OBJECTIVE: To investigate the effects of 4-methylcatechol (4MC) on the migration and inflammatory response in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), as well as its underlying mechanisms of action. METHODS: RA-FLS was isolated from synovial tissue donated by RA patients, and the optimal concentration of 4MC was determined by cell counting kit 8 method for subsequent experiments, and the effect of 4MC on the migratory ability of RA-FLS was evaluated via a cell scratch assay. An inflammation model of RA-FLS was induced by tumor necrosis factor α (TNF-α). Real-time fluorescence quantitative PCR and ELISA were employed to detect the gene and protein expression levels of interleukin-1β (IL-1β) and IL-6 in RA-FLS and their culture supernatants, respectively, thereby investigating the anti-inflammatory effects of 4MC. Western blot was used to examine the expressions of nuclear factor κB (NF-κB) signaling pathway-related proteins, including inhibitor of NF-κB-α (IKBα), phosphorylated (P)-IκBα, NF-κB-inducing kinase α (IKKα), P-IKKαβ, P-p65, and p65. Cellular immunofluorescence was utilized to detect the expression and localization of p65 in RA-FLS, exploring whether 4MC exerts its anti-inflammatory effects by regulating the NF-κB signaling pathway. Finally, a collagen-induced arthritis (CIA) mouse model was established. The anti-RA effect of 4MC in vivo was evaluated by gross observation and histological examination. RESULTS: 4MC inhibited RA-FLS migration in a concentration-dependent manner. In the TNF-α-induced RA-FLS inflammation model, 4MC significantly decreased the gene and protein expression levels of IL-1β and IL-6. Furthermore, 4MC markedly reduced the ratios of P-IΚBα/IΚBα, P-IKKαβ/IKKα, and P-p65/p65, thereby blocking the transcriptional activity of p65 by inhibiting its nuclear translocation. This mechanism effectively suppressed the activation of the TNