ObjectiveTo investigate the therapeutic effect of Astragali Radix-mediated changes in gut microbiota on treating type 2 diabetes （T2DM）. MethodsA 12-week randomized， placebo-controlled clinical trial enrolled eighty patients with newly diagnosed type 2 diabetes and poor glycemic control in the Qi deficiency type. All patients received insulin therapy. The observation group （40 cases） was administered with Astragali Radix Granules， while the control group （40 cases） received a placebo. Both treamtents were taken orally twice daily. Changes in gut microbiota were assessed by 16s rDNA sequencing. Serum glucagon-like peptide-1 （GLP-1） levels were measured using enzyme-linked immunosorbent assay （ELISA）. Glucose metabolism indicators including fasting blood glucose （FPG）， 2-hour postprandial blood glucose （2 h PG），glycated albumin（GA）， and glycated hemoglobin （HbA1c） were evaluated. Pancreatic function was evaluated using fasting C-peptide （FCP）， 2-hour postprandial C-peptide （2 h CP）， and C-peptide area under the curve （AUC_cp）. Traditional Chinese medicine （TCM） syndrome scores， clinical efficacy， and safety indicators were also observed. ResultsIn terms of glucose metabolism indicators， compared with the baseline， both groups exhibited significantly lower FPG， 2 h PG， GA and HbA1C （P<0.01），while FCP， 2 h CP and AUC_cp were significantly higher （P<0.01）. Compared with the control group after the treatment， the observation group showed significantly lower FPG， 2 h PG， GA and HbA1C（P<0.05， P<0.01），and significantly higher FCP， 2 h CP and AUC_cp （P<0.05， P<0.01）， indicating that Astragali Radix can improve glucose metabolism. In terms of the diversity of gut microbiota， no significant differences were detected in the Chao1， Shannon and Simpson indexes of the two groups compared with their respective baselines. However， compared with the post-treatment control group， the observation group demonstrated significant increases in the Chao1， Shannon and Simpson indexes （P<0.05， P<0.01）. The β-diversity analysis showed significant separation in gut microbiota composition before and after treatment in both groups， indicating that Astragali Radix can significantly alter the structure and improve the diversity of gut microbiota. At the phylum level， compared with the baseline， both groups showed a significant increase in the relative abundance of Bacteroidota（P<0.01）. The relative abundance of the potentially harmful phylum Proteobacteria was significantly lower in the observation Group after treatment （P<0.01）. Compared with the post-treatment control group， the observation group had a significantly higher relative abundance of Bacteroidota（P<0.01）. No significant difference was found in Firmicutes/Bacteroidota （F/B） ratio between the two groups after treatment， and other phyla showed no significant differences. At the genus level， compared with the baseline， the observation group exhibited a significant increase in Bacteroides （P<0.01） and a significant decrease in Escherichia-Shigella （P<0.01）， whereas no significant difference was seen in the control group . Compared with the control group after treatment， the observation group after treatment had a significantly higher relative abundance of Bacteroides （P<0.01）. No significant differences were seen in other genera. Linear discriminant analysis （LDA） identified potential characteristics taxa： in the observation group， Bacteroidota at the phylum level and Bacteroides and Dubosiella at the genus level， in the control group， Proteobacteria at the phylum level as well as Barnesiella and Staphylococcus at the genus level. Correlation analysis based on a heatmap revealed that GLP-1 levels were positively correlated with Firmicutes， F/B ratio and Fusobacterium， and negatively correlated with Bacteroidota， Proteobacteria， Bacteroides and Escherichia-Shigella. In terms of clinical efficacy， compared with the control group， the total effective rate of the observation group was significantly higher （P<0.05）. Compared with the baseline， the scores for shortness of breath， fatigue， weakness， spontaneous sweating and reluctance to speak significantly decreased in both groups （P<0.01）. Compared with the control group after treatment， the score for weakness was significantly lower in the observation group （P<0.01），indicating that Astragali Radix could improve clinical symptoms and alleviate weakness symptoms. In terms of safety， compared with the baseline， alanine aminotransferase （ALT） levels significantly decreased in both groups （P<0.05，P<0.01），indicating that Astragali Radix did not induce any significant abnormalities in liver and kidney functions. ConclusionAstragali Radix demonstrates the potential to significantly improve the gut microbiota environment in patients of newly diagnosed type 2 diabetes with Qi deficiency. The therapeutic effect may contribute to glycemic control， possibly mediated by an elevation in GLP-1 level. These findings may support its further clinical investigations and potential applications.

