[To discuss the minimally invasive glaucoma surgery related to trabeculotomy from the perspective of physiological function of trabecular meshwork drainage pathway].

The advent of minimally invasive glaucoma surgery (MIGS) has broadened the therapeutic options for managing glaucoma. In recent years, MIGS procedures targeting the trabecular meshwork-Schlemm's canal aqueous outflow resistance site have garnered significant attention. This focus has extended to the pathophysiological changes occurring within the aqueous outflow pathway. However, questions persist regarding the efficacy of near-peripheral or peripheral trabeculotomy in achieving the anticipated reduction of outflow resistance and the suitability of MIGS surgery for patients with primary open-angle glaucoma. By integrating clinical experience with pertinent clinical research, this paper advocates for a reevaluation of MIGS procedures to aid clinicians in making informed decisions regarding various glaucoma surgical interventions.

[Effects of different types of intraocular lens implantation on patient's visual quality and function after phacoemulsification].

Objective: To explore the effects of different types of intraocular lens (IOL) implantation on patient's visual quality and function after phacoemulsification. Methods: The clinical data of patients with monocular cataract who underwent phacoemulsification in the Department of Ophthalmology, People's Hospital Affiliated to Shandong First Medical University between December 2021 and May 2023 were retrospectively analyzed. According to the types of IOL, the patients were divided into monofocal group, bifocal group and depth of focus extension group. Three months later, uncorrected distance visual acuity (UCDVA), best corrected distance visual acuity (BCDVA), uncorrected intermediate visual acuity (UCIVA), best corrected intermediate visual acuity (BCIVA), uncorrected near visual acuity (UCNVA) and best corrected near visual acuity (BCNVA) were detected. Contrast sensitivity and total wavefront aberration were measured by visual function analyzer. Satisfaction with visual quality was evaluated by hospital-made satisfaction questionnaire. Results: A total of 92 patients were included, with 31 males and 61 females, and their age was (61.8±5.2) years. There were 43, 28 and 21 cases in monofocal group, bifocal group and depth of focus extension group, respectively. No statistically significant difference was found in clinical baseline data among the three groups. UCIVA, UCDVA, BCIVA and BCDVA in depth of focus extension group were 1.01±0.13, 0.92±0.18, 1.21±0.19 and 1.20±0.23, respectively, which were higher than those in monofocal group (0.62±0.12, 0.74±0.13, 1.02±0.17, 1.07±0.19, respectively) and bifocal group (0.67±0.15, 0.78±0.14, 1.01±0.16, 1.01±0.18, respectively), while absolute value of spherical equivalent [(-0.42±0.07) D] was lower than that in the other two groups [ (-0.49±0.05) D and (-0.45±0.08) D] (both P<0.05). UCNVA and BCNVA in bifocal group were 0.91±0.18 and 1.25±0.18, which were higher than those in depth of focus extension group (0.63±0.24 and 1.19±0.17) (both P<0.05). There were no significant differences in contrast sensitivity among the three groups under day vision or between monofocal group and bifocal group under night vision (all P>0.05), but the contrast sensitivity was higher in depth of focus extension group under night vision (3.0, 6.0, 12.0 c/d) than other two groups (all P<0.05). The score of ocular discomfort was the highest in bifocal group, followed by depth of focus extension group and monofocal group (both P<0.05). The score of visual interference in bifocal group was lower than that in monofocal group and depth of focus extension group (both P<0.05). The scores of subjective feeling in bifocal group and depth of focus extension group were higher than that in monofocal group (both P<0.05). The reading score was the highest in bifocal group, followed by depth of focus extension group and monofocal group (both P<0.05). There was no significant difference in total low-order aberration among the three groups (P=0.472). The total aberration and higher-order aberration [(0.74±0.35) µm and (0.41±0.12) µm] were the highest in monofocal group, followed by bifocal group [(0.61±0.21) µm and (0.22±0.09) µm] and depth of focus extension group [(0.46±0.13) µm and (0.06±0.09) µm] (all P<0.05). Conclusions: IOL implantation with depth of focus extension can enhance visual range, night vision and contrast sensitivity, and thus effectively improve postoperative visual quality and function in cataract patients. The bifocal IOL can better improve the patient's UCNVA and BCNVA, resulting in high satisfaction with visual quality.

