Association between urinary arsenic level and serum testosterone in Chinese men aged 18 to 79 years / 中华预防医学杂志

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m2 group (Pinteraction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.

Recognition of the membrane anatomy-based laparoscopic assisted right hemicolectomy / 中华胃肠外科杂志

Although it has become a consensus in the field of colorectal surgery to perform radical tumor treatment and functional protection under the minimally invasive concept, there exist many controversies during clinical practice, including the concept of embryonic development of abdominal organs and membrane anatomy, the principle of membrane anatomy related to right hemicolectomy, D3 resection, and identification of the inner boundary. In this paper, we analyzed recently reported literature with high-level evidence and clinical data from the author's hospital to recognize and review the membrane anatomy-based laparoscopic assisted right hemicolectomy for right colon cancer, emphasizing the importance of priority of surgical dissection planes, vascular orientation, and full understanding of the fascial space, and proposing that the surgical planes should be dissected in the parietal-prerenal fascial space, and the incision should be 1 cm from the descending and horizontal part of the duodenum. The surgery should be performed according to a standard procedure with strict quality control. To identify the resection range of D3 dissection, it is necessary to establish a clinical, imaging, and pathological evaluation model for multiple factors or to apply indocyanine green and nano-carbon lymphatic tracer intraoperatively to guide precise lymph node dissection. We expect more high-level evidence of evidence-based medicine to prove the inner boundary of laparoscopic assisted radical right colectomy and a more rigorous consensus to be established.

Evaluation of thermal environment and human thermal comfort in 8 types of public places from 2019 to 2021 / 中华劳动卫生职业病杂志

Objective: To evaluate the thermal environment of different types of public places and the thermal comfort of employees, so as to provide scientific basis for the establishment of microclimate standards and health supervision requirements. Methods: From June 2019 to December 2021, 50 public places (178 times) of 8 categories in Wuxi were selected, including hotels, swimming pools (gymnasiums), bathing places, shopping malls (supermarkets), barber shops, beauty shops, waiting rooms (bus station) and gyms. In summer and winter, microclimate indicators such as temperature and wind speed were measured in all kinds of places, combined with the work attire and physical activity of employees in the places. Fanger thermal comfort equation and center for the built environment (CBE) thermal comfort calculation tool were used to evaluate the predicted mean vote (PMV), predicted percent dissatisfied (PPD) and standard effective temperature (SET) according to the American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE) 55-2020. The modification effects of seasonal and temperature control conditions on thermal comfort were analyzed. The consistency of GB 37488-2019 "Hygienic Indicators and Limits in Public Places" and ASHRAE 55-2020 evaluation results on thermal environment was compared. Results: The thermal sensation of hotel, barber shop staff and the gym front-desk staff were moderate, while the thermal sensation of swimming place lifeguard, bathing place cleaning staff and gym trainer were slightly warm in summer and winter. Waiting room (bus station) cleaning and working staff, shopping mall staff felt slightly warm in summer and moderate in winter. Service staff in bathing places felt slightly warm in winter, while staff in beauty salons felt slightly cool in winter. The thermal comfort compliance of hotel cleaning staff and shopping mall staff in summer was lower than that in winter (χ(2)=7.01, 7.22, P=0.008, 0.007). The thermal comfort compliance of shopping mall staff in the condition of air conditioning off was higher than that in the condition of air conditioning on (χ(2)=7.01, P=0.008). The SET values of front-desk staff in hotels with different health supervision levels were significantly different (F=3.30, P=0.024). The PPD value and SET value of the front-desk staff, and the PPD value of cleaning staff of hotels above three stars were lower than those of hotels below three stars (P<0.05). The thermal comfort compliance of front-desk staff and cleaning staff in hotels above three stars was higher than that in hotels below three stars (χ(2)=8.33, 8.09, P=0.016, 0.018). The consistency of the two criteria was highest among waiting room (bus station) staff (100.0%, 1/1) and lowest among gym front-desk staff (0%, 0/2) and waiting room (bus station) cleaning staff (0%, 0/1) . Conclusion: There are different degrees of thermal discomfort in different seasons, under the condition of air conditioning and health supervision, and the microclimate indicators can not fully reflect the thermal comfort of human body. The health supervision of microclimate should be strengthened, the applicability of health standard limit value should be evaluated in many aspects, and the thermal comfort of occupational group should be improved.

Association between urinary arsenic level and serum testosterone in Chinese men aged 18 to 79 years / 中华预防医学杂志

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urine arsenic and urine creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urine arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urine arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/L and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m2 group (Pinteraction<0.05). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18-79 years.

