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 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 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 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 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 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 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.