Objective·To compare the safety and short-term outcomes of robot-assisted versus laparoscopic-assisted proximal gastrectomy combined with double-flap esophagogastrostomy in the treatment of early upper gastric cancer.Methods·A retrospective cohort study was conducted to analyze the clinical and pathological data of 31 early gastric cancer patients who underwent proximal gastrectomy combined with double-flap esophagogastrostomy for gastrointestinal reconstruction at the Department of Gastrointestinal Surgery,Renji Hospital,Shanghai Jiao Tong University School of Medicine,from September 2023 to March 2024.Based on the surgical approach,patients were divided into the robot-assisted surgery group(robotic group,20 cases)and the laparoscope-assisted surgery group(laparoscopic group,11 cases).General clinical data,intraoperative conditions,and postoperative recovery between the two groups were compared.At the 6-month postoperative follow-up,upper gastrointestinal radiography and esophagogastroscopy were performed to assess anastomotic stricture and gastroesophageal reflux disease.Additionally,the gastric cancer-specific module of the European Organization for Research and Treatment of Cancer(EORTC),Quality of Life Questionnaire-Stomach 22(QLQ-STO22),was used to evaluate the patients' quality of life.Results·The general data of the two groups,including gender,age,preoperative comorbidities,American Society of Anesthesiologists(ASA)classification,Siewert classification,and pathological staging of tumors,showed no statistically significant differences(all P>0.05).All patients successfully underwent the procedure without conversion to open surgery.The time for gastroesophageal anastomosis was significantly shorter in the robotic group compared to the laparoscopic group[(31.09±8.23)min vs(43.73±8.83)min,P<0.001],while there were no statistically significant differences in other intraoperative and postoperative parameters,including operative time,intraoperative blood loss,number of lymph nodes removed,duration of gastric tube placement,time to start a liquid diet,length of postoperative hospital stay,and incidence of postoperative complications(all P>0.05).At the 6-month postoperative follow-up,30 patients completed the follow-up,with one patient lost to follow-up in the robotic group.Upper gastrointestinal radiography and esophagogastroscopy results showed that only one patient in the laparoscopic group developed an anastomotic stricture,while one patient in the robotic group developed grade A and one developed grade B gastroesophageal reflux disease(GERD).In addition,one patient in the laparoscopic group also developed grade B GERD.The incidences of GERD and anastomotic stricture showed no statistically significant differences between the two groups(both P>0.05).EORTC QLQ-STO22 results indicated that the robotic group had significantly lower scores in the dimensions of dysphagia,gastroesophageal reflux,and dietary restrictions,as well as in the total score,compared to the laparoscopic group(all P<0.05).Conclusion·Robot-assisted proximal gastrectomy combined with double-flap esophagogastrostomy is safe and feasible.It shortens anastomosis time and offers potential advantages in postoperative functional recovery and quality of life improvement.

Objective:To investigate the metabolic pathways and potential molecular targets associated with dapagliflozin in the treatment of type 2 diabetes mellitus.Methods:Plasma samples from patients with type 2 diabetes mellitus were collected before and after 12 months of dapagliflozin treatment and analyzed using UPLC-VION IMS Q-Tof-based metabolomics and timsTOF Pro2 diaPASEF-based proteomics. Multivariate statistical analyses were performed to identify significant differences pre- and post-treatment. Correlation analysis was then conducted to assess relationships between differentially expressed metabolites and proteins closely associated with type 2 diabetes mellitus. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were used to construct metabolic pathway maps and predict therapeutic targets.Results:After 12 months of dapagliflozin treatment, 162 differential metabolites were identified, with 59 upregulated and 103 downregulated. A total of 440 differentially expressed proteins were detected, of which 272 were upregulated and 168 were downregulated. The main classes of differential metabolites included sphingolipids, glycerophospholipids, and glycosphingolipids. Key differentially expressed proteins included importin subunit alpha-11, synemin, Janus kinase 1, and far upstream element-binding protein 2. Correlation analysis revealed 98 shared enriched pathways between differential metabolites and proteins, involving neurotrophin signaling, chemokine signaling, and B cell receptor signaling pathways. Metabolic pathway analysis suggested that dapagliflozin might regulate insulin secretion by modulating glucose-dependent insulinotropic polypeptide, calmodulin-dependent protein kinase, and diacylglycerol levels.Conclusion:Dapagliflozin may exert therapeutic effects in type 2 diabetes mellitus through multiple mechanisms, including the modulation of metabolic and proteomic profiles, participation in key cellular signaling pathways, and regulation of insulin secretion.

