Objective To evaluate the effect of donor gender on short-term survival rate of lung transplant recipients. Methods A retrospective analysis was conducted on the data of 1 066 lung transplant recipients. The log-rank test was used to evaluate the differences in short-term fatality among different donor gender groups and donor-recipient gender combination groups. Multivariate Cox regression, propensity score (PS) regression, and propensity score matching (PSM) were employed to control for confounding factors and further assess the differences in fatality. Subgroup analyses were also performed based on donor gender. Results Multivariate Cox regression analysis showed no statistically significant differences in fatality at 30 days, 1 year, 2 years and 3 years postoperatively between male and female donor groups (all P>0.05). After PS regression and PSM, univariate Cox regression analysis indicated that recipients from female donors had a higher fatality at 2 years postoperatively compared to those from male donors, with hazard ratios (95% confidence intervals) of 1.29 (1.01-1.65) and 1.36 (1.03-1.80) respectively. Multivariate Cox regression analysis also revealed no statistically significant differences in fatality at various follow-up time points among different donor-recipient gender combination groups (all P>0.05). Subgroup analyses based on donor sex showed no statistically significant differences in fatality among recipients of different gender within either male or female donor groups (all P>0.05). Conclusions Female donors may reduce the short-term postoperative survival rate of lung transplant recipients, but this negative impact is not sustainable in the long term. At present, there is no evidence to support the inclusion of sex as a factor in lung allocation rules.

ObjectiveTo deeply understand the lived experience and needs of patients with end-stage heart failure， and to provide references for better implementing hospice care for patients with heart failure. MethodsA qualitative phenomenological research method was adopted to conduct in-depth interviews with 15 patients with end-stage heart failure. The Colaizzi 7-step analysis method was used to code， analyze， and extract themes from the interview data. ResultsFour themes and 10 sub-themes were identified： first， experiencing physical and psychological distress （a desire for relief from physical pain and a need for psychological counseling）； second， ambivalence towards family support （yearning for care but feeling guilty）； third， actively seeking social support （expecting to be understood and valued， facilitating access to support from the medical system， and differing perceptions of doctor-patient shared decision-making）； fourth， complex psychological experience regarding prognosis （experiencing fear and worry， feeling disappointed， living in the moment， and accepting death）. ConclusionMedical staff， family caregivers， and society should jointly pay attention to the physical and mental feelings and needs of patients with end-stage heart failure and provide targeted care. It is recommended to implement multidisciplinary team management， promote doctor-patient shared decision-making， meet individualized needs， and provide appropriate education on life and death concepts， thereby establishing a palliative and hospice care service model for end-stage heart failure with characteristics.

In China, the number of chronic pain patients has exceeded 300 million, making chronic pain the third major health problem after tumors and cardiovascular diseases. Particularly concerning is the gradual emergence of hypertension and chronic low back pain as public health problems that threaten public health and increase the global economic burden. Modern research shows that the incidence of coexisting hypertension is higher among patients with chronic low back pain. Additionally, evidence indicates that the use of NSAIDs for pain relief can have adverse effects on blood pressure, and some antihypertensive medications may trigger symptoms of low back pain. Thus, addressing chronic pain in hypertensive patients while stabilizing blood pressure is one of the important research questions in the modern treatment of hypertension among middle-aged and elderly individuals. From ancient to modern traditional Chinese medicine(TCM) theory, kidney deficiency has been regarded as the core pathogenesis of low back pain. Recent clinical practices and literature indicate that kidney deficiency plays a crucial role in the modern pathogenesis of hypertension. Both hypertension and chronic low back pain are closely associated with kidney deficiency in TCM theory, revealing a potential mechanism linking the two conditions. Combining the theories of " kidney-essence-marrow" and " nourishing water to moisten wood", a therapeutic strategy centered on tobifying kidney was proposed, including selecting single drugs with kidney-tonifying effects as well as compound formulations and elaborating modern research evidence. The aim is to achieve stable blood pressure control in hypertension patients with chronic low back pain while providing a new treatment perspective for chronic low back pain. This article systematically elaborates on the understanding of hypertension combined with chronic low back pain from both TCM and modern medicine, as well as the therapeutic strategy involving kidney-tonifying drugs, to offer useful references for clinical practice.
Humans ; Hypertension/complications* ; Low Back Pain/complications* ; Drugs, Chinese Herbal/therapeutic use* ; Kidney/drug effects* ; Medicine, Chinese Traditional ; Chronic Pain/drug therapy*

