Comparison of aspirin treatment strategies for primary prevention of cardiovascular diseases: A decision-analytic Markov modelling study / 北京大学学报(医学版)

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.

Genotype-environment interaction on arterial stiffness: A pedigree-based study / 北京大学学报(医学版)

OBJECTIVE@#To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects.@*METHODS@#Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles.@*RESULTS@#A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness.@*CONCLUSION@#The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.

Application of discrete event simulation model in analysis on cost-effectiveness of epidemiology screening / 中华流行病学杂志

Discrete event simulation (DES) model is based on individual data, by which discrete events over time are simulated to reflect disease progression. The effects of individual characteristics on disease progression could be considered in the DES model. Moreover, unlike state-transition models, DES model without setting of fixed cycle can contribute to more accurate estimation of event time, especially in the evaluation of the long-term effectiveness of screening strategies for complex diseases in which time dimension needs to be considered. This article introduces the general principles, construction steps, analytic methods and other relevant issues of the DES model. Based on a research case of estimating the cost-effectiveness of screening for abdominal aortic aneurysms in women aged 65 years and above in the United Kingdom, key points in applications of the DES model in analysis on effectiveness of complex disease screening are discussed in detail, including model construction and analysis and interpretation of the results. DES model can predict occurring time of discrete events accurately by establishing the distribution function of their occurring time and is increasingly used to evaluate the screening strategies for complex diseases in which time dimension needs to be considered. In the construction of DES model, it is necessary to pay close attention to the clear presentation of model structure and simulation process and follow the relevant reporting specification to conduct cost-effectiveness analysis to ensure the transparency and repeatability of the research.

Effectiveness of different screening strategies for type 2 diabete on preventing cardiovascular diseases in a community-based Chinese population using a decision-analytic Markov model / 北京大学学报(医学版)

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.

Effectiveness of statin treatment strategies for primary prevention of cardiovascular diseases in a community-based Chinese population: A decision-analytic Markov model / 北京大学学报(医学版)

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.

Effect of transfer RNA-derived molecule fragment 770 on proliferation of breast cancer cells by targeting cytoskeletal-associated protein 2 / 肿瘤研究与临床

Objective:To explore the effect of transfer RNA-derived small molecule fragment 770(tRF-770) on proliferation of breast cancer cells through regulating cytoskeletal-associated protein 2 (CKAP2).Methods:Chromosome localization of tRF-770 was identified using the MINTbase database v2.0 sequence alignment with mature tRNA in the genome. TA cloning assay was used to identify tRF-770; TargetScan and miRBase database were used to analyze and predict the target genes of tRF-770. The expression of CKAP2 in breast cancer was analyzed by using the data from The Cancer Genome Atlas (TCGA) database. Breast cancer cell lines MDB-MA-231 and MCF7 were selected and divided into three groups: blank control group (without any treatment), tRF-770 overexpression group (transfected with tRF-770 overexpression sequence) and negative control group (transfected with negative control sequence). In addition, tRF-770 overexpression+CKAP2-HA group was established (co-transfected with tRF-770 overexpression sequence and CKAP2 overexpression sequence). Real-time quantitative fluorescence polymerase chain reaction (qRT-PCR) was used to detect the relative expression of tRF-770 in breast cancer cells. CCK-8 assay was used to detect the proliferation of breast cancer cells and perform rescue experiment. Dual luciferase reporter gene assay was used to verify the target genes of tRF-770. The protein expression of CKAP2-ERK2 signaling pathway was detected by Western blotting.Results:tRF-770 completely matched 5' UTR spliced and modified by 9 kinds of tRNA. TA clone sequencing verification results showed that the product size and bases were consistent with the expected tRF-770 sequences. CKAP2 was highly expressed in breast cancer tissues based on analysis of the data from TCGA database ( t = 7.21, P < 0.05). qRT-PCR showed that the relative expressions of tRF-770 in MDA-MB-231 cells of blank control group, negative control group and tRF-770 overexpression group were 1.00±0.00, 2.42±0.11 and 3.75±0.01, respectively, and the difference was statistically significant ( F = 1 395.00, P < 0.001). The relative expressions of tRF-770 in MCF7 cells of 3 groups were 1.00±0.00, 2.45±0.21 and 3.26±0.16, respectively, and the difference was statistically significant ( F = 169.30, P < 0.001). Compared with blank control group and negative control group, the relative expression of tRF-770 in tRF-770 overexpression group in 2 cell lines was increased (all P < 0.05). Dual luciferase reporter assay showed that tRF-770 bound to CKAP2 mRNA 3'UTR. CCK-8 assay showed that in MDA-MB-231 and MCF7 cells, the cell proliferation ability of tRF-770 overexpression group on the 3rd and 4th day was lower than that of blank control group and negative control group (both P < 0.05); there were significant differences in cell proliferation ability between the negative control group and tRF-770 overexpression group on the 3rd and 4th day (all P < 0.05). CCK-8 assay showed that in 2 breast cancer cell lines, the cell proliferation ability of tRF-770 overexpression+ CKAP2-HA group was higher than that of tRF-770 overexpression group since the second day after transfection (all P < 0.05). Western blotting showed that the expressions of CKAP2, p-ERK2 and PCNA proteins in tRF-770 overexpression group were decreased compared with the negative control group (all P < 0.05). The change of ERK2 protein expression was small in MDA-MB-231 cells, but the expression of protein in tRF-770 overexpression group in MCF7 cells was decreased. Conclusions:tRF-770 may inhibit the proliferation of breast cancer cells through CKAP2-ERK2 signaling pathway.

