To observe the clinical efficacy and safety of rituximab injection combined with valsartan capsules in the treatment of patients with chronic glomerulonephritis.

The patients with chronic glomerulonephritis were randomly divided into control group and treatment group. The control group was given valsartan capsules 80 mg each time, qd, orally; on the basis of control group, the treatment group was combined with rituximab 1 000 mg per time, intravenous infusion, once on the 1st and 15th day. Two groups were treated for 12 months. The clinical efficacy, inflammatory indexes, renal function, disease recurrence and safety were compared between two groups.

Seventy-eight cases were enrolled in the treatment group, 9 cases were dropped out, and finally 69 cases were included in the statistical analysis; 79 cases were enrolled in the control group, 8 cases were dropped out, and finally 71 cases were included in the statistical analysis. After treatment, the total effective rates of treatment and control groups were 88.41% (61 cases/69 cases) and 61.97% (44 cases/71 cases), with significant difference (P<0.05). After treatment, the levels of interleukin-1 in the treatment and control groups were (73.88±9.91) and (86.47±10.27) pmol·L^-1, the levels of tumor necrosis factor-α were (42.17±5.66) and (47.94±5.52) pg·mL^-1, the levels of interferon-γ were (13.29±3.86) and (17.72±4.08) pg·mL^-1, the levels of creatinine were (82.17±12.23) and (87.89±10.21) μmol·L^-1, the levels of urea nitrogen were (4.66±1.26) and (5.71±1.65) mmol·L^-1, the 24-hour urinary protein quantifications were (3.55±1.12) and (4.69±1.57) g, the recurrence rates were 1.64% and 18.18%, and the differences were statistically significant (all P<0.05). The adverse drug reactions of treatment group were infection, neutropenia, nausea and vomiting, and leukopenia, while those in the control group were angioedema, nausea and vomiting, and neutropenia. The total incidences of adverse drug reactions in the treatment and control groups were 7.25% and 4.23%, without significant difference (P>0.05).

The clinical efficacy of rituximab injection combined with valsartan capsules in the treatment of patients with chronic glomerulonephritis is better than valsartan capsules alone, without increasing the incidence of adverse drug reactions.

To observe the clinical efficacy and safety of caffeine citrate injection combined with poractant alfa injection in the treatment of respiratory distress syndrome (RDS) in premature infants.

RDS premature infants were divided into control group and treatment group according to the cohort method. The control group was given 100-200 mg·kg^-1 of poractant alfa injection by endotracheal tube injection and added 100 mg·kg^-1 after 12 h, whereas the treatment group received intravenous injection of caffeine citrate injection on the basis of the control group (with the initial loading dose of 20 mg·kg^-1 for 30 min, followed by an additional maintenance dose of 5 mg·kg^-1 for 10 min every 24 h). Both groups were treated continuously for 7 days. The clinical efficacy, treatment-related indicators, blood gas indicators, serological indicators and complications were compared between groups, and the safety evaluation was performed.

There were 57 cases in treatment group and 51 cases in control group. After treatment, the total effective rates in treatment group and control group were 94.74% (54 cases/57 cases) and 78.43% (40 cases/51 cases), respectively (P<0.05). After treatment, the mechanical ventilation time in treatment group and control group was (101.29±22.24) and (113.57±27.55) h; oxygen therapy time was (199.21±43.28) and (238.72±44.01) h; the hospitalization time was (25.63±3.37) and (29.98±4.90) d; the partial pressure of arterial blood oxygen (PaO₂) values were (79.55±7.27) and (74.83±6.16) mmHg; the arterial partial pressure of carbon dioxide (PaCO₂) values were (40.65±3.94) and (45.72±4.46) mmHg; blood pH values were 7.40±0.05 and 7.34±0.05; adrenocorticotropic hormone (ACTH) levels were (30.71±6.92) and (36.80±7.04) pg·mL^-1; cortisol (Cor) levels were (272.90±34.51) and (306.47±30.11) ng·mL^-1; interleukin-6 (IL-6) levels were (35.10±8.49) and (42.55±9.72) pg·mL^-1, and compared with control group, the above indicators in treatment group were statistically different (all P<0.05). During treatment, the incidence rates of complications in treatment group and control group were 3.51% (2 cases/57 cases) and 5.88% (3 cases/51 cases), respectively (P>0.05). There were no adverse drug reactions such as hypotension, bradycardia and irritability in both groups during treatment.

Caffeine citrate injection combined with poractant alfa injection in the treatment of RDS in premature infants can improve the efficacy, shorten the mechanical ventilation time, oxygen therapy time and hospitalization time, improve the blood gas and serum oxidative stress and inflammatory indicators, and the safety is good.

To investigate the mechanism of Jianpi Yishentongqiao granule (JPYSTQG) in the intervention of spleen-kidney Yang deficiency type allergic rhinitis (AR) rats based on metabolomics.

