Objective To investigate the inhibitory effect of ursolic acid in Hippophae rhamnoides L. on hepatocyte apoptosis in rats with alcoholic liver disease based on the mitochondria-cytochrome c pathway. Methods A total of 50 specific pathogen-free male Wistar rats were divided into normal control group, alcohol model group, and low-, middle-, and high-dose ursolic acid groups using a random number table, with 10 rats in each group. The rats in the normal control group were given normal saline by gavage once a day for 8 weeks; the rats in the alcohol model group were given alcohol at increasing concentrations by gavage for 8 consecutive weeks; the rats in the low-, middle-, and high-dose ursolic acid groups were given ursolic acid at a dose of 50, 100, and 150 mg/kg, respectively, followed by an equal volume of alcohol as the model group 1 hour later. Serum liver function parameters were measured for each group; HE staining was used to observe liver histopathology; an electron microscope was used to observe hepatocyte ultrastructure; the TUNEL method was used to measure hepatocyte apoptosis; Western Blotting was used to measure the protein expression levels of cytochrome c and activated caspase-3 in hepatocyte mitochondria and cytoplasm. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the alcohol model group, the middle- and high-dose ursolic acid groups had significant reductions in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase (all P < 0.05). The rats in the alcohol model group had disordered arrangement of hepatic cords with marked hepatocyte edema and fatty degeneration, while those in the middle- and high- dose ursolic acid groups had basically normal arrangement of hepatic cords and a significant improvement in hepatocyte fatty degeneration, as well as a significant increase in the number of hepatocyte mitochondria and a significant improvement in morphology. Compared with the alcohol model group, the middle- and high-dose ursolic acid groups had significantly lower hepatocyte apoptosis rate and protein expression levels of cytochrome c and caspase-3 in cytoplasm (all P < 0.05). Conclusion Ursolic acid in Hippophae rhamnoides L. can improve the liver function and histomorphology of rats with alcoholic liver disease, possibly by inhibiting the release of cytochrome c in hepatocyte mitochondria, the activation of caspase-3, and the apoptosis of hepatocytes via the mitochondria-cytochrome c pathway.

This study was aimed to understand the current status of the antimicrobial resistance and molecular distribution of Campylobacter in various poultry in Jiaodong area,to provide a basis for effective prevention and control of the Campy-lobacter risk to poultry products and human health.Campylobacter was isolated and identified from 565 cloacal samples collect-ed in the Jiaodong area from August to October 2021 through conventional bacterial isolation and culture,mass spectrometry,microbroth dilution and multilocus sequence typing(MLST).The drug resistance and molecular typing of 131 representative strains(67 Campylobacter jejuni and 64 Campylobacter coli)were studied separately.Antimicrobial resistance analysis indica-ted that 131 isolates were highly resistant to ciprofloxacin,nalixic acid and tetracycline,with resistance rates of 96.21％,96.21％and 95.45％,respectively.Except for 2 strains,62 strains of C.coli were completely resistant to these three drugs(100％).A total of 65 strains of 131 strains were multidrug re-sistant,and the overall multidrug resistance rate was 49.62％,among which 11 strains(16.42％)of C.jejuni were resistance to 3-5 antibiotics,and 54 strains(84.38％)of C.coli were re-sistance to 3-6 antibiotics.Among the isolates from different poultry sources,waterfowl isolates were the most resistant,fol-lowed by broiler isolates.The MLST typing results revealed 72 alleles and 35 sequence types obtained from 67 strains of C.je-juni,and the distribution was relatively dispersed,without a dominant ST type and homologous complex.A total of 27 alleles and 19 sequence types were obtained from 64 strains of C.coli.Moreover,59.38％(38/64)strains were homologous complex CC-828,in which the ST-1586 sequence type was most frequent,followed by ST-825.ST-1586,ST-9944 and ST-3735 were the main sources of C.coli in broilers,and ST-825 and ST-1586 were the main sources of C.coli in waterfowl.Differences in C.jejuni and C.coli carriage were observed among poultry in the Jiaodong area.Carriage of the two bacteria was more common in laying hens than in broilers and waterfowl.C.jejuni from poultry in the Jiaodong area was highly resistant to ciprofloxacin,nalixic acid and tetracycline,but had good sensitivity to other drugs.C.coli was highly resistant to a variety of antibiotics,and multiple drug resistance was common.St-type dispersal of C.jejuni showed high genetic diversity.C.coli was cloned and transmitted mainly by ST-1586 in broiler chickens and waterfowl.Poultry carry C.jejuni,which can cause serious diseases in humans.Therefore,dynamic monitoring of Campylobacter from poultry should be strengthened.

