Advances in animal models of chronic heart failure and its applications in traditional Chinese medicine / 中国中药杂志

Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.

Transsphenoidal surgery for prolactinomas in male patients: a retrospective study / 亚洲男科学杂志(英文版)

Male patients with prolactinomas usually present with typical hyperprolactinemia symptoms, including sexual dysfunction and infertility. However, clinical factors related to sexual dysfunction and surgical outcomes in these patients remain unclear. This study aimed to investigate the outcomes of male patients with prolactinomas after transsphenoidal surgery and the risk factors affecting sexual dysfunction. This study was conducted on 58 male patients who underwent transsphenoidal surgery for prolactinomas between May 2014 and December 2020 at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. We evaluated the sexual function of patients before and after surgery through International Index of Erectile Function-5 scores, libido, and frequency of morning erection. Of the 58 patients, 48 (82.8%) patients had sexual intercourse preoperatively. Among those 48 patients, 41 (85.4%) patients presented with erectile dysfunction. The preoperative International Index of Erectile Function-5 scores in patients with macroprolactinomas were significantly higher than those in patients with giant prolactinomas (17.63 ± 0.91 vs 13.28 ± 1.43; P = 0.01). Postoperatively, the incidence of erectile dysfunction was 47.9%, which was significantly lower than that preoperatively (85.4%; P = 0.01). Twenty-eight (68.3%) patients demonstrated an improvement in erectile dysfunction. Tumor size and invasiveness were significantly correlated with the improvement of erectile dysfunction. Preoperative testosterone <2.3 ng ml-1 was an independent predictor of improvement in erectile dysfunction. In conclusion, our results indicated that tumor size and invasiveness were important factors affecting the improvement of sexual dysfunction in male patients with prolactinoma. The preoperative testosterone level was an independent predictor related to the improvement of erectile dysfunction.

Role of umbilical cord mesenchymal stem cell-derived exosomes in acute skin wound healing / 中华皮肤科杂志

Objective:To investigate the role of umbilical cord mesenchymal stem cell-derived exosomes (ucMSC-exos) in acute skin wound healing in mice.Methods:ucMSC-exos were extracted by ultracentrifugation, and identified by transmission electron microscopy, Western blot analysis of exosome surface markers CD63 and TSG101, and particle size analysis. Firstly, in vitro cultured third- to fifth-passage human skin fibroblasts (HSF) were incubated with high-glucose Dulbecco′s modified Eagle′s medium (DMEM) containing 0, 1 and 2 μg/ml exosome suspension for 24 hours (negative control group, 1- and 2-μg/ml groups, respectively) , and cell counting kit-8 (CCK8) assay was performed to evaluate the effect of ucMSC-exos on the proliferative activity of HSF. Secondly, 24 male BALB/c mice aged 8 weeks were selected to construct a mouse model of full-thickness skin wound, and then divided into ucMSC-exos group and phosphate-buffered saline (PBS) group by using a random number table to be subcutaneously injected with exosome suspension and PBS respectively at multiple equidistant sites located about 1 mm apart from the wound edge. On days 0, 4, 7, 10 and 14 after operation, the wounds in mice were observed, and the percentage of residual wound area was calculated in the above two groups. On days 7 and 14 after operation, wound tissues were resected and subjected to hematoxylin and eosin (HE) and Masson staining to observe structural changes of skin tissues. On day 14 after operation, wound tissues were collected in the two groups, and real-time quantitative PCR (qRT-PCR) and Western blot analysis were performed to determine the mRNA and protein expression of type Ⅰ collagen, fibronectin and vascular endothelial growth factor, respectively. Statistical analysis was carried out by using one-way analysis of variance, least significant difference- t test, two-way repeated measures analysis of variance and unpaired t-test. Results:Under the transmission electron microscope, the ucMSC-exos were oval in shape with a diameter of about 100 nm; Western blot analysis showed positive expression of ucMSC-exos surface proteins CD63 and TSG101; particle size analysis showed that 96.2 % of the ucMSC-exos had diameters of 30 - 150 nm. CCK8 assay showed that the relative proliferative activity of HSF was significantly higher in the 1- and 2-μg/ml groups (0.97 ± 0.05, 1.08 ± 0.07, respectively) than in the negative control group (0.71 ± 0.04; t = 2.00, 7.05, respectively, both P < 0.05) , and significantly higher in the 2-μg/ml group than in the 1-μg/ml group ( t = 5.09, P < 0.05) . On days 4, 7, 10 and 14 after operation, the percentage of residual wound area was significantly lower in the ucMSC-exos group than in the PBS group (all P < 0.05) . HE and Masson staining showed increased numbers of hair follicles, glands and granulation tissues, more neovascularization, and neater arrangement of collagens in neonatal skin tissues of the mice in the ucMSC-exos group compared with the PBS group. qRT-PCR and Western blot analysis showed significantly increased mRNA and protein expression of type Ⅰ collagen, fibronectin and vascular endothelial growth factor in the ucMSC-exos group compared with the PBS group (all P < 0.01) . Conclusion:Subcutaneous injections of ucMSC-exos can promote acute skin wound healing in mice, likely by promoting the synthesis of extracellular matrix and vascular endothelial growth factor in wound tissues of mice and proliferation of HSF.

