[摘 要] 目的：系统评价CD19 CAR-T细胞免疫疗法对比标准治疗在复发/难治性弥漫性大B细胞淋巴瘤（R/R DLBCL）患者中疗效与安全性，通过探索性分析探索不同CAR-T细胞产品对疗效的潜在影响，为临床治疗决策提供循证参考。方法：计算机检索中国知网、万方数据库、维普期刊数据库、中国生物医学文献数据库、PubMed、Embase和Cochrane Library数据库，搜集CD19 CAR-T细胞疗法对比标准治疗用于R/R DLBCL的随机对照试验（RCT），检索时限均为建库至2025年10月25日。由2位研究者独立进行文献筛选、数据提取和质量评价，采用R4.2.2软件进行Meta分析。结果：共纳入2项Ⅲ期RCT研究（ZUMA-7、TRANSFORM），各结局指标均根据异质性检验结果选择固定效应模型合并数据。疗效方面，CD19 CAR-T细胞疗法可显著改善患者无事件生存期（HR=0.455，95%CI：0.363~0.570，P < 0.001）和降低死亡风险（HR = 0.738，95%CI：0.575~0.947，P = 0.017）；同时可显著提高完全缓解率（RR = 1.879，95%CI：1.574~2.242，P < 0.001）。按产品类型的探索性分析显示，liso-cel和axi-cel均优于标准治疗（liso-cel：HR = 0.380，95%CI：0.260~0.540，P < 0.001；axi-cel：HR = 0.510，95%CI：0.380~0.680，P < 0.001），但该分析为不同试验间的对比，证据等级有限。安全性结局显示：CAR-T细胞疗法的免疫效应细胞相关神经毒性综合征（ICANS）发生率显著升高（RR = 22.387，95%CI：4.353~115.132，P < 0.001）；≥3级细胞因子释放综合征（CRS）发生率数值升高（RR = 8.181，95%CI：0.935~71.574，P = 0.058），差异无统计学意义。纳入研究的偏倚风险整体为低；敏感性分析证实结果稳健。结论：基于2项RCT的Meta分析结果，CD19 CAR-T细胞（liso-cel/axi-cel）可作为R/R DLBCL二线治疗的选择之一，其疗效优于标准治疗，且特征性不良反应（CRS/ICANS）经规范管理后可控，可根据患者基线状态个体化选择CAR-T细胞产品。本研究证据基础薄弱，上述结论尚需更多高质量、大样本RCT验证。

[摘 要] 目的：探讨细胞色素c氧化酶组装因子6（COA6）在胃癌中的表达特征、临床意义及其对胃癌细胞恶性生物学行为的调控作用与分子机制。方法：通过TIMER 2.0、人类蛋白质图谱（HPA）和UALCAN等公共数据库分析COA6在多种肿瘤组织中的mRNA表达水平及部分蛋白表达信息，并分析其与临床病理特征的关联。构建靶向COA6的敲低和过表达慢病毒载体，分别转染SGC-7901和MGC-803细胞，构建COA6稳定修饰细胞模型。敲低体系设置shCOA6‑1、shCOA6‑2、shCOA6‑3实验组及阴性对照shCOA6-NC组；过表达体系设置COA6过表达（OE）组与空载病毒（Vector）对照组，采用WB法验证各组COA6的敲低与过表达效率。随后，分别采用细胞计数实验检测细胞增殖活性，Transwell实验评价细胞侵袭能力，划痕愈合实验观测细胞迁移能力，Annexin V-FITC/PI双染色流式检测细胞凋亡水平，同时利用WB法检测AMPK/mTOR通路核心蛋白的磷酸化水平。结果：COA6在多种肿瘤中呈异常表达，且其表达水平与胃癌临床分期、病理分级、淋巴结转移及TP53突变状态有关联。功能实验表明，敲低COA6可显著抑制胃癌细胞增殖、侵袭和迁移，并促进凋亡（均P < 0.000 1）；而过表达COA6则产生相反效应。机制研究发现，COA6敲低导致p-AMPK表达上调、p-mTOR表达下调，AMPK抑制剂Compound C处理可逆转COA6敲低诱导的p-AMPK升高和p-mTOR降低，提示COA6可能与AMPK活化受抑和mTOR磷酸化增强有关。结论：COA6在胃癌中高表达且与部分临床病理特征有关联，其可能通过调控AMPK/mTOR信号通路促进胃癌细胞增殖、侵袭和迁移，并抑制凋亡。

