Diabetic peripheral neuropathy (DPN) is the most prevalent chronic complication among diabetic patients and a primary risk factor contributing to the deterioration of diabetic foot conditions. The pathogenesis of DPN remains complex and not fully understood, and there are hardly any effective treatment drugs. Maltol (3-hydroxy-2-methyl-4-pyranone) has demonstrated antioxidant and anti-inflammatory properties. However, the potential role of maltol in the treatment of DPN remains unclear. This study aimed to assess maltol’s effects on DPN rats and high glucose (HG)/palmitic acid (PA)-induced rat Schwann cells (RSC96). The results indicated maltol’s capacity to enhance peripheral nerve function in DPN rats. In RSC96 cells stimulated with high HG and PA, maltol treatment reduced DPN markers and apoptosis-related proteins. Functional enrichment analysis of differentially expressed genes revealed that endoplasmic reticulum (ER) stress pathways were involved in this process. Western blot results demonstrated the activation of ER stress pathway in HG/PA-induced RSC96 cells, with maltol attenuating ER stress-related protein expression. Furthermore, the knockdown of Membrane metallo-endopeptidase (MME) reversed maltol’s effects on apoptosis-related protein expression, suggesting a potential therapeutic role for maltol via MME in treating DPN. These findings indicate that maltol may hold promise as a therapeutic agent for DPN treatment.

Background: Pharmacist clinics offer professional pharmaceutical services that can improve public health outcomes. However, primary healthcare staff in China face various barriers and challenges in implementing such clinics. To identify existing problems and provide recommendations for the implementation of pharmacist clinics, this study aims to assess the knowledge, attitudes, and practices of pharmacist clinics among primary healthcare providers. Methods: A cross-sectional survey based on the Knowledge-Attitude-Practice (KAP) model, was conducted in community health centers (CHCs) and private hospitals in Shanghai, China in May, 2023. Descriptive analytics and the Pareto principle were used to multiple-answer questions. Chi-square test, Fisher’s exact test, and binary logistic regression models were employed to identify factors associated with the knowledge, attitudes, and practices of pharmacist clinics. Results: A total of 223 primary practitioners participated in the survey. Our study revealed that most of them had limited knowledge (60.1%, n = 134) but a positive attitude (82.9%, n = 185) towards pharmacist clinics, with only 17.0% (n = 38) having implemented them. The primary goal of pharmacist clinics was to provide comprehensive medication guidance (31.5%, n = 200), with medication education (26.3%, n = 202) being the primary service, and special populations (24.5%, n = 153) identified as key recipients. Logistic regression analysis revealed that education, age, occupation, position, work seniority, and institution significantly influenced their perceptions. Practitioners with bachelor’s degrees, for instance, were more likely than those with less education to recognize the importance of pharmacist clinics in medication guidance (aOR: 7.130, 95%CI: 1.809–28.099, p-value = 0.005) and prescription reviews (aOR: 4.675, 95% CI: 1.548–14.112, p-value = 0.006). Additionally, practitioners expressed positive attitudes but low confidence, with only 33.3% (n = 74) feeling confident in implementation. The confidence levels of male practitioners surpassed those of female practitioners (p-value = 0.037), and practitioners from community health centers (CHCs) exhibited higher confidence compared to their counterparts in private hospitals (p-value = 0.008). Joint physician-pharmacist clinics (36.8%, n = 82) through collaboration with medical institutions (52.0%, n = 116) emerged as the favored modality. Daily sessions were preferred (38.5%, n = 86), and both registration and pharmacy service fees were considered appropriate for payment (42.2%, n = 94). The primary challenge identified was high outpatient workload (30.9%, n = 69). Conclusions: Although primary healthcare practitioners held positive attitudes towards pharmacist clinics, limited knowledge, low confidence, and high workload contributed to the scarcity of their implementation. Practitioners with diverse sociodemographic characteristics, such as education, age, and institution, showed varying perceptions and practices regarding pharmacist clinics.

The organellar Ca2+-activated K+ channels share a similar ability to transfer the alteration of Ca2+ concentration to membrane conductance of potassium. Multiple effects of Ca2+-activated K+ channels on cell metabolism and complex signaling pathways during organ development have been explored. The organellar Ca2+-activated K+ channels are able to control the ionic equilibrium and are always associated with oxidative stress in different organelles and the whole cells. Some drugs targeting Ca2+-activated K+ channels have been tested for various diseases in clinical trials. In this review, the known roles of organellar Ca2+-activated K+ channels were described, and their effects on different diseases, particularly on diabetes, cardiovascular diseases, and neuro-logical diseases were discussed. It was attempted to summarize the currently known operational modes with the involvement of organellar Ca2+-activated K+ channels. This review may assist scholars to more comprehensively understand organellar Ca2+-activated K+ channels and related diseases.

Rhabdomyolysis is a life-threatening syndrome associated with direct or indirect muscle damage that is rarely reported with dipeptidyl peptidase (DPP)-4 inhibitors. Here we presented a case in which a 58-year-old female suffered from severe swelling and pain in bilateral lower limbs and oliguria after a suicidal vildagliptin overdose. Drug-induced rhabdomyolysis and drug-induced liver injury were diagnosed based on laboratory and radiological findings. The patient was treated with fluid resuscitation, insulin, electrolyte replacement, diuretics, urine alkalizing agents, anticoagulants, antioxidants, and 24-h bedside ECG monitoring and suicide prevention. After 20 days of hospitalization and close monitoring, the patient was discharged without sequelae. Risk factors, diagnostic criteria, disease mechanisms, and outcomes were also discussed. This case illustrated that overdose of oral anti-diabetic medications may result in clinically significant adverse events, such as rhabdomyolysis in this case with a DPP-4 inhibitor. Although the incidence is low, special attention should be paid to intentional or accidental exposure to anti-diabetic medications during suicide attempts, especially in depressed patients with diabetes.

Background: Fluoxetine is widely prescribed to treat depression but exhibits high inter-individual and inter-ethnic pharmacokinetic (PK) variability. Most published population pharmacokinetic (PopPK) models were derived from Western patients, and their applicability to Chinese patients remains uncertain. Methods: A systematic review of the published fluoxetine PopPK models was carried, and the relevant demographic and model parameters were extracted. A retrospective real-world dataset from Chinese psychiatric patients was then collected. External evaluation was conducted to assess the model’s predictive performance. Subsequently, a joint parent–metabolite PopPK model was developed to better characterize fluoxetine and its active metabolite norfluoxetine in Chinese patients. Finally, Monte Carlo simulations were performed to evaluate once-daily dosing regimens of 10–60 mg for 30 days, focusing on the probability of achieving target (PTA) steady-state trough concentrations (C_min,ss). Results: Two published PopPK models were identified and externally evaluated using data from 198 Chinese patients with 241 fluoxetine and 241 norfluoxetine plasma concentrations. Both models were shown to have prediction discrepancy. The parent drug–metabolite model was used to describe the characteristics of fluoxetine and norfluoxetine in the Chinese population. Sex was identified as the significant covariate, and males exhibited a 16.5% higher clearance than females. The simulation results indicate that the maximum effective dose for females is 30 mg once daily, and for males, it is 40 mg once daily. Conclusions: This study provides the first comprehensive external evaluation of published fluoxetine PopPK models and establishes a tailored joint model that incorporates sex effects to explain trough variability in Chinese psychiatric patients. The findings support 30–40 mg once daily as a practical dosing range for Chinese adults and adolescents, with males more likely to require the higher dose.