Application of blended learning in medical education in the world / 中华医学教育探索杂志

Objective:To discuss the application and effects of blended learning (B-Learning) mode in medical courses and education at home and abroad.Methods:Based on the identified keywords, the research retrieved 93 relevant literature from 2000 to 2017 in journal databases (e.g. Premier, Cinahl and Medline), and published journals. After two rounds of analysis, 19 domestic and foreign literature were obtained, which evaluated the application and teaching effects of the B-Learning mode in the context of medical education. Among them, there were control studies and qualitative studies.Results:There are differences in the implementation and implementation of the B-Learning model in various countries; the teaching intervention measures and the scope of intervention of the B-Learning teaching model are diverse; the B-Learning model can make up for the gap between the theoretical and practical courses in the medical education process. It helps medical students to master their knowledge and improve their clinical skills; it is necessary for teachers to carefully design teaching courses and teaching research before class to improve the teaching effect of B-Learning.Conclusion:Combining modern educational technology with traditional teaching methods can effectively improve the medical knowledge level and clinical practice skills of medical students.

Prognostic significance of IKZF1 gene deletions in patients with B-cell acute lymphoblastic leukemia / 中华血液学杂志

Objective: This study aimed to investigate the prognostic significance of IKZF1 gene deletion in patients with acute B lymphoblastic leukemia (B-ALL) . Methods: The clinical data of 142 patients with B-ALL diagnosed in Nanfang Hospital between March 2016 and September 2019 were analyzed. Results: IKZF1 deletion was found in 36.0% of the 142 patients with B-ALL, whereas exon 4-7 deletion was found in 44.0% . White blood cell counts were higher in patients with the IKZF1 deletion (52.0% and 28.3% , P=0.005) ; these patients also experienced worse effects of mid-term induction therapy (40.0% and 70.7% , P<0.001) and had a higher proportion of Philadelphia chromosome-positive (52.0% and 21.7% , respectively, P<0.001) . Univariate analysis revealed that the 3-year overall survival rate (OS) and event-free survival rate (EFS) in the IKZF1 deletion group were significantly lower than the IKZF1 wild-type group [ (37.1±7.3) % vs (54.7±5.4) % , (51.8±7.9) % vs (73.9±4.7) % ; P=0.025, 0.013, respectively]. Multivariable analysis showed that harboring IKZF1 deletion was an adverse factor of EFS and OS (HR=1.744, 2.036; P=0.022, 0.020, respectively) . Furthermore, the IKZF1 deletion/chemotherapy group had significantly lower 3-year OS, EFS, and disease-free survival rates than other subgroups. In the IKZF1 deletion cohort, allo-hematopoietic stem cell transplantation (HSCT) significantly improved OS and EFS compared to non-allo-HSCT[ (67.9±10.4) % vs (31.9±11.0) % , (46.6±10.5) % vs (26.7±9.7) % ; P=0.005, 0.026, respectively]. Conclusion: Pediatric-inspired chemotherapy was unable to completely reverse the negative effect of IKZF1 deletion on prognosis. Pediatric-inspired regimen therapy combined with allo-HSCT, in contrast, significantly improved the overall prognosis of IKZF1 deletion B-ALL.

Treatment of Psoriasis Vulgaris with Medicated Thread Moxibustion of Zhuang Medicine: A Multicenter Randomized, Parallel Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To explore the efficacy and safety of Zhuang medicine medicated thread moxibustion (ZMTM) on psoriasis vulgaris.@*METHODS@#A multicenter, randomized, parallel controlled clinical trial was designed. A total of 241 outpatients with psoriasis vulgaris were randomly divided into a control group (120 cases) and a treatment group (121 cases) using a central block randomization from June 2015 to May 2018. The control group was treated with Western medicines alone including pidotimod dispersible tablets, vitamin B compound tablets, and compound cod liver oil-zinc oxide ointment. The treatment group was treated with ZMTM every 2 days combined with Western medicines. The two groups received continuous intervention for 30 days. The primary outcome was Psoriasis Area and Severity Index (PASI), and the secondary outcomes included Itch Rating Scale, Dermatology Quality of Life Index (DLQI), Hamilton Anxiety Rating Scale (HAMA), as well as PASI response rate. Meanwhile, adverse events were evaluated during the whole clinical trial. Follow-up was carried out 30 days after treatment.@*RESULTS@#There were 5 cases of shedding in this trial. In intention-to-treat analysis, 236 cases were included and each group contained 118 cases. On the 30th and 60th days, PASI scores of patients in each group were significantly lower than that at baseline (P<0.01) and the PASI score reduction of the treatment group was greater than that of the control group (P<0.01). Itch Rating Scale, DLQI, and HAMA scale were decreased in both groups after treatment, and the treatment group showed a better therapeutic effect (P<0.01). The response rates of PASI 50 and 75 were significantly higher than those in the control group [81.4% (96/118), 43.2% (51/118) vs. 41.5% (49/118), 11.0% (13/118), respectively, P<0.05]. During follow-up, the improvements in scores of PASI, Itch Rating Scale, DLQI, and HAMA of the treatment group were significantly greater than those of the control group (P<0.01). The response rates of PASI 50 and 75 in the treatment group were significantly higher than those in the control group, respectively (both P<0.05). No obvious adverse reaction was found in either group.@*CONCLUSION@#ZMTM combined with Western medicines showed a better therapeutic effect in the treatment of psoriasis vulgaris without obvious adverse reaction. (Trial Registration No. ChiCTR-IOR-16008159).

