Identification of tumor-suppressor genes in lung squamous cell carcinoma through integrated bioinformatics analyses

Lung cancer is a prevalent malignancy,and fatalities of the disease exceed 400,000 cases worldwide.Lung squamous cell carcinoma(LUSC)has been recognized as the most common pathological form of lung cancer.The comprehensive understanding of molecular features related to LUSC progression has great significance in LUSC prognosis assessment and clinical management.In this study,we aim to identify a panel of signature genes closely associated with LUSC,which can provide novel insights into the progression of LUSC.Gene expression profiles were retrieved from public resources including gene expression omnibus(GEO)and the cancer genome atlas(TCGA)database.Differentially expressed genes(DEGs)between LUSC specimens and normal lung tissues were identified by bioinformatics analyses.A total of 66 DEGs were identified based on two cohorts of data.CytoHubba plugin of Cytoscape software was utilized for the further analyses of the top 10 candidate hub genes including OGN,ABI3BP,MAMDC2,FGF7,FAM107A,SPARCL1,DCN,COL14A1,and MFAP4 and CHRDL1,which showed significant downregulation in LUSC.Two LUSC cell lines were used to validate the functions of CHRDL1 and FAM107A through overexpression experiment.Together,our data revealed novel candidate tumor-suppressor genes in LUSC,suggesting previously unappreciated mechanisms in the progression of LUSC.

Surgical management of duodenal Crohn's disease

BACKGROUND The case of Crohn's disease involving the duodenum is rare,and its surgical management requires a thorough understanding.AIM To investigate the surgical management of duodenal Crohn’s disease.METHODS We systematically reviewed patients diagnosed with duodenal Crohn's disease who underwent surgery in the Department of Geriatrics Surgery of the Second Xiangya Hospital of Central South University from January 1,2004,to August 31,2022.The general information,surgical procedures,prognosis,and other information of these patients were collected and summarized.RESULTS A total of 16 patients were diagnosed with duodenal Crohn’s disease,where 6 cases had primary duodenal Crohn’s disease,and 10 had secondary duodenal Crohn’s disease.Among patients with primary disease,5 underwent duodenal bypass and gastrojejunostomy,and 1 received pancreaticoduodenectomy.Among those with a secondary disease,6 underwent closure of duodenal defect and colectomy,3 received duodenal lesion exclusion and right hemicolectomy,and 1 underwent duodenal lesion exclusion and double-lumen ileostomy.CONCLUSION Crohn's disease involving the duodenum is a rare condition.Different surgical management should be applied for patients with Crohn's disease presenting with different clinical manifestations.

Correlation of S1P1 and ERp29 expression to progression, metastasis, and poor prognosis of gallbladder adenocarcinoma

BACKGROUND: Gallbladder cancer (GBC) is one of the most aggressive malignant neoplasms with an extremely poor prognosis. Early diagnosis significantly increases the survival rate. The present study was undertaken to evaluate the diagnostic and prognostic value of sphingosine-1-phosphate receptor 1 (S1P1) and endoplasmic reticulum protein 29 (ERp29) in benign and malignant gallbladder lesions and to develop a possible alternative treatment for GBC. METHODS: A total of 100 gallbladder adenocarcinoma, 46 peritumoral, 30 gallbladder adenomatous, 15 gallbladder polyp and 35 chronic cholecystitis tissues were included. S1P1 and ERp29 expressions were evaluated by immunohistochemistry The correlation between S1P1 and ERp29 expression and tumor pathological features and prognosis was analyzed. RESULTS: S1P1 positive rate was significantly higher in gallbladder adenocarcinomas than that in peritumoral adenomatous, polyp, and chronic cholecystitis tissues. On the contrary, ERp29 positive rate was significantly lower in adenocarcinomas than that in peritumoral, adenomatous polyp, and chronic cholecystitis tissues. Benign lesions with positive S1P1 or negative ERp29 expression showed moderate or severe atypical hyperplasia in the gallbladder epithelium The overexpression of S1P1 or non-expression of ERp29 was significantly associated with tumor differentiation, tumor mass, lymph node metastasis, and adenocarcinoma invasion Univariate Kaplan-Meier analysis showed that the elevated S1P1 (P=0.008) or absence of ERp29 (P=0.043) was closely associated with decreased survival rate. Multivariate Cox regression analysis showed that S1P1 positive (P=0.004) or ERp29 negative (P=0.029) was an independent predictor of poor prognosis in gallbladder adenocarcinoma.CONCLUSION: S1P1 overexpression or ERp29 absence is related to the carcinogenesis and progression, and may be potential biomarkers for early detection of gallbladder adenocarcinoma.