The AR rat model of spleen-kidney-yang deficiency type was constructed by ovalbumin intraperitoneal injection sensitization + hydrocortisone intraperitoneal injection + rhubarb irrigation combined with modeling, and was randomly divided into model group and experimental group, with 10 rats in each group. Another 10 normal rats were selected as blank group. The experimental group was given 472.5 mg·mL^-1 JPYSTQG solution, the blank group and model group were given equal volume 0.9% NaCl. The rats in the three groups were administrated by gavage three times a day for 14 days. Serum levels of interleukin-4 (IL-4), immunoglobulin E (IgE) and interferon-γ (IFN-γ) were detected by enzyme-linked immunosorbent assay. Differential metabolites were screened by metabolomics and enriched by Kyoto Encyclopedia of Genes and Genomes.

The serum IgE levels in experimental, model and blank groups were (21.23±0.40), (23.80±0.67) and (20.03±1.42) ng·mL^-1; IL-4 levels were (111.00±5.86), (119.79±7.07) and (99.24±1.03) pg·mL^-1; IFN-γ levels were (1 980.63±15.63), (1 602.50±50.00) and (2 136.88±315.63) mg·mL^-1, respectively. Compared with the model group, the differences of experimental and blank groups were statistically significant (all P<0.01). Thirty-seven potential biomarkers of JPYSTQG intervention in spleen-kidney-yang deficiency rats were screened, mainly through arginine biosynthesis and tumor-related pathways.

JPYSTQG can regulate the expression of cytosine and other substances through arginine metabolism pathway, reduce IL-4, IgE and other inflammatory indicators, and thus have therapeutic effect on the allergic rhinitis rats with spleen-kidney-yang deficiency.

To establish a method for the quantification of aripiprazole in male SD rats muscle, and apply it to the research of drug residue at injection site in rats after administration of long-acting aripiprazole injection (LAI), and to compare the pharmacodynamics in mice.

An ultra-high performance liquid chromatography tandem mass spectroscopy (UPLC-MS/MS) assay was used to determine the concentration of aripiprazole in rats muscle. Sample pre-treatment: Muscle tissue was homogenized in a 30% acetonitrile solution containing 5% acetic acid, and then precipitated with 0.1% formic acid in acetonitrile for detection. Chromatography column: Waters HSS T3^TM C₁₈ column (2.1 mm×50.0 mm, 1.8 μm). Mobile phase: 5% acetonitrile and 95% acetonitrile both containing 0.1% formic acid. Flow rate: 0.6 mL·min^-1. Injection volume: 5 μL. Mass spectrometry conditions: electrospray ion-source positive ions mode, multiple reaction monitor (MRM) scanning mode. After intramuscular administration of 25 mg·mL^-1 aripiprazole microspheres for injection (MS) or long-acting aripiprazole for injection (brand name: Abilify Maintena^®, AM), the drug residue in male SD rats was determined using an UPLC-MS/MS method. The hyperlocomotion model was established by acute administration of phencyclidine (PCP). And a comparative study was conducted on the efficacy of MS (40, 80, 240 mg·kg^-1) and AM (80 mg·kg^-1).

After 28 days of administration, the drug residue ratio of MS group was 6.27%-12.38%, while that of AM group was 23.31%. After 35 days of administration, the average drug residue ratios were 0.58%-2.94% and 10.28%-18.87%, respectively. Both the AM group and each dose (40, 80, 240 mg·kg^-1) of MS group could inhibit the spontaneous movement of mice induced by PCP.

The inhibitory effect of Aripiprazole Microsphere for injection is comparable to that of Abilify Maintena on the spontaneous movement of mice caused by PCP. And there is a certain dose-response relationship for MS, while the drug residue at the injection site of MS is much lower than that of Abilify Maintena.

To explore the protective mechanism of Celosin Ⅰ on retinal ganglion cells by regulating reactive oxygen species (ROS) mediated mitochondrial apoptosis pathway.

Twenty-four New Zealand white rabbits were randomly divided into sham-operation, model, control and experimental groups, with 6 rabbits per group. The sham-operation group only had the bulbar conjunctiva cut and sutured, the other 3 groups were received with optic nerve clamp injury to contruct the optic nerve injury model. The sham-operation and model groups were given equal volumes of physiological saline by gavage, the control group was given a dose of 0.15 mg·kg^-1 mecobalamine solution by gavage, and the experimental group was given a dose of 30 mg·kg^-1 Celosin Ⅰ solution by gavage. Four groups were administered a daily gavage treatment for four consecutive weeks. The Tunnel method was used to detect apoptosis of retinal ganglion cells, and immunofluorescence was employed to detect the expression of ROS, superoxide dismutase (SOD) and caspase in retinal tissues. The expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-like protein 1 (Bcl-xl), Bcl-2-associated X protein (Bax), and cytochrome C (CytC) proteins in retinal tissues were assessed using Western blotting.

