Myocardial ischemia–reperfusion injury (MIRI) remains a major challenge in reperfusion therapy for acute myocardial infarction. The role of deubiquitinating enzyme ubiquitin-specific protease 43 (USP43) in this process, however, remains largely unexplored. In this study, we found that USP43 expression was significantly upregulated in murine hearts subjected to ischemia/reperfusion and in primary cardiomyocytes following hypoxia/reoxygenation. Genetic knockout of Usp43 conferred substantial protection against ischemia/reperfusion-induced myocardial injury, inflammation, and cardiomyocyte death, whereas cardiac-specific overexpression of USP43 exacerbated these detrimental effects. Consistent with these findings, USP43 knockdown attenuated hypoxia/reoxygenation-induced damage in primary cardiomyocytes, while its overexpression promoted cell death. Mechanistically, integrated transcriptomic and biochemical assays revealed apoptosis signal-regulating kinase 1 (ASK1) as a key USP43 substrate. USP43 directly binds to ASK1 and removes its K48-linked ubiquitin chains, thereby shielding ASK1 from proteasomal degradation. This post-translational modification leads to ASK1 protein stabilization and hyperactivation of the downstream ASK1-JNK/P38 mitogen-activated protein kinase (MAPK) signaling. Importantly, pharmacologically inhibiting ASK1 rescued the detrimental phenotype caused by USP43 overexpression. In summary, we identify USP43 as a novel regulator that exacerbates MIRI by promoting ASK1-mediated cell death. Targeting the USP43-ASK1 signaling axis may therefore warrant further investigation as a research target to elucidate the mechanisms of MIRI.

This study investigated the role of long-chain acyl-CoA dehydrogenase (ACADL) in lung adenocarcinoma (LUAD). ACADL was significantly downregulated in human LUAD tissues compared to normal lung tissues. In vitro, ectopic expression of ACADL in murine LLC cells decreased cell viability, migration, and invasion, while ACADL knockdown exhibited the opposite effect. In vivo, ACADL overexpression impeded tumor growth and metastasis. Mechanistically, ACADL hindered tumor progression by inducing cell cycle arrest, promoting apoptosis, and suppressing the epithelial-mesenchymal transition (EMT) process. These findings suggest ACADL acts as a tumor suppressor in LUAD progression.

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence and mortality rates. NFKBIZ, a member of the nuclear factor kappa B inhibitory family, is closely related to tumor progression. However, the precise role of NFKBIZ in HCC remains unclear. To explore this, we conducted a series of experiments from clinic to cells. Western blot and qPCR revealed a significant downregulation of NFKBIZ in human HCC tissues. Clinical character analysis showed that the patients with lower NFKBIZ expression had poorer prognosis and higher clinical stage. By using CCK-8, wound healing, transwell invasion and migration assay, we discovered that NFKBIZ expression was reversely associated with the proliferation, invasion, and migration ability of HCC cells in vitro. Additionally, the results obtained from xenograft assay and lung metastasis models showed that NFKBIZ overexpression inhibited the growth and metastasis of HCC cells in vivo. Western blot and immunofluorescence assay further revealed that NFKBIZ mediated HCC cell growth and migration by regulating NFκB signaling transduction. Finally, flow cytometry, protein degradation assay and Co-immunoprecipitation indicated that TRIM16 can enhance NFKBIZ ubiquitination by direct interactions at its K48 site, which may thereby alleviate HCC cell apoptosis to induce the insensitivity to sorafenib. In conclusion, our study demonstrated that NFKBIZ regulated HCC tumorigenesis and metastasis by mediating NFκB signal transduction and TRIM16/NFKBIZ/NFκB axis may be the underlying mechanism of sorafenib insensitivity in HCC.

Primary liver cancer is known for its high incidence and fatality rate. Over the years, therapeutic strategies for primary liver cancer have advanced significantly. Nonetheless, a substantial number of patients have not benefited from these methods, underscoring the pressing need for new and effective treatments for primary liver cancer. Ubiquitination is a critical post-translational modification that enables proteins to fulfill their normal biological functions and maintain their expression stability within cells. Importantly, increasing evidence suggests that the progression of liver cancer cells is often accompanied by disruptions in protein ubiquitination and deubiquitination processes. In this comprehensive review, we have compiled pertinent research about dysregulated ubiquitination in hepatocellular carcinoma (HCC) to broaden our understanding in this field. We elucidate the connections between the ubiquitination proteasome system, deubiquitination, and HCC. Furthermore, we shed light on the role of ubiquitination in cells situated within the tumor microenvironment of HCC including its involvement in mediating the activation of oncogenic pathways, reprogramming metabolic processes, and perturbing normal cellular functions. In conclusion, targeting the dysregulation of ubiquitination in HCC holds promise as a prospective and complementary therapeutic approach to existing treatments.

