuous variables. For categorical variables, the proportion of patients in each category was calculated. One-way analysis of variance, the Kruskal–Wallis rank-sum test, and the chi-square test, as appropriate, were used to compare baseline characteristics among the 4 groups. For analyses of differences in time to fever resolution among 4 treatment groups, an accelerated failure time model (19) was used to estimate median time to fever resolution and percentage change in time to fever resolution, with adjustment for stratified randomization centers and time since onset of illness less than 48 hours versus 48 to 72 hours. The final model was based on the log-normal distribution. Log-logistic and Weibull models were also considered, but the log-normal model fit the best. Interactions between treatment and center and between treatment and time since onset of illness were tested. Changes in viral titer from baseline to day 5 were assessed with a generalized linear mixed model using PROC GLIMMIX in SPSS. Bonferroni adjustment was performed for multiple comparisons of 4 groups. The interaction of time with treatment was also analyzed in the model. Data on time to fever resolution were missing for 1 participant in the control group. For the primary outcome analysis, this participant was considered as a censored observation in the accelerated failure time models. A P value less than 0.05 was considered statistically significant. All analyses were done by using SPSS for Windows, version 13.0, except for analyses of primary outcome and changes in viral titer; these were performed by using SAS software, version 9.1.3 (SAS Institute, Cary, North Carolina). Role of the Funding Source The Beijing Science and Technology Project and the Beijing Nova Program provided funding for the trial. The funding agencies were involved in study design, data collection, data analysis, and manuscript preparation. All authors had full access to the data, participated in data analysis and manuscript development, and gave final approval of the manuscript. Drs. Bin Cao and Chen Wang were involved in the study design and made final decisions on manuscript content. Previous Section Next Section Results Participant Characteristics We recruited 410 participants aged 15 to 69 years from 11 sites. The mean age was 19.0 years (SD, 6.4), and 57.1% of participants were men. Follow-up lasted 12 hours to 16 days (median, 5.0 days). The median time from onset of illness to randomization was 34.5 hours (interquartile range, 18.0 to 48.0 hours) and did not significantly differ among groups. The Figure shows the disposition of the study participants. Of the 410 participants, 102, 103, and 102 were randomly assigned to receive oseltamivir, maxingshigan–yinqiaosan, and combination therapy, respectively. Baseline demographic characteristics, clinical features, and laboratory findings were similar among the 4 groups ( Table 1 ). View larger version: In this page In a new window Download as PowerPoint Slide Figure. Study flow diagram. MY = maxingshigan–yinqiaosan. * These patients were discharged early and declined to return. View this table: In this window In a new window Table 1. Patient Characteristics Use of antibiotics was similar among all groups at baseline (4.9% to 7.8%; P = 0.88) but was much more frequent in the control group after enrollment (34.3% vs. 15.7% in the oseltamivir group, 9.7% in the maxingshigan–yinqiaosan group, and 7.8% in the combination therapy group; P 0.001). First- or second-generation cephalosporins, clindamycin, azithromycin, levofloxacin, and moxifloxacin were the agents chosen by the attending physicians ( Table 2 ). View this table: In this window In a new window Table 2. Use of Acetaminophen and Antibiotics Clinical Outcomes Table 3 shows the effects of the interventions and control on alleviating illness. According to the accelerated failure time model, the estimated median time to fever resolution was significantly reduced in the oseltamivir group (35% ; P 0.001), the maxingshigan–yinqiaosan group (37% ; P 0.001), and the combination therapy