Objective The rabbit knee osteoarthritis(KOA)model was established by simple anterior cruciate ligament disruption.Methods The selected 40 adult white rabbits were randomly divided into two groups,blank group with 6 rabbits and model group with 34 rabbits.The rabbits in model group were given the disruption of anterior cruciate ligament of right knee joint.In the fourth,eighth and the twelfth weeks of modeling,different degrees of degenerative changes have been ob-served on the rabbits articular cartilages from both macroscopic and microscopic aspects.Results At 4,8 and 12 weeks after modeling,the articular cartilage of the rabbits in the model group showed degenerative changes in different degrees.At 8 and 12 weeks,the typical pathological manifestations of KOA in the middle and late stages were found in the infrapatellar fat pad and synovium,respectively.There were no changes in articular cartilage,infrapatellar fat pad and synovial membrane in the blank group at the same time.There were significant differences in the gross score between the model group and the blank group at 4 weeks[(1.300±0.674)vs 0.000],8 weeks[(2.400±0.516)vs 0.000]and 12 weeks[(3.583±0.668)vs 0.000](P＜0.05),the histopathological scores were significantly different,at 4 weeks[(2.900±0.567)vs 0.000],8 weeks[(7.500±1.178)vs(0.500±0.707)],12 weeks[(11.833±1.337)vs(1.500±0.707)],(P＜0.05).Conclusion The establishment of rabbit knee arthritis model by simply cutting the anterior cruciate ligament is simple and feasible,with good stability,high success rate,small trauma,short modeling cycle and less changes in animal physiological structure.The rabbit knee arthritis model es-tablished by simply cutting the anterior cruciate ligament has good modeling effect on different stages and grades of knee os-teoarthritis,and the postoperative infection and trauma can be controlled,which can meet the test requirements.

OBJECTIVE: To compare the expected population impact of benefit and risk of aspirin treatment strategies for the primary prevention of cardiovascular diseases recommended by different guidelines in the Chinese Electronic Health Records Research in Yinzhou (CHERRY) study. METHODS: A decision-analytic Markov model was used to simulate and compare different strategies of aspirin treatment, including: Strategy ①: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk, recommended by the 2020 Chinese Guideline on the Primary Prevention of Cardiovascular Diseases; Strategy ②: Aspirin treatment for Chinese adults aged 40-59 years with a high 10-year cardiovascular risk, recommended by the 2022 United States Preventive Services Task Force Recommendation Statement on Aspirin Use to Prevent Cardiovascular Disease; Strategy ③: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk and blood pressure well-controlled (< 150/90 mmHg), recommended by the 2019 Guideline on the Assessment and Management of Cardio-vascular Risk in China. The high 10-year cardiovascular risk was defined as the 10-year predicted risk over 10% based on the 2019 World Health Organization non-laboratory model. The Markov model simulated different strategies for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Quality-adjusted life year (QALY) and the number needed to treat (NNT) for each ischemic event (including myocardial infarction and ischemic stroke) were calculated to assess the effectiveness of the different strategies. The number needed to harm (NNH) for each bleeding event (including hemorrhagic stroke and gastrointestinal bleeding) was calculated to assess the safety. The NNT for each net benefit (i.e., the difference of the number of ischemic events could be prevented and the number of bleeding events would be added) was also calculated. One-way sensitivity analysis on the uncertainty of the incidence rate of cardiovascular diseases and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted. RESULTS: A total of 212 153 Chinese adults, were included in this study. The number of people who were recommended for aspirin treatment Strategies ①-③ was 34 235, 2 813, and 25 111, respectively. The Strategy ③ could gain the most QALY of 403 [95% uncertainty interval (UI): 222-511] years. Compared with Strategy ①, Strategy ③ had similar efficiency but better safety, with the extra NNT of 4 (95%UI: 3-4) and NNH of 39 (95%UI: 19-132). The NNT per net benefit was 131 (95%UI: 102-239) for Strategy ①, 256 (95%UI: 181-737) for Strategy ②, and 132 (95%UI: 104-232) for Strategy ③, making Strategy ③ the most favorable option with a better QALY and safety, along with similar efficiency in terms of net benefit. The results were consistent in the sensitivity analyses. CONCLUSION The aspirin treatment strategies recommended by the updated guidelines on the primary prevention of cardiovascular diseases showed a net benefit for high-risk Chinese adults from developed areas. However, to balance effectiveness and safety, aspirin is suggested to be used for primary prevention of cardiovascular diseases with consideration for blood pressure control, resulting in better intervention efficiency.
Adult ; Humans ; Aspirin/therapeutic use* ; Cardiovascular Diseases/epidemiology* ; Gastrointestinal Hemorrhage ; Myocardial Infarction/prevention & control* ; Primary Prevention/methods* ; Middle Aged ; Aged

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Aim To investigate the mechanism of eata- pol (CAT) inhibiting differentiation and glyeolysis of Thl7 eel Is through miR-143-3p.Method The peripheral hloorl CD4 ∗ T eells of HA patients were obtained to deteet the expression of miR-143-3p and the mRNA levels of key glycolytic enzymes, ineluding glucose transporter 1 ( Glutl ) , hexokinase 2 ( HK2 ) , pyruvate kinase 2 (PKM2) , laetate dehydrogenase A ( LDHA).The differentiation of Thl7 eells was induced in vitro, and the ShRNA/lentivirus was applied to achieve the overexpression or knockdown of miR- 143-3 p.Un-transfected eells were divided into control group and CAT group (20, 40, 80 mg • L 1 ) , and transfected eells were divided into four groups: negative control group, miR-143-3p inhibitor group, miR- 143-3p mimies group, miR-143-3p inhibitor + CAT group.The percentage of Thl7 eells was deteeted by flow cytometry, and the level of IL-17A was detected by EL1SA.Quantitative real-time PCR was used to detect the mRNA expression of miR-143-3p and key glycolytic enzymes, and the levels of pyruvate and lactate were also detected.Results The mRNA expression of miR-143-3p in RA peripheral blood CD4 ∗ T cells was negatively correlated with disease severity ( DAS28 ) , transcription factor ROR-yt, and the key glycolytic enzymes Glutl/HK2/LDHA.Compared with negative control group, the down-expression of miR-143-3p markedly elevated the mRNA expression of ROR-yt, Glutl, HK2, LDHA, and the levels of IL-17A, pyruvate, lactate.Catalpol groups significantly up-regula- ted the expression of miR-143-3p, decreased the mRNA expression of HK2/LDHA and the levels of pvru- vate/lactate, and inhibited Thl7 cells differentiation.Compared with miR - 1 4 3 - 3 p inhibitor group , catapol could significantly inhibit the abnormal up-regulated of HK2/LDHA mRNA relative expression, pyruvate/lactate levels and the abnormal differentiation of Thl7 eells.Conclusion MiR-143-3p inhibits the differentiation and glycolysis of Thl7 cells.Catalpol could sup-press the glycolysis and differentiation of Thl7 eells by regulating mill-143-3p.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Objective: To investigate death and attrition in HIV-infected children under initial antiretroviral therapy (ART) and associated factors in Guangxi Zhuang autonomous region. Methods: This retrospective cohort study was conducted in HIV-infected children under initial ART in Guangxi from 2004 to 2019, data from ART information system of National comprehensive AIDS prevention and treatment information system. Cox proportional hazards models were used to assess factors associated with the death and attrition. Results: In 943 HIV-infected children, the overall mortality and attrition rates were 1.00/100 person-years and 0.77/100 person-years, respectively. The mortality and attrition rates within the first year of ART were 3.90/100 person-years and 1.67/100 person-years, respectively. The cumulative survival rate during the first, second, fifth and tenth year after ART was 96.14%, 95.80%, 93.68% and 91.54%, respectively. Multivariate Cox proportional hazards models results showed that being female (aHR=2.00, 95%CI: 1.17-3.40), CD4⁺T lymphocytes (CD4) counts before ART <200 cells/μl (aHR=2.79, 95%CI: 1.54-5.06), weight-for-age Z score before ART <-2 (aHR=2.38, 95%CI: 1.32-4.26), hemoglobin before ART <80 g/L (aHR=2.47, 95%CI: 1.24-4.92), initial ART with LPV/r (aHR=5.05, 95%CI: 1.15-22.12) were significantly associated with death; being female (aHR=2.23, 95%CI: 1.22-4.07) and initial ART with LPV/r (aHR=2.02, 95%CI: 1.07-3.79) were significantly associated with attrition. Conclusions: The effect of ART in HIV-infected children in Guangxi was better, but the mortality and attrition rates were high within the first year of treatment. It is necessary to strengthen the training in medical staff and health education in HIV-infected children and their parents in order to improve the treatment effect.
