The application of Multiple Instance Learning (MIL) for classifying Whole Slide Images (WSIs) has gained extensive use in recent years, primarily due to the high cost and time consumption associated with pixel-level annotation of WSIs, which is challenging to accomplish. The advancements in MIL for WSIs have predominantly concentrated on two fronts: the development of superior feature extractors (for instance, utilizing self-supervised learning for training feature extractors) and the formulation of enhanced instance aggregation strategies. Regrettably, the majority of the most advanced approaches have neglected phenotypic variances among instances when employing attention mechanisms. To capitalize on the disparities between instance tissues, we have introduced a phenotypic self-distillation approach to MIL. Our framework is composed of three components: i) a self-supervised feature extractor based on contrastive learning and a phenotype extractor pre-trained on the Kather100K dataset, which automatically provides 9-class tissue phenotype labels (e.g., tumor epithelium, stroma, lymphocytes) without requiring manual annotation, ii) the incorporation of a self-distillation loss between the features of instances and their phenotypes to augment the informational content of both perspectives, and iii) the aggregation of MIL instances for the final MSI prediction. The efficacy of this framework was evaluated on two datasets: the TCGA-CRC dataset was used for training and internal testing with a fixed 70%/30% split, while the Tangshan People's Hospital cohort served as an independent external validation set. On the TCGA-CRC dataset (n = 360; 65 MSI-H, 295 MSS), our model achieved an AUC of 0.8846 and an accuracy of 0.84, using a fixed 70%/30% train-test split. On the Tangshan People's Hospital dataset (n = 472; 56 MSI-H, 426 MSS), the model attained an AUC of 0.7258 and an accuracy of 0.70.

Protein immunotherapies can elicit potent tumor rejection, but reversible target engagement, incomplete tumor retention, and systemic leakage often erode spatial control. Here, we develop covalently anchored tumor immunotherapeutic proteins (CATIPs), a modular platform that uses proximity-enabled covalent chemistry to immobilize immune cues on tumor-cell surfaces after intratumoral administration. CATIPs combine tumor-targeting nanobodies with payloads for T cell engagement, co-stimulation, and cytokine support. In human PBMC-reconstituted NSG mice, CATIPs completely eradicated treated EGFR-positive tumors, outperforming matched noncovalent proteins while limiting redistribution, systemic T cell activation, cytokine release, xGVHD-associated morbidity, and on-target, off tumor toxicity. In immunocompetent melanoma models, CATIPs remodeled the tumor microenvironment, expanded antigen-specific CD8+ T cells, induced antigen-restricted abscopal control, and generated durable protection against local and metastatic rechallenge. CATIP-engineered tumor cells further functioned as whole-cell vaccines. Thus, covalent tumor anchoring converts local protein delivery into tumor-surface immune programming, enabling systemic, tumor-specific, durable antitumor immunity while limiting systemic immunopathology.

M2 macrophages constitute a major stromal component of gastric cancer (GC) and actively contribute to tumor progression through angiogenesis, tissue remodeling, and epithelial–mesenchymal transition (EMT). Our previous study identified CD44 variant 9 (CD44v9) expression in cytokeratin-negative stromal compartments as a marker with diagnostic and prognostic significance in gastric adenocarcinoma (GA); however, its cellular localization within the tumor microenvironment and functional relevance remain unclear. In this study, public single-cell RNA sequencing datasets from the Human Protein Atlas were analyzed to characterize CD44 expression across gastric tissue cell populations. Multiplex immunofluorescence was performed to validate the spatial distribution of CD44v9-positive cells in clinical GA specimens. CD44v9 expression was predominantly enriched in macrophages and showed significant co-localization with stromal M1 macrophages (CD68+CD86+CD163−), M2 macrophages (CD68+CD86−CD163+), and regulatory T (Treg) cells (CD3+CD4+FOXP3+CD8−). Functionally, CD44v9 was overexpressed in THP-1-derived M2 macrophages through lentiviral transduction, and these modified cells retained their inherent M2 macrophage phenotype. CD44v9 overexpression significantly enhanced TNF-α secretion (P < 0.05), without affecting IL-6 production (P > 0.05). In a co-culture system, CD44v9 overexpression M2 macrophages markedly promoted GC cell proliferation, migration, and invasion. These pro-tumorigenic effects were accompanied by EMT induction, characterized by decreased E-cadherin and increased N-cadherin and Vimentin (all P < 0.05) expression, along with elevated MMP2 and MMP9 (P < 0.05) levels in AGS cells. Collectively, these findings demonstrate that CD44v9 expression in stromal M2 macrophages promotes a pro-tumorigenic phenotype, possibly through TNF-α-mediated tumor-stroma crosstalk, thereby promoting EMT and enhancing cancer cell aggressiveness. CD44v9 expressed by M2 macrophages may represent a promising biomarker and therapeutic target in GA development.