Study on improvement effect mechanism of Xibining prescription on knee osteoarthritis model rats based on AMPK/mTOR signaling pathway / 中国药房

OBJECTIVE To investigate the improvement effect mechanism of Xibining prescription （XBN） on knee osteoarthritis （KOA） model rats based on AMP-activated protein kinase（AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. METHODS Totally 36 rats were randomly divided into blank group， model group， XBN group （12.56 g/kg）， XBN+metformin （AMPK agonist） group （12.56 g/kg XBN+100 mg/kg metformin）， with 9 rats in each group. Except for blank group， KOA model was induced by anterior cruciate ligament transection in other groups. After modeling， each group was given relevant medicine/normal saline， XBN and normal saline intragastrically， once a day， and metformin intraperitoneally， every other day， for 4 consecutive weeks. The pathomorphological changes of cartilage tissue in rats were observed and Mankin scoring was conducted. The expression level of Aggrecan in rat cartilage， mRNA and protein expressions of platelet reactive protein disintegrin and metalloproteinase with thrombospondin motifs 4 （ADAMTS-4）， ADAMTS-5， matrix metalloproteinase 3 （MMP-3） and MMP- 13， and the phosphorylation level of AMPK and mTOR proteins were detected. RESULTS Compared with blank group， the structure of cartilage tissue in the model group was disordered， the matrix of cartilage layer was lightly stained，the tide line was distorted or interrupted， and Mankin score was significantly increased （P＜0.05）. The protein expression of Aggrecan in cartilage tissue and the phosphorylation level of AMPK protein were all decreased significantly （P＜0.05）； mRNA and protein expressions of ADAMTS-4， ADAMTS-5， MMP-3 and MMP-13 and the phosphorylation levels of mTOR protein were significantly increased in cartilage tissues （P＜0.05）. Compared with model group， the pathological morphology of cartilage was improved significantly in each administration group， and above score or indexes were reversed significantly （P＜0.05）. Compared with XBN group， the degree of cartilage lesions in rats was further alleviated in XBN+ metformin group， and the levels of above score or indicators were further improved （P＜0.05）. CONCLUSIONS XBN can ameliorate cartilage injury in KOA model rats， promote cartilage synthesis and reduce cartilage degradation， the mechanism of which may be associated with activating AMPK/mTOR signaling pathway.

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell Transplantation with Decitabine-containing Regimen in Myelodysplastic Syndromes and Myelodysplastic Syndromes Transformed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML).@*METHODS@#The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m2 /d×3 d).@*RESULTS@#Among the 93 patients, 63 males and 30 females, were diagnosed as MDS（n ＝77）, MDS-AML（n ＝16）. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease（aGVHD） and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease（cGVHD） and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS（P =0.008）and DFS (P =0.019).@*CONCLUSION@#Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.

Diagnosis and treatment of multiple myeloma in Hunan Province / 中南大学学报(医学版)

OBJECTIVES@#There is less clinical data on multiple myeloma (MM) in China, and the aim of this study was to collect and analyze the clinical data of newly diagnosed multiple myeloma (NDMM) patients in Hunan Province during 1 year, to understand the real clinical features and treatment outcome for Hunan Province patients with MM, and to strengthen the understanding of the standardized diagnosis process and treatment plan of MM.@*METHODS@#The clinical data of 529 patients with NDMM in 12 large-scale general hospitals in Hunan Province from January 1 to December 31, 2019 were collected and analyzed, including baseline data, treatment regimens, duration of treatment, and adverse reactions. The clinical characteristics, treatment, and safety of patients were analyzed by SPSS 21.0.@*RESULTS@#Among the 529 NDMM patients, the age was 33-90 (median 64) years and the male-female ratio was 1.38꞉1. The clinical features ranged from high to low were as follows: Bone pain (77.7%), anemia (66.8%), renal insufficiency (40.6%), hypercalcemia (15.1%). Typing: IgG 46.5%, IgA 24.6%, IgD 2.6%, IgM 0.8%, light chain 15.7%, double clone 3.0%, no secretion 0.6%, absence 6.2%. Staging: Durie-Salmon stage I, II, and III were 4.5%, 10.6%, 77.3%, respectively, and 40 cases (7.6%) missed this data. International Staging System (ISS) stage I, II, and III were 10.4%, 24.4%, and 47.6%, respectively, and 93 cases (17.6%) were missing. Revised International Staging System (R-ISS) stage I, II, and III were 5.5%, 27.0%, 23.1%, respectively, and 235 cases (44.4%) missed this data. Among the 98 NDMM patients in the Third Xiangya Hospital, Central South University, Durie-Salmon (DS) stage missing 2.0%, ISS stage missing 12.3%, and R-ISS stage missing 12.3%.Treatment: Among the 529 patients,475 received treatment, the rate of treatment was 89.8%; 67.4% of the patients were able to complete four courses of chemotherapy at induction phase, 90.3% of the patients received proteasome inhibitor based combination chemotherapy regimen more than once, 67.2% received immunomodulator based regimen more than once, and 59.8% of the patients received proteasome inhibitor and immunomodulator based combination chemotherapy regimen more than once. Curative: Overall response rate (ORR) and high quality response rate (HQR) of the 4-course group were better than those of the 2-course group (ORR: 85% vs 65%, P=0.006; HQR: 68.3% vs 24.0%, P<0.001). The HQR of the standard chemotherapy group was better than that of the non-standard chemotherapy group (65.1% vs 48.2%, P=0.035). Adverse reactions during treatment included hematologic toxicity (17.5%), peripheral neuropathy (24.8%), gastrointestinal adverse events (23.8%), pulmonary infection (25.9%), herpes zoster (4.6%), and venous thrombotic events (1.7%).@*CONCLUSIONS@#In 2019, the missed diagnosis rate of MM patients was high, the medium age of diagnosis was older, and the accuracy of patient diagnosis was not high. There is a great difference among medical centers, especially in the stage and risk stratified, nearly half of NDMM patients are not diagnosed with R-ISS stage; the lack of cytogenetic data needs to be supplemented by follow-up studies. A high proportion of patients with NDMM present with bone pain and anemia.Patients received treatment have higher use of chemotherapy regimens containing proteasome inhibitors and/or immunomodulators, but there is a significant gap among different medical centers, and standardized treatment needs to be strengthened. The safety during chemotherapy is controllable.

