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

Objective:Mendelian randomization analysis (MR) was used to investigate the causal association between nine cathepsins and cholelithiasis.Methods:Single nucleotide polymorphism (SNP) sites closely associated and mutually independent with nine cathepsins and cholelithiasis were screened out from the Genome-Wide Association Study database and the FinnGen Biobank database, respectively. SNP corresponding to exposure factors were selected as instrumental variables. Two-sample bidirectional MR analysis was conducted with methods of inverse variance weighted (IVW), weighted median and MR-Egger regression. Additionally, multivariable Mendelian randomization (MVMR) was conducted to estimate the direct effect of cathepsins on cholelithiasis. Cochran's Q test, MR-PRESSO method and MR Egger regression were used to evaluate the levels of heterogeneity and pleiotropy. And the leave-one-out method was performed for the sensitivity analysis. Results:The univariable Mendelian randomization analysis results indicated that elevated cathepsin B levels increased the overall risk of cholelithiasis (IVW: OR=1.054, 95% CI: 1.025-1.083, P<0.001). The reverse MR analyses did not support a causal effect of cholelithiasis on cathepsin B (IVW: OR=0.998, 95% CI: 0.920-1.083, P=0.969). A multivariable analysis showed that elevated cathepsin B levels were still strongly associated with an increased risk of cholelithiasis (IVW: OR=1.038, 95% CI: 1.003-1.073, P=0.031). None evidence of significant pleiotropy and heterogeneity was observed, which was verified by sensitivity analysis. Conclusion:Cathepsin B may serve as a marker for cholelithiasis, and has important guiding significance in cholelithiasis treatment.

Objective To investigate the effects and mechanism of Linggui Qihua Prescription against myocardial inflammation and fibrosis in heart failure with preserved ejection fraction(HFpEF).Methods Totally 40 spontaneously hypertensive rats(SHR)were equally divided into model group,Entresto group(18 mg/kg)and Linggui Qihua Prescription low-and high-dosage groups(3.87,7.74 g/kg),the HFpEF model was induced using a 16-week high fat-salt-sugar diet and 8-week streptozotocin intraperitoneal injection.Ten WKY rats(WKY group)and 10 SHR(SHR group)served as control.After successful modeling,the groups were subjected to a 6-week corresponding intervention.Left ventricular end diastolic diameter(LVEDD),left ventricular end-diastolic volume(LVEDV),relative ventricular wall thickness(RWT),left ventricular fractional shortening(LVFS),isovolumic relaxation time(IVRT),mitral annular early and late diastolic velocities of motion(e? and a?),global longitudinal strain(GLS)and global longitudinal strain rate(GLSr)were measured by echocardiography;serum tumor necrosis factor-α(TNF-α)and soluble growth stimulation expressed gene 2 protein(sST2)contents were detected by ELISA;the morphology of myocardial tissue was observed by HE staining;myocardial fibrosis was assessed by Masson staining;the mRNA and protein expressions of myocardial tissue vascular cell adhesion molecule-1(VCAM-1),intercellular adhesion molecule-1(ICAM-1),growth differentiation factor-15(GDF-15)and sST2 were detected by qPCR and Western blot.Results Compared with the WKY group and SHR group,the model group exhibited significant increase in LVEDV,RWT,IVRT,along with significant decrease in e?,a? and absolute values of GLS and GLSr(P<0.05,P<0.01),the serum contents of TNF-α and sST2 significantly increased(P<0.01);there was pronounced myocardial inflammatory infiltration and collagen fiber deposition,while the mRNA and protein expression of VCAM-1,ICAM-1,GDF-15 and sST2 significantly increased(P<0.05,P<0.01).Compared with the model group,Entresto group and Linggui Qihua Prescription low-and high-dosage groups demonstrated significant decrease in LVEDV,RWT,IVRT,along with significant increases in e?,a? and absolute values of GLS and GLSr(P<0.05,P<0.01),the serum contents of TNF-α and sST2 significantly decreased(P<0.01);myocardial inflammatory infiltration and collagen fiber deposition were reduced,the mRNA and protein expressions of ICAM-1,GDF-15 and sST2 decreased in Linggui Qihua Prescription high-dosage group(P<0.01).Conclusion Linggui Qihua Prescription may inhibit chronic inflammation and fibrosis of the myocardium in HFpEF rats by regulating the expressions of ICAM-1,VCAM-1,GDF-15 and sST2,improving cardiac remodeling and functional impairment.

