Aim: To study pharmacokinetics of aconitine,mesaconitine and hypaconitine in rats after single oral administration of decoctions composed with Radix Aconiti Lateralis.Methods: Four groups of rats were orally administered four decoctions including decoction a(Sini decoction),decoction b(decoction composed with Radix Aconiti Lateralis),decoction c(decoction composed with Radix Aconiti Laterali and Radix et Rhizoma Glycyrrhizae Praeparata Cum Melle)and decoction d(decoction composed with Radix Aconiti Laterali and Rhizoma Zingiberis),respectively.Quantitative analysis of aconitine,mesaconitine and hypaconitine in rat plasma was achieved using a liquid chromatography-electrospray ionization/tandem mass spectrometry method.Pharmacokinetic parameters were estimated using DAS 2.0.Results: Pharmacokinetic parameters of aconitine,mesaconitine and hypaconitine were different after oral administration of four decoctions according to Radix Aconiti Laterali combined with different herbal medicines.Multiple peaks were observed in plasma concentration-time curve after oral administration of the decoction of herb couple Radix Aconiti Laterali and Radix et Rhizoma Glycyrrhizae Praeparata Cum Melle,and the results showed a delay in tmax and a prolonger in MRT0-t compared with the decoction of Radix Aconiti Latera-lis.When Radix Aconiti Lateralis was combined with Radix et Rhizoma Glycyrrhizae Praeparata Cum Melle and Rhizoma Zingiberis at the same time in Sini decoction,tmax was delayed too but MRT0-t,was shorten than that of the group of Radix Aconiti Lateralis.Conclusion: The pharmacokinetic parameters of the three compounds obtained in this work shows that the pharmacokinetics of aconitine,mesaconitine and hypaconitine were influenced diversely when Radix Aconiti Laterali was combined with different herbal medicines.

Objective To investigate the effects of high-fat diet on pancreatic acinar cells' IP3 expression and CCK-induced amylase release in rats.Methods Male Wistar rats were divided into high-fat diet group and normal diet group,they were fed for 4 weeks.Blood triglycerides,cholesterol,amylase and glucose levels were determined by automatic biochemical analyzer.Pancreatic tissues were taken for histopathological observations.Pancreatic acinar cells were isolated and cultured,and intracellular inositol 1,4,5-trisphosphate (IP3) was detected using a commercial kit.Amylase release rates were measured after CCK-8 stimulation.Results The rats in high-fat diet group appeared hyperlipidemia,vacuolization of acinar cells and the lymphocytes appeared around the acinar cells can be seen on the pancreatic tissue pathology staining.The levels of IP3 in acinar cells of rats fed a high-fat diet were higher than that of normal rats [(31.807 ± 3.448) pmol/106 cells vs (24.632 ± 3.649) pmol/106 cells,t=7.479,P＜0.001];and amylase release rate in these rats'acinar cells were also higher than those of normal rats [when CCK-8=0.01 nmol/L:( 11.056 ±3.369)％ vs (7.354 ± 2.181) ％,t=3.912,P＜0.001;when CCK-8=1 nmol/L:( 13.854 ± 4.087 ) ％ vs (9.432 ±2.477) ％,t=3.939,P＜0.001 ) after CCK-8 stimulation in different concentrations.Additionally,there was a positive co-relationship between acinar cell's IP3 level and amylase release (r=0.896,P＜0.001 ).Conclusion Chronic high-fat diet induces hypersensitivity for pancreatic acinar cells' exocrine function,and IP3 as a signal molecule may play an important role in this process.

