To evaluate the effects of dapagliflozin tablets on metabolic and cardiovascular system in patients with chronic kidney disease (CKD).

CKD patients hospitalized in our institution who underwent coronary computed tomography angiography (CCTA) were divided into dapagliflozin group and non-dapagliflozin group according to treatment regimens. Levels of uric acid, creatinine, uric acid reduction rate, creatinine reduction rate and coronary artery calcium score (CACS) were compared between the two groups. Univariate and multivariate logistic regression analyses were performed to assess the independent risk factors of dapagliflozin on coronary artery calcification (CAC).

A total of 30 cases were included in dapagliflozin group, 60 cases were included in non-dapagliflozin group. After treatment, uric acid levels were (182.31±52.56) and (221.75±73.45) μmol·L^-1, creatinine levels were (49.27±15.33) and (55.20±16.43) μmol·L^-1, CACS were 0 (0, 0) and 0 (0, 28.93) points, uric acid reduction rates were (46.34±7.45)% and (25.81±4.56)%, creatinine reduction rates were (27.23±5.53)% and (9.12±2.46)%, and CAC incidence rates were 3.33% and 20.00% in the dapagliflozin group and non-dapagliflozin group, respectively. All the above indicators showed statistically significant differences between the two groups (all P<0.05). Multivariate logistic regression analysis showed that, after adjusting for confounding factors including sex, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), uric acid, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and glycated hemoglobin (HbA1c), dapagliflozin remained an independent protective factor against CAC (OR=0.128, 95% CI: 0.03-0.62, P<0.05). The main adverse drug reactions of dapagliflozin group were mild genitourinary infection and postural hypotension; hypoglycemia and urinary tract infection were the main adverse drug reaction in non-dapagliflozin group. The total incidence of adverse drug reactions in dapagliflozin group and non-dapagliflozin group were 10.00% and 6.67%, respectively, with no significant difference in statistics (P>0.05), demonstrating good safety profile.

Dapagliflozin tablets can significantly reduce uric acid, creatinine and CACS levels in CKD patients, and may serve as a potential protective factor against coronary artery calcification.

To investigate the therapeutic effects and safety of the combination of azithromycin (injection and granules) and montelukast sodium tablets on the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children of different severity.

The children with MPP treated in our hospital were divided into control group and treatment group based on the treatment method. All children received intravenous infusion of azithromycin injection at a dose of 10 mg·kg^-1 qd for 5 days until body temperature returned to normal, followed by oral administration of azithromycin granules at the same dose for 3 days, then 4 days off, for a total course of 3 weeks. On this basis, the treatment group was additionally given montelukast sodium tablets, with a dose of 4 mg·d^-1 for children ≤5 years old, and 5 mg·d^-1 for children over 5 years old, for a total course of 3 weeks. According to the severity of MPP, patients were divided into mild MPP group and severe MPP group. After treatment, the clinical efficacy, NLRP3 inflammasome pathway-related indicators and small airway function indicators were compared between the two groups of children with different severity levels; multiple linear regression was used to analyze the correlation between NLRP3 inflammasome pathway-related indicators and small airway function; and generalized estimating equation (GEE) model was used to analyze the changes in NLRP3 inflammasome pathway-related indicators at different time points, in different groups, and with different severities.

This study included a total of 92 patients, with 46 cases in each group. Confounding factors were adjusted using propensity score matching (PSM), and after matching, 40 cases were included in each group, while 47 cases in mild MPP group and 33 cases in severe MPP group. The white blood cell count (WBC) in severe MPP and mild MPP groups were (10.82±1.59) and (10.06±1.47) ×10⁹·L^-1, C-reactive protein (CRP) were (19.45±8.94) and (8.67±4.08) mg·L^-1, interleukin-6 (IL-6) were (18.25±4.48) and (13.65±4.33) pg·mL^-1, and interleukin-10 (IL-10) were (6.70±1.89) and (5.26±1.35) pg·mL^-1. Comparisons of these indicators between subgroups showed statistically significant differences (all P<0.05). The effective treatment rates of children with mild MPP in treatment group and control group were 100.00% (22 cases/22 cases) and 88.00% (22 cases/25 cases), respectively; the effective treatment rates of children with severe MPP were 88.89% (16 cases/18 cases) and 60.00% (9 cases/15 cases), respectively. Comparisons between groups showed that these differences were statistically significant (all P<0.05). After treatment, the mild and severe MPP children in treatment group had NLRP3 mRNA levels of 0.89±0.11 and 1.11±0.10, apoptosis-associated speck-like protein (ASC) mRNA levels of 0.77±0.10 and 0.95±0.15, caspase-1 mRNA levels of 0.69±0.09 and 0.82±0.10; forced expiratory flow at 25% of the pulmonary volume (FEF25%) levels were (2.72±0.24) and (2.28±0.19) L·s^-1, forced expiratory flow at 50% (FEF50%) levels were (2.90±0.40) and (2.37±0.31) L·s^-1, forced expiratory flow at 75% (FEF75%) levels were (2.13±0.32) and (1.73±0.35) L·s^-1, all showing statistically significant differences (all P<0.05). Correlation analysis showed that in children with MPP, the NLRP3 inflammasome pathway-related indicators NLRP3, ASC and caspase-1 mRNA were all negatively correlated with small airway function indicators FEF25%, FEF50% and FEF75%, and the negative correlations were statistically significant (all P<0.001). GEE results indicated that the reduction in NLRP3 mRNA levels in treatment group was greater than that in control group. In mild MPP, the estimated values for treatment and control groups were -0.76 and -0.56, respectively; the reduction in ASC mRNA in treatment group was greater than in the control group, with estimated values of -0.56 and -0.26, respectively; the reduction in caspase-1 mRNA in treatment group was greater than in control group, with estimated values of -0.32 and -0.26, respectively, and all interaction terms were statistically significant (all P<0.05).

Azithromycin combined with montelukast sodium can significantly improve the clinical efficacy of children with different severity of MPP, reduce the excessive inflammatory response of children with different severity of MPP by targeting and inhibit the NLRP3 inflammasome pathway, and improve the function of the small airway, especially in children with mild disease.

To observe the effectiveness and hepatorenal safety of Fule Cream alone or in combination with topical corticosteroids (TCS)/calcineurin inhibitors (TCI) in treating pediatric skin diseases.

Children prescribed Fule cream in our hospital were enrolled and categorized into monotherapy cohort (Fule Cream alone) and combination cohort (Fule cream with TCS/TCI) based on medication use. The changes in liver and kidney function indicators, the incidence of drug-induced liver injury (DILI), acute kidney injury (AKI) and clinical effectiveness were compared between the two cohorts. Outcome variables for effectiveness were constructed by extracting efficacy descriptions from medical record texts.

