The construction of a training system for visiting physicians in the department of rare diseases in China is an important measure to improve the overall diagnosis and treatment capacity for rare diseases and address the critical challenge of insufficient knowledge and skills among clinicians in practice. This article systematically describes the visiting physician training system established by the Department of Rare Diseases at Peking Union Medical College Hospital. It summarizes the training objectives and positioning, design logic, and learning modules of the system, aiming to provide a reference for the construction of the specialized talent team for rare diseases in China.

Objective To investigate the cross-sectional associations between different fatty liver classifications and cardiac structure and function in people undergo health examination. Methods A total of 6 545 adults who underwent health examinations at the Health Management Center of Zhongshan Hospital, Fudan University between January 1 and December 31, 2017, were retrospectively included. Demographic characteristics and laboratory data were collected. The hepatic steatosis was graded by ultrasonography. And patients with fatty liver were further stratified according to alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, as well as the degree of liver fibrosis. Cardiac morphology and function were assessed by transthoracic echocardiography, and left ventricular geometric patterns were classified accordingly. Multivariate logistic regression analysis was performed to evaluate the associations between fatty liver classifications and cardiac abnormalities. Results There were 2 795 patients (42.7%) with fatty liver, of whom 832 (29.8%) had significant cardiac structural alterations and 1 500 (53.7%) had diastolic dysfunction. Severe fatty liver was risk factor for concentric remodeling and increased relative wall thickness (RWT), with odds ratios (ORs) of 1.27 (P＝0.012) and 1.27 (P＝0.009), respectively. Fatty liver accompanied by elevated ALT or AST was risk factor for concentric remodeling (OR＝1.45,1.56; P＝0.001, 0.001), increased RWT (OR＝1.48,1.57; P＜0.001, ＜0.001), and diastolic dysfunction (OR＝1.27, 1.32; P＝0.035, 0.040), respectively. Fatty liver with liver fibrosis was risk factor for concentric remodeling (OR＝1.83, P＝0.046) and diastolic dysfunction (OR＝2.64, P＝0.034). Conclusions Advanced fatty liver, including severe hepatic steatosis, accompanied by elevated liver enzymes or liver fibrosis, could increase risks of cardiac remodeling and diastolic dysfunction, while systolic function is preserved. For patients with fatty liver, it is recommended to undergo regular ultrasonography examination.

Objective To establish a method for simultaneous determination of four high-molecular-weight thiol derivatives (TDs) in workplace air by gas chromatography. Methods The four kinds of vapor-phase macromolecular TDs (1-pentanethiol, 1-hexanethiol, 1-benzyl mercaptan, and n-octanethiol) in the workplace air were collected using the GDH-1 air sampling tubes, desorbed with anhydrous ethanol, separated on a DB-FFAP capillary column, and determined by flame ionization detector. Results The quantitation range of the four TDs was 0.30-207.37 mg/L, with the correlation coefficients greater than 0.999 00. The minimum detection mass concentrations and minimum quantitation mass concentrations were 0.18-0.32 and 0.60-1.05 mg/m³, respectively (both calculated based on the 1.5 L sample and 3.0 mL desorption solvent). The mean desorption efficiencies ranged from 87.07% to 103.59%. The within-run and between-run relative standard deviations were 1.92%-8.22% and 1.89%-8.45%, respectively. The samples can be stored at room temperature or 4 ℃ for three days and up to 7 days at -18 ℃. Conclusion This method is suitable for the simultaneous determination of four vapor-phase TDs in workplace air.

Objective:To explore the effectiveness of nursing based on the Roy model in patients with Guillain-Barre syndrome (GBS) .Methods:Convenience sampling was used to select 55 patients with GBS at the First People's Hospital of Shangqiu between January 2020 and May 2024 as study subjects. Patients were divided into an intervention group ( n=28) and a control group ( n=27). Control group received conventional nursing, while intervention group received nursing based on Roy adaptation model. The recovery time, psychological state, and social support of the two groups of patients were compared. Results:Intervention group demonstrated shorter recovery times, lower anxiety and depression scores, and higher Social Support Rating Scale scores compared to control group, with all differences being statistically significant ( P<0.05) . Conclusions:The Roy model nursing in this study of GBS patients, effectively improves recovery outcomes, psychological state, and social support among GBS patients through comprehensive assessment, personalized nursing intervention, and ongoing evaluation.