Objective:To observe the effect of metformin on the polarization state and photoreceptor cell activity of microglia (BV2 cells) in a high glucose environment.Methods:An experimental study. BV2 cells were divided into a control group, a high glucose group, and a metformin+high glucose group. The cells in the high glucose group were cultured with 75 mmol/L glucose in the medium; the cells in the metformin+high glucose group were pretreated with 2 mmol/L metformin for 12 h and then placed in 75 mmo/L glucose concentration medium. The relative expression of M1 marker inducible nitric oxide synthase (iNOS), CD86 and M2 markers arginase 1 (Arg-1), and CD206 protein were detected by Western blot. Interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-4 were detected by enzyme-linked immunosorbent assay (ELISA). BV2 cells were co-cultured with mouse retinal photoreceptor cells (661W cells) for 24 h. The proliferation rate of 661W cells in each group was measured by methyl thiazolyl tetrazolium (MTT) colorimetric assay; the apoptosis rate of 661W cells in each group was measured by flow cytometry and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). An independent sample t-test was used for comparison between groups. Results:Western blot assay showed that the relative expression of iNOS and CD86 protein was increased and the relative expression of Arg-1 and CD206 protein was decreased in BV2 cells in the high glucose group compared with the control group, and the differences were all statistically significant ( t=-16.783, -11.605, 4.325, 4.649; P<0.05); compared with the high glucose group, the relative expression of iNOS and CD86 protein was decreased and the relative expression of Arg-1 and CD206 protein was increased in BV2 cells in the metformin + high glucose group compared with the high glucose group, and the differences were all statistically significant ( t=7.231, 5.560, -8.035, -8.824; P<0.01). ELISA results showed that compared with the control group, the BV2 cells in the high glucose group had increased IL-6, TNF-α content and IL-4 content was decreased in BV2 cells in the high glucose group compared with the control group, and the differences were all statistically significant ( t=-64.312, -127.147, 71.547; P<0.001); compared with the high glucose group, IL-6 and TNF-α content was significantly decreased and IL-4 content was significantly increased in BV2 cells in the metformin+high glucose group, and the differences were all statistically significant ( t=44.426, 83.232,-143.115; P<0.001). After co-culture of BV2 cells with 661W cells for 24 h, the results of MTT colorimetric assay showed that compared with the control group, the activity of 661W cells in the high glucose group was significantly reduced, and the difference was statistically significant ( t=7.456, P<0.01); compared with the high glucose group, the activity of 661W cells in the metformin+high glucose group was increased ( t=-3.076, P<0.05). TUNEL method and flow cytometry showed that the apoptosis rate of 661W cells in the high glucose group was significantly higher compared with the control group, and the differences were both statistically significant ( t=-22.248, -22.628; P<0.001); compared with the high glucose group, the apoptosis rate of 661W cells in the metformin+high glucose group was significantly decreased, and the difference was statistically significant ( t=11.767, 6.906; P<0.001, 0.01). Conclusion:In the high glucose environment, metformin inhibited the inflammatory response and attenuated the apoptosis of photoreceptor cells by regulating the polarization of microglia toward the M2 type.

OBJECTIVETo investigate the effects of ambient conditions on the antibacterial activity of inorganic antibacterial agent based on sodium titanium phosphate.

METHODSThe number of live E. Coli ATCC 44113 was counted after the suspension was shaken and incubated in flask with antibacterial agent under ambient conditions.

RESULTThe number of live bacteria increased when the concentration of bacteria increased in the range of 1.2 x 10(2) to 1.2 x 10(8) cfu/ml. The antibacterial activity increased with the increase of ambient temperature in the range of 16 approximately 46 degrees C, showing good antibacterial activity at human body temperature. With the increase of the concentrations of co-existing NaCl and protein, the antibacterial activity was found to decrease at first and level off at 0.01 g/ml and 0.0005 g/ml respectively.

CONCLUSIONThe antibacterial agent has to be used together with organic antibacterial agent in order to achieve good antibacterial effect when the ambient bacterial concentration is high. The antibacterial agent is promising to be used in the preparation of antibacterial cloth because it is highly effective at body temperature and expected to remain antibacterial in perspiration.