Objective: To analyze the status of early use of oral β-blocker and its relationship with in-hospital outcomes in eligible patients with acute coronary syndrome (ACS). Methods: The study was based on the Improving Care for Cardiovascular Disease in China (CCC)-ACS project. The data of ACS patients that collected during 2014 to 2019 from 230 collaborating hospitals across China were analyzed. Propensity score matching method and Cox multivariate regression analysis were used to analyze the association between early use of oral β-blocker and in-hospital outcomes within 15 days. Results: A total of 38 663 eligible ACS patients were included in this study. The mean age was (57.0±9.0), and 78.8% of the ACS patients (30 470/38 663) were male. The proportion of early use of oral β-blockers was 64.9% (25 112/38 663), but varied substantially, in the 230 hospitals with a range from 0 to 100%. Compared with the patients no early use of oral β-blocker, the patients receiving early oral β-blocker had significantly lower incidence of major cardiovascular adverse events (MACEs) (3.4% (395/11 536) vs. 2.9%(339/11 536), P=0.036)and less occurrences of heart failure (2.7% (316/11 536) vs. 2.1% (248/11 536), P=0.004). Multivariate Cox regression analyses showed the patients receiving early oral β-blocker had 15.5%, 23.1%, and 35.3% lower risks of MACEs, heart failure and cardiogenic shock respectively than the patients no early oral β-blocker. Conclusions: Compared with the patients no early oral β-blocker, the patients receiving early oral β-blocker had lower risks of MACEs events, heart failure and cardiogenic shock. However, the early use of oral β-blocker in ACS patients was generally insufficient with huge differences among different hospitals in China.
Acute Coronary Syndrome/drug therapy* ; Adrenergic beta-Antagonists/therapeutic use* ; Heart Failure ; Hospitals ; Humans ; Male ; Shock, Cardiogenic

Objective: To investigate the association between smoking and the severity of coronary lesions among young and middle-aged female patients with acute coronary syndrome (ACS). Methods: Data of this study were derived from the Improving Care for Cardiovascular Disease in China (CCC)-ACS project, a collaborative study of the Chinese Society of Cardiology and the American Heart Association. Since 2014, the CCC-ACS project consecutively enrolled inpatients with ACS, systematically collected their clinical data and evaluated medical quality of these patients from 158 tertiary hospitals and 82 secondary hospitals across China. This study enrolled female patients less than 60 years old with initial ACS, who received coronary angiography in CCC-ACS project. Patients were divided into two groups according to smoking status. A multivariate logistic regression analysis was used to analyze the association between smoking and the severity of coronary lesions among young and middle-aged female patients with ACS. Results: A total of 2 863 female patients younger than 60 years old with initial ACS, who received coronary angiography, were enrolled. Among them, 12% (340 cases) was smokers. Proportion of patients younger than 45 years old was higher (13.2% (45/340) vs. 8.5% (215/2 523), P<0.01) and prevalence of hypertension (59.4% (202/340) vs. 66.7% (1 683/2 523), P<0.01) and diabetes (39.4% (134/340) vs. 44.2% (1 116/2 523), P=0.09) was lower in smoker group than in non-smoker group. However, prevalence of ST-elevation myocardial infarction (66.8% (227/340) vs. 53.7% (1 354/2 523), P<0.01), coronary multi-vessel lesions (39.1% (133/340) vs. 32.6% (822/2 523), P<0.01) and severe stenosis in either single-vessel (56.2% (109/194) vs. 46.1% (706/1 530), P<0.01) or multi-vessel (63.2% (84/133) vs. 58.2% (478/822), P=0.29) was significantly higher in smoker group than in non-smoker group. Multivariate logistic regression analyses showed that after adjusting for age, hypertension, diabetes, elevated low-density lipoprotein cholesterol, lower high-density lipoprotein cholesterol, elevated triglyceride, renal insufficiency, family history of coronary heart disease and types of ACS, smokers faced a higher risk of coronary multi-vessel lesions, coronary multi-vessel severe lesions and coronary severe lesions with the odds ratios and 95% confidence interval of 1.41 (1.11-1.79), 1.40 (1.10-1.78) and 1.78 (1.11-2.87), compared with non-smokers. Conclusions: Smoking is significantly associated with an increased risk of extensive and severe coronary lesions among young and middle-aged female patients with ACS. This study provides crucial evidence for further understanding the harms of smoking and the need to strengthen the tobacco control education and smoking cessation guidance for young and middle-aged women.
Acute Coronary Syndrome ; Adult ; China ; Coronary Angiography ; Female ; Humans ; Middle Aged ; Risk Factors ; Smoking

