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.

Shared Decision-Making （SDM） is a crucial concept in modern medicine， emphasizing the joint participation of doctors and patients in the medical decision-making process. However， the authoritative position of doctors and the passive role of patients in traditional medical models often overlook the personal wishes and needs of patients， leading to tense doctor-patient relationships and medical disputes. By listening to and understanding their stories， narrative medicine helps doctors gain a more comprehensive understanding of patients’ situations and balances medical advice with patient needs in the decision-making process. Through systematic literature analysis and theoretical exploration， this paper investigated the application effects and mechanisms of narrative medicine in different medical contexts， as well as analyzed its specific role in the process of SDM. The aim is to explore the value of narrative medicine in bridging differences in SDM， revealing its role in promoting doctor-patient communication， enhancing decision-making participation， and improving medical outcomes. Researches had found that narrative medicine enhanced doctors’ “narrative ability”， promoted emotional communication and trust between doctors and patients， reduced conflicts and misunderstandings in decision-making， and improved patients’ sense of participation and trust， thus playing an important role in SDM. Therefore， by enhancing doctor-patient communication and understanding， promoting SDM and treatment selection between doctors and patients， personalized care and treatment optimization， advocating for doctor-patient co-construction， improving consultation efficiency， restoring the patient’s subject position， and other methods， it can bridge doctor-patient differences， promote communication and enhance decision-making participation， and improve medical outcomes and patient satisfaction.

ObjectiveTo investigate the value of Fried Frailty Phenotype （FFP）， liver frailty index （LFI）， and Short Physical Performance Battery （SPPB） in predicting 2-year all-cause mortality and decompensation events in patients with liver cirrhosis. MethodsA total of 277 patients with liver cirrhosis who were hospitalized in Beijing Friendship Hospital， Capital Medical University， from December 2020 to December 2021 were enrolled， and FFP， LFI， and SPPB were used to assess the state of frailty. Based on the scores of each tool， these patients were divided into frail and non-frail groups. These three tools were compared in terms of consistency and independent predictive performance. The primary endpoints were 2-year all-cause mortality rate and composite endpoints （death+decompensation events）， and the Cox regression analysis， the receiver operating characteristic （ROC） curve， net reclassification index （NRI）， and integrated discrimination improvement （IDI） index were used to analyze the predictive value of the three tools. Normally distributed continuous data were compared between two groups using the independent samples t-test， while non-normally distributed continuous data were compared using the Mann-Whitney U test. Categorical data were compared between groups using the chi-square test or Fisher’s exact test. The agreement among different frailty tools was evaluated using Cohen’s Kappa statistic. The Kaplan-Meier survival curve was plotted， and a survival analysis was performed using the log-rank test. ResultsThe prevalence rate of frailty assessed by FFP， LFI， and SPPB was 37.2%， 22.4%， and 20.2%， respectively， with a moderate consistency between FFP and LFI/SPPB （κ=0.57， 95% confidence interval ［CI］： 0.47 — 0.67； κ=0.51， 95%CI： 0.41 — 0.62） and a relatively high consistency between LFI and SPPB （κ=0.87， 95%CI： 0.80 — 0.94）. Compared with the non-frailty group， the frailty group had significantly higher all-cause mortality rate and incidence rate of composite endpoints （P0.001）. After multivariate adjustment， FFP， LFI， and SPPB had a hazard ratio of 2.42（95%CI： 1.51 — 5.11）， 2.21（95%CI： 1.11 — 4.42）， and 2.21（95%CI： 1.14 — 4.30）， respectively， in predicting all-cause mortality， as well as a hazard ratio of 2.51（95%CI： 1.61 — 3.91）， 2.40（95%CI： 1.51 — 3.80）， and 2.20（95%CI： 1.39 — 3.47）， respectively， in predicting composite endpoints. Compared with Child-Pugh score， FFP had a significantly greater area under the ROC curve （AUC） in predicting all-cause mortality （0.79 vs 0.69， P=0.032） and composite endpoints （0.75 vs 0.68， P=0.044）. Frailty assessment tools combined with Child-Pugh score significantly improved the performance in predicting all-cause mortality and composite endpoints， with an AUC of 0.81 — 0.82 and 0.77 — 0.78， respectively （P0.05）. NRI and IDI analyses further confirmed the improvement of the combined model in classification （all P0.001）. ConclusionFFP， LFI， and SPPB can independently predict adverse outcomes in patients with liver cirrhosis， among which FFP has the best predictive performance， and the combination of frailty assessment tools with Child-Pugh score can significantly enhance the accuracy of prognostic evaluation.

