As one of the common chronic bacterial infections, Helicobacter pylori (Hp) infection is a key pathogenic factor of chronic gastritis, peptic ulcer and gastric cancer. In the formation of gastric ulcer, Hp virulence factors directly damage the gastric mucosal barrier, induce the local inflammation and immune response, interfere with the regulation of gastric acid secretion, and ultimately destroy the mucosal stability. In the occurrence of gastric cancer, Hp-driven chronic inflammation is the basis of inflammation-cancer transformation, and it induces the genomic instability and epigenetic changes by interfering with key signaling pathways in host cells, thereby promoting malignant transformation. This paper systematically reviews the related mechanisms of Hp-induced gastric ulcer and gastric cancer in recent years, holding great significance for the development of new intervention strategies and the precise prevention and treatment of gastric cancer.

Objective:To evaluate the feasibility of " two-stitch" fashion in laparoscopic pancreaticojejunostomy (PJ) for patients with fine pancreatic duct (<3 mm).Methods:Clinical data of 32 patients with pancreatic duct diameter <3 mm undergoing laparoscopic PJ using the " two-stitch" fashion between Apr 2021 and Jun 2024 were retrospectively analyzed, including 20 males and 12 females, aged (61.2±23.7) years. Among the patients, there were 23 (71.9%) patients of periampullary tumor and 9 (28.1%) of central pancreatic tumor. 23 (71.9%) patients underwent laparoscopic pancreatoduodenectomy (LPD) and nine (28.1%) underwent laparoscopic central pancreatectomy (LCP). All patients underwent the " two-stitch" fashion of laparoscopic PJ (one stitch each on the ventral and dorsal sides of pancreas for duct-to-mucosal anastomosis). The operation time, PJ time, postoperative hospital stay, postoperative complications (pancreatic fistula, gallbladder leakage, abdominal cavity infection, etc) and mortality were recorded.Result:All patients underwent the " two stitch" laparoscopic PJ successfully, 23(71.9%) patients underwent laparoscopic pancreatoduodenectomy (LPD) and nine (28.1%) underwent laparoscopic central pancreatectomy (LCP). The operation time was (279.3±115.8) min, the PJ time was (31.9±12.2) min, and the postoperative hospital stay was (13.4±8.3) d. Grade B pancreatic fistula occurred in six cases (18.8%, four of LPD and two of LCP), delayed gastric emptying in one case of LPD (3.1%), abdominal infection in three cases (9.4%, two of LPD and one of LCP), biliary fistula in two cases (6.3%, LPD). There were no grade C pancreatic fistula. All patients with postoperative complications were managed with conservative treatment.Conclusion:Laparoscopic " two stitch" PJ for patients with fine pancreatic duct (<3 mm) is safe and feasible.

Objective:To evaluate the feasibility of " two-stitch" fashion in laparoscopic pancreaticojejunostomy (PJ) for patients with fine pancreatic duct (<3 mm).Methods:Clinical data of 32 patients with pancreatic duct diameter <3 mm undergoing laparoscopic PJ using the " two-stitch" fashion between Apr 2021 and Jun 2024 were retrospectively analyzed, including 20 males and 12 females, aged (61.2±23.7) years. Among the patients, there were 23 (71.9%) patients of periampullary tumor and 9 (28.1%) of central pancreatic tumor. 23 (71.9%) patients underwent laparoscopic pancreatoduodenectomy (LPD) and nine (28.1%) underwent laparoscopic central pancreatectomy (LCP). All patients underwent the " two-stitch" fashion of laparoscopic PJ (one stitch each on the ventral and dorsal sides of pancreas for duct-to-mucosal anastomosis). The operation time, PJ time, postoperative hospital stay, postoperative complications (pancreatic fistula, gallbladder leakage, abdominal cavity infection, etc) and mortality were recorded.Result:All patients underwent the " two stitch" laparoscopic PJ successfully, 23(71.9%) patients underwent laparoscopic pancreatoduodenectomy (LPD) and nine (28.1%) underwent laparoscopic central pancreatectomy (LCP). The operation time was (279.3±115.8) min, the PJ time was (31.9±12.2) min, and the postoperative hospital stay was (13.4±8.3) d. Grade B pancreatic fistula occurred in six cases (18.8%, four of LPD and two of LCP), delayed gastric emptying in one case of LPD (3.1%), abdominal infection in three cases (9.4%, two of LPD and one of LCP), biliary fistula in two cases (6.3%, LPD). There were no grade C pancreatic fistula. All patients with postoperative complications were managed with conservative treatment.Conclusion:Laparoscopic " two stitch" PJ for patients with fine pancreatic duct (<3 mm) is safe and feasible.