Background Metastasis-associated in colon cancer-1 (MACC1) is a novel oncogene involved in the growth and metastasis of tumors, which is overexpression in various tumors. MACC1 could promote the growth, invasion, and metastasis of colorectal cancer (CRC) by activating the HGF/MET signaling pathway in vivo . It has been confirmed that MACC1 mainly promotes the Warburg effect in gastric cancer cells through the PI3 K/AKT signaling pathway. Objective Here, we mainly investigated the association between MACC1 and the glycolysis process in CRC cells. Methods The expression of MACC1 in CRC and its relationship with the patient's survival were analyzed by TCGA database. We used different concentrations of glucose medium to culture HT-29 and HCT-116 with or without siMACC1. Cell Counting Kit-8 assay was used to detect cell proliferation. The content of lactic acid and glucose in cells was examined by enzyme-linked immunosorbent assay, and extracellular acidification rate was also determined with Seahorse XFe96 Extracellular Flux Analyzer. Western blot was used to detect the protein expressions related to glycolysis. Immunofluorescence was conducted to observe the expression and distribution of GLUT4. Results In this study, we observed that MACC1 was highly expressed in CRC and negatively correlated with the survival of patients. The expression of glycolysis related enzymes was significantly increased under the stimulation of different concentrations of glucose in HT-29 and HCT-116 cells. However, MACC1 knockdown could significantly reduce high glucose-induced the expressions of glycolysis-related enzymes. Besides, MACC1 knockdown could decrease the content of glucose and lactate, and inhibit glycolytic function in HT-29 and HCT-116 cells. Moreover, the expression of GLUT4 was significantly decreased in the two cell lines treated by 4.5 g/L or 9.0 g/L glucose with MACC1 knockdown. Additionally, MACC1 knockdown could inhibit high glucose-induced membrane translocation of GLUT4. Conclusions MACC1 knockdown can attenuate glucose metabolism by inhibiting the membrane translocation of GLUT4 in CRC cells.

Recent studies indicate that circular RNAs (circRNAs) are crucial in the progression of colorectal cancer (CRC). Eukaryotic translation initiation factor 4A3 (EIF4A3) has been identified as a promoter of circRNA production. The biological roles and mechanisms of EIF4A3-derived circRNA (circEIF4A3) in CRC cell autophagy remain poorly understood. This study explores the effects of circEIF4A3 on CRC cell growth and autophagy, aiming to elucidate the underlying molecular mechanisms. We discovered that EIF4A3 and circEIF4A3 synergistically enhance CRC cell growth. CircEIF4A3 sequesters miR-3126–5p, consequently upregulating EIF4A3. Further, circEIF4A3 increases EIF4A3 expression, which promotes autophagy by stabilizing ATG5 mRNA and enhances ATG7 protein stability through the stabilization of USP14 mRNA, a deubiquitinating enzyme. Upregulation of ATG5 and ATG7 counteracts the growth-inhibitory effects of EIF4A3 knockdown on CRC cells. Moreover, our findings demonstrate that EIF4A3 induces the formation of circEIF4A3 in CRC cells. In conclusion, a positive feedback loop between circEIF4A3 and EIF4A3 supports CRC cell growth by facilitating autophagy.