Comparison of survival between adolescent and young adult vs older patients with hepatocellular carcinoma

BACKGROUND Due to the special clinical features and biologic characteristics of adolescent and young adult(AYA)cancers,AYA cancers are different from cancers in children and elderly individuals.However,there are few reports on AYA hepatocellular carcinoma(HCC).AIM To investigate the overall survival(OS)of AYA(15-39 years)and elderly(40-74 years)patients with HCC.METHODS The data of all the HCC cases were extracted from the Surveillance,Epidemiology,and End Results database from 2004 to 2015 and were then divided into two groups based on age:AYA group(15-39 years)and older group(40-74 years).Kaplan-Meier curves and log-rank tests were used to compare the OS of the two groups.Propensity score matching(PSM)was employed to analyze the OS difference between the two groups.The Cox proportional hazards regression model was used to perform multivariate analysis to explore the risk factors for OS of HCC patients.RESULTS Compared to elderly cancer patients,AYA patients with HCC had a worse Surveillance,Epidemiology,and End Results stage,including the distant stage(22.1%vs 15.4%,P<0.001),and a more advanced American Joint Committee on Cancer(AJCC)stage,including AJCC III and IV(49.2%vs 38.3%,P<0.001),and were more likely to receive surgery(64.5%vs 47.5%,P<0.001).Before PSM,the AYA group had a longer survival in months(median:20.00,interquartile range[IQR]:5.00-62.50)than the older group(median:15.00,IQR:4.00-40.00)(P<0.001).After PSM,the AYA group still had a longer survival in months(median:21.00,IQR:5.00-64.50)than the older group(median:18.00,IQR:6.00-53.00)(P<0.001).The Cox proportional hazards regression model showed that advanced age(hazard ratio[HR]=1.405,95%CI:1.218-1.621,P<0.001)was a risk factor for OS of HCC patients.In the subgroup analysis,the Cox proportional hazards regression model showed that in AJCC I/II HCC patients,advanced age(HR=1.749,95%CI:1.352-2.263,P<0.001)was a risk factor for OS,while it was not a risk factor in AJCC III/IV HCC patients(HR=1.186,95%CI:0.997-1.410,P=0.054)before PSM.After PSM,advanced age(HR=1.891,95%CI:1.356-2.637,P<0.001)was still a risk factor for OS in AJCC I/II HCC patients,but was not a risk factor for OS in AJCC III/IV HCC patients(HR=1.192,95%CI:0.934-1.521,P=0.157)after PSM.CONCLUSION AYA patients with HCC have different clinical characteristics from older adults.In different AJCC stages,the two groups of patients have different OS:In AJCC I/II HCC patients,advanced age is a risk factor for OS,but it is not a risk factor for OS in the AJCC III/IV HCC patient group.

