Integrating bioinformatics and machine learning methods to analyze diagnostic biomarkers for HBV-induced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor. It is estimated that approximately 50-80% of HCC cases worldwide are caused by hepatitis b virus (HBV) infection, and other pathogenic factors have been shown to promote the development of HCC when coexisting with HBV. Understanding the molecular mechanisms of HBV-induced hepatocellular carcinoma (HBV-HCC) is crucial for the prevention, diagnosis, and treatment of the disease. In this study, we analyzed the molecular mechanisms of HBV-induced HCC by combining bioinformatics and deep learning methods. Firstly, we collected a gene set related to HBV-HCC from the GEO database, performed differential analysis and WGCNA analysis to identify genes with abnormal expression in tumors and high relevance to tumors. We used three deep learning methods, Lasso, random forest, and SVM, to identify key genes RACGAP1, ECT2, and NDC80. By establishing a diagnostic model, we determined the accuracy of key genes in diagnosing HBV-HCC. In the training set, RACGAP1(AUC:0.976), ECT2(AUC:0.969), and NDC80 (AUC: 0.976) showed high accuracy. They also exhibited good accuracy in the validation set: RACGAP1(AUC:0.878), ECT2(AUC:0.731), and NDC80(AUC:0.915). The key genes were found to be highly expressed in liver cancer tissues compared to normal liver tissues, and survival analysis indicated that high expression of key genes was associated with poor prognosis in liver cancer patients. This suggests a close relationship between key genes RACGAP1, ECT2, and NDC80 and the occurrence and progression of HBV-HCC. Molecular docking results showed that the key genes could spontaneously bind to the anti-hepatocellular carcinoma drugs Lenvatinib, Regorafenib, and Sorafenib with strong binding activity. Therefore, ECT2, NDC80, and RACGAP1 may serve as potential biomarkers for the diagnosis of HBV-HCC and as targets for the development of targeted therapeutic drugs.

International standard of Traditional Chinese Medicine Techniques: Traditional Chinese Medicine guidelines for acute primary headache (2022).

OBJECTIVE: To summarize the evidence from Traditional Chinese Medicine (TCM) practice in the treatment of acute primary headache and provide clinical practice guidance. METHODS: The guidelines were developed in accordance with the World Health Organization guideline development manual. After the establishment of steering committee, panel and the registration and protocol formulation, the evidence on TCM for acute primary headache from published guidelines, clinical evidence, and expert experience and consensus were collected. The grading of recommendations assessment, development and evaluation method was used to grade the evidence and make the recommendations. RESULTS: Based on the available evidence, the guidelines recommended three TCM herbal decoctions, six Chinese patent medicines, and two kinds of external application of Chinese herbal medicines. Diagnostic recommendations based on the expert experience and consensus were also included in the guidelines. CONCLUSION: TCM diagnosis and treatment of decoction, Chinese patent medicine and external application for treating acute primary headache were recommended. We hope these guidelines will be helpful in standardize the TCM acute treatment of primary headache.

Clinical Comprehensive Evaluation of Oral Anticoagulants Based on A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition) / 医药导报

Objective A comprehensive evaluation of oral anticoagulants(OACs)was conducted using the A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition),to provide a reference for drug selection and clinical medication decisions in medical institutions.Methods Evaluation evidence was collected,and the drugs included in the evaluation were quantified on four dimensions of clinical properties(efficiency and safety),pharmaceutical properties,economy and others.Results All oral anticoagulants included in the evaluation had a score of 70 or higher in the comprehensive evaluation,while warfarin had the highest overall score.Clinical properties and pharmacologic properties were identified as the core attributes for drug selection evaluation.When considering only these factors,edoxaban received the highest score.Conclusion OACs are the preferred option for patients requiring long-term anticoagulation therapy.Various OACs offer distinct clinical advantages.Utilizing the Guidelines(Second Edition)for oral anticoagulant selection and evaluation can offer visual evidence for drug selection and promote the scientific,rational,and safe use of drugs in clinical management.

