A deficiency of fatty acid oxidation (FAO) is the key hallmark in renal tubular epithelial cells (TECs) under high-altitude hypoxia (HH), reflecting their physiological reliance on FAO as a major energy source. The resulting lipid accumulation is likely to promote lipotoxicity-induced pathological injury in renal tissue. However, the molecular mechanisms underlying HH-induced renal lipotoxic injury remain poorly understood. This study identifies hepatocyte nuclear factor 4α (HNF4α) as a key regulator of lipid metabolism. HNF4α expression in kidney tissues was significantly downregulated after HH exposure. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis revealed that HNF4α directly binds to and regulates the transcription of the Acyl-CoA Oxidase 1 (ACOX1), a key gene involved in FAO, in the kidney of hypoxia-exposed rats. Further functional studies indicated that lentivirus-mediated overexpression of HNF4α significantly alleviated hypoxia-induced lipid accumulation and the decrease in adenosine triphosphate (ATP) production, while effectively inhibiting cell apoptosis. In contrast, knockdown of HNF4α markedly aggravated cellular lipotoxicity, as evidenced by increased intracellular lipid accumulation, reduced ATP levels, and enhanced apoptosis. Mechanistically, HNF4α directly activates ACOX1 transcription and modulates Carnitine Palmitoyltransferase1A (CPT1A) expression, thereby enhancing FAO capacity. This leads to reduced reactive oxygen species (ROS) accumulation, improved mitochondrial membrane potential, and promoted ATP synthesis, ultimately mitigating hypoxia-related cellular injury. Overall, our findings uncover a previously unrecognized role for HNF4α in maintaining lipid homeostasis in TECs under hypoxic conditions and provide novel mechanism and target for HH-associated kidney injury.

Pulmonary mesenchymal cystic hamartoma (MCH) is an exceptionally rare benign tumor characterized by cystic-solid architecture and biphasic epithelial-mesenchymal components. We report a 56-year-old woman with a 2.6-cm right lower lobe mass, histologically composed of pseudostratified ciliated epithelium, glandular components, and primitive mesenchymal cells with cartilaginous/adipose differentiation. Tumor cells showed diffuse moderate cytoplasmic BCL-2/CD56 staining, weak-moderate nuclear PR positivity, and a low Ki-67 index (< 2

AbstractBackgroundAlthough there have been significant advancements in the treatment modalities for gastric cancer (GC) in recent years, the overall prognosis remains poor, particularly for individuals in advanced stages. The absence of a sensitive tumor marker in GC is a crucial factor contributing to this challenge.MethodsOur study focused on investigating a newly discovered long noncoding RNA (lncRNA) known as TCONS_00251376, which has been confirmed to exhibit differential expression in GC compared to adjacent tissues. To further validate these expression differences, we collected 22 pairs of GC and adjacent noncancerous tissues. Subsequent cell function experiments and animal studies were conducted to elucidate the role and underlying mechanisms of lncRNA TCONS_00251376 in the development of GC.ResultsThe study revealed a significant upregulation of lncRNA TCONS_00251376 in cancer tissues (p < 0.01) and a consistent upregulation in GC cell lines (AGS, MKN45, BGC‐823, and MGC‐803). Furthermore, it was observed that lncRNA TCONS_00251376 played a promotive role in the proliferation, migration, and invasion of GC cells. Subsequent analysis indicated that lncRNA TCONS_00251376 could upregulate the expression of ETV1, a factor associated with the prognosis of GC.ConclusionsTherefore, our findings suggest that lncRNA TCONS_00251376 functions as an oncogenic lncRNA, promoting tumorigenesis and progression by regulating the expression of ETV1 gene. This highlights its potential as an effective target for treating GC.