Fork head box M1 regulates vascular endothelial growth factor-A expression to promote the angiogenesis and tumor cell growth of gallbladder cancer

BACKGROUND Gallbladder cancer(GBC)is an aggressive type of biliary tract cancer that lacks effective therapeutic targets.Fork head box M1(FoxM1)is an emerging molecular target associated with tumor progression in GBC,and accumulating evidence suggests that vascular endothelial growth factor(VEGF)promotes various tumors by inducing neoangiogenesis.AIM To investigate the role of FoxM1 and the angiogenesis effects of VEGF-A in primary GBC.METHODS Using immunohistochemistry,we investigated FoxM1 and VEGF-A expression in GBC tissues,paracarcinoma tissues and cholecystitis tissues.Soft agar,cell invasion,migration and apoptosis assays were used to analyze the malignant phenotype influenced by FoxM1 in GBC.Kaplan-Meier survival analysis was performed to evaluate the impact of FoxM1 and VEGF-A expression in GBC patients.We investigated the relationship between FoxM1 and VEGF-A by regulating the level of FoxM1.Next,we performed MTT assays and Transwell invasion assays by knocking out or overexpressing VEGF-A to evaluate its function in GBC cells.The luciferase assay was used to reveal the relationship between FoxM1 and VEGF-A.BALB/c nude mice were used to establish the xenograft tumor model.RESULTS FoxM1 expression was higher in GBC tissues than in paracarcinoma tissues.Furthermore,the high expression of Foxm1 in GBC was significantly correlated with a malignant phenotype and worse overall survival.Meanwhile,high expression of FoxM1 influenced angiogenesis;high expression of FoxM1 combined with high expression of VEGF-A was related to poor prognosis.Attenuated FoxM1 significantly suppressed cell proliferation,transfer and invasion in vitro.Knockdown of FoxM1 in GBC cells reduced the expression of VEGF-A.Luciferase assay showed that FoxM1 was the transcription factor of VEGF-A,and knockdown VEGF-A in FoxM1 overexpressed cells could partly reverse the malignancy phenotype of GBC cells.In this study,we found that FoxM1 was involved in regulation of VEGF-A expression.CONCLUSION FoxM1 and VEGF-A overexpression were associated with the prognosis of GBC patients.FoxM1 regulated VEGF-A expression,which played an important role in the progression of GBC.

Potential roles of vitamin D binding protein in attenuating liver injury in sepsis

Background:In sepsis,vitamin D binding protein(VDBP)has been shown to be low-expressed.The current study examined the relationship between serum VDBP level and liver injury in sepsis patients,as well as in a mouse model for sepsis and in cultured liver epithelial cell line exposed to lipopolysaccharide(LPS).Methods:The human study included 78 sepsis patients and 50 healthy volunteers.Sepsis patients were categorized into sepsis survivor group(n=43)and sepsis non-survivor group(n=35)based on 28-day mortality for data analysis.Adult male C57BL/6 mice were subjected to cecal ligation and puncture(CLP).Serum samples were collected on day 1,3,5 and 7 to determine the levels of VDBP,25-hydroxyvitamin D[25(OH)D_(3)],1,25-dihydroxyvitamin D[1,25(OH)_(2)D_(3)],interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α).Potential protective effects of VDBP overexpression against LPS-induced liver damage were examined in cultured THLE2 cells.Results:Serum levels of VDBP,25(OH)D_(3),and 1,25(OH)_(2)D_(3)were significantly lower in sepsis patients vs.the healthy control(P<0.001),as well as in the sepsis non-survivor group vs.the sepsis survivor group(P<0.001,P=0.0338,or P=0.0013,respectively).Lower serum VDBP level was associated with higher Acute Physiology and Chronic Health Evaluation(APACHE)II score(r=−0.2565,P=0.0234)and Sequential Organ Failure Assessment score(r=−0.3522,P=0.0016),but lower serum albumin(ALB,r=0.4628,P<0.001)and total protein(TP,r=0.263,P=0.02).In CLP mice,there was a 5-day period of serum VDBP reduction,followed by return towards the baseline on day 7.VDBP was also decreased in LPS-treated THLE2 cells(P<0.001).VDBP overexpression reduced LPS-induced THLE2 damage.Reduced damage was associated with decreased oxidative stress and inactivation of the c-Jun N-terminal kinase signaling pathway.Conclusion:VDBP may be protective against sepsis-induced liver injury.