Application of an extreme learning machine network with particle swarm optimization in syndrome classification of primary liver cancer / 中西医结合学报

OBJECTIVE@#By optimizing the extreme learning machine network with particle swarm optimization, we established a syndrome classification and prediction model for primary liver cancer (PLC), classified and predicted the syndrome diagnosis of medical record data for PLC and compared and analyzed the prediction results with different algorithms and the clinical diagnosis results. This paper provides modern technical support for clinical diagnosis and treatment, and improves the objectivity, accuracy and rigor of the classification of traditional Chinese medicine (TCM) syndromes.@*METHODS@#From three top-level TCM hospitals in Nanchang, 10,602 electronic medical records from patients with PLC were collected, dating from January 2009 to May 2020. We removed the electronic medical records of 542 cases of syndromes and adopted the cross-validation method in the remaining 10,060 electronic medical records, which were randomly divided into a training set and a test set. Based on fuzzy mathematics theory, we quantified the syndrome-related factors of TCM symptoms and signs, and information from the TCM four diagnostic methods. Next, using an extreme learning machine network with particle swarm optimization, we constructed a neural network syndrome classification and prediction model that used "TCM symptoms + signs + tongue diagnosis information + pulse diagnosis information" as input, and PLC syndrome as output. This approach was used to mine the nonlinear relationship between clinical data in electronic medical records and different syndrome types. The accuracy rate of classification was used to compare this model to other machine learning classification models.@*RESULTS@#The classification accuracy rate of the model developed here was 86.26%. The classification accuracy rates of models using support vector machine and Bayesian networks were 82.79% and 85.84%, respectively. The classification accuracy rates of the models for all syndromes in this paper were between 82.15% and 93.82%.@*CONCLUSION@#Compared with the case of data processed using traditional binary inputs, the experiment shows that the medical record data processed by fuzzy mathematics was more accurate, and closer to clinical findings. In addition, the model developed here was more refined, more accurate, and quicker than other classification models. This model provides reliable diagnosis for clinical treatment of PLC and a method to study of the rules of syndrome differentiation and treatment in TCM.

A multicenter retrospective study on the real-world outcomes of autologous vs. allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma in China / 中华医学杂志(英文版)

BACKGROUND@#There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.@*METHODS@#From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n  = 72) or allo-HSCT (n  = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.@*RESULTS@#Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300).@*CONCLUSIONS@#Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.

Analysis of Factors Influencing Autologous Peripheral Blood Stem Cells Mobilization in Patients with Lymphoma and Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To analyze the factors influencing the mobilization of autologous peripheral blood stem cells (auto-PBSCs) in patients with lymphoma and multiple myeloma, and provide reference for optimizing the autologous stem cell mobilization regimen.@*METHODS@#Clinical data of 33 multiple myeloma and lymphoma patients received auto-PBSCs mobilization in our center from January 2015 to December 2018 were collected, the correlation of mobilization failure rate with gender, age, courses of chemotherapy before mobilization, does of recombinant human granulocyte colony stimulating factor (rhG-CSF), type of disease, and chemotherapy regimen were retrospectively analyzed.@*RESULTS@#Type of disease and course of pre-mobilization chemotherapy could affect the mobilization failure rate (P0.05).@*CONCLUSION@#Multi-course chemotherapy before collection and lymphoma patients are poor factors negatively impacting on auto-PBSCs mobilization.

