Gastric cancer (GC) ranks as the fifth most prevalent cancer on a global scale, with HER2-positive GC representing a distinct subtype that exhibits more intricate biological characteristics. Conventional chemotherapy typically exhibits restricted efficacy in the management of HER2-positive GC. In light of the incessant advancement in molecular targeted therapies, targeting HER2 has emerged as a promising therapeutic approach for this subtype. The advent of antibody-drug conjugates (ADCs) and chimeric antigen receptor T-cell therapy (CAR-T) has furnished novel treatment alternatives for HER2-positive GC. Nevertheless, owing to the pronounced heterogeneity of GC and the complex tumor microenvironment, drug resistance frequently emerges, thereby substantially influencing the effectiveness of HER2-targeted therapy. This article comprehensively summarizes and deliberates upon the strategies of HER2-targeted therapy as well as the underlying resistance mechanisms.

新冠传染病在全世界的大流行客观上加速了信息技术的应用普及,信息技术与教育的融合也越来越紧密.在教育领域,师生对教学的交互性、沉浸性和多元性的需求日益增加,元宇宙能将虚实共融的智慧学习环境进行进一步的重塑.自2021年以来,全球的每一个角落都出现了对元宇宙的研究,并且研究热度呈现爆发式的增长,其对变革人类教育具有巨大的应用价值,尤其是在医学教育领域蕴含有相当大的潜能.本文对元宇宙与教育的关系以及元宇宙在临床医学教育中的应用展开讨论,为今后临床医学教育教学的改革与创新提供思路.

膜转运蛋白的溶质载体(solute carrier,SLC)是位于细胞表面和细胞器膜中的完整细胞膜蛋白,主要参与调节细胞基本生物分子和药物跨膜转运以及亚细胞成分的流入和流出.SLC在肿瘤发生发展的各个过程起调节作用,如增殖、迁移、血管生成、上皮-间充质转化、表观遗传修饰、化疗耐药、免疫调节、肿瘤代谢等.目前,许多针对 SLC 家族成员的治疗方法已经在其他癌症临床试验中得到检验,但 SLC在胃癌中的价值在很大程度上仍未得到探索.本文总结了 SLC 在胃癌中的最新研究现状,旨在为深入探索 SLC在胃癌中的作用提供参考.

BackgroundLymph node status is an important factor in determining the prognosis of patients with early gastric cancer (EGC) and preoperative diagnosis of lymph node metastasis (LNM) has some limitations. This study explored the risk factors and independent prognostic factors of LNM in EGC patients and constructed a clinical prediction model to predict LNM.MethodsClinicopathological data of EGC patients was collected from the public Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression was used to identify risk factors for LNM in EGC patients. The performance of the LNM model was evaluated by C-index, calibration curve, receiver operating characteristic (ROC) curve, decision curve analysis (DCA) curve, and clinical impact curve (CIC) based on the results of multivariate regression to develop a nomogram. An independent data set was obtained from China for external validation. The Kaplan-Meier method and Cox regression model were used to identify potential prognostic factors for overall survival (OS) in EGC patients.ResultsA total of 3993 EGC patients were randomly allocated to a training cohort (n=2797) and a validation cohort (n=1196). An external cohort of 106 patients from the Second Hospital of Lanzhou University was used for external validation. Univariate and multivariate logistic regression showed that age, tumor size, differentiation, and examined lymph nodes count (ELNC) were independent risk factors for LNM. Nomogram for predicting LNM in EGC patients was developed and validated. The predictive model had a good discriminatory performance with a concordance index (C-index) of 0.702 (95% CI: 0.679-0.725). The calibration plots showed that the predicted LNM probabilities were the same as the actual observations in both the internal validation cohort and external validation cohort. The AUC values for the training cohort, internal validation cohort and external validation cohort were 0.702 (95% CI: 0.679-0.725), 0.709 (95% CI: 0.674-0.744) and 0.750(95% CI: 0.607-0.892), respectively, and the DCA curves and CIC showed good clinical applicability. The Cox regression model identified age, sex, race, primary site, size, pathological type, LNM, distant metastasis, and ELNC were prognostic factors for OS in EGC patients, while a year at diagnosis, grade, marital status, radiotherapy, and chemotherapy were not independent prognostic factors.ConclusionIn this study, we identified risk factors and independent prognostic factors for the development of LNM in EGC patients, and developed a relatively accurate model to predict the development of LNM in EGC patients.