Anti-HIV Agents/therapeutic use* ; Child ; China/epidemiology* ; Female ; HIV Infections/drug therapy* ; Humans ; Male ; Proportional Hazards Models ; Retrospective Studies

Objective: To explore the possibility that the intestinal flora profile in complex anal fistula patients is different to that of healthy controls. This was assessed by sequencing of 16S rDNA in fecal samples from cohorts representing these populations. Methods: Fecal samples were collected from 30 complex anal fistula patients and 30 matched healthy controls. Patients were included if they met the diagnostic criteria of cryptoglandular anal fistula and had exhibited symptoms for more than 3 months. Complex anal fistula is diagnosed under the following circumstances: if the fistula in question spans 2/3 or more of the diameter of the anal sphincter; if there are more than two external orifices or fistula tracks; or if recurrence is observed after previous anal fistula surgery. Patients were excluded if there were comorbities including inflammatory bowel disease (as assessed by colonoscopy), chronic diarrhea, chronic constipation, diabetes, gastrointestinal malignancies, liver/ kidney dysfunction, or cognitive impairment. Patients whose anal fistulas were caused by Crohn's disease, trauma, special infections (such as actinomycosis and tuberculosis) were also excluded, as were those who had used antibiotics, prebiotics, or probiotics that may affect intestinal microecology in the month prior to the study. Total bacterial genomic DNA was extracted by PCR amplification of the V4 hypervariable region of the 16S rRNA sequences. High-throughput sequencing and data analysis were performed on the Illumina Miseq platform. Finally, operational taxonomic unit (OTU) clustering, alpha diversity and LEfSE data analysis were carried out. The larger the Chao or ACE index is, the higher the species abundance of the microflora is expected to be. Similarly, a smaller value for the Simpson index or a larger value for the Shannon index indicates greater microflora diversity. There was no statistically significant difference in gender, age, body mass index (BMI), drinking history, or smoking history between the two groups (P>0.05), indicating that they were comparable. Results: The α-diversity analysis including ACE, Chao, Shannon and Simpson indexes indicated a richer diversity of intestinal microflora in complex anal fistula patients than in healthy controls. In both patients and controls, OUT cluster analysis demonstrated that 93.4%±32.0% and 87.4%±41.2% of sequences were from Firmicutes and Bacteroidetes spp., respectively. On a genus level, samples from anal fistula patients showed a greater abundance of Prevotella spp. (4.9%±7.4% vs. 0.1%±1.1%, P<0.001), Megamonas (3.9%±8.2% vs. 0.5%±4.2%, P<0.05) and Lachnospira (2.6%±5.7% vs. 0.1%±3.4%, P<0.05), while showing a lesser abundance of Proteobacteria spp. (0.02%±4.2% vs. 9.3%±14.4%, P<0.01), Enterococcus (0.02%±2.3% vs. 9.3%±19.6%, P<0.05), Bacteroides (24.7%±9.9% vs. 29.8%±9.1%, P<0.05) and Klebsiella (0.4%±4.2% vs. 3.9%±7.3%, P<0.05) compared with healthy controls. Intestinal flora diversity in the complex anal fistula group was richer than in controls, as indicated by a higher ACE index (293.30±44.00 vs. 218.75±33.83, t=102.069, P<0.001), a higher Chao index (318.40±41.99 vs. 250.00±46.38, t=77.818, P=0.028), a higher Shannon index (3.36±0.29 vs. 2.43±0.34, t=9.657, P=0.001), and a lower Simpson index (0.103±0.013 vs. 0.131±0.013, t=5.551, P=0.046). LDA effect size analysis suggests that the main strains of Veillonellaceae, Selenemondales and Negativicutes, which all belong to the phylum Firmicutes, have the greatest influence on the above difference (LDA>4). Conclusions: The diversity of intestinal flora in patients with complex anal fistula is greater than in healthy controls, suggesting that these bacteria or their metabolites may be involved in the occurrence and development of anal fistulas.
