OBJECTIVE: To explore the genotype-phenotype correlation in a Chinese family with structural brain abnormalities due to variant of the TUBB gene. METHODS: A family undergoing prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital in October 2024 was selected as the study subject. Clinical data were collected. Amniotic fluid sample was subjected to chromosomal copy number variation sequencing (CNV-seq). Trio whole-exome sequencing (Trio-WES) was carried out on the amniotic fluid and parental blood samples, and candidate variant was verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-KY-076-01). RESULTS: Both prenatal ultrasound and fetal MRI showed deviation of brain midline, unilateral lateral ventriculomegaly, and bilateral gyral asymmetry. Trio-WES revealed that the fetus has harbored a maternally derived heterozygous missense variant of the TUBB gene [NM_178014.4: c.155A>G (p.N52S)]. Sanger sequencing confirmed that the woman and a previously terminated fetus both harbored the same variant. Both the proband and two fetuses exhibited similar neuroimaging abnormalities including midline deviation and asymmetrical gyri. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PS2_Moderate+PS3). CONCLUSION The heterozygous c.155A>G (p.N52S) variant was the TUBB gene probably underlay the pathogenesis of the structural brain abnormalities in this family. Above findings have expanded the phenotypic spectrum associated with the variant and facilitated the prenatal diagnosis for this family.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis ; Tubulin/genetics* ; Adult ; Brain/diagnostic imaging* ; Male ; Pedigree ; DNA Copy Number Variations/genetics* ; Exome Sequencing ; Genetic Association Studies ; Magnetic Resonance Imaging

BACKGROUND: Spatiotemporal disparities exist in the disease burden of non-communicable diseases (NCDs) attributable to kidney dysfunction, which has been poorly assessed. The present study aimed to evaluate the spatiotemporal trends of the global burden of NCDs attributable to kidney dysfunction and to predict future trends. METHODS: Data on NCDs attributable to kidney dysfunction, quantified using deaths and disability-adjusted life-years (DALYs), were extracted from the Global Burden of Diseases Injuries, and Risk Factors (GBD) Study in 2019. Estimated annual percentage change (EAPC) of age-standardized rate (ASR) was calculated with linear regression to assess the changing trend. Pearson's correlation analysis was used to determine the association between ASR and sociodemographic index (SDI) for 21 GBD regions. A Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2040. RESULTS: Between 1990 and 2019, the absolute number of deaths and DALYs from NCDs attributable to kidney dysfunction increased globally. The death cases increased from 1,571,720 (95% uncertainty interval [UI]: 1,344,420-1,805,598) in 1990 to 3,161,552 (95% UI: 2,723,363-3,623,814) in 2019 for both sexes combined. Both the ASR of death and DALYs increased in Andean Latin America, the Caribbean, Central Latin America, Southeast Asia, Oceania, and Southern Sub-Saharan Africa. In contrast, the age-standardized metrics decreased in the high-income Asia Pacific region. The relationship between SDI and ASR of death and DALYs was negatively correlated. The BAPC model indicated that there would be approximately 5,806,780 death cases and 119,013,659 DALY cases in 2040 that could be attributed to kidney dysfunction. Age-standardized death of cardiovascular diseases (CVDs) and CKD attributable to kidney dysfunction were predicted to decrease and increase from 2020 to 2040, respectively. CONCLUSION NCDs attributable to kidney dysfunction remain a major public health concern worldwide. Efforts are required to attenuate the death and disability burden, particularly in low and low-to-middle SDI regions.
Humans ; Noncommunicable Diseases/epidemiology* ; Global Burden of Disease ; Disability-Adjusted Life Years ; Male ; Female ; Risk Factors ; Middle Aged ; Kidney Diseases/epidemiology* ; Bayes Theorem ; Adult ; Aged ; Global Health ; Quality-Adjusted Life Years

