To explore the main active components, potential targets and mechanisms of Yinpu Jiedu tablets in the treatment of diabetic renal inflammation by using network pharmacological methods and molecular docking techniques.

The active ingredients of Yinpu jiede tables and therapeutic targets for diabetic kidney inflammation were retrieved from databases including TCMSP, PubChem, SwissTargetPrediction and GeneCards. A protein-protein interaction (PPI) network was constructed using Venny, STRING, Metascape, Bioinformatics and Cytoscape, followed by gene enrichment analysis. Molecular docking was performed using AutoDock, and the results were visualized with PyMOL. Furthermore, a lipopolysaccharide (LPS)-induced cellular model of diabetic kidney inflammation was established. The experiment included control group, model group (4 μmol·L^-1 LPS) and experimantol group (30 μg·mL^-1 Yinpu jiede tables). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to measure the messenger ribonucleic acid (mRNA) relative expression levels of AKT1 serine/threonine kinase 1(Akt1), tumor protein p53(Tp53), tumor necrosis factor-α (Tnf-α) and interleukin-6 (IL-6) to validate the network pharmacology predictions.

A total of 30 active ingredients and 435 potential targets of Yinpu jiede tables were identified. The core active ingredients included quercetin, luteolin, acacetin, morin and pelargonin. Intersection analysis between disease-related targets and drug-targets yielded 71 key genes, from which 4 core targets, inducling AKT1, TNF-α, IL-6 and TP53. Molecular docking results indicated strong binding affinity between the core active ingredients and the core targets. gene ontolog (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses suggested that Yinpu jiede tables exerts its therapeutic effects on diabetic kidney inflammation primarily through pathways such as pathways in cancer, the JAK-STAT signaling pathway, the AMPK signaling pathway and the Wnt signaling pathway. Cellular experiments confirmed that LPS induction significantly upregulated the mRNA expression of Akt1, Tp53, TNF-α, and IL-6 in podocytes, while treatment with Yinpu jiede tables effectively reversed this trend, restoring their expression to near-normal levels, thereby validating its regulatory role on the predicted targets and inflammatory pathways.

Yinpu jiede tables may act on signal pathways such as JAK-STAT, AMPK, and Wnt through core targets such as AKT1, TNF, IL-6, and TP53, and exert therapeutic effects on diabetic kidney inflammation.

To investigate the inhibitory effect of different doses of metformin on colorectal cancer (CRC) and its mechanism involving the regulation of bile acid metabolism and the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway.

A total of 60 BALB/c mice were divided into control, model, low-dose metformin, medium-dose metformin and high-dose metformin groups. A CRC model was induced using azoxymethane (AOM)/dextran sodium sulfate (DSS). Tumor number and diameter were measured with a caliper; fecal bile acid levels were detected by liquid chromatography-mass spectrometry (LC-MS); and protein expression of COX-2 and PGE2 in colon tissue was determined by immunohistochemistry.