After four weeks of intervention, the apoptosis rates of ganglion cells in the experimental, control, model and sham-operated groups were (7.65±1.20)%, (11.65±1.29)%, (17.66±0.93)% and (0.97±0.14)%; the expression levels of ROS in retinal tissues were 6.14±0.57, 8.25±0.96, 16.51±1.07 and 2.05±0.23; the expression levels of SOD were 2.45±0.33, 1.48±0.23, 0.74±0.13 and 3.19±0.30; the expression levels of caspase-3 were 8.55±1.11, 12.68±0.92, 18.74±1.97 and 3.08±0.20; the expression levels of caspase-9 were 3.69±1.20, 7.79±1.13, 12.81±1.72 and 2.31±0.30; the relative expression levels of Bcl-2 were 0.46±0.02, 0.64±0.07, 0.77±0.05 and 0.20±0.03; the relative expression levels of Bcl-xl were 0.46±0.05, 0.61±0.05, 0.78±0.03, and 0.20±0.03; the relative expression levels of Bax were 0.50±0.07, 0.69±0.18, 0.82±0.13 and 0.14±0.04; the relative expression levels of CytC were 0.43±0.15, 0.80±0.14, 1.08±0.19 and 0.26±0.07. The differences in the aforementioned indicators in the experimental group compared with control group were statistically significant (all P<0.05).

Celosin Ⅰ reduces ROS levels in retinal tissue of a model of optic nerve injury, inhibits the expression of mitochondrial apoptosis related proteins in retinal ganglion cells, and reduces retinal ganglion cell apoptosis.

To investigate the mechanism of action of bezafibrate (BEZ) targeting nuclear factor of activated T cells 5 (NFAT5) through microribonucleic acid (miR)-486-5p on the kidney tissues of mice with diabetic nephropathy.

Db/m mice were used as control group. Db/db mice were used to construct a diabetic nephropathy model, which was divided into 4 groups according to the random number table method: Model group, experimental group (75 mg·kg^-1·d^-1 BEZ), miR-486-5p antagomir group (75 mg·kg^-1·d^-1 BEZ+10 mg·kg^-1 miR-486-5p antagomir), sh-NFAT5 group (75 mg·kg^-1·d^-1 BEZ+10 mg·kg^-1 miR-486-5p antagomir+recombinant adenovirus containing NFAT5 knockdown plasmid). The kit was used to detect the levels of renal function and oxidative stress in mice; and the expression levels of glucose metabolism and renal fibrosis-related proteins in renal tissues of mice in each group were detected by Western blot.

The levels of malondialdehyde (MDA) in the control group, model group, experimental group, miR-486-5p antagomir group, and sh-NFAT5 group were (2.78±0.56), (4.96±0.97), (3.02±0.54), (4.51±0.79) and (3.24±0.58) nmol·mg^-1, respectively; the levels of aldose reductase (AR) were 1.00±0.12, 3.61±0.43, 1.82±0.29, 3.09±0.58 and 2.25±0.47, respectively; the levels of pyruvate dehydrogenase (PDH) were 1.00±0.11, 0.53±0.10, 0.91±0.15, 0.64±0.12 and 0.82±0.14, respectively; the levels of pyruvate dehydrogenase E1 subunit α1 (PDHA1) were 1.00±0.14, 0.36±0.07, 0.83±0.16, 0.51±0.11 and 0.74±0.13, respectively; the levels of pyruvate dehydrogenase kinase (PDK) were 1.00±0.10, 2.59±0.52, 1.34±0.31, 2.11±0.43 and 1.56±0.39, respectively; the levels of transforming growth factor-β1 (TGF-β1) were 1.00±0.11, 3.15±0.52, 1.43±0.38, 2.72±0.43 and 1.89±0.57, respectively; the levels of fibronectin (FN) were 1.00±0.09, 2.84±0.57, 1.46±0.41, 2.59±0.52 and 1.73±0.49, respectively; the levels of collagen type I (Collagen I) were 1.00±0.13, 4.28±0.71, 2.03±0.46, 3.64±0.68 and 2.51±0.53, respectively. The above indicators of the control group were compared with the model group, the above indicators of the model group were compared with the experimental group, the above indicators of the experimental group were compared with the miR-486-5p antagomir group, and the above indicators of the miR-486-5p antagomir group were compared with the sh-NFAT5 group. The differences were statistically significant (P<0.05, P<0.01, P<0.001).

BEZ can effectively protect the kidney tissue of mice with diabetic nephropathy, and the mechanism may be realized through the miR-486-5p/NFAT5 signaling pathway.

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.