Objective To investigate the effects of peripheral blood neutrophil infiltration on the polarization regulation of cerebral resident microglia under a permanent ischemic stroke model.Methods Fifty-eight C57BL/6 mice were divided into two groups.One group was sham group,and the other group of mice was subjected to permanent middle cerebral artery occlusion surgery.Mice were euthanized 48 hours,7 days,14 days,and 30 days after surgery for tissue collection.Western blotting was used to detect expression levels of M1 microglia markers CD 16,M2 microglia marker arginase 1(Arg1),inflammatory cytokine interleukin-1 β(IL-1β),and neutrophil marker myeloperoxidase(MPO)in brain tissue.Immunofluorescence histochemical staining was used to assess neutrophil infiltration and M2 microglial distribution around the infarct area in brain sections.In vitro,purified neutrophils were co-cultured with BV2 microglial cells.After lipopolysaccharide stimulation,the phagocytosis of neutrophils by BV2 cells was observed,and the expression levels of CD16 and Arg1 proteins in BV2 cells were detected.Results Western blotting showed that the levels of CD16(P＜0.05),IL-1β(P＜0.001),and MPO(P＜0.05)in brain tissue increased significantly 48 hours and 7 days after surgery,then decreased,with MPO expression returning to normal levels 30 days after surgery.Immunofluorescence showed a significant increase of MPO-positive cells around the infarct area of the mouse cerebral cortex 48 hours after surgery(P＜0.001),followed by a decrease(P＜0.05).The number of ionized calcium binding adapter molecule 1(Iba1)and MPO double-positive cells gradually increased after surgery,and reached their peak at 14 days(P＜0.05).Iba1 and Arg1 double-positive cells also increased significantly 7 days(P＜0.05)and 14 days(P＜0.01)after surgery.In vitro,co-culture experiments showed that after BV2 phagocytosing neutrophils,CD 16(P＜0.05)significantly decreased and Arg1 significantly upregulated(P＜0.05).Conclusion In a permanent ischemic stroke model,microglia transition from M1 to M2 type after phagocytosing neutrophils,and the injured brain area changes from pro-inflammatory state to anti-inflammatory state.

Objective: To investigate whether zerumbone ( ZER) has the effect of preventing cisplatin ( Cis) -induced acute kidney injury (Cis-AKI) . Methods: The MTT method was used to detect the effect of different concentrations of ZER on the cell viability of Cis-AKI. The in vivo and in vitro models of Cis-AKI mice were estab- lished by dividing into control group , separate administration group , model group , and dose group. Western blot and immunofluorescence experiments were used to detect the expression changes of kidney injury marker-1 ( KIM- 1) , phosphorylated NF-κB p65 ( P-p65 ) , Cleaved casepase3 , receptor interacting protein kinase 1 ( RIPK1) , RIPK3 , and tumor necrosis factor-α (TNF-α) . Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the mRNA expression of KIM-1 , TNF-α , interleukin-6 ( IL-6) , and monocyte chemoattractant protein-1(MCP-1) . Periodic acid-Schiff (PAS) staining confirmed the therapeutic effect of ZER on Cis-AKI. RNA-seq and cell thermal shift (CETSA) were used to explore possible target proteins. Results : MTT results showed that ZER could alleviate the decrease in cell viability of Cis-AKI ; in vivo and in vitro studies showed that compared with the model group , after treatment with ZER , its KIM-1 , P-p65 , Cleaved casepased3 , RIPK1 , RIPK3 , TNF -α expres- sion decreased significantly , and the mRNA expression of KIM-1 , TNF-α , IL-6 mRNA , and MCP-1 decreased. PAS staining showed that ZER had a therapeutic effect on Cis-AKI. RNA-seq and CETSA analysis showed that ZER might prevent and treat Cis-AKI by targeting the PIM1 protein. Conclusion ZER may alleviate Cis-AKI and im- prove inflammatory response and necroptosis by regulating PIM1 protein. ZER is expected to be a potential drug for the prevention and treatment of Cis-AKI.

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 optimize the extraction process for Bletillae Rhizoma,and to evaluate its anti-oxidant,tyrosinase inhibitory activities.METHODS With ultrasound time,ethanol concentration and solid-liquid ratio as influencing factors,the total extraction content of gastrodin,protocatechualdehyde,p-hydroxybenzaldehyde,1,4-bis[4-(gluconoxy)benzyl]-2-isobutylmalate-2-glucoside,1,4-bis[4-(gluconoxy)benzyl]-2-isobutylmalate,yam Ⅲ,dihydropinosin and 3'-O-methylyam Ⅲ as an evaluation index,the extraction process was optimized by Box-Behnken response surface method.Subsequently,the extract's scavenging effects on DPPH,ABTS+free radicals,and inhibitory ability on tyrosinase were determined.RESULTS The optimal conditions were determined to be 49 min for ultrasound time,55％for ethanol concentration,1∶30 for solid-liquid ratio,and 2 times for extraction frequency,the total extraction content was 13.18 mg/g.The extract demonstrated the IC50 of 10.12,314.07 and 1.70 μg/g on DPPH,ABTS+free radicals and tyrosinase,respectively.CONCLUSION This simple,reliable and stable method can be used for the extraction for Bletillae Rhizoma with strong anti-oxidant,tyrosinase inhibitory activities.

