BackgroundNeoadjuvant immunotherapy combined with chemotherapy has revolutionized the treatment of locally advanced gastric cancer (LAGC), yet optimizing patient selection remains challenging due to heterogeneous responses. This study aimed to evaluate the divergent predictive values of nutritional and inflammatory biomarkers—specifically the Prognostic Nutritional Index (PNI), Systemic Immune-inflammation Index (SII), and Creatinine to Cystatin C Ratio (CCR)—for short-term pathological response and long-term survival.MethodsA prospective cohort of 132 LAGC patients receiving neoadjuvant nivolumab plus chemotherapy followed by curative resection was analyzed. Logistic regression and a decision tree model were employed to identify predictors of pathological complete response (pCR). Furthermore, univariate and multivariate Cox proportional hazards regression analyses were performed to determine independent prognostic factors for overall survival (OS).ResultsIn this study, patients with pCR showed significantly better OS and disease-free survival (DFS) compared to patients with non-pCR (both P < 0.01). Additionally, patients in the pCR group exhibited a significant decrease in the SII levels, while PNI and CCR were significantly increased (all P < 0.05). Restricted Cubic Spline (RCS) analysis confirmed that these indices were significantly linearly correlated with survival risks (all P < 0.05), and Kaplan-Meier curves revealed that patients with low SII, high PNI and CCR levels had longer OS and DFS (all P < 0.0001). Based on decision tree analysis, a prediction model was constructed by combining PNI, SII, CCR and CA199, which significantly enhanced the predictive ability of pCR (Area Under the Curve, AUC = 0.917). Finally, the nomogram models for OS and DFS also demonstrated good calibration and discrimination.ConclusionsNutritional and inflammatory status (SII, PNI, CCR) and CA199 serve as a sensitive marker for immediate pathological response, SII, PNI and CA125 are more indicative of long-term prognosis. Integrating these distinct biomarkers into phase-specific predictive models facilitates precise risk stratification and personalized management for patients undergoing neoadjuvant immunotherapy.

Fork-head box protein M1 (FOXM1) plays critical roles in development and progression of multiple cancers, including hepatocellular carcinoma (HCC). However, the exact regulatory hierarchy of FOXM1 remains unclear. Here, a genome-wide screen is performed to identify intranuclear proteins that promote FOXM1 transcription activity via liquid–liquid phase separation (LLPS). Abnormal spindle-like microcephaly associated (ASPM) is identified to interact with FOXM1 protein via LLPS and enhance its stability by preventing proteasome-mediated degradation. ChIP-sequencing data show ASPM and FOXM1 co-occupy the promoters of multiple genes to promote their transcription, enhancing FOXM1-driven oncogenic progression. In functional experiments, inhibition of ASPM suppresses tumor growth of HCC cells in vivo and in vitro, while overexpression of ASPM has opposite effects. Importantly, reconstitution of FOXM1 partially compensates for the weakened proliferative capacity of HCC cells caused by ASPM silencing. Intriguingly, FOXM1 binds to the promoter region of ASPM and transcriptionally activates ASPM expression in HCC cells. Furthermore, we find that a higher co-expression of ASPM and FOXM1 significantly correlates with poor prognosis in HCC patients. It indicates a double positive feedback loop between ASPM and FOXM1 which coordinately promotes the aggressive progression of HCC. Collectively, we demonstrate that LLPS and transcriptional regulation form an oncogenic double positive feedback loop between ASPM and FOXM1. This provides a rationale strategy to treat HCC by targeting this mechanism.

