Fetal genetically determined birth weight plays a causal role in earlier puberty timing: evidence from human genetic studies.

STUDY QUESTION: Does fetal genetically determined birth weight associate with the timing of puberty? SUMMARY ANSWER: Lower fetal genetically determined birth weight was causally associated with an earlier onset of puberty, independent of the indirect effects of the maternal intrauterine environment. WHAT IS KNOWN ALREADY: Previous Mendelian randomization (MR) studies have indicated a potential causal link between birth weight, childhood BMI, and the onset of puberty. However, they did not distinguish between genetic variants that have a direct impact on birth weight through the fetal genome (referred to as fetal genetic effects) and those that influence birth weight indirectly by affecting the intrauterine environment (known as maternal genetic effects). It is crucial to emphasize that previous studies were limited because they did not account for the potential bias caused by unaddressed correlations between maternal and fetal genetic effects. Additionally, the proportion of birth weight variation explained by the fetal genome is considerably larger than that of the maternal genome. STUDY DESIGN, SIZE, DURATION: We performed two-sample MR analyses to investigate the causal effect of fetal genetically determined birth weight on puberty timing using summary data from large-scale genome-wide association studies (GWASs) in individuals of European ancestry. PARTICIPANTS/MATERIALS, SETTING, METHODS: From the two most recent GWASs specifically centered on birth weight, which included 406 063 individuals and 423 683 individuals (63 365 trios) respectively, we identified genetic variants associated with fetal genetically determined birth weight, while adjusting for maternal genetic effects. We identified genetic variants associated with childhood BMI from an independent GWAS involving 21 309 European participants. On this basis, we employed two-sample MR techniques to examine the possible causal effects of fetal genetically determined birth weight on puberty timing using a large-scale GWAS of puberty timing (including 179 117 females of European ancestry). Furthermore, we employed advanced analytical methods, specifically MR mediation and MR-Cluster, to enhance our comprehension of the causal relationship between birth weight determined by fetal genetics and the timing of puberty. We also explored the pathways through which childhood BMI might act as a mediator in this relationship. MAIN RESULTS AND THE ROLE OF CHANCE: In the univariable MR analysis, a one SD decrease in fetal genetically determined birth weight (∼ 418 g) was associated with a 0.16 (95% CI [0.07-0.26]) years earlier onset of puberty. The multivariable MR analysis including fetal genetically determined birth weight and childhood BMI in relation to puberty timing provided compelling evidence that birth weight had a direct influence on the timing of puberty. Lower birth weight (one SD) was associated with an earlier onset of puberty, with a difference of 0.23 (95% CI [0.05-0.42]) years. We found little evidence to support a mediating role of childhood BMI between birth weight and puberty timing (-0.07 years, 95% CI [-0.20 to 0.06]). LIMITATIONS, REASONS FOR CAUTION: Our data came from European ancestry populations, which may restrict the generalizability of our results to other populations. Moreover, our analysis could not investigate potential non-linear relationships between birth weight and puberty timing due to limitations in genetic summary data. WIDER IMPLICATIONS OF THE FINDINGS: Findings from this study suggested that low birth weight, determined by the fetal genome, contributes to early puberty, and offered supporting evidence to enhance comprehension of the fetal origins of disease hypothesis. STUDY FUNDING/COMPETING INTEREST(S): C.Z. was funded by the Sichuan Province Science and Technology Program [grant number 2021JDR0189]. J.Z. was supported by grants from the National Natural Science Foundation of China [grant number 82373588]. No other authors declare any sources of funding. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

The effect of gradually lifting the two-child policy on demographic changes in China.

Low-fertility rate has been a common problem in many industrialized countries. To reverse the declining trend of new births, Chinese government gradually lifted its restrictions on the number of births per family, allowing for a household to have no more than two children. Little is known about the additional births or population increase contributed by the gradual relaxation of birth restrictions. To fill this gap, this quasi-experimental design study including data from 124 regions used the synthetic control method and controlled interrupted time series analysis to evaluate the differences in birth rates and rates of natural population increase between China and its synthetic control following implementation of the two-child policy from 2011 to 2020. A total of 123 regions were included in the control pool. Data collected during 1990-2010 were used to identify the synthetic China for each study outcome. The mean rate differences of birth rates and rates of natural increase between China and synthetic China after two-child policy implementation were 1.16 per 1000 population and 1.02 per 1000, respectively. These rate differences were distinguished from variation due to chance (one-sided pseudo-P-values: P for birth rates = 0.047, P for rates of natural increase = 0.020). However, there were statistically significant annual reductions in the pre-post trend of birth rates and rates of natural increase compared with those of controls of <0.340 per 1000 population per year [P = 0.007, 95% CI = (-0.584, -0.096)] and <0.274 per 1000 per year [P = 0.028, 95% CI = (-0.518, -0.031)]. The results suggested that lifting birth restrictions had a short-term effect on the increase in birth rates and rates of natural population increase. However, birth policy with lifting birth restrictions alone may not have sustained impact on population growth in the long run.