Phosphorus fluoride exchange (PFEx), recently debuted in small molecules, represents the forefront of click chemistry. To explore PFEx's potential in biological settings, we developed amino acids phosphoramidofluoridate tyrosine (PFY) and phosphoramidofluoridate lysine (PFK) featuring phosphoramidofluoridates and incorporated them into proteins through genetic code expansion. PFY/PFK selectively reacted with nearby His, Tyr, Lys, or Cys in proteins, both in vitro and in living cells, demonstrating that proximity enabled PFEx reactivity without external reagents. The reaction with His showed unique pH -dependent properties and created thermally sensitive linkages. Additionally, Na 2 SiO 3 enhanced PFEx reactions with Tyr and Cys. PFEx, by generating defined covalent P-N/O linkages, extends the utility of phosphorus linkages in proteins, aligning with nature's use of phosphate connectors in other biomolecules. More versatile and durable than sulfur fluoride exchange (SuFEx), PFEx in proteins expands the latent bioreactive arsenal for covalent protein engineering and will facilitate the broad application of this potent click chemistry in biological and biomedical fields.

The specificity and sensitivity of the current diagnostic and prognostic biomarkers for gastric cancer (GC) are limited. The present study aimed to evaluate the diagnostic and prognostic significance of cluster-of-differentiation gene 44 variant isoform 9 (CD44v9) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) expression levels alone or combined in the tumor tissues of patients with GC and reveal the roles of CD44v9 and TIM3 in the cytokeratin (CK)(+) and CK- regions. Multiplex immunofluorescence staining was performed for CD44v9, TIM3 and CK using a tissue microarray. The tissues were divided into three regions based on CK expression: Total, CK+, and CK- regions. The diagnostic and prognostic value was evaluated using receiver operating characteristic curves, Kaplan-Meier and Cox regression analyses. The results demonstrated that the density of cells expressing CD44v9, TIM3 and co-expressing CD44v9 and TIM3 (CD44v9/TIM3) in both the CK+ and CK- regions of tumor tissues was significantly higher than those in normal tissues (P<0.001). Moreover, the expression of CD44v9 in the CK- region was significantly positively correlated with age and tumor grade (P<0.05), and the expression of CD44v9/TIM3 in the CK- region of tumor tissues was significantly positively correlated with age, tumor grade and metastasis (P<0.05). Furthermore, the area under the curve for TIM3 expression in the CK+ region was 0.709, with a sensitivity of 45.83% and a specificity of 85.54% (P<0.001). High expression of CD44v9 in the CK- region was also significantly associated with poor survival and independently predicted a poor prognosis in patients with GC (hazard ratio, 2.387; 95% confidence interval, 1.384-4.118; P<0.01). In conclusion, dividing tissue regions based on CK expression is important for the diagnosis of GC. The expression of TIM3 in the CK+ region demonstrated diagnostic potential for GC, and high expression of CD44v9 in the CK- region was an independent prognostic risk factor for patients with GC.

Objective To investigate the effect of Huangkui Capsules on urinary albumin excretion rate and oxidative stress in patients with early diabetic kidney disease. Methods A total of 60 patients with stage Ⅳ diabetic nephropathy admitted and diagnosed in Tangshan People’s Hospital of Hebei Province from December 2019 to December 2021 were selected as the study objects. They were divided into control group and observation group by random number table method, with 30cases in each group. The control group was treated with Valsartan 80 mg once a day, and the observation group was treated with Huangkui Capsules three times a day on the basis of the control group, and observed for sie mouths weeks. The clinical efficacy, urinary protein excretion rate（UARE）, blood creatinine（SCr）, blood β2-microglobulin（β2-MG）, blood superoxide dismutase（SOD）, blood malondialdehyde（MDA） and blood glutathione peroxidase（GSH-Px） before and after treatment were compared between the two groups. Results The clinical efficacy of the observation group was better than that of the control group, and the difference was statistically significant（P＜0.05）. After treatment, UAER, blood β2-MG, Scr and MDA in two groups were lower than those before treatment, GSH-PX and SOD were higher than before treatment, and UAER, bloodβ2-MG, Scr and MDA in observation group were lower than control group, while GSH-PX and SOD in observation group were higher than control group, the differences were statistically significant（P＜0.05）. Conclusion Huangkui Capsules adjuvant treatment can effectively reduce the levels of UARE, β2-MG and Scr in patients with diabetic kidney disease. The mechanism may be that Huangkui Capsules can inhibit oxidative stress by reducing serum MDA, and increasing SOD and GSH-PX, so as to exert renal protective effect.

