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Objective: This study aimed to analyze the pharmacokinetic (PK) characteristics, safety, and bioequivalence (BE) of a test (T) preparation of a nifedipine controlled-release tablet and the reference (R) drug (Adalat GTIS) in Chinese study participants in the context of fasting and postprandial states., Materials and Methods: An open-label, single-center, randomized, single-dose, two-period study was designed including two separate arms, one with administration under fasting conditions and one with administration under postprandial conditions (high-fat, high-calorie breakfast). After oral administration, the nifedipine concentrations in plasma were quantitatively analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) at regular intervals. Primary PK parameters, including the area under the concentration curve from 0 to infinity (AUC 0-∞ ), the area under the concentration profile from 0 to the last measurable concentration time (AUC 0-t ), and maximal measured plasma concentration (C max ) were log-transformed with BE limits of 80 - 125% to evaluate BE. All adverse events (AEs) were wholly supervised., Results: The PK profiles of the T and R formulations were comparable to each other under both fasting and postprandial conditions. The 90% confidence intervals (CIs) of the AUC 0-∞ , AUC 0-t , and C max were 92.69 - 106.06%, 93.32 - 107.05%, and 99.53 - 116.71%, respectively, under the fasting state. The 90% CIs of the AUC 0-∞ , AUC 0-t , and C max were 105.05 - 117.40%, 105.43 - 117.82%, and 102.66 - 116.30%, respectively, in the postprandial arm. 47 cases of drug-associated AEs were noted in the entire research., Conclusion: Under both the fasting and postprandial states, the two nifedipine controlled-release formulations were bioequivalent and safe in healthy Chinese subjects.

Objective: To identify the risk factors for placenta accreta spectrum (PAS) disorders in women without prior cesarean section (CS)., Methods: This retrospective case-control study investigated patients without prior CS who gave birth at Peking University Third Hospital between January 1, 2015 and December 31, 2021. Patients diagnosed with PAS according to the clinical diagnostic criteria of the 2019 International Federation of Gynecology and Obstetrics (FIGO) classification were included as the study group. Patients were matched as the control group according to delivery date and placenta previa, in a 1:2 allocation ratio. Maternal characteristics were compared between the two groups., Results: The study included 348 patients in the study group and 696 in the control group. The multivariate analysis showed that the independent risk factors of PAS consisted of operative hysteroscopy (once: adjusted odds ratio [aOR] 2.38, 95% CI 1.28-4.24, P = 0.006; twice or more: aOR 5.43, 95% CI 1.04-28.32, P = 0.045), uterine curettage (once: aOR 2.54, 95% CI 1.80-3.58, P < 0.001; twice: aOR 3.01, 95% CI 1.81-5.02, P < 0.001; three or more times: aOR 9.18, 95% CI 4.64-18.18, P < 0.001), multifetal pregnancy (aOR 5.64, 95% CI 3.01-10.57, P < 0.001), adenomyosis (aOR 2.77, 95% CI 1.23-6.22, P = 0.014), in vitro fertilization (aOR 1.51, 95% CI 1.04-2.20, P = 0.030) and pre-eclampsia (aOR 2.72, 95% CI 1.36-5.45, P = 0.005), and the independent protective factor was being multiparous (aOR 0.37, 95% CI 0.25-0.54, P < 0.001)., Conclusion: After controlling the effect of placenta previa, we found that patients with PAS without prior CS had unique maternal characteristics. Classification and quantification of the intrauterine surgeries they have undergone is essential for identifying high-risk patients. Early identification of high-risk groups by risk factors has the potential to improve the prognosis considerably., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: As a key agricultural region in China, Heilongjiang Province has experienced significant carbon emissions over the past few decades. To understand the underlying factors and future trends in these emissions, a comprehensive analysis was conducted from 1993 to 2030., Methods: The agricultural carbon emissions from 1993 to 2020 were estimated using the emission factor method. To analyze the influencing factors and future trends of these emissions, the study employed the Logarithmic Mean Divisia Index (LMDI) and integrated it with the Stochastic Impacts by Regression on Population, Affluence, and Technology (STIRPAT) model., Results: Results showed that (1) the agricultural carbon emissions in Heilongjiang were primarily driven by rice cultivation, followed by fertilizer production and irrigation electricity. (2) The economic and labor structure effects were the main driving factors of agricultural carbon emissions, while the population, demographic, and intensity effects were the main inhibitors. (3) Agricultural carbon emissions in Heilongjiang Province peaked in 2016 with 69.6 Mt CO 2 -eq and could subsequently decline by -3.92% to -4.52% between 2020 and 2030 in different scenario simulations. In the future, Heilongjiang Province should prioritize the reduction of agricultural carbon emissions from rice production. Adjusting the planting structure, managing the layout of rice paddies, and promoting the cultivation of dry rice varieties would significantly contribute to mitigating agricultural carbon emissions., Competing Interests: The authors declare there are no competing interests., (©2024 Zhang et al.)

River water quality has been increasingly deteriorated because of the influence of natural process and anthropogenic activities. Quantifying the influence of landscape metrics, namely topography and land use pattern, which encompass land use composition and landscape configuration, across different spatial and seasonal scales that reflect natural process and anthropogenic activities, is highly beneficial for water quality protection. In this study, we focused on investigating the effects of topography, landscape configuration and land use composition on water quality at different spatial scales, including 1-km buffer and sub-watershed, and seasonal scales, including wet and dry season, based on the monthly water quality data in 2016 of Dongting Lake in China. Multivariate statistical analysis of redundancy analysis and partial redundancy analysis was used to quantify the contributions of these factors under different scales. Our results showed that among the three environmental groups, topography made the greatest pure contribution to water quality, accounting for 11.4 to 30.9% of the variation. This was followed by landscape configuration, which accounted for 9.4 to 23.0%, and land use composition, which accounted for 5.9 to 15.7%. More specifically, water body made the greatest contribution to the water quality variation during dry season at both spatial scales, contributing 16.6 to 17.2% of the variation. In contrast, edge density was the primary interpreter of the variability in water quality during wet season at both spatial scales, accounting for 9.9 to 11.1% of the variation. The spatial variability in the influence of landscape metrics on water quality was not markedly distinct. However, these metrics have a minimal impact difference on water quality at the buffer scale and the sub-watershed scale. Moreover, the contribution of landscape configuration varied the most from the buffer to sub-watershed scales, indicating its importance for the spatial scale difference in water quality. The findings of this study offer useful insights into enhancing water quality through improved handling of landscape metrics., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Breast cancer is the most common cancer in women, and first-degree relatives (FDRs) of breast cancer patients have a significantly higher risk of developing breast cancer. However, the factors affecting breast cancer screening behavior of FDRs in China remain unclear., Objective: The aim of this study was to determine the social cognitive theory factors influencing screening behaviors of FDRs., Methods: A cross-sectional survey was conducted, and 430 FDRs were recruited. Data were collected using demographic information and self-reported questionnaire based on the social cognitive theory. The structural equation modeling method was used to analyze the influence of social cognitive factors on breast cancer screening behavior., Results: The model showed a good fit (goodness of fit = 0.462). Goal setting and self-regulation (β = 0.631, P < .001) and positive outcome expectation (β = 0.098, P = .042) were positively related to breast cancer screening behavior. Negative outcome expectation was negatively related to breast cancer screening behavior (β = -0.102, P = .024). In addition, positive outcome expectation, negative outcome expectation, and goal setting and self-regulation are mediators of self-efficacy (β = 0.475, P < .001) to breast cancer screening behavior., Conclusion: Goal setting and self-regulation are important influences on breast cancer screening behavior. The social cognitive theory is both applicable to and effective in explaining and predicting breast cancer screening behavior., Implications for Practice: Health professionals can develop appropriate intervention strategies based on the social cognitive theory among FDRs. It is necessary to focus on the people who influence women, such as spouses, mothers, or daughters., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background & Aims: Epidemiology of primary sclerosing cholangitis (PSC) is lacking in China. We aimed to estimate the period prevalence and depict the clinical features of PSC in China., Methods: We identified and included PSC cases between 2000 and 2023 from two sources: electronic medical records (EMR) and systematical literature retrieval (SLR). The period prevalence of PSC was estimated by the multiplier method. Rate ratios (RRs) for PSC prevalence in relation to macroeconomic indicators were calculated by the negative binomial regression model., Results: A total of 1358 PSC cases were retrieved from 299 hospitals (162 from EMR and 1196 from SLR). Males accounted for 55.7 % of the PSC cases and 25.7 % had concomitant inflammatory bowel disease (IBD). The estimated period prevalence of PSC from 2000 to 2023 was 2.36 (95 % CI: 1.82, 3.34) per 100,000. Males had a numerically higher PSC prevalence than females (2.56, 95 % CI: 1.97, 3.63 vs. 2.14, 95 % CI: 1.65, 3.04 per 100,000). The highest prevalence of PSC was in East China at 4.87 (95 % CI: 3.44, 7.18) per 100,000, followed by North China at 2.94 (95 % CI: 2.33, 3.74) per 100,000, and the lowest in South China at 0.92 (95 % CI: 0.66, 1.30) per 100,000. Regional per capita GDP (RR 1.65, 95 % CI: 1.03, 2.65) and healthcare expenditure (RR 1.94, 95 % CI: 1.13, 3.38) were identified to be associated with PSC prevalence., Conclusion: Our study showed the estimated PSC prevalence varied within China, but was generally lower than that in Western countries., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB). Methods: The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications. Results: A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines. Conclusion: The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.

