Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

In order to further standardize the vaccination of kidney transplant candidates and recipients in China, the Branch of Organ Transplantation of Chinese Medical Association has organized experts in kidney transplantation and infectious diseases. Based on the "Vaccination of Solid Organ Transplant Candidates and Recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice", and in combination with the clinical reality of infectious diseases and vaccination after organ transplantation in China, as well as referring to relevant recommendations from home and abroad in recent years, these guidelines are formulated from aspects such as epidemiology, types of vaccines, vaccination principles, target population, and specific vaccine administration. The "Guidelines for Vaccination of Kidney Transplant Candidates and Recipients in China" aims to provide theoretical reference for medical workers in the field of kidney transplantation in China, regarding the vaccination of kidney transplant candidates and recipients. It is expected to better guide the vaccination of kidney transplant candidates and recipients, reduce the risk of postoperative infection, and improve survival outcomes.

ObjectiveTo investigate the mechanism by which Feixin decoction treats hypoxic pulmonary hypertension （HPH） by regulating the peroxisome proliferator-activated receptor gamma （PPARγ）/nuclear factor-kappa B （NF-κB）/NOD-like receptor pyrin domain containing 3 （NLRP3） signaling pathway. MethodsForty-eight male SD rats were randomly allocated into normal， hypoxia， and low-， medium- and high-dose （5.85， 11.7， 23.4 g·kg^-1， respectively） Feixin decoction groups， with 8 rats in each group. Except the normal group， the remaining five groups were placed in a hypoxia chamber with an oxygen concentration of （10.0±0.5）% for 8 h per day， 28 days， and administrated with corresponding drugs during the modeling process. After 4 weeks of treatment， echocardiographic parameters ［pulmonary artery acceleration time （PAT）， pulmonary artery ejection time （PET）， right ventricular anterior wall thickness （RVAWd）， and tricuspid annular plane systolic excursion （TAPSE）］ were measured for each group. The right ventricular systolic pressure （RVSP） was measured by the right heart catheterization method， and the right ventricular hypertrophy index （RVHI） was calculated by weighing the heart. The pathological changes in pulmonary arterioles were observed by hematoxylin-eosin staining. The co-localization of α-smooth muscle actin （α-SMA） with NLRP3， N-terminal gasdermin D （N-GSDMD）， and cysteinyl aspartate-specific proteinase-1 （Caspase-1） in pulmonary arteries was detected by immunofluorescence. The protein levels of PPARγ， NF-κB， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， N-GSDMD， interleukin-1β （IL-1β）， interleukin-18（IL-18）， and cleaved Caspase-1 in the lung tissue was determined by Western blot. The ultrastructural changes in pulmonary artery smooth muscle cells （PASMCs） were observed by transmission electron microscopy. ResultsCompared with the normal group， the hypoxia group showed increased RVSP and RVHI （P<0.01）， decreased right heart function （P<0.01）， increased pulmonary vascular remodeling （P<0.01）， increased co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 in pulmonary arterioles （P<0.01）， up-regulated protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， a down-regulated protein level of PPARγ （P<0.05， P<0.01）， and pyroptosis in PASMCs. Compared with the hypoxia group， Feixin decoction reduced RVSP and RVHI， improved the right heart function and ameliorated pulmonary vascular remodeling （P<0.05， P<0.01）， decreased the co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， up-regulated the protein level of PPARγ （P<0.05， P<0.01）， and alleviated pyroptosis in PASMCs. ConclusionFeixin decoction can ameliorate pulmonary vascular remodeling and right heart dysfunction in chronically induced HPH rats by regulating pyroptosis in PASMCs through the PPARγ/NF-κB/NLRP3 pathway.

ObjectiveJunctophilin-2 (JPH2) is an essential structural protein that maintains junctional membrane complexes (JMCs) in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum, thereby facilitating excitation-contraction (E-C) coupling. Mutations in JPH2 have been associated with hypertrophic cardiomyopathy (HCM), but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus (MORN) repeat motifs remain incompletely understood. This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis. MethodsA recombinant N-terminal fragment of mouse JPH2 (residues1-440), encompassing the MORN repeats and an adjacent helical region, was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain. Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features. Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells. In addition, site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations, including R347C, was used to evaluate their effects on membrane interaction and subcellular localization. ResultsThe crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6 Å, revealing a compact, elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration, forming a continuous hydrophobic core stabilized by alternating aromatic residues. A C-terminal α-helix further reinforced structural integrity. Conservation analysis identified the inner groove of the MORN array as a highly conserved surface, suggesting its role as a protein-binding interface. A flexible linker segment enriched in positively charged residues, located adjacent to the MORN motifs, was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes. Functional assays demonstrated that mutation of these basic residues impaired membrane association, while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays, despite preserving the overall MORN-Helix fold in structural modeling. ConclusionThis study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2, highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions. The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis. These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.

