Objective:To explore the impacts of remimazolam(REM)on the proliferation,migration,and invasion of hepatocellular carcinoma cells by regulating sphingosine kinase 1/sphingosine 1-phosphate/sphingosine 1-phosphate receptor 3(SPHK1/S1P/S1PR3)signaling pathway.Methods:Human hepatocellular carcinoma cell line HepG2 was treated with REM at concentrations of 0,20,40,80,160,and 320 μmol/L respectively.Cell survival rate was measured,and drug concentrations were screened.Based on the results of cell survival rate,the logarithmic phase cells were di-vided into five groups:Control group,low,medium,and high concentrations of remifentanil groups(REM-L,REM-M,REM-H groups;20,40 and 80 μmol/L),and high concentrations of remifentanil+SPHK1 activator group(REM-H+K6PC-5 group).MTT assay was used to detect the survival rate of HepG2 cells.Plate cloning experiment was performed to de-tect cell proliferation ability.Scratch experiment was performed to detect cell migration ability.Transwell chamber method was performed to detect cell invasion ability.Flow cytometry was used to detect cell apoptosis.Western blot was used to detect the SPHK1,S1P,S1PR3,Bax,and Bcl-2 proteins in cells.Results:For the Control group,the REM-L,REM-M,and REM-H groups showed that the number of HepG2 cell clones,scratch healing rate,invasion rate,Bcl-2,SPHK1,S1P,S1PR3,and N-cadherin proteins gradually decreased with increasing REM concentration,while the apoptosis rate and Bax,E-cadherin proteins showed an opposite trend(P<0.05).For the REM-H group,the REM-H+K6PC-5 group showed a clear increase in the number of HepG2 cell clones,scratch healing rate,invasion rate,Bcl-2,SPHK1,S1P,S1PR3,and N-cadherin proteins,and a clear decrease in the apoptosis rate and Bax,E-cadherin proteins(P<0.05).Conclusion:REM may inhibit the proliferation,migration,and invasion of hepatocellular carcinoma cells and promote cell apoptosis by suppressing SPHK1/S1P/S1PR3 signaling pathway.

Objective:To explore the impacts of remimazolam(REM)on the proliferation,migration,and invasion of hepatocellular carcinoma cells by regulating sphingosine kinase 1/sphingosine 1-phosphate/sphingosine 1-phosphate receptor 3(SPHK1/S1P/S1PR3)signaling pathway.Methods:Human hepatocellular carcinoma cell line HepG2 was treated with REM at concentrations of 0,20,40,80,160,and 320 μmol/L respectively.Cell survival rate was measured,and drug concentrations were screened.Based on the results of cell survival rate,the logarithmic phase cells were di-vided into five groups:Control group,low,medium,and high concentrations of remifentanil groups(REM-L,REM-M,REM-H groups;20,40 and 80 μmol/L),and high concentrations of remifentanil+SPHK1 activator group(REM-H+K6PC-5 group).MTT assay was used to detect the survival rate of HepG2 cells.Plate cloning experiment was performed to de-tect cell proliferation ability.Scratch experiment was performed to detect cell migration ability.Transwell chamber method was performed to detect cell invasion ability.Flow cytometry was used to detect cell apoptosis.Western blot was used to detect the SPHK1,S1P,S1PR3,Bax,and Bcl-2 proteins in cells.Results:For the Control group,the REM-L,REM-M,and REM-H groups showed that the number of HepG2 cell clones,scratch healing rate,invasion rate,Bcl-2,SPHK1,S1P,S1PR3,and N-cadherin proteins gradually decreased with increasing REM concentration,while the apoptosis rate and Bax,E-cadherin proteins showed an opposite trend(P<0.05).For the REM-H group,the REM-H+K6PC-5 group showed a clear increase in the number of HepG2 cell clones,scratch healing rate,invasion rate,Bcl-2,SPHK1,S1P,S1PR3,and N-cadherin proteins,and a clear decrease in the apoptosis rate and Bax,E-cadherin proteins(P<0.05).Conclusion:REM may inhibit the proliferation,migration,and invasion of hepatocellular carcinoma cells and promote cell apoptosis by suppressing SPHK1/S1P/S1PR3 signaling pathway.