OBJECTIVE To investigate the mechanism of Shenling baizhu san （SLBZS） in ameliorating ulcerative colitis （UC）. METHODS Mice were randomly divided into normal group， model group， and low-， medium-， high-dose SLBZS groups （3， 6， 12 g/kg）， with 10 mice in each group. Except for the normal group， mice in other groups were given free access to 3% dextran sulfate sodium solution for 7 days to establish UC models. Simultaneously， mice in each group were intragastrically administered corresponding medicinal liquid or double-distilled water once a day for consecutive 7 days. After the last administration， the histopathological morphology of colon tissues was observed； the serum levels of inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and IL-18 were detected； the total bile acid contents in liver， gallbladder and colon tissues were determined； the expression level of NOD-like receptor family pyrin domain-containing protein 3 （NLRP3） in colon tissues was tested. The expression levels of flora metabolism-related proteins [G protein-coupled receptor 41（GPR41），GPR43，farnesoid X receptor （FXR）， G protein-coupled bile acid receptor 1 （TGR5）， flavin-containing monooxygenase 3 （FMO3）， cytochrome P450 family 27 subfamily A member 1 （CYP27A1）， CYP7A1] in liver or colon tissues， as well as the proteins related to Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB）/NLRP3 inflammatory axis [TLR4， NF-κB， phosphorylated NF-κB （p-NF-κB）， myeloid differentiation factor 88 （MyD88）， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， caspase-1] in colon tissues were measured. RESULTS Compared with the model group， the colon tissue injury and inflammatory cell infiltration were alleviated in medium- and high-dose SLBZS groups. The serum levels of TNF-α， IL-1β and IL-18， total bile acid contents in liver and colon tissues， as well as the protein expression levels of FMO3 and CYP7A1 in liver tissues， TLR4， p-NF-κB， NF-κB， MyD88， NLRP3， ASC and caspase-1 in colon tissues were significantly decreased （P＜0.05）. Meanwhile， the total bile acid content in gallbladder， the protein expression levels of GPR41 and GPR43 in colon tissues， along with CYP27A1， FXR and TGR5 in liver tissues were significantly increased （P＜0.05）. CONCLUSIONS SLBZS may relieve colonic inflammatory injury and ameliorate UC by regulating the expression of flora metabolism-related proteins and inhibiting the abnormal activation of TLR4/NF-κB/NLRP3 inflammatory axis.

[摘 要] 目的：探讨细胞色素c氧化酶铜伴侣蛋白17（COX17）是否参与去甲泽拉木醛（DML）抑制胃癌细胞增殖和侵袭的作用。方法： 采用5、10和20 μmol/L DML处理MGC-803细胞，通过显微镜计数和Transwell实验评价DML对细胞增殖和侵袭的影响；采用非标记定量蛋白质组学比较DML处理组与DMSO组的蛋白表达谱，结合差异表达分析和GO功能富集筛选候选蛋白，并采用Western blotting验证DML处理后COX17蛋白表达变化。分别构建COX17敲低和过表达稳定细胞株，通过细胞计数和Transwell实验评价COX17对MGC-803细胞增殖和侵袭的影响。采用分子对接和50 ns分子动力学模拟分析DML与COX17的潜在结合模式及复合物构象稳定性；进一步通过COX17过表达回复实验评价COX17在DML抑制细胞增殖和侵袭过程中的作用。结果：DML显著抑制MGC-803细胞增殖和侵袭，且随DML浓度升高，抑制作用逐渐增强（均P < 0.000 1）。蛋白质组学共筛选出72个差异表达蛋白，其中21个上调、51个下调；结合差异表达特征、GO功能富集结果及前期研究基础，选取COX17进行后续验证。DML可显著下调MGC-803细胞中COX17蛋白表达（P < 0.000 1）。敲低COX17可抑制细胞增殖和侵袭，过表达COX17则促进上述表型。分子对接提示DML与COX17之间可能存在疏水接触、氢键和盐桥等相互作用，对接评分为−6.8 kcal/mol；分子动力学模拟显示DML-COX17复合物在50 ns模拟过程中整体趋于相对稳定。COX17过表达可部分减弱DML对MGC-803细胞增殖和侵袭的抑制作用（P < 0.01）。结论：DML可抑制MGC-803细胞增殖和侵袭并下调COX17蛋白表达，COX17可能参与DML对胃癌细胞恶性表型的调控。

Objective To analyze the global pattern, long-term trends, and regional and population heterogeneity in the burden of 375 diseases and injuries and 88 risk factors from 1990 to 2023 using data from the Global Burden of Disease Study 2023 (GBD 2023). Methods Publicly available GBD 2023 estimates were extracted for incidence, deaths, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life years (DALYs), and age-standardized rates at the global level and by socio-demographic index (SDI), GBD region, age group, and sex. Descriptive analysis, ranking comparison, stratified analysis, and trend analysis were performed, and 95% uncertainty interval was used to assess the stability of estimates. Results In 2023, non-communicable diseases were the leading contributor to global DALYs, accounting for 64.39% of DALYs across the three major disease and injury groups (communicable, maternal, neonatal, and nutritional diseases, non-communicable diseases, and injuries), and also had the highest age-standardized DALYs rate. From 1990 to 2023, age-standardized DALYs rates declined for three major disease and injury groups, with estimated annual percentage changes of −2.69%, −0.78%, and −1.47%, respectively. Cardiovascular diseases ranked first by both DALYs and deaths in 2023, whereas respiratory infections and tuberculosis ranked first by incidence. Non-communicable diseases were the leading cause of disease burden across all SDI strata. As the SDI level declined, the burden of communicable, maternal, neonatal, and nutritional diseases, as well as injuries, increased markedly. Behavioral and metabolic risks remained the main contributors to attributable deaths and DALYs. Conclusion From 1990 to 2023, the global burden of disease continues to shift toward non-communicable diseases; however, some regions still face a double burden of infectious, maternal and child, injury-related, and chronic diseases. Integrating deaths, DALYs, YLLs, YLDs, and risk-attributable burden helps identify priority areas for prevention and resource allocation across regions and populations.