Tumor numbers in the control, model, low-, medium- and high-dose groups were 0, 11.58±7.13, 7.83±3.38, 3.33±2.06 and 2.83±1.40, respectively; tumor diameters were 0, (2.91±0.32), (2.43±0.31), (2.11±0.37) and (1.98±0.38) mm, respectively; total bile acid concentrations were (20 989.00±306.69), (43 256.50±187.08), (32 265.26±325.08), (23 035.72±136.33) and (22 351.51±145.36) ng·g^-1, respectively; deoxycholic acid (DCA) concentrations were (3 160.14±113.31), (16 684.58±4.39), (11 544.47±7.86), (5 472.60±25.03) and (5 201.36±79.95) ng·g^-1, respectively; lithocholic acid (LCA) concentrations were (2 140.43±76.23), (14 452.6±47.82), (9 085.87±11.14), (3 145.09±54.20) and (2 955.51±38.02) ng·g^-1, respectively; cholic acid (CA) concentrations were (6 917.71±51.12), (2 051.41±88.47), (3 181.64±23.79), (5 564.01±35.45) and (5 866.10±63.80) ng·g^-1, respectively; chenodeoxycholic acid (CDCA) concentrations were (5 720.33±53.07), (1 135.43±48.38), (1 530.56±37.57), (4 060.14±37.09) and (4 542.83±27.39) ng·g^-1, respectively; taurocholic acid (TCA) concentrations were (497.24±59.29), (1 560.15±26.03), (958.13±28.00), (705.21±3.66) and (669.24±33.00) ng·g^-1, respectively; taurochenodeoxycholic acid (TCDCA) concentrations were (1 027.96±84.28), (2 918.60±122.90), (2 518.23±70.50), (1 411.36±49.15) and (1 389.87±5.80) ng·g^-1, respectively; COX-2 staining scores in the model, low-, medium- and high-dose groups were (5.75±0.97), (4.50±1.78), (2.75±1.66) and (2.67±0.89) points, respectively; PGE2 staining scores were (5.75±0.97), (4.50±1.93), (2.67±1.67) and (2.50±0.90) points, respectively; compared with the control group, the aforementioned indicators in the model group showed statistically significant differences; compared with the model group, the indicators in the low-, medium- and high-dose groups showed statistically significant differences (all P<0.05). The medium- and high-dose groups were significantly more effective than the low-dose group in reducing tumor number and diameter and regulating bile acid metabolism (P<0.05). The inhibition of COX-2/PGE2 expression was negatively correlated with the dose of metformin.

Metformin exerts anti-CRC effects through dose-dependent regulation of bile acid metabolism (reducing DCA, LCA, TCA, TCDCA and restoring CA and CDCA levels) and inhibition of the COX-2/PGE2 signaling pathway. The medium- and high-dose groups (250-500 mg·kg^-1·d^-1) show more significant effects.

To explore the effect of Gallic acid on liver tissue damage in autoimmune hepatitis (AIH) mice by adjusting adenosine monophosphate-activated protein kinase (AMPK) / acetyl-coa carboxylase (ACC) signaling pathway.

An AIH mouse model was established by injecting 15 mg·kg^-1 concanavalin A through the tail vein. The mice were randomly divided into model group, low-dose experimental group (50 mg·kg^-1), high-dose experimental group (100 mg·kg^-1), AMPK inhibitor group (5 μmol·L^-1), gallic acid + AMPK inhibitor group and normal mice group with the same volume of phosphate-buffered solution as control group. After the intervention, the automatic biochemical analyzer was used to analyze glutamic pyruvic transaminase (GPT), the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in liver homogenate were detected by enzyme-linked immunosorbent assay (ELISA), and the levels of interleukin (IL)-10, IL-6 and tumor necrosis factor (TNF-α) in serum supernatant were also measured. The histopathological changes were detected by the hematoxylin-eosin (HE) staining method; the apoptosis status was examined by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. The relative expression levels of phosphorylated (p-) AMPK/AMPK, Bcl-2 related X protein (Bax), B-cell lymphoma/leukemia-2 protein (Bcl-2) and ACC protein were detected by Western blotting.

The glutamic-oxalacetic transaminase (GOT) levels in control group, model group, low-dose experimental group, high-dose experimental group, AMPK inhibitor group and high-dose experimental+AMPK inhibitor group were (82.05±8.31), (210.20±21.14), (135.26±14.64), (91.02±9.21), (308.15±30.85) and (129.84±13.08) U·L^-1, respectively; the GPT levels were (50.23±5.11), (324.85±33.25), (152.34±15.48), (88.64±8.95), (482.62±50.02) and (148.85±15.02) U·L^-1, respectively; the TNF-α levels were (41.06±4.37), (149.85±15.28), (88.39±8.97), (51.06±5.21), (267.85±27.18) and (154.62±15.68) pg·mL^-1, respectively; the IL-6 levels were (48.42±4.92), (134.52±13.58), (75.42±7.61), (57.85±5.81), (215.84±21.98) and (78.62±7.98) pg·mL^-1, respectively; the IL-10 levels were (486.52±49.02), (188.72±19.08), (318.54±32.08), (445.67±45.11), (114.21±11.94) and (324.15±32.67) pg·mL^-1, respectively; the SOD levels were (48.26±4.99), (19.52±2.11), (32.25±3.44), (44.21±4.57), (11.37±1.21) and (31.24±3.22) U·mg^-1, respectively; the MDA levels were (0.28±0.03), (0.84±0.09), (0.56±0.06), (0.31±0.04), (1.31±0.15) and (0.64±0.07) nmol·mg^-1, respectively; the tissue pathological scores were 0, 2.64±0.27, 2.27±0.24, 1.22±0.14, 3.54±0.36 and 2.19±0.23, respectively; the apoptosis rates were (5.24±0.54)%, (23.62±2.44)%, (16.42±1.72)%, (8.52±0.89)%, (34.85±3.61)% and (17.06±1.75)%, respectively. The above indexes of model group were compared with those of control group; low-dose and high-dose experimental group were compared with those of model group and high-dose experimental+AMPK inhibitor group were compared with those of high-dose experimental group, there were statistically significant differences (all P<0.05).

