To observe the protective effect of resveratrol on kidney of diabetic rats through lipid metabolism pathway.

The SD rats were randomly divided into control group, model group and experimental -L, -M, -H groups. The control group was fed with normal feed, while the other four groups were all based on high-fat and high-sugar feed feeding + intraperitoneal injection of streptozotocin to establish diabetic rat models. After successful modeling, the control group and the model group were given the same amount of normal saline, while the experimental-L, -M, -H groups were given 5, 25, 50 mg·kg^-1 concentration of resveratrol once a day, and were given continuous gavage for 10 weeks. Kidney function levels [cystatin C (Cys-C), serum creatinine (SCr), blood urea nitrogen (BUN)]were determined by enzyme-linked immunosorbent assay. The expressions of peroxissome proliferator-activated receptor γ (PPARγ), fatty acid- binding protein (FABP1), peroxisomal acyl-coenzyme A oxidase 1 (ACOX) 2 and ACOX1 were detected by Western blot.

The Cys-C levels of experimental -M, -H groups, control group, model group were (1.85±0.15), (1.39±0.11), (0.78±0.11) and (2.42±0.32) mg·L^-1; SCr levels were (55.74±7.02), (48.15±6.97), (32.41±4.22) and (68.15±8.48) μmol·L^-1; BUN levels were (10.37±1.02), (9.41±0.87), (7.12±1.12) and (14.48±2.45) mmol·L^-1; the relative expression levels of PPARγ protein were 0.74±0.08, 0.92±0.10, 1.22±0.15 and 0.39±0.05; the relative expression levels of FABP1 protein were 0.64±0.08, 0.81±0.07, 0.98±0.09 and 0.30±0.05; the relative expression levels of ACOX2 protein were 0.59±0.06, 0.72±0.07, 0.85±0.13 and 0.27±0.05; the relative expression levels of ACOX1 protein were 0.58±0.06, 0.67±0.05, 0.78±0.06 and 0.24±0.03. The differences of above indexes were statistically significant between the experimental-M, -H groups and control group and the model group (all P<0.05).

Resveratrol may play a protective role on kidney of diabetic rats by regulating lipid metabolism pathway.

To investigate the protective effect of icariin on recurrent spontaneous abortion (RSA) mice and its potential mechanism.

Female CBA/J mice were randomly divided into control group (mated with male BALB/c mice), model group (modeling mating with male DBA/2 mice), experimental-L group (after modeling, 25.00 mg·kg^-1 icariin was given by intragastric administration), experimental-H group (50.00 mg·kg^-1 icariin was given by intragastric administration after modeling), positive group (2.6 mg·kg^-1 desdrogesterone was given by intragastream after modeling), uterine tissue was collected after 14 days of treatment for follow-up experiments. Embryo absorption rate was observed and recorded. The levels of interleukin (IL) -4 and interferon γ (IFN-γ) were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of Foxp3 and Toll-like receptor 4 (TLR4) were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Western blot assay was used to detect the expression of TLR4 and phosphorylated nuclear transcription factor-κB (p-NF-κB) protein.

The absorption rates of mouse embryos in control group, model group, experimental-L group, experimental-H group and positive group were 7.37% (7 cases/95 cases), 37.33% (28 cases/75 cases), 20.93% (18 cases/86 cases), 13.79% (12 cases/87 cases) and 12.22% (11 cases/90 cases), respectively; IL-4 expression levels were (33.84±5.71), (10.71±2.34), (16.86±1.13), (26.91±3.04) and (19.56±1.79) pg·mL^-1, respectively; the expression levels of IFN-γ were (25.97±1.40), (63.38±5.39), (47.23±6.78) (34.80±4.08) and (29.61±3.25) pg·mL^-1, respectively; the relative expression levels of Foxp3 mRNA were 1.00±0.07, 0.57±0.05, 0.72±0.06, 0.90±0.05 and 0.66±0.06, respectively; the relative expression levels of TLR4 mRNA were 1.00±0.10, 2.32±0.17, 1.78±0.14, 1.40±0.08 and 2.05±0.26, respectively; the relative expression levels of TLR4 protein were 0.31±0.05, 0.90±0.11, 0.68±0.05, 0.55±0.05 and 0.79±0.10, respectively; the relative expression levels of p-NF-κB protein were 0.27±0.02, 0.82±0.13, 0.66±0.04, 0.42±0.05 and 0.75±0.09, respectively. The above indicators in the model group compared with the control group, the experimental-L and experimental-H groups were compared with the model group, and the differences were statistically significant (all P<0.05).