Bloqueadores de los canales de calcio frente a otras clases de fármacos para la hipertensión: una revisión Cochrane / Calcium channel blockers versus other classes of drugs for hypertension: a Cochrane review

¿Cuál es el objetivo de esta revisión? En esta primera actualización de una revisión publicada en 2010. Se pretendía averiguar si los bloqueadores de los canales del calcio (BCC) pueden prevenir eventos cardiovasculares perjudiciales, como el ictus, el infarto de miocardio y la insuficiencia cardiaca, en comparación con otros antihipertensivos (hipotensores) utilizados en personas con presión arterial elevada (hipertensión). Fundamento. La disminución adecuada de la presión arterial elevada en personas con hipertensión puede reducir la cantidad de complicaciones importantes de la hipertensión, como el ictus, el infarto de miocardio, la insuficiencia cardiaca congestiva e incluso la muerte. Los BCC se utilizan como medicación de primera línea para reducir la presión arterial, pero se ha debatido si esta es la mejor forma de reducir los eventos cardiovasculares nocivos. Fecha de búsqueda. La evidencia está actualizada hasta el 1 de septiembre de 2020. Características del estudio. Se encontraron 23 estudios relevantes realizados en Europa, Norteamérica, Oceanía, Israel y Japón. Los estudios compararon el tratamiento con tratamiento con BCC frente al tratamiento con otras clases de fármacos hipotensores en personas con hipertensión e incluyeron 153.849 participantes. El seguimiento de los participantes en los ensayos osciló entre 2 y 5,3 años. Resultados clave. No hubo diferencias en las muertes por todas las causas entre los BCC y otros fármacos hipotensores. Los diuréticos probablemente reducen los eventos cardiovasculares totales y la insuficiencia cardiaca congestiva más que los BCC. Los BCC probablemente reducen los eventos cardiovasculares totales más que los bloqueadores beta... (AU)

Bloqueadores de los canales de calcio frente a otras clases de fármacos para la hipertensión: una revisión Cochrane / Calcium channel blockers versus other classes of drugs for hypertension: a Cochrane review

¿Cuál es el objetivo de esta revisión? En esta primera actualización de una revisión publicada en 2010. Se pretendía averiguar si los bloqueadores de los canales del calcio (BCC) pueden prevenir eventos cardiovasculares perjudiciales, como el ictus, el infarto de miocardio y la insuficiencia cardiaca, en comparación con otros antihipertensivos (hipotensores) utilizados en personas con presión arterial elevada (hipertensión). Fundamento. La disminución adecuada de la presión arterial elevada en personas con hipertensión puede reducir la cantidad de complicaciones importantes de la hipertensión, como el ictus, el infarto de miocardio, la insuficiencia cardiaca congestiva e incluso la muerte. Los BCC se utilizan como medicación de primera línea para reducir la presión arterial, pero se ha debatido si esta es la mejor forma de reducir los eventos cardiovasculares nocivos. Fecha de búsqueda. La evidencia está actualizada hasta el 1 de septiembre de 2020. Características del estudio. Se encontraron 23 estudios relevantes realizados en Europa, Norteamérica, Oceanía, Israel y Japón. Los estudios compararon el tratamiento con tratamiento con BCC frente al tratamiento con otras clases de fármacos hipotensores en personas con hipertensión e incluyeron 153.849 participantes. El seguimiento de los participantes en los ensayos osciló entre 2 y 5,3 años. Resultados clave. No hubo diferencias en las muertes por todas las causas entre los BCC y otros fármacos hipotensores. Los diuréticos probablemente reducen los eventos cardiovasculares totales y la insuficiencia cardiaca congestiva más que los BCC. Los BCC probablemente reducen los eventos cardiovasculares totales más que los bloqueadores beta... (AU)

Incidence trends of primary liver cancer in different geographical regions of China from 1978 to 2012 and projections to 2032: An age-period-cohort analysis.

