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

Iron is an essential trace element for the human body and is critical for vital cellular processes,such as DNA synthesis,respiration,and oxygen transport.The body maintains iron homeostasis through a coordinated balance of absorption,utilization,storage,and distribution.Both iron deficiency and excess can lead to pathologies,with the latter triggering lipid peroxidation and DNA mutations via the Fenton reaction,potentially causing iron-induced cell death in severe cases.Although iron overload can inflict severe damage on multiple organs,including the brain,liver,spleen,heart,ovaries,and kidneys,the mechanisms that regulate iron homeostasis in response to overload are not fully understood.Various animal models have been developed to help elucidate these mechanisms,each reflecting different aspects of iron overload relevant to human diseases,and selection of the most appropriate animal model is needed for the accurate simulation of the pathological and physiological states associated with human iron overload-related diseases.This review synthesizes recent literature on animal models pertinent to iron overload,to offer insights to support the development and analysis of models for diseases related to iron overload.

Objective:To assess the fall risk of hospitalized patients with cardiovascular diseases, analyze the related influencing factors, and construct a prediction model based on machine learning technology, so as to provide a basis for the fall management of hospitalized patients with cardiovascular diseases.Methods:This study was a retrospective cohort study. A total of 450 patients admitted to the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University from June 2017 to June 2024 were selected as the research objects by convenience sampling method. By reviewing electronic medical records, trained nurses extracted the patients' general information and Activities of Daily Living Scale (ADL) scores during hospitalization. Lasso regression was used to screen risk factors, and machine learning libraries were used to construct support vector machine (SVM), decision tree, XGBoost, and neural network models. Bootstrap resampling method and area under the curve (AUC) were used to verify the model performance.Results:Among the 450 patients, there were 261 males and 189 females, with a mean age of (66.0 ± 8.4) years. Among them, 90 patients fell during hospitalization and 360 patients did not fall. The results of Lasso regression showed that ADL score ≤60 points, use of hypnotics, hypokalemia, nighttime toilet visits≥2 times, use of antihypertensive drugs, no caregiver, and history of atrial fibrillation were all risk factors for falls in hospitalized patients with cardiovascular diseases (regression coefficients ranging from 0.61 to 1.20, all P<0.01). Among the machine learning models, XGBoost had the best comprehensive performance (AUC=0.98), which was better than decision tree (AUC=0.66), SVM (AUC=0.95), and neural network (AUC=0.87). Conclusions:The fall risk of hospitalized patients with cardiovascular diseases is jointly affected by physiological, medication and behavioral factors, and the XGBoost model can effectively identify high-risk groups. In actual clinical work, nursing strategies can be optimized in combination with risk factors, and the application of intelligent fall prediction and assessment tools can be promoted.

Objective To analyze the distribution and drug resistance patterns of pathogenic bacteria in bile and blood cultures obtained from patients with biliary stones accompanied by acute biliary tract infection,to evaluate the clinical appropriate-ness of antibiotic use based on drug sensitivity results,and to provide evidence for empirical antibiotic treatment in such patients.Methods The clinical data of 161 patients with biliary calculi complicated by acute biliary tract infection who were admitted to the First People's Hospital of Neijiang from 2017 to 2023 were retrospectively analyzed.The results of microbial culture,drug sensitivity analysis,and patient characteristics were assessed to evaluate the appropriateness of clinical antimicrobial therapy.Results Among the 161 patients with positive cultures,212 strains of pathogenic bacteria were detected.The predominant patho-gens were Escherichia coli,Klebsiella pneumoniae subspecies,and Enterococcus faecium.Age and underlying diseases significantly affected the distribution of Escherichia coli and Klebsiella pneumoniae subspecies.Within the gram-negative bacterial group,Esche-richia coli and Klebsiella pneumoniae subspecies exhibited higher drug resistance to commonly used broad-spectrum penicillin,third-generation cephalosporin and quinolones but lower resistance rates to piperacillin and tazobactam;furthermore,elderly indi-viduals aged ≥65 years showed higher resistance rates to ceftriaxone than those under age 65 while people with drug exposure history had higher ceftazidime resistance rates that were statistically significant.In contrast to Enterococcus faecalis which displayed low antimicrobial resistance rates for most drugs tested in this study,Enterococcus faecium demonstrated high levels of antibiotic resistance;however,both Enterococcus faecalis and Enterococcus faecium exhibited zero-resistance rates against vancomycin and tigecycline although this may be attributed to their small sample size in our study cohort.Finally,we found that empirical anti-in-fective drugs,as well as target anti-infective drugs,were not prescribed rationally among these patients due mainly to inappropriate combinations of antibiotics or incorrect dosages.Conclusions The predominant pathogens in patients with acute biliary tract infection are gram-negative bacteria,Gram-positive bacteria,and fungi;however,the potential involvement of anaerobic bacteria should not be overlooked.Vancomycin exhibits sensitivity against gram-positive bacteria,yet the overall rationality of antibiotic usage remains suboptimal.Enhanced clinical testing for pathogenic microorganisms is imperative in the management of biliary stones accompanied by acute biliary tract infection.In contrast,clinical pharmacists should provide comprehensive training on anti-infective drugs to clinicians to facilitate their judicious selection of antibiotics based on drug sensitivity results and prevent the e-mergence of multidrug-resistant bacteria.