Could extracellular vesicles derived from mesenchymal stem cells be a potential therapy for acute pancreatitis-induced cardiac injury?

Acute pancreatitis(AP)often leads to a high incidence of cardiac injury,posing significant challenges in the treatment of severe AP and contributing to increased mortality rates.Mesenchymal stem cells(MSCs)release bioactive molecules that participate in various inflammatory diseases.Similarly,extracellular vesicles(EVs)secreted by MSCs have garnered extensive attention due to their comparable anti-inflammatory effects to MSCs and their potential to avoid risks associated with cell transplantation.Recently,the therapeutic potential of MSCs-EVs in various inflammatory diseases,including sepsis and AP,has gained increasing recognition.Although preclinical research on the utilization of MSCs-EVs in AP-induced cardiac injury is limited,several studies have demonstrated the positive effects of MSCs-EVs in regulating inflammation and immunity in sepsis-induced cardiac injury and cardiovascular diseases.Furthermore,clinical studies have been conducted on the therapeutic application of MSCs-EVs for some other diseases,wherein the contents of these EVs could be deliberately modified through prior modulation of MSCs.Consequently,we hypothesize that MSCs-EVs hold promise as a potential therapy for AP-induced cardiac injury.This paper aims to discuss this topic.However,additional research is essential to comprehensively elucidate the underlying mechanisms of MSCs-EVs in treating AP-induced cardiac injury,as well as to ascertain their safety and efficacy.

Glucose metabolism in gastric cancer:The cutting-edge

Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis(Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for early detection, diagnosis, prognosis, and chemosensitivity prediction of gastric cancer. Interfering with the process of glycolysis in cancer cells may provide a new and promising therapeutic strategy for gastric cancer. In this article, we present a brief review of recent studies of glucose metabolism in gastric cancer, with primary focus on the clinical applications of new biomarkers and their potential therapeutic role in gastric cancer.

Magnetic-assisted laparoscopic liver transplantation in swine

Background:Although laparoscopic technology has achieved rapid development in the surgical field,it has not been applied to liver transplantation,primarily because of difficulties associated with laparoscopic vascular anastomosis.In this study,we introduced a new magnetic-assisted vascular anastomosis technique and explored its application in laparoscopic liver transplantation in pigs.Methods:Two sets of magnetic vascular anastomosis rings(MVARs)with different diameters were developed.One set was used for anastomosis of the suprahepatic vena cava(SHVC)and the other set was used for anastomosis of the infrahepatic vena cava(IHVC)and portal vein(PV).Six laparoscopic orthotopic liver transplantations were performed in pigs.Donor liver was obtained via open surgery.Hepatectomy was performed in the recipients through laparoscopic surgery.Anastomosis of the SHVC was performed using hand-assisted magnetic anastomosis,and the anastomosis of the IHVC and PV was performed by magnetic anastomosis with or without hand assistance.Results:Liver transplants were successfully performed in five of the six cases.Postoperative ultrasonographic examination showed that the portal inflow was smooth.However,PV bending and blood flow obstruction occurred in one case because the MVARs were attached to each other.The durations of loading of MVAR in the laparoscope group and manual assistance group for IHVC and PV were 13±5 vs.5±1 min(P<0.01)and 10±2 vs.4±1 min(P<0.05),respectively.The durations of MVAR anastomosis in the laparoscope group and manual assistance group for IHVC and PV were 5±1 vs.1±1 min(P<0.01),and 5±1 vs.1±1 min(P<0.01),respectively.The anhepatic phase was 43±4 min in the laparoscope group and 23±2 min in the manual assistance group(P<0.01).Conclusions:Our study showed that magnetic-assisted laparoscopic liver transplantation can be successfully carried out in pigs.