Literature Analysis for Network Pharmacology Research of TCM Compound Prescription / 中国药房

OBJECTIVE：To comprehensi vely evaluate the application progress of network pharmacology methods in TCM compound prescription research ，and to provide reference for modernization of TCM compound prescription research. METHODS ： Taking“network pharmacology ”and“TCM compound prescription ”as keywords ，the literatures were retrieved from CNKI ， Wanfang database and VIP during May 2006 to May 2020. Screening literature ，the databases ，analysis platforms ，and software used of the literature were summarized ；on the basis of quantitative analysis ，the application of network pharmacology in the research of traditional Chinese medicine compound were summarized. RESULTS & CONCLUSIONS ：There were a total of 761 valid literatures ，among which the number of literatures that could be retrieved in 2019 reached 313. In the modernization research of TCM compound prescription ，network pharmacology methods were mainly usedmechanism ，material basis of pharmacodynamics ， compatibility law ，compound optimization ，and“effect-toxic”network. Commonly used databasesand platforms included traditional chinese medicine information database （TCMSP and TCMID ），therapeutic target database （TTD，OMIM），drug targets and target prediction platform （Drugbank，SwissTargetPrediction，TargetNet，PharmMapper），network pharmacology analysis and prediction software and platform （CytoScape），etc. Network pharmacology method was widely used in the field of TCM compound prescription research ，and provided new ideas and methods for the modernization of TCM compound prescription research. In the future，the related research can be combined with the pharmacokinetic parameters ，the efficacy of active compounds and related basic experiments ，use the weighted method to carry out network pharmacology analysis ，and integrate the information of multiple databases to improve the scientificity of research results.

Meta-analysis of Oral Chinese Medicine for Adjuvant Treatment of Primary Hepatic Carcinoma and Screening of Basic Chinese Herbs / 中国实验方剂学杂志

Objective:To systematically evaluate the efficacy of oral Chinese herbal prescriptions combined with transcatheter arterial chemoembolization （TACE） against primary hepatic carcinoma （PHC） and screen the basic Chinese herbs，in order to provide certain reference for clinical medication. Method:The randomized controlled trials concerning the treatment of PHC with oral Chinese herbal prescriptions plus TACE were retrieved from CBM，China National Knowledge Infrastructure （CNKI），Chongqing Weipu Database for Chinese Technical Periodicals （VIP），and Wanfang Data Knowledge Service Platform.The quality of the included trials was evaluated by Cochrane handbook，and the Meta-analysis was performed using RevMan 5.3.The enumeration data were expressed by odds ratio （OR），the measurement data by mean difference （MD） or standardized mean difference （SMD），and the effect size by 95% confidence interval （CI）.The data of oral Chinese herbal prescriptions involved in trials were sorted out and subjected to association rule analysis and frequency analysis based on the Traditional Chinese Medicine Inheritance Support System （TCMISS），for exploring the basic Chinese herbs and their dosages against PHC. Result:A total of 75 randomized controlled trials were included，involving 7 406 cases. As revealed by the Meta-analysis，oral Chinese herbal prescriptions combined with TACE was significantly better than TACE alone in improving the short-term curative effect ［OR=2.05，95%CI（1.83，2.29）］，decreasing alpha fetoprotein （AFP） ［MD=-59.02，95%CI（-79.03，-39.01）］，ameliorating liver function ［SMD=-1.23，95%CI（-1.58，-0.88）］，boosting immunity ［SMD=1.08，95%CI（0.84，1.32）］，adjusting Karnofsky Performance Status （KPS） scale score ［OR=2.7，95%CI（1.11，11.02）］，elevating survival rate ［OR=2.31，95%CI（1.96，2.71）］，and reducing adverse reactions ［OR=0.38，95%CI（0.34，0.43）］.Data mining results showed that the basic Chinese herbs against PHC were Bupleuri Radix，Paeoniae Alba Radix，Atractylodis Macrocephalae Rhizoma，Poria，and Glycyrrhizae Radix et Rhizoma，with their clinical dosages listed as follows：6-15 g for Bupleuri Radix，10-15 g for Paeoniae Alba Radix，9-15 g for Atractylodis Macrocephalae Rhizoma，10-15 g for Poria，and 3-10 g for Glycyrrhizae Radix et Rhizoma. Conclusion:The oral Chinese herbal prescriptions combined with TACE produce better effects in treatment of PHC as compared with TACE alone.These five basic Chinese herbs have anti-cancer effect，and their dosages are within the ranges stipulated in 2020 edition of <italic>Chinese Pharmacopoeia.</italic>This Meta-analysis has provided certain reference for clinical medication.

