Determination of 27 volatile organic compounds in exhaled breath by thermal desorption-gas chromatography-mass spectrometry / 环境与职业医学

Background Volatile organic compounds (VOCs) in exhaled breath are closely associated with respiratory diseases and are linked to various metabolic reactions in the human body. A quantitative analytical method can provide technical support for studying VOCs related to various diseases. Objective To establish a thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) method for the determination of 27 VOCs in exhaled breath. Methods VOCs in exhaled breath were collected using a Bio-VOC sampler and enriched with Tenax TA thermal desorption tubes before TD-GC-MS analysis. Standards were collected using thermal desorption tubes and optimized for thermal desorption conditions as well as chromatographic and mass spectrometric conditions: The separation of the 27 VOCs was achieved by an optimized temperature program, the improvement of sensitivity by optimizing quantitative ions, and the increase of VOCs desorption efficiency by optimizing thermal desorption time and temperature. Limit of detection, limit of quantification, accuracy, precision, and stability of the proposed method were investigated by spiking with a blank gas bag, and exhaled breath samples from 20 healthy individuals were collected for an application study of the proposed method. Results The thermal desorption temperature was 280 ℃, and desorption time was 6 min. A VF-624ms chromatographic column was selected for the separation of target substances. The initial temperature of heating program was 35 ℃, maintained for 1 min, and then increased to 100 ℃ at a heating rate of 3 ℃·min−1 for 1 min, followed by increasing to 210 ℃ at a heating rate of 28 ℃·min−1 for 5 min. A quantitative analysis was conducted with a single ion monitoring (SIM) mode. Under these conditions, the 27 VOCs showed good linear relationships in their respective concentration ranges and the correlation coefficients were higher than 0.9990. The limits of detection of the method were in the range of 0.01-0.13 nmol·mol−1, the limits of quantification were in the range of 0.02-0.44 nmol·mol−1, and the spiked recoveries were in the range of 80.1%-120.5%, with intra-batch and inter-batch precision ≤ 18.8% and 17.9% respectively. All substances can be stored at room temperature (23-28 °C) for 7 d and at 4 °C for 14 d. The proposed method was applied to exhaled breath samples from 20 subjects with detection rates≥ 80% (except for trans-2-pentene and decane) and a concentration range of 0.00-465.50 nmol·mol−1. Conclusion The established TD-GC-MS method for quantification of VOCs in exhaled breath is characterized by high sensitivity and good accuracy, and is suitable for quantitative determination of VOCs in exhaled breath, which can provide technical support for the study of exhaled breath VOCs.

Correlation of telomere length of bone marrow mononuclear cells with relapse after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia / 白血病·淋巴瘤

Objective:To investigate the relationship between telomere length of bone marrow mononuclear cells and prognosis of patients with acute myeloid leukemia (AML) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Telomere length of bone marrow mononuclear cells before transplantation, after transplantation and before donor mobilization as well as information related to follow-up of 33 AML patients who received allo-HSCT in the Affiliated Hospital of Guizhou Medical University between June 2020 and June 2021 were retrospectively analyzed. Telomere length was detected by using telomeric terminal restriction fragment (TRF) method. Telomere length was compared among patients with different prognoses. The recurrence within 1 year was treated as the gold standard and receiver operating characteristic (ROC) curve was used to analyze the effect of telomere length before transplantation or before donor mobilization in the judgement of the recurrence within 1 year after transplantation. The patients were stratified according to the optimal threshold value of telomere length for patients or donors, and Kaplan-Meier method was used to compare the progression-free survival (PFS) of patients with different stratification, and log-rank test was performed.Results:The median age of 33 patients was 34 years (14-61 years), and there were 17 males and 16 females; 31 patients were initially diagnosed with AML, 1 patient transferred from myelodysplastic syndrome (MDS) to AML, and 1 patient transferred from chronic granulocytic leukemia (CML) to AML; 14 received identical sibling transplantation and 19 received haploidentical sibling transplantation. The median age of the donors was 30 years (20-65 years), including 24 males and 9 females. Telomere length of bone marrow mononuclear cells before mobilization in 33 donors was longer than that in patients before transplantation (33 cases) and at +30 d after transplantation (31 cases) [(6.67±0.31) kb, (6.40±0.33) kb, (6.48±0.33) kb, respectively; all P < 0.05], and the difference between patients before and at +30 d after transplantation was not statistically significant ( t = 0.89, P = 0.378), and the telomere length of bone marrow mononuclear cells in 11 patients +180 d after transplantation was (6.66±0.18) kb. The incidence of acute graft-versus-host disease (aGVHD) after transplantation was 45.5% (15/33), the incidence of infection with clear imaging and pathogenic basis was 39.4% (13/33), the mortality rate within 1 year after transplantation was 3.0% (1/33), and the recurrence rate within 1 year after transplantation was 15.2% (5/33). There were no statistically significant differences in telomere length of donor pre-mobilization bone marrow mononuclear cells between the groups with and without aGVHD and between the infected and non-infected groups (all P > 0.05).Compared with patients who had not relapsed within 1 year after transplantation, telomere length of donor pre-mobilization bone marrow mononuclear cells was shorter in patients who relapsed within 1 year after transplantation [(6.39±0.19) kb vs. (6.72±0.30) kb, t = -3.23, P = 0.011], telomere length was longer in patients before transplantation [(6.75±0.16) kb vs. (6.35±0.36) kb, t = 4.17, P = 0.001]. ROC curve analysis showed that the optimal threshold values for telomere length of pre-transplantation and donor pre-mobilization bone marrow mononuclear cells were 6.48 and 6.42 kb, respectively for patients who relapsed within 1 year after transplantation. PFS in patients with pre-transplantation bone marrow mononuclear cells telomere length < 6.48 kb was better than that in patients with telomere length ≥ 6.48 kb ( P = 0.003); PFS in patients with pre-mobilization bone marrow mononuclear cells telomere length>6.42 kb was better than that in patients with telomere length ≤ 6.42 kb ( P < 0.001). Conclusions:In allo-HSCT for AML, patients have an increased risk of relapse within 1 year after transplantation when their pre-transplantation bone marrow mononuclear cells telomere length is long and the donor bone marrow mononuclear cells telomere length is short.

