Research progress in targeted therapies of chronic lymphocytic leukemia / 上海交通大学学报（医学版）

Chronic lymphocytic leukemia(CLL)is one of small B-cell lymphomas and leukemias,characterized as a clonal disease of mature B cells.The disease is remarkably heterogeneous,with the majority of patients having an indolent course,yet they are currently incurable.Abnormal signaling pathways are indispensable in the pathogenesis of CLL.In CLL,the common abnormalities of signaling pathways include B-cell receptor(BCR)signaling,apoptosis,nuclear factor kappa B(NF-κB)signaling and Notch signaling.According to the target in signaling pathways,a series of targeted drugs,such as Bruton's tyrosine kinase(BTK)inhibitors(ibrutinib,zanubrutinib),phosphorylate phosphoinositide 3-kinase(PI3K)inhibitor(duvelisib)and B-cell leukemia/lymphoma 2(BCL2)inhibitor(venetoclax),which have significantly changed the prognosis of patients in clinic.Other targeted drugs,such as fenebrutinib,nemtabrutinib and umbralisib,as well as chimeric antigen receptor T-cell(CAR-T)therapy developed in the field of immuno-oncology and T cell engineering,are currently under trial,with more personalized treatment modalities being explored,which may become potential drug targets in the future.In this paper,relevant literature of CLL was reviewed,and recent research progress in molecular pathogenesis and targeted therapies of chronic lymphocytic leukemia was reviewed.

Predictors and prognostic analysis of pathological complete response of axillary metastatic lymph nodes after neoadjuvant chemotherapy in breast cancer / 中国现代医生

@#Objective To investigate the clinicopathological factors associated with pathological complete response(pCR)of axillary metastatic lymph nodes in breast cancer patients after neoadjuvant chemotherapy(NAC),and to analyze the postoperative survival.Methods A total of 116 patients with breast cancer with axillary lymph node metastasis were collected from Jiaxing Hospital of TCM,Jiaxing Maternity and Child Health Care Hospital and The First Hospital of Jiaxing.Univariate analysis was used to analyze the relationship between clinicopathological factors and the pCR of axillary lymph node metastasis in breast cancer after NAC.Binary Logistic regression was used to analyze the independent predictors of the pCR of axillary lymph node metastasis in breast cancer after NAC.Kaplan-Meier survival curve was used to analyze the disease-free survival rate and overall survival rate of patients with and non-pCR of axillary metastatic lymph nodes.Results Among 116 patients,52 cases of axillary metastatic lymph nodes achieved pCR after NAC,accounting for 44.83%.Univariate analysis showed that age,vascular invasion,pCR of primary breast tumor,the difference of Ki67 before and after NAC,NAC regimen,and the efficacy of NAC were statistically significant between breast cancer patients with pCR and those non-pCR(P<0.05).Binary Logistic regression analysis showed that age,vascular invasion and pCR of primary breast tumor were independent predictors of pCR of axillary metastatic lymph nodes(P<0.05).The 5-year disease-free survival rate(80.40%vs.54.60%)and overall survival rate(90.4%vs.70.10%)of patients with pCR and non-pCR of axillary metastatic lymph nodes were compared.Conclusion Some breast cancer patients with axillary lymph node metastasis can reach pCR in lymph nodes after NAC.Analyzing the correlation between clinical pathological factors and pCR of axillary metastatic lymph nodes after NAC,it was found that pCR of axillary metastatic lymph nodes after NAC is related to age≤50 years old,no vascular infiltration,and primary breast tumor pCR.At the same time,it was found that patients with axillary metastatic lymph node pCR had a better prognosis than those with non-pCR.

Expression and clinical significance of FAM83H-AS1 in breast cancer based on bioinformatics analysis / 中国现代医生

@#Objective To analyze the expression and clinical treatment and prognosis assessment significance of FAM83H-AS1 in breast cancer by bioinformatics analysis.Methods The expression of FAM83H-AS1 in various cancer types was analyzed in the Cancer Genome Atlas(TCGA)database by R language.Additionally the expression in breast cancer was examined by Gene Expression Profiling Interactive Analysis(GEPIA)online database.Survival data were downloaded from TCGA to analyze the correlation between FAM83H-AS1 expression levels and prognosis among breast cancer patients.GEPIA and Kaplan-Meier Plotter were used for dual verification.Clinical information was obtained from TCGA for further analysis on the relationship between FAM83H-AS1 and clinical characteristics.And the relationship between FAM83H-AS1 and tumor microenvironment,immunodetection point-related genes and tumor mutation burden(TMB)was analyzed using R language.Gene set enrichment analysis(GSEA)was performed.Results The expression of FAM83H-AS1 was abnormal in many cancers,particularly exhibiting a significant increase in breast cancer.High expression of FAM83H-AS1 is associated with significantly reduced overall survival in breast cancer patients.Furthermore,the expression level of FAM83H-AS1 varies among breast cancer patients with different clinical stages.FAM83H-AS1 exhibits negative correlation with stromal cell score and immune cell score in breast cancer samples,and correlated with immune detection point-related gene.TMB radar map results suggest that the expression of FAM83H-AS1 in breast cancer is positively correlated with tumor mutational burden.GSEA revealed a positive correlation between the expression of FAM83H-AS1 and the function of mismatch repair.Conclusion FAM83H-AS1 is highly expressed in breast cancer,and is related to poor prognosis.Its expression correlates with clinicopathological stage,tumor microenvironment and TMB of breast cancer patients.Furthermore,FAM83H-AS1 exhibits associations with certain immune checkpoint-related genes and mismatch repair genes.These findings provide a important theoretical basis for clinical treatment,prognosis prediction and development of gene-target drugs.

