ObjectiveTo investigate the expression levels of miR-128-3p， SIRT1， and AMPK in the peripheral blood of patients with type 2 diabetes mellitus （T2DM） comorbid with nonalcoholic fatty liver disease （NAFLD）， as well as the role of miR-128-3p in predicting NAFLD in T2DM patients. MethodsA total of 80 patients with T2DM who were hospitalized in The First Affiliated Hospital of Anhui University of Chinese Medicine from September 2022 to August 2023 were enrolled and divided into T2DM group with 40 patients and NAFLD group with 40 patients， and according to the NAFLD fibrosis score （NFS）， the patients were further divided into progressive liver fibrosis group with 16 patients and non-progressive liver fibrosis group with 64 patients. General data and biochemical parameters were collected； quantitative real-time PCR was used to measure the mRNA expression levels of miR-128-3p， SIRT1， and AMPK in peripheral blood， and Western blot was used to measure the protein expression levels of SIRT1 and AMPK. The independent-samples t test was used for comparison of normally distributed data between two groups， and the Mann-Whitney U test was used for comparison of data with skewed distribution between two groups； the chi-square test was used for comparison of categorical data between two groups. The logistic regression analysis was used to identify the influencing factors for the presence of NAFLD and progressive liver fibrosis， and the receiver operating characteristic （ROC） curve analysis was used to determine the optimal cut-off value of miR-128-3p for predicting NAFLD. ResultsThere were significant differences between the NAFLD group and the non-NAFLD group in body mass index， fasting plasma glucose， glycated hemoglobin， fasting insulin， fasting C-peptide， alanine aminotransferase （ALT）， aspartate aminotransferase， gamma-glutamyl transpeptidase， alkaline phosphatase， fibronectin， triglycerides， high-density lipoprotein cholesterol， total triiodothyronine （TT3）， Homeostasis Model Assessment of Insulin Resistance （HOMA-IR）， and NFS （all P<0.05）. Compared with the non-NAFLD group， the NAFLD group had a significantly higher mRNA expression level of miR-128-3p in peripheral blood （t=-8.765， P<0.001） and significant reductions in the mRNA and proteins expression levels of SIRT1 and AMPK （P<0.001）. There were significant differences between the progressive liver fibrosis group and the non-progressive liver fibrosis group in age， ALT， free triiodothyronine， TT3， superoxide dismutase， and miR-128-3p （all P<0.05）. The logistic regression analysis showed that miR-128-3p was an independent risk factor for the development of NAFLD （odds ratio ［OR］=8.221， 95% confidence interval ［CI］： 2.735 — 24.714， P<0.001） and progressive liver fibrosis （OR=1.493， 95%CI： 1.117‍ ‍—‍ ‍1.997， P=0.007）. The ROC curve analysis showed that miR-128-3p had an area under the ROC curve of 0.890 （95%CI： 0.829 — 0.950）， with an optimal cut-off value of 13.165， a sensitivity of 89.3%， and a specificity of 72.7%. ConclusionThere is an increase in the expression of miR-128-3p in peripheral blood of T2DM patients with NAFLD， while there are reductions in the expression levels of SIRT1 and AMPK， suggesting that miR-128-3p has a certain diagnostic value in identifying NAFLD and liver fibrosis in such population.

MRGPRX2 antagonists possess the potential for the treatment of allergic rhinitis, atopic dermatitis, and chronic urticaria. Previously, we identified a class of diaryl urea (DPU) MRGPRX2 antagonists with sub-micromolar IC₅₀ values in vitro. However, the structure-activity relationship remains unclear. Herein, we adopted a "relative symmetry with electronegativity of different key-groups" strategy for further modification of DPUs to achieve a promising MRGPRX2 antagonist with higher activity and safety. Electrostatic potential energy analysis and biological evaluation revealed that B-1023 and B-5023, that possess relatively symmetric electron-withdrawing substituents, remarkable inhibited mast cell degranulation at a sub-micromolar IC₅₀ in vitro and alleviated anaphylactic symptoms. Furthermore, B-1023, mitigated antigen-induced pulmonary inflammation (AIPI) in mice and competitively bonded to MRGPRX2. In summary, the "relative symmetry with electronegativity of different key-groups" strategy provided a drug design pattern for MRGPRX2 antagonists and identified promising antiallergic precursors for AIPI treatment.