中华优秀传统文化,是中华民族最基本的文化基因.病理学是联系基础医学和临床医学的重要桥梁学科,在医学教育中起着不可或缺的作用.为有效地推进中华优秀传统文化融入病理学思政教学中,本文从挖掘中华传统文化融入病理学思政教学的融合点、可行性案例的列举及"混合式"多元教学体系的形成等方面进行了探索.浅析了中国传统文化融入病理学思政教学中的意义,"融合性"成效性评价准则已经初现雏形.为推动中华优秀传统文化融入病理学思政教学中提供理论依据和实践方案.

Breast cancer (BC) is the leading cause of cancer-related mortality in women, necessitating the development of novel therapeutic targets. While cytochrome b561 (CYB561) expression is associated with poor prognosis in BC, the precise role of CYB561 in BC and its potential mechanisms remain unclear. In the present study, we found that CYB561 plays an essential role in BC growth. CYB561 expression was up-regulated in surgically resected cancerous tissues and in six BC cell lines. Lentivirus-mediated CYB561 knockdown in BC cells significantly reduced their proliferation, migration, and invasiveness. CYB561 participates in the regulation of iron metabolism in BC. CYB561 knockdown reduced total iron content, increased ferrous iron content, and down-regulated the expression of proteins associated with iron metabolism (transferrin receptor 1, divalent metal transporter 1, and ferritin heavy chain 1). Conversely, up-regulation of CYB561 through co-incubation with exogenous iron (ferric ammonium citrate) produced contrary outcomes. Additionally, CYB561 activated the protein kinase B/ mammalian target of rapamycin (Akt/mTOR) signaling pathway in BC cells. Down-regulation of CYB561 expression inhibited the Akt/mTOR signaling pathway activity. The application of an mTOR agonist (MHY1485) rescued this negative effect, as well as the inhibitory effect of CYB561 knockdown on cell proliferation. Importantly, the dual mTOR inhibitor MLN0128 (50 nM, 48 h) down-regulated CYB561 expression and the iron metabolism-related proteins transferrin receptor, divalent metal transporter 1, and ferritin heavy chain 1, whereas the mTOR agonist MHY1485 rescued the down-regulation of CYB561 knockdown on iron metabolism related proteins. We conclude that CYB561 promotes the proliferation of BC cells by regulating iron metabolism through the activation of the Akt/mTOR signaling pathway.

目的 检测RAS相关结构域家族成员6基因(RASSF6)及MST1在非小细胞肺癌(NSCLC)中的表达情况,并探讨二者对NSCLC患者的病理意义.方法 利用GEPIA2数据库测定肺腺癌(LUAD)和肺鳞癌(LUSC)中RASSF6和MST1基因表达水平;通过qRT-PCR实验测定NSCLC新鲜组织中RASSF6、MST1 mRNA表达水平;免疫组化法检测石蜡标本中RASSF6、MST1蛋白表达.Spearman探讨二者的相互关系.结果 与癌旁正常肺组织比较,NSCLC的RASSF6 mRNA和蛋白表达水平均明显增加(P＜0.05),但MST1 mRNA和蛋白表达水平均明显降低(P＜0.05).RASSF6及MST1蛋白表达均与临床分期、淋巴结转移相关(P＜0.05),而与NSCLC患者的年龄、性别、组织分型及分化程度无关(P＞0.05);且RASSF6与MST1呈负相关(rs=-0.227,P＜0.05).结论 RASSF6和MST1可能与NSCLC的进展有关,有望成为NSCLC患者新的潜在治疗靶点.