group (47% ; P 0.001) compared with the control group (26.0 hours ) ( Appendix Figure 1 ). When the active treatments were compared with one another, however, only the percentage difference in median time to fever resolution with combination therapy versus oseltamivir alone (−19% ) reached borderline statistical significance. Interactions between treatment and center (randomization strata) and between treatment and time since onset of illness were not statistically significant ( P = 0.51 and P = 0.72, respectively). View this table: In this window In a new window Table 3. Accelerated Failure Time Model Estimates for Median Time to Fever Resolution and Difference in Time to Resolution View larger version: In this page In a new window Download as PowerPoint Slide Appendix Figure 1. Fitted curves from accelerated failure time models for median time to fever resolution. MY = maxingshigan–yinqiaosan. The median baseline symptom score was 3 and did not differ among the 4 groups ( Appendix Table 2 ). No difference in any individual symptom, including cough, sore throat, headache, or fatigue, was observed after treatment. View this table: In this window In a new window Appendix Table 2. Change in Symptom Scores During the Study Period Virologic Outcomes Both baseline swab specimens and specimens collected on days 1 to 5 for evaluation of virus shedding were available for 148 participants. Compared with the 262 patients without viral shedding measurements, these 148 patients had lower symptom scores; a lower proportion of cough, headache, and fatigue; lower leukocyte counts; and longer time from onset of illness to randomization. Therefore, the virus shedding results from these 148 patients were not representative of the entire study population ( Appendix Table 3 ). View this table: In this window In a new window Appendix Table 3. Complications and Adverse Events In this subgroup, the median viral titer in throat swabs at enrollment was similar, and a rapid decrease in virus shedding was observed in all 4 groups ( P 0.001) ( Table 4 and Appendix Figure 2 ). Changes in virus shedding from baseline to day 5 did not differ by treatment group ( P = 0.69 for time-by-treatment interaction) ( Appendix Figure 2 ). View this table: In this window In a new window Table 4. Changes in Viral Titer on Real-Time Reverse-Transcriptase Polymerase Chain Reaction View larger version: In this page In a new window Download as PowerPoint Slide Appendix Figure 2. Mean viral titer among 148 participants for whom results were available. MY = maxingshigan–yinqiaosan. Safety Two patients in the maxingshigan–yinqiaosan group had nausea and vomiting. No side effects were observed in the control, oseltamivir, or combination therapy group ( Appendix Table 4 ). No difference in complications after treatment was observed among the 4 groups: 1 case of pulmonary tuberculosis in the control group, 2 cases of pneumonia in the oseltamivir group, 1 case of bronchitis in the maxingshigan–yinqiaosan group, and no complications in the combination therapy group ( Appendix Table 4 ). View this table: In this window In a new window Appendix Table 4. Baseline Characteristics of Patients Without and Those With Viral Titer Measurements Previous Section Next Section Discussion To our knowledge, this is the first registered randomized, controlled trial to investigate the efficacy and safety of oseltamivir, TCM, and no treatment in H1N1 influenza A. We found that resolution of fever was faster with maxingshigan–yinqiaosan than no intervention, but the improvement in symptoms was not significantly more rapid. Compared with active treatments, the reduction in median time to fever resolution between oseltamivir plus maxingshigan–yinqiaosan and oseltamivir (20.0 hours vs. 16.0 hours ) was only 19% (CI, −34% to −0.3%); this reached borderline statistical significance, but the difference was less than the margin of 12 hours. Therefore, with regard to clinical implication, we could not conclude that maxingshigan–yinqiaosan was superior to oseltamivir. We did not find evidence for differences