Objective:To explore the regulation and mechanism of human placental extract(HPE)on lipopolysaccharide(LPS)-induced BV2 microglial cell inflammation.Methods:Microglia cell lines(BV2)were cultured in vitro and divided into PBS group,HPE group,LPS group and LPS+HPE group.BV2 cell viability was measured by CCK-8 analysis.A fluorescent probe targeting reactive oxygen species(ROS)was to detect the level of intracellular ROS.The mRNA levels of TNF-α,IL-1β and IL-6 were detected by RT-qPCR.The supernatants of different treatment groups were collected.The content of nitric oxide(NO)was detected by the Griess method,and the secretion levels of TNF-α,IL-1β and IL-6 were detected by the flow magnetic bead microarray(CBA)method.The indirect contact co-culture system between BV2 and mouse hippocampal neurons cell line HT22 cells was established to evaluate the neurotoxicity of HPE by the assessment of the cell viability and apoptosis of HT22 cells using CCK-8 or flow cytometry.The potential signaling molecules of NF-κB signaling pathway was detected by flow cytometry.Results:Compared with the PBS group,1.2 μg/ml LPS and 50 ng/ml HPE significantly inhibited the activity of BV2 cells.Compared with the PBS group,the mRNA levels of TNF-α,IL-1β and IL-6 in BV2 cells of the LPS group were significantly increased(P<0.05),and the secretion levels of NO,TNF-α,IL-1βand IL-6 in the supernatant were also significantly upregulated(P<0.05).The expressions of related signaling pathway molecules Toll-like receptor 4(TLR4),pIκBα and pNF-κB p65 were significantly increased(P<0.05).Compared with the LPS group,the mRNA levels of TNF-α,IL-1β and IL-6 in BV2 cells,the secretion levels of NO,TNF-α,IL-1β and IL-6,the neurotoxicity and neuronal apoptosis induced by microglial conditional medium,and the expressions of TLR4,pIκBα and pNF-κB p65 in the LPS+HPE group were significantly downregulate(P<0.05).Conclusion:HPE may alleviate the microglial inflammation,possibly through the TLR4/NF-κB signaling pathway.

Objective:To investigate the protective effects of resveratrol (RSV) on human sperm cryopreservation and explore its underlying protective mechanisms.Methods:A total of 165 normal fresh semen samples were collected from the Reproductive Medicine Center, Department of Obstetrics and Gynecology and Human Sperm Bank of the First Affiliated Hospital of Anhui Medical University between December 2022 and December 2024. Among them, 65 samples were used to obtain semen parameters before and after conventional freezing. Each sample of the other 104 samples was mixed at a 2∶1 volume ratio with cryoprotectant containing 0, 10 -?, 10 -?, or 10 -? mol/L RSV, followed by cryopreservation in liquid nitrogen for 24 h. Post-thaw assessments included routine sperm parameters, sperm DNA fragmentation index (DFI) evaluated by sperm chromatin dispersion assay, reactive oxygen species (ROS) levels measured via flow cytometry, RSV and nuclear factor erythroid 2-related factor 2 (NRF2) interactions examined by molecular docking and cellular thermal shift assay (CETSA), NRF2 protein contents analyzed by immunofluorescence and Western blotting, mRNA levels of NRF2 and downstream antioxidant proteins Heme Oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) quantified by qRT-PCR and effects of NRF2 inhibitor ML385 on sperm parameters. Results:Compared with fresh samples, conventional cryopreservation significantly reduced sperm motility (all P<0.001). The addition of 10 -? mol/L RSV significantly improved the percentage of forward motile sperm after freezing (26.98%±8.98% vs. 19.61%±8.03%, P<0.001) while reducing DFI (9.84%±3.81% vs. 15.06%±4.22%, P<0.001) and ROS levels ( P<0.001) compared with the post-freezing group without the addition of RSV. Both molecular docking analysis and CETSA confirmed that RSV interacted with NRF2. Notably, sperm cryopreserved with 10 -? mol/L RSV exhibited significantly higher contents of NRF2 and its downstream effectors HO-1 and NQO1 compared with the post-freezing group without the addition of RSV (all P<0.001). This protective effect was markedly attenuated by co-treatment with the NRF2 inhibitor ML385, as evidenced by a significant decline in sperm motility ( P<0.001). Conclusion:RSV exerts cryoprotective effects likely through NRF2-mediated antioxidant pathways, reducing oxidative stress and enhancing post-thaw sperm quality.