Objective·To compare the safety and short-term outcomes of robot-assisted versus laparoscopic-assisted proximal gastrectomy combined with double-flap esophagogastrostomy in the treatment of early upper gastric cancer.Methods·A retrospective cohort study was conducted to analyze the clinical and pathological data of 31 early gastric cancer patients who underwent proximal gastrectomy combined with double-flap esophagogastrostomy for gastrointestinal reconstruction at the Department of Gastrointestinal Surgery,Renji Hospital,Shanghai Jiao Tong University School of Medicine,from September 2023 to March 2024.Based on the surgical approach,patients were divided into the robot-assisted surgery group(robotic group,20 cases)and the laparoscope-assisted surgery group(laparoscopic group,11 cases).General clinical data,intraoperative conditions,and postoperative recovery between the two groups were compared.At the 6-month postoperative follow-up,upper gastrointestinal radiography and esophagogastroscopy were performed to assess anastomotic stricture and gastroesophageal reflux disease.Additionally,the gastric cancer-specific module of the European Organization for Research and Treatment of Cancer(EORTC),Quality of Life Questionnaire-Stomach 22(QLQ-STO22),was used to evaluate the patients' quality of life.Results·The general data of the two groups,including gender,age,preoperative comorbidities,American Society of Anesthesiologists(ASA)classification,Siewert classification,and pathological staging of tumors,showed no statistically significant differences(all P>0.05).All patients successfully underwent the procedure without conversion to open surgery.The time for gastroesophageal anastomosis was significantly shorter in the robotic group compared to the laparoscopic group[(31.09±8.23)min vs(43.73±8.83)min,P<0.001],while there were no statistically significant differences in other intraoperative and postoperative parameters,including operative time,intraoperative blood loss,number of lymph nodes removed,duration of gastric tube placement,time to start a liquid diet,length of postoperative hospital stay,and incidence of postoperative complications(all P>0.05).At the 6-month postoperative follow-up,30 patients completed the follow-up,with one patient lost to follow-up in the robotic group.Upper gastrointestinal radiography and esophagogastroscopy results showed that only one patient in the laparoscopic group developed an anastomotic stricture,while one patient in the robotic group developed grade A and one developed grade B gastroesophageal reflux disease(GERD).In addition,one patient in the laparoscopic group also developed grade B GERD.The incidences of GERD and anastomotic stricture showed no statistically significant differences between the two groups(both P>0.05).EORTC QLQ-STO22 results indicated that the robotic group had significantly lower scores in the dimensions of dysphagia,gastroesophageal reflux,and dietary restrictions,as well as in the total score,compared to the laparoscopic group(all P<0.05).Conclusion·Robot-assisted proximal gastrectomy combined with double-flap esophagogastrostomy is safe and feasible.It shortens anastomosis time and offers potential advantages in postoperative functional recovery and quality of life improvement.

Objective:To investigate the effect of miR-22-3p and apoptosis-inducing factor,mitochondrion-associated 1(AIFM1)on mitochondrial homeostasis and apoptosis of pulmonary artery smooth muscle cells(PASMCs)under hypoxic conditions by establishing an in vitro model of pulmonary hypertension(PAH).Methods:PASMCs were cultured under hypoxic conditions to establish an in vitro model of PAH,and the expression levels of AIFM1 and miR-22-3p were upregulated or downregulated.Reverse transcription quantita-tive polymerase chain reaction(RT-qPCR)and Western blotting were used to measure the expression levels of AIFM1,miR-22-3p,and cleaved cysteine-aspartic protease-3(Cleaved Caspase-3).cell counting kit-8(CCK-8)assay was used to measure the prolifera-tive activity of cells,and flow cytometry was used to measure cell apoptosis.Mitochondrial superoxide indicator(mitoSOX)and adenos-ine triphosphate(ATP)assay kits were used to observe mitochondrial function and dynamics,and Mito-Tracker Red CMXRos(Mito-Tracker)was used to measure the change in mitochondrial circum-ference.Dual-luciferase reporter assay was used to validate the interaction between AIFM1 and miR-22-3p.Results:Hypoxia increased the content of mitochondrial ROS,reduced the level of ATP,promoted mitochondrial fission,and reduced cell apoptosis in PASMCs.AIFM1 overexpression improved mitochondrial homeo-stasis and increased cell apoptosis,while miR-22-3p negatively regulated AIFM1 and reversed the effect of AIFM1 overexpression.Conclusion:This study shows that miR-22-3p enhances mitochon-drial homeostasis,proliferation,and apoptosis in hypoxia-induced PASMCs by targeting AIFM1,which provides a potential theoretical basis for the prevention and treatment of PAH.