China accounted for 45.3% of new cases of primary liver cancer (PLC) worldwide in 2020. While variations in PLC incidence between different regions of China and decreasing incidence in overall China have been reported, incidence patterns have not been thoroughly explored by region. We examined the nearly status and temporal trends of PLC incidence in different geographical regions in China and project future trends. The age-standardized incidence rate (ASR) was estimated for 1978 to 2012 by different geographical regions and gender in China. Age-period-cohort model was adopted to evaluate age and birth cohort effects on the temporal trend of five registries of China (Hong Kong, Shanghai, Jiashan, Harbin and Zhongshan), Bayesian age-period-cohort model was adopted to project future trends for 2013 to 2032. PLC incidence in China exhibits marked geographical disparity, with the highest incidence in Southwest China, and gender differences being particularly pronounced in South China. While other registries exhibited decreasing trend, Zhongshan exhibited an increasing trend, with the cohort effect showing a marked upward trend for females born in 1916 to 1949 and males born in 1916 to 1962. During 2013 to 2032, the ASR appears to increase by 86.9% for men and 40.0% for women in Zhongshan, while the remaining registries will decline by around 50%. Since the high incidence of hepatitis B virus infection in early birth cohort, recent rise of nonviral risk factors and the severe aging of the Chinese population, it may be critical to tailor future prevention and control strategies for PLC to the distribution of risk factors in different geographical regions.

Genetically predicted plasma levels of amino acids and metabolic dysfunction-associated fatty liver disease risk: a Mendelian randomization study.

BACKGROUND: Emerging metabolomics-based studies suggested links between amino acid metabolism and metabolic dysfunction-associated fatty liver disease (MAFLD) risk; however, whether there exists an aetiological role of amino acid metabolism in MAFLD development remains unknown. The aim of the present study was to assess the causal relationship between circulating levels of amino acids and MAFLD risk. METHODS: We conducted a two-sample Mendelian randomization (MR) analysis using summary-level data from genome-wide association studies (GWAS) to evaluate the causal relationship between genetically predicted circulating levels of amino acids and the risk of MAFLD. In the discovery MR analysis, we used data from the largest MAFLD GWAS (8434 cases and 770,180 controls), while in the replication MR analysis, we used data from a GWAS on MAFLD (1483 cases and 17,781 controls) where MAFLD cases were diagnosed using liver biopsy. We used Wald ratios or inverse variance-weighted (IVW) methods in the MR main analysis and weighted median and MR-Egger regression analyses in sensitivity analyses. Furthermore, we performed a conservative MR analysis by restricting genetic instruments to those directly involved in amino acid metabolism pathways. RESULTS: We found that genetically predicted higher alanine (OR = 1.43, 95% CI 1.13-1.81) and lower glutamine (OR = 0.83, 95% CI 0.73-0.96) levels were associated with a higher risk of developing MAFLD based on the results from the MR main and conservative analysis. The results from MR sensitivity analyses and complementary analysis using liver proton density fat fraction as a continuous outcome proxying for MAFLD supported the main findings. CONCLUSIONS: Novel causal metabolites related to MAFLD development were uncovered through MR analysis, suggesting future potential for evaluating these metabolites as targets for MAFLD prevention or treatment.

The initial treatment in convulsive status epilepticus in China: A multi-center observational study.

OBJECTIVE: To investigate the initial treatment of patients with convulsive status epilepticus (CSE) in a resource-limited region of China, and to discuss the difference of in-hospital outcomes and economic costs between those with guideline-recommended initial treatment and those without. METHODS: In this retrospective study, we screened adult patients discharged with the diagnosis of CSE in four centers in west China. Individuals with different exposure to the initial drug were divided into benzodiazepine (BDZ) and non-BDZ group for outcome comparison. The primary outcomes were seizure control, and the ratio of patients who developed refractory SE. The secondary outcomes included in-hospital mortality, the modified Rankin Scale (mRS) score at discharge, in-hospital respiratory support rate, length, and cost of the stay. RESULTS: Three-hundred and thirteen patients (127, 40.6% were women) with CSE were included. The median age was 43 (range 16-92). There were 152 (48.6%) patients initially treated with BDZ. Among the 36 who received midazolam as initial treatment, twenty-six received an insufficient dose. The other 116 (76.3%) patients in the BDZ group chose diazepam as initial treatment. Fifteen of them (12.9%) were treated underdose. In the non-BDZ group (161, 51.4%), antiseizure medications (ASMs) and/or coma-induced drugs were used as initial treatment. Among those initially administrated ASMs, intramuscular phenobarbital (38,37.6%) and valproate (46, 52.3%) were most frequently seen. There was a significant difference in the time latency to initial treatment and etiology between BDZ and non-BDZ group. The non-BDZ group reported a higher cessation rate after initial treatment compared to the BDZ group (P = 0.012). No significant difference in other primary and secondary outcomes. SIGNIFICANCE: Non-adherence and underdosing of the initial treatment of SE were common in China. However, the non-BDZ group showed a better seizure control rate. The effect came from early aggressive medication, that is, the combination of ASMs and anesthesia. Non-BDZ group was not inferior to BDZs in terms of seizure control, the occurrence of in-hospital death, and poor outcome at discharge. More robust evidence is needed in developing settings when choosing the initial treatment.

