Beijing Municipal Science Research Articles

Safety and efficacy of intravenous recombinant human prourokinase for acute ischaemic stroke within 4·5 h after stroke onset (PROST-2): a phase 3, open-label, non-inferiority, randomised controlled trial

Intra-arterial prourokinase has been shown to be a promising thrombolytic agent in patients with acute ischaemic stroke. Given the global shortage of thrombolytics, we aimed to assess the non-inferiority of intravenous recombinant human prourokinase compared with alteplase in patients with acute ischaemic stroke who were ineligible for or who refused endovascular thrombectomy. PROST-2 was a phase 3, open-label, non-inferiority, randomised controlled trial conducted at 61 hospitals in China. Patients older than 18 years with acute ischaemic stroke, who were ineligible for or who refused endovascular thrombectomy, were randomly assigned in a 1:1 ratio within 4·5 h of stroke onset to receive intravenous recombinant human prourokinase (15 mg bolus followed by 20 mg infusion within 30 min) or intravenous alteplase (0·9 mg per kg, maximum dose 90 mg; 10% bolus followed by remainder as infusion over 60 min). The primary efficacy outcome was the proportion of patients with a modified Rankin Scale score of 0 or 1 at 90 days, assessed via masked review in the intention-to-treat population, with a non-inferiority margin for the risk ratio of 0·93. The primary safety outcome was the incidence of symptomatic intracranial haemorrhage within 36 h. This trial is registered with ClinicalTrials.gov (NCT05700591) and is now completed. Between Jan 29, 2023, and March 14, 2024, 1552 patients were randomly assigned: 775 received recombinant human prourokinase and 777 received alteplase. The primary outcome of a modified Rankin Scale score of 0 or 1 at 90 days was reached by 558 (72·0%) of 775 patients in the recombinant human prourokinase group versus 534 (68·7%) of 777 in the alteplase group (risk ratio 1·04 [95% CI 0·98 to 1·10]; p<0·0001 for non-inferiority). The frequency of symptomatic intracranial haemorrhage within 36 h was lower in the recombinant human prourokinase group than in the alteplase group (two [0·3%] of 770 patients vs ten [1·3%] of 775, risk difference -1·0 percentage points [95% CI -2·1 to -0·1]; p=0·021), as was the incidence of major bleeding at 7 days (four [0·5%] vs 16 [2·1%]; -1·5 percentage points (-2·8 to -0·4); p=0·0072). All-cause mortality within 7 days did not differ between groups (five [0·6%] deaths in the recombinant human prourokinase group vs 13 [1·7%] in the alteplase group; risk difference -1·0 percentage points; 95% CI -2·3 to 0·1]; p=0·060). In our trial, recombinant human prourokinase was shown to be non-inferior to alteplase for achieving excellent functional outcome, with no difference between groups in safety endpoints. These findings support the use of recombinant human prourokinase as a viable alternative to alteplase for patients with ischaemic stroke who are eligible for intravenous thrombolysis therapy but ineligible for or who have refused endovascular thrombectomy. Tasly Biopharmaceuticals, National Key R&D Program of China, National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Beijing Municipal Science & Technology Commission. For the Chinese translation of the abstract see Supplementary Materials section.

A deep learning model for personalized intra-arterial therapy planning in unresectable hepatocellular carcinoma: a multicenter retrospective study

Unresectable Hepatocellular Carcinoma (uHCC) poses a substantial global health challenge, demanding innovative prognostic and therapeutic planning tools for improved patient management. The predominant treatment strategies include Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC). Between January 2014 and November 2021, a total of 1725 uHCC patients [mean age, 52.8±11.5 years; 1529 males] received preoperative CECT scans and were eligible for TACE or HAIC. Patients were assigned to one of the four cohorts according to their treatment, four transformer models (SELECTION) were trained and validated on each cohort; AUC was used to determine the prognostic performance of the trained models. Patients were stratified into high and low-risk groups based on the survival scores computed by SELECTION. The proposed AI-based treatment decision model (ATOM) utilizes survival scores to further inform final therapeutic recommendation. In this study, the training and validation sets included 1448 patients, with an additional 277 patients allocated to the external validation sets. The SELECTION model outperformed both clinical models and the ResNet approach in terms of AUC. Specifically, SELECTION-TACE and SELECTION-HAIC achieved AUCs of 0.761 (95% CI, 0.693-0.820) and 0.805 (95% CI, 0.707-0.881) respectively, in predicting ORR in their external validation cohorts. In predicting OS, SELECTION-TC and SELECTION-HC demonstrated AUCs of 0.736 (95% CI, 0.608-0.841) and 0.748 (95% CI, 0.599-0.865) respectively, in their external validation sets. SELECTION-derived survival scores effectively stratified patients into high and low-risk groups, showing significant differences in survival probabilities (P<0.05 across all four cohorts). Additionally, the concordance between ATOM and clinician recommendations was associated with significantly higher response/survival rates in cases of agreement, particularly within the TACE, HAIC, and TC cohorts in the external validation sets (P<0.05). ATOM was proposed based on SELECTION-derived survival scores, emerges as a promising tool to inform the selection among different intra-arterial interventional therapy techniques. This study received funding from the Beijing Municipal Natural Science Foundation, China (Z190024); the Key Program of the National Natural Science Foundation of China, China (81930119); The Science and Technology Planning Program of Beijing Municipal Science & Technology Commission and Administrative Commission of Zhongguancun Science Park, China (Z231100004823012); Tsinghua University Initiative Scientific Research Program of Precision Medicine, China (10001020108); and Institute for Intelligent Healthcare, Tsinghua University, China (041531001).

