BACKGROUND:Gastric cancer (GC) seriously affects the life and health of patients, and the role of Elp3 in GC is still unclear; therefore, the aim of this study was to investigate the role and mechanism of Elp3 overexpression in GC. METHODS:Elp3-overexpressing HGC27 cells were constructed with an overexpression plasmid, and Elp3-overexpressing GC nude mice were prepared, which were intervened by histone acetylation inhibitor (SAHA) or JNK pathway inhibitor (SP600125). The protein interactions between Elp3 and JNK1 were verified by Co-immunoprecipitation (Co-IP) assay. Cell proliferation, migration, invasion, JNK/MAPK pathway, and histopathological changes were evaluated with CCK-8, clone formation assay, scratch assay, Transwell, qRT-PCR, western blot, and HE staining. RESULTS:Elp3 interacted with JNK1 protein, and Elp3 overexpression promoted GC proliferation, invasion, migration, elevated HAT activity, and activation of the JNK/MAPK pathway. A histone acetylation inhibitor attenuated the promotional effect of Elp3 overexpression on GC and activation of the JNK/MAPK pathway. Further, inhibition of the JNK/MAPK pathway also suppressed the promotion of GC by Elp3 overexpression. CONCLUSION:Elp3 may be involved in GC progression by activating the JNK/MAPK pathway through histone acetylation.

Bile reflux, resulting from pancreaticobiliary reflux (PBR), not only alters the chemical of bile but also constitutes a significant risk factor for the occurrence and development of gallbladder cancer. In previous studies, the authors identified a marked elevation of palmitic acid (PA) levels in the bile of patients with PBR. This study seeks to elucidate the mechanisms of promoting the migration of gallbladder cancer cells, with the objective of contributing novel strategies and theoretical foundations for the treatment of gallbladder cancer. We performed a cytotoxicity screening on the NOZ and GBC-SD human gallbladder cancer cell line using varying concentrations of palmitic acid. These following methodologies were employed to investigate the mechanism of PA in NOZ and GBC-SD cells. Intracellular lipid droplet accumulation was assessed using Oil red O staining, while cell migration capability was evaluated through the Transwell migration assay. Reactive oxygen species (ROS) levels were quantified using the superoxide anion fluorescent probe, Dihydroethidium (DHE), in conjunction with a ROS detection kit. The expression levels of relevant genes and proteins were analyzed using Western blot (WB), quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence (IF) techniques. In NOZ and GBC-SD cells, it was observed that palmitic acid facilitates the accumulation of intracellular lipid droplets and diminishes cellular activity while augmenting the cells’ migratory capacity. Furthermore, elevated concentrations of PA have been shown to increase ROS levels in NOZ and GBC-SD cells. This elevation also activates the Nuclear factor-kappa B (NF-κB) and the Nuclear factor erythroid 2-related factor 2 (NRF2)/Antioxidant Response Element (ARE) signaling pathways. The addition of the ROS inhibitor N-acetylcysteine (NAC) to NOZ and GBC-SD cells treated with high concentrations of PA effectively inhibits the enhancement of cell migration and epithelial-mesenchymal transition (EMT) induced by PA. PA promotes EMT in human gallbladder cancer cells by overproducing ROS and activating the NF-κB and NRF2/ARE signaling pathways, thereby facilitating increased migration.

