The association of long-term trajectories of BMI, its variability, and metabolic syndrome: a 30-year prospective cohort study.

Background: Limited data exists on how early-life weight changes relate to metabolic syndrome (MetS) risk in midlife. This study examines the association between long-term trajectories of body mass index (BMI), its variability, and MetS risk in Chinese individuals. Methods: In the Hanzhong Adolescent Hypertension study (March 10, 1987-June 3, 2017), 1824 participants with at least five BMI measurements from 1987 to 2017 were included. Using group-based trajectory modeling, different BMI trajectories were identified. BMI variability was assessed through standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Logistic regression analyzed the relationship between BMI trajectory, BMI variability, and MetS occurrence in midlife (URL: https://www.clinicaltrials.gov; Unique identifier: NCT02734472). Findings: BMI trajectories were categorized as low-increasing (34.4%), moderate-increasing (51.8%), and high-increasing (13.8%). Compared to the low-increasing group, the odds ratios (ORs) [95% CIs] for MetS were significantly higher in moderate (4.27 [2.63-6.91]) and high-increasing groups (13.11 [6.30-27.31]) in fully adjusted models. Additionally, higher BMI variabilities were associated with increased MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 2.30 [2.02-2.62], 1.22 [1.19-1.26], and 4.29 [3.38-5.45]). Furthermore, BMI trajectories from childhood to adolescence were predictive of midlife MetS, with ORs in moderate (1.49 [1.00-2.23]) and high-increasing groups (2.45 [1.22-4.91]). Lastly, elevated BMI variability in this period was also linked to higher MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 1.24 [1.08-1.42], 1.00 [1.00-1.01], and 1.21 [1.05-1.38]). Interpretation: Our study suggests that both early-life BMI trajectories and BMI variability could be predictive of incident MetS in midlife. Funding: This work was supported by the National Natural Science Foundation of China No. 82070437 (J.-J.M.), the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University of China (No. XJTU1AF-CRF-2022-002, XJTU1AF2021CRF-021, and XJTU1AF-CRF-2023-004), the Key R&D Projects in Shaanxi Province (Grant No. 2023-ZDLSF-50), the Chinese Academy of Medical Sciences & Peking Union Medical College (2017-CXGC03-2), and the International Joint Research Centre for Cardiovascular Precision Medicine of Shaanxi Province (2020GHJD-14).

Adjusted win ratio using the inverse probability of treatment weighting.

The win ratio method has been increasingly applied in the design and analysis of clinical trials. However, the win ratio method is a univariate approach that does not allow for adjusting for baseline imbalances in covariates, although a stratified win ratio can be calculated when the number of strata is small. This paper proposes an adjusted win ratio to control for such imbalances by inverse probability of treatment weighting (IPTW) method. We derive the adjusted win ratio with its variance and suggest three IPTW adjustments: IPTW-average treatment effect (IPTW-ATE), stabilized IPTW-ATE (SIPTW-ATE) and IPTW-average treatment effect in the treated (IPTW-ATT). The proposed adjusted methods are applied to analyse a composite outcome in the CHARM trial. The statistical properties of the methods are assessed through simulations. Results show that adjusted win ratio methods can correct the win ratio for covariate imbalances at baseline. Simulation results show that the three proposed adjusted win ratios have similar power to detect the treatment difference and have slightly lower power than the corresponding adjusted Cox models when the assumption of proportional hazards holds true but have consistently higher power than adjusted Cox models when the proportional hazard assumption is violated.

New insights from trio whole-exome sequencing in the children with kidney disease: A single-center retrospective cohort study.

