To investigate the mechanism of soyisoflavones (SIF) alleviate the rats with polycystic ovary syndrome (PCOS) by regulating the miR-29a-3p/insulin-like growth factor 1 (IGF1) molecular axis.

The female SD rats were divided into normal, model and experimental groups, with 12 rats in each group. The model and experimental groups were induced with gavage letrozole to construct the PCOS rat model. After successful modeling, the normal and model groups were given 100 mg·kg^-1 cellulose sodium carboxymethyl by gavage, and the experimental group was given 100 mg·kg^-1 SIF by gavage. Three groups were treated for 21 d with once a day. The apoptosis rate of ovarian tissues was detected by TdT-mediated dUTP nick-end labeling, the serum sex hormone levels were detected by enzyme-linked immunosorbnent assay, the expression levels of miR-29a-3p and IGF1 were detected by real-time fluorescence quantitative plymerase chain reaction, and the positive expression level of IGF1 was detected by immunohistochemistry in ovarian tissues. Ovarian granulosa cells from PCOS model rats were divided into blank group (normal culture), experimental group (100 μg·L^-1 SIF), miR-29a-3p group (after transfection with miR-29a-3p inhibitor, 100 μg·L^-1 SIF culture was given) and IGF1 group (after transfection with miR-29a-3p inhibitor and si-IGF1, 100 μg·L^-1 SIF culture was given). Apoptosis of ovarian granulosa cells was measured by mitochondrial membrane potential analysis, and the expression level of apoptosis-related proteins was detected by Western blotting.

In the animal experiments, the apoptosis rates of experimental, model and normal groups were (16.14±4.09)%, (23.75±5.68)% and (10.83±3.54)%; the luteinizing hormone levels were (26.81±5.99), (41.55±9.84) and (17.63±3.19) mU·mL^-1; the follicle stimulating hormone levels were (51.09±8.72), (41.66±9.87) and (67.91±18.58) pg·mL^-1; the relative expression levels of miR-29a-3p were 0.89±0.08, 0.47±0.06 and 1.00±0.11; the relative expression levels of IGF1 mRNA were 1.42±0.39, 2.36±0.54 and 1.00±0.07; the positive expression levels of IGF1 were 1.37±0.31, 1.98±0.41 and 1.00±0.12, respectively. The differences of above indexes in the experimental and normal groups were statistically different from those in the model group (all P<0.05). In the cell experiments, the mitochondrial membrane potentials of the experimental, miR-29a-3p, IGF1 and blank groups were 1.28±0.13, 0.66±0.05, 1.47±0.19 and 0.54±0.06; the relative expressions levels of the B-cell lymphoma-2-associated X protein were 0.73±0.06, 0.97±0.11, 0.62±0.07 and 1.00±0.08; the relative expression levels of B-cell lymphoma-2 were 1.74±0.23, 1.14±0.18, 2.11±0.37 and 1.00±0.05, respectively. The differences of above indexes in the experimental and IGF1 groups were statistically different from those in the miR-29a-3p group (all P<0.05).

SIF may delay the progression of PCOS rats by regulating miR-29a-3p/IGF1 pathway to mediate the apoptotic process in ovarian cells.

To explore the effect of fingolimod (FTY720) on depressive behavior in depressive disorder rats and its related mechanism.

The SD rats were divided into the following groups: Control group (normal feeding), model group (depression model construction), and low, medium, high groups (administering 0.1, 0.3 and 1.0 mg·kg^-1 FTY720 prior to constructing the depression model, respectively), with 10 rats in each group. The hippocampal tissue morphology was assessed using hematoxylin-eosin (HE) staining; depression symptoms were evaluated through the sucrose preference test; cognitive function was assessed using the Morris water maze test; neuronal apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL); levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway-related proteins were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence; dopamine (DA) content in different brain regions was analyzed by high-performance liquid chromatography.

