To investigate the protective effect of hedysarum polybotrys polysacchcaide (HPS) on intestinal mucosal barrier in rats with splenic deficiency type diabetic gastroparesis.

The rat model of spleen deficiency DGP was prepared by multifactorial combined with low-dose intraperitoneal injection of Stretocin. The rats were randomly divided into blank group (pure water gavage), model group (pure water gavage), positive control group (0.09 g·kg^-1 metformin hydrochloride sustained-release tablet) and experimental-H,-M,-L groups (0.20, 0.10, 0.05 g·kg^-1 HPS), each group was administered by gavage once a day for 8 W. Measured blood glucose, diamine oxidase (DAO), lipopolysaccharides (LPS), D-lactate contents (D-LA) in serum by enzyme linked immunosorbent assay method; Claudin-1, Occludin, Zonula Occluden-1 (ZO-1) mRNA and protein expressions in lleal tissue were detected by reverse transcription-polymerase chain reaction and Western blot.

The blood glucose in the blank group, model group, positive control group, experimental-H,-M,-L groups were (5.04±0.40), (30.71±1.21), (18.63±6.72) and (19.90±3.30)mmol·L^-1; the DAO were (49.56±6.13), (192.19±24.40), (130.63±19.90) and (120.24±17.53) pg·mL^-1; the LPS were (41.11±4.56), (99.67±6.63), (64.51±8.59) and (63.07±4.89) ng·L^-1; the D-LA were (506.45±52.22), (1 826.49±224.17), (1 166.47±121.78) and (1 344.82±130.65) μg·L^-1; the relative expression levels of Claudin-1 mRNA were 1.03±0.32, 0.25±0.12, 0.94±0.40 and 0.71±0.21; the relative expression levels of Occludin mRNA were 1.07±0.48, 0.26±0.06, 1.23±0.42 and 0.99±0.47; the relative expression levels of ZO-1 mRNA were 1.00±0.13, 0.43±0.18, 0.85±0.07 and 0.69±0.08; the relative expression levels of Claudin-1 protein were 1.00±0.00, 0.21±0.19, 0.56±0.31 and 0.87±0.31; the relative expression levels of Occludin protein were 1.01±0.27, 0.38±0.11, 0.88±0.10 and 0.85±0.18; the relative expression levels of ZO-1 protein were 1.00±0.14, 0.43±0.04, 0.77±0.02 and 0.67±0.16. Compared with the the blank group, the above indexes in the model group had statistical significance (P<0.01, P<0.05); compared with the model group, the above indexes in the experimental-H had statistical significance (P<0.01, P<0.05).

HPS can reduce intestinal mucosal injury and maintain the integrity of the intestinal mucosal barrier in spleen deficiency DGP rats.

To evaluate the bioequivalence of domestic bromhexine hydrochloride granules and imported bromhexine hydrochloride fine granules in Chinese healthy subjects under fasting and fed states.

A single-center, randomized, open-label, fasting and fed single-dose, two-preparation, two-sequence, and two-period crossover study design was used. Forty-eight Chinese healthy subjects were enrolled in fasting and fed trial, respectively. A random crossover, single-dose of bromhexine hydrochloride granules 0.4 g(containing 8 mg bromhexine) or bromhexine hydrochloride fine granules 0.4 g (containing 8 mg bromhexine) were orally given to subjects. Blood samples were collected at different time points, and plasma concentrations of bromhexine were measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Phoenix WinNonlin 8.3 software was used for data analysis.

In the fasting group, the main pharmacokinetic parameters of bromhexine in plasma after taking the test and reference preparations: C_max were (18.29±7.80) and (19.92±10.23) ng·mL^-1, AUC_0-t were (31.52±12.23) and (32.22±12.32) ng·h·mL^-1, AUC_0-∞ were (34.43±13.60) and (34.84±13.36) ng·h·mL^-1, respectively. In the fed group, the main pharmacokinetic parameters of bromhexine in plasma after taking the test and reference preparations: C_max were (12.55±6.27) and (12.64±6.51) ng·mL^-1, AUC_0-t were (58.86±24.38) and (60.60±26.44) ng·h·mL^-1, AUC_0-∞ were (68.27±30.76) and (94.01±113.13) ng·h·mL^-1, respectively. The 90% confidence intervals of the geometric mean ratio of the two preparations in fasting group: C_max was 88.79%-101.49%, AUC_0-t was 93.69%-102.15%, AUC_0-∞ was 94.59%-102.95%; in fed group: C_max was 93.08%-106.82%, AUC_0-t was 94.30%-102.80%, AUC_0-∞ was 92.97%-103.89%.