Effectiveness of different screening strategies for cardiovascular diseases prevention in a community-based Chinese population: A decision-analytic Markov model / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the potential effectiveness of different screening strategies for cardiovascular diseases prevention in a community-based Chinese population from economically developed area of China.@*METHODS@#Totally 202 179 adults aged 40 to 74 years without cardiovascular diseases at baseline (January 1, 2010) were enrolled from the Chinese electronic health records research in Yinzhou (CHERRY) study. Three scenarios were considered: the screening strategy based on risk charts recommended by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases in Chinese adults aged 40-74 years (Strategy 1); the screening strategy based on the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) models recommended by the 2019 Guideline on the assessment and management of cardiovascular risk in China in Chinese adults aged 40-74 years (Strategy 2); and the screening strategy based on the China-PAR models in Chinese adults aged 50-74 years (Strategy 3). According to the guidelines, individuals who were classified into medium- or high-risk groups after cardiovascular risk assessment by the corresponding strategies would be introduced to lifestyle intervention, while high-risk population would take medication in addition. Markov model was used to simulate different screening scenarios for 10 years (cycles), using parameters mainly from the CHERRY study, as well as published data, Meta-analyses and systematic reviews for Chinese populations. The life year gained, quality-adjusted life year (QALY) gained, number of cardiovascular disease events/deaths could be prevented and number needed to be screened (NNS) were calculated to compare the effectiveness between the different strategies. One-way sensitivity analysis on uncertainty of cardiovascular disease incidence rate and probabilistic sensitivity analysis on uncertainty of distributions for the hazard ratios were conducted.@*RESULTS@#Compared with non-screening strategy, QALYs gained were 1 433 [95% uncertainty interval (UI): 969-1 831], 1 401 (95%UI: 936-1 807), and 716 (95%UI: 265-1 111) for the Strategies 1, 2, and 3; and the NNS per QALY in the above strategies were 141 (95%UI: 110-209), 144 (95%UI: 112-216), and 198 (95%UI: 127-529), respectively. The Strategies 1 and 2 based on different guidelines showed similar effectiveness, while more benefits were found for screening using China-PAR models in adults aged 40-74 years than those aged 50-74 years. The results were consistent in the sensitivity analyses.@*CONCLUSION@#Screening for cardiovascular diseases in Chinese adults aged above 40 years seems effective in coastal developed areas of China, and the different screening strategies based on risk charts by the 2020 Chinese guideline on the primary prevention of cardiovascular diseases or China-PAR models by the 2019 Guideline on the assessment and management of cardiovascular risk in China may have similar effectiveness.