Background Aberrant alternative splicing (AS) events could be viewed as prognostic indicators in a large number of malignancies. This study aims to identify prognostic AS events, illuminate the function of the splicing variants biomarkers and provide reliable evidence for formulating public health strategies for gastric cancer (GC) surveillance. Methods RNA-Seq data, clinical information and percent spliced in (PSI) values were available in The cancer genome atlas (TCGA) and TCGA SpliceSeq data portal. A three-step regression method was conducted to identify prognostic AS events and construct multi-AS-based signatures. The associations between prognostic AS events and splicing factors were also investigated. Results We identified a total of 1,318 survival-related AS events in GC, parent genes of which were implicated in numerous oncogenic pathways. The final prognostic signatures stratified by seven types of AS events or not stratified performed well in risk prediction for GC patients. Moreover, five signatures based on AA, AD, AT, ES and RI events function as independent prognostic indicators after multivariate adjustment of other clinical variables. Splicing network also showed marked correlation between the expression of splicing factors and PSI value of AS events in GC patients. Conclusion Our findings provide a landscape of AS events and regulatory network in GC, indicating that AS events might serve as prognostic biomarkers and therapeutic targets for GC.

目的:评估经肛门灌洗(transanal irrigation,TAI)在治疗低前切除术综合征(low anterior resection syn-drome,LARS)中的作用及其对患者生活质量的影响.方法:纳入2018年5月-2019年2月在本院行低位直肠癌前切除术的78例患者.依据随机数字表法将患者分为TAI组和对照组,每组39例.TAI组使用了PeristeenTM系统进行灌洗,对照组采用常规护理,两组共干预6个月.在干预开始前和结束后,评估患者LARS评分、纪念斯隆-凯特林癌症中心肠道功能问卷(MSKCC BFI)和生活质量评价量表(SF-36).结果:TAI组有38例,对照组36例患者完成了整个研究过程.两组受试者的人口学和病情资料差异无统计学意义(P>0.05).与对照组相比较,TAI组干预结束后LARS评分和MSKCC BFI评分的各个维度及其总分差异均有统计学意义(P<0.001);与干预前比较,TAI组干预后的LARS评分和MSKCC BFI评分的各维度及其总分差异均有统计学意义(P<0.001),而对照组干预前后的两项评分差异均没有统计学意义(P>0.05).干预结束后两组受试者SF-36量表的躯体疼痛、社会功能、精神健康和情感职能4个维度得分差异有统计学意义(P<0.05),同样,TAI组干预前后这4个维度的评分差异也有统计学意义(P<0.05),而对照组SF-36量表所有维度在治疗前后差异均无统计学意义(P>0.05).结论:TAI是可以有效改善LARS患者的LARS评分、MSKCC BFI评分和生活质量,有进一步研究和推广的价值.

目的:评价结直肠癌患者肌少症的发生率及其对术后感染和住院时间的影响.方法:回顾性分析了2013年4月至2019年10月在我院接受原发性结肠直肠癌根治术患者的临床数据.从病例资料中采集患者人口学和疾病资料,利用术前2周内拍摄的CT图像分析第3腰椎骨骼肌指数(L3 skeletal muscle index,L3 SMI).以男性L3 SMI<52.4 cm2/m2,女性<38.5 cm2/m2,作为肌肉减少症的诊断标准.结果:共纳入234例符合入排标准的患者,其中91例(38.9％)患有肌少症.≥65岁的患者肌少症发病率高于<65岁的患者(48.6％vs 30.1％,P=0.004).39例(16.7％)患者有术后感染记录.肌少症患者的感染记录高于非肌少症患者(23.1％vs 12.6％,P=0.036),在≥65岁的患者中尤其显著.肌少症患者的住院时间长于非肌少症患者,差异有统计学意义(P<0.05).在多因素Logistic回归分析中,肌少症[OR(95％CI):4.6(1.5～13.9),P=0.007]和年龄≥65岁[OR(95％CI):4.7(1.5～8.6),P<0.001]是术后感染的独立预测因子.结论:肌少症预示着结肠直肠癌患者术后感染风险增加和住院时间延长,老年患者表现尤为突出.建议术前利用常规CT检查对患者肌肉减少情况进行评估,并以此作为评估患者术后感染的重要指标.

