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

Objective To investigate the current symptom status of maintenance hemodialysis(MHD)patients,analyze the influencing factors from the perspective of multidimensional symptom burden,extract symptom groups,and construct a symptom network.Methods A total of 490 patients who received MHD at the blood purification center of a tertiary hospital in Shanghai from March to April 2025 were selected using a convenience sampling method.30 symptoms of MHD patients were investigated using a modified dialysis symptom index table.SPSS and R software were utilized to analyze the influencing factors,extract symptom groups,and construct a multidimensional symptom network.Results A total of 488 valid questionnaires were collected,with a valid questionnaire recovery rate of 99.59％.The median number of symptoms experienced by patients was 6(interquartile range:4,8),with the top 5 symptoms being dry skin(69.88％),fatigue or tiredness(56.97％),itching(56.97％),worry(50.20％),and dry mouth(46.31％).Multidimensional analysis indicated that age,duration of dialysis,education level,and complications were influencing factors of symptom burden scores across different dimensions.6 stable symptom groups were extracted,namely skin discomfort,fatigue and pain,gastrointestinal tract,sleep disorders,water-electrolyte imbalance,and uremia.The results of the symptom network analysis revealed that difficulty of falling asleep had the highest intensity centrality(rs=2.18,2.25,2.12).Conclusion The symptom association is relatively stable,and difficulty of falling asleep is the core symptom.This finding can assist clinical medical staff in achieving efficiency and precision in symptom group management.

Melatonin is widely used as an over-the-counter medication to treat insomnia in children with autism spectrum disorder (ASD) and neurogenetic disorders (NGD). However, there is still a lack of research on its efficacy and safety, and clinical practice standards are to be established. In response, the International Pediatric Sleep Association (IPSA) convened an expert panel and developed a consensus statement:"Melatonin Use in Managing Insomnia in Children with Autism and Other Neurogenetic Disorders-an Assessment by the International Pediatric Sleep Association (IPSA)", which was published in Sleep Medicine, April 2024. The consensus focused on the efficacy and adverse effects of melatonin treatment for insomnia in children with ASD and NGD-including Smith-Magenis syndrome, Rett syndrome, Angelman syndrome, and tuberous sclerosis complex. It systematically reviews randomized controlled trials (RCTs) conducted between 2012 and 2022, and integrates current best clinical practices to formulate 10 consensus recommendations. Despite these contributions, the consensus has limitations: a small number of included RCTs, a lack of grading for evidence quality, and recommendation strength. Furthermore, the study population is primarily composed of children from Western countries. This article seeks to interpret the consensus to improve standardized use of melatonin for insomnia in Chinese children with ASD and NGD, and to provide a reference for the future development of localized evidence-based guidelines.

