ObjectiveTo investigate the effects of Maimendong Yinzi （MMDYZ） on cough with Yin deficiency and lung heat syndrome and explore its potential mechanism of action. MethodsForty-eight Institute of Cancer Research （ICR） mice were randomly divided into a control group， a model group， a Baihe Gujin Tablet （BHGJP） group （1.36 g·kg^-1）， and low-dose， medium-dose， and high-dose MMDYZ groups （5， 10， 20 g·kg^-1·d^-1， based on the weight of crude drug）， with eight mice in each group. The mouse model of cough with Yin deficiency and lung heat syndrome was prepared by a combination of smoke exposure， nasal drip of lipopolysaccharide （LPS）， intragastric gavage with thyroxine， and capsaicin atomization. After successful modeling， drug interventions were administered for seven days. During modeling， the mice were observed for changes in general status， anal temperature， fecal water content， and water intake. After medication， the above indicators were evaluated again， along with assessments of spontaneous activity， cough sensitivity， lung function， lung index， and tracheal phenol red secretion. Bronchoalveolar lavage fluid （BALF） was analyzed for cell differential counts， and the level of cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， tumor necrosis factor-α （TNF-α）， and interleukin-6 （IL-6） in serum was measured via enzyme linked immunosorbent assay （ELISA）. Lung injury was assessed via hematoxylin-eosin （HE） staining. Network pharmacology was employed to predict the potential mechanism of MMDYZ in alleviation cough with Yin deficiency and lung heat syndrome. Western blot （WB） was used to measure protease-activated receptor1 （PAR1） and GTPhase α_i subunit （Gα_i） protein expressions in lung tissue. ELISA was used to determine lung cAMP content， and immunohistochemistry （IHC） was employed to evaluate transient receptor potential vanilloid subtype 1 （TRPV1） expression. ResultsCompared with the control group， the model group exhibited significantly increased water intake and anal temperature and significantly decreased fecal water content （P<0.05）. The total distance traveled in 5 min and the central zone duration were reduced， while standing frequency significantly increased （P<0.05）. Cough sensitivity and enhanced pause （PenH） were elevated. Peak expiratory flow （PEF） significantly declined （P<0.05）. BALF neutrophil （NEU） and white blood cell （WBC） counts rose. Serum cAMP and cAMP/cGMP ratio significantly increased， and cGMP significantly decreased （P<0.05）. Serum TNF-α and IL-6 levels were significantly elevated （P<0.05）. The lung injury was obvious， and the lung index was significantly elevated （P<0.05）. Compared with the model group， the medium-dose and high-dose MMDYZ groups and the BHGJP group showed significantly improved indicators mentioned above. Additionally， network pharmacology suggested that MMDYZ might alleviate cough with Yin deficiency and lung heat syndrome via cAMP， hypoxia inducible factor-1 （HIF-1）， and TNF signaling pathways. WB， ELISA， and IHC revealed that， compared with the control group， the model group exhibited significantly upregulated PAR1， Gα_i， and TRPV1 expressions and significantly downregulated cAMP in lung tissue （P<0.05）. Compared with the model group， MMDYZ reduced PAR1 （P<0.01）， Gα_i （P<0.05）， and TRPV1 （P<0.01） while increasing cAMP level （P<0.01）. ConclusionMMDYZ may alleviate cough with Yin deficiency and lung heat syndrome by modulating the PAR1/Gα_i/cAMP pathway and TRPV1 expression.

Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

This paper reports a case of a rare patient with inherited thrombophilia leading to mesenteric venous thrombosis and secondary small bowel obstruction. The diagnosis of the patient was confirmed through multidisciplinary team collaboration, and the intestinal obstruction was finally relieved through small bowel endoscopic treatment and surgical treatment. This paper also discusses the differential diagnosis and treatment of small bowel stricture lesions for peer reference.