OBJECTIVE:To compare the efficacy and safety of radical extrahepatic cyst excision (REC), which includes the intrapancreatic bile duct (IPBD), and subtotal extrahepatic cyst excision (SEC), which preserves the IPBD, in treating Todani type I congenital bile duct dilation with IPBD involvement (I-IPBD). BACKGROUND:The application of REC and SEC in I-IPBD remains debated. METHODS:The multicenter study recruited I-IPBDs who underwent REC or SEC from 5 centers between 2006 and 2024. The primary endpoint was occurrence of long-term complications, including recurrent cholangitis, pancreatitis, and IPBD stones. The secondary outcomes included readmission, reoperation, life quality assessed by Mayo score, carcinogenesis, and perioperative complications categorized as overall, severe, pancreas-related, and severe pancreas-related. RESULTS:Three hundred fifty-five I-IPBDs were included and divided into the REC group (175 cases) and SEC (180 cases) from 722 type I congenital bile duct dilations. The REC group demonstrated better long-term complication-free survival compared with SEC group (log-rank P < 0.001; hazard ratio = 0.08, 95% CI: 0.04-0.15, P < 0.001). The REC group had lower rates of readmission, reoperation, and carcinogenesis, and achieved a superior Mayo score ( P < 0.05). No significant differences were observed between the REC and SEC groups in overall perioperative complications, severe perioperative complications, and severe pancreas-related perioperative complications ( P > 0.05). Furthermore, subgroup analysis by age demonstrated similar trends in primary and secondary outcomes compared with the overall analysis. CONCLUSIONS:REC was an effective and safe surgical approach for I-IPBD compared with SEC, thus it should be recommended routinely for these patients.

To compare the efficacy and safety of radical extrahepatic cyst excision (REC), which includes the intrapancreatic bile duct (IPBD), and subtotal extrahepatic cyst excision (SEC), which preserves the IPBD, in treating Todani type I congenital bile duct dilation with IPBD involvement (I-IPBD). The application of REC and SEC in I-IPBD remains debated. The multicenter study recruited I-IPBDs who underwent REC or SEC from 5 centers between 2006 and 2024. The primary endpoint was occurrence of long-term complications, including recurrent cholangitis, pancreatitis, and IPBD stones. The secondary outcomes included readmission, reoperation, life quality assessed by Mayo score, carcinogenesis, and perioperative complications categorized as overall, severe, pancreas-related, and severe pancreas-related. Three hundred fifty-five I-IPBDs were included and divided into the REC group (175 cases) and SEC (180 cases) from 722 type I congenital bile duct dilations. The REC group demonstrated better long-term complication-free survival compared with SEC group (log-rank P < 0.001; hazard ratio = 0.08, 95% CI: 0.04–0.15, P < 0.001). The REC group had lower rates of readmission, reoperation, and carcinogenesis, and achieved a superior Mayo score (P < 0.05). No significant differences were observed between the REC and SEC groups in overall perioperative complications, severe perioperative complications, and severe pancreas-related perioperative complications (P > 0.05). Furthermore, subgroup analysis by age demonstrated similar trends in primary and secondary outcomes compared with the overall analysis. REC was an effective and safe surgical approach for I-IPBD compared with SEC, thus it should be recommended routinely for these patients.

Hypoxia is a hallmark of solid tumors. Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment, and CAF-derived exosomes are involved in cancer genesis and progression. Here, this work investigated the role and mechanism of exosomal circHIF1A derived from hypoxia-induced CAFs in hepatocellular carcinoma (HCC) tumorigenesis. CAFs isolated from fresh HCC tissues were incubated in normoxia or hypoxia condition (N/CAFs or H/CAFs), and then the exosomes from N/CAFs or H/CAFs were isolated for functional analysis. Cell proliferation, migration and invasion were analyzed by cell counting kit-8, colony formation, and transwell assays. Immune evasion was evaluated by measuring the cytotoxicity and viability of CD8+T cells. qRT-PCR and western blotting analyses were used for the level measurement of genes and proteins. The binding between Hu antigen R (HuR) and circHIF1A or Programmed death ligand 1 (PD-L1) was analyzed by RNA immunoprecipitation assay. Functionally, we found that CAFs, especially CAFs under hypoxic stress (H/CAFs), promoted the proliferation, migration, invasion and EMT progression in HCC cells, as well as induced immune escape by suppressing CD8+T cell cytotoxicity and activity in an exosome-dependent manner. H/CAFs-derived exosomes showed highly expressed circHIF1A, and could secrete circHIF1A into HCC cells via exosomes. The oncogenic effects of H/CAFs-secreted exosomes were abolished by circHIF1A knockdown. Mechanistically, circHIF1A interacted with HuR to stabilize PD-L1 expression in HCC cells. Meanwhile, circHIF1A silencing suppressed HCC cell proliferation, mobility and immune escape by regulating PD-L1 expression. In all, exosomal circHIF1A derived from hypoxic-induced CAFs promoted the proliferation, migration, invasion, EMT progression and immune escape in HCC cells by up-regulating PD-L1 expression in a HuR-dependent manner.