Gallic acid can inhibit the inflammatory response and oxidative stress level in AIH mice, reduce cell apoptosis, improve liver function, alleviate liver tissue pathological damage, down-regulate Bax and ACC expression, up-regulate p-AMPK/AMPK and Bcl-2 expression; the AMPK inhibitor reverses the protective effect of high-dose gallic acid on AIH mice. Gallic acid activates the AMPK/ACC signaling pathway to alleviate liver tissue damage in AIH mice.

To investigate the effect of total flavonoids from Patrinia on neuroprotection in rats with ischemic stroke (IS) by Rat sarcoma virus oncogene homolog (Ras) homolog gene family member (Rho) A/Rho-associated kinase (ROCK) signaling pathway.

The IS rat model was established by the suture method, and was randomly divided into B group (IS), C group (total senna flavonoids low dose), D group (total senna flavonoids high dose), E group (positive drug), F group (high dose of total senna flavonoids+U-46619F) and A group (the sham operation), where group A and group B were given intragastric and intraperitoneal injections of normal saline; group C was given 100 mg·kg^-1 total senna flavonoids by intragastric administration; group D was given 200 mg·kg^-1 total senna flavonoids by intragastric administration; group E was given 1.0 mg·kg^-1 nimodipine by intraperitoneal injection; group F was given intragastric administration of 200 mg·kg^-1 total senna flavonoids and 30 μg·kg^-1 U-46619 by intraperitoneal injection; each group was administered once a day for two consecutive weeks. After the intervention, the modified neurological severity (mNSS) score was used to evaluate the nerve injury; the triphenyltetrazolium chloride staining (TTC) was used to detect the ratio of cerebral infarction area; the brain tissue was separated, and hematoxylin-eosin was used for pathological changes; the expression of nerve growth factor (NGF) was detected by immunohistochemistry; the apoptosis changes of striatal dopaminergic neurons were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method (TUNEL); the relative expression levels of Bcl-2 related X protein (Bax), RhoA, ROCK and B-cell lymphoma factor 2 (Bcl-2) proteins were detected by immunoblotting.

The nerve injury scores for groups A, B, D, E, and F were (0.15±0), (11.24±1.26), (4.06±0.42), (3.52±0.38) and (7.18±0.73) points, respectively; the ratio of infarct area were (0±0)%, (27.86±2.81)%, (11.57±1.27)%, (12.07±1.24)% and (18.07±1.88)%; the relative expression levels of NGF were 34.11±3.51, 15.86±1.61, 32.07±3.28, 32.11±3.32 and 22.87±2.31; the apoptosis of dopaminergic neurons were (6.57±0.68)%, (27.81±2.82)%, (12.75±1.31)%, (12.52±1.27)% and (20.47±2.11)%; the aforementioned indicators of group B were compared with those of group A; those of groups C and D were compared with group B; and those of group F were compared with group D, all showing statistically significant differences (all P<0.05).

The total flavonoids of Cynanchum paniculatum have neuroprotective effects on IS rats, and the mechanism may be related to the activation of the RhoA/ROCK signaling pathway.

To investigate the efficacy and safety of anlotinib combined with neoadjuvant chemotherapy (NAC) in elderly patients with triple-negative breast cancer (TNBC).