Objective:To investigate the metabolic pathways and potential molecular targets associated with dapagliflozin in the treatment of type 2 diabetes mellitus.Methods:Plasma samples from patients with type 2 diabetes mellitus were collected before and after 12 months of dapagliflozin treatment and analyzed using UPLC-VION IMS Q-Tof-based metabolomics and timsTOF Pro2 diaPASEF-based proteomics. Multivariate statistical analyses were performed to identify significant differences pre- and post-treatment. Correlation analysis was then conducted to assess relationships between differentially expressed metabolites and proteins closely associated with type 2 diabetes mellitus. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were used to construct metabolic pathway maps and predict therapeutic targets.Results:After 12 months of dapagliflozin treatment, 162 differential metabolites were identified, with 59 upregulated and 103 downregulated. A total of 440 differentially expressed proteins were detected, of which 272 were upregulated and 168 were downregulated. The main classes of differential metabolites included sphingolipids, glycerophospholipids, and glycosphingolipids. Key differentially expressed proteins included importin subunit alpha-11, synemin, Janus kinase 1, and far upstream element-binding protein 2. Correlation analysis revealed 98 shared enriched pathways between differential metabolites and proteins, involving neurotrophin signaling, chemokine signaling, and B cell receptor signaling pathways. Metabolic pathway analysis suggested that dapagliflozin might regulate insulin secretion by modulating glucose-dependent insulinotropic polypeptide, calmodulin-dependent protein kinase, and diacylglycerol levels.Conclusion:Dapagliflozin may exert therapeutic effects in type 2 diabetes mellitus through multiple mechanisms, including the modulation of metabolic and proteomic profiles, participation in key cellular signaling pathways, and regulation of insulin secretion.

Objective:To analyze the clinical efficacy and prognostic factors of intracranial primary diffuse large B-cell lymphoma (DLBCL).Methods:Clinical data of 205 patients pathologically diagnosed with intracranial primary DLBCL at Sun Yat-sen University Cancer center from March 2001 to September 2020 were retrospectively analyzed. Among them, 101 patients were male and 104 female, the median age was 54 years old. Non-germinal center B cell (GCB) subtype accounted for 74.1%(126/170). A total of 177 patients received high-dose methotrexate (HD-MTX) and 91 patients received rituximab. After induction chemotherapy, 59 patients (30.4%) achieved complete response (CR), 112 patients (57.7%) achieved partial response (PR) or stable disease (SD). A total of 83 patients received consolidation or salvage radiotherapy, and only 14 patients received autologous stem cell transplantation (ASCT). The influence of pathological type, chemotherapy, rituximab treatment, radiotherapy and radiotherapy mode, ASCT and other factors on the overall survival (OS) and progression free survival (PFS) was evaluated. The survival rate was calculated by Kaplan-Meier method. Univariate prognostic analysis was performed by log-rank test. Multivariate prognostic analysis was conducted by COX model.Results:The median follow-up time was 34 months. The 5-year OS and PFS rates were 55.6% and 44.2%, respectively. GCB subtype, chemotherapy with HD-MTX, rituximab treatment, remission status after induction chemotherapy, and radiotherapy were favorable prognostic factors for OS or PFS, in which the last three were the independent prognostic factors. Consolidation radiotherapy in patients who obtained CR after induction chemotherapy did not significantly improve survival, while salvage radiotherapy in patients who achieved PR/SD after induction chemotherapy significantly improved both OS and PFS(both P<0.01). Consolidation radiotherapy showed no significant survival difference compared with consolidation ASCT. Conclusions:The non-GCB subtype of intracranial primary DLBCL is related to poor prognosis. The addition of rituximab to HD-MTX based induction chemotherapy can improve survival. Radiotherapy is still an important treatment for intracranial primary DLBCL, and there are limitations of ASCT in practical clinical application.