[Comparison of aspirin treatment strategies for primary prevention of cardiovascular diseases: A decision-analytic Markov modelling study].

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.

[Immune function and research progress of pentraxin 3 in pulmonary infectious diseases].

Pentraxins3 (PTX3) is an acute-phase protein of the pentraxin family that is synthetized and stored in a variety of cells. As an important mediator of innate immunity, PTX3 is rapidly released during microbial invasion and inflammatory response. It promotes the recognition of pathogens by myeloid cells through regulating complement activation. Recent studies have indicated that PTX3 concentrations in peripheral blood or tissues increase rapidly after infection, and the increased level is associated with the severity of the disease. Thus, PTX3 appears to be a vital clinical biomarker in the diagnosis and prognosis of pulmonary infectious diseases.

[Therapeutic efficacy of hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome in 60 children].

Objective: To evaluate the therapeutic efficacy of hematopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome (WAS), and to analyze the factors related to the outcomes. Methods: The clinical data of 60 children with WAS received HSCT in Shanghai Children's Medical Center from January 2006 to December 2020 were retrospectively analyzed. All cases were treated with a myeloablative conditioning regimen with busulfan and cyclophosphamide, and a graft-versus-host disease (GVHD) prevention regimen based on cyclosporine and methotrexate. Implantation, GVHD, transplant-related complications, immune reconstitution and survival rate were observed. Survival analysis was performed by Kaplan-Meier method, and Log-Rank method was used for univariate comparison. Results: The 60 male patients had main clinical features as infection and bleeding. The age at diagnosis was 0.4 (0.3, 0.8) years, and the age at transplantation was 1.1 (0.6, 2.1) years. There were 20 cases of human leukocyte antigen matched transplantation and 40 mismatched transplantation; 35 patients received peripheral blood HSCT, and 25 cord blood HSCT. All cases were fully implanted. The incidence of acute GVHD (aGVHD) was 48% (29/60) and only 2 (7%) developed aGVHD of grade Ⅲ; the incidence of chronic GVHD (cGVHD) was 23% (13/56), and all cases were limited. The incidence of CMV and EBV infection was 35% (21/60) and 33% (20/60) respectively; and 7 patients developed CMV retinitis. The incidence of sinus obstruction syndrome was 8% (5/60), of whom 2 patients died. There were 7 cases (12%) of autoimmune hemocytopenia after transplantation. Natural killer cells were the earliest to recover after transplantation, and B cells and CD4+T cells returned to normal at about 180 days post HSCT. The 5-year overall survival rate (OS) of this group was 93% (95%CI 86%-99%), and the event free survial rate (EFS) was 87% (95%CI 78%-95%). EFS of non-CMV reactivation group is higher than that of CMV reactivation group (95% (37/39) vs.71% (15/21), χ2=5.22, P=0.022). Conclusions: The therapeutic efficacy of HSCT for WAS is satisfying, and the early application of HSCT in typical cases can achieve better outcome. CMV infection is the main factor affecting disease-free survival rate, which can be improved by strengthening the management of complications.

[Application of discrete event simulation model in analysis on cost-effectiveness of epidemiology screening].

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.

[Effect of postoperative adjuvant chemotherapy on prognosis of patients with intrahepatic cholangiocarcinoma:a multicenter retrospective study].