Expression and Clinical Significance of Serum MiR-424 and MiR-765 in Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and clinical significance of miR-424 and miR-765 in patients with multiple myeloma (MM).@*METHODS@#The eighty-one MM patients admitted to Sanya Central Hospital from January 2017 to July 2020 were divided into phase Ⅰ (n=16), phase Ⅱ (n=25) and phase Ⅲ (n=40) according to the international staging system, while they were divided into IgG type (n=46), IgA type (n=19), light chain type (n=10) and non secretory type (n=6) according to the results of immunotyping. Another 50 healthy normal persons in the same period were selected as the control group. The levels of serum miR-424, miR-765 and Cystatin C (Cys-C) were measured in each group. The diagnostic value of serum miR-424, miR-765 and Cys-C in MM was estimated by ROC curve. Pearson correlation was used to analyze the correlation between serum levels of miR-424, miR-765 and Cys-C in MM patients.@*RESULTS@#The serum levels of miR-424 (2.74±1.30 vs 0.85±0.26), miR-765 (2.05±0.82 vs 0.63±0.17) and Cys-C ［(2.18±0.86 vs 0.72±0.15) mg/L］ in MM group were significantly higher than those in control group (P<0.001). The serum levels of miR-424 (5.08±2.36 vs 1.12±0.34, 2.24±0.93), miR-765 (3.50±1.52 vs 0.74±0.20, 1.78±0.65) and Cys-C ［(3.81±1.30 vs 0.92±0.24, 1.68±0.55) mg/L］ in MM patients at stage Ⅲ were significantly higher than those in patients at stage Ⅰ and Ⅱ (P<0.001). Also the serum levels of the three molecules in phase II were significantly higher than those in phase I (P<0.001). The serum levels of miR-424 and miR-765 in MM patients at IgG type were significantly higher than those at IgA, light chain and non secretory types (P<0.001). ROC curve analysis showed that the area under the curve (0.952，95%CI: 0.890-0.993) was greatest for the combination of miR-424, miR-765 and Cys-C for diagnosis of MM, and its sensitivity and specificity were 95.0% and 87.2%. The results of correlation analysis showed that the serum levels of miR-424 and miR-765 were positively correlated with Cys-C (r=0.795，r=0.760).@*CONCLUSION@#The serum levels of miR-424 and miR-765 in MM patients are significantly increased in the pattern increasing with the progression of MM stage. Combined with Cys-C, miR-424 and miR-765 have high value in the diagnosis of MM.

Lowered expression of CCN5 in endometriotic tissues promotes proliferation, migration and invasion of endometrial stromal cells / 南方医科大学学报

OBJECTIVE@#To explore the expression of CCN5 in endometriotic tissues and its impact on proliferation, migration and invasion of human endometrial stromal cells (HESCs).@*METHODS@#We collected ovarian endometriosis samples from 20 women receiving laparoscopic surgery and eutopic endometrium samples from 15 women undergoing IVF-ET for comparison of CCN5 expression. Cultured HESCs were transfected with a recombinant adenovirus Ad-CCN5 for CCN5 overexpression or with a CCN5-specific siRNA for knocking down CCN5 expression, and the changes of cell proliferation, migration and invasion were evaluated using CCK-8 assay, wound healing assay and Transwell chamber assay. RT-qPCR and Western blotting were used to examine the expression levels of epithelial-mesenchymal transition (EMT) markers including E-cadherin, N-cadherin, Snail-1 and vimentin in HESCs with CCN5 overexpression or knockdown.@*RESULTS@#CCN5 expression was significantly decreased in ovarian endometriosis tissues as compared with eutopic endometrium samples (P < 0.01). CCN5 overexpression obviously inhibited the proliferation, migration and invasion of HESCs, significantly increased the expression of E-cadherin and decreased the expressions of N-cadherin, Snail-1 and vimentin (P < 0.01). CCN5 knockdown significantly enhanced the proliferation, migration and invasion of HESCs and produced opposite effects on the expressions of E-cadherin, N-cadherin, Snail-1 and vimentin (P < 0.01).@*CONCLUSION@#CCN5 can regulate the proliferation, migration and invasion of HESCs and thus plays an important role in EMT of HESCs, suggesting the potential of CCN5 as a therapeutic target for endometriosis.

