This study analyzes the application value of extended multi-organ resection in the treatment of locally advanced gastric cancer, and to provide reference for the clinical diagnosis and treatment of locally advanced gastric cancer patients. From January 2016 to April 2022, 64 cases of locally advanced gastric cancer admitted to our hospital were analyzed retrospectively. Combined multiple organ resection was used as the treatment strategy, and the general information and surgical data of patients were analyzed to evaluate the prognosis of extended multi-organ resection in the treatment of locally advanced gastric cancer and the factors affecting these clinical outcomes. A total of 64 patients with locally advanced gastric cancer were included, including 34 males and 30 females, with an average age of 57.28 ± 12.27 years. Among them, combined pancreatectomy was performed in 25 cases, splenectomy in 20 cases, hepatectomy in 12 cases, pancreaticoduodenectomy in 5 cases, pancreaticoduodenectomy and right colon resection in 1 case, and colon resection in 1 case. The average operation time was 159.64 ± 25.19 minutes and the median intraoperative bleeding was 150 mL. All 64 patients achieved R0 resection, and all patients were followed up. Postoperative complications occurred in 18 cases, of which the mortality rate was 16.67% (3/18). The 1-year, 3-year, and 5-year survival rates were 59.4%, 35.9%, and 14.6%, respectively. It is feasible to treat locally advanced gastric cancer by extended combined organ resection. As long as the indications are strictly grasped, the overall prognosis of patients can be improved.

Abdominal aortic aneurysm (AAA) is a serious vascular condition that significantly endangers the lives of patients. Although there have been improvements in early detection and treatment methods, considerable challenges persist regarding the timely identification and evaluation of risk associated with this disease. Therefore, there is an immediate requirement for novel biomarkers that can enhance the early diagnosis and risk evaluation of AAA, thus allowing for more accurate and individualized medical interventions. In this study, we identified key diagnostic markers for AAA using various machine learning algorithms, and we explored the functions of these genes in AAA through gene enrichment analysis. A diagnostic model for AAA was constructed based on multiple machine learning algorithms, with the random forest algorithm highlighting the central role of ARHGAP9. In vitro experiments confirmed the influence of ARHGAP9 on vascular smooth muscle cells (VSMCs). Our findings indicate that the key genes identified are associated with the immune microenvironment and metabolism in AAA samples. The validated diagnostic model exhibited excellent predictive performance. Knockdown of ARHGAP9 significantly inhibited the proliferative capacity of VSMCs. In conclusion, our results suggest that ARHGAP9 may serve as a diagnostic and therapeutic marker for AAA.

ObjectiveTo establish a gallstone mouse model using a lithogenic diet and investigate changes in the gut microbiota of gallstone mice at different altitudes.MethodsSixty mice were randomly assigned to four groups: plain healthy, plain stone, high-altitude healthy, and high-altitude stone. Mice were raised in either plain or high-altitude environments, and a lithogenic diet was used to induce gallstone formation. After 8 weeks, the mice were euthanized, and stone formation was assessed. Blood samples were collected to measure serum total cholesterol (T-CHO), triglycerides (TG), and bile acid (TBA) levels. Fecal samples were also collected for 16S rDNA high-throughput sequencing to analyze the gut microbiota.ResultsTG and T-CHO levels were significantly elevated in gallstone mice in the plain and high-altitude groups. Differential microbiota analysis indicated a decrease in Bacteroidetes and an increase in Firmicutes in the gallstone groups. Several specific bacterial genera showed significant changes in the gallstone mice compared to the healthy controls.Conclusion1) Gut microbiota imbalance likely contributes to gallstone formation in mice, and higher microbiota diversity may reduce the incidence of gallstones. 2) The incidence of gallstones is higher at high altitudes than at lower altitudes, possibly due to hypoxic conditions and elevated inflammation levels.

