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 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 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 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 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 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 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.