circRNAs have been considered as a rising factor in cancers. However, the roles and mechanisms of circ-sirt1 in gastric cancer (GC) remain largely unknown. In this study, we found that the expressions of sirt1 and circ-sirt1 are decreased in tissues or serums of GC patients by real-time quantitative PCR (RT-qPCR). The expressions of miR-132-3p/miR-212-3p showed an opposite tendency in these samples. The co-transfection of miR-132-3p/miR-212-3p mimics counteracted the enhancement of sirt1 expression induced by circ-sirt1. The results of cell colony-formation assay and transwell assays demonstrated that the proliferation, migration, and invasion activities of BGC-823 cells were inhibited by circ-sirt1 overexpression or miR-132-3p/miR-212-3p knockdown, respectively. The xenograft tumor model result indicated that the circ-sirt1 overexpression suppressed the tumor growth of BGC-823 cells. The regulation of miR-132-3p/miR-212-3p between circ-sirt1 and sirt1 was verified in the mice tumor tissues. Thus, circ-sirt1 inhibited tumor growth and invasion probably by sponging miR-132-3p/miR-212-3p and upregulating sirt1 expression in GC. These findings may provide a theoretical basis for the classification of GC and a novel therapeutic target for GC patients.

circRNAs have been considered as a rising factor in cancers. However, the roles and mechanisms of circ-sirt1 in gastric cancer (GC) remain largely unknown. In this study, we found that the expressions of sirt1 and circ-sirt1 are decreased in tissues or serums of GC patients by real-time 24 quantitative PCR (RT-qPCR). The expressions of miR-132-3p/miR-212-3p showed an opposite 25 tendency in these samples. The co-transfection of miR-132-3p/miR-212-3p mimics counteracted the 26 enhancement of sirt1 expression induced by circ-sirt1. The results of cell colony-formation assay and Transwell assays demonstrated that the proliferation, migration, and invasion activities of 28 BGC-823 cells were inhibited by circ-sirt1 overexpression or miR-132-3p/miR-212-3p knockdown, 29 respectively. The xenograft tumor model result indicated that the circ-sirt1 overexpression 30 suppressed the tumor growth of BGC-823 cells. The regulation of miR-132-3p/miR-212-3p 31 between circ-sirt1 and sirt1 was verified in the mice tumor tissues. Thus, circ-sirt1 inhibited tumor 32 growth and invasion probably by sponging miR-132-3p/miR-212-3p and upregulating sirt1 33 expression in GC. These findings may provide a theoretical basis for the classification of GC and a novel therapeutic target for GC patients. those the tissues and healthy subjects, respectively. These results demonstrated that sirt1 and circ-sirt1 are both lower expressed in GC tissues than in the noncancerous tissues, and the level of circ-sirt1 in serums from GC patients is lower than that noted from the healthy subjects. The data suggested that The data confirmed the anti-tumor function of circ-sirt1 and its downstream mechanism of miR-132-3p, miR-212-3p and sirt1 in mice model. The present work demonstrates that circ-sirt1 and sirt1 levels were decreased in tissues and serums of patients with GC, while miR-132-3p/miR-212-3p expressions show an opposite tendency in the GC patients. The miR-132-3p and miR-212-3p were downregulated in GC cells with circ-sirt1 overexpression, while sirt1 was upregulated at both mRNA and protein levels. The co-transfection of miR-132-3p/miR-212-3p mimics counteracted the enhanced expression of sirt1 induced by circ-sirt1 overexpression in BGC-823 cells. The circ-sirt1 was identified as a candidate from the sirt1 host gene in the human genome in our previous study, which expression is decreased during neointimal formation and acts as a novel biomarker of atherosclerosis. The circ-sirt1 could promote sirt1 expression mediating by miR-132/212. The present study found that circ-sirt1 acted as a suppressor in proliferation, migration and invasion in GC cells by sponging miR-132-3p/miR-212-3p to regulate the expression of sirt1. These suggested a similar function of circ-sirt1 in vascular smooth muscle cells and Glandular epithelial cells of stomach. However, if there is a positive feedback loop between circ-sirt1 and sirt1 in GC, as well as the expression and role of circ-sirt1 in other cancers, still need to be clarified in future study. to the enhancement of miR-132-3p/miR-212-3p induced by circ-sirt1. Overexpression circ-sirt1 suppressed the cell proliferation, migration and invasion in vitro and inhibited tumor growth in vivo . Our findings provide new sights into a novel molecular and the signaling of circ-sirt1/miR-132-3p/miR-212-3p/ sirt1 in GC development. in 293T cells was verified by RT-qPCR. C) The circ-sirt1 expressions in GES-1, AGS-1 and BGC-823 cells were analyzed by RT-qPCR, with GAPDH as internal control. D) The levels of circ-sirt1 in BGC-823 cells transfected with circ-sirt1 plasmid or vector were detected by RT-qPCR. GAPDH was used as the housekeeping gene. E) The protein levels of sirt1 were detected by Western blot with GAPDH as internal control. F) Clone formation, G) cell migration and invasion assays of BGC-823 cells transfected with pcDNA3/circ-sirt1 plasmid or pcDNA3.1 after 48 h. Results are representative of three independent experiments.