目的 评估基于淋巴结比率(LNR)所建立的新的rAJCC TNM分期预测模型(rAJCC分期系统)在临床中的应用价值.方法 收集兰州大学第二医院诊断为非转移性胃癌并进行了D2淋巴结清扫术的患者数据,分别利用AJCC及rAJCC分期系统对患者进行分期并比较,评估rAJCC的rN分期与第八版AJCC分期的每个N分期对患者预后的影响.结果 以LNR截点重新定义AJCC N分期,rN0、rN1、rN2、rN3a和rN3b对应的5年OS率分别为71.9％、56.6％、52.3％、34.3％和33.1％(log-rank检验P<0.01),而rAJCC rN分期各期患者的5年OS率分别为84.6％(rIA期)、77.4％(rIB期)、43.8％(rⅡA期)、71.1％(rⅡB期)、37.4％(rⅢA期)、56.3％(rⅢB期)和27.4％(rⅢC期)(log-rank检验P<0.001),rAJCC分期系统的判别能力和预后同质性同比均优于第八版AJCC分期.结论 基于LRN的新的rAJCC TNM分期预测模型在胃癌患者的分期及对患者的预后预测能力上具有一定优势,对胃癌患者的临床管理具有指导意义.

The postoperative pathological staging system (pTNM) has become an important reference for the selection of various tumor treatment strategies and prognosis evaluation at a global scale, and is a powerful predictor of the prognosis of a variety of solid tumors, but the prognosis is still different in patients with the same pTNM staging. In recent years, studies have confirmed that the negative lymph nodes count (NLNC) is related to the prognosis of a variety of solid tumors. Higher NLNC can improve the prognosis of cancer patients, and NLNC can reduce staging migration, which is expected to be a supplement to the pTNM staging system. This article reviews the value of NLNC in the prognosis of solid tumors.

Objective To explore the influence of negative lymph node count (NLNC) on the prognosis of patients with gastric signet ring cell carcinoma (GSRC) and develop a prognostic nomogram based on NLNC. Methods On the basis of the SEER database, 2 101 patients diagnosed with GSRC were collected and randomly divided into the modeling group and validation group to test the relationship between clinicopathological characteristics and the prognosis of GSRC. The multivariate Cox proportional hazard regression model was used to analyze the independent risk factors affecting overall survival and establish a prognostic prediction model. The consistency index (C-index), calibration curve, net reclassification index (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) were used to evaluate the accuracy and clinical applicability of the nomogram. Results All patients were divided according to the ratio of 7:3, with 1 473 in the modeling group and 628 in the validation group. NLNC > 10 (HR=0.578, 95%CI: 0.504-0.662, P < 0.001) was a protective factor for the prognosis of patients with GSRC, and the nomogram model was established based on multivariate Cox proportional hazards model. The C-index values of the nomogram were 0.737 (95%CI: 0.720-0.753) and 0.724 (95%CI: 0.699-0.749) in the modeling and validation groups, respectively, showing good discrimination. The calibration curves showed high consistency of the model. NRI=17.77%, continuous NRI=36.34%, and IDI=4.2% indicated that the model had positive returns compared with the traditional model. The DCA was far from the baseline, indicating that the model had good clinical applicability. Conclusion The increase in NLNC is a favorable factor for the prognosis of patients with GSRC, and a relatively accurate nomogram was established to predict the prognosis of patients with GSRC and help clinicians conduct individualized prognostic evaluations.