Stability study of umbilical cord mesenchymal stem cells formulation in large-scale production / 药学学报

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Correlation between Helicobacter pylori infection and gastrointestinal tumor in the physical examination population in Xi'an City / 公共卫生与预防医学

Objective To analyze the spatial distribution of Helicobacter Pylori (Hp) infection and its correlation with gastrointestinal tumors in the physical examination population of Xi'an city, and to provide reference for the prevention of gastrointestinal tumors in this area. Methods A total of 23 200 subjects who underwent physical examination in 25 public hospitals in Xi'an from January 2019 to January 2023 were selected as the research objects. The basic Information of the patients was derived through the Hospital Information System (HIS), and all subjects underwent 13C-breath test and gastroenterological endoscope. ArcGIS 10.6 software was used to draw a statistical map of Hp infection in Xi 'an for spatial autocorrelation analysis. Hp infection in patients with different gastrointestinal tumors was analyzed. Results In this study population, there were 10 858 cases of Hp infection , with an infection rate of 46.80% ; among them , 5 491 cases were male, with an infection rate of 46.60% , and 5,367 cases were female, with an infection rate of 47.01% , and there was no significant difference in the infection rate between genders (P>0.05). The prevalence of HP infection was higher in the 30-year-old and 20-year-old groups, 55.62% and 42.71%, respectively, and the infection rate showed a first increase and then a decreasing trend with age (χ2trend = 6201.21, 6945.22 , P2=13.49, 16.16, 17.27, 24.66, P<0.05 for all). Conclusion The distribution of Hp infection in the physical examination population of Xi'an city has the characteristics of spatial aggregation and is related to gastrointestinal tumor diseases. It is suggested to carry out Hp infection education for the population in key areas to prevent the occurrence of gastrointestinal tumor diseases.

Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells / 中国结合医学杂志

OBJECTIVE@#To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action.@*METHODS@#This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor- α (TNF- α), interleukin-1 β (IL-1 β), IL-6, IL-12, IL-17 and interferon-γ (IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot, respectively.@*RESULTS@#GSE reduced the secretion of TNF-α, IL-1 β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P<0.01), inhibited the secretion of TNF-α, IL-1 β, IL-6, IL-12, IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (P<0.05 or P<0.01), and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (P<0.01). GSE significantly improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKII, P<0.05 or P<0.01), and inhibited the secretion of inflammatory factors (P<0.01 or P<0.05). In the central nervous system, GSE inhibited the infiltration of CD45+CD11b+ and CD45+CD4+ cells, and weakened the differentiation of Th1 and Th17 (P<0.05). Moreover, it reduced the secretion of inflammatory factors (P<0.01), and prevented the activation of microglia (P<0.05).@*CONCLUSION@#GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.

Evaluation of the analgesic efficacy and safety of ketorolac in patients undergoing percutaneous vertebroplasty / 中国药师

Objective To evaluate the effect and safety of ketorolac on postoperative analgesia in patients undergoing percutaneous vertebroplasty.Methods The clinical data of patients who underwent percutaneous vertebroplasty in Xi'an Labor Union Hospital from January 2020 to May 2023 were retrospectively analyzed,and the patients were divided into ketorolac group and control group according to whether they were given ketorolac after surgery.The visual analogue pain score(VAS)before,6 h,24 h and 48 h after surgery,postoperative fentanyl usage(dosage,time of first compression analgesic pump,number of compressions),Oswestry disability index(ODI)before,3 days,1 month and 6 months after surgery,bone mineral density and bone metabolism indexes before,3 month and 6 month after surgery,the incidence of adverse reactions within 72 hours after surgery and satisfaction with pain intervention were compared between the two groups.Results A total of 90 patients were included in the study,including 48 patients in the ketorolac group and 42 patients in the control group.At 6 h,24 h and 48 h after surgery,the VAS score of the ketorolac group was significantly lower than that of the control group(P<0.05).The amount of fentanyl and the number of compressions in the ketorolac group were significantly lower than those in the control group,and the time of the first compression analgesic pump was significantly longer than that in the control group(P<0.05).There was no significant difference in bone mineral density,serum bone-specific alkaline phosphatase(BALP)and type I collagen C-terminal peptide(CTX-I)levels between the two groups before surgery(P>0.05).At 3 months and 6 months after surgery,the bone mineral density,serum BALP and CTX-I levels of the two groups were significantly improved compared with those before surgery(P<0.05).At 3 days,1 month and 6 months after surgery(P<0.05),the ODI of patients in both groups was significantly improved compared with that before surgery.There was no significant difference in the incidence of adverse reactions at 72 hours after surgery between patients in the ketorolac group and the control group(P>0.05).In addition,the satisfaction with pain relief in the ketorolac group was significantly higher than that in the control group(P<0.05).Conclusion Ketorlac can effectively improve the postoperative pain of patients with PVP without affecting the postoperative recovery of patients,with a low incidence of adverse reactions and a high safety profile,which can effectively improve patients'satisfaction with pain relief.