目的 探讨复方斑蝥胶囊联合mFOLFOX6化疗方案(奥沙利铂、5-氟尿嘧啶、亚叶酸钙)对胃癌术后患者疗效及免疫功能的影响.方法 选取2017年2月～2019年5月河北省唐山市人民医院收治的胃癌术后患者1 18例,根据乱数表法将患者分为研究组和对照组,每组各59例.对照组予以mFOLFOX6化疗方案治疗,研究组在对照组基础上联合复方斑蝥胶囊治疗,均治疗8个疗程.比较两组临床疗效、血清肿瘤标志物及免疫功能情况,记录两组治疗期间不良反应状况.结果 治疗8个疗程后,研究组的总有效率高于对照组(P＜0.05).两组血清癌胚抗原、糖类抗原125、糖类抗原199水平均下降,且研究组低于对照组(P＜0.05).两组CD3+、CD4+、CD4+/CD8+水平均下降,但研究组高于对照组(P＜ 0.05).两组患者治疗期间不良反应总发生率比较,差异无统计学意义(P＞0.05).结论 胃癌术后患者经复方斑蝥胶囊联合mFOLFOX6化疗方案治疗后,疗效确切,可有效阻止疾病进展,减轻免疫抑制,且用药安全性较好,具有一定的临床应用价值.

目的 探讨微小RNA-133b(miRNA-133b)在胃癌组织中的表达情况及其对基质金属蛋白酶9(MMP-9)表达的影响.方法 选取2015年12月至2018年1月于该院胃肠外科住院行胃癌根治手术的患者78例,留取胃癌组织及癌旁组织(距肿瘤边界6 cm以上),实时荧光定量PCR(RT-qPCR)检测miRNA-133b与MMP-9 mRNA在两组标本中的表达水平,免疫组织化学(IHC)方法检测MMP-9在两组标本中的蛋白表达,应用Spearman相关性分析法对miRNA-133b和MMP-9 mRNA的表达量进行相关性分析,采用受试者工作特征(ROC)曲线分析胃癌组织中miRNA-133b表达水平对胃癌诊断的价值.结果 与癌旁组织比较,胃癌组织中miRNA-133b的相对表达量明显下调,MMP-9 mRNA及蛋白表达水平明显升高,差异均有统计学意义(1.01±0.30 vs.0.45±0.19,1.06±0.44 vs.2.03±0.55,20.51％vs.65.38％,P<0.05);且胃癌组织中miRNA-133b表达水平与MMP-9 mRNA表达量呈明显负相关性(r=-0.667,P<0.05).胃癌组织中miR-NA-133b表达水平预测胃癌的ROC曲线下面积为0.942(95％CI:0.909～0.974,P<0.05),最优截断点为0.78,预测胃癌的灵敏度和特异度分别为91.02％和80.77％.结论 胃癌组织中miRNA-133b表达降低可能通过靶向上调MMP-9的表达,促进胃癌细胞的浸润和转移,从而在胃癌发生、发展中起作用,且miRNA-133b表达水平对胃癌的诊断有重要价值.