Application of the China-PAR stroke risk equations in a rural northern Chinese population / 北京大学学报(医学版)

OBJECTIVE@#To validate five-year risk prediction models for stroke in a contemporary rural Northern Chinese population.@*METHODS@#Totally 6 483 rural adults aged 40 to 79 years without cardiovascular diseases were enrolled at baseline between June and August 2010, and followed up through January 2017. Expected prediction risk using the China-PAR (prediction for atherosclerotic cardiovascular disease risk in China) stroke risk equations were compared with the new Framingham stroke risk profile (FSRP). The recalibrated models were applied by adjusting the five-year baseline survival rate and the mean score to our rural northern Chinese population, while keeping other coefficient parameters the same as the original models. Kaplan-Meier analysis was used to obtain the observed event (nonfatal or fatal stroke) rate for the five years, and the expected-observed ratios were calculated to evaluate overestimation or underestimation in the cohort. The models were assessed by discrimination C statistic, calibration χ2, and calibration charts and plots for illustration as well.@*RESULTS@#Over an average of (5.83 ± 1.14) years of the follow-up in this validation cohort with 6 483 rural Chinese participants, 438 subjects deve-loped a first stroke event. Recalibrated China-PAR stroke risk equations and FSRP well-performed for predicting five-year stroke risk in men, and had C statistics of 0.709 (95%CI, 0.675 - 0.743) and 0.721 (95%CI, 0.688 - 0.754), with calibration χ2 values being 5.7 (P = 0.770) and 13.6 (P = 0.137), respectively. However, both China-PAR and FSRP overestimated stroke events by 11.6% and 30.0% in women, and had C statistics of 0.713 (95%CI, 0.684-0.743) and 0.710 (95%CI, 0.679-0.740), respectively. Calibration χ2 values in women were 12.5 (P = 0.188) for China-PAR and 24.0 (P = 0.004) for FSRP. In addition, the calibration charts and plots illustrated good agreement between the observations and the predictions only in the China-PAR stroke risk equations, especially for men.@*CONCLUSION@#In this validation cohort of rural northern Chinese adults, the China-PAR models had better performance of five-year stroke risk prediction than the FSRP, indicating that recalibrated China-PAR stroke risk equations might be appropriate tools for risk assessment and primary prevention of stroke in China.

Association of obesity and brachial-ankle pulse wave velocity among type 2 diabetes patients / 中华疾病控制杂志

Objective The aim of this study was to investigate associations of overall obesity (OO) and abdominal obesity (AO) with brachial-ankle pulse wave velocity (baPWV) among type 2 diabetes(T2DM) patients. Methods A community-based study for T2DM patients was conducted in rural communities in Beijing．Every patient completed a questionnaire to collect demography, lifestyle and diseases history, and underwent physical examinations, baPWV assessments and blood biochemical tests. Multivariate linear regression was used to assess the relationship between obesity index and baPWV. Abnormal baPWV was defined as patients with baPWV≥1,700 cm/s. Logistic regression model was performed to explore the risk of abnormal baPWV after adjusting for poetential confounders step by step. Results A total of 2 048 T2DM patients were recruited. The average age was (59.2±8.3) years and total prevalence of abnormal baPWV was 49.7%. After multivariable adjustment, linear regression showed that there was a negative correlation between body mass index(BMI) and baPWV and a positive correlation between waist-to-hip ratio (WHR) and baPWV. Compared to normal weight group, those with BMI≥28 kg/m2 had lower risk of abnormal baPWV (OR=0.59, 95% CI: 0.44-0.78，P<0.001), but there was an increased risk of 46% among patients with obesity in WHR (OR=1.46, 95% CI:1.07-2.00，P=0.018). Compared to those without OO and AO, patients without OO but with AO had a 1.67-fold increasesd risk of abnormal baPWV (OR=1.67, 95% CI: 1.19-2.35，P=0.003). Conclusions Abdominal obesity is related with arterial stiffnening among T2DM patients, and it is critical to evaluate arterial stiffness of T2DM patients with abdmonal obesity and normal BMI in order to reduce future risk of cardiovascular diseases.

