The study aims to elucidate the existence forms(original constituents and metabolites) of Notoginseng Radix et Rhizoma in rats and reveal its metabolic pathways. After Notoginseng Radix et Rhizoma was administered orally once a day for seven consecutive days to rats, all urine and feces samples were collected for seven days, while the blood samples were obtained 6 h after the last administration. Using the ultra high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technique, this study identified 6, 73, and 156 existence forms of Notoginseng Radix et Rhizoma in the rat plasma, urine, and feces samples, respectively. Among them, 101 compounds were identified as new existence forms, and 13 original constituents were identified by comparing with reference compounds. The metabolic reactions of constituents from Notoginseng Radix et Rhizoma were mainly deglycosylation, dehydration, hydroxylation, hydrogenation, dehydrogenation, acetylation, and amino acid conjugation. Furthermore, the possible in vivo metabolic pathways of protopanaxatriol(PPT) in rats were proposed. Through comprehensive analysis of the liquid chromatography-mass spectrometry(LC-MS) data, isomeric compounds were discriminated, and the planar chemical structures of 32 metabolites were clearly identified. According to the literature, 48 original constituents possess antitumor and cardiovascular protective bioactivities. Additionally, 32 metabolites were predicted to have similar bioactivities by SuperPred. This research lays the foundation for further exploring the in vivo effective forms of Notoginseng Radix et Rhizoma.
Animals ; Rats ; Drugs, Chinese Herbal/pharmacokinetics* ; Rhizome/metabolism* ; Male ; Rats, Sprague-Dawley ; Chromatography, High Pressure Liquid ; Panax notoginseng/chemistry* ; Tandem Mass Spectrometry ; Feces/chemistry*

This study investigated the mechanism by which Jianpi Bushen Yiqi Decoction promotes acetylcholine receptor(AChR) clustering in myasthenia gravis through the Agrin/low-density lipoprotein receptor-related protein 4(LRP4)/muscle-specific receptor tyrosine kinases(MuSK) signaling pathway. A total of 114 female C57BL/6J mice were divided into the normal group, modeling group, and solvent control group. The normal group and the solvent control group were immunized with phosphate-buffered saline(PBS), while the modeling group was established as an experimental autoimmune myasthenia gravis(EAMG) model using the murine-derived AChR-α subunit R97-116 peptide fragment. After successful modeling, the mice were randomly assigned to the model group, the low-, medium-, and high-dose Jianpi Bushen Yiqi Decoction groups, and the prednisone group. After four weeks of continuous treatment, muscle strength was assessed using Lennon scores and grip strength tests. Immunofluorescence staining was conducted on differentiated C2C12 myotubes incubated with a drug-containing serum to observe the number of AChR clusters. The integrity of AChR on myofilaments in mouse gastrocnemius muscles was further assessed by immunofluorescence staining. Hematoxylin-Eosin(HE)staining was applied to examine pathological changes in the gastrocnemius muscles of EAMG mice treated with Jianpi Bushen Yiqi Decoction. Western blot was utilized to detect the expression of key proteins in the Agrin/LRP4/MuSK signaling pathway in both C2C12 myotubes and mouse gastrocnemius muscles. The results demonstrated that compared to the model group, the prednisone group exhibited a significant decrease in the body weights of mice, whereas no significant differences in the body weights of mice were observed among the low-, medium-, and high-dose Jianpi Bushen Yiqi Decoction groups. All treatment groups showed significantly improved grip strength and Lennon scores. Additionally, the formula promoted AChR clustering on myotubes and enhanced AChR integrity in gastrocnemius myofilaments and reduced inflammatory infiltration between muscle tissue and fibrous hyperplasia. Furthermore, Jianpi Bushen Yiqi Decoction upregulated the protein expression of AChRα1, Agrin, and p-MuSK in C2C12 myotubes and increased the protein expression of AChRα1, Agrin, MuSK, p-MuSK, LRP4, and docking protein 7(Dok-7)in gastrocnemius tissue. In conclusion, Jianpi Bushen Yiqi Decoction may promote AChR clustering by targeting key proteins in the Agrin/LRP4/MuSK signaling pathway, thereby improving neuromuscular junction function and enhancing muscle strength.
Animals ; Agrin/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Receptors, Cholinergic/genetics* ; Female ; Mice, Inbred C57BL ; Receptor Protein-Tyrosine Kinases/genetics* ; Neuromuscular Junction/metabolism* ; Myasthenia Gravis, Autoimmune, Experimental/physiopathology* ; Humans ; LDL-Receptor Related Proteins