A total of 2 439 children were included for safety analysis and 741 for effectiveness analysis. Effectiveness analysis showed that the combination cohort had a significantly higher response rate of 77.93% (505 cases/648 cases) than the monotherapy cohort 56.99% (53 cases/93 cases) with an odds ratio (OR) of 0.38 (95% CI: 0.24-0.59). Regarding safety, after treatment, The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in cohort 1 and cohort 2 were significantly decreased after treatment (all P<0.05). The incidence of DILI and AKI was low. Data quality analysis revealed a high missing rate for follow-up laboratory tests and a lack of standardized efficacy evaluations.

The Fule Cream combined with TCS/TCI regimen demonstrated not only superior effectiveness but also no increased clinically significant hepatorenal risk in a real-world setting. Although data missingness may affect the precision of effect estimates, sensitivity analyses support the robustness of the primary conclusions. These findings provide real-world evidence supporting the clinical use of Fule Cream and highlight the necessity of enhancing data governance to generate higher-quality real-world evidence.

To observe the clinical efficacy and safety of remimazolam injection combined with fentanyl injection in the induction of general anesthesia for pediatric laparoscopic hernia surgery.

The children who underwent elective laparoscopic hernia surgery in our hospital were divided into successful sedation group and failed sedation group according to whether laryngeal mask placement was completed under sedation remedy. Remimazolam injection was administered intravenously, using an initial dose of 0.3 mg·kg^-1 with a dose increment of 0.05 mg·kg^-1. The dose for the next patient was determined according to the modified Dixon sequential method. Patients who successfully underwent laryngeal mask insertion were included in the sedation success group, while those requiring additional intravenous propofol for sedation to complete laryngeal mask insertion were included in the sedation failure group. Remimazolam injection combined with fentanyl injection was calculated by modified Probit regression for the induction of half effective dose (ED₅₀) and 95% effective dose (ED₉₅) and its 95% confidence interval (CI) in pediatric laparoscopic hernia induction of general anesthesia. Recorded vital signs during anesthesia induction, preoperative, dosage and intraoperative procedures, and evaluated for safety.

A total of 42 children who were planned for laparoscopic hernia surgery were screened in this study, of which were excluded due to abnormal preoperative examination (4 cases), parental refusal to participate (2 cases) and difficult airway (1 case), and finally, 35 hospitalized children who met the criteria were included. All enrolled children successfully completed the study process and no case dropped out, 18 cases of successful sedation and 17 cases of failed sedation. The ED₅₀ of remimazolam combined with fentanyl for general anesthesia induction in pediatric laparoscopic surgery was 0.22 mg·kg^-1, CI was (0.19~0.26), ED₉₅ was 0.32 mg·kg^-1, and CI was (0.28~0.51). The time from anesthesia induction to intubation in the successful and failed sedation groups were 4.58 (3.00, 5.00) and 4.63 (3.25, 5.75) min, respectively; the time of surgery were 13.63 (7.00, 17.00) and 14.00 (6.50, 18.00) min, respectively; the time from discontinuation to extubation were 17.84 (7.00, 21.00) and 16.50 (6.40, 22.75) min, respectively; and the stay time after resuscitation were 38.42 (30.00, 40.00) and 41.56 (22.10, 49.25) min, respectively. There was no significant difference between the above indicators in the successful sedation group and the failed sedation group (all P>0.05). The main adverse drug reactions in the successful sedation group were drowsiness, hypotension and hypoxemia, and in the sedation failure group were drowsiness and hypotension. The total incidence of adverse drug reactions in the successful sedation group and the failed sedation group were 22.22% (4 cases/18 cases) and 17.65% (3 cases/17cases). There was no significant difference between the above indicators in the successful sedation group and the failed sedation group (P>0.05).

The ED₅₀ of remimazolam combined with fentanyl for inserting a laryngeal mask in pediatric general anesthesia is 0.22 mg·kg^-1, with a CI of (0.19~0.26).

To observe the clinical efficacy and safety of combining nebulized budesonide suspension with microscopic support laryngoscope cool plasma radiofrequency ablation in the treatment of early glottic carcinoma (EGC).

EGC patients were divided into control group and treatment group based on different treatment regimens. Both groups underwent microscopic support laryngoscope cool plasma radiofrequency ablation. Postoperatively, the control group was administered oral cefaclor extended-release capsules at a dose of 0.5 g per time, twice daily, for 2 consecutive days. The treatment group was given inhaled budesonide suspension at a dosage of 1 mg for nebulization, twice a day, starting one week after surgery, and after one week, switched to nebulization with saline for 3 weeks based on control group. The clinical efficacy, laryngeal morphological indicators, objective voice acoustic indicators, voice disorder index and postoperative follow-up results were compared between the two groups, and conducted a safety assessment.

A total of 98 patients were included, 51 in control group and 47 in treatment group. After treatment, the overall effective rates for control and treatment groups were 84.31% (43 cases/51 cases) and 89.36% (42 cases /47 cases), respectively, with no statistically significant difference (P>0.05). At 4 weeks postoperatively, the morphological scores for the vocal folds in control and treatment groups were (1.45±0.73) and (1.13±0.74) points, respectively; the fundamental frequencies were (168.71±22.58) and (158.02±23.83) Hz, respectively; the frequency perturbations were (0.72±0.11)% and (0.67±0.13)% , respectively; the amplitude perturbations were (4.16±0.56)% and (3.89±0.47)%, respectively; the harmonic-to-noise ratios were (21.39±2.32) and (23.34±2.43) dB, respectively; the physiological scores were (18.45±2.89) and (17.00±3.16) , respectively, with all differences being statistically significant between the two groups (all P<0.05). One case of gastrointestinal reaction occurred in control group; one case of rash and two cases of gastrointestinal reaction occurred in treatment group. The total incidence of adverse drug reactions in treatment and control groups were 6.38% (3 cases/47 cases) and 1.96% (1 case/51 cases), respectively, with no statistically significant difference (P>0.05). The progression-free survival rates for control and treatment groups were 91.30% (42 cases/46 cases) and 95.45% (42 cases /44 cases), respectively, with no statistically significant difference (P>0.05).

Nebulized budesonide budesonide inhalation therapy combined with microscopic support laryngoscope cool plasma radiofrequency ablation provides comparable treatment efficacy to isolated microscopic support laryngoscope cool plasma radiofrequency ablation in patients with EGC, but the former demonstrates more significant improvement in vocal fold morphology and voice quality.

