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 observe the clinical efficacy and safety of different doses of esketamine injection combined with sevoflurane inhalation in the treatment of children undergoing laparoscopic surgery.

The elective laparoscopic surgery children with general anesthesia were randomly divided into control group and treatment -L, -H groups. Three groups received anesthesia induction with 2%-3% sevoflurane + 2-3 μg·kg^-1 fentanyl + 0.15 mg·kg^-1 remimazolam. Five minutes before the start of the surgery, the treatment -L group was administered 0.25 mg·kg^-1 esketamine + 2%-3% sevoflurane for anesthesia maintenance, the treatment -H group received 0.50 mg·kg^-1 esketamine + 2%-3% sevoflurane for anesthesia maintenance, the control group was given an equal volume of 0.9% NaCl + 2%-3% sevofluran for anesthesia maintenance, sevoflurane inhalation was stopped 10 minutes before the end of the surgery. The pediatric anesthesia emergence delirium (PAED) score at the time of entering the post-anesthesia care unit (PACU), face, legs, activity, cry, consolability (FLACC) score at 6 h after surgery, wakefulness time and safety were compared among three groups.

Treatment -L group was enrolled 94 cases, 5 cases dropped out, and 89 cases were finally included in the statistical analysis; treatment -H group was enrolled 94 cases, 1 case dropped out, and 93 cases were finally included in the statistical analysis; control group was enrolled 88 cases, 2 cases dropped out, and 86 cases were finally included in the statistical analysis. The PAED scores at the time of entering the PACU in treatment -L, -H groups and control group were (9.15±1.30), (7.03±1.24) and (12.45±1.43) points; the FLACC scores at 6 h after surgery were (1.54±0.58), (1.22±0.51) and (2.26±0.64) points; the wakefulness time was (10.84±2.25), (15.92±2.62) and (10.56±2.19) min, respectively; the differences of above indexes were statistically significant between the treatment -L and control groups and the treatment -H group (all P<0.05). The adverse drug reactions of treatment -L and treatment-H groups were drowsiness and tachycardia, while those in the control group were experienced laryngospasm, respiratory depression and tachycardia. The incidences of total adverse drug reactions in treatment -L, treatment -H and control groups were 7.87%, 8.60% and 8.14%, respectively, without significant differences (all P>0.05).

Esketamine injection combined with sevoflurane inhalation can help to maintain children’s hemodynamic stability undergoing laparoscopic surgery, the dose of 0.25 mg·kg^-1·h^-1 of esketamine can improve analgesia efficacy without prolonging the recovery time and increasing the incidence of adverse drug reactions.

To analysis the relationship between urinary albumin creatinine ratio (UACR) and heart rate variability (HRV) in patients with type 2 diabetes mellitus (T2DM).

Patients with T2DM were divided into control group (patients with T2DM only) and treatment group (patients with T2DM and proteinuria) using the cohort method. The treatment group was further divided into a microalbuminuria subgroup (UACR 30 - 300 mg·g^-1) and a macroalbuminuria subgroup (UACR≥300 mg·g^-1). Collected general clinical data, biochemical indicators and 24-hour holter electrocardiogram reports from patients, recorded HRV-related indicators [including pairs of normal N-N Intervals differ by more than 50 ms (PNN50), standard deviation of normal-to-normal R-R intervals (SDNN), etc] of each group of patients, and calculated body mass index (BMI) and estimated glomerular filtration rate (eGFR). Compared the differences in clinical data and HRV parameters among groups, analyzed the impact of UACR on HRV and their interrelationships, and used the receiver operating characteristic curve (ROC) to predict the optimal cutoff point for the occurrence of proteinuria in T2DM patients.

