Traditional treatment for type 1 diabetes mellitus （T1DM） primarily involves insulin replacement， yet some patients encounter issues such as significant blood glucose fluctuations， high risk of hypoglycemia， and weight gain. In recent years， the adjuvant therapeutic role of non-insulin hypoglycemic drugs in T1DM has gradually gained attention. This article reviews the mechanisms of action and clinical research progress of five types of non-insulin hypoglycemic drugs in the treatment of T1DM： amylin analogues （pramlintide）， biguanides （metformin）， sodium-glucose co-transporter 2 inhibitor， dipeptidyl peptidase-4 inhibitor， and glucagon-like peptide-1 receptor agonist. It is found that these drugs can enhance clinical benefits for T1DM patients by improving insulin sensitivity， delaying gastric emptying， promoting urinary glucose excretion， and regulating incretin levels， thereby reducing glycated hemoglobin levels， decreasing insulin dosage， and managing body weight. Simultaneously， these drugs also present limitations such as low patient compliance due to complex dosing regimens， increased risk of diabetic ketoacidosis， and heterogeneity in glycemic control. Future research could focus on developing individualized treatment strategies， combining pharmacogenomics with novel biomarkers to precisely identify subpopulations of patients who may benefit， and delving into the potential value of these drugs in delaying diabetic vascular complications and improving patients’ quality of life.

ObjectiveTo investigate the short-term efficacy and safety of different doses of Botulinum toxin type A (BTX-A) injected under ultrasound guidance combined with modified catheter-balloon localization for post-stroke cricopharyngeal dysfunction (CPD), and to explore a relatively appropriate dose. MethodsA total of 136 patients with post-stroke CPD admitted to Taizhou Hospital of Zhejiang Province from December, 2023 to February, 2026 were randomly assigned into control group, 50 U group, 70 U group and 100 U group, with 34 patients in each group. The control group received conventional rehabilitation, whereas the three BTX-A groups received conventional rehabilitation plus the corresponding dose of BTX-A injected under ultrasound guidance combined with modified catheter-balloon localization. Videofluoroscopic Swallowing Study (VFSS) scores, Functional Oral Intake Scale (FOIS) scores, Yale Pharyngeal Residue Severity Rating Scale (YPR-SRS) grades, Murray Secretion Severity Scale (MSS) grades and ultrasonographic parameters were compared before and two weeks after intervention. ResultsAfter intervention, FOIS scores improved significantly in all groups (|Z| > 2.843, P < 0.01), and YPR-SRS and MSS grades also showed significant improvements in all BTX-A groups (|Z| > 4.147, P < 0.001). Pairwise comparisons revealed that the order of improvement from best to worst for FOIS, YPR-SRS and MSS grades was the 100 U group, followed by 70 U group, and then 50 U group (P < 0.05). For VFSS scores, the effect of time, group and interaction were all significant (F > 9.68, P < 0.001); pairwise comparisons showed that 100 U group achieved the best outcomes (P < 0.001). Regarding the activity and velocity of the geniohyoid muscle, the effects of time, group and interaction were also significant (F > 7.34, P < 0.001); pairwise comparisons indicated that 100 U group outperformed the other groups in both activity and velocity (P < 0.001). For hyoid bone displacement distance and shortening rate, the effects of time and interaction were significant (F > 3.07, P < 0.05), and the main effects of time on duration and velocity were significant (P < 0.01); pairwise comparisons showed that the 100 U group had superior displacement distance and shortening rate compared to the other groups (P < 0.05). During the treatment and follow-up periods, no serious adverse event occurred in any group. ConclusionUltrasound-guided BTX-A injection assisted by modified catheter-balloon localization may further improve short-term swallowing function in patients with post-stroke CPD， with a dosage of 100 U.

Objective:To investigate the clinical features and prognostic factors of primary tonsil lymphoma(PTL).Methods:The clinical data of 41 patients diagnosed with PTL and treated in the Affiliated Hospital of Xuzhou Medical University from January 2015 to December 2022 were collected and retrospectively analyzed.Their clinical features and prognostic factors were analyzed.Results:All the 41 patients were newly diagnosed with PTL,and the median age of onset was 58(19-85)years.Among them,19 patients started with pharyngeal pain,12 patients presented with dysphagia,8 patients presented with pharyngeal mass,and 2 patients presented with blurred articulation.The most common pathological type was diffuse large B-cell lymphoma(24 cases,58.54％).All patients received chemotherapy,and 3 patients were combined with hematopoietic stem cell transplantation.Among 41 patients,11(26.83％)achieved complete response,14(34.15％)achieved partial response,and the total response rate was 60.98％(25/41).The median follow-up time was 37(6-107)months,the 5-year overall survival(OS)rate was 70.81％and 5-year progression-free survival(PFS)rate was 66.20％.Univariate analysis showed that B symptoms,Ki-67,β2-MG and IPI score had significant effects on PFS and OS of patients(all P＜0.05).Multivariate analysis showed that IPI score was an independent risk factor for PFS and OS of patients(P＜0.05).Conclusion:The clinical manifestations of PTL lack specificity,and the prognosis is relatively good.Most patients can achieve long-term survival after treatment.IPI score is related to the prognosis.