Meta analysis of the application of ERAS concept in orthopedic surgery / 中国医师杂志

Objective:To evaluate the value and effectiveness of the enhanced recovery after surgery (ERAS) theory in orthopedic surgery, and to provide a theoretical basis for optimizing rehabilitation plans during the perioperative period of orthopedic surgery.Methods:Relevant literature on the application of accelerated rehabilitation in orthopedic perioperative period officially published in Pubmed and the Chinese Medical Journal Database From January 2000 to October 2022 was searched and included in randomized controlled and clinical case studies. The patients were divided into the experimental group (ERAS group) and the control group (conventional treatment group). The patients in the experimental group were treated with ERAS mode after surgery, while the patients in the control group were treated with conventional rehabilitation mode after surgery. The hospital stay, postoperative complications, postoperative nausea and vomiting, and postoperative incidence rate of deep vein thrombosis in the two groups were statistically analyzed.Results:Finally, a total of 1 301 patients were included in 9 articles, divided into an experimental group (ERAS group, n=643) and a control group (conventional treatment group, n=652). There was a statistically significant difference in hospital stay between the experimental group and the control group ( MD=-4.11, 95% CI: -6.73 to -1.49, P=0.002); The overall effect tendency of the incidence of complications between the experimental group and the control group was statistically significant ( P=0.005); Compared with the control group, the incidence rate of postoperative nausea and vomiting in the experimental group was lower ( P=0.04); The incidence rate of postoperative deep vein thrombosis in the experimental group was lower than that in the control group ( P=0.02). Conclusions:The application of accelerated rehabilitation concept in orthopedic surgery patients can reduce the length of hospital stay, and reduce the incidence rate of postoperative complications, nausea and vomiting, and deep vein thrombosis.

Meta-analysis and trial sequential analysis of Chaihuang Granules in treatment of upper respiratory tract infection in children / 中国中药杂志

This study aimed to evaluate the efficacy and safety of Chaihuang Granules in the treatment of upper respiratory tract infection in children. The databases such as CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, Web of Science, Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched for randomized controlled trial(RCT) of Chaihuang Granules for the treatment of upper respiratory tract infection in children, and supplemented by manual searching of gray literature. Two investigators independently screened the literature, extracted data, and assessed the methodological quality. Meta-analysis was performed using RevMan 5.4 software, trial sequential analysis was conducted using TSA 0.9.5.10 Beta software, and evidence quality evaluation was carried out using GRADE profiler 3.6.1 software. Eighteen RCTs involving 2 459 patients(1 262 in the treatment group and 1 197 in the control group) were included. Meta-analysis showed that compared with conventional therapy alone, Chaihuang Granules significantly improved the total effective rate(RR=1.18, 95%CI[1.15, 1.22], P<0.000 01), reduced the disappearance time of symptoms/signs(MD=-1.39, 95%CI[-1.66,-1.12], P<0.000 01), improved cytokine levels(MD=-2.40, 95%CI[-3.80,-1.00], P=0.000 8), improved humoral immune levels(MD=0.75, 95%CI[0.60, 0.90], P<0.000 01), and reduced the recurrence rate(MD=-2.11, 95%CI[-2.98,-1.25], P<0.000 01). However, the incidence of adverse reactions was not increased(RR=0.94, 95%CI[0.59, 1.49], P=0.78). Subgroup analysis showed that:(1) both Chaihuang Granules used alone(RR=1.19, 95%CI[1.11, 1.27], P<0.000 01) and in combination with other therapies(RR=1.18, 95%CI[1.14, 1.22], P<0.000 01) effectively improved the total effective rate.(2) In terms of symptoms/signs disappearance time, Chaihuang Granules effectively reduced the duration of fever(MD=-1.18, 95%CI[-1.78,-0.58], P=0.000 1), cough with sputum(MD=-1.82, 95%CI[-2.38,-1.25], P<0.000 01), cough(MD=-1.31, 95%CI[-1.89,-0.74], P<0.000 01), sore throat(MD=-1.57, 95%CI[-2.25,-0.89], P<0.000 01), and lung rales(MD=-1.49, 95%CI[-2.06,-0.92], P<0.000 01).(3) Regarding cytokine levels, Chaihuang Gra-nules effectively improved the levels of interleukin(IL)-2(MD=-0.94, 95%CI[-1.16,-0.72], P<0.000 01), IL-6(MD=-4.71, 95%CI[-6.39,-3.03], P<0.000 01), and tumor necrosis factor-α(TNF-α)(MD=-2.07, 95%CI[-2.43,-1.71], P<0.000 01).(4) In terms of cellular immune levels, Chaihuang Granules effectively improved the levels of CD3~+(MD=4.11, 95%CI[1.53, 6.69], P=0.002), CD4~+(MD=4.21, 95%CI[1.69, 6.73], P=0.001), CD8~+(MD=-2.65, 95%CI[-3.93,-1.37], P<0.000 1), and CD4~+/CD8~+(MD=0.25, 95%CI[0.14, 0.37], P<0.000 1).(5) In terms of humoral immune levels, Chaihuang Granules effectively improved the levels of IgA(MD=0.44, 95%CI[0.23, 0.64], P<0.000 1), IgM(MD=0.31, 95%CI[0.15, 0.46], P=0.000 1), and IgG(MD=2.02, 95%CI[1.60, 2.43], P<0.000 01). Trial sequential analysis showed that the cumulative Z-curve of the total effective rate crossed the boundary value, further confirming its clinical efficacy. The GRADE evidence quality evaluation showed that the evidence quality of the above outcome indicators was low or very low, and the recommendation strength was weak. Compared to conventional therapy alone, Chaihuang Granules can effectively improve the total effective rate of treatment, alle-viate symptoms and signs of upper respiratory tract infection in children, improve inflammatory conditions, enhance immune function, and reduce the recurrence rate. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.