IntroductionIn most instances, liver transplantation (LT) is the only available treatment for end‐stage liver diseases. However, LT could also induce serious liver diseases or injury, and the underlying mechanisms of LT-induced complications remain largely unknown, especially the mechanisms of the dysfunction of the immune system mediated by long noncoding RNAs (lncRNAs).MethodsIn this study, we globally analyzed the proportion of immune cells by using the transcriptome sequencing data (RNA-seq) of needle-core liver biopsies from pre- and post-transplantation recipients. Dysregulated lncRNAs were found to be correlated with the altered fractions of immune cells. We finally explored the potential targets of dysregulated lncRNAs and analyzed their functions in LT.ResultsWe found that in the samples, some immune cells changed significantly after LT, including CD4 T cells, NK cells and mast cells. The proportion of macrophages in different polarization states also changed significantly, with M0 macrophages increasing and M2 macrophages decreasing. Through weighted gene co-expression network analysis (WGCNA), 7 gene expression modules related to LT were identified. These modules were related to changes in the proportion of different immune cells. The functions of these modules represent the response modes of different functional genes after LT. Among these modules, MEtan and MEyellow modules were primarily enriched in apoptosis and inflammatory pathways. Twelve immunity-related lncRNAs were identified for the first time, and the regulatory network co-changing with immune cells was also identified. The co-expressed genes of these lncRNAs were highly enriched in apoptosis-related pathways. Many apoptosis-related genes were found to be up-regulated after LT.DiscussionIn summary, we speculated that the expression and regulation of these apoptotic genes may be related to the changes in the proportion of immune cells. Some of these lncRNAs and apoptosis-related genes have been reported to be related to cell proliferation and apoptosis. They are also potential biomarkers or therapeutic targets.

目的 分析甲状腺切除术后病人血清钙、甲状旁腺激素(parathyroid hormone,PTH)及中央区引流液PTH水平的变化特点,探讨监测上述指标对甲状腺术后评估甲状旁腺功能的临床意义.方法 2018年1月～2021年1月就诊于我院普外科行甲状腺切除、中央区淋巴结清扫术病人112例,根据术中甲状旁腺原位保留0枚、1枚、2枚,分为A0、A 1、A2组,测定病人术前及术后1～4天血钙、血PTH、中央区引流液PTH水平.结果 112例病人发生低钙血症23例,其中A0组15例、A 1组6例、A2组2例.各组血钙较术前均显著下降,A0组下降最明显,且在术后1～4天无明显升高趋势,而A1、A2组呈逐渐升高趋势,A2组升高更快;各组血PTH较术前均显著下降,A0组下降最明显,且在术后1～4天无明显升高趋势,A1、A2组血清PTH水平呈上升趋势,但术后4天内,上述两组血PTH均未上升至术前水平.各组引流液PTH水平差异显著,A2组均值最高,A1组次之,A0组最低;随着时间的推移,A0组无明显变化,A1、A2组病人引流液PTH水平总体呈下降趋势,A1组较A2组下降更快.结论 甲状腺术后监测血钙、血PTH、引流液PTH可有效地评估原位保留甲状旁腺功能恢复情况,而中央区引流液PTH可直接反映原位保留甲状旁腺的活性,术后引流液维持在一个高水平是原位保留的甲状旁腺存活的直接证据.

Helminth infection affects over 1 billion people worldwide. However, its relationship with the gut mycobiome remains unknown.

目的 探讨慢病毒短发夹RNA(shRNA)介导的多形性腺瘤基因样蛋白2(PLAGL2)沉默对肝癌细胞恶性行为的影响及其机制.方法 Real-time PCR与Western blotting分别检测肝癌组织及癌旁组织中PLAGL2的表达水平;体外培养肝癌细胞MHCC97-L,构建慢病毒载体质粒PLAGL2-shRNA与对照NC-shRNA,转染MHCC97-L细胞,采用嘌呤霉素筛选稳转株;CCK-8、Transwell小室实验检测沉默PLAGL2后MHCC97-L细胞的增殖活力以及迁移和侵袭数量;Western blotting检测p-PI3K和p-Akt蛋白表达.用PI3K/Akt信号通路激活剂处理MHCC97-L细胞,检测细胞增殖、迁移及侵袭能力.结果 肝癌组织中PLAGL2表达水平显著升高(P＜0.05);9株MHCC97-L细胞转染PLAGL2-shRNA可明显降低PLAGL2表达水平,同时,细胞增殖、迁移、侵袭能力减弱(P＜0.05),p-PI3K、p-Akt表达受抑制(P＜0.05);PI3K/Akt激活剂可明显逆转上述现象.结论 慢病毒shRNA载体介导的PLAGL2沉默,可显著抑制肝癌细胞恶性行为,其作用机制可能与抑制PI3K/Akt信号通路的激活有关.

