BackgroundSeveral RET-targeted agents, including highly selective RET inhibitors (SRIs) and multi-kinase inhibitors (MKIs), have been approved for the treatment of advanced medullary thyroid cancer (MTC). Despite these agents targeting the same pathway, direct comparative data is lacking. This study aims to evaluate the relative efficacy and safety of these agents via network meta-analysis (NMA).MethodsWe systematically searched PubMed, Embase, Cochrane Library, Web of Science, and CNKI (up to March 2026) for RCTs evaluating RET-targeted therapies for advanced MTC. The primary outcome was progression-free survival (PFS); secondary outcomes included objective response rate (ORR) and ≥Grade 3 adverse events (AEs). A frequentist random-effects model was employed, and treatments were ranked using P-scores. The study was registered in PROSPERO (CRD420261342793).ResultsFive RCTs (n = 1,076) were included. Selpercatinib demonstrated the most significant PFS benefit (HR = 0.10, 95% CI: 0.05–0.18; P-score = 0.999), outperforming cabozantinib (HR = 0.28) and vandetanib (HR = 0.46). It also ranked first for ORR (OR = 122.6, 95% CI: 34.5–435.6). Regarding safety, selpercatinib showed no significant difference in ≥Grade 3 AEs compared to placebo (OR = 1.34), whereas anlotinib exhibited the highest toxicity (OR = 12.00). Although selpercatinib was associated with hepatotoxicity (OR = 4.20), it avoided the off-target toxicities typical of MKIs, such as hypertension and diarrhea.ConclusionThis network meta-analysis demonstrates that selpercatinib exhibits superior efficacy (PFS and ORR) and a more favorable safety profile compared to MKIs for advanced MTC. These results support its role as a recommended first-line option for advanced MTC. However, due to the heterogeneity of included populations (mixed RET mutation status and therapy lines), clinicians should interpret these findings with caution regarding the generalizability to strictly defined RET-mutant populations. Clinical decisions should be individualized.Systematic review registration:https://www.crd.york.ac.uk/PROSPERO/view/CRD420261342793, identifier CRD420261342793.

Background Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory condition characterized by weight loss as a prominent feature. Non-alcoholic fatty liver disease (NAFLD), typically linked to obesity and metabolic dysregulation, is increasingly recognized as being influenced by the gut-liver axis. Notably, IBD patients exhibit a heightened susceptibility to NAFLD, although the underlying mechanisms remain poorly understood. Intestinal alkaline phosphatase (IAP), an endogenous enzyme, plays a critical role in preventing intestinal bacterial translocation. We hypothesized that IAP may serve as a potential therapeutic agent for mitigating IBD-associated NAFLD. Methods An IBD model was established using three cycles of 2 % dextran sulfate sodium (DSS) administration. Mice were subsequently treated with L-phenylalanine or IAP. The activity of stool IAP, gut microbiota composition, hepatic lipid accumulation, inflammatory markers, and gut microbiome diversity were assessed. Results DSS treatment markedly reduced IAP levels. Suppression of IAP significantly increased gut permeability and exacerbated hepatic inflammation and lipid deposition. Conversely, IAP supplementation restored these parameters, improved gut microbial diversity, and normalized microbiota composition. However, IAP failed to ameliorate hepatic inflammation and lipid accumulation in Toll-like receptor 4 (TLR4) knockout mice. Conclusion Deficiency in endogenous IAP contributes to the onset of NAFLD in the context of IBD. Oral IAP supplementation enhances gut barrier integrity, stabilizes gut microbiota, and prevents NAFLD development in IBD through a TLR4-dependent mechanism.

BACKGROUND:Intrahepatic infiltration of neutrophils is a character of alcoholic hepatitis (AH) and neutrophil extracellular traps (NETs) are an important strategy for neutrophils to fix and kill invading microorganisms. The gut-liver axis has been thought to play a critical role in many liver diseases also including AH. However, whether NETs appear in AH and play role in AH is still unsure.METHODS:Serum samples from AH patients were collected and LPS and MPO-DNA were detected. WT, NE KO, and TLR4 KO mice were used to build the AH model, and the intestinal bacteria were eliminated at the same time and LPS was given. Then the formation of NETs and AH-related markers were detected.RESULTS:The serum MPO-DNA and LPS concentration was increased in AH patients and a correlation was revealed between these two indexes. More intrahepatic NETs formed in AH mice. NETs formation decreased with antibiotic intervention and restored with antibiotic intervention plus LPS supplement. While NETs formation failed to change with gut microbiome or combine LPS supplement in TLR4 KO mice. As we tested AH-related characters, liver injury, intrahepatic fat deposition, inflammation, and fibrosis alleviated with depletion of NE. These related marks were also attenuated with gut sterilization by antibiotics and recovered with a combined treatment with antibiotics plus LPS. But the AH-related markers did show a difference in TLR4 KO mice when they received the same treatment.CONCLUSION:Intestinal-derived LPS promotes NETs formation in AH through the TLR4 pathway and further accelerates the AH process by NETs.