The treatment group enrolled 190 cases, and the control group enrolled 184 cases; the microalbuminuria subgroup enrolled 120 cases, and the macroalbuminuria subgroup enrolled 70 cases. The levels of UACR in the treatment and control groups were 113.99 and 12.76 mg·mmol^-1 Cr, the levels of UAER were 74.81 and 10.92 μg·min^-1, the levels of UA were (353.83±96.41) and (326.17±81.64) μmol·L^-1, the levels of PNN50 were 2.25 and 3.95, the levels of SDNN were 102.83±38.10 and 114.14±31.23, the levels of HRV triangular index were 20.80 and 25.55, respectively; the differences of above results were statistically significant between two groups (all P<0.05). In the macroalbuminuria and microalbuminuria subgroups, the levels of UACR were 1 088.17 and 64.64 mg·mmol^-1 Cr, the levels of UAER were 878.65 and 44.26 μg·min^-1, the levels of UA were (375.88±97.58) and (340.97±93.74) μmol·L^-1, the levels of PNN50 were 1.50 and 2.70, the levels of SDNN were 88.00 and 108.00, the levels of HRV triangular index were 19.49±7.77 and 24.48±8.84, respectively; the differences of above results were statistically significant between two subgroups (all P<0.05). Logistic regression analysis showed that the duration of diabetes mellitus, fasting blood glucose (FPG) and HRV triangle index were the influencing factors for the occurrence of proteinuria in patients with type 2 diabetes mellitus. ROC showed that HRV triangle index had the largest area under ROC curve, with 66.10% sensitivity and 63.00% specificity.

UACR in T2DM patients is closely related to the duration of DM, FPG and HRV triangle index, with the increase of UACR in T2DM patients, the risk of cardiovascular autonomic neuropathy increases.

To observe the clinical efficacy and safety of citric acid solution anticoagulant hemodialysis combined with tacrolimus tablets in the treatment of patients with nephrotic syndrome complicated with acute kidney injury.

The patients with nephrotic syndrome complicated with acute kidney injury were randomly divided into control group and treatment group. The control group was given low molecular weight heparin anticoagulation (initial dose 2 000-3 000 U, additional dose 500-1 000 U·h^-1) hemodialysis + oral tacrolimus capsule, oral tacrolimus capsules at an initial dose of 0.05 mg·kg^-1·d^-1, twice a day. The treatment group was given 180 mL·h^-1 4% sodium citrate anticoagulant hemodialysis + oral tacrolimus capsules, with an initial dose of 0.05 mg·kg^-1·d^-1 twice a day. Two groups were treated for 4 weeks. The clinical efficacy, renal function, coagulation function and safety were compared between the two groups.

Treatment group was enrolled 85 cases, 2 cases dropped out, and 83 cases were finally included in the statistical analysis. Control group was enrolled 84 cases, 3 cases dropped out, and 81 cases were finally included in the statistical analysis. After treatment, the total effective rates of treatment group and control group were 96.38% (80 cases/83 cases) and 92.59% (75 cases /81 cases), without statistical significance (P>0.05). After treatment, the albumin levels of treatment group and control group were (40.19±7.01) and (35.72±6.12) g·L^-1, the serum creatinine levels were (82.39±12.66) and (73.65±11.27) μmoL·L^-1, the 24 h urinary proteins were (1.41±0.26) and (1.75±0.31) g, the prothrombin time was (15.32±1.61) and (18.71±1.74) s, the activated partial thrombin time was (46.29±3.08) and (50.23±3.12) s, the thrombin time was (18.01±1.73) and (21.04±1.85) s, the urine output was (1 358.79±397.22) and (1 283.02±378.97) mL·d^-1, and the differences of above indexes were statistically significant between two groups (all P<0.05). The adverse drug reactions of treatment group were metabolic alkalosis, metabolic acidosis, hypocalcemia and citric acid accumulation, while those in the control group were bleeding, metabolic alkalosis and metabolic acidosis. The incidences of total adverse drug reactions in treatment and control groups were 16.87% and 14.81%, without statistical significance (P>0.05).

Compared with lower molecular weight heparin calcium anticoagulant hemodialysis combined with tacrolimus tablets, sodium citrate anticoagulant hemodialysis combined with tacrolimus tablets can more effectively improve renal function and coagulation function in patients with nephrotic syndrome and acute kidney injury, and will not increase the incidence of adverse drug reactions.

To observe the clinical efficacy and safety of salmon calcitonin nasal spray combined with calcium carbonate D₃ tablets in the treatment of disuse osteoporosis patients after ankle fracture surgery.

The disuse osteoporosis patients with postoperative ankle fractures were randomly divided into control group and treatment group using a random number table method. The control group was treated with calcium carbonate D₃ tablets 600 mg per time, twice daily, while the treatment group received salmon calcitonin nasal spray 200 U per time, once daily, in addition to the treatment in the control group. Both groups were treated for 6 months. The clinical efficacy, bone metabolic markers (osteocalcin, alkaline phosphatase), changes in bone mineral density (BMD) and postoperative pain level (VAS) were compared between the two groups, the safety evaluation was also conducted.