Application and progress of data mining in study of compatibility law of traditional Chinese medicine / 中国中药杂志

Data mining is an important method to obtain the key information from a large amount of data, and it is widely applied in the research on the modernization of traditional Chinese medicine(TCM). The compatibility law of herbs is a key issue in the research of TCM prescriptions. This reflects the flexibility and effectiveness of TCM prescriptions, and it is also a crucial link to the development of TCM modernization. Therefore, it is the core purpose of the research on TCM prescriptions to find the compatibility law of herbs and clarify the scientific connotation. Data mining, as an effective method and an important approach, has formed a standardized system in the research of compatibility law of herbs, which can reveal the relationship between different Chinese herbs and summarize the internal rules in compatibility. Two hundred and twenty two effective papers were sorted out and categorized in this article. The results showed that data mining was mainly applied in finding the core Chinese herb pairs, summarizing the utility and attributes of TCM prescriptions, revealing the relationship between prescriptions, Chinese herbs and syndromes, finding the optimal dose of Chinese herbs, and producing the new prescriptions. The problems of data mining in research of herbs compatibility rules were summarized, and its development and trend in current researches were discussed in this article to provide useful references for the in-depth study of data mining in the compatibility law of Chinese herbs.

The key role of gut-liver axis in pyrrolizidine alkaloid-induced hepatotoxicity and enterotoxicity

Pyrrolizidine alkaloids (PAs) are the most common phytotoxins with documented human hepatotoxicity. PAs require metabolic activation by cytochromes P450 to generate toxic intermediates which bind to proteins and form protein adducts, thereby causing cytotoxicity. This study investigated the role of the gut-liver axis in PA intoxication and the underlying mechanisms. We exposed mice to retrorsine (RTS), a representative PA, and for the first time found RTS-induced intestinal epithelium damage and disruption to intestinal barrier function. Using mice with tissue-selective ablation of P450 activity, we found that hepatic P450s, but not intestinal P450s, were essential for PA bioactivation. Besides, in RTS-exposed, bile duct-cannulated rats, we found the liver-derived reactive PA metabolites were transported by bile into the intestine to exert enterotoxicity. The impact of gut-derived pathogenic factors in RTS-induced hepatotoxicity was further studied in mice with dextran sulfate sodium (DSS)-induced chronic colitis. DSS treatment increased the hepatic endotoxin level and depleted hepatic reduced glutathione, thereby suppressing the PA detoxification pathway. Compared to RTS-exposed normal mice, the colitic mice displayed more severe RTS-induced hepatic vasculature damage, fibrosis, and steatosis. Overall, our findings provide the first mode-of-action evidence of PA-induced enterotoxicity and highlight the importance of gut barrier function in PA-induced liver injury.

Analysis of Medication Rules of TCM Prescription against Primary Hepatic Carcinoma Based on TCM Data Analysis Platform Based on Strategy Pattern / 中国药房

OBJECTIVE：To estab lish“TCM Data Analysis Platform Based on Strategy Pattern ”（TCMDP），and to analyze the medication rules of TCM prescription against primary hepatic carcinoma （PHC），so as to provide reference for TCM prescription screening. METHODS ：According to the idea of strategy pattern ，TCMDP software was developed ，and the frequency statistics，association，clustering，classification and other methods and the different algorithms covered were encapsulated. Effective TCM prescriptions against PHC were collected and screened from 4 tertiary-grade class-A hospitals in Nanchang city and CNKI ， PubMed. A database of prescriptions for PHC （PDOPHC）was established ，and TCM prescriptions in the data base were put into TCMDP. Clustering algorithm modified by CMC-DD ，modified WD-Get Rules algorithm after merging depth and width search and frequency statistics were used to analyze the distribution of prescription syndrome. Taking phlegm-blood stasis syndrome type （TYPHC）as example ，data mining was carried out on drug efficacy category ，four properties ，five flavors and channel tropism ， drug property combination ，key couplet medicines and key drug combination. RESULTS ：A total of 907 TCM prescriptions against PHC were collected ，mainly involving 10 syndrome types ，such as phlegm-blood stasis syndrome ，deficiency of the vital essential and blood stasis syndrome and liver and spleen blood stasis syndrome. TCM related to TYPHC commonly used in pre- scriptions were tonifying deficiency medicine ， phlegm-re- solving medicine ，promoting blood circulation and removing blood stasi s medicine ，etc．Four properties were mostly cold ，warm and calm ；the five flavors were most ly swe et，bitter and pungent ；channel tropism were mostly spleen ，liver，stomach， lung，heart and kidney ；drug combination were mostly warming-sweet-spleen ，warming-pungent-spleen and cold-bitter-liver ，etc.； there were 36 couplet medicines with frequency ≥30 times；there were 31 strong association rules and 8 key drug combinations in the prescriptions. WD-Get Rules results showed that in the TCM prescriptions against PHC ，Atractylodes macrocephala ，Codonopsis pilosula，Poria cocos and Glycyrrhiza uralensis were in the key position. They were often combined with many kinds of drugs ， which were related to the effect of Sijunzi decoction on strengthening Qi and tonifying spleen. CMC-DD results showed that therapy for TYPHC focused on strengthening the spleen and stomach ，replenishing Qi and blood ；and at the same time ，it treated TYPHC with phlegm-blood stasis syndrome from multiple angles ，such as soothing the liver and regulating Qi ，eliminating phlegm ，clearing heat and detoxification ，promoting blood circulation and nourishing Yin. CONCLUSIONS ：Clinical treatment of TYPHC mainly adopts the methods of invigorating the spleen and replenishing Qi ，soothing the liver and regulating Qi ，promoting blood circulation and removing blood stasis ，which conforms to the medication principle of “strengthening the body and eliminating pathogenic factors”. The application of TCMDP can realize the data mining and analysis of TCM in multi-level and multi-directional way ， which provides a new and effective way for the mining and research of compatibility rules of TCM prescriptions.

