Obｊective To investigate the protective mechanism of tricholoma matsutake polysaccharides(TMP) against 1-methy-4-pehnyl-pyridine ion (MPP

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Objective To analyze the independent influencing factors of intimate partner homicide(IPH)cases,construct an IPH prediction model,and provide a basis for criminal profiling.Methods A total of 476 convicted homicide cases in Guangdong Province from January 1,2014,to December 31,2020,were collected as modeling dataset.They were divided into the IPH group(n=180)and the non-intimate partner homicide(N-IPH)group(n=296)based on whether the offender and victim were intimate partners.Logistic regression was used to build the model,the model was evaluated through the receiver operating characteristic(ROC)curve analysis and a nomogram was drawn.Inter-nal validation was conducted using ten-fold cross-validation method.A total of 126 court judgments from outside Guangdong Province from January 1,2011,to December 31,2020,were randomly col-lected for external validation.Results Through multi-factor Logistic regression analysis,7 variables were ultimately selected for inclusion in the model.The Hosmer-Lemeshow goodness of fit test result of the model was χ2=13.158,P=0.068.The ROC area under the curve(AUC)of the model was 0.939(95%CI:0.919-0.959),the cut-off value was 0.292,the sensitivity was 0.900,and the specificity was 0.865.The calibration curve was close to the ideal curve.The ten-fold cross-validation showed the accuracy of 0.863 and a Kappa value of 0.708.The external validation results showed an AUC of 0.922(95%CI:0.872-0.971),a cut-off value of 0.292,a sensitivity of 0.890,and a specificity of 0.886.The calibration curve tended to the ideal curve.Conclusion The IPH prediction model based on forensic field indicators has good predictive ability,reliable accuracy and stability,and can provide a scientific method for criminal profiling.

Objective:To study influence of Status-Background-Assessment-Recommendation(SBAR)communi-cation mode intervention on patients with heart failure(HF).Methods:According to intervention method,a total of 187 HF patients treated in our hospital were divided into routine intervention group(n=96,received routine in-tervention based on routine treatment)and SBAR group(n=91,received SBAR communication mode intervention based on routine treatment).Both groups were intervened for six months.General clinical data,LVEF,left ven-tricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),scores of Morisky medi-cation compliance scale and the medical outcomes study 36-item short-form heath survey(SF-36),patients'satis-faction and incidence rate of major adverse cardiovascular events(MACE)within six-month follow-up were com-pared between two groups.Results:Compared with routine intervention group,after intervention,there were sig-nificant rise in LVEF[(53.44±2.11)%vs.(57.72±1.80)%],scores of Morisky medication compliance scale[(2.00±0.77)scores vs.(3.63±1.07)scores]and SF-36[(68.83±7.62)scores vs.(76.81±9.68)scores],and significant reductions in LVEDV[(132.63±5.59)ml vs.(119.15±6.89)ml]and LVESV[(64.36±5.82)ml vs.(56.62±4.21)ml]in SBAR group(P=0.001 all).Patients'satisfaction of SBAR group was significantly higher than that of routine intervention group(89.01%vs.73.96%,χ2=6.958,P=0.008),and incidence rate MACE during follow-up was significantly lower than the latter(5.49%vs.15.63%,LogRankχ2=5.043,P= 0.025).Conclusion:SBAR communication mode intervention can significantly improve heart function,medication compliance and quality of life in patients with heart failure,with high patients'satisfaction.

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

OBJECTIVE: To express and purify the antigenic peptide of adeno-associated virus (AAV) capsid conserved regions in prokaryotic cells and prepare its rabbit polyclonal antibody. METHODS: The DNA sequence encoding the conserved regions of AAV capsid protein was synthesized and cloned into the vector pET30a to obtain the plasmid pET30a-AAV-CR for prokaryotic expression and purification of the conserved peptides. Coomassie blue staining and Western blotting were used to identify the AAV conserved peptides. Japanese big ear white rabbits were immunized with AAV conserved region protein to prepare polyclonal antibody, with the rabbits injected with PBS as the control group. The antibody titer was determined with ELISA, and the performance of the antibody for recognizing capsid protein sequences of AAV1-AAV10 was assessed with Western blotting and immunofluorescence assay. RESULTS: The plasmid pET30a-AAV-CR was successfully constructed, and a recombinant protein with a relative molecular mass of 17000 was obtained. The purified protein induced the production of antibodies against the conserved regions of AAV capsid in rabbits, and the titer of the purified antibodies reached 1:320 000. The antibodies were capable of recognizing a wide range of capsid protein sequences of AAV1-AAV10. CONCLUSION We successfully obtained the polyclonal antibodies against AAV capsid conserved region protein from rabbits, which facilitate future studies of AAV vector development and the biological functions of AAV.
Animals ; Antibodies ; Capsid ; Capsid Proteins/genetics* ; Dependovirus/genetics* ; Prokaryotic Cells ; Rabbits ; Recombinant Proteins/genetics*