Spinocerebellar ataxia (SCA) patients' reports of their own experiences are essential to the outcome evaluation in clinical trials. To better understand the health condition and well-being of ataxia population, Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia) was developed. The aim of our study was to culturally adapt the PROM-Ataxia into Chinese version and assess its correlation with canonical clinical assessments. We translated the PROM-Ataxia into Chinese following the ISPOR TCA Task Force guidelines and evaluated its correlation with measures of motor ataxia, non-ataxia signs, quality of life, and mental health in 92 Chinese SCA participants. Nearly all the participants found this questionnaire complete and intelligible but some items were found repetitive or ambiguous. The total score of PROM-Ataxia from stage 0 to stage 3 was 23.24 ± 18.53, 79.11 ± 40.45, 144.30 ± 41.30, and 176.20 ± 31.74, respectively (p < 0.0001). It was strongly correlated with the Scale for the Assessment and Rating of Ataxia (SARA) (r = 0.832, p < 0.0001). Physical and activities domain of PROM-Ataxia were correlated with measures of motor ataxia, quality of life, and psychological health while mental health domain was correlated with all the clinical assessments including inventory of non-ataxia signs and cognitive assessment. We translated the PROM-Ataxia into Chinese for the first time, which allows transnational comparability in future studies. Our study validated the responsiveness of PROM-Ataxia to established clinical measures in Chinese SCA patients and implied its potential to evaluate the therapeutic effect and optimize the sensitivity of changes in clinical outcome assessments., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Control of schistosomiasis japonica, endemic in Asia, including the Philippines, China, and Indonesia, is extremely challenging. Schistosoma japonicum is a highly pathogenic helminth parasite, with disease arising predominantly from an immune reaction to entrapped parasite eggs in tissues. Females of this species can generate 1000-2200 eggs per day, which is about 3- to 15-fold greater than the egg output of other schistosome species. Bovines (water buffalo and cattle) are the predominant definitive hosts and are estimated to generate up to 90% of parasite eggs released into the environment in rural endemic areas where these hosts and humans are present. Here, we highlight the necessity of developing veterinary transmission-blocking vaccines for bovines to better control the disease and review potential vaccine candidates. We also point out that the approach to producing efficacious transmission-blocking animal-based vaccines before moving on to human vaccines is crucial. This will result in effective and feasible public health outcomes in agreement with the One Health concept to achieve optimum health for people, animals, and the environment. Indeed, incorporating a veterinary-based transmission vaccine, coupled with interventions such as human mass drug administration, improved sanitation and hygiene, health education, and snail control, would be invaluable to eliminating zoonotic schistosomiasis.

Heavy-duty diesel trucks (HDDTs) have caused serious environmental pollution in China. Accurate estimation of their pollutant emission characteristics is essential to reduce emissions and associated environmental and public health impacts. To achieve sustainable development for transport emissions in Northeast China, we developed localized emission factors and a high-resolution emission inventory of HDDTs, based on on-board test, Guidebook and international vehicle emission (IVE) model. The results show that the total emissions of CO, NO, NO 2 , and PM from HDDTs in Northeast China in 2020 were 172.2 kt, 531.5 kt, 11.2 kt, and 921.4 t, respectively. In terms of spatial distribution, emissions decreased from the city center to the city fringe. Temporally, the NOx emission variation curves of different types of roads presented a "single-peak" emission characteristic, which was different from the peak of traffic flow. Three emission reduction scenarios are further developed in the paper. Scenario analysis shows that elimination of HDDTs that follow the old China III emission standard and installing tailpipe treatment devices are the most effective pollutant reduction measure. The reduction percentages for CO, NO, NO 2 , and PM ranged from 62.9 to 83.89%. The results of our study could inform policymakers to devise feasible strategies to reduce vehicle pollution in Northeast China., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

It is critical to determine the real-world performance of vaccines against coronavirus disease 2019 (COVID-19) so that appropriate treatments and policies can be implemented. There was a rapid wave of infections by the Omicron variant in Jilin Province (China) during spring 2022. We examined the effectiveness of inactivated vaccines against Omicron using real-world data from this epidemic. This retrospective case-case study of vaccine effectiveness (VE) examined infected patients who were quarantined and treated from April 16 to June 8, 2022 and responded to an electronic questionnaire. Data were analyzed by univariable and multivariable analyses. A total of 2968 cases with SARS-CoV-2 infections (asymptomatic: 1061, mild disease: 1763, pneumonia: 126, severe disease: 18) were enrolled in the study. Multivariable regression indicated that the risk for pneumonia or severe disease was greater in those who were older or had underlying diseases, but was less in those who received COVID-19 vaccines. Relative to no vaccination, VE against the composite of pneumonia and severe disease was significant for those who received 2 doses (60.1%, 95%CI: 40.0%, 73.5%) or 3 doses (68.1%, 95%CI: 44.6%, 81.7%), and VE was similar in the subgroups of males and females. However, VE against the composite of all three classes of symptomatic diseases was not significant overall, nor after stratification by sex. There was no statistical difference in the VE of vaccines from different manufacturers. The inactivated COVID-19 vaccines protected patients against pneumonia and severe disease from Omicron infection, and booster vaccination enhanced this effect.

Purpose: This study aimed to explore the internal determinants affecting patients' utilization of online medical services (OMS) based on the information-motivation-behavioral skills model from a behavioral perspective., Design: A cross-sectional study., Setting: This study was conducted in three medical institutions in Jiangsu Province, China., Subjects: 470 internet users were enrolled from patients who came to the outpatient clinics., Measures: A self-administered questionnaire with feasible reliability and validity was used to investigate the demographic characteristics and OMS utilization-related information, motivation, behavioral skills, intention, and behavior., Analysis: According to the constructed framework, structural equation modeling was used to test the relationships between those factors and OMS utilization behaviors., Results: All direct paths are established except the path between information and intention. Information and motivation positively affected OMS utilization behavior through behavioral skills and intention ( P < .001). Motivation and behavioral skills could positively influence OMS utilization behavior through intention ( P < .01). Motivation was found to be the largest predictor of OMS utilization behavior. Moreover, gender played a moderating role in the interpretation of the behavior., Conclusions: Interventions should be conducted regarding information, motivation, and behavioral skills to promote patients' use of OMS. At the same time, the impact of gender on intervention effectiveness should also be considered.