Circadian rhythm genes were reported to be strongly associated with the development and prognosis of circadian rhythm disorders related to stomach adenocarcinoma (STAD), which is one of the most prevalent cancers. This study aimed to identify a circadian rhythm-related gene signature that could help predict STAD outcome. Using bioinformatics analysis approaches, 105 genes were examined in 350 patients with STAD. Overall, six hub-type circadian rhythm-associated genes (GNA11, PER1, SOX14, EZH2, MAGED1, and NR1D1) were identified using univariate and multivariate Cox regression analyses. These genes were then used to build a genetic predictive model, which was further validated using a publicly available dataset (GSE26899). Overall, genes associated with the circadian rhythm were found to be substantially correlated with the characteristics of the STAD patients (grade, sex, and M stage). In addition, the circadian rhythm-related gene signature was significantly associated with the MAPK and Notch signaling pathways, which are known risk factors for poorer STAD outcome. Taken together, these findings suggest that the herein proposed prognostic model based on six circadian rhythm-associated genes may have predictive value and potential application for clinical decision-making and for personalized treatment of STAD.

"临床技能学"是为临床医学专业学位研究生开设的一门核心课程,课程聚焦新形势下专业型医学研究生的培养需求,分析新型医学人才培养目标及一流研究生课程建设中存在的核心问题,通过更新教学理念、创新课程体系模式、加强教师队伍建设、深化思政教育,探索并初步建设了集理论性、指导性、前沿性、应用性和思政性于一体的全方位的"临床技能学"核心课程体系,旨在提升临床医学生的专业技能、临床素养,进一步提升研究生教学质量.

目的 探索研究《临床基本操作》课程形成性考核评价体系的应用效果.方法 选取2020年3月13日至2021年5月13日在某院参与《临床基本操作》课程的2017-2018级临床专业学生为研究对象,按照入学年份分为两组,2017级学生共80人为对照组,采用传统终结性考核模式;2018级学生共96人为研究组,采用以提升学生临床胜任力为导向的形成性考核+终结性考核模式.通过对比两组学生《临床基本操作》课程终结性考核成绩、学生对形成性考核的评价及带教教师对两组学生问卷评分情况,评估形成性考核对学生临床基本操作和临床思维能力培养的影响.结果 研究组实践考核成绩(49.38±4.56)、理论考核成绩(31.21±3.31)和最终考核成绩(80.59±6.58)明显高于对照组实践考核成绩(47.46±3.93)、理论考核成绩(29.96±3.96)和最终考核成绩(77.42±5.74),差异均具有统计学意义(t=2.292-3.370,P＜0.05);90％以上学生认为开展形成性考核可明显提升学生对课程的学习兴趣、技能的操作能力及知识的掌握能力,有93.7％学生认为有必要继续开展形成性考核;研究组学生临床操作水平、临床思维与判断能力、人文关怀意识、团队合作意识、应急处理能明显高于对照组学生,且结果具有统计学意义(t=2.006-4.664,P＜0.05).结论 以提升学生临床胜任力为导向的形成性考核体系能够提升临床基本操作课程的教学效果和课堂教学质量,有效提升学生的临床综合素质.

目的 探讨惰性T淋巴母细胞增生(indolent T-lymphoblastic proliferation,iT-LBP)的临床病理学特征、诊断、鉴别诊断及预后.方法 回顾性分析6例iT-LBP的临床资料,对其行HE染色、免疫组化EnVision两步法染色、EBER原位杂交及TCR重排检测,结合文献总结其临床病理特征、预后及鉴别诊断.结果 6例iT-LBP患者年龄3～51岁(中位年龄20岁),男女比为1:1,4例为Castleman病合并iT-LBP.镜下特点为淋巴滤泡结构保存完好,滤泡间区小～中等淋巴细胞增生,片状或簇状分布,无明显异型.免疫表型:肿瘤细胞TDT及CD3阳性(6/6),CD1a(2/2)、CD99(1/1)、CD4(3/3)及CD8(3/3)阳性;LMO2(3/3)、CD34(1/1)及EBER(1/1)阴性,Ki-67增殖指数40％～75％.所有病例均接受手术治疗,行完全手术切除5例,行治疗性切除并化疗1例.随访时间3～88个月,中位时间52个月,均未出现复发与转移.结论 根据组织学、免疫表型和分子特征以及密切的临床随访可以为iT-LBP准确诊断提供必要的信息.