Objective: To assess the expanding needs on lipid-lowering treatment in patients with acute coronary syndrome (ACS) by applying newly issued definition of extreme high-risk, which is proposed by Chinese expert consensus on lipid management of extreme high-risk atherosclerotic cardiovascular disease (ASCVD) patients of Chinese Society of Cardiology (CSC). Methods: Data of this study was derived from the Improving Care for Cardiovascular Disease in China (CCC) project, which was a case-based nationwide registry study and launched as a collaborative initiative by the American Heart Association and the CSC. The project consecutively recruited ACS patients from158 tertiary hospitals and 82 second hospitals across China, and detailed clinical information of patients was collected. This study enrolled ACS inpatients in CCC project from November 2014 to July 2019. The proportion of extreme high-risk patients, their characteristics, mean LDL-C levels at admission, the gap between measured LDL-C level and the new target, and lipid-lowering therapy at discharge were assessed. Results: Among 104 516 ACS inpatients enrolled in this study, 75.1% (78 527/104 516) met the criteria of extreme high-risk and were expected to achieve the new LDL-C goal. Among patients at extreme high-risk, 21.2% (16 651/78 527) had multiple severe ASCVD events and 78.8% (61 876/78 527) had 1 severe ASCVD event and at least two high-risk factors. For the extreme high-risk patients, the mean level of LDL-C at admission was (2.8±1.0) mmol/L, prevalence of LDL-C ≥1.4 mmol/L was 93.4% (73 307/78 527) and the median gap between LDL-C level at admission and the target of 1.4 mmol/L was 1.3 (0.8, 2.0) mmol/L. If LDL-C could be further reduced to 50% of the admission level, we estimated that 55.6% (43 632/78 527) of the extreme high-risk patients would achieve the new LDL-C goal. Among 40 875 patients with information about discharge statin dosage, 93.5% (28 004/29 947) of the extreme high-risk patients were prescribed with statins at discharge, and among them 95.1% (26 632/28 004) received statin monotherapy and 91.1% (25 501/28 004) were at moderate doses of statins. Conclusion: About three fourth of inpatients with ACS were categorized as extreme high-risk based on the new definition of CSC expert consensuses, nine out of ten patients at extreme high-risk didn't achieve the new LDL-C target at admission, and the intensity of lipid-lowering therapy was insufficient in clinical practice. There are substantially expanding needs for implementing more intensive and effective lipid-lowering strategies.
Acute Coronary Syndrome/drug therapy* ; Asians ; Cardiology ; China ; Cholesterol, LDL ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lipids ; United States

