ABSTRACT Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of malignant tumors; however, their clinical efficacy remains constrained by primary or acquired resistance and immune‐related adverse events (irAEs). To improve the overall efficacy of immunotherapy, the development of synergistic strategies with high efficacy and low toxicity has emerged as a critical research direction. Natural products, characterized by their multi‐target properties and low toxicity, exhibit unique advantages in enhancing immunotherapy responses and represent promising immunotherapeutic adjuvants. This review systematically delineates the underlying mechanisms of ICI resistance and immune‐related adverse events. It further provides a comprehensive summary of the currently elucidated mechanisms by which natural products function as immunotherapeutic adjuvants, focusing on three interconnected dimensions of synergistic enhancement: enhancing T cell function through epigenetic and metabolic reprogramming to reverse T cell exhaustion and promote memory T cell generation; remodeling the immune microenvironment by inducing immunogenic cell death and regulating immunosuppressive cells; and modulating the gut microbiota‐immune axis to remotely activate systemic anti‐tumor immunity through gut microbiota and their metabolites. The three aspects are interdependent and form a synergistic regulatory network. This review aims to provide a theoretical basis and strategic reference for the development and application of natural products in combination immunotherapy.

OBJECTIVE:To evaluate the comparative efficacy and safety of standard lymphadenectomy (D2) versus extended lymphadenectomy (D2+) in gastric cancer surgery. Additionally, we explored the relationship between the number of dissected lymph nodes, the magnitude of postoperative inflammatory response, and long-term survival outcomes. METHODS:A retrospective cohort was conducted on clinical data from 421 patients diagnosed with gastric cancer and treated between April 2019 and January 2022. Among them, 189 underwent standard D2 dissection and 232 received extended D2+ lymph node dissection. All patients received neoadjuvant chemotherapy followed by radical gastrectomy. Baseline characteristics, intraoperative and postoperative outcomes, inflammatory markers including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), complication rates, and survival metrics (3-year overall survival (OS) and progression-free survival (PFS)) were compared between groups. Univariate and multivariate Cox proportional hazards models were applied to identify survival-associated factors. Kaplan-Meier survival curves were constructed for subgroup analysis by TNM (tumor-node-metastasis) stage. RESULTS:There were no significant differences in baseline characteristics between the D2 and D2+ groups (P > 0.05). Compared to the D2 group, the D2+ group exhibited significantly longer operative times, greater intraoperative blood loss, and more lymph nodes dissected (all P < 0.001), while the length of hospital stay remained similar between the two groups (P = 0.708). Postoperative levels of CRP, TNF-α, and IL-6 were significantly elevated in the D2+ group (all P < 0.001), correlating positively with the number of lymph nodes removed (all P < 0.001). The incidence of postoperative complications did not differ between groups (P > 0.05). Notably, the D2+ group demonstrated a superior 2-year OS rate (P = 0.002) and significantly improved 3-year OS in patients with stage II disease (P = 0.018). However, no significant differences were observed in 1-year OS (P = 0.067), 3-year OS (P = 0.699), or 3-year OS for stage III patients (P = 0.428). Multivariate Cox regression analysis identified extended D2+ dissection, younger age, lower TNM stage, and higher tumor differentiation as independent protective factors for PFS (all P < 0.05). CONCLUSION:Extended D2+ lymph node dissection improves survival outcomes, particularly in stage II gastric cancer patients, without increasing postoperative complication risk. However, it induces a more robust inflammatory response. These findings suggest that D2+ dissection should be selectively considered, weighing the oncological benefits against the potential inflammatory burden, particularly in stage II patients.