Anti-Bacterial Agents ; Bacteria/genetics* ; DNA, Ribosomal ; Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S/genetics* ; Rectal Fistula/surgery*

Objective: To systematically introduce the design of case-cohort study and the statistical methods of relative risk estimation and their application in the design. Methods: First, we introduced the basic principles of case-cohort study design. Secondly, Prentice's method, Self-Prentice method and Barlow method were described in the weighted Cox proportional hazard regression models in detail, finally, the data from the Shanghai Women's Health Study were used as an example to analyze the association between obesity and liver cancer incidence in the full cohort and case-cohort sample, and the results of parameters from each method were compared. Results: Significant association was observed between obesity and risk for liver cancer incidence in women in both the full cohort and the case-cohort sample. In the Cox proportional hazard regression model, the partial regression coefficients of the full cohort and the case-cohort sample fluctuated with the adjustment of confounding factors, but the hazard ratio estimates of them were close. There was a difference in the standard error of the partial regression coefficient between the full cohort and the case-cohort sample. The standard error of the partial regression coefficient of the case-cohort sample was larger than that of the full cohort, resulting in a wider 95% confidence interval of the relative risk. In the weighted Cox proportional hazard regression model, the standard error of the partial regression coefficient of Prentice's method was closer to the parameter estimates from full cohort than Self-Prentice method and Barlow method, and the 95% confidence interval of hazard ratio was closer to that of the full cohort. Conclusions: Case-cohort design could yield parameter results closer to the full cohort by collecting and analyzing data from sub-cohort members and patients with the disease, and reduce sample size and improve research efficiency. The results suggested that Prentice's method would be preferred in case-cohort design.
China/epidemiology* ; Cohort Studies ; Female ; Humans ; Proportional Hazards Models ; Risk ; Sample Size

OBJECTIVE: To evaluate the effectiveness of statin treatment strategies based on risk assessment for the primary prevention of cardiovascular diseases by the Western guidelines in a community-based Chinese population from economically developed areas using data from the Chinese electronic health records research in Yinzhou (CHERRY) study. METHODS: A Markov model was used to evaluate the effectiveness of the following statin treatment strategies, including: (1) usual care without cardiovascular risk assessment(Strategy 0); (2) using the World Health Organization (WHO) non-laboratory-based risk charts with statin treatment for high-risk group (risk ≥ 20%) (Strategy 1); (3) using the WHO laboratory-based risk charts with statin treatment for high-risk group (risk ≥ 20%) (Strategy 2); and (4) using the Prediction for Atherosclerotic cardiovascular disease Risk in China (China-PAR) model with statin treatment for high-risk group (risk ≥ 10%, Strategy 3). According to the guidelines, adults in the medium-risk group received lifestyle intervention, and adults in the high-risk group received life-style intervention and statin treatment under these strategies. The Markov model simulated different strategies for ten years (cycles) using parameters from the CHERRY study, published data, meta-analyses and systematic reviews for Chinese. The number of cardiovascular events or deaths, as well as the number need to treat (NNT) with statin per cardiovascular event or death prevented, were calculated to compare the effectiveness of different strategies. One-way sensitivity analysis on the uncertainty of incidence rate of cardiovascular diseases, and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted. RESULTS: Totally 225 811 Chinese adults aged 40-79 years without cardiovascular diseases at baseline were enrolled. In contrast to the usual care without risk assessment-based statin treatment strategy, Strategy 1 using the WHO non-laboratory-based risk charts could prevent 3 482 [95% uncertainty interval (UI): 2 110-4 661] cardiovascular events, Strategy 2 using the WHO laboratory-based risk charts could prevent 3 685 (95%UI: 2 255-4 912) events, and Strategy 3 using the China-PAR model could prevent 3 895 (95%UI: 2 396-5 181) events. NNTs with statin per cardiovascular event prevented were 22 (95%UI: 14-54), 21 (95%UI: 14-52), and 27 (95%UI: 17-67), respectively. Strategy 3 could prevent more cardiovascular events, while Strategies 1 and 2 required fewer numbers need to treat with statin per cardiovascular event prevented. The results were consistent in the sensitivity analyses. CONCLUSION The statin treatment strategies based on risk assessment for the primary prevention of cardiovascular diseases recommended by the Western guidelines could achieve substantive health benefits in adults from developed areas of China. Using the China-PAR model for cardiovascular risk assessment could prevent more cardiovascular diseases while using the WHO risk charts seems more efficient.