Icariin may play a protective role in improving RSA immune response by inhibiting TLR4/NF-κB pathway.

To establish an animal model of polycystic ovary syndrome (PCOS) characterized by kidney deficiency and blood stasis, and to evaluate its efficacy.

SD rats were randomly divided into normal group, PCOS group, model group and formula counter-evidence group, with 10 rats in each group. The normal group was given 1 mg·kg^-1 1% sodium carboxymethyl cellulose daily by intragastric administration; PCOS group was given 1 mg·kg^-1 letrozole daily by intragastric administration; on the basis of PCOS group, the model group was injected subcutaneously with 0.6 mg·kg^-1 epinephrine hydrochloride solution daily for 2 weeks from day 21. On the basis of the model group, the formula counter-evidence group was given 12.51 g·kg^-1 Zhu’s Tiaojing decoction daily for 2 weeks from the 21st day. After 35 days of intervention, the indexes of ovarian index, testosterone, vitamin D and whole blood low shear rate were compared.

The ovarian indexes of normal, PCOS, model and formula counter-evidence groups were (6.39±0.58)×10^-4, (5.32±0.71)×10^-4, (5.05±0.29)×10^-4 and (8.17±0.65)×10^-4; testosterone concentrations were (7.10±0.97), (9.22±0.43), (9.06±1.21) and (7.73±0.76) nmol·L^-1; vitamin D levels were (1 850.98±227.95), (986.10±152.50), (1 220.67±64.35) and (1 598.20±294.75) pg·mL^-1; whole blood low shear rates were (13.00±1.79), (13.37±0.54), (16.38±1.51) and (11.43±2.77) mPa·s, respectively. The above indexes in the model group were statistically significant compared with the formula counter-evidence group and the normal group (all P<0.05).

Letrozole combined with epinephrine hydrochloride can stably replicate the PCOS rat model with kidney deficiency and blood stasis syndrome.

To study the bioequivalence of two formulations of haloperidol tablets in healthy Chinese subjects.

The randomized, open, single dose, two periods, crossover study design was adopted in the study. Twenty-eight healthy subjects were enrolled under fasting condition and given either test preparation or reference preparation 2 mg respectively in one period. After collecting plasma samples, the plasma concentrations of haloperidol were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated by WinNonlin 8.0 and the bioequivalence was evaluated using the average bioequivalence (ABE) method.

The pharmacokinetic parameters of haloperidol of the test preparation or reference preparation were as follow: C_max were (719.50±378.43) and (703.43±329.63) pg·mL^-1, AUC_0-t were (1.94×10⁴±6 766.21) and (1.94×10⁴±6 522.79) pg·h·mL^-1, AUC_0-∞ were (2.31×10⁴±7 693.66) and (2.30×10⁴±7 309.97) pg·h·mL^-1. The 90% confidence intervals (CI) of the geometric mean ratio (GMR) were 92.46%-114.76%, 96.70%-108.15%, 96.36%-111.34% for C_max, AUC_0-t and AUC_0-∞, respectively, which were within the acceptance criteria of 80.00%-125.00%.

The two preparations of haloperidol tablets were bioequivalent in Chinese healthy subjects.

To establish a pharmacodynamic model of sodium-glucose transporter 2 inhibitors (SGLT-2i) in order to evaluate the efficacy characteristics of the drugs.

A model-based meta-analysis was used. By searching randomized controlled trials of SGLT-2i monotherapy in patients with type 2 diabetes (T2DM) in databases, the change in glycosylated hemoglobin (HbA1c) from baseline was used as the efficacy indicator. The pharmacodynamic models of SGLT-2i and placebo were constructed, and the covariates were screened to determine the factors affecting the drug’s efficacy.