Phenotypic subgroup in serologically active clinically quiescent systemic lupus erythematosus: A cluster analysis based on CSTAR cohort

Serologically active clinically quiescent (SACQ) is a state within systemic lupus erythematosus (SLE) characterized by elevated serologic markers without clinical activity. The heterogeneity in SACQ patients poses challenges in disease management. This multicenter prospective study aimed to identify distinct SACQ subgroups and assess their utility in predicting organ damage. SACQ was defined as a sustained period of at least 6months with persistent serologic activity, marked by positive anti-double-stranded DNA (dsDNA) antibodies and/or hypocomplementemia, and without clinical activity. Cluster analysis was employed, utilizing 16 independent components to delineate phenotypes. Among the 4,107 patients with SLE, 990 (24.1%) achieved SACQ within 2.0± 2.3 years on average. Over a total follow-up of 7,105.1 patient years, 340 (34.3%) experienced flares, and 134 (13.5%) developed organ damage. Three distinct SACQ subgroups were identified. Cluster 1 (n= 219, 22.1%) consisted predominantly of elderly males with a history of major organ involvement at SLE diagnosis, showing the highest risk of severe flares (16.4%) and organ damage (27.9%). Cluster 2 (n= 279, 28.2%) was characterized by milder disease and a lower risk of damage accrual (5.7%). Notably, 86 patients (30.8%) in cluster 2 successfully discontinued low-dose glucocorticoids, with 49 of them doing so without experiencing flares. Cluster 3 (n= 492, 49.7%) featured the highest proportion of lupus nephritis and a moderate risk of organ damage (11.8%), with male patients showing significantly higher risk of damage (hazard ratio [HR]= 4.51, 95% confidence interval [CI], 1.82-11.79). This study identified three distinct SACQ clusters, each with specific prognostic implications. This classification could enhance personalized management for SACQ patients. This work was funded by the National Key R&D Program (2021YFC2501300), the Beijing Municipal Science& Technology Commission (Z201100005520023), the CAMS Innovation Fund (2021-I2M-1-005), and National High-Level Hospital Clinical Research Funding (2022-PUMCH-D-009).

Permanent pacemaker reduction using temporary-permanent pacemaker as a 1-month bridge after transcatheter aortic valve replacement: a prospective, multicentre, single-arm, observational study

The permanent pacemaker (PPM) implantation and pacemaker dependency rates after transcatheter aortic valve replacement (TAVR) are highly variable as some of the conduction disturbances are reversible. It remains poorly investigated how to optimise temporary pacing in these patients. This study aimed to explore the potential reduction in the PPM implantation rate using temporary-permanent pacemaker (TPPM) as a 1-month bridge. This is a prospective, multicentre, single-arm, observational study. Consecutive patients undergoing TAVR from March 1, 2022 to March 1, 2023 in 13 tertiary hospitals in China were screened. Patients who developed high-degree atrioventricular block, complete heart block, or first-degree atrioventricular block plus new onset left bundle branch block during the TAVR procedure or within 1 month after TAVR were included to receive TPPM. Patients with pre-existing PPM implantation or indications for PPM implantation before the TAVR procedure were excluded. Patients with TPPM were monitored to determine whether the conduction disturbances persisted or recovered. The primary endpoint was the rate of freedom from indications for PPM implantation 1 month after TAVR. This study is registered with ChiCTR, ChiCTR2200057931. Of 688 patients who have undergone TAVR, 71 developed conduction disturbance and met the inclusion criteria, 1 patient withdrew due to noncompliance, 70 patients received TPPM and completed follow-up. There were 41 (58.6%) men and 29 (41.4%) women in the study, with a mean age of 74.3±7.3 years. At 1 month follow-up, 75.7% (53/70) of the patients with TPPM did not require PPM implantation. For 688 patients who have undergone TAVR, the rate of PPM implantation at 1 month was 2.47% (17/688, 95% CI 1.55%-3.92%), representing a significant reduction in self-comparison with the rate at 48 h after TPPM (2.47% vs. 8.28% [95% CI 6.45%-10.58%], P<0.0001). Similar results were obtained in the subgroup analysis of patients with HAVB/CHB. Multivariate analysis revealed the baseline PR interval, difference between the membranous septum length and implantation depth, and timing of postprocedural conduction disturbance occurrence were independent predictors of freedom from indications for PPM implantation at 1 month after TAVR. Using TPPM as a 1-month bridge allows for a buffer period to distinguish whether conduction disturbances are reversible or persistent, resulting in a significant reduction in the PPM implantation rate after TAVR when compared with the current strategy. However, this is an observational study, the results need to be confirmed in a randomized trial. Beijing Science and Technology Plan 2022 from Beijing Municipal Science & Technology Commission.