Objective To explore the potential categories of frailty development trajectories in patients undergoing cardiac surgery from pre-operation to 6 months post-operation,and analyze the influencing factors.Methods By a longitudinal study design,patients undergoing elective heart valve replacement surgery or coronary artery bypass grafting in a tertiary general hospital in Zunyi City from August 2022 to June 2023 were selected by the convenience sampling method.Tilburg frailty scale was used to investigate the frailty level of cardiac surgery patients 1 day before surgery(T0),1 month(T1),3 months(T2)and 6 months after surgery(T3).The growth mixture model was used to identify the trajectory categories,and the influencing factors of different frailty trajectories were analyzed by binary Logistic regression.Results 261 patients were enrolled at T0,with 22,9,and 3 patients lost at T1 to T3,and 227 patients were finally included in the analysis.There were 2 types of trajectories being identified as the low frailty decline group and the high frailty maintenance group.Age,use of sedative and analgesic drugs,pace,and depression were the factors influencing the frailty in cardiac surgery patients(P＜0.05).Conclusion There are 2 kinds of frailty development trajectories in patients undergoing cardiac surgery.Medical staff should fonnulate precise interventions and nursing measures according to the factors influencing frailty,so as to improve frailty degree and quality of life of patients undergoing cardiac surgery.

Aim To investigate the effect of Brusatol a-gainst small cell lung cancer(SCLC)and its potential mechanism.Methods CCK-8 assay and flow cytome-try were used to detect the cytotoxic effect of Brusatol on SCLC cells.Western blot was employed to measure the expression levels of apoptosis-related proteins,in-cluding cleaved poly(ADP-ribose)polymerase(cleaved-PARP),B-cell lymphoma 2(Bcl-2)and Bcl-2-associated X protein(Bax).Network pharma-cology databases were utilized to identify common tar-gets of Brusatol,SCLC,and apoptosis.Kyoto Encyclo-pedia of Genes and Genomes(KEGG)and Gene On-tology(GO)enrichment analyses were performed on the intersecting genes.Molecular docking simulations between Brusatol and core targets were conducted using the CB-DOCK2 online platform to calculate binding en-ergies and sites.Western blot was further applied to detect the expression levels of signal transducer and ac-tivator of transcription 3(STAT3)and phosphorylated-STAT3(p-STAT3).Results Brusatol inhibited SCLC cell growth and induced apoptosis,significantly downregulating Bcl-2 and cleaved-PARP while upregu-lating Bax expression(P＜0.05).Network pharma-cology analysis revealed 108 common targets of Brusa-tol and SCLC,with the top three core targets being ep-idermal growth factor receptor(EGFR),STAT3,and tumor necrosis factor(TNF).Molecular docking re-sults indicated strong binding affinity between bruceine D and these core targets.Western blot validation con-firmed that bruceine D suppressed the expression of STAT3 and p-STAT3.Conclusion Brusatol exerts anti-SCLC effects by inhibiting STAT3 to induce apop-tosis in SCLC cells.

OBJECTIVE To explore the clinical effect of Kangfuxin solution on wound healing,wound stromal cell-derived factor-1a(SDF-1a),vascular endothelial growth factor(VEGF)and angiopoietin-2(ANG-2)of the peri-anal abscess patients complicated with wound infection.METHODS A total of 118 perianal abscess patients compli-cated with postoperative wound infection who were treated in Wuhan Eighth Hospital from Jun.2018 to Oct.2023 were enrolled in the study and were randomly divided into the Kangfuxin solution group and the potassium per-manganate group,with 59 cases in each group.Both groups were treated with debridement of infection foci in a timely manner,the potassium permanganate group was given potassium permanganate for daily cleaning and treat-ment,and the Kangfuxin solution group was given Kangfuxin solution for daily treatment.The wound healing time,time of disappearance of wound edema and shedding time of slough were recorded,and the reduced rate of wound surface was determined after the treatment.The pain degree was evaluated by visual analogue scale(VAS)after the treatment,and the levels of wound SDF-1a,VEGF and Ang-2 levels were detected.RESULTS The wound healing time[(12.53±2.57)days],time of disappearance of wound edema[(6.89±1.06)days]and shed-ding time of slough[(3.06±0.68)days]were shorter in the Kangfuxin solution group than in the potassium per-manganate group(P＜0.05).The reduced rates of wound surface were higher after the treatment for 2,7 and 14 days,the VAS score was lower,and there were significant differences(P＜0.05).The levels of SDF-1a,VEGF and Ang-2 of the two groups were higher after the treatment than before the treatment,the levels of SDF-1a,VEGF and Ang-2 of the Kangfuxin solution group were higher than those of the potassium permanganate group,and there were significant differences(P＜0.05).CONCLUSIONS Kangfuxin solution can be used for wound repair of the perianal abscess patients complicated with wound infection,which may accelerate the wound healing.The action mechanisms may be associated with the regulation of expressions of wound SDF-1a,VEGF and Ang-2.