43岁男性患者，咳嗽、呼吸困难半个月。既往于外院确诊气管远段腺样囊性癌，并接受内镜下治疗，未能根治。入院后行气管镜及胸部CT检查示病变长约2 cm，下缘距离隆凸约2 cm，上缘距声带约8 cm。在体外膜肺氧合辅助下，行机器人辅助气管远段肿瘤切除+气管端端吻合术。术后顺利出院，随访未见气管吻合口狭窄或复发。

In this study we sought to analyze the critical role of oxidized phospholipid (OxPL) in the progression of calcific aortic valve disease (CAVD) with the involvement of activating transcription factor 4 (ATF4). Differentially expressed genes related to CAVD were identified using bioinformatics analysis. Expression of ATF4 was examined in mouse models of aortic valve calcification (AVC) induced by the high cholesterol (HC) diet. Valvular interstitial cells (VICs) were then isolated from mouse non-calcified valve tissues, induced by osteogenic induction medium (OIM) and co-cultured with OxPAPC-stimulated macrophages. The effect of OxPLs regulating ATF4 on the macrophage polarization and osteogenic differentiation of VICs was examined with gain- and loss-of-function experiments in VICs and in vivo. In aortic valve tissues and OIM-induced VICs, ATF4 was highly expressed. ATF4 knockdown alleviated the osteogenic differentiation of VICs, as evidenced by reduced expression of bone morphogenetic protein-2 (BMP2), osteopontin (OPN), and osteocalcin. In addition, knockdown of ATF4 arrested the AVC in vivo. Meanwhile, OxPL promoted M1 polarization of macrophages and mediated osteogenic differentiation of VICs. Furthermore, OxPL up-regulated ATF4 expression through protein kinase R-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2 subunit alpha (eIF2α) pathway. In conclusion, OxPL can potentially up-regulate the expression of ATF4, inducing macrophages polarized to M1 phenotype, osteogenic differentiation of VICs and AVC, thus accelerating the progression of CAVD.

The tumor microenvironment (TME) has become a major research focus in recent years. The TME differs from the normal extracellular environment in parameters such as nutrient supply, pH value, oxygen content, and metabolite abundance. Such changes may promote the initiation, growth, invasion, and metastasis of tumor cells, in addition to causing the malfunction of tumor-infiltrating immunocytes. As the neoplasm develops and nutrients become scarce, tumor cells transform their metabolic patterns by reprogramming glucose, lipid, and amino acid metabolism in response to various environmental stressors. Research on carcinoma metabolism reprogramming suggests that like tumor cells, immunocytes also switch their metabolic pathways, named “immunometabolism”, a phenomenon that has drawn increasing attention in the academic community. In this review, we focus on the recent progress in the study of lipid metabolism reprogramming in immunocytes within the TME and highlight the potential target molecules, pathways, and genes implicated. In addition, we discuss hypoxia, one of the vital altered components of the TME that partially contribute to the initiation of abnormal lipid metabolism in immune cells. Finally, we present the current immunotherapies that orchestrate a potent antitumor immune response by mediating the lipid metabolism of immunocytes, highlight the lipid metabolism reprogramming capacity of various immunocytes in the TME, and propose promising new strategies for use in cancer therapy.

Objective. To clarify the protective effect of simvastatin on myocardial ischemia reperfusion injury (MIRI) and the underlying mechanism. Materials and Methods. The MIRI model in rats was firstly constructed. Twenty-four male rats were randomly assigned into the sham group, ischemia-reperfusion (I/R) group, and simvastatin group, with 8 rats in each group. Contents of superoxide dismutase (SOD) and malondialdehyde (MDA), as well as serum levels of CK and inflammatory factors, in rats were determined by the enzyme-linked immunosorbent assay (ELISA). Lactate dehydrogenase (LDH) activity in the three groups was examined. Through flow cytometry and Cell Counting Kit-8 (CCK-8) assay, apoptosis and viability in each group were detected, respectively. Relative levels of HMGB1, Kruppel-like factor 2 (KLF2), eNOS, and thrombomodulin (TM) were finally determined. Results. Simvastatin treatment markedly enhanced SOD activity and reduced contents of MDA, LDH, and creatine kinase (CK) in MIRI rats. The increased apoptosis and decreased viability following MIRI were partially reversed by simvastatin treatment. Besides, MIRI resulted in the upregulation of inflammatory factors and chemokines. Their elevations were abolished by simvastatin. In MIRI rats, simvastatin upregulated KLF2 and p-eNOS. Conclusions. Simvastatin protects inflammatory response at post-MIRI through upregulating KLF2, thus improving cardiac function.