Birds are descended from non-avialan theropod dinosaurs of the Late Jurassic period, but the earliest phase of this evolutionary process remains unclear owing to the exceedingly sparse and spatio-temporally restricted fossil record 1-5 . Information about the early-diverging species along the avialan line is crucial to understand the evolution of the characteristic bird bauplan, and to reconcile phylogenetic controversies over the origin of birds 3,4 . Here we describe one of the stratigraphically youngest and geographically southernmost Jurassic avialans, Fujianvenator prodigiosus gen. et sp. nov., from the Tithonian age of China. This specimen exhibits an unusual set of morphological features that are shared with other stem avialans, troodontids and dromaeosaurids, showing the effects of evolutionary mosaicism in deep avialan phylogeny. F. prodigiosus is distinct from all other Mesozoic avialan and non-avialan theropods in having a particularly elongated hindlimb, suggestive of a terrestrial or wading lifestyle-in contrast with other early avialans, which exhibit morphological adaptations to arboreal or aerial environments. During our fieldwork in Zhenghe where F. prodigiosus was found, we discovered a diverse assemblage of vertebrates dominated by aquatic and semi-aquatic species, including teleosts, testudines and choristoderes. Using in situ radioisotopic dating and stratigraphic surveys, we were able to date the fossil-containing horizons in this locality-which we name the Zhenghe Fauna-to 148-150 million years ago. The diversity of the Zhenghe Fauna and its precise chronological framework will provide key insights into terrestrial ecosystems of the Late Jurassic., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Inequality of opportunity (IOp) stemming from social circumstances exists in outpatient service utilization for the multimorbid elderly in China. However, little is known regarding the magnitude of the IOp and its composition. Therefore, this study aims to measure the IOp in outpatient expenditure and provide potential pathways for policy reform by assessing the contribution of each circumstance., Methods: This study included 3527 elderly aged ≥ 65 years with multimorbidity from the Chinese Longitudinal Healthy Longevity Study conducted in 2017-2018. An ordinary least squares regression model was used to analyze the circumstance-influencing factors of outpatient expenditure. The parametric approach was performed to quantify the IOp in outpatient expenditure and the Shapley value decomposition method was employed to determine the contribution of each circumstance. By extracting heterogeneity in the residual of the circumstance-dependent equation of outpatient expenditure across circumstance groups divided based on cluster analysis, we captured the effect of unobserved circumstances., Results: Except for pension and distance to health facilities, all the associations between circumstance and outpatient expenditure were statistically significant. The inequality caused by circumstances accounted for 25.18% of the total inequality. The decomposition results revealed that the reimbursement rate contributed 82.92% of the IOp, followed by education duration (4.55%), household registration (3.21%), household income (3.18%), pension (1.49%), medical insurance (1.26%), physical labor (0.99%), unobserved circumstances (0.86%), distance to health facilities (0.83%) and region (0.71%)., Conclusions: The priority of policy enhancement is to effectively improve the outpatient reimbursement benefit for treating chronic diseases. Additional crucial actions include enhancing the health literacy of the multimorbid elderly to promote the shift from medical needs to demands and accelerating the construction of rural capacity for providing high-quality healthcare to the elderly with multimorbidity., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

We aim to investigate the impact of different clinical phases' definitions of chronic hepatitis B (CHB) infection on the profiles of grey zone, based on HBV guidelines set by the Chinese Society of Hepatology and Chinese Society of Infectious Diseases (CSH/CSID, 2022 version) and guidelines set by the American Association for the Study of Liver Diseases (AASLD, 2018 version). We retrospectively examined untreated CHB patients enrolled in the China Registry of Hepatitis B database. Patients' clinical phases were determined as per CSH/CSID and AASLD. Liver fibrosis was estimated by FIB-4 and/or APRI. Among 3462 CHB patients, 56.9% and 41.7% fell into the grey zone based on AASLD and CSH/CSID. Compared with grey zone patients as per AASLD, those under CSH/CSID guidelines showed lower levels of median ALT (26.0 vs. 37.0 U/L, p < 0.001), AST (25.0 vs. 29.4 U/L, p < 0.001) and APRI (0.3 vs. 0.4, p < 0.001), and lower rates of advanced fibrosis estimated by APRI (7.9% vs. 11.4% p = 0.001), but comparable rates by FIB-4 (13.0% vs. 14.1%, p = 0.389). With the stepwise lowering of ALT upper limits of normal (ULN) values from 50/40 U/L for males/females to 40/40 U/L, 35/25 U/L and 30/19 U/L, the proportions of grey zone patients as per CSH/CSID declined from 46.7% to 41.7%, 34.3% and 28.8%, respectively, whereas they remained stable (55.7%, 56.2%, 56.9% and 57.0%) as per AASLD. Compared with the AASLD guidelines, CSH/CSID guidelines leave fewer and less severe patients in the grey zone. Lowering ALT ULN values reduces the number of grey zone patients as per CSH/CSID, but not under AASLD guidelines.

Objectives: Anti-melanoma differentiation-associated gene 5 positive (anti-MDA5+) DM has a close relationship with rapidly progressive interstitial lung disease (RPILD) and is associated with high mortality. However, data regarding the time-dependent risk of RPILD and deaths during disease progression are limited. We conducted this study to investigate whether the risk of RPILD and death were time-dependent or not in anti-MDA5+ DM., Methods: We assessed a cohort of 272 patients with anti-MDA5+ DM. The clinical characteristics of patients with anti-MDA5+ were collected, and COX regression was used to analyse independent risk factors for RPILD and death. We also described changes in risk of RPILD and death over time and their potential clinical implications., Results: There were 272 anti-MDA5+ DM patients enrolled in this study. According to the multivariate cox regression analysis, short disease course, high CRP level, anti-Ro52 positive and anti-MDA5 titre (++∼+++) were independent risk factors of RPILD. High creatine kinase level, high CRP level and RPILD were independent risk factors for death, and >90% RPILD and 84% mortality occurred in the first 6 months after disease onset. Notably, the first 3 months is a particularly high-risk period, with 50% of RPILD and 46% of deaths occurring. Hazards regarding RPILD and mortality diminished over time during a median follow-up of 12 months., Conclusion: These results suggest significant, time-dependent changes in RPILD and mortality risk in anti-MDA5+ DM patients, providing a cut-off time window to estimate disease progression and poor prognosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The source region of the Yellow River (SRYR) is an important water conservation and farming area in China. Under the dual influence of the natural environment and external pressure, ecological patches in the region are becoming increasingly fragmented, and landscape connectivity is continuously declining, which directly affect the landscape patch pattern and SRYR sustainable development. In the SRYR, morphological spatial pattern analysis (MSPA) and landscape index methods were used to extract ecologically important sources. Based on the minimum cumulative resistance model (MCR), Linkage Mapper was used to generate a potential corridor, and then potential stepped stone patches were identified and extracted by the gravity model and betweenness centrality to build an optimal SRYR ecological network. The distribution of patches in the core area of the SRYR was fragmented, accounting for 80.53% of the total grassland area. The 10 ecological sources based on the landscape connectivity index and 15 important corridors identified based on the MCR model were mainly distributed in the central and eastern regions of the SRYR. Through betweenness centrality, 10 stepped stone patches were added, and 45 planned ecological corridors were obtained to optimize the SRYR ecological network and enhance east and west connectivity. Our research results can provide an important reference for the protection of the SRYR ecosystem, and have important guiding significance and practical value for ecological network construction in ecologically fragmented areas.

Wearable health devices (WHDs) have become increasingly advantageous in long-term health monitoring and patient management. However, most people have not yet benefited from such innovative technologies, and the willingness to accept WHDs and their influencing factors are still unclear. Based on two behavioral theories: the theory of planned behavior (TPB) and the diffusion of innovation (DOI), this study aims to explore the influencing factors of willingness to use WHDs in community residents from the perspective of both internal and external factors. A convenience sample of 407 community residents were recruited from three randomly selected Community Health Service Centers (CHSCs) in Nanjing, China, and were investigated with a self-developed questionnaires. The mean score of willingness to use WHDs was 17.00 (range 5-25). In the dimensions of TPB, perceived behavioral control (β = 1.979, p < 0.001) was the strongest influencing factor. Subjective norms (β = 1.457, p < 0.001) and attitudes (β = 0.651, p = 0.016) were also positively associated with willingness. In innovation characteristics of DOI, compatibility (β = 0.889, p < 0.001) and observability (β = 0.576, p = 0.003) had positive association with the willingness to wear a WHD. This study supports the applicability of the two behavioral theories to interpret the willingness to use WHDs in Chinese community residents. Compared with the innovative features of WHDs, individual cognitive factors were more critical predictors of willingness to use.

The land use and ecological risk patterns in Guilin, which is the only innovation demonstration zone under the National Sustainable Development Agenda in China with a focus on the sustainable use of natural resources, have changed significantly as a result of the combined impact of climate change and human activities, thus presenting challenges to the sustainable development of the local area. This research employs an ecological risk assessment model and spatial analysis techniques in order to analyze the spatial correlation between land use and ecological risk, and to evaluate the spatial and temporal evolution characteristics of ecological risk at the overall and county scales in Guilin. The results reveal the following: (1) A total of 1848.6 km 2 land types in Guilin have changed from 2000 to 2020, and construction land has gradually expanded from the central urban area to the suburbs with increasing internal stability each year. (2) The ecological risk level in Guilin showed a decreasing trend at the city scale, but some regions still showed an increasing trend at the county distribution scale. (3) The ecological risk value in Guilin has significant spatial correlation, and the spatial distribution showed a clustering effect, which was consistent with the spatial distribution of ecological risk class areas. The research results can provide a reference for ecological risk control and sustainable development of landscape resource cities.