Network Meta-analysis of oral Chinese patent medicine in adjuvant treatment of rotavirus gastroenteritis in children / 中国中药杂志

This study aimed to evaluate the efficacy and safety of various oral Chinese patent medicines in the adjuvant treatment of rotavirus gastroenteritis(RVGE) in children based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicine in the adjuvant treatment of RVGE in children was retrieved from the databases such as CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science from database inception to October 22, 2022. The quality of the included RCT was evaluated according to the Cochrane risk-of-bias tool, and the data were analyzed by RevMan 5.4 and Stata 16 software. Sixty-three RCTs were included, with 11 oral Chinese patent medicines involved, including Xingpi Yanger Granules, Weichang'an Pills, Qiuxieling Mixture, Erxieting Granules, and Changyanning Granules/Syrup. The results of the network Meta-analysis showed that in terms of clinical total effective rate, the top 3 optimal interventions were Changyanning Granules/Syrup, Xiaoer Guangpo Zhixie Oral Liquid, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of the anti-diarrheal time, the top 3 optimal interventions were Shenling Baizhu Granules, Qiuxieling Mixture, and Shuangling Zhixie Oral Liquid combined with conventional western medicine. In terms of the antiemetic time, the top 3 optimal interventions were Changyanning Granules/Syrup, Xingpi Yanger Granules, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of the antipyretic time, the top 3 optimal interventions were Shenling Baizhu Granules, Xiaoer Shuangjie Zhixie Granules, and Qiuxieling Mixture combined with conventional western medicine. In terms of the negative conversion rate of rotavirus, the top 3 optimal interventions were Xingpi Yanger Granules, Erxieting Granules, and Cangling Zhixie Oral Liquid combined with conventional western medicine. In terms of reducing creatine kinase isoenzyme MB(CK-MB) level, the top 3 optimal interventions were Weichang'an Pills, Xingpi Yanger Granules, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of adverse reactions, no se-rious adverse reactions were reported in all studies. Oral Chinese patent medicines in the adjuvant treatment of children with RVGE have their own advantages, Specifically, Changyanning Granules/Syrup + conventional western medicine focuses on improving the clinical total effective rate and shortening the antiemetic time, Shenling Baizhu Granules + conventional western medicine on shortening the anti-diarrheal time and antipyretic time, Xingpi Yanger Granules + conventional western medicine on improving the negative conversion rate of rotavirus, and Weichang'an Pills + conventional western medicine on reducing the CK-MB level. Limited by the quantity and quality of literature included in this study, the results need to be verified by high-quality RCT with a larger sample size.