in reductions in viral shedding; however, viral outcomes were available only for a subgroup of patients who had fewer symptoms and longer time from illness onset to randomization. The mechanism of TCM in the treatment of influenza is complex. Zhao and colleagues (21) found that maxingshigan regulated the percentage of T-cell subpopulation in mice exposed to influenza virus A. Investigators also found that maxingshigan had inhibitory effects on influenza virus A by directly killing the virus, interfering with virus adsorption, inhibiting virus proliferation, and protecting the cells from being infected with virus. Except in terms of inhibiting virus proliferation, maxingshigan performed much better than ribavirin (22, 23) . During the outbreak of the severe acute respiratory syndrome in Hong Kong, Poon and associates (24) showed that 2 herbal formulas had immunomodulating effects. In their study of healthy volunteers, they found that the CD4–CD8 ratio of T lymphocytes was significantly increased after participants received Chinese herbal medicine for 14 days (24) . Administration of Chinese herbs may have beneficial immunomodulatory effects for rapid recovery of viral infections. More studies are needed to clarify the mechanisms of TCM. The preparations of maxingshigan–yinqiaosan that we used are those that have been standard for decades, but their safety has not been fully investigated. In our study, 2 of 103 patients (1.9% ) in the maxingshigan–yinqiaosan group experienced nausea and vomiting, and no adverse effects were reported in the oseltamivir and combination therapy groups. The empirical use of certain Chinese medicines in combination with oseltamivir is advocated for the treatment of influenza in Asia, but little is known about the potential for drug interactions in such combinations. A study from Hong Kong showed that TCM preparations may significantly reduce active metabolism of oseltamivir in plasma, most likely owing to suppression of oseltamivir metabolism and possibly enhanced renal clearance (25) . Given the relatively short course of our study and the relatively healthy participants, more evidence on safety of maxingshigan–yinqiaosan is needed before this agent is used widely. In the United States and Canada, marketing of ephedra and ephedrine-containing stimulant combinations for weight loss and bodybuilding is now restricted or illegal because myocardial infarctions, strokes, and deaths associated with these supplements have been reported (26, 27) . The ban on ephedra-containing supplements continues to be controversial. Ephedra is legal in such countries as Germany, Japan, India, and China, where it is widely used. There is general agreement that ephedra treats symptoms of the common cold, allergic rhinitis, and obstructive sleep apnea. In China, Herba Ephedrae is not used for weight loss, bodybuilding, or increased energy. A large follow-up case study found no evidence of severe cardiovascular risk with prescribed ephedrine (28) , and the suspicion of cardiovascular toxicity of ephedrine was mainly based on spontaneous reporting (29–31) . According to a Chinese pharmacopoeia (15) , Herba Ephedrae (mahuang) has a total alkaloid content of 1% by dry weight, and honey-frying (32) decreases the alkaloid content by 0.194%. The safe daily dose of Herba Ephedrae is 2 to 9 g/d. Overdose of Herba Ephedrae causes serious adverse effects. Oseltamivir is a potent and specific influenza neuraminidase inhibitor and inhibits replication of influenza A and B viruses in vitro (33) . However, direct evidence of clinical effectiveness and safety of oseltamivir in treating the 2009 H1N1 influenza A pandemic is limited. Studies in healthy adults with influenza in the United States and Europe showed that early treatment of oseltamivir (usually within 36 hours of onset) could reduce the median duration of illness by 30% (17, 18) . In a recent systematic review and meta-analysis, Jefferson and colleagues concluded that the efficacy of oral oseltamivir, 150 mg/d, against symptomatic laboratory-confirmed influenza was 