Objective The study aimed to investigate the value of solute carrier organic anion transporter family member 4A1 (SLCO4A1) in thyroid cancer mainly from three aspects: expression, prognosis, and biological function analyses. Methods Based on various bioinformatic approaches, genes co-expressed with vascular endothelial growth factor C (VEGFC) in thyroid cancer were used for further survival and expression analyses to identify the target gene. After evaluation of the SLCO4A1 expression levels in thyroid cancer, Cox regression analysis was utilized to predict the risk factors for survival of thyroid cancer patients. And receiving operating characteristic curve analysis was performed to validate the prognostic value of SLCO4A1. Additionally, WebGestalt was employed for enrichment analysis of SLCO4A1 and its co-expressed genes. Further, the relation between SLCO4A1 and neutrophil was analyzed, followed by exploring the association of SLCO4A1 with immunomodulators. Results A total of 38 consistent VEGFC co-expressed genes were generated, and SLCO4A1 was selected as the target gene due to its oncogenic characteristics. SLCO4A1 was highly expressed in thyroid cancer at both gene and protein levels, and SLCO4A1 mRNA expression was significantly associated with the cancer stage (all P <0.05). Besides, high SLCO4A1 expression led to unfavorable progression-free survival (PFS) of thyroid cancer patients (P =0.0066). Further, Cox regression analysis indicated that high SLCO4A1 expression was an independent predictor of poor PFS in patients with papillary thyroid cancer, particularly in patients at stage 1 and female patients (all P <0.001). The enrichment analysis results showed that SLCO41A was involved in the neutrophil-mediated immunity pathway. Moreover, SLCO4A1 had a positive relation with neutrophils (all P <0.05). Finally, a significant correlation between SLCO4A1 and immunomodulators was observed (all P <0.001). Conclusion SLCO4A1 was a potential prognostic biomarker for papillary thyroid cancer patients. And SLCO4A1 might affect PFS in thyroid cancer patients by positive regulation of neutrophil-mediated immunity pathway.

目的 探讨抗菌肽LL-37对人胃癌细胞系AGS细胞凋亡的影响及其分子机制.方法 不同浓度(0、10、20、40μmol/L)LL-37处理胃癌AGS细胞24 h,采用MTT法检测细胞增殖活性,Annexin V-FITC/PI双染流式细胞术法检测细胞凋亡,qRT-PCR法检测细胞中p53 mRNA表达水平,免疫荧光法检测细胞中p53蛋白定位,Western blot法检测细胞核中p53蛋白表达以及细胞中Cleaved-caspase-3、PUMA、Bcl-2和Bax等凋亡相关蛋白表达;干扰p53基因表达验证LL-37通过激活p53信号通路诱导胃癌AGS细胞凋亡.结果 LL-37可剂量依赖性抑制胃癌AGS细胞增殖,提高细胞凋亡率,上调p53 mRNA和蛋白表达水平并促进p53蛋白核转位,同时促进凋亡蛋白Cleaved-caspase-3、PUMA和Bax表达,抑制抗凋亡蛋白Bcl-2表达.干扰p53基因表达可抑制LL-37诱导的AGS细胞凋亡.结论 LL-37可诱导胃癌AGS细胞凋亡,其机制可能与激活p53表达有关.