目的 探讨Ras相关结构域家族成员7(Ras-association domain family 7,RASSF7)在结直肠癌(colorectal cancer,CRC)组织中的表达及对CRC细胞系生物学特性的影响.方法 应用免疫组化法检测RASSF7在80例CRC组织中的表达,并分析其与各临床病理特征的关系;Western blot实验检测RASSF7在CRC细胞系中的表达,选出RASSF7高、低表达的CRC细胞株各一种,应用RASSF7过表达质粒和敲除质粒瞬时转染CRC细胞,MTT和Transwell实验分别检测RASSF7对CRC细胞增殖及侵袭的影响.结果 免疫组化结果显示:CRC组织中RASSF7高表达50例,低表达30例,CRC组织中RASSF7表达明显高于癌旁正常组织,RASSF7高表达与患者年龄(P=0.238)、性别(P=0.065)及肿瘤分化程度(P=0.238)无关,而与TNM分期(P<0.001)及淋巴结转移(P=0.030)相关;RASSF7过表达可促进CRC细胞的增殖及侵袭能力(P<0.01),而敲除RASSF7则作用相反(P<0.01).结论 RASSF7在CRC中可能发挥促癌基因的作用,其高表达可显著促进CRC细胞的增殖及侵袭能力.

The expression of cytochrome B561 (CYB561) and its role in breast cancer (BC) prognosis remain unclear. We analyzed the differential expression and prognostic value of CYB561 using online databases and a clinical cohort through bioinformatics and immunohistochemistry. The differential expression of CYB561 and its association with BC were analyzed using the tumor immune estimation resource (TIMER), gene expression profiling interaction analysis2 (GEPIA2), Human Protein Atlas, Cancer Cell Line Encyclopedia, and Kaplan–Meier Plotter website. Important pathways of CYB561 enrichment were explored using gene set enrichment analysis. Immunohistochemistry detected CYB561 expression in normal breast, breast hyperplasia, ductal carcinoma in situ (DCIS), para-cancer, and invasive BC groups. Association between CYB561 expression and BC prognosis was analyzed using Kaplan–Meier and Cox regression analyses. CYB561 mRNA expression was higher in GEPIA and TIMER BC patients than in para-cancer tissues. CYB561 was expressed in the glandular epithelium and myoepithelium, with positive localization in the cytoplasm and cell membrane. CYB561 protein expression significantly differed among the groups. CYB561 expression was correlated with ERBB2/HER2 and infiltrating CD4+ T cells in GEPIA and TIMER BC patients and associated with HER2 status, histological grade, and molecular subtypes in the clinical cohort but not related to tumor-infiltrating lymphocytes. CYB561 mRNA overexpression predicted reduced recurrence-free survival and overall survival in BC. Patients with CYB561 expression had significantly reduced overall survival and increased risk of death. CYB561 can serve as an effective clinical prognostic biomarker for BC.

1 病例资料 患者女性,40岁,藏族牧民,因体检发现肝包虫病30年, 2020年12月12日收住青海大学附属医院肝胆胰外科.临床诊断:肝泡型包虫病侵犯肝后下腔静脉.既往无高血压、糖尿病、冠心病史,有藏区长期生活史及放牧史.查体:腹壁无静脉曲张,右上腹压痛,浅触诊可触及包块,移动性浊音阴性,双下肢无水肿.血液系统检查:血常规、血生化、凝血功能指标良好,包虫特异性抗体阳性,无乙型、丙型肝炎等肝脏基础疾病.

肝多房棘球蚴病病灶对人体重要的脉管系统(血管、胆管、淋巴结)是否侵犯及其侵犯程度,直接影响患者的手术治疗方式.目前,临床对于血管侵犯、胆管侵犯及淋巴结转移的病理状态、检查指征及治疗方式的关系尚不明确.本文综合国内外最新研究进展,对肝多房棘球蚴病的增殖与转移机制,病灶的病理分区,及脉管侵犯的肉眼、影像、显微镜下的特点进行深入阐述,以期推进肝多房棘球蚴病脉管侵犯诊断与治疗等研究的发展.