目的:探讨腹腔镜中低位直肠癌根治术(Dixon)经肛加固吻合口对预防直肠癌术后吻合口瘘的可行性.方法:收集2019年08月至2022年05月我院普外科行腹腔镜中低位直肠癌根治手术(Dixon)患者共127例.根据指南,中低位直肠癌为肿瘤下缘距离肛门10 cm以内,根据吻合口加固方式不同分为三组:经肛连续缝合组(n=43);经肛间断缝合组(n=42);对照组(未经肛门缝合组)(n=42).对患者一般资料、手术时间、术中出血量、肛门首次排气时间、进流食时间、术后住院时间、吻合口瘘、吻合口出血、切口感染、肛周疼痛进行比较.结果:三组患者一般资料比较无统计学差异(P>0.05),与对照组比较,经肛连续缝合组和经肛间断缝合组在手术时间、术中出血量、进流食时间、术后肛门排气时间、切口感染、肛周疼痛无统计学差异(P>0.05),而吻合口瘘方面,连续缝合组为4.65％,间断缝合组为4.76％,对照组为16.67％,三组间比较虽无统计学差异(P=0.079),但提示经肛缝合可降低吻合口瘘的发病,术后住院时间,间断缝合组为(8.17±1.52)d,连续缝合组为(8.15±1.69)d,对照组为(12.13±1.57)d,有统计学差异(P=0.035),经肛连续缝合组和经肛间断缝合组间比较术后住院时间无统计学差异(P>0.05).C级吻合口瘘对照组例数为3例,多于经肛缝合组1例.结论:腹腔镜中低位直肠癌根治手术经肛连续吻合口加固和经肛间断吻合口加固能降低术后吻合口瘘,技术操作简单,并缩短住院时间,可以临床推广应用.

Objective:To investigate the profile of PLXDC2 expression in gastric cancer tissues and the molecular mechanism by which PLXDC2 promotes the proliferation and clonal formation of gastric cancer cells.Methods:By retrieving the GEPIA and TCGA databases, the genes highly expressed in gastric cancer (tumor/normal>2) and significantly related to the clinical prognosis of gastric cancer were screened for overlap analysis. The target genes were determined by gene expression heatmap and the principle of high-expression-poor-prognosis. QRT-PCR and Western blotting were used to examine the expression of the target gene in 30 pairs of clinical gastric cancer tissue and normal adjacent tissue samples. After knock-down of target gene by transfection with interference siRNA, MTT cell proliferation assay, plate clone formation assay and flow cytometry were used to verify the effect of target genes on proliferation, clonal formation and cell cycle of gastric cancer. By retrieval and analysis of bioinformatics database for signal pathways involved in co-expression of the target gene, the potential molecular mechanism by which the target genes work in gastric cancer was explored and further determined.Results:The PLXDC2 mRNA (5.62±1.35) and protein (4.13±0.35) levels in gastric cancer tissues were significantly higher than those in cancer-adjacent normal tissues [mRNA (4.22±0.86) , protein (1.24±0.23) (both P<0.001) ]. With higher malignancy of gastric cancer, the PLXDC2 expression gradually increased, showing a clinical pattern of high-expression-poor-prognosis ( P<0.05) . On day 5 after culture with transfection, the proliferation rates of BGC-823 cells in the siPLXDC2#1 group (0.41±0.05) and siPLXDC2#2 group (0.35±0.07) were significantly lower than that in the siCTL group (0.58±0.08) ( P<0.01) . The rates of clonal formation in the siPLXDC2#1 group (0.49±0.07) and siPLXDC2#2 group (0.21±0.04) were significantly lower than that in the siCTL group (1.00±0.01) ( F=218.773, P<0.001) , and in these two groups, the cell cycle was significantly arrested at G1 phase. In the siPLXDC2#1 and siPLXDC2#2 groups, the levels of p-PI3K and P-AKT were significantly lower than those in the siCTL group ( P<0.001) , and the total expression of PI3K and AKT remained unchanged. Co-transfection with pcDNA3.1-PLXDC2 to the siPLXDC2 group of cells significantly reversed the inhibitory effects of siPLXDC2 on proliferation, clonal formation and signaling pathways of gastric cancer cells, and the cell level was shown to largely resume normal. Conclusion:The highly expressed PLXDC2 in gastric cancer may activate the PI3K/AKT signaling pathway, promote proliferation and clonal formation of gastric cancer cells, accelerate cell cycling, and participate in the development and progression of gastric cancer.