Background: Unhealthy gestational weight gain is a modifiable risk factor for adverse maternal and child health. Appropriate and effective intervention strategies that focus on behavioral change or maintenance are critical in weight management during pregnancy. Our aim was to uncover the influencing factors and psychosocial mechanisms of gestational weight control behavior, and to construct a behavioral model suitable for intervention based on Information-Motivation-Behavioral skills (IMB) model., Methods: A sample of 559 pregnant women from a municipal maternal and child healthcare facility in Jiangsu Province, China was enrolled in this cross-sectional empirical study. Partial least square structural equation modelling was used to verify the hypothesized model, and post hoc analyses was used to test the effect of parity and pre-pregnancy BMI on the model., Results: The IMB model elements can predict gestational weight management (GWM) behavior well, with information being the most influential factor. As predicted, information affects GWM directly (β = 0.325, p < 0.05) and indirectly (β = 0.054, p < 0.05) through behavioral skills. Likewise, motivation has direct (β = 0.461, p < 0.05) effects on GWM, and has indirect (β = 0.071, p < 0.05) effects through behavioral skills. Behavioral skills have a direct impact (β = 0.154, p < 0.05). The model had a goodness of fit (GOF = 0.421) and was robust when tested in subgroups of different parity or pre-pregnancy BMI., Conclusion: Findings from this study supported the predictions of the IMB model for GWM behavior, and identified its modifiable determinants. The tested behavior model for GWM can serve as a new validated intervention strategy in weight management among pregnant women., (© 2023. The Author(s).)

Noncommunicable chronic diseases among the elderly population represent a significant economic burden in China. However, previous disease-related health cost studies lacked representation of older adults and comparability of the burden of multiple chronic diseases. The objective of this study was to determine the fraction of health care costs attributable to the 6 most prevalent chronic diseases and comorbidities in the sample of older adults. This study employed data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), with 3 waves in 2011, 2014, and 2018, and included 18 349 observations in total. Outpatient costs, inpatient costs, and total health care costs were included in this study. Based on a 2-part random effects model, the effect of chronic disease on health service utilization was first explored by constructing a dummy variable for whether or not to utilize health care, followed by estimation of attributable costs in the population with health care utilization. Among the older adults in the sample, hypertension, heart disease, cataracts, arthritis, stroke or Cerebrovascular disease (CVD) and chronic lung disease are the 6 most prevalent chronic conditions. The costs attributable to the 6 chronic diseases mentioned above were 36.00% of outpatient costs, 55.92% of inpatient costs, and 45.05% of total health care costs for older adults. Of these, heart disease, stroke or CVD, and chronic lung disease accounted for 22.11%, 13.24%, and 10.56% of total health care costs, respectively. Moreover, the proportion of health care costs attributable to chronic diseases was higher for older adults who were male, lived in urban areas, and had a lower level of education. The proportion of health care costs attributable to chronic diseases is substantial among older adults in China. Health care costs associated with chronic diseases can be decreased with well-targeted interventions and comprehensive access to health services., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Adherence to the use of child restraint system (CRS) can greatly reduce child casualties in road traffic accidents. This study aims to develop the behavior maintenance model of CRS use based on the health action process approach (HAPA) theory to explore the maintenance mechanisms, suggesting appropriate intervention strategies., Methods: Adopting the multi-stage stratified cluster random sampling method, a cross-sectional survey for guardians recruited from kindergarten and primary school was conducted using the questionnaire developed based on the HAPA theory in Nanjing, China, and 1135 valid samples were finally obtained. Rigorous analysis procedures of the partial least squares structural equation modeling (PLS-SEM) method were applied by using SmartPLS3.3.2 software., Results: The results confirmed that action self-efficacy ( β  = 0.479, P  < 0.001) and negative outcome expectancy ( β = -0.187, P  < 0.001) were valid predictors of intention in the non-intentional stage, intention ( β  = 0.488, P  < 0.001) and maintenance self-efficacy ( β  = 0.334, P  < 0.001) contributed significantly to action planning in the intentional stage, while action planning ( β  = 0.470,  P  < 0.001) and recovery self-efficacy ( β  = 0.256, P  < 0.001) jointly determined behavior maintenance in the action stage. It was also revealed that action planning fully mediated the relation between intention and behavior maintenance ( β  = 0.229, P  < 0.001)., Conclusion: Based on the above mechanisms, interventions aimed at the stages of non-intention, intention, and action should be designed and implemented, with the participation of the government, automobile dealers, and communities to promote the maintenance of improved CRS use behavior.

Objective: Hypothalamic dysfunction is characterized by complex aetiologies, multiple forms of onset and various clinical symptoms. This study aims to explore the clinical and metabolic characteristics of hypothalamic dysfunction in Chinese children and adolescents., Design: This study is a single-centre, retrospective study that covers patients from 1989 to 2019., Patients: We included 40 children and adolescents with hypothalamic dysfunction from our medical centre in Beijing, China., Results: Intracranial tumour (37.5%) was the most common aetiology of children and adolescents with hypothalamic dysfunction, especially germ cell tumours, hypopituitarism (82.5%), weight gain (72.5%) and central diabetes insipidus (70.0%) were the most common symptoms in these patients. Furthermore, serum alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, uric acid, total cholesterol, triglycerides and low-density lipoprotein cholesterol was significantly higher in hypothalamic dysfunction patients than sex- and age-matched controls and sex, age and body mass index (BMI)-matched controls (all p < 0.05). However, albumin and high-density lipoprotein cholesterol were lower (p< 0.05). Moreover, 95% (38/40) of the patients had metabolic diseases. In addition, the incidence of dyslipidaemia and hyperuricemia in children and adolescents with hypothalamic dysfunction was significantly higher than both sex- and age-matched controls and sex-, age- and BMI-matched controls (both p < 0.05) as well., Conclusions: Intracranial tumour was the most common aetiology in children and adolescents with hypothalamic dysfunction. In addition, these patients presented a worse metabolic profile on average than healthy patients., (© 2022 John Wiley & Sons Ltd.)

(1) Background: Research indicates that most elderly widows are at a high risk of experiencing negative psychological symptoms. It is common for elderly women in rural and remote areas to live alone without family support to cope with stress due to the mass rural-to-urban migration of China’s youth labor force. Such a situation further worsens their psychological health and well-being. However, the prevalence of and risk factors associated with negative psychological symptoms (loneliness, depression, and anxiety) among remote elderly widows living alone in China are currently unclear; (2) Methods: A cross-sectional study was conducted in Hunan Province, China. The loneliness was assessed through the University of California at Los Angeles Loneliness Scale (ULS-8). The depression and anxiety were assessed with the Short Form Geriatric Depression Scale (GDS-15) and Generalized Anxiety Disorder Scale (GAD-7), respectively. The Chi-square test and correlation analysis were conducted to identify factors associated with negative psychological symptoms. Logistic regression was performed to predict risk and protective factors contributing to loneliness, depression, and anxiety symptoms. The significance level was set as p < 0.05; (3) Results: A total of 271 remote elderly widows living alone were enrolled in the present study. Additionally, 234 valid questionnaires were returned (valid response rate = 86.3%). The prevalence of loneliness, depression and anxiety was 8.1%, 44.0%, and 16.7%, respectively. Acute or chronic medical conditions, marital happiness, being the primary caregiver before widowhood and anticipating the death of the spouse differed significantly in the distribution of negative psychological symptoms. Logistic regression analysis predicted that participants who were satisfied with their marriage had a lower likelihood to experience loneliness, depression, and anxiety (p < 0.05). Being the spouse’s primary caregiver before widowhood was more likely to have symptoms of loneliness (p < 0.01). Those with various acute or chronic medical conditions were more likely to suffer from depression (p < 0.01); (4) Conclusions: Remote elderly widows living alone in China are prone to loneliness, depression, and anxiety symptoms. Being the primary caregiver before widowhood and having many acute or chronic medical conditions are risk factors for loneliness and depression, respectively. Marital happiness is the protective factor against negative psychological symptoms. To accomplish the goal of equitable access to mental health care in China, evidence-based policy and resource development to support psycho-social interventions that prevent and manage negative psychological symptoms for remote elderly widows living alone are urgently needed.