Technical points of human use experience of ethnic medicine / 中国中药杂志

Ethnic medicine has a rich history of application. Because of the large number of ethnic groups, wide geographical distribution, and unique medical systems in China, the research on the human use experience(HUE) of ethnic medicine should combine the characteristics of ethnic medicine, be based on practical experience, and respect folk practice and tradition. The clinical positioning of ethnic medicine should consider three factors, i.e., population region, dominant diseases, and clinical demand. We should consider the development of traditional preparations that meet the needs of ethnic regions and encourage the development of new drugs that can be popularized and used nationwide for the dominant diseases of ethnic medicines. Attention should be paid to the problems such as a large number of customary articles or substitutes of ethnic medicinal materials, the phenomena of foreign bodies with the same name and different names for the same substance, the different standards of medicinal materials, and the poor processing standards. The name, processing method, source, medicinal parts, and dosage of ethnic medicinal materials or decoction pieces should be determined, and resources should be carefully evaluated to ensure the safety of medicinal resources and ecology. The preparation of ethnic medicine is mostly in the form of pills, powder, ointment, etc., with simple processing technology. The problems of low-quality stan-dards of some preparations, different prescriptions with the same name, and inconsistent processing technology should be overcome, and the process route and main process parameters should be clarified to lay the foundation for the subsequent empirical research on HUE. In the collection and analysis of the HUE data of ethnic medicine, the core guiding ideology of "patient-centered" should be established, and the experience data of patients should be collected. The problems of weak links existing in the inheritance of ethnic medicine should be solved, and flexible and diverse methods should be adopted. Meanwhile, on the premise of complying with the requirements of the principles of medical ethics, we should respect the religion, culture, and customs of ethnic areas to obtain the key HUE information of ethnic medicine. On the basis of the patient preference information and differences in regional disease epidemiology, population characteristics, and medical practice, whether the HUE conclusions of ethnic medicine can be extrapolated to patients outside the region is evaluated from the aspects of clinical benefits, risk tolerance, risk acceptance, etc. The HUE research on ethnic medicine is carried out in a clear way to guide the research and development of new ethnic medicines.

Expression of SEC61G in Oral Squamous Cell Carcinoma and Its Prognostic Value / 肿瘤防治研究

Objective To analyze the expression of SEC61G in oral squamous cell carcinoma (OSCC) tissues and cell lines and determine its correlations with the clinicopathological features and prognosis of patients with OSCC. Methods The expression of SEC61G in OSCC tissues and its diagnostic and prognostic value were detected in the TCGA database. The expression levels of SEC61G in paraffin-embedded OSCC tissues and adjacent normal tissue specimens of 64 patients with OSCC were detected by immunohistochemistry. The correlation of SEC61G expression in OSCC tissues with the clinicopathological features was analyzed. Kaplan-Meier survival curve analysis showed that the expression of SEC61G correlated with the overall survival time of patients with OSCC. Cox regression analysis was used to analyze prognostic influence factors. Results The expression of SEC61G in OSCC tissues was significantly higher than that in para-carcinoma tissues (P < 0.05), consistent with the results of the TCGA database analysis, and its expression was closely related to N stage and clinical stage (P < 0.05). The overall survival of patients with OSCC in the group with low SEC61G expression was significantly higher than that in the high SEC61G expression group (P < 0.05). N stage and SEC61G expression were the prognostic influence factors for patients with OSCC (P < 0.05). SEC61G expression was an independent predictor of the prognosis of patients with OSCC (P < 0.05, AUC=0.923). Conclusion SEC61G is highly expressed in OSCC tissues and associated with N stage and clinical stage. Its high expression is associated with poor prognosis of patients. It may be a diagnostic biomarker for OSCC.

Thyroxine promotes the progression of integrin α vβ 3-positive differentiated thyroid cancer through the ERK1/2 pathway / 中华核医学与分子影像杂志

Objective:To explore whether thyroxine (T 4) could promote differentiated thyroid cancer (DTC) progression by binding to integrin α vβ 3in vitro and its downstream mechanism. Methods:Papillary thyroid cancer cell lines TPC-1, K1 and follicular thyroid cancer (FTC) cell line FTC133 were cultured in vitro, and the expressions of integrin α vβ 3 in those 3 DTC cell lines were determined with immunofluorescence and flow cytometry analysis. After the treatment of T 4, tetraiodo thyroacetic acid (Tetrac) and Arg-Gly-Asp (RGD) peptide alone or in combination, the proliferation and metastatic potential of DTC cell lines were detected by cell counting kit-8 (CCK-8), Transwell migration and invasion assays. The small interfering RNA (siRNA) transfection was used to verify whether integrin α v or β 3 subunit knockdown could reverse the effect of T 4 on DTC cells. The expression levels of downstream signaling proteins phosphorylated extracellular signal-regulated kinase (p-ERK)1/2 and total extracellular signal-regulated kinase (ERK)1/2 were detected by Western blot. The effects of mitogen-activated protein kinase kinase (MEK)1/2 inhibitor (GSK1120212) on the proliferation, migration and invasion of T 4-treated cells were detected. One-way analysis of variance and Tukey test were used for data analysis. Results:The integrin α vβ 3 expressions in TPC-1, K1 and FTC133 cells were all positive, with the relative mean fluorescence intensity (MFI) of 61.93±18.61, 16.89±2.43 and 32.36±0.83, and the percentages of positive cells of (94.38±1.30)%, (74.11±3.87)% and (50.67±1.78)%, respectively ( F values: 13.36 and 217.30, P=0.006 and P<0.001). Compared with control group, the proliferation, migration and invasion in the three DTC cell lines treated with T 4 were significantly enhanced (96 h, F values: 62.67-297.50, q values: 13.15-20.73, all P<0.001). T 4-induced cell proliferation, migration and invasion were markedly reversed by Tetrac or RGD (96 h, q values: 8.61-17.54, all P<0.001). T 4-induced cell proliferation, migration and invasion were also significantly inhibited by the knockdown of integrin α v or β 3 subunit (72 h, F values: 7.75-70.98, q values: 4.77-15.21, all P<0.05). Western blot results showed that the phosphorylation levels of ERK1/2 in DTC cells were significantly increased by T 4 treatment, and the T 4-induced activation of ERK1/2 signaling pathway could be blocked by Tetrac, RGD, integrin α v or β 3 subunit knockdown. T 4-induced cell proliferation, migration and invasion were significantly reversed by GSK1120212 (96 h, F values: 47.53-151.40, q values: 10.32-16.65, all P<0.001). Conclusion:T 4 can promote cell proliferation and metastasis of DTC cells by binding to integrin α vβ 3 and activating the ERK1/2 pathway.