OBJECTIVES: To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels. METHODS: The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT). RESULTS: The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049). CONCLUSIONS The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans ; Adult ; Male ; Attention/physiology* ; Female ; Middle Aged ; Reproducibility of Results ; Young Adult ; Psychometrics

Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1(SOS1-IT1)affects enhancer of zeste homolog 2(EZH2)protein expression in endometrial cancer cells Ishikawa and RL95-2.Methods Lentiviral transfection of short hairpin RNA(shRNA)and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1.The mechanism of EZH2 expression regulation was studied using Real-time PCR,Western blotting,and chromatin immunoprecipitation.Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues.Knocking down SOS1-IT1 significantly reduces the expression of EZH2,inhibited the proliferation and migration of Ishikawa and RL95-2 cells,and could reduced the acetylation of histone H3 at position 27(H3K27)and the enrichment of CREB binding protein(CBP)in the EZH2 gene promoter region.Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP.CBP could bind to SOS1-IT1 RNA,and this binding ability was weakened when CBP was knocked down.Conclusion SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region,thereby affecting the proliferation and migration ability of endometrial cancer cells.

ObjectiveTo understand the awareness of knowledge about chronic obstructive pulmonary disease （COPD） and influencing factors among residents in Yangpu District， Shanghai. MethodsWe used cluster random sampling method to conduct face-to-face questionnaire surveys on selected household residents in 12 streets of Yangpu District. The survey questions included their understanding of COPD name， lung function test， and COPD related knowledge. Multivariate logistic regression analysis was used to analyze the influencing factors of awareness rate. ResultsA total of 1 440 people were ultimately included in the analysis， and the awareness rates of COPD name， lung function test， and COPD awareness were 19.93%， 18.61%， and 14.95%， respectively. Among the people who knew the name of COPD， awareness rate of shortness of breath or dyspnea was the highest （84.12%） in the three main symptoms of COPD. Among the main risk factors of COPD， second-hand smoke（86.78%）and smoking （85.82%） were the highest. The main ways to obtain knowledge of COPD names were through television （12.60%） and the internet （11.97%）. The results of multivariate logistic regression analysis showed that men were significantly higher than women in the awareness of COPD name， lung function test， and COPD knowledge， with the OR values of （OR=1.39， 95%CI：1.08‒1.79）， （OR=1.47，95%CI：1.12‒1.92） and （OR=1.37，95%CI：1.02‒1.84）， respectively. The awareness rate of COPD names and lung function tests was the highest among people aged ≥ 65 years old， while the awareness rate of COPD knowledge was the highest among people aged 35‒50 years old. The awareness rate of COPD names was the highest among people with college education or above， civil servants， teachers， and medical staff， people with an annual household income of 100 000‒200 000 yuan. ConclusionThe overall awareness rate of COPD names， lung function tests， and COPD related knowledge among residents in Yangpu District is still at a low level. We should intensify the promotion and education of COPD among key groups such as women， young people， and those with low income， in order to improve the overall awareness rate of COPD among the population.