Purpose To explore the effect of Calumenin(CALU)on migration and invasion ability of gastric cancer cells,as well as epithelial-mesenchymal transition(EMT).Methods The immunohistochemical experiments and Western blot were applied to evaluate the protein level of CALU in gastric cancer.After constructing a gastric canc-er cell line with low expression of CALU,CCK8 assay,wound-healing analysis and Transwell migration and invasion assays were performed to determine cell proliferation,Migration and invasion ability.Western blot was performed to an-alyse the effect of CALU knockdown on EMT molecules.Results CALU expression was significantly higher in gastric cancer tissues compared to normal gastric tissues(P＜0.05),and high CALU expression was significantly associated with TNM stage and lymph node metastasis(P＜0.05).Compared with GES-1 cells,the protein expression of CALU upregulated in gastric cancer cells(P＜0.05).CALU knockdown suppressed the proliferation,migration,invasion of BGC823 cells and SGC7901 cells(P＜0.05).Rescue experimental evidence showed that synonymous mutations of CALU could reverse the inhibitory effect of CALU knockdown on the proliferation,migration,and invasion ability of gastric cancer cells(P＜0.05).Knockdown of CALU resulted in the downregulation of vimentin and Snail expression,while E-cadherin and β-catenin expression were upregulated in human gastric cancer cells(P＜0.05).Conclusion CALU knockdown inhibits the proliferation,migration,invasion,and EMT of human gastric cancer cells.

Background and Aims:Microsatellite-stable(MSS)colorectal cancer(CRC)generally exhibits poor responsiveness to immune checkpoint inhibitors(ICIs),and effective immunotherapy strategies remain lacking.Anti-angiogenic agents such as bevacizumab(BEV)can improve the tumor immune microenvironment and act synergistically with ICIs.This multicenter real-world study compared the efficacy of different immunotherapy-based combination regimens in patients with MSS/MSI-L/pMMR advanced CRC,aiming to identify the optimal treatment strategy.Methods:A total of 100 patients with MSS/MSI-L/pMMR advanced CRC who received systemic treatment between November 2019 and February 2025 at four tertiary hospitals in Hunan,China,were retrospectively enrolled.Patients were classified into six treatment groups:chemotherapy alone,chemotherapy+targeted therapy,immunotherapy alone,immunotherapy+chemotherapy,immunotherapy+targeted therapy,and immunotherapy+chemotherapy+targeted therapy.The primary endpoints were overall survival(OS)and progression-free survival(PFS),while secondary endpoints were objective response rate(ORR)and disease control rate(DCR).Additionally,among patients receiving immunotherapy,subgroup analysis was performed according to BEV administration.Results:Among all 100 patients,the immunotherapy+chemotherapy+targeted therapy group achieved the highest ORR(32.0%)and DCR(76.0%)and was the only regimen yielding a complete response(CR).Compared with chemotherapy or immunotherapy alone,the triplet regimen significantly improved OS(P<0.05);although PFS improvement did not reach statistical significance,a clear late-stage separation of survival curves was observed.In the immunotherapy subgroup,BEV-containing regimens achieved markedly better outcomes than non-BEV regimens,with DCR of 75.0%vs.48.8%,median OS of 18.9 vs.11.5 months,and median PFS of 13.8 vs.7.2 months(all P<0.001).Cox regression analysis showed that compared with chemotherapy alone,the triplet regimen significantly reduced the risk of death(HR=0.11)and disease progression(HR=0.25)(both P=0.002).Vascular invasion was identified as an adverse prognostic factor for PFS(HR=3.0,P=0.007).Conclusion:This multicenter real-world study demonstrated that combining immunotherapy with chemotherapy and targeted therapy significantly improves DCR and survival outcomes in patients with MSS/MSI-L/pMMR advanced CRC,with BEV-containing triplet regimens providing the most pronounced benefit.BEV may enhance immune responsiveness by modulating the tumor microenvironment and promoting effector T-cell infiltration,offering a promising therapeutic direction for"immune-cold"CRC.Prospective randomized studies are warranted to further validate its clinical value and define appropriate patient populations.