Anti-Bacterial Agents ; pharmacology ; Bacteria ; drug effects ; Body Temperature ; Environment ; Microbial Sensitivity Tests ; Sodium ; chemistry ; Titanium ; pharmacology

Objective: To investigate the effects of miR-124a on proliferation, migration and invasion in rheumatoid arthritis synovial fibroblasts (RASFs) and the underlying mechanisms. Methods: RASFs were isolated and cultured from synovial tissue, then qRT-PCR was used to detect the levels of AKT2 mRNA and miR-124a in RASFs. Western blot was applied to determin the expression level of AKT2 protein. RASFs were transfected with miR-124a, anti-miR-124a, si-AKT2 or pcDNA-AKT2 to up-regulate or down-regulate the expression level of miR-124a or AKT2 protein. The cells were divided into normal group of normal synovial tissue, control NC group, miR-con group, miR-124a group, si-con group, si-AKT2 group, miR-124a+pcDNA group and miR-124a+pcDNA-AKT2 group. MTT assay was carried out to measure the proliferation of RASFs. Transwell assay was carried out to detect the migration and invasion cell number of RASFs. Dual-luciferase reporter assay system was implemented to verify the relationship between miR-124a and AKT2. Independent sample t-test and one way analysis of variance (ANOVA) test (square deviation) were used for statistical analysis. Results: ① Compared with normal group, the expression of miR-124a (0.92±0.19) decreased significantly (t=5.788, P<0.01), AKT2 mRNA (3.15±0.63) increased significantly (t=-3.486, P=0.025), AKT2 protein (2.09±0.64) increased significantly (t=-2.959, P=0.042). ② Ccompared with NC group and miR-con group, miR-124a expression (4.17±0.46) increased significantly (F=131.830, P<0.01), migration cell number (34±6) decreased significantly, invasion cell number (14.5±3.1) decreased significantly (F₁=35.788, F₂=27.211, P<0.01). ③ Compared with mir-con group (1.02±0.18), WT-AKT2 in miR-124a group showed a significant decrease in its relative activity (0.31±0.11) (t=5.830, P<0.01). ④ Compared with NC group and si-con group, the expression of AKT2 protein (0.97±0.03) in si-AKT2 group decreased significantly (F=128.056, P<0.01), the number of migrating cells (32±4), and the number of invasive cells (18.6±2.2) (F₁=-70.082, F₂=36.524, P<0.01) were decreased significantly. ⑤ Compared with miR-con group, AKT2 protein expression in miR-124a group decreased significantly (0.21±0.03); compared with miR-124a+pcDNA group, AKT2 protein expression in miR-124a+pcDNA-AKT2 group was increased significantly (F=52.487, P<0.01). ⑥ Compared with miR-con group, the number of RASFs migrating cells (30±5) and invasive cells (12.5±1.8) in miR-124a group were significantly decreased; compared with miR-124a+pcDNA group, the number of RASFs migrating cells (71±4) and invasive cells (26.4±4.5) in miR-124a+pcDNA-AKT2 group were significantly increased (F₁=30.957, F₂=49.960, P<0.01). Conclusion MiR-124a can inhibite the proliferation, migration and invasion of RASFs by targeting AKT2 gene. MiR-124a is expected as a molecular target for diagnosis and treatment of rheumatoid arthritis.

This study summarizes the application of automatic recognition technologies for patient-ventilator asynchrony(PVA)during mechanical ventilation.In the early stages,the method of setting rules and thresholds relied on manual interpretation of ventilator parameters and waveforms.While these methods were intuitive and easy to operate,they were relatively sensitive in threshold setting and rule selection and could not adapt well to minor changes in patient status.Subsequently,machine learning and deep learning technologies began to emerge and develop.These technologies automatically extract and learn data characteristics through algorithms,making PVA detection more robust and universal.Among them,logistic regression,support vector machines,random forest,hidden Markov models,convolutional autoencoders,long short-term memory networks,one-dimensional convolutional neural networks,etc.,have all been successfully used for PVA recognition.Despite the significant advancements in feature extraction through deep learning methods,their demand for labelled data is high,potentially consuming significant medical resources.Therefore,the combination of reinforcement learning and self-supervised learning may be a viable solution.In addition,most algorithm validations are based on a single dataset,so the need for cross-dataset validation in the future will be an important and challenging direction for development.