Objective:To explore and analyze the correlation between miR-31 in peripheral blood and oxidative stress indicators of diabetic nephropathy.Methods:A total of 94 patients with diabetic nephropathy who were admitted to Affiliated Hospital of Jining Medical College from September 2019 to September 2020 were selected. Patients were divided into mild diabetic nephropathy [estimated glomerular filtration rate (eGFR) 60-90 ml/min, 36 cases] group, moderate diabetic nephropathy (eGFR 30-60 ml/min, 27 cases) group and severe diabetic nephropathy (eGFR 0-30 ml/min, 31 cases) group according to the severity of the disease, and 30 healthy people in the same period were selected as the control group. Real time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-31 in peripheral blood. Serum superoxide dismutase (SOD), malondialdehyde (MDA), advanced oxidation protein products (AOPP) and other oxidative stress indicators, as well as serum urea nitrogen, creatinine and glomerular filtration rate. Pearson was used to analyze the correlation between peripheral blood miR-31 and oxidative stress indexes and renal function.Results:The expression of miR-31 in peripheral blood of patients with diabetic nephropathy was significantly lower than that in the control group, and the expression of miR-31 in peripheral blood of patients in severe and moderate diabetic nephropathy group was significantly lower than that in the mild diabetic nephropathy group (all P<0.05), with statistically significant difference (all P<0.05). Pearson correlation analysis showed that serum miR-31 expression was negatively correlated with the severity of diabetic nephropathy ( r=-0.526, P<0.05). The levels of serum MDA, SOD and AOPP in the diabetic nephropathy group were significantly higher than those in the control group, and the levels of serum MDA, SOD and AOPP in the severe and moderate diabetic nephropathy groups were higher than those in the mild diabetic nephropathy group, with statistically significant difference (all P<0.05). The levels of serum creatinine and blood urea nitrogen in the diabetic nephropathy group were higher than those in the control group, and the glomerular filtration rate was lower than that in the control group (all P<0.05). The levels of serum creatinine and blood urea nitrogen in the severe and moderate diabetic nephropathy group were higher than those in the mild diabetic nephropathy group, while the level of glomerular filtration rate was lower than that in the mild diabetic nephropathy group, with statistically significant difference (all P<0.05). Pearson correlation analysis showed that the expression of miR-31 in peripheral blood was negatively correlated with the levels of MDA, SOD, AOPP, serum creatinine and urea nitrogen (all P<0.05), but positively correlated with glomerular filtration rate ( P<0.05). Conclusions:The expression of miR-31 in peripheral blood gradually decreases with the severity of renal damage. Its level is negatively correlated with oxidative stress indicators of diabetic nephropathy, and positively correlated with glomerular filtration rate, which can be used for for clinical treatment and disease evaluation.