BACKGROUND:Studies have shown that coagulation and fibrinolysis (CFR) are correlated with Hepatocellular carcinoma (HCC) progression and prognosis. We aim to build a model based on CFR-correlated genes for risk assessment and prediction of HCC patient. METHODS:HCC samples were selected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases respectively. The Molecular Signatures Database (MSigDB) was used to select the CFR genes. RiskScore model were established by single sample gene set enrichment analysis (ssGSEA), weighted correlation network analysis (WGCNA), multivariate Cox regression analysis, LASSO regression analysis. RESULTS:PCDH17, PGF, PDE2A, FAM110D, FSCN1, FBLN5 were selected as the key genes and designed a RiskScore model. Those key genes were Differential expressions in HCC cell and patients. Overexpression PDE2A inhibited HCC cell migration and invasion. The higher the RiskScore, the lower the probability of survival. The model has high AUC values in the first, third and fifth year prediction curves, indicating that the model has strong prediction performance. The difference analysis of clinicopathological features found that a great proportion of high clinicopathological grade samples showed higher RiskScore. RiskScore were positively correlated with immune scores and TIDE scores. High levels of immune checkpoints and immunomodulators were observed in high RiskScore group. High RiskScore groups may benefit greatly from taking traditional chemotherapy drugs. CONCLUSIONS:We screened CFR related genes to design a RiskScore model, which could accurately evaluate the prognosis and survival status of HCC patients, providing certain value for optimizing the clinical treatment of cancer in the future.

Gastric cancer is the most common digestive tract malignancy in China and has a poor prognosis, with a 5-year overall survival rate of only 35.1%. Because its early symptoms are not obvious and early diagnosis is complicated, there is an urgent need to find biological targets for diagnosis and treatment. This research detected the expression of STAT3 in gastric cancer tissues and adjacent tissues by Western blot and immunohistochemical experiments and conducted corresponding basic experiments to explore the role of STAT3 in inhibiting the proliferation of cisplatin-resistant gastric cancer cells and promoting their apoptosis, including the construction of cisplatin-resistant gastric cancer cell line, the knock-out STAT3 in drug-resistant gastric cancer cells by CRISPR-Cas9, and the comparison of the proliferation and apoptosis of drug-resistant cells and drug-resistant cells STAT3(-). The mechanism provides a possible intervention target for clinically improving the prognosis of patients with cisplatin-resistant gastric cancer.

目的 探索导师制结合PBL教学模式在普通外科临床教学中的作用.方法 选择西安交通大学第二附属医院五年制见习学生,抽取2个班分为对照组与实验组,每组20人.对照组采用传统的教学方法,实验组采用导师制结合PBL教学模式,学习结束后对两组的教学效果 进行评估.结果 实验组教师教学效果评估及学生成绩评估均优于对照组(P＜0.05).结论 导师责任制结合PBL教学模式可以弥补单独使用PBL 教学模式的不足,有助于培养全面发展的适应新时代社会发展需要的高素质医学人才.