Intracytoplasmic sperm injection versus conventional in-vitro fertilisation for couples with infertility with non-severe male factor: a multicentre, open-label, randomised controlled trial

Introduced in 1992, intracytoplasmic sperm injection (ICSI) was initially indicated for severe male infertility; however, its use has since been expanded to non-severe male infertility. We aimed to compare the efficacy and safety of ICSI versus conventional in-vitro fertilisation (IVF) in couples with infertility with non-severe male factor. We conducted an investigator-initiated, multicentre, open-label, randomised controlled trial in ten reproductive medicine centres across China. Couples with infertility with non-severe male factor without a history of poor fertilisation were randomly assigned (1:1) to undergo either ICSI or conventional IVF. The primary outcome was live birth after first embryo transfer. We performed the primary analysis in the intention-to-treat population using log-binomial regression models for categorical outcomes or linear regression models for continuous outcomes, adjusting for centre. This trial is registered with Clinicaltrials.gov, NCT03298633, and is completed. Between April 4, 2018, and Nov 15, 2021, 3879 couples were screened, of whom 2387 (61·5%) couples were randomly assigned (1184 [49·6%] to the ICSI group and 1203 [50·4%] to the conventional IVF group). After excluding couples who were ineligible, randomised twice, or withdrew consent, 1154 (97·5%) in the ICSI group and 1175 (97·7%) in the conventional IVF group were included in the primary analysis. Live birth after first embryo transfer occurred in 390 (33·8%) couples in the ICSI group and in 430 (36·6%) couples in the conventional IVF group (adjusted risk ratio [RR] 0·92 [95% CI 0·83-1·03]; p=0·16). Two (0·2%) neonatal deaths were reported in the ICSI group and one (0·1%) in the conventional IVF group. In couples with infertility with non-severe male factor, ICSI did not improve live birth rate compared with conventional IVF. Given that ICSI is an invasive procedure associated with additional costs and potential increased risks to offspring health, routine use is not recommended in this population. National Natural Science Foundation of China, National Key Research and Development Program, Beijing Municipal Science & Technology Commission, and Peking University Third Hospital.

The mortality and years of life lost for community-acquired pneumonia before and during COVID-19 pandemic in China

Community-acquired pneumonia (CAP) is a leading cause of mortality worldwide, but disease burden of CAP is not clear so far. We aim to explore the spatial and temporal trends of mortality and years of life lost (YLL) due to CAP during 2013-2021 in mainland China, especially the mortality changes before and during COVID-19 pandemic due to COVID-19 related non-pharmaceutical interventions (NPIs). We used data from the National Mortality Surveillance System to estimate the age-standardized rates of death and YLL of CAP at national and provincial level in China during 2013-2021. Monthly and provincial NPIs data were obtained from Oxford COVID-19 Government Response Tracker. The Average annual percentage change (AAPC) and mortality reduction were estimated by log-linear regression and interrupted time series, respectively. In China, most CAP that caused deaths had no clear etiology, and bacterial pneumonia and viral pneumonia were the leading 2 causes among CAP deaths with determined etiology before and during COVID-19 pandemic. The age-standardized CAP mortality rate decreased from 11.18 per 100,000 in 2013 to 8.76 per 100,000 in 2019, and to 5.74 per 100,000 in 2021 (AAPC-4.51% vs-7.89%). Trends were similar in age-standardized rate of YLL. Both rates declined more for viral pneumonia, compared with bacterial pneumonia. After adjusting for NPIs at provincial level after 2020, the NPIs for COVID-19 was associated with significant reductions in CAP mortality (-0.34 per 100,000,-0.41 to-0.27; p<0.0001), and provinces that economically developed and conducted strict regular NPIs against COVID-19 contributed the most reduction. We observed a decreasing trend of age-standardized CAP mortality from 2013 to 2019, and a dramatical reduction during COVID-19 pandemic, especially for viral pneumonia. Our study provided the evidence for the effectiveness of regular NPIs on the significant reductions in CAP mortality. This work has been supported by Beijing Municipal Science and Technology Project Z191100006619101, Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-048), CAMS Institute of Respiratory Medicine Grant for Young Scholars (2023-ZF-8) and the New Cornerstone Science Foundation.

1177-P: Maternal Insulin Intervention Improves Offspring Glucose Metabolism via Long Noncoding RNA

Maternal high fat (HF) during pregnancy is known to have numerous adverse effects on offspring, including increased adiposity and impaired glucose tolerance later in life. The aim of this study was to determine if prebiotic early intervention could mitigate some of the negative effects of maternal HF and involved mechanism. C57BL mice were fed a HF diet, normal diet or a HF diet with prebiotic supplementation during pregnancy and lactation. At 8 weeks of age, glucose tolerance were measured in the offspring. And offspring livers were obtained to assay lncRNA and mRNA profiles to investigate the effects of early maternal inulin intervention on offspring. Offspring from HF-fed dams displayed glucose intolerance and an insulin resistance phenotype at 8 weeks of age. Early maternal inulin intervention improved glucose metabolism in male offspring of mothers fed a HF during gestation and lactation. The lncRNA and mRNA profile data revealed that compared with the offspring from HF dams, offspring from the early inulin intervention dams had 99 differentially expressed hepatic lncRNAs and 529 differentially expressed mRNAs. The differentially expressed lncRNA-mRNA coexpression analysis demonstrated that early maternal inulin intervention may change hepatic lncRNA expression in offspring. These lncRNAs are involved in metabolic pathways and the AMP-activated protein kinase signaling pathway. Importantly, the early maternal inulin intervention alleviated glucose metabolism by inhibiting the lncRNA Serpina4-ps1/let-7b-5p/Ppargc1a as a competing endogenous RNA in male offspring. Disclosure Q.Zhang: None. X.Xiao: None. M.Li: None. Funding National Natural Science Foundation of China (82170854, 81870579, 81870545, 81570715, 81170736); Beijing Natural Science Foundation (7202163); Beijing Municipal Science &amp; Technology Commission (Z201100005520011); National High Level Hospital Clinical Research Funding (2022-PUMCH-C-019); National Key Research and Development Program of China (2018YFC2001100); CAMS Innovation Fund for Medical Sciences (CIFMS2021-1-I2M-002, CIFMS2017-I2M-1-008)