Sepsis is a life-threatening organ dysfunction caused by the host's dysregulated response to infection, with a complex pathogenesis and high mortality rate. Currently, there are no clear and effective treatment drugs available. Epigenetic modification serves as a major mechanism regulating gene expression under pathological and physiological conditions, and it has been shown to play a critical role in regulating the occurrence and development of sepsis. Histone acetylation modification, as a sophisticated epigenetic modification mechanism, plays a crucial regulatory role in many aspects of life. It can jointly regulate the acetylation status of histones through histone acetyltransferase (HAT) and histone deacetylase (HDAC), thereby changing DNA expression and dynamically regulating sepsis related gene expression at the epigenetic level. Previous studies have shown that histone acetylation can participate in the progression of sepsis by regulating inflammatory mediators, nuclear factor-ΚB (NF-ΚB) signaling pathway, autophagy, efferocytosis, ferroptosis, pyroptosis. These mechanisms are promising targets for novel sepsis treatments. In addition, with the deepening of research, it has been found that various selective/non selective histone deacetylase inhibitors (HDACI) can regulate histone acetylation status by acting on different HDAC targets, which has been shown to alleviate organ damage caused by sepsis and improve prognosis in septic animal models. This article further summarizes the role and potential applications of histone acetylation in sepsis, providing new ideas for the treatment of sepsis.
Sepsis/metabolism* ; Acetylation ; Humans ; Histones/metabolism* ; Histone Acetyltransferases/metabolism* ; Histone Deacetylase Inhibitors ; Epigenesis, Genetic ; Histone Deacetylases/metabolism* ; Signal Transduction ; NF-kappa B/metabolism* ; Animals

ObjectiveTo investigate the association of particulate matter and ozone with the prevalence of non-alcoholic fatty liver disease (NAFLD) in a district of Shanghai, and to provide epidemiological evidence for the further identification of early health hazards of air pollution and for the prevention and control of NAFLD. MethodsBased on Songjiang Sub-cohort of Shanghai Natural Population Cohort, a cross-sectional survey design was used to recruit participants from 2016 to 2017. Annual average exposure levels to air pollution from 2009 to 2017 were matched to the participant’s residential address using a high-resolution and high-quality ambient air pollutants dataset in China. NAFLD was diagnosed according to the “Guidelines for the prevention and treatment of metabolism⁃associated (non⁃alcoholic) fatty liver disease” by the Chinese Medical Association. Multivariate logistic regression models were employed to analyze the association between air pollution and the prevalence of NAFLD, and stratified analyses were used to compare differences by age, gender, obesity, and lifestyle habits within subgroups. ResultsA total of 32 791 individuals were included in the study. The prevalence of NAFLD among community residents in suburban Shanghai was 38.88%. For every 1 μg·m^-3 increase in PM₁, PM_2.5, PM₁₀, or O₃, the risk of NAFLD increased correspongdinglt, with the odds ratios (95%CI) of 1.071 (1.043‒1.099), 1.065 (1.042‒1.089), 1.041 (1.027‒1.055), or 1.061 (1.032‒1.091), respectively. There were differences in effects across different gender, age, and obesity status subgroups. ConclusionPM₁, PM_2.5, PM₁₀, and O₃ are positively associated with an increased risk of NAFLD. Stratified analyses reveal that individuals aged 65 years old or above exhibited greater susceptibility to PM₁, PM_2.5, and O₃, whereas those aged less than 65 years old are more vulnerable to PM₁₀. Males are more sensitive to PM₁ and O₃, and females are more susceptible to PM_2.5 and PM₁₀. The association between air pollutant exposure and NAFLD risk is more pronounced among obese participants compared to that in non-obese counterparts.