Background:Gastric cancer ranks as the fifth most prevalent cancer and the third leading cause of cancer-related mortality worldwide, Statins, renowned for their cholesterol-lowering effects, have garnered interest for their potential roles in cancer prevention and treatment due to their pleiotropic effects, such as anti-proliferative, pro-apoptotic, and anti-inflammatory properties. This study aims to investigate the therapeutic potential of simvastatin, a widely prescribed statin, in the context of gastric cancer using Mendelian randomization (MR) to explore a possible causal relationship between simvastatin use and gastric cancer risk. Methods:We conducted a two-sample MR analysis utilizing summary statistics from genome-wide association studies (GWAS). Data from the Integrative Epidemiology Unit (IEU) Open GWAS project included 462,933 participants and 9,851,867 single nucleotide polymorphisms (SNPs) for simvastatin, and 476,116 participants with 24,188,662 SNPs for gastric cancer. Instrumental variables screening criteria were stringent, resulting in 41 valid SNPs as instrumental variables. The MR analysis was performed using the inverse variance weighting (IVW), supplemented by MR-Egger, weighted median estimator (WME), weighted mode, and simple mode approaches. Heterogeneity and pleiotropy were assessed using IVW, MR-Egger tests, and the MR-PRESSO method. Results:The IVW and WME analyses indicated a significant protective effect of simvastatin against gastric cancer [IVW: odds ratio (OR) =0.1459, 95% confidence interval (CI): -3.502 to -0.346, P=0.01; WME: OR =0.0347, 95% CI: -3.521 to 0.1610, P=0.03]. There was no significant difference between the results of the two MR analyses before and after the removal of outliers (P=0.76), and the Egger-intercept for horizontal pleiotropy testing was not significant (P=0.38). Leave-one-out sensitivity analysis supported the robustness of our findings. Conclusions:This MR study provides evidence for a potential protective effect of simvastatin against gastric cancer, suggesting its consideration as an adjunct to traditional cancer therapies.

Background: Endoscopic transaxillary approaches to thyroidectomy have been well described and gasless transaxillary endoscopic thyroidectomy (GTET) is the most popular method. However, this require a single long axillary incision which is longer than most remote access thyroidectomy procedures. We improved the GTET and provided a novel way to access the thyroid. The purpose of this study was to test the feasibility of our novel transaxillary thyroidectomy procedure and to attempt to reduce the size of the scar and reduce the flap creation area. Methods: 116 patients who underwent our novel transaxillary thyroidectomy procedure were compared with the patients who underwent open and GTET procedures. The patients’ demographics, outcomes, and complications were analyzed. Results: Although the operation time (121.48±23.91mins) was longer in the novel endoscopic group compare to the open group, it was shorter than GTET group. Intraoperative blood loss was similar between the groups. However, the novel procedure group had more drainage volume within 48 postoperative hours compare to other two groups. Despite the VAS pain score didn’t reveal a difference between the open and novel endoscopic procedure, it was lower in the novel procedure than GTET. The hospital stay days didn’t show a difference between the two groups. The number of resected central lymph nodes was similar between the groups. Differences didn’t reveal between the groups regarding to the complications rate. Conclusion: Our results showed that our novel transaxillary thyroidectomy procedure is feasible and safe. This procedure can be an alternative endoscopic transaxillary method for thyroidectomy.

目的 系统评价经口腔前庭入路与经全乳晕入路腔镜手术治疗甲状腺乳头状癌的疗效和安全性.方法 通过中国知网、中国生物医学文献数据库、万方数据库、PubMed、EMBASE、MEDLINE、SpringerLink、John Wiley、Ovid?、Cochrane Library等数据库,以及Google Scholar搜索引擎平台,检索经口腔前庭入路与经全乳晕入路腔镜手术治疗甲状腺乳头状癌的相关文献.筛选文献后对文献进行偏倚风险评估,采用RevMan 5.4统计软件进行Meta分析.结果 共纳入7篇文献,共595例患者.Meta分析结果显示,经口腔前庭入路腔镜甲状腺乳头状癌手术的淋巴结清扫数目多于经全乳晕入路,术中出血量少于经全乳晕入路(均P<0.05),而两种入路腔镜甲状腺乳头状癌手术的手术时间及手术并发症发生率的比较,差异均无统计学意义(均P>0.05).结论 相较于经全乳晕入路,经口腔前庭入路进行腔镜甲状腺乳头状癌手术具有淋巴结清扫数目多、术中出血量少的优点,同时不增加手术时间及手术并发症发生率.