Adult ; Cardiovascular Diseases/prevention & control* ; China/epidemiology* ; Cost-Benefit Analysis ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Primary Prevention

OBJECTIVE: To evaluate the effectiveness of different screening strategies for type 2 diabetes to prevent cardiovascular disease in a community-based Chinese population from economically developed areas based on the Chinese electronic health records research in Yinzhou (CHERRY) study. METHODS: A Markov model was used to simulate different systematic diabetes screening strategies, including: (1) screening among Chinese adults aged 40-70 years recommended by the 2020 Chinese Guideline for the prevention and Treatment of Type 2 Diabetes (Strategy 1); (2) screening among Chinese adults aged 35 to 70 years recommended by the 2022 American Diabetes Association Standard of Medical Care in Diabetes (Strategy 2); and (3) screening among Chinese adults aged 35-70 years with overweight or obesity recommended by the 2021 United States Preventive Services Task Force Recommendation Statement on Screening for Prediabetes and Type 2 Diabetes (Strategy 3). According to the guidelines, individuals who were screened positively (fasting plasma glucose ≥ 7.0 mmol/L) would be introduced to intensive glycemic targets management (glycated hemoglobin < 7.0%).The Markov model simulated different screening scenarios for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Number of cardiovascular disease events or deaths could be prevented and number needed to screen (NNS) were calculated to compare the effectiveness of the different strategies. One-way sensitivity analysis on the sensitivity of screening methods and probabilistic sensitivity analysis on uncertainties of diabetes incidence, the sensitivity of screening methods, and intensive glycemic management effects were conducted. RESULTS: Totally 289 245 Chinese adults aged 35-70 years without cardiovascular diseases or diagnosed diabetes at baseline were enrolled. In terms of the number of cardiovascular disease events could be prevented, Strategy 1 for systematic diabetes screening among the adults aged 35-70 years was 222 (95%UI: 180-264), Strategy 2 for systematic diabetes screening among the adults aged 40-70 years was 227 (95%UI: 185-271), and Strategy 3 for systematic diabetes screening among the adults aged 35-70 years with obesity or overweight (body mass index ≥ 24 kg/m²) was 131 (95%UI: 98-164), compared with opportunistic screening. NNS per cardiovascular disease event for the strategies 1, 2 and 3 were 1 184 (95%UI: 994-1 456), 1 274 (95%UI: 1 067-1 564) and 814 (95%UI: 649-1 091), respectively. Compared with Strategy 1, NNS per cardiovascular disease event for Strategy 2 increased by 90 (95%UI: -197-381) with similar effectiveness of cardiovascular prevention; however, NNS per cardiovascular disease event for Strategy 3 was reduced by 460 (95%UI: 185-724) in contrast to the Strategy 2, suggesting that the Strategy 3 was more efficient. The results were consistent in multiple sensitivity analyses. CONCLUSION Systematic screening for diabetes based on the latest guidelines in economically developed areas of China can reduce cardiovascular events and deaths. However, merely lowering the starting age of screening from 40 to 35 years seems ineffective for preventing cardiovascular disease, while screening strategy for Chinese adults aged 35-70 years with overweight or obesity is recommended to improve efficiency.
Adult ; Cardiovascular Diseases/prevention & control* ; China/epidemiology* ; Cost-Benefit Analysis ; Diabetes Mellitus, Type 2/prevention & control* ; Humans ; Mass Screening/methods* ; Obesity ; Overweight ; United States