AIM To investigate the effects of Shuyu Pills combined with evolimus on the epithelial mesenchymal transformation of triple negative breast cancer cells 4T1 and MDA-MB-231 induced by TGF-β1.METHODS The 4T1 and MDA-MB-231 cells were divided into the blank group and the induction group to induce the epithelial mesenchymal transformation with TGF-β1 cytokine treatment,followed by the assignment into the model group,the Shuyu Pills group,the everolimus group and the Shuyu Pills combined with everolimus group.CCK8 method,plate cloning method,cell scratch test and Transewll test were used to detect the proliferation,cloning formation,migration and invasion ability of the cells whose expressions of E-cadherin,N-cadherin,Vimentin,MMP9,MMP2 and pathway proteins PTEN,PI3K,Akt and mTOR were detected by Western blot.RESULTS Compared with the blank group,the induction group displayed a cell morphological change from epithelioid to stromal,decreased expression of E-cadherin protein(P＜0.01);and increased protein expressions of N-cadherin and Vimentin(P＜0.05).Compared with the model group,each group intervened with the medicine displayed decreased proliferation,clone formation,migration and invasion ability of both kinds of cells(P＜0.01);increased protein expressions of PTEN and E-cadherin(P＜0.05,P＜0.01);and decreased protein expressions of PI3K,Akt,mTOR,N-cadherin,Vimentin,MMP9 and MMP2(P＜0.05,P＜0.01);and more significantly in the Shuyu Pills combined with evolimus group(P＜0.05,P＜0.01).CONCLUSION With a more ideal effect than the single uses in inhibiting the TGF-β1-induced epithelial mesenchymal transformation of triple-negative breast cancer cells,the combination use of Shuyu Pills and everolimus may work through the regulation of PI3K/Akt/mTOR signaling pathway.

BACKGROUND: Senescent human skin primary fibroblast (FB) models have been established for studying aging-related, proliferative, and inflammatory skin diseases. The aim of this study was to compare the transcriptome characteristics of human primary dermal FBs from children and the elderly with four senescence models. METHODS: Human skin primary FBs were obtained from healthy children (FB-C) and elderly donors (FB-E). Senescence models were generated by ultraviolet B irradiation (FB-UVB), D-galactose stimulation (FB-D-gal), atazanavir treatment (FB-ATV), and replication exhaustion induction (FB-P30). Flow cytometry, immunofluorescence staining, real-time quantitative polymerase chain reaction, co-culturing with immune cells, and bulk RNA sequencing were used for systematic comparisons of the models. RESULTS: In comparison with FB-C, FB-E showed elevated expression of senescence-related genes related to the skin barrier and extracellular matrix, proinflammatory factors, chemokines, oxidative stress, and complement factors. In comparison with FB-E, FB-UVB and FB-ATV showed higher levels of senescence and expression of the genes related to the senescence-associated secretory phenotype (SASP), and their shaped immune microenvironment highly facilitated the activation of downstream immune cells, including T cells, macrophages, and natural killer cells. FB-P30 was most similar to FB-E in terms of general transcriptome features, such as FB migration and proliferation, and aging-related characteristics. FB-D-gal showed the lowest expression levels of senescence-related genes. In comparisons with the single-cell RNA sequencing results, FB-E showed almost complete simulation of the transcriptional spectrum of FBs in elderly patients with atopic dermatitis, followed by FB-P30 and FB-UVB. FB-E and FB-P30 showed higher similarity with the FBs in keloids. CONCLUSIONS Each senescent FB model exhibited different characteristics. In addition to showing upregulated expression of natural senescence features, FB-UVB and FB-ATV showed high expression levels of senescence-related genes, including those involved in the SASP, and FB-P30 showed the greatest similarity with FB-E. However, D-galactose-stimulated FBs did not clearly present aging characteristics.
Humans ; Fibroblasts/drug effects* ; Cellular Senescence/physiology* ; Skin/metabolism* ; Child ; Transcriptome/genetics* ; Aged ; Ultraviolet Rays ; Cells, Cultured ; Galactose/pharmacology*