Endoscopic transaxillary thyroidectomy is a common method for remote-access thyroidectomy. The approach typically uses a gasless method, and a long incision to insert a special retractor. In addition, it is considered only suitable for unilateral lobectomy because of problems accessing contralateral parts of the thyroid gland. We describe here, a case of a young woman who had a total thyroidectomy performed using an endoscopic approach. We reduced the non-inflated 4–6 cm incision that is usually required, into three holes, and performed unilateral transaxillary thyroidectomy; this was verified by radioactive iodine uptake and thyroglobulin levels during follow-up. The approach was clinically successful and resulted in minimal scarring. More studies are required to optimize this promising technique.

Background: In the original axillary approach described by Ikeda et al. with three points incisions, they began by accessing the central neck region by dissecting the sternocleidomastoid muscle (SCM) off from the sternohyoid muscle. Later this approach was modified by utilizing a gasless approach that is popularized worldwide. The central neck region was accessed directly by dissociation of the sternal and clavicular heads of the SCM. However, this procedure required a 5–6 cm incision and also place a special static retractor. We modified the conventional gasless transaxillary thyroidectomy procedure to a transaxillary gas insufflation approach with shorter incisions, and a smaller flap creation area. This video is aimed to describe the step-by-step procedure of a case of modified endoscopic transaxillary gas insufflation thyroidectomy (ETGT).

目的 基于生物信息学方法分析β-1,3-N-乙酰氨基葡萄糖转移酶7(B3 GNT7)基因在甲状腺癌组织中的表达水平及其对免疫细胞浸润的影响.方法 在肿瘤免疫评估资源数据库、GEPIA2数据库、UALCAN数据库中检索B3 GNT7基因在甲状腺癌患者癌组织和癌旁组织中的表达情况,分析不同临床特征、病理分期甲状腺癌患者癌组织中B3 GNT7基因的表达水平,采用多因素COX回归模型分析B3 GNT7基因表达水平与甲状腺癌患者预后的关系,采用Spearman相关性模型分析B3 GNT7基因表达水平与甲状腺癌组织中免疫细胞浸润丰度的相关性,以及B3 GNT7基因表达水平与免疫细胞标志物、T淋巴细胞标志物、免疫检查点基因表达水平的相关性.结果 B3 GNT7基因在甲状腺癌患者癌组织中的表达高于癌旁组织(P<0.05).不同病理分期的甲状腺癌患者癌组织中的B3GNT7基因表达水平具有差异性(P<0.05).多因素COX分析结果显示,CD8+T淋巴细胞、B3 GNT7基因表达水平是甲状腺癌患者预后的影响因素(均P<0.05).Spearman相关性分析结果显示,B3GNT7基因表达水平与B淋巴细胞、CD4+T淋巴细胞、CD8+T淋巴细胞、巨噬细胞、树突状细胞、中性粒细胞的浸润丰度,以及细胞毒性T淋巴细胞相关蛋白4(CTLA4)的表达水平密切相关(均P<0.05),还与多种免疫标志物的表达水平相关.结论 B3 GNT7基因在甲状腺癌组织中呈高表达,其表达水平与甲状腺癌患者的病理分期密切相关,B3GNT7基因与甲状腺癌组织中B淋巴细胞、CD4+T淋巴细胞、CD8+T淋巴细胞、巨噬细胞、树突状细胞、中性粒细胞的浸润丰度相关,且与CTLA4表达密切相关.