Da Chaihu decoction is a classic prescription for the treatment of cholecystitis that is widely used in clinical practice, and has a definite curative effect. However, due to its diverse components and complex functions, the traditional indexes fail to capture its overall efficacy. Therefore, this study analyzed and predicted the quality markers (Q-markers) of Da Chaihu decoction based on specific chromatogram and network pharmacology to provide a reference for the comprehensive control of the quality. The study obtained 35 potential practical components of Da Chaihu decoction through virtual screening. The specific chromatogram of 15 batches of Da Chaihu decoction was established by HPLC-DAD with neohesperidin as a reference. Compared with the chromatographic peaks and the reference substance, the chemical components were assigned to predict the nine components of albiflorin, paeoniflorin, naringin, hesperidin, neohesperidin, baicalin, wogonoside, saikosaponin b₂, saikosaponin b₁ as Q-markers of Da Chaihu decoction. Finally, the network of the "components-key targets-signal pathways-biological processes" was constructed by network pharmacology to explore the mechanism of Da Chaihu decoction in treating cholecystitis to clarify the accuracy of Q-markers. The results indicated that potential Q-markers could act on multiple targets to regulate inflammatory and metabolism, and then combine to treat cholecystitis. Q-markers could combine with the pharmacologic action of Da Chaihu decoction, which could elucidate the overall efficacy of Da Chaihu decoction. This study explored the Q-markers of Da Chaihu decoction combined with the specific chromatogram and network pharmacology, which provided a basis for the quality control and evaluation of Da Chaihu decoction.

Essential fatty acids are those that could not be synthesized by the body itself but crucial for health and life. Studies have shown that ω-3 fatty acids may facilitate human physiological functions. Mammals lack ω-3 desaturase gene, and the Δ15 fatty acid desaturase (Δ15 Des) from Caenorhabditis elegans can transform the ω-6 polyunsaturated fatty acids (PUFAs) into ω-3 PUFAs. Transgenic mice expressing Δ15 Des enzyme activity was constructed by using a PiggyBac transposon (PB). Homozygous transgenic mice with stable inheritance was bred in a short time, with a positive rate of 35.1% achieved. The mice were fed with 6% ω-6 PUFAs and the changes of fatty acids in mice were detected by gas chromatography (GC). The expression level of Δ15 Des in mice was detected by quantitative PCR (qPCR) and Western blotting (WB). qPCR and GC analysis revealed that the percentage of positive mice harboring the active gene was 61.53%. Compared with traditional methods, the transformation efficiency and activity of Δ15 Des were significantly improved, and homozygotes showed higher activity than that of heterozygotes. This further verified the efficient transduction efficiency of the PiggyBac transposon system.
Animals ; Caenorhabditis elegans/genetics* ; Fatty Acid Desaturases/genetics* ; Fatty Acids ; Fatty Acids, Omega-3 ; Mice ; Mice, Transgenic

Studies have found that metformin is not only the preferred drug for lowering blood sugar, but also shows lipid-lowering and weight-loss effects. The purpose of this study was to use a hyperlipidemia hamster model to investigate the lipid-lowering effect of metformin and its effect on important metabolic pathways in lipid metabolism disorders. Fifty golden hamsters were divided into a control group, a model group, metformin high- and low-dose groups, and a simvastatin group. A high-fat diet was fed for 1 week to create the model, and then drug was administered for 11 weeks with the high-fat diet. Serum was taken for measurement of blood lipid and blood glucose at 2, 6, and 9 weeks after administration, and at weeks 3, 5, and 9 feces and urine were collected for ¹H NMR metabolomics tests. After 11 weeks of intravenous injection of [U-¹³C₆] glucose, serum was collected for a ¹³C NMR metabolic flux test. The results showed that the administration of metformin can significantly reduce blood lipids and glucose levels and can significantly affect metabolic pathways such as sugar metabolism, lipid metabolism, ketone metabolism, amino acid metabolism, and intestinal flora metabolism. The results of the metabolic flux analysis showed that the high-fat diet reduced the metabolism of tricarboxylic acids by 37.48%. After administration of low and high doses of metformin the metabolism of tricarboxylic acid increased by 98.14% and 143.10%, respectively. After administration of simvastatin tricarboxylic acid metabolism increased by 33.18%. The results indicate that metformin has a significant effect on promoting energy metabolism. This study used a combination of metabolomics and metabolic flow to explore the effect of metformin on lipid metabolism disorders and quantifies changes in the key pathway of energy metabolism-the tricarboxylic acid cycle. This study provides useful information for the study of the efficacy and mechanism of metformin, as well as a practical technical method for the screening of lipid-lowering drugs based on a hamster model.

OBJECTIVE: To understand the true perception and attitude of the healthcare workers(HCWs) on the workplace violence(WPV) in a secondary Grade A hospital.METHODS: A total of 27 HCWs in a secondary Grade A hospital were selected as study subjects using a typical sampling method. Semi-structured interviews were conducted to collect the information of their perception and attitude on the types and effects of WPV, as well as on the coping measures and the work stress. The characteristics of WPV in the hospital were analyzed. RESULTS: The interviewees believed that verbal abuse was the most common type of WPV received by HCWs. Nurses and female workers were the main victims of WPV. Horizontal violence among colleagues and sexual harassment should not be ignored. Common causes of violent incidents for patients and their family members against HCWs included the fees for treatment, doctor-patient communication, patients alcohol abuse and treatment outcomes not meeting patients′ expectation. About half of the interviewees said that WPV had serious impact on their mental health. The follow-up coping measures to violent incidents were mostly to reassurance to patients with unconditional apology from the HCWs. More than half of the interviewees considered that they had acceptable workload, while some interviewees considered their work to be stressful. The interviewees suggested that improving doctor-patient communication, hospital systems, and the professional knowledge of HCWs were the recommended means to prevents and control the WPV. CONCLUSION: The perception and attitude of HCWs on WPV in this hospital are relatively scattered. Considering the complex causes, the serious consequences, and difficult coping measures, the hospitals, HCWs and all sectors of society need to take comprehensive measures to prevent WPV towards HCWs.