In this study, the test preparation bromhexine hydrochloride granules and the reference preparation bromhexine hydrochloride fine granules were bioequivalent in healthy Chinese subjects.

To explore the underlying mechanism of TanshinoneⅡA (TanⅡA) exerted in myocardial infarction (MI) through nuclear factor E2-related factor 2 (NRF2)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/pyroptosis axis.

SD rats were randomly divided into sham operation group [only exposed the heart without left anterior descending (LAD) ligation], model group (LAD ligation) and experimental group (LAD ligation and 10 mg·kg^-1 TanⅡA). 2,3,5-Triphenyte-trazoliumchloride (TTC) staining was used to detect the area of infarction; Western blot was utilized to investigate the expression level of NRF2, NLRP3 and gasdermin D (GSDMD) in myocardial tissue. The H9c2 cells were divided into blank group (normal culture), model group [oxygen-glucose deprivation (OGD) culture], control group (normal culture and 40 μmol·L^-1 TanⅡA) and combined group (OGD culture and 40 μmol·L^-1 TanⅡA). Western blot was utilized to investigate the expression level of NRF2, GSDMD in cardiomyocyte. Creatine kinase MB (CK-MB) in cell culture supernatant were detected by automatic biochemical analyzer.

The proportion of myocardial infarction area in the sham operation group, model group and experimental group were 0, (58.64±13.41)% and (41.69±8.73)%, respectively; the relative expression of NLRP3 protein were 1.01±0.10, 2.12±0.26 and 1.48±0.11, respectively; the relative expression of GSDMD protein were 1.03±0.17, 2.22±0.20 and 1.40±0.17, respectively; the relative expression of NRF2 protein were 1.12±0.29, 0.51±0.02 and 0.96±0.10, respectively; the indicators of the model group compared with the sham operation group, and the indicators of the experimental group were compared with the model group, the differences were statistically significant (all P<0.05). The CK-MB in blank group, model group, control group and combined group were (54.30±19.24), (208.60±38.19), (46.76±13.63) and (126.10±42.87) U·L^-1, respectively; the relative expression of NRF2 protein were 1.37±0.14, 0.44±0.08, 1.34±0.17 and 0.79±0.11, respectively; the relative expression of GSDMD protein were 0.95±0.26, 1.97±0.17, 1.04±0.20 and 1.16±0.16, respectively. The indicators of the model group compared with the blank group, and the indicators of the combined group were compared with the model group, the differences were statistically significant (all P<0.05).

TanⅡA can alleviate myocardial infarction-induced myocardial injury through regulation NRF2/NLRP3/pyroptosis axis.

To investigate the protective effects of monosialotetrahexosylganglioside (GM1) on hypoxic-ischemic brain damage (HIBD) in neonatal rats based on the ubiquitin C-terminal hydrolase L1 (UCH-L1)/brain-derived neurotrophic factor (BDNF) signaling pathway.

Twenty-day-old SD rats were randomly divided into model group, sham group and experimental group, with 10 rats in each group. Rats in model group and experimental group were lapped with left common carotid artery and placed in anoxic chamber with a certain oxygen to nitrogen ratio (8∶92) for 2 h to construct HIBD model. After the successful construction of the model, the experimental group was intraperitoneally injected with 20 mg·kg^-1·d^-1GM1, and the model group and sham group were injected with 0.9 % NaCl (0.25 mL·kg^-1). The modified neurological severity score (mNSS) was used to evaluate the degree of neurological damage in the treated rats. Cerebral infarction was detected by 2,3,5-triphenyte-trazoliumchloride staining method; cerebral water content was determined by wet and dry weight method; cognitive ability was assessed by Morris water maze test; apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; inflammatory factors were detected by enzyme-linked immunosorbent assay; UCH-L1 and BDNF protein levels were detected by Western blot.