Spatiotemporal evolution of COVID-19 epidemic in the early phase in China / 中华流行病学杂志

Objective: Based on the geographic information systems, we exploreed the spatiotemporal clustering and the development and evolution of COVID-19 epidemic at prefectural level in China from the time when the epidemic was discovered to the time when the lockdown ended in Wuhan. Methods: The information and data of the confirmed COVID-19 cases from December 8, 2019 to April 8, 2020 were collected from 367 prefectures in China for a spatial autocorrelation analysis with software GeoDa, and software ArcGIS was used to visualize the results. Software SatScan was used for spatiotemporal scanning analysis to visualize the hot-spot areas of the epidemic. Results: The incidence of new cases of COVID-19 had obvious global autocorrelation and the partial autocorrelation results showed that incidence of COVID-19 had different spatial distribution at different times from December 8, 2019 to March 4, 2020. There was no significant difference in global autocorrelation coefficient from March 5, 2020 to April 8, 2020. The statistical analysis of spatiotemporal scanning identified two kinds of spatiotemporal clustering areas, the first class clustering areas included 10 prefectures, mainly distributed in Hubei, from January 13 to February 25, 2020. The secondary class clustering areas included 142 prefectures, mainly distributed in provinces in the north and east of Hubei, from January 23 to February 1, 2020. Conclusions: There was a clear spatiotemporal correlation in the distribution of the outbreaks in the early phase of COVID-19 epidemic (December 8, 2019-March 4, 2020) in China. With the decrease of the case and effective prevention and control measures, the epidemics had no longer significant correlations among areas from March 5 to April 8. The study results showed relationship with time points of start and adjustment of emergency response at different degree in provinces. Furthermore, improving the early detection of new outbreaks and taking timely and effective prevention and control measures played an important role in blocking the transmission.

Immune-related myositis induced by immune checkpoint inhibitors: two case reports and literature review / 中华风湿病学杂志

Objective:To investigate the clinical features and treatment status of immune-related myositis (IRM) caused by immune checkpoint inhibitors (ICIs) in order to improve the diagnosis and treatment rate of the disease.Methods:Two cases of IRM combined with the diagnosis and treatment were described and the literature about IRM in the past 10 years was reviewed, and the clinical data of 59 patients were analyzed.Results:IRM was more common in males, with a total of 47 (79.7%). IRM usually occurred after 45 days of medication or after two doses. The clinical manifestations were mainly myalgia and muscle weakness, which were more common in the limbs. The initial symptoms were ptosis and diplopia. Fifty patients (84.7%) had serum creatine kinase (CK) levels higher than twice the upper limit of normal (UNL). In immunological examinations, 18 patients were found to be positive for anti-rhabdoid muscle antibody (AsM-Ab), while most of the myositisspecific antibodies (MSAs) and myositis-associated antibodies (MAAs) were negative. Thirty-four patients (75.6%) had abnormal EMG, and most patients showed myogenic injury. Muscle magnetic resonance imaging (MRI) showed muscle edema and inflammation in 8 patients. Muscle biopsies from 18 (45.0%) patients showed varying degrees of necrotic myofibers. Fifty-seven patients (96.6%) discontinued ICIs after developing IRM, 54(91.5%) received cortico-steroids, and 20(33.9%) received other treatments including intravenous immuno-globulin (IVIG), plasma exchange.Conclusion:IRM can occur in the early stage of ICIs treatment. Electro-myography, muscle MRI and muscle biopsy in suspicious cases can improve the diagnosis rate of the disease. Early use of corticoteroid, IVIG and other immunotherapy can effectively alleviate the disease.