甲状腺滤泡癌合并鳞状细胞癌非常罕见，本例肿瘤具有滤泡癌和鳞状细胞癌的组织学特点，两种成分存在移行和过渡，诊断依靠形态学结合免疫组织化学染色和详尽的全身检查。该病进展较快，预后不一，规范治疗后需长期随访。

目的 探讨CDl38表达水平对不同免疫表型弥漫大B细胞淋巴瘤(DLBCL)患者预后的临床价值.方法 选取自2014年1月至2016年1月就诊的103例DLBCL患者为研究对象.采用免疫组化EnVision法对研究对象的组织标本进行CDl38表达水平的检测,同时测定CD10、MUM1以及bcl-6表达水平辅助完成免疫分型,比较两种免疫学分型患者CD138表达水平的差异,分析患者的存活率,并对CD138与患者总生存期的相关性进行Cox回归分析.结果 GCB型和非GCB型患者分别为53例和50例.GCB型和非GCB型患者在性别、年龄、原发部位、Ann Arbor分期及国际预后指数(IPI)等方面比较,差异均有统计学意义(P＜0.05).GCB型和非GCB型患者免疫组化检出CD138阳性率分别为15.1％(8/53)和14.0％(7/50),差异无统计学意义(P＞0.05).GCB型中,CD138阳性患者的生存期为(11.22±4.60)个月,1年存活率为35.8％(19/53);CD138阴性患者的生存期为(16.92±4.38)个月,1年存活率为47.2％(25/53),CD138阳性GCB型患者的生存期,1年存活率均低于CD138阴性GCB型患者,差异有统计学意义(P＜0.05).在非GCB型中,CD138阳性患者的生存期为(11.08±4.41)个月,1年存活率为40.0％(20/50);CD138阴性非GCB型患者的生存期为(17.01±4.57)个月,1年存活率为50.0％(25/50),CD138阳性非GCB型患者的生存期、1年存活率显著低于CD138阴性非GCB型患者,差异均有统计学意义(P＜0.05).Cox回归模型分析CD138与患者生存期相关性提示,CD138阳性是生存期降低的危险因素(OR=1.399,95％可信区间为1.022～1.914,P＜0.05).结论 不同免疫分型DLBCL患者CD138阳性状态下生存期、1年生存率均较低;CD138阳性是造成患者生存期短的危险因素.

为探讨青藏高原喜马拉雅旱獭适应高原低氧机理,分析其血液生理特征和心肺组织学改变.选择连续海拔段的青海省乌兰县(海拔3200—3400 m)、囊谦县(3600—3800 m)、兴海县(3800—4000 m)和泽库县(4000—4200 m)作为现场采样点,采用圈套法捕获喜马拉雅旱獭样本,记录标本采集信息和生境类型,静脉注射5％戊巴比妥钠麻醉旱獭后,心脏采血3—5 mL并置于抗凝管中.处死旱獭后迅速摘取心脏和肺脏,并将样本放入4％甲醛溶液中.利用全自动血液分析仪测定红细胞(RBC)、血红蛋白(HGB)、血细胞比容(HCT)、平均红细胞体积(MCV)和血小板(PLT)等生理指标.固定后的心肺样本按常规方法切片(厚4μm),HE染色后光镜观察.结果发现乌兰县喜马拉雅旱獭的HBC、HGB、HCT最高,而囊谦县旱獭的RBC、HGB、HCT数值最低.MCV随海拔的升高而降低,而PLT则相反,随海拔的升高而增加.显微镜下观察喜马拉雅旱獭心肺组织的HE染色切片,4个地区的心肺切片中均有不同程度的损伤.说明该动物对高原低氧环境有一定的生理适应性.

