Objective:To investigate the expression level of NME3 in gastric cancer and its correlation with clinicopathological characteristics and prognosis.Methods:A retrospective case series study was conducted. The clinicopathological data of 156 patients with gastric cancer who received radical gastrectomy in Zhejiang Cancer Hospital between January 2013 and December 2017 were collected. The samples of cancer tissues and paracancerous tissues were taken and partial paracancerous tissues were not meet the standard. Finally, immunohistochemical staining was conducted on both cancer tissues (156 cases) and paracancerous tissues (139 cases) to detect the expression of NME3 protein; H scoring system was used to score the expression of NME3 protein and the patients were divided into NME3 high expression group (H score ≥ 6 points) and NME3 low expression group (H score < 6 points). The clinicopathological characteristics of the 2 groups were analyzed. Kaplan-Meier method was used for overall survival (OS) analysis of the 2 groups, and log-rank test was used for comparison. Univariate and multivariate Cox proportional risk models were used to determine the poor independent factors affecting the poor OS in patients with gastric cancer.Results:The median age of the 156 patients was 61 years (53 years, 68 years), including 110 males (70.5%) and 46 females (29.5%). The proportion of patients with NME3 high expression in cancer tissues was lower than that in paracancerous tissues [51.9% (81/156) vs. 75.5% (105/139)], and the difference was statistically significant ( χ2 = 17.60, P < 0.001). The proportion of patients with NME3 high expression in moderate-low differentiation and moderate differentiation group was lower than that of those in low-differentiation group [63.3% (50/79) vs. 39.4% (28/71)], the proportion of patients with NME3 high expression in pTNM staging group Ⅲ-Ⅳ was higher than that of those in pTNM staging group Ⅰ-Ⅱ [55.5% (76/137) vs. 26.3% (5/19)], and the difference was statistically significant (both P < 0.05). The proportion of patients with NME3 high expression was 62.2% (46/74), 52.0% (13/25), 39.3% (22/56), respectively in patients with Lauran intestinal type, mixed type and diffused type, and the differences were statistically significant ( χ2 = 6.69, P = 0.035). In addition, OS of patients with the NME3 high expression group was better than that of those with the NME3 low expression group, and the difference was statistically significant ( P < 0.001). The further analysis of gender subgroup showed that OS of male patients with the NME3 high expression group was better than that of those with the NME3 low expression group, and OS of female patients with the NME3 high expression group was better than that of those with the NME3 low expression group, and the differences was statistically significant (all P < 0.05). Univariate and multivariate Cox regression analysis showed that the expression of NME3 in cancer tissues (high expression vs. low expression: HR = 0.342, 95% CI: 0.207-0.564, P < 0.001), family history (yes vs. no: HR = 2.240, 95% CI: 1.285-3.907, P = 0.004), pN staging (N 2-3vs. N 0-1: HR = 2.133, 95% CI: 1.114-4.083, P = 0.022), pM staging (M 1vs. M 0: HR = 2.761, 95% CI: 1.386-5.500, P = 0.004), carcinoma embryonic antigen (CEA) level (CEA > 5 ng/ml vs. CEA ≤ 5 ng/ml: HR = 1.688, 95% CI: 1.018-2.798, P = 0.042), carbohydrate antigen 125 (CA125) level (CA125 > 35 U/ml vs. CA125 ≤ 35 U/ml: HR = 2.913, 95% CI: 1.403-6.047, P = 0.004) were independent factors influencing OS in patients with gastric cancer. Conclusions:NME3 is lowly expressed in gastric cancer tissues, and it is highly expressed in higher-differentially, late staged and intestinal type gastric cancer. NME3 low expression is an independent risk factor for the poor prognosis of gastric cancer. It is speculated that NME3 may play a inhibitory role in gastric cancer.

Objective:To investigate the metabolic disorder of gut microbiota and short-chain fatty acids (SCFAs) in patients with hypertensive intracerebral hemorrhage and their correlations with the poor outcomes.Methods:Thirty-eight patients with hypertensive intracerebral hemorrhage within 7 d of onset and 32 healthy controls were enrolled prospectively. Fecal samples were collected for 16S rRNA sequencing and SCFAs levels detection. The outcome was evaluated by the modified Rankin Scale at 90 d after the onset, and >2 points were defined as a poor outcome. Multivariate logistic regression model was used to determine the correlations between the gut microbiota and the fecal SCFAs levels and outcomes. Results:The gut microbiota of patients with hypertensive intracerebral hemorrhage was significantly different from that of healthy control group. It is manifested as a decrease in α diversity, a difference in β diversity, an increase in the abundance of potential undesirable bacteria, a decrease in the abundance of common SCFA-producing bacteria and a decrease in the fecal SCFAs levels. In patients with hypertensive intracerebral hemorrhage, compared with the good outcome group, the α diversity of the gut microbiota, the abundance of SCFA-producing bacteria such as Lacetospirillum and Bacteroides, and the total SCFAs, acetic acid and propionic acid levels decreased in the poor outcome group. Multivariate logistic regression analysis showed that after adjusting for potential confounding factors, the decrease of fecal SCFAs levels after log2 conversion was significantly and independently correlated with the poor outcomes. Conclusion:Patients with hypertensive intracerebral hemorrhage have gut microbiota and SCFAs metabolic disorder, the latter is significantly correlated with the poor outcomes. Gut microbiota and SCFAs may become an outcome marker and treatment target for patients with hypertensive intracerebral hemorrhage

Objective:To explore the mechanism of Jianpi Qingchang Decoction in the treatment of UC by integrating network pharmacology, bioinformatics, molecular docking and experimental verification.Methods:The effective components and targets of Jianpi Qingchang Decoction were obtained from TCMSP database, and UC data sets GSE16879, GSE48958 and GSE75214 were obtained from GEO database, and differentially expressed genes were screened; intersection targets were obtained through Venn diagram, and GO function and KEGG pathway enrichment analysis was performed. An intersection target PPI network was constructed using STRING database and topology analysis was performed; hub genes were screened through lasso regression and the expression consistency of core targets in the dataset was verified through logistic regression. A UC mouse model was established and hub genes were validated.Results:A total of 213 drug targets of Jianpi Qingchang Decoction were obtained, and 499 common intersection targets of GSE16879, GSE48958 and GSE75214 were obtained by differential gene expression analysis. Thirty intersection targets of Jianpi Qingchang Decoction and UC were obtained, mainly acting on IL-17 signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications, etc. PPI network topology analysis obtained 7 common intersection targets, including PTGS2, IL-1B, IL-6, MMP9, CXCL8, CCL2 and MMP2. IL-6 and MMP2 were selected as hub genes by lasso regression. Logistics regression analysis showed that IL-6 and MMP2 were risk factors for the disease. Compared with the model group, the expressions of IL-6 and MMP2 mRNA and protein in the colon tissue of the TCM group decreased ( P<0.05), and the morphology of colon tissue was improved compared with the model group. Conclusion:IL-6 and MMP2 are risk factors for UC, the therapeutic effect of Jianpi Qingchang Decoction is to mediate Il-17 signal pathway, TNF signal pathway and AGE-RAGE signal pathway in diabetic complications through the targets of IL-6, and MMP2, thereby treating UC.