Impact of spectrum irradiation combined with operative laparoscopy on inflammatory reaction and immune function in children with appendicitis / 中国内镜杂志

Objective To study the effect of spectrum irradiation combined with operative laparoscopy on inflammatory reaction and immune function in children with appendicitis.Methods 120 children with appendicitis from January 2022 to January 2023 were selected as the study subjects,randomly divided them into two groups using a random number table method:the control group(n = 60)and the study group(n = 60).The control group underwent laparoscopic minimally invasive appendectomy,and the study group underwent spectrum irradiation combined with laparoscopic minimally invasive appendectomy.The two groups compared perioperative recovery,procalcitonin(PCT),C-reactive protein(CRP)level,cellular immune function(CD4+,CD8+,and CD4+/CD8+),humoral immune function[immunoglobulin M(IgM),immunoglobulin G(IgG),C3,and C4],pain visual analogue scale(VAS),Alvarado score,and treatment effect and postoperative complication rate.Results Compared with the control group,the study group showed a significant reduction in the time to first anal exhaust and hospital stay after surgery,the differences were statistically significant(P<0.05).Compared with preoperative levels,the levels of PCT and CRP in both groups of patients increased at 12 and 24 h postoperatively,with the highest levels occurring at 12 h postoperatively;The PCT and CRP levels in the study group were lower than those in the control group at 12 and 24 h after surgery,the differences were statistically significant(P<0.05).Compared with preoperative data,the CD4+,CD8+,and CD4+/CD8+ levels decreased in both groups at 12 and 24 h postoperatively,with the lowest levels observed at 12 h postoperatively;The CD4+,CD8+,and CD4+/CD8+ levels in the study group were higher than those in the control group at 12 and 24 h after surgery,the differences were statistically significant(P<0.05).Compared with preoperative levels,the levels of IgM,IgG,C3,and C4 in both groups of patients decreased after surgery,with the lowest levels occurring 12 h after surgery;The levels of IgM,IgG,C3,and C4 in the study group were higher than those in the control group at 12 and 24 h after surgery,the differences were statistically significant(P<0.05).Compared with preoperative conditions,the VAS and Alvarado scores in both groups of patients decreased at 12 and 24 h after surgery.The VAS and Alvarado scores of the study group were lower than those of the control group at 12 and 24 h after surgery,the differences were statistically significant(P<0.05).Compared with the control group,the study group had a higher overall effective rate and a lower total incidence of complications,the differences were statistically significant(P<0.05).Conclusion Spectrum irradiation combined with operative laparoscopy can reduce postoperative inflammatory reaction,and improve immune function in children with appendicitis,shorten inflammatory reaction and immunosuppression time,reduce pain,and have a low incidence of postoperative complications,with ideal effect.

Mechanism of Xiezhuo Jiedu Recipe in Preventing Colorectal Adenoma in Mice Through miRNA-34a-5p/PI3K/Akt Signalling Pathway / 中国实验方剂学杂志

ObjectiveKey microRNAs （miRNAs） of colorectal adenoma （CRA） were identified and analyzed by bioinformatics methods， and differentially expressed genes （DEGs） were screened to construct regulatory relationships. The mechanism of Xiezhuo Jiedu recipe in preventing CRA was speculated and verified by animal experiments. MethodThe miRNAs dataset GSE50194 was obtained from the Gene Expression Omnibus （GEO） database of intestinal mucosal tissue of CRA patients， and the differentially expressed miRNAs were screened by GEO2R and Excel. TargetScan， miRTarbase， and miRDB databases were used to predict the target genes of the differentially expressed miRNAs， and an intersection was obtained. Key DEGs were screened through the STRING database and Cytoscape software， and the TRRUST database was used to predict downstream binding transcription factors （TFs）. The mRNA intersection was enriched by gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） in the Metascape database. DIANA TOOLS were applied to perform KEGG enrichment analysis of key miRNAs， and the key signaling pathways were selected for animal experiments. In animal experiments， the CRA mice model was established by using sodium glycan sulfate （DSS） drinking combined with intraperitoneal injection of azomethane oxide （AOM）， and Xiezhuo Jiedu recipe and aspirin were given by intragastric administration at the same time. The experiment lasted for nine weeks. The pathological changes in intestinal tissue were observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-34a-5p in adenoma tissue. Protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， phosphoryl-PI3K （p-PI3K）， phosphoryl-Akt （p-Akt）， and B cell lymphoma （Bcl）-2 were detected by Western blot. The expression of Cyclin D1 （CCND1） was detected by immunohistochemistry （IHC）. In situ terminal transferase labeling （TUNEL） was used to detect apoptosis of adenoma tissue cells. ResultThe GEO database screened the GSE50194 dataset， and miR-34a-5p was selected as the research object from CRA and normal tissue. A total of 93 DEGs were selected. Among them， GO and KEGG enrichment analyses were closely related to biological processes such as transcriptional regulatory complex， RNA polymerase Ⅱ transcriptional regulatory complex， enzyme-linked receptor protein signaling pathway， and DNA-binding transcriptional activator activity， cancer pathway， PI3K/Akt pathway， etc. miR-34a-5p is mainly enriched in PI3K/Akt， cell cycle， and colorectal cancer pathways. Five key DEGs were screened out through the Matescape database， among which Bcl-2 and CCND1 were the key DEGs of miR-34a-5p. Further screening of the TFs of key DEGs revealed that E2F transcription factor 1 （E2F1） and tumor protein P53 （TP53） were the main TFs of Bcl-2 and CCND1. Animal experiments showed that Xiezhuo Jiedu recipe could effectively up-regulate mRNA level of miR-34a-5p， down-regulate the expression of PI3K， Akt， Bcl-2， p-PI3K， and p-Akt proteins in the intestinal tissue of CRA mice， down-regulate the positive expression rate of CCND1， and increase the apoptosis rate of intestinal epithelial cells. ConclusionIt is speculated that Xiezhuo Jiedu recipe may inhibit the abnormal proliferation and promote the apoptosis of intestinal epithelial cells in CRA mice by regulating the miR-34a-5p/PI3K/Akt signaling pathway， thus playing a role in the prevention of CRA.