1099-P: Plasma Amino Acid Profiles in Childhood Predict 10-Year Risk of Insulin Resistance in Adulthood—The BCAMS Study

Objective Insulin resistance (IR) is the critical step in the development of type 2 diabetes. Recent cross-sectional studies in children demonstrate plasma amino acids such as branched-chain and aromatic amino acids are associated with IR, however, information is scant regarding whether these associations in childhood persist over time and predict diabetes risk in young adults. We aimed to examine whether circulating amino acids in childhood predict 10-year risk of IR in early adulthood. Research design and Methods: This was a 10-year longitudinal study from childhood to early adulthood. A total of 961 subjects aged 6-18 years at baseline participated in the Beijing Child and Adolescent Metabolic Syndrome study (BCAMS). Serum insulin was determined by in-house ELISA with no cross-reaction with proinsulin, and plasma amino acids were profiled using targeted LC-MS/MS. IR was determined by the homeostatic model assessment of insulin resistance (HOMA-IR). Results: At baseline, after adjusting for age, gender, tanner stage, diet score, exercise, residence and BMI, 17 amino acids were closely correlated with HOMA-IR and nine with impaired fasting glucose (IFG) in childhood (p &amp;lt; 0.05 for all). Among them, Isoleucine showed the strongest association with IR (OR=2.04, 95% CI 1.65-2.54, P&amp;lt;0.001), and alanine was the strongest predictor of IFG (OR =1.52, 95%CI 1.22-1.91, P&amp;lt;0.001). Prospectively, after adjusting for the covariates at baseline, four amino acids have a significant predictive effect on the risk of IR at 10-years follow-up, of which alanine was the strongest predictor [OR=1.38, 95% CI (1.02, 1.85), P=0.035]. Conclusion: Our findings suggest the changes in amino acid metabolism not only link IR in childhood, but also persist into adulthood and may heighten type 2 diabetes risk later in life. Disclosure S.Gao: None. M.Li: None. Bcams group: n/a. Funding National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014); National Natural Science Foundation of China (81970732, 82270924); CAMS Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-016); Capital's Funds for Health Improvement and Research (2020-2Z-40117); Key Program of Beijing Municipal Science &amp;Technology Commission (D111100000611001, D111100000611002)

Association between genetic predisposition and disease burden of stroke in China: a genetic epidemiological study

Stroke ranks second worldwide and first in China as a leading cause of death and disability. It has a polygenic architecture and is influenced by environmental and lifestyle factors. However, it remains unknown as to whether and how much the genetic predisposition of stroke is associated with disease burden. Allele frequency from the whole genome sequencing data in the Chinese Millionome Database of 141,418 individuals and trait-specific polygenic risk score models were applied to estimate the provincial genetic predisposition to stroke, stroke-related risk factors and stroke-related drug response. Disease burden including mortality, disability-adjusted life years (DALYs), years of life lost(YLLs), years lived with disability (YLDs) and prevalence in China was collected from the Global Burden Disease study. The association between stroke genetic predisposition and the epidemiological burden was assessed and then quantified in both regression-based models and machine learning-based models at a provincial resolution. Among the 30 administrative divisions in China, the genetic predisposition of stroke was characterized by a north-higher-than-south gradient (p<0.0001). Genetic predisposition to stroke, blood pressure, body mass index, and alcohol use were strongly intercorrelated (rho >0.6; p<0.05 after Bonferroni correction for each comparison). Genetic risk imposed an independent effect of approximately 1-6% on mortality, DALYs and YLLs. The distribution pattern of stroke genetic predisposition is different at a macroscopic level, and it subtly but significantly impacts the epidemiological burden. Further research is warranted to identify the detailed aetiology and potential translation into public health measures. Beijing Municipal Science and Technology Commission (Z191100006619106), CAMS Innovation Fund for Medical Sciences (CAMS-I2M, 2023-I2M-1-001), the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17), National Natural Science Foundation of China (32000398, 32171441 to X.J.), Natural Science Foundation of Guangdong Province, China (2017A030306026 to X.J.), and National Key R&D Program of China (2022YFC2502402).