Objective:To evaluate the clinical efficacy of modified Qiwei Baizhu Powder combined with conventional therapy in the treatment of type 2 diabetes mellitus (T2DM) with abnormal lipid metabolism.Methods:A total of 96 patients with T2DM and abnormal lipid metabolism from March 2018 to March 2021 in Anhui Integrated Traditional Chinese and Western Medicine Hospital who met the inclusion criteria were divided into 2 groups according to the random number table method, with 48 in each group. The control group was treated with conventional western medicine, while the observation group was treated with modified Qiwei Baizhu Powder and treatment of the control group. Both groups were treated for 3 months. TCM syndrome scores were performed before and after treatment. Fasting blood glucose (FPG) and 2 hPG were detected by glucose oxidase method, HbA1c was detected by HPLC, TC, TG, HDL-C and LDL-C were detected by cholesterol peroxidase method, glycerophosphate oxidase method, direct inhibition method and direct surfactant clearance method. Adverse events during treatment were recorded and clinical efficacy was evaluated.Results:The total effective rate was 93.8% (45/48) in the observation group and 79.2% (38/48) in the control group, with a statistically significant difference between the two groups ( χ2=4.36, P=0.037). After treatment, the scores of dry mouth, fatigue, anorexia, dizziness, tongue, pulse and total scores in the observation group were significantly lower than those in the control group ( t values were 3.58, 3.17, 3.24, 3.59, 3.58, 2.76 and 8.44, respectively, all Ps<0.05); the levels of FPG, 2 hPG and HbA1c in the observation group were significantly lower than those in the control group ( t values were 3.37, 2.05 and 3.73 respectively, all Ps<0.05). After treatment, the levels of TC [(4.30±0.85) mmol/L vs. (4.78±0.94) mmol/L, t=2.62], TG [(3.00±0.37) mmol/L vs. (3.19±0.54) mmol/L, t=2.01], LDL-C [(2.60±0.71) mmol/L vs. (2.95±0.44) mmol/L, t=2.90] were significantly lower than those in the control group ( P<0.05). After treatment, the HDL-C [(2.07±0.63) mmol/L vs. (1.82±0.55) mmol/L, t=2.01] level was significantly higher than that of the control group ( P<0.05). Conclusion:Modified Qiwei Baizhu Powder combined with conventional therapy can improve blood glucose and blood lipid levels in T2DM patients with abnormal lipid metabolism, relieve clinical symptoms and improve curative effect.

Objective: To evaluate the severity of median nerve damage in patients with carpal tunnel syndrome (CTS) , and to analyze its relationship with body mass index (BMI) and wrist joint index. Methods: From May 2016 to January 2017, 23 patients with mild CTS (mild group) and 35 patients with moderate to severe CTS (moderate to severe group) were enrolled in this study. And 22 healthy volunteers matched for sex and age were selected as control group. The neuroelectrophysiological monitor was used to measure the median nerve movement and sensory nerve conduction in the subjects. The BMI and wrist joint index were calculated. The relationship of neuroelectrophysiological parameters with BMI and wrist joint index was analyzed in the CTS patients. Results: Compared with the control group, the mild group and the moderate to severe group had significantly higher wrist joint index, significantly longer distal motor latency (DML) of the median nerve, and significantly lower sensory nerve conduction velocity (SNCV) and sensory nerve action potential (SNAP) amplitude of the finger 1-wrist and finger 3-wrist (P<0.01) ; the moderate to severe group had significantly higher BMI and significantly lower composite muscle action potential (CMAP) amplitude (P<0.01) . The wrist joint index and BMI were positively correlated with DML of the median nerve and negatively correlated with SCV and SNAP amplitude of the finger 1-wrist and finger 3-wrist (all P<0.05) . The patients with a wrist joint index of >0.73 had a significantly higher risk of CTS than those with a wrist joint index of <0.73 (odd ratio=30.67, 95% confidence interval: 3.79-248.36) . Conclusion A wrist joint index of >0.73 is an independent risk factor for CTS in manual laborers. CTS should be prevented in the manual laborers with high wrist joint index and BMI.

Objective To investigate the P2X3 receptor expression and electrophysiological characteristics in dorsal root ganglion (DRG) in rat with neuropathic pain caused by chronic constriction injury of sciatic nerve (CCI) Methods P2X3 receptor expressions in L4,L5 and L6 DRG following CCI were observed by using a polyclonal antibody to label the P2X3 receptor ATP-activated currents in corresponding DRG neurons following CCI were observed by using electrophysiological technique Results A significant increase in P2X3 immunoreactivity was observed in the ipsilateral (injured) L4,L5 and L6 DRG and spinal cord on 7,14 d after CCI In small diameter neurons,a significant increase in the number of cells exhibiting a transient current to ATP was observed on 7,14 d after CCI Moreover,amplitude of these currents was increased Conclusion After CCI,the expression and function of P2X3 receptor in corresponding DRG are increased

Objective Glucocorticoid hormone may nongenomically affect cell functions in addition to its classic effects on gene expression. The purpose of present study was to explore whether dexamethasone, a synthetical glucocorticoid hormone, has a rapid nongenomic effect on ATP-induced currents in rat dorsal root ganglion (DRG) neurons and the related signal transduction pathway. Methods The effects of dexamethasone on ATP-induced currents were studied on cultured DRG neurons using patch clamp technique. Results Three types of currents (transient, sustained and biphasic) were evoked by ATP (100 ?mol/L) in cultured DRG neurons. When DRG neurons were pretreated with dexamethasone (0.01-10?mol/L) for 30s, inhibition of the transient current and the transient component of the biphasic current evoked by ATP in DRG neurons was observed. The inhibitory effect of dexamethasone was dose-dependent. However, dexamethasone did not seem to affect the sustained current and the sustained component of the biphasic current induced by ATP. The inhibitory effect of dexamethasone on ATP-induced currents was blocked by glucocorticoid receptor antagonist RU38486 (10?mol/L) and protein kinase A inhibitor H-89 (10?mol/L), but not by G protein inhibitor GDP-?-S (0.2mmol/L) and protein kinase C inhibitor chelerythrine chloride (10?mol/L). Conclusions Dexamethasone can selectively inhibit the transient current mediated by P2X3 receptors in DRG neurons. The inhibitory effect of dexamethasone might be mediated by glucocorticoid receptor through activating PKA signal pathway. These results suggest that glucocorticoid hormone might participate in the control of pain by modulating the actions of extracellular ATP in sensory neurons.