OBJECTIVES: To investigate the clinical characteristics and drug resistance profile of invasive non-typhoidal Salmonella (NTS) enteritis in children in Chengdu, China, providing a reference for rational drug use and empirical treatment in clinical practice. METHODS: A retrospective analysis was conducted on the clinical data of 130 children with invasive bacterial enteritis due to NTS identified by fecal bacterial culture and the results of drug sensitivity tests for NTS in Chengdu from January 2022 to December 2023. RESULTS: NTS infections were mainly observed from April to September (113 cases, 86.9%), with a peak in August (36 cases, 27.7%). Children aged <36 months accounted for 86.2% (112/130) of all cases, and the main symptoms were diarrhea (130 cases, 100%), fever (123 cases, 94.6%), and hematochezia (112 cases, 86.2%). The 130 NTS isolates exhibited a sensitivity rate of 64.6% to ceftriaxone and 63.8% to cefotaxime, and a sensitivity rate of >90.0% to piperacillin-tazobactam and nitrofurantoin (nitrofurans). The detection rate of multidrug-resistant strains was 48.5% (63/130), and the clinical efficacy of third-generation cephalosporins used in 38 patients (29.2%) was inconsistent with the results of drug sensitivity tests. CONCLUSIONS The peak of invasive NTS enteritis in children aged 0-6 years occurs in August in the Chengdu area, with a relatively high incidence rate in children aged <36 months. The situation of drug resistance is severe for NTS, and piperacillin-tazobactam may be an effective option for treating multidrug-resistant NTS infections in children, while nitrofuran antibiotics might be used to treat such infections.
Humans ; Infant ; Child, Preschool ; Enteritis/microbiology* ; Retrospective Studies ; Male ; Salmonella Infections/microbiology* ; Female ; Child ; Salmonella/drug effects* ; Infant, Newborn ; Microbial Sensitivity Tests ; Anti-Bacterial Agents/therapeutic use*

OBJECTIVES: To evaluate the therapeutic effect of gastrodin against hypoxic-ischemic brain damage (HIBD) in neonatal mice and explore the role of GPX4/SLC7A11/FTH1 signaling in mediating its effect. METHODS: Twenty-four 9- to 11-day-old C57BL/6J mice were randomized equally into 4 groups for sham operation, HIBD modeling by right common carotid artery ligation and subsequent exposure to hypoxia for 1 h, or gastrodin treatment at 100 or 200 mg/kg before and at 1 and 2 days after modeling. The mice then underwent neurological assessment (Zea-Longa scores), and the cerebral cortical penumbra tissue were collected for HE and Nissl staining, detection of ferroptosis biomarkers and protein expressions of GPX4, SLC7A11, and FTH1 with Western blotting and immunofluorescence co-localization, and observation of mitochondrial ultrastructure with electron microscopy. In cultured HT22 neuronal cells with oxygen-glucose deprivation (OGD) for 2 h, the effects of pretreatments with 0.5 mmol/L gastrodin, 10 μmol/L RSL3 (a GPX4 inhibitor), alone or in combination, were analyzed on expressions of ferroptosis-related proteins, cellular Fe²⁺, ROS, lipid peroxidation, MDA, and GSH levels, mitochondrial membrane potential (JC-1), and cell viability. RESULTS: Gastrodin treatment at the two doses both significantly ameliorated HIBD and neurological deficits of the mice, reduced mitochondrial damage and Fe²⁺, MDA and ROS levels, increased GSH level, and upregulated GPX4, SLC7A11, and FTH1 protein expressions. In HT22 cells, gastrodin pretreatment obviously attenuated OGD-induced ferroptosis and improved cell viability and mitochondrial function. Co-treatment with RSL3 potently abrogated the inhibitory effects of gastrodin on Fe²⁺, ROS, BODIPY-C11, and MDA levels and attenuated its protective effects on GSH level, cell viability, and mitochondrial membrane potential. CONCLUSIONS Gastrodin provides neuroprotective effects in neonatal mice with HIBD by suppressing neuronal ferroptosis via upregulating the GPX4/SLC7A11/FTH1 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Hypoxia-Ischemia, Brain/drug therapy* ; Mice ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Glucosides/pharmacology* ; Animals, Newborn ; Benzyl Alcohols/pharmacology* ; Amino Acid Transport System y+/metabolism*