OBJECTIVES: Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial. This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression. METHODS: Patients with bipolar Ⅱ depression were enrolled in this prospective, two-center, randomized, 12-week pilot trial. The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale (MADRS) of ≥50%. All eligible patients initially received four weeks of lurasidone monotherapy. Patients who responded well continued to receive this kind of monotherapy. However, no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks. By comprehensively comparing the results of MADRS over a period of 4‍‒‍12 weeks, a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression. RESULTS: Thirty-seven patients responded to lurasidone monotherapy, and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks. After two weeks of combined valproate or vortioxetine treatment, the MADRS score in the vortioxetine group was significantly lower than that in the valproate group. There was no difference in the MADRS scores between the two groups at 8 and 12 weeks. The incidence of side effects did not significantly differ between the valproate and vortioxetine groups. Importantly, three patients in the vortioxetine group appeared to switch to mania or hypomania. CONCLUSIONS This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage, while disease progression should be monitored closely for the risk of switching to mania.
Humans ; Bipolar Disorder/drug therapy* ; Vortioxetine/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; Valproic Acid/administration & dosage* ; Lurasidone Hydrochloride/administration & dosage* ; Prospective Studies ; Treatment Outcome ; Pilot Projects ; Drug Therapy, Combination ; Sulfides/therapeutic use* ; Antidepressive Agents/therapeutic use*

Objective To design and manufacture a stoma bag changer,and explore its application effect in patients with high displacement stoma.Methods The stoma bag changer consists of a communicating tube,an air bag,a collecting bag,an air pressure valve and a tube body.The convenience sampling method was used to select 2023.From December to March 2024,patients with ileal high-displacement stoma who were treated or hospitalized in the outpatient clinics of 15 tertiary hospitals in Zhejiang Province were used as research subjects.The subjects were randomly divided into an experimental group and a control group,with 35 cases in each group.The experimental group used the stoma bag changer to assist bag change,and the control group used the routine method.Data were collected continuously for 1 week through the questionnaire star platform,and differences of the single ostomy bag replacement time,the number of perioral skin cleaning treatments,and effective wearing time of ostomy bag were compared.Results In the end,all 70 patients completed the trial without stoma complications.In the experimental group,the time of single ostomy bag replacement,around the stoma number of skin cleaning treatments were significantly lower than those of the control group,and the effective wearing time of ostomy bag was significantly longer than that of the control group.In the control group,the differences were statistically significant(all P＜0.05).Conclusion The stoma bag changer is used in patients with high ileal displacement stoma,which can effectively shorten the single stoma bag replacement time and reduce the number of skin cleaning around the stoma,and prolong the use of a stoma bag.

AIM:This study aims to investigate the expression and prognostic value of ubiquitin-conjugating enzyme E2C(UBE2C)in hepatocellular carcinoma(HCC),and to explore its impact on cancer stemness and the regulato-ry mechanisms.METHODS:(1)The TCGA and GEO databases were used to analyze UBE2C mRNA expression levels in HCC tissues and their correlation with prognosis using bioinformatics techniques,and these findings were further vali-dated in postoperative specimens from 107 HCC patients.The GEPIA database was used to analyze the correlation be-tween UBE2C and steroid receptor coactivator(SRC).(2)The CCK8,colony formation,wound healing,and spheroid formation assays were used to assess the effects of UBE2C on HCC cell proliferation,migration,and stemness.The inter-action between UBE2C and signal transducer and activator of transcription 3(STAT3),as well as its regulatory mecha-nism,was examined by Western blot and co-immunoprecipitation assays.(3)The subcutaneous xenograft model in nude mice was employed to validate the role of UBE2C in tumor growth in vivo.RESULTS:(1)Bioinformatics analysis re-vealed that UBE2C expression was significantly up-regulated in HCC tissues compared with adjacent normal tissues(P<0.05 in TCGA,and P<0.01 in GEO).Consistently,analysis of HCC specimens confirmed that high UBE2C expression was associated with shortened overall survival and disease-free survival of HCC patients(P<0.05).Furthermore,analysis using the GEPIA database revealed a positive correlation between UBE2C and SRC(P<0.01).(2)In vitro experiments demonstrated that UBE2C significantly promotes the proliferation and migration of HCC cells.Based on these findings,we presumed that UBE2C may regulate the phosphorylation of STAT3 at the Y705 site by modulating SRC activity,thereby in-fluencing the stemness characteristics of tumor cells.(3)In vivo experiments further confirmed that UBE2C inhibition sig-nificantly suppressed tumor growth.CONCLUSION:The UBE2C promoted proliferation and migration of HCC cells and regulated the stemness of HCC cells by interacting with STAT3.

AIM:This study aims to investigate the regulatory effects of caffeic acid phenethyl ester(CAPE)on metabotropic glutamate receptor 5(mGluR5)and tyrosine kinase Fyn,and to explore its role in alleviating neuroinflam-mation and pathological features of Alzheimer disease(AD).METHODS:In vitro,the murine neuroblastoma N2a cell line was treated with amyloid β-protein 42 oligomers(Aβ42Os;10 nmol/L to 10 μmol/L)for 24 h.Cell viability was as-sessed by MTT assay.Western blot analyzed mGluR5 expression and Fyn phosphorylation(Tyr416).Pharmacological modulators(CHPG/MPEP)were used to evaluate mGluR5-mediated inflammatory cytokine regulation(qPCR)and Fyn ac-tivation.In vivo,wild-type(WT)and 5×FAD mice(WT,WT+CAPE,5×FAD and 5×FAD+CAPE)were analyzed for AD-related proteins,neuroinflammation(ELISA),glial activation(GFAP/Iba-1 immunofluorescence),and β-amyloid deposi-tion(thioflavin S).RESULTS:(1)Treatment with 1 μmol/L Aβ42Os increased mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01)without affecting N2a cell viability.Intracerebral Aβ42Os injection similarly up-regulated hip-pocampal mGluR5 and Fyn(P<0.01).(2)MPEP reduced mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01),while suppressing tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)mRNA levels(P<0.01).(3)CAPE decreased mGluR5-Fyn activation in N2a cells,neurons,and 5×FAD mice(P<0.01).(4)CAPE-treated 5×FAD mice exhibited reduced neuroinflammation markers(GFAP,Iba-1,TNF-α,IL-1β,and IL-6),Aβ plaques,and p-APP levels(P<0.01).CONCLUSION:Treatment with CAPE inhibits Aβ42Os-induced mGluR5-Fyn signaling activation,thereby attenuating neuroinflammation and the pathology associated with AD.

Objective:To analyze the efficacy of different doses of esketamine in maintaining general anesthesia in elderly patients undergoing radical resection of esophageal cancer.Methods:A total of 98 elderly patients who underwent radical resection of esophageal cancer and admitted from Jun. 2023 to May. 2025 in Shangqiu First People’s Hospital were selected and divided into Group A ( n=50, 0.25 mg·kg -1·h -1) and Group B ( n=48,0.5 mg·kg -1·h -1) according to the dose of esketamine. The following situations between the two groups were compared: (1) hemodynamics [mean arterial pressure (MAP), heart rate (HR) ] before anesthesia induction (T0), 30 minutes after the start of the operation (T1), and at extubation (T2) ; (2) Stress inflammatory indicators [norepinephrine (NE), C-reactive protein (CRP) ] before the operation and 1 day after the operation; (3) Analgesia status [Dosage of propofol and remifentanil, remedial analgesia rate, and the degree of analgesia was evaluated by visual analogue scale (VAS) 2 hours after the operation]; (4) Postoperative recovery [postoperative eye-opening time, extubation time, anesthesia recovery time, and postoperative recovery quality was evaluated using the Chinese version of the 15-item Quality of Recovery (QoR-15) Scale 1 day after the operation]; (5) Safety. Results:(1) At time T1, MAP of both groups was lower than that at time T0,and at time T2, MAP of group B was higher than that at time T1 ( P<0.05). At times T1 and T2, HR of both groups was lower than that at time T0, and HR of both groups at time T2 was higher than that at time T1 ( P<0.05). At time T1, MAP and HR in group B were lower than those in group A ( P<0.05). (2) The dosages of propofol and remifentanil in group B were lower ( P<0.05) ,while the comparison of remedial analgesia rate and VAS score between the two groups showed P>0.05. (3) One day after the operation,the levels of serum NE and CRP in both groups were higher than those before the operation,while those in group B were even lower ( P<0.05). (4) The incidence of adverse reactions in group B (20.83%) was slightly higher than that in group A (10.00%). (5) The eye-opening time,extubation time and anesthesia recovery time after surgery in group B were all longer than those in group A ( P<0.05), while the comparison of QoR-15 scores between the two groups showed P>0.05. Conclusions:In the maintenance of general anesthesia for elderly patients undergoing radical resection of esophageal cancer, the intraoperative hemodynamic fluctuations of low-dose esketamine are smaller. Although the dosages of propofol and remifentanil are higher and the postoperative recovery time is longer, there are no significant differences in analgesic effect, adverse reactions or recovery quality, while the stress and inflammatory responses of high-dose esketamine are smaller.

Objective:The Social Isolation Scale for people with type 2 diabetes mellitus (T2DM) was developed and tested for reliability and validity, which provided an effective tool for measuring the social isolation level of patients with T2DM.Methods:The initial scale was developed through literature review, qualitative interviews, and expert consultation. Convenience sampling method was used to select T2DM patients who met the inclusion and exclusion criteria for questionnaire survey. The item analysis method was used to select the items of the scale. Exploratory and confirmatory factor analyses were used to evaluate construct validity. The content validity of the scale was evaluated by the scale-level content validity index and the item-level content validity index. The criterion validity was verified by using the Lubben Social Network Scale-6 and the De Jong Gierveld Loneliness Scale. Reliability was tested through internal consistency and test-retest reliability.Results:Through literature review and qualitative interviews, 30 items of the scale were selected to form the first version scale. After two rounds of inquiries from 16 experts (expert authority coefficient = 0.897), the second version of the scale was formed. A total of 407 questionnaires were distributed in two stages using the second version scale. Among the 407 patients, there were 214 males and 193 females. Exploratory factor analysis extracted 4 common factors, with a cumulative variance contribution rate of 61.338%. The final scale was determined to include 4 dimensions and 16 items, with the dimensions being "social support network", "frequency of social participation", "satisfaction with interpersonal relationships", and "diabetes-related sense of isolation".The average content validity index at the scale level was 0.929, the content validity index at the item level was 0.830 - 1.000, and the criterion validity was - 0.647 and 0.681. The Cronbach′s α coefficient of the total scale was 0.822, and the test-retest reliability was 0.858.Conclusions:The Social Isolation Scale for people with T2DM has good reliability and validity. It is a reliable and valid tool for assessing social isolation in T2DM patients.

Objective:To analyze the efficacy of different doses of esketamine in maintaining general anesthesia in elderly patients undergoing radical resection of esophageal cancer.Methods:A total of 98 elderly patients who underwent radical resection of esophageal cancer and admitted from Jun. 2023 to May. 2025 in Shangqiu First People’s Hospital were selected and divided into Group A ( n=50, 0.25 mg·kg -1·h -1) and Group B ( n=48,0.5 mg·kg -1·h -1) according to the dose of esketamine. The following situations between the two groups were compared: (1) hemodynamics [mean arterial pressure (MAP), heart rate (HR) ] before anesthesia induction (T0), 30 minutes after the start of the operation (T1), and at extubation (T2) ; (2) Stress inflammatory indicators [norepinephrine (NE), C-reactive protein (CRP) ] before the operation and 1 day after the operation; (3) Analgesia status [Dosage of propofol and remifentanil, remedial analgesia rate, and the degree of analgesia was evaluated by visual analogue scale (VAS) 2 hours after the operation]; (4) Postoperative recovery [postoperative eye-opening time, extubation time, anesthesia recovery time, and postoperative recovery quality was evaluated using the Chinese version of the 15-item Quality of Recovery (QoR-15) Scale 1 day after the operation]; (5) Safety. Results:(1) At time T1, MAP of both groups was lower than that at time T0,and at time T2, MAP of group B was higher than that at time T1 ( P<0.05). At times T1 and T2, HR of both groups was lower than that at time T0, and HR of both groups at time T2 was higher than that at time T1 ( P<0.05). At time T1, MAP and HR in group B were lower than those in group A ( P<0.05). (2) The dosages of propofol and remifentanil in group B were lower ( P<0.05) ,while the comparison of remedial analgesia rate and VAS score between the two groups showed P>0.05. (3) One day after the operation,the levels of serum NE and CRP in both groups were higher than those before the operation,while those in group B were even lower ( P<0.05). (4) The incidence of adverse reactions in group B (20.83%) was slightly higher than that in group A (10.00%). (5) The eye-opening time,extubation time and anesthesia recovery time after surgery in group B were all longer than those in group A ( P<0.05), while the comparison of QoR-15 scores between the two groups showed P>0.05. Conclusions:In the maintenance of general anesthesia for elderly patients undergoing radical resection of esophageal cancer, the intraoperative hemodynamic fluctuations of low-dose esketamine are smaller. Although the dosages of propofol and remifentanil are higher and the postoperative recovery time is longer, there are no significant differences in analgesic effect, adverse reactions or recovery quality, while the stress and inflammatory responses of high-dose esketamine are smaller.