Objective:To analyze the causal relationship between lifestyle-based factors and the occurrence and development of hepatobiliary malignancies by Mendelian randomization study method,and to provide the potential clinical evidence for the prevention and treatment of hepatobiliary malignancies.Methods:The data from large-scale,independent genome-wide association studies(GWAS)were selected,and seven-step inclusion criteria for the instrumental variable screening were set up.The exposure lifestyles included the percentage of carbohydrate intake,percentage of fat intake,percentage of protein intake in the diet,coffee intake,weekly alcohol consumption times,leisure electronic screen exposure time,moderate to vigorous intensity physical activity(MVPA)during leisure time,sedentary behavior at work,age at first smoking,daily smoking quantity,current smoking status,and past smoking status,totaling 12 phenotypes.The primary analysis method used was the random effect model of the inverse variance weighted(IVW)method,and the heterogeneity was detected by Cochrane's Q test and the horizontal pleiotropy was detected by MR-Egger intercept method.Results:The current smoking status was significantly positively correlated with the increasing risk of extrahepatic cholangiocarcinoma(OR=1.607,95%CI:1.113-2.322,P=0.011).Higher coffee intake was causally linked to a higher risk of liver cancer and intrahepatic cholangiocarcinoma(OR=1.000,95%CI:0.999-1.000,P=0.012).In the physical activity,more MVPA was associated with the lower risk of liver cancer and intrahepatic cholangiocarcinoma(OR=0.998,95%CI:0.996-0.999,P=0.002).The Cochrane's Q test results showed that there was mild heterogeneity between MVPA and extrahepatic cholangiocarcinoma(Q=18.354,P=0.049)as well as the percentage of protein intake and intraphepatic cholangiocarainoma(Q=12.715,P=0.026),and the MR-Egger intercept method results showed there was no horizontal pleiotropy.Conclusion:There is a causal relationship between current smoking status and extrahepatic cholangiocarcinoma,and there is a causal relationship between more MVPA and the lower risk of liver cancer and intrahepatic cholangiocarcinoma.Education on smoking and physical activity for the patients may offer potential benefits for the prevention of hepatobiliary malignancies.

Objective: To evaluate the consistency between prostate biopsy and postoperative pathological grade, analyze the influencing factors that may lead to upgrade or downgrade, and to establish a prediction model. Methods: The clinical data of biopsy GS3+ 3=6(GR1, 330 cases) and GS3+ 4=7(GR2, 340 cases) patients from January 2013 to December 2018 in the first affiliated hospital, College of Medicine of Zhejiang university were retrospectively analyzed. The median age was 67 years old(ranging 35 to 100 years old). The median BMI was 23.74 kg/m²(ranging 16.22-38.74 kg/m²). The Median tPSA was 10.266 ng/ml(ranging 0.017-147.575 ng/ml). The median prostate volume was 29.43 ml(5.92-187.20 ml). The median PSAD was 0.34 (ranging 0.01-4.02). The median percentage of positive puncture cores was 0.25 (ranging 0.08-1.00). There were 161 patients in clinical stage ≤T_1c, 344 patients in T_2a-T_2c and 165 patients in clinical stage ≥T₃. 670 cases all accepted the radical prostatectomy. Consistency of prostate biopsy and radical prostatectomy Gleason grade was recorded. If the postoperative Gleason grade was higher than that in biopsy, it was defined as upgrade. Otherwise, it was defined as downgrade. Multivariate logistic regression model was used to evaluate the influencing factors leading to upgrades in GR1 patients or downgrades in GR2 patients. Nomograms were drawn based on the models with AUC and Horsmer-Lemeshaw test conducted to test the discrimination and calibration of the models. Results: Among the 670 patients included, 165 cases (50.0% of GR1) upgrades and 27 cases (7.9% of GR2) downgrades. PSAD≥0.25(OR=3.015) and clinical stage≥T_2b(OR=7.185)were independent influencing factors for the upgrade in GR1 patients, while PSAD<0.15(OR=4.208) and clinical stage≤T_1c(OR=4.530) were independent influencing factors for downgrade. The nomograms were drawn with the above variables. The AUC of the model (0.781 for GR1 group, 0.741 for GR2 group) and the hosmer-remeshaw test results (P=0.993 for GR1 group, P=0.234 for GR2 group) show that the nomograms have good discrimination and calibration. Conclusions PSAD and clinical stage are independent influencing factors for the upgrade or downgrade. Nomograms may provide help for clinicians to judge the accuracy of prostate biopsy. However, the nomograms still needs to be verified in clinical practice