Gut microbiota and precision drug therapy / 医学研究生学报

With the initiation and development of the Human Microbiome Project (HMP) and the Project on Metagenomics of the Human Intestinal Tract (MetaHIT), the studies of the gut microbiota (GMB) have entered a fast lane and proved that GMB is associated with several diseases. Recent studies have confirmed that GMB affects and modulates pharmacokinetics (PK) and pharmacodynamics (PD) of drugs, making it one of the potential focuses of precision medicine. This article presents an overview of the potential mechanisms of GMB affecting drug treatment and advances in the relevant studies, hoping to shed some new light on the precision therapeutic strategy.

Distal Chevron osteotomy of the first metatarsal and soft-tissue release for hallux valgus / 中国骨伤

OBJECTIVE@#To explore distal Chevron osteotomy of the first metatarsal and soft-tissue release for the treatment of mild and moderate hallux valgus.@*METHODS@#From June 2015 to June 2017, 32 patients(40 feet) with mild and moderate hallux valgus were treated with distal Chevron osteotomy with soft tissue release. including 3 males(3 feet) and 29 females (37 feet), aged from 22 to 80 years old with an average of 57.57 years old. The courses of disease ranged from 2 to 32 years with an average of 14 years. Among them, 9 feet were mild, 31 feet were moderate. Patients were combined with bunion, pain around the first metatarsal joint, and pain increased during weight-bearing walking before opertaion. AP and lateral X-rays on weight-bearing were performed, hallux valgus angle(HVA) and intermetatarsal angle(IMA) between the first and the second metatarsal were examined before and after operation. AOFAS score was applied to evaluate clinical effects.@*RESULTS@#All patients were followed up from 12 to 24 months with an average of 15.2 months.Fracture wounds were healed well without infection and metatarsal head necrosis occurred. Preoperative HVA (32.08±5.59)° and IMA (11.63±2.24)° decreased to (10.31±4.36)° and (5.02°±2.34)°after operation at 12 months, and had statistical difference before and after operation (<0.05). AOFAS score increased from 56.75±6.42 before operation to 88.80±3.99 after operation at 12 months(<0.05).@*CONCLUSIONS@#Distal Chevron osteotomy of the first metatarsal and soft-tissue release for the treatment of mild and moderate hallux valgus could obtain good effects and provide more options for hallux valgus treatment.

Observation on dynamic changes of gastrointestinal mucosal injury in rats with acute stage of cerebral infarction / 中国中西医结合急救杂志

Objective To investigate the dynamic characteristic changes of gastrointestinal mucosa and its relationship with disease progression in rats with acute cerebral infarction. Methods Fifty-six male Wistar rats were selected as the study subjects, and they were divided into three groups: normal control, sham operation and cerebral infarction model groups by random number table method. The middle cerebral artery occlusion (MCAO) model was prepared by the modified Longa thread embolic method. The levels of gastrin (GAS) were monitored in each group after modeling for 24 hours, 4 days and 7 days; after the rats were killed, the sections of gastric antrum and small intestine were taken and stained with hematoxylin-eosin (HE) staining method, the histopathological changes of gastric and small intestinal mucosa were observed under light microscope, in the mean time the gastric and small intestinal mucosal pathological scores were also performed, and the differences of pathological scores among the three groups were compared. Results There were no statistical significant differences in GAS, gastrointestinal mucosa and small intestinal mucosal pathological scores between the normal control group and sham operation group at each time point (all P > 0.05); the GAS level in cerebral infarction model group was decreased gradually with time prolongation, reaching the lowest level 7 days after modeling, but the GAS level in cerebral infarction model group was significantly higher than that in normal group and shamoperation group (ng/L: 205.02±7.68 vs. 130.51±8.03, 145.29±7.68, both P < 0.05). The pathological scores of gastrointestinal mucosa and small intestinal mucosa in the cerebral infarction model group were increased first and then decreased with time prolongation, peaked on 4th day and decreased significantly on 7th day, the pathological scores of gastrointestinal mucosa and small intestinal mucosa in the cerebral infarction model group at each time point were significantly higher than those in the normal control group and sham-operated group (gastric mucosal pathological score: 82.50±2.95 vs. 21.38±1.57, 36.10±3.41; small intestinal mucosal pathological score: 62.00±2.78 vs. 18.25±1.39, 25.55±1.75, all P < 0.05). Under light microscopy, the normal control group showed complete normal morphological appearance, normal structure, orderly arrangement of villi and no infiltration of inflammatory cells; in shamoperation group, inflammatory cells infiltrated the lamina propria at each time point, and there were villi slightly uneven, enlarged stroma, congestion, edema occasionally seen and no obvious ulcer; in cerebral infarction model group, the various layers of gastrointestinal mucosal were not very clear, the glands were arranged irregularly and the capillaries dilated, and in part of tissues, congestion, hemorrhage, edema and inflammatory cell infiltration were seen obviously. Conclusion The injury of gastrointestinal mucosa in acute stage of cerebral infarction should be related to the stress stimulation and disease progress of cerebral infarction itself, not due to the abnormal secretion of GAS.