BACKGROUND: Kidney disease of children markedly affects their health and development. Limited clinical data of early-stage kidney disease render a tremendous challenge for the accurate diagnosis. Trio whole-exome sequencing (Trio-WES) is emerging as a first-line diagnostic strategy in pediatric kidney disease, and shows important implications for the precision medicine strategies of children with kidney disease. METHODS: Trio-WES was performed in 133 Chinese children with kidney disease and their parents. The results for casual variants in genes known to cause kidney disease were analyzed. We further assessed the genetic diagnostic yield and the clinical implications of genetic testing. RESULTS: An overall diagnostic yield of 52.63% (70/133) was found, and the diagnostic rates ranged from 44.74% to 59.62% in different clinical phenotypes. The diagnostic yield of the three groups of simple proteinuria, renal insufficiency, and "other" was 50%, 50%, and 54.55%, respectively. Eight-seven diagnostic variants were identified in 70 probands with variants spanning 30 genes. The top 7 genes with diagnostic variants were COL4A5 (23, 26.44%), COL4A4 (13, 14.94%), ADCK4 (7, 8.05%), CLCN5 (3, 3.45%), ACE (3, 3.45%), PKD1 (3, 3.45%), and SLC12A3 (3, 3.45%), accounting for 63.22% of all variations in the cohort. CONCLUSIONS: The retrospective cohort study summarized the clinical utility of genetic testing in 133 probands, and expanded the phenotypic and genetic profiles of kidney disease in children. Trio-WES is an efficient diagnostic tool for children with kidney disease, which facilitates the clinical diagnosis and treatment. Our findings have important implications for the precise diagnosis of childhood nephropathy and may provide clinical guideline for disease management.

A win ratio approach for comparing crossing survival curves in clinical trials.

Many clinical trials include time-to-event or survival data as an outcome. To compare two survival distributions, the log-rank test is often used to produce a P-value for a statistical test of the null hypothesis that the two survival curves are identical. However, such a P-value does not provide the magnitude of the difference between the curves regarding the treatment effect. As a result, the P-value is often accompanied by an estimate of the hazard ratio from the proportional hazards model or Cox model as a measurement of treatment difference. However, one of the most important assumptions for Cox model is that the hazard functions for the two treatment groups are proportional. When the hazard curves cross, the Cox model could lead to misleading results and the log-rank test could also perform poorly. To address the problem of crossing curves in survival analysis, we propose the use of the win ratio method put forward by Pocock et al. as an estimand for analysing such data. The subjects in the test and control treatment groups are formed into all possible pairs. For each pair, the test treatment subject is labelled a winner or a loser if it is known who had the event of interest such as death. The win ratio is the total number of winners divided by the total number of losers and its standard error can be estimated using Bebu and Lachin method. Using real trial datasets and Monte Carlo simulations, this study investigates the power and type I error and compares the win ratio method with the log-rank test and Cox model under various scenarios of crossing survival curves with different censoring rates and distribution parameters. The results show that the win ratio method has similar power as the log-rank test and Cox model to detect the treatment difference when the assumption of proportional hazards holds true, and that the win ratio method outperforms log-rank test and Cox model in terms of power to detect the treatment difference when the survival curves cross.

Differences between Two Groups of Burmese Vipers (Viperidae: Azemiops) in the Proteomic Profiles, Immunoreactivity and Biochemical Functions of Their Venoms.

Two recently revised Azemiops snakes with apparent differences in their external appearances and skeletal morphologies but unclear genetic boundaries have been proposed. Some researchers have refrained from using the newly proposed taxonomy because these two "species" might be two clades corresponding to different geographical populations of Azemiops feae. To improve the understanding of the kinship of these two Burmese viper groups, more of their characteristics should be explored in depth. We performed a comparative analysis of the proteomic profiles and biochemical activities of snake venoms from these two groups (Sichuan A. feae and Zhejiang A. feae) and evaluated the immunorecognition capacity of commercial antivenoms toward them. Eight protein families were identified in venoms from these two groups, while phospholipase B was only detected in venom from Sichuan A. feae. These protein families displayed varying degrees of differences in relative abundance between venoms, and phospholipase A2 (Sichuan A. feae: 57.15%; Zhejiang A. feae: 65.94%) was the predominated component. Gloydius brevicaudus antivenom exhibited the strongest capacity to immunologically recognize these two venoms, but this was mainly limited to components with high molecular masses, some of which differed between venoms. Additionally, Zhejiang A. feae venom was more toxic than Sichuan A. feae venom, and the venoms expressed remarkable differences in enzymatic activities, probably resulting from the variation in the relative abundance of specific protein families. Our findings unveil differences between the two Burmese viper groups in terms of proteomic profiles, immunoreactivity, and the biochemical functions of their venoms. This information will facilitate the management of snakebites caused by these snakes.