This study compared the clinical characteristics of brucellosis,tuberculosis,and their co-infections,to improve dif-ferential diagnosis and disease management.A retrospective analysis was conducted on 41 patients with brucellosis,38 co-infected pa-tients,and 95 patients with tuberculosis admitted to Beijing Chest Hospital,Capital Medical University,between January 2017 and December 2024.Clinical manifestations,laboratory findings,and complications were analyzed statistically.Brucellosis and tuberculo-sis shared clinical similarities,such as presentation with prolonged fever.However,patients with brucellosis tended to exhibit muscle pain,night sweats,and loss of appetite,whereas patients with tuberculosis frequently presented with cough,sputum production,and lymphadenopathy.Co-infected patients had a higher fever incidence,and elevated hs-CRP and ESR levels.Whereas spinal spondyli-tis was more frequent in brucellosis,pulmonary infections and pleural effusion were predominant in tuberculosis.Co-infected patients exhibited characteristics of both diseases,and showed more severe systemic inflammation and prolonged illness.In conclusion,al-though elevated hs-CRP and ESR might aid in differentiation,pathogen detection is crucial for accurate diagnosis.Strengthening screening in patients with persistent fever and systemic inflammation may improve early identification,optimize treatment,and en-hance outcomes.

This paper reports a case of a rare patient with inherited thrombophilia leading to mesenteric venous thrombosis and secondary small bowel obstruction. The diagnosis of the patient was confirmed through multidisciplinary team collaboration, and the intestinal obstruction was finally relieved through small bowel endoscopic treatment and surgical treatment. This paper also discusses the differential diagnosis and treatment of small bowel stricture lesions for peer reference.

Neutrophils, as the most abundant immune cells in the human body, possess the inherent ability to rapidly migrate to sites of inflammation and infection. Novel drug delivery systems leveraging neutrophils capitalize on their natural targeting and phagocytic capabilities to achieve precise drug delivery. Efficient drug loading into neutrophils within neutrophil-based delivery systems can be achieved through physical adsorption, chemical conjugation, and phagocytosis. Design strategies emphasize carrier selection and targeting ligand design to enhance delivery precision. Compared to traditional drug delivery systems, neutrophil-based systems offer significant advantages, including excellent biocompatibility and strong tissue penetration. These properties can significantly improve drug bioavailability and reduce adverse reactions associated with non-target tissue accumulation. However, these systems also face several challenges that require resolution, such as difficulties in cell collection and preservation, the need for stability optimization, challenges in large-scale production, and a lengthy clinical translation cycle. In disease treatment applications, neutrophil-based drug delivery systems enable precise delivery of anti-cancer drugs to tumor sites, potentially disrupting immunosuppression of the tumor microenvironment and enhancing therapeutic efficacy. For brain diseases, their unique ability to cross the blood-brain barrier facilitates effective drug delivery. In chronic inflammatory diseases, neutrophil-based systems can precisely deliver anti-inflammatory agents to mitigate inflammation. Performance enhancements for neutrophil-based systems can be achieved by the development of novel nanomaterials and optimization of targeting ligand affinity, thereby improving the accuracy and efficiency of drug delivery. This review comprehensively explores the design strategies, advantages, challenges, and future directions of neutrophil-based drug delivery systems. It summarizes research progress in disease treatment applica-tions, aiming to offer key insights for the development of novel drug delivery systems and advance precision medicine and targeted therapy.
Humans ; Drug Delivery Systems/methods* ; Neutrophils ; Phagocytosis ; Drug Carriers ; Blood-Brain Barrier ; Neoplasms/drug therapy*