Objectives: To examine the influence of adjuvant chemotherapy after radical resection on the survival of patients with intrahepatic cholangiocarcinoma(ICC) and to identify patients who may benefit from it. Methods: The clinical and pathological data of 654 patients with ICC diagnosed by postoperative pathology from December 2011 to December 2017 at 13 hospitals in China were collected retrospectively. According to the inclusion and exclusion criteria,455 patients were included in this study,including 69 patients (15.2%) who received adjuvant chemotherapy and 386 patients (84.8%) who did not receive adjuvant chemotherapy. There were 278 males and 177 females,with age of 59 (16) years (M(IQR))(range:23 to 88 years). Propensity score matching (PSM) method was used to balance the difference between adjuvant chemotherapy group and non-adjuvant chemotherapy group. Kaplan-Meier method was used to plot the survival curve,the Log-rank test was used to compare the difference of overall survival(OS) and recurrence free survival(RFS)between the two groups. Univariate analysis was used to determine prognostic factors for OS. Multivariate Cox proportional hazards models were then performed for prognostic factors with P<0.10 to identify potential independent risk factors. The study population were stratified by included study variables and the AJCC staging system,and a subgroup analysis was performed using the Kaplan-Meier method to explore the potential benefit subgroup population of adjuvant chemotherapy. Results: After 1∶1 PSM matching,69 patients were obtained in each group. There was no significant difference in baseline data between the two groups (all P>0.05). After PSM,Cox multivariate analysis showed that lymph node metastasis (HR=3.06,95%CI:1.52 to 6.16,P=0.039),width of resection margin (HR=0.56,95%CI:0.32 to 0.99,P=0.044) and adjuvant chemotherapy (HR=0.51,95%CI:0.29 to 0.91,P=0.022) were independent prognostic factors for OS. Kaplan-Meier analysis showed that the median OS time of adjuvant chemotherapy group was significantly longer than that of non-adjuvant chemotherapy group (P<0.05). There was no significant difference in RFS time between the adjuvant chemotherapy group and the non-adjuvant chemotherapy group (P>0.05). Subgroup analysis showed that,the OS of female patients,without HBV infection,carcinoembryonic antigen<9.6 µg/L,CA19-9≥200 U/ml,intraoperative bleeding<400 ml,tumor diameter>5 cm,microvascular invasion negative,without lymph node metastasis,and AJCC stage Ⅲ patients could benefit from adjuvant chemotherapy (all P<0.05). Conclusion: Adjuvant chemotherapy can prolong the OS of patients with ICC after radical resection,and patients with tumor diameter>5 cm,without lymph node metastasis,AJCC stage Ⅲ,and microvascular invasion negative are more likely to benefit from adjuvant chemotherapy.

[Relationship between expression of NLRP3 inflammasome and improvement of macular structure in patients with wet age-related macular degeneration after anti-vascular endothelial growth factor therapy].

Objective: To explore the relationship between expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and improvement of macular structure in patients with wet age-related macular degeneration (wAMD) after anti-vascular endothelial growth factor (VEGF) therapy. Methods: A before-after study was carried out. A total of 110 patients (110 eyes) with wAMD who were admitted to Department of Ophthalmology, People's Hospital Affiliated to Shandong First Medical University between August 2019 and December 2021 were enrolled, and all patients were given vitreous injection of anti-VEGF drug (ranibizumab or bevacizumab). The aqueous humor was collected to detect mRNA levels of NLRP3, cysteinyl aspartate specific protease-1 (Caspase-1), apoptosis-associated speck-like protein (ASC) and interleukin (IL) 1ß by fluorescence quantitative PCR. The levels of IL-1ß, IL-18, tumor necrosis factor α (TNF-α) and VEGF in aqueous humor were detected by enzyme-linked immunosorbent assay (ELISA). The correlation between the above indexes and central macular thickness (CMT) in wAMD patients was analyzed by multivariate linear regression analysis. Results: In the 110 wAMD patients, there were 68 males and 42 females, with a mean age of (68.7±7.6) years. Compared with those before treatment, mRNA levels of NLRP3 (1.65±0.27, 1.34±0.19 vs 1.97±0.23, both P<0.017), Caspase-1 (1.47±0.15, 1.29±0.17 vs 1.53±0.18, both P<0.017), ASC (1.33±0.14, 1.21±0.18 vs 1.47±0.12, both P<0.017) and IL-1ß (1.78±0.21, 1.46±0.17 vs 2.21±0.24, both P<0.017), and levels of IL-1ß [(26.9±5.7), (20.3±4.6) vs (33.6±8.3) ng/L, both P<0.017], IL-18 [(32.7±7.6), (23.3±6.9) vs (46.4±9.4) ng/L, both P<0.017], TNF-α [(39.4±6.6), (21.7±6.3) vs (52.9±9.1) ng/L, both P<0.017] and VEGF [(35.7±10.2), (23.4±6.7) vs (65.4±19.3) ng/L, both P<0.017] were decreased after the first and second injection. Moreover, the above-mentioned indexes after second injection were lower than those after the first injection (all P<0.017). The results of multivariate linear regression analysis showed that NLRP3 mRNA (the first injection: ß=53.750, P<0.001; the second injection: ß=94.648, P<0.001), IL-1ß (the first injection: ß=1.356, P=0.021; the second injection: ß=2.008, P=0.003), IL-18 (the first injection: ß=1.984, P<0.001; the second injection: ß=1.251, P=0.003) and VEGF (the first injection: ß=1.875, P<0.001; the second injection: ß=2.119, P<0.001) had linear relationships with CMT. Conclusion: The decrease of NLRP3 inflammasome and its products in aqueous humor may be related to the improvement of macular structure in wAMD patients after anti-VEGF therapy.