Effect of Toxoplasma gondii Chinese 1 genotype infections on brain iron metabolism in mice / 中国血吸虫病防治杂志

Objective To investigate the effect of Toxoplasma gondii Chinese 1 genotype infections on host brain iron metabolism and brain damages. Methods Twenty C57BL/6 mice, each weighing 15 to 17 g, were randomly divided into the control and infection groups, of 10 mice in each group. Each mouse in the infection group was injected intraperitoneally with 4 000 tachyzoites of the TgCtwh3 isolate with Chinese 1 genotype, while each mouse in the control group was injected with an equal amount of sterile phosphate-buffered saline (PBS). All mice were sacrificed 6 day post-infection and brain tissues were sampled. The iron levels were measured in mouse brain specimens using inductively coupled plasma mass spectrometry (ICP-MS). The differentially expressed genes were determined between the experimental and control groups using RNA chips and Gene Ontology (GO) term enrichment analysis of differentially expressed genes was performed. The mRNA expression of Toxoplasma gondii surface antigen 1 (TgSAG1) gene and some Zrt- and Irt-like protein (ZIP) family member coding genes was detected by quantitative real-time PCR (qPCR) assay. The ultrastructure of the hippocampus dentate gyrus in mouse brain specimens was observed using optical and electronic microscopy. The glutathione peroxidase 4 (GPx4) expression was determined using Western blotting, and malondialdehyde (MDA) level was measured using thiobarbituric acid (TBA) test. In addition, the optical density (OD) of vascular endothelial growth factor (VEGF) protein was measured using immunohistochemistry. Results Optical microscopy showed cell necrosis in the hippocampus dentate gyrus of mouse brain specimens in the infection group, and electronic microscopy cytoplasmic vacuolization, nuclear atrophy and necrosis, disruption of cristae mitochondriales and increased autophagosome levels in the mouse brain hippocampus specimens in the infection group. The iron level was significantly greater in mouse brain specimens in the infection group than in the control group [(32.92 ± 0.90) μg/g vs. (37.72 ± 1.10) μg/g; t = 3.397, P < 0.01]. RNA chips revealed 721 up-regulated genes and 276 down-regulated genes in mouse brain specimens between the infection and control groups, and the differentially expressed genes were significantly enriched in metal ion binding ability (molecular function). Elevated expression of metal element transporter ZIP2 mRNA (t = 8.659, P < 0.05), reduced GPx4 expression [(1.046 ± 0.025) vs. (0.720 ± 0.101); t = 3.129, P < 0.01], increased MDA level [(4.37 ± 0.33) nmol/mgprot vs. (5.93 ± 0.54) nmol/mgprot; t = 2.451, P < 0.05], and up-regulated mean OD of VEGF protein [(0.348 3 ± 0.017 8) vs. (0.490 6 ± 0.010 5); t = 6.641, P < 0.01] were found in mouse brain specimens in the infection group than in the control group. Conclusions Chinese 1 genotype T. gondii infection results in iron accumulation in brain tissues, reduced antioxidant ability and elevated levels of oxidative stress in mice, suggesting that T. gondii infection may cause brain damages through affecting iron metabolism in host brain tissues.

Screening methods of traditional Chinese medicine for coronary heart disease and angina pectoris: an exploration based on core outcome set and fuzzy comprehensive evaluation / 中国中药杂志

It was pointed out in Opinions on Promoting the Inheritance, Innovation and Development of Traditional Chinese Medicine issued by the State Council in 2019 that 100 varieties of traditional Chinese medicine(TCM) with unique curative effects should be screened out within about three years. Due to the multi-component and multi-target mechanisms of TCM varieties, it is difficult to directly and simply evaluate their multi-dimensional clinical value using methods applicable to chemical or biological agents. The heterogeneity of outcomes for similar TCM makes it difficult to determine the advantages of similar products. The fuzzy comprehensive evaluation method that is developed on the basis of core outcome set and fuzzy mathematics for clinical efficacy evaluation of TCM may solve these problems. This study developed a fuzzy comprehensive evaluation model for the clinical efficacy evaluation of Chinese patent me-dicines for coronary heart disease and angina pectoris, and selected the previous normative studies with complete or incomplete data for verifying the model application. The results showed that original studies with complete data failed to evaluate and compare the comprehensive efficacy of different interventions. The original research only mentioned the advantages and disadvantages of different interventions in different aspects. The comprehensive clinical efficacy of three different interventions obtained through fuzzy comprehensive evaluation was all graded as level Ⅱ. The original research with incomplete data drew the same conclusions as the fuzzy comprehensive evaluation, and the results of fuzzy comprehensive evaluation can provide more comprehensive information. Therefore, the fuzzy comprehensive evaluation shows the products with overall advantages of clinical efficacy, which may become a feasible method for the screening of TCM.