方法:前路锁定钢板联合加压螺钉行踝关节融合治疗创伤性踝关节炎临床效果.方法:选择2010年1月—2016年12月在我院接受治疗的创伤性踝关节炎患者35例,均经前路锁定钢板联合加压螺钉行踝关节融合术进行治疗,术后随访12个月,分析治疗效果.结果:创伤性踝关节炎35例均达到骨性融合标准,融合时间3～7个月,平均(3.51±0.75)个月,末次随访VAS评分0～5(1.18±0.49)分显著低于术前5～9(7.42±0.67)分(P<0.05);末次随访AOFAS评分72～90(83.55±5.34)分显著高于术前的16～45(31.86±7.70)分(P<0.05).结论:前路锁定钢板联合加压螺钉行踝关节融合治疗创伤性踝关节炎临床效果较好.

目的 探讨加长型股骨近端防旋髓内钉(proximal femoral nail anti-rotation,PFNA)内固定在股骨近端伴股骨干骨折患者中的应用效果.方法 选取舞阳县妇幼保健院2014年5月至2017年5月收治的86例股骨近端伴股骨干骨折患者,依据手术方式分为对照组(Gamma钉内固定治疗)与观察组(加长型PFNA内固定治疗),各43例.比较两组手术情况(手术时间、股骨近端骨折时间、股骨干骨折愈合时间)及关节功能恢复情况.结果 观察组手术时间、股骨近端骨折及股骨干骨折愈合时间短于对照组,差异有统计学意义(P<0.05);观察组关节功能恢复优良率(97.67％)高于对照组(74.42％),差异有统计学意义(P<0.05).结论 加长型股骨近端防旋髓内钉内固定治疗股骨近端伴股骨干骨折的效果显著,可缩短手术时间、股骨干骨折愈合时间、股骨近端骨折愈合时间,改善关节功能,值得推广应用.

目的 调查心脏机械瓣膜置换术后患者华法林抗凝治疗依从性及其影响因素.方法 采用便利抽样法,选取2016年5月至2017年2月于郑州大学第一附属医院心脏外科行心脏机械瓣膜置换术后应用华法林抗凝治疗的185例患者,术后3个月调查其华法林用药知识水平及服药依从性,并探讨华法林抗凝治疗依从性的影响因素.结果 心脏机械瓣膜置换术后应用华法林抗凝治疗依从性良好者占75.1％,依从性较差者占24.9％.Logistic回归分析显示,文化程度越高、疾病严重程度越重、华法林用药知识水平越高的患者,华法林抗凝治疗依从性越高.结论 心脏机械瓣膜置换术后患者华法林抗凝治疗依从性欠佳,文化程度、疾病严重程度、华法林用药知识水平影响患者华法林抗凝治疗依从性.

Objective To evaluate the short-term follow-up of valve-sparing aortic root replacement in Marfan syndrome. Methods 54 patients, 38 males and 16 females;aged(20-50) years, mean(31. 26 ± 7. 80) years old. They were all diag-nosed with Marfan syndrome according to the criteria of Ghent in 1996. Preoperative ultrasound showed 5 cases with trace aortic valve regurgitation, a small amount of reflux in 12 cases, 22 cases in the middle amount of regurgitation, 15 cases with a large number of reflux. According to the surgery program it was devided into 2 groups, Bentall group(35 cases, Bentall surgery) and David group(19 cases, David surgery). Follow-up 12 months to 48 months, to compare the differences of the efficacy of differ-ent surgical options,before and after surgery. Results 2 cases died after operation, one patient in group bentall died of uncon-trollable bleeding and the other in group David died of pulmonary infection, multiple organ failure, and the remaining 52 cases recoveredwell.GroupbentallwhichCPB(141.09±15.483)min,aorticocclusion(93.82±15.06)min. GroupDavid,CPB (186.32 ±23.96)min, aortic occlusion(140.21 ±22.13) min. There are significant differences in postoperative EF value, left ventricular diameter and postoperative left ventricular systolic volume ( ESV ) , postoperative left ventricular end-diastolic volume(EDV), FS improvement with preoperative data(P<0. 05), and there were no significant differences(P>0. 05) be-tween the two groups. The early postoperative complications were no significant difference between the tuo groups, bue the late complications in group bentall was significantly higher than groups David. Patients were followed up for 12 months to 48 months, one patient in David group underwent aortic valve replacement surgery because of severe aortic regurgitation. One case ( abdominal aorta) in group Bentall underwent surgery due to recurrent dissection and 6 cases with bleeding, embolic complica-tions because of warfarin. Conclusion Valve sparing root replacement has provided satisfactory short-term outcomes for Marfan syndrome.