Acupoint application for exogenous fever: a multi-central retrospective cohort study / 中国针灸

OBJECTIVE@#To explore the effectiveness on exogenous fever and the characteristics of effective population, as well as the specialties of prescription of acupoint application.@*METHODS@#Using the internet electronic diagnosis and treatment platform (Spring Broadcast Wanxiangyun Clinic Database, and the main TCM suitable technology promoted by this platform is acupoint application therapy), from August 24, 2020 to November 5, 2020, the patients complained with fever and diagnosed as common cold, with a record of initial visit and at least one return visit, were included as the subjects. According to whether acupoint application therapy was received or not, the subjects were divided into an exposure group (with acupoint application therapy, 26 664 cases) and a non-exposure group (without acupoint application therapy, 515 cases). Using the propensity score, the mixed factors, e.g. age and sex, were matched between the two groups. The disappearance rate of fever (within 2 days) and the time for the first fever disappearance were taken as the effect indexes. The association rules extraction was adopted to analyze the characteristics of effective population and acupoint application prescription in treatment of exogenous fever.@*RESULTS@#After propensity score matching, there were 1 229 cases in the application group and 423 cases in the non-application group. The disappearance rate of fever in the application group was 1.82 times as high as that in the non-application group (P<0.05). The time for the first fever disappearance in the application group was shorter than the non-application group (P<0.01). A total of 5 370 cases were effective with acupoint application therapy, of which, the median age was 2 years old and the proportion of children patients under 6 years old was relatively high. In the effective crowd, the most commonly-used acupoints were Shenque (CV 8), Dazhui (GV 14), Yongquan (KI 1) and Tiantu (CV 22), etc. Shenque (CV 8) and Dazhui (GV 14) were highly associated and the support was 62.57%. The most common herbal materials in the acupoint application therapy included Radix et Rhizoma Rhei, Natrii Sulfas, Radix Scutellariae, Herba Ephedrae and Radix Bupleuri, etc. Radix et Rhizoma Rhei and Natrii Sulfas were most commonly used at Shenque (CV 8) and the supports were 57.49% and 57.21% respectively. Herba Ephedrae was most commonly applied to Shenque (CV 8) and Dazhui (GV 14) and the supports were 48.21% and 43.91% respectively. Radix Bupleuri was the most common herb at Dazhui (GV 14) with the support of 46.61%. Besides, the most commonly combined western drugs included cefixime and keteling in the acupoint application therapy and the supports were 13.07% and 12.72% respectively.@*CONCLUSION@#Acupoint application is effective on exogenous fever. The common therapy refers to Radix et Rhizoma Rhei and Natrii Sulfas plaster at Shenque (CV 8), while Herba Ephedrae and Radix Bupleuri at Dazhui (GV 14).

Influence of acupoint application on clinical use of antibiotics: a real world study of 1.23 million primary clinic patients / 中国针灸

OBJECTIVE@#To observe the influence of acupoint application on the use of antibiotics in primary clinic practice, and explore the effect of acupoint application and its influence on the use of antibiotics based on common diseases in primary clinic (fever, cough, diarrhea, sore throat).@*METHODS@#With the help of the internet electronic diagnosis and treatment platform (the main TCM suitable technology promoted by this platform is acupoint application therapy), the diagnosis and treatment data of 1.23 million patients in 2 000 primary clinics from August 24, 2020 to March 31, 2021 were collected. The patients were divided into an application group (acupoint application treatment) and a non-application group (non-acupoint application treatment), and the proportion of antibiotic use in the two groups was compared. The propensity score was used to match age, gender, concomitant symptoms, diagnosed diseases and other confounding factors of treatment, and the disappearance rate of symptoms (fever, cough, diarrhea, sore throat) and the time to first disappearance of symptoms were compared between the two groups.@*RESULTS@#A total of 1 230 923 patients were analyzed, including 1 048 382 cases in the application group, accounting for 85.2%; 182 541 cases in the non-application group, accounting for 14.8%. The most patients who used acupoint application treatment were 0-2 years old, followed by 3-6 years old, and the patients over 15 years old who did not use acupoint application treatment were the most. The proportion of antibiotic use in the application group was 2.4%, lower than that in the non-application group (44.2%, P<0.001). The proportion of antibiotic use in all ages of patients in the application group was lower than that in the non-application group (P<0.001). Among the common diseases in primary clinic (fever, cough, diarrhea and sore throat), the proportion of antibiotic use in the application group was lower than that in the non-application group (P<0.01); the disappearance rate of symptoms in the application group was higher than that in the non-application group, and the time to first disappearance of symptoms was shorter than that in the non-application group (P<0.001).@*CONCLUSION@#Acupoint application has a certain influence on the use of antibiotics in primary clinic patients. In the treatment of common diseases, patients treated with acupoint application have better curative effect and lower proportion of antibiotic use.

Complications and management of penile augmentation with hyaluronic acid injection / 亚洲男科学杂志(英文版)

Hyaluronic acid injection is becoming a popular way for penile augmentation. However, only few studies and follow-ups have investigated the various complications of hyaluronic acid injection and their corresponding management. In this study, a total of 230 patients who had penile augmentation with hyaluronic acid injection from January 2018 to December 2019 were examined on follow-up for penile girth, complications, and their corresponding management. At 1-month, 3-month, and 6-month postoperative follow-ups, the penile circumference had increased by 2.66 ± 1.24 cm, 2.28 ± 1.02 cm, and 1.80 ± 0.83 cm, respectively. During the entire 6-month follow-up, 4.3% had complications such as subcutaneous bleeding, subcutaneous nodules, and infection. There were no systemic or local allergic reactions among all the patients. All complications were treated accordingly, and no further deterioration or severe sequelae were observed. Although complications of hyaluronic acid injections are mild and rare, these may affect the patient's satisfaction postoperatively. Preoperative redundant prepuce may increase the incidence of penile edema or postoperative gel migration. Standardization of the surgery protocol and elucidation of the effects of other injection parameters are still lacking. Nevertheless, it still highlights the importance of preoperative preparation and surgical technique.