A baseline sarcopenia index based on creatinine/cystatin C for the prediction of stroke recurrence and mortality in older survivors of first ischemic strokes.

Objective: Older adults individuals have a higher risk of stroke recurrence, leading to high mortality and disability rates, which, in turn, hinders the achievement of healthy aging. This study aimed to assess the utility of a baseline sarcopenia index (SI) based on serum creatinine (Cr)/cystatin C (CysC) as a prognostic marker for the risk of stroke recurrence and mortality in first-ever ischemic stroke older survivors (ISOS). Materials and methods: Data were obtained from an ischemic stroke cohort study. The baseline information was collected from medical records and face-to-face interviews with patients admitted between January 2010 and June 2016. Follow-up information was obtained from telephone interviews every 3 months to determine stroke recurrence and survival status. The SI was calculated from the Cr and CysC values in the medical records as Cr/CysC × 100. Using the first quantile of the SI as the cut-off value, the study participants were divided into the low muscle-mass group (low SI) and the high muscle-mass group (high SI). Cox regression analysis was used to assess the association between SI and recurrence and mortality. Results: A total of 415 first-ever ISOS were enrolled, including 242 (58.31%) male and 173 (41.69%) female participants. In the high-SI group, the relapse and mortality rates were lower than those in the low-SI group (relapse: 20.58% vs. 30.77%; mortality:13.5% vs. 29.81%). After adjusting for confounding factors, the high-SI group was found to have a lower risk of relapse and mortality than the low-SI group (relapse: HR = 0.571; mortality: HR = 0.294). Conclusion: The SI was predictive of the long-term prognosis of IS recurrence and mortality in first-ever ISOS. After discharge, in addition to conventional medication, it is recommended that patients with low SI values actively receive treatment for sarcopenia to reduce the risk of stroke recurrence and mortality and promote healthy aging.

The predictive performance of artificial intelligence on the outcome of stroke: a systematic review and meta-analysis.

Objectives: This study aimed to assess the accuracy of artificial intelligence (AI) models in predicting the prognosis of stroke. Methods: We searched PubMed, Embase, and Web of Science databases to identify studies using AI for acute stroke prognosis prediction from the database inception to February 2023. Selected studies were designed cohorts and had complete data. We used the Quality Assessment of Diagnostic Accuracy Studies tool to assess the qualities and bias of included studies and used a random-effects model to summarize and analyze the data. We used the area under curve (AUC) as an indicator of the predictive accuracy of AI models. Results: We retrieved a total of 1,241 publications and finally included seven studies. There was a low risk of bias and no significant heterogeneity in the final seven studies. The total pooled AUC under the fixed-effects model was 0.872 with a 95% CI of (0.862-0.881). The DL subgroup showed its AUC of 0.888 (95%CI 0.872-0.904). The LR subgroup showed its AUC 0.852 (95%CI 0.835-0.869). The RF subgroup showed its AUC 0.863 (95%CI 0.845-0.882). The SVM subgroup showed its AUC 0.905 (95%CI 0.857-0.952). The Xgboost subgroup showed its AUC 0.905 (95%CI 0.805-1.000). Conclusion: The accuracy of AI models in predicting the outcomes of ischemic stroke is good from our study. It could be an assisting tool for physicians in judging the outcomes of stroke patients. With the update of AI algorithms and the use of big data, further AI predictive models will perform better.

Trajectories of post-stroke quality of life and long-term prognosis: Results from an eleven-year prospective study.

PURPOSE: The relationship between quality of life (QoL) and long-term prognosis in stroke patients is still unclear. We explored physical and mental QoL trajectories during the first six months after stroke and determined the associations between trajectories and long-term prognosis in patients with first-ever ischemic stroke. METHODS: Included were 733 participants from a prospective study. QoL was assessed with the 12-item Short Form Survey (SF-12) at baseline, 3 and 6 months. Patients' prognoses (stroke recurrence and death) were identified from 2010 to 2021. The latent class growth model (LCGM) was used to identify distinct trajectories of physical and mental QoL measured over the first 6 months. We employed the Cox model or Fine-Gray model for prognoses to examine the associations between QoL trajectories and prognosis. RESULTS: Five trajectories of physical QoL and five trajectories of mental QoL were identified. For physical QoL of the Poor-Improved, and Moderate-Impaired trajectory versus Moderate-Improved trajectory, the hazard ratio (HR) for death was 2.39 (1.14 to 5.02), and 2.03(0.93 to 4.44); the HR for recurrence was 1.56 (0.83 to 2.94) and 2.33 (1.28 to 4.24). For mental QoL of the Moderate-Impaired trajectory versus the Moderate-Improved trajectory, the HR for death was 2.48 (1.21 to 5.07). The results were robust in the sensitivity analysis. CONCLUSION: QoL during the first six months after ischemic stroke can be categorized into distinct groups. Change in QoL was associated with long-term survival. Secondary prevention of recurrent strokes might rely more on improving patients' physical QoL.