Alzheimer’s disease (AD) is a heterogeneous disease with complex clinicopathological characteristics. To date, the role of m6A RNA methylation in monocyte-derived macrophages involved in the progression of AD is unknown. In our study, we found that methyltransferase-like 3 (METTL3) deficiency in monocyte-derived macrophages improved cognitive function in an amyloid beta (Aβ)-induced AD mouse model. The mechanistic study showed that that METTL3 ablation attenuated the m6A modification in DNA methyltransferase 3A (Dnmt3a) mRNAs and consequently impaired YTH N6-methyladenosine RNA binding protein 1 (YTHDF1)-mediated translation of DNMT3A. We identified that DNMT3A bound to the promoter region of alpha-tubulin acetyltransferase 1 (Atat1) and maintained its expression. METTL3 depletion resulted in the down-regulation of ATAT1, reduced acetylation of α-tubulin and subsequently enhanced migration of monocyte-derived macrophages and Aβ clearance, which led to the alleviated symptoms of AD. Collectively, our findings demonstrate that m6A methylation could be a promising target for the treatment of AD in the future.

临床基本操作课程是基层军医卫勤指挥、专科培训、特定任务卫勤保障培训的重要内容,围绕提升军事医学人才的职业特质、专业技能、综合素养等,全面分析基层部队卫生专业人员的学习特点,建设以紧贴实战的围伤(病)期救治技术为主要内容的高质量在线慕课.在此基础上,研究分析临床基本操作慕课在军事医学职业教育中的应用成效,证明其对于完善军事医学职业教育体系、培养三位一体新型军事人才具有重要意义.

目的 探讨新医科背景下临床整合课程的教学改革与教学管理方式.方法 分别随机选取在我院参与临床课程学习的2016级和2017级临床专业学生各50名,分为对照组和研究组;研究组采用临床整合课程进行教学,对照组采用传统临床教学课程进行教学,采用Mini-CEX的量化评价表进行评价.课程结束后,对2017级和2018级临床专业376名学生进行整合课程满意度问卷调查.结果 与对照组相比,研究组50名学生基本操作技能、临床思维能力和人文关怀意识均有提高,且差异具有统计学意义(P＜0.05).学生对整合课程整体满意度达95.79％,对临床操作和思维能力提高、人文关怀意识和科学研究精神提升满意度均超过90％.结论 通过科学管理,新医科背景下的临床整合课程改革能有效提高医学生的临床操作能力和思维能力,激发学生的学习兴趣,全面提升临床医学教学质量.

现代战场环境下,一线战士战创伤救治是战时减少部队人员伤亡的重要保障.专业的军事医学院校及卫勤培训基地无法大规模地对一线战士进行战伤救治能力的培训.笔者提出充分利用基层军医的专业知识背景和水平,发挥其作为部队卫勤保障核心力量的作用,通过提升基层军医的战创伤救治水平,由他们向一线战士进行推广的模式.通过建规范、创教法、考实操的培训策略,切实提升一线战士的战创伤救治水平.

目的 探讨基于线上学习平台联合翻转课堂教学法在临床基本操作实验教学中的应用和效果.方法 于2021年3—6月将空军军医大学2017级120名临床医学专业五年制本科生随机分成两组,分别作为对照组与试验组,其中,传统教学模式下的课堂作为对照组,基于线上学习平台下的翻转课堂作为试验组.结果 试验组学生的实验完成时间、实验动物意外死亡数以及平均实践考核成绩均高于对照组,差异有统计学意义(P<0.05),并且试验组学生主观认为线上学习平台联合翻转课堂的实践教学模式能够改善实训课学习效果.结论 将基于线上学习平台联合翻转课堂教学方式用于临床基本操作实验教学,这种教学模式可以帮助学生更快更高质量地掌握知识,同时潜移默化中激发学生的学习兴趣.

