Objective: To evaluate the clinical effects of low- and intermediate-dose factor Ⅷ (F Ⅷ) prophylaxis in Chinese adult patients with severe hemophilia A. Methods: Thirty adult patients with severe hemophilia A who received low- (n=20) /intermediate-dose (n=10) F Ⅷ prophylaxis at Nanjing Drum Tower Hospital affiliated with Nanjing University Medical College were included in the study. The annual bleeding rate (ABR), annual joint bleeding rate (AJBR), number of target joints, functional independence score of hemophilia (FISH), quality of life score, and health status score (SF-36) before and after preventive treatment were retrospectively analyzed and compared. Results: The median follow-up was 48 months. Compared with on-demand treatment, low- and intermediate-dose prophylaxis significantly reduced ABR, AJBR, and the number of target joints (P<0.05) ; the improvement in the intermediate-dose prophylaxis group was better than that in the low-dose prophylaxis group (P<0.05). Compared with on-demand treatment, the FISH score, quality of life score, and SF-36 score significantly improved in both groups (P<0.05), but there was no significant difference between the two groups (P>0.05) . Conclusion: In Chinese adults with severe hemophilia A, low- and intermediate-dose prophylaxis can significantly reduce bleeding frequency, delay the progression of joint lesions, and improve the quality of life of patients as compared with on-demand treatment. The improvement in clinical bleeding was better with intermediate-dose prophylaxis than low-dose prophylaxis.
Humans ; Hemophilia A/drug therapy* ; Factor VIII/therapeutic use* ; Quality of Life ; Retrospective Studies ; Hemarthrosis/prevention & control* ; Hemorrhage/drug therapy*

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.
Humans ; Female ; Cost-Benefit Analysis ; Cost-Effectiveness Analysis ; Disease Progression

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

Medicinal plants have provided numerous medicinal active ingredients for thousands of years and these ingredients have been used in Chinese medicine (CM) and traditional pharmacologies worldwide. Recently, the exploitation and utilisation of medicinal plant resources has increased significantly. The results of the studies have led to the identification of many active components, such as steroidal alkaloids, saponins, terpenoids, and glycosides, in various medicinal plants with different evolutionary levels. Moreover, research on the chemical classification, molecular phylogeny, and pharmacological activity of medicinal plants is increasing in popularity. Pharmacophylogeny is an interdisciplinary topic that studies the correlation between plant phylogeny, chemical composition, and curative effects (pharmacological activity and the traditional curative effect) of medicinal plants. In addition, it provides the basic tools to enable research and development of CM resources. This literature review, based on the genetic relationship between phytogroup and species, highlights the formation process, research content, applications, and future directions of pharmacophylogeny.
Alkaloids ; Glycosides ; Plant Extracts/chemistry* ; Plants, Medicinal/chemistry* ; Saponins ; Terpenes

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

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

Objective: To understand the health literacy and relevant factors of cancer prevention consciousness in Chinese urban residents from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The self-designed questionnaire was used to collect the information of demographic characteristics and cancer prevention consciousness focusing on nine common risk factors, including smoking, alcohol, fiber food, food in hot temperature or pickled food, chewing betel nut, helicobacter pylori, moldy food, hepatitis B infection, estrogen, and exercise. The logistic regression model was adopted to identify the influencing factors. Results: The overall health literacy of the cancer prevention consciousness was 77.4% (24 980 participants), with 77.4% (12 018 participants), 79.9% (6 406 participants), 77.2% (1 766 participants) and 74.5% (4 709 participants) in each group (P<0.001). The correct response rates for nine risk factors ranged from 55.2% to 93.0%. The multivariate logistic regression analysis showed that compared with community residents, people with primary school level education or below, and the number of people living together in the family <3, the cancer risk assessment/screening intervention population, cancer patients, those with junior high school level educationor above and the number of people living in the family ≥3 had better health literacy of the cancer prevention consciousness (all P values <0.05). Compared with females, 39 years old and below, government-affiliated institutions or civil servants, from the eastern region, males, older than 40 years, company or enterprise employees, and from the middle or western region had worse health literacy of the cancer prevention consciousness (all P values <0.05). Conclusion The health literacy of the cancer prevention consciousness in Chinese urban residents should be improved. The cancer screening intervention, gender, age, education, occupation, the number of people co-living in the family, and residential region were associated with the health literacy of the cancer prevention consciousness.

Objective: To understand the consciousness of the cancer early detection among urban residents and identify the influencing factors from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. Self-designed questionnaires were used to collect population, socioeconomic indicators, self-cancer risk assessment, regular participation in physical examination and other information. The multivariate logistic regression model was used to identify the factors of people who had not regularly participated in the regular physical examination in the past five years. Results: The self-assessment results of 32 357 residents showed that there were 27.54% (8 882) of total study population with self-reported cancer risk, 45.48% (14 671) without cancer risk and 26.98% (8 704) with unclear judgement on their own cancer risk. Among population with cancer risk, 79.84% (7 091) considered physical examination accounted. In the past five years, there were 21 105 (65.43%) residents participated in regular physical examination and 11 148 (34.56%) participated in non-scheduled one, respectively. The multivariate logistic regression analysis showed that compared with unmarried and western region residents, divorced, middle and eastern region residents had a stronger consciousness to participate in the regular physical examination (P<0.05). Compare with residents with annual household income less than 20 000 CNY in 2014, cancer risk assessment/screening intervention population, and self-assessment with cancer risk, residents with annual household income between 20 000 CNY and 59 000 CNY in 2014, occupational population, community residents, cancer patients, self-reported cancer-free risk, and self-assessment with unclear judgement of cancer risk were less likely to participate in the regular physical examination (all P values <0.05). Conclusion From 2015 to 2017, the Chinese urban residents had a acceptable consciousness of the cancer early detection. The marital status, annual household income, population group and self-assessment of cancer risk were related to the consciousness of the cancer early detection of people who had not participated in the regular physical examination in the past five years.

Objective: To understand the consciousness of the cancer early diagnosis among urban residents and identify the related factors from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The general demographic characteristics, the consciousness of the cancer early diagnosis (whether people would have a willingness or encourage their relatives/friends to confirm the abnormal results once which were detected from the physical examination) and other information were collected by using the self-designed questionnaire. The non-conditional logistic regression model was used to identify the relateol factors related to the consciousness of the cancer early diagnosis. Results: As for residents with abnormal result from the physical examination, 89.29% (28 802) of residents would choose to seek medical treatment for further diagnosis. If their relatives/friends had abnormal results from the physical examination, 89.55% (28 886) of residents would encourage their relatives/friends to confirm the diagnosis in time. The non-conditional logistic regression model analysis showed that compared with the public institution staff/civil servants, annual household income less than 20 000 CNY, the western region and the cancer risk assessment/screening intervention population, the company staff, annual household income about 40 000 CNY and more, and the residents from the middle and eastern region had a stronger consciousness to seek further diagnosis; while the unemployed residents and community residents were less likely to seek further diagnosis (P<0.05). Conclusions From 2015 to 2017, the Chinese urban residents had a good consciousness of the cancer early diagnosis. Occupation, annual household income, residential region and population group were related to the consciousness of the cancer early diagnosis.