Colorectal cancer (CRC) is one of the most common cancers worldwide, and genetic variations exert distinct roles in its pathogenesis. Single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL1A) were reported to be correlated to the susceptibility of diverse cancers. The aim of this study was to assess the association of IL1A SNPs with the risk of colorectal cancer in a Chinese Han population. To evaluate the correlation between IL1A polymorphisms and CRC risk, Agena MassARRAY platform was used for genotype determination among 248 CRC patients and 463 controls. The relationships between IL1A variants and CRC susceptibility were examined by logistic regression analysis. Stratified analysis was conducted for the association detection in males and females. Haplotype construction and analysis were applied to evaluate the potential relationship between the genetic block and the risk of CRC. SNP functional exploration was performed with available bioinformatics datasets. After adjusting for age and gender, the “AA” genotype of rs2856838 exhibited a risk association with colorectal cancer in the recessive model (adjusted OR = 1.98, 95% CI: 1.05–3.72, p = 0.036). With stratified analysis, the recessive models of rs3783550 (OR = 2.17, 95% CI: 1.03–4.60, p = 0.043), rs2856838 (OR = 2.58, 95% CI: 1.13–5.87, p = 0.024), rs1609682 (OR = 2.20, 95% CI: 1.04–4.65, p = 0.040), and rs3783521 (OR = 2.13, 95% CI: 1.01–4.49, p = 0.048) revealed significant relationships between these variants and an increased CRC risk only in females. Bioinformatics analysis also revealed the putative functions of the selected SNPs. This study demonstrated that rs2856838 could influence the susceptibility to CRC in Chinese Han population from northwest China. IL1A variants rs3783550, rs2856838, rs1609682, and rs3783521 were associated with CRC risk only in females.

Background: The present meta-analysis was aimed to evaluate the effects of postoperative adjuvant chemotherapy/transarterial chemoembolization (TACE) on the survival/diseasefree survival (DFS) rate in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). Methods: The relevant trials were collected using a database search of MEDLINE, Embase, Cochrane Library, Web of Science, ScienceDirect, the China Journal Full-text Database, and the National Institute of Health Clinical Trials Database. The 1-, 3-, and 5-year survival/DFS rates were considered to be the primary end points. A sensitivity analysis was conducted by reanalyzing the data using different statistical approaches. Results: Eight studies met the inclusion criteria. When compared with surgery alone, the pooled OR showed that the postoperative adjuvant therapy significantly increased the 1-, 3-, and 5-year survival rates for HCC patients with PVTT (the pooled OR and 95% CI of the 1-, 3-, and 5-year survival rates, respectively, were as follows: 2.72, 1.98-3.74; 1.62, 1.13-2.33; 1.99, 1.20-3.29). In addition, when compared with surgery alone, subgroup analysis showed that the postoperative chemotherapy improved the 1-, 3-, and 5-year survival rates of HCC patients with PVTT. Conclusion: Compared with surgery alone, postoperative adjuvant chemotherapy can improve the 1-, 3- and 5-year survival rates of HCC patients with PVTT. However, postoperative TACE can only increase the 1-year survival rate. However, due to the limitations of this meta-analysis, additional relevant trials are required to confirm these findings.

目的 探讨Zuckerkandl结节(Zuckerkandl's tubercle,ZT)的解剖意义.方法 对102例甲状腺腺叶手术切除患者(共145侧甲状腺)进行回顾性分析,观察ZT的有无、大小及其与喉返神经、上甲状旁腺的关系,所有患者均按照PELIZZO分度标准对ZT进行分级,按YUN等报道的方法对RLN与ZT的位置关系进行分类.结果 ZT发生率为85.5％(与既往研究报道一致),0级以上数量与0级对比有明显差异;ZT的出现与术后声音嘶哑、SP是否显露具有相关性;ZT级别越高,A型数量越多;ZT级别越低,D型数量越多.结论 ZT可以作为喉返神经和上甲状旁腺的定位与解剖标志,以避免术中损伤喉返神经和上甲状旁腺.

The merger of postgraduate education in clinical medicine and resident standardized training is an effective way to cultivate high-quality clinical medical talents. Combined with our own experience, we have made an analysis from the following aspects: training objectives, training methods, tutorial idea renewal, the relationship between the clinical skills and scientific research, the medical humanities education importance and living subsidies, and so on. To explore how to improve the quality system training, perfecting the system of continuing medical education.