The best practice for microbiome analysis using R

With the gradual maturity of sequencing technology, many microbiome studies have published, driving the emergence and advance of related analysis tools. R language is the widely used platform for microbiome data analysis for powerful functions. However, tens of thousands of R packages and numerous similar analysis tools have brought major challenges for many researchers to explore microbiome data. How to choose suitable, efficient, convenient, and easy-to-learn tools from the numerous R packages has become a problem for many microbiome researchers. We have organized 324 common R packages for microbiome analysis and classified them according to application categories (diversity, difference, biomarker, correlation and network, functional prediction, and others), which could help researchers quickly find relevant R packages for microbiome analysis. Furthermore, we systematically sorted the integrated R packages (phyloseq, microbiome, MicrobiomeAnalystR, Animalcules, microeco, and amplicon) for microbiome analysis, and summarized the advantages and limitations, which will help researchers choose the appropriate tools. Finally, we thoroughly reviewed the R packages for microbiome analysis, summarized most of the common analysis content in the microbiome, and formed the most suitable pipeline for microbiome analysis. This paper is accompanied by hundreds of examples with 10,000 lines codes in GitHub, which can help beginners to learn, also help analysts compare and test different tools. This paper systematically sorts the application of R in microbiome, providing an important theoretical basis and practical reference for the development of better microbiome tools in the future. All the code is available at GitHub github.com/taowenmicro/EasyMicrobiomeR.

Distribution of memory B cell subsets in peripheral blood of children with frequently relapsing nephrotic syndrome / 中国当代儿科杂志

OBJECTIVES@#To investigate the change in the distribution of memory B cell subsets in children with frequently relapsing nephrotic syndrome (FRNS) during the course of the disease.@*METHODS@#A total of 35 children with primary nephrotic syndrome (PNS) who attended the Department of Pediatrics of the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2021 were enrolled as subjects in this prospective study. According to the response to glucocorticoid (GC) therapy and frequency of recurrence, the children were divided into two groups: FRNS (n=20) and non-FRNS (NFRNS; n=15). Fifteen children who underwent physical examination were enrolled as the control group. The change in memory B cells after GC therapy was compared between groups, and its correlation with clinical indicators was analyzed.@*RESULTS@#Before treatment, the FRNS and NFRNS groups had significantly increased percentages of total B cells, total memory B cells, IgD+ memory B cells, and IgE+ memory B cells compared with the control group, and the FRNS group had significantly greater increases than the NFRNS group (P<0.05); the FRNS group had a significantly lower percentage of class-switched memory B cells than the NFRNS and control groups (P<0.05). After treatment, the FRNS and NFRNS groups had significant reductions in the percentages of total B cells, total memory B cells, IgM+IgD+ memory B cells, IgM+ memory B cells, IgE+ memory B cells, IgD+ memory B cells, and IgG+ memory B cells (P<0.05) and a significant increase in the percentage of class-switched memory B cells (P<0.05). The FRNS group had a significantly higher urinary protein quantification than the NFRNS and control groups (P<0.05) and a significantly lower level of albumin than the control group (P<0.05). In the FRNS group, urinary protein quantification was negatively correlated with the percentage of class-switched memory B cells and was positively correlated with the percentage of IgE+ memory B cells (P<0.05).@*CONCLUSIONS@#Abnormal distribution of memory B cell subsets may be observed in children with FRNS, and the percentages of IgE+ memory B cells and class-switched memory B cells can be used as positive and negative correlation factors for predicting recurrence after GC therapy in these children.