Mechanism of Xiezhuo Jiedu Recipe Regulating Ferroptosis in Treatment of Ulcerative Colitis Based on Bioinformatics and Animal Experiments / 中国实验方剂学杂志

ObjectiveThe bioinformatics method was used to screen ferroptosis differential genes （FRGs） closely related to ulcerative colitis （UC）， and animal experiments were conducted to verify whether the mechanism of Xiezhuo Jiedu recipe in treating UC is related to the regulation of ferroptosis. MethodThe differentially expressed genes （DEGs） of colonic mucosa tissue of UC patients were obtained from the GEO database， and the intersection of the genes with ferroptosis genes was used to obtain FRGs. The core FRGs were obtained by cluster analysis， minimum absolute contraction and selection operator （LASSO） regression， and receiver operating characteristic curve （ROC） curve analysis. In animal experiments， the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate （DSS）. Xiezhuo Jiedu recipe and mesalazine were given by gavage for seven days， and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of E3 ubiquitin ligase （FBXW7）， zinc finger protein （ZFP36）， solute carrier family 7 member 11 （SLC7A11）， and Toll-like receptor 4 （TLR4） in colon tissue. The protein expression levels of FBXW7， ZFP36， SLC7A11， and TLR4 in colon tissue were detected by Western blot. ResultDataset GSE87466 was screened from the GEO database， and its intersections with the ferroptosis gene were analyzed to obtain 21 FRGs. After cluster analysis， LASSO regression， and ROC analysis， core FRGs （FBXW7， ZFP36， SLC7A11， and TLR4） were obtained. Immunoinfiltration analysis showed significant differences in the expression of initial B cells， M1 macrophages， plasma cells， and M2 macrophages in the colonic mucosa tissue of UC mice， and there was a significant correlation between core FRGs and these immune cells. Further animal experiments showed that the colonic mucosa tissue of mice in the model group was disorganized and infiltrated by a large number of inflammatory cells. The inflammation of the colonic mucosa tissue of mice in each group was relieved to varying degrees after treatment with Xiezhuo Jiedu recipe and mesalazine， while the colonic mucosa tissue of mice in the high-dose group of Xiezhuo Jiedu recipe showed almost no inflammatory changes. Compared with the normal group， the protein and mRNA expressions of FBXW7， ZFP36， SLC7A11， and TLR4 in the model group were significantly increased， and the expression of core FRGs in colonic mucosa tissue of mice in all groups was significantly down-regulated after treatment with Xiezhuo Jiedu recipe and mesalazine. ConclusionFBXW7， ZFP36， SLC7A11， and TLR4 are ferroptosis genes closely related to the pathogenesis of UC， and Xiezhuo Jiedu recipe can significantly alleviate colonic mucosa inflammation in mice by down-regulating core ferroptosis genes.