To systematically evaluate the effects of Tripterygium Glycosides Tablets alone or in combination with methotrexate(MTX) and leflunomide(LEF) on the levels of pro-inflammatory cytokines in patients or animal models with rheumatoid arthritis(RA), and to provide reference for clinical application and related basic research, this study systematically searched databases of CNKI, VIP, WanFang, PubMed, Embase and Cochrane Library, collected relevant clinical or animal experimental studies, used risk assessment tools to evaluate the quality of research, and used Revman 5.3 software to conduct Meta-analysis or descriptive analysis of the outcome indicators included in the literatures. Of the 1 709 papers retrieved, 3 clinical studies and 12 animal experiments were included. The results showed that compared with MTX alone, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of peripheral blood TNF-α(SMD=-8.88,95%CI[-10.77,-6.99],P<0.000 01),IL-1β(P<0.000 01) and IL-6(SMD=-8.63, 95%CI[-10.57,-6.69], P<0.000 01) in RA patients. Compared with LEF alone, the combination of Tripterygium Glycosides Tablets and LEF could not further reduce the expression levels of TNF-α(P=0.20), IL-1β(P=0.17), IL-6(P=0.31). In RA animal model, compared with model group, Tripterygium Glycosides Tablets could reduce the expression levels of peripheral blood IL-1β(SMD=-6.29,95%CI[-9.64,-2.93],P<0.000 2)in peripheral blood(SMD=-1.39,95%CI[-1.77,-1.02],P<0.000 01), joint fluid(P<0.000 01) and paw plasma(P=0.02), and also reduce the expression levels of TNF-α in RA animal model group. Compared with MTX alone, Tripterygium Glycosides Tablets alone reduced the same levels of TNF-α(P=0.42) and IL-6(P=0.08) in joint fluid, while Tripterygium Glycosides Tablets combined with MTX could further reduce the levels of IL-6(P=0.000 1) in joint fluid; compared with LEF alone, Tripterygium Glycosides Tablets have the similar effects on reducing the expression levels of peripheral blood TNF-α(P=0.16), IL-1β(P=0.32), IL-6(P=0.12), while Tripterygium Glycosides Tablets combined with LEF could further reduce the expression levels of TNF-α(P=0.008), IL-1β(P=0.02), IL-6(P<0.000 1) in peripheral blood. Therefore, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of pro-inflammatory cytokines in peripheral blood of RA patients. Tripterygium Glycosides Tablets alone could reduce the expression levels of pro-inflammatory cytokines in peripheral blood and local joint of RA animal models. Tripterygium Glycosides Tablets combined with MTX or LEF could further reduce the express levels of pro-inflammatory cytokines in peripheral blood of RA animal models. Due to the limitation of literature, this conclusion needs to be further validated.
Animals ; Arthritis, Rheumatoid/drug therapy* ; Cytokines ; Drugs, Chinese Herbal/therapeutic use* ; Glycosides/therapeutic use* ; Humans ; Leflunomide/therapeutic use* ; Methotrexate/therapeutic use* ; Tablets ; Tripterygium/chemistry*

To evaluate the clinical efficacy of single administration of Tripterygium Glycosides Tablets(TGT) or combined administration with methotrexate(MTX) against rheumatoid arthritis(RA) based on American College of Rheumatology(ACR) efficacy standard. Six databases, namely CNKI, WanFang, VIP, PubMed, Embase and Cochrane Library, were retrieved for randomized controlled trials(RCT), and clinical trials were screened out according to the preset inclusion and exclusion criteria. Then, the study quality was evaluated by the risk assessment tools. Data extraction and analysis were performed by using RevMan 5.3 software for Meta-analysis. Sensitivity analysis and publication bias analysis were made to test the stability and reliability of results. Until December 2018, a total of 1 709 articles were obtained, and finally 10 clinical RCT studies with a total of 1 184 patients were included. As a result, the single administration of TGT showed a significantly better ACR efficiency(RR=1.31, 95%CI[1.15, 1.49], P<0.000 1) than methotrexate(MTX). The combined administration of TGT and MTX showed a significantly better ACR efficiency(RR=1.28, 95%CI[1.20, 1.38], P<0.000 01) than the single administration of MTX. In conclusion, the single administration of TGT and the combined administration of TGT and MTX were more effective in achieving ACR20, ACR50, ACR70 compliance than the single administration of MTX. Further validations based on more RCT studies with high-quality are required.
Antirheumatic Agents/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Drug Therapy, Combination ; Drugs, Chinese Herbal/therapeutic use* ; Glycosides/therapeutic use* ; Humans ; Methotrexate/therapeutic use* ; Randomized Controlled Trials as Topic ; Reproducibility of Results ; Tablets ; Treatment Outcome ; Tripterygium/chemistry*