Effect of MiR-424-5p on the Drug Resistance of Diffuse Large B-Cell Lymphoma Cells by Regulating PD-1/PD-L1 Signaling Pathway / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of microRNA-424-5p (miR-424-5p) on the drug resistance of diffuse large B-cell lymphoma (DLBCL) cells by regulating the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling pathway.@*METHODS@#Human DLBCL cell line CRL2631 cells were induced to construct CRL2631-CHOP resistant cell line. RT-qPCR and Western blot were used to detect the expression levels of MiR-424-5p, PD-L1 mRNA and protein, and multidrug resistance gene-1 (MDR-1) protein in CRL2631 cells and CRL2631-CHOP cells, respectively. The target genes of MiR-424-5p was verified by dual luciferase reporter assay. The miRNA simulation/interference technology and thiazole blue (MTT) method were used to detect the resistance of CRL2631 cells and CRL2631-CHOP cells to CHOP.@*RESULTS@#Compared with CRL2631 cells, the drug resistance of CRL2631-CHOP cells to CHOP and the levels of MDR-1 protein (P<0.05), PD-L1 mRNA and protein in the cells were significantly increased (both P<0.001), while the relative level of MiR-424-5p was significantly reduced (P<0.001). The result of the dual luciferase reporter assay showed that PD-L1 was the direct downstream target gene of MiR-424-5p (P<0.001). After transfection of MiR-424-5p inhibitor, the resistance of CRL2631 cells to CHOP drugs increased, and the expression level of MDR-1 protein (P<0.01), PD-L1 mRNA and protein also increased significantly (both P<0.01). After transfection of MiR-424-5p mimics, the resistance of CRL2631-CHOP cells to CHOP drugs decreased, and the expression level of MDR-1 protein (P<0.001), PD-L1 mRNA and protein also decreased significantly (both P<0.001). Overexpression of PD-L1 could reverse the inhibitory effect of upregulating MiR-424-5p on PD-L1 (P<0.001).@*CONCLUSION@#Down-regulation of MiR-424-5p enhances the drug resistance of DLBCL cells by regulating the PD-1/PD-L1 signaling pathway.

Recognition of abnormal changes in echocardiographic videos by an artificial intelligence assisted diagnosis model based on 3D CNN / 中华心血管病杂志

Objective: To investigate the diagnostic efficiency and clinical application value of an artificial intelligence-assisted diagnosis model based on a three-dimensional convolutional neural network (3D CNN) on echocardiographic videos of patients with hypertensive heart disease, chronic renal failure (CRF) and hypothyroidism with cardiac involvement. Methods: This study is a retrospective study. The patients with hypertensive heart disease, CRF and hypothyroidism with cardiac involvement, who admitted in Henan Provincial People's Hospital from April 2019 to October 2021, were enrolled. Patients were divided into hypertension group, CRF group, and hypothyroidism group. Additionally, a simple random sampling method was used to select control healthy individuals, who underwent physical examination at the same period. The echocardiographic video data of enrolled participants were analyzed. The video data in each group was divided into a training set and an independent testing set in a ratio of 5 to 1. The temporal and spatial characteristics of videos were extracted using an inflated 3D convolutional network (I3D). The artificial intelligence assisted diagnosis model was trained and tested. There was no case overlapped between the training and validation sets. A model was established according to cases or videos based on video data from 3 different views (single apical four chamber (A4C) view, single parasternal left ventricular long-axis (PLAX) view and all views). The statistical analysis of diagnostic performance was completed to calculate sensitivity, specificity and area under the ROC curve (AUC). The time required for the artificial intelligence and ultrasound physicians to process cases was compared. Results: A total of 730 subjects aged (41.9±12.7) years were enrolled, including 362 males (49.6%), and 17 703 videos were collected. There were 212 cases in the hypertensive group, 210 cases in the CRF group, 105 cases in the hypothyroidism group, and 203 cases in the normal control group. The diagnostic performance of the model predicted by cases based on single PLAX view and all views data was excellent: (1) in the hypertensive group, the sensitivity, specificity and AUC of models based on all views data were 97%, 89% and 0.93, respectively, while those of models based on a single PLAX view were 94%, 95%, and 0.94, respectively; (2) in the CRF group, the sensitivity, specificity and AUC of models based on all views data were 97%, 95% and 0.96, respectively, while those of models based on a single PLAX view were 97%, 89%, and 0.93, respectively; (3) in the hypothyroidism group, the sensitivity, specificity and AUC of models based on all views data were 64%, 100% and 0.82, respectively, while those of models based on a single PLAX view were 82%, 89%, and 0.86, respectively. The time required for the 3D CNN model to measure and analyze the echocardiographic videos of each subject was significantly shorter than that for the ultrasound physicians ((23.96±6.65)s vs. (958.25±266.17)s, P<0.001). Conclusions: The artificial intelligence assisted diagnosis model based on 3D CNN can extract the dynamic temporal and spatial characteristics of echocardiographic videos jointly, and quickly and efficiently identify hypertensive heart disease and cardiac changes caused by CRF and hypothyroidism.