Liver cancer is the third most common cancer, with increasing morbidity and mortality rates worldwide. Despite the increasing occurrence of liver cancer, it has a poor prognosis and potential treatment options are still lacking. The current study aimed to explore the anticancer potential of arbutin against diethylnitrosamine (DEN)-triggered liver carcinogenesis in rats. Liver cancer was initiated in rats via the administration of DEN (200 mg/kg) and then treated with 30 mg/kg of arbutin. Albumin, globulin, and total protein were quantified using kits. Antioxidant, liver injury marker, and tumor biomarker contents were quantified using marker-specific assay kits. The inflammatory markers c-JNK, TRAIL, caspase-8, and p53 contents were also detected using kits. Reverse transcription PCR analysis was used to study the expression of chaperones GRP78, GRP94, and PDIA4 as well as ERDJ4, ATF4, and GADD34. Liver histology was studied microscopically. The arbutin treatment effectively improved body weight and reduced liver weight in animals with DEN-provoked liver cancer. The treatment also improved the albumin, globulin, and total protein contents and antioxidants. In addition, arbutin reduced liver injury marker enzyme function and improved c-JNK, TRAIL, caspase-8, and p53 contents. Arbutin supplementation also decreased the expression of GRP78, PDIA4, GRP94, ERDJ4, ATF4, and GADD34 in the liver tissues of DEN-provoked animals. Arbutin effectively ameliorated the DEN-provoked histological alterations. Altogether, our findings show that arbutin has anti-inflammatory, antioxidant, and anticarcinogenic activities against DEN-provoked liver cancer in rats.

miR-613 has been demonstrated to play critical roles in tumorigenesis and progression of a various type of cancers. However, its role and expression significance remain unclear in gastric cancer (GC). We detected the expression of miR-613 in 176 paired GC tissues and adjacent normal tissues, and found that miR-613 was significantly downregulated in GC tissues and its downregulation was correlated with T stage, lymph node invasion and advanced AJCC stages. Moreover, miR-613 expression could be an independent prognostic factor of GC. Biological function analysis indicated that miR-613 inhibited cell proliferation and invasion. Further analysis suggested that miR-613 inhibited Warburg effect of GC cells. Mechanically, we identified that miR-613 could directly bind to the 3′UTR of PFKFB2, thereby suppressing the expression of PFKFB2, which in turn, regulating glycolysis metabolism and cell growth. In conclusion, miR-613 served as a tumor suppressor by targeting PFKFB2, indicating that detecting miR-613 and modulation of miR-613 expression could be potential marker and clinical approach in GC patients.

Objective:To investigate the prognostic significance of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients with gastric cancer (GC) in areas of high GC incidence. Methods:The clinical data of 98 patients with GC who underwent surgical treatment were collected and follow-up was conducted. The serum level of CEA and CA19-9 was detected by electro-chemiluminescence immunoassay. Results:The proportion of patients with positive CEA in the depth of tumor invasion (T3 + T4) group was higher than that of the depth of tumor invasion (T1 +T2) group (χ2 =9.934, P =0.007). The proportion of patients with CEA positive in the tumor high/moderate differentiation group was higher than that of low differentiation group (χ2 =4. 401,P =0.036). The proportion of patients with CA19-9 positive in lymph node metastasis N2 group was higher than that in other groups(χ2 =9.105,P =0.028). The postoperative serum CEA level was(2. 33±1.90)ng/mL,lower than preoperative (10. 01 ±28. 32) ng/mL(Z=-5.468,P =0.000). The survival rate of serum CA19-9 positive group was lower than that of CA19-9 negative group (χ2 =5.017,P =0.017). Abnormal increase of pretreatment serum CA19-9 was an independent risk factor for postoperative long-term survival in patients with GC (HR:2.186, 95 ％ CI:1.095 ～4. 366, P =0.027). Conclusion:The detection of serum CEA and CA19-9 levels is of great value in the diagnosis of GC and in the evaluation of prognosis. It is worthy of clinical application.

BACKGROUND:Digestive system cancers are recognized as associated with high morbidity and mortality. It is generally accepted that N-myc downstream-regulated gene 1 (NDRG1) is aberrantly overexpressed or downregulated in digestive system cancers, and its prognostic value remains controversial. Accordingly, we herein conducted a meta-analysis to explore whether NDRG1 expression is correlated with overall survival (OS) and clinicopathological characteristics of patients with digestive system cancers. METHODS:We systematically searched PubMed, EMBASE, and Web of Science for eligible studies up to June 6, 2017. In all, 19 publications with 21 studies, were included. RESULTS:The pooled results showed that low NDRG1 expression was significantly associated with worse OS in colorectal cancer (pooled HR = 1.67, 95% CI: 1.22-2.28, P < .001) and pancreatic cancer (pooled HR = 1.87, 95% CI: 1-3.5, P < .0001). Moreover, the relationships between low NDRG1 expression and higher OS ratio of patients with liver cancer (pooled HR = 0.44, 95% CI: 0.32-0.62, P = .009) and gallbladder cancer (pooled HR = 0.56, 95% CI: 0.23-1.38, P = .01) were observed. Nevertheless, no significant association was observed between low NDRG1 expression and OS in gastric cancer (pooled HR = 0.81, 95% CI: 0.45-1.43, P = .46) or esophageal cancer (pooled HR = 0.76, 95% CI: 0.26-2.24, P = .62). CONCLUSION:The prognostic significance of NDRG1 expression varies according to cancer type in patients with DSCs. Considering that several limitations existed in this meta-analysis, more studies are required to further assess the prognostic value of NDRG1 expression in patients with DSCs and relevant mechanisms.

