Preplanned Studies: Orofacial Clefts in High Prevalence Area of Birth Defects — Five Counties, Shanxi Province, China, 2000–2020

What is already known on this topic?: The prevalence of structural birth defects, especially neural tube defects, decreased after national folic acid (FA) supplementation initiation. / What is added by this report?: The prevalence of orofacial clefts (OFCs) in five counties of Shanxi Province in northern China, including most subtypes except cleft palate, showed a downward trend in the past two decades. In this study, pre-perinatal prevalence increased due to earlier detection. / What are the implications for public health practice?: Periconceptional supplementation with FA may contribute to the decline in OFCs prevalence, while the effect on the OFCs subtype needs further investigation. Continuing to advocate for earlier supplementation (3 months before conception) and increased supplementation frequency (daily consumption) could promote further reduction in the prevalence of OFCs. Specific surveillance of this effect in the era of universal three-child policy is warranted

Non-Isolated Neural Tube Defects with Comorbid Malformations Are Responsive to Population-Level Folic Acid Supplementation in Northern China

Objective: Comorbid congenital malformation of multiple organs may indicate a shared genetic/teratogenic causality. Folic acid supplementation reduces the population-level prevalence of isolated neural tube defects (NTDs), but whether complex cases involving independent malformations are also responsive is unknown. We aimed to describe the epidemiology of NTDs with comorbid malformations in a Chinese population and assess the impact of folic acid supplementation. Study Design: Data from five counties in Northern China were obtained between 2002 and 2021 through a population-based birth defects surveillance system. All live births, stillbirths, and terminations because of NTDs at any gestational age were recorded. NTDs were classified as spina bifida, anencephaly, or encephalocele. Isolated NTDs included spina bifida cases with presumed secondary malformations (hydrocephalus, hip dislocation, talipes). Non-isolated NTDs were those with independent concomitant malformations. Results: A total of 296,306 births and 2031 cases of NTDs were recorded from 2002–2021. A total of 4.8% of NTDs (97/2031) had comorbid defects, which primarily affected the abdominal wall (25/97), musculoskeletal system (24/97), central nervous system (22/97), and face (15/97). The relative risk of cleft lip and/or palate, limb reduction defects, hip dislocation, gastroschisis, omphalocele, hydrocephalus, and urogenital system defects was significantly greater in infants with NTDs than in the general population. Population-level folic acid supplementation significantly reduced the prevalence of both isolated and non-isolated NTDs. Conclusion: Epidemiologically, non-isolated NTDs follow similar trends as isolated cases and are responsive to primary prevention by folic acid supplementation. Various clinically-important congenital malformations are over-represented in individuals with NTDs, suggesting a common etiology

Epidemiological changes and molecular characteristics of Brucella strains in Ningxia, China

ObjectiveHuman brucellosis causes serious public health concerns in Ningxia, China.MethodsThis study employed epidemiological, bacteriological, and multiple-locus variable-number tandem repeat analysis (MLVA) methods to conduct an epidemiological investigation, which is necessary for devising tailored control strategies.ResultsBetween 1958 and 2022, 29,892 cases were reported, with an average annual number of cases and incidence of 467 and 7.1/100,000, respectively. The epidemic situation gradually worsened, with cases escalating from 26 cases in 2005 to 6,292 in 2022, with the incidence rate rising from 0.441 in 2005 to 86.83 in 2022. Geographically, the disease spread from a single affected county in 2004 to encompass all 22 counties in 2022. Yanchi County had the highest incidence, followed by the Hongsibao and Tongxin counties. These data suggest that Brucella infection has become a rampant regional concern in human brucellosis. Between 1958 and 2019, a total of 230 Brucella strains were identified across four studied hosts. These strains comprised four species with 12 biovars, including B. melitensis bv. 1, bv. 2, bv. 3, B. abortus bv. 1, bv. 3, bv. 4, bv. 5, bv. 6, bv. 7, B. suis bv. 1 and bv. 3, and B. canis. These data highlight the high species/biovars and host diversity of the Brucella population, posing a substantial challenge to brucellosis surveillance. There was an apparent transition from multiple species/biovars historically to the current dominance of a single species, B. melitensis, emphasizing the requirement for strengthening surveillance of B. melitensis. Genotypes 42 and 116, constituting 96.2% of the total number of genotypes, predominated in panel 1 and MLVA-11, indicating that all strains belong to the East Mediterranean lineage. MLVA cluster analysis revealed persistent transmission of dominant circulating genotypes, presenting an epidemic pattern characterized primarily by epidemiologically related cases with a few sporadic cases. Strains in this study exhibited high genetic homogeneity with strains from the Northwest, and those from Kazakhstan and Mongolia.ConclusionThe epidemic situation of human brucellosis has gradually worsened; the rampant epidemic of the disease has become a regional concern. The present study highlights that implementing the of targeted surveillance and intervention strategies is urge