Objective To analyze the influencing factors of poor anal function after laparoscopic intersphincteric resection(Lap-ISR)for extremely low rectal cancer,and to construct and verify a prediction model based on this model,in order to provide guidance for improving the anal function of patients with extremely low rectal cancer after Lap-ISR.Method A total of 127 patients with extremely low rectal cancer who underwent Lap-ISR in Taizhou People's Hospital from June 2020 to June 2022 were retrospectively selected.Patients were followed up for 12 months after surgery,and postoperative anal function was evaluated by the anal incontinence score(Wexner).According to Wexner score,the patients were divided into good anal function group(106 cases)and poor anal function group(21 cases).The clinical data of patients were collected and the risk factors affecting postoperative poor anal dysfunction were analyzed,and a Nomogram model was constructed to predict the risk of postoperative anal dysfunction in patients after Lap-ISR,and the receiver operating characteristic curve(ROC)was drawn.The area under the curve(AUC)was used to analyze the predictive efficacy of the prediction model for poor anal dysfunction after Lap-ISR.Result The incidence of anal dysfunction after Lap-ISR in patients with extremely low rectal cancer was 16.54％(21/127).Univariate analysis showed that there was no significant difference in gender,age,body mass index,clinical stage,combined underlying diseases,operation time,intraoperative blood loss,anastomosis method,and the distance from the lower edge of the tumor to the dentate line between the two groups(P＞0.05).The proportion of tumor diameter≥5 cm,the proportion of neoadjuvant chemotherapy,the distance between anastomosis and anal verge＜2 cm,and the proportion of anastomotic leakage in the anal dysfunction group were higher than those in the good anal function group(P＜0.05).Cox multivariate regression analysis showed that tumor diameter≥5 cm(OR=5.124),neoadjuvant chemotherapy(OR=5.761)and anastomotic leakage(OR=6.881)were risk factors for postoperative anal function(P＜0.05).Wexner score of patients with tumor diameter ≥5 cm was higher than that of patients with tumor diameter＜5 cm,Wexner score of patients with neoadjuvant chemotherapy was higher than that of patients without neoadjuvant chemotherapy,and Wexner score of patients with anastomotic leakage was higher than that of patients without anastomotic leakage(P＜0.05).Internal validation of Bootstrap method showed that the C-index was 0.785(95％CI:0.692-0.851).The results of ROC curve showed that the sensitivity and specificity of the nomogram model in predicting postoperative poor anal function of patients were 85.70％and 88.70％,respectively,and the AUC was 0.895(95％CI:0.795-0.984).Conclusion Tumor diameter,neoadjuvant chemotherapy and anastomotic leakage are risk factors for poor anal function after Lap-ISR in patients with extremely low rectal cancer.The nomogram risk prediction model based on the above risk factors has a good risk efficiency in evaluating the risk of postoperative anal dysfunction in patients.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Objective:To investigate the effect of hsa-miR-199a-5p on keloid fibroblasts (KFs) fibrosis and its relationship with TGF-β/Smad signaling pathway in vitro. Methods:KFs were infected with the lentiviral vector carrying hsa-miR-199a-5p (hsa-miR-199a-5p group) or the blank vector (rLv-NC group), and a blank control group was set. The proliferation status of KFs were detected by CCK-8 assay. At 48 hours after infection, the expression of hsa-miR-199a-5p in KFs were detected by quantitative real-time PCR (qRT-PCR); cell apoptosis was detected by flow cytometry analysis; cell invasion ability was detected by Transwell; The mRNA and protein levels of collagen Ⅰ, collagen Ⅲ, α-smooth muscle actin(α-SMA), Smad3 and TGF-β1 were detected by qRT-PCR and Western blotting, respectively.Results:At 48 hours after infection with RLV-hsa-miR-199a-5p lentiviral vector, the mRNA expression level of hsa-miR-199a-5p in hsa-miR-199a-5p group KFs was significantly higher than that in rLv-NC group and blank control group, and the difference was statistically significant ( P<0.01). Compared with the rLv-NC and blank control groups, the proliferation rate and invasiveness of the hsa-miR-199a-5p group decreased, the apoptosis rate increased, with statistical significance ( P<0.01); the mRNA and protein expression levels of collagen Ⅰ, collagen Ⅲ, α-SMA, Smad3 and TGF-β1 in hsa-miR-199a-5p group were significantly lower than those in rLv-NC group and blank control group, with statistical significance ( P<0.01). Conclusions:hsa-miR-199a-5p may inhibit the proliferation and invasion of KFs by inhibiting TGF-β/Smad pathway, and promote the apoptosis of KFs, thus inhibiting keloid fibrosis.

