ObjectiveTo construct a risk prediction model for frequent acute exacerbations of chronic obstructive pulmonary disease （COPD） under disease-syndrome combination， thus providing decision support for precise clinical intervention. MethodsA total of 2 029 patients with acute exacerbations of COPD admitted to the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2020 to August 2024 were retrospectively included. These patients were classified into groups of frequent acute exacerbations （≥2 times/year） and infrequent acute exacerbations （<2 times/year） according to the hospitalization times per year. Risk factors were screened by LASSO regression combined with logistic regression， and a nomogram model was constructed. The model performance was assessed based on the area under the curve （AUC）， calibration curves， and decision curve analysis （DCA）. ResultsThe differences in baseline characteristics between the frequent acute exacerbations group （1 196 cases） and infrequent acute exacerbations group （833 cases） were not statistically significant. LASSO regression combined with multivariate logistic regression screened the following independent risk factors： body mass index （BMI）， hospitalization days， number of smoking years， place of residence， use of noninvasive ventilators， oxygen-demanding therapy， liver cirrhosis， use of systemic glucocorticosteroids， and traditional Chinese medicine syndrome （phlegm and stasis obstructing the lung）. The nomogram model showed good discrimination and calibration in both the training set （AUC=0.748） and validation set （AUC=0.774）. ConclusionThe risk prediction model for frequent acute exacerbations of COPD， integrating traditional Chinese medicine syndrome， constructed in this study has high accuracy. It can provide a scientific basis for early clinical identification of high-risk patients and individualized intervention.

ObjectiveTo investigate the effects of hypoxia-treated mesenchymal stem cell （MSCs） exosomes （Exo） and their loading with curcumin on microglial inflammatory responses， and to explore the enhancing effect of hypoxia treatment on the function of MSCs Exo. MethodsThe supernatants of human umbilical cord （hUC）-MSCs cultured under normal and hypoxic conditions were collected， and Exo were isolated using ultracentrifugation. After identification by transmission electron microscopy and Western blot， curcumin was loaded using the co-incubation method. The lipopolysaccharide （LPS）-induced microglial inflammation model was treated with dimethyl sulfoxide （DMSO）， curcumin， normoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin， respectively. The expression of the M1-type marker inducible nitric oxide synthase （iNOS） in BV2 cells was detected by immunofluorescence （IF）. Western blot and enzyme-linked immunosorbent assay （ELISA） were used to measure the expression and secretion levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and IL-6 in the cells and their culture supernatants. ResultsNormoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin exhibited a "saucer-like" shape with a diameter ranging from 30~150 nm， and the expression of exosomal markers CD9， CD81， and TSG101 were positive. After treating the BV2 cell inflammation model， IF results showed that， compared with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression of iNOS. Moreover， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， the expression level of iNOS significantly decreased after treatment with hypoxic Exo loaded with curcumin. The results of Western blot and ELISA indicated that， in comparison with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression and secretion of the inflammatory cytokines TNF-α， IL-1β， and IL-6. Additionally， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， both the expression and secretion of TNF-α， IL-1β， and IL-6 significantly decreased after treatment with hypoxic Exo loaded with curcumin. ConclusionHypoxia preconditioning can enhance the ability of hUC-MSCs-Exo in the inhibition of microglial polarization and inflammatory factors’ secretion. Additionally， using Hypoxia-MSCs-Exo as a drug-delivery carrier of curcumin can improve its solubility and stability， facilitating its absorption by cells and exerting the therapeutic effect of combination therapy.