AMIGO2 attenuates innate cisplatin sensitivity by suppression of GSDME-conferred pyroptosis in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer. Cisplatin is commonly used in the treatment of many malignant tumours including NSCLC. The innate drug sensitivity greatly affects the clinical efficacy of cisplatin-based chemotherapy. As a plasma membrane adhesion molecule, amphoterin-induced gene and ORF-2 (AMIGO2) initially identified as a neurite outgrowth factor has been recently found to play a crucial role in cancer occurrence and progression. However, it is still unclear whether AMIGO2 is involved in innate cisplatin sensitivity. In the present study, we provided the in vitro and in vivo evidences indicating that the alteration of AMIGO2 expression triggered changes of innate cisplatin sensitivity as well as cisplatin-induced pyroptosis in NSCLC. Further results revealed that AMIGO2 might inhibit cisplatin-induced activation of (caspase-8 and caspase-9)/caspase-3 via stimulating PDK1/Akt (T308) signalling axis, resulting in suppression of GSDME cleavage and the subsequent cell pyroptosis, thereby decreasing the sensitivity of NSCLC cells to cisplatin treatment. The results provided a new insight that AMIGO2 regulated the innate cisplatin sensitivity of NSCLC through GSDME-mediated pyroptosis.

Association between post-stroke smoking and stroke recurrence in first-ever ischemic stroke survivors: based on a 10-year prospective cohort.

BACKGROUND: Whether smoking is a risk factor for ischemic stroke (IS) recurrence in IS survivors is still uncovered, and evidences are sparse. Meanwhile, an add-on effect of clopidogrel was observed in myocardial infarction patients who smoked, but whether the paradox exists in IS patients is still unsolved. The objectives of this study are to explore the association between smoking behavior after index stroke and IS recurrence and to explore whether the paradox exists. METHODS: A prospective cohort of first-ever IS patients was conducted between 2010 and 2019. The prognosis and smoking features of enrolled patients were obtained via telephone follow-up every 3 months. Fine-gray model with interaction terms was applied to measure the relationships between stroke recurrence and smoking behaviors after index stroke and to explore the add-on effect of clopidogrel in smoking patients. RESULTS: There were 171 (24.26%) recurrences and 129 (18.30%) deaths during follow-up in 705 enrolled IS patients. One hundred forty-six (20.71%) patients smoked after index stroke. The hazard ratios (HRs) and 95% confidence intervals (CIs) of interaction terms between antiplatelet drug and follow-up smoking (smoking status and daily smoking amount) were 1.092 (95% CI: 0.524, 2.276) and 0.985 (95% CI: 0.941, 1.031), respectively. A significantly higher risk of recurrence was observed in patients with a higher daily smoking amount during follow-up (per cigarette), with HR being 1.027 (95% CI: 1.003, 1.052). CONCLUSIONS: Smoking could elevate the risk of IS recurrence, and IS survivor should be advised to quit or smoke less. Add-on effect of clopidogrel may not exist in smoking strokers taking clopidogrel.

Specific changes and clinical significance of plasma D-dimer during pregnancy and puerperium: a prospective study.