Chromatin topology reorganization and transcription repression by PML-RARα in acute promyeloid leukemia.

BACKGROUND: Acute promyeloid leukemia (APL) is characterized by the oncogenic fusion protein PML-RARα, a major etiological agent in APL. However, the molecular mechanisms underlying the role of PML-RARα in leukemogenesis remain largely unknown. RESULTS: Using an inducible system, we comprehensively analyze the 3D genome organization in myeloid cells and its reorganization after PML-RARα induction and perform additional analyses in patient-derived APL cells with native PML-RARα. We discover that PML-RARα mediates extensive chromatin interactions genome-wide. Globally, it redefines the chromatin topology of the myeloid genome toward a more condensed configuration in APL cells; locally, it intrudes RNAPII-associated interaction domains, interrupts myeloid-specific transcription factors binding at enhancers and super-enhancers, and leads to transcriptional repression of genes critical for myeloid differentiation and maturation. CONCLUSIONS: Our results not only provide novel topological insights for the roles of PML-RARα in transforming myeloid cells into leukemia cells, but further uncover a topological framework of a molecular mechanism for oncogenic fusion proteins in cancers

Nuclear pore protein NUP210 depletion suppresses metastasis through heterochromatin-mediated disruption of tumor cell mechanical response.

Mechanical signals from the extracellular microenvironment have been implicated in tumor and metastatic progression. Here, we identify nucleoporin NUP210 as a metastasis susceptibility gene for human estrogen receptor positive (ER+) breast cancer and a cellular mechanosensor. Nup210 depletion suppresses lung metastasis in mouse models of breast cancer. Mechanistically, NUP210 interacts with LINC complex protein SUN2 which connects the nucleus to the cytoskeleton. In addition, the NUP210/SUN2 complex interacts with chromatin via the short isoform of BRD4 and histone H3.1/H3.2 at the nuclear periphery. In Nup210 knockout cells, mechanosensitive genes accumulate H3K27me3 heterochromatin modification, mediated by the polycomb repressive complex 2 and differentially reposition within the nucleus. Transcriptional repression in Nup210 knockout cells results in defective mechanotransduction and focal adhesion necessary for their metastatic capacity. Our study provides an important role of nuclear pore protein in cellular mechanosensation and metastasis

Regional variations in and correlates of disability-free life expectancy among older adults in China

<p>Abstract</p> <p>Background</p> <p>Considerable socioeconomic and health inequalities have been reported in China. However, because of a lack of appropriate data, limited research has been conducted on variations in disability-free life expectancy (DFLE) among older adults. This study aimed to use the most up-to-date disability survey data to explore geographical variations in DFLE at age 60 in China and to identify the socioeconomic and health care factors that partially account for these variations.</p> <p>Methods</p> <p>This study used 2006 mortality data extrapolated from the 1990 and 2000 Census and disability data from a national disability survey conducted in 2006. Disability was performance based and was diagnosed by trained physicians. DFLE was calculated by region using the Sullivan method. Multiple linear regression models by gender were conducted to explore correlates of DFLE.</p> <p>Results</p> <p>DFLE at age 60 varied widely by region, from 11.2 to 20.8 years in 2006. Per capita gross domestic product, proportion of urban residents, and access to health care were the primary factors associated with geographical variations in DFLE.</p> <p>Conclusion</p> <p>The pattern of differences in DFLE by region mirrors the pattern of regional economic development in China. Countermeasures to decrease regional differences in DFLE include accelerating regional economic development and improving health care distribution.</p