Level of evidence supporting the Chinese cardiovascular disease clinical practice guidelines and its evolution in the past two decades

Clinical practice is guided by guidelines in the era of evidence-based medicine to improve healthcare. The consistency between the strength of recommendations and the underlying quality of evidence in clinical guidelines and its evolution dynamically reflects the status of medical practice in important aspects. This study aimed to evaluate the levels of evidence (LOEs) supporting different classes of recommendations (CORs) in Chinese cardiovascular disease (CVD) guidelines between 2003 and 2021, and changes over time. Clinical guideline documents on cardiovascular topics issued by leading professional organizations were retrieved in the Databases of SinoMed and Wanfang Med Online from inception to June 2021. All guidelines were screened through abstract and full-text reading, and included if satisfying the pre-specified criteria. 79 Chinese guideline documents on 12 sub-topics including a total of 5195 recommendations and the designated CORs/LOEs, were abstracted. The number of recommendations of Class Ⅰ, Class Ⅱ, Class Ⅲ, LOE A, LOE B, and LOE C were identified for each guideline document. The proportion of CORs, LOEs, and COR-LOE combinations in guidelines and the changes among those with ≥2 versions. A total of 79 guidelines were included in the analysis. When examining the status of current guidelines, among the 3325 recommendations derived from 59 documents during 2011-2021, 735 recommendations (22.1%) were classified as LOE A, 1280 (38.5%) as LOE B, and 1310 (39.4%) as LOE C. 596 recommendations (17.9%) were characterized as Class Ⅰ-LOE A, accounting for the majority of LOE A recommendations but only one-third of Class I recommendations. Evidence levels varied greatly across different sub-topics and individual guidelines. There are 9 guidelines on 5 sub-topics having ≥2 versions. When analyzing the changes over time, although an increase was observed in the total number of recommendations, the proportion of recommendations designated as Class Ⅰ-LOE A did not significantly improve (19.1% [current] vs 19.0% [prior], p=0.97). In current Chinese CVD guidelines, the high level of evidence lacks, and its alignment with strong recommendations is deficient. Although it shows moderate improvements in certain major topics (e.g., coronary artery disease, interventional therapy, surgery) in the past two decades, the overall proportion of Class I-LOE A recommendations remains small, suggesting that conduction, and particularly translation, of high-quality studies like RCTs addressing CVDs-related questions are still essential and demanded, especially for areas with less attention. This study was supported by Beijing Nova Program from Beijing Municipal Science & Technology Commission (Z211100002121063, Z201100006820002); Fundamental Research Funds for the Central Universities (3332022023); National Key R&D Program of China (2020YFC2004705); CAMS Innovation Fund for Medical Sciences (2021-I2M-5-003); National Natural Science Foundation of China (81825003, 91957123, 82270376).

Rapid identification of chronic kidney disease in electronic health record database using computable phenotype combining a common data model.

Rapid identification of chronic kidney disease in electronic health record database using computable phenotype combining a common data model.

Twice-daily injections and multiple daily injections of insulin in toddlers with type 1 diabetes: a retrospective cohort study.

Twice-daily injections and multiple daily injections of insulin in toddlers with type 1 diabetes: a retrospective cohort study.

Association between atherogenic index of plasma and colorectal neoplasms in patients with hypertension.

Association between atherogenic index of plasma and colorectal neoplasms in patients with hypertension.

A Bayesian network model for prediction of low or failed fertilization in assisted reproductive technology based on a large clinical real-world data

Study questionTo construct prediction models based on the Bayesian network (BN) learning method for the probability of fertilization failure (including low fertilization rate [LRF] and total fertilization failure [TFF]) in assisted reproductive technology (ART) treatment.Summary answerA BN model was developed to predict TFF/LFR. The model showed relatively high calibration in external validation, which could facilitate the identification of risk factors for fertilization disorders and improve the efficiency of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment.What is known alreadyThe prediction of TFF/LFR is very complex. Although some studies attempted to construct prediction models for TFF/LRF, most of the reported models were based on limited variables and traditional regression-based models, which are unsuitable for analyzing real-world clinical data. Therefore, none of the reported models have been widely used in routine clinical practice. To date, BN modeling analysis is a prominent and increasingly popular machine learning method that is powerful in dealing with dynamic and complex real-world data.Study design, size, durationA retrospective study was performed with 106,640 fresh embryo IVF/ICSI cycles from 2009 to 2019 in one of China's largest reproductive health centers.Participants/materials, setting, methodsA total of 106, 640 cycles were included in this study, including 97,102 controls, 4,339 LFR cases, and 5,199 TFF cases. Twenty-four predictors were initially included, including 13 female-related variables, five male-related variables, and six variables related to IVF/ICSI treatment. BN modeling analysis with tenfold cross-validation was performed to construct the predictive model for TFF/LFR. The receiver operating characteristic (ROC) curves and the corresponding area under the curves (AUCs) were used to evaluate the performance of the BN model.Main results and the role of chanceAll twenty-four predictors were first organized into seven hierarchical layers in a theoretical BN model, according to prior knowledge from previous literature and clinical practice. A machine-learning BN model was generated based on real-world clinical data, containing a total of eighteen predictors, of which the infertility type, ART method, and number of retrieved oocytes directly influence the probabilities of LFR/TFF. The prediction accuracy of the BN model was 91.7%. The AUC of the TFF versus control groups was 0.779 (95% CI: 0.766-0.791), with a sensitivity of 71.2% and specificity of 70.1%; the AUC of of TFF versus LFR groups was 0.807 (95% CI: 0.790-0.824), with a sensitivity of 49.0% and specificity of 99.0%.Limitations, reason for cautionFirst, our study was based on clinical data from a single center, and the results of this study should be further verified by external data. In addition, some critical data (e.g., the detailed IVF laboratory parameters of the sperm and oocytes used for insemination) were not available in this study, which should be given full consideration when further improving the performance of the BN model.Wider implications of the findingsBased on extensive clinical real-world data, we developed a BN model to predict the probabilities of fertilization failures in ART, which provides new clues for clinical decision-making support for clinicians in formulating personalized treatment plans and further improving ART treatment outcomes.Study funding/competing interest(s)Dr. Y. Wang was supported by grants from the Beijing Municipal Science & Technology Commission (Z191100006619086). We declare that there are no conflicts of interest.Trial registration numberN/A.