BACKGROUND: Pregnant and puerperal women are high-risk populations for developing venous thromboembolism (VTE). Plasma D-dimer (D-D) is of good value in the diagnosis of exclusion of VTE in the nonpregnant population. Since there is no consensus reference range of plasma D-D applicable to pregnant and puerperal women, the application of plasma D-D is limited. To investigate the change characteristics and the reference range of plasma D-D levels during pregnancy and puerperium and to explore the pregnancy- and childbirth-related factors affecting plasma D-D levels and the diagnostic efficacy of plasma D-D for excluding VTE during early puerperium after caesarean section. METHODS: A prospective cohort study was conducted with 514 pregnant and puerperal women (cohort 1), and 29 puerperal women developed VTE 24-48 h after caesarean section (cohort 2). In cohort 1, the effects of the pregnancy- and childbirth-related factors on the plasma D-D levels were analyzed by comparing the differences in plasma D-D levels between different groups and between different subgroups. The 95th percentiles were calculated to establish the unilateral upper limits of the plasma D-D levels. The plasma D-D levels at 24-48 h postpartum were compared between normal singleton pregnant and puerperal women in cohort 2 and women from the cesarean section subgroup in cohort 1, binary logistic analysis was used to analyze the relevance between plasma D-D level and the risk of VTE developing 24-48 h after caesarean section, and a receiver operating characteristic (ROC) curve was used to assess the diagnostic efficacy of plasma D-D for excluding VTE during early puerperium after caesarean section. RESULTS: The 95% reference ranges of plasma D-D levels in the normal singleton pregnancy group were ≤ 1.01 mg/L in the first trimester, ≤ 3.17 mg/L in the second trimester, ≤ 5.35 mg/L in the third trimester, ≤ 5.47 mg/L at 24-48 h postpartum, and ≤ 0.66 mg/L at 42 days postpartum. The plasma D-D levels of the normal twin pregnancy group were significantly higher than those of the normal singleton pregnancy group during pregnancy (P < 0.05), the plasma D-D levels of the GDM group in the third trimester were significantly higher than those of the normal singleton pregnancy group (P < 0.05). The plasma D-D levels of the advanced age subgroup at 24-48 h postpartum were significantly higher than those of the nonadvanced age subgroup (P < 0.05), and the plasma D-D levels of the caesarean section subgroup at 24-48 h postpartum were significantly higher than those of the vaginal delivery subgroup (P < 0.05). The plasma D-D level was significantly correlated with the risk of VTE developing at 24-48 h after caesarean section (OR = 2.252, 95% CI: 1.611-3.149). The optimal cut-off value of plasma D-D for the diagnosis of exclusion of VTE during early puerperium after caesarean section was 3.24 mg/L. The negative predictive value for the diagnosis of exclusion of VTE was 96.1%, and the area under the curve (AUC) was 0.816, P < 0.001. CONCLUSIONS: The thresholds of plasma D-D levels in normal singleton pregnancy and parturient women were higher than those of nonpregnant women. Plasma D-D had good value in the diagnosis of exclusion of VTE occurring during early puerperium after caesarean section. Further studies are needed to validate these reference ranges and assess the effects of pregnancy- and childbirth-related factors on plasma D-D levels and the diagnostic efficacy of plasma D-D for excluding VTE during pregnancy and puerperium.

The hepato-ovarian axis: genetic evidence for a causal association between non-alcoholic fatty liver disease and polycystic ovary syndrome.

BACKGROUND: Recent studies found associations between non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS), but the causal nature of this association is still uncertain. METHODS: We performed a bidirectional two-sample Mendelian randomization (MR) analysis to test for the causal association between NAFLD and PCOS using data from a large-scale biopsy-confirmed NAFLD genome-wide association study (GWAS) (1483 cases and 17,781 controls) and PCOS GWAS (10,074 cases and 103,164 controls) in European ancestries. Data from glycemic-related traits GWAS (in up to 200,622 individuals) and sex hormones GWAS (in 189,473 women) in the UK Biobank (UKB) were used in the MR mediation analysis to assess potential mediating roles of these molecules in the causal pathway between NAFLD and PCOS. Replication analysis was conducted using two independent datasets from NAFLD and PCOS GWASs in the UKB and a meta-analysis of data from FinnGen and the Estonian Biobank, respectively. A linkage disequilibrium score regression was conducted to assess genetic correlations between NAFLD, PCOS, glycemic-related traits, and sex hormones using full summary statistics. RESULTS: Individuals with higher genetic liability to NAFLD were more likely to develop PCOS (OR per one-unit log odds increase in NAFLD: 1.10, 95% CI: 1.02-1.18; P = 0.013). Indirect causal effects of NAFLD on PCOS via fasting insulin only (OR: 1.02, 95% CI: 1.01-1.03; P = 0.004) and further a suggestive indirect causal effect via fasting insulin in concert with androgen levels were revealed in MR mediation analyses. However, the conditional F statistics of NAFLD and fasting insulin were less than 10, suggesting likely weak instrument bias in the MVMR and MR mediation analyses. CONCLUSIONS: Our study suggests that genetically predicted NAFLD was associated with a higher risk of developing PCOS but less evidence for vice versa. Fasting insulin and sex hormones might mediate the link between NAFLD and PCOS.

Cost-effectiveness of two screening strategies based on Chinese diabetes risk score for pre-diabetes in China.