[Study of transmissibility of 2019-nCoV Omicron variant in Beijing].

Objective: To evaluate the transmissibility of 2019-nCoV Omicron variant under the current prevention and control strategy in Beijing, and provide evidence for the prevention and control of COVID-19. Methods: The information of 78 Omicron variant infection cases involved in clear transmission chains in Beijing during 7-25 March, 2022 were collected, the incubation period and serial interval of the disease were fitted by using Gamma and Weibull distribution. Markov Chain Monte Carlo approach was used to estimate the time-varying reproduction number (Rt). Results: The median of the incubation period (Q1, Q3) of Omicron variant infection was 4.0 (3.0, 6.0) days, and the serial interval was 3.0 (2.0, 5.0) days. The median of the serial interval (Q1, Q3) was 2.0 (1.0, 4.0) days in unvaccinated cases and 4.0 (2.0, 6.0) days in vaccinated cases (Z=-2.12, P=0.034), and 2.0 (1.5, 3.0) days in children and 4.0 (2.0, 6.0) days in adults, respectively (Z=-2.02,P=0.044), the differences were significant. The mean of Rt was estimated to be 4.98 (95%CI: 2.22-9.04) for Omicron variant in this epidemic. Conclusion: Omicron variant has stronger transmissibility compared with Delta variant. It is necessary to strengthen the routine prevention and control COVID-19, promote the vaccination and pay close attention to susceptible population, such as children.

[Estimation of molecular clock of Mycobacterium tuberculosis based on whole genome sequencing data].

Objective: To analyze the genomic mutation of Mycobacterium tuberculosis (M. tuberculosis) isolated in endogenous activation period and estimate the molecular clock based on the whole genome sequencing data. Methods: Literatures of the whole genome research of endogenous reactivated tuberculosis were retrieved, and the corresponding whole genome sequencing data were downloaded. We extracted the single nucleotide polymorphisms (SNPs) and strain isolation time of initial treatment and relapse of tuberculosis cases, explored the relationship between the different SNPs and interval between initial treatment and relapse by Poisson regression model, calculated the M. tuberculosis molecular clock, and estimated the mutation rate. Results: When the generation time of M. tuberculosis was 18 hours, the mutation rate in 0-2 years, i.e. short-term endogenous activation, was 6.47×10-10 (95%CI: 5.59×10-10-7.44×10-10), which was significantly higher than that in 2-14 years in long term endogenous activation (3.27×10-10, 95%CI: 2.88×10-10-3.69×10-10). The mutation rates of 0-, 1-, 2-, 3-, 5- and 7-14 years were 7.10×10-10, 6.06×10-10, 4.24×10-10, 5.34×10-10, 2.59×10-10 and 1.26×10-10 respectively. Conclusions: In the period of endogenous reactivation, the mutation rate of M. tuberculosis decreases with the interval time between initial treatment and relapse, which verifies the clinically observed phenomenon that the relapse often occurs within two years after the initial treatment of tuberculosis.

[Progress in research of chronic obstructive pulmonary disease and risk factors].

Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable chronic airway disease characterized by persistent airflow restriction and associated respiratory symptoms. COPD is the main cause of morbidity and mortality of chronic diseases and one of the top three causes of death in the world. The prevalence of COPD among provinces in China are at a high levels for years. The prevalence of COPD varies from country to country, region to region, and population to population, and the incidence and development of COPD are influenced by multi risk factors, including individual genetic factors, age, sex, body mass index, abdominal obesity and physical activity and environment factors, such as smoking, indoor and outdoor air pollution, and occupational exposure.

[Applications of microsimulation model for cost-effectiveness analysis on screening in epidemiology].