A total of 3 cases dropped out during the trial. Ultimately, the treatment group and the control group included 63 and 62 patients, respectively. After treatment, the overall effective rates for the treatment group and the control group were 93.65% (59 cases/63 cases) and 75.81% (47 cases/62 cases), respectively, with statistically significant difference (P<0.01). After 3 months of treatment, the BMD of the control and treatment groups were (0.87±0.09) and (0.93±0.08) g·cm^-2, respectively; serum osteocalcin levels were (20.10±3.20) and (22.80±3.50) ng·mL^-1, respectively; alkaline phosphatase levels were (74.50±12.30) and (80.10±13.20) U·L^-1, respectively; after 6 months of treatment, the BMD values for the control and treatment groups were (0.90±0.08) and (1.01±0.07) g·cm^-2, respectively; serum osteocalcin levels were (21.00±3.40) and (24.60±3.40) ng·mL^-1, respectively; alkaline phosphatase levels were (76.00±12.50) and (84.90±13.80) U·L^-1, respectively; statistically significant differences were observed for the above indicators between the experimental and control groups (P<0.05, P<0.001). After 3 months of treatment, the visual analog scale (VAS) scores of the control and treatment groups were (5.30±1.30) and (4.50±1.20) points, respectively; after 6 months of treatment, the VAS scores were (4.20±1.10) and (2.90±1.00) points, respectively; the differences between the treatment and control groups were statistically significant (all P<0.001). The main adverse drug reactions in the treatment group were nasal discomfort and nausea, while the control group were gastrointestinal discomfort. The total incidence of adverse drug reactions in the treatment and control groups were 7.94% (5 cases/63 cases) and 4.84% (3 cases/62 cases), respectively, without statistically significant difference between the two groups (P>0.05).

Salmon calcitonin nasal spray combined with calcium carbonate D₃ tablets can significantly increases BMD in disuse osteoporosis patients after ankle fracture surgery, reduce the risk of disuse osteoporosis, with good safety.

To investigate the protective effects of Angelicae and Astragalus ultra-filtration (AAU) on H₉C₂ myocardial cell injury induced by X-ray radiation based on NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome.

The H₉C₂ myocardial cells were divided into blank group, model group and experimental -L, -M, -H groups. The H₉C₂ myocardial cells injury model of model group and experimental -L, -M, -H groups were constructed with X-ray 6 Gy irradiation. After successful modeling, the blank and model groups were treated with 0.9% NaCl; the experimental -L, -M, -H groups were treated with 2%, 5%, 10% AAU drug-containing serum 0.5 mL, respectively. After 24 h of treatment, EdU staining was used to observe cell survival rate, Western blot was used to detect the expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) and Caspase-1 protein.

The cell viability rates of the experimental -M, -H groups, model group and blank group were (89.91±1.16)%, (91.66±1.93)%, (78.61±1.30)% and (98.10±0.20)%; the relative expression levels of NLRP3 protein were 0.79±0.05, 0.74±0.04, 0.94±0.02 and 0.53±0.12; the relative expression levels of ASC protein were 0.40±0.04, 0.41±0.07, 0.48±0.01 and 0.22±0.02; the relative expression levels of Caspase-1 protein were 0.25±0.03, 0.23±0.01, 0.58±0.04 and 0.18±0.01; the relative expression levels of IL-18 protein were 0.67±0.03, 0.62±0.02, 0.91±0.07 and 0.61±0.03; the relative expression levels of IL-1β protein were 0.41±0.06, 0.38±0.02, 0.78±0.02 and 0.34±0.09, respectively. Compared with the experimental -M, -H groups, the differences of above indicators in the model group were statistically significant (all P<0.05).

AAU may protect H₉C₂ myocardial cells from injury induced by X-ray radiation by regulating NLRP3 inflammasome.

To explore the regulation by cardamonin through targeting family 110 member A (FAM110A) regulate Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway on human breast cancer cells MCF-7 and effects of aerobic glycolysis and epithelial-mesenchymal transformation.

