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: 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

Lattice strain ruthenium nanoparticles uniformly and stably supported on nitrogen-modified carbon nanosheets(RuNPs/NC)were prepared via simple wet-chemical and subsequent pyrolysis method.The nitrogen doped NC could effectively improve their uniform dispersion and lattice compression of RuNPs.Through changing the pyrolysis temperature,the nitrogen content,types and degree of lattice strain of RuNPs could be effectively tuned,which could be used to adjust and control their peroxidase-like activity.The as-prepared RuNPs/NC-900 exhibited highest peroxidase-like activity,and could catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine(TMB)to produce a blue product with the maximum absorption at 652 nm in the presence of H2O2.The steady-state kinetic analysis indicated that the reaction catalyzed by RuNPs/NC followed the Michaelis-Menten kinetic model.Tannic acid(TA),gallic acid(GA)and ascorbic acid(AA)could effectively inhibit the RuNPs/NC-H2O2-triggered chromogenic reaction of TMB,resulting in color fading and decrease in absorbance.Based on this,a sensitive and accurate system was constructed for detection of TA,GA and AA.The detection limits(3σ/S)for TA,GA and AA were 0.014,0.014 and 0.29 μmol/L,respectively.This study not only developed a colorimetric sensing method based on RuNPs/NC nanozyme but also offered a new approach for the sensitive detection of antioxidants in food.

BACKGROUND:The appearance of the crescent sign in femoral head necrosis is a"turning point"in the progression of the disease,and repairing and stabilizing the bone-cartilage interface is particularly important in preventing further progression and collapse of the femoral head.Tissue engineering offers potential advantages in the simultaneous repair and integration of the bone-cartilage interface. OBJECTIVE:To review potentially suitable techniques addressing the subchondral separation in femoral head necrosis. METHODS:Relevant articles from January 1970 to April 2023 were searched in PubMed,Web of Science,and China National Knowledge Infrastructure(CNKI)using English search terms"femoral head necrosis,avascular necrosis of femoral head,osteonecrosis of femoral head"and Chinese search terms"femoral head necrosis,subchondral bone,cartilage,integration of cartilage and subchondral bone".A total of 114 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)Structural defects,ischemic and hypoxic environment,inflammatory factors,and stress concentration may cause subchondral separation in osteonecrosis of the femoral head.Subchondral bone collapse and failure of hip-preserving surgery may be associated.Integration of tissue engineering scaffolds with the bone-cartilage interface is one potential approach for treating subchondral separation in osteonecrosis of the femoral head.(2)Current literature suggests that multiphase scaffolds,gradient scaffolds,and composite materials have shown improvements in promoting cell adhesion,proliferation,and deposition of bone and cartilage matrix.These advancements aid in the integration of scaffolds with the bone-cartilage interface and have implications for the treatment of subchondral separation in osteonecrosis of the femoral head.(3)Surface modifications of scaffolds can enhance interface integration efficiency,but they have their advantages and disadvantages.Scaffolds providing different environments can induce differentiation of mesenchymal stem cells and facilitate integration between different interfaces.(4)Future scaffolds for subchondral separation in osteonecrosis of the femoral head are expected to be composite materials with gradient and differentiated biomimetic structures.Surface modifications and stem cell loading can promote integration between the bone-cartilage interface and scaffolds for therapeutic purposes,but further experimental verification is still needed.Challenges include synchronizing scaffold degradation rate with repair progress and ensuring stability between different interfaces.

AIM To explore the clinical effects of Bushen Huoxue Ointment Formula on patients with ankylosing spondylitis of Kidney Deficiency and Blood Stasis Pattern.METHODS One hundred and sixty-seven patients were randomly assigned into control group(55 cases)for 2-year intervention of conventional treatment,exposure group(54 cases)for 2-year intervention of both Bushen Huoxue Decoction and conventional treatment,and high exposure group(58 cases)for 2-year intervention of Bushen Huoxue Ointment Formula,Bushen Huoxue Decoction and conventional treatment.The changes in clinical effects,BASDAI score,ASDAS-CRP,BASFI score,spinal pain score,PGA score,BASMI score,ASQoL score,SPARCC score,Kidney Deficiency and Blood Stasis Pattern score,ESR,CRP,IL-6,TNF-α,IL-17,IL-23,IL-35,NLR,PLR and safety indices were detected.RESULTS The high exposure group demonstrated more ASAS40,ASASAS5/6,BASDAI50 cases than the exposure group and the control group(P<0.05).After the treatment,the high exposure group displayed lower BASDAI score,ASDAS-CRP,BASFI score,spinal pain score,PGA score,BASMI score,SPARCC score,ASQoL score,Kidney Deficiency and Blood Stasis Pattern score,ESR,CRP,IL-6,TNF-α,IL-17,IL-23 than the other two groups(P<0.05),and higher IL-35(P<0.05).After adjusting confounding factors by logistic regression analysis,Bushen Huoxue Decoction and Bushen Huoxue Ointment Formula reduced BASDAI score,ASDAS-CRP(P<0.05),and enhanced clinical effects(P<0.05).No serious adverse reactions were found in the three groups.CONCLUSION For the patients with ankylosing spondylitis of Kidney Deficiency and Blood Stasis Pattern,Bushen Huoxue Ointment Formula can safely and effectively inhibit inflammation,reduce disease activity,alleviate bone marrow edema,improve clinical symptoms,and enhance joint functions and life quality.