Stroke remains the major complication among patients on dialysis.In chronic hemodialysis patients,prevalence and incidence of stroke are higher than those in general population.This article provides an overview of stroke in patients on dialysis,including clinical features,early warning and recognition,prevention and treatment.

目的 探讨胃癌患者HER-2的过表达及临床病理学意义.方法 选取2013年1月至2014年6月在兰州大学第二医院收治的经病理确诊的胃癌患者共540例.IHC法检测胃腺癌患者中HER-2的表达,以改良Hercep Test评分标准进行HER-2免疫组化结果 判读,用卡方检验分析HER-2蛋白在胃腺癌组织中的表达与临床病理学参数的相关性.结果540例患者平均年龄56.5岁,男女比例3.5:1.HER-2蛋白过表达(IHC3+)共88例,总过表达率为16.3%.胃癌患者HER-2蛋白的过表达与肿瘤发生部位、肿瘤分化程度、有无淋巴结转移、是否有神经血管侵犯有关(P<0.05),而与患者的性别、年龄、肿瘤大小、肿瘤浸润深度、TNM分期、有无远处转移无相关性(P>0.05).结论 胃癌患者HER-2蛋白总过表达率为16.3%.胃癌组织中HER-2蛋白的过表达与肿瘤发生部位、分化程度、有无淋巴结转移、是否有神经血管侵犯相关.

阑尾黏液腺癌(mucinous adenocarcinoma of the ap-pendix,MAA)临床罕见,目前未发现明确致癌因素.MAA术前诊断困难,没有特征性临床表现,与急、慢性阑尾炎表现相似,大多数MAA是在阑尾切除标本中发现,故多数病人在发现时已属晚期,不但局部浸润明显,并可能有远处转移,晚期MAA有时局部可扪到包块,B超和CT检查可发现占位性病变,钡餐X线检查可发现回盲部有不规则占位[1].结合我院近期诊治的1例阑尾黏液腺癌,现报告如下.

在我国,胃癌发病率具消化系统肿瘤之首,其治疗采取以手术为主的综合治疗策略.胆囊结石为肝胆系统常见的良性疾病,其在胃癌术后的高发病率及对术后患者生活质量的影响逐渐引起医学界的重视.胃癌术后胆囊结石的形成与胃癌手术切除范围、消化道重建方式、淋巴结清扫范围及术后管理有关,并通过保留迷走神经干和(或)分支胃癌根治术、腹腔镜胆囊切除术、胃癌根治同期合并胆囊切除术等进行处理.

Objective To observed the expression of serum TNF-α and IL-10 in rats with severe acute pancreatitis (SAP) at different altitudes,and to explore the relationships between TNF-α and IL-10,the pathological changes of the pancreas,and the experimental basis for clinical diagnosis and treatment of SAP.Methods 72 specific pathogen free (SPF) Wistar male rats were divided randomly into three groups:1 500 meters altitude (group L),3 300 meters altitude (group M),and 4 300 meters altitude (group H).These three groups were then each divided randomly into four subgroups:control (group n),6 hours after pancreatitis (group p 6 h),12 hours after pancreatitis (group p 12 h),and 24 hours after pancreatitis (group p 24 h).Pancreatitis was induced by intraductal administration of 5％ sodium taurocholate hydrate (NaTc).The rats were killed at 6,12,and 24 hours after NaTc injection in groups p.The group n rats were killed after 6 hours of pancreas observation.Blood samples and pancreatic tissues were collected post mortem and enzyme-linked immunosorbent assay (ELISA) measured serum TNF-α and IL-10.Results Compared with the control (group n),histopathological scores,IL-10,and TNF-α in the same altitude had a significant difference (P ＜ 0.05) in group p at each time point.In the same altitude of group p,histopathological scores and IL-10 were increased with time elapsed (P ＜ 0.05),while TNF-α was decreased with time elapsed (P ＜ 0.05).There was a significant difference between group Mp and Lp in histopathological scores,IL-10,and TNF-α (P ＜ 0.05),and the same result between group Hp and Lp (P ＜ 0.05),but there was no significant difference between group Hp and Mp (P ＜ 0.05).Meanwhile,IL-10 had a positive relationship with histopathological score,but TNF-α had a negative relationship with histopathological score.Conclusions The level of TNF-α increased with increasing altitude but significantly reduced with elapsed time.The level of IL-10 increased with both increasing altitude elapsed time.These results suggested that TNF-o and IL-10 might play a important role at different times in severe acute pancreatitis.