Objective:To investigate the expression of 3’-phosphoadenosine-5’-phosphosulfate synthase 2 (PAPSS2) in gastric cancer tissues and cells and its effects on the invasion and migration of gastric cancer cells.Methods:The expression of PAPSS2 in gastric cancer were analyzed using the GEPIA database. The tissue specimens of 40 gastric cancer patients from October 2016 to June 2018 in Shaanxi Provincial People’s Hospital were collected for immunohistochemical staining. The association between PAPSS2 expression and clinicopathological data and prognosis of the gastric cancer patients was analyzed. The expression levels of PAPSS2 in gastric cancer cells (HGC-27, SNU-1, AGS and SGC-7901) and normal gastric mucosa cell line (GES-1) were tested by qPCR and Western blotting. The expression of PAPSS2 in gastric cancer cells was knocked down using shRNA, its effect on cell activity was detected using MTT, and its effect on invasion and migration ability was detected using Transwell method.Results:(1) PAPSS2 was highly expressed in gastric cancer tissues according to GEPIA database (P<0.05). The overall survival rate (HR=1.5, P=0.017) and disease-free survival rate (HR=1.6, P=0.014) of patients with high PAPSS2 expression was significantly reduced. (2) Immunohistochemical staining revealed that the expression of PAPSS2 was significantly higher in gastric cancer tissues than in the corresponding paracancerous tissues (7.100±3.169 vs 3.425±2.263, P<0.001). Patients with high PAPSS2 expression had greater depth of invasion (P=0.015) and a higher rate of lymphatic metastasis (P=0.005). (3) qPCR results showed that the mRNA expression levels of PAPSS2 in gastric cancer cells (HGC-27, SNU-1, AGS and SGC-7901) were significantly higher than those in GES-1 cells. Similar results were obtained by Western blotting. (4) MTT assay showed that the knockdown of PAPSS2 had no significant effect on the activity of AGS and SGC-7901 cells. (5) The invasion and migration ability of AGS cells and SGC-7901 cells was significantly reduced after the PAPSS2 knockdown (P<0.05).Conclusion:PAPSS2 is highly expressed in tissues and cells of gastric cancer, and its high expression promotes the invasion and metastasis of gastric cancer cells, which may be one of the important reasons for the poor prognosis of patients with gastric cancer.

BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed and treated in advanced tumor stages with poor prognosis. More effective screening programs and novel therapeutic means are urgently needed. Recent studies have regarded tight junction protein claudin 18.2 (CLDN18.2) as a candidate target for cancer treatment, and zolbetuximab (formerly known as IMAB362) has been developed against CLDN18.2. However, there are few data reported thus far related to the clinicopathological characteristics of CLDN18.2 expression for PDAC.AIM:To investigate the expression of CLDN18.2 in PDAC patients and subsequently propose a new target for the treatment of PDAC.METHODS:The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, and European Genome-phenome Archive databases were first employed to analyze the CLDN18 gene expression in normal pancreatic tissue compared to that in pancreatic cancer tissue. Second, we analyzed the expression of CLDN18.2 in 93 primary PDACs, 86 para-cancer tissues, and 13 normal pancreatic tissues by immunohistochemistry. Immunostained tissues were assessed applying the histoscore. subsequently, they fell into two groups according to the expression state of CLDN18.2. Furthermore, the correlations between CLDN18.2 expression and diverse clinicopathological characteristics, including survival, were investigated.RESULTS:The gene expression of CLDN18 was statistically higher (P < 0.01) in pancreatic tumors than in normal tissues. However, there was no significant correlation between CLDN18 expression and survival in pancreatic cancer patients. CLDN18.2 was expressed in 88 (94.6%) of the reported PDACs. Among these tumors, 50 (56.8%) cases showed strong immunostaining. The para-cancer tissues were positive in 81 (94.2%) cases, among which 32 (39.5%) of cases were characterized for strong staining intensities. Normal pancreatic tissue was identified solely via weak immunostaining. Finally, CLDN18.2 expression significantly correlated with lymph node metastasis, distant metastasis, nerve invasion, stage, and survival of PDAC patients, while there was no correlation between CLDN18.2 expression and localization, tumor size, patient age and sex, nor any other clinicopathological characteristic.CONCLUSION:CLDN18.2 expression is frequently increased in PDAC patients. Thus, it may act as a potential therapeutic target for zolbetuximab in PDAC.