Objective To establish a management scheme for the prevention and control of sudden respiratory infectious diseases on hospital ships and to evaluate its application.Methods The clinical practice,guidelines,expert consensus and systematic evaluation on the prevention and control of sudden respiratory infectious diseases at home and abroad were systematically retrieved.At the same time,the research team proposed a preliminary draft of the management scheme for the prevention and control of sudden respiratory infectious diseases on hospital ships by referring to the literatures on the management of major epidemics at home and abroad in recent years.After 2 rounds of discussion and amendment suggested by expert demonstration meetings,the management scheme for the prevention and control of sudden respiratory infectious diseases on hospital ships was finally formed,and preliminary verification was carried out in"Mission Harmony-2022".Results The hospital ship management scheme for the prevention and control of sudden respiratory infectious diseases included 6 first-level items,22 second-level items,and 40 third-level items(including 34 level-A recommended indicators and 6 level-B recommended indicators).The scheme was applied in"Mission Harmony-2022"and the task was successfully completed.Conclusion The management scheme for the prevention and control of sudden respiratory infectious diseases on hospital ships is systematic,comprehensive,rigorous,practical and scientific,and can provide a guiding reference for the rescue task of sudden respiratory infectious diseases on hospital ships.

Objective To investigate the prevalence of metabolic associated fatty liver disease(MAFLD)and its correlation with metabolic components among personnel on tropical islands.Methods The data of personnel who received health examination on islands in 2024 were analyzed,and they were grouped with the age limit of 30 years old to compare the detection rates of MAFLD and metabolic components in different age groups.In people aged≥ 30 years old,the age,gender,body mass index(BMI),waist circumference(WC),fasting blood glucose,blood lipids,liver function,kidney function and other indexes were compared between MAFLD and non-MAFLD groups.Univariate and multivariate logistic regression models were conducted to analyze the factors affecting the occurrence of MAFLD.The effects of various metabolic components on the risk of MAFLD in different age groups were analyzed by subgroup analyses.Results Among 1213 personnel,175(14.4％)cases had MAFLD,of which 141(80.6％)cases were mild,32(18.3％)were moderate,and 2(1.1％)were severe.The detection rates of MAFLD(25.6％[74/289]vs 10.9％[101/924])and overweight/obesity(55.7％[161/289]vs 37.7％[348/924])in age ≥ 30 years old were significantly higher than those in age＜30 years old(both P＜0.001).In people aged≥ 30 years old,compared with the non-MAFLD group,the BMI,WC,systolic blood pressure,diastolic blood pressure,triglyceride(TG),low density lipoprotein-cholesterol,alanine transaminase,aspartate transaminase,gamma glutamyltransferase and uric acid(UA)in the MAFLD group were significantly higher(all P＜0.05),and the high density lipoprotein-cholesterol(HDL-C)was significantly lower(P＜0.05).There were no significant differences in age,gender,fast blood glucose,total cholesterol,alkaline phosphatase,total bilirubin,serum creatinine,or blood urea nitrogen(all P＞0.05).Logistic regression analysis showed that WC was an independent risk factor for MAFLD(odds ratio[OR]=1.101,95％confidence interval[95％CI]1.030-1.176,P=0.004);HDL-C was an independent protective factor for MAFLD(OR=0.071,95％CI0.016-0.323,P=0.001);and BMI ≥24.0 kg/m2 and WC≥90 cm were positively correlated with MAFLD(both P＜0.01).In people aged≥30 years old,the risk of MAFLD was increased in those with overweight/obesity,arterial blood pressure≥ 130/85 mmHg(1 mmHg=0.133 kPa),TG≥1.7 mmol/L,HDL-C≤1.0 mmol/L and UA＞420 μmol/L(all P＜0.05),and the risk of MAFLD was most significantly increased in overweight/obesity people(hazard ratio[HR]=5.088,95％CI 2.724-9.504,P＜0.001).Among people aged＜30 years old,the risk of MAFLD was increased in those with overweight/obesity and UA＞420 μmol/L(both P＜0.01),and the risk of MAFLD was most significantly increased in overweight/obesity individuals(HR=6.305,95％CI3.973-10.006,P＜0.001).Conclusion The detection rates of MAFLD and various metabolic components are higher in the personnel on tropical islands,and the risk of MAFLD is higher in those with overweight/obesity,TG≥1.7 mmol/L and hyperuricemia.