China has been piloting the catastrophic medical insurance (CMI) program since 2012 and rolled it out nationally in 2016 to reduce the incidence of catastrophic health expenditure among Chinese residents. Few studies have been conducted to determine its effect on healthcare expenditures, particularly among the elderly. The purpose of this study is to examine the effect of CMI on healthcare expenditures among China's elderly population. The data for this study were derived from 4 waves of the Chinese Longitudinal Healthy Longevity Survey, which included 344 and 1199 individuals in the treatment and control groups, respectively. To examine the effect of CMI on healthcare expenditures among the elderly, we used difference-in-differences and fixed-effects models. Additionally, a heterogeneity analysis was used to examine the differences in the impact of CMI on different groups. Finally, we confirmed the robustness of the results using robustness and placebo tests. CMI increased total health and out-of-pocket expenditures significantly, as well as inpatient and corresponding out-of-pocket expenditures. The reassults of the heterogeneity analysis indicated that CMI had a greater impact on elderly residents of rural areas. Economic burden protection has been enhanced for low-income groups and patients with serious diseases over the last two years. Our research indicated that CMI can promote the use of inpatient medical services for the elderly to a certain extent. Targeted measures such as expanding the CMI compensation list, establishing a more precise compensation scheme, and specific diseases associated with high healthcare expenditures can be considered in the practice of CMI implementation.

Purpose: To investigate the relationship between fibrinogen-like protein 1 (FGL-1) concentrations and various metabolic characteristics in patients with polycystic ovary syndrome (PCOS) and explore whether FGL-1 could be a predictive biomarker for PCOS., Methods: This case-control study included 136 patients with PCOS and 34 normal controls recruited in the Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital between May 2017 and June 2021. Anthropometric characteristics, metabolic parameters, and reproductive hormones were collected. Serum FGL-1 measurement was conducted using enzyme-linked immunosorbent assay (ELISA) kits., Results: Serum FGL-1 concentrations were higher in patients with PCOS than in control subjects in body mass index (BMI) subgroups, insulin resistance (IR) subgroups, and hepatic function subgroups, respectively. Serum FGL-1 concentrations were significantly associated with BMI, glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), high-density lipoprotein cholesterol (HDL-c), and serum uric acid (SUA) in all individuals. The receiver operating characteristic (ROC) curve analysis revealed that the best cutoff value for FGL-1 levels to predict PCOS was 21.02 ng/ml with a sensitivity of 74.3% and a specificity of 70.6%. Both univariate and multiple logistic regressions indicated that the odds ratio (OR) for PCOS significantly increased in the subjects with high levels of FGL-1., Conclusion: In our study, FGL-1 was associated with serum aminotransferase and various metabolic indexes. Moreover, the high risk of PCOS was independently associated with the increased FGL-1 levels, which suggested that FGL-1 could be a predictive biomarker for PCOS., (© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

An aerobic, yellow-pigmented and Gram-stain-negative strain, designated as O-35  T , was isolated from a tidal flat sediment collected in Dangjiang Town, the southern China. Colonies of strain O-35  T were circular with 0.5-1.0 mm in diameter, convex and smooth. Cells of strain O-35  T were coccoid-shaped, non-spore forming, non-motile and the strain could reduce nitrate. Growth of strain O-35  T was observed at 15-40 °C (optimum 30 °C), at pH 6.0-9.5 (optimum 7.5-8.0) and in 0.5-5.0% NaCl (optimum 2%, w/v). Strain O-35  T showed 16S rRNA gene sequence identities of 97.3-97.5% with Sphingomicrobium lutaoense CC-TBT-3  T and Sphingomicrobium aestuariivivum AH-M8 T , higher than the rest of Sphingomicrobium type strains. Phylogenetic trees based on the 16S rRNA gene and the core-genome sequences demonstrated that strain O-35  T was affiliated within the genus Sphingomicrobium. Overall genome relatedness index calculations revealed that strain O-35  T had < 75.8% of average nucleotide identity and < 19.2% of digital DNA-DNA hybridization values with Sphingomicrobium type strains. The sole isoprenoid quinone was ubiquinone-10. The major fatty acids (> 10%) were summed feature 8, summed feature 3, C 16:0 and C 18:1 2-OH. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, sphingoglycolipid, two unidentified glycolipids, one unidentified lipid and one unidentified phospholipid. On the basis of the phenotypic, chemotaxonomic and genomic properties, strain O-35  T represents a novel species in the genus Sphingomicrobium, for which the name Sphingomicrobium nitratireducens sp. nov. is proposed. The type strain is O-35  T (= KCTC 92308  T  = MCCC 1K07589 T )., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

An undesirable psychological state may deteriorate individual's weight management-related behaviors. This study aims to see if ineffective weight control measures were linked to depressive symptoms during pregnancy. We conducted a cross-sectional questionnaire survey of 784 pregnant women and collected information on sociodemographic factors, maternal characteristics, depression, and weight management activities throughout pregnancy (exercise management, dietary management, self-monitoring regulation, and management objectives). About 17.5% of pregnant women exhibited depressive symptoms. The mean score on dietary management was upper-middle, exercise management and self-monitoring regulation were medium, and management objectives were lower-middle. Multivariable linear regression analysis revealed that pregnant women with depressive symptoms had lower levels of exercise management (β = -1.585, p = 0.005), dietary management (adjusted β = -0.984, p = 0.002), and management objectives (adjusted β = -0.726, p = 0.009). However, there was no significant relationship between depressive symptoms and pregnant women's self-monitoring regulating behavior ( p > 0.05). The findings indicated the inverse association between depressive symptoms and gestational weight management behaviors. These results offer important indications for pregnancy weight management professionals by highlighting the need for mental health interventions for pregnant women experiencing depressive symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Peng, Zhou, Ge, Zhou, Walker and You.)

Background and Aims: Immunoglobulin G4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition. The aim of the present study was to characterize the clinical features and therapeutic response of patients with IgG4-RD and identify risk factors for disease relapse., Methods: We collected baseline data of eligible patients with IgG4-RD and analyzed clinical features by interview and review of medical records. The patients who received glucocorticoids (GC) therapy with at least 3 months follow-up were used to characterize the therapeutic response and identify risk factors for relapse., Result: Totally 127 IgG4-RD patients, including 92 males and 35 females, were enrolled in the present study. The median age of onset was 63.0 years, ranging from 23 to 86. The pancreas, bile duct and lymph nodes were the most frequently involved organs. The serum IgG4 level was elevated in 94.5% of the patients and was correlated with the number of organs involved. Patients classified as head and neck limited group were more likely to be female. Compared to Mikulicz syndrome and systemic involvement group, pancreato-hepatobiliary group had higher aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, bilirubin and lower IgG4 level. Mikulicz syndrome and systemic involvement group had the highest IgG4-RD RI score, IgG level. Among 92 patients who received medical therapy with at least 3 months follow-up, 76 received GC alone or in combination with immunomodulator (IM) and 16 patients did not take GC. 74 out of the 76 patients (97.3%) achieved remission, with 59 of them remained in remission and 15 of them relapsed. Whereas 16 patients did not take GC, among them, 6 patients achieved remission with one relapsed. On multivariate analysis, higher initial score of ACR/EULAR IgG4-RD Classification Criteria and GC withdrawal were independent predictors for relapse., Conclusion: Four phenotypes of IgG4-RD showed different demographic and serological features. GC + IM therapy was safe and effective and might protect patients from relapse. The independent risk factors of relapse were GC withdrawal and higher score of ACR/EULAR IgG4-RD Classification Criteria., (© 2022. The Author(s).)

Background: The national essential public health service (NEPHS) has been in operation for more than a decade. Numerous studies examined the utilization of NEPHS by migrants and the factors that influence it, but few examined the effect of NEPHS awareness and utilization on the health of inhabitants, particularly migrants. The purpose of this study is to ascertain the level of awareness and utilization of NEPHS, as well as to examine their health-improving effects on migrants., Methods: Based on the data from the 2017 China Migrants Dynamic Survey, linear probability model, ordered logit model and the propensity score matching methods were employed to investigate impact of awareness and utilization of NEPHS on the health among Chinese migrants. Mediating effect model were used to identify the mechanism of the impact of NEPHS on health., Results: The findings indicated that migrants' awareness and utilization of NEPHS are still insufficient. After adjusting for other factors, the study discovered that increased awareness and use of NEPHS had a beneficial influence on migrants' self-rated health. Further heterogeneity analysis revealed significant disparities in the health consequences of NEPHS awareness and utilization across subgroups. The effect of increased awareness and usage of NEPHS on health is stronger for middle-aged and elderly people, women, and low-educated migrants with urban household registration. The estimated results of the mediating effect model supported the mechanism that increased NEPHS awareness among the floating population could encourage its utilization and further improve the floating population's health., Conclusions: Given that migrants' NEPHS utilization is still low and that NEPHS utilization has a positive effect on health, some targeted strategies, such as a variety of new media communication methods, health education related to occupational disease and tuberculosis prevention, and targeted NEPHS projects for specific groups, such as men, young and middle-aged groups, those with a high level of education, and rural migrants, should be conducted to improve the health of migrants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Zhang, You and Wu.)