心肌肌钙蛋白(cTnT)和N-末端脑钠肽前体(NT-proBNP)水平是临床常用的心脏生物标记物.研究发现,部分慢性肾脏病(CKD)患者,即使无心肌缺血和心力衰竭(心衰),其血清cTnT和NT-proBNP亦可升高,且与心脑血管事件及死亡显著相关[1-2].本研究通过检测CKD 3～4期患者心脏生物标记物水平,以探究其与CKD患者预后的相关性.

本文报道了1例Cushing病伴罕见严重低钾血症患者,通过病例报道及对以往相关文献进行复习,加深对Cushing病及严重低钾血症的认识.

Objective To investigate the alterations of blood coagulation and fibrinolysis system in murine experimental severe acute pancreatitis (SAP) at different altitudes.Methods 72 Wistar male rats were divided into three groups randomly (n =24 in each group):4300 metres' altitude(group H),3300metres' altitude group(group M) and 1500 metres' altitude group(group L).Each group was further divided into four subgroups (n =6 in each subgroup):normal group (group N),6 hour after SAP model establishment group(group p6 h),12 hour after SAP model group(group p12 h),24 hour after SAP model group(group p24 h).Retrograde pancreatic duct injection of 5％ sodium taurocholate (NaTc) method was used to establish SAP animal model.The levels of amylase (AMY),D-dimer,prothrombin time (PT),activated partial thromboplastin time (APTT),fibrinogen (FIB) and the contents of antithrombin Ⅲ (AT-Ⅲ) in serum were measured.Pancreatic tissues were sampled and studied by hematoxylin-eosin(HE) staining.Results (1)Compared to group N,the pancreas pathology score,AMY,Fib and D-dimer in serum increased significantly (P ＜ 0.05) and PT,APTT and AT-Ⅲ lowered significantly (P ＜ 0.05) at each time point in group P in the same altitude.In group P,the contents of Fib and D-dimer and pathological score gradually increased with time (P ＜ 0.05),AT-Ⅲ activitise gradually decreased with time (P ＜ 0.05) ; there was a significant difference (P ＜ 0.05) when Fib,D-dimer,AT-Ⅲ was compared among three altitude's group P.(2) There was a significant difference (P ＜ 0.05) between histological scores,PT and APTT in group Hp and group Lp,and the same result (P ＜ 0.05) between group Mp and group Lp.There was no significant difference between group Hp and group Mp (P ＞ 0.05).(3) There was a positive correlation between histological scores and Fib,D-dimer (P ＜ 0.05) in group P in the same altitude ; AT-Ⅲ and histological scores,Fib,D-dimer (P ＜ 0.05) have a negative correlation in group P in the same altitude.Conclusions More severe damage of pancreatic tissues and disorders of coagulation and fibrinolysis system were observed in rats with severe acute pancmatitis at high altitudes.Changes in blood coagulation and fibrinolysis system may be involved in the severity of acute pancreatitis.

胰腺癌是一高度恶性肿瘤.临床上,胰腺癌的主要症状包括消化不良、恶心、体重减轻、黄疸、脂肪泻、疼痛和抑郁.实际上黄疸和腹痛出现时,病变多属进展期,而在此之前有些非特异症状,如消化不良和体重减轻很易误为其他疾病和功能异常,所以在确诊后绝大多数患者失去了治愈的机会.临床上将直径<2.0 cm的胰腺癌称为小胰癌,是能否手术切除的重要指标.