After different treatments, the mNSS scores of sham group, model group and experimental group were (0.10±0.02), (2.60±0.45) and (1.50±0.20) points; the cerebral infarction rates were (0.89±0.11)%, (32.56±4.12)% and (18.56±2.52)%; the cerebral water content were (68.25±7.05)%, (88.87±9.26)% and (71.11±8.11)%; the latent period were (22.60±2.86), (38.60±4.11) and (25.50±3.33) s; the platform residence time were (125.50±17.68), (80.60±9.68) and (115.80±13.89) s; the platform crossing times were (2.80±0.35), (0.70±0.09) and (1.80±0.30) times; the apoptosis rates were (6.65±0.74)%, (21.88±3.05)% and (13.62±2.62)%; the tumor necrosis factor-α levels were (30.05±3.85), (121.61±18.85) and (82.14±11.65) pg·mL^-1; the levels of interleukin-1 beta were (92.55±12.15), (321.25±41.24) and (212.32±25.61) pg·mL^-1; interleukin-6 levels were (184.32±20.54), (275.62±31.12) and (208.65±22.65) pg·mL^-1; UCH-L1 protein levels were 1.00±0.22, 1.75±0.34 and 1.40±0.28; BDNF protein levels were 1.00±0.21, 1.68±0.38 and 2.54±0.41. There were statistically significant differences between sham group and model group (P<0.01, P<0.001). There were statistically significant differences between model group and experimental group (P<0.05, P<0.001).

GM1 can improve nerve cell apoptosis and inflammatory response by activating UCH-L1/BDNF signaling pathway, and play a protective role in neonatal rat HIBD.

To investigate the protective effect of Danzhi Jiangtang capsule on kidney of db/db mice with diabetic kidney disease (DKD) and its effects on the autophagy-lysosomal pathway.

The db/db mice were randomly divided into model group (0.2 mL·d^-1 0.9% NaCl), positive control group (45 mg·kg^-1·d^-1 irbesartan) and experimental-H, -M, -L groups (1 800, 900 and 450 mg·kg^-1·d^-1 Danzhi Jiangtang capsule), and another db/m mice were taken as blank group (0.2 mL·d^-1 0.9% NaCl), which were continuously infused for 8 weeks. The expression levels of sequestosome1 (P62), microtubule-associated protein light chain 3 (LC3), transcription factor EB (TFEB), lysosomal associated membrane protein 1 (LAMP-1) and cathepsin D (CTSD) were detected in renal tissues by Western blot.

The relative expression levels of P62 protein in blank group, model group, positive control group and experimental-H,-M,-L groups were 1.00±0.04, 7.66±0.27, 3.52±0.11, 2.21±0.09, 2.86±0.10 and 4.05±0.16; the LC3Ⅱ/Ⅰ levels were 1.00±0.02, 0.17±0.01, 0.71±0.08, 0.86±0.05, 0.80±0.04 and 0.73±0.06; the TFEB protein levels were 1.00±0.01, 0.17±0.01, 0.30±0.01, 0.63±0.01, 0.45±0.01 and 0.42±0.01; the LAMP-1 protein levels were 1.00±0.01, 0.28±0.02, 0.42±0.01, 0.77±0.00, 0.55±0.03 and 0.40±0.02; the CTSD protein levels were 1.00±0.04, 0.27±0.03, 0.47±0.04, 0.73±0.02, 0.63±0.01 and 0.52±0.02. The differences between the above indexes in the experimental-H, -M, -L groups and the model group were statistically significant (all P<0.01).

Danzhi Jiangtang capsule can improved renal damage in db/db mice, which may be related to the repair of autophagy-lysosome pathway, accelerate clearance of abnormal proteins and degradation of organelles.

To investigate the intervention effect and mechanism of β-ecdyssterone on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) based on the regulation of autophagy by the adenosine 5′-monophosphate kinase-activated protein (AMPK)/mammalian target of rapamycin (mTOR).

BMSCs cells were divided into control group (normal culture), low-, middle- and high-dose groups (intervened with 0.01, 0.10 and 1.00 μmol·L^-1 ecdysterone). The expression of cell genes was determined by real-time quantitative polymerase chain reaction (qRT-PCR); and the relative expression level of cell proteins was determined by immunofluorescence (IF).