Objective:To explore the current status of lipid-lowering therapy, the distribution of low-density lipoprotein cholesterol (LDL-C) levels and the risk assessment of cardiovascular events recurrence in patients with coronary heart disease (CHD) complicated by hypertension.Methods:This was a cross-sectional study. Patients with CHD combined with hypertension were hospitalized in the Department of Cardiology, General Hospital of Chinese People′s Liberation Army from August 5, 2008 to July 22, 2018 were included, and were divided into standard group and substandard group according to whether LDL-C reached the standard. Study data were obtained from inpatient coronary angiography records and electronic medical records database of Department of Cardiology, General Hospital of Chinese People′s Liberation Army, who used data from the first diagnosis of CHD. Clinical data of the selected patients were collected. Multivariate logistic regression model was used to analyze the associated factors of whether LDL-C reached the standard in CHD patients with hypertension.Results:A total of 18 800 patients were selected from 31 provinces/autonomous regions/municipalities directly under the central government in China, with Beijing accounting for the largest proportion (5 692 patients (30.28%)), followed by Hebei (3 621 patients (19.26%)), Henan (1 837 patients (9.77%)), and Shandong (1 618 patients (8.61%)). Among the selected patients, 1 493 had LDL-C<1.4 mmol/L (standard group), and 17 307 had LDL-C&ge;1.4 mmol/L (substandard group). Only 1 493 patients (7.94%) had LDL-C<1.4 mmol/L. There were 4 518 patients (24.03%), 4 366 patients (23.22%), 6 924 patients (36.83%) and 1 499 patients (7.97%) with LDL-C for 1.4-<2.0, 2.0-<2.5, 2.5-<3.8 and&ge;3.8 mmol/L levels, respectively. 17 855 patients (95.15%) were treated with statins, but only 1 334 patients (7.10%) were treated with statins and ezetimibe. Of the selected patients, 4 986 patients (26.52%) were at low risk, 6 515 patients (34.65%) were at intermediate risk, and 7 299 patients (38.82%) were at high risk. The combined lipid-lowering treatment rates of statin and ezetimibe in the middle-and high-risk patients were 7.43% (484/6 515) and 7.48% (546/7 299), respectively. The results of multivariate logistic regression analysis showed that increasing age, male, diabetes mellitus, stroke, and history of percutaneous coronary intervention (PCI) were positively associated with LDL-C standards in patients with CHD and hypertension, whereas obesity and acute myocardial infarction (AMI) were negatively associated with LDL-C standards (all P<0.01). Conclusions:The rate of achieving the standard LDL-C in patients with CHD combined with hypertension was low in China. Although the majority of patients had received moderate-intensity statin therapy, the proportion of statin-treated patients combined with ezetimibe was extremely low. The proportion of high-risk patients with recurrent cardiovascular events was higher in patients with CHD and hypertension in China, whereas the proportion of such patients receiving statin combined with ezetimibe lipid-lowering therapy was lower. This study also found that increasing age, male, diabetes mellitus, stroke, and history of PCI were positively associated with LDL-C standards, while obesity and AMI were negatively associated with LDL-C standards in patients with CHD and hypertension.

Objective To investigate the overweight and obesity of primary and middle school students in Sijing area of Shanghai from 2020 to 2022,so as to provide scientific basis for the intervention of childhood obesity.Methods In October 2020 and October 2022,all primary and middle school students in Sijing area underwent physical examination by cluster sampling method.A cross-sectional study was conducted to investigate the obesity and overweight in primary and middle school students of different ages and genders in Sijing area.Results In 2020 and 2022,7 766 and 10 594 students completed physical examination,respectively,and 4 626 of them underwent two consecutive physical examinations.The incidences of overweight and obesity were 15.14%and 21.89%in 2020,respectively.The incidences of overweight and obesity were 15.41%and 21.11%in 2022,respectively.There were no significant differences in the incidences of overweight or obesity between 2020 and 2022(P>0.05).In 2020,the incidences of overweight and obesity of male students were 14.91%and 24.70%;the incidences of overweight and obesity of female students were 15.40%and 18.80%,respectively.In 2022,the incidences of overweight and obesity of male students were 15.04%and 24.14%;the incidences of overweight and obesity of female students were 15.82%and 17.82%,respectively.There was no significant difference in the overweight rate between males and females(P>0.05).The incidence of obesity of male students was significantly higher than that of female students in both 2020 and 2022(P<0.05).In the students aged 12 years old,the incidence of obesity was 27.42%in 2022,which was significantly higher than that in 2020(P<0.05).There was no significant difference in the incidence of obesity between other age groups(P>0.05).Among the 4 626 children who participated in two consecutive physical examinations,the overweight/obesity rates were 14.46%/21.25%in 2020 and 16.04%/21.78%in 2022;there was significant difference in the overweight rates(P<0.05),while no significant difference was found in obesity rates(P>0.05).Among the 4 626 children,there were 2 402 boys and 2 224 girls.In 2020,the overweight/obesity rates were 13.70%/24.48%in these boys and 15.29%/17.76%in these girls.In 2022,the overweight/obesity rates were 16.07%/25.44%in these boys and 16.01%/17.72%in these girls.There was no significant difference in the incidence of overweight between these girls and boys in 2020 and 2022(P>0.05),but the obesity rate of boys was significantly higher than that of girls(P<0.05).Conclusion There are high incidences of overweight and obesity among primary and middle school students in Sijing area of Shanghai,and dietary and exercise guidances should be strengthened.Meanwhile,the incidences of overweight and obesity are higher among boys,and obesity prevention and control measures should be strengthened for boys.

