This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

Aim To explore the mechanism of Con-grong Shujing granule(CSGs)in the treatment of Par-kinson's disease(PD)by network pharmacology,mo-lecular docking and parallel reaction monitoring(PRM)technology.Methods The active components of CSGs and the target genes of Parkinson's disease were obtained through the database.The intersection targets of drugs and diseases were selected to construct the"drug-active ingredient-target"and protein interac-tion network.The intersection target genes were impor-ted into David database for GO and KEGG enrichment analysis,and the main components were docked with key targets.27 SD rats were randomly divided into the normal group(n=9),model group(n=9)and treat-ment group(n=9).On day 1,7 and 14 of treatment,PRM analysis was used to detect the changes in the specific peptides of key target proteins in the substantia nigra of rats.Results The main components of CSGs wereTanshialdehyde,Baicalein,Quercetin and Kaempferol.The most important targets for the treat-ment of PD were TP53,AKT1,EGFR,HSP90 AA1 and STAT3.KEGG analysis mainly enriched MAPK,PI3K-Akt and neurotrophic factor signaling pathway.The molecular docking between core components and core targets showed that the binding of drugs and targets had good activity.PRM analysis of key proteins found that the target peptide expression levels of ASK1,JNK1 and JNK3 were different among groups(P＜0.05).Con-clusion CSGs can alleviate ERS,inhibit apoptosis and play a neural protective role through the ASK1-JNK pathway.

Aim To explore the mechanism of Con-grong Shujing granule(CSGs)in the treatment of Par-kinson's disease(PD)by network pharmacology,mo-lecular docking and parallel reaction monitoring(PRM)technology.Methods The active components of CSGs and the target genes of Parkinson's disease were obtained through the database.The intersection targets of drugs and diseases were selected to construct the"drug-active ingredient-target"and protein interac-tion network.The intersection target genes were impor-ted into David database for GO and KEGG enrichment analysis,and the main components were docked with key targets.27 SD rats were randomly divided into the normal group(n=9),model group(n=9)and treat-ment group(n=9).On day 1,7 and 14 of treatment,PRM analysis was used to detect the changes in the specific peptides of key target proteins in the substantia nigra of rats.Results The main components of CSGs wereTanshialdehyde,Baicalein,Quercetin and Kaempferol.The most important targets for the treat-ment of PD were TP53,AKT1,EGFR,HSP90 AA1 and STAT3.KEGG analysis mainly enriched MAPK,PI3K-Akt and neurotrophic factor signaling pathway.The molecular docking between core components and core targets showed that the binding of drugs and targets had good activity.PRM analysis of key proteins found that the target peptide expression levels of ASK1,JNK1 and JNK3 were different among groups(P＜0.05).Con-clusion CSGs can alleviate ERS,inhibit apoptosis and play a neural protective role through the ASK1-JNK pathway.

Aim To investigate the effect of recombi-nant glycoprotein hormone β5/α2(rCGH)on lipolysis in 3T3-L1 adipocytes,and explore the underlying mechanism.Methods 3T3-L1 preadipocytes were cultured and induced to differentiate into mature adipo-cytes,then treated with different concentrations of rCGH for 24 h in vitro.Cell viability of 3T3-L1 adipo-cytes was evaluated by CCK-8 assay,the levels of in-tracellular triglyceride(TG)and glycerol in the culture supernatant were measured by enzymatic method,and the changes of lipid droplets were observed by oil red O staining.The expression levels of HSL and ATGL lipo-lytic proteins in adipocytes were detected by Western blot.To carry out the intervention experiment with dif-ferent concentrations of rCGH with or without the PKA inhibitor,H89,on the mature 3T3-L1 adipocytes,the cultured cells were divided into the control group,H89 pre treatment group,1 μmol·L-1 rCGH group,and(1 μmol·L-1 rCGH+H89)combined intervention group.The contents of intracellular TG and free glycer-ol were measured by enzymatic method,and the ex-pression of CREB and lipolysis-related proteins was de-tected using Western blot.Results Different concen-trations of rCGH(0.25,0.5,1,and 2 μmol·L-1)had no significant effect on the cell viability of adipo-cytes(P＞0.05).Compared with the control group,the treatment with rCGH significantly decreased the size of lipid droplets and intracellular TG content,while significantly elevated glycerol concentration in cell supernatant.rCGH treatment also stimulated the protein expression of p-HSL,ATGL,and p-PKA.In addition,the addition of a PKA inhibitor,H89,atten-uated the effects of rCGH on free glycerol level,intra-cellular TG content,and the expression of p-HSL,p-PLIN1,and p-CREB.Conclusions rCGH enhances the lipolysis of 3T3-L1 adipocytes by up-regulating the activities of HSL,ATGL and PKA,promoting glycerol release,inhibiting TG synthesis and lipid accumula-tion,and its mechanism of action is related to the acti-vation of cAMP/PKA/CREB signaling pathway.

