ObjectiveThe accuracy of Y-chromosome haplogroup assignment is crucial for tracing paternal lineage in male samples. With the advancement of high-throughput sequencing technologies, high-density Y-SNP genotyping from whole-genome or array-based data has become a standard method for determiningY-chromosome haplogroups. This study systematically evaluated the performance of 4 commonly used high-density SNP genotyping systems—namely, the Global Screening Array (GSA), Chinese Genotyping Array (CGA), Affymetrix array, and the 1240K capture panel—for haplogroup assignment. This work provides a reference for data comparison across different systems. MethodsWe extracted genotype data for the 4 Y-SNP panels from 30× whole-genome sequencing (WGS) data of 1 590 male samples from the 1000 Genomes Project. Additionally, GSA array genotype data from 384 relative pairs (spanning 1st- to 12th-degree relationships) from 109 Chinese Han families were collected. Haplogroup assignment was performed using Y-LineageTracker v1.3.0 software. We assessed the concordance and resolution of haplogroup assignments between the four Y-SNP panels and the WGS data. The consistency and resolution of haplogroup assignments were also evaluated for both the 1000 Genomes Project samples and the 109 family samples collected in this study. Furthermore, the impact of varying numbers of Y-SNPs on haplogroup assignment was examined. ResultsThe GSA and CGA panels demonstrated superior resolution and discrimination of haplogroup subclades compared with the other two panels. The haplogroup assignments from the GSA, CGA, and 1240K panels showed high concordance with WGS data, with consistency rates exceeding 88.70%, whereas the Affymetrix platform exhibited a significantly lower consistency rate of 61.89%. Specifically, the GSA and CGA panels consistently demonstrated superior performance compared with the other two panels in the assignment of haplogroups O-M175 and H-L901, achieving complete concordance (100%) for both haplogroups. In contrast, the Affymetrix panel erroneously assigned all individuals belonging to haplogroup O-M175 to haplogroup K2-M526. Furthermore, its accuracy for haplogroup H-L901 was exceedingly low, at merely 1.41%. This poor performance was characterized by the misassignment of 98.59% of H-L901 samples—specifically, 1.41% to J-M304 and a predominant 97.18% to F-M89. For haplogroup R-M207, all four panels exhibited uniformly high levels of consistency, with concordance values exceeding 94.00%. Notably, for haplogroup E-M96, the 1240K and Affymetrix panels outperformed the GSA and CGA panels in terms of concordance, representing the first instance in which these two panels surpassed the latter. Conversely, for haplogroups J-M304, Q-M242, and I-M170, all 4 panels showed relatively elevated misclassification rates, with the Affymetrix array demonstrating the poorest overall performance. None of the four panels showed any discordant haplogroup assignments among the familial relative pairs analyzed. A positive correlation was observed between the number of Y-SNPs (ranging from 1 000 to 10 000) and classification consistency; however, classification consistency plateaued when the number of Y-SNPs exceeded 10 000. Furthermore, a random sampling analysis conducted on the GSA and CGA panels demonstrated that the haplogroup misclassification rate exhibited negligible fluctuation across the Y-SNP range of 500 to 1 000. Conversely, a marked enhancement in classification consistency was observed as the number of markers increased from 1 000 to 5 000, ultimately reaching a plateau within the interval of 5 000 to 8 000 markers. ConclusionThese findings indicate that the GSA and CGA panels provide high resolution and concordance, delivering reliable Y-haplogroup assignment for forensic investigations.

