To investigate the effect and underlying mechanism of Sijunzi Decoction in ameliorating insulin resistance (IR) within the pancreatic islets of rats with type 2 diabetes mellitus (T2DM).

A total of 40 Sprague-Dawley (SD) rats were randomly divided into control group (n=10, fed with normal diet) and high-sugar and high-fat group [n=30, fed with high-sugar and high-fat diet coupled with intraperitoneal injection of streptozotocin (STZ) to create a type 2 diabetes mellitus (T2DM) model]. The smoothly modeled SD rats were further randomly assigned into model group, positive control group (0.003 g·mL^-1) and experimental group (0.848 g·mL^-1). The normal group and model group were given distilled water by gavage, while the other two groups were administered the corresponding drugs by gavage for 4 consecutive weeks. Fasting blood glucose (FBG) was measured using a blood glucose meter. Serum levels of fasting insulin (FINS), total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) in rats of each group were detected with commercial assay kits. The pancreatic index (PI) was calculated based on the detection of pancreatic tissue. Reverse transcription-polymerase chain reaction (RT-PCR) was employed to determine the mRNA expression levels of related proteins, and Western blotting was performed to ascertain the formulation standards of correlated total proteins.

The FBG, FINS, TC, TG, HDL-C, LDL-C and PI in the model group and experimental group were (13.60±0.61) mmol·L^-1 vs. (9.73±0.43) mmol·L^-1, (15.24±0.76) mIU·L^-1 vs. (12.39±1.13) mIU·L^-1, (5.42±0.41) mmol·L^-1 vs. (3.76±0.26) mmol·L^-1, (1.49±0.26) mmol·L^-1 vs. (0.65±0.05) mmol·L^-1, (0.82±0.06) mmol·L^-1 vs. (1.12±0.08) mmol·L^-1, (4.82±0.43) mmol·L^-1 vs. (3.02±0.42) mmol·L^-1, and (0.27±0.09)% vs. (0.34±0.02)%, respectively. The mRNA expression levels of INSR, IRS-1, PI3K, AKT, GLUT4, GSK-3β, and FOXO1 were 0.44±0.16 vs. 0.61±0.16, 0.48±0.13 vs. 0.72±0.16, 0.62±0.30 vs. 0.84±0.12, 0.74±0.20 vs. 0.92±0.02, 0.48±0.22 vs. 0.78±0.24, 1.90±0.16 vs. 1.56±0.25, and 1.83±0.16 vs. 1.60±0.21, respectively. The total protein expression levels of INSR, IRS-1, PI3K, AKT, GLUT4, GSK-3β, and FOXO1 were 0.59±0.29 vs. 0.82±0.18, 0.65±0.28 vs. 0.72±0.16, 0.49±0.14 vs. 0.74±0.15, 0.50±0.17 vs. 0.68±0.12, 0.65±0.28 vs. 0.86±0.14, 2.73±0.19 vs. 2.50±0.22, and 1.61±0.49 vs. 1.21±0.35, respectively. Compared with the model group, all the above indicators in the experimental group showed statistically significant differences (P<0.001, P<0.01, P<0.05).

Sijunzi Decoction can improve pancreatic insulin resistance (IR) in rats with type 2 diabetes mellitus (T2DM) by regulating the expression of 7 signaling factors in the upstream, middle and downstream of the PI3K/AKT signaling pathway.

To investigate the association between CAPN10 rs3792269 and SLC47A2 rs12943590 gene polymorphisms and the efficacy of metformin in type 2 diabetes mellitus (T2DM) patients receiving metformin monotherapy in Xinjiang, providing references for individualized drug therapy in local patients.

A total of 450 T2DM patients who had been regularly taking metformin monotherapy for ≥3 months from July 2024 to July 2025 in a tertiary hospital in Xinjiang were selected. Clinical data were collected and target locus genotypes were detected. Using glycated hemoglobin (HbA1c%) as the efficacy indicator, patients were divided into wild-type homozygous and mutant genotype groups. Propensity score matching (PSM) was employed to analyze the association between gene polymorphisms and efficacy, followed by post hoc power analysis.

The PSM analysis revealed that the CAPN10 rs3792269 A>G variant was an independent protective factor for good glycemic control (PSM-adjusted OR=0.478, 95%CI 0.266-0.862, P<0.05). In contrast, the SLC47A2 rs12943590 polymorphism showed no significant association with treatment efficacy. For the CAPN10 rs3792269 locus, the absolute difference in glycemic control rates between the two groups was 17.3%, with OR=2.10 and statistical power of approximately 90%. For the SLC47A2 rs12943590 locus, the absolute difference was 2.5%, with OR=0.91 and statistical power of only 7%.