Analysis of clinical research outcome indicators of traditional Chinese medicine in treatment of diabetic foot / 中国中药杂志

To analyze the outcome indicators from the randomized controlled trials(RCTs) on traditional Chinese medicine(TCM) treatment for diabetic foot, and to lay a foundation for the establishment of the core index set of the clinical trials on TCM treatment of diabetic foot. Computer retrieval of RCTs on TCM treatment of diabetic foot was performed in CNKI, Wanfang, SinoMed, PubMed, Cochrane Library, EMbase and Web of Science databases. Literature screening and data extraction were conducted independently by two researchers in strict accordance with inclusion and exclusion criteria. Any difference was resolved through discussion. A total of 72 RCTs involving 5 791 patients were included and 204 indicators were used. The number of indicators used in a single study was 2-22, with an average of 3 indicators used for each RCT. The indicators with top 16 frequency were clinical total effective rate, ankle brachial index(ABI), ulcer area, TCM syndrome integral, fibrinogen(FIB), fasting blood glucose(FBG), plasma viscosity(PV), c-reactive protein(CRP), saccharification blood of eggs(HbAlc), 2 h postprandial blood glucose(2 hPG), wound healing time, triglyce-rides(TC), TCM efficacy for syndromes, total cholesterol(TG), percutaneous oxygen partial pressure(TCPO2) and TCM symptom scores. The difference in selection of RCT indicators was large among TCM treatment methods for diabetic foot, and the combination of outcome indicators was arbitrary. The description on indexes was not standardized. Some non-laboratory examination indicators, some indicators not recommended in guidelines or not recognized in clinical practice, and some self-made indicators were not explained in detail. There was a lack of standardized evaluation criteria for indicators. The indicators had large time-point difference in measurement, and the time points were not distinguished in the measurement for diabetic foot patients with different degrees of severity. In addition, the patients with long course of treatment weren't timely measured. The characteristics of TCM or significant endpoint indicators were insufficient. It was urgent to establish the core index set of TCM in treating diabetic foot.

Chronic sleep deprivation exacerbates cognitive and pathological impairments in APP/PS1/tau triple transgenic Alzheimer's disease model mice / 生理学报

Sleep exerts important functions in the regulation of cognition and emotion. Recent studies have found that sleep disorder is one of the important risk factors for Alzheimer's disease (AD), but the effects of chronic sleep deprivation on the cognitive functions of AD model mice and its possible mechanism are still unclear. In the present study, 8-month-old male APP/PS1/tau triple transgenic AD model (3xTg-AD) mice and wild type (WT) mice (n = 8 for each group) were subjected to chronic sleep deprivation by using the modified multiple platform method, with 20 h of sleep deprivation each day for 21 days. Then, open field test, elevated plus maze test, sugar water preference test, object recognition test, Y maze test and conditioned fear memory test were performed to evaluate anxiety- and depression-like behaviors, and multiple cognitive functions. In addition, the immunohistochemistry technique was used to observe pathological characteristics in the hippocampus of mice. The results showed that: (1) Chronic sleep deprivation did not affect anxiety- (P = 0.539) and depression-like behaviors (P = 0.874) in 3xTg-AD mice; (2) Chronic sleep deprivation exacerbated the impairments of object recognition memory (P < 0.001), working memory (P = 0.002) and the conditioned fear memory (P = 0.039) in 3xTg-AD mice; (3) Chronic sleep deprivation increased amyloid β (Aβ) deposition (P < 0.001) and microglial activation (P < 0.001) in the hippocampus of 3xTg-AD mice, without inducing abnormal tau phosphorylation and neurofibrillary tangles. These results indicate that chronic sleep deprivation exacerbates the impairments of recognition memory, working memory and conditioned fear memory in 3xTg-AD mice by aggravating Aβ deposition and the excessive activation of microglia in the hippocampus.