Objective The study aimed to elucidate the evolution of the syndromes in Traditional Chinese Medicine(TCM)and TCM syndrome elements in different chronic stages of psoriasis vulgaris.Methods A database was constructed using electronic medical records collected from July 2019 to March 2024 from 1,049 patients with psoriasis vulgaris.The study used Sankey diagrams and network association graphs to analyze the evolution of TCM syndromes and their elements in patients at the different stages:initial diagnosis,progressive stage(Week 2-3),progressive stage(Week 4-5),skin lesion improvement stage(Week 6-7),and remission stage.The syndrome elements network was constructed using community detection algorithms,and the association rules between local skin lesion syndrome differentiation and overall syndrome differentiation were displayed using heatmaps.Results(ⅰ)Initial diagnosis.In the syndrome differentiation of local skin lesions,blood heat syndrome was the most common(79.79％);among the disease location of TCM syndrome elements(called"disease location"),liver was the most prevalent(35.62％);and among the pathological factors of TCM syndrome elements(called"pathological factors"),fire(heat)was the most common(75.48％).(ⅱ)Active stage(Week 2-3).In the syndrome differentiation of local skin lesions,blood heat syndrome remained the most prevalent(73.13％);among the disease location,liver was still the most prevalent(31.71％);and among the pathological factors,fire(heat)continued to be the most common(82.11％),while dampness(22.26％)and qi stagnation(8.39％)began to increase.(ⅲ)Active stage(Week 4-5).The syndrome differentiation of local skin lesions was dominated by blood heat syndrome(45.91％)and blood dryness syndrome(37.19％);among disease location,the interior was the most prevalent(15.25％);and among the pathological factors,fire(heat)remained the most common(50.66％),with an increase in yin deficiency(34.26％).(ⅳ)Skin lesion improvement stage(Week 6-7).In the syndrome differentiation of local skin lesions,both blood dryness syndrome(49.44％)and blood stasis syndrome(33.33％)increased;among the disease location,meridians increased most significantly and became the most prevalent(13.44％);and among the pathological factors,blood stasis increased most significantly and became the most prevalent(28.20％).(ⅴ)Remission stage.In the syndrome differentiation of local skin lesions,blood stasis syndrome became the primary(55.69％),while the percentage of blood dryness syndrome decreased(21.16％);meridians(25.71％)and blood stasis(62.34％)remained the most predominant syndrome elements related to disease location or pathological factors.Conclusion The overall pattern of TCM syndromes in psoriasis vulgaris evolved from excess to deficiency.From the initial diagnosis to the active phase(Week 2-3),heat syndrome dominated;during the active phase(Week 4-5),heat syndrome coexisted with damp syndrome or yin deficiency syndrome;changes in the syndrome element network were the most significant during the lesion improvement phase,with blood stasis gradually increasing and peaking during the remission phase.Blood stasis,dampness,and qi stagnation were pervasive throughout psoriasis vulgaris;qi stagnation and blood stasis may be the main elements causing further deterioration and prolonged course of the disease during the active phase in patients.

Energy metabolism is fundamental for life.It encompasses the utilization of carbohydrates,lipids,and proteins for internal processes,while aberrant energy metabolism is implicated in many diseases.In the present study,using three-dimensional(3D)printing from polycarbonate via fused deposition modeling,we propose a multi-nuclear radiofrequency(RF)coil design with integrated 1H birdcage and interchangeable X-nuclei(2H,13C,23Na,and 31P)single-loop coils for magnetic resonance imaging(MRI)/magnetic resonance spectroscopy(MRS).The single-loop coil for each nucleus attaches to an arc bracket that slides unrestrictedly along the birdcage coil inner surface,enabling convenient switching among various nuclei and animal handling.Compared to a commercial 1H birdcage coil,the proposed 1H birdcage coil exhibited superior signal-excitation homogeneity and imaging signal-to-noise ratio(SNR).For X-nuclei study,prominent peaks in spectroscopy for phantom solutions showed excellent SNR,and the static and dynamic peaks of in vivo spectroscopy validated the efficacy of the coil design in structural imaging and energy metabolism detection simultaneously.