The breast cancer cells MCF-7 were divided into control group (cultured normally), experimental group (cells treated with 20 μmol·L^-1 cardamonin), oe-NC group (transfected with negative control plasmid oe-NC on the basis of experimental group), oe-FAM110A group (transfected with overexpressed plasmid oe-FAM110A on the basis of experimental group). Quantitative real-time polymerase chain reaction was used to detect the relative expression levels of FAM110A messenger RNA (mRNA) in each group of cells. The relative expression levels of FAM110A protein and the expression of E-cadherin and N-cadherin, which are related to epithelial mesenchymal transformation, were detected by immunofluorescence assay. Detection indexes of aerobic glycolysis in each group were detected by kit. The JAK2/STAT3 signaling pathway related protein phosphorylation level in each group was detected by Western blot.

The relative expression levels of FAM110A mRNA in control group and experimental group were 1.00±0.12 and 0.54±0.10, respectively, and the relative expression levels of FAM110A protein were 1.00±0.15 and 0.13±0.03, respectively; the mRNA and protein relative expression levels of FAM110A in experimental group were significantly different from those in control group (all P<0.05). The relative expression levels of E-cadherin protein in control group, experimental group, oe-NC group and oe-FAM110A group were 1.00±0.14, 2.98±0.51, 3.00±0.54 and 1.47±0.26, respectively; the relative expression levels of N-cadherin protein were 1.00±0.11, 0.41±0.08, 0.47±0.10 and 0.94±0.17; the relative lactic acid production were 1.00±0.19, 0.61±0.11, 0.59±0.09 and 0.98±0.16, respectively; the relative glucose absorption values were 1.00±0.16, 0.41±0.08, 0.42±0.08 and 0.88±0.15, respectively; the relative adenosine triphosphate production were 1.00±0.20, 0.29±0.05, 0.33±0.06 and 0.96±0.18, respectively; the phospho-JAK2/JAK2 levels were 1.00±0.17, 0.54±0.11, 0.58±0.10 and 0.91±0.15, respectively; the phospho-STAT3/STAT3 levels were 1.00±0.14, 0.37±0.06, 0.38±0.06 and 0.92±0.12, respectively; the above indexes in the experimental group were significantly different from those in the control group, and those in the oe-FAM110A group were significantly different from those in the oe-NC group (all P<0.05).

Cardamonin can inhibit aerobic glycolysis and epithelial-mesenchymal transition in breast cancer cells MCF-7, and the mechanism may be through down-regulating FAM110A and inhibiting JAK2/STAT3 signaling pathway.

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 study the effects and safety of silica nanoparticles (SiNPs) on platelets and coagulation system, and initially to explore the mechanism related to the procoagulation of SiNPs.

Blood from the abdominal aorta of rats was taken for in vitro experiments to evaluate the blood safety of 10, 50, 100, 200 μg·mL^-1 of SiNPs. Hematological toxicity was studied using hemolysis assay and lactate dehydrogenase assay. Platelet aggregation was detected by light transmission aggregometry. Platelet activation was detected by platelet surface activation receptor P-selectin. The effects of SiNPs on coagulation were also determined by activated partial tromboplastin time (APTT), thrombin time (TT), prothrombin time (PT) and fibrinogen (Fib).

In platelet-related studies, the max platelet aggregation was (49.38±13.66)% with SiNPs concentration of 200 μg·mL^-1 and platelet activation occurred with 50 μg·mL^-1 SiNPs exposing P-selectin. In coagulation sudies, the PT in 0.9% NaCl and 100 μg·mL^-1 of SiNPs were (9.04±0.20) and (8.36±0.32) s, the blood coagulation indexes were (100.00±0.00)% and (90.06±7.81)%, and the differences were statistically significant (all P<0.05).

High concentrations of SiNPs can cause platelet aggregation and activation, shorten PT and promote blood coagulation.

To explore the mechanism of remimazolam improving learning and memory ability and brain injury in postoperative cognitive impairment (POCD) mice by regulating NOD-like receptor heat protein domain associated protein 3 (NLRP3).