Objective:To compare the effects and multi-organ intervention of tripterygium glycosides(TG) tablet from Hunan Qianjin Xieli (QJ) and Zhejiang Deende (DED) on type Ⅱ collagen-induced arthritis (CIA) in rats. Method:The 72 SD rats were randomly divided into normal group, model group, QJ TG clinical group 2 times, 6 times equivalent dose group (QJ-TG 0.018, 0.054 g·kg^-1), derende TG clinical group 2 times, 6 times equivalent dose group (DED-TG 0.018, 0.054 g·kg^-1). The intragastric administration was started on the day after the first immunization, once a day. After the second immunization, the symptoms such as redness and swelling of joints were observed, and the clinical score of arthritis were evaluated. The materials were taken for pathological examination of the inflammatory joints on the 21^th and 42^th day. The concentration of alkaline phosphatase(ALP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), gamma-glutamyltransferase(GGT), total bilirubin(TBIL), creatinine(CRE) and urea(UREA) in serum were detected by enzymatic assay. The rate of sperm deformity, testicular and ovarian tissue damage in the rat epididymis was assessed. Result:TG from two manufacturers attenuated the inflammation, redness, swelling and deformity of joints in CIA rats, reduced the clinical score and incidence of arthritis in CIA rats. Meanwhile, it also exhibited obvious reduction in all pathological features such as joint synovitis, pannus, cartilage erosion and bone destruction. There were significant differences between the QJ-TG high and low dose groups and the DED-TG high dose group compared with the model group (P<0.05, P<0.01). There was no significant change in the low dose group of DED-TG compared with the model group.Compared with the same dose of TG in the two manufacturers, the DED-TG 0.054 g·kg^-1 group had a significant inhibitory effect on the clinical scores on the 15th and 18th days than the QJ-TG same dose group (P<0.05).In addition to 0.054 g·kg^-1 dose of DED-TG, the white blood cell count and spleen index were significantly increased.At the same time, two different manufacturers of TG had no effect on body weight, organ index, digestive system, liver and kidney function, liver and kidney pathology of CIA model rats. QJ-TG and DED-TG all significantly increased the rate of male rats sperm malformation and significant damage to testicular seminiferous tubules and the toxicity increased with the increase of dose and time. while the mole reproductive toxicity of DED-TG was higher than that of QJ-TG at the same dose. In the DED-TG 0.054 g·kg^-1 and QJ-TG 0.054 g·kg^-1 group, there were only the reduction of vascular distribution in the ovarian tissue and the reduction of the corpus luteum, and no other toxic effects were observed. Conclusion:Two manufacturers TG2 times (0.018 g·kg^-1) and 6 times (0.054 g·kg^-1) clinical equivalent dose can delay the onset of CIA in rats, reduce the clinical score of arthritis, improve the pathological changes of joints, but have a certain degree of male reproductive toxicity. The high-dose DED-TG is more toxic than the QJ-TG.

Objective The purpose of this study was to investigate the prevalence of vitamin D deficiency and hypertension in Henan rural residents, and to explore the association between vitamin D and risk of hypertension. Methods 2 013 Henan rural participants aged 18-80 years were recruited from a cross-sectional study. Logistic regression models and restricted cubic spline model were used to evaluate odds ratios (OR), 95% confidence intervals (95% CI) and dose-response relationship between vitamin D and risk of hypertension. Results In total population, the prevalence of hypertension was 40.34% (30.64% after age-standard), and the mean serum 25-(OH)D was (24.50 ± 16.18) ng/ml, and 53.95% of all participants were presenting vitamin D deficiency. Compared with non-hypertension, a lower level of serum 25-(OH)D was observed in people with hypertension. The prevalence of hypertension was 45.21% in vitamin D deficient group which was higher than in the vitamin D sufficient group (31.07%). Compared with the vitamin D sufficient group, the risk of hypertension was increase in the vitamin D deficient group (OR=1.59, 95% CI: 1.21-2.10), and the risk of hypertension decreased by 14% for every 10 ng/ml increase in serum 25-(OH) D levels. Moreover, an L-shaped relationship was observed between 25-(OH)D concentration and risk of hypertension. Conclusion Vitamin D deficiency is associated with risk of hypertension and there is an L-shaped relationship between 25-(OH)D concentration and risk of hypertension.

Aged ; Case-Control Studies ; China ; epidemiology ; Diabetes Mellitus, Type 2 ; epidemiology ; genetics ; Exercise ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Calcitriol ; genetics ; Risk ; Rural Population