目的:研究姜黄素对亚急性肝内胆汁淤积(intrahepatic cholestasis,IHC)大鼠肠内菌群变化的影响,并分析相关机制.方法:38只IHC大鼠随机分为模型组(9只)、姜黄素低剂量组(9只)、姜黄素高剂量组(10只)、阳性药物组(10只),9只健康大鼠设置为对照组.姜黄素低、高剂量组姜黄素200、400 mg·kg-1灌胃;阳性药物组熊去氧胆酸60 mg· kg-1灌胃;对照组与疾病组等量生理盐水灌胃.均为每天一次;干预14 d.检测肝功能指标、胆红素代谢指标、炎症指标;qRT-PCR反应定量检测肠内菌群;Western blot检测肝组织核转录因子-κB(NF-κB) p65、p-NF-κB p65、核因子抑制蛋白(IκBα)、p-IκBα蛋白相对表达量.结果:与疾病组比较,姜黄素低、高剂量组、阳性药物组碱性磷酸酶(ALP)、丙氨酸氨基转移酶(ALT)、谷草转氨酶(AST)、γ-谷氨酰转肽酶(GGT)、总胆红素(TBIL)、直接胆红素(DBIL)、总胆汁酸(TBA)、白介素-1β(IL-1β)、白介素-6(IL-6)、转化生长因子β1(TGF-β1)均降低,白介素-10(IL-10)均升高,乳酸杆菌、双歧杆菌均增加,大肠杆菌均减少(P＜0.05);与姜黄素低剂量组比较,姜黄素高剂量组、阳性药物组ALP、ALT、AST、GGT、TBIL、DBIL、TBA、IL-1β、IL-6、TGF-β1均降低,IL-10均升高,乳酸杆菌、双歧杆菌均增加,大肠杆菌均减少(P＜0.05).与疾病组比较,姜黄素低、高剂量组、阳性药物组p-NF-κB p65/NF-κB p65,p-IκBα/IκBα均降低(P＜0.05);与姜黄素低剂量组比较,姜黄素高剂量组、阳性药物组p-NF-cB p65/NF-κB p65,p-IκBα/IκBα均降低(P＜0.05).结论:姜黄素可改善亚急性IHC模型大鼠肝功能、胆红素代谢、肠道菌群,减轻炎症反应及肝脏组织病理变化,且具有剂量依赖性,推测其作用机制与抑制NF-κB信号通路有关.

ObjectiveTo investigate the postoperative complications of ex vivo liver resection combined with autologous liver transplantation in the treatment of end-stage hepatic alveolar echinococcosis at high altitude and related prevention and treatment strategies. MethodsSurgical data and follow-up data were collected from 11 patients with end-stage hepatic alveolar echinococcosis who underwent autologous liver transplantation in Qinghai People’s Hospital from January 2013 to March 2019, and intraoperative and postoperative conditions were analyzed. ResultsAll 11 patients underwent autologous liver transplantation successfully, without intraoperative death, among whom 2(18.18%) underwent hemi-extracorporeal hepatectomy and 9 (81.82%) underwent total extracorporeal hepatectomy. For the reconstruction of the retrohepatic inferior vena cava, 2 patients (18.18%) underwent reconstruction with the autologous great saphenous vein, 4 patients (36.36%) underwent reconstruction with artificial vessels, and the autologous retrohepatic inferior vena cava was preserved in 5 patients (45.45%). For biliary reconstruction, 8 patients (72.73%) underwent choledochoenterostomy and 3 (27.27%) underwent choledochocholedochostomy. The main postoperative complications of the 11 patients included bleeding in 2 patients (18.18%), bile leakage and abdominal infection in 4 patients (36.36%), bilioenteric anastomotic stenosis in 1 patient (9.09%), thrombus in 2 patients (1818%), pulmonary infection and pleural effusion in 2 patients (18.18%), and echinococcosis recurrence in 1 patient (9.09%). Of all 11 patients, 2 (18.18%) died during the perioperative period, and the other 9 patients (81.82%) were improved and discharged. Conclusion Bleeding, biliary complications, and infection are the main causes of death in patients undergoing autologous liver transplantation at high altitude. An accurate understanding of surgical indication, careful multidisciplinary evaluation before surgery, superb operation during surgery, standardized surgical procedures, and fine perioperative management are the key to reducing perioperative mortality, avoiding and reducing postoperative complications, and achieving good long-term survival in patients undergoing autologous liver transplantation.