Improvement of Colonic Mucosa Inflammatory Response in Mice with Ulcerative Colitis by Xiezhuo Jiedu Recipe Through miRNA-155-5p/JAK2/STAT3 Pathway / 中国实验方剂学杂志

ObjectiveThe differential expression of microRNAs （miRNAs） between the active stage and the remission stage of ulcerative colitis （UC） was analyzed by bioinformatics method， and the regulatory relationship was constructed by screening the differentially expressed genes （DEGs）. The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments. MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database （GEO）， and the most differentially expressed miRNAs were screened by GEO2R， Excel， and other tools as research objects. TargetScan， miRTarbase， miRDB， STRING， TRRUST， and Matescape databases were used to screen key DEGs， predict downstream transcription factors （TFs）， gene ontology （GO）， and conduct Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments， the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate （DSS）. Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days， and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor （SOCS1）， phosphorylated transcriptional signal transductor and activator 3 （p-STAT3）， phosphorylated Janus kinase 2 （p-JAK2）， and retinoic acid-associated orphan receptor-γt （ROR-γt）. The expression levels of transforming growth factor-β （TGF-β）， interleukin-17 （IL-17）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in serum were detected by enzyme linked immunosorbent assay （ELISA）. ResultThe GSE48957 dataset was screened from the GEO database， and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation， as well as signaling pathways such as stem cell signaling pathway， IL-17 signaling pathway， and helper T cell 17 （Th17） cell differentiation. The Matescape database was used to screen out 10 key DEGs， among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3， p-JAK2， and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice， up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10， increase the level of anti-inflammatory factors， and reduce inflammatory cell infiltration. ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice， inhibit the phosphorylation of STAT3， inhibit the differentiation of CD4+ T cells into Th17 cells， reduce the levels of pro-inflammatory factors （IL-17 and IL-6）， and increase the levels of anti-inflammatory factors （TGF-β and IL-10）. As a result， the inflammation of colon mucosa in UC mice was alleviated.

Efficacy of XELOX regimen neoadjuvant chemotherapy in the treatment of stage Ⅱ(T4)and Ⅲ colon cancer / 临床外科杂志

Objective To evaluate the efficacy of XELOX regimen as neoadjuvant chemotherapy in the treatment of stage Ⅱ and Ⅲ colon cancer.Methods The clinical data of 50 patients with clinical stage Ⅱ(T4)Ⅲ colon cancer who underwent laparoscopic radical resection at general surgery department of our hospital from January 1,2012 to January 1,2021 were retrospectively analyzed.Patients were divided into neoadjuvant chemotherapy group(NACT)and adjuvant chemotherapy group(ACT)according to whether they received neoadjuvant chemotherapy with XELOX regimen.The general clinical data,adverse reactions of chemotherapy,surgical complications,operation time,intraoperative blood loss,hospitalization time,hospitalization cost,negative conversion rate of tumor markers,tumor remission rate,tumor downstaging rate,tumor response grade after chemotherapy,postoperative disease-free survival curve,and overall survival curve were retrospectively analyzed and compared among the groups.Results There were no significant differences in operative complications,postoperative exhaust time and hospital stay between NACT group and ACT group(P＞0.05).The adverse reactions of chemotherapy,the negative conversion rate of postoperative CEA and CA19-9,the duration of operation,the amount of bleeding,and the hospitalization cost in NACT group were significantly better than those in ACT group(P＜0.05).In terms of DFS and OS survival curves,with the extension of time,the decline of the NACT survival curve was smaller than that of the ACT group,and there was a significant difference in DFS survival curve(P＜0.05),but no significant difference in OS survival curve(P＞0.05).Conclusion XELOX neoadjuvant chemotherapy is safe and effective in the treatment of stage Ⅱ(T4)and stage Ⅲcolon cancer.

Meta-synthesis of qualitative research on the experience of kinesiophobia in patients with cardiac rehabilitation / 中华护理杂志

Objective To systematically review and synthesize the psychological experience of kinesiophobia in patients with cardiac rehabilitation.Methods PubMed,Web of science,Journals@Ovid,Embase,CINAHL,PsycINFO,Cochrane Library,CNKI,SinoMed,WanFang Database,Vip Database,American Heart Association,European Society of Cardiology and American Association of Cardiovascular and Pulmonary Rehabilitation were searched to collect qualitative research on the psychological experience of cardiac rehabilitation patients with kinesiophobia.The retrieval time was from the establishment of the databases to Jun 2023.The literature was evaluated using the Australian JBI Quality Evaluation Criteria for Qualitative Research in Evidence-based Health Care Centres(2016),and the results were consolidated using an aggregative integration approach.Results A total of 45 results were extracted from 14 studies.Similar results were summarized into 10 groups,and 3 integrated results were synthesized as followed.Kinesiophobia was influenced by many factors;kinesiophobia affects the life experience of patients;strategies to reduce the level of kinesiophobia.Conclusion Nurses should pay more attention to psychological experience of kinesiophobia,and take the corresponding intervention measures to help patients overcome the psychological barriers of kinesiophobia,perfect personalized exercise programs,and improve the level of physical activity.