The C57BL/6J mice were divided into sham group (exposure of the tibia only without truncation), model group (tibia ampution method to construct POCD model), oe-NC group (modeling+15 mg·kg^-1 remimazolam treatment+tail vein injection of 60 nmol·L^-1oe-NC), oe-NLRP3 group (modeling+15 mg·kg^-1 remimazolam treatment+tail vein injection of 60 nmol·L^-1oe-NLRP3), experimental-L, -M, -H groups (after modeling, 5, 10, 15 mg·kg^-1 remimazolam was respectively given intraperitoneal injection), 12 rats per group. For the treated mice, the Morris water maze and step - down test were used to evaluate their learning and memory abilities. The expression levels of NLRP3, interleukin-1β (IL-1β), IL-10 and tumor necrosis factor-α (TNF-α) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The level of reactive oxygen species (ROS) was detected by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining, and the level of glial fibrillary acidic protein (GFAP) was detected by immunofluorescence.

The platform crossing times of sham operation group, model group and experimental-L, -M, -H groups were (4.58±0.91), (0.73±0.15), (0.92±0.18), (1.58±0.31) and (2.75±0.55), respectively; the error times were (0.50±0.11), (2.08±0.41), (1.75±0.35), (1.58±0.31) and (1.25±0.25), respectively; the relative expression levels of NLRP3 mRNA were 1.00±0.15, 3.51±0.69, 2.94±0.59, 2.57±0.51 and 1.91±0.38, respectively; the relative expression levels of IL-1β mRNA in sham operation group, model group, experimental-H group, control group and oe-NLRP3 group were 1.00±0.17, 2.72±0.54, 1.87±0.37, 1.91±0.38 and 2.66±0.53, respectively; the relative expression levels of IL-10 mRNA were 1.00±0.16, 0.51±0.10, 0.78±0.15, 0.73±0.15 and 0.56±0.11, respectively; the relative expression levels of TNF-α mRNA were 1.00±0.21, 3.08±0.61, 1.77±0.35, 1.82±0.36 and 2.65±0.53, respectively; the relative fluorescence intensities of ROS were 1.00±0.16, 7.22±1.45, 3.05±0.61, 3.13±0.63 and 6.75±1.31, respectively; the relative fluorescence intensities of GFAP were 1.00±0.18, 6.71±1.13, 3.38±0.63, 3.50±0.72 and 5.94±1.19, respectively. The above indexes in the sham operation group were compared with the model group, the above indexes in the experimental-H group were compared with the model group, the above indexes in the oe-NLRP3 group were compared with the control group, and the differences were statistically significant (all P<0.05).

Remimazolam improves postoperative cognitive function in mice by a mechanism that may be related to the inhibition of neuroinflammatory and oxidative stress damage by down-regulating NLRP3 expression.

To observe the effects of different dosage forms of Yupingfeng powder on lipopolysaccharide induced pyroptosis of mouse lung macrophages.

The RAW264.7 cells were randomly divided into normal, model, decoction piece and granule groups. Except for normal group, the other 3 groups were used lipopolysaccharide concentration to conduct a cellular inflammation model. No drug will be given to the normal group, and normal cultivation; the model group was treated with lipopolysaccharide; the decoction piece group was treated with lipopolysaccharide and decoction piece containing serum; the granule group was treated with lipopolysaccharide and granule containing serum. The macrophage inflammatory factor was detected by enzyme-linked immunosorbent assay. The expression levels of cell pyroptosis pathway protein were detected by Western blot.

The tumor necrosis factor -α (TNF-α) contents in cell supernatant of normal, model, decoction piece and granule groups were (48.19±12.00), (154.48±34.84), (125.80±29.66) and (125.73±28.88) pg·mL^-1; the interleukin (IL) -18 levels were (21.36±4.36), (78.33±14.41), (49.77±9.50) and (49.27±9.40) pg·mL^-1; the Caspase-1 levels were (39.72±10.58), (149.49±20.92), (93.25±16.73) and (91.93±16.45) pg·mL^-1; the IL-1β levels were (17.14±3.41), (74.43±16.04), (45.01±9.40) and (43.34±8.96) pg·mL^-1; the relative expression levels of TNF-α mRNA were 1.00±0.05, 2.17±0.07, 1.50±0.20 and 1.35±0.08; the relative expression levels of nuclear factor kappa-B mRNA were 1.00±0.01, 2.02±0.01, 1.52±0.01 and 1.50±0.03; the relative expression levels of IL-18 mRNA were 1.00±0.03, 1.48±0.04, 1.18±0.04 and 1.13±0.10; the relative expression levels of Caspase-1 mRNA were 1.00±0.04, 1.90±0.03, 1.59±0.04 and 1.49±0.10; the relative expression levels of IL-1β mRNA were 1.00±0.10, 1.74±0.08, 1.26±0.06 and 1.23±0.13, respectively. Compared with the model group, there were statistically significant differences of the above indicators in the granule group and the decoction piece group (P<0.05, P<0.01), but there were no statistically significant differences in the above indicators between the decoction piece group and the granule group (all P>0.05).