To evaluate the effects of centella asiatica acid (AA) on the apoptosis of cardiac microvascular endothelial cells (CMECs) and vascular regeneration by modulating the Toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa B/nucleotide-binding oligomerization domain-like receptor protein 3 (TLR4/MyD88/NF-κB/NLRP3) pathway.

The homocysteine (HCY)-induced rat CMECs were used to simulate and construct a coronary heart disease injury cell model, and the success of model construction was verified using the cell counting kit-8 (CCK8) method. The cells were divided into control group (normal culture), model group (modeling), centella asiatica acid group (modeling + 10 μmol·L^-1 AA) and combined group (modeling + 1 μg·mL^-1 lipopolysaccharide + 10 μmol·L^-1 AA). Cell viability was detected using CCK8, apoptosis was assessed by flow cytometry, and the relative expression levels of apoptosis-related proteins, pathway-related proteins and vascular regeneration-related proteins were measured by Western blot.

The cell viability of control group, model group, asiatica acid group and combination group were 0.92±0.01, 0.61±0, 0.75±0.01 and 0.50±0.02, respectively; the apoptosis rates were (4.96±0.53)%, (24.98±1.68)%, (18.22±0.96)% and (34.17±0.49)%, respectively; the relative protein expression levels of B-cell lymphoma/leukemia 2-associated X protein (Bax) were 0.12±0.01, 0.63±0, 0.42±0.02 and 0.96±0.01, respectively; the relative expression levels of Bcl-2 protein were 0.99±0.02, 0.34±0.01, 0.69±0.01 and 0.10±0.01, respectively; the relative expression levels of TLR4 protein were 0.19±0.01, 0.65±0, 0.41±0.01 and 0.84±0.01, respectively; the relative expression levels of Myd88 protein were 0.29±0.02, 0.77±0, 0.61±0.01 and 0.95±0.02, respectively; the relative expression levels of NF-κ B protein were 0.22±0.01, 0.82±0.02, 0.53±0.02 and 0.84±0.02, respectively; the relative expression levels of NLRP3 protein were 0.17±0.02, 0.75±0.03, 0.50±0.01 and 0.98±0.01, respectively; the relative expression levels of vascular endothelial growth factor (VEGF) protein were 0.95±0.01, 0.44±0.02, 0.68±0.02 and 0.23±0.01, respectively; the relative expression levels of platelet endothelial cell adhesion molecule-1 (CD31) protein were 1.01±0.01, 0.44±0.02, 0.58±0 and 0.38±0.01, respectively. The above indicators of model group were compared with control group, the above indicators of the oxalic acid group were compared with the model group, and the above indicators of the combination therapy group were compared with the asiatica acid group, the differences were all statistically significant (all P<0.01).

AA can alleviate HCY induced apoptosis of cardiac microvascular endothelial cells and promote vascular regeneration by inhibiting TLR4/MyD88/NF-κB pathway.

To explore the possible mechanisms through which corilagin affects high-glucose-induced oxidative stress and apoptosis in podocytes to alleviate diabetic nephropathy (DN).

MPC5 cells in the logarithmic growth phase were divided into 5 groups: control group (5 mmol·L^-1 glucose), model group (30 mmol·L^-1 glucose), corilagin group (30 mmol·L^-1 glucose plus 50 μM corilagin treatment), corilagin + pcDNA3.1 group (30 mmol·L^-1 glucose plus corilagin 50 μM treatment after transfection with pcDNA3.1), and corilagin + pcDNA3.1-transcription factor 7 (TCF7) group (30 mmol·L^-1 glucose plus corilagin 50 μM treatment after transfection with pcDNA3.1-TCF7). Real-time quantitative polymerase chain reaction (qPCR) was used to detect the expression of long non-coding RNA (LncRNA) TCF7; terminal deoxynucleotidyl transferase dUTP nick-end labeling was employed to assess the apoptosis rate; Western blot was used to analyze the expression of Cleaved caspase-9, Cleaved caspase-3, and proteins related to the glycogen synthase kinase 3 beta (GSK3β)/nuclear factor erythroid-2-related factor2 (Nrf2) signaling pathway; 2′,7′-dichlorofluorescein diacetate fluorescent probe was utilized to measure reactive oxygen species (ROS) levels; and immunofluorescence was used to examine the expression of nephrin and podocin.

The apoptosis rates for the control, model, corilagin, corilagin + pcDNA3.1 and corilagin + pcDNA3.1-TCF7 groups were (5.72±0.49)%, (31.14±5.46)%, (17.01±2.75)%, (16.21±2.83)% and (25.80±3.42)%, respectively; the relative expression levels of Cleaved caspase-9 were 1.00±0.11, 3.91±0.41, 2.43±0.29, 2.49±0.33 and 3.88±0.37, respectively; the relative expression levels for Cleaved caspase-3 were 1.00±0.08, 5.04±0.63, 3.35±0.48, 3.29±0.45 and 4.78±0.56, respectively; the ROS levels were 1.00±0.14, 6.27±1.16, 2.29±0.32, 2.41±0.38 and 5.17±1.08, respectively; malondialdehyde (MDA) levels were (2.33±0.35), (9.26±2.23), (4.80±0.86), (4.47±0.74) and (7.52±1.36) nmol·mg^-1, respectively; superoxide dismutase (SOD) levels were (41.34±6.13), (12.15±1.99), (33.38±4.55), (30.01±4.70) and (24.16±3.71) U·mg^-1, respectively; and catalase (CAT) levels were (68.22±5.45), (28.27±3.48), (52.13±6.06), (50.24±7.43) and (41.91±5.39) U·mg^-1, respectively. When the above indicators in control group compared with those in model group, the above indicators in model group compared with those in the corilagin group, and the above indicators in the corilagin+pcDNA3.1 group compared with those in the corilagin+pcDNA3.1-TCF7 group, all differences showed statistically significant (P<0.05, P<0.01, P<0.001).

Corilagin can inhibit high-glucose-induced oxidative stress and apoptosis in podocytes, thereby alleviating DN, possibly related to its regulation of the GSK3β/Nrf2 signaling pathway by LncRNA TCF7.

To investigate the effects and mechanism of equol on podocyte injury in diabetic nephropathy (DN) by regulating the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway by coiled-coil domain containing 92 (CCDC92).