Trace therapeutic substances of traditional Chinese medicine: great resources of innovative drugs derived from traditional Chinese medicine / 中国中药杂志

The traditional Chinese medicine(TCM) contains very complex constituents. Besides the major constituents, there are a large number of unclear trace constituents with novel skeletons and potent bioactivities, which have been regarded as one of the important therapeutic substances and the great resources of innovative drugs derived from TCM. The present review highlighted that the development of the trace therapeutic substances of TCM is closely depends on the advanced technologies for their identification, isolation, structure elucidation, and bioactivity evaluation. Additionally, this paper reviewed the novel trace compounds derived from Chinese herbal medicines which have been published in Organic Letters during 2001-2021, and summarized the important licensed drugs originated from the trace therapeutic substances and the discovery and development of trace therapeutic substances of 8 kinds of Chinese herbal medicines. This review provides references for the research and development of TCM therapeutic substances and innovative drugs.

Establishment of multiple evidence-integrated evaluation and prediction method for "toxic" Chinese medicines / 中国中药杂志

Traditional Chinese medicine(TCM) carries the experience and theoretical knowledge of the ancients, and the use of "toxic" Chinese medicines is a major feature and advantage of TCM. "Toxic" Chinese medicines have unique clinical value and certain medication risk under the guidance of TCM theories such as compatibility for detoxification and treatment based on syndrome differentiation. In recent years, the safety events of Chinese medicines have occurred frequently, which has made the safety of Chinese medicine a public concern in China and abroad. However, limited by conventional cognitive laws and technical methods, basic research on toxicity of Chinese medicines fails to be combined with the clinical application. As a result, it is difficult to identify the clinical characteristics of, predict toxic and side effects of, or form a universal precise medication regimen for "toxic" Chinese medicines, which restricts the clinical application of them. In view of the problem that the toxicity of "toxic" Chinese medicines is difficult to be predicted and restricts the clinical application, the evidence-based research concept will provide new ideas for safe applcation of them in clinical practice. The integrated development of multiple disciplines and techniques in the field of big data and artificial intelligence will also promote the renewal and development of the research models for "toxic" Chinese medicines. Our team tried to propose the academic concept of evidence-based Chinese medicine toxicology and establish the data-intelligence research mode for "toxic" Chinese medicines and the intelligent risk prediction method for medicinal combination in the early stage, which provided methodological supports for solving the above problem. Thus, on the basis of summarizing the research status and problems of the clinical medication regimen of "toxic" Chinese medicines, our team took the evidence-based toxicology of TCM as the core concept, and tried to construct the multiple-evidence integrated evaluation and prediction method for "toxic" Chinese medicine, so as to guide the establishment of the non-toxic medication regimen of "toxic" Chinese medicines. Specifically, through the analysis of multivariate data obtained from the basic research, the evidence-based toxicology database of Chinese medicines and the individualized "toxicity-effect" intelligent prediction platform were built based on the disease-syndrome virtual patients, so as to identify the clinical characteristics and risks of "toxic" Chinese medicines and develop individualized medication regime. This study is expected to provide a methodological reference for the establishment of medication regimen and risk prevention strategy for "toxic" Chinese medicines. The method established in this study will bridge clinical research and basic research, enhance the transformation of the scientific connotation of attenuated compatibility, promote the development of evidence-based Chinese medicine toxicology, and ensure the clinical safety of "toxic" Chinese medicines.

Technical services of family planning operations in Pudong New Area of Shanghai from 2011 through 2018 / 上海预防医学

Objective:To determine the change in the number of family planning technical services in Pudong New Area of Shanghai from 2011 through 2018， and provide scientific evidence for improving reproductive health care for women of childbearing age. Methods:Trend analysis was performed according to the data of family planning technical service and obstetric service records by all medical and health care facilities in Pudong New Area from 2011 through 2018. Results:Top four family planning operations were vacuum aspiration， intrauterine device （IUD） removal， IUD insertion and medical abortion. The average annual number of family planning operations was 77 320， which declined over years with an average reduction rate of 3.32%. The average reduction rate of contraceptive and induced abortion was 5.87% and 1.6%， respectively. The reduction rate of IUD insertion was higher than that of IUD removal. Vacuum aspiration was the leading method of induced abortion， accounting for 77.9%， in which 79.27% was performed with intravenous anesthesia. Among the women receiving induced abortion， majority of them were married and non-local residents. The ratio of induced abortion to the live birth decreased over years from 2011 through 2018. Conclusion:Number of family planning technical services in Pudong New Area of Shanghai decreases from 2011 through 2018. Vacuum aspiration and IUD removal are the main operations in family planning surgery. With the decrease of long-term medically controlled contraceptive and birth control measures， it is necessary to strengthen the correct and effective use of self-controlled contraceptive measures for women of childbearing age， especially for those non-local married women， so as to reduce unwanted pregnancies and repeated induced abortions.