A total of 39 studies were included, involving 96 trial groups, 8 534 participants, and 13 drugs (dapagliflozin, canagliflozin, empagliflozin, ipragliflozin, luseogliflozin, ertuglilfozin, enavogliflozin, henagliflozin, licogliflozin, sotagliflozin, bexagliflozin, janagliflozin and tofogliflozin). The time-effect relationships of the drug group and the placebo group were consistent with the E_max model, and fasting plasma glucose baseline had an effect on the pharmacodynamic parameters of SGLT-2i.

The final model can describe the pharmacodynamic characteristics of the drug and placebo groups, and there is a significant association between FPB baseline and drug efficacy.

To investigate the effect of pyrotinib on ferroptosis in gastric cancer cells through the regulation of the tumor protein 53 (p53)/solute carrier family 7 member 11 (SLC7A11) axis by the long noncoding RNA small nucleolar RNA host gene 16 (LncRNA SNHG16).

Human gastric cancer cells (NCI-N87) were selected and divided into NCI-N87 group (NCI-N87 cells were cultured normally without treatment), experimental group (NCI-N87 cells treated with 0.5 μmol·L^-1 pyrotinib for 72 h), and oe-NC group (based on the transfection of oe-NC in experimental group), LncRNA SNHG16 group (based on experimental group transfected with oe-LncRNA SNHG16). Real-time fluorescence quantitative polymerase chain reaction and fluorescence in situ hybridisation were used to determine the expression level of LncRNA SNHG16, cell viability was detected by cell counting kit-8; invasive ability was detected by Transwell assay; reactive oxygen species (ROS) fluorescence level was detected by fluorescent probe staining of dihydroethidium (DHE); malondialdehyde (MDA) level and glutathione (GSH) activity were detected by kits; and the expression level of p53 and SLC7A11 protein was detected by Western blot.

The relative expression levels of LncRNA SNHG16 in the NCI-N87 group, the experimental group, the oe-NC group and the LncRNA SNHG16 group were 1.00±0.18, 0.39±0.06, 0.41±0.07 and 0.80±0.15, respectively; the relative fluorescence intensities of LncRNA SNHG16 were 1.00±0.16, 0.27±0.05, 0.23±0.04 and 0.81±0.17, respectively; the number of cell invasion was (82.16±14.67), (29.03±4.75), (31.82±5.69) and (74.98±11.34) pieces, respectively; the relative fluorescence levels of ROS were 1.00±0.15, 4.57±0.86, 3.95±0.61 and 1.54±0.33, respectively; MDA levels were (5.49±1.08), (11.27±1.93), (10.85±1.64) and (6.73±0.95) μmol·mg^-1, respectively; GSH relative activities were 1.00±0.00, 0.54±0.09, 0.56±0.07 and 0.83±0.14, respectively; the relative expression levels of p53 protein were 1.00±0.17, 2.26±0.38, 1.98±0.32 and 1.24±0.19, respectively; the relative expression levels of SLC7A11 protein were 1.00±0.13, 0.34±0.05, 0.41±0.09 and 0.79±0.11, respectively. The differences in the above indicators between the NCI-N87 group and the experimental group, as well as between the oe-NC group and the LncRNA SNHG16 group, were all statistically significant (P<0.001).

Pyrotinib can regulate the p53/SLC7A11 signaling pathway by inhibiting the expression of LncRNA SNHG16 to induce ferroptosis of gastric cancer cells and inhibit the proliferation and invasion of gastric cancer cells.

To analyze iron death genes and related pathogenesis in chronic thromboembolic pulmonary hypertension (CTEPH) based on bioinformatics, and to screen potential traditional Chinese medicine (TCM) active ingredients for treating CTEPH through iron death related pathways.

The differentially expressed genes in dataset GSE130391 were analyzed by R language, and the genes related to iron death were obtained from FerrDB database. The intersection of the two genes was selected, and the intersection genes were enriched by Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO). The intersection genes were analyzed by random forest algorithm, and the key genes were obtained. The immune infiltration analysis of GSE130391 was performed by cibesort algorithm. Potential TCM active ingredients were screened by cMAP database, and the binding stability and affinity of TCM active ingredients and key targets were analyzed by molecular docking and molecular dynamics simulation.