ObjectiveThe accuracy of Y-chromosome haplogroup assignment is crucial for tracing paternal lineage in male samples. With the advancement of high-throughput sequencing technologies, high-density Y-SNP genotyping from whole-genome or array-based data has become a standard method for determiningY-chromosome haplogroups. This study systematically evaluated the performance of 4 commonly used high-density SNP genotyping systems—namely, the Global Screening Array (GSA), Chinese Genotyping Array (CGA), Affymetrix array, and the 1240K capture panel—for haplogroup assignment. This work provides a reference for data comparison across different systems. MethodsWe extracted genotype data for the 4 Y-SNP panels from 30× whole-genome sequencing (WGS) data of 1 590 male samples from the 1000 Genomes Project. Additionally, GSA array genotype data from 384 relative pairs (spanning 1st- to 12th-degree relationships) from 109 Chinese Han families were collected. Haplogroup assignment was performed using Y-LineageTracker v1.3.0 software. We assessed the concordance and resolution of haplogroup assignments between the four Y-SNP panels and the WGS data. The consistency and resolution of haplogroup assignments were also evaluated for both the 1000 Genomes Project samples and the 109 family samples collected in this study. Furthermore, the impact of varying numbers of Y-SNPs on haplogroup assignment was examined. ResultsThe GSA and CGA panels demonstrated superior resolution and discrimination of haplogroup subclades compared with the other two panels. The haplogroup assignments from the GSA, CGA, and 1240K panels showed high concordance with WGS data, with consistency rates exceeding 88.70%, whereas the Affymetrix platform exhibited a significantly lower consistency rate of 61.89%. Specifically, the GSA and CGA panels consistently demonstrated superior performance compared with the other two panels in the assignment of haplogroups O-M175 and H-L901, achieving complete concordance (100%) for both haplogroups. In contrast, the Affymetrix panel erroneously assigned all individuals belonging to haplogroup O-M175 to haplogroup K2-M526. Furthermore, its accuracy for haplogroup H-L901 was exceedingly low, at merely 1.41%. This poor performance was characterized by the misassignment of 98.59% of H-L901 samples—specifically, 1.41% to J-M304 and a predominant 97.18% to F-M89. For haplogroup R-M207, all four panels exhibited uniformly high levels of consistency, with concordance values exceeding 94.00%. Notably, for haplogroup E-M96, the 1240K and Affymetrix panels outperformed the GSA and CGA panels in terms of concordance, representing the first instance in which these two panels surpassed the latter. Conversely, for haplogroups J-M304, Q-M242, and I-M170, all 4 panels showed relatively elevated misclassification rates, with the Affymetrix array demonstrating the poorest overall performance. None of the four panels showed any discordant haplogroup assignments among the familial relative pairs analyzed. A positive correlation was observed between the number of Y-SNPs (ranging from 1 000 to 10 000) and classification consistency; however, classification consistency plateaued when the number of Y-SNPs exceeded 10 000. Furthermore, a random sampling analysis conducted on the GSA and CGA panels demonstrated that the haplogroup misclassification rate exhibited negligible fluctuation across the Y-SNP range of 500 to 1 000. Conversely, a marked enhancement in classification consistency was observed as the number of markers increased from 1 000 to 5 000, ultimately reaching a plateau within the interval of 5 000 to 8 000 markers. ConclusionThese findings indicate that the GSA and CGA panels provide high resolution and concordance, delivering reliable Y-haplogroup assignment for forensic investigations.

Objective This study conducted molecular biological identification of the viruses carried by Culex pipiens pallens specimens collected in Shunyi District, Beijing in 2023, and observed the changes in the infection rate of the viruses carried by Cx. pipiens pallens at different collection times. Methods Cx. pipiens pallens were collected using carbon dioxide mosquito traps. The mosquito samples were ground in batches and analyzed by molecular biology technologies. The virus infection rate at different collection times was analyzed statistically. Results 17 strains of Culex pipiens pallens densovirus(CppDNV)were identified from Cx. pipiens pallens samples collected in Shunyi District, Beijing, in 2023. The nucleotide sequence analysis of the virus genome coding region showed that CppDNV was a single-stranded DNA virus with a total length of 3 335 nt, encoding 2 non-structural proteins(NS1, NS2)and 1 capsid protein(VP). The nucleotide(amino acid)sequence lengths of the three proteins were 2 376 nt(791 aa),1 092 nt(363 aa)and 1 071 nt(356 aa), respectively. Phylogenetic analysis showed that CppDNV was located in genus Brevihamaparvovirus. Statistical analysis showed no significant difference in infection rates across collection times(χ2=4.429, P=0.194). Conclusions CppDNV was identified in Cx. pipiens pallens in Beijing, and it was stably maintained in this natural population.