Background: In the field of neuroscience research, executive functions (EFs) are of great significance. Patients with Parkinson’s disease (PD) often encounter the problem of EFs impairment, which severely affects their lives and health.However, currently, the methods for evaluating EFs in experimental mice are limited, and there is a lack of effective evaluation indicators for touchscreen behavioral tests in different disease model mice. This study aims to establish a paradigm process and an evaluation baseline for touchscreen behavioral analysis in PD model mice, deeply explore the mechanisms of EFs impairment in PD, and provide a crucial foundation for subsequent research and treatment. Methods: Thirty clean - grade SNCA*A53T transgenic mice and forty clean - grade C57BL/6J wild - type mice were selected. For A53T mice, genetic identification was carried out. Molecular biology techniques such as PCR were used to determine their genetic characteristics. Protein detection was conducted through methods like Western blot to clarify the expression of relevant proteins. In terms of behavioral tests, the five - choice serial reaction time task (5 - CSRT) was adopted, and various behavioral data of mice in this task were recorded. Four groups were set up: the control group, the MPTP group. Different groups of mice were given specific treatments. For example, the MPTP group of mice was injected with MPTP to construct a drug - induced PD model. Principal component analysis (PCA) and receiver operating characteristic (ROC) curves were used to analyze the obtained touchscreen behavioral baseline indicators of mice, and key indicators were screened and evaluated. Results: In the 5 - CSRT, the optimal stage for wild - type C57 mice to achieve an accuracy rate of ≥ 80% was from the 11th to the 13th cycle, while for A53T mice, it was the 11th cycle. The EFs of A53T mice were impaired, with abnormalities in the accuracy rate, trace number, and number of punished times in the 5 - CSRT. When identifying drug - induced PD models, the 13th cycle of the 5 - CSRT was more effective; when identifying transgenic PD models, the 11th cycle was more suitable. Interventions could be carried out after the baseline accuracy rate reached 80%. Through the “genetic - environmental” dual - axis drive, the “chronic - acute” time - dimension complementarity, and the “mechanism - transformation” multi - level verification, the A53T and MPTP dual models were used to comprehensively cover the pathological cycle of PD EFs impairment. Conclusions This study has successfully established a paradigm process and an evaluation baseline for touchscreen behavioral analysis in PD model mice. This provides an important basis for a deep understanding of the mechanisms of EFs impairment in PD patients, has potential guiding significance for the development of intervention strategies and treatment methods for EFs impairment in PD patients, and is expected to promote new progress in PD research in the field of neuroscience.

Non-small cell lung cancer(NSCLC)is one of the most common and deadly malignant tumors worldwide,with surgical resection being the primary treatment for early-stage NSCLC.Tumor spread through air spaces(STAS)is a novel pattern of tumor dissemination into the air spaces in the lung.Its occurrence after sublobar resection is closely associated with recurrence and distant metastasis,making its con-sideration a vital factor in surgical strategy selection and prognostic evaluation.Patients with STAS-positive status exhibit significantly higher postoperative recurrence rates than do STAS-negative patients,with molecular mechanisms involving tumor microenvironment remodeling,specific genetic mutations,and epithelial-mesenchymal transition(EMT).Imaging techniques including computed tomography(CT)and positron emission tomography/CT have shown potential for preoperative STAS prediction,although their accuracy and practicality require improvement.This paper reviews the definition,pathological characteristics,and related mechanisms of STAS,with a focus on surgical ap-proach selection for STAS-positive patients and its role in cancer recurrence after sublobar resection of early-stage NSCLC.Future research directions include optimization of preoperative diagnostic methods for STAS,exploration of molecular targeted therapies,and development of imaging-based precision prediction models.

Non-small cell lung cancer(NSCLC)is one of the most common and deadly malignant tumors worldwide,with surgical resection being the primary treatment for early-stage NSCLC.Tumor spread through air spaces(STAS)is a novel pattern of tumor dissemination into the air spaces in the lung.Its occurrence after sublobar resection is closely associated with recurrence and distant metastasis,making its con-sideration a vital factor in surgical strategy selection and prognostic evaluation.Patients with STAS-positive status exhibit significantly higher postoperative recurrence rates than do STAS-negative patients,with molecular mechanisms involving tumor microenvironment remodeling,specific genetic mutations,and epithelial-mesenchymal transition(EMT).Imaging techniques including computed tomography(CT)and positron emission tomography/CT have shown potential for preoperative STAS prediction,although their accuracy and practicality require improvement.This paper reviews the definition,pathological characteristics,and related mechanisms of STAS,with a focus on surgical ap-proach selection for STAS-positive patients and its role in cancer recurrence after sublobar resection of early-stage NSCLC.Future research directions include optimization of preoperative diagnostic methods for STAS,exploration of molecular targeted therapies,and development of imaging-based precision prediction models.