Objective To investigate the current status of acceptance of disability(AOD)among young and middle-aged spinal cord injury patients and analyze the factors influencing it,in order to provide a basis for nursing managers to develop targeted interventions.Methods From February to July 2024,a convenience sample of 330 young and middle-aged spinal cord injury patients who were hospitalized in 3 tertiary-level hospitals in Henan Province was selected.The survey was conducted using a general information questionnaire,the Brief Adaptation to Disability Scale-Revised,Perceived Social Support Scale,Connor-Davidson Resilience Scale-10 item,Brief Illness Perception Questionnaire,Medical Coping Modes Questionnaire.Results A total of 322 patients were included in the final analysis,yielding a valid response rate of 97.58％.The AOD score for young and middle-aged spinal cord injury patients was(25.99±6.68).Multiple linear regression analysis revealed that gender,education level,type of paralysis,injury duration,pain intensity,social support,psychological resilience,disease perception,and coping styles(confrontation and submission)were influencing factors of AOD(P＜0.05).Conclusion AOD among young and middle-aged spinal cord injury patients is at a moderate level.Healthcare professionals should pay particular attention to male patients,those with low literacy,quadriplegia,shorter injury durations,high pain intensity,low social support,weak psychological resilience,strong disease perception,and yielding coping styles.Timely interventions are recommended to enhance AOD,strengthen rehabilitation outcomes,and improve prognosis.

Purpose This study aimed to investigate the expression of CTLA-4 and PD-L1 in pulmonary lympho-epithelial carcinoma(PLEC)and to explore their relationships with patient prognosis and with tumor-infiltrating lym-phocytes(TILs).Methods Fifty cases of PLEC were retrospectively collected,together with 23 samples of adjacent normal lung tissue.Immunohistochemistry was performed to detect CTLA-4 and PD-L1 expression in both PLEC and adjacent normal lung tissues,as well as to quantify CD4+and CD8+T-lymphocytes infiltration within the tumor micro-environment.CTLA-4,PD-L1,and the distributions of CD4+T cells and CD8+T cells were then correlated with the clinicopathological features of PLEC.Results The positive rate of CTLA-4 in PLEC was significantly higher than that in adjacent normal lung tissue(P＜0.05).PD-L1 expression differed significantly across TNM stages of PLEC(P＜0.05)and was positively correlated with TNM stages(r=0.31,P=0.03).CD4+and CD8+T-lymphocytes were pre-dominantly localized in the tumor stroma,with CD4+T cells density exceeding that of CD8+(P＜0.05).Within canc-er nests,CD8+T cells density was significantly higher than CD4+(P＜0.05).Conclusion Both PD-L1 and CTLA-4 are frequently expressed in PLEC,suggesting they represent potential immunotherapeutic targets.In the PLEC micro-environment,lymphocytes primarily infiltrated the stromal compartment,and CD4+T cells are more abundant than CD8+T cells in that locale.

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

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

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.