Application of Quality Evaluation of Blind Method in Clinical Trials of Traditional Chinese Medicine / 中国实验方剂学杂志

The quality evaluation of the blind method is to evaluate the clinical blind data obtained from clinical trials adopting the blind method and judge the effectiveness of the blind method by investigating the blind effect of different blind objects. A successful blind method can avoid the influence of subjective factors on the test results of subjects and researchers to a certain extent. The quality evaluation of the blind method can reflect not only the effectiveness of the blind method but also the accuracy and credibility of clinical trial results. In recent years， randomized controlled trials have been widely used in the evaluation of the clinical efficacy of traditional Chinese medicine （TCM）， but the quality of the implementation of blind methods is uneven， and the evaluation criteria have not yet been formed. In this paper， the data collection methods， calculation principles， advantages， and disadvantages of two quantitative quality evaluation methods of blind methods， namely James Blinding Index （JBI） and Bang Blinding Index （BBI）， were introduced. The two indexes were analyzed in a randomized controlled trial of acupuncture and moxibustion to relieve postoperative oral pain. The calculation process of the results was demonstrated by R software and visualized by forest map. At the same time， a tool table was designed to facilitate the collection of evaluation data of blind methods in TCM clinical trials at different stages. Finally， the necessity and feasibility of quality evaluation of blind method in TCM research were discussed to provide a basis for evaluating and improving the quality of blind method implementation in TCM clinical trials.

Randomized Controlled Trial Design Based on Patient Cohorts： Methods and Applications of Trials Within Cohorts / 中国实验方剂学杂志

Trials within cohorts （TwiCs） are design methods derived from randomized controlled trials （RCTS）. They have been widely used in chronic disease areas such as tumors and cardiovascular diseases. The basis of the TwiCs design is a prospective cohort of specific diseases. When RCTS need to be implemented， some patients meeting the inclusion and exclusion criteria are randomly sampled from the cohort to receive "trial interventions"， while the remaining patients in the cohort who meet the inclusion and exclusion criteria continue to receive conventional treatment as control groups. By comparing the efficacy differences between the intervention measures of the trial group and the control group， the efficacy of intervention measures was evaluated. Within the cohort， the same process could be repeated to carry out multiple RCTS， so as to evaluate different intervention measures or compare the efficacy of different doses or timing of interventions. Compared with classical RCTS， TwiCs make it easier to recruit patients from the cohort and have higher external validity， providing a new research paradigm for improving the efficiency and applicability of RCTS in clinical practice. However， TwiCs may also face the challenge of poor compliance of patients in the cohort. Researchers need to take effective measures to control these patients in the design and operation of TwiCs. This article focused on the methodological key points during the implementation of TwiCs， including multi-stage informed consent （patients are informed of consent at three stages： entering the cohort， entering the trial group， and after the trial）， randomization procedures （only random sampling of patients from the cohort to receive "trial interventions"）， sample size calculation， and statistical analysis methods. The article also compared the differences between TwiCs and traditional RCTS and illustrated TwiCs research design and analysis with examples， so as to provide new research ideas and methods for clinical researchers.

Analysis of research hotspots and trend of the clinical comprehensive evaluation of Chinese patent medicine in China / 中国药房

OBJECTIVE To analyze the research status， hotspots， and trend of the clinical comprehensive evaluation of Chinese patent medicine in China. METHODS Based on CNKI， VIP and Wanfang database， clinical comprehensive evaluation of Chinese patent medicine was used as the subject of retrieval， and the retrieval time was from the inception to October 30th， 2022. CiteSpace 6.1.R3 and VOSviewer were used to conduct a visualization analysis of the relative literature of clinical comprehensive evaluation of Chinese patent medicine in terms of annual publication quantity， authors， institutions， keywords， etc. RESULTS & CONCLUSIONS A total of 1 460 pieces of literature related to the clinical comprehensive evaluation of Chinese patent medicine were included. The overall annual publication quantity showed a growth trend. There were 714 authors in the included literature. The institutions with a large publication quantity included the Chinese Academy of Traditional Chinese Medicine， Beijing University of Chinese Medicine， Tianjin University of Traditional Chinese Medicine， etc.， and there was little cooperation among the authors and institutions. High-frequency keywords included Chinese patent medicine， safety， adverse drug reactions， rational drug use， etc. Research hotspots focused on the safety and effectiveness evaluation of Chinese patent medicine. It may be a research trend in this field to strengthen the prescription review of Chinese patent medicine， and build a multi-dimensional and multi-criteriaclinical comprehensive evaluation system for the rational use of Chinese patent medicine.

