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 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.

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 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 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 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 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 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 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.