Objective To compare the therapeutic efficacy and identify differences between haploidentical hematopoietic stem cell transplantation combined with mesenchymal stem cells (Haplo-MSC) and umbilical cord blood hematopoietic stem cell transplantation combined with mesenchymal stem cells (UCB-MSC) in mice with bone marrow acute radiation syndrome (ARS). Methods Eight-to ten-week-old CB6F1 mice were exposed to 8 Gy of ⁶⁰Co γ-ray irradiation to establish a bone marrow-type ARS model.The mice were then randomly assigned to three groups: the Haplo-MSC group (haploidentical hematopoietic stem cells combined with MSCs), the UCB-MSC group (umbilical cord blood stem cells combined with MSCs), and a saline control group. The survival rate, peripheral blood cell counts, pathological changes in target organs, colony formation of bone marrow cells, and graft-versus-host disease (GVHD) were observed. Results All mice in the saline control group died within 14 days, with a median survival time of 8.9 days. The 30 day survival rate was 65% in the Haplo-MSC group and 60% in the UCB-MSC group. The Log-rank test showed no significant difference in survival time between the two transplantation groups (P=0.561). At 28 days post-transplantation, no significant differences were observed in WBC, PLT, RBC, or Hb counts between the two groups (P=0.151, 0.733, 0.856, and 0.300, respectively). Pathological changes in bone marrow cells showed that bone marrow failure occurred later in the UCB-MSC group than in the Haplo-MSC group. In contrast, the Haplo-MSC group exhibited faster hematopoietic stem cell engraftment. Furthermore, the numbers of CFU-E, CFU-GM, and CFU-GEMM differed significantly between the two groups (P<0.05). Conclusion Both the Haplo-MSC and UCB-MSC regimens promoted hematopoietic engraftment and reconstitution in mice with lethal-dose radiation-induced bone marrow ARS. However, the onset of bone marrow failure was delayed in mice treated with the UCB-MSC regimen. In contrast, mice treated with the Haplo-MSC regimen showed faster engraftment.

ObjectiveTo establish three standardized rehabilitation unit models covering acute, critical and comprehensive recovery stages for traumatic brain injury (TBI) that fit the whole-course characteristics, clarify their multidisciplinary collaborative framework, standardized procedures, and information management system, and verify the clinical effectiveness of this staged rehabilitation unit on long-term functional prognosis and in-hospital complications of TBI patients. MethodsThis study was conducted at two stages: model construction and efficacy verification. At the first stage, TBI rehabilitation units for acute, critical and recovery stages were established in the Department of Neurosurgery, Intensive Care Unit and Department of Rehabilitation Medicine, respectively, with unified multidisciplinary team configuration, standardized assessment and treatment protocols, collaborative workflows, and a dedicated information management system. At the second stage, 324 TBI patients admitted to the newly built rehabilitation units from July, 2023 to July, 2025 were enrolled as the observation group, and 167 TBI patients receiving traditional management from January, 2018 to December, 2022 were retrospectively selected as the control group. The primary outcomes were 1-year post-injury Glasgow Outcome Scale (GOS) and Disability Rating Scale (DRS) scores. Secondary outcomes included the incidence of in-hospital complications and the mean indwelling time of tracheal intubation, gastric tube and urinary catheter. ResultsThe 1-year GOS score was significantly higher (t = -7.836, P < 0.001), and the DRS score was significantly lower (t = -6.742, P < 0.001) in the observation group than in the control group. The overall incidence of complications was significantly lower in the observation group than in the control group (χ² = 18.762, P < 0.001). The incidences of pulmonary infection, urinary tract infection, pressure ulcer, lower extremity venous thrombosis and joint contracture deformity were all significantly reduced (χ² > 4.328, P < 0.05). The indwelling time of tracheal intubation, gastric tube and urinary catheter was significantly shorter in the observation group than in the control group (t > 10.276, P < 0.001). ConclusionThe acute-critical-comprehensive three-stage standardized TBI rehabilitation unit could significantly improve the long-term functional outcomes of TBI patients, reduce the incidence of complications, and shorten the indwelling time of invasive tubes through multidisciplinary collaboration, whole-course standardized management and information-based quality control. This model conforms to the pathological and functional laws of TBI, realizes seamless whole-course connection from acute treatment to recovery rehabilitation, and has good clinical feasibility and promotion value. It can provide evidence-based evidence and practical reference for the homogenized and standardized development of TBI rehabilitation in China.