Objectives: To evaluate the therapeutic effects and complications of simplified pericardial devascularization for patients with portal hypertension. Methods: By means of prospective study, 212 patients who underwent simplified pericardial devascularization (Group A) and 309 patients who underwent traditional pericardial devascularization (Group B) were followed up from 2003' to 2011'. Results were performed with the general condition of the patients and the incidence of complications to assess the value of the two operating methods. Results: The operating time was 1.0-3.83 hours (mean 1.94 +/- 0.32 hours) in Group A versus 1.67-4.50 hours (mean 2.86 +/- 0.40 hours) in Group B. The amount of bleeding, postoperative hospital stay and hospitalization expenses were 110-500 ml (mean 224.81 +/- 78.44 ml), 7-22 days (mean 10.41 +/- 4.01 days) and 15700-27500 yuan with an average of 19300 +/- 1600 yuan in Group A and 200-700 ml (mean 423.50 +/- 85.19 ml), 9-32 days (mean 14.76 +/- 4.52 days) and 18700-44500 yuan with an average of 23400 +/- 2200 yuan in Group B. In September 2012', successful follow-up was completed for 438 patients, of which, 181 underwent the simplified devascularization with 31 patients lost (follow-up rate 85.4%). Meanwhile, 257 patients in Group B were followed up completely and 52 patients were lost (follow-up rate 83.2%). The follow-up time ranged from 1 to 9.5 years and the average time was 5.03 +/- 2.13 years. The mortality, rebleeding rate, rate of hepatic encephalopathy, rate of ascites and the incidence of gastric fistula and (or) esophageal fistula were 6.1%, 6.1%, 1.7%, 8.3% and 0 in Group A versus 14.0%, 15.2%, 4.3%, 17.7% and 3.1% in Group B. Conclusions: The final results suggested that simplified pericardial devascularization performed more effectively and conveniently than the traditional method, depending on the mitigated operative wound and the shortened operation time. We concluded that simplified pericardial devascularization was better in treatment of portal hypertension compared than the traditional method.

背景:建立人肝细胞体外缺氧再给氧损伤模型,模拟移植器官缺血再灌注损伤,从细胞分子水平探讨缺血再灌注所致纤维形肌动蛋白微丝损伤的机制,目前尚无相关研究报道.目的:分析缺氧再给氧对肝细胞膜纤维形肌动蛋白微丝损伤的分子机制.方法:建立体外大鼠肝细胞缺氧再给氧模型.肝细胞随机分为正常对照组、缺氧再给氧组.缺氧再给氧组又分为缺氧再给氧2h、缺氧再给氧4h、缺氧再给氧6h组(分别为细胞缺氧3h后再给氧2,4,6h).光镜观察细胞形态,电镜观察超微结构的改变,共聚焦激光显微镜观察纤维形肌动蛋白微丝含量变化,Real-time PCR检测HSP27、丝切蛋白基因的转录水平,Western blot检测HSP27、丝切蛋白蛋白的表达水平.结果与结论:光镜下缺氧再给氧各组梭形细胞显著增多,且脱落细胞明显增多;透射电镜下缺氧再给氧组与对照组相比内质网数量明显减少,线粒体密度深,糖原消失;共聚焦激光显微镜可见缺氧再给氧组纤维形肌动蛋白纤维荧光紊乱,形态明显改变,荧光染色明显减弱,平均荧光强度缺氧再给氧各组明显低于对照组(P＜0.05);Real-time PCR和Westem blot检测H/R各组HSP27、丝切蛋白基因转录和蛋白表达水平显著低于正常对照组(P＜0.05).表明缺氧再给氧可能是通过抑制肝细胞内HSP27、丝切蛋白的蛋白表达和基因转录,从而影响纤维形肌动蛋白微丝的正确装配以及减弱纤维形肌动蛋白的正常循环,进而改变纤维形肌动蛋白微丝骨架.