ObjectiveA rapid method for identification of chemical constituents in Baoyuantang reference sample was established in order to clarify the material basis of this formula. MethodBased on ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） and self-established database information， the chemical components in Baoyuantang were systematically characterized and identified. The chromatography was performed on a Waters ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with mobile phase of 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） for gradient elution（0-3 min， 2%-19%B； 3-8 min， 19%B； 8-8.1 min， 19%-22%B； 8.1-14 min， 22%-29%B； 14-16 min， 29%B； 16-32 min， 29%-45%B； 32-32.1 min， 45%-90%B； 32.1-35 min， 90%-95%B； 35-36 min， 95%-98%B； 36-37 min， 98%-2%B； 37-40 min， 2%B）. Based on electrospray ionization（ESI）， continuum data format was collected in both positive and negative ion modes with a scanning range of m/z 50-1 500. Chemical constituents in the decoction of Baoyuantang were systematically analyzed by UNIFI 1.9.4 software matching， control comparison， The Encyclopedia of Traditional Chinese Medicine（ETCM） database search and literature reports. ResultA total of 229 components were identified under negative ion mode and 181 under positive ion mode， with a total of 322 components after removing duplicates， including 116 triterpene saponins， 66 flavonoids， 19 organic acids， 6 gingerphenols， 6 gingerols， 5 gingerones， 10 amino acids， 7 saccharides， 5 coumarins and 82 other components. Among them， 83， 141， 39， 35 and 38 components were attributed to Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Astragali Radix， Cinnamomi Cortex and Zingiberis Rhizoma Recens， respectively. ConclusionIn this study， the rapid characterization and identification of multi-class components in Baoyuantang was realized， and it was confirmed that the material basis of this formula was mainly triterpenoid saponins， flavonoids， gingerols and organic acids， and the chemical composition was attributed and analyzed， which provided a reference for the subsequent quality control research.

OBJECTIVE: To establish and validate predictive nomogram for liver fibrosis in patients with Wilson disease (WD) showing abnormal lipid metabolism. METHODS: We retrospectively collected the clinical data of 500 patients with WD showing abnormalities in lipid metabolism, who were treated in the Department of Encephalopathy of the First Affiliated Hospital of Anhui University of Chinese Medicine from December, 2018 to December, 2021 and divided into modeling group and validation group. The independent risk factors of liver fibrosis in these patients were screened using LASSO regression and multivariate logistic regression analysis for establishment of the predictive nomogram. The area under the curve (AUC), calibration curve and decision curve of the receiver-operating characteristic curve (ROC) were used for internal and external verification of the nomogram in the modeling and validation group and evaluating the differentiation, calibration and clinical practicability of the model. RESULTS: Triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (Apo-B) were independent risk factors for the development of liver fibrosis in patients with WD and abnormal lipid metabolism (P < 0.05). The predictive nomogram showed good discrimination, calibration and clinical utility in both the modeling and validation groups. CONCLUSION The established predictive nomogram in this study has a high accuracy for early identification and risk prediction of liver fibrosis in patients with WD having abnormal lipid metabolism.
Humans ; Hepatolenticular Degeneration ; Lipid Metabolism ; Retrospective Studies ; Liver Cirrhosis ; Cholesterol, LDL

OBJECTIVEThis study was aimed to investigate the effects of carbon monoxide releasing molecule (CORM-2), a novel carbon monoxide carrier, on the reendothelialization of carotid artery in rat endothelial denudation model.

METHODSMale rats subjected to carotid artery balloon injury were treated with CORM-2, inactive CORM-2 (iCORM-2) or dimethyl sulfoxide (DMSO). The reendothelialization capacity was evaluated by Evans Blue dye and the immunostaining with anti-CD31 antibody. The number of circulating endothelial progenitor cells (EPCs) was detected by flow cytometry. The proliferation, migration, and adhesion of human umbilical vein endothelial cells (HUVECs) were assessed by using [3H]thymidine, Boyden chamber and human fibronectin respectively. The expressions of protein were detected by using western blot analysis.

RESULTSCORM-2 remarkably accelerated the re-endothelialization 5 d later and inhibited neointima formation 28 d later. In addition, the number of peripheral EPCs significantly increased in CORM-2-treated rats than that in iCORM-2 or DMSO-treated rats after 5 d later. In vitro experiments, CORM-2 significantly enhanced the proliferation, migration and adhesion of HUVECs. The levels of Akt, eNOS phosphorylation, and NO generation in HUVECs were also much higher in CORM-2 treated group. Blocking of PI3K/Akt/eNOS signaling pathway markedly suppressed the enhanced migration and adhesion of HUVECs induced by CORM-2.

CONCLUSIONCORM-2 could promote endothelial repair, and inhibit neointima formation after carotid artery balloon injury, which might be associated with the function changes of HUVECs regulated by PI3K/Akt/eNOS pathway.