After different treatments, the sugar-water preference rates in control, model and low, medium, high groups were (81.95±9.06)%, (59.72±8.32)%, (62.34±7.58)%, (68.08±7.94)% and (79.61±9.25)%, respectively; the escape latencies were (18.73±2.06), (34.25±3.87), (31.64±2.92), (25.97±2.43) and (19.86±1.95) s, respectively; apoptosis rates were (3.93±0.65)%, (28.75±5.94)%, (24.63±3.21)%, (15.27±2.58)% and (6.08±1.74)%, respectively; NLRP3 mRNA relative expression levels were 1.00±0.17, 4.89±0.64, 4.31±0.72, 2.52±0.58 and 1.87±0.25; ASC mRNA relative expression levels were 1.00±0.14, 2.67±0.53, 2.28±0.39, 1.54±0.26 and 1.39±0.21; DA contents in PFC region were (795.42±64.38), (547.93±52.65), (571.08±51.97), (662.45±73.89) and (748.96±81.53) μg·g^-1; DA contents in NAc region were (2 186.53±124.97), (1 672.84±109.25), (1 769.65±112.14), (1 904.27±106.63) and (2 065.92±127.58) μg·g^-1; DA contents in the VTA region were (1 765.83±108.29), (1 316.73±115.84), (1 378.52±94.36), (1 494.76±103.21) and (1 653.94±108.45) μg·g^-1. Compared with the control group, the above indexes in the model group were statistically significant (all P<0.001). Compared with the model group, the above indexes in the middle dose group were statistically significant (all P<0.05). Compared with the model group, the above indexes in the high dose group were statistically significant (all P<0.001).

FTY720 can regulate neuronal damage and cognitive function in depressed model rats, and its antidepressant mechanism may be related to inhibiting the activation of NLRP3 inflammasome pathway and increasing the content of DA in the neural circuit of PFC-ARC-VTA.

To investigate prescription of semaglutide and analyzed status of semaglutide administration in China’s real-world.

The prescription including semaglutide were extracted from 9 cities across China in first quarter of 2023. We analyzed the current administration of semaglutide and risk factors of off-label use of semaglutide by multivariant logistic regression.

A total of 10 884 patients were included after data screening, about 70% patients were 34-64 years old. Endocrinology was the most common prescription department. Diabetes was diagnosed in 76.78% patients and 765 patients combined chronic complications of diabetes, of which diabetic neuropathy (470 cases, 4.32%) and diabetic nephropathy (248 cases, 2.28%) were the most common complications. Cardiovascular diseases and risk factors were diagnosed in 2 429 patients. Hypertension (1 379 cases, 12.67%) and hyperlipemia (1 342 cases, 11.31%) were the most common cardiovascular disease and risk factors. While 56.74% (6 176 cases) patients were treated by semaglutide singe-agent in general, 36.79% (3 075 cases/ 8 357 cases) patients with diabetes combined oral hypoglycemic drugs or insulin, and biguanides and sodium-dependent glucose transporters 2 inhibitors were used mostly. About 1/4 patients without diabetes off-label administrated semaglutide. According to the logistic regression, risk factors of off-label use were elder age, came from first-tier cities, prescription from endocrinology and a greater number of combined cardiovascular diseases and risk factors.

Semaglutide -based therapy regimens in patients with diabetes are fairly standardized according to clinical guidelines, while off-label use in patients without diabetes are supported by clinical evidence and guidelines to some extent.

To evaluate the bioequivalence of rotigotine patches after a single dose in healthy Chinese subjects.

Using randomized, open, fasting, single-dose, two-preparation, four-cycle, two-sequence exact repeat crossover design, 24 healthy subjects applied one of the test preparation or reference preparation (4.5 mg·10 cm^-2) to the abdominal skin. To determine the drug concentration in human plasma by liquid chromatography-tandem mass spectrometry. Pharmacokinetic software was used to calculate the relevant pharmacokinetic parameters, and the bioequivalence evaluation was carried out.

The C_max of the test preparation and the reference preparation of rotigotine patches were (275.04±98.93) and (277.11±96.78) pg·mL^-1, the AUC_0-t were (5 011.91±2 015.32) and (4 934.28±2 095.76) h·pg·mL^-1, the AUC_0-∞ were (5 092.68±2 033.23) and (5 160.61±2 052.04) h·pg·mL^-1, respectively. C_max, AUC_0-t and AUC_0-∞ geometric mean (90% confidence interval) were all in the equivalent interval of 80.00%-125.00%.

The test preparation and reference preparation of rotigotine patches are bioequivalent in healthy Chinese subjects.

To observe the analgesic effects and safety of flurbiprofen axetil injection combined with dezocine injection in postoperative patient-controlled intravenous analgesia (PCIA) for patients with intertrochanteric femoral fractures (IFF).