Objective:To analyze the current status of clinical research registration on TCM prevention and treatment of malignant tumors in the Chinese Clinical Trail Registry (ChiCTR); To summarize its characteristics and shortcomings.Methods:Clinical studies on the TCM prevention and treatment for malignant tumors registered from the establishment of ChiCTR database to July 15, 2024 were retrieved. Excel 2019 software was used to sort out the data, including basic research information (registration time, registration number status, registration title, test organizer, research implementation location, etc.), design scheme (disease type, research type, intervention measures, sample size, blind method, etc.), research funding or material sources, as well as other information such as human specimen collection and recruitment of research objects. SPSS 27.0 software was used for frequency statistics.Results:A total of 891 registered studies were included, including 783 interventional studies and 108 observational studies; the areas with a large number of registrations were mainly Shanghai, Beijing, Guangdong Province, etc. ; the research funds mainly came from local finance; a total of 46 tumor diseases were involved in the study, with the largest number of lung cancer (209 items), followed by tumor-related syndromes (155 items), colorectal cancer (148 items), and breast cancer (136 items); the type of research design was mainly random parallel control; the main intervention measures were TCM decoction or herbal decoction pieces (373 items), and the dosage form was mostly decoction (216 items), followed by granules (94 items); single-blind or double-blind design was used in 217 registered trials; 663 registration trials involved the collection of human samples.Conclusions:The number of clinical research registrations on the TCM prevention and treatment for malignant tumors is increasing day by day. The shortcomings such as insufficient standardization of research design and lack of research transparency still exists. In the future, TCM researchers need to strengthen cooperation with international traditional medicine clinical trial registry, giving full play to the leading role of standardization of TCM trials, and using registration as a starting point to improve the quality of clinical research.

Objective To evaluate the clinical value of multiplex polymerase chain reaction(mPCR),serum IgM and urinary Legionella pneumophila antigen detection in the diagnosis and treatment of adult community-acquired pneumonia(CAP)for Mycoplasma pneumoniae(MP),Chlamydia pneumoniae(CP)and Legionella pneumophila(LP).Methods A total of 275 inpatients diagnosed with CAP from October 2018 to January 2022 in Beijing Tongren Hospital were selected as the study objects.275 lower respiratory tract samples,195 serum samples and 50 urine samples were collected for sanger sequencing,mPCR,serum IgM and urinary LP antigen test,respectively.With the result of sanger sequencing as the reference standard,the clinical application value of the three detection methods was evaluated.Results The infection rate of atypical pathogens in adult patients with CAP was 26.5%(73/275).The infection rates of MP,CP and LP were 21.8%(60/275),2.2%(6/275)and 2.5%(7/275),respectively.The sensitivity of mPCR,serum IgM and urinary LP antigen test were 100%(72/72),31.0%(18/58),100%(7/7),and the specificity were 99.5%(202/203),76.6%(105/137),100%(43/43),respectively.The sensitivity of serum IgM was significantly decreased in patients with time≤7 days compared to patients with time>7 days from onset to sampling(41.9%vs 14.3%),the difference was statistically significant(χ2=5.483,P<0.05).The proportion of false negative for serum IgM was the highest in 25～<41 years old(57.5%),and the difference was statistically significant among all age groups(χ2=25.069,P<0.001).The proportion of false positive for serum IgM was the highest among 41～<66 years old(37.5%),and there was no significant difference among all age groups(χ2=6.404,P=0.171).The IgM cross-reactivity rate of the three atypical pathogens was 33.3%(13/39).Conclusion Serum IgM is not suitable for the diagnosis of atypical pathogen infection in adults alone,mPCR and urinary LP antigen test have obvious advantages in the early diagnosis of CAP in adults.

OBJECTIVE To analyze the differences in chemical composition of mussels from Shengsi,Zhoushan in different har-vest months,and to compare the differences in the composition of mussels from different origins,so as to provide ideas for the compre-hensive utilization of its resources.METHODS Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry(UHPLC-QqQ-MS)and spectrophotometry were used to analyze and evaluate the contents of nucleosides,amino acids,water-soluble proteins,total sugars and polysaccharides in mussels from Shengsi,Zhoushan in 12 months of the year and from 5 different origins;principal component analysis(PCA),partial least squares discriminant method(PLS-DA)and TOPSIS method were used to compre-hensively evaluate mussels.RESULTS A total of 16 amino acids and 11 nucleosides were detected in mussels.The average content of total amino acids in Shengsi mussels throughout the year was 4 851.74 μg·g-1,the average content of total nucleosides was 921.40 μg·g-1,and the average contents of water-soluble protein,polysaccharides,and total sugars were 51.32 mg·g-1,74.39 μg·g-1,and 417.22 mg·g-1,respectively.The nucleosides of Shengsi mussels were the highest in March and April,the ami-no acids and water-soluble proteins were the highest in April and May,and the polysaccharides and total sugars were the highest in Oc-tober and November.The PCA and PLS-DA results of the chemical components of different resources showed that there were great differences in Shengsi mussel samples harvested in different seasons.The entropy weight TOPSIS analysis showed that the comprehen-sive scores of Shengsi mussels in March and April(S7 and S8)were better than those in other areas,and the comprehensive score of Shengsi mussels in April(S8)was the highest,which was determined to be the best harvesting month.CONCLUSION The comparison results of multi-type resource chemistry show that there are great differences in the chemical compo-sition of Shengsi mussels in different harvesting seasons;the quality of Shengsi mussels is better than that of other areas;April is the best harvesting season,providing a reference for the quality evaluation and comprehensive development and utilization of mussels.