目的 评价肝动脉化疗栓塞(TACE)联合门静脉化疗(PVC)对手术或非手术肝癌患者的疗效.方法 通过计算机检索PubMed、EMBASE、Cochrane Library (CENTRAL) databases、Web of Science、Sciencedirect、NationalInstitute of Health Clinical Trials Database、中国知网、万方数据库和维普网获取相关文献.使用Revman 5.1软件进行统计分析.结果 通过检索及筛选,共有10篇相关文献符合纳入标准.其中术后组6篇,未手术组4篇.所有亚组分析各组间异质性均无统计学意义.统计学分析均显示TACE+PVC可明显改善患者1年和2/3年总体生存率和无瘤生存率.术后组:1年无瘤生存率OR=2.09,95％ CI=1.21 ～ 3.61;3年无瘤生存率OR=3.62,95％ CI=1.88～6.97;1年总生存率总OR=2.25,95％ CI=1.30 ～ 3.87;3年总生存率OR=1.96,95％ CI=1.20～3.21.未手术组:1年总生存率OR=3.90,95％ CI=2.33～6.54;2年总生存率OR=5.30,95％ CI=1.87～15.06.结论 术后辅助TACE联合PVC治疗较单纯辅助TACE治疗可显著改善肝癌患者1年及3年无瘤生存率和总生存率.而对于无手术指征的患者,TACE联合PVC可明显改善患者的1年及2年总生存率.但由于本文纳入高质量文献较少,临床医师在参考本文进行临床决策时应谨慎.

Hepatic stellate cells (HSCs) are the primary sources of extracellular matrix (ECM) in normal and fibrotic liver. Peroxisome proliferator-activated receptor gamma (PPARγ) maintains HSCs in a quiescent state, and its downregulation induces HSC activation. MicroRNAs (miRNAs) can induce PPARγ mRNA degradation, but the mechanism by which miRNAs regulate PPARγ in rat HSCs is unclear. This study aimed to investigate some miRNAs which putatively bind to the 3′-untranslated region (3′-UTR) of PPARγ mRNA, and increase expression of ECM genes in rat HSCs. In carbon tetrachloride injection (CCl4) and common bile duct ligation (CBDL) liver fibrosis models, miRNAs miR-130a, miR-130b, miR-301a, miR-27b and miR-340 levels were found to be increased and PPARγ expression decreased. Overexpression of miR-130a and miR-130b enhanced cell proliferation by involving Runx3. MiR-130a and miR-130b decreased PPARγ expression by targeting the 3′-UTR of PPARγ mRNA in rat HSC-T6 cells. Transforming growth factor-β1 (TGF-β1) may mediate miR-130a and miR-130b overexpression, PPARγ downregulation, and ECM genes overexpression in cell culture. These findings suggest that miR-130a and miR-130b are involved in downregulation of PPARγ in liver fibrosis.

Pancreatic cancer (PC) is an aggressive and devastating disease with a poor prognosis. Cisplatin, a commonly used chemotherapeutic agent for solid tumors, is effective as a single agent or in combination with other drugs for the treatment of PC. Previous studies have suggested that Twist and growth differentiation factor 15 (GDF15) are involved in the progression of PC. However, the role of Twist and GDF15 in PC remains to be elucidated. In the present study, the individual effect of and interaction between Twist and GDF15 in PC cell invasion and chemoresistance to cisplatin was examined. Twist and/or GDF15 were stably overexpressed or knocked down in ASPC‑1 and BXPC‑3 human PC cells. Overexpression of Twist in the two cell lines markedly increased GDF15 expression, cell invasion, matrix metalloproteinase‑2 expression/activity and the half maximal inhibitory concentration (IC50) values of cisplatin, which was eradicated by GDF15 knockdown or the selective p38 mitogen‑activated protein kinase (MAPK) inhibitor SB203580 (10 µM). By contrast, Twist knockdown significantly decreased GDF15 expression, cell invasion, matrix metalloproteinase‑2 expression/activity and the IC50 values of cisplatin, which was completely reversed by overexpression of GDF15. In addition, while overexpression and knockdown of Twist increased and decreased p38 MAPK activity, respectively, GDF15 demonstrated no significant effect on p38 MAPK activity in PC cells. In conclusion, the present study, for the first time, to the best of our knowledge, demonstrated that Twist promotes PC cell invasion and cisplatin chemoresistance through inducing GDF15 expression via a p38 MAPK‑dependent mechanism. The present study provides new insights into the molecular mechanisms underlying PC progression and chemoresistance.