Animals ; Carbon Monoxide ; metabolism ; pharmacology ; Carotid Artery Injuries ; drug therapy ; immunology ; metabolism ; pathology ; Carotid Artery, Common ; drug effects ; immunology ; metabolism ; pathology ; Cell Adhesion ; drug effects ; Disease Models, Animal ; Endothelial Cells ; drug effects ; immunology ; metabolism ; pathology ; Endothelium, Vascular ; drug effects ; metabolism ; pathology ; Humans ; Male ; Rats ; Rats, Sprague-Dawley

BACKGROUNDWhether an addition of OAC to double antiplatelet therapy for patients with an indication of chronic oral anticoagulation undergoing PCI-S may improve clinical outcomes is still debated. This meta-analysis aimed to update and re-compare the benefits and risks of triple antithrombotic therapy (TT) with double anti-platelet therapy (DAPT) after in patients who requiring oral anticoagulation after percutaneous coronary interventions with stenting (PCI-s).

METHODSTen reports of observational retrospective or prospective studies were retrieved, including a total of 6296 patients, follow-up period ranging from 1 year to 2 years.

RESULTSBaseline characteristics were similar in both groups. The main finding of this study is the overall incidence of major adverse cardiovascular events (MACE), myocardial infarction (MI) and stent thrombosis was comparable between two groups. Patients with TT was associated with significant reduction in ischemic stroke (OR: 0.27; 95%CI: 0.13 - 0.57; P = 0.0006) as compared to DAPT. We reaffirmed triple therapy significantly increased the risk of major bleeding (OR: 1.47; 95%CI: 1.22 - 1.78; P < 0.0001) and minor bleeding (OR: 1.55; 95%CI: 1.07 - 2.24; P = 0.02).

CONCLUSIONSTriple therapy is more efficacious in reducing the occurrence of ischemic stroke in PCI-s patients with an indication of chronic oral anticoagulation (OAC), compared with DAPT. However, it significantly increased major and minor risk of bleeding. It is imperative that further prospective randomized controlled trials are required to defne the best therapeutic strategy for patients with an indication of chronic OAC undergoing PCI-s.

Aged ; Anticoagulants ; therapeutic use ; Drug Therapy, Combination ; Female ; Fibrinolytic Agents ; administration & dosage ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; administration & dosage ; Publication Bias ; Stents

To compare the differences on current ethical issues in the areas of epidemiological practice between China and America,to identify the major ethical problems existing in the epidemiological studies in China.Through searching and reviewing papers published on Chinese Journal of Epidemiology and American Journal of Epidemiology from Jan.2006 to Dec.2010,we made a comparison on ethical issues involved in the original studies that focusing on human beings.In total,749 Chinese articles and 1221 American articles were recruited,with the following findings: (1)The proportion with announcements of “Informed consent by the subjects” was 29.24％ in Chinese literature and 38.08％ in the Americans (x2=16.02,P＜0.001 ).The proportion with “having had approvals from the ethic committees” was 29.24％ in Chinese,while 38.08％ in American ( x2=604.40,P＜ 0.0001 ).(2) Both in China and America,there had been an increase of ethical issues in the last 5 years.(3)Articles derived from trial studies had better involvement on ethics than those from observational studies.(4) The level on ethical issues in the American Research Institutes exceeded those in China (5)American studies also had showed better ideas on Ethic issues on biological specimens collection and privacy protection,than those in Chinese studies.Among the studies on Chinese Journal of Epidemiology,the proportion of ‘informed consent' was higher than in ethical review,but both ethical review and awareness on ‘informed consent' had left far behind than the American Journal of Epidemiology.This could be seen at the institution level of the writers,during specimen collection and privacy protection,as well as at the overall level.The results reminded us that the Departments of Technology Management should spend more efforts on the improvement of public education regarding ethics for researchers and to update the process of edition for Journals as well as to reinforce the rules of ethics in epidemiological research.

BACKGROUNDRecent studies indicate that bone marrow-derived cells may significantly contribute to atherosclerosis, post-angioplasty restenosis and transplantation-associated vasculopathy. The responsible bone marrow (BM) cells and mechanisms regulating the mobilization of these cells are currently unclear. The purpose of this study was to investigate the expression of granulocyte colony-stimulating factor (G-CSF) on injured arteries and its effects on mesenchymal stem cells (MSCs) differentiation into vascular smooth muscle cells (VSMCs) in the process of vascular remodeling.

METHODSBalloon-mediated vascular injury was established in female rats (n = 100) which received radioprotective whole female BM cells by tail vein injection and male MSCs through a tibial BM injection after lethal irradiation. The injured and contralateral carotid arteries were harvested at 3, 7, 14 and 28 days after treatment.

RESULTSMorphometric analysis indicated that intima to media area-ratio (I/M ratio) significantly increased at 28 days, 0.899 ± 0.057 (P < 0.01), compared with uninjured arteries. Combining fluorescence in situ hybridization (FISH) and immunohistochemical analysis showed that a significant number of the neointimal cells derived from MSCs, (45.2 ± 8.5)% at 28 days (P = 0.01), compared with (23.5 ± 6.3)% at 14 days. G-CSF was induced in carotid arteries subject to balloon angioplasty (fold mRNA change = 8.67 ± 0.63 at three days, relative G-CSF protein = 0.657 ± 0.011 at three days, P < 0.01, respectively, compared with uninjured arteries). G-CSF was chemotactic for MSCs but did not affect the differentiation of MSCs into smooth-muscle-like cells.