Reactive oxygen species-based nanomaterials for the treatment of myocardial ischemia reperfusion injuries

Interventional coronary reperfusion strategies are widely adopted to treat acute myocardial infarction,but morbidity and mortality of acute myocardial infarction are still high.Reperfusion injuries are inevitable due to the generation of reactive oxygen species(ROS)and apoptosis of cardiac muscle cells.However,many antioxidant and anti-inflammatory drugs are largely limited by pharmacokinetics and route of administration,such as short half-life,low stability,low bioavailability,and side effects for treatment myocardial ischemia reperfusion injury.Therefore,it is necessary to develop effective drugs and technologies to address this issue.Fortunately,nanotherapies have demonstrated great opportunities for treating myocardial ischemia reperfusion injury.Compared with traditional drugs,nanodrugs can effectively increase the therapeutic effect and reduces side effects by improving pharmacokinetic and pharmacodynamic properties due to nanodrugs’size,shape,and material characteristics.In this review,the biology of ROS and molecular mechanisms of myocardial ischemia reperfusion injury are discussed.Furthermore,we summarized the applications of ROS-based nanoparticles,highlighting the latest achievements of nanotechnology researches for the treatment of myocardial ischemia reperfusion injury.

Who benefits from RO resection?A single-center analysis of patients with stage Ⅳ gallbladder cancer

Objectives:Most patients with gallbladder cancer(GBC)present with advanced-stage disease and have a poor prognosis.Radical resection remains the only therapeutic option to improve survival in patients with GBC.This study aimed to analyze the prognostic factors in patients with stageⅣGBC and to identify a subgroup of patients who might benefit from RO resection.Methods:A total of 285 patients with stageⅣGBC were retrospectively analyzed at our institution from January 2008 to December 2012.Factors potentially influencing the prognosis of GBC after surgery were analyzed by univariate and multivariate analyses.Results:The 1-,3-,and 5-year overall survival rates were 6.6%(15/229),0.9%(2/229),and 0(0/229),respectively.Ascites(relative risk[RR]=1.631,95%confidence interval[C/]:1.221-2.180,P=0.001),pathological grade(RR=1.337,95%Cl:1.050-1.702,P=0.018),T stage(RR=1.421,95%Cl:1.099-1.837,P=0.000),M stage(RR=1.896,95%Cl:1.409-2.552,P=0.000),and surgery(RR=1.542,95%Cl:1.022-2.327,P=0.039)were identified as independent risk factors influencing prognosis.The median survival time(MST)was significantly higher in patients undergoing R0 resection than in those undergoing R1/R2 resection(6.0 vs.2.7 months;P<0.001).In subgroup analyses,stage IVA patients benefited from R0 resection(MST for R0 vs.R1/R2,11.0 vs.4.0 months;P=0.003),while R0 resection had a significant survival benefit than R1/R2 resection in patient with stage IVB GBC without distant metastasis(MST for R0 vs.R1/R2,6.0 vs.3.0 months;P=0.007).Conclusion:Ascites,pathological grade,T stage,M stage,and surgery were independent risk factors influencing prognosis in patients with stageⅣGBC.N2 lymph node metastasis did not preclude curative resection,and radical resection should be considered in patients with stageⅣGBC without distant metastasis once R0 margin was achieved.