Microsimulation model simulates individuals and estimates transition probabilities within the population using individual participant data. This approach could deal with the heterogeneous characteristics among the people or personal history of diseases and may be relevant in addressing cost-effectiveness problems of screening for complex conditions in epidemiology. This paper introduces the general principles, basic steps involved in implementation, analytic methods, and other related issues of the microsimulation model. Based on a practical research case of estimating the cost-effectiveness of microalbuminuria screening for chronic kidney disease in the United States, critical points in applications of the microsimulation model for cost-effectiveness analysis of screening were discussed in detail, including model development, model analysis, and the interpretation of the results. The microsimulation model considers the dynamic nature of complex diseases by estimating a broad range of individual characteristics and increasingly used to provide insights into complex problems that the Markov model does not efficiently address. For better supporting evidence-informed decision-making in public health, future studies should be aware of the accuracy of parameters in the decision-analytic model and the transparency of the models and results, as well as complying with the relevant reporting standards.

[Applications of the NDR and DIAL models for risk prediction on cardiovascular disease in patients with type 2 diabetes in Ningbo].

Objective: To validate the performance of cardiovascular risk prediction models based on the Sweden National Diabetes Register (NDR) and Diabetes Lifetime-perspective prediction (DIAL) model for assessing risks of 5-year and 10-year cardiovascular disease (CVD) among Chinese patients with type 2 diabetes. Methods: Based on the Chinese Electronic Health Records Research in Yinzhou study, 83 503 patients with type 2 diabetes aged 30-75 years without a history of CVD at baseline were included from January 1, 2010 to December 31, 2020. Recalibrated NDR model was used to estimate 5-year risk, while the recalibrated DIAL model was used to predict 5-year and 10-year risks. The competing events adjusted Kaplan-Meier analysis was used to obtain the observed cardiovascular events. Discrimination C statistics evaluated model accuracy, calibration χ2 value, and calibration plots. Results: Through a median follow-up of 7.0 years, 7 326 cardiovascular events, and 2 937 non-vascular deaths were identified among a total of 83 503 subjects. The recalibrated NDR model overestimated 5-year risk by 39.4% in men and 8.6% in women, whereas the overestimation for the recalibrated DIAL model was 14.6% in men and 50.1% in women. The DIAL model had a better discriminative ability (C-statistic=0.681, 95%CI: 0.672-0.690) than NDR model (C-statistic=0.667, 95%CI: 0.657-0.677) in 5-year risk prediction for men, and the models had a similar ability for women (C-statistic=0.699, 95%CI: 0.690-0.708 for NDR and C-statistic=0.698, 95%CI: 0.689-0.706 for DIAL). The prediction accuracy of the DIAL model was improved in the 10-year risk, with the underestimation being 1.6% for men and the overestimation being 12.8% for women. Conclusions: Both recalibrated NDR and DIAL models overestimated 5-year cardiovascular risk in Chinese patients with type 2 diabetes, while the higher overestimation was shown using the DIAL model. However, the improvement was found in predicting 10-year CVD risk using the DIAL model, which suggested the value of lifetime risk prediction and indicated the need for research on the lifetime risk prediction model for cardiovascular risk assessment in Chinese patients with type 2 diabetes.

[Effectiveness of statin treatment strategies for primary prevention of cardiovascular diseases in a community-based Chinese population: A decision-analytic Markov model].

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.

[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].

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.

Impacts of international food and feed trade on nitrogen balances and nitrogen use efficiencies of food systems.

International trade of agricultural products has greatly increased over time, but its impacts on sustainable development are debated. It may contribute to food security in importing countries, increases the dependency between countries, and has been implicated in displacement of environmental pollution and resource depletion. There is also discussion about the relationships between trade and nitrogen (N) balances and N use efficiencies (NUE). We explored relationships between changes in the trade of food and feed and in N balances and NUE of the food supply systems through simulation modeling and an analysis of empirical data of 115 countries (representing 91% of global population) for the period 1961-2011. In the empirical analysis, 64 main importing countries and 14 main exporting countries, were distinguished. Importing countries had on average a higher population density than exporting countries but rather similar protein intake and GDP per capita. The empirical analysis indicate that main importing countries had on average higher N fertilizer inputs to their food supply systems, and also higher N surpluses and higher NUE than main exporting countries. The overall mean NUE of the food supply system of main importing countries decreased with increasing import, but the relationships between import and NUE were diverse when these countries were grouped according to population density and GDP per capita. We compared N balances and partial N balances, and three methodologies commonly used for estimating NUE. We observed that NUE2 provides an unbiased estimate for both importing and exporting countries. Our study contributes to the understanding of the diverse relationships between international trade, N balances and NUE of food systems.