目的 探究免疫球蛋白结构域的跨膜蛋白1(TMIGD1)在胃癌组织中的表达情况及其与胃癌细胞侵袭、迁移、黏附的关系.方法 收集60份胃癌患者病理组织标本,通过免疫组化染色检测TMIGD1的表达情况,并分析其与患者临床指标的关系.进一步挖掘TCGA数据库,通过Transwell、Western Blotting、细胞黏附率实验探究过表达TMIGD1对胃癌细胞侵袭、迁移、黏附的影响.结果 TMIGD1在胃癌组织中呈低表达,TMIGD1阳性组黏液腺癌、发生淋巴脉管浸润的占比低于TMIGD1阴性组(P<0.05).过表达TMIGD1可明显抑制胃癌细胞株AGS与BGC803的侵袭、迁移能力,提高细胞黏附能力(P<0.05).结论 TMIGD1在胃癌组织中呈低表达,过表达TMIGD1能够通过促进胃癌细胞黏附来抑制细胞侵袭、迁移.

目的 探讨脉管浸润在胃癌患者预后预测中的作用.方法 回顾性分析2012年1月至2017年1月在陕西省人民医院普外科接受根治性胃癌手术患者的临床资料,采用HE染色和免疫组化两种方法对患者进行脉管浸润的评估.采用χ2检验分析脉管浸润与患者临床病理特征之间的关系,采用单因素和多因素分析法来确定影响患者无病生存期和总生存期的预后因素.结果 在273例胃癌手术患者中,26.0％(71/273)被诊断为脉管浸润,22例为单纯的血管浸润,25例为单纯的淋巴管浸润,剩余24例患者同时存在淋巴管与血管浸润.进一步分析发现,随着肿瘤TNM分期的升高,脉管浸润的发生率呈递增趋势,从Ⅰ期胃癌的7.7％上升到Ⅲ期胃癌的36.8％(P<0.05);脉管浸润还与胃癌的肿瘤部位、病理T分期和病理N分期有关(P<0.05).脉管浸润是胃癌患者无病生存期(相对风险比为1.5,95％置信区间为1.1～2.2,P=0.018)和总生存期(相对风险比为1.8,95％置信区间为1.3～2.6,P=0.001)的独立预测因子.结论 脉管浸润是可手术胃癌患者复发和转移的高危因素,同时也是胃癌预后不佳的独立预测因子,在完善胃癌的TNM分期和监测术后复发转移中发挥重要作用.

Objective: To explore the effect of propofol (Prof) on the proliferation, migration and invasion of human gastric cancer cell MGC-803 and its molecular mechanism. Methods: The MTT method was used to study the effects of Prof with different doses and durations on the viability of MGC-803 cells. Hoechst 33258 staining and electron microscopy were used to detect the effects of Prof on MGC-803 cell apoptosis. Transwell experiments were used to detect the effects of Prof on the migration and invasion of MGC-803 cells. RT-PCR detects the effect of Prof on the expression of miR-195 in MGC-803 cells, and Western Blot detects the effect of Prof on the protein expression of JAK/STAT signaling pathway. Results: Compared with 0mg/ml Prof, 5mg/ml, 10mg/ml and 20mg/ml Prof treatment with 24h, 48h and 72h can significantly reduce cell viability (P <0.05). Compared with the Control group, the percentage of Hoechst 33258 staining positive cells in the Prof group and the apoptosis rate under the electron microscope were significantly increased (P <0.05). Compared with the Control group, the cell migration rate and invasion rate of the Prof group were significantly reduced (P <0.05). Compared with the Control group, the expression of miRNA-195 in the Prof group cells was increased significantly (P <0.05). Compared with the Control group, the activity of p-Jak1 and p-STAT3 proteins in the Prof group were significantly reduced (P <0.05). Conclusion: Prof can reduce the cell viability, migration and invasion of gastric cancer cell MGC-803, and promote its apoptosis. Its mechanism may be related to the promotion of miR-195 expression and inhibition of JAK/STAT signal pathway activity.