The booster vaccination of COVID-19 is being implemented in most parts of the world. This study used behavioral psychology to investigate the predictors of parents' intentions regarding the COVID-19 booster vaccination for their children. This is a cross-sectional study with a self-designed questionnaire based on two behavioral theories-protective motivation theory (PMT) and theory of planned behavior (TPB). A stratified multi-stage sampling procedure was conducted in Nanjing, China, and multivariable regression analyses were applied to examine the parents' intentions. The intention rate was 87.3%. The response efficacy (ORa = 2.238, 95% CI: 1.360-3.682) and response cost (ORa = 0.484, 95% CI: 0.319-0.732) in the PMT, were significant psychological predictors of parents' intentions, and so were the attitude (ORa = 2.619, 95% CI: 1.480-4.636) and behavioral control (ORa = 3.743, 95% CI: 2.165-6.471) in the TPB. The findings of crucial independent predictors in the PMT and TPB constructs inform the evidence-based formulation and implementation of strategies for booster vaccination in children.

Backgrounds: Hereditary hemochromatosis (HH) is mainly caused by homozygous p.C282Y mutations in HFE in the Caucasians. We recently reported non-HFE mutations constitute the major cause of HH in Chinese. However, there is still a relatively high proportion of cases with primary iron overload from unexplained causes. We aimed to explore novel non-HFE mutations in Chinese patients with primary iron overload., Methods: Whole exome sequence was conducted to screen mutations in novel HH-related genes in the 9 cases with unexplained primary iron overload. Then the representative candidate genes were screened for mutations in another cohort of 18 HH cases. The biological function of the selected genes and variants were analyzed in vitro., Results: Whole exome sequencing of 9 cases with unexplained primary iron overload identified 42 missense variants in 40 genes associated with iron metabolism pathway genes such as UBE2O p.K689R and PCSK7 p.R711W. Subsequent Sanger sequencing of the UBE2O and PCSK7 genes in the 27 cases with primary iron overload identified p.K689R in UBE2O, p.R711W and p.V143F in PCSK7 at frequency of 2/27,1/27 and 2/27 respectively. In vitro siRNA interference of UBE2O and PCSK7 resulted in down-regulated HAMP mRNA expression. Adenovirus generation of UBE2O p.K689R in cell lines resulted in increased expression of SMAD6 and SMAD7 and downregulation of p-SMAD1/5 and HAMP expression, and the reduction of hepcidin level., Conclusions: Our study identified a series of novel candidate non-HFE mutations in Chinese patients with HH. These may provide insights into the genetic basis of unexplained primary iron overload., (© 2022. The Author(s).)

Cancer is a growing global health threat. Examining the determinants of cancer incidence can benefit for cancer treatment and prevention. Farmland transfer relates to the risk factors of esophageal cancer including environmental pollution, services access, and habits. This study characterizes the associations between farmland transfer and esophageal cancer incidence rate (ECI) that integrate mediated effect of pollution-related agricultural input intensity in Xiaoshan District, China. The state-space model is employed to quantify the relationships among farmland transfer, pollution-related agricultural input intensity, and ECI. The results showed that (1) Total effects of the proportion of transferred farmland (TFA) area cause a reduction in the ECI. Besides, the total positive effects of the proportion of transferred farmland cultivated non-grain crop (NGC) and proportion of farmland transferred to non-farmer users (NFU) show a downward trend. (2) The raise of TFA can result in the reduction of chemical fertilizer use intensity. Meanwhile, the raise of NGC and NFU can result in the growth of pollution-related agricultural input intensity. But these increasing effects generally show a downward trend. (3) Increasing chemical fertilizer use intensity and pesticide use intensity results in the rise of esophageal cancer incidence rate as a whole. (4) In general, farmland transfer has positive direct effects on esophageal cancer incidence rate. (5) The average proportions of mediated effects in all state-space models are larger than 10%. These findings can raise land reform policy designers' awareness of the risk of public health since the land transfer markets are emerging rapidly in land reform in many developing countries to improve agricultural production., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The mutations in modifier genes may contribute to some inherited diseases including Wilson disease (WD). This study was designed to identify potential modifier genes that contribute to WD. A total of 10 WD patients with single or no heterozygous ATP7B mutations were recruited for whole-exome sequencing (WES). Five hundred and thirteen candidate genes, of which the genetic variants present in at least two patients, were identified. In order to clarify which proteins might be involved in copper transfer or metabolism processes, the isobaric tags for relative and absolute quantitation (iTRAQ) was performed to identify the differentially expressed proteins between normal and CuSO4-treated cell lines. Thirteen genes/proteins were identified by both WES and iTRAQ, indicating that disease-causing variants of these genes may actually contribute to the aberrant copper ion accumulation. Additionally, the c.86C > T (p.S29L) mutation in the SLC31A2 gene (coding CTR2) has a relative higher frequency in our cohort of WD patients (6/191) than reported (0.0024 in gnomAD database) in our healthy donors (0/109), and CTR2S29L leads to increased intracellular Cu concentration and Cu-induced apoptosis in cultured cell lines. In conclusion, the WES and iTRAQ approaches successfully identified several disease-causing variants in potential modifier genes that may be involved in the WD phenotype., (© The Author(s) 2022. Published by Oxford University Press.)

The ecological security pattern is an important way to coordinate the contradiction between regional economic development and ecological protection and is conducive to promoting regional sustainable development. This study examines Guangxi, a karst region in China. The ecosystem service function and ecological environment sensitivity were both selected to evaluate the ecological conservation importance, and based on the results of the ecological conservation importance evaluation, suitable patches were selected as ecological sources. Meanwhile, resistance factors were selected from both natural factors and human activities to construct a comprehensive resistance surface, circuit theory was used to identify ecological corridors, ecological pinch points, and ecological barrier points, and ecological protection suggestions were then proposed. The results show that there are 50 patches of ecological sources in Guangxi, with a total area of 60,556.99 km 2 ; 115 ecological corridors, with the longest corridor reaching 194.97 km; 301 ecological pinch points, whose spatial distribution is fragmented; and 286 ecological barrier points, most of which are concentrated in the central part of Guangxi. The results of this study provide a reference for the construction of ecological security patterns and ecological conservation in developing countries and karst areas.

Purpose: This study aimed to explore the psychological cognitive factors of weight management during pregnancy based on protective motivation theory (PMT)., Design: Cross-sectional study., Setting: Participants were recruited at the Maternal and Child Health Hospital of Changzhou City, Jiangsu Province, China., Sample: A sample of 533 pregnant women was enrolled in the study., Measures: Measures was a self-design questionnaire, comprising of demographics, cognition of weight management during pregnancy, and weight management behavior during pregnancy., Analysis: Structural equation modeling was used to examine the weight management's cognitive factors, path relationships, and the influence of maternal characteristics., Results: Self-efficacy cognition could promote gestational weight management behavior (b = .22, P < .001), but response cost cognition hindered gestational weight management (b = -.21, P < .001). Parity moderated pregnant women's self-efficacy cognition (diff b = .24, P < .01), where the self-efficacy of nullipara promoted weight management behaviors, but the self-efficacy of multipara had no significant effect. Also, the response cost factors stably existed in primipara and multipara groups, with multipara, being positively affected by response efficacy ( b = .15, P < .05)., Conclusion: Findings highlight the need for psychological and cognitive interventions. Intervention strategies that focus on enabling women to correctly understand response cost and make an active response, improve self-efficacy cognition especially among primipara, and strengthening multipara's response efficacy among pregnant are required.

Environmental deterioration in urbanizing areas increases the risks of sudden death as well as chronic, infectious, and psychological diseases. Quantifying health-related physical environment can assess the health risk of urban residents. This study uses an integrated evaluation method to simulate the health-related physical environment in the four dimensions of acoustic, wind, thermal, and landscape. According to the case study of one university campus in an urbanizing area in China, results show that (1) areas with unqualified equivalent A sound levels are generally the sports area, green square 1 and laboratory areas, and residents who stay in these areas for a long time suffer the risks of hearing loss and mental stress. (2) The windless area ratio of teaching area 1 and dormitory area 4 is larger than 20%, and respiratory health risks increase because these areas relate to relatively wind discomfort. (3) The high-temperature zone ratio of sports area and green square 2 is larger than 50%, and heatstroke risks increase since these areas relate with low thermal comfort. (4) The overall landscape perception level of dormitories and dining areas is lower than that of the teaching area, and it can cause anxiety and irritability. (5) The sports area has the lowest average overall score of the health-related physical environment among all functional areas, followed by laboratory areas. These findings indicate that the proposed model and method can be valuable tools for the pre-evaluation and optimization of urban planning. It can reduce the health risks of residents in urbanizing areas and can benefit residents' health and urban sustainable development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Wu, Qiu, Wang, Yao, Li, You, Zhang, Xia and Guo.)