Objective:To explore the clinical features and molecular characteristics of myeloproliferative neoplasms (MPNs) patients with NFE2 gene mutations.Methods:Gene targeted sequencing was used to detect NFE2 gene mutation in 723 patients diagnosed with MPNs who were admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between April 2021 and June 2023. The association between NFE2 gene mutations and clinical features and molecular characteristics of MPNs patients were retrospectively analyzed.Results:Among 723 patients with MPNs, NFE2 gene mutations were found in 41 cases (5.7%) . NFE2 gene mutations were predominantly frameshift mutations (44.4%) , followed by nonsense mutations (33.3%) . The median number of mutations in patients with NFE2 gene mutations (4 [2,5]) was higher compared to the group without NFE2 gene mutations (2, [1,3]) ( P<0.001) . NFE2 gene mutations frequently co-occurred with mutations in MPL, ATM, PPM1D, and TET1. NFE2 gene mutations were mostly sub-clonal events, with 80.5% occurring after MPNs driver mutations (JAK2, CALR, or MPL) . NFE2 mutations were correlated with older age [median age: 60 (54, 67) years vs 54 (41, 63) years, P=0.001]. Patients with NFE2 gene mutations had a higher incidence of pre-diagnosis thrombosis (39.0% vs 22.0%, P=0.012) and pre-diagnosis arterial thrombosis (36.6% vs 20.4%, P=0.014) . Using a logistic regression analysis model adjusting for age and comorbidities (including chronic infections, malignancies, and autoimmune diseases) , NFE2 gene mutation was identified as an independent determinant of elevated tumor necrosis factor-alpha (TNF-α) ( OR=2.747, 95% CI: 1.143-6.605, P=0.024) , interferon-gamma (IFN-γ) ( OR=2.689, 95% CI: 1.191-6.076, P=0.017) , IL-10 ( OR=3.219, 95% CI: 1.343-7.717, P=0.009) , IL-12P70 ( OR=3.397, 95% CI:1.003-11.508, P=0.049) , IL-17 ( OR=2.284, 95% CI: 1.017-5.127, P=0.045) . In polycythaemia vera (PV) patients with the NFE2 gene mutation, the proportion of those classified as high-risk is notably higher in both the IWG-PV and mutation-enhanced international prognostic systems for PV (MIPSS-PV) (66.7% vs 25.3% for IWG-PV, P=0.033; 22.2% vs 2.0% for MIPSS-PV, P=0.013) . Similarly, for essential thrombocythaemia (ET) patients, the proportion in the high-risk group of the mutation-enhanced international prognostic systems for ET (MIPSS-ET) is significantly higher (15.4% vs 6.1%, P=0.021) . No statistically significant differences were observed in overall survival or cumulative incidence of thrombosis between NFE2-mutated (38 cases) and non-mutated MPNs patients (671 cases, P>0.05) . Conclusion:NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene mutations were correlated with older age, elevated levels of several inflammatory factors (including TNF-α、IFN-γ、IL-10、IL-12P70、IL-17) , and they mostly occurred in late-stage of MPNs.

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.

Abdominoplasty is one of the most widely performed plastic surgeries globally, with steadily increasing cases in China. Stress urinary incontinence is one important characteristic of pelvic organ prolapse, significantly impacting patients’ quality of life and contributing to increased healthcare burdens on society. This review tries to explore the impact of abdominoplasty on stress urinary incontinence in females and provides more information on their relationship.