Both formulations of Yupingfeng powder can reduce the expression level of proteins on the cell pyroptosis pathway and inhibit inflammatory response.

To investigate the mechanism of Banxia-Huanglian (BX-HL) in improving diabetic gastroparesis based on dopaminergic synaptic pathway.

The possible signaling pathways of BX-HL on the treatment of diabetic gastroparesis (DGP) were carried out by network pharmacology methods. The DGP model was constructed by intraperitoneal injection of 60 mg·kg^-1 streptozotocin (STZ) + high-sugar and high-fat diet. The DGP rats were randomly divided into model group and experimental group, with 10 rats in each group; another 10 normal rats were taken as the normal group. The experimental group was administered by gavage with BX-HL solution at a dose of 1.35 g·kg·d^-1, while the normal group and model group were administered by gavage with an equal volume of 0.9% NaCl once a day. The rats in the three groups were administered once a day for 21 days. The gastric emptying rate and intestinal propulsion rate of rats were measured by activated charcoal administration, the levels of neurotransmitter dopamine (DA) in brain tissues were determined by enzyme-linked immunosorbent assay, and the expression levels of protein kinase B (Akt) and glycogen synthase kinase-3 (GSK-3) proteins in brain tissues were determined by Western blotting.

The effective components and corresponding signaling pathways, such as dopaminergic synapses, were screened by various databases for BX-HL on the treatment of diabetic gastroparesis. The fasting blood glucose levels in the normal group, model group and experimental group were (5.61±0.36), (23.40±1.58) and (6.18±0.42) mmol·L^-1; the gastric emptying rates were (71.33±1.23)%, (35.43±3.12)% and (61.59±4.66)%; the intestinal transit rates were (53.19±3.48)%, (29.33±1.91)% and (38.53±2.80)%; the DA contents in brain tissue were (42.43±2.97), (88.20±8.46) and (52.64±5.03) pmol·L^-1; the relative protein expression levels of Akt were 0.67±0.00, 1.35±0.04 and 0.94±0.01; the relative protein expression levels of GSK-3 were 0.96±0.01, 1.24±0.05 and 0.91±0.01, respectively. The above indexes of the experimental group showed statistical significance compared to the model group (all P<0.001).

BX-HL has an ameliorative effect on diabetic gastroparesis in rats, which is mainly reflected in the lowering of blood glucose, the promotion of gastric emptying and intestinal propulsion, the reduction of neurotransmitter DA level, its mechanism may be related to inhibite the Akt/GSK-3 protein expression of dopaminergic synaptic pathway.

To study the effect of etanercept on retinopathy in diabetic rats and explore its mechanism.

Diabetic rat model was established by streptozotocin. The rats were randomly divided into control group (normal feeding), model group (diabetic rat model was established), experimental group (after modeling, etanercept 2 mg·kg^-1 was injected subcutaneously into the abdomen twice a week for 12 weeks), and combined group [based on the experimental group, 100 nmol·mL^-1 microRNA (miR)-30a inhibitor was injected into the tail vein]. The pathological morphology of retina was observed by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was used to detect the levels of serum inflammatory factors. The positive expression of glial fibrillary acidic protein (GFAP) in retinal of rats was detected by immunofluorescence staining. The relative expression level of miR-30a in retina was detected by reverse transcription real-time fluorescence quantitative polymerase chain reaction.

In the model group, pathological changes occurred in each layer of retina, while in the experimental group, the pathological changes were alleviated, retinal edema was alleviated, cell arrangement was more regular, and the structural boundaries of each layer were clear. In control group, model group and experimental group, the serum levels of interleukin-6 (IL-6) were (0.42±0.07), (1.21±0.16) and (0.69±0.11) μg·L^-1, respectively; the levels of IL-1β were (0.26±0.05), (1.82±0.29) and (0.74±0.16) μg·L^-1, respectively; the levels of tumour necrosis factor-α(TNF-α) were (0.49±0.08), (1.25±0.17) and (0.72±0.13) μg·L^-1, respectively; the relative expression levels of GFAP in retinal tissues were 1.00±0.17, 3.18±0.56 and 1.45±0.23, respectively; the relative expression levels of miR-30a in retinal tissues were 1.00±0.19, 0.61±0.10, and 0.89±0.15, respectively; there were statistical differences between the model group and the control group, and between the experimental group and the model group (all P<0.05).