Mouse MPC5 cells were divided into five groups: the control group (without any treatment), the model group (treated with 30 mmol·L^-1 glucose for 48 h), the experimental group (treated with 1 μmol·L^-1 equol for 24 h on the basis of the model group), the AAV-NC group (transfected with AAV-NC on the basis of the experimental group) and the AAV-CCDC92 group (transfected with AAV-CCDC92 on the basis of the experimental group). Cell viability was detected by the methyl thiazolyl tetrazolium assay. The mRNA level of CCDC92 was determined by real-time fluorescence quantitative polymerase chain reaction. Cell invasive ability was assessed by the transwell assay. The protein relative expression levels of Podocin and Nephrin were detected by immunofluorescence assay. The protein relative expression levels of microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ (LC3Ⅱ/Ⅰ), Beclin-1, AMPK and mTOR related proteins were measured by Western blot.

The cell viability rates of the control group, model group and experimental group were (100.00±2.84)%, (64.91±9.57)% and (81.36±13.19)%, respectively; the relative expression levels of CCDC92 mRNA in the control group, model group, experimental group, AAV-NC group and AAV-CCDC92 group were 1.00±0.12, 2.26±0.35, 1.42±0.19, 1.48±0.22 and 2.05±0.34, respectively; the number of invasive cells were (79.35±11.62), (25.81±4.06), (53.69±7.95), (60.46±10.58) and (41.13±7.27) cells, respectively; the relative expression levels of Nephrin protein were 1.00±0.14, 0.31±0.05, 0.65±0.09, 0.58±0.08 and 0.39±0.06, respectively; the relative expression levels of Podocin protein were 1.00±0.17, 0.28±0.04, 0.61±0.11, 0.56±0.09 and 0.32±0.06, respectively; the relative expression levels of LC3Ⅱ/Ⅰ protein were 1.00±0.17, 0.26±0.04, 0.74±0.12, 0.69±0.11 and 0.41±0.08, respectively; the relative expression levels of Beclin1 protein were 1.00±0.15, 0.32±0.06, 0.68±0.10, 0.75±0.12 and 0.46±0.07, respectively; the relative expression levels of phosphorylated (p)-AMPK/AMPK protein were 1.00±0.19, 0.23±0.04, 0.86±0.17, 0.89±0.16 and 0.38±0.07, respectively; the relative expression levels of p-mTOR/mTOR protein were 1.00±0.16, 3.16±0.53, 1.72±0.31, 1.65±0.29 and 2.91±0.52, respectively. There were statistically significant differences in the above indicators between the model group and the control group, between the experimental group and the model group and between the AAV-CCDC92 group and the AAV-NC group (P<0.05, P<0.01, P<0.001).

Equol can alleviate podocyte injury in DN through CCDC92, and the effects may be related to regulating the AMPK/mTOR pathway and improving autophagy level.

To investigate the regulatory effects of paeonol on autophagy and the NOD-like receptor protein 3 (NLRP3) inflammasome in human renal proximal tubular epithelial cells (HK-2) induced by human serum albumin (HSA).

HK-2 cells were cultured in vitro and randomly assigned to control group, model group, as well as low-, medium- and high-dose experimental groups. Cells in the control group were cultured under normal conditions; those in the model group were treated with 20 mg·mL^-1 HSA for 24 h; and cells in the low-, medium- and high-dose experimental groups were administered 25, 50 and 100 μmol·L^-1 paeonol, respectively, for 24 h on the basis of the model group intervention. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the concentrations of kidney injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), interleukin 1β (IL-1β) and caspase-1 in the cell supernatant. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of KIM-1 and MCP-1. Western blotting was applied to measure the protein expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), interleukin-1β (IL-1β), microtubule-associated protein 1 light chain 3 (LC3), sequestosome 1(p62), Beclin-1, PTEN-induced kinase 1 (PINK1) and Parkin.

The concentrations of KIM-1 in the cell supernatant of the control group, model group, and low-, medium- and high-dose experimental groups were (8.65±0.53), (17.33±2.04), (10.76±1.41), (8.48±0.47) and (8.47±0.24) pg·mL^-1, respectively; the contents of MCP-1 were (531.38±15.64), (2 198.55±148.21), (1 966.29±53.52), (1 605.49±234.68) and (937.33±36.96) pg·mL^-1, respectively; the secretion levels of IL-1β were (71.66±2.29), (109.92±4.41), (91.68±4.75), (80.66±4.00) and (62.38±3.24) pg·mL^-1, respectively; the contents of caspase-1 were (66.57±10.52), (210.50±17.50), (201.88±7.22), (195.42±13.95) and (129.81±13.20) pg·mL^-1, respectively; the relative expression levels of KIM-1 mRNA in each group were 1.05±0.05, 2.38±0.45, 1.58±0.20, 1.44±0.08 and 1.38±0.22, respectively; while those of MCP-1 were 1.04±0.04, 1.53±0.08, 1.32±0.16, 1.16±0.16 and 0.62±0.13, respectively; the relative expression levels of NLRP3 protein were 0.89±0.08, 1.13±0.07, 1.00±0.07, 0.84±0.12 and 0.55±0.16, respectively; those of ASC were 0.23±0.03, 0.87±0.19, 0.81±0.16, 0.78±0.08 and 0.46±0.05, respectively; those of IL-1β were 0.49±0.12, 1.46±0.29, 1.10±0.26, 0.71±0.06 and 0.53±0.13, respectively; the LC3Ⅱ/Ⅰ ratios were 1.08±0.04, 0.90±0.06, 1.00±0.02 and 1.05±0.04, respectively; the expression levels of p62 protein were 0.38±0.06, 1.23±0.11, 1.05±0.20 and 0.62±0.19, respectively; those of Beclin-1 were 0.82±0.07, 0.59±0.06, 0.90±0.07 and 0.93±0.09, respectively; those of PINK1 were 1.10±0.03, 0.68±0.07, 0.78±0.11 and 1.03±0.08, respectively; those of Parkin were 0.64±0.06, 0.46±0.05, 0.58±0.08 and 0.79±0.12, respectively. Compared with the control group, all the above indicators in the model group exhibited statistically significant differences (P<0.05, P<0.01, P<0.001). Moreover, the indicators in the high-dose experimental group showed statistically significant differences compared with the model group (P<0.05, P<0.01, P<0.001).

Paeonol may alleviate albumin-induced renal tubular injury by promoting mitophagy and inhibiting the activation of the NLRP3 inflammasome.

To explore the molecular mechanism by which curcumin (CUR) and chidamide (CHI) synergistically inhibit the malignant behaviors of breast cancer (BC) cells through the interferon (IFN)-retinoic acid-inducible gene Ⅰ (RIG-Ⅰ)-mitochondrial antiviral-signaling protein (MAVS) pathway.