Methods: This study established the MFSM method. To demonstrate its effectiveness, we applied this novel approach to analyze Danxi Granules (丹膝颗粒, DXG) and its constituent herbal materials. To begin with, the ultra-performance liquid chromatography (UPLC) was applied to obtain the chromatographic fingerprints of DXG and its constituent herbal materials. Next, the MFSM was leveraged to compress and integrate them into a new fingerprint with fewer analytical units. Then, we characterized the properties and variability of both the original and integrated fingerprints by calculating total quantum statistical moment (TQSM) parameters, information entropy and information amount, along with their relative standard deviation (RSD). Finally, we compared the TQSM parameters, information entropy and information amount, and their RSD between the traditional and novel fingerprints to validate the new analytical method. Results: The chromatographic peaks of DXG and its 12 raw herbal materials were divided and integrated into peak families by the MFSM method. Before integration, the ranges of the peak number, three TQSM parameters, information entropy and information amount for each peak or peak family of UPLC fingerprints of DXG and its 12 raw herbal materials were 95.07 − 209.73, 9390 − 183064 μv·s, 5.928 − 21.33 min, 22.62 − 106.69 min2, 4.230 − 6.539, and 50530 − 974186 μv·s, respectively. After integration, the ranges of these parameters were 10.00 − 88.00, 9390 − 183064 μv·s, 5.951 − 22.02 min, 22.27 − 104.73 min2, 2.223 − 5.277, and 38159 − 807200 μv·s, respectively. Correspondingly, the RSD of all the aforementioned parameters before integration were 2.12% − 9.15%, 6.04% − 49.78%, 1.15% − 23.10%, 3.97% − 25.79%, 1.49% − 19.86%, and 6.64% − 51.20%, respectively. However, after integration, they changed to 0.00%, 6.04% − 49.87%, 1.73% − 23.02%, 3.84% − 26.85%, 1.17% − 16.54%, and 6.40% − 48.59%, respectively. The results demonstrated that in the newly integrated fingerprint, the analytical units of constituent herbal materials, information entropy and information amount were significantly reduced (P < 0.05), while the TQSM parameters remained unchanged (P > 0.05). Additionally, the RSD of the TQSM parameters, information entropy, and information amount didn’t show significant difference before and after integration (P > 0.05), but the RSD of the number and area of the integrated analytical units significantly decreased (P < 0.05). Conclusion The MFSM method could reduce the analytical units of constituent herbal materials while maintain the properties and variability from their original fingerprint. Thus, it could serve as a feasible and reliable tool to reduce difficulties in analyzing multi-components within CMMs and facilitating the evaluation of their quality.

ObjectiveBased on the network pharmacology system and quantitative spectroscopy of traditional Chinese medicine（TCM） compounds， a topological network analysis method with equilibrium constant as the core was established to further explore the interaction between allergenic components and their network targets in Shuanghuanglian injection（SHLI）， in order to provide new ideas and experimental basis for identifying and screening potential allergens of SHLI. MethodAfter one week of adaptive feeding， 72 SPF-grade SD male rats were randomly divided into blank group， SHLI standard group， Lonicerae Japonicae Flos（LJF） group， Scutellariae Radix（SR） group， Forsythiae Fructus（FF） group， and 7 groups of SHLI matching groups（groups 1-7）， with 6 rats in each group. Rats in each group were administered the drug intravenously and blood samples were taken after steady state， high performance liquid chromatography（HPLC） characterization profiles of the testing drugs and plasma components in each group were established， and the peak area changes of the drugs and plasma components in each group were calculated after the component groups were classified. Enzyme-linked immunosorbent assay（ELISA） was used to determine the changes of immunoglobulin E（IgE）， histamine（HIS）， tryptase（TPS）， total complement（CH50） and terminal complement complex（C5b-9） in animal blood samples. MATLAB R2020b v9.9.0 software was used to calculate the network balance constants of the component groups with the targets， and the eigenvalues of the matrices composed of network equilibrium constants were calculated and ranked according to their values. ResultELISA results showed that， compared with the blank group， groups 1-3 could significantly increase the IgE level， groups 1-2， groups 4-6 and SHLI standard group could significantly increase the HIS level， group 4 could significantly increase the CH50 level， groups 1， 3-4， LJF group and FF group could significantly increase the TPS level， SR group could significantly increase the C5b-9 level， and the differences were all statistically significant（P<0.05）. According to the retention time of chromatographic peaks， it was classified into 6 component groups from C1 to C6 by HPLC. The order of the network balance constants of each component group was C6>C4>C1>C5>C3>C2， indicating that C6 had the greatest effect on the allergic reaction， and was most likely to be the allergen. The sequence of eigenvalues was C2>C5b-9>C3>C1>CH50>C6>C5>IgE>TPS>C4>HIS， indicating that component group C2 had the greatest contribution to the whole network. ConclusionBased on the correlation analysis of SHLI component group and allergy-like target network， this study clarified that component group C6 may be a potential allergen in SHLI， and the component group C2 may be a key node in the mechanism of drug action， which can provide new strategies and methods for the screening of allergens in TCM injections.