Backgrounds: Intrahepatic infiltration of neutrophils is a character of alcoholic acute-on-chronic liver failure (AACLF) and neutrophil extracellular traps (NETs) are an important strategy for neutrophils to fix and kill invading microorganisms. Intestinal bacteria and the gut-liver axis have been thought to play a key role in many liver diseases also including AACLF. However, whether NETs appear in AACLF and play a role in AACLF is still unsure. Methods: WT, NE KO, and TLR4 KO mice were used to build the AACLF model, and the intestinal bacteria were eliminated at the same time and LPS was given. Then the formation of NETs and AACLF related markers were detected. Results: The serum MPO-DNA and LPS concentration was increased in AACLF patients and a correlation was revealed between these two indexes. More intrahepatic NETs formed in AACLF mice by testing MPO-DNA, Cit H3, and NE. These markers decreased with gut detergent and restored markers with gut detergent plus LPS supplement. While NETs formation failed to change with gut microbiome or combine LPS supplement in TLR4 KO mice. As we tested AACLF related characters, liver injury, intrahepatic fat deposition, inflammation, and fibrosis alleviated with depletion of NE. These related marks were also attenuated with gut sterilization by antibiotics and recovered with combined treatment with antibiotics plus LPS. But the liver injury, intrahepatic fat, fibro deposition, and liver inflammation-related markers did show a significant difference in TLR4 KO mice when they received the same treatment. Conclusion: Intestinal-derived LPS promotes NETs formation in AACLF through the TLR4 pathway and further accelerates the AACLF process by NETs.

Background/Aims Binge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs). Methods Serum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used. Results A marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated. Conclusions Formation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.

目的 采用生物信息学方法分析甲状腺乳头状癌(PTC)脑转移差异表达基因的生物学功能,并筛选PTC脑转移的关键调控基因.方法 从GEO数据库获取基因芯片GSE66463,利用GEO2R中GEOquery、limma包筛选PTC脑转移灶癌组织差异表达基因,对差异表达基因进行基因本体论(Gene Ontology,GO)功能注释,利用京都基因和基因组数据库对差异表达基因的信号通路进行富集分析.通过String数据库构建差异表达基因的蛋白互作网络,筛选可能参与PTC脑转移的关键调控基因,分别基于GEPIA数据库、人类蛋白质表达图谱数据库数据分析PTC脑转移关键调控基因及蛋白与PTC患者预后的关系.结果 PTC脑转移灶癌组织中共183个差异表达基因,其中表达上调82个、下调101个.PTC脑转移灶癌组织差异表达基因生物学功能主要有金属离子动态平衡、小分子转运及分子细胞间黏附等,信号通路主要集中在风湿性炎症信号通路、NF-kB信号通路及IL17信号通路等.β-1,3-N-乙酰氨基葡萄糖氨基转移酶(B3GNT7)、丝氨酸/苏氨酸激酶(BUB1)、细胞分裂周期蛋白20(CDC20)、集落刺激因子2(CSF2)、趋化因子CXC配体2、白细胞介素1α(IL1α)、IL1β、骨诱导因子、骨调蛋白、脯氨酸/精氨酸丰富端亮氨酸丰富重复蛋白可能是参与PTC脑转移的关键调控基因.与B3GNT7低表达者比较,B3GNT7基因及蛋白高表达的PTC患者预后较好(P均<0.05).结论 PTC脑转移的差异表达基因的生物学功能主要有金属离子动态平衡、小分子转运及分子细胞间黏附等.PTC脑转移的关键调控基因主要有B3GNT7、BUB1及CDC20等.

ObjectiveTo evaluate the effectiveness and advantages of a new method for calculating breast tumor volume based on an automated breast ultrasound system (ABUS).MethodsA total of 42 patients (18–70 years old) with breast lesions were selected for this study. The Ivenia ABUS 2.0 (General Electric Company, USA) was used, with a probe frequency of 6–15 MHz. Adobe Photoshop CS6 software was used to calculate the pixel ratio of each ABUS image, and to draw an outline of the tumor cross-section. The resulting area (in pixels) was multiplied by the pixel ratio to yield the area of the tumor cross-section. The Wilcoxon signed rank test and Bland-Altman plot were used to compare mean differences and mean values, respectively, between the two methods.ResultsThere was no significant difference between the tumor volumes calculated by pixel method as compared to the traditional method (P>0.05). Repeated measurements of the same tumor volume were more consistent with the pixel method.ConclusionThe new pixel method is feasible for measuring breast tumor volume and has good validity and measurement stability.

Mini-CEX和DOPS作为两种新提出的临床教学评估方法,已经在欧美国家应用,并被认为能有效提高医学生实践水平,但是否同样适合我国外科教学仍需检验.在问卷星平台构建Mini-CEX以及DOPS评价量表,将其应用于本科生外科实习教学中,并对其评价得分、考试成绩、满意度做出统计分析.实践表明,在我国本科生外科实习中应用Mini-CEX联合DOPS的方法能够有效提高教学效果及操作水平,并且具有较传统教学方法更高的满意度.