北京主要气传致敏花粉年浓度峰值日期预测

PDF HTML阅读 XML下载 导出引用 引用提醒 北京主要气传致敏花粉年浓度峰值日期预测 DOI: 10.5846/stxb202202220416 作者: 作者单位: 作者简介: 通讯作者: 中图分类号: 基金项目: 北京市科技计划课题（Z191100009119013） Prediction of date of annual maximum concentration of main airborne allergenic pollen in Beijing Author: Affiliation: Fund Project: Beijing Municipal Science and Technology Project(Z191100009119013) 摘要 | 图/表 | 访问统计 | 参考文献 | 相似文献 | 引证文献 | 资源附件 | 文章评论 摘要:花粉是我国北方引发过敏性鼻炎最主要过敏原，花粉症发病期与花粉浓度高峰期吻合。基于北京地区2012至2020年花粉季多站、逐日分类花粉浓度观测数据分析，得出北京地区花粉浓度在3月上旬至5月中旬（可进一步划分为3月中旬至4月上旬和4月下旬至5月上旬两个高峰期）和8月中旬至9月中旬分别存在两个高峰期，第一个高峰期内优势致敏花粉种类为柏科、杨柳科和松科，第二个高峰期内优势致敏花粉种类为桑科、菊科蒿属和藜科。根据优势致敏花粉年浓度峰值日期观测数据，使用与花粉采样站点位置相匹配的逐日气象观测数据累积值，基于作物模型概念和模糊逻辑原理建立了北京地区主要气传致敏花粉年浓度峰值日期预测模型。经检验，柏科、杨柳科、松科、桑科、菊科蒿属和藜科花粉模型预测准确率分别为87.8%、80.0%、64.4%、86.7%、78.8%和81.8%。基于北京地区主要气传致敏花粉年浓度峰值日期预测模型可为本地花粉症防治提供理论参考。 Abstract:The prevalence and severity of pollen-induced pollinosis has been increasing yearly worldwide in recent years. Pollen is the main allergen causing allergic rhinitis in North China and the onset period of airborne allergenic pollen-induced pollinosis coincides with the peak period of pollen concentration. As one of the mega-cities in the northern region of China, Beijing is becoming increasingly aware of the problems caused by allergenic pollen. Based on the analysis of 12 pollen sampling stations daily classified pollen concentration observation data during pollen season in Beijing from 2012 to 2020, there were two peak periods of pollen concentration in Beijing from early March to mid-May (it could be further divided into two peak periods from mid-March to early April and from late April to early May) and from mid-August to mid-September, respectively. The dominant allergenic pollen species in the first peak period were Cupressaceae, Salicaceae (from early March to mid-April, the annual average concentration accounted for 39.1% and 18.2% respectively) and Pinaceae (from mid-April to early May, the annual average concentration accounted for 18.2%), and the dominant allergenic pollen species in the second peak period were Moraceae, Artemisia and Chenopodiaceae (from mid-August to mid-September, the annual average concentration accounted for 34.4%, 30.4% and 12.7% respectively). The annual maximum concentration of dominant airborne allergenic pollen in Beijing varied significantly among stations and pollen seasons, and fluctuated significantly. In contrast, the variation of the dates of annual maximum pollen concentration of the same species is relatively stable, and its prediction research work is more meaningful for pollen-induced pollinosis control. Based on the observation data of annual maximum concentration of dominant airborne allergenic pollen and the cumulative value of daily meteorological observation data matched with the location of pollen sampling stations, a prediction model of date of annual maximum concentration of main airborne allergenic pollen in Beijing is established based on the principle of crop growth model and fuzzy logic. The results showed that the prediction accuracy of pollen models of Cupressaceae, Salicaceae, Pinaceae, Moraceae, Artemisia and Chenopodiaceae were 87.8%, 80.0%, 64.4%, 86.7%, 78.8% and 81.8%, respectively. Using a model based on fuzzy logic principle and driven by the cumulative values of daily meteorological elements for pollen annual maximum concentration date, combined with the high-resolution regional numerical weather prediction model in Beijing, we can make a reasonable prediction of the time of maximum pollen concentration of different airborne allergenic pollens and provide a theoretical reference for the prevention and control of local airborne allergenic pollen-induced pollinosis. 参考文献 相似文献 引证文献

A Stochastic Approximation Method for Simulation-Based Quantile Optimization

We present a gradient-based algorithm for solving a class of simulation optimization problems in which the objective function is the quantile of a simulation output random variable. In contrast with existing quantile (quantile derivative) estimation techniques, which aim to eliminate the estimator bias by gradually increasing the simulation sample size, our algorithm incorporates a novel recursive procedure that only requires a single simulation sample at each step to simultaneously obtain quantile and quantile derivative estimators that are asymptotically unbiased. We show that these estimators, when coupled with the standard gradient descent method, lead to a multitime-scale stochastic approximation type of algorithm that converges to an optimal quantile value with probability one. In our numerical experiments, the proposed algorithm is applied to optimal investment portfolio problems, resulting in new solutions that complement those obtained under the classical Markowitz mean-variance framework. History: Accepted by Alice E. Smith, Editor-in-Chief; Bruno Tuffin, Area Editor for Simulation. Funding: The work of Y. Peng was supported in part by the National Natural Science Foundation of China (NSFC) [Grants 72022001, 92146003, and 71901003], and by the Key Research and Development Programof Beijing Municipal Science and Technology Commission. Supplemental Material: The e-companion is available at https://doi.org/10.1287/ijoc.2022.1214 .