The p21-activated kinase 4 (PAK4), a key regulator of malignancy, is negatively correlated with immune infiltration and has become an emergent drug target of cancer therapy. Given the lack of high efficacy PAK4 inhibitors, we herein reported the identification of a novel inhibitor 13 bearing a tetrahydrobenzofuro[2,3-c]pyridine tricyclic core and possessing high potency against MIA PaCa-2 and Pan02 cell lines with IC₅₀ values of 0.38 and 0.50 μmol/L, respectively. This compound directly binds to PAK4 in a non-ATP competitive manner. In the mouse Pan02 model, compound 13 exhibited significant tumor growth inhibition at a dose of 100 mg/kg, accompanied by reduced levels of PAK4 and its phosphorylation together with immune infiltration in mice tumor tissue. Overall, compound 13 is a novel allosteric PAK4 inhibitor with a unique tricyclic structural feature and high potency both in vitro and in vivo, thus making it worthy of further exploration.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease primarily affecting the joints of the limbs. As the disease progresses, it can involve multiple organ systems. Interstitial lung disease (ILD) is the most common pulmonary manifestation of RA. Reported animal models of RA-ILD include adjuvant-induced arthritis (AA), collagen-induced arthritis (CIA), and transgenic mouse arthritis. However, the establishment criteria and evaluation methods for these models lack uniform standards, and they fail to fully replicate the clinicopathological characteristics of RA-ILD. This limitation significantly hinders research into the pathogenesis and development of therapeutic drugs for RA-ILD. Objective: The aim of the study was to review literature in China and abroad on RA-ILD animal models, analyze current research progress, identify existing issues, and propose research recommendations. Methods: Literature searches were conducted using the English keywords “rheumatoid arthritis, interstitial lung disease, model” and the Chinese keywords “(rheumatoid arthritis), (interstitial lung disease), (model)” or “(rheumatoid arthritis), (lung interstitial lesions), (model).” The search was performed in PubMed, Web of Science, CNKI, Wanfang Data, and VIP (China Science and Technology Journal Database) for articles published before November 2024. A total of 41 articles were included. Results and conclusions: The CIA model and the CIA model combined with bleomycin are commonly used due to their similarities to the histopathology and disease manifestations of human RA-ILD. Additionally, these models have appropriate cost and modeling duration, along with a high success rate, making them preferable choices. Transgenic animal models exhibit pathological features similar to the nonspecific interstitial pneumonia subtype of human RA-ILD and are useful for studying the genetic effects on RA-ILD. However, they have drawbacks such as high economic costs, long modeling durations, and a low success rate in some cases. The AA model is easy to establish, requires a short modeling period, and has low experimental costs. However, it lacks the chronic pathological development characteristic of human RA and exhibits a degree of self-limitation in lesion progression. Among other models, the comprehensive HLA-DQ8 transgenic mouse model can be used to study the combined effects of genetic and environmental factors on RA-ILD. The collagen autoantibody-induced arthritis model combined with bleomycin has a short modeling period, but it does not align well with the disease course of RA-ILD. These established animal models provide valuable insights into the pathogenesis of RA-ILD, the identification of novel biomarkers, and the development of new therapeutic approaches. Future research should focus on identifying an animal model that better replicates the physiological and pathological changes of clinical RA-ILD while being more convenient, cost-effective, and comprehensive in reflecting disease progression.