目的 探讨内镜黏膜下剥离术(ESD)与经肛门镜微创手术(TEM)对早期结直肠肿瘤的微创治疗效果.方法 选取2010年5月—2016年5月河北省唐山市人民医院收治的结直肠肿瘤(uTis-uT1)患者211例,根据手术方式分为ESD组(98例)和TEM组(113例).比较两种手术方式的手术时间、住院时间,术中出血、肿瘤完整切除、肿瘤残留及复发例数;比较两组术后出血、穿孔、梗阻、狭窄等并发症的发生情况.结果 ESD组手术时间、住院时间短于TEM组,差异有高度统计学意义(P<0.01);两组术中出血、瘤完整切除率、肿瘤残留率及复发率比较,差异无统计学意义(P>0.05).两组并发症发生率比较,差异无统计学意义(P>0.05).结论 ESD与TEM对于治疗早期直肠癌均安全有效,但ESD的手术时间及住院事件明显缩短.

目的 探讨微小RNA(miR)-582-5p靶向程序性细胞死亡因子10(PDCD10)对胃癌细胞迁移、侵袭、凋亡的影响.方法 常规培养人正常胃黏膜上皮细胞株(GES-1)、胃癌细胞系(HGC-27、MKN74、NUGC-4),用qPCR法检测细胞中miR-582-5p表达,筛选miR-582-5p表达最低的HGC-27作为实验细胞.将对数生长期的HGC-27随机分为8组,各组采用脂质体转染法分别转染miR-582-5p模拟物(使miR-582-5p过表达)、miR-582-5p抑制剂(使miR-582-5p低表达)、miR-582-5p模拟物阴性对照miR-NC、miR-582-5p抑制剂阴性对照anti-miR-NC、PDCD10小干扰RNA si-PDCD10(使PDCD10低表达)、PDCD10小干扰RNA阴性对照si-NC、PDCD10过表达载体pcDNA-PD-CD10(使PDCD10过表达)、过表达载体阴性对照pcDNA-NC.用qPCR法检测细胞内miR-582-5p、PDCD10 mRNA表达,证实转染成功.用Western blotting法检测细胞内PDCD10、活化半胱氨酸天冬氨酸蛋白水解酶3(Cleaved-caspase-3)、基质金属蛋白酶2(MMP2)、MMP9蛋白表达,用流式细胞术测算细胞凋亡率,用Transwell小室法检测细胞迁移和侵袭能力,用双荧光素酶报告基因检测法验证miR-582-5p与PDCD10的靶向调控关系.结果 与miR-NC组比较,miR-582-5p组Cleaved-caspase-3蛋白相对表达量高,MMP2、MMP9蛋白相对表达量低,细胞凋亡率高,细胞迁移数、侵袭数少(P均<0.05).与si-NC组比较,Cleaved-caspase-3蛋白相对表达量低,MMP2、MMP9蛋白相对表达量高,细胞凋亡率低,细胞迁移数、侵袭数多(P均<0.05).miR-582-5p与PDCD10的3'UTR存在靶向结合位点.miR-582-5p与WT-PDCD10报告质粒共转染HGC-27后的荧光素酶活性低于miR-NC与WT-PDCD10报告质粒共转染(P<0.05);miR-582-5p或miR-NC与MUT-PDCD10报告质粒共转染HGC-27后的荧光素酶活性比较差异无统计学意义(P>0.05).与miR-NC组比较,miR-582-5p组PDCD10蛋白相对表达量低(P<0.05);与anti-miR-NC组比较,anti-miR-582-5p组PDCD10蛋白相对表达量高(P<0.05).与miR-582-5p+pcDNA-NC组比较,miR-582-5p+pcDNA-PDCD10组Cleaved-caspase-3蛋白相对表达量低,MMP2、MMP9蛋白相对表达量高,细胞凋亡率低,细胞迁移数、侵袭数多(P均<0.05).结论 miR-582-5p可通过靶向抑制PDCD10表达诱导胃癌细胞凋亡,抑制细胞迁移、侵袭.