Inappropriate gestational weight gain has become a public health concern that threatens maternal and child health. Pregnant women's ability to manage their weight during pregnancy directly impacts their weight gain. In this study, we integrated the protection motivation theory and the information-motivation-behavioral skills model to develop an integrative theoretical model suitable for pregnancy weight management and reveal significant explainable factors of weight management behaviors during pregnancy. Based on a cross-sectional survey of 550 pregnant women from Jiangsu province, we came up with our findings. The results showed that several factors influenced pregnancy weight management behavior. According to the research, information, self-efficacy, response costs, and behavioral skills were significantly associated with weight management behaviors during pregnancy, while behavioral skills were also significant mediators of information, self-efficacy, and behavior. Furthermore, the information related to pregnancy weight management had the biggest impact on weight management behavior during pregnancy. The results of the model fit were acceptable and the integrative model could explain 30.6% of the variance of weight management behavior during pregnancy, which implies that the integrative theoretical model can effectively explain and predict weight management behaviors during pregnancy. Our study provides practical implications for the integrative model in improving pregnancy weight management behavior and offers a theoretical base for the weight management of pregnant women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ge, Zhao, Peng, Walker, Yang, Zhou, Wang, Zhang, Zhou and You.)

Due to ecological environmental fragility and soil erosion in Guangxi, studies of landscape patterns and associated ecological risks are needed to guide sustainable land development and ecologically sensitive land management. This study assesses dynamic spatial and temporal change patterns in land use and ecological risks based on 30 m land-use data, analyzes spatial correlations with ecological risks, and explores natural and socio-economic factor impacts on ecological risks. The results reveal: (1) A rapid and sizeable construction land increase in Guangxi from 2000 to 2018 associated mainly with loss of woodland and grassland. (2) Guangxi had the highest number of arable land patches from 2000 to 2018, and the distribution tended to be fragmented; moreover, the construction land gradually expanded outward from concentrated areas to form larger aggregates with increasing internal stability each year. (3) Guangxi ecological risk levels were low, low-medium, and medium, with significantly different spatial distributions observed for areas possessing different ecological risk levels. Regional ecological risk gradually decreased from the middle Guangxi regions to the surrounding areas and was positively correlated with spatial distribution. (4) Socio-economic factor impacts on ecological risk exceeded natural factor impacts. These results provide guidance toward achieving ecologically sensitive regional land-use management and ecological risk reduction and control, it can also provide a reference for ecological risk research in other similar regions in the world.

Introduction: Excessive gestational weight gain poses a significant threat to maternal and child health. The healthy behaviour theory has been increasingly applied to weight management during pregnancy, but research is still insufficient. The successful application of the protection motivation theory (PMT) and the information-motivation-behavioural skills (IMB) model in the field of healthy behaviour laid the foundation for this intervention study. The overall aim of this study is to test the effectiveness of interventions based on the behaviour model integrated with the PMT and IMB model (PMT-IMB model) on weight management and provide feasible methods for weight management during pregnancy., Methods and Analysis: This prospective, single-centre, randomised controlled trial involves two steps. First, based on the PMT-IMB model, evaluation tools and intervention materials will be developed. Second, more than 800 women in the first trimester of pregnancy will be randomly assigned to two groups and will be followed until 1 week after delivery. The control group will receive standardised antenatal care (ANC), whereas the experimental group will receive both standardised ANC and interventions based on the PMT-IMB model. After three surveys (at enrolment, at 28 weeks of gestation, and on the day of hospitalisation for delivery), primary outcomes (scores of the subscales of the PMT-IMB model, scores of the pregnancy weight management strategy scale, and gestational weight gain) and secondary outcomes (pregnancy outcomes and pregnancy complications) will be obtained. Differences in outcomes between the two groups will be analysed to evaluate the effectiveness of the intervention., Ethics and Dissemination: The study protocol has been approved by the ethics committee of Nanjing Medical University. All participants will sign an informed consent form prior to enrolment. The findings of the study will be published in peer-reviewed journals and presented at conferences., Trial Registration Number: ChiCTR2100043231., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aim: Autoantibody production are the main risk factors for inflammation of rheumatoid arthritis (RA). This study aimed to investigate differences in B lymphocyte subsets (native B, memory B, and plasmablasts) and several cytokines in RA patients and their correlation with the clinical parameters., Methods: In total, 81 RA patients (active RA and inactive RA) and 40 healthy subjects were recruited between September 2018 and October 2020. The distribution of B lymphocyte subsets in peripheral blood samples was measured via flow cytometry and the plasma cytokines were detected by enzyme linked immunosorbent assay. The receiver operating characteristic curve (ROC) was used to evaluate the value of each index for RA diagnosis and activity prediction., Results: The percentages of native B and memory B cells in RA patients did not differ significantly from the percentages of those in healthy controls. However, the percentage of plasmablasts in active RA patients was significantly higher compared with healthy subjects and inactive RA patients. The percentage of plasmablasts was significantly related to C reaction protein. ROC curve analysis showed that when the best cutoff value of plasmablasts/B cell was 1.08%, the area under the curve (AUC) for diagnosing RA was 0.831 (95% CI 0.748 ~ 0.915), the specificity was 91.4%, and the sensitivity was 67.5%. The AUC predicted by the combination of plasmablast and anti-CCP for active RA patients was 0.760, which was higher than that of plasmablast and anti-CCP., Conclusion: In conclusion, the percentage of plasmablast varies among RA patients in different stages. The percentage of plasmablasts can be used as an early diagnosis marker for RA., (© 2021. The Author(s).)

Background: The outbreak of COVID-19 in China occurred around the Chinese New Year (January 25, 2020), and infections decreased continuously afterward. General adoption of preventive measures during the Chinese New Year period was crucial in driving the decline. It is imperative to investigate preventive behaviors among Chinese university students, who could have spread COVID-19 when travelling home during the Chinese New Year break., Objective: In this study, we investigated levels of COVID-19-related personal measures undertaken during the 7-day Chinese New Year holidays by university students in China, and associated COVID-19-related cognitive factors., Methods: A cross-sectional anonymous web-based survey was conducted during the period from February 1 to 10, 2020. Data from 23,863 students (from 26 universities, 16 cities, 13 provincial-level regions) about personal measures (frequent face-mask wearing, frequent handwashing, frequent home staying, and an indicator that combined the 3 behaviors) were analyzed (overall response rate 70%). Multilevel multiple logistic regression analysis was performed., Results: Only 28.0% of respondents (6684/23,863) had left home for >4 hours, and 49.3% (11,757/23,863) had never left home during the 7-day Chinese New Year period; 79.7% (19,026/23,863) always used face-masks in public areas. The frequency of handwashing with soap was relatively low (6424/23,863, 26.9% for >5 times/day); 72.4% (17,282/23,863) had frequently undertaken ≥2 of these 3 measures. COVID-19-related cognitive factors (perceptions on modes of transmission, permanent bodily damage, efficacy of personal or governmental preventive measures, nonavailability of vaccines and treatments) were significantly associated with preventive measures. Associations with frequent face-mask wearing were stronger than those with frequent home staying., Conclusions: University students had strong behavioral responses during the very early phase of the COVID-19 outbreak. Levels of personal prevention, especially frequent home staying and face-mask wearing, were high. Health promotion may modify cognitive factors. Some structural factors (eg, social distancing policy) might explain why the frequency of home staying was higher than that of handwashing. Other populations might have behaved similarly; however, such data were not available to us., (©Joseph Lau, Yanqiu Yu, Meiqi Xin, Rui She, Sitong Luo, Lijuan Li, Suhua Wang, Le Ma, Fangbiao Tao, Jianxin Zhang, Junfeng Zhao, Dongsheng Hu, Liping Li, Guohua Zhang, Jing Gu, Danhua Lin, Hongmei Wang, Yong Cai, Zhaofen Wang, Hua You, Guoqing Hu, COVID-19 University Student Research Group. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 07.10.2021.)