AIM:This study aims to investigate the regulatory effects of caffeic acid phenethyl ester(CAPE)on metabotropic glutamate receptor 5(mGluR5)and tyrosine kinase Fyn,and to explore its role in alleviating neuroinflam-mation and pathological features of Alzheimer disease(AD).METHODS:In vitro,the murine neuroblastoma N2a cell line was treated with amyloid β-protein 42 oligomers(Aβ42Os;10 nmol/L to 10 μmol/L)for 24 h.Cell viability was as-sessed by MTT assay.Western blot analyzed mGluR5 expression and Fyn phosphorylation(Tyr416).Pharmacological modulators(CHPG/MPEP)were used to evaluate mGluR5-mediated inflammatory cytokine regulation(qPCR)and Fyn ac-tivation.In vivo,wild-type(WT)and 5×FAD mice(WT,WT+CAPE,5×FAD and 5×FAD+CAPE)were analyzed for AD-related proteins,neuroinflammation(ELISA),glial activation(GFAP/Iba-1 immunofluorescence),and β-amyloid deposi-tion(thioflavin S).RESULTS:(1)Treatment with 1 μmol/L Aβ42Os increased mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01)without affecting N2a cell viability.Intracerebral Aβ42Os injection similarly up-regulated hip-pocampal mGluR5 and Fyn(P<0.01).(2)MPEP reduced mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01),while suppressing tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)mRNA levels(P<0.01).(3)CAPE decreased mGluR5-Fyn activation in N2a cells,neurons,and 5×FAD mice(P<0.01).(4)CAPE-treated 5×FAD mice exhibited reduced neuroinflammation markers(GFAP,Iba-1,TNF-α,IL-1β,and IL-6),Aβ plaques,and p-APP levels(P<0.01).CONCLUSION:Treatment with CAPE inhibits Aβ42Os-induced mGluR5-Fyn signaling activation,thereby attenuating neuroinflammation and the pathology associated with AD.

Objective To design and manufacture a stoma bag changer,and explore its application effect in patients with high displacement stoma.Methods The stoma bag changer consists of a communicating tube,an air bag,a collecting bag,an air pressure valve and a tube body.The convenience sampling method was used to select 2023.From December to March 2024,patients with ileal high-displacement stoma who were treated or hospitalized in the outpatient clinics of 15 tertiary hospitals in Zhejiang Province were used as research subjects.The subjects were randomly divided into an experimental group and a control group,with 35 cases in each group.The experimental group used the stoma bag changer to assist bag change,and the control group used the routine method.Data were collected continuously for 1 week through the questionnaire star platform,and differences of the single ostomy bag replacement time,the number of perioral skin cleaning treatments,and effective wearing time of ostomy bag were compared.Results In the end,all 70 patients completed the trial without stoma complications.In the experimental group,the time of single ostomy bag replacement,around the stoma number of skin cleaning treatments were significantly lower than those of the control group,and the effective wearing time of ostomy bag was significantly longer than that of the control group.In the control group,the differences were statistically significant(all P＜0.05).Conclusion The stoma bag changer is used in patients with high ileal displacement stoma,which can effectively shorten the single stoma bag replacement time and reduce the number of skin cleaning around the stoma,and prolong the use of a stoma bag.