Etanercept can reduce the level of inflammatory factors in diabetic rats, and has a protective effect on diabetic rats retinopathy, its mechanism may be related to the regulation of miR-30a to activate insulin receptor substrate 1/phosphatidylinositol 3 kinase/protein kinase B signaling pathway.

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 role of the receptor-interacting protein kinase 3 (RIP3)-mediated necroptosis pathway in penile tissue damage in diabetes mellitus-induced erectile dysfunction (DMED) rats and the effects of GSK872 and Yimusake intervention in DMED rats.

Male SD rats with normal sexual function were selected, and diabetic rats were constructed by 2 consecutive days injections of streptozotocin (45 mg·kg^-1), DMED rats were screened and randomly divided into model group, experimental group, Yimusake group and combined group. The normal and model groups were injected intraperitoneally with an equal amount of 0.9% NaCl and gavaged with an equal amount of distilled water; the experimental group was injected intraperitoneally with 1 mg·kg^-1 GSK872 and gavaged with an equal amount of distilled water; the Yimusake group was injected intraperitoneally with an equal amount of 0.9% NaCl and gavaged with 250 mg·kg^-1 Yimusake; the combined group was injected intraperitoneally with 1 mg·kg^-1 GSK872 and gavaged with 250 mg·kg^-1 Yimusake. The expression of RIP3, mixed lineage kinase domain like protein (MLKL) and transient receptor potential melastatin 7 (TRPM7) were detected by immunohistochemistry and immunofluorescence, α-smooth muscle actin (α-SMA) and Collagen Ⅰ were detected by Western blotting in rat penile tissues.

The positive area ratios of RIP3 in the penile tissues of normal, model, experimental, Yimusake and combined groups were (7.71±1.92)%, (35.72±2.73)%, (20.20±2.51)%, (19.94±2.66)% and (9.31±1.98)%; MLKL positive area ratios were (7.39±1.73)%, (26.48±1.74)%, (15.66±1.87)%, (15.88±1.59)% and (8.45±1.65)%; TRPM7 positive area ratios were (6.43±2.10)%, (35.77±1.78)%, (23.76±1.79)%, (25.24±2.08)% and (9.39±1.72)%; α-SMA protein relative expression levels were 1.53±0.13, 0.39±0.08, 0.88±0.14, 0.86±0.12 and 1.52±0.12; Collagen Ⅰ protein relative expression levels were 0.29±0.10, 1.20±0.14, 0.73±0.07, 0.71±0.11 and 0.31±0.10. The differences between the above indices in the model group compared with the normal group, the above indices in the experimental group compared with the model group, the above indices in the Yimusake group compared with the model group and the above indices in the combined group compared with the model group were all statistically significant (all P<0.05).

RIP3/MLKL/TRPM7 necroptosis pathway may participate in regulating the progression of DMED rats by promoting cell death and fibrosis, while GSK872 and Yimusake may ameliorate penile injury in rats by inhibiting this pathway.

To explore the effects and mechanism of zoledronic acid on bone metabolism in osteoporosis rats under hypoxic environment.

The rat model of osteoporosis in hypoxia environment was established by bilateral ovary extraction combined with low-pressure oxygen chamber feeding, and was randomly divided into model group, control group and experimental -L, -M, -H groups, with 10 rats per group; another 10 normal rats were selected as the normal group. Experimental -L, -M, -H groups were given 2.5, 5.0 and 10.0 mg·kg^-1 zoledronic acid by subcutaneous injection, once a week. Control group was given 0.105 mg·kg^-1 estradiol valerate by intragastric administration, once a day. Normal and model groups were injected with equivalent 0.9% NaCl by subcutaneous injection. Six groups were treated for 4 weeks. The serum levels of tartrate-resistant acid phosphatase (TRAP), alkaline phosphatase (ALP) and bone gla protein (BGP) were detected by enzyme-related immunosorbent assay. The bone mineral density (BMD) was measured by dual-energy X-ray. The expression levels of mitogen extracellular signal-regulated kinase (MEK)/extracellular regulated protein kinases (ERK) in femur were detected by Western blot.