目的 探讨抑制甲胎蛋白(AFP)表达对肝癌小鼠模型肝脏损伤修复的作用机制.方法 将建立肝癌模型的小鼠随机平分为三组:模型组、对照组与实验组,对照组每只瘤内直接注射p-siRNA 50μl/0.1 ml,实验组每只瘤内直接注射p-siRNA-AFP 50μl/0.1 ml,模型组以等剂量的生理盐水代替,每7天注射1次,连续注射3次.计算各组小鼠的移植瘤重量和抑瘤率.采用酶联免疫法检测血清AFP与血管内皮生长因子(VEGF)含量.采用TUNEL染色法计算凋亡指数.采用Western印迹检测Beclin-1、LC3表达水平.结果 实验组的移植瘤重量显著低于模型组与对照组(P<0.05),抑瘤率显著高于模型组与对照组(P<0.05),模型组与对照组比较差异无统计学意义(P>0.05).实验组的血清AFP与VEGF含量显著低于模型组与对照组(P<0.05),模型组与对照组比较差异无统计学意义(P>0.05).实验组移植瘤的凋亡指数显著高于模型组与对照组(P<0.05),模型组与对照组比较差异无统计学意义(P>0.05).实验组移植瘤的Beclin-1、LC3蛋白相对表达水平显著高于模型组与对照组(P<0.05),模型组与对照组比较差异无统计学意义(P>0.05).结论 抑制AFP表达在肝癌小鼠模型中的应用能促进肿瘤细胞自噬与凋亡,抑制VEGF的表达,能抑制肿瘤增殖,提高抑瘤率,从而发挥肝脏损伤修复作用.

目的 探究沉默信息调节蛋白2(SIRT2)在结直肠癌肝转移患者中的表达及临床意义.方法 选取我院2018年6月～2019年6月收治的结直肠癌肝转移患者56例(肝转移组织、肿瘤原发组织、正常黏膜组织),采用免疫组织化学法检测上述标本内SIRT2表达,并分析结直肠癌肝转移患者不同部位标本中SIRT2表达水平、预后关系、细胞侵袭能力.结果 SIRT2在正常黏膜组织中阳性率50.00％高于肝转移组织、肿瘤原发组织14.29％、3.57％(P<0.05);结直肠癌肝转移患者中SIRT2低表达者生存时间短于SIRT2高表达者(P<0.05);过表达SIRT2后结直肠癌细胞SW480侵袭能力显著减弱.结论 SIRT2在结直肠癌肝转移患者中呈低表达,影响结直肠癌细胞浸润能力,对评估结直肠癌肝转移患者预后具有一定临床价值.

Background: Intraductal papillary mucinous neoplasm of the bile ducts (IPMN-B) is a rare malignant tumor originated from the epithelium of the bile duct. It can secrete a large amount of mucin to cause biliary obstruction. This disease has just been recognized in recent years.Case presentation: We found a 60-year-old woman with intermittent right upper abdominal pain. Imaging examination showed that the left intrahepatic bile duct was dilated with a solid mass. We had left hepatectomy. During the operation, there was colloidal mucus in the bile duct. There was a papillary mass on the wall of the bile duct. -to have developed into invasive adenocarcinoma. At a postoperative 6 months follow-up, the patient had no recurrence and is in good conditions. Conclusion: In our case, IPMN-B has underwent a malignant transformation at the early stage. Therefore, we think that surgical resection should be done as early as possible after the diagnosis of IPMN-B, so as to get a favorable prognosis.

目的 观察CXC趋化因子配体(CXCL)4L1及其受体CXCR3在胰腺癌中的表达,并探讨二者在胰腺癌转移中的作用.方法 RT-PCR检测CXCL4和CXCL4L1胰腺腺癌细胞BxPC3和胰腺导管癌细胞Panc-1中的mRNA水平,免疫荧光检测CXCL4L1在BxPC3细胞和经成肌纤维细胞共培养的BxPC3细胞中的表达,CXCR3在BxPC3和Panc-1细胞中的表达.免疫组化检测CXCL4L1及其受体CXCR3在胰腺腺癌组织和肺转移的组织中的表达.结果 CXCL4在胰腺腺癌细胞BxPC3和胰腺导管癌细胞Panc-1中均有表达,但差异无统计学意义(P>0.05),且CXCL4L1在胰腺导管癌细胞Panc-1中mRNA相对表达量显著高于胰腺腺癌细胞BxPC3(P<0.05);CXCL4L1的相对荧光表达量在BxPC3与成肌纤维细胞共培养时显著高于单独BxPC3细胞培养时的相对荧光表达量(P<0.05);CXCR3在胰腺导管癌细胞Panc-1的相对荧光表达量显著高于胰腺腺癌细胞BxPC3(P<0.05);免疫组化检测结果显示,CXCL4L1在肺转移的胰腺导管癌组织中的阳性表达显著高于胰腺导管癌原发肿瘤组织,CXCR3在肺转移组织中的阳性表达显著高于胰腺导管癌原发肿瘤组织(均P<0.05).结论 趋化因子CXCL4L1和CXCR3受体在胰腺癌肺转移的组织中高表达,其可能对胰腺癌的转移具有促进作用.