目的:探讨miR-526b-3p对肝癌细胞增殖、迁移及侵袭的影响及其潜在的作用机制.方法:运用qRT-PCR检测人肝癌细胞HepG2、SMMC-7721、BEL-7402和正常肝细胞L02中miR-526b-3p和TNKS2的mRNA表达水平.建立miR-526b-3p过表达和TNKS2抑制表达的HepG2细胞株,采用MTT法检测细胞增殖活力,Transwell小室检测细胞的迁移及侵袭能力,Western blot检测TNKS2蛋白的表达水平;双荧光素酶报告基因分析法验证miR-526b-3p可能的靶基因.结果:与正常肝细胞L02相比,肝癌细胞HepG2、SMMC-7721及BEL-7402中miR-526b-3p的表达显著降低(P<0.05),TNKS2的表达显著升高(P<0.05).过表达miR-526b-3p或抑制表达TNKS2均可抑制HepG2细胞的增殖、迁移及侵袭(P<0.05).TNKS2是miR-526b-3p的靶基因.过表达TNKS2可部分逆转过表达miR-526b-3p对HepG2细胞增殖、迁移及侵袭的抑制作用.结论:miR-526b-3p可通过下调TNKS2的表达,从而抑制肝癌细胞的增殖、迁移及侵袭能力.

目的 探讨长基因间非编码RNA 1980(LINC01980)对微小RNA-335-5p(miR-335-5p)的靶向调控作用及胃癌细胞迁移侵袭的影响.方法 采用实时荧光定量PCR(qPCR)检测人胃黏膜上皮细胞GES-1及胃癌细胞(AGS、HGC-27、MKN-45和MGC80-3)的LINC01980和miR-335-5p水平,双荧光素酶报告基因实验验证LINC01980与miR-335-5p的相互关系;将MGC80-3细胞分为4组:对照组(未转染)、LINC01980干扰(si-LINC01980)组(转染si-LINC01980+miR-335-5p无关序列miR-NC)、miR-335-5p抑制物inhibitor(miR-inhibitor)组(转染无关序列si-NC+miR-335-5p inhibitor)和共转染组(转染si-LINC01980+miR-335-5p inhibitor).MTT、划痕实验和Transwell小室实验分别检测细胞增殖活力、迁移和侵袭能力.结果 与GES-1细胞相比,胃癌细胞的LINC01980水平升高,而miR-335-5p水平降低(P<0.05).野生型LINC01980序列与miR-335-5p模拟物共转染细胞的荧光素酶活性降低且MGC80-3细胞转染si-LINC01980后的miR-335-5p水平升高(P<0.05).对照组、si-LINC01980组、miR-inhibitor组和共转染组的细胞活力分别为1.508±0.101、0.944±0.077、1.856±0.117和1.404±0.082,划痕愈合率分别为(65.552±3.701)％、(19.920±2.571)％、(88.133±1.264)％和(75.433±7.313)％,穿膜细胞数分别为(80.349±8.763)、(31.151±1.338)、(114.064±2.983)和(78.920±7.811)个,与对照组相比,si-LINC01980组的细胞活力、划痕愈合率和穿膜细胞数均降低(P<0.05),miR-inhibitor组均升高(P<0.05),而共转染组的无明显变化(P>0.05).结论 干扰LINC01980可能通过增强miR-335-5p表达来抑制胃癌的进展,LINC01980/miR-335-5p轴有望成为胃癌治疗的潜在靶点.

OBJECTIVE:To analyze the sequences of the cytochrome C oxidase subunit I (Cox1) gene of various Echinococcus granulosus genotypes that are currently recorded in the GenBank database, so as to investigate the genetic variation and differentiation of the E. granulosus genotypes across the world.METHODS:The sequences of the Cox1 gene of various E. granulosus genotypes that are currently recorded in the GenBank database were collected, and the same sequences of the Cox1 gene identified from a region were excluded. The mutation sites among the Cox1 gene sequences were identified and a phylogenetic tree was created based on the Cox1 gene.RESULTS:Transversion mutation was the predominant type of mutation in the Cox1 gene of E. granulosus. The same Cox1 gene sequence was found in E. granulosus G1, G6 and G7 genotypes isolated from various geographical locations across the world, with the corresponding GenBank accession numbers of KY766891, MH300971 and MH301007, respectively. Phylogenetic analysis revealed that E. granulosus G10 genotype had a remarkable geographical aggregation.CONCLUSIONS:E. granulosus G1, G6 and G7 genotypes have primitive Cox1 gene sequences. There is a geographical aggregation of the E. granulosus G10 genotype in the phylogenetic tree, which has a tendency towards reproductive isolation.