Distribution and drug resistance of pathogenic bacteria in lower respiratory tract of 276 hospitalized children / 公共卫生与预防医学

Objective To analyze the epidemiological characteristics and drug resistance of pathogenic bacteria in 276 hospitalized children with lower respiratory tract infection to facilitate prevention and treatment. Methods Among of 276 hospitalized children with lower respiratory tract infection from January 2019 to December 2021 were analyzed. Data on the distribution of pathogenic bacteria were collected and analyzed. At the same time, the information on drug resistance was collected, and the potential relationship between pathogen distribution and drug resistance was briefly analyzed and discussed. Results A total of 532 strains of pathogenic bacteria were detected in the blood samples from 276 patients in this study. There were 207 strains of Gram-positive bacteria, including 104 strains of Staphylococcus aureus, 96 strains of Staphylococcus epidermidis and 7 strains of others. Gram negative bacteria (325 strains) were 172 strains of Klebsiella and 153 strains of Escherichia coli. The distribution of pathogenic bacteria in different gender and age groups (under 5 years old, 5-10 years old, and over 10 -14 years old) was calculated separately. The results showed that the distribution of pathogenic bacteria in female children under 5 years old (n=49 cases) was different from the total population: the infection of Gram-positive bacteria was higher than that of Gram-negative bacteria, and the proportion of Staphylococcus epidermidis was the highest (P<0.05). The distribution characteristics of children of other ages and sexes were consistent with the total distribution characteristics. The resistance rate of Gram-positive bacteria to penicillin, erythromycin and clarithromycin was high, while the resistance rate of Gram-negative bacteria to ampicillin, cefazolin and cefuroxime was high. The distribution characteristics were the same in children of different sex and age. Conclusion The pathogenic bacteria in children with lower respiratory tract infection in pediatric ward are mainly Gram-negative bacteria, and the main pathogenic bacteria have a high resistance rate to common drugs. The distribution of pathogenic bacteria in female children under 5 years old is unique: the infection of Gram-positive bacteria is higher than that of Gram-negative bacteria, and the proportion of Staphylococcus epidermidis is the highest, which deserves attention. The clinical drug sensitivity test can be used as an important reference for the treatment of drugs to guide the rational selection of antibiotics.

Guidelines for TCM Intervention After Conventional Western Medicine Treatment for Stage Ⅰ-Ⅲ Colorectal Cancer / 中国实验方剂学杂志

Colorectal cancer is one of the common malignant tumors with high morbidity， and changes in lifestyle， dietary structure and environment in China in recent decades have been associated with an increase in the incidence of colorectal cancer. A large number of studies have shown that traditional Chinese medicine（TCM） can be used as a complementary and alternative treatment for colorectal cancer after conventional western medicine treatment. TCM physicians have accumulated a lot of clinical experience in the treatment of patients with stage Ⅰ-Ⅲ colorectal cancer， and have proved that TCM has unique efficacy， but there is still a lack of relevant clinical practice guidelines to standardize and guide the diagnosis and treatment of TCM. Based on this， according to the guideline development process of the World Health Organization Handbook for Guideline Development and the Clinical Evidence Grading Criteria on TCM Based on Evidence Body， under the framework of relevant laws， regulations and technical guidance documents， combined with the evidence of relevant domestic and foreign clinical research in recent years for evidence grading and opinion recommendation， and then the Guidelines for TCM Intervention After Conventional Western Medicine Treatment for Stage Ⅰ-Ⅲ Colorectal Cancer were developed by expert consensus. This guideline introduces the etiology， pathogenesis， syndrome differentiation and treatment of TCM intervention for colorectal cancer， which can provide guiding opinions for TCM clinicians and clinicians of integrated traditional Chinese and western medicine engaged in the prevention and treatment of colorectal cancer.