Big Data ; Humans ; Data Management

OBJECTIVE: Investigating the clinical efficacy of treating dorsally displaced distal radial double-column Die-punch fractures using a dorsal approach external fixator combined with Kirschner wires. METHODS: Retrospectively analyzed the clinical data of 15 patients with distal radial double-column Die-punch fractures treated with an external fixator combined with Kirschner wire between July 2020 and January 2023. There were 10 males and 5 females;6 cases on the left side and 9 on the right;age ranged from 22 to 76 years old. Recorded the preoperative and the final follow-up Cooney wrist function scores for the patients. The fracture healing time, and occurrence of complications were recorded. RESULTS: All 15 patients were followed up ranged from 12 to 16 months post-operation. All fractures achieved bony union, healing time ranging form 8 to 16 weeks. Not a single patient exhibited complications such as surgical site infection, fracture redislocation, or tendon injury. All individuals had their Kirschner wires and external fixation devices removed six weeks post-operatively and commenced rehabilitative therapy for wrist articulation. The Cooney wrist function scores at preoperative and ranged from 5 to 45 scores, at the latest follow-up ranged from 65 to 100 scores. At the final follow-up, the results were assessed as excellent in 10 patients, good in 4 patients, and fair in 1 patient. CONCLUSION The clinical efficacy of treating distal radial double-column Die-punch fractures using a dorsal approach external fixator combined with Kirschner wires is satisfactory.
Humans ; Male ; Female ; Middle Aged ; Adult ; External Fixators ; Bone Wires ; Aged ; Retrospective Studies ; Radius Fractures/physiopathology* ; Young Adult ; Fracture Fixation/methods*

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Nitrogen narcosis is a neurological syndrome that manifests when humans or animals encounter hyperbaric nitrogen, resulting in a range of motor, emotional, and cognitive abnormalities. The anterior cingulate cortex (ACC) is known for its significant involvement in regulating motivation, cognition, and action. However, its specific contribution to nitrogen narcosis-induced hyperlocomotion and the underlying mechanisms remain poorly understood. Here we report that exposure to hyperbaric nitrogen notably increased the locomotor activity of mice in a pressure-dependent manner. Concurrently, this exposure induced heightened activation among neurons in both the ACC and dorsal medial striatum (DMS). Notably, chemogenetic inhibition of ACC neurons effectively suppressed hyperlocomotion. Conversely, chemogenetic excitation lowered the hyperbaric pressure threshold required to induce hyperlocomotion. Moreover, both chemogenetic inhibition and genetic ablation of activity-dependent neurons within the ACC reduced the hyperlocomotion. Further investigation revealed that ACC neurons project to the DMS, and chemogenetic inhibition of ACC-DMS projections resulted in a reduction in hyperlocomotion. Finally, nitrogen narcosis led to an increase in local field potentials in the theta frequency band and a decrease in the alpha frequency band in both the ACC and DMS. These results collectively suggest that excitatory neurons within the ACC, along with their projections to the DMS, play a pivotal role in regulating the hyperlocomotion induced by exposure to hyperbaric nitrogen.
Animals ; Gyrus Cinguli/drug effects* ; Male ; Mice, Inbred C57BL ; Locomotion/drug effects* ; Neurons/drug effects* ; Mice ; Nitrogen/toxicity* ; Inert Gas Narcosis/physiopathology* ; Corpus Striatum/physiopathology*

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

Norepinephrine (NE) modulates synaptic transmission and long-term plasticity through distinct subtype adrenergic receptor (AR)-mediated-intracellular signaling cascades. However, the role of NE modulates glutamatergic long-term potentiation (LTP) in the hypothalamic paraventricular nucleus (PVN) magnocellular neuroendocrine cells (MNCs) is unclear. We here investigate the effect of NE on high frequency stimulation (HFS)-induced glutamatergic LTP in rat hypothalamic PVN MNCs in vitro, by whole-cell patch-clamp recording, biocytin staining and pharmacological methods. Delivery of HFS induced glutamatergic LTP with a decrease in N2/N1 ratio in the PVN MNCs, which was enhanced by application of NE (100 nM).HFS-induced LTP was abolished by the blockade of N-methyl-D-aspartate receptors (NMDAR) with D-APV, but it was rescued by the application of NE. NE failed to rescue HFS-induced LTP of MNCs in the presence of a selective β1-AR antagonist, CGP 20712. However, application of β1-AR agonist, dobutamine HCl rescued HFS-induced LTP of MNCs in the absence of NMDAR activity. In the absence of NMDAR activity, NE failed to rescue HFS-induced MNC LTP when protein kinase A (PKA) was inhibited by extracellular applying KT5720 or intracellular administration of PKI. These results indicate that NE activates β1-AR and triggers HFS to induce a novel glutamatergic LTP of hypothalamic PVN NMCs via the postsynaptic PKA signaling pathway in vitro in rats.