[目的]探讨miR-144-5p在胃癌组织和细胞中的表达及生物学功能.[方法]采用qRT-PCR检测miR-144-5p在胃癌组织和细胞系中的表达水平,并验证miR-144-5p mimics的转染效率;分别采用CCK-8法、克隆形成实验、流式细胞仪、Transwell实验检测miR-144-5p mimics对胃癌细胞AGS和HGC-27增殖、克隆形成能力、细胞周期和侵袭能力的影响.[结果]MiR-144-5p在胃癌组织的表达水平明显低于癌旁组织(0.607±0.257 vs 1.000±0.360,t=5.616,P＜0.001).MiR-144-5p低表达与胃癌患者的肿瘤浸润深度、淋巴结转移、远处转移、TNM分期显著相关(P＜0.05).MiR-144-5p在胃癌细胞SNU-1、HGC-27、SGC-7901、KATO Ⅲ及AGS中表达水平显著低于正常人胃黏膜上皮细胞GES-1(F=12.17,P＜0.001).转染miR-144-5p mimics 后,AGS(t=4.902,P=0.001)和 HGC-27(t=4.154,P=0.003)细胞中 miR-144-5p 的表达水平显著增高;AGS和HGC-27细胞的增殖能力、克隆形成能力、侵袭能力均被抑制(P＜0.05),G1期细胞比例增加、而S期的细胞比例减少(P＜0.05).[结论]MiR-144-5p在胃癌组织和细胞中表达降低,与胃癌患者的TNM分期较晚和胃癌细胞恶性程度较高有关,提示miR-144-5p在胃癌的恶性进程中起重要作用.

目的 分析MYBL2在胃癌组织中的表达水平及其与患者预后、免疫细胞浸润的关系.方法 采用肿瘤免疫评估资源(TIMER)数据库分析MYBL2在泛癌中的差异性表达;采用Kaplan-Meier plotter数据库分析MYBL2表达水平与患者预后的关系;采用TIMER数据库分析MYBL2表达水平与免疫细胞浸润的关系.结果 在胃腺癌(STAD)患者中,肿瘤组织的MYBL2表达水平明显高于正常组织(P<0.001).Kaplan-Meier生存曲线显示,MYBL2高表达患者第一次进展时间为12.1个月,短于低表达患者的24.8个月(P=8.5e-05);MYBL2高表达患者的中位生存期为20.5个月,短于低表达患者的33.2个月(P=0.0011).MYBL2高表达与B细胞(r=-0.165,P=1.48e-03)、CD8+T细胞(r=-0.169,P=1.12e-03)、CD4+T细胞(r=-0.146,P=5.07e-03)、巨噬细胞(r=-0.364,P=4.74e-13)、中性粒细胞(r=-0.158,P=2.28e-03)、树突状细胞(r=-0.233,P=5.86e-06)浸润程度呈负相关,与纯度无相关性(r=0.115,P=2.53e-02).结论 MYBL2在胃癌患者中高表达,可作为预后不佳的预测指标.MYBL2高表达可抑制免疫细胞浸润,实现肿瘤细胞的免疫逃逸,促进肿瘤进展.

目的:检测miR-383、miR-515在胃癌组织中的表达及意义,并探讨其与临床病理特征及预后的关系.方法:选取2016年2月—2017年3月住院治疗的60例胃癌患者,收集切除的癌组织及癌旁组织分别作为胃癌组、癌旁组织组.实时荧光定量PCR(qRT-PCR)法检测胃癌组织中miR-383、miR-515表达水平;Kaplan-meier法分析胃癌组织中miR-383、miR-515表达水平与预后关系,采用Cox回归模型分析影响胃癌患者预后的危险因素.结果:胃癌组中miR-383表达水平明显低于癌旁组织组(P<0.05),miR-515表达水平明显高于癌旁组织组(P<0.05).胃癌患者中miR-383表达、miR-515表达与肿瘤直径、血管浸润、淋巴结转移密切相关(P<0.05),而与患者年龄、性别、肿瘤位置、组织学分级、肿瘤类型无相关性(P>0.05).Kaplan-meier法分析显示,胃癌组织中miR-383高表达组平均生存时间及3年内总生存率显著高于miR-383低表达组(Log-rank P=0.003),miR-515低表达组平均生存时间及3年内总生存率高于miR-515高表达组(Log-rank P=0.009).多因素分析显示,miR-383、miR-515表达和肿瘤分化程度是影响胃癌患者预后的独立危险因素(P<0.05).结论:胃癌组织中miR-383表达水平降低,miR-515表达水平升高,两者可能作为临床预后判断的靶点,为临床诊治提供一定参考.

