OBJECTIVE: By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage. METHODS: The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed. RESULTS: After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same. CONCLUSION HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Hematologic Diseases/blood* ; Follicle Stimulating Hormone/blood* ; Triiodothyronine/blood* ; Luteinizing Hormone/blood* ; Thyroid Gland/metabolism* ; Estradiol/blood* ; Thyrotropin/blood* ; Gonads/metabolism* ; Adult ; Middle Aged ; Adrenocorticotropic Hormone/blood* ; Hormones/metabolism* ; Adrenal Cortex/metabolism* ; Prolactin

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

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: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

The medulla oblongata,situated at the caudal portion of the brainstem,serves as a critical regulatory center responsible for maintaining fundamental vital functions including respiratory and cardiovascular homeostasis.As a pivotal hub within the autonomic nervous system,it orchestrates the coordinated control of afferent and efferent neural pathways.Dysfunction of this region may precipitate life-threatening cardiorespiratory arrest,associated with substantial mortality rates.This case report presents a patient who developed acute extensive anterior myocardial infarction during treatment with dual antiplatelet therapy and moderate-intensity statins following acute medullary infarction.It is hypothesized that the pathogenesis may involve the acceleration of plaque erosion by the stroke-heart syndrome.This clinical case provides valuable insights into the complex neurocardiac interplay,particularly highlighting the imperative for enhanced recognition of brain-heart axis interactions in cerebrovascular pathology.

The medulla oblongata,situated at the caudal portion of the brainstem,serves as a critical regulatory center responsible for maintaining fundamental vital functions including respiratory and cardiovascular homeostasis.As a pivotal hub within the autonomic nervous system,it orchestrates the coordinated control of afferent and efferent neural pathways.Dysfunction of this region may precipitate life-threatening cardiorespiratory arrest,associated with substantial mortality rates.This case report presents a patient who developed acute extensive anterior myocardial infarction during treatment with dual antiplatelet therapy and moderate-intensity statins following acute medullary infarction.It is hypothesized that the pathogenesis may involve the acceleration of plaque erosion by the stroke-heart syndrome.This clinical case provides valuable insights into the complex neurocardiac interplay,particularly highlighting the imperative for enhanced recognition of brain-heart axis interactions in cerebrovascular pathology.

Objective To analyze the epidemiological characteristics of human papillomavirus(HPV)infection in women in the Zhongguancun area of Beijing,and to evaluate the infection rates and genotype distribution between different populations and age groups.Methods A retrospective analysis was conducted on HPV genotyping results of 13,105 women who visited the gynecology outpatient department or underwent routine health check-ups at Zhongguancun Hospital from March 2019 to April 2024.High-risk HPV genotypes(15 types)were detected using a fluorescence PCR assay.Positive cases were classified as single,dual or multiple(≥3)infections based on the number of genotypes.Subjects were stratified into six age groups(≤30,31-40,41-50,51-60,61-70,and≥71 years),and the characteristics of infection by type and age group were analyzed.Results The overall HPV positivity rate was 10.78%(1,413/13,105),with a significantly higher rate in the outpatient group than that in the health check-up group(16.36%vs.6.06%,P<0.01).The three most prevalent genotypes were HPV52(18.83%),HPV58(13.85%),and HPV16(11.28%).Single infections accounted for 79.19%of cases,dual infections for 15.93%and multiple infections for 4.88%.Age distribution showed a U-shaped pattern,with higher infection rate in women aged≤30 years(15.06%)and 61-70 years(13.19%),and the lowest rate in the≥71 years(8.09%).Notably,women aged≤30 years had the highest proportion of multiple infections(31.72%).Conclusion These findings provide a basis for cervical cancer screening strategies,HPV vaccination promotion and individualized prevention of cervical cancer in this region.

Objective To retrieve,evaluate,and integrate evidence related to the operational proce-dures of ambulatory blood pressure monitoring(ABPM)in adults,aiming to enhance the accuracy and effec-tiveness of ambulatory blood pressure monitoring.Methods A systematic search was conducted following the"6S"pyramid model of evidence-based resources to identify literature pertaining to ABPM operations in adults from relevant domestic and international databases and websites,with the search period spanning from the inception of each database to April 2024.After screening the literature,the methodological quality of the included studies was evaluated.Evidence was extracted and summarized according to thematic categories.Results Based on the inclusion and exclusion criteria,15 publications were ultimately included,comprising 1 clinical decision,10 guidelines,1 best practice summary,and 3 expert consensus documents.A total of 32 evidence items were synthesized.Conclusions This study consolidates evidence related to ABPM operational procedures,providing an evidence-based foundation for standardizing ABPM practices among healthcare pro-fessionals.