Guidelines for Traditional Chinese Medicine Diagnosis and Treatment of Metastatic Colorectal Cancer / 中国实验方剂学杂志

Colorectal cancer is one of the most common malignant tumors of digestive tract. In 2020， 1.93 million new cases of colorectal cancer were diagnosed globally， ranking third in the global incidence spectrum， and 930 000 new deaths were reported， ranking second in the global cause of death spectrum. Meanwhile， the medical cost of metastatic colorectal cancer is the highest among all stages. A large number of studies have demonstrated that traditional Chinese medicine（TCM） treatment can bring clinical benefits to patients with metastatic colorectal cancer with unique efficacy. In order to further standardize the TCM diagnosis and treatment for metastatic colorectal cancer and improve the level of TCM diagnosis and treatment， Xiyuan Hospital， China Academy of Chinese Medical Sciences， together with other relevant units in China， according to the guideline development process of the World Health Organization Handbook for Guideline Development and the relevant requirements of the Clinical Evidence Grading Criteria on TCM Based on Evidence Body， the Regulations for Group Standards of China Association of Chinese Medicine and others， combined with the characteristics of TCM diagnosis and treatment and the actual situation in China， the Guidelines for TCM Diagnosis and Treatment of Metastatic Colorectal Cancer was developed in accordance with the Catalogue of TCM Diagnosis and Treatment Plans for 105 Diseases in 24 Specialties issued by Department of Medical Administration of National Administration of TCM.

Effects of Xianglian Huazhuo Decoction on Wnt1, GSK-3β and β-catenin in chronic atrophic gastritis rats / 国际中医中药杂志

Objective:To investigate the mechanism of Xianglian Huazhuo Decoction in treating chronic atrophic gastritis (CAG) rats by detecting the protein and gene expressions of Wnt1, GSK-3β, β-catenin in Wnt signaling pathway.Methods:Totally 60 Wistar rats were randomly divided into blank group and model group. The CAG model was established by MNNG free drink combined with sodium salicylate gavage combined with abnormal hunger and satiety. After model establishment, the rats were randomly divided into model group, Xianglian Huazhuo Group and folic acid group. Folic acid group received the folic acid water solution 1.3 mg/kg for gavage; the Xianglian Huazhuo Group received Xianglian Huazhuo Decoction 15.5 g/kg for gavage; the blank group and the model group received the same volume of purified water for gavage. After 8 weeks of intervention, the general state and the atrophic degree of gastric mucosa were observed. The expressions of Wnt1, GSK-3β and β-catenin were detected by immunohistochemical method, and the mRNA expression of β-catenin expression was detected by real-time quantitative polymerase chain reaction PCR.Results:The general condition of rats in Xianglian Huazhuo group was improved, the atrophy of gastric mucosa was improved, and the effect was better than that in folic acid group. Compared with the model group, the positive area ratio of Wnt1 decreased in Xianglian Huazhuo group ( P<0.05), and the positive area ratio of β-catenin decreased in folic acid group and Xianglian Huazhuo group ( P<0.05 or P<0.01), the positive area ratio of GSK-3β increased ( P<0.05), and the β-catenin mRNA level of Xianglian Huazhuo group decreased ( P<0.05). Conciusion 　Xianglian Huazhuo Decoction may increase GSK-3β by downregulating abnormal expression of Wnt1, promoting β-catenin to degrade normally, thereby blocking the abnormal activation of the Wnt signaling pathway, delaying or reversing CAG carcinogenesis to a certain extent, and exerting therapeutic effects.

Study on the mechanism of Tianshui Dichang Decoction in the treatment of ulcerative colitis based on network pharmacology and experimental verification / 国际中医中药杂志

Objective:To explore the potential mechanism of Tianshui Dichang Decoction in the treatment of ulcerative colitis through network pharmacology and experimental verification.Methods:The active components and targets of Tianshui Dichang Decoction were screened by TCMSP. The related targets of ulcerative colitis were screened by OMIM, GeneCard and TTD databases, and the effective component targets of Tianshui Dichang Decoction were intersected with the potential targets of ulcerative colitis. The PPI network was constructed by STRING database to screen the core targets, and the "Chinese materia medica-disease-active components-target" network was constructed by Cytoscape 3.8.0 software. GO function and KEGG pathway enrichment analysis were carried out using Metascape database. 48 mice were divided into control group, model group, mesalazine group (0.3 g/kg) and Tianshui Dichang Decoction low-, medium-, and high-dosage groups (7.5,15 and 30 g/kg) according to random number table method, with 8 mice in each group. Except the control group, the ulcerative colitis model was established in other groups. After 7 days of intervention with corresponding drugs, the disease activity index (DAI) was scored, the pathological changes of colon were observed by HE staining, and the expressions of IL-6, STAT3mRNA and protein in colon tissue were detected by PCR and Western blot methods.Results:Totally 127 active components in Tianshui Dichang Decoction and 560 targets of ulcerative colitis were obtained. 89 intersecting targets of Tianshui Dichang Decoction and ulcerative colitis were obtained, and the core targets included IL6, TNF, IL1B, AKT1, TP53, VEGFA, JUN, PTGS2, CXCL8, CCL2, STAT3, MMP9 and so on. Oxidative stress response, lipopolysaccharide metabolism, bacterial response, signal transduction and other biological processes were mainly involved, mainly through the cancer pathway, IL17, TNF, MAPK and other signal pathways to play a role in the treatment of ulcerative colitis. The results of experimental verification showed that the DAI score, the expressions of IL-6 and STAT3 protein in colon tissue of Tianshui Dichang Decoction medium- and high-dosage groups.decreased ( P<0.05). The levels of IL-6 and STAT3 mRNA in colon tissue decreased in the Tianshui Dichang Decoction low-, medium- and high-dosage groups.groups ( P<0.05). Conclusion:Tianshui Dichang Decoction has a certain therapeutic effect on UC through component-multitarget-signal pathway, and its mechanism is related to regulating IL-6/STAT3 signal pathway and inhibiting intestinal mucosal inflammation.