73% (34) . However, the benefit of oseltamivir was somewhat less than that reported in randomized, controlled trials of its use in seasonal influenza, and in our trial the duration of fever was shortened by 6 hours in the oseltamivir group compared with the control group. In addition, oseltamivir provides no additional benefit in terms of decrease in symptom scores during treatment. This lesser benefit may be due to delayed initiation of treatment with oseltamivir while awaiting results of real-time RT-PCR for H1N1 influenza A virus. In our study, the median time from onset of illness to randomization was 34.5 hours; 23.2% of patients presented 48 to 72 hours after the onset of symptoms. Participants in our study were relatively young and largely had very mild disease. They were admitted to hospitals for quarantine purposes, not because of the severity of the illness. Because disease was mild in these patients, we could not detect a difference in the rate of improvement of symptoms, except fever, in the intervention groups compared with control. Our findings suggest that maxingshigan–yinqiaosan does not act as an antiviral, whereas the benefit of oseltamivir derives entirely from its antiviral activity. The prudent use of antivirals stems from concern that resistance to these agents develops quickly (35) , and we agree that healthy young adults who are not at risk (unlike infants, children, pregnant women, elderly persons, and patients with chronic comorbid conditions) do not need antivirals to treat influenza (8) . In these persons, maxingshigan–yinqiaosan may be used instead of oseltamivir. Our study has limitations. First, it was not a double-blind, placebo-controlled clinical trial. Oseltamivir was given as capsules, and maxingshigan–yinqiaosan was given as a decoction. During the first months of the pandemic, we could not find appropriate placebos for maxingshigan–yinqiaosan that had a similar color and taste (brown and bitter) before the trial began. However, because we included patients who received no treatment as a control group, we were able to prove that the improvement in fever was not due to the placebo effect. In addition, measurements of temperature and virus shedding are objective findings, and the nurses who measured patients' temperature were unaware of study group assignment. Second, the use of acetaminophen and antibiotics was decided by the attending physicians; however, the proportion and extent of use of acetaminophen was similar in the 4 groups at baseline ( Table 2 ). Acetaminophen was used infrequently and probably had no effect on temperature change. More patients in the control group received antibiotics after enrollment. This is similar to many other febrile illnesses, in which physicians respond to persistent temperature elevation by administering antibiotics. Usually, antibiotics are not called for in that situation. Third, both baseline swab and swabs collected on days 1 to 5 for evaluation of virus shedding were available for only 148 participants. Compared with the 262 patients for whom viral shedding measurements were not available, the 148 patients had lower symptom scores, lower leukocyte counts, and a longer interval between onset of illness and randomization, which means that the virus shedding results from the 148 patients were not representative of the overall study population. The lesser extent of disease and longer interval between onset of illness and randomization might explain why changes in virus shedding from baseline to day 5 did not differ by treatment group. In conclusion, in previously healthy young adults and adolescents who presented with uncomplicated 2009 H1N1 influenza A virus infection, therapy with oseltamivir and maxingshigan–yinqiaosan (alone and in combination) was associated with faster resolution of fever. Maxingshigan–yinqiaosan can be used as an alternative treatment of H1N1 influenza A virus infection when oseltamivir is not available. Previous Section Next Section Article and Author Information Note: Drs. C. Wang, B. Cao, Q.Q. Liu, Z.Q. Zou, Z.A. Liang, L. Gu, J.P. Dong, and