Objective: Studies have shown that screening for pre-diabetes mellitus (pre-DM) is essential to prevent type 2 diabetes mellitus (T2DM). This study evaluates the cost-effectiveness of two screening strategies that apply the Chinese Diabetes Risk Score (CDRS) to screen for pre-DM in China. Methods: A Markov microsimulation model was conducted from a social perspective, and the input parameters were obtained from published literature or publicly available data. Two screening strategies for pre-DM based on CDRS were built and compared with the control group to determine the cost-effective strategy. The screening strategy of the control group was screening for pre-DM by fasting plasma glucose (FPG) test in adults undergoing annual health examination and no screening in adults without an annual health examination (status quo). Two screening strategies were strategy 1: screening for pre-DM using CDRS in all adults (including with or without an annual health examination); and strategy 2: supplemental self-screening for pre-DM using CDRS in adults without an annual health examination, based on the status quo. We focus on the cumulative prevalence of T2DM and the incremental cost-effectiveness ratio which signifies the cost per case of T2DM prevented. We also evaluated the cost-effectiveness from the health system perspective. One-way and probabilistic sensitivity analyses were conducted to verify the robustness of the results. Results: The costs a case of T2DM prevented for strategy 1 compared with the control group and strategy 2 were $299.67 (95% CI 298.88, 300.46) and $385.89 (95% CI 381.58, 390.20), respectively. In addition, compared with the control group, the cost of strategy 2 to prevent a case of T2DM was $272.23 (95% CI 271.50, 272.96). Conclusions: Screening for pre-DM using CDRS in all adults was the most cost-effective health policy. We suggest that medical institutions replace FPG with CDRS for pre-DM screening; at the same time, self-screening for pre-DM using CDRS is widely promoted among adults without an annual health examination. There were still some disputes about how CDRS is included in the health examination projects, so strategy 2 should be considered as an alternative screening strategy. Findings provide a reference for the application of the CDRS in pre-DM screening and contribute to T2DM prevention.

[Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for Predicting Preeclampsia During Pregnancy].

Objective: To investigate the changes of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in women with normal pregnancy women and pregnant women with preeclampsia (PE) and the value of using NLR and PLR in the first trimester to predict PE. Methods: We retrospectively collected the clinical data of 485 pregnant women (97 had PE and 388 were of normal pregnancy) who were admitted to West China Second University Hospital and had their babies delivered there between January 1 and December 31, 2016 and 30 healthy women who were not pregnant and who had physical examination at the hospital over the same period. The subjects' NLR and PLR were calculated and compared. Logistic regression analysis was done to study the risk factors of PE, and the receiver operating characteristic curves were used to assess the value of using NLR and PLR in the first trimester to predict PE. Results: There was no significant difference in NLR or PLR between the PE group and the normal pregnancy group in the first, second and third trimesters. Compared with that of the normal non-pregnant group, the NLR of the PE group and the normal pregnancy group started to rise in the first trimester, reached the maximum in the second trimester, and decreased in the third trimester; PLR started to decrease in the second trimester and reached the lowest level in the third trimester, exhibiting significant differences ( P<0.05). In the three trimesters, NLR and PLR were not associated with the severity of PE, maternal age, or pre-pregnancy BMI. The predictive model combining factors including pre-pregnancy obesity, advanced maternal age, and nulliparity showed an area under the curve ( AUC) of 0.84 for predicting PE. When NLR in the first trimester or PLR in the first trimester were added to the combined model of pre-pregnancy obesity, advanced maternal age, and nulliparity, the AUC subsequently derived were both 0.85. Conclusion: NLR and PLR are not independent influencing factors of PE and cannot improve the predictive value for PE.

Examining the dimensionality, reliability, and invariance of the Chinese version of the Resilience Scale-14: A multicenter cross-sectional survey in Chinese junior nurses.

Background: This study aimed to present the psychometric properties (dimensionality, reliability, and invariance) of the Chinese 14-Item Resilience Scale (RS-14) within Chinese register nurses (RNs) with less than 3 years work experiences. And we aimed to compare the fit of a unidimensional model and a bifactor model. Materials and methods: This multicenter cross-sectional survey was conducted from August to September in 2019. A total of 7,231 registered nurses from 90 hospitals were recruited. Data was anonymously obtained through online questionnaires. Both reliability and validity of Chinese RS-14 were assessed. The confirmatory factor analyses (CFA) were used to compare the fit of two different factor structures of the RS-14 (unidimensional model vs. a bifactor model). Moreover, multigroup CFA (MGCFA) were applied to evaluate the measurement invariance (MI) across sociodemographic parameters (gender, educational level, marital status, and et al.). Design: Cross-sectional quantitative analyses. Results: Our study confirmed that the bifactor model presented the best fit within Chinese nurses (CFI = 0.924, TLI = 0.909, RMSEA = 0.095, SRMR = 0.043), and found strong factorial invariance across gender, marital status, and status of receiving standardized training. The reliability of RS-14 was high with a Cronbach's alpha coefficient of 0.939. Moreover, RS-14 was positively correlated with the social support and was negatively correlated with workplace bullying. Conclusion: This is the first study to explore the latent factor structure for the RS-14 among Chinese RNs and evaluated MI across a series of sociodemographic variables. Based on our findings, the Chinese version RS-14 is both valid and reliable.

Fecal fungal microbiota alterations associated with clinical phenotypes in Crohn's disease in southwest China.