Prophylactic interventions for preventing macular edema after cataract surgery in patients with diabetes: A Bayesian network meta-analysis of randomized controlled trials

SummaryBackgroundDiabetes significantly increases the risk of postoperative macular edema (PME) after cataract surgery, leading to potential worst post-operative outcomes. This study aims to compare the effect of different prophylactic interventions in improving postoperative anatomic and visual acuity outcomes of diabetes patients who underwent cataract surgery.MethodsWe searched MEDLINE, Embase, Web of Science databases from inception until February 2nd, 2022, for studies including studies reporting PME events and/or best-corrected visual acuity (BCVA) outcomes. Random-effects Bayesian network meta-analysis was performed to compare the efficiency of intravitreal anti-vascular endothelial growth factor injections (anti-VEGF), nonsteroidal anti-inflammatory drugs (NSAIDs) and topical steroids eye drop at 1 week, 1 month, 3 months, 6 months after cataract surgery.FindingsThe total of 2566 participants from 17 randomized controlled trials were included in the network meta-analysis, with moderate risk of bias and no evidence of publication of bias. Compared to placebo/steroid eye drop alone, patients received additional topical NSAIDs or intravitreal anti-VEGF injections had lower risk of PME at 1 month (NSAIDs: OR=0·221, 95% Confidence interval [CI], 0·044–0·755, I2=0·0%, 5 studies; anti-VEGF: OR=0·151, 95%CI, 0·037–0·413, I2=0·0%, 5 studies) and 3 month (NSAIDs: OR=0·370, 95%CI, 0·140–0·875, I2=0·0%, 8 studies; anti-VEGF: OR=0·203, 95%CI, 0·101–0·353, I2=0·0%, 4 studies) after cataract surgery. Further, additional anti-VEGF exhibited better BCVA outcome at 1 month (mean difference of LogMAR: -0·083, 95%CI, -0·17 to -0·014, I2=62·0%, 5 studies), and 3 months (mean difference of LogMAR: -0·061, 95%CI, -0·11 to -0·011, I2=0·0%, 5 studies) after cataract surgery. Such additional benefits did not reach statistic significant at 6 months after surgery.InterpretationOur data suggests that compared to placebo/steroid eye drop alone, additional prophylactic anti-VEGF intervention could be considered for preventing the occurrence of PME after cataract surgery in patients with diabetes.FundingResearch and Development of Special (2020-1-2052); Science & Technology Project of Beijing Municipal Science & Technology Commission (Z201100005520045, Z181100001818003).

Association between high-sensitivity C-reactive protein, functional disability, and stroke recurrence in patients with acute ischaemic stroke: A mediation analysis.

SummaryBackgroundPost-stroke inflammation biomarker high-sensitivity C-reactive protein (hsCRP) increases cerebral infarct size and results in functional disability directly, it also contributes to the formation and maturation of atherosclerotic plaques, which increase the risk of stroke recurrence and results in functional disability indirectly. However, no study has quantified how much functional disability was mediated by stroke recurrence.MethodsPatients with acute ischaemic stroke within 7 days and admitted to 169 hospitals in the Third China National Stroke Registry were analyzed. Blood samples were collected within 24 h of admission. Stroke recurrence and functional disability (defined as a modified Rankin scale score ≥ 2) were assessed via face-to-face interviews at three months. Mediation analysis under the counterfactual framework was performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between hsCRP and functional outcome. Sensitivity analyses were performed across different subgroups and on different scales of hsCRP measurement.FindingsOf the 7603 analyzed patients (mean [SD] age, 62.3 [11.3] years; 2392 [31.5%] women), the median (interquartile range [IQR]) of NIHSS score was 3.0 (1.0–6.0). The median (IQR) level of hsCRP was 1.73 (0.81–4.38) mg/L. A total of 496 (6.5%) cases of stroke recurrence and 1884 (24.8%) cases of functional disability were observed at the 90-day follow-up. Each SD increase in the concentration of hsCRP was associated with an increased risk of stroke recurrence (adjusted odds ratio [aOR], 1.11; 95% CI, 1.04–1.18) and disability (aOR, 1.14; 95% CI, 1.08–1.20) within 90 days. Of 1884 functionally disabled patients, only 16.0 % (n = 302) of patients experienced stroke recurrence before functional disability. Stroke recurrence during follow-up explained 16.52% (95% CI, 5.79%–27.25%) of the relationship between hsCRP and functional disability. Sensitivity analyses in different subgroups and on different scales of hsCRP measurement showed comparable results.InterpretationStroke recurrence mediates less than 20% of the association between hsCRP and functional disability at 90 days among patients with acute ischaemic stroke. In addition to typical secondary prevention strategies for preventing stroke recurrence, more attention should be paid to novel anti-inflammatory therapy to improve functional outcomes.FundingBeijing Natural Science Foundation, the National Key R&D Program of China, the National Natural Science Foundation of China, and the Beijing Municipal Science & Technology Commission.