[摘 要] 目的：探讨细胞色素c氧化酶铜伴侣蛋白17（COX17）在胃癌中的表达及其对胃癌细胞恶性生物学行为的调控作用。方法：运用TIMER、UALCAN、TCGA、HPA、Kaplan‑Meier Plotter数据库，分析COX17基因在泛癌、胃癌及正常胃组织中的表达差异及其与胃癌临床病理特征和预后的关系；通过STRING数据库构建COX17蛋白质相互作用网络并进行GO功能注释与KEGG通路分析；通过TIMER数据库分析COX17表达水平与免疫细胞浸润程度的相关性。采用慢病毒系统构建稳定敲低或过表达COX17的SGC-7901细胞，Western blotting法验证COX17敲低与过表达效率。通过细胞计数法检测稳转细胞模型增殖能力，Transwell细胞侵袭实验评估细胞侵袭能力；划痕愈合实验检测细胞迁移能力。结果：数据库分析显示胃癌组织及细胞中COX17 mRNA呈高表达；COX17 mRNA高表达的胃癌患者总生存期（OS）、无进展生存期（PFS）及进展后生存期（PPS）更长；COX17及其相关基因主要参与线粒体细胞色素c氧化酶、电子传递链等功能，富集于非酒精性脂肪性肝病、氧化磷酸化、产热等KEGG通路；COX17表达水平与CD4⁺ T细胞、巨噬细胞浸润呈负相关。成功构建稳定敲低或过表达COX17的胃癌细胞。功能实验表明，敲低COX17可显著抑制胃癌细胞增殖、侵袭和迁移（均P < 0.000 1）；而过表达COX17则产生相反效应（均P < 0.000 1）。结论：COX17 mRNA在胃癌组织和细胞中高表达，其高表达与胃癌患者较好的生存预后相关；但体外功能实验显示COX17可促进胃癌SGC-7901细胞增殖、侵袭和迁移。COX17在胃癌中的作用可能具有复杂性，其临床预后意义与体外恶性表型调控之间的差异尚需进一步研究。

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Objective Feasibility application of microelectrode recording(MER)during sub thalamic nucleus deep brain stimulation(STN-DBS)implantation under desflurane general anesthesia(GA)in patients with Par-kinson's disease(PD).Methods A prospective cohort of 20 PD patients undergoing STN-DBS under desflurane general anesthesia were enrolled.Intraoperative MER quality,pos-operative acute pain,cognitive function,anxi-ety/depression status,quality of life,and clinical efficacy of DBS were evaluated.Results Among the patients,14 were male with average PD duration of(8.1±3.6)years.Hoehn-Yahr staging averaged 2.8±0.5 in"on"state and 2.3±0.5 in"off"state.The mean DBS surgery duration was 87.4 minutes.Highly normalized root-mean-square(NRMS)signals were successfully recorded in all cases,with remedial measures applied in 4 pa-tients to achieve satisfactory MER signals.Post-operative Visual Analogue Scale(VAS)pain scores on days 1,2,and 3 were 3.7±2.2,2.8±1.6,and 1.8±2.0,respectively.Montreal Cognitive Assessment(MoCA)scores showed no statistical difference during hospitalization as compared to pre-operative values,but significantly de-creased at 6-month follow-up(24.3±4.1 vs.21.5±3.5,P＜0.05).All patients demonstrated significant reduc-tion in Hamilton Anxiety Scale(HAMA),Hamilton Depression Rating Scale(HAMD),and Parkinson's disease Questionnaire-39(PDQ-39)scores at 6-month follow-up.The unified Parkinson's disease rating scale(UPDRS-Ⅲ)improvement rates were 51.4%±39.2%(medication-on)and 61.6%±26.8%(medication-off)respectively with Levodopa Equivalent Daily Dose(LEDD)improvement rate of 48.6%±23.0%.Conclusions Desflurane general anesthesia is safe and feasible for electrods implantation in STN-DBS of PD patients,without interfering with intra-operative MER or postoperative outcomes.

Research on immune checkpoints such as programmed death protein-1(PD-1)and cytotoxic T lymphocyte antigen-4(CTLA-4)has provided new directions for tumor treatment.V-domain immunoglobulin suppressor of T-cell activation(VISTA)is an emerging immune checkpoint within the B7 family.Functioning as both a ligand and a receptor,VISTA is an inhibitory immune checkpoint molecule expressed in tumor cells,myeloid cells and T lymphocytes.It plays a crucial role in regulating autoimmunity,inflammatory response and tumor immunity.The non-redundant interactions between VISTA and other immune checkpoints,such as PD-1,may offer new therapeutic strategies and serve as a new target for overcoming immunotherapy resistance.This review summarizes the recent research progress on VISTA in hematological tumors,aiming to provide new insights into its application in the treatment of these malignancies.