目的探讨肾康注射液对糖尿病肾病患者肾功能及血清肿瘤坏死因子α（tumor necrosis factor-α,TNF-α）、单核细胞趋化蛋白1（monocyte chemoattractant protein-1,MCP-1）、白细胞介素6（interleukin-6,IL-6）的影响。方法选取2型糖尿病合并肾病患者160例作为研究对象,采用随机数字表法分为对照组和观察组各80例,2组均接受常规治疗。对照组采用缬沙坦治疗,观察组在对照组基础上加用肾康注射液治疗,2组均治疗4周。比较2组治疗前后24 h尿蛋白定量（24-hour urinary protein quantification,UTP）、血肌酐（serum creatinine,SCr）、胱抑素C（Cystatin C）、血钾及血清TNF-α、MCP-1、IL-6水平。结果治疗后,2组患者UTP、SCr、Cystatin C及血清TNF-α、MCP-1、IL-6水平均明显低于治疗前,且观察组UTP、SCr、Cystatin C及血清TNF-α、MCP-1、IL-6水平均低于对照组,差异有统计学意义（P＜0.05）,治疗前后2组血钾水平差异无统计学意义（P＞0.05）。结论肾康注射液可以有效降低糖尿病肾病患者UTP、SCr、Cystatin C水平,其机制可能是通过降低血清TNF-α、MCP-1、IL-6水平抑制炎症反应,发挥肾保护作用。

分析、总结采用中医药方法治疗截瘫疾病(Paraplegia)的临床效果,为中医药治疗截瘫提供相应的理论依据和临床数据.分析2018年5月至2019年6月间进行相应治疗的20例截瘫患者的临床资料.包括对患病时间较长的,在医学角度上认为恢复希望很小的截瘫患者,通过中医方法治疗,观察知觉、肢体运动功能等的恢复情况.本组20例截瘫患者,治疗几周内都开始不同程度逐渐恢复.治疗一段时间后有的患者出现大小便功能的改善,有的患者逐渐恢复了行走能力.遵循传统的中医理论,使用中药内服,中药体外热敷,用针灸推拿作为辅助,在截瘫疾病患者的康复治疗中具有较为显著的临床应用效果,进行长期治疗可能会使患病较为严重的患者可以重新行走,且具备较高的治疗安全性,具有着一定的临床应用价值,值得推广应用.

目的 探讨二甲双胍对进展期胃癌合并2型糖尿病患者行胃癌根治术后生存期的影响.方法 选取2011年1月至2015年10月胃肠外科收治的进展期胃癌且合并2型糖尿病患者87例,其中42例应用二甲双胍控制血糖(试验组),45例应用其他降糖药物控制血糖(对照组),术后进行随访观察,比较2组的无病生存率(PFS)及总生存率(OS).结果 二甲双胍组进展期胃癌患者3年-DFS和OS分别为52.4％和69.0％,显著高于对照组进展期胃癌患者的31.1％和46.7％(P<0.05).多因素COX分析显示二甲双胍是进展期胃癌合并2型糖尿病术后患者3年-DFS和3年-OS的独立保护因素(P<0.05).结论 二甲双胍可显著提高进展期胃癌合并2型糖尿病术后患者的无病生存率及总生存率,延长患者的生存时间.