[Effects of CACNA1H gene knockout on autistic-like behaviors and the morphology of hippocampal neurons in mice].

OBJECTIVE: To investigate the effects of CACNA1H gene knockout (KO) on autistic-like behaviors and the morphology of hippocampal neurons in mice. METHODS: In the study, 25 CACNA1H KO mice of 3-4 weeks old and C57BL/6 background were recruited as the experimental group, and 26 wild type (WT) mice of the same age and background were recruited as the control group. Three-chamber test and open field test were used to observe the social interaction, anxiety, and repetitive behaviors in mice. After that, their brain weight and size were measured, and the number of hippocampal neurons were observed by Nissl staining. Furthermore, the CACNA1H heterozygote mice were interbred with Thy1-GFP-O mice to generate CACNA1H-/--Thy1+(KO-GFP) and CACNA1H+/+-Thy1+ (WT-GFP) mice. The density and maturity of dendritic spines of hippocampal neurons were observed. RESULTS: In the sociability test session of the three-chamber test, the KO mice spent more time in the chamber of the stranger mice than in the object one (F1, 14=95.086, P < 0.05; Post-Hoc: P < 0.05), without any significant difference for the explored preference index between the two groups (t=1.044, P>0.05). However, in the social novelty recognition test session, no difference was observed between the time of the KO mice spend in the chamber of new stranger mice and the stranger one (F1, 14=18.062, P < 0.05; Post-Hoc: P>0.05), and the explored preference index of the KO mice was less than that of the control group (t=2.390, P < 0.05). In the open field test, the KO mice spent less time in the center of the open field apparatus than the control group (t=2.503, P < 0.05), but the self-grooming time was significantly increased compared with the control group (t=-2.299, P < 0.05). Morphological results showed that the brain weight/body weight ratio (t=0.356, P>0.05) and brain size (t=-0.660, P>0.05) of the KO mice were not significantly different from those of the control group, but the number of neurons were significantly reduced in hippocampal dentate gyrus compared with the control group (t=2.323, P < 0.05). Moreover, the density of dendritic spine of dentate gyrus neurons in the KO-GFP mice was significantly increased compared with the control group (t=-2.374, P < 0.05), without any significant difference in spine maturity (t=-1.935, P>0.05). CONCLUSION: CACNA1H KO mice represent autistic-like behavior, which may be related to the decrease in the number of neurons and the increase in the density of dendritic spine in the dentate gyrus.

[Effects and mechanism of hydrogen peroxide pretreatment with low molarity on oxidative stress induced apoptosis of mouse bone marrow mesenchymal stem cells].