心脏血管瘤是一种十分罕见的原发性良性肿瘤,其临床表现主要取决于肿瘤的部位和大小,最常见的症状为心慌、胸闷、憋气及胸痛等.组织学上可将心脏血管瘤分为海绵状血管瘤、毛细血管瘤、蔓状血管瘤等,毛细血管瘤和海绵状血管瘤发生率相对较高[1].心脏海绵状血管瘤为体积小、有蒂或无蒂、海绵状结构,瘤体由不规则的血窦构成,窦间以纤维小梁分隔,瘤体与心壁间界限不清晰,即使在瘤体中心部的血管窦纤维间隔有时亦可见散在的心肌细胞[2].本研究选取郑州大学第一附属医院收治1例右心室海绵状血管瘤患者,对其临床特点、组织病理学检查结果进行总结,具体如下.

Objective To establish the original generation of myocardial cells in vitro anoxia/reoxygenation (H/R) model,then to explore the optimum concentration of curcumin post-processing on protection of primary Myocardial cell during hypoxia/reoxygenation (H/R) Injury.Methods The experimental group was divided into 5 groups:normal control group;H/R group;Curcumin concentrations (1,5,10 μmol/L) + H/R group.Through the cell activity determined by methyl thiazol tetrazolium (MTr)method and test lactate dehydrogenase (LDH) activity and malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity evaluation of cell damage;To detect apoptosis rate by TdT-mediated dUTP nick end labeling (TUNEL) method.Results Compared with control group,cell activity decrease in H/R group (P =0.001),the curcumin group significantly enhanced the activity of cells,especially in the 10 μmol/L group (P =0.017);Compared with control group,the curcumin group of different concentrations significantly decreased the activity of LDH,decreased MDA concentration,increased SOD activity and improve the myocardial cell apoptosis after H/R damage rate significantly.Among them,the effect of 10 μmol/L group was the most obvious (P =0.011,0.001,0.009,0.007),and there was no significant difference compared with the control group (P =0.129,0.083,0.134).Conclusion On the basis of the success of the model,curcumin of different concentrations have protective effects on myocardial cells,anti oxidative stress and anti apoptosis,the concentration of 10 μmol/L is optimum.

OBJECTIVE:To summarize the outcome of tricuspid valve replacement.METHODS:A total of 28 patients (15 males and 13 females) underwent tricuspid valve replacement from March 2000 to February 2015 in the First Affiliated Hospital of Zhengzhou University were recruited. Among them, 16 patients were Ebstein's anomaly, 7 had rheumatic valve heart disease, 3 and 2 suffered from infective endocarditis and degenerative tricuspid lesions, respectively.RESULTS:One patient died of multiple organ failure. Four patients were implanted permanent cardiac pacemaker because of third degree atrioventricular block occurring in the 5th day (2 patients) and in the 9th day (2 patients) after the operation, respectively. Twenty-seven patients were followed up from 1 month to 15 years. The prosthetic valves and permanent pacemakers worked well.CONCLUSION:Third degree of atrioventricular block, mostly appearing in early postoperative period, is the most common and severe complication of tricuspid valve replacement. The key point for prevention of damage is to accurately identify the anatomical relationship among the tricuspid valve, atrioventricular node, and conduction bundle.

主动脉窦瘤是一种临床上少见的心脏疾病，病情凶险，需尽早手术。由主动脉窦瘤破裂所引起的感染性心内膜炎（ infective endocarditis ， IE ），更增加了手术的难度及凶险。2008年1月至2015年1月，作者共收治了16例主动脉窦瘤破裂（ ruptured sinus of valsalva aneurysm，RSVA）合并IE的患者，术后效果满意，现总结治疗体会，报道如下。

小左心室及中重度肺动脉高压是二尖瓣狭窄的终末期病理改变,其诊断标准[1]多采用左心室舒张末期容积指数≤60ml/m2,肺动脉高压中重度以SPAP>50mmHg为划分标准. 临床手术治疗风险较大,其在手术治疗及围术期处理方面存在争论及特殊之处,我科于2010年1月~2015 年6月手术治疗此重症患者78例,现报道如下.

目的 总结心脏肿瘤的诊断与治疗经验.方法 回顾性分析我院2011～2014年103例心脏肿瘤患者的临床资料,其中男38例、女65例,年龄3个月至82岁,平均(59.71±13.80)岁.分析患者年龄分布、临床表现,肿瘤大小及分布位置、手术治疗方式及其效果.结果 全组患者无手术死亡,术后早期并发症有心律失常47例,电解质紊乱13例,心功能不全9例.B细胞非何奇金淋巴瘤患者因术后心功能不全而自动出院,术后随访1个月至4年,心脏粘液瘤患者均无复发,2例脂肪瘤患者无复发,1例良性肌源性肿瘤患者失访,6例恶性肿瘤患者远期预后差,2例患者失访,4例患者1年内由于肿瘤复发死亡.结论 心脏肿瘤外科手术切除仍然是最有效、最主要的治疗手段.