Associations between sleep duration and different ischemic stroke subtypes / 中华疾病控制杂志

Objective To explore the relationship between sleep duration and different ischemic stroke (IS) subtypes. Methods Participants in the study were recruited from rural communities in Beijing. The survey questionnaires, physical examination and biochemical tests were performed. Sleep duration was categorized into 5 groups, namely ≤5 hours/day, 6 hours/day (5.5-6.5 h/d), 7 hours/day (6.5-7.5 h/d), 8 hours/day (7.5-8.5 h/d) and ≥9 hours/day(≥8.5 h/d). Classification of ischemic stroke was based on Trial of org 10172 in acute stroke treatment(TOAST)classification. Logistic models were used to evaluate the associations between sleep duration and different IS subtypes. Results A total of 6 370 participants were recruited. The average age was (58.34±9.37) years old. Logistic regression analysis showed that after adjusting for age, sex, behavioral lifestyle, socioeconomic status and health status, compared to subjects with 7 hours/day, subjects with sleep duration ≤5 hours/day was significantly associated with increased risk of IS (OR=1.75, 95% CI: 1.42-2.15, P<0.001), large-artery atherosclerosis (OR=1.98, 95% CI:1.46-2.70, P<0.001), small-artery occlusion lacunar (OR=5.73, 95% CI:3.34-9.83, P<0.001) and stroke of undetermined etiology (OR=4.43, 95% CI:1.86-10.53, P=0.001). Subjects with sleep duration 8 hours/day and ≥9 hours/day was only found to be significantly associated with IS and large-artery atherosclerosis (P<0.05). Conclusions Short sleep duration is associated with increased risk of IS, large-artery atherosclerosis, small-artery occlusion lacunar and stroke of undetermined etiology. But long sleep duration is only associated with increased risk of IS and large-artery atherosclerosis.

Isolation and identification of endophytic fungi from Chelidonium majus and their antifungal activity / 中国中药杂志

In order to find new source of antifungal agents, eleven cultivable endophytic fungi were isolated from the roots,stems and leaves of Chelidonium majus by traditional method. Seven of them were identified as Colletotrichum(L1, L2, L3, S1, S3, S4, S5), and three of them were identified as Fusarium(R1,R2,R3) by morphological features and molecular biological technology. The antifungal activity test showed that all the tested fungi displayed some inhibitory activity against five common plant pathogens(C. gloeosporioides, Curvularia lunata, Pyricularia oryza, Alternaria alternate and A. brassicae), and their inhibition rate of some test items were over 60%. Among them, R1, S2, S3 and S4 were more potent than others. This study enriches the understanding of endophytes from Ch. majus and provides a basis for the study of new microbial fungicides.

Treatment of chronic tibial osteomyelitis of Cierny-Mader type Ⅳ with Ilizarov technique and lesion osteotomy / 中华创伤骨科杂志

Objective To evaluate surgical treatment of chronic tibial osteomyelitis of Cierny-Mader type Ⅳ with Ilizarov technique and lesion osteotomy. Methods From January 2010 to May 2016, 39 patients with chronic tibial osteomyelitis of Cierny-Mader type Ⅳ were treated at our center. They were 33 males and 6 females, 8 to 54 years of age (average, 33.8 years). After debridement and lesion osteotomy, the tibia was fixated with Ilizarov external fixator. Bone was transported to the bone defect after corticotomy was performed on the proximal and/or distal tibial metaphyses simultaneously. Bifocal corticotomy was per-formed in 11 cases, proximal corticotomy in 21 cases, and distal corticotomy in 7 cases. The transport began 3 to 5 days after operation at a speed of 0.5 to 1.0 mm/d initially. The speed was lowered according to the bone healing and pain. Radiographic examination was done every 2 weeks to observe transporting deviation and osteogenesis in the transporting area. The transporting was adjusted whenever any abnormality was observed. The bone transporting lasted for 50 to 130 days (average, 62.4 days). Results The patients were fol-lowed up for 11 to 49 months (average, 21 months). All the soft tissue wounds healed uneventfully and there was no relapse of osteomyelitis. The bone defects in the 32 cases were reconstructed primarily. Nonunion of fracture ends happened in 5 cases and nonunion of the bone lengthening zone in 2 cases. The 7 cases of nonunion were healed after secondary bone grafting. Malalignment happened in 5 cases, 4 of which responded to timely adjustment of the external fixation and one of which had to receive secondary bone grafting after failure in adjustment of the external fixation. Ankle joint dysfunction occurred in 7 cases, 5 of which re-sponded to functional exercise and 2 of which accepted joint dysfunction because they refused surgery after unsatisfactory functional exercise. Pin tract infection of different severities occurred in 9 cases, one of which was treated by replacement of the K-wires under local anesthesia and the other 8 of which responded to rein-forced dressing change. Conclusions Chronic tibial osteomyelitis of Cierny-Mader typeⅣcan be treated by Ilizarov technique and lesion osteotomy. However, the Ilizarov technique should be improved because of the risks of multiple complications which can be reduced significantly by strengthening postoperative instruction, nursing, and regular follow-up.