Methods for development of a core outcome set for clinical trials integrating traditional Chinese medicine and Western medicine / 中西医结合学报

Clinical trial outcome reporting differs between studies integrating traditional Chinese medicine (TCM) and Western medicine, so that some clinical trials are not eligible for inclusion in a systematic review. The excluded studies are therefore less widely disseminated, and even valid studies are less likely to yield impact. This problem may be addressed by developing core outcome sets (COSs) for integrative medicine in specific healthcare areas. The first stage of development is to define the scope of the COS for integrative medicine, the second stage is to establish the need for such a COS, and the third stage is to develop a protocol and register the COS. The final stage involves three steps: (i) development of a comprehensive list of outcomes (including efficacy outcomes and safety outcomes and TCM syndromes) using systematic review, qualitative or cross-sectional research, and reviews of package inserts and medical records; (ii) merging and grouping of outcomes within domains; (iii) conducting two rounds of Delphi survey and consensus meetings with a range of stakeholders. The final COS will include a general COS and core TCM syndrome- set. Development of COSs for clinical trials of integrative medicine may help to standardize outcome reporting and reduce publication bias in the future.

Evaluating the methodology of studies conducted during the global COVID-19 pandemic: A systematic review of randomized controlled trials / 中西医结合学报

BACKGROUND@#The therapeutic evidence collected from well-designed studies is needed to help manage the global pandemic of the coronavirus disease 2019 (COVID-19). Evaluating the quality of therapeutic data collected during this most recent pandemic is important for improving future clinical research under similar circumstances.@*OBJECTIVE@#To assess the methodological quality and variability in implementation of randomized controlled trials (RCTs) for treating COVID-19, and to analyze the support that should be provided to improve data collected during an urgent pandemic situation.@*SEARCH STRATEGY@#PubMed, Excerpta Medica Database, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP, and the preprint repositories including Social Science Research Network and MedRxiv were systematically searched, up to September 30, 2020, using the keywords "coronavirus disease 2019 (COVID-19)," "2019 novel coronavirus (2019-nCoV)," "severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2)," "novel coronavirus pneumonia (NCP)," "randomized controlled trial (RCT)" and "random."@*INCLUSION CRITERIA@#RCTs studying the treatment of COVID-19 were eligible for inclusion.@*DATA EXTRACTION AND ANALYSIS@#Screening of published RCTs for inclusion and data extraction were each conducted by two researchers. Analysis of general information on COVID-19 RCTs was done using descriptive statistics. Methodological quality was assessed using the risk-of-bias tools in the Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0). Variability in implementation was assessed by comparing consistency between RCT reports and registration information.@*RESULTS@#A total of 5886 COVID-19 RCTs were identified. Eighty-one RCTs were finally included, of which, 45 had registration information. Methodological quality of the RTCs was not optimal due to deficiencies in five main domains: allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, and selective reporting. Comparisons of consistency between published protocols and registration information showed that the 45 RCTs with registration information had common deviations in seven items: inclusion and exclusion criteria, sample size, outcomes, research sites of recruitment, interventions, and blinding.@*CONCLUSION@#The methodological quality of COVID-19 RCTs conducted in early to mid 2020 was consistently low and variability in implementation was common. More support for implementing high-quality methodology is needed to obtain the quality of therapeutic evidence needed to provide positive guidance for clinical care. We make an urgent appeal for accelerating the construction of a collaborative sharing platform and preparing multidisciplinary talent and professional teams to conduct excellent clinical research when faced with epidemic diseases of the future. Further, variability in RCT implementation should be clearly reported and interpreted to improve the utility of data resulting from those trials.

Differences of heart rate variability in cardioinhibitory type vasovagal syncope children with different body mass index / 中国小儿急救医学

Objective:To investigate the difference of heart rate variability in cardioinhibitory type vasovagal syncope(VVS-CI) children with different body mass index(BMI).Methods:Clinical data of thirty-four children with syncope or pre-syncope were retrospectively analyzed, who visited specialist clinic for syncope and diagnosed as VVS-CI at the Second Xiangya Hospital of Central South University from January 2012 to December 2019.BMI was calculated based on height and weight, and divided into lean group(BMI≤18.4 kg/m 2, n=19) and normal group(BMI 18.5-23.9 kg/m 2, n=15). Heart rate variability(HRV) of 24 h dynamic electrocardiogram was analyzed using linear analysis method.Time domain index included SDNN, SDANN, rMSSD and pNN50.Frequency domain index included total power(TP), ultra low frequency power(ULF), very low frequency power(VLF), low frequency power(LF), high frequency power(HF) and LF/HF. Results:There was no significant difference in SDNN, SDANN and rMSSD between lean and normal group( P>0.05), but pNN50 increased in lean group( P<0.05). No significant differences were found in TP, ULF, LF, HF and LF/HF between two groups( P>0.05), while VLF was lower in lean group than that in normal group( P<0.05). There was no statistical difference in time domain index and frequency domain index between different gender between lean and normal group( P>0.05). SDNN, SDANN and LF were higher in<12 years old than those in≥12 years old in lean group( P<0.05). There was no statistical difference in rMSSD, pNN50, TP, ULF, VLF, HF and LF/HF( P>0.05). ULF increased and LF decreased in<12 years old compared to ≥12 years old in normal group( P<0.05). No statistical differences were found in SDNN, SDANN, rMSSD, pNN50, TP, VLF, HF and LF/HF( P>0.05). Conclusion:The autonomic nervous regulation function of VVS-CI children with low BMI and normal BMI is different, resulting in HRV difference.There were also differences in HRV between<12 years old and ≥12 years old with the same BMI.