Objective:To investigate the effect of metformin on the microRNA (miRNA) expression and screen potential target with network pharmacology analysis in patients with type 2 diabetes.Methods:Fifteen patients with new diagnosed type 2 diabetes admitted to our hospital were selected, who received metformin during hospitalization and after discharge. The expression of serum matrix metalloproteinase (MMP)-9, transforming growth factor (TGF)-β1, and myocardial fibrosis related miRNAs were compared before and 6 month after metformin treatment. In addition, gene ontology (GO) and KEGG pathway enrichment analysis were applied to analyze differential expression miRNAs showing statistical significance. Meanwhile, the network figure was established to reflect the target gene messenger RNA (mRNA) corresponding to differentially expressed miRNA.Results:Compared with pre-medication, the serum level of MMP-9 was significantly decreased after treatment ( P<0.05). Besides, the expression of homo sapiens microRNA (hsa-miR)29a-3p, hsa-miR133a-5p, hsa-miR21-5p, hsa-miR30c-5p, and hsa-miR1-3p in patients with type 2 diabetes were dramatically down-regulated by metformin ( P<0.05 or P<0.01). Results of GO analysis and KEGG pathway enrichment analysis showed that differentially expressed miRNAs were mainly concentrated in endoplasmic reticulum lumen, synapse, basement membrane and other cell components. The molecular functions such as Rho GTPase binding and participation in extracellular matrix structural constituent were exerted through biological processes such as collagen catabolic process, regulation of short-term neuronal synaptic plasticity, and axon extension, which were mainly enriched in advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications, tumor necrosis factor (TNF) signaling pathway, and Wnt signaling pathway, etc. The outcome of miRNA-mRNA network analysis demonstrated that there were 230 target genes mRNAs corresponding to differentially expressed miRNA. Conclusion:Metformin could play its role in the treatment of type 2 diabetes by down regulating the expression of miRNA, participating in the transduction of related cellular signaling pathways, regulating chromatin, nucleic acid binding, and enzyme activities.

Objective: To explore the blood lead level and its relationship with behavior in school-age children from rural areas of Chongqing. Methods: A total of 697 students from grades 3 to 6 in the fall semester of 2014 from 14 rural townships in one district of Chongqing was selected by using the random cluster sampling method. Blood were sampled to analyze the lead level. Neurobehavioral tests were performed to determine their personal cognitive and memory ability. Questionnaires and physical examinations were administered to obtain the information of confounding factors. All students were divided into Q₁-Q₄ groups according to the quartile of their blood lead level. The relationship between the blood lead level and behavior was analyzed by multivariate logistic regression model and restricted spline regression model. Results: The mean age of 697 students was (10.07±1.36) years old, and the median (interquartile range) of their blood lead level was 44.31 (35.42) μg/L. Multivariate logistic regression model showed that after adjusting for age, gender, body mass index and maternal culture level, compared with Q₁ group, the OR (95%CI) values of high digit symbol substitution test (DSST) scores and high overall memory quotient (MQ) scores in Q₃ group were 1.65 (1.01-2.70) and 2.10 (1.21-3.62), and the OR (95%CI) value of high long term memory (LTM) scores in Q₄ group was 0.53 (0.31-0.92). The results of the restricted spline regression model showed that the dose-response curves between the blood lead level and MQ/LTM test scores were both parabolic (P<0.05). Conclusion The blood lead level of school-age children from rural areas of Chongqing is the same as that from other areas of China, but slightly higher than that from other areas of Chongqing. Children with higher blood lead level have poor long-term memory ability.

Objective To explore the blood lead level and its relationship with behavior in school?age children from rural areas of Chongqing. Methods A total of 697 students from grades 3 to 6 in the fall semester of 2014 from 14 rural townships in one district of Chongqing was selected by using the random cluster sampling method. Blood were sampled to analyze the lead level. Neurobehavioral tests were performed to determine their personal cognitive and memory ability. Questionnaires and physical examinations were administered to obtain the information of confounding factors. All students were divided into Q1-Q4 groups according to the quartile of their blood lead level. The relationship between the blood lead level and behavior was analyzed by multivariate logistic regression model and restricted spline regression model. Results The mean age of 697 students was (10.07±1.36) years old, and the median (interquartile range) of their blood lead level was 44.31 (35.42) μg/L. Multivariate logistic regression model showed that after adjusting for age, gender, body mass index and maternal culture level, compared with Q1 group, the OR (95%CI ) values of high digit symbol substitution test (DSST) scores and high overall memory quotient (MQ) scores in Q 3 group were 1.65 (1.01-2.70) and 2.10 (1.21-3.62), and the OR (95%CI ) value of high long term memory (LTM) scores in Q4 group was 0.53 (0.31-0.92). The results of the restricted spline regression model showed that the dose?response curves between the blood lead level and MQ/LTM test scores were both parabolic (P<0.05). Conclusion The blood lead level of school?age children from rural areas of Chongqing is the same as that from other areas of China, but slightly higher than that from other areas of Chongqing. Children with higher blood lead level have poor long?term memory ability.