Objective: To study the expression of long non-coding RNA LINC01152 in glioma and its influence on the malignant biological behavior of glioma cells． Methods: LINC01152 expression in glioma was analyzed by LncSpA V2．0 and GEPIA database．qRT-PCR was applied to detect the expression of LINC01152 mRNA in 10 samples of human normal brain tissues，40 samples of glioma tissues and 5 glioma cell lines．GO and KEGG enrichment analysis of LINC01152 co-expressed genes were performed using the DAVID database to predict the related functions． The AnoLnc2，TargetScan，LinkedOmics and miRDB databases were used to predict the LINC01152 related miRNAs and target genes to construct a ceRNA regulatory network．LINC01152 expression was knocked down in glioma cell lines by small interfering RNA (siRNA) transfection．The CCK-8 test，scratch healing experiments，Transwell，flow cytometry and Western blot experiments were used to measure the influence of LINC01152 on the proliferation，migra- tion，invasion and apoptosis of glioma cells. Results : Database analysis showed that compared with other tumor types，LINC01152 was highly expressed in glioblastoma (GBM) and low grade glioma (LGG) ，and was higher than normal brain tissue．qRT-PCR showed that the expression of LINC01152 mRNA in glioma tissues was significantly higher than that in normal brain tissues (P＜0. 01)．The expression of LINC01152 was correlated with Ki-67 (P < 0. 05) ，but not with clinical parameters such as gender，age，tumor size，P53 protein，glial fibrillary acidic protein (GFAP) ，O-6-methylguanine-DNAmethyltransferase ( MGMT) and WHO grade of glioma patients． Functional enrichment analysis of co-expressed genes indicated that the LINC01152 was mainly involved in biological processes such as cell adhesion and synaptic signaling．LINC01152-miRNA-mRNA regulatory network was constructed according to predicted target genes．After down-regulation of LINC01152 expression，the proliferation，migration and invasion abilities of A172 and U87 cells decreased(P＜0. 01) ，while the apoptosis of glioma cells significantly increased (P＜0. 001) ． Conclusion LINC01152 is highly expressed in glioma，which can promote the malignant biological behavior of glioma cells by enhancing proliferation，migration as well as invasion and inhibition of apoptosis.