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 investigate the efficacy and safety of Linggui Qihua No.2 Prescription(LGQH2)in patients with heart failure with preserved ejection fraction(HFpEF).Methods Totally 60 HFpEF patients were randomly divided into experimental group and control group according to random number table method,with 30 patients in each group.On the basis of standardized treatment for heart failure,the experimental group was given LGQH2 granules,13 g/time,twice a day,orally;the control group was given placebo granules of LGQH2,with the same administration method as the experimental group.The treatment course for both groups was 4 weeks.6-minute walking distance(6MWD),Kansas City Cardiomyopathy Questionnaire(KCCQ)score,TCM syndrome score and serum NT-proBNP levels.Echocardiography was used to detect the ratio of early diastolic blood flow velocity(E)at the mitral valve to early diastolic myocardial motion velocity(e')at the mitral annulus,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD)and interventricular septal thickness(IVST).Adverse reactions and events were also recorded.Results Compared with before treatment,both groups showed significant improvement in 6MWD,KCCQ score,TCM syndrome score,serum NT proBNP,and E/e'after treatment(P<0.05),and there was no statistical significance in LAD,LVEDD and IVST between the two groups(P>0.05);after treatment,the experimental group showed better improvement in 6MWD,KCCQ score,TCM syndrome score and E/e'compared to the control group(P<0.05).During the research process,neither group of patients experienced any adverse reactions or events.Conclusion LGQH2 Prescription can effectively enhance exercise tolerance and cardiac function of HFpEF patients,alleviate symptoms,improve quality of life,and inhibit diastolic dysfunction of the heart,without notable adverse reactions.

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

Objective:To compare the clinical and laboratory characteristics and survival between Chinese and Western patients with myelodysplastic neoplasms (MDS) .Methods:Clinical and laboratory data were collected from 1,464 primary adult patients diagnosed with MDS at the Institute of Hematology & Blood Diseases Hospital from August 2016 to June 2024. Collected data were retrospectively analyzed and compared with 2,191 patients from the International Working Group for the Prognosis of Myelodysplastic Syndromes (IWG-PM) .Results:Chinese patients were significantly younger (median age: 56 years vs. 72 years, P<0.001) and experienced more severe hematopenia ( P<0.001) compared with patients from the IWG-PM. Further, Chinese patients exhibited a higher percentage of isolated del (20q), +8, and complex karyotypes as well as a lower percentage of normal karyotypes, del (5q), and -Y ( P<0.001). Higher U2AF1, NRAS, and NPM1 mutation rates and lower ASXL1, SF3B1, and RUNX1 mutation rates were observed in Chinese patients than in participants from the IWG-PM ( P<0.05). No significant difference in overall survival (OS) was found between the two groups (median OS: 48 [95% CI: 40 - 56]months, vs. 45[95% CI: 40 - 49] months; P=0.449). Among participants aged ≤45 years, Chinese patients demonstrated more trisomy 8 ( P=0.070) and U2AF1 mutation ( P<0.001) and higher 4-year OS rate compared with those from the IWG-PM (75.5% vs. 62.1%, P=0.001). Among participants aged ≥70 years, Chinese patients exhibited more complex karyotypes but fewer del (5q) as well as more NPM1 but less SF3B1 and TET2 compared with those from the IWG-PM ( P<0.05). Chinese patients demonstrated shorter survival (median OS: 20 [95% CI: 13 - 27] months vs. 37 [95% CI: 32 - 42] months, P<0.001) . Conclusion:Chinese and Western MDS patients differ in age of onset, clinical features, and cytogenetic or molecular genetic abnormalities, with significant differences persisting in age-matched groups. Although the OS is similar, disparities exist in survival for younger and older patients between the two populations.

Objective:To investigate the clinical, laboratory, and prognostic features of myelodysplastic neoplasm (MDS) patients harboring acute myeloid leukemia (AML) -like mutations.Methods:We retrospectively analyzed clinical, molecular, and outcome data from 1 464 adults with primary MDS diagnosed at the Institute of Hematology and Blood Diseases Hospital from August 2016 to June 2024.Results:AML-like mutations were detected in 64 patients (4.4% ). Compared with patients without AML-like mutations, those with AML-like mutations were younger [median 50 ( IQR 39–60) vs 56 (45, 65) years; P=0.001], more often female (51.6% vs 35.4% ; P=0.009), had higher bone marrow blast percentage [6.5% (3.0%, 10.5% ) vs 2.5% (1.0%, 7.0% ) ; P<0.001], a higher rate of normal karyotype (75.0% vs 48.1% ; P<0.001), and lower hemoglobin levels [73 (67, 82) g/L vs 80 (66, 98) g/L; P=0.006]. The AML-like group had a higher number of gene mutations than the non-AML-like group [3 ( IQR 2–4) vs 2 (1, 3) ; P<0.001). It was enriched for mutations in NPM1, DNMT3A, WT1, PTPN11, NRAS, BCOR, FLT3, CEBPA, and MYC (all P<0.05) and had lower rates of U2AF1, ASXL1, and TP53 mutations (all P<0.05). Overall survival (OS) did not differ between groups ( P=0.730) ; however, the AML-like group had significantly shorter leukemia-free survival (LFS) [19 months (95% CI: 13–25) vs 46 months (95% CI: 38–54) ; P=0.012] and a higher 2-year cumulative incidence of AML transformation [ (41.7±9.1) % vs (10.4±1.1) % ; P<0.001]. Within the AML-like group, OS, LFS, and cumulative incidence of AML transformation did not differ between patients with low blasts and those with excess blasts (IB). Multivariable Cox regression identified age ≥60 years and PTPN11 mutations as independent adverse prognostic factors for OS, while DNMT3A, PTPN11, and FLT3 mutations independently predicted leukemic transformation. Conclusions:MDS patients harboring AML-like mutations exhibit distinct clinical and molecular features and a higher risk of progression to AML.