炎症相关caspase介导的细胞焦亡:机制、调控及对炎症性肠病的潜在治疗价值

作为程序性细胞死亡的一种新的形式,细胞焦亡是由细胞内病原体感染诱发的炎症反应。如果细胞焦亡被过度激活,会导致一些代谢性疾病、动脉粥样硬化以及重要器官损害。巨噬细胞是介导细胞焦亡的主要细胞,其模式识别受体可以识别宿主细胞胞质溶胶内的危险信号和病原微生物。炎症相关caspase的激活可诱发细胞焦亡并产生促炎细胞因子,如IL-1β和IL-18。炎性程序性细胞死亡基于炎症相关caspase的不同可分为经典途径和非经典途径,前者包括caspase-1(人类和小鼠),后者包括caspase-11(小鼠)或caspase-4和-5(人类)。炎症相关caspase的激活可切割成孔效应蛋白gasdermin-D,引起细胞渗透压的改变,继而导致胞膜破裂。炎症相关caspase可能成为炎症性肠病的潜在治疗靶点,而细胞焦亡在其中具有重要作用。本文对细胞焦亡的机制进行综述,并重点探讨了炎症相关caspase的调控及其对炎症性肠病的潜在治疗价值.

术后内脏脂肪组织及体质指数过度增加会引起回肠储袋不良结 局

背景:全结直肠切除、回肠储袋肛管吻合(IPAA)术后,内脏脂肪组织(VAT)的变化对于预后的影响,目前尚无相关报道。本项回顾性队列研究旨在评估VAT过度增加对行IPAA术的炎性肠病(IBD)患者临床结局的影响。方法:收集2002-2014年间我们的前瞻性储袋炎登记病例中,储袋手术后至少接受了2次序贯CT检查的患者。通过CT图像分析计算内脏脂肪面积(VFA)。将VAF增加>15%者归入研究组,VAF增长不足15%者作为对照组。储袋不良结局定义为在初次CT检查后出现储袋慢性炎症进展(慢性储袋炎、慢性封套炎或储袋克罗恩病)、储袋窦道形成或储袋失败,前两项统称为储袋混合事件。结果:在1564例登记病例中,59例(3.8%)在储袋手术后接受了至少2次CT检查,其中29例(49.2%)归入研究组,30例(50.8%)作为对照组。全组病例初次CT检查至最近一次CT检查的中位间隔时间为552天(312~598天)。两组患者储袋慢性炎症进展发生率分别为13.8%vs 3.3%(p=0.195),储袋窦道形成发生率分别为10.3%vs 0%(P=0.112),储袋混合事件发生率分别为24.1%vs 3.3%(P=0.026),储袋失败率分别为10.3%vs 6.7%(P=0.671)。Kaplan-Meier曲线显示,体质指数(BMI)过度增加(>10%)患者无储袋失败生存时间明显缩短(P=0.011)。多因素逐步回归分析显示,VAT过度增加是储袋不良结局的独立危险因素(OR=12.608,95%CI:1.190~133.538,P=0.035)。结论:在本组回肠储袋患者队列中,储袋手术后VAT或BMI的过度增加长远来看都可能导致储袋不良结局。

p53过表达可预测具有不典型增生不确定型黏膜改变的炎性肠病患者的瘤变风险

背景和目的:我们之前研究发现,具有不典型增生不确定型黏膜改变(IND)的炎性肠病(IBD)患者具有较高的瘤变风险,同时发现,p53和细胞角蛋白7免疫组化检测对于IBD相关的瘤变具有潜在的诊断价值。本研究旨在初步论证这两种标记物对于IBD-IND患者瘤变风险的预测价值。方法:我们从病理数据库中筛选出了44例符合研究纳入标准且经组织学证实的IBD-IND患者。采用免疫组化方法对所有结肠标本进行p53和细胞角蛋白7的半定量检测,分析这两种标记物的表达、人口统计学特征及临床资料与结直肠瘤变的相关性。结果:本组病例平均年龄(46.6–15.1)岁,男性患者25例(56.8%)。在IND诊断后,中位随访101(6–247)月。11例(25%)患者在随访期间发生瘤变,其中低级别上皮内瘤变6例,高级别上皮内瘤变3例,癌变3例。这11例患者的中位随访时间为66(19–145)月。单因素分析显示,年龄和p53过表达与瘤变相关。结论:有25%的IBD-IND患者会进展为不典型增生或癌。p53过表达和年龄与IND-IBD的瘤变相关。