Arbutin relieves lipopolysaccharide-induced oxidative stress,apoptosis and inflammatory response in H9c2 cardiomyocytes / 免疫学杂志

This study was performed to investigate the effects of Arbutin(Ar)on oxidative stress,apoptosis level and inflammatory response of H9c2 cardiomyocytes induced by lipopolysaccharide(LPS).H9c2 cardiomyocytes were randomly divided into blank control group,lipopolysaccharide group(LPS),LPS+Ar(25 μmol/L)group,LPS+Ar(50 μmol/L)group,LPS+Ar(100 μmol/L)group and Ar(50 μmol/L)group.CCK-8 was used to detect the cell viability of H9c2 cardiomyocytes after LPS treatment and Ar treatment;DCFH-DA fluorescence labeling was used to detect the ROS levels of H9c2 cardiomyocytes;flow cytometry was applied to detect cell apoptosis rate;Western blot was used to detect the expression of apoptosis-related proteins(Caspase-3)and inflammatory proteins(IL-1β and TNF-α).Data showed that compared with the LPS group,the cell viabilities were recovered after Ar treatment.The level of oxidative stress markers(ROS),apoptosis rate,and inflammatory factor levels(IL-1β and TNF-α)in the LPS+Ar groups were significantly reduced compared with the LPS group(P<0.05).In conclusion,Ar can alleviate the damage,apoptosis,oxidative stress and inflammatory response of LPS-induced H9c2 cardiomyocytes.

Target Trial Emulation and Feasibility in Traditional Chinese Medicine Researches / 中医杂志

Target trial emulation， using observational data to emulate a target trial， applies the study design principles of randomized controlled trials to observational studies that aim to estimate the effect of an intervention. The advantage of target trial emulation is that observational data is used to emulate a target trial when it is not appropriate to conduct randomized controlled trials. Target trial emulation can control bias caused by the design of observational studies， and improve the effectiveness of causal inference from observational data. This paper introduced the methodological framework and key points in terms of eligibility criteria， treatment strategies， assignment procedures， grace period， outcomes， follow-up period， effect contrasts， and statistical plan for implementing target trial emulation. This article elucidated the feasibility and necessity of applying target trail emulation in the realm of traditional Chinese medicine researches， and highlighted the challenges encountered in its implementation， such as the need for specialized personnel， data collection and integration， and the control of confounding factors.

Treatment progress of pulmonary hypertension associated with bronchopulmonary dysplasia in preterm infants / 国际儿科学杂志

Pulmonary hypertension(PH)is commonly seen in preterm infants with bronchopulmonary dysplasia(BPD)and is significantly associated with increased mortality.The pathophysiological basis of PH is pulmonary vascular dysplasia or remodeling, and airways hyperresponsiveness.At present, management of BPD-PH should be comprehensive supportive therapy and focus on targeted pharmacotherapies, including various pulmonary vasodilators with different vasoactive mechanisms, such as phosphodiesterase inhibitors, endothelin receptor antagonists and prostaglandins analogs.However, although expert consensus recommends targeted pulmonary arterial hypertension therapy, high-quality clinical studies on the safety and efficacy of these drugs are few.Pulmonary vascular remodeling inhibitors and stem cell therapy have enormous potential to reduce pulmonary hypertension and further research and more data are needed.