MP22-12 CLINICAL APPLICATION OF DOUBLE-MODIFIED SULFATED BACTERIAL CELLULOSE SCAFFOLD MATERIAL LOADED WITH FGFR2-MODIFIED ADIPOSE STEM CELLS IN LOWER URINARY TRACT RECONSTRUCTION

You have accessJournal of UrologyCME1 May 2022MP22-12 CLINICAL APPLICATION OF DOUBLE-MODIFIED SULFATED BACTERIAL CELLULOSE SCAFFOLD MATERIAL LOADED WITH FGFR2-MODIFIED ADIPOSE STEM CELLS IN LOWER URINARY TRACT RECONSTRUCTION Zhenpeng Zhu, Jiayu Yang, Xing Ji, Yudong Zheng, Jian Lin, and Liqun Zhou Zhenpeng ZhuZhenpeng Zhu More articles by this author , Jiayu YangJiayu Yang More articles by this author , Xing JiXing Ji More articles by this author , Yudong ZhengYudong Zheng More articles by this author , Jian LinJian Lin More articles by this author , and Liqun ZhouLiqun Zhou More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002561.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urethral stricture and restenosis is one of the thorny problems in urology, and both autologous tissues and synthetic materials previously used in clinical lower urinary tract repair have certain shortcomings.Autologous tissues are prone to many problems such as limited access sites and access site complications. Previously used materials such as ADMG or SIS are more expensive and have poor results, especially in patients with long urethral strictures. This study focuses on novel tissue-engineered urethra, which provides new ideas and methods for urethral repair in clinical practice. METHODS: The doubly modified sulfated bacterial cellulose (BC) scaffold material (DMBC) was constructed from bacterial extracts by dual modification (laser perforation and selective sulfur modification) and tested for mechanical properties and cytotoxicity. Subsequently, adipose stem cells (ASCs) were isolated from in vitro adipose tissue and were continuously overexpressed with FGFR2 factor by constructing FGFR2 overexpression vector and lentiviral infection, and the corresponding functional assays were performed. FGFR2-modified ASCs were subsequently loaded on DMBC and applied to a New Zealand rabbit urethral defect model, and histological and imaging assays were performed postoperatively. RESULTS: The dual-modified DMBC scaffold material is a novel tissue-engineered scaffold material with good biocompatibility, low cytotoxicity and degradability. By constructing the tissue-engineered urethra with the dual-modified DMBC scaffold material and FGFR2-modified ASCs, it could be better used for the repair of urethral defects in the New Zealand rabbit urethral defect model, which showed good efficacy after surgery, and histology and imaging showed that the repaired site tissue was close to normal urethral tissue. CONCLUSIONS: Dual-modified DMBC scaffold material loaded with FGFR2-modified ASCs can be used as a novel tissue-engineered urethral material for injury repair of the lower urinary tract. Source of Funding: This work was financially supported by National Natural Science Foundation of China (Grant No.51973018, 51773018, 82070704); Beijing Municipal Science and Technology Commission Projects (No. Z191100002019017, Z171100001017093); Fundamental Research Funds for the Central Universities (FRF-TP-17-001A2); Key Research and Development Projects of People’s Liberation Army (BWS17J036) © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e376 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zhenpeng Zhu More articles by this author Jiayu Yang More articles by this author Xing Ji More articles by this author Yudong Zheng More articles by this author Jian Lin More articles by this author Liqun Zhou More articles by this author Expand All Advertisement PDF DownloadLoading ...

Response prediction and risk stratification of patients with rectal cancer after neoadjuvant therapy through an analysis of circulating tumour DNA

SummaryBackgroundMultiple approaches based on cell-free DNA (cfDNA) have been applied to detect minimal residual disease (MRD) and to predict prognosis or recurrence. However, a comparison of the approaches used in different cohorts and studies is difficult. We aimed to compare multiple approaches for MRD analysis after neoadjuvant therapy (NAT) in patients with locally advanced rectal cancer (LARC).MethodsSixty patients with LARC from a multicentre, phase II/III randomized trial were included, with tissue and blood samples collected. For each cfDNA sample, we profiled MRD using 3 approaches: personalized assay targeting tumour-informed mutations, universal panel of genes frequently mutated in colorectal cancer (CRC), and low depth sequencing for copy number alterations (CNAs).FindingsPositive MRD based on post-NAT personalized assay was significantly associated with an increased risk of recurrence (HR = 27.38; log-rank P < 0.0001). MRD analysis based on universal panel (HR = 5.18; log-rank P = 0.00086) and CNAs analysis (HR = 9.24; log-rank P = 0.00017) showed a compromised performance in predicting recurrence. Both the personalized assay and universal panel showed complementary pattern to CNAs analysis in detecting cases with recurrence and the combination of the two types of biomarkers may lead to better performance.InterpretationThe combination of mutation profiling and CNA profiling can improve the detection of MRD, which may help optimize the treatment strategies for patients with LARC.