Objective To develop a health belief model(HBM)based adolescent alcohol-related cognition scale to measure adolescent alcohol-related cognition and test its reliability and validity.Methods The adolescents'alcohol-related cognitive scale was developed based on HBM model.By using purposive sampling,three general high schools in Qingpu District,Shanghai were selected.One-third of the classes from grades 10 and 11 in each school were randomly selected,and the students from these classes were surveyed as the research subjects.Exploratory factor analysis and confirmatory factor analysis were used to analyze its reliability(internal consistency reliability and combination reliability)and validity(structural validity,convergent validity,discriminative validity and criterion validity).Results A total of 970 questionnaires were collected,of which 948 were valid,with an effective rate of 97.7%.The adolescents'alcohol-related cognitive scale contained 22 items.Five common factors were extracted from exploratory factor analysis,including perceived susceptibility,perceived severity,perceived benefits,perceived obstacles,and self-efficacy.The cumulative variance contribution rate reached 83.89%.The results of confirmatory factor analysis confirmed the overall fit of the model.The average variance extracted value(AVE)of each dimension was greater than 0.5,and the convergent validity of the model was ideal.The AVE square root of each dimension of the scale was greater than its correlation coefficient,indicating good discrimination validity.Cronbach's α coefficient of the total volume table was 0.892,indicating good overall reliability.Conclusion The adolescents'alcohol-related cognitive scale developed in this study has good reliability and validity,which can be used to measure adolescents'alcohol-related perceptions.

In order to study the compounds from Glechoma longituba (Nakai) Kupr. and explore the substance bases of its dissipating blood stasis, MCI, silica gel, Sephadex LH-20, ODS column chromatography and preparative thin layer chromatography were used to isolate and purify the compounds. The structures were identified by MS, 1D NMR, and 2D NMR spectra analysis, etc. Eight triterpenoids were isolated from dichloromethane fraction of ethanol extract from G. longituba and identified as 2α,3α,16β-trihydroxy-13α,27-cyclours-11-en-28-oic acid (1), 28-norurs-12-ene-3β,17β-diol (2), 28-norolean-12-ene-3β,17β-diol (3), oleanonic acid (4), 3β,13β-dihydroxyurs-11-en-28-oic acid (5), uvaol (6), oleanolic acid (7), ursolic acid (8). Compound 1 is a new hexacyclic triterpene with 13α,27-cyclopropane structure, named euscaphic acid H; compounds 2 and 3 were isolated from Lamiaceae for the first time while compounds 4 and 5 were isolated from this genus. The in vitro anticoagulant activity of triterpenoids was evaluated by four coagulation indexes (activated partial thromboplastin time, APTT; thrombin time, TT; prothrombin time, PT; fibrinogen, FIB). Among them, compounds 1 and 6 showed obvious anticoagulant effects.

OBJECTIVE To evaluate the effect and mechanism of Qili Huanshao Formula(QLHSF)in ameliorating sex hormone disturbance and oxidative damage in testicular tissues of D-galactose-induced subacute aging mice.METHODS 105 male mice were randomly divided into the normal group,model group,low,medium and high doses of QLHSF group,vitamin E(VE)group and Jin Gui Shen Qi Wan(JGSQW)group.The subacute senescence model was established by continuous intraperitoneal injection of D-galac-tose(D-gal)and treated by intragastric administration,as well.The testicular histopathological damage was detected by HE staining.The levels of relevant sex hormones in serum were detected by ELISA.The expression of oxidative stress factors was detected by related kits.The apoptotic cells in testicular tissue were detected by TUNEL assay,and the expressions of oxidative stress and apop-totic related proteins in the testicular tissues of mice were detected by Western blot.RESULTS Compared to the aging model mice,all dose groups of QLHSF could obviously improve testicular tissue pathological damage.The levels of T,E2 and GnRH levels were in-creased,while LH and FSH were decreased in serum(P<0.01).Meanwhile,the SOD activity(P<0.01)and the levels of GSH(P<0.01)were increased,while MDA levels(P<0.01)were decreased in serum and testicular tissues.The medium dose group of QLHSF significantly inhibited testicular cell apoptosis(P<0.01),increased the expression of Nrf2,HO-1 protein and Bcl-2/Bax ratio(P<0.05),and down-regulated the expressions of Cleaved-Caspase-3/Caspase-3,Cleaved-Caspase-9/Caspase-9 apoptotic protein in the testis of mice(P<0.05).CONCLUSION QLHSF can effectively improve sex hormone disturbance and protect testicular tissue in aging mice,and the mechanism of action might be related to the inhibition of oxidative stress-induced apoptosis in testicular tissues.The study will provide reference and lay the foundation for the clinical application and functional anti-aging product develop-ment of Lycium barbarum and its formulations.