思政教育的理念对我国医学教育改革产生了深远的影响,强调将课程作为"主阵地",致力于实现"思想政治工作贯穿教育教学全过程",促进教育教学深化改革,全方位优化课程思政供给.新教学模式的探索和医学人才培养模式的改革是促进医学教育高质量发展的关键,以"三全育人"作为"以德树人"理念和使命下课程建设的有力抓手,在各高校中掀起了"三全育人"综合改革实践新征程.《临床基本操作》是我校一门纵、横向特色性整合的临床医学课程,创新性改革以学科为中心的传统构架,以"系统-疾病"为主线建立全面完整的知识结构体系.结合"三全育人"理念,从"三全"模式的构建、无菌术课程教学的思政设计、无菌术课程教学的实践以及考核评价体系四个方面展开研究和实践,并通过调查问卷分析等方法对教学效果进行深度剖析,对新教学模式进行总结、凝练,并上升为理论素材,旨在将"三全育人"贯彻到医学临床基本操作课程教学中,为建设临床基本操作一流本科课程奠定基础.

目的 肾混合性上皮间质肿瘤的临床表现及影像学特点不典型,术前诊断困难,需病理确诊,本研究总结其临床病理特征及预后,以提高对此疾病的病理诊断及鉴别诊断.方法 回顾性分析7例肾混合性上皮间质肿瘤,结合文献分析其临床病理特征、预后及鉴别诊断.结果 7例肾混合性上皮间质肿瘤患者全部为女性,年龄为24～55岁,平均年龄45岁.肿瘤全部为单发,大体表现为多房囊性或囊实性.组织学形态特点为上皮组织和间质组织混合组成.免疫组化染色显示上皮细胞表达AE1/AE3阳性(6/6),间质细胞表达PR阳性(6/6),ER阳性(6/6),Actin 阳性(2/5),Desmin 阳性(6/6),SMA 阳性(3/3),CD34 阳性(0/4),S-100 阳性(0/2),HMB45 阳性(0/3),Ki-67增殖指数比较低.所有病例均接受手术治疗,其中行根治性肾切除术5例,行肾部分切除术2例.术后随访13～175个月,中位随访115个月,患者均未发现肿瘤复发与转移.结论 肾混合性上皮间质肿瘤是非常少见的良性肿瘤,其诊断和治疗仍以手术切除为主,预后好.本病比较少见及报道病例不多,因此,还需要进一步了解其发病机制、临床行为、恶性潜能及治疗管理.

目的 探讨抛锚式教学法联合Mini-CEX在临床基本操作教学中的应用效果.方法 将2020年3—6月参与临床基本操作课程的60名学生作为研究对象,采用随机数字表法进行分组,研究组和对照组分别30名学生.研究组采用抛锚式教学法联合Mini-CEX进行教学,在教学过程中进行四次Mini-CEX考核;对照组使用传统方式进行教学.最终两组采用相同的理论与实践考核方式进行比较.结果 初次Mini-CEX考核结果与末次相比,研究组学生基本操作技能和临床思维能力均有提高,且差异具有统计学意义(P<0.05).与对照组相比,研究组学生的最终考核成绩均有显著提高,差异具有统计学意义(P<0.05).结论 抛锚式教学法联合Mini-CEX应用效果显著,能有效提高学生基本操作技能和临床思维能力.

N6-methyladenosine (m6A) is a reversible mRNA modification that has been shown to play important roles in various biological processes. However, the roles of m6A modification in macrophages are still unknown. Here, we discover that ablation of Mettl3 in myeloid cells promotes tumour growth and metastasis in vivo. In contrast to wild-type mice, Mettl3-deficient mice show increased M1/M2-like tumour-associated macrophage and regulatory T cell infiltration into tumours. m6A sequencing reveals that loss of METTL3 impairs the YTHDF1-mediated translation of SPRED2, which enhances the activation of NF-kB and STAT3 through the ERK pathway, leading to increased tumour growth and metastasis. Furthermore, the therapeutic efficacy of PD-1 checkpoint blockade is attenuated in Mettl3-deficient mice, identifying METTL3 as a potential therapeutic target for tumour immunotherapy.