Objective: To investigate the effects and mechanism of hydrogen peroxide (HP) pretreatment with low molarity on oxidative stress induced apoptosis of mouse bone marrow mesenchymal stem cells (BMSCs). Methods: The experimental research methods were used. BMSCs were isolated and cultured from two 2-week-old male BALB/c mice by the whole bone marrow culture method. The 3rd-7th passages of cells in logarithmic growth phase were used for the experiments after identification. According to the random number table (the same grouping method below), the cells were divided into 0 µmol/L HP group (without HP, the same below), 25 µmol/L HP group, 50 µmol/L HP group, 100 µmol/L HP group, 150 µmol/L HP group, 200 µmol/L HP group, 250 µmol/L HP group, and 300 µmol/L HP group in which cells were treated by the corresponding final molarity of HP, respectively. The apoptosis rate was detected by flow cytometry (n=4) after 24 hours of culture. The cells were divided into 0 µmol/L HP group, 25 µmol/L HP group, 50 µmol/L HP group, and 100 µmol/L HP group in which cells were treated by the corresponding final molarity of HP, respeclively. After 24 hours of culture, the protein expressions of B-lymphoma-2 (Bcl-2) and Bcl-2-related X protein (Bax) were detected by Western blotting, and the Bcl-2/Bax ratio was calculated (n=3). The cells were divided into 0 µmol/L HP group, 25 µmol/L HP group, 50 µmol/L HP group, 100 µmol/L HP group, 200 µmol/L HP group, and 300 µmol/L HP group in which cells were treated by the corresponding final molarity of HP, respectively. After 24 hours of culture, the protein expressions of glycogen synthase kinase-3ß (GSK-3ß) and phosphorylated GSK-3ß (p-GSK-3ß) were detected by Western blotting (n=3). The cells were divided into 0 µmol/L HP group, 50 µmol/L HP group, and 300 µmol/L HP group in which cells were treated by the corresponding final molarity of HP, respeclively, and HP pretreatment group with 50 µmol/L HP being added in advance for 12 h and then 300 µmol/L HP being added. After 24 hours of culture, the morphology and growth of cells were observed by inverted fluorescence microscopy (non-fluorescent condition) and immunofluorescence method, the apoptosis rate was detected by flow cytometry, the protein expressions of Bcl-2, Bax, cysteine aspartic acid specific protease-3 (caspase-3), caspase-9, cleavage caspase-3, cleavage caspase-9, GSK-3ß, and p-GSK-3ß were detected by Western blotting, and the Bcl-2/Bax ratio was calculated, with all the number of samples being 3. Data were statistically analyzed with one-way analysis of variance and Bonferroni test. Results: After 24 hours of culture, compared with that in 0 µmol/L HP group, the apoptosis rate of cells did not change significantly in 25 µmol/L HP group, 50 µmol/L HP group, or 100 µmol/L HP group (P>0.05) but increased significantly in 150 µmol/L HP group, 200 µmol/L HP group, 250 µmol/L HP group, and 300 µmol/L HP group (P<0.01). After 24 hours of culture, compared with that in 0 µmol/L HP group, the Bcl-2/Bax ratio of cells increased significantly in 25 µmol/L HP group and 50 µmol/L HP group (P<0.05 or P<0.01) but decreased significantly in 100 µmol/L HP group (P<0.05). After 24 hours of culture, compared with those in 0 µmol/L HP group, the protein expression of GSK-3ß in cells showed no significant change in 25 µmol/L HP group and 50 µmol/L HP group (P>0.05), the protein expressions of p-GSK-3ß in cells significantly increased in 25 µmol/L HP group and 50 µmol/L HP group (P<0.01), the protein expressions of GSK-3ß and p-GSK-3ß in cells in 100 µmol/L HP group showed no significant change (P>0.05), the protein expressions of GSK-3ß in cells in 200 µmol/L HP group and 300 µmol/L HP group were significantly increased (P<0.05). but the protein expression of p-GSK-3ß in cells in 200 µmol/L HP group and 300 µmol/L HP group was significantly decreased (P<0.05). After 24 hours of culture, the morphology and growth of cells in 0 µmol/L HP group and 50 µmol/L HP group were similar and normal; in contrast, the cells in 300 µmol/L HP group became smaller and round, with the cell protrusions being shorter or disappeared, the nucleus being cavitated, and the cell abscission being increased significantly; the morphology of most cells in HP pretreatment group was normal, with the shedding of cells being less than that in 300 µmol/L HP group, and the morphology of nucleus being normal. After 24 hours of culture, the protein expression of caspase-9 was similar among the four groups (P>0.05). Compared with that in 0 µmol/L HP group, the apoptosis rate and the protein expressions of cleavage caspase-9, caspase-3, and cleavage caspase-3 of cells in 50 µmol/L HP group showed no significant changes (P>0.05), the Bcl-2/Bax ratio of cells in 50 µmol/L HP group increased significantly (P<0.05), the apoptosis rate and the protein expressions of cleavage caspase-9, caspase-3, and cleavage caspase-3 of cells in 300 µmol/L HP group were significantly increased (P<0.01), while the Bcl-2/Bax ratio of cells in 300 µmol/L HP group was significantly decreased (P<0.05). Compared with those in 300 µmol/L HP group, the apoptosis rate and the protein expressions of cleavage caspase-9, caspase-3, and cleavage caspase-3 of cells were significantly decreased in HP pretreatment group (P<0.05 or P<0.01), while the Bcl-2/Bax ratio of cells was significantly increased in HP pretreatment group (P<0.01). After 24 hours of culture, the protein expressions of GSK-3ß and p-GSK-3ß of cells in 0 µmol/L HP group, 50 µmol/L HP group, 300 µmol/L HP group, and HP pretreatment group were 1.09±0.14, 0.62±0.17, 1.35±0.21, 0.74±0.34, 0.68±0.03, 0.85±0.08, 0.38±0.10, and 0.54±0.09, respectively. Compared with those in 0 µmol/L HP group, the protein expression of p-GSK-3ß of cells was significantly increased in 50 µmol/L HP group (P<0.05) but significantly decreased in 300 µmol/L HP group (P<0.01), while the protein expression of GSK-3ß of cells was significantly increased in 300 µmol/L HP group (P<0.05). Compared with those in 300 µmol/L HP group, the protein expression of GSK-3ß of cells was significantly decreased in HP pretreatment group (P<0.01), while the protein expression of p-GSK-3ß of cells was significantly increased in HP pretreatment group (P<0.01). Conclusions: The molarity of 50 µmol/L may be the optimal molarity of HP to pretreat mouse BMSCs, and 50 µmol/L HP pretreatment can antagonize mitochondrial pathway of oxidative stress induced apoptosis by inhibiting the activity of GSK-3ß.