Level and determinants of willingness to donate organs among the general public: A cross-sectional survey in China.

This study aims to assess the level and determinants of the general public's willingness to organ donation. We conducted a population-based cross-sectional study of 4261 participants in China. The primary outcome was the willingness to donate organs. Logistic regression modelling was used to determine the factors that affect willingness to donate organs. Overall, the proportion of participants who showed a willingness to donate organs was 47.45% (95%CI: 0.46, 0.49) in this study. Logistic regression modelling showed participants from Western (OR = 1.33, 95%CI = 1.11-1.59) and Eastern China (OR = 1.40, 95%CI = 1.19-1.65) were more willing to donate organs compared with those from Central China. The odds of being willing to donate organs was higher in females than males (OR = 1.35, 95%CI = 1.17-1.55); and was higher in those participants with experience of organ donation (OR = 1.58, 95%CI = 1.13-2.21), experience of caring for organ transplant patients (OR = 1.45, 95%CI = 1.01-2.07), and those undertaking related voluntary activities (OR = 1.67, 95%CI = 1.45-1.94), than those without. The general public's level of willingness to organ donation was not high in this study. Geographical region, gender, experience of organ donation related activities, taking care of organ transplant patients and volunteering in related activities were independently associated with participants' willingness to donate organs.

Early plasma exchange for treating ricin toxicity in children after castor bean ingestion.

Plasma exchange (PE) for the treatment of ricin toxicity has not been previously reported. Here we describe the use of PE to treat children who experienced ricin toxicity after ingesting castor beans. Seven children (median age: 8.1 years) who consumed castor beans (median: 5 beans) were treated with PE. All had bradycardia and sinus arrhythmia, and most had experienced episodes of vomiting and/or diarrhea. PE settings were blood flow, 50-80 mL/min; PE rate, 600-800 mL/h; volume of exchange, 1440-1950 mL. Median time from ingestion to PE was 73 h. All clinical symptoms disappeared and vital signs rapidly returned to normal after PE; no severe organ dysfunction occurred. All children were discharged and recovered uneventfully. Concentrations of all serum biochemical parameters significantly decreased immediately after PE. Some, but not all, of these parameters were also significantly decreased at 48 and 72 h after PE compared with before PE. Our findings suggest that PE can be an effective early intervention in the treatment of ricin toxicity due to castor bean ingestion.

[Species sensitive distribution for aquatic biota exposed to triazophos].

The increasing pollution of organophosphorus pesticides (OP) in water have been of concerns. Taking the widely used triazophos as the object, a species sensitivity distribution (SSD) model was developed using a log-logistic distribution based on the median effective concentrations (EC50) of triazophos to aquatic species at various trophic levels, and then the model was tested and evaluated using probability plots and good-of-fit tests. The results showed that the SSD for aquatic biota exposed to triazophos was well fitted by a log-logistic distribution, which was totally determined by the two parameters, alpha = -0.4788 and beta = 0.7546, with standard error 0.2381 and 0.1078 respectively. Based on the SSD model, the hazardous concentration for 5% of the species (HC5) and the criteria maximum concentration (CMC) of triazophos were 1.992 x 10(-3) mg/L and 9.96 x 10(-4) mg/L, respectively. Through comparing the HC5 and CMC with the safe concentration for single-species, it could be found that environmental quality criteria derived from the SSD model was more strict, and closed to the real ecological environment. In addition, according to the reported data, the potentially affected fraction (PAF) of species exposed to triazophos in the Laizhou Bay (Bohai Sea, China) area was 0.36% predicted by the SSD model, and the corresponding risk might not be significant.