Objective:To investigate the effect of propofol on the proliferation, migration and invasion of human gastric cancer cells and its molecular mechanism.Methods:The cell viabilities of human gastric MGC-803 and HGC-27 cells under different concentration of propofol were detected by methyl thiazolyl tetrazolium (MTT) method. MGC-803 cells were divided into control group and propofol group. Hoechst 33258 staining and electron microscopy were used to detect the apoptosis rates of the two groups of cells. Transwell experiment was used to detect the migration and invasion rates of the two groups of cells. The cells were then divided into control group, propofol group and propofol + miR-195i group. Real-time fluorescent quantitative PCR (qRT-PCR) was used to detect the relative expression of miR-195 in the cells. Western blotting was used to detect the expressions of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway proteins.Results:At 24 h, the cell viabilities of MGC-803 cells under the action of 0, 1, 5, 10 and 20 mg/L propofol respectively were (100.00±4.96)%, (94.63±3.15)%, (77.38±6.73)%, (63.82±8.42)% and (35.94±7.01)%, with a statistically significant difference ( F=5.148, P<0.001). The cell viabilities of MGC-803 cells under the action of 5, 10 and 20 mg/L propofol were decreased significantly compared to that under the action of 0 mg/L propofol (all P<0.05). At the same time, the effects of propofol for 48 and 72 h could also significantly reduce the viabilities of MGC-803 cells. Similar results were also detected in HGC-27 cells. The results of Hoechst 33258 staining showed that the percentage of positive cells in the control group was (3.73±1.81)%, and that in the propofol group was (25.44±1.05)%, with a statistically significant difference ( t=6.415, P<0.001). The results of electron microscopy showed that the apoptosis rate in the control group was (4.60±1.36)%, and that in the propofol group was (28.15±1.99)%, with a statistically significant difference ( t=10.729, P<0.001). Transwell results showed that the cell migration rate in the control group was (53.94±4.62)%, and that in the propofol group was (21.28±3.98)%; the cell invasion rate in the control group was (62.38±6.75)%, and that in the propofol group was (33.81±4.92)%, and there were statistically significant differences ( t=4.628, P<0.001; t=6.418, P<0.001). qRT-PCR results showed that the relative expressions of miR-195 in the control group, propofol group and propofol + miR-195i group were 0.58±0.09, 1.24±0.22 and 0.63±0.16, with a statistically significant difference ( F=1.547, P=0.001). miR-195 expression was increased significantly in the propofol group compared to the control group ( P<0.001). Compared with the propofol group, miR-195 expression in the propofol + miR-195i group was decreased significantly ( P<0.001). Western blotting results showed that the relative expressions of phosphorylase Janus kinase 1 (p-JAK1) protein in the control group, propofol group and propofol + miR-195i group were 1.18±0.36, 0.27±0.08 and 0.58±0.11; the relative expressions of phosphorylase signal transducer and activator of transcription 3 (p-STAT3) protein in the three groups were 0.83±0.16, 0.21±0.07 and 0.72±0.13, and there were statistically significant differences ( F=1.655, P<0.001; F=2.520, P<0.001). The expressions of p-JAK1 and p-STAT3 protein in the propofol group were decreased significantly compared to the control group ( P<0.001; P=0.001). The expressions of p-JAK1 and p-STAT3 protein in the propofol + miR-195i group were increased significantly compared to the propofol group ( P=0.003; P=0.004). Conclusion:Propofol can inhibit the cell proliferation, migration and invasion of gastric cancer MGC-803 cells, and promote its apoptosis. Its mechanism may be related to the promotion of miR-195 expression and inhibition of JAK/STAT signal pathway activity.

目的:探讨分析P504S、Ki-67在老年人群中萎缩性胃炎、低级别上皮内瘤变、高级别上皮内瘤变、早期胃癌中的表达情况及其与幽门螺旋杆菌感染的相关性.方法:应用免疫组化法检测2018年3月至2019年3月陕西省人民医院胃镜活检标本157例(其中包括43例慢性萎缩性胃炎伴肠上皮化生、42例低级别上皮内瘤变、39例高级别上皮内瘤变及33例高分化腺癌)标本中P504S、Ki-67的表达情况及HP感染情况.结果:在慢性萎缩性胃炎伴肠化、低级别上皮内瘤变、高级别上皮内瘤变及高分化腺癌标本中,P504S、Ki-67的表达呈逐渐增高的趋势,并且与HP感染与否没有显著相关性.结论:P504S和Ki-67在胃的癌前病变及早期胃癌中的表达与疾病的发生、发展具有一定的相关性,可以作为老年人群胃癌癌前病变及早期胃癌的辅助诊断手段,且与HP感染不具相关性.