Treatment of spinal burst fractures with pedicle screw fixation at high altitude area / 中国骨伤

OBJECTIVE@#According to the characteristics of spinal burst fractures in high-altitude areas and the local medical conditions, to explore the clinical efficacy of short-segment fixation with pedicle screws combined with screw placement in injured vertebrae in the treatment of thoracolumbar burst fractures.@*METHODS@#From August 2018 to December 2021, 12 patients with single-vertebral thoracolumbar burst fractures without neurological symptoms were treated with injured vertebral screw placement technique, including 7 males and 5 females;aged 29 to 54 years old, with an average of(42.50±7.95) years old;6 cases of traffic accident injury, 4 cases of high fall injury, 2 cases of heavy object injury;2 cases of T11, 4 cases of T12, 3 cases of L1, 2 cases of L2, and 1 case of L3. In the operation, screws were first placed in the upper and lower vertebrae of the fracture, pedicle screws were placed in the injured vertebra, and connecting rods were installed, and the fractured vertebral body was reset by positioning and distraction. Visual analogue scale (VAS) and Japanese Orthopedic Association (JOA) scoring were used to evaluate the changes in pain and quality of life of patients, and the kyphotic correction rate and correction loss rate of the injured segment were measured by X-ray.@*RESULTS@#All operations were successful without significant intraoperative complications. All 12 patients were followed up, the duration ranged from 9 to 27 months, with an mean of (17.75±5.79) months. VAS at 3 days after operation was significantly higher than that at admission (t=6.701, P=0.000). There was significant difference in JOA score between 9 months after operation and at admission (t=5.085, P=0.000). Three days after operation, Cobb angle was (4.42±1.16)°, and the correction rate was (82±5)% compared with (25.67±5.71)° at admission. Cobb angle was (5.08±1.24) °at 9 months after operation, with a corrected loss rate of (16±13)%. No loosening or breakage of internal fixation was found.@*CONCLUSION@#Under the high-altitude hypobaric and hypoxic environment, the effect of the operation should be ensured while reducing the trauma. The application of the technique of placing screws on the injured vertebra can effectively restore and maintain the height of the injured vertebra, with less bleeding and shorter fixed segments, which is an effective method.

Clinical effect of Kirschner wire intramedullary fixation in the treatment of pediatric both-bone forearm fractures at high altitude area / 中国骨伤

OBJECTIVE@#To explore the clinical effect of Kirschner wire intramedullary fixation in the treatment of both-bone forearm fractures in children of high altitude area.@*METHODS@#From August 2020 to December 2021, 19 children were treated with Kirschner wire intramedullary fixation including 11 males and 8 females, aged from 4 to 13 years old with an average of (8.16±2.71) years old. The course of disease was 1 to 10 days, with a mean of (4.11±2.51) d. First, close reduction was performed. If the reduction was unsuccessful, limited open reduction was performed, followed by Kirschner wire intramedullary fixation of the radius and ulna. The fracture healing was evaluated by X-ray after operation, and the curative effect was evaluated by Anderson forearm function score standard.@*RESULTS@#The wound healed well after operation, 2 cases had clinical manifestations of needle tail irritation after operation, and the symptoms disappeared after removing the internal fixation. The average follow-up time was(7.68±3.50) months (3 to 14 months). X-ray showed that all fracture healing in follow-up, Anderson forearm function score showed excellent in 16 cases, good in 2 cases and fair in 1 case at the final follow-up.@*CONCLUSION@#Children with fractures in plateau areas often have delayed medical treatment, lack of medical conditions and insufficient compliance. Based on these characteristics, Kirschner wire intramedullary fixation for the treatment of children's double forearm fractures has the advantages of small injury and rapid recovery. It is a kind of operation method that can be popularized.

Comparison of chemical compositions of different parts of Xanthoceras sorbifolium seeds based on UHPLC-Q-Orbitrap HRMS / 中国中药杂志