IFF patients were divided into control group and treatment group based on cohort method. The control group was given 0.5 mg·kg^-1 dezocine injection diluted with 100 mL of 0.9% NaCl and then injected with analgesic pump. The treatment group was given 1.0 mg·kg^-1 flurbiprofen axetil injection + 0.3 mg·kg^-1 dezocine injection diluted with 100 mL of 0.9% NaCl and then injected with analgesic pump Postoperative visual analog scale (VAS), Ramsay sedation score (RSS), mini-mental state examination (MMSE), hemodynamic parameters (heart rate, mean arterial pressure), and safety evaluations were compared between the two groups.

A total of 67 patients were enrolled in the control group; and 53 patients were enrolled in the treatment group. Postoperative VAS scores at 2, 12 and 24 h were (1.95±0.39), (2.52±0.31) and (2.21±0.40) points in the treatment group, and (2.47±0.44), (3.17±0.34) and (2.76±0.37) points in the control group. RSS scores at the same time were (3.15±0.33), (3.39±0.35) and (3.72±0.46) points for the treatment group, and (2.79±0.54), (3.16±0.43) and (3.28±0.68) points for the control group. MMSE scores at 1, 3, and 7 days postoperatively were (25.08±2.40), (26.80±2.01) and (27.64±2.59) points in the treatment group, and (22.36±2.24), (24.53±2.25) and (25.37±1.84) points in the control group. Thirty minutes after surgery, the heart rate was (86.61±4.80) beat·min^-1 in the treatment group and (82.74±4.17) beat·min^-1 in the control group, while the mean arterial pressure was (74.28±4.49) mmHg and (71.76±3.42) mmHg, respectively. These indicators in the treatment group showed statistically significant differences compared to the control group (all P<0.05). The main adverse drug reactions in the treatment group were dizziness, fatigue, drowsiness, and nausea/vomiting, while the control group also had respiratory depression in addition to dizziness, fatigue, drowsiness, and nausea/vomiting. The total incidence of adverse drug reactions was 7.55% (4 cases/53 cases) in the treatment group and 20.90% (14 cases/67 cases) in the control group, with statistically significant difference (P<0.05).

Flurbiprofen axetil injection combined with dezocine injection for postoperative PCIA in IFF patients provides superior analgesic and sedative effects compared to dezocine monotherapy, enhances cognitive function, stabilizes hemodynamics, and has good safety.

To explore the effect and mechanism of circular RNA RAS p21 protein activator 2 (circRASA2) mediated by nobiletin (NOB) on lipopolysaccharide (LPS)-induced hPDLCs in periodontal ligament cells.

hPDLCs cells were divided into control group, model group (hPDLCs cells were treated with 10 μg·mL^-1 LPS for 24 h), NOB-H group (Based on the model group, 20 μmol·L^-1 NOB was given for 24 h), NOB+oe-NC group (hPDLCs cells transfected with oe-NC were treated with 20 μmol·L^-1 NOB) and NOB+oe-circRASA2 group (hPDLCs cells transfected with oe-circRASA2 were treated with 20 μmol·L^-1 NOB). Quantitative real time polymerase chain reaction was used to detect the mRNA expression levels of circRASA2. The secretion levels of inflammation-related factors were detected by enzyme-linked immunosorbent assay. Western blot analysis of slit homolog 2 (Slit2)/mitogen-activated protein kinase (MAPK) signaling pathway related protein expression levels.

The relative expression levels of circRASA2 in control group, model group and NOB-H group were 1.00±0.15, 2.83±0.50 and 1.36±0.27, respectively. The levels of interleukin-1β in control group, model group, NOB-H group, NOB+oe-NC group and NOB+oe-circRASA2 group were (144.82±24.89), (367.54±65.73), (228.51±40.24), (219.78±36.94) and (324.25±61.57) mg·mL^-1, respectively; interleukin-18 levels were (167.50±27.33), (394.68±74.96), (212.47±39.51), (205.93±41.18) and (358.11±66.27) mg·mL^-1, respectively; the relative expression levels of Slit2 protein were 1.00±0.18, 2.35±0.41, 1.61±0.29, 1.57±0.27 and 2.14±0.38, respectively; the ratios of phospho-p38 mitogen-activated protein kinase/p38 mitogen-activated protein kinase protein were 1.00±0.16, 2.08±0.37, 1.39±0.25, 1.33±0.21 and 1.92±0.34, respectively. The above indexes in the model group were compared with the control group, the NOB-H group was compared with the model group, and the NOB+oe-circRASA2 group was compared with the NOB+oe-NC group, and the differences were statistically significant (all P<0.05).