L.R. Liang contributed equally to this article. Acknowledgment: The authors thank Drs. Jing Zhao, Lai-Ying Fang, Zhi-Tao Tu, Chun Huang, Xiao-Hui Zhai, Xiao-Li Li, Wei Wu, Ran Li, Yi-Qun Guo, Jing-Ya He, Yong Guo, Yu-Dong Yin, Shufan Song, Na Cui, Lu Bai, and Ling-Ling Su, who participated in collection of clinical data, and Drs. Getu Zhaori, Weili Zhang, and Yiqing Song for assistance in careful editing of the manuscript. They also thank Drs. Hua-Xia Chen, Chun-Jiang Zhao, Xiao-Min Yu, Ran Miao, Ying-Mei Liu, and Li-Li Ren, and Mr. Xiang-Yang Ding for technical support. Grant Support: By the Beijing Science and Technology Project (grants Z08050700020801and Z09000700090903) and the Beijing Nova Program (grant 2007A037). Potential Conflicts of Interest: None disclosed. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-2829 . Reproducible Research Statement: Study protocol and data set: Not available. Statistical code: Available from Dr. B. Cao (e-mail, caobin1999@gmail.com ). Requests for Single Reprints: Bin Cao, MD, Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Gongti South Road, No. 8, Beijing, 100020 China (e-mail, caobin1999@gmail.com ), or Chen Wang, MD, Department of Respiratory Medicine, Capital Medical University; Beijing Institute of Respiratory Medicine; Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders; Beijing Hospital, Ministry of Health, Beijing, 100020 China (e-mail, cyh-birm@263.net ). Current Author Addresses: Dr. C. Wang: Department of Respiratory Medicine, Capital Medical University; Beijing Institute of Respiratory Medicine; Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders; Beijing Hospital, Ministry of Health, Beijing, 100020 China. Drs. B. Cao and Gu: Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Gongti South Road, No. 8, Beijing, 100020 China. Drs. Q.Q. Liu and Jiang: Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Hai Yuncang Road, No. 5, Beijing, 100700 China. Drs. Zou and Guo: Yantai Infectious Disease Hospital, Huan Shan Road, No. 62, Yantai, Shandong Province, 341000 China. Dr. Z.A Liang: West China Medical School, West China Hospital, Sichuan University, Wainan Guoxue Road, No. 37, Chengdu, Sichuan Province, 610041 China. Dr. Dong: Beijing Haidian Hospital, Haidian Road, Beijing, 100080 China. Drs. L.R. Liang, Yang, and Z.X. Cao: Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Gongti South Road, No. 8, Beijing, 100020 China. Drs. Li and Y.G. Wang: Beijing Ditan Hospital, Institute of Infectious Diseases, Capital Medical University, Jingshun East Road, Beijing, 100018 China. Dr. Hu: Renmin Hospital of Wuhan University, Ziyang Road No. 99, Wuhan, Hubei Province, 430060 China. Dr. He: Changxindian Hospital of Fengtai District of Beijing, Beijing, 100072 China. Dr. Sun: Second Hospital of Chaoyang District of Beijing, Jintai Road, No. 13, Beijing, 100026 China. Dr. An: Second Hospital of Beijing, Xi Rongxian Road, No. 9, Beijing, 100031 China. Drs. Wen and Y.L. Liu: Chengdu Infectious Disease Hospital, Jingjusi South Road, Chengdu, Sichuan Province, 610061 China. Author Contributions: Conception and design: C. Wang, B. Cao, Q.Q. Liu, L. Gu, J.P. Dong, Z.X. Cao, L.D. Jiang. Analysis and interpretation of the data: B. Cao, L. Gu, L.R. 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中文名称：中医学 英文名称： traditional Chinese medicine 定义：以中医药理论与实践经验为主体，研究人类生命活动中健康与疾病转化规律及其预防、诊断、治疗、康复和保健的综合性科学。 应用学科：中医药学（一级学科）；中医药学总论（二级学科） 中医学是研究人体 生理 病理，疾病诊断与防治以及摄生康复的一门传统医学科学，至今已有数千年的历史。按照中国 全国科学技术名词审定委员会 审定的名词，中医学是“以中医药理论与实践经验为主体，研究人类生命活动中医学中健康与疾病转化规律及其预防、诊断、治疗、康复和保健的综合性科学”。 http://baike.baidu.com/view/56220.htm#2 中医 ，是“起源与形成于中国，具有整体观念、辨证论治等特点的医学”。中医至今已有数千年的历史。同时 中医 也指“中医药学科的专业职业队伍”，即 中医师 。 广义的中医，指的是中国境内所有的民族医学和宗教医学。如汉医、藏医、蒙医、苗医等，佛医、道医等等。 狭义的中医，指的则是汉医。1949年之前，汉医一词比较普遍。清后民国，也用国医来称呼。汉医，一是来自日本之称，一是来自清代的称呼。 日本 的 汉方医学 ， 韩国 的 韩医学 ， 朝鲜 称的 高丽医学 、 越南 的 东医学 都是以中医为基础发展起来的。在现今世界的医疗体系中，中医学被归类为 替代医学 中的一支。 