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

Objective:To sort out and analyze the current situation of research related to patient privacy protection in China in the context of healthcare data sharing,with a view to providing a reference for future research in related fields.Methods:Journal articles related to patient privacy protection were retrieved from China National Knowledge Infrastructure and Wanfang databases from 2018 to 2023.The Cite Space 6.2.R 5 software was used to conduct analysis of keyword cluster and keyword burst.Combined with the specific contents of literature,the current situation of research on patient privacy protection in China was sorted out.Results:A total of 1,590 articles were included for analysis.The core journal with the most publications was China Medical Ethics(54 articles,3.40%).The current situation of research in the field of patient privacy protection in China can be summarized as the privacy issues related to medical care activities,privacy issues caused by new technologies of medical services,and privacy issues in special situations.The results of keyword burst analysis showed that"personal information"and"data sharing"were current hot research topics.Conclusion:In the context of healthcare data sharing,patient privacy protection is still a research hot focus.The current research on the definition of patient privacy protection is relatively limited.It is recommended to deeply explore the understanding of multiple parties on privacy protection and enrich the connotation of patient privacy protection from multiple perspectives in the future.In addition,it is necessary to strengthen medical staff's awareness and behavioral practice of patient privacy protection,continuously practice the safety and effectiveness of patient privacy protection technology,and further improve legislation related to personal privacy protection in special periods and in the context of health data sharing.

Objective To investigate the effects of total flavones from Oxytropis falcata Bunge on hepatic fibrosis(HF)induced by carbon tetrachloride and liver transforming growth factor(TGF-β)/Smad signaling pathway.Methods Forty-eight male rats were randomly divided into normal group(intraperitoneal injection of peanut oil,intragastric administration of 0.9％NaCl),model group(intraperitoneal injection of 40％CC14 peanut oil solution induced HF model,intragastric administration of 0.9％NaCl),positive control group(modeling,intragastric administration of 0.2 mg·kg-1 of colchicine),experimental-L,-M,-H groups(modeling,intragastric administration of 100,200 and 400 mg·kg-1 of total flavonoid extract of Oxytropis falcata Bunge),8 individuals in each group,for 4 consecutive weeks.The histopathological changes were observed by hematoxylin-eosin and Masson staining.Serum liver function and liver fibrosis were measured;erum inflammatory factors were detected;fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine gene expression in liver.Results The pathological injury of liver tissue in the model group was serious,and a large number of inflammatory factors and collagen fibers were accumulated,while the rest of the treatment groups had different degrees of remission.In normal group,model group,positive control group,experimental-L,-M,-H groups,glutamic-pyruvic transaminase levels were(49.28±12.44),(5 885.42±948.37),(4 454.60±489.27),(4 650.47±843.53),(3 761.75±887.30)and(3 544.90±1 066.75)μg·L-1;glutamic-oxaloacetic transaminase levels were(186.90±46.89),(5 936.23±793.81),(3 971.37±780.28),(4 360.30±863.35),(3 943.10±439.47)and(3 971.38±631.08)μg·L-1;hyaluronic acid levels were(45.08±17.16),(104.32±36.06),(66.83±20.09),(70.30±21.07),(60.00±9.68)and(59.02±10.73)μg·L-1;laminin levels were(23.13±3.89),(60.85±13.66),(35.67±9.92),(39.98±9.39),(36.55±12.21)and(34.68±24.83)μg·L-1;type Ⅲ procollagen level were(24.98±5.34),(82.58±30.14),(40.70±16.14),(51.08±23.21),(43.60±12.48)and(44.20±11.66)p±g·L-1;interleukin(IL)-1β levels were(37.63±1.24),(46.10±3.23),(39.22±2.36),(41.33±0.93),(40.25±2.04)and(39.18±2.23)pg·mL-1;tumor necrosis factor-α levels were(314.58±20.56),(383.71±16.97),(349.00±7.93),(348.88±25.11),(325.75±27.84)and(335.07±21.33)pg·mL-1;TGF-β1 mRNA expression of relative quantity respectively were 1.00±0.00,60.99±15.70,9.61±1.59,7.37±1.09,6.41±0.64,6.87±1.09;Smad7 mRNA relative expression were 1.00±0.00,0.34±0.05,0.21±0.03,0.35±0.02,0.38±0.02,0.42±0.03.The above indexes in the model group were compared with the normal group,and the above indexes in the experimental-M,-H groups were compared with the model group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Total flavonoids of Oxytropis falcata Bunge have protective effects on CC14-induced liver fibrosis in rats,and the mechanism may be related to the regulation of TGF-β/Smad pathway.