[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。

[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。

[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。

Objective To investigate the protective effect of β-glucan(BG)against intestinal ischemia reperfusion(II/R)injury by regulating the secretion of glucagon-like peptide-1(GLP-1).Methods Male C57BL/6 mice(6～8 weeks old)were subjected,and finally,the experiments had sham group,II/R group,II/R+BG group(0.1 mg/mL BG in drinking water for 2 weeks before modeling),II/R+liraglutide(LLT,GLP-1 analogue)group(0.2 μg/g LLT injected every 12 hours for 3 consecutive days before modeling),and II/R+BG+Ex9-39(GLP-1 R antagonist)group(intraperitoneal injection of 2 μg/g Ex9-39 1 h before modeling).After modeling,HE staining was used to observe intestinal morphological changes,and RT-qPCR and Western blotting were employed to evaluate the molecules(Occludin,ZO-1 and Claudin-1)related to intestinal barrier damage.The effect of 0.1 mg/mL BG treatment on the GLP-1 level in the serum and intestinal tissues of normal mice was determined with ELISA and immunofluorescence assay,respectively,and RT-PCR for the molecules related to GLP-1 expression(Gcg,Pcsk1/2,GIP and Foxa2).The effects of LLT and Ex9-39 pretreatment on intestinal morphology and intestinal barrier damage were also determined by morphological observation and expression levels of related molecules.Results II/R induced significant decreases in the mRNA levels of Occludin,ZO-1 and Claudin-1 and increase in Chiu's score when compared with sham control mice(P＜0.05).While,the mRNA levels of the 3 molecules were obviously higher and the Chiu's score was lower in the II/R+BG group than the II/R group(P＜0.05).BG pretreatment induced notably enhanced secretion of GLP-1 in the serum and intestinal tract of normal mice,and improved the mRNA expression of GLP-1-related molecules(P＜0.05).The intervention of GLP-1 analogue LLT could attenuate the II/R damage and decreased Chiu's score,with statistical difference in comparison with the II/R group(P＜0.05).GLP-1 receptor antagonist Ex9-39 reversed the protective effects of BG pretreatment against II/R damage,with notably differences in the expression of Occludin,ZO-1 and Claudin-1 and Chiu's score(P＜0.05).Conclusion BG can attenuate intestinal mucosal and functional injury after II/R by promoting intestinal GLP-1 secretion.

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.

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.

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.