Xanthoceras sorbifolium seeds have a wide range of applications in the food and pharmaceutical industries. To compare and analyze the chemical compositions of different parts of X. sorbifolium seeds and explore the potential value and research prospects of non-medicinal parts, this study used ultra-high-performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) to detect the chemical composition of various parts of the seeds. A total of 82 components were preliminary identified from X. sorbifolium seeds, including 5 amino acids, 4 polyphenols, 3 phenylpropionic acids, 7 organic acids, 15 flavonoids, 6 glycosides, and 23 saponins. Mass spectrometry molecular networking(MN) analysis was conducted on the results from different parts of the seeds, revealing significant differences in the components of the seed kernel, seed coat, and seed shell. The saponins and flavonoids in the seed kernel were superior in terms of variety and content to those in the seed coat and shell. Based on the chromatographic peaks of different parts from multiple batches of samples, multivariate statistical analysis was carried out. Four differential components were determined using HPLC, and the average content of these components in the seed kernel, seed coat, and seed shell were as follows: 0.183 6, 0.887 4, and 1.440 1 mg·g~(-1) for fraxin; 0.035 8, 0.124 1, and 0.044 5 mg·g~(-1) for catechin; 0.032 9, 0.072 0, and 0.221 5 mg·g~(-1) for fraxetin; 0.435 9, 2.114 7, and 0.259 7 mg·g~(-1) for epicatechin. The results showed that catechin and fraxetin had relatively low content in all parts, while fraxin had higher content in the seed coat and seed shell, and epicatechin had higher content in the seed kernel and seed coat. Therefore, the seed coat and seed shell possess certain development value. This study provides rapid analysis and comparison of the chemical compositions of different parts of X. sorbifolium seeds, which offers an experimental basis for the research and clinical application of medicinal substances in X. sorbifolium seeds.

Meta-analysis and trial sequential analysis of Compound Qinlan Oral Liquid in treatment of acute upper respiratory tract infection / 中国中药杂志

This study aims to evaluate the efficacy and safety of Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. Computer-based online searching of CNKI, VIP, SinoMed, Wanfang, ChiCTR, ClinicalTrials.gov, Cochrane Library, PubMed, EMbase, and Web of Science was performed to retrieve the randomized controlled trial(RCT) regarding Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. In addition, manual searching of gray literature was conducted. After two evaluators independently selected articles, extracted data, and evaluated the quality of methodology included in the studies, Meta-analysis was carried out in RevMan 5.4 and trial sequential analysis(TSA) in TSA 0.9.5.10 Beta. GRADE profiler 3.6.1 was employed to evaluate the evidence quality. A total of 21 RCTs were included in this study, involving 2 651 patients(1 330 patients in the observation group and 1 321 patients in the control group). Meta-analysis showed that compared with conventional western medicine alone, Compound Qinlan Oral liquid improved the total response rate(RR=1.15, 95%CI[1.12, 1.19], P<0.000 01) without increasing the incidence of adverse reactions(RR=0.77, 95%CI[0.47, 1.25], P=0.16). The results of subgroup analysis are described as follows:(1) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid improved the total response rate(RR=1.10, 95%CI[1.05, 1.14], P<0.000 01) and shortened the time to symptom relief(SMD=-0.76, 95%CI[-1.02,-0.51], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=1.16, 95%CI[0.54, 2.47], P=0.71).(2) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid + conventional western medicine improved the total response rate(RR=1.20, 95%CI[1.15, 1.25], P<0.000 01), decreased traditional Chinese medicine(TCM) syndrome scores(MD=-0.58, 95%CI[-0.75,-0.41], P<0.000 01), shortened the time to symptom relief(SMD=-2.44, 95%CI[-3.09,-1.80], P<0.000 01) and physical sign improvement(MD=-2.57, 95%CI[-4.11,-1.04], P=0.001), lowered the serum levels of inflammatory cytokines(SMD=-2.16, 95%CI[-2.61,-1.70], P<0.000 01), improved respiratory function indicators(SMD=1.48, 95%CI[1.00, 1.96], P<0.000 01), and enhanced the humoral immunity(MD=0.94, 95%CI[0.69, 1.18], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=0.57, 95%CI[0.29, 1.09], P=0.09). TSA showed that the cumulative Z curve of total response rate crossed the traditional threshold and TSA threshold, further confirming the clinical efficacy of Compound Qinlan Oral Liquid. The GRADE graded the evidence of the above outcome indicators as low or extremely low, and yielded weak recommendation. Compared with conventional western medicine alone, Compound Qinlan Oral Liquid can improve the total effective rate and reduce the time to symptom relief. The combination of Compound Qinlan Oral Liquid and conventional western medicine can improve the total response rate, mitigate the symptoms and improve the physical signs, reduce inflammation, and improve respiratory function and immunity of the patients with acute upper respiratory tract infection. In view of the limited number and quality of the included studies, the above conclusions still require high-quality RCT to provide evidence support.

A nonlinear relationship between the hemoglobin level and prognosis of elderly patients with sepsis: an analysis based on MIMIC-IV / 中华危重病急救医学