NOB alleviates LPS-induced inflammation and inhibits pyroptosis in hPDLCs cells by inhibiting circRASA2 expression, possibly by inhibiting Slit2/MAPK signaling pathway.

To analyze the clinical characteristics of patients infected with emphysematous pyelonephritis (EPN) and the drug resistance of the strains. To enhance the understanding of EPN, provide a basis for the selection of antibacterial drugs in clinical practice.

Evaluated 15 EPN patients’ clinical characteristics and outcome, analysis of pathogenic bacteria and drug resistance.

Among the 15 EPN patients, 66.67% (10 cases/15 cases) patients were cured, 13.33% (2 cases/15 cases) patients died, and 20.00% (3 cases/15 cases) patients were adverse. Fluid cultures identified 12 strains of pathogenic bacteria, with Escherichia coli being the most prevalent (66.67%, 8 cases/12 cases), followed by Klebsiella pneumoniae (25.00%, 3 cases/12 cases), and Pseudomonas aeruginosa was the least common (8.33%, 1 cases/12 cases), 75.00% (9 cases/12 cases) of the strains were multi-drug resistant. The drug sensitivity test results showed that amikacin, cefotetan, and cefoperazone sulbactam were 100.00% sensitive antibiotics; the sensitivity rates of meropenem, imipenem, and ertapenem were 91.67%.

Patients with EPN have high mortality and poor prognosis. Escherichia coli was the most common pathogenic bacteria, followed by Klebsiella pneumoniae, and the proportion of multi-drug resistant strains was high. We recommend the use of over 90% of the pathogen-sensitive drugs with susceptibility about 90% identified in this study.

To investigate the possible mechanism of action of sinomenine (Sin) in the treatment of collagen-induced arthritis (CIA) rats by regulating macrophage polarization.

Wistar rats were randomly divided into control group (normal diet and care), model group (CIA model was established with bovine type Ⅱ collagen at the tail), experimental-L, -M, -H groups (all on the basis of the model group, 40, 80 and 160 mg·kg^-1 Sin by gavage respectively), inh-NC group and inh-miR-885-5p group[on the basis of the experimental-H group, the two groups were injected with a negative control of microRNA-885-5p (miR-885-5p) and miR-885-5p inhibitor in the tail vein, respectively)], for four weeks, with 10 rats in each group. The arthritis index (AI) and plantar swelling of rats in each group were statistically analyzed. The pathological conditions of the synovial tissue of the ankle joint were observed by hematoxylin-eosin staining. Real-time fluorescent quantitative polymerase chain reaction was performed to examine the relative expression level of miR-885-5p in rat synovial tissue. Western blot was carried out to detect the expression of related proteins in the synovial tissue of rats. Enzyme-linked immunosorbent assay was used to detect the level of serum inflammatory factors. Terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) was used to detect the apoptosis of rat synovial cells.

The AI scores of the control group, model group and experimental-H group were 0, (7.20±1.38) and (5.50±1.10) scores, respectively; the paw swelling were 35.32±7.05, 72.46±14.47 and 51.65±10.31, respectively; the relative expression levels of miR-885-5p were 1.00±0.18, 0.52±0.10 and 0.71±0.14, respectively. The relative expression levels of suppressor of cytokine signaling 1 (SOCS1) protein in the control, model group, experimental-H group, inh-NC group and inh-miR-885-5p group were 1.00±0.18, 0.51±0.10, 0.75±0.15, 0.71±0.14 and 0.55±0.11, respectively; the levels of interleukin (IL)-6 were (35.29±7.05), (215.82±43.15), (121.33±24.25), (115.62±23.08) and (207.39±41.36) pg·mL^-1, respectively; the apoptosis rates were (31.47±6.29)%, (12.19±2.43)%, (22.03±4.41)%, (20.16±4.03)% and (13.37±2.66)%, respectively. The above indexes in the experimental-L, -M, -H groups were dose-dependent, and the differences in the above indexes between the experimental-H group and the control group were statistically significant compared with the model group (P<0.05, P<0.01, P<0.001), and the differences in the above indexes between the inh-miR-885-5p group and the inh-NC group were also all statistically significant (all P<0.05).

Sin can regulate macrophage polarization, and improve synovial inflammation in CIA rats, which may be related to the up-regulation of miR-885-5p expression and activation of SOCS1/signal transducer and activator of transcription 3 (STAT3) signaling pathway.