Objective:To analyze research trends, hotspots, and international collaboration in temporomandibular disorders (TMD) from 2010 to 2024 using bibliometric methods.Methods:A total of 4 368 articles published between January 2010 to December 2024 were retrieved from PubMed using the search strategy temporomandibular disorders[MeSH Terms] OR temporomandibular joint disorders[Title/Abstract]. The R package"bibliometrix" was employed to analyze publication statistics, author collaboration networks, and keyword co-occurrence.Results:The annual publication volume in the TMD field increased 3.4-fold from 2010 to 2024, with an average annual output of 291.2 articles. MANFREDINI DANIELE was identified as the most prolific author (74 articles). The Journal of Oral Rehabilitation ranked first in terms of publication quantity (454 articles). The University of S?o Paulo (Brazil) emerged as the leading contributor, followed by Sichuan University (China) globally. Research hotspots predominantly focused on the DC/TMD diagnostic criteria and pain mechanisms. Analysis of international collaboration networks revealed that core authors (e.g., Lobbezoo F, Manfredini D) have driven advancements in the field through multidisciplinary collaboration (dentistry+psychology+medical imaging). The high-frequency occurrence of the imaging keyword "magnetic resonance imaging (MRI)" underscores its pivotal role in diagnosing disc displacement. Chinese institutions (Sichuan University, Peking University) ranked second globally in research output; however, interdisciplinary international collaboration remained limited, with multiple-country publications (MCP) accounting for only 13.0%. Conclusions:TMD research demonstrates interdisciplinary integration, highlighting the need for future emphasis on Asian population studies and innovative diagnostic/therapeutic technologies.

Objective:To evaluate the long-term protective efficacy of the recombinant Chinese hamster ovary cell-derived hepatitis B vaccine（CHO-HepB）26 years post-vaccination in the rural China.Methods:Zhengding county，Hebei province was designated as a rural monitoring site for CHO-HepB efficacy. Study participants included individuals born between 1997 and 1999 who had completed the three-dose CHO-HepB primary series without booster doses. A cross-sectional survey was conducted in late 2024 using random sampling. Demographic and vaccination history data were collected via questionnaires，and hepatitis B virus（HBV）serological markers were detected using chemiluminescence. Historical surveillance data were integrated to infer infection statuses of HBsAg-positive individuals and evaluate longitudinal trends in anti-HBs seropositivity and antibody titers.Results:Among 178 participants（mean time since vaccination：26.2 years），the seroprevalence rates were 0.6% for HBsAg（95% CI：0.0%-1.6%），64.6% for anti-HBs（95% CI：57.6%-71.6%），and 1.1% for anti-HBc（95% CI：0.0%-2.7%）. Compared to the pre-vaccination baseline HBsAg positivity of 11.3% in children under 10 years of age，the estimated vaccine protection rate was 95%. Two notable cases were identified：one with concurrent HBsAg and anti-HBc positivity and one with anti-HBs and anti-HBc positivity，suggestive of transient HBV exposure（1999—2009）without chronicity. Natural immune boosting was inferred for the latter case based on anti-HBs titer dynamics. Longitudinal analysis of four prior cross-sectional surveys（2005，2009，2013，and 2017）revealed no significant upward trends in HBsAg and anti-HBc positivity（both P>0.05）over 26 years，while anti-HBs seropositivity declined significantly（ P<0.05）from 6 to 26 years post-vaccination. Conclusion:The CHO-HepB vaccine demonstrates sustained immunological persistence and robust long-term protection up to 26 years post-immunization. Continued emphasis on rigorous implementation of mother-to-child transmission prevention strategies is critical for future hepatitis B control.