CONCLUSIONIncreased expression of G-CSF by injured arteries plays an essential role in contribution to recruitment and homing of MSCs to the site of the arterial lesion.

Angioplasty, Balloon ; Animals ; Blotting, Western ; Carotid Arteries ; surgery ; Cell Differentiation ; Cell Movement ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Female ; Granulocyte Colony-Stimulating Factor ; metabolism ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Mesenchymal Stromal Cells ; cytology ; Myocytes, Smooth Muscle ; cytology ; Neointima ; surgery ; therapy ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular System Injuries ; surgery ; therapy

OBJECTIVETo study the main risk factors of low back pain of workers ina foundry factory of the automobile company using cross sectional epidemiological investigation, and to provide scientific base for preventing the disorder.

METHODSThe low back pain and work loads of 1340 workers in a foundry factory of the automobile company were investigated using questionnaire, and logistic regression analysis was used to analyze the risk factors.

RESULTSThe one-year morbidity of low back pain in workers was 58.9% the morbidities of low back pain in workers engaged in foundry, transportation and modeling were 64.6%, 64.6% and 62.5%, respectively. The lifting with squat postures, bending trunk heavily, bending trunk with twisting and moving the heavy objects were found to be the most dominant risk factors for low-back pain, the OR values were 2.085, 1.961, 1.967 and 1.956, respectively. The distributions of risk factors were different among the different jobs. The logistic regression analysis showed that moving the heavy objects, lifting with squat postures, bending trunk heavily, bending trunk with twisting existed simultaneously, also the work years and gender were the risk factors.

CONCLUSIONThe manual moving heavy objects, awkward working posture or both were the most important risk factors for low-back pain. The intervene ergonomic study should be performed in future to reduce the morbidity of low-back pain.

Adult ; Automobiles ; Cross-Sectional Studies ; Female ; Humans ; Industry ; Logistic Models ; Low Back Pain ; epidemiology ; Male ; Middle Aged ; Occupational Diseases ; epidemiology ; Risk Factors ; Surveys and Questionnaires ; Workplace ; Young Adult

OBJECTIVETo study the predictive value of ALT, HBeAg and HBV DNA levels at baseline and HBV DNA levels at week 12 adefovir dipivoxil (ADV) treatment to the efficacy of it at week 52 in patients with HBeAg-positive chronic hepatitis B (CHB).

METHODSNinety-eight HBeAg-positive CHB patients with serum HBV DNA>or=1x10(6) copies/ml and ALT levels between 1.5 to 10 times of upper limits of normal (ULN) were enrolled in the study. Ten mg/d of ADV was administered for 52 weeks. Line serum samples were collected for measuring HBV DNA and HBV markers. The efficacy of the treatment at week 52 was evaluated in patients with different ALT, HBeAg and HBV DNA levels at baseline and HBV DNA levels at week 12 after treatment.

RESULTSAt week 52 of ADV treatment, the rates of HBV DNA<10(3) were 72.7%, 66.7% and 53.0% respectively in patients with ALT>5xULN, HBeAg350 s/co (30.2%, P<0.01) and HBV DNA>10(8) copies/ml (34.4%, P<0.05) at baseline. HBeAg seroconversion rates were 42.2% and 7.5% (P<0.01) in patients with HBeAg titer350 S/co at baseline. In patients with HBV DNA<10(3), 10(3)-10(5) and >10(5) copies/ml at week 12, the ratios of them with HBV DNA<10(3) less than 1000 copies/ml at week 52 were 82.6%, 57.1% and 17.5% and significant differences were found between these groups (P<0.05); HBeAg seroconversion rates were 52.2%, 25.7% and 5.0% (P<0.05); ALT normalization rates were 100%, 83% and 75%, significantly higher in patients with HBV DNA<10(3) copies/ml than those with HBV DNA>10(5) copies/ml (P<0.05) at week 12. HBV DNA and HBeAg seroconversion at week 52 correlated with HBV DNA levels at week 12 (r=0.6 and r=0.5 respectively, P<0.01).

CONCLUSIONSIn HBeAg-positive CHB patients treated with adefovir dipivoxil, HBV DNA levels at week 12 can be used to predict the efficacy at week 52. HBV DNA<10(3) copies/ml at week 12 predict a better treatment result at week 52.

Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Male ; Organophosphonates ; therapeutic use ; Predictive Value of Tests ; Treatment Outcome ; Young Adult