This study clarifies that the CAPN10 rs3792269 A>G variant is significantly associated with improved efficacy of metformin in the Xinjiang population of China, while the SLC47A2 rs12943590 locus shows no association in this sample. The influence of genetic factors on metformin efficacy exhibits population heterogeneity. The sample size in this study provids sufficient power for detecting moderate to large effects, which may serve as a reference for individualized medication and blood glucose management in local patients.

To explore the effects of apple polyphenols (AP) on lung function and immune imbalance in rats with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) by adjusting the miR-21-5p/SKP2 pathway.

The stable stage of COPD was established by cigarette smoking and endotoxin infusion, and then AECOPD rats were established by nasal infusion of Staphylococcus aureus bacterial solution. They were randomly assigned into the AECOPD group, the AP-25 group, the AP-100 group, the dexamethasone group, the AP-100+NC agomir group, and the AP-100+miR-21-5p agomir group. And rats intervened with normal saline were as the control group. Subsequently, tracheal intubation was performed to measure the peak expiratory and inspiratory flow rates (PEF, PIF), and the ratio of forced expiratory volume to forced vital capacity in 0.3 seconds (FEV0.3/FVC). Serum was collected to measure the levels of tumor necrosis factor -α (TNF-α) and interleukin-6 (IL-6). Bronchoalveolar lavage fluid (BALF) was recovered, and the numbers of neutrophils, lymphocytes and macrophages were determined. Left lung lobe sections were prepared, and lung tissue lesions and scores were observed. The right lung tissue of rats was taken. The proportions of Th17 and Treg cells, the mRNA expression of miR-21-5p and SKP2, and the protein expression of retinoic acid-related orphan receptor γt (RORγt), IL-17A, forkhead box protein P3 (Foxp3), IL-10 and SKP2 in the lung tissue were detected.

The AECOPD group had higher RORγt, IL-17A, miR-21-5p, TNF-α, IL-6, macrophages, neutrophils, lymphocytes, Th17 cell proportion, and Th17/Treg than the control group, and had lower Foxp3, IL-10, SKP2 mRNA and protein expression, Treg cell proportion, PEF, PIF, and FEV0.3/FVC than the control group (P<0.05). The AP-25 group, AP-100 group and dexamethasone group had lower RORγt, IL-17A, miR-21-5p, TNF-α, IL-6, macrophages, neutrophils, lymphocytes, Th17 cell proportion, and Th17/Treg than the AECOPD group, and had higher Foxp3, IL-10, SKP2 mRNA and protein expression, Treg cell proportion, PEF, PIF, and FEV0.3/FVC than the AECOPD group (P<0.05). In addition, miR-21-5p agomir reversed the protective effect of AP on AECOPD rats.

AP improves lung function and immune imbalance in AECOPD rats by inhibiting the miR-21-5p/SKP2 pathway.

To evaluate the uncertainty for the determination of 10,11-dihydro-10-hydroxycarbazepine (MHD) in human plasma by ultra performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).

An isotope-labeled internal standard was employed. Chromatographic separation was achieved within 3 min on a BEH C₁₈ column (2.1 mm×50.0 mm, 1.7 μm) using a gradient elution at a flow rate of 0.4 mL·min^-1, with a mobile phase consisting of methanol containing 0.1% formic acid and water containing 5% methanol plus 0.1% formic acid. Plasma sample concentrations were determined by UHPLC-MS/MS with electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode. The method was validated for selectivity, calibration curve, lower limit of quantification, precision, recovery, matrix effect, and stability. The influencing factors in the quantification of MHD were analyzed and evaluated to calculate the individual uncertainties, combined uncertainty, and finally the expanded uncertainty.

MHD demonstrated good linearity within the range of 0.03 to 6.00 mg·L^-1. The accuracy (bias from the theoretical concentration) for within-run and between-run analyses was within ±15%, and the precision (coefficient of variation) was within 13.32%. Plasma samples showed good stability under the following conditions: 9 hours at 25 ℃, 5 hours at 4 ℃, three freeze-thaw cycles, and storage at -80 ℃ for 18 days. Based on the calculated uncertainty values for each contributing factor, repeatability, matrix effect, and recovery represented the major sources of uncertainty for the low-concentration quality control (QC) sample, with values of 1.96×10^-2, 5.49×10^-2, and 7.25×10^-2, respectively. For the high-concentration QC sample, matrix effect and recovery contributed substantially to the overall uncertainty, with values of 4.92×10^-2 and 2.01×10^-2, respectively. The expanded uncertainties (P=95%, k=2) for MHD at low (0.09 mg·L^-1) and high (4.50 mg·L^-1) concentrations in human plasma were 1.62×10² mg·L^-1 and 0.48 mg·L^-1, respectively.