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies

OBJECTIVE: To establish the occupational exposure limit for trimethyltin chloride(TMT) in workplace air. METHODS:According to the GBZ/T 210.1-2008 Guide for Establishing Occupational Health Standards--Part 1: Occupational Exposure Limits for Airborne Chemicals in the Workplace, the relevant literatures on toxicology, population epidemiology and foreign occupational exposure limit of TMT were collected and analyzed. A total of 276 workers with TMT occupational exposure were selected as the exposure group and 25 workers without TMT occupational exposure were selected as the control group.Worksite survey of occupational health and occupational medical examination were carried out. Combined with the literature data, the occupational exposure limit of TMT in the workplace air was calculated by using the 90% medical reference level(internal exposure limit) of the urine TMT level of workers who exposed to TMT without moderate hypokalemia. RESULTS: The time-weighted average of TMT in the workplace air is 0.100 mg/m~3 and the short-term exposure limit is 0.200 mg/m~3 in the United States based on total organic tin. The highest concentration of TMT in the workplace air in Germany is 0.005 mg/m~3. The literature data analysis results showed that the incubation period of TMT poisoning is mostly 3-6 days, and the main symptoms of TMT poisoning are hypokalemia in the early stage, followed by neuropsychiatric symptoms such as headache, memory loss and aggressive behavior. The median(M) and the 0-100 th percentile(P_0-P_(100)) of exposure to TMT were 8.35(< 0.20-91.40) μg/m~3 in the exposure group. The individual TMT exposure level of workers in different positions from high to low were crushing, granulation, withdrawal and assembly positions. The M(P_0-P_(100)) of urinary TMT level in the exposure group was 16.94(<0.50-591.14) μg/L. There was a positive correlation between the individual TMT exposure level and urine TMT level in the exposure group(Spearman correlation coefficient=0.62, P<0.01). The detection rate of hypokalemia in the exposure group was higher than that in the control group(26.1% vs 4.0%, P < 0.05). However, there was no significant difference in the detection rate of moderate hypokalemia between the two groups(3.3% vs 0.0%, P>0.05). The 90% medical reference value of urine TMT was 89.90 μg/L in workers exposed to TMT without moderate hypokalemia. CONCLUSION: In order to prevent acute hypokalemia damage caused by TMT, we recommended that the occupational exposure limit of TMT in the workplace air should be set at 0.025 mg/m~3 in China, and this limit should be the maximum allowable concentration.

Objective: To learn the awareness rate of adverse events following immunization ( AEFI ) among Chinese parents, so as to provide suggestions for promoting vaccination. Methods: We searched relevant articles published before 24th June, 2020 from CNKI, Wanfang, VIP, CBM, PubMed and Web of Science, calculated the pooled awareness rate and 95% confidence interval ( CI ) , conducted Egger＇s test for publication bias and sensitivity analysis for stability of results. Results: Eight articles using cross-sectional design were included after screening from 235 initial records. Among 5 433 subjects, the pooled awareness rate of AEFI was 66.76% ( 95%CI: 52.75%-78.33% ) . Non-immigrant population possessed a higher awareness rate ( 67.32% ) compared with the immigrant population ( 56.54% ) . The parents with different levels of education showed various awareness rate of AEFI ( P<0.05 ) . The awareness rates of "children should be observed for at least 30 minutes after vaccination","slight adverse effects were commonly seen after vaccination","local redness and induration might occur after diphtheria-tetanus-pertussis ( DTP ) immunization","polio vaccine might bring mild diarrhea" were 86.18%, 66.76%, 41.89% and 30.22%, respectively. Egger＇s test showed that there was no publication bias. Sensitivity analysis indicated that the results were robust. Conclusion The pooled awareness rate of AEFI among Chinese parents is 66.76%, with lower rates found in the parents who are immigrants and have lower level of education.