CD137-CD137L interaction induced the calcification of mouse smooth muscle cells via P38 MAPK signaling / 中华心血管病杂志

Objective@#To explore whether CD137-CD137L interaction could induce mouse vascular smooth muscle cells(VSMCs) calcification via P38 MAPK signaling.@*Methods@#(1) Mouse VSMCs obtained from 8-week old male C57 mice were cultured by using method of tissue piece inoculation.The cells from 3 to 8 passage were divided into 4 groups: control group, agonist-CD137 group(recombinant CD137L protein), anti-P38 group(agonist-CD137 group+P38 inhibitor), single anti-P38 group(P38 inhibitor). The calcification was induced by adding a mixture of 10 mmol/L β-glycerophosphate+10-8 mol/L dexamethasone+10-7 mol/L insulin in the culture medium.Immunofluorescence was used to observe the changes of VSMCs markers(α-SMA and OPN).Real time-PCR was used to observe the mRNA expression of OPN and RUNX-2. Western blot was used to observe the protein expression of p-P38, OPN and RUNX-2. The level of cell calcification was observed by detecting alkaline phosphatase activity and calcium concentration. (2) The degeree of local calcium deposition was also tested on Von Kossa staining and Alizarin red staining methods in following 5 mouse VSMCs groups: control group, agonist-CD137 group(recombinant CD137L protein), anti-P38 group (agonist-CD137 group+P38 inhibitor), anti-CD137 group (agonist-CD137 group+CD137 inhibitor),agonist-P38 group(anti-CD137 group+P38 agonist).@*Results@#(1) Compared with the control group, the fluorescence intensity of α-SMA was lower in the agonist-CD137 group(2.79±0.25 vs. 5.42±0.47,P<0.05), while the fluorescence intensity of OPN was higher(4.91±0.23 vs. 1.63±0.26, P<0.05). The fluorescence intensity of α-SMA was partly recovered after adding P38 inhibitor(4.48±0.27 vs. 2.79±0.25,P<0.05),but it was still lower than the control group (4.48±0.27 vs. 5.42±0.47, P<0.05),the fluorescence intensity of OPN decreased(2.66±0.15 vs. 4.91±0.23,P<0.05),but it was still higher than that in the control group (2.66±0.15 vs. 1.63±0.26,P<0.05).The fluorescence intensity of α-SMA and OPN(5.32±0.67 vs. 5.42±0.47,1.82±0.30 vs.1.63±0.26,both P>0.05) was similar between the control group and single anti-P38 group.(2) Compared with the control group, the protein level of p-P38(4.15±0.24 vs. 3.48±0.26, P<0.05), OPN(2.43±0.21 vs. 1.53±0.08, P<0.05), RUNX-2(3.20±0.23 vs. 1.13±0.10, P<0.05) was significantly increased in agonist-CD137 group,the above effects were blocked by adding specific P38 inhibitor SB203580(1.16±0.12 vs. 4.15±0.24, 0.50±0.02 vs. 2.43±0.21,and 1.74±0.14 vs. 3.20±0.23,all P<0.05);the protein level of p-P38(2.93±0.60 vs. 3.48±0.26,P>0.05),OPN (1.4±0.64 vs. 1.53±0.08,P>0.05),RUNX-2(1.26±0.26 vs.1.13±0.10, P>0.05) was similar between single anti-P38 group and the control group. (3) Compared with the control group, the mRNA level of OPN (1.51±0.34 vs. 1, P<0.05) and RUNX-2(2.67±0.19 vs. 1, P<0.05) was significantly upregulated in agonist-CD137 group, and these effects were blocked by adding specific P38 inhibitor SB203580(0.33±0.14 vs. 1 and 0.45±0.03 vs. 1,P<0.05);the mRNA level of OPN (1.05±0.09 vs. 1, P>0.05) and RUNX-2(1.18±0.10 vs. 1, P>0.05) was similar between the single anti-P38 group and the control group.(4) Compared with the control group,the ALP activity and calcium concentration(2.40±0.25 vs. 1.40±0.21,5.51±0.33 vs. 3.15±0.31,both P<0.05) were significantly increased in agonist-CD137 group,while the effects could be blocked by adding specific P38 inhibitor SB203580((1.99±0.07) king unit/gprot vs. (2.40±0.25) king unit/gprot, (3.74±0.20) mmol/gprot vs. (5.51±0.33) mmol/gprot, both P<0.05).The ALP activity and calcium concentration was similar between single anti-P38 group and the control group((1.60±0.25) king unit/gprot vs. (1.40±0.21)king unit/gprot, (2.66±0.28) mmol/gprot vs. (3.15±0.31) mmol/gprot, both P>0.05). (5) Compared with the control group,the calcification of VSMCs in the agonist-CD137 group was significantly increased,while the calcification in the anti-P38 group was significantly reduced.Compared with the agonist-CD137 group,the level of calcification in the anti-CD137 group was obviously increased,and the calcification in the agonist-P38 group was significantly higher than that in the anti-CD137 group and the control group.@*Conclusion@#These findings suggest that CD137-CD137L signaling may regulate VSMCs calcification via modulating P38 pathway.