OBJECTIVE To evaluate the clinical effectiveness and safety of domestic generic and imported original clopidogrel for antiplatelet therapy in patients with acute coronary syndrome （ACS）. METHODS The clinical data of ACS patients in Nanjing Drum Tower Hospital of China Pharmaceutical University from January 2020 to June 2021 were retrospectively collected by using electronic medical record system， and the patients were divided into original drug group （321 cases） and generic drug group （328 cases） according to the drug use. Both groups were given dual antiplatelet therapy with clopidogrel and aspirin. The effectiveness and safety outcomes of the two groups were followed up for 12 months and compared， the related influential factors were analyzed. RESULTS Major adverse cardiovascular events （MACE） occurred in 16 and 22 patients in original drug group and generic drug group respectively， including nonfatal myocardial infarction （4 and 5 cases）， stroke （2 and 4 cases）， revascularization （8 and 3 cases）， cardiovascular related death （2 and 4 cases）， and all-cause death （4 and 6 cases）. There were 12 and 7 patients with major bleeding events， 38 and 29 patients with minor bleeding events， and 33 and 21 patients with non-bleeding adverse events. There was no statistically significant difference in the cumulative incidence of related events （P values of Log-Rank tests were all greater than 0.05）. Cox regression analysis showed that the use of generic clopidogrel did not increase the risk of MACE and major bleeding events in ACS patients [hazard ratio of 1.305 and 0.416， 95% confidence interval of （0.678， 2.512） and （0.155， 1.117）， respectively， P＞0.05]， and the combination of proton pump inhibitors （PPI） could reduce the risk of major bleeding events [hazard ratio of 0.196， 95% confidence interval of （0.063， 0.611）， P＜0.05]. CONCLUSIONS Compared with imported original drug， domestic generic clopidogrel has similar clinical effectiveness and good safety. Combined use of PPI may be a beneficial factor to reduce the occurrence of major bleeding events in patients.

Objective: To understand the depression status and its influencing factors in elderly patients with MS in China and to explore the correlation between various components of elderly MS and depression. Methods: This study is based on the "Prevention and Intervention of Key Diseases in Elderly" project. We used a multi-stage stratified cluster random sampling method to complete 16 199 elderly aged 60 years and above in 16 counties (districts) in Liaoning, Henan, and Guangdong Provinces in 2019, excluding 1 001 missing variables. Finally, 15 198 valid samples were included for analysis. The respondents' MS disease was obtained through questionnaires and physical examinations, and the respondents' depression status within the past half month was assessed using the PHQ-9 Depression Screening Scale. The correlation between elderly MS and its components and depression and its influencing factors were analyzed by logistic regression. Results: A total of 15 198 elderly aged 60 years and above were included in this study, with the prevalence of MS at 10.84% and the detection rate of depressive symptoms in MS patients at 25.49%. The detection rates of depressive symptoms in patients with 0, 1, 2, 3, and 4 MS abnormal group scores were 14.56%, 15.17%, 18.01%, 25.21%, and 26.65%, respectively. The number of abnormal components of MS was positively correlated with the detection rate of depressive symptoms, and the difference between groups was statistically significant (P<0.05). The risk of depression symptoms in patients with MS, overweight/obesity, hypertension, diabetes, and dyslipidemia was 1.73 times (OR=1.73, 95%CI:1.51-1.97), 1.13 times (OR=1.13, 95%CI:1.03-1.24), 1.25 times (OR=1.25, 95%CI:1.14-1.38), 1.41 times (OR=1.41, 95%CI:1.24-1.60), 1.81 times (OR=1.81,95%CI:1.61-2.04), respectively, more than those without the disease. Multivariate logistic regression analysis showed that the detection rate of depressive symptoms in patients with sleep disorders was higher than that with normal sleep (OR=4.89, 95%CI: 3.79-6.32). The detection rate of depressive symptoms in patients with cognitive dysfunction was 2.12 times higher than that in the average population (OR=2.12, 95%CI: 1.56-2.89). The detection rate of depressive symptoms in patients with impaired instrumental activities of daily living (IADL) was 2.31 times (OR=2.31, 95%CI: 1.64-3.26) higher than that in the average population. Tea drinking (OR=0.73, 95%CI: 0.54-0.98) and physical exercise (OR=0.67, 95%CI: 0.49-0.90) seemed to be protective factors for depression in elderly MS patients (P<0.05). Conclusions: Older patients with MS and its component abnormalities have a higher risk of depression than the average population. Sleep disorders, cognitive impairment, and IADL impairment are important influencing factors for depression in elderly MS patients, while tea drinking and physical exercise may help to reduce the risk of the disease.
Aged ; Humans ; Metabolic Syndrome/epidemiology* ; Activities of Daily Living/psychology* ; Depression/epidemiology* ; China/epidemiology* ; Tea ; Risk Factors