A cellular model was established using MCF-7 breast cancer cells. The cells were divided into five groups: blank group(normol cuttured), CUR group(20 μmol·L^-1 CUR), CHI group(10 μmol·L^-1 CHI), combination group(20 μmol·L^-1 CUR+10 μmol·L^-1 CHI) and inhibitor group(sh-IFN+20 μmol·L^-1 CUR+10 μmol·L^-1 CHI). Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation capacity was evaluated by plate colony formation assay. Cell migration ability was examined using Transwell and wound healing assays. The relative expression levels of apoptosis-related proteins and IFN-RIG-I-MAVS pathway-associated proteins were detected by Western blotting (WB).

Under CUR concentrations of 0, 10, 20 and 40 μmol·L^-1, the half-maximal inhibitory concentrations (IC₅₀) of CHI were (31.48±2.01), (17.57±0.65), (7.56±0.32) and (0.21±0.02) μmol·L^-1, respectively. Statistically significant dose-dependent reductions in IC₅₀ were observed for CHI when combined with 10, 20 and 40 μmol·L^-1 CUR compared to 0 μmol·L^-1 CUR (all P<0.05). The colony formation numbers were (201.28±23.96) cells for the control group, (113.43±15.59) cells for the CUR group, (109.93±11.64) cells for the CHI group, (59.57±6.91) cells for the combination group, and (87.43±5.04) cells for the inhibitor group, respectively; the numbers of invasive cells were (115.03±13.05), (86.51±9.13), (77.82±6.68), (39.54±5.43) and (68.92±3.95) cells, respectively; the wound closure rates were (51.29±5.17)%, (32.80±2.94)%, (31.23±3.10)%, (16.07±2.11)% and (26.94±1.95)%, respectively; the apoptosis rates were (2.21±0.16)%, (12.03±0.85)%, (12.89±0.99)%, (31.62±2.98)% and (16.85±1.04)%, respectively; the relative expression levels of Caspase-3 were 0.38±0.03, 0.55±0.03, 0.52±0.04, 1.12±0.07 and 0.97±0.05, respectively; the relative expression levels of Caspase-9 levels were 0.33±0.02, 0.53±0.02, 0.55±0.04, 1.05±0.06 and 0.60±0.05, respectively; the relative expression levels of Bax levels were 0.34±0.03, 0.52±0.03, 0.53±0.03, 1.08±0.07 and 0.69±0.06, respectively; the relative expression levels of IFN-β levels were 0.33±0.03, 0.46±0.04, 0.53±0.04, 1.09±0.10 and 0.45±0.03, respectively; the relative expression levels of RIG-Ⅰ levels were 0.32±0.02, 0.57±0.05, 0.65±0.04, 1.02±0.11 and 0.59±0.05, respectively; and the relative expression levels of MAVS levels were 0.34±0.02, 0.41±0.03, 0.49±0.04, 1.04±0.12 and 0.51±0.04, respectively. Statistically significant differences were observed when comparing the CUR and CHI groups to the control group, the combination group to the CUR and CHI groups, and the inhibitor group to the combination group (all P<0.05).

CUR enhances the sensitivity of BC cells to CHI and synergistically exerts anti-BC effects with CHI, and its mechanism of action is related to the activation of the IFN-RIG-I-MAVS pathway by CUR.

To investigate the effects and mechanism of artesunate on hippocampal neuronal damage in schizophrenia rats by adjusting Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.

This study induced a rat model of schizophrenia using ketamine and divided them into model group, low-dose experimental group (5 mg·kg^-1 artesunate), medium-dose experimental group (10 mg·kg^-1 artesunate), and high-dose experimental group (20 mg·kg^-1 artesunate), each with 12 rats. Another 12 rats were considered as normal group. After 21 days of administration, the open field test and three box social behavior experiment were used to detect schizophrenia symptoms in rats; hematoxylin-eosin (HE) staining was used to observe hippocampal neural tissue; Nissl staining was used to observe neuronal damage; terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) staining was used to detect neuronal apoptosis in the hippocampus; enzyme-linked immunosorbent assay (ELISA) was used to detect brain-derived neurotrophic factor (BDNF) in the hippocampus; Western blotting was used to detect JAK1 and STAT3-related protein expression in the hippocampus.

The intersection distances of the central areas of blank group, model group and low, medium and high dose experimental groups were (0.65±0.08), (1.48±0.18), (1.27±0.15), (1.08±0.13) and (0.77±0.09) m, respectively; social interaction times are (63.53±7.39), (31.73±4.09), (38.38±5.32), (44.97±5.13) and (54.78±6.27) s, respectively ; the number of Nissl-positive cells in the hippocampus were (121.38±13.54), (62.63±6.87), (80.85±8.93) , (98.24±9.49) and (118.23±12.63) cells, respectively ; the apoptosis rates were (2.94±0.46)%, (34.73±3.83)%, (25.75±2.92)%, (16.49±2.21)% and (6.83±1.02)%, respectively; the levels of BDNF were (172.58±19.48), (68.49±8.31), (92.26±10.22), (115.08±13.34) and (142.82±16.37) pg·mg^-1, respectively; p-JAK1 protein relative expression levels were 0.38±0.05, 0.87±0.09, 0.73±0.09, 0.60±0.08 and 0.44±0.06, respectively ; p-STAT3 protein relative expression levels were 0.31±0.04, 0.79±0.09, 0.66±0.08, 0.53±0.06 and 0.38±0.05, respectively, when comparing the above indicators between model group and blank group, comparing the above indicators between low, medium, high dose experimental groups and model group, there were statistically significant differences (all P<0.05).

Artesunate may improve hippocampal neuronal damage in schizophrenia rats by inhibiting JAK1/STAT3 signaling pathway.

To investigate the preventive and therapeutic effects of Tanshinone ⅡA on radiation-induced heart disease (RIHD) through the regulation of the phosphoinositide 3-kinase/AKT/mechanistic target of rapamycin (PI3K/AKT/mTOR) signaling pathway, and to elucidate its underlying mechanisms based on animal and cellular experiments, thereby providing a theoretical foundation for developing targeted clinical prevention and treatment strategies.