Elderly patients with TNBC who underwent NAC followed by modified radical mastectomy were enrolled and divided into control group and treatment group based on their treatment regimens. Control group received the TEC regimen as preoperative NAC, while treatment group received additional oral administration of anlotinib hydrochloride capsules (12 mg once daily, in a 2-weeks-on/1-week-off cycle) for 4 cycles. Carbohydrate antigen 153 (CA153), carcinoembryonic antigen (CEA), growth differentiation factor-3 (GdF3), carbohydrate antigen 19-9, Ki-67 positive rate, cyclooxygenase-2 (COX2), vascular endothelial growth factor (VGEF), bone sialoprotein, prolactin, insulin-like growth factor-1, clinical efficacy and long-term survival outcomes were compared between the two groups, and the safety was conducted.

A total of 93 patients were enrolled and divided into control group (n=48) and treatment group (n=45). After treatment, the objective response rates (ORR) were 43.75% (21 cases/48 cases) in control group and 64.44% (29 cases /45 cases) in treatment group, respectively; while the disease control rates (DCR) were 70.83% (34 cases /48 cases) and 88.89% (40 cases /45 cases), respectively; CA 153 levels were (24.59±3.57) and (22.21±3.86) μ·mL^-1, respectively; GdF3 levels were (117.53±18.29) and (102.24±15.47) ng·L^-1, respectively; CEA levels were (4.19±0.85) and (3.72±0.64) ng·L^-1, respectively; the Ki-67 positivity rates were 37.50% and 17.78%, respectively; COX-2 levels were (88.73±21.64) and (74.38±19.51) ng·L^-1, respectively; VEGF levels were (38.23±7.15) and (34.74±6.32) ng·L^-1, respectively; the progression-free survival (PFS) rates were 33.33% (16 cases/48 cases) and 46.67% (21 cases/45 cases), respectively. Statistically significant differences were observed in all the above indicators between the two groups (all P<0.05, P<0.01, P<0.001). The adverse drug reactions during chemotherapy in treatment group and control group included anemia, decreased appetite, neutropenia, leukopenia, thrombocytopenia, headache, hypertension, nausea and vomiting, fatigue, elevated thyroid hormones, diarrhea, constipation, infection, alopecia, impaired liver and kidney function, and hand-foot syndrome. The total incidence of adverse drug reactions was 64.58% (31 cases/48 cases) in control group and 71.11% (32 cases /45 cases) in treatment group, with no statistically significant difference between the groups (P>0.05). The overall survival (OS) rate was 60.42% (29 cases /48 cases) in control group and 68.89% (31 cases /45 cases) in treatment group, and the difference was not statistically significant (P>0.05).

Anlotinib combined with NAC regimen for elderly TNBC patients shows good efficacy, can improve Ki-67 positive rate and serum COX-2 and vascular endothelial growth factor levels, improve long-term survival, and has high safety.

To investigate and analyze the current state of professional training for clinical research coordinators (CRCs), explore the differences in CRC cultivation between clinical trial institutions and site management organizations (SMOs), and provide references for optimizing the CRC training system.

A total of 613 active CRCs was conducted using convenience sampling method and quota sampling method. The questionnaire includes basic information, induction teaching methods, training frequency, training content, training satisfaction and training needs, etc. Data were collected by the ‘questionnaire star’, statistically analyzed using SAS 9.3 software, and differences were compared using the chi-square test.

There were significant differences between institutions and SMO companies in the education, professional background and working years of CRC (All P<0.05). Institutional CRC generally has a higher degree and more nursing background, while SMO company CRC contains a certain proportion of people with non-medical background. In terms of training, institutional CRC prefers moderate frequency training (6 to 12 times per year), while SMO CRC prefers more frequent high frequency training (more than 12 times per year). SMO company has a high utilization rate of online training, and institutional CRC has some deficiencies in communication skills training. Overall, the CRC is relatively satisfied with the existing training system.

Institutions and SMO companies should develop reasonable training plans according to their own characteristics and reduce unnecessary training burden to improve the work efficiency and clinical trial quality of CRC. It is recommended to adopt more offline training forms, and to conduct targeted training according to the individual needs of CRC.