Prevalence of diabetes in Chinese adults: a Meta-analysis / 中华流行病学杂志

Objective To evaluate the prevalence and trend of diabetes mellitus among Chinese adults during the past thirty years.Methods Papers,published before October 1,2017 and related to the prevalence of diabetes mellitus among Chinese adults,were searched through PubMed,China Knowledge Resource Integrated Database,Wanfang Digital Database and VIP Citation Databases.Stata 13.0 software was used to estimate the prevalence of diabetes mellitus,with pooled prevalence calculated based on random effects.Subgroup analysis was conducted based on time,sex,areas and body mass index groups of investigation.Continuous fractional polynomial regression model on the midpoint of each survey period,weighted by the number of participants in each study,was used to estimate and illustrate the trends of prevalence of diabetes over the years.Results In total,15 studies were included and two of them were excluded in the primary analysis with the age limitation of participants as ≥40 years old,for recruitment.The average prevalence of diabetes among Chinese adults was 6.3％ (95％CI:4.6％-8.0％),during the past thirty years.The pooled prevalence appeared higher in urban than in rural areas and higher in men than in women.Between 1980 and 2013,the increase of Chinese diabetes prevalence did not follow the linear trend.Before 2000,the average prevalence showed as 3.5％ (95％CI:2.0％-4.9％),with an annual increase rate as 0.17％.Since 2000,the average annual prevalence of diabetes mellitus had appeared around 8.0％ (95％CI:6.0％-10.1％),with an annual growth rate of 0.72％ (95％CI:0.34％-1.10％).Conclusion The prevalence of diabetes in Chinese adults had been rapidly increasing since the year 2000,indicating that efforts should be strengthened for diabetes prevention,in China.

Progress in research of family-based cohort study on common chronic non-communicable diseases in rural population in northern China / 中华流行病学杂志

Family-based cohort study is a special type of study design,in which biological samples and environmental exposure information of the member in a family are collected and related follow up is conducted.Family-based cohort study can be applied to explore the effect of genetic factors,environmental factors,gene-gene interaction,and gene-environment interaction in the etiology of complex diseases.This paper summarizes the objectives,methods and results,as well as the opportunities and challenges of the family-based cohort study on common chronic non-communicable diseases in rural population in northern China.

Prevalence of diabetes in Chinese adults: a Meta-analysis / 中华流行病学杂志

Objective To evaluate the prevalence and trend of diabetes mellitus among Chinese adults during the past thirty years.Methods Papers,published before October 1,2017 and related to the prevalence of diabetes mellitus among Chinese adults,were searched through PubMed,China Knowledge Resource Integrated Database,Wanfang Digital Database and VIP Citation Databases.Stata 13.0 software was used to estimate the prevalence of diabetes mellitus,with pooled prevalence calculated based on random effects.Subgroup analysis was conducted based on time,sex,areas and body mass index groups of investigation.Continuous fractional polynomial regression model on the midpoint of each survey period,weighted by the number of participants in each study,was used to estimate and illustrate the trends of prevalence of diabetes over the years.Results In total,15 studies were included and two of them were excluded in the primary analysis with the age limitation of participants as ≥40 years old,for recruitment.The average prevalence of diabetes among Chinese adults was 6.3％ (95％CI:4.6％-8.0％),during the past thirty years.The pooled prevalence appeared higher in urban than in rural areas and higher in men than in women.Between 1980 and 2013,the increase of Chinese diabetes prevalence did not follow the linear trend.Before 2000,the average prevalence showed as 3.5％ (95％CI:2.0％-4.9％),with an annual increase rate as 0.17％.Since 2000,the average annual prevalence of diabetes mellitus had appeared around 8.0％ (95％CI:6.0％-10.1％),with an annual growth rate of 0.72％ (95％CI:0.34％-1.10％).Conclusion The prevalence of diabetes in Chinese adults had been rapidly increasing since the year 2000,indicating that efforts should be strengthened for diabetes prevention,in China.

