BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

PURPOSE: The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery. METHODS: A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications. RESULTS: In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram. CONCLUSION Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans ; COVID-19/complications* ; Male ; Female ; Middle Aged ; Postoperative Complications/epidemiology* ; SARS-CoV-2 ; Orthopedic Procedures/adverse effects* ; Aged ; Nomograms ; Adult ; Retrospective Studies ; Risk Factors

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVES: Injury to human cardiac microvascular endothelial cells (HCMECs) compromises myocardial microcirculation and may contribute to major cardiovascular events such as coronary heart disease, posing a serious health threat. Understanding the mechanisms of hypoxia-induced HCMEC damage is thus of great clinical relevance. This study aims to investigate the protective effects and underlying mechanisms of Li Qi Huo Xue Di Wan against hypoxia-induced HCMEC injury. METHODS: HCMECs were cultured under hypoxic conditions for 24 hours to establish a cellular model of hypoxic injury. Cells were divided into six groups: normal control, hypoxia, hypoxia + low-dose Li Qi Huo Xue Di Wan, hypoxia + medium-dose, hypoxia + high-dose, and hypoxia + salvianolic acid B (positive control). Cell viability was assessed using the MTS assay. Lactate dehydrogenase (LDH) release and malondialdehyde (MDA) content were measured to evaluate cytotoxicity and oxidative stress. Activities of superoxide dismutase (SOD), catalase (CAT), caspase-3, and caspase-8 were determined with corresponding assay kits. Apoptosis was analyzed by flow cytometry, and expression of necroptosis-related proteins, receptor-interacting protein kinase 1 (RIPK1) and its phosphorylated form (p-RIPK1), receptor-interacting protein kinase 3 (RIPK3) and its phosphorylated form (p-RIPK3), mixed lineage kinase domain-like protein (MLKL) and its phosphorylated form (p-MLKL), was examined via Western blotting. RESULTS: Compared with the control group, hypoxia significantly decreased cell viability (P<0.01), increased MDA levels (P<0.05), and reduced CAT and SOD activity (P<0.05), accompanied by elevated apoptosis (P<0.01) and increased levels of p-RIPK1, p-RIPK3, and p-MLKL (P<0.05). High-dose Li Qi Huo Xue Di Wan significantly improved cell viability (P<0.01), reduced MDA content (P<0.05), increased CAT activity (P<0.05), and suppressed necroptosis-related protein expression (P<0.05) compared with the hypoxia group. CONCLUSIONS Li Qi Huo Xue Di Wan exerts a protective effect against hypoxia-induced injury in HCMECs. This effect is mediated by attenuation of oxidative stress, thereby reducing both apoptosis and necroptosis.
Humans ; Apoptosis/drug effects* ; Necroptosis/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Cell Hypoxia/drug effects* ; Endothelial Cells/pathology* ; Oxidative Stress/drug effects* ; Cells, Cultured ; Cell Survival/drug effects* ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective: To investigate the significant factors influencing the need for perioperative blood transfusion in patients undergoing hepatectomy. Methods: Medical records of patients who underwent elective hepatectomy in our hospital from January 2020 to December 2021 were retrospectively collected. Variables associated with transfusion were analyzed using traditional logistic regression (LR) and machine learning algorithm, the Classification and Regression Tree (CRT). The predictive values of the two methods were compared by the area under the curve (AUC) of the ROC curve. Results: Among the 402 patients, 82(20.4%) received blood transfusions. Multivariable logistic regression analysis identified several risk factors for perioperative blood transfusion, including vascular invasion, preoperative hemoglobin level, intraoperative blood loss, duration of surgery, postoperative hemoglobin level, and postoperative complications (P<0.05). In the CRT model for predicting blood transfusion, intraoperative blood loss (cutoff: 450 mL) was the parent node, with preoperative Hb, postoperative complications, and hospital stay as child nodes. The LR model demonstrated superior predictive performance compared to the CRT model, with an AUC of 0.971 (95% CI: 0.956-0.985) vs 0.937 (95% CI: 0.909-0.965). The difference in AUC between the two methods was statistically significant (P<0.05). Conclusion: Although the CRT model did not outperform logistic regression in overall predictive accuracy, it still provides a valuable tool for assisting clinicians in making decisions about blood transfusion in the perioperative period of hepatectomy, thereby facilitating more individualized guidance for preoperative blood preparation in clinical practice.

Resident training is a necessary path to cultivate excellent clinical doctors. Based on the Consensus on Core Competency Framework for Residency Education Among China Consortium of Elite Teaching Hospitals for Residency Education, Department of Neurology from Peking Union Medical College Hospital has established a training program for neurology residents with a graded evaluation system and a progressive clinical responsibility concept guided by core competency. Overcoming the teaching difficulties of neurology and considering the clinical characteristics of neurology, we have established a series of replicable and promotable neurology residency training curriculum through inheritance and innovation, which provides reference for the continuous improvement of China's neurology residency training program.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To study the mechanism of icariin inhibiting the proliferation of human PCa PC-3 cells based on cell metabolomics technology.Methods:We determined the proliferation activity of human PC-3 cells by methyl thiazolyl tetrazolium(MTT)assay,and compared the proliferation of the PC-3 cells among the control,5-fluorouracil and icariin intervention groups.Using the Bligh Dyer method,we extracted endogenous metabolites from the cells,analyzed the metabolic profile by ultra-high pressure liquid chromatography tandem quadrupole time-of-flight mass spectrometry,identified the differential metabolites by principal component anal-ysis and orthogonal partial least-squares discrimination analysis,and enriched the metabolic pathways based on the MetaboAnalyst data-base.Results:Icariin significantly inhibited the proliferation of human PCa PC-3 cells.A total of 89 differential metabolites were i-dentified,mainly including amino acids,phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine,and lysophosphati-dylethanolamine,all with the tendency to return to the normal level after icariin intervention.Icariin significantly downregulated the metabolic levels of the glycerophospholipid metabolites phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine and ly-sophosphatidylethanolamine,and upregulated those of amino acid metabolites tryptophan,leucine,and proline in the PC-3 cells.Conclusion:Icariin inhibits the proliferation of human PCa PC-3 cells,which may be closely related to its regulatory effect on lipid metabolism(glycerophospholipid metabolism)and amino acid metabolism.