Application of real world study and human use experience in research and development of new traditional Chinese medicine drugs / 中国中药杂志

Real world study(RWS) refers to the process of collecting real world data related to the health of research subjects in the real world environment for pre-set clinical problems and obtaining the status of drug use and potential benefits/risks through analysis. The data are derived from the hospital information system(HIS), medical insurance system, disease registration system, adverse drug reaction monitoring system, etc. Human use experience of traditional Chinese medicine(TCM) is a new concept put forward by experts after summarizing the problems existing in clinical trials of new TCM drugs. The data come partially from the real world, and more importantly, such key elements as the formulated prescriptions of new TCM drugs, principles and methods, and clinical applications should be covered. RWS is mainly used for adverse drug reaction monitoring after marketing, benefit evaluation of listed drugs, decision-making of medical treatment and medical insurance, as well as supervision and approval of special medical devices and special drugs. It is complementary to randomized controlled clinical trials. Human use experience is suitable for the research and development of Chinese medicinal compound preparations and the expansion of functions and indications. There are no special provisions for clinical indications and target population. There exists a sequential relationship between the human use experience and clinical trials. Specifi-cally, the summarization of human use experience provides good support for the design and implementation of clinical trials, which is an important segment in the research and development of new TCM drugs. The correlation between real-world data and research results and their reliability should be ensured in RWS, and the unreality should be avoided. The key to summarizing the human use experience is to identify the clinical orientation, target population, course of treatment, usage and dosage of new TCM drugs, and it should be noted that human use experience does not only mean clinical experience. Experimental clinical trial(PCT), a type of study in the real world, has been commonly employed for the summary of human use experience. RWS and human use experience are different research designs targeting different clinical questions in the research and development of new TCM drugs, which can be flexibly selected depending on the actual situation.

Expert consensus on key issues of quality control in clinical trials of new drugs of traditional Chinese medicine / 中国中药杂志

Since "the implementation of good clinical practice"(GCP), especially after 2015, the overall quality of new drug cli-nical trials in China has made significant progress, but compared with developed countries, there are still some obvious quality problems in clinical trials in China. Clinical trials of new drugs of traditional Chinese medicine are an important part of clinical trials of new drugs in China. In addition to some common problems in all clinical trials, there are also some special quality problems. In terms of security data, such as the collection of human safety data is not standardized, the management and judgment of unexpected serious adverse reactions(SUSAR) were not professional and timely, the relationship between adverse events and trial drug was not fully judged by investigator, In terms of effective data, such as primary efficacy outcome of the scale cannot be traced, TCM syndrome data cannot meet the requirements of "source data" in the revised GCP and the quality of traditional Chinese medicine placebo is not high, in terms of overall quality system construction, the sponsors and research institutions have not established a quality assurance system that conforms to the characteristics of new drug research of traditional Chinese medicine, etc. The quality of clinical trials of new drugs of traditional Chinese medicine is based on the current GCP and ICH-GCP in China, we should also consider the characteristics of clinical trials of new traditional Chinese medicine drugs, and formulate targeted quality control measures according to the characteristics of these new drugs of traditional Chinese medicine, to improve the overall quality of clinical trials of new drugs of traditional Chinese medicine in China, which has important strategic significance for promoting the research and development of new drugs of traditional Chinese medicine in China.

Consensus on collaborative ethical review of multi-center clinical trials of new drugs of traditional Chinese medicine (version 1.0) / 中国中药杂志

At present, the issues regarding multi-center clinical trials of new drugs of traditional Chinese medicine(TCM) remain: the lack of agreement on the content and scope of the ethical review among the ethics committee members of the center and the participating units results in repeated review, which leads to a time-consuming ethical review process. Moreover, the review capabilities of the ethics committees of various research centers are uneven, which is not necessarily beneficial to the protection of subjects' rights and safety. In view of the existing problems, to improve the efficiency of ethical review of multi-center clinical trials of new drugs of TCM and avoid repeated reviews, the TCM Clinical Evaluation Professional Committee of Chinese Pharmaceutical Association organized experts to formulate the "Consensus on collaborative ethical review of multi-center clinical trials of new drugs of TCM(version 1.0)"(hereinafter referred to as "Consensus"). The "Consensus" is formulated in accordance with the requirements of relevant documents such as but not limited to "the opinions on deepening the reform of the evaluation and approval system to encourage the innovation of pharmaceutical medical devices", "the regulations of ethical review of biomedical research involving human subjects". The "Consensus" covers the scope of application, formulation principles, conditions for the ethics committee of the center, sharing of ethical review resources, scope and procedure of collaborative review, rights and obligations, etc. The aims of the "Consensus" is to preliminarily explore and establish a scientific and operable ethical review procedure. Additionally, on the basis of fully protecting the rights and interests of the subjects, a collaborative ethical review agreement needs to be signed to clarify the ethical review responsibilities of all parties, to avoid repeated review, and to improve the efficiency and quality of ethical review in multi-center clinical trials of new drugs of TCM.