http://zh.wikipedia.org/wiki/%E4%B8%AD%E5%8C%BB%E5%AD%A6 National Library of Medicine - Medical Subject Headings 2011 MeSH MeSH Descriptor Data Return to Entry Page Standard View. Go to Concept View ; Go to Expanded Concept View MeSH Heading Medicine, Chinese Traditional Tree Number E02.190.488.585.520 Tree Number I01.076.201.450.654.558.520 Annotation is not medicine in China ( = MEDICINE + CHINA ); Manual 32.13 ; medicinal plants in Chinese med: consider DRUGS, CHINESE HERBAL ; index differentiation of signs symptoms (bianzheng shizhi) under MEDICINE, CHINESE TRADITIONAL (IM) + DIAGNOSIS, DIFFERENTIAL (IM); Oriental taking of pulses = PULSE + appropriate acupuncture or Oriental medicine terms; DF: MED CHINESE TRADITIONAL Scope Note A system of traditional medicine which is based on the beliefs and practices of the Chinese culture.一个基于中国文化理念与实践的传统医学体系 Entry Term Chinese Medicine, Traditional Entry Term Chinese Traditional Medicine Entry Term Chung I Hsueh Entry Term Traditional Chinese Medicine Entry Term Traditional Medicine, Chinese Entry Term Zhong Yi Xue See Also Acupuncture Therapy See Also Drugs, Chinese Herbal See Also Medicine, Tibetan Traditional See Also Yang Deficiency See Also Yin Deficiency Allowable Qualifiers AE EC HI IS MT PX ST TD UT Entry Version MED CHINESE TRADITIONAL Online Note to search MEDICINE, CHINESE CHINESE MEDICINE use MEDICINE, CHINESE TRADITIONAL 1975-83 MEDICINE, ORIENTAL TRADITIONAL 1967-74 History Note 88(84); was see under MEDICINE, ORIENTAL TRADITIONAL 1984-87; was MEDICINE, CHINESE see under MEDICINE, ORIENTAL 1981-83; was CHINESE MEDICINE see under MEDICINE, ORIENTAL 1967-80 Date of Entry 19990101 Unique ID D008516 MeSH Tree Structures Therapeutics Complementary Therapies Medicine, Traditional Medicine, East Asian Traditional Medicine, Chinese Traditional Medicine, Kampo Medicine, Korean Traditional Medicine, Mongolian Traditional Social Sciences Anthropology Anthropology, Cultural Culture Medicine, Traditional Medicine, East Asian Traditional Medicine, Chinese Traditional Qi + Yin-Yang Medicine, Kampo Medicine, Korean Traditional Medicine, Mongolian Traditional Medicine, Tibetan Traditional http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi Traditional Chinese Medicine ( simplified Chinese : 中医 ; traditional Chinese : 中醫 ; pinyin : zhōng yī : " Chinese Medicine ") refers to a broad range of medicine practices sharing common theoretical concepts which have been developed in China and look back on a tradition of more than 2000 years, including various forms of herbal medicine , acupuncture , massage therapy , and dietary therapy. These practices are a common part of medical care throughout East Asia, but are considered alternative medicine in the western world. http://en.wikipedia.org/wiki/Traditional_Chinese_medicine 目录 1 历史 1.1 古代（经典）中医史 1.2 现代中医史 2 基础理论 2.1 古典基础理论 2.1.1 精气学说 2.1.2 阴阳学说 2.1.3 五行学说 2.1.4 藏象学说 2.1.5 气血津液 2.1.6 经络学说 2.1.7 病因学说 2.1.7.1 发病 2.1.7.2 病机 2.2 现代中医基础理论 3 诊断方法 4 治疗方法 5 学科分类 6 中医学典籍 7 流派及医家 8 中西医学的异同 8.1 医学理论体系 8.2 诊断疾病的思维方式 8.3 治疗的思维及方法 8.4 疗效验证方法 8.5 知识传播方式 9 反中医运动历史与观点 10 节日、文化遗产
中医药学是研究人体生命、健康、疾病的医学科学，其基础理论包括阴阳五行、藏象经络、气血津液、病因病机、辨证论治、药性归经等，其实践包括草药、针灸、食疗和推拿等，可追溯至石器时代。阴阳五行和经络理论，以及《黄帝内经》和《本草纲目》等经典著作，为中医药学的发展和普及作出了巨大的贡献。 整体观念、辨证论治、治未病是中医药学的临床精髓。《黄帝内经》云：“是故圣人不治已病治未病，不治已乱治未乱。” “治未病”对养生保健、防病治病有着重要的指导作用。当前，我国疾病预防控制形势严峻。人口老龄化，慢性非传染性疾病日益普遍。中医药学是值得探索和完善的宝贵财富，在疾病预防和治疗中具有重要的作用。在机遇与挑战并存的当今时代，在“中西医并重”、“大力扶持中医药和民族医药发展”的中医药政策的鼓舞下，近年来中医药学在各个方面取得了较大的进展，焕发出强大的生命力。 在主编、编委和作者们的大力支持下，Frontiers of Medicine 2011年第二期将发表中医药学研究领域前沿的多篇综述、研究论文和治疗案例报道，内容全面，探索深入：介绍新世纪的中医药学发展趋势；诠释中医药学基础理论的特点及其研究方向；比较中西医的差别，探讨中医药学自身的发展规律，论述中医药学从经验医学转向循证医学过程中存在的问题；探索循证中医临床路径的方法和应用；探讨风湿性关节炎中医辨证与基因表达之间的关系；介绍中医药学特色鲜明的理论特征和诊疗模式及其对统计学提出的诸多新的方法学挑战。本期内容还将涉及：脉络学说的理论构建；药用植物基因组计划；中药质量标准；道地药材的普遍性状、质量特点和形成机制；中药与HIV感染/艾滋病治疗究；中医药防治肿瘤；针刺技术用于阿片类药物成瘾治疗；西方针灸研究进展；针灸在辅助生殖技术中的应用；针刺不同穴位对内脏感觉-运动的调控机制和规律；癫痫宁临床疗效再评价；中医药知识保护；等等。 相信Frontiers of Medicine 2011年第二期将会为国内外中医药学研究领域的科研人员以及产业研发人员带来兼具深度和广度的中医药最新文献，提供较为广阔的视野，为推动我国中医药发展略尽绵薄之力。敬请关注。 Frontiers of Medicine（2011年前曾用名Frontiers of Medicine in China）从2010年1月起被国际权威的生物医学文摘索引数据库MEDLINE收录。 了解期刊详情，敬请浏览 http://journal.hep.com.cn 热忱期待您的投稿 http://journalsubmission.hep.com.cn 高等教育出版社自然科学期刊分社 北京市朝阳区惠新东街4号富盛大厦15层 100029 电话：010-58556319 Email：mojsh@hep.com.cn
标签: 中医药学