OBJECTIVE@#To investigate the correlation of hemoglobin (Hb) level with prognosis of elderly patients diagnosed as sepsis.@*METHODS@#A retrospective cohort study was conducted. Information on the cases of elderly patients with sepsis in the Medical Information Mart for Intensive Care-IV (MIMIC-IV), including basic information, blood pressure, routine blood test results [the Hb level of a patient was defined as his/her maximum Hb level from 6 hours before admission to intensive care unit (ICU) and 24 hours after admission to ICU], blood biochemical indexes, coagulation function, vital signs, severity score and outcome indicators were extracted. The curves of Hb level vs. 28-day mortality risk were developed by using the restricted cubic spline model based on the Cox regression analysis. The patients were divided into four groups (Hb < 100 g/L, 100 g/L ≤ Hb < 130 g/L, 130 g/L ≤ Hb < 150 g/L, Hb ≥ 150 g/L groups) based on these curves. The outcome indicators of patients in each group were analyzed, and the 28-day Kaplan-Meier survival curve was drawn. Logistic regression model and Cox regression model were used to analyze the relationship between Hb level and 28-day mortality risk in different groups.@*RESULTS@#A total of 7 473 elderly patients with sepsis were included. There was a "U" curve relationship between Hb levels within 24 hours after ICU admission and the risk of 28-day mortality in patients with sepsis. The patients with 100 g/L ≤ Hb < 130 g/L had a lower risk of 28-day mortality. When Hb level was less than 100 g/L, the risk of death decreased gradually with the increase of Hb level. When Hb level was ≥ 130 g/L, the risk of death gradually increased with the increase of Hb level. Multivariate Logistic regression analysis revealed that the mortality risks of patients with Hb < 100 g/L [odds ratio (OR) = 1.44, 95% confidence interval (95%CI) was 1.23-1.70, P < 0.001] and Hb ≥ 150 g/L (OR = 1.77, 95%CI was 1.26-2.49, P = 0.001) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (OR = 1.21, 95%CI was 0.99-1.48, P = 0.057). The multivariate Cox regression analysis suggested that the mortality risks of patients with Hb < 100 g/L [hazard ratio (HR) = 1.27, 95%CI was 1.12-1.44, P < 0.001] and Hb ≥ 150 g/L (HR = 1.49, 95%CI was 1.16-1.93, P = 0.002) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (HR = 1.17, 95%CI was 0.99-1.37, P = 0.053). Kaplan-Meier survival curve showed that the 28-day survival rate of elderly septic patients in 100 g/L ≤ Hb < 130 g/L group was significantly higher than that in Hb < 100 g/L, 130 g/L ≤ Hb < 150 g/L and Hb ≥ 150 g/L groups (85.26% vs. 77.33%, 79.81%, 74.33%; Log-Rank test: χ2 = 71.850, P < 0.001).@*CONCLUSIONS@#Elderly patients with sepsis exhibited low mortality risk if their 100 g/L ≤ Hb < 130 g/L within 24 hours after admission to ICU, and both higher and lower Hb levels led to increased mortality risks.

Analysis of flavonoids and phenylethanoid glycosides in the Tibetan herb Lagotis brevituba Maxim based on UHPLC-LTQ-orbitrap-MS / 药学学报

Ultra high performance liquid chromatography tandem linear ion trap orbitrap mass spectrometry (UHPLC-LTQ-orbitrap-MS) was applied to analyze and identify flavonoids and phenylethanoid glycosides in the Tibetan herb Lagotis brevituba Maxim. A method of data-dependent scan coupling with dynamic exclusion was developed for analyzing flavonoids and phenylethanoid glycosides under positive and negative ion mode of electrospray ionization (ESI). The compounds of Lagotis brevituba Maxim. were systematically identified through exact molecular mass, fragmentation patterns, retention time and reported references. A total of 167 compounds were detected, of which 84 were flavonoids and 83 were phenylethanoid glycosides, which greatly enriched the number and types of flavonoids and phenylethanol glycosides in Lagotis genus medicinal plants. Baohuoside Ⅰ, 4 disaccharide O-glycoside flavonoids (composed of deoxyhexose and glucuronic acid), 9 C-glycoside flavonoids, 15 tetrasaccharide phenylethanoid glycosides and 5 phenylethanoid glycosides with substituents on the β-position of the phenylethyl group were identified in Lagotis genus medicinal plants for the first time. This study provides scientific support for elucidating the material basis and improving the quality control of Lagotis brevituba Maxim.

"4+4" Clinical Medicine Program: comparison and thinking on the model of America and Shanghai Jiao Tong University School of Medicine / 中华医学教育探索杂志

Learning from the clinical medicine program of North American medical schools, Shanghai Jiao Tong University School of Medicine (SJTUSM) has taken the lead in carrying out the "4+4" program of clinical medicine specialty in China since 2002, recruiting outstanding non-medical graduates to study for four years of medical courses. After 20 years of practice, SJTUSM has accumulated a series of effective school-running experience with Chinese characteristics, but there are also problems and puzzles. Based on the analysis and comparison of the "4+4" Clinical Medicine Program of SJTUSM with leading medical schools in the United States, such as Harvard Medical College and Stanford University Medical College, this paper discusses the training objectives, enrollment methods and scale, curriculum setting, degree-granting standards, etc. SJTUSM needs to strengthen the educational reform, improve the enrollment methods and curriculum system, strengthen the characteristics of compound talents training, and rationally balance the training of clinical and scientific research ability, so as to help promote the "4+4" clinical medical talents training mode to excellent.