Development of clinical trial of new drugs of traditional Chinese medicines / 中国中药杂志

The relevant laws and regulations of drug clinical trials were introduced in this paper. It is pointed out that with drug re-gulatory laws and technological advances, clinical trials have become an important link in the development of new drugs of traditional Chinese medicines(TCM). Clinical trials of new drugs of TCM must comply with the requirement of "Good Clinical Practice for Trial on Medicinal Products". In view of the particularities of clinical trials of new drugs of TCM, China has established an ethical review system for clinical research in TCM and carried out ethical review and certification of TCM research. In order to guide the development of clinical trials of new drugs of TCM, relevant departments have promulgated a series of guidelines for clinical trials of it, and established a new review system and technical requirements for clinical trials. Since 1983, the "national clinical pharmacology base" has been established. At present, there are 96 drug clinical trial institutions and 32 phase I clinical research wards in TCM hospitals, which can meet the development of clinical trials of new drugs of TCM. In the long-term practice, the technical team has continued to grow and develop, the research experience and technical strength have been significantly improved, and a large number of experts have become the backbone of clinical research in Chinese medicine. It is pointed out that we should attach importance to risk and benefit assessment, human experience, select scientific, objective and appropriate effectiveness indexes, evaluate the efficacy of TCM syndromes, and encourage the use of electronic methods in clinical research of new drugs of TCM. Based on the analysis of clinical trials of TCM in recent five years, it is pointed out that the active degree of clinical trials of new drugs of TCM is not high, the innovation ability of it is insufficient and the ability and enthusiasm of all aspects need to be improved. It is of great significance to carry out clinical trials of new traditional Chinese medicines to upgrade the TCM industry and produce high-level evidence-based medicine evidences. The high quality development of TCM can be promoted by strengthening clinical trials of new drugs of TCM.

Theoretical thinking on guiding research and development of new drugs of traditional Chinese medicine / 中国中药杂志

This article proposes that the research and development of new Chinese medicines should be based on the clinical values of traditional Chinese medicine(TCM), and expounds the multiple clinical values of new Chinese medicines such as therapeutic effects, adjuvant treatment effects, improvement of disease symptoms, improvement of quality of life, prevention of diseases, etc., so as to broaden the clinical indications of new Chinese medicines. It is pointed out that the clinical value of TCM determines the clinical efficacy evaluation method of new Chinese medicines, so as to construct a clinical evaluation system of new Chinese medicines with the characteristics of TCM. It is proposed that the clinical value of new Chinese medicines should be found under the guidance of TCM theo-ry and clinical practice, and the theoretical innovation of TCM should be emphasized. There is no difference in the clinical value of drugs, and the key is to meet the clinical needs of patients. The research and development of new Chinese medicines ignores the theoretical guidance of Chinese medicine, and relying solely on animal experiment data may lead to failure of clinical trials. Different from the individualized treatment of TCM clinical syndrome differentiation, summarizing the core pathogenesis of TCM is the basis for the development of new Chinese medicines. It is necessary to summarize the pathogenesis of the disease under the guidance of TCM theory and encourage the application of modern medical methods to clarify the diagnosis of the disease. In view of the characteristics of new Chinese medicine research and development, it is proposed that the supporting role of human experience should be emphasized, and the technical points of clinical trials of new syndrome-type Chinese medicines should be explained.The use of objective indicators for syndrome evaluation, the selection of appropriate scales, and the formulation of reasonable treatment courses are advocated. During the research and development of new Chinese medicines, it is not only necessary to pay attention to modern medical safety indicators, but also to observe the evolution of TCM syndromes and specific TCM symptoms.

Systematic review and Meta-analysis of safety of Sanfu acupoint herbal patching in randomized controlled trial / 中国中药杂志

In order to systematically evaluate the safety of Sanfu acupoint herbal patching, CNKI, SinoMed, VIP, Wanfang, PubMed, Medline, EMbase, and Cochrane Library were searched in accordance with PICOS principles, with a time limit from database establishment to December 2019. Meta-analysis was used for a single-group rate analysis and a weighted combination of these two groups on rates of adverse reactions. A total of 9 articles meeting the inclusion criteria were included in the analysis, involving 2 119 patients. The single-group rate Meta-analysis showed that the adverse reactions incidence was 9% in the treatment group(OR=0.10,95%CI[0.06, 0.19], P<0.000 01), and 9% in the control group(OR=0.10, 95%CI[0.07, 0.13], P<0.000 01). In combined statistics of all samples OR=1.81, 95%CI[1.04, 3.15], P=0.04, the incidence of adverse reactions in the treatment group was slightly higher than that of the control group. In the subgroup analysis, the incidence of adverse reactions in terms of both single-group rate and weighed rate in the treatment group was higher than that in the control group in the asthma subgroup, rhinitis subgroup, ≥18 years old subgroup, and application time 2 h subgroup, with statistically significant differences(P<0.05). The results of the Meta-analysis and systematic review suggested that the incidence of adverse reactions in clinical use of the Sanfu acupoints herbal patching was relatively low. The main types of adverse reactions were skin ulcers, blisters and other skin symptoms. The symptoms were relatively mild, which could be relieved by drug withdrawal or symptomatic treatment. It shows that the safety of the Sanfu acupoint herbal patching was relatively high, and the occurrence of adverse reactions was related to the original disease and age, mainly in asthma and rhinitis or patients over 40 years old. Affected by clinical heterogeneity, the conclusions of the application time subgroup need to be further improved.