Objective:To investigate intraoperative pathological findings and the interventional effects of "deep cervical lymphaticovenous anastomosis+" (dcLVA+) on deep cervical lymphatic drainage as well as the blood flow of carotid artery and jugular vein in elderly patients with cognitive impairment, and to put forward the thoughts based on the findings from the surgery.Methods:Between May 2024 and December 2024, retrospective analysis of Microsurgery Hospital, Fengcheng Hospital, Xi'an Medical College performed dcLVA+ between the deep cervical lymphatics or lymph nodes and jugular veins in 50 elderly patients with cognitive impairment (19 males and 31 females, aged 55-88 years with 69.94 years in average). Nine patients were found with Clinical Dementia Rating (CDR) score at 1 (mild), 7 with CDR score at 2 (moderate) and 34 with CDR score at 3 (severe). Intraoperative observations based on literature reviews had identified anatomical relationships between the lymphatic sacs containing cervical lymphatic chain and the carotid sheath. The lymph node count, size, distribution, thickness of fat tissue and conditions of lymphatic vessels were documented. Ultrasound was used to compare the blood flow of carotid artery and jugular vein as well as the cross-sectional areas at the planes of hyoid and cricoid cartilage before and after the closure of incisions under anaesthesia in 39 patients. Correlation analyses for Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCa), Activities of Daily Living (ADL) and Agitation behavior score before and 1 week after surgery were performed using Spearman's correlation and Wilcoxon paired tests. P<0.05 was considered statistically significant. Postoperative follow-ups were conducted via the visit of outpatient clinic and WeChat and telephone interviews. Results:In surgery, the cervical lymphatic chain was found running within an almost enclosed sac surrounding the carotid sheath. There were enlarged lymph nodes, increased fat deposition, lymphatic dilation or fibrosis in the sac. The preoperative blood flow in the carotid artery at the planes of hyoid and cricoid cartilage in the 39 patients was recorded at 150.52 ml/min±40.33 ml/min and 358.29 ml/min±129.30 ml/min, while that in the jugular vein was at 172.50 ml/min±63.94 ml/min and 317.00 ml/min±105.21 ml/min, respectively, both were far lower than the normal blood flow. There were statistically significant differences in the blood flow of carotid artery and jugular vein before and after surgery ( P<0.01). It was found that the preoperative blood flow of the internal carotid artery at the plane of hyoid was positively correlated with the preoperative scores of MMSE ( P<0.01), MoCa ( P<0.05) and ADL ( P<0.01). The blood flow of the common carotid artery at the plane of cricoid cartilage was found significantly and positively correlated with the preoperative scores of MMSE ( P<0.05). It was also noted that the blood flow of the internal carotid artery at the plane of hyoid was significantly and positively correlated with the postoperative ADL ( P<0.01) but negatively correlated with the Agitation behavior score ( P<0.05). The blood flow of the common carotid artery at the plane of cricoid cartilage was significantly and positively correlated with the postoperative scores of MMSE and MoCa ( P<0.05). The blood flow of the internal jugular vein at the plane of hyoid was negatively correlated with the Agitation behavior score ( P<0.01). The cross-sectional area of carotid artery at the plane of left hyoid was significantly and positively correlated with the MMSE score ( P<0.05). Statistically significant differences were observed in MMSE, MoCa, ADL and Agitation behavior score before and after surgery ( P<0.01). Conclusion:dcLVA+ shows a certain therapeutic benefit to the elderly patients with cognitive impairment. The intraoperatively observed pathological changes in cervical lymphatic sacs affect deep cervical lymphatic drainage and the blood flow of carotid artery and jugular vein. Further studies are necessary to find out whether the findings from this study would be the specific pathological changes and the morbidity mechanisms among the elderly patients with cognitive impairment.

Objective:To investigate the pathogenetic characteristics of clinical isolates of Streptococcus suis in Henan Province from 2020 to 2023. Methods:Eight clinical isolates of S. suis in Henan Province from 2020 to 2023 were identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and real-time fluorescence polymerase chain reaction (PCR). Serotype and virulence genes were detected by the serum agglutination test and PCR, and antibiotic susceptibility was evaluated using the microbroth dilution method. Multilocus sequence typing (MLST), minimum core genome (MCG), identification of antibiotic resistance genes, and core genome single nucleotide polymorphism (cgSNP) analysis were conducted using whole genome sequencing. Results:The results showed that eight S. suis strains isolated from humans were mainly serotype 2 (75.0%), while the rest were serotype 14 (25.0%). ST353 (62.5%) was the predominant genotype, followed by ST1 (25.0%) and ST7 (12.5%). All isolates belonged to the MCG1 group. The virulence genotypes of these isolates were primarily mrp(NA2)/ sly+/ ef+/ gapdh+(75.0%), while the remaining were mrp(EU)/ sly+/ ef+/ gapdh+(25.0%). These isolates carried tetracycline, macrolide, lincosamide and aminoglycoside resistance genes, and their resistance rates to tetracycline, erythromycin and clindamycin were 100.0%, 87.5% and 87.5%, respectively, and 62.5% strains were intermediate-resistant to penicillin. The cgSNP analysis indicated that these isolates were closer to the isolates from Guangdong, Zhejiang and Guangxi Provinces, with five ST353 strains and one ST7 strain belonging to Clade Ⅰ, and two ST1 strains belonging to Clade Ⅱ. Conclusion:The human isolates of S. suis in Henan Province are mainly ST353, harboring multiple virulence and antibiotic resistance genes.

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.