Objective To explore the clinical efficacy of Chaiqi Ningshen Anmian Decoction(CNAD)combined with wrist ankle acupuncture(WAA)in treating chronic insomnia(CI)patients with heart and spleen deficiency.Methods CI patients diagnosed and treated at the Beijing Huairou Hospital of Traditional Chinese Medicine from April 2022 to April 2023 were selected,and patients were randomly divided into the Eszolam(ET)group and the combination group(CNAD combined with WAA)according to the random number table method,with 50 cases in each group.The primary outcome was clinical efficacy[evaluated by the Traditional Chinese Medicine Syndrome Integral(TCMSI)].Secondary outcomes included changes in cognitive function[assessed by the Montreal Cognitive Assessment(MoCA)],anxiety level[assessed by the Hamilton Anxiety Scale(HAMA)],sleep quality[assessed by the Pittsburgh Sleep Quality Index(PSQI)],glycated serum albumin(GA),serotonin(5-HT),interleukin-1 β(IL-1β),and C-reactive protein(CRP)before and after treatment in both groups.Results Before treatment,there was no significant differences in total TCMSI between the two groups(P＞0.05).After treatment,the total TCMSI of the combination group was significantly lower than that of the ET group(P＜0.05),and the treatment effectiveness rate was significantly higher in the combination group(P＜0.05).Before treatment,there were no significant differences in MoCA score,HAMA score,PSQI score,serum GA level,serum 5-HT level,serum IL-1 level and serum CRP level between the groups(P＞0.05).After treatment,the MoCA score,serum GA level,and serum 5-HT level in the combination group were significantly higher than those in the ET group(P＜0.05),while the HAMA score,PSQI score,serum IL-1β level,and serum CRP level were significantly lower in the combination group(P＜0.05).Conclusion Compared with ET,CNAD combined with WAA significantly improves insomnia symptoms in CI patients with heart and spleen deficiency,enhances cognitive function and sleep quality,and reduces anxiety levels.This may be related to the upregulation of serum 5-HT,IL-1 β and the inhibition of the inflammatory response.

Cardiac arrest most commonly occurs outside of the hospital, known as out-of-hospital cardiac arrest (OHCA), and is an important global health problem. Approximately 40% of cardiac arrest has no clear cause. Hereditary arrhythmias and cardiomyopathies factors contribute to cardiac arrest. The identification of genetic factors for cardiac arrest after its occurrence is of great value not only for the individual, but also for relatives who may be at risk for the disease in their family. In the United States, there are over 350?000 cases of OHCA and over 200?000 cases of in-hospital cardiac arrest (IHCA) each year, and in Western Europe, cardiac arrest accounts for 15%-20% of all adult natural deaths and 50% of all cardiovascular deaths. In order to reduce the burden caused by cardiac arrest within society, it is essential to further understand its etiological factors, such as incidence in different regions, risk factors, and populations at higher risk. For each individual, cardiac arrest is the result of a complex interaction of genetic and acquired factors. Understanding the complex interplay of pathogenic factors in cardiac arrest and the development of individualized prevention and treatment approaches requires the collection of clinical data from cardiac arrest populations and multimodal analysis in order to identify epidemiological features and risk factors for cardiac arrest. Recently, cardiac arrest-related data are being collected and integrated in Europe in different regions and populations. As a result of the commitment to the creation of large datasets of clinical information on cardiac arrest populations, the knowledge of the pathology of cardiac arrest pathogenesis as well as risk factors is steadily increasing. This article reviews the epidemiologic data of cardiac arrest in recent years and the associated risk factors, thus providing ideas for developing better strategies for the prevention and treatment of cardiac arrest.