A total of 878 DEGs were obtained, 264 iron death related genes and 14 intersection genes were obtained from FerrDB database. There were 630 items in GO enrichment analysis, and 13 pathways were enriched by KEGG. Three key genes were obtained by random forest algorithm. Immunoinfiltration analysis showed that dendritic cells and mast cells were inhibited in CTEPH group, and immunoinfiltration correlation showed that mast cells were strongly correlated with M1 macrophages, M1 macrophages were strongly correlated with T cells, and the key gene arachidonic acid 12-lipoxygenase 12R type (ALOX12B) was positively correlated with M2 macrophages. Cytokine signal transduction inhibitor 1 (SOCS1) was negatively correlated with M2-type macrophages. The active ingredients of traditional Chinese medicine were ononanthine and rotensin screened in cMAP database. Molecular docking and molecular dynamics simulation analysis showed that rotensin and ALOX12B had stable binding energy and strong affinity.

The therapeutic targets related to iron death in CTEPH are found by bioinformatics method and the active components of Chinese medicine that can be targeted for intervention are screened.

To investigate the effects of Tonglagat-5, a Mongolian drug, on bone microstructure and bone metabolism in osteoporotic mice, and to explore the possible mechanisms of action based on phosphatase and tensin homologue-induced kinase 1 (PINK1)/Parkin-mediated mitophagy.

Osteoporotic mouse model was established by ovariectomy (OVX). Osteoporotic model mice were randomly divided into model group (equal volume 0.9% NaCl by gavage), control group (estradiol valerate 1 mg·kg^-1 by gavage), experimental group (0.05 g·kg^-1 Tonglagat-5 solution by gavage) and combined group (0.05 g·kg^-1 Tonglagat-5 solution by gavage + 50 mg·kg^-1 Mdivi-1 by intraperitoneal injection), with 10 mice per group; ten mice were randomly selected as the sham-operation group. After 10 consecutive weeks of treatment, the bone mineral density (BMD) was measured by Micor-CT assay, the bone metabolism marker assay [C-terminal telopeptide of type Ⅰ collagen (CTx-Ⅰ), alkaline phosphatase (ALP) and bone Gla-protein (BGP)] were detected by kit, and the protein expression levels of translocase of outer mitochondrial membrane 20 (Tomm20), p62, PINK1 and Parkin were performed by Western blot.

The BMD in the sham-operation, model, control, experimental and combined groups were (0.23±0.02), (0.09±0.01), (0.22±0.03), (0.23±0.01) and (0.11±0.02) g·mm^-3; the levels of CTx-Ⅰ were (14.58±1.22), (26.62±2.04), (16.44±2.31), (12.31±1.98) and (22.76±2.52) ng·mL^-1; the levels of ALP were (4.87±1.12), (1.41±1.10), (3.03±1.07), (4.44±1.15) and (2.05±1.41) U·L^-1; the levels of BGP were (9.35±1.06), (5.28±0.84), (7.76±0.35), (8.34±0.87) and (6.12±0.81) ng·mL^-1; the relative expression levels of Tomm20 protein were 0.93±0.08, 0.10±0.01, 0.37±0.03, 0.84±0.06 and 0.28±0.03; the relative expression levels of p62 protein were 0.15±0.02, 0.93±0.09, 0.65±0.06, 0.37±0.04 and 0.86±0.06; the relative expression levels of PINK1 protein were 0.87±0.09, 0.14±0.02, 0.32±0.03, 0.69±0.06 and 0.26±0.03; the relative expression levels of Parkin protein were 0.79±0.08, 0.12±0.02, 0.26±0.04, 0.58±0.05 and 0.23±0.03, respectively. The above indexes in model group were compared those in sham-operation, control and experimental groups, the differences were statistically significant (all P<0.05).

Tonglagat-5 is able to improve bone microstructure and bone metabolism and reduce bone loss in OVX mice, and the mechanism may be related to the activation of PINK1/Parkin pathway-mediated mitophagy to exert osteoprotective effects.