Objective: To investigate the influencing factors for kinesiophobia among elderly patients with chronic obstructive pulmonary disease (COPD), so as to provide the reference for alleviating kinesiophobia among COPD patients. Methods: From December 2023 to July 2024, COPD patients aged 60 years and above who sought medical treatment at a tertiary grade-a hospital in Guiyang City were selected. Demographic information was collected through questionnaire surveys. Kinesiophobia, exercise self-efficacy, social support, type D personality and coping styles were assessed using the Chinese version of Tampa Scale for Kinesiophobia, the Chinese version of the Self-Efficacy for Exercise Scale, Social Support Rating Scale, Type D Personality Scale and Chinese version of the Medical Coping Modes Questionnaire, respectively. Factors affecting kinesiophobia among elderly patients with COPD were analyzed using a multiple linear regression model. Results: A total of 300 COPD patients were surveyed, including 238 males (79.33%) and 62 females (20.67%). The majority of patients had a disease duration of less than 5 years, with 130 cases (43.33%). The average kinesiophobia score was (48.01±7.74) points. The average exercise self-efficacy score was (3.39±1.01) points. The average social support score was (34.42±6.76) points. There were 280 patients (93.33%) with type D personality. The average scores of the confrontation, avoidance, and resignation dimensions of coping styles were (17.42±5.00), (13.76±1.91), and (11.81±2.95) points, respectively. Multiple linear regression analysis showed that age (70-<80 years, β'=0.124; ≥80 years, β'=0.205), educational level (primary school and below, β'=0.228; junior high school, β'=0.182), household monthly income per capita (<3 000 yuan, β'=0.234; 3 000~<5 000 yuan, β'=0.165), social support (β'=0.294), type D personality (β'= 0.170), and coping styles (confrontation dimension, β'=-0.140; avoidance dimension, β'=0.154; resignation dimension, β'=0.175) statistically associated with kinesiophobia among elderly patients with COPD. Conclusion Kinesiophobia among elderly patients with COPD is associated with age, educational level, household monthly income per capita, social support, type D personality and coping styles.

Objective:To evaluate the efficacy of 3D printing technology combined with computer navigation-assisted screw implantation in the treatment of atlantoaxial instability (AAI) complicated by vertebral artery anomalies.Methods:A retrospective case series study was conducted to analyze the clinical data of 23 patients with AAI complicated by vertebral artery anomalies who were admitted to Honghui Hospital of Xi′an Jiaotong University between January 2019 and January 2023, including 10 males and 13 females, aged 19-70 years [(51.0±13.3)years]. Vertebral artery anomalies were categorized into unilateral high-riding vertebral artery with unilateral dominance ( n=14), bilateral high-riding vertebral arteries with unilateral dominance ( n=6), and ponticulus posticus ( n=3). All the patients underwent preoperative planning using a 3D-printed model of the atlantoaxial complex with the vertebral artery, followed by posterior atlantoaxial pedicle screw fixation with computer-assisted navigation. Operative duration and intraoperative blood loss were recorded. The accuracy of pedicle screw placement was assessed at 3 days postoperatively using the Gertzbein-Robbins classification. Visual analogue scale (VAS) scores and Japanese Orthopedic Association (JOA) scores were evaluated preoperatively, at 3 days, 3 months postoperatively, and at the last follow-up. Bony fusion was assessed using cervical CT with 3D reconstruction at the last follow-up. Complications were also observed. Results:All the patients were followed up for 12-19 months [(15.1±1.9)months]. The operative duration was 125-167 minutes [(140.6±10.9)minutes] and intraoperative blood loss was 200-600 ml [(295.7±77.8)ml]. At 3 days postoperatively, all the 66 pedicle screws were safely placed, with 60 screws (91%) rated as Gertzbein-Robbins Grade 0 and 6 screws (9%) as Grade 1. At 3 days and 3 months postoperatively, and at the last follow-up, the VAS scores were (4.0±1.0)points, (2.0±0.6)points, and (1.3±0.5)points, and the JOA scores were (14.2±1.2)points, (16.0±0.8)points, and (16.6±0.5)points, both of which were not only significantly improved compared with preoperative (5.6±1.3)points and (12.8±1.5)points, but also further improved over time ( P<0.05). At the last follow-up, 22 patients (96%) achieved satisfactory atlantoaxial bony fusion. No vertebral artery injury, spinal cord or nerve injury, cerebrospinal fluid leakage, or screw loosening were observed in any patients. Conclusion:For patients with AAI complicated by vertebral artery anomalies, 3D printing combined with computer navigation-assisted navigation for atlantoaxial pedicle screw implantation offers multiple advantages, including minimal surgical trauma, high screw placement accuracy, pain relief, neurological function improvement, high fusion rate, and lowered incidence of complications.