OBJECTIVE: To investigate the genetic etiology of six adult patients with Dilated cardiomyopathy (DCM), and analyze the structure of the identified variants, for providing reference for the diagnosis of DCM. METHODS: Six adult patients with DCM (patients 1-6) admitted to the Department of Cardiology of Zhumadian Central Hospital from January 2023 to December 2023 were recruited. Clinical data of the patients were retrospectively collected. And 5 mL of peripheral blood was collected from each patient. Pathogenic variants of the patients were detected by whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. The possible functional significance of the identified missense variants was evaluated using software including SIFT, PolyPhen-2 and Mutation Taster. Specific regions of the MYBPC protein encoded by the MYBPC3 gene from different species were aligned using Mutation Taster. The wild-type and mutant MYBPC proteins were constructed using homologous modeling software MODELLER v10.4 and three-dimensional structures were visualized using PyMOL software. The molecular interaction between MYBPC-C5 domain and myosin with or without the mutation was further analyzed using ZDOCK module in Discovery Studio 2019 software. Pathogenicity ratings for the detected variant sites were performed in accordance with the Standards and Guidelines for the Interpretation of Sequence variants by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG Guidelines). This study was reviewed and approved by the Ethics Committee of Zhumadian Central Hospital (Approval No. 2022092007). RESULTS: The six DCM patients had typical symptoms of heart failure, and echocardiography showed whole-heart dilation and decreased ventricular wall motion, left ventricular end-diastolic dimension (LVEDD) was 59-74 mm, left ventricular ejection fraction (LVEF) was 35%-43%, and left ventricular fractional shortening (LVFS) was 17%-28%. Variations of the DCM related genes, including a c.98473A>T (p.Lys32825*) variation of the TTN gene and a c.1976T>C (p.Ile659Thr) variation of the MYBPC3 gene, were identified in two patients. Multiple software predicted that both mutations were deleterious. MYBPC3-Ile659Thr mutation affected the highly conserved residue within the C5 domain of MYBPC. Three-dimensional structural analysis of homologous modeling revealed the alterations in amino acid properties and interactions with surrounding amino acids caused by the MYBPC3-Ile659Thr mutation. Further molecular docking analysis showed that the Ile659Thr mutation altered both the hydrogen bond and salt-bridge interactions between the MYBPC-C5 domain and the ligand myosin. CONCLUSION Two mutations associated with DCM were identified in this study. The abnormal conformation of the mutant protein further affected its interaction with the ligand myosin, resulting in the phenotype of DCM.
Humans ; Cardiomyopathy, Dilated/genetics* ; Male ; Adult ; Female ; Carrier Proteins/chemistry* ; Middle Aged ; Mutation ; Exome Sequencing ; Mutation, Missense ; Retrospective Studies ; Myosin Binding Protein C

OBJECTIVE: To explore the prenatal features and genetic etiology of a fetus with Short-rib cage dysplasia (SRTD) due to variants of DYNC2H1 gene. METHODS: A pregnant women presented at Xinxiang Central Hospital in June 2020 for abnormal prenatal ultrasound findings was selected as the study subject. With informed consent obtained, amniotic fluid sample was extracted from the woman, and clinical data of the fetus were collected. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of Xinxiang Central Hospital [Ethics No.: 2025-214-01(K)]. RESULTS: At 25⁺⁶ weeks gestation, genetic testing revealed that the fetus has harbored compound heterozygous variants of the DYNC2H1 gene, namely c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly), which were derived from its father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly) variants were classified as pathogenic (PVS1+PM2_supporting+PM3+PP5) and likely pathogenic (PM1+PM2_supporting+PM3+PP3), respectively. Bioinformatics analysis suggested that both variants may affect the 3D structure of the DYNC2H1 protein. CONCLUSION The compound heterozygous variants of c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly) of the DYNC2H1 gene probably underlay the pathogenesis of SRTD in the fetus. Above findings had facilitated prenatal diagnosis and genetic counseling for the couple.
Humans ; Female ; Pregnancy ; Cytoplasmic Dyneins/chemistry* ; Prenatal Diagnosis ; Adult ; Short Rib-Polydactyly Syndrome/diagnostic imaging* ; Mutation ; Exome Sequencing ; Fetus/abnormalities* ; Ultrasonography, Prenatal

Objective:To standardize the management of Investigator-Initiated Trials(IITs) and improve the quality of research projects, this study takes a tertiary hospital in Beijing as an example to analyze the key risk points in the implementation process of IITs and proposes countermeasures based on the issues identified during the management process.Methods:The study analyzed the IITs conducted at in the hospital from 2022 to 2023, focusing on 4 aspects: project classification evaluation and management (risk management), project implementation quality (process management), collaboration and support conditions(contract review and execution), and participant protection (medical ethics). It examined the key points and difficulties in project process management to standardize the quality management of IITs.Results:The implementation process management of IITs in medical institutions was an essential component for standardized clinical research management and an effective means to ensure the scientific nature of clinical research and the quality of data.Conclusions:Medical institutions should establish an effective and feasible IIT quality management system to comprehensively enhance the quality of IIT project, aiming to produce high-quality clinical research outcomes.

In order to establish a simple,sensitive and specific diagnostic method for the simultane-ous detection of Mycoplasma hyorhinis(Mhr)and Mycoplasma hyopneumoniae(Mhp)in swine,specific primers and probes were designed using the Mhr p37 and Mhp p36 gene sequences as the target genes,and the dual LFD-RPA rapid test was established by screening the primers and probes,optimizing primer ratios and evaluating its effectiveness through the sensitivity,reproduc-ibility and clinical sample testing.The sensitivity,specificity,reproducibility and clinical samples were evaluated.The results showed that the established dual LFD-RPA assay could complete the amplification in 15 min at 39 ℃,and its optimal primer ratio was 1.6∶0.8,and the lowest detection limits were up to 3.63 and 3.60 copies/μL,respectively;the reproducibility was stable;and there was no cross-reactivity with Pasteurella multocida,Bordetella bronchiseptica,Haemophilus pa-rasuis,Actinobacillus pleuropneumoniae,Escherichia coli.The test successfully established a dual LFD-RPA assay,which can detect Mhr and Mhp simultaneously,and is simple,sensitive and spe-cific without relying on specialized equipment,and is suitable for carrying out on-site rapid diagno-sis of Mhr and Mhp.