Diagnostic efficacy and prognostic evaluation value of QT interval dispersion in children and adolescents with cardioinhibitory vasovagal syncope / 中国小儿急救医学

Objective:To study the diagnostic efficacy and prognostic evaluation value of QT interval dispersion (QTd) in children and adolescents with cardioinhibitory vasovagal syncope (VVS-CI).Methods:From July 2010 to January 2020, 80 children and adolescents who received their first visit or admission to the Pediatric Syncope Clinic of The Second Xiangya Hospital of Central South University and definite diagnosed of VVS-CI due to syncope or presyncope were selected as the VVS-CI group, meanwhile, 80 children and adolescents who had physical examination in the hospital were selected as the control group.QT interval were measured by 12-lead electrocardiogram at the baseline.Results:(1) Comparison between the two groups: Compared with the control group, the VVS-CI group had a significantly lower heart rate ( P<0.05) and significantly longer QT interval, such as the maximum QT interval (QTmax), minimum QT interval (QTmin), QTd, corrected maximum QT interval (QTcmax) and corrected QT interval dispersion (QTcd) ( P<0.05). After follow-up 84 (45, 127) days, compared with the responsive group, the non-responsive group had a significantly longer QT interval, such as QTmax, QTd, QTcmax, corrected minimum QT interval (QTcmin)and QTcd ( P<0.05). (2) Diagnostic efficiency: QTmax, QTmin, QTd, QTcmax and QTcd had a certain diagnostic value in children and adolescents with VVS-CI ( P<0.001). QTd had the largest area under the curve (AUC) (0.914), and had a sensitivity of 86.30% and a specificity of 84.95% at the optimal cut-off value of 28.50 ms for VVS-CI diagnosis.(3) Prognostic evaluation value: QTmax, QTd, QTcmax, QTcmin, QTcd had an estimated value for the prognosis of VVS-CI in children and adolescents ( P<0.05 or 0.01). QTd had the largest AUC (0.906) and the best cut-off value was 34.50 ms, the sensitivity to predict response to VVS-CI intervention was 90.00%, and the specificity was 82.35%. Conclusion:QTd of electrocardiogram has a good estimation value in the diagnosis and prognosis of VVS-CI in children and adolescents.

The relationship between heart rate and heart rate difference at different time points in head-up tilt test and the occurrence of postural tachycardia syndrome in children and adolescents / 中国小儿急救医学

Objective:To discuss the relationship between heart rate (HR) and heart rate differences (HRD) at different time points in head-up tilt test (HUTT) and the occurrence of postural tachycardia syndrome(POTS) in children and adolescents.Methods:A total of 217 children and adolescents diagnosed as POTS, who complained of syncope or presyncope, were chosen as POTS group (aged 6 to 16 years). During the same period, 73 healthy children and adolescents with matching gender and age were selected as control group.All subjects underwent HUTT from October 2000 to November 2019.Get HR (HR0, HR5, HR10) in baseline, HUTT 5 min and 10 min, HRD (HRD5, HRD10) of HR in HUTT 5 min and 10 min minus HR in baseline.Results:(1) HR5, HR10, HRD5, and HRD10 were higher in the POTS group than those in the control group( P<0.05). (2) Univariate Logistic regression: There was a correlation between HR5, HR10, HRD5, HRD10 and the risk of POTS( P<0.01). (3) Multivariable Logistic regression: For each additional unit of HRD5 and HRD10, the risk of POTS increased by 27% ( OR=1.27, 95% CI1.16 to 1.36) and 28% ( OR=1.28, 95% CI1.20 to 1.38). Conclusion:HR and HRD are related with the occurrence of POTS in children and adolescents, but HR and HRD at different time points of HUTT play the little role on the effect size of the occurrence of POTS.