Gastric cancer (GC) is one of the most common malignancies of the digestive system worldwide. Multiple long noncoding RNAs (lncRNAs) participate in the regulation of GC development and metastasis. In this study, we aimed to elucidate the expression and function of lncRNA IGFL2-AS1 in GC. We found that IGFL2-AS1 was highly expressed in GC tissues and cell lines. Knockdown of IGFL2-AS1 suppressed GC cell proliferation, migration, and invasion in vitro. Furthermore, we identified that IGFL2-AS1 exerted its function as a molecular sponge of miR-802. MiR-802 was demonstrated to be a tumor suppressor, and overexpression of miR-802 suppressed GC cell growth, migration, and invasion. Mechanistically, we revealed that the cAMP-regulated phosphoprotein 19 (ARPP19) was a direct target of miR-802 and could reverse the inhibitory function of miR-802. Moreover, our results confirmed that knockdown of IGFL2-AS1 inhibited GC tumor development in an in vivo GC tumor xenograft model. In summary, our data suggest that the IGFL2-AS1/miR-802/ARPP19 axis plays a critical role in the progression and metastasis of GC. Therapies targeting the IGFL2-AS1/miR-802/ARPP19 axis can potentially improve GC treatment.

BACKGROUND: Low-density lipoprotein receptor-related protein 4 (LRP4) has been reported to be implicated in multiple types of cancers. However, the significance of LRP4 in gastric cancer (GC) remains poorly elucidated. Therefore, it’s urgent to investigate the importance and underlying mechanisms of LRP4 in GC. OBJECTIVE: To investigate the clinical roles of LRP4 in GC. METHODS: The LRP4 mRNA and miR-140-5p was measured by qRT-PCR. The protein expression was determined Western blot. Kaplan-Meier survival curves and Cox proportional hazard regression models were performed to evaluate prognosis. RESULTS: We demonstrated that LRP4 mRNA and protein was up-regulated in GC tissues for the first time. Its high expression was significantly correlated with malignant clinical features including TNM stage and lymph-node metastasis and poor prognosis for GC patients. LRP4 promotes migration, invasion and epithelial-mesenchymal transition (EMT) progress of GC cells. Mechanically, LRP4 regulated PI3K/AKT in GC cells. AKT inhibitors reversed the effects of LRP4. Finally, LRP4 was regulated by miR-140-5p in GC. CONCLUSIONS: Our findings showed that LRP4 has an important function in GC progression and promotes GC migration, invasion and EMT by regulating PI3K/AKT under regulation of miR-140-5p, providing a potential therapeutic target for GC.

目的 :探讨对行腹腔镜辅助腹会阴联合切除(APR)直肠癌根治术病人采用乙状结肠腹膜外造口 、一期乳头成形联合生物补片重建盆底的可行性与安全性.方法 :收集同时行腹膜外乙状结肠造口一期乳头成形和生物补片盆底重建的病例15例(试验组),以及腹膜内乙状结肠造口和未行盆底腹膜重建的病例50例(对照组),比较两种术式在造口手术所用时间 、术后首次排气时间 、术后造口相关并发症 、术后肠梗阻发生率等方面的差异.结果 :对照组发生术后肠梗阻与造口并发症共17例(肠梗阻6例,造口附近皮肤溃疡3例,造口黏膜脱垂2例,造口回缩1例,造口狭窄1例,造口旁疝4例),试验组发生术后肠梗阻和造口相关并发症共3例(肠梗阻 、造口溃疡 、造口狭窄各1例).对照组术后肠梗阻和造口相关并发症发生数量明显超过试验组(P<0.05),且试验组无一例发生补片排异反应.结论 :腹膜外乙状结肠造口一期乳头成形联合盆底生物补片重建术在腹腔镜辅助腹会阴联合直肠癌根治术(APR)的术后肠梗阻发生率和造口相关并发症更低,是更加安全可靠的手术方式.