目的:本研究通过建立慢病毒介导的NCL基因沉默的胃癌细胞系,研究NCL沉默对胃癌细胞增殖能力的影响,为深入探究胃癌发生发展的分子机制提供理论基础.方法:利用小发卡RNA(shRNA)介导的慢病毒系统沉默胃癌细胞中的NCL,并利用RT-qPCR和免疫印迹检测基因沉默效果;并利用CCK-8实验和平板克隆形成实验检测胃癌细胞的增殖能力的改变.结果:琼脂糖凝胶电泳实验检测经酶切鉴定的pKLO.1-NCL载体,显示5000 bp和2000 bp两条带,测序峰图显示与设计序列一致;利用HEK293T包装病毒,感染胃癌细胞SGC-7901,免疫印迹结果显示sh NCL组NCL蛋白水平显著低于对照组,RT-qPCR结果显示,sh NCL组NCL表达量显著降低,为对照组的0.4209±0.087倍(P＜0.001);CCK-8实验结果显示,sh NCL组在第5天的吸光值较对照组显著降低(P＜0.001),平板克隆形成实验结果显示,sh NCL组克隆形成能力较对照组显著降低,克隆形成数量显著低于对照组(P＜0.01).结论:建立了慢病毒介导的NCL基因沉默的胃癌细胞系SGC-7901,并利用此系统研究了NCL基因对胃癌细胞增殖能力的影响,证明了NCL基因能够促进胃癌细胞的增殖,为后续研究NCL基因在胃癌细胞中的作用提供基础.

目的 建立一种四环素(tetracycline,DOX)诱导的基因敲减系统,并利用此系统研究YAP1对胃癌细胞功能的影响.方法 构建pLKO.1-tetON-YAP1敲减的慢病毒载体,酶切和测序方法检测载体构建成功与否;慢病毒感染胃癌细胞系SGC-7901和MKN-28,建立DOX诱导的YAP1敲减的胃癌细胞系;RT-PCR检测YAP1 mRNA相对表达量,Western blotting检测YAP1蛋白水平变化;平板克隆实验检测细胞增殖情况;划痕实验和Transwell实验检测细胞迁移的情况.结果 构建四环素诱导的YAP1敲减的病毒质粒,酶切鉴定结果显示,在6000 bp和3000 bp处各有一条带,测序结果与设计的shRNA序列一致.包装慢病毒并感染胃癌细胞系SGC-7901和MKN-28,DOX诱导组中,感染pLKO.1-tetON-YAP1的病毒的细胞中YAP1 mRNA的相对表达量和蛋白水平明显下调;而未诱导组则无明显变化.平板克隆形成实验结果显示,DOX诱导后shYAP1组克隆形成数明显降低;未诱导组无明显变化.划痕实验和Transwell迁移实验结果显示,DOX诱导后shYAP1组表达后细胞迁移能力受到抑制,未诱导组无明显变化.结论 成功建立了四环素诱导的慢病毒系统,利用此系统敲减胃癌细胞YAP1基因,胃癌细胞增殖和迁移能力受到抑制.

目的 观察腹腔镜手术中猪的麻醉效果,总结较为理想、实用的麻醉方法.方法 对42例小型猪进行陆眠宁肌肉注射,在基础麻醉下行气管插管,术中持续吸入七氟烷维持麻醉,观察麻醉效果.结果 2例猪未能成功插管死亡,40例插管成功并维持理想麻醉状态至手术结束.结论 采用陆眠宁行基础麻醉,七氟烷持续吸入维持麻醉的方法用于猪腹腔镜手术,简便易操作,麻醉效果好.