Magnolol, a hydroxylated biphenyl extracted from Magnolia officinalis, has recently drawn attention due to its anticancer potential. The present study was aimed to explore the effects of Magnolol on restraining the proliferation, migration and invasion of pancreatic cancer in vivo and in vitro. Magnolol showed significant anti-growth effect in an orthotopic xenograft nude mouse model, and immunohistochemical staining of the xenografts revealed that Magnolol suppressed vimentin expression and facilitated E-cadherin expression. The cytoactive detection using CCK-8 assay showed Magnolol inhibited PANC-1 and AsPC-1 concentration-dependently. Scratch healing assay and the Transwell invasion assay proved the inhibiting effects of Magnolol on cellular migration and invasion at a non-cytotoxic concentration. Western blot and rt-PCR showed that Magnolol suppressed epithelial-mesenchymal-transition by increasing the expression level of E-cadherin and decreasing those of N-cadherin and vimentin. Magnolol suppressed the TGF-β/Smad pathway by negatively regulating phosphorylation of Smad2/3. Moreover, TGF-β1 impaired the antitumor effects of Magnolol in vivo. These results demonstrated that Magnolol can inhibit proliferation, migration and invasion in vivo and in vitro by suppressing the TGF-β signal pathway and EMT. Magnolol could be a hopeful therapeutic drug for pancreatic malignancy.

目的:以COX2-PGE2通路为靶标,探讨其调控髓源抑制性细胞(myeloid-derived suppressor cell,MDSC)增殖及活化,进而影响肝细胞肿瘤(hepatocelluar carcinoma,HCC)进展的可能机制.方法:建立小鼠肝细胞肿瘤模型,利用流式细胞术分析外周血及脾脏组织中的MDSC比例,CFSE标记法分析肿瘤浸润MDSCs对T淋巴细胞增殖的影响,ELISA检测肿瘤组织体外培养上清中PGE2水平,Western blot检测肿瘤组织中COX-2表达,最终腹腔注射COX2-PGE2通路的小分子抑制剂吲哚美辛,证实该通路在调控MDSCs增殖活化,进而影响肿瘤进展过程中具有重要作用.结果:随着HCC的进展,小鼠外周血及脾脏中MDSC比例逐渐升高,其对T淋巴细胞增殖的抑制作用,即免疫抑制功能显著增加;肿瘤组织COX-2及PGE2表达水平较正常肝脏显著升高,腹腔注射吲哚美辛能够有效抑制肿瘤生长;过继回输MDSC则在一定程度上降低吲哚美辛的肿瘤抑制作用.结论:HCC发展过程中,肿瘤细胞通过COX2-PGE2通路活化MDSC,促进肿瘤进展.COX2-PGE2通路抑制剂吲哚美辛可通过抑制MDSC介导的免疫抑制作用,减缓肿瘤进程.

目的:探讨锌指蛋白217(ZNF217)在胰腺癌组织中的表达,分析其与胰腺癌患者临床特征的关系.方法:收集61例胰腺癌患者术后切除的胰腺癌组织及癌旁组织标本,各61例;采用免疫组化法检测组织标本中ZNF217蛋白表达,分析ZNF217蛋白表达与胰腺癌患者临床病理特征(性别、年龄、瘤体直径、TNM分期、组织学分级及淋巴结转移)的关系.结果:免疫组织化学染色结果显示,胰腺癌组织ZNF217蛋白阳性着色强度大于癌旁组织,阳性细胞比例高于癌旁组织,胰腺癌组织ZNF217蛋白阳性率及免疫组织化学评分显著高于癌旁组织,差异有统计学意义(P＜0.01);分析发现,胰腺癌男性与女性患者、年龄＜50岁与年龄≥50岁患者、组织学分级G1～G2级与G3级患者间ZNF217蛋白阳性表达率比较,差异无统计学意义(P＞0.05);而瘤体直径≥2 cm、TNM分期Ⅲ～Ⅳ期及淋巴结转移患者ZNF217蛋白阳性表达率分别显著高于瘤体直径＜2 cm、TNM分期Ⅰ～Ⅱ期及无淋巴结转移患者,差异有统计学意义(P＜0.05、或P＜0.01).结论:胰腺癌组织ZNF217蛋白阳性表达率显著高于癌旁组织,且ZNF217蛋白阳性表达与瘤体直径增大、高TNM分期及淋巴结转移有关.