Study on morning blood pressure surge and circadian rhythm of blood pressure in children with neurally mediated syncope / 中华实用儿科临床杂志

Objective:To investigate the circadian rhythm of blood pressure and morning blood pressure surge (MBPS) in children with neurally mediated syncope (NMS).Methods:From July 2018 to June 2019, 135 cases [aged 3-16 years old (10.12±2.53) years old, with 74 males and 61 females] with unexplained syncope, presyncope, and symptoms such as headache, dizziness, chest pain, and chest tightness were collected in the Second Xiangya Hospital, Central South University for the first time.The 24 hour ambulatory blood pressure monitoring (24 h ABPM) was completed on the same day of the head-up tilt test (HUTT). Patients were divided into HUTT negative and positive groups, and dippers and non-dippers groups. MBPS (sleep-trough surge) was calculated and compared respectively.Results:(1) There were 51 patients in the HUTT positive group, including 27 patients with vasovagal syncope, 23 patients with postural orthostatic tachycardia syndrome, and 1 patient with orthostatic hypotension. In HUTT positive group, there were 22 cases (43.14%) of dippers and 29 cases of non-dippers.There were 84 patients in the HUTT negative group, there were 32 cases (38.10%) of dippers and 52 cases of non-dippers. There were no statistical significances in the dipper proportion between HUTT positive and negative group ( χ2=1.305, P>0.05). (2) Sleep-trough systolic blood pressure (SBP) surge was 1-45 mmHg [(15.97±8.03) mmHg](1 mmHg=0.133 kPa), and sleep-trough diastolic blood pressure (DBP) surge was -6-43 mmHg[(14.05±7.97) mmHg]. There were no statistical significances in sleep-trough surge between the HUTT negative and positive group (all P>0.05). (3) The age in the dipper group was higher than that in the non-dipper group [(10.72±2.20) years old vs. (9.72±2.66) years old, t=2.288, P<0.05]. The daytime average SBP [(110.20±8.33) mmHg vs.(105.54±7.51) mmHg, t=3.381, P<0.01], and morning peak SBP [(109.99±10.19) mmHg vs.(106.63±8.71) mmHg, t=2.045, P<0.05] of the dipper group were higher than those of the non-dipper group.The nighttime average SBP[(95.41±7.50) mmHg vs.(98.59±6.88) mmHg, t=2.540, P<0.01], nighttime average DBP[(48.61±4.52) mmHg vs.(52.28±4.65) mmHg, t=4.547, P<0.01], nocturnal minimum SBP[(89.62±8.18) mmHg vs.(93.60±7.38) mmHg, t=2.940, P<0.01], and nocturnal minimum DBP[(44.99±5.32) mmHg vs.(49.01±5.54) mmHg, t=4.205, P<0.01] of the dipper group were lower than that of the non-dipper group.Nocturnal SBP reduction rate [(13.42±2.68)% vs.(6.48±2.49)%, t=15.384, P<0.01], nocturnal DBP reduction rate[(19.98±4.92)% vs.(12.46±5.05)%, t=8.561, P<0.01], sleep-trough SBP surge[(20.37±8.30) mmHg vs.(13.03±6.36) mmHg, t=5.800, P<0.01], and sleep-trough DBP surge[(16.91±8.06) mmHg vs.(12.13±7.36) mmHg, t=3.554, P<0.01] of the dipper group were higher than those of the non-dipper group. Conclusions:Nocturnal blood pressure reduction and sleep-trough surge decreased in NMS children, and there is a circadian rhythm disorder of blood pressure.

The relationship between body mass index and response time of cardioinhibitory type vasovagal syncope in children / 中华实用儿科临床杂志

Objective:To investigate the relationship between body mass index (BMI) and response time of cardioinhibitory type vasovagal syncope (VVS-CI) in children.Methods:The clinical data of 56 children with syncope or pre-syncope were retrospectively analyzed and they visited specialist clinic for syncope and were diagnosed as VVS-CI in the Second Xiangya Hospital, Central South University from December 2012 to September 2019.Based on height and weight, BMI was calculated, and divided into low BMI group (35 cases) and normal BMI group (21 cases). Between the 2 groups, baseline heart rate, head-up tilt test (HUTT) positive response heart rate, baseline head-up tilt test (BHUT) positive response time, and sublingual nitroglycerin-provocated HUTT (SNHUT) positive response time were compared.The correlation between BMI and positive response time was analyzed.SPSS 22.0 software was applied for statistical analysis.Results:There were no significant differences in age, sex, duration of disease and number of syncope between the 2 groups (all P>0.05). No significant differences were found in baseline heart rate and positive response heart rate between the 2 groups [(78.5±15.3) times/min vs.(72.8±8.7) times/min, t=1.223, P=0.230; (44.0±13.9) times/min vs.(47.0±10.0) times/min, t=-0.664, P=0.511]. Compared with normal BMI group, BHUT positive patients/SNHUT positive patients were higher in low BMI group (27/8 cases vs.9/12 cases, χ2=4.839, P=0.027), and the positive response time of BHUT was shorter [(13.1±4.6) min vs.(23.7±9.5) min, t=-2.691, P=0.023]. There were no significant differences in SNHUT positive response time between the 2 groups ( P>0.05). Low BMI was correlated with BHUT positive response time ( r=0.750, P=0.005). Normal BMI was not associated with BHUT positive response time ( r=0.316, P=0.217). There was no correlation between low BMI and normal BMI and SNHUT positive response time ( r=0.177, P=0.431; r=0.021, P=0.940). Conclusions:Low BMI is positively correlated with BHUT positive response time of children with VVS-CI.The time it takes for syncope occurrence was shorter in children with low BMI than that in normal BMI.