The TRAP levels of experimental-M, experimental -H, control, model and normal groups were (78.06±1.16), (69.39±1.44), (70.19±1.24), (94.39±1.04) and (64.95±1.19) U·L^-1; the ALP levels were (61.72±3.10), (45.40±0.82), (43.53±1.52), (88.69±2.29) and (42.01±1.56) U·L^-1; the BGP levels were (14.82±0.28), (12.29±0.28), (12.92±0.29), (19.96±0.46) and (11.79±0.59) ng·mL^-1; the BMD levels were (0.28±0.02), (0.35±0.04), (0.38±0.03), (0.16±0.02) and (0.41±0.06) g·cm^-2; the relative expression levels of p-MEK protein were 0.64±0.06, 0.84±0.05, 0.78±0.01, 0.15±0.06 and 0.88±0.04; the relative expression levels of p-ERK protein were 0.70±0.03, 0.95±0.02, 0.84±0.07, 0.29±0.03 and 0.97±0.06, respectively. Compared with the model group, the above indexes in the experimental-M, -H groups and control group were statistically significant (all P<0.05).

Zoledronic acid can improve bone mineral density and bone metabolism in hypoxic osteoporosis rats, the mechanism may be related to the regulation of MEK/ERK pathway.

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 establish in vitro and in vivo correlations from in vitro dissolution data and in vivo data from animals.

In vitro method: an aqueous gelatin solution was first prepared with alkaline gelatin, paliperidone palmitate was added into the solution and mixed well, gelatin hydrogel was obtained by refrigerating in the refrigerator for 1-2 h. The hydrogel was put into paddle dissolution apparatus for dissolution experiments, the concentration of the drug was detected by high-performance liquid chromatography and the degree of release was calculated. In vivo method: Timing was started after paliperidone palmitate was injected into Beagle dogs via intramuscular injection, blood was collected at 0 h before and 6 h-36 d after drug administration, respectively, the blood concentration was detected by liquid chromatography-tandem mass spectrometry (LC/MS/MS) technique and the blood concentration-time curve was plotted. Finally, the obtained in vitro data were fitted by Weibull function, the in vivo data were transformed by Nelson-Wagner method and area under the curve method. Graphs were constructed to evaluate the correlation between in vivo and in vitro drug release.

The in vitro release was approaching 100% by day 13, while the in vivo release was approaching 100% by day 30-36. Both Nelson-Wagner method and area under the curve method yielded that in vivo and in vitro were correlated.

It is feasible to establish in vitro correlations from in vivo dissolution data and in vivo data from animals.

To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of crizotinib in human plasma and apply this method to determine its concentration in patients with non-small cell lung cancer after administrating.

Osimertinib was employed as the internal standard. The plasma samples were performed through protein precipitation with acetonitrile and chromatographed on Agilent Eclipse XDB C₁₈ (2.1 mm×100.0 mm, 3.5 μm), mobile phase was consisted of acetonitrile containing 0.1% formic acid - 10 mmol·L^-1 ammonium acetate containing 0.1% formic acid, flow rate was 0.25 mL·min^-1, the column temperature was 30 ℃. The whole analytical time was 3 min. The detection was performed by positive ion electrospray ionization in multiple reaction monitoring mode, the quantitative analysis ion pairs were m/z 450.1→259.2 and m/z 500.2→72.1. The specificity, standard curve and lower limit of quantitation, precision and recovery, stability, matrix effect and residual effect of the method were investigated. After full validation, the method was applied to the determination of crizotinib in human plasma.

Good linearity was observed over the concentration range of 10.0-2 500.0 μg·L^-1, the calibration curve was y=4.54×10^-3x+3.22×10^-2 (r=0.992 7). The accuracies were between 97.66%-105.55%. The relative standard deviation of inter-day and intra-day precision were less than 8.49%. The average recoveries and matrix effects were between 80.10%- 86.05% and 95.22%-110.66%.

The LC-MS/MS method is developed which meets the requirements of biological sample analysis and it can quickly, accurately monitor the concentration of crizotinib.