Adverse childhood experiences from family and society contribute to increased risk of depressive symptoms and cognitive impairment: a cross-sectional study

Background Family environments can shape children’s personalities and social networks, rendering distinguishing adverse childhood experiences (ACEs) from family and society essential, but related evidence remains limited.Aims This cross-sectional study aimed to investigate the correlations between intrafamilial and social ACEs, their associations with depressive symptoms and cognitive impairment and the (education-moderated) mediating role of social ACEs.Methods Data for this cross-sectional study were from the China Health and Retirement Longitudinal Study. Nine intrafamilial (0, 1, 2, 3, and 4 or more) and three social (0, 1, and 2 or more) ACEs were identified. Depressive symptoms were assessed using the 10-item Center for Epidemiological Studies Depression Scale. Global cognition, including episodic memory and mental intactness, was calculated as z scores. Binary and ordered logistic regressions, generalised linear models with Gaussian family and identity link, and mediation analysis were used.Results 13 435 participants aged 59.0 (51.0–66.0) were included. Compared with participants with no intrafamilial ACEs, those with 1, 2, 3, and 4 or more intrafamilial ACEs tended to develop more social ACEs, with odds ratios (ORs) of 1.55 (95% confidence interval (CI): 1.36 to 1.76), 2.36 (95% CI: 2.08 to 2.68), 3.46 (95% CI: 3.02 to 3.96) and 6.10 (95% CI: 5.30 to 7.02), respectively. Both intrafamilial and social ACEs were associated with depressive symptoms (OR &gt;3 for four or more intrafamilial ACEs and two or more social ACEs) and global cognition (β=−0.26 for four or more intrafamilial ACEs and β=−0.29 for two or more social ACEs). Social ACEs mediated the associations of intrafamilial ACEs with depressive symptoms and global cognition by 12.3% and 13.1%, respectively. Furthermore, as education levels increased, the impact of intrafamilial ACEs on depressive symptoms was increasingly mediated through social ACEs, while the mediating role of social ACEs between intrafamilial ACEs and cognitive impairment gradually diminished.Conclusions Improving children’s social environments and elevating general education can prevent later-life depressive symptoms and cognitive impairment attributed to ACEs in China

Periconceptional folic acid supplementation and sex difference in prevention of neural tube defects and their subtypes in China: results from a large prospective cohort study

Abstract Background Folic acid (FA) supplementation is known to prevent neural tube defects (NTDs). We examined whether this preventive effect differs by the sex of the infant. Methods Data were gathered from a large population-based cohort study in China that evaluated the effects of FA supplementation on NTDs. All births at 20 complete gestational weeks, including live births, stillbirths, and pregnancy terminations, and all NTDs, regardless of gestational age, were recorded. In a northern China province, a total of 30,801 singleton live births to women whose use of FA supplements during the first trimester was known at the time were included in the study. The birth prevalence of NTDs was classified by sex, subtype, and maternal FA supplementation. Male to female rate ratios [RR] and their 95% confidence intervals [CI] were calculated. Results A total of 106 NTDs cases were recorded. The overall prevalence of NTDs was 2.5‰ among males and 4.4‰ among females; NTDs were less prevalent among males than among females (RR, 0.58; 95% CI, 0.54–0.63). There was a higher prevalence of anencephaly (RR, 0.34; 95% CI, 0.27–0.43) and spina bifida (RR, 0.73; 95% CI, 0.63–0.84) among females. However, FA supplementation led to significantly greater decreases in the rates of anencephaly (4.8‰) and total NTDs (7.6‰) in females than in males (1.6‰ and 2.8‰, respectively). Conclusions FA supplementation successfully reduces the prevalence of NTDs in both male and female infants, although we found a significantly greater decrease in anencephaly and total NTDs in females than in males. How the protective effects of FA supplementation affect the sexes differently needs to be studied further