Erectile dysfunction (ED) is prevalent among men, but its relationship with dietary habits is uncertain. The aim of our study was to assess whether dietary patterns enhance erectile function by reviewing the literature published before August 1, 2022, via PubMed, Web of Science, and EMBASE databases. The data compiled included author details; publication dates, countries, treatments, patient numbers, ages, follow-ups, and clinical trial outcomes, such as ED cases, odds ratios (ORs), confidence intervals (CIs), and International Index of Erectile Function-5 (IIEF-5) scores with means and standard deviations. An analysis of 14 studies with 27 389 participants revealed that plant-based diets (OR = 0.71, 95% CI: 0.66-0.75; P < 0.00001), low-fat diets (OR = 0.27, 95% CI: 0.13-0.53; P = 0.0002), and alternative diets such as intermittent fasting and organic diets (OR = 0.54, 95% CI: 0.36-0.80; P = 0.002) significantly reduced ED risk. High-protein low-fat diets (hazard ratio [HR] = 1.38, 95% CI: 1.12-1.64; P < 0.00001) and high-carb low-fat diets (HR = 0.79, 95% CI: 0.55-1.04; P < 0.00001) improved IIEF-5 scores. Combined diet and exercise interventions decreased the likelihood of ED (OR = 0.49, 95% CI: 0.28-0.85; P = 0.01) and increased the IIEF-5 score (OR = 3.40, 95% CI: 1.69-5.11; P < 0.0001). Diets abundant in fruits and vegetables (OR = 0.97, 95% CI: 0.96-0.98; P < 0.00001) and nuts (OR = 0.54, 95% CI: 0.37-0.80; P = 0.002) were also correlated with lower ED risk. Our meta-analysis underscores a strong dietary-ED association, suggesting that low-fat/Mediterranean diets rich in produce and nuts could benefit ED management.
Humans ; Male ; Erectile Dysfunction/epidemiology* ; Diet ; Diet, Fat-Restricted ; Feeding Behavior ; Penile Erection/physiology* ; Diet, Vegetarian

OBJECTIVES: To investigate the role and mechanism of fibroblast growth factor (FGF) 19 in inflammation-induced injury of vascular endothelial cells caused by high glucose (HG). METHODS: Human umbilical vein endothelial cells (HUVECs) were randomly divided into four groups: control, HG, FGF19, and HG+FGF19 (n=3 each). The effect of different concentrations of glucose and/or FGF19 on HUVEC viability was assessed using the CCK8 assay. Flow cytometry was utilized to examine the impact of FGF19 on HUVEC apoptosis. Levels of interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were measured by ELISA. Real-time quantitative PCR and Western blotting were used to determine the mRNA and protein expression levels of vascular endothelial growth factor (VEGF), nuclear factor erythroid 2 related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Cells were further divided into control, siRNA-Nrf2 (siNrf2), HG, HG+FGF19, HG+FGF19+negative control, and HG+FGF19+siNrf2 groups (n=3 each) to observe the effect of FGF19 on oxidative stress injury in HUVECs induced by high glucose after silencing the Nrf2 gene. RESULTS: Compared to the control group, the HG group exhibited increased apoptosis rate, increased IL-6, iNOS and MDA levels, and increased VEGF mRNA and protein expression, along with decreased T-SOD activity and decreased mRNA and protein expression of Nrf2 and HO-1 (P<0.05). Compared to the HG group, the HG+FGF19 group showed reduced apoptosis rate, decreased IL-6, iNOS and MDA levels, and decreased VEGF mRNA and protein expression, with increased T-SOD activity and increased Nrf2 and HO-1 mRNA and protein expression (P<0.05). Compared to the HG+FGF19+negative control group, the HG+FGF19+siNrf2 group had decreased T-SOD activity and increased MDA levels (P<0.05). CONCLUSIONS FGF19 can alleviate inflammation-induced injury in vascular endothelial cells caused by HG, potentially through the Nrf2/HO-1 signaling pathway.
Humans ; NF-E2-Related Factor 2/genetics* ; Signal Transduction ; Human Umbilical Vein Endothelial Cells/drug effects* ; Fibroblast Growth Factors/pharmacology* ; Heme Oxygenase-1/physiology* ; Apoptosis/drug effects* ; Glucose ; Inflammation ; Interleukin-6/analysis* ; Vascular Endothelial Growth Factor A/genetics* ; Nitric Oxide Synthase Type II/analysis* ; Cells, Cultured

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].