Background and Aims:Microsatellite-stable(MSS)colorectal cancer(CRC)generally exhibits poor responsiveness to immune checkpoint inhibitors(ICIs),and effective immunotherapy strategies remain lacking.Anti-angiogenic agents such as bevacizumab(BEV)can improve the tumor immune microenvironment and act synergistically with ICIs.This multicenter real-world study compared the efficacy of different immunotherapy-based combination regimens in patients with MSS/MSI-L/pMMR advanced CRC,aiming to identify the optimal treatment strategy.Methods:A total of 100 patients with MSS/MSI-L/pMMR advanced CRC who received systemic treatment between November 2019 and February 2025 at four tertiary hospitals in Hunan,China,were retrospectively enrolled.Patients were classified into six treatment groups:chemotherapy alone,chemotherapy+targeted therapy,immunotherapy alone,immunotherapy+chemotherapy,immunotherapy+targeted therapy,and immunotherapy+chemotherapy+targeted therapy.The primary endpoints were overall survival(OS)and progression-free survival(PFS),while secondary endpoints were objective response rate(ORR)and disease control rate(DCR).Additionally,among patients receiving immunotherapy,subgroup analysis was performed according to BEV administration.Results:Among all 100 patients,the immunotherapy+chemotherapy+targeted therapy group achieved the highest ORR(32.0%)and DCR(76.0%)and was the only regimen yielding a complete response(CR).Compared with chemotherapy or immunotherapy alone,the triplet regimen significantly improved OS(P<0.05);although PFS improvement did not reach statistical significance,a clear late-stage separation of survival curves was observed.In the immunotherapy subgroup,BEV-containing regimens achieved markedly better outcomes than non-BEV regimens,with DCR of 75.0%vs.48.8%,median OS of 18.9 vs.11.5 months,and median PFS of 13.8 vs.7.2 months(all P<0.001).Cox regression analysis showed that compared with chemotherapy alone,the triplet regimen significantly reduced the risk of death(HR=0.11)and disease progression(HR=0.25)(both P=0.002).Vascular invasion was identified as an adverse prognostic factor for PFS(HR=3.0,P=0.007).Conclusion:This multicenter real-world study demonstrated that combining immunotherapy with chemotherapy and targeted therapy significantly improves DCR and survival outcomes in patients with MSS/MSI-L/pMMR advanced CRC,with BEV-containing triplet regimens providing the most pronounced benefit.BEV may enhance immune responsiveness by modulating the tumor microenvironment and promoting effector T-cell infiltration,offering a promising therapeutic direction for"immune-cold"CRC.Prospective randomized studies are warranted to further validate its clinical value and define appropriate patient populations.

Aim To investigate the effect of Brusatol a-gainst small cell lung cancer(SCLC)and its potential mechanism.Methods CCK-8 assay and flow cytome-try were used to detect the cytotoxic effect of Brusatol on SCLC cells.Western blot was employed to measure the expression levels of apoptosis-related proteins,in-cluding cleaved poly(ADP-ribose)polymerase(cleaved-PARP),B-cell lymphoma 2(Bcl-2)and Bcl-2-associated X protein(Bax).Network pharma-cology databases were utilized to identify common tar-gets of Brusatol,SCLC,and apoptosis.Kyoto Encyclo-pedia of Genes and Genomes(KEGG)and Gene On-tology(GO)enrichment analyses were performed on the intersecting genes.Molecular docking simulations between Brusatol and core targets were conducted using the CB-DOCK2 online platform to calculate binding en-ergies and sites.Western blot was further applied to detect the expression levels of signal transducer and ac-tivator of transcription 3(STAT3)and phosphorylated-STAT3(p-STAT3).Results Brusatol inhibited SCLC cell growth and induced apoptosis,significantly downregulating Bcl-2 and cleaved-PARP while upregu-lating Bax expression(P＜0.05).Network pharma-cology analysis revealed 108 common targets of Brusa-tol and SCLC,with the top three core targets being ep-idermal growth factor receptor(EGFR),STAT3,and tumor necrosis factor(TNF).Molecular docking re-sults indicated strong binding affinity between bruceine D and these core targets.Western blot validation con-firmed that bruceine D suppressed the expression of STAT3 and p-STAT3.Conclusion Brusatol exerts anti-SCLC effects by inhibiting STAT3 to induce apop-tosis in SCLC cells.