The relative expression levels of alkaline phosphatase (ALP) mRNA in the control group, low-, middle and high-dose groups were 1.01±0.14, 1.22±0.05, 1.28±0.05, 1.59±0.20; the relative protein expression levels of Runt-related transcription factor 2 (RUNX2) mRNA were 1.00±0.07, 1.45±0.07, 2.11±0.32, 4.67±1.45; the relative protein expression levels of phosphorylated AMPK protein were 0.07±0.01, 0.11±0.01, 0.06±0.01, 0.18±0.01; and the relative protein expression levels of Sequestosome 1 (p62/SQSTM1) protein were 1.72±0.02、1.67±0.02、0.94±0.01、0.04±0.01; the relative protein expression levels of p-mTOR protein were 0.66±0.01, 0.40±0.01, 0.42±0.01, 0.04±0.01; and the relative protein expression levels of microtubule-associated protein 1 light chain 3 beta (LC3B) protein were 0.07±0.01, 0.20±0.01, 0.87±0.05, 1.27±0.04, respectively. There were statistically significant differences between the low-, middle-, and high-dose groups and the control group (P<0.05, P<0.001).

β-ecdyssterone can regulate autophagy and promote osteogenic differentiation of BMSCs by activating the AMPK/mTOR pathway.

To investigate the factors affecting the quality of warfarin anticoagulation therapy in elderly patients with nonvalvular atrial fibrillation (NVAF) and to assess the effect of the combined physician-pharmacist outpatient model on improving the quality of anticoagulation.

In this study, elderly NVAF patients treated with warfarin were divided into combined physician-pharmacist outpatient group and general outpatient group to assess the impact of different anticoagulation management strategies on patients. On this basis, patients were further classified into good anticoagulation quality group (TTR≥60%) and poor anticoagulation quality group (TTR<60%) based on the percentage of time (TTR) that their international normalised ratio (INR) was within the therapeutic target range, and the clinical prognosis and adverse events that occurred in both groups were analysed.

The mean TTR of patients in the combined physician-pharmacist outpatient group was (64.00±24.40)%, which was significantly higher than that of the general outpatient group, which was (42.10±30.20)% (P<0.05). Multifactorial logistic regression analysis showed that the number of comorbidities≥4 was an independent risk factor for poor anticoagulation quality (OR: 0.44, 95%CI: 0.23-0.87, P<0.05), whereas the combined physician-pharmacist outpatient clinic model significantly improved the anticoagulation quality of warfarin (OR: 3.50, 95%CI: 1.85-6.60, P<0.05). Although there were no significant differences between the two groups in the incidence of thromboembolic and bleeding events, the model showed potential advantages in the management of complex patients.

The combined physician-pharmacist outpatient model effectively improves the quality of anticoagulation therapy in elderly patients with NVAF by providing personalized anticoagulation treatment plans and medication management services. This model has a particularly positive impact on patients with multiple comorbidities, demonstrating its significant value in clinical practice.

To evaluate the bioequivalence of montelukast sodium chewable tablets test formulation and reference formulation in Chinese healthy subjects.

A single-center, single-dose, two-period, randomized, open-label, self-cross-over design was designed. A single oral dose of montelukast sodium chewable tablets 5 mg was administered under fasting or fed conditions in each period. The blood concentration of montelukast in plasma was determined by liquid chromatography-mass spectrometry, and pharmacokinetic parameters were calculated by SAS 9.4 software.

Twenty-six and 30 cases healthy subjects were included in the fasting and fed groups, respectively. The main pharmacokinetics (PK) parameters of the test formulation and reference formulation in the fasting group: C_max were (331.00±86.00) and (327.08±76.03) ng·mL^-1; AUC_0-t were (2 265.12±560.34) and (2 318.56±589.51) ng·mL^-1·h; AUC_0-∞ were (2 352.60±591.43) and (2 409.12±636.79) ng·mL^-1·h, respectively. The main PK parameters of the test formulation and reference formulation in the fed group: C_max were (262.07±52.94) and (256.73±63.07) ng·mL^-1; AUC_0-t were (2 014.43±356.47) and (2 071.53±462.56) ng·mL^-1·h; AUC_0-∞ were (2 072.30±384.30) and (2 138.57±509.46) ng·mL^-1·h, respectively. The 90% confidence intervals of the geometric mean ratios of the main PK parameters of montelukast in the test formulation and reference formulation in fasting and fed groups were all within 80.00%-125.00%. In the fasting test, a total of 8 cases (32.00%) subjects had 11 adverse reactions, and in the fed test, a total of 11 cases (36.67%) subjects had 18 adverse reactions.

The test and reference montelukast sodium chewable tablets were bioequivalent under fasting and fed conditions.