Objective: Pulmonary arterial hypertension (PAH) is a life-threatening complication of systemic lupus erythematosus (SLE). However, there is no algorithm to identify those at high risk. This study was undertaken to develop a prediction model for PAH in patients with lupus that provides individualized risk estimates., Methods: A multicenter, longitudinal cohort study was undertaken from January 2003 to January 2020. The study collected data on 3,624 consecutively evaluated patients diagnosed as having SLE. The diagnosis of PAH was confirmed by right-sided heart catheterization. Cox proportional hazards regression and least absolute shrinkage and selection operator were used to fit the model. Model discrimination, calibration, and decision curve analysis were performed for validation., Results: Ninety-two lupus patients (2.54%) developed PAH during a median follow-up of 4.84 years (interquartile range 2.42-8.84). The final prediction model included 5 clinical variables (acute/subacute cutaneous lupus, arthritis, renal disorder, thrombocytopenia, and interstitial lung disease) and 3 autoantibodies (anti-RNP, anti-Ro/SSA and anti-La/SSB). A 10-year PAH probability-predictive nomogram was established. The model was internally validated by Harrell's concordance index (0.78), the Brier score (0.03), and a satisfactory calibration curve. According to the net benefit and predicted probability thresholds, we recommend annual screening in high-risk (>4.62%) lupus patients., Conclusion: We developed a risk stratification model using routine clinical assessments. This new tool may effectively predict the future risk of PAH in patients with SLE., (© 2021, American College of Rheumatology.)

Background: Hereditary hemochromatosis (HH) is widely recognized and clinical manifestations of hemochromatosis-related (HFE-related) HH is well studied in European populations. Less is known about the clinical and laboratory characteristics of non-HFE related HH in Asian population. We aimed to explore the relationship between genotype and clinical phenotype in Chinese patients with non-HFE related hereditary hemochromatosis., Methods: Peripheral blood samples and clinical data of patients with primary iron overload were collected from the China Registry of Genetic/Metabolic Liver Diseases. Sanger sequencing was performed in cases with primary iron overload, for 5 known HH related genes (HFE, HJV, HAMP, TFR2 and SLC40A1) and 2 novel iron homeostasis-related genes (DENND3 and SUGP2). The correlation of genotype and clinical phenotype in these patients was analyzed., Results: Of the 32 patients with primary iron overload (23 were males and 9 were females), non-HFE variants were detected in 31 (31/32, 97%), including 8 pathogenic variants in HJV, 7 pathogenic variants in SLC40A1, 8 likely pathogenic variants in SUGP2 and 5 likely pathogenic variants in DENND3 cases. Among these 31 cases, 4 cases harbored homozygous variants, 2 cases harbored homozygous + heterozygous variants, 19 cases harbored heterozygous or combined heterozygous variants, and 6 cases harbored no any damaging variants. None of investigated cases carried damaging HAMP and TFR2 variants were found. 8 cases were classified as type 2A HH and 6 cases as type 4 HH, 10 cases as non-classical genotype, and 6 cases had no pathogenic variants from 31 cases. During the statistical analysis, we excluded one case (SLC40A1 IVS3 + 10delGTT + SUGP2 p. R639Q(homo)) with difficulty in grouping due to combined damaging variants. Cases with type 2A HH have an earlier age at diagnosis (p = 0.007). The iron index of cases in type 2A HH and type 4 HH was higher than that in other groups (p = 0.01). Arthropathy was relatively rare in all groups. None of cases with type 2A HH developed cirrhosis. Cirrhosis and diabetes are more prevalent in type 4 HH. The incidence of cirrhosis (p = 0.011), cardiac involvement (p = 0.042), diabetes (p = 0.035) and hypogonadism (p = 0.020) was statistically significant in the four groups. However, due to the limited sample size, the pairwise comparison showed no significant difference., Conclusions: This is the first comprehensive analysis about the gene variant spectrum and phenotypic aspects of non-HFE HH in China. The results will be useful to the identification, diagnosis and management of HH in China., (© 2021. The Author(s).)

Objective: Although specific anti-phospholipid antibodies (aPLs) have been used in the diagnosis of the antiphospholipid syndrome (APS) for years, new biomarkers are required to increase its diagnostic and risk-predictive power. This study aimed to explore the value of several non-criteria aPLs in a Chinese cohort., Methods: A total of 312 subjects, namely, 100 patients diagnosed with primary APS, 51 with APS secondary to SLE, 71 with SLE, and 90 healthy controls, were recruited. Serum anticardiolipin (aCL) IgG/IgM/IgA, anti-β2-glycoprotein I (aβ2GPI) IgG/IgM/IgA, anti-phosphatidylserine/prothrombin antibodies (aPS/PT) IgG/IgM, and anti-annexin A5 antibodies (aAnxV) IgG/IgM were tested using ELISA kits., Results: Of the total number of patients, 30.46% and 6.62% with APS were positive for aCL or aβ2GPI IgA, respectively, while 39.07% and 24.50% were positive for aAnxV or aPS/PT for at least one antibody (IgG or IgM). The addition test of aCL IgA and aAnxV IgM assists in identifying seronegative APS patients, and IgG aPS/PT was linked to stroke., Conclusion: Detection of aCL IgA, aβ2GPI IgA, aAnxV IgG/M, and aPS/PT IgG/M as a biomarker provides additive value in APS diagnosis and would help in risk prediction for APS patients in medical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hu, Li, Xie, You, Jiang, Shi, Qi, Zhao, Wang, Tian, Li, Zhao and Zeng.)

Online medical services (OMS) have become increasingly advantageous, but there are still several barriers to utilization among patients. This study aims to explore the factors influencing OMS utilization (OMSU) for patients in micro-, meso-, and macrosystems based on socioecological theory (SET) and from the perspective of the information-motivation-behavioral skills (IMB) model. We selected 1065 participants through multistage stratified cluster random sampling in Jiangsu, China. In microsystems, information and behavioral skills were positively associated with intention (β = 0.84; β = 3.21) and actual utilization (OR = 1.69; OR = 1.69). Education level (β = 0.83) and personal motivation (β = 1.68) were positively related to intention. Chronic diseases (OR = 2.03) had a positive relationship with actual use. In mesosystems, recommendations from people around the patients (β = 1.14; OR = 1.99), provision of OMS in the nearest primary medical facility (β = 0.98; OR = 3.60), and provision of instructional information by medical institutions (β = 1.01; OR = 1.65) were related to OMSU. The average monthly household income (β = 0.54) was related to intention. Patients who had information about the OMSU experiences of people around them (OR = 1.73) correlated with actual utilization. In macrosystems, the social medical insurance type (OR = 0.66) was associated with OMSU. This study supports the applicability of the SET and IMB model to interpret patients' OMSU., (© 2021 New York Academy of Sciences.)

Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

Objective: Osteonecrosis (ON), which can lead to physical disability, is a common complication of systemic lupus erythematosus (SLE). The purpose of this study was to determine the prevalence of ON and identify possible risk factors in Chinese SLE patients., Methods: SLE patients who fulfilled the 1997 American College of Rheumatology SLE classification criteria were recruited from the Peking Union Medical College Hospital. The chi-square test (χ 2 test) and multivariate regression analyses were used to evaluate risk factors. The Cox proportional-hazards model was used to construct the survival curves and estimate the simultaneous effects of prognostic factors on survival., Results: We consecutively enrolled 1,158 patients, of which 88 patients (7.6%) developed ON. Among ON patients, 57.1% of patients had isolated femoral head necrosis and 42.9% had multiple joint involvement. The mean age of ON patients (24.62 ± 8.89 years) was significantly younger than SLE patients without ON (27.23 ± 10.16 years, p  = 0.09). The ON group presented with a much longer disease course (10.68 ± 5.97 years, p  < 0.001) and increased incidence of arthritis, kidney, and central nervous system (CNS) involvement (65.9% [ p  < 0.05], 57.6% [ p  < 0.05], and 16.5% [ p  < 0.05], respectively, in the ON group). ON patients were more likely to be treated with glucocorticoid (GC) and to receive a high dose of prednisolone at the initial stage of SLE ( p  < 0.05). The percentage of patients who received hydroxychloroquine was much higher in the control group ( p  < 0.001). Cox regression analysis suggested that CNS involvement and GC therapy were two independent risk factors for ON in SLE patients. The presence of anti-phospholipid antibodies (aPLs) was a risk factor for multiple joint necrosis (odds ratio: 6.28, p  = 0.009)., Conclusions: ON remains a serious and irreversible complication in SLE. In addition to glucocorticoid therapy, we found that CNS system involvement was a risk factor for ON, while the administration of hydroxychloroquine was a protective factor. The clinical characteristics of multiple site ON patients were distinct from isolated femoral head necrosis patients. The presence of aPLs was a risk factor for multiple site osteonecrosis.