Progress in research of family-based cohort study on common chronic non-communicable diseases in rural population in northern China / 中华流行病学杂志

Family-based cohort study is a special type of study design,in which biological samples and environmental exposure information of the member in a family are collected and related follow up is conducted.Family-based cohort study can be applied to explore the effect of genetic factors,environmental factors,gene-gene interaction,and gene-environment interaction in the etiology of complex diseases.This paper summarizes the objectives,methods and results,as well as the opportunities and challenges of the family-based cohort study on common chronic non-communicable diseases in rural population in northern China.

Lithium chloride arrests HK-2 cell cycle in G2 phase through AKT/GSK-3β signal pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of lithium chloride (LiCl) on cell cycle of HK-2 cells and explore the possible pathways involved.</p><p><b>METHODS</b>HK-2 cells were treated with LiCl at different concentrations (5, 12.5, 20, and 25 mmol/L) for 12, 24, 48, or 72 h, and the changes in cell cycle and viability were detected using flow cytometry and CCK-8 assay, respectively. Western blotting was used to analyze the changes in the expressions of cyclin B1 and CDK1 (the two G2 phase-related proteins) and those of AKT/GSK-3β signaling pathway-related proteins in the treated cells.</p><p><b>RESULTS</b>LiCl treatment time- and concentration-dependently increased HK-2 cell percentage in G2 phase and decreased the cell vitality. The expressions of cyclin B1, CDK1, p-GSK-3β, and β-catenin increased and the expression of p-AKT decreased significantly in the cells as LiCl treatment time and concentration increased.</p><p><b>CONCLUSION</b>LiCl may cause HK-2 cell cycle arrest in G2 phase through activation of the AKT/GSK-3β signaling pathway.</p>

Effectiveness of different screening strategies for primary prevention of cardiovascular diseases in a rural northern Chinese population / 北京大学学报(医学版)

OBJECTIVE@#To estimate the potential health benefit of screening strategies for cardiovascular diseases primary prevention in a rural northern Chinese population.@*METHODS@#A total of 6 221 adults aged 40-74 years old, from rural Beijing, China and free from cardiovascular diseases at baseline were included. The following screening strategies were compared: Strategy 1, the strategy based on numbers of risk factors recommended by the Chinese Guideline for Prevention of Cardiovascular Diseases in people aged 40-74; Strategy 2, screening people aged 40-74 based on the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) risk prediction model; Strategy 3, screening people aged 50-74 using the China-PAR risk prediction model. Participates who were classified into medium- or high-risk by the corresponding strategies would be introduced to lifestyle intervention, while high risk population would take medication in addition. Markov model was used to compare the potential health benefits within 10 years in each scenario, which applied the parameters from this rural northern Chinese cohort, published literatures, meta-analyses and systematic reviews, clinical trials and other cohort studies of Chinese population. Quality-adjusted life year (QALY) gained, cardiovascular diseases (CVD) events/deaths could be prevented and number needed to be screened (NNS) per QALY gained/per CVD event prevented/per CVD death prevented were calculated to compare the effectiveness. One-way sensitivity analysis concerning uncertainty of cardiovascular disease incidence rate and probabilistic sensitivity analysis about the uncertainty of hazard ratios were conducted.@*RESULTS@#Compared with non-screening strategy, the potential health benefits of each strategy were: Strategy 1 would gain QALY of 498 (95%CI: 103-894) and prevent 298 (95%CI: 155-441) CVD events; Strategy 2 would gain QALY of 691 (95%CI: 233-1 149) and prevent CVD events of 374 (95%CI: 181-567); Strategy 3 would gain QALY of 654 (95%CI: 199-1 108) and prevent CVD events of 346 (95%CI: 154-538). Screening strategy based on ChinaPAR risk prediction model (strategy 2 or 3) would be generally better in terms of QALY gained, CVD events/deaths prevented and NNS than the strategy based on numbers of CVD risk factors (all P<0.05 except NNS per QALY gained and NNS per CVD event prevented in 40-74 years). Similar benefits were obtained for the strategy 2 and 3. The results were consistent in the sensitivity analyses on the parameters of incidence rates and hazard ratios.@*CONCLUSION@#Screening people to target increased risks of cardiovascular diseases in this rural northern Chinese population is necessary. Screening strategy based on China-PAR risk prediction model could gain more health benefits than that based on numbers of CVD risk factors.