Alveolar echinococcosis is a parasitic zoonosis that severely damages human health. Currently, radical surgical resection is the first choice for hepatic alveolar echinococcosis. For the advanced hepatic echinococcosis patients with refractory radical resection, the palliative surgery combined with chemotherapy, liver transplantation, drug therapy, and radiofrequency microwave ablation may provide comprehensive tools. This article reviews the current situation and progress of comprehensive treatments for hepatic alveolar echinococcosis.

目的 探讨腹腔镜下腹股沟疝修补术对手术效果及T淋巴细胞百分比的影响.方法 选取2017年1月-2019年1月腹股沟疝患者280例作为研究对象,随机分为对照组(n=140)和观察组(n=140).对照组采用开放无张力疝修补术,观察组采用腹腔镜下无张力疝修补术,术后7 d对患者治疗效果进行评估,比较两组手术指标、疼痛视觉模拟评分(VAS)、T淋巴细胞百分比及术后并发症.结果 观察组与对照组手术时间比较,差异无统计学意义(P>0.05);观察组出血量、术后自主活动时间及VAS评分少于对照组(P<0.05);观察组治疗费用多于对照组(P<0.05);观察组手术后7 d CD3+、CD4+和CD4+/CD8+百分比高于对照组(P<0.05);观察组手术后7 d CD8+百分比低于对照组(P<0.05);观察组手术后切口疼痛、尿潴留、阴囊水肿及切口感染发生率与对照组比较,差异均无统计学意义(P>0.05).结论 将腹腔镜手术用于腹股沟疝患者中,手术创伤较小,能改善患者T淋巴细胞百分比,未增加术后并发症发生率,值得推广应用.

This study examined Echinococcus spp. genotypes and genetic variants isolated from humans as well as domestic and wild animals from the Qinghai-Tibetan Plateau Area using the cox1 gene. All samples except the pika isolates were identified as the Echinococcus granulosus sensu stricto. Sixteen different haplotypes with considerable intraspecific variation were detected and characterized in mitochondrial cox1 sequences. The parsimonious network of cox1 haplotypes showed star-like features, and the neutrality indexes computed via Tajima's D and Fu's Fs tests showed high negative values in E. granulosus s. s., indicating deviations from neutrality; the Fst values were low among the populations, implying that the populations were not genetically differentiated. The pika isolates were identified as E. multilocularis and E. shiquicus. Only one haplotype was recognized in the pika isolates. E. granulosus s. s. was the predominant species found in animals and humans, followed by E. multilocularis and E. shiquicus, with high genetic diversity circulating among the animals and humans in this area. Further studies are needed to cover many sample collection sites and larger numbers of pathogen isolates, which may reveal abundant strains and/or other haplotypes in the hydatid cysts infecting human and animal populations of the QTPA, China.

This study was conducted to investigate the efficacy of a new formulation of MBZ oily suspension (MBZ-OS) in experimentally Echinococcus multilocularis-infected mice. MBZ-OS was prepared and administered to mice infected with E. multilocularis at 12.5 and 25 mg/kg for 14 consecutive days. Then, the cysts were collected, weighed and histologically examined. The results showed that the reduction rate of cyst weight induced by MBZ-OS at two doses was 95.23% and 92.67%, which was significantly higher than that of MBZ-1% tragacanth (positive control) at corresponding concentrations (87.41% and 69.47%), indicating that the treatment of alveolar echinococcosis at lower doses could be achieved by the use of MBZ-OS. This finding shows that MBZ-OS is also a promising formulation for alveolar echinococcosis as well as cystic echinococcosis and deserves to be investigated in clinical applications against echinococcosis.