In animal experiments, SPF-grade rats and mice were respectively divided into blank control group, model group and experimental group. A single dose of X-ray irradiation (25 Gy for rats, 20 Gy for mice) was administered to establish the RIHD model. The blank control group received normal feeding. The model group received normal feeding after modeling. The experimental group received daily intraperitoneal injections of Tanshinone ⅡA sulfonate sodium injection (1 mg/10 g body weight) for one week following modeling. In cell experiments, H9C2 cardiomyocytes were divided into normal cell group, injury-induced group and a drug-treated group. A radiation-induced RIHD cell model was established. The normal cell group was cultured under standard conditions. The injury-induced group was cultured normally after modeling. The drug-treated group was administered Tanshinone ⅡA sulfonate sodium (1μL·mL^-1 culture medium) immediately after modeling. Body weight changes and myocardial histopathological characteristics were dynamically monitored. Transcriptome sequencing was performed on cardiac apex tissues from both rats and mice for joint analysis, aiming to screen for common differentially expressed genes and enriched pathways. Cell viability was assessed using the cell counting kit-8 (CCK-8) assay. Cell membrane damage was evaluated by the lactate dehydrogenase (LDH) release assay. The expression levels of key genes in PI3K/AKT/mTOR pathway, including angiopoietin-2 (ANGPT2) and cyclin D1 (CCND1), as well as the protein levels of phosphorylated phosphoinositide 3-kinase (P-PI3K) and phosphorylated AKT serine/threonine kinase (P-AKT) were detected using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively.

Animal experiments showed that after the intervention, the body weights of rats in the blank control group, model group and experimental group were (434.37±8.52), (341.61±8.73) and (410.13±10.05) g, respectively; the body weights of mice were (30.97±0.89), (26.24±0.86) and (30.96±0.87) g, respectively; AST levels were (159.92±3.83), (171.04±2.63) and (149.63±10.55) U·L^-1, respectively; CK-MB levels were (219.00±5.83),(455.42±32.76) and (248.36±15.25) U·L^-1, respectively; LDH levels were (677.20±21.22),(864.63±6.39) and (635.77±22.72) U·L^-1, respectively; BNP levels were (29.37±6.04),(241.69±12.75) and (134.23±13.57) pg·mL^-1, respectively; GSH levels were (160.73±4.65), (330.38±9.41) and (116.71±11.29) U·L^-1, respectively. All the aforementioned indicators in model group showed statistically significant differences compared to blank control group, and all indicators in the experimental group showed statistically significant differences compared to model group (all P<0.001). In the cell experiments, joint transcriptome analysis revealed that 72% of homologous differentially expressed genes (624 in rats, 341 in mice) exhibited consistent expression trends in both species. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis indicated that ANGPT2, CCND1, THBS1, COL4A1, FN1 and COL4A2 were primarily enriched in the PI3K/AKT/mTOR pathway (all P<0.05), and PCR validation confirmed this consistent trend. In vitro experiments confirmed that the cell viabilities in normal cell group, injury-induced group and drug-treated group were (118.40±8.63)%, (73.10±6.12)% and (91.57±8.08)%, respectively. The differences between injury-induced group and normal cell group, as well as between drug-treated group and injury-induced group, were statistically significant (both P<0.001). The LDH release levels in injury-induced group and drug-treated group were (1.03±0.02) and (0.77±0.01)-fold that of normal cell group, respectively. The difference between the drug-treated group and the injury-induced group was statistically significant (P<0.001). The relative expression levels of P-PI3K in normal cell group, injury-induced group and drug-treated group were 0.92±0, 0.76±0.01 and 0.85±0.02, respectively; the relative expression levels of P-AKT were 0.79±0.01, 0.70±0.01 and 0.76±0.01, respectively. The differences between the injury-induced group and the normal cell group, as well as between the drug-treated group and the injury-induced group were statistically significant (all P<0.05).

Tanshinone ⅡA mitigates radiation-induced cardiac injury by activating the PI3K/AKT/mTOR signaling pathway, upregulating key phosphorylated proteins (p-PI3K and p-AKT), reducing radiation toxicity and enhancing cellular viability.

To investigate the impact of quercetin (Que) on myocardial ischemia-reperfusion injury in rats and to elucidate its underlying mechanisms.

A rat model of myocardial ischemia-reperfusion was created by occluding the left anterior descending artery. A total of 60 SD rats were randomly divided into sham group, model group, low-dose experimental group (20 mg·kg^-1 Que), high-dose experimental group (80 mg·kg^-1 Que) and inhibitor group (80 mg·kg^-1 Que+3 mg·kg^-1 MCC950), with 12 rats in each group. Echocardiography was conducted after 14 days of continuous administration to assess the relevant indicators of cardiac function. Rat serum was taken and the amounts of serum myocardial damage indicators and inflammatory factors were detected by kit method. Western blotting was used to determine the relative expression levels of Toll-like receptor 2 (TLR2)/ nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) - related proteins in the rat myocardial tissue.

The left ventricular ejection fraction of rats in sham group, model group, low-dose experimental group, high-dose experimental group and inhibitor group were (79.36±5.37)%, (42.85±3.96)%, (48.51±4.20)%, (71.66±5.14)% and (55.73±4.68)%, respectively; the troponin Ⅰ (cTnⅠ) levels were (0.07±0.01), (0.38±0.03), (0.25±0.03), (0.13±0.01) and (0.20±0.02) ng·mL^-1, respectively; the interleukin-1β (IL-1β) levels were (1.01±0.15), (3.43±0.22), (2.65±0.26), (1.39±0.23) and (1.61±0.13) ng·mL^-1, respectively; the relative expression levels of TLR2 protein were 0.33±0.05, 1.01±0.07, 0.73±0.05, 0.45±0.03 and 0.50±0.06, respectively; the relative expression levels of NLRP3 protein were 0.34±0.06, 1.05±0.09, 0.86±0.07, 0.39±0.06 and 0.56±0.05, respectively. Compared with sham group, the model group showed statistically significant differences in the above indicators (all P<0.05); compared with model group and high-dose experimental group, the low-dose experimental group also exhibited statistically significant differences in the above indicators (all P<0.05).

Quercetin can alleviate myocardial ischemia-reperfusion (I/R) injury in rats and improve cardiac function. The mechanism may be related to the inhibition of the TLR2/NLRP3 inflammatory signaling pathway. Quercetin may exert its cardioprotective effect by down-regulating the expression of TLR2, thereby blocking its activation of the downstream NLRP3 inflammasome, containing NLRP3 and apoptosis-associated speck-like protein containing a CARD (ASC) and ultimately reducing the release of pro-inflammatory factors such as IL-1β.

To investigate the effects of telmisartan tablets (Tel) on viral myocardialtis (VM) mice through microRNA-320 (miR-320) and its mechanism.