To explore the clinical efficacy and safety of different doses of buspirone hydrochloride tablets combined with venlafaxine hydrochloride sustained-release tablets in the treatment of elderly patients with generalized anxiety disorder (GAD) accompanied by depression.

Elderly patients with GAD accompanied by depression were taken as the research subjects. The control group was given oral treatment with venlafaxine hydrochloride sustained-release tablets (75 mg·d^-1, once daily) and buspirone hydrochloride tablets (the initial dose was 5 mg each time, and it was increased by 5 to 10 mg every 2 to 3 days according to the patient’s tolerance, and then increased to 10 mg each time, twice daily after 2 weeks). The treatment group was treated with venlafaxine hydrochloride sustained-release tablets on the basis of the control group. Different doses of buspirone hydrochloride tablets were given orally for treatment (the initial dose was 5 mg each time, and it was increased by 5 to 10 mg every 2 to 3 days according to the patient’s tolerance, and then increased to 20 mg each time, twice a day after 2 weeks). Both groups were treated continuously for 8 weeks. The clinical efficacy, Hamilton anxiety scale (HAMA) scores, anxiety and depression scores, sleep conditions, levels of neurotransmitters for mood regulation, neurological function levels and endocrine metabolic levels of the two groups of patients were compared, and the safety was evaluated.

A total of 100 cases were screened, and 95 cases were enrolled, including 49 cases in the control group and 46 cases in the treatment group. In the control group, 3 cases dropped out due to loss to follow-up, and eventually 46 cases were included in the statistical analysis. There were no patients with dropout in the treatment group. Eventually, 46 cases were included in the statistical analysis. After 8 weeks of treatment, the HAMA scores of the treatment group and the control group were (17.93±2.85) and (19.51±2.96) points, respectively; the Hamilton depression scale scores were (18.85±3.11) and (20.37±3.08) points, respectively; the scores of the Beck despair scale were (4.64±1.44) and (5.37±1.53) points, respectively; the scores of the Chinese version of the self-rating scale for constrained neurosis were (25.63±4.17) and (27.73±4.31) points, respectively; the scores of melatonin were (38.83±5.78) and (36.24±5.27) pg·mL^-1, respectively; the cortisol levels were (109.36±11.92) and (115.41±12.17) ng·mL^-1, respectively; and the Pittsburgh sleep quality index scores were (8.28±2.35) and (9.48±2.46) points, respectively; the values of substance P were (112.17±10.66) and (117.61±11.37) ng·L^-1, respectively; and those of γ -aminobutyric acid were (5.65±0.65) and (5.31±0.67) μmol·L^-1, respectively; the glutamic acid were (25.02±3.22) and (26.75±3.28) mg·L^-1, respectively; the brain-derived neurotrophic factor were (14.33±1.56) and (13.54±1.46) ng·mL^-1, respectively; the glial cell-derived neurotrophic factor were (556.41±62.12) and (525.57±64.72) pg·mL^-1, respectively; and the glial fibrillary acidic protein were (2.51±0.28) and (2.67±0.35) ng·mL^-1, respectively; the free thyroxine were (13.33±1.96) and (12.41±1.85) pmol·L^-1, respectively; and the 25-hydroxyvitamin D₃ was (33.46±4.39) and (31.57±3.14) ng·mL^-1, respectively; the prolactin levels were (22.56±3.94) and (24.59±3.78) ng·mL^-1, respectively. The differences in the above indicators of the treatment group were statistically significant with control group (all P<0.05). Two groups of patients experienced adverse drug reactions such as dizziness, headache, nausea and vomiting, constipation and dry mouth. The total effective rates of the treatment group and the control group were 82.61% and 73.91%, respectively, and the total incidences of adverse drug reactions were 15.22% and 13.04%, respectively. There were no statistically significant differences between the two group (all P>0.05).

The application of 20 mg buconspirone tablets combined with venlafaxine tablets in the treatment of elderly patients with GAD and depression can improve sleep conditions and clinical symptoms, regulate neurological function and endocrine metabolism, and has certain safety.