The measurement uncertainty of MHD concentration in human plasma determined by UHPLC-MS/MS is primarily contributed by repeatability, matrix effect and recovery at low concentration levels, while dominated by matrix effect and recovery at high concentrations

To explore changes in serum diamine oxidase (DAO) levels and their clinical significance in patients with gastrointestinal toxicity induced by fluorouracil antineoplastic drugs.

Patients with gastrointestinal tumors receiving fluorouracil-based antineoplastic therapy were divided into treatment group and control group according to whether gastrointestinal toxicity occurred during chemotherapy. The treatment group was further subdivided into ≤grade Ⅱ group and grade Ⅲ group based on the severity of gastrointestinal toxicity. General clinical data were collected, and serum DAO levels before chemotherapy and 7 days after chemotherapy were compared between treatment and control groups, as well as among patients with different grades of gastrointestinal toxicity. Logistic regression model was used to analyze the relationship between DAO levels and gastrointestinal toxicity, and receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of serum DAO levels 7 days after chemotherapy for the occurrence of gastrointestinal toxicity.

A total of 50 patients were ultimately included as study subjects, with 26 in treatment group and 24 in control group. The serum DAO levels 7 days after chemotherapy were (14.71±3.44) and (10.89±3.67) U·L^-1 in treatment and control groups, respectively. The serum DAO level in treatment group was significantly higher than that in control group 7 days after chemotherapy (P<0.05). The serum DAO levels 7 days after chemotherapy in ≤grade Ⅱ subgroup and grade Ⅲ subgroup were (13.38±3.06) and (16.37±3.25) U·L^-1, respectively. The serum DAO level in the ≤grade Ⅱ subgroup was significantly lower than that in the grade Ⅲ subgroup (P<0.05). Multivariate logistic regression analysis indicated that the serum DAO level 7 days after chemotherapy was an influencing factor for the occurrence of gastrointestinal toxicity in patients (P<0.001). ROC curve analysis showed that the optimal threshold for serum DAO in predicting gastrointestinal toxicity after chemotherapy was 11.92 U·L^-1, with an area under the curve (AUC) of 0.79 (P<0.05). The sensitivity and specificity were 77.78% and 86.96%, respectively.

Chemotherapy with fluorouracil-based antineoplastic drugs can lead to elevated serum DAO levels in patients with gastrointestinal tumors. The serum DAO level is associated with the severity of gastrointestinal toxicity and the grade of adverse drug reactions, and may serve as a predictive indicator for the occurrence of gastrointestinal toxicity following chemotherapy.

To evaluate the differences in clinical efficacy between continued azithromycin therapy and switching to tetracycline antibiotics (doxycycline/minocycline) in children with macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP).

Children with MUMPP hospitalized in our hospital were divided into treatment group and control group according to the secondary antibiotic selection after ineffective initial macrolide treatment for 72 hours. The control group continued to receive azithromycin for injection at a dose of 10 mg·kg^-1 once a day for a 7-day course of treatment. The treatment group was switched to oral tetracycline antibiotics: minocycline capsules at 2 mg·kg^-1 twice a day, or doxycycline enteric-coated capsules at 2.2 mg·kg^-1 twice a day, with a total course of 10 days. The time to defervescence, treatment effectiveness rate, and changes in white blood cell count (WBC), neutrophil percentage (NE%) and C-reactive protein (CRP) levels were compared between the two groups, and a safety evaluation was performed.

A total of 107 cases were included in this study, with 87 cases in the treatment group and 20 cases in the control group. The total clinical effective rates of the treatment group and the control group were 90.80% (79 cases /87 cases) and 85.00% (17 cases /20 cases), respectively, and the difference was not statistically significant (P>0.05). The antipyretic time of the treatment group and the control group was (6.82±1.71) and (7.75±2.12) days, respectively, with statistically significant difference (P<0.05). Before conversion therapy, the white blood cell counts of the control group and the treatment group were (8.58±3.67) and (6.77±2.59) ×10⁹·L^-1, respectively, and the CRP levels were (14.44±8.58) and (26.43±26.53) mg·L^-1, respectively; both differences were statistically significant (all P<0.05). The neutrophil percentages of the control group and the treatment group were (57.93±9.39)% and (62.43±10.79)%, respectively, the lymphocyte percentages were (32.43±8.46)% and (28.60±9.57)%, respectively, the monocyte percentages were (7.63±2.01)% and (7.43±2.53)%, respectively, none of these differences were statistically significant (all P>0.05). The total incidence of adverse drug reactions in the treatment group and the control group was 1.15% and 0, respectively, with no statistically significant difference (P>0.05).