Although previous studies reported that gut fungal microbiota was associated with Crohn's disease (CD), only a few studies have focused on the correlation between gut fungi and clinical phenotypes of CD. Here, we aimed to analyze the association between intestinal fungi and the occurrence of CD, disease activity, biological behaviors, and perianal lesions. Stool samples from subjects meeting the inclusion and exclusion criteria were collected for running internal transcribed spacer 2 (ITS2) high-throughput sequencing. Then, correlation analysis was conducted between intestinal fungi and different clinical groups. There were 45 patients with CD and 17 healthy controls (HCs) enrolled. Results showed that two phyla, Rozellomycota and Mortierellomycota, were not present in patients with CD compared to HCs. At the same time, there was a higher abundance of fungal genera and species belonging to the phylum Ascomycota in patients with CD. SparCC network analysis showed fewer interactions among the fungal communities in patients with CD compared to HCs. Exophiala dermatitidis was positively associated with the clinical active stage and platelet count. The genus Candida was with significantly higher abundance in the non-B1 CD group based on the Montreal classification. Clonostachys, Humicola, and Lophiostoma were significantly enriched in patients with CD with perianal lesions. Our results demonstrated that the composition of the intestinal fungal microbiota in patients with CD and HCs was markedly different, some of which might play a pathogenic role in the occurrence of CD and perianal lesions. Exophiala dermatitidis and genus Candida might be associated with active disease stage and type non-B1 CD (CD with intestinal stenosis or penetrating lesions, or both), respectively.

Association between usual alcohol consumption and risk of falls in middle-aged and older Chinese adults.

BACKGROUND: Previous studies exploring usual alcohol consumption and falls risk were scarce in China. In addition, the dose-response relationship has not been explored so far. This study aims to estimate the association between usual alcohol consumption and risk of falls among middle-aged and older Chinese adults based on data from the China Health and Retirement Longitudinal Study (CHARLS), which is representative of the population of the entire country. METHODS: Baseline survey data in 2015 and follow-up data in 2018 in CHARLS were utilized. Alcohol consumption was calculated in grams per day (gr/day) according to self-reported drinking data and categorized accordingly to The Dietary Guidelines for Chinese Residents (DGC) 2016. Fall was obtained from self-reported information. Multivariable logistic regression analyses were performed to estimate the association of usual alcohol consumption with risk of falling. The dose-response relationship was also explored using restricted cubic splines. RESULTS: A total of 12,910 middle-aged and older participants were included from the CHARLS 2015, of which 11,667 were followed up in 2018. We found that former, moderate, and excessive drinkers were at higher fall risk compared to never drinkers (former: OR, 1.24; 95% CI, 1.05-1.46; moderate: OR, 1.22; 95% CI, 1.06-1.41; excessive: OR, 1.36; 95% CI, 1.15-1.61) in the longitudinal analysis. Similarly, individuals with moderate and excessive alcohol consumption were at increased risk of falling in the cross-sectional analysis (moderate: OR, 1.18; 95% CI, 1.02-1.37; excessive: OR, 1.32; 95% CI, 1.11,1.57). No significant increased risk of falls was found for former drinkers (former: OR, 1.13; 95% CI, 0.96-1.34). We observed a significant non-linear relationship. CONCLUSIONS: Our study suggests that usual alcohol consumption was associated with a higher risk of falls, highlighting the key role of alcohol intake on the fall risk, which needed consideration in developing intervention and prevention strategies for reducing falls among middle-aged and older Chinese adults.

Gender disparities in incidence and projections of lung cancer in China and the United States from 1978 to 2032: an age-period-cohort analysis.

PURPOSE: Lung cancer incidences tend to be higher among males than females in both China and the United States, yet secular incidence patterns are different due to distinct population and environmental exposures. We examined long-term and future trends of lung cancer incidence, as well as the associations of age, period, and cohort effects with gender disparities. METHODS: Using data from the Cancer Incidence in Five Continents from 1978 to 2012, we calculated age-standardized, age-specific incidence, and male-to-female incidence rate ratios (IRR), and conducted an age-period-cohort analysis. The average annual percentage change (AAPC) of the trends was obtained by Joinpoint Regression. Bayesian age-period-cohort analysis was also conducted to project incidences to 2032. RESULTS: In China, age-standardized incidence revealed a decreasing trend among males, but showed increasing trends among the younger age groups (30-54 years) in females. Age-standardized incidence rates of males decreased but remained stable among females from 1972 to 2012 in the United States. Male-to-female incidence rate ratios narrowed in both countries and reversed among younger birth cohorts in the United States. Gender disparities are expected to continue to diminish in both countries, and incidence among females appears to exceed that of males in the United States by around 2023-2027. CONCLUSION: Gender disparities in lung cancer incidence persist and will continue into the future in both countries, but our findings suggested that smoking may play different roles in gender disparities in lung cancer incidence between the two countries. Further population-based epidemiological studies among females in China are imperative.