目的 探讨脑源性神经营养因子(BDNF)和酪氨酸蛋白激酶受体(Trk)B在食管癌组织中的表达,并观察外源性BDNF对食管癌细胞生物学行为的影响.方法 采用免疫组织化学方法检测食管癌和癌旁组织中BDNF、TrkB的表达;以两种食管癌细胞株ECA109、TE-1和正常食管永生化上皮细胞株HET-1A作为实验对象,用RT-PCR和Western印迹法分别检测3种细胞中BDNF、TrkB mRNA和蛋白的表达;CCK8、Transwell实验观察外源性BDNF对食管细胞增殖和侵袭能力的影响.结果 在食管癌组织中BDNF和TrkB的阳性表达率明显高于癌旁组织(P<0.05),并且两者的表达与组织学分级、浸润深度、淋巴结转移和TNM分期有关(P<0.05);外源性BDNF能够促进TE-1细胞的增殖,具有剂量时间依赖性;Transwell实验结果显示80 ng/ml BDNF能够促进TE-1细胞侵袭.结论 BDNF和TrkB与食管癌的发生发展密切相关,BDNF能够提高食管癌细胞的增殖活力,促进细胞的侵袭.

目的:探讨核糖核酸还原酶1(RRM1)和核糖核酸还原酶2(RRM2)在青海地区胃癌中的表达及其与患者临床病理特征的关系.方法:应用免疫组织化学染色S-P法检测82例胃癌患者中RRM1和RRM2的表达,并分析与肿瘤大小、浸润、分期、分化、转移等的相关性.结果: RRM1及RRM2在胃癌中表达均显著高于正常胃组织(P＜0.05),且在低分化胃癌中的表达显著高于高分化胃癌(P＜0.05),在淋巴转移胃癌中表达显著高于无淋巴转移胃癌(P＜0.05),在浸润穿过浆膜层的肿瘤组织中表达显著高于未穿过浆膜层的胃癌组织,在直径大于5cm肿瘤组织中表达显著高于小于5cm肿瘤组织.但在不同性别、年龄及不同分期、分型中表达无差异.结论: RRM1和RRM2的高表达与胃癌大小、浸润、分化、转移密切相关,可作为肿瘤预后不佳的标记物.

患者,女,70岁,汉族,青海西宁人.2016年8月11日因间断右上腹痛1月于青海大学附属医院肝胆胰外科住院入院治疗.患者1月前无明显诱因出现右上腹部疼痛不适,呈间断性胀痛,消化、循环、呼吸等其他系统无特殊症状,自行口服“消炎利胆片”后症状无明显缓解.入院前半个月上述症状明显加重,甚至无法行走.入院查体:体温36.2℃,心率80次/min,呼吸20次/min,血压115/70 mm Hg(1 mm Hg=0.133 kPa);神志清,精神欠佳,应答切题,思维敏捷;全身皮肤黏膜及巩膜无黄染,浅表淋巴结无肿大,无肝掌及蜘蛛痣,无明显腹壁静脉曲张.双肺呼吸音清,未闻及明显干湿性啰罗音,心律齐,无心脏杂音;全腹稍紧张,右上腹可明显触及一包块,约15 cm×10 cm,压痛阳性,质硬,活动度欠佳;无反跳痛,肝肋下三指余,脾肋下未触及,移动性浊音阴性.