For children with MUMPP, tetracycline antibiotics provide faster fever resolution, but the overall efficacy of both regimens is comparable. Clinical decisions should consider the child’s age (tetracyclines preferred for those ≥8 years) and parental informed consent. Continued azithromycin therapy is recommended in combination with glucocorticoids to control excessive inflammatory responses.

To explore the mechanism by which hedysarum polybotrys polysaccharide (HPS) improves iron death of steatotic hepatocytes through the protein kinase RNA-like endoplasmic reticulum kinase- nuclear factor-erythroid 2-related factor 2 (PERK-Nrf2) signaling pathway.

The cells were cultured with 0.6 mmol·L^-1 fatty acids to replicate the non-alcoholic fatty liver disease cell model. The LO-2 cell were divided into normal group (complete medium), model group (0.6 mmol·L^-1 fatty acid solution), positive control group (0.6 mmol·L^-1 fatty acid solution+24 μmol·L^-1 liproxstain-1) and experimental group (0.6 mmol·L^-1 fatty acid solution + 50 mg·L^-1 HPS), culture for 24 h. Stain with Oil Red O was used to analyze the positive area (%Area) of cell lipid deposition; the content of lipid peroxide(LPO), 4-hydroxynonenal(4-HNE), glutathione(GSH) and superoxide dismutase(SOD) was detected by enzyme-linked immunosorbent assay(Elisa) method; the relative expressions levels of PERK-Nrf2 signaling pathway protein in hepatocytes were detected by Western blot; immunofluorescence assay was used to detect the relative expression levels of GPX4 and SLC7A11 proteins.

The % Area of cell lipid deposition in hepatocytes of normal group, model group, control group and experimental group were 0.02±0.01, 0.26±0.08, 0.09±0.02 and 0.15±0.04; the contents of LPO were (2.62±0.17), (13.47±1.55), (6.31±1.12) and (5.71±1.50) nmol·mL^-1; the contents of 4-HNE were (8.06±0.40), (14.60±2.02), (9.40±0.81) and (12.94±0.56) ng·L^-1; the contents of GSH were (120.73±7.75), (34.60±2.98), (67.86±2.08) and (59.33±7.46) mg·L^-1; the contents of SOD were (7.25±0.61), (3.77±0.44), (5.22±0.76) and (8.12±0.78) U·mL^-1; the levels of Grp78 mRNA were 1.01±0.15, 1.47±0.11, 1.41±0.08 and 1.02±0.05; the levels of PERK mRNA were 1.00±0.09, 1.85±0.16, 1.02±0.27 and 1.16±0.01; the levels of Nrf2 mRNA were 1.01±0.12, 0.26±0.07, 0.68±0.09 and 0.66±0.05; the levels of GPX4 mRNA were 1.00±0.05, 0.79±0.02, 0.87±0.17 and 0.83±0.10; the levels of SLC7A11 mRNA were 1.01±0.17, 0.50±0.14, 0.91±0.09 and 0.98±0.05; the relative expression levels of Grp78 protein were 1.00±0.11, 2.72±0.07, 1.83±0.04 and 2.24±0.06; the relative expression levels of PERK protein were 1.00±0.06, 1.21±0.08, 1.03±0.07 and 0.95±0.06; the relative expression levels of p-PERK protein were 1.00±0.04, 2.70±0.08, 1.40±0.07 and 1.76±0.06; the relative levels of PERK protein phosphorylation were 1.00±0.09, 2.24±0.21, 1.36±0.03 and 1.85±0.09; the relative expression levels of Nrf2 protein were 1.00±0.03, 0.52±0.01, 0.73±0.02 and 0.84±0.02; the protein fluorescence intensity of GPX4 were 24.34±0.86, 13.86±1.65, 18.01±2.03 and 16.20±1.55; the protein fluorescence intensity of SLC7A11 were 69.58±4.13, 34.24±6.73, 60.75±9.35 and 45.18±6.46. Compared with the normal group, there were significant differences in the above indexes of model group (all P<0.05) ; compared with the model group, there were significant differences in the above indexes of experimental group (all P<0.05).

HPS may protect liver cells by regulating the PERK-Nrf2 signaling pathway, reducing lipid peroxidation and iron death in liver cells.