CD137-CD137L signaling influences the autophagy via JNK pathway in mouse vascular smooth muscle cells / 中华心血管病杂志

Objective@#To investigate whether CD137-CD137L signaling can affect the autophagy of mouse vascular smooth muscle cells(VSMCs) through JNK signal pathway.@*Methods@#Primary culture of C57BL/6J mouse thoracic aorta VSMCs was performed by tissue block adherence method. VSMCs between the third to fifth passages were isolated and cultured. VSMCs were divided into 4 groups: control group, CD137 agonist group, JNK inhibition group, and DMSO group. VSMCs in CD137 agonist group were treated with recombinant protein of CD137L (10 μg/ml), VSMCs in JNK inhibition group were treated with JNK inhibitor SP600125 (10 μmol/L) for 30 minutes followed by recombinant protein of CD137L (10 μg/ml) and DMSO group was treated with the same amount of DMSO in JNK inhibition group for 30 minutes, then added recombinant protein of CD137L (10 μg/ml). Western blot was used to detect the protein expression of p-JNK, LCⅡ and p62 in each group. Fluorescence microscopy was used to track the changes of autophagy in cells which was infected with adenovirus expressing tandem mRFP-GFP-LC3. Transmission electron microscope (TEM) was used to observe intracellular autophagosomes and autolysosomes.@*Results@#(1) Compared with the control group, stimulating CD137-CD137L axis by recombinant protein of CD137L significantly upregulated the expression of p-JNK, LCⅡ and p62 (1.15±0.19 vs. 0.72±0.21, P<0.05;1.03±0.13 vs. 0.59±0.15, P<0.05, and 1.10±0.19 vs. 0.76±0.15, P<0.05). These effects could be reduced by JNK inhibitor (0.61±0.21 vs. 1.15±0.19, P<0.05;0.74±0.11 vs. 1.03±0.13, P<0.05, and 0.21±0.12 vs. 1.10±0.19, P<0.05). The expression of these proteins in DMSO group remained unchanged compared with CD137 agonist group (P>0.05). (2) Changes of autophagy in cells of various group: the number of total fluorescent spots and yellow fluorescent spots in CD137 agonist group was significantly increased compared to control group (total fluorescent spots:(93.00±14.11)/cell vs. (52.33±9.61)/cell, P<0.05, and (64.33±6.81)/cell vs. (25.67±3.51)/cell, P<0.05), moreover, the number of yellow fluorescent spots was higher than the red fluorescent spots fluorescent spots in CD137 agonist group. Compared with CD137 agonist group, pretreatment with JNK inhibitor significantly reduced the number of total fluorescent spots and yellow fluorescent spots ((53.00±3.17)/cell vs. (93.00±14.11)/cell, P<0.05,and (15.33±4.51)/cell vs. (64.33±6.81)/cell, P<0.05). The red fluorescent spots were higher than the yellow fluorescent spots in JNK inhibition group. The number of total fluorescent spots and yellow fluorescent spots in CD137 agonist group was not affected by pretreatment with DMSO (P>0.05). (3) The number of intracellular autophagosomes and autolysosomes was significantly higher in CD137 agonist group than in control group((17.67±6.03)/cell vs. (5.67±2.52)/cell, P<0.05), and the number of autophagosomes was higher than that of autolysosomes in CD137 agonist group((14.00±4.00)/cell vs. (3.67±2.08)/cell, P<0.05). The number of intracellular autophagosomes and autolysosomes was significantly lower in JNK inhibition group compared to CD137 agonist group((5.67±4.04)/cell vs. (17.67±6.03)/cell, P<0.05) and the number of autophagosomes was lower than that of autolysosomes in JNK inhibition group((1.33±1.53)/cell vs. (4.33±2.52)/cell, P<0.05). The number of intracellular autophagosomes and autolysosomes was similar between DMSO group and CD137 agonist group (P>0.05).@*Conclusion@#CD137-CD137L signal may influence autophagy of mouse VSMCs via JNK pathway.