[Immunogenicity and influencing factors of hepatitis B vaccination based on different vaccination schedules among chronic kidney disease patients].

Objective: To explore the immunogenicity and influencing factors of hepatitis B vaccination based on different vaccination schedules among chronic kidney disease (CKD) patients. Methods: CKD patients who participated in randomized controlled trials in four hospitals in Shanxi province and completed three doses of 20 µg vaccination (at months 0, 1 and 6) and four doses of 20 µg or 60 µg vaccination (at months 0, 1, 2, and 6) were surveyed from May 2019 to July 2020.According to the ratio of 1∶1∶1, 273 CKD patients were divided into 3 groups randomly. Quantification of the anti-hepatitis B surface antigen-antibody (anti-HBs) in serum samples was performed using chemiluminescent microparticle immunoassay at months 1 and 6 after the entire course of the vaccinations. The positive rate, high-level positive rate, geometric mean concentration (GMC) of anti-HBs, and the influencing factors were analyzed by χ2 tests, analysis of variance, unconditional logistic regression analysis. Results: A total of 273 CKD patitents were participants.The positive rates in the CKD patients with four doses of 20 µg vaccination (92.96%,66/71) or 60 µg vaccination (93.15%, 68/73) were higher than that in the CKD patients with three doses of 20 µg vaccination (81.69%, 58/71) at month one after the full course of the vaccinations (P<0.05). The GMCs of anti-HBs showed similar results (2 091.11 mIU/ml and 2 441.50 mIU/ml vs. 1 675.21 mIU/ml) (P<0.05). The positive rate was higher in the CKD patients with four doses of 60 µg vaccination (94.83%,55/58) than in those with three doses of 20 µg vaccination (78.79%,52/66) (P<0.05) at month six after the full course of the vaccinations. And the GMC of anti-HBs in the patients with four doses of 60 µg vaccination (824.28 mIU/ml) was significantly higher than those in the patients with 3 or 4 doses of 20 µg vaccination (639.74 mIU/ml and 755.53 mIU/ml) (P<0.05). After controlling the confounding factors, the positive rate in the CKD patients with four doses of 60 µg vaccination were 3.19 (95%CI: 1.02-9.96) and 5.32 (95%CI: 1.27-22.19) times higher than those in the patients with three doses of 20 µg vaccination at months 1 and 6 after the full course of the vaccinations, respectively. The positive rate in CKD patients without immune suppression or hormone therapy was 3.33 (95%CI: 1.26-8.80) and 4.78 (95%CI: 1.47-15.57) times higher than those in the patients with such therapy, respectively. Conclusions: Four doses of 20 µg or 60 µg hepatitis B vaccination could improve the immunogenicity in patients with CKD. And four doses of 60 µg vaccination might play a positive role in maintaining anti-HBs in this population. The immunogenicity in the CKD patients with immune suppression or hormone therapy was poor.