Incidence and risk factors of chronic kidney disease in community-based patients with diabetes / 北京大学学报(医学版)

OBJECTIVE@#To estimate the incidence rate and effects of risk factors on chronic kidney disease (CKD) in Chinese patients with diabetes, based on Electronic Health Records (EHRs) from the Chinese Electronic health Records Research in Yinzhou (CHERRY) Study.@*METHODS@#Using the CHERRY cohort study with the individual-level information on chronic disease management; and health administrative, clinical and laboratory databases, patients with diabetes without kidney disease at baseline were enrolled and followed up from January 2009 through December 2016. CKD was defined as the estimated glomerular filtration rate(eGFR) <60 mL/(min×1.73 m2) or urine albumin/creatinine ratio (ACR)≥3 mg/mmol. Standardized incidence rates of CKD in diabetic population were calculated according to the 2010 China census data. Cox proportional hazards models were used to explore the association of risk factors on CKD in patients with diabetes.@*RESULTS@#Over a median 3.2 years of follow-up, 13 829 patients with diabetes were included in this analysis and 1 087 developed CKD. The crude and standardized incidence rate was 23.7(95%CI: 22.3-25.2) and 14.8(95%CI:12.1-17.6) per 1 000 person-years respectively. The incidence rate for developing CKD in patients with diabetes aged over 60 years was higher than those aged 60 and below (26.6 vs. 11.5 per 1 000 person-years, P<0.05). Cox proportional hazards models showed that age over 60 years(HR=1.88, 95%CI: 1.51-2.35), hypertension (HR=1.81, 95%CI: 1.56-2.10), total cholesterol (HR=1.07, 95%CI: 1.00-1.14) and duration of diabetes (HR per year increment=1.02, 95%CI: 1.00-1.03) and the level of high density lipoprotein cholesterol (HDLC, HR=0.49, 95%CI: 0.40-0.61) were significantly associated with CKD. No statistical significance was found for sex, smoking status, alcohol use and average level of fasting glucose (All P>0.05). Subgroup analysis indicated that even when the lipid levels were well-controlled, comorbidity of hypertension was still associated with CKD in the patients with diabetes.@*CONCLUSION@#Incidence rate of chronic kidney disease in this Chinese population with diabetes was high. Age and comorbidity of hypertension were the most important risk factors for CKD, suggesting the priority for CKD screening in patients with diabetes in China. Control of blood pressure and lipid were especially crucial to prevent CKD in patients with diabetes.

CDH13 Genetic Polymorphisms, Adiponectin and Ischemic Stroke: a Chinese Family-based Sib-pair Study / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To understand the relationships between CDH13 (T-cadherin) genetic polymorphisms, adiponectin levels and ischemic stroke, and possible interactions between CDH13 polymorphisms and other risk factors.</p><p><b>METHODS</b>We recruited 342 Chinese ischemic stroke sib pairs. We genotyped rs4783244 and rs7193788 on CDH13 using time-of-flight mass spectrometry genotyping technology and measured total and high-molecular weight (HMW) adiponectin levels. We investigated associations between SNPs and ischemic stroke, and interactions between SNPs and other risk factors using multi-level mixed-effects regression model.</p><p><b>RESULTS</b>In individuals without ischemic stroke, CDH13 rs4783244 was associated with total adiponectin levels (per T: Coef = -0.257, P = 0.001). CDH13 rs7193788 was associated with total adiponectin levels (per A: Coef = -0.221, P = 0.001) and HMW adiponectin levels (per A: Coef = -0.163, P = 0.003). rs7193788 was significantly associated with ischemic stroke (GA/AA vs. GG: OR = 1.55, 95% CI: 1.07 to 2.24, P = 0.020) after Bonferroni correction (α = 0.025). There was an interaction between rs7193788 and diabetes (P = 0.036). Compared to diabetes-free individuals with rs7193788 GG genotype, diabetes patients with rs7193788 GA/AA genotypes had higher risks for ischemic stroke (OR = 2.64, 95% CI: 1.58-4.40, P < 0.001).</p><p><b>CONCLUSION</b>CDH13 genetic polymorphisms are associated with adiponectin levels and ischemic stroke. An interaction is found between CDH13 SNP and diabetes for ischemic stroke.</p>