Objective To investigate the expression level of ARID2 gene in hepatocellular carcinoma(HCC)tissues and cell lines, and to explore its effect on HCC cell proliferation and cell cycle. Methods The expression of ARID2 was detected by immunohisto-chemistry in specimens of primary cancer and their adjacent non-cancerous tissues in 60 patients with HCC. The expression of ARID2 was detected by qPCR in different differentiation of HCC cell lines. The small interfering RNA(siRNA)targeting ARID2 was transfect-ed into HepG2 cells,and the cell cycle changes and proliferation were detected by flow cytometry and MTT,respectively. Results The expression level of ARID2 in HCC tissues was significantly higher than that in adjacent tissues(P<0.01). The expression of AR-ID2 in HCC cell lines was significantly higher than that in LO2 cell lines(P<0.05). After siRNA targeting ARID2 was transfected, the cells in the G1phase were significantly increased(P<0.01),the S phase cells decreased significantly(P<0.01)and proliferation ability(P<0.05)of HepG2 cells were inhibited. Conclusion ARID2 can be used as an important biomarker for HCC,and it can affect the cell cycle and proliferation by targeting ARID2.

Hypoxia-reoxygenation (H/R) injury hepatocyte models were established to simulate the ischemia/reperfusion injury of transplanted organ. Through the study of the molecular mechanism of H/R on the F-actin damage of the liver cytomembrane, the mechanism of F-actin damage induced by ischemia and reperfusion was studied from the level of cell and molecule.The hypoxic environment of cells in vitro was simulated by chemical hypoxia agent CoCl2. Liver cells were detected by MTT, H/R group was subdivided into 3 subgroups: H/R 2, 4, and 6 h. Changes of cell shape and the growth state, apoptosis, ultrastructural changes, and the changes in F-actin microfilament content were observed. Heat shock protein 27 (HSP27), Cofilin, and F-actin gene and protein levels were determined by real-time polymerase chain reaction and western blot assay, respectively.Cells showed circular adherence growth under normal circumstances, while the spindle cells and shedding cells were significantly increased in H/R groups. Apoptosis cells in H/R group were increased significantly with the extension of hypoxia time. The number of endoplasmic reticulum was decreased significantly in the H/R group, the mitochondrion hydropic was degenerated and the glycogen was disappeared. The F-actin fibers in the H/R group were disordered, the morphology of the fibers was obviously decreased, and the fluorescence staining decreased obviously (P < .05). The transcription and expression levels of HSP27, Cofilin, and F-actin were significantly lower than those in the control group (P < .05).These results demonstrate that H/R can affect the correct assembly of F-actin microfilaments and weakens the normal cycle of F-actin microfilaments through inhibiting the protein expression and gene transcription of HSP27 and Cofilin in hepatocytes, thereby changing the skeleton of F-actin microfilaments.

Objective CD133 is a surface marker of tumor stem cells .The aim of this study was to investigate the expression of CD133 in hilar cholangiocarcinoma and its effect on the proliferation of cholangiocarcinoma QBC 939 cells. Methods The expres-sion of CD133 was detected by immunohistochemistry in hilar cholangiocarcinoma and adjacent bile duct tissue in 32 patients, followed by analysis of the relationship between the expression level of CD 133 and clinical pathological characteristics of the malignancy .CD133 siRNA was transfected into the QBC 939 cells, the expression of CD133 mRNA in the cells determined by real-time PCR, and the status of transfection assessed after 24, 48, and 72 hours by CCK-8. The cells were divided into a transfection group ( CD133 siRNA gene transfected into QBC 939 cells ) , a negative control group ( negative control primers transfected into QBC 939 cells ) , and a blank control&nbsp;group (no primer transfected into QBC939 cells), and the experiment was repeated 3 times in each group. Results The positive ex-pression of CD133 was significantly higher in cholangiocarcinoma than in the adjacent tissue (62.5%[20/32] vs 28.1%[9/32], P=0.008 2) and it was closely related to the degree of tumor differentiation , TNM stage and lymph node metastasis ( P<0.05) .The rela-tive expression of CD133 mRNA was markedly lower in the transfection than in the blank control group (0.437±0.014 vs 0.826±0.022, P<0.05).At 24, 48 and 72 hours after transfection, the proliferation activity of the cells was significantly inhibited as compared with that in the negative control or blank control group ( P<0.05) . Conclusion CD133 is highly expressed in cholangiocarcinoma and as-sociated with tumor differentiation , TNM stage, and lymph node metastasis .The proliferation of cholangiocarcinoma QBC 939 cells can be inhibited by suppressing the expression of CD 133 in them.