A total of 60 BALB/c mice were divided into control group, model group, experimental group, Tel+rAAV-NC group and Tel+rAAV-miR-320 group, with 12 mice in each group. Except for control group, VM mouse models were established by intraperitoneal injection of coxsackievirus B3 0.1 mL containing 100 TCID50. Experimental group was given 10 mg·kg^-1 Tel intragastrically for 7 days. Based on experimental group, rAAV-NC was injected into the tail vein (1×10¹¹ viral copy number, dissolved in PBS 100 μL) in Tel+rAAV-NC group; based on experimental group, rAAV-miR-320 was injected into the tail vein (1×10¹¹ viral copy number, dissolved in PBS 100 μL) in Tel+rAAV-miR-320 group. The relative expression levels of miR-320 were detected by quantitative real time polymerase chain reaction. Creatine kinase isoenzyme, myoglobin and troponin were detected by enzyme-linked immunosorbent assay. TdT-mediated dUTP nick end labeling was used to detect apoptosis. The relative expression levels of peroxiredoxin-like protein NOX1 (PKNOX1)/B-cell lymphoma 10 (BCL10)/mucosa associated lymphoid tissue lymphoma translocation gene 1 (MALT1) signaling pathway were detected by Western blot.

The relative expression levels of miR-320 in control group, model group, experimental group, Tel+rAAV-NC group and Tel+rAAV-miR-320 group were 1.00±0.18, 4.06±0.73, 1.82±0.34, 1.95±0.36 and 3.47±0.61, respectively; creatine kinase isoenzyme were (36.09±4.82), (125.18±19.67), (49.73±8.04), (55.62±8.25) and (103.56±17.49) U·mL^-1, respectively; myoglobin were (72.35±11.46), (368.29±61.83), (93.62±15.27), (90.74±16.18) and (316.51±57.92) μg·L^-1, respectively; troponin were (17.42±2.53), (64.74±10.90), (28.59±4.16), (32.45±5.98) and (53.91±9.64) μg·L^-1, respectively; the apoptosis rates were (3.17±0.52)%, (28.46±5.39)%, (6.97±1.24)%, (8.01±1.53)% and (24.89±4.16)%, respectively; the relative expression levels of PKNOX1 protein were 1.00±0.15, 2.07±0.36, 1.43±0.19, 1.39±0.20 and 1.91±0.32, respectively; the relative expression levels of BCL10 protein were 1.00±0.18, 1.95±0.34, 1.48±0.22, 1.41±0.21 and 1.84±0.35, respectively; the relative expression levels of MALT1 protein were 1.00±0.13, 1.90±0.32, 1.26±0.15, 1.37±0.18 and 1.69±0.27, respectively. Statistical comparisons revealed significant differences between model group and control group, as well as between experimental group and model group, and between Tel+rAAV-miR-320 group and Tel+rAAV-NC group (all P<0.05).

By inhibiting the expression of miR-320, Tel alleviates myocardial injury and inhibits apoptosis in VM mice, which may be achieved by inhibiting PKNOX1/BCL10/MALT1 signaling pathway.

To analyze the potential mechanism of naringenin in improving diabetes-related intestinal inflammation.

In cell experiment, STC-1 cells were randomized into blank group, advanced glycation end products (AGEs) group, experimental-L group (AGEs+25 μg·mL^-1 naringenin) and experimental-H group (AGEs+50 μg·mL^-1 naringenin). In animal experiment, male C57BL/6J mice were randomly divided into control group, model group (to construct diabetes-related intestinal injury model), experimental-L group (modeling +25 mg·kg^-1 naringenin), experimental-H group (modeling +75 mg·kg^-1 naringenin) and metformin group (modeling +0.5 g·kg^-1 metformin). STC-1 cell necroptosis was detected using the Hoechst 33342/propidium iodide (PI) double staining method. Glycolipid metabolism indicators and pro-inflammatory factor levels were measured by enzyme-linked immunosorbent assay (ELISA). The expression of phosphorylated mixed lineage kinase domain-like (p-MLKL) protein and Occludin protein was assessed by Western blotting.

In cell experiment, PI-positive rates of blank, AGEs, experimental-L and experimental-H groups were (4.36±0.30)%, (19.37±1.58)%, (15.90±1.03)% and (12.85±1.51), respectively; IL-6 levels were (17.74±2.23), (71.46±6.54), (42.39±5.34) and (33.63±1.82) pg·mL^-1, respectively; p-MLKL relative expression levels were 0.39±0.05, 0.83±0.10, 0.74±0.07 and 0.58±0.04, respectively. All indicators showed significant differences between AGEs group and blank group, experimental-L group or experimental-H group and AGEs group (P<0.05, P<0.01). In animal experiment, post-intervention FBG levels of blank control group, model group, experimental-L group, experimental-H group and metformin group were (4.89±0.54), (26.88±1.96), (18.47±1.53), (14.96±1.67) and (13.91±1.16) mmol·L^-1, respectively; TG levels were (0.43±0.06), (1.70±0.15), (1.46±0.14), (1.13±0.10) and (0.81±0.09) mmol·L^-1, respectively; IL-6 levels were (13.59±1.06), (62.02±5.92), (50.19±4.44), (37.78±3.58) and (48.91±8.46) pg·mL^-1, respectively; the relative expression levels of p-MLKL were 0.38±0.05, 1.07±0.13, 0.79±0.08, 0.61±0.05 and 0.80±0.09, respectively; the relative expression levels of Occludin were 0.97±0.07, 0.35±0.04, 0.61±0.05, 0.83±0.07 and 0.43±0.06, respectively. Significant differences were observed between model group and blank control group, experimental-L group or experimental-H group or metformin groups and model group (P<0.05, P<0.01).

Naringenin can improve the function of intestinal endocrine cells and protect against diabetes-related intestinal injury, which may be related to the mechanism of necrotic apoptosis mediated by MLKL.

To investigate the potential mechanism of propofol in improving intestinal ischemia-reperfusion injury (IIRI).

SD rats were randomly divided into sham group, model group (the superior mesenteric artery was clamped for 45 min and reperfusion for 2 h), experimental-L group (injection of 30 mg·kg^-1 propofol before ischemia), experimental-M group (injection of 45 mg·kg^-1 propofol before ischemia), experimental-H group (injection of 60 mg·kg^-1 propofol before ischemia); after reperfusion, the rats were killed and intestinal tissues were taken for use. Hematoxylin-eosin (HE) staining was used to observe the intestinal histopathological changes, Western blot assay was used to detect the expression of Bcl-2 antagonist killer(BAK), Bcl-2 associated X(BAX) and other proteins, and real-time quantitative polymerase chain reaction (RT-qPCR) assay was used to detect the expression of cytoplasmic mitochondrial DNA (mtDNA). The enzyme activity and enzyme-linked immunosorbent assay was used to detect the expression of adenosine triphosphate (ATP) and interleukin (IL)-1β in intestinal tissue.