Objective:To investigate the effect of hsa-miR-199a-5p on keloid fibroblasts (KFs) fibrosis and its relationship with TGF-β/Smad signaling pathway in vitro. Methods:KFs were infected with the lentiviral vector carrying hsa-miR-199a-5p (hsa-miR-199a-5p group) or the blank vector (rLv-NC group), and a blank control group was set. The proliferation status of KFs were detected by CCK-8 assay. At 48 hours after infection, the expression of hsa-miR-199a-5p in KFs were detected by quantitative real-time PCR (qRT-PCR); cell apoptosis was detected by flow cytometry analysis; cell invasion ability was detected by Transwell; The mRNA and protein levels of collagen Ⅰ, collagen Ⅲ, α-smooth muscle actin(α-SMA), Smad3 and TGF-β1 were detected by qRT-PCR and Western blotting, respectively.Results:At 48 hours after infection with RLV-hsa-miR-199a-5p lentiviral vector, the mRNA expression level of hsa-miR-199a-5p in hsa-miR-199a-5p group KFs was significantly higher than that in rLv-NC group and blank control group, and the difference was statistically significant ( P<0.01). Compared with the rLv-NC and blank control groups, the proliferation rate and invasiveness of the hsa-miR-199a-5p group decreased, the apoptosis rate increased, with statistical significance ( P<0.01); the mRNA and protein expression levels of collagen Ⅰ, collagen Ⅲ, α-SMA, Smad3 and TGF-β1 in hsa-miR-199a-5p group were significantly lower than those in rLv-NC group and blank control group, with statistical significance ( P<0.01). Conclusions:hsa-miR-199a-5p may inhibit the proliferation and invasion of KFs by inhibiting TGF-β/Smad pathway, and promote the apoptosis of KFs, thus inhibiting keloid fibrosis.

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10^-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10^-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

Objective:To investigate the effect of S-phase kinase-associated protein 2 (SKP2) expression level on radiosensitivity of human hepatocellular carcinoma (HCC) cells and the correlation of SKP2 expression with clinical prognosis of patients with HCC.Methods:The expression levels of SKP2 gene in liver cancer tissues and normal tissues were validated and its correlation with clinical prognosis of HCC patients was analyzed based on the TCGA database. Western blot was used to determine the SKP2 protein levels in HCC cell lines before and after radiation. CRISPR/Cas9 technology was employed to delete the promoter and first exon of SKP2 gene in PLC/PRF/5 (PLC) and Hep3B HCC cells for generating the SKP2 knockout cell lines. The difference of radiosensitivity and cell survival rate between normal (SKP2 +/ +) and SKP2 knockout (SKP2 -/ -) HCC cells was determined by using cell clonogenic assay and CCK8 kit. Results:Compared with normal tissues, the expression levels of SKP2 gene in HCC were increased based on the results of TCGA database analysis. K-M analysis showed that the HCC patients with high SKP2 expression had relatively poor prognosis. The 5-year overall survival (OS) was 34.6% in high SKP2 expression HCC patients and 50.6% in low SKP2 expression HCC patients, respectively ( HR=2.18, 95% CI=1.46-3.27, P<0.001). In vitro experiment showed that the expression levels of SKP2 were significantly increased after radiation in HCC cells. Simultaneously, deletion of SKP2 significantly increased the radiosensitivity of HCC cells. Conclusion:The expression level of SKP2 gene is increased in HCC patients, and patients with high SKP2 expression have worse prognosis than those with low expression. Radiation can upregulate the SKP2 expression levels in HCC cells, while the radiosensitivity of the cells is significantly increased after SKP2 deletion.

Objective:To investiagte the ability of albumin-indocyanine green (ALICE) score, albumin-bilirubin (ALBI) score and Child-Pugh score in predicting postoperative liver failure (PHLF) in patients with hepatocellular carcinoma, and to determine the clinical value of ALICE score.Methods:The clinical data of 397 patients with hepatocellular carcinoma who underwent hepatectomy in the Department of Hepatobiliary and Pancreatic Surgery, Jinhua Hospital Affiliated to Zhejiang University from June 2015 to June 2021 were retrospectively analyzed, including 350 males and 47 females, aged (58.9±11.2) years. Univariate and multivariate logistic regression were used to analyze the risk factors of PHLF. The predictive ability of ALICE score for PHLF was evaluated by receiver operating characteristic (ROC) curve, and compared with ALBI score and Child-Pugh score.Results:There were 74 patients with PHLF and 323 patients without PHLF. Multivariate logistic regression analysis showed that Child-Pugh score ( OR=1.630, 95% CI: 1.251-2.486, P=0.034), ALBI score ( OR=1.863, 95% CI: 1.028-3.119, P=0.049) and ALICE score ( OR=1.759, 95% CI: 1.216-3.078, P=0.038) were independent risk factors for PHLF in patients with hepatocellular carcinoma, and the risk of PHLF increased with the increase of grade. The area under the ROC curve of ALICE score predicting PHLF in patients with hepatocellular carcinoma was 0.613 (95% CI: 0.564-0.662), the area under the ALBI score was 0.612 (95% CI: 0.563-0.661), and the area under the Child-Pugh score was 0.555 (95% CI: 0.505-0.605). The ALICE score was better than the Child-Pugh score, and the difference was statistically significant ( z=2.04, P=0.041). In small liver resection patients, ALICE score was better than Child-Pugh score ( z=2.61, P=0.009). There was no significant difference betwenn ALICE score and ALBI score ( z=0.06, P=0.954). Conclusion:ALICE score can predict the occurrence of PHLF in patients with hepatocellular carcinoma, especially in patients with small liver resection, its value is similar to ALBI score, but better than Child-Pugh score.