The pathological injury scores (Chiu’s methods) in sham group, model group, experimental-L group, experimental-M group and experimental-H group were (0±0), (4.20±0.60), (3.00±0.45), (2.20±0.40) and (1.00±0.77) points, respectively; the relative expression levels of BAK protein were 0.24±0.03, 0.66±0.08, 0.56±0.08, 0.40±0.05 and 0.34±0.03, respectively; the relative expression levels of BAX protein were 0.35±0.03, 0.79±0.11, 0.62±0.03, 0.51±0.05 and 0.40±0.04, respectively; the relative expression levels of NOD-like receptor pyrin domain-containing protein 3 (NLRP3) protein were 0.32±0.03, 1.05±0.12, 0.81±0.11, 0.64±0.08 and 0.49±0.08, respectively; the relative expression levels of Cyclic guanosine monophosphate adenosine synthase (cGAS) protein were 0.23±0.02, 0.97±0.10, 0.78±0.08, 0.63±0.07 and 0.45±0.07, respectively; the relative expression levels of the NADH dehydrogenase subunit (ND)1 mRNA were 1.00±0.08, 2.23±0.29, 1.79±0.13, 1.59±0.11 and 1.34±0.09, respectively; the levels of ATP production were 1.00±0.14, 0.47±0.03, 0.65±0.07, 0.80±0.06 and 0.81±0.12, respectively. Compared model group with the sham group and compared experimental-L, M, H group with model group, the differences of above indicators were all statistically significant (all P<0.05).

Propofol can dose-dependently improve intestinal injury in IIRI rats and this protective effect was accompanied by downregulation of BAK/BAX protein expression, reduction of mtDNA release, and decreased activity of the downstream cGAS/NLRP3 inflammatory pathway.

To evaluate the effects of itraconazole capsules on the pharmacokinetics of a single oral dose of ADC189 and its metabolite ADC189-I07 in Chinese healthy subjects, and to assess the safety of their co-administration.

This was a single-center, open-label, non-randomized, two-period, fixed-sequence trial, using itraconazole as an inhibitor of cytochrome P450 3A4 (CYP3A4), P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Analyze the impact of repeated administration of itraconazole capsules on the pharmacokinetic characteristics of ADC189 and its major metabolite ADC189-I07.

After co-administration of ADC189 with itraconazole, there was no difference in the maximum plasma concentration (C_max) of the active metabolite ADC189-I07 in plasma compares with ADC189 alone; the geometric mean ratio was 106.64%, with a 90% confidence interval (CI) of 84.12%-135.16%. The area under the curve (AUC_0-t) and AUC_0-∞ increased by approximately 42.00% and 47.00%, respectively, with geometric mean ratios and 90% confidence intervals of 142.48% (120.84%-167.98%) and 147.25% (123.95%-174.91%), respectively. The 90% CIs for all three parameters did not fall entirely within the no-effect boundary of 80.00%-125.00%. The median time to peak drug concentration (t_max) of ADC189-I07 was 4.00 (3.00-4.00) after administration alone and 4.00 (3.00-12.00) h after co-administration; non-parametric tests showed no statistically significant difference in t_max (P>0.05). All adverse events (AEs) during the trial were grade 1 or 2, resolved spontaneously, and the safety risk was controllable.

When ADC189 tablets are used clinically with a strong CYP3A4 inhibitor, no dosage adjustment is required for concomitant use.

To systematically evaluate the efficacy and safety of dapagliflozin (Forxiga^TM) combined with metformin (MET) in the treatment of type 2 diabetes mellitus (T2DM).

Several databases such as China National Knowledge Infrastructure (CNKI) and PubMed were searched by computer. To collect a randomized controlled trial of dapagliflozin combined with metformin in the treatment of type 2 diabetes. Quality evaluation, data extraction and data analysis of the literature were condueted. Glycosylated hemoglobin level, fasting blood glucose, 2 h postprandial blood glucose, fasting insulin, islet β - cell function, insulin resistance index, the incidence of adverse events, hypoglycemia and urinary tract infection were analyzed by RevMan5.4 software.

A total of 9 eligible randomized controlled trials (RCTs) involving 867 type 2 diabetes mellitus patients were included in the final analysis. As it turns out, the efficacy of dapagliflozin combined with MET group was significantly better than that of metformin alone (P<0.05), and the safety of the combined group had no statistically significant differince (P>0.05).

Compared with metformin monotherapy, the combination therapy of dapagliflozin and metformin yields significantly improved clinical outcomes in T2DM patients without increasing the incidence of adverse drug reactions. These findings provide robust scientific evidence for the rational clinical application of this therapeutic regimen.

To investigate the potential mechanisms and related signaling pathways of mitophagy in the occurrence and development of autosomal dominant polycystic kidney disease (ADPKD) using bioinformatics techniques.

The gene expression omnibus (GEO) dataset GSE7869 was downloaded and processed. Differentially expressed genes (DEGs) were identified using the R limma package. Mitophagy-related genes were retrieved from the GeneCards database and intersected with the DEGs to obtain candidate genes. A protein-protein interaction (PPI) network was constructed using STRING, and core genes were identified in Cytoscape using the maximalclique centrality (MCC) algorithm. Gene set enrichment analysis (GSEA) was conducted based on albumin (ALB) expression levels, and R packages including clusterProfiler, ggplot2 and enrichplot were used to visualize and interpret the enrichment results.

A total of 248 DEGs were obtained, including 61 up-regulated and 187 down-regulated genes. After intersecting with mitophagy-related genes, 38 candidate DEGs were identified. ALB was identified as the core differentially expressed gene through PPI analysis and Cytoscape. GSEA results indicated that the mitophagy-related gene ALB may play a role in ADPKD by regulating pathways such as extracellular matrix (ECM)-receptor interaction and branched-chain amino acid (BCAA) metabolism, as well as biological processes including organic acid and amino acid metabolism and organization of collagen fibrils.

ALB expression levels were significantly associated with pathways including ECM-receptor interaction and branched-chain amino acid metabolism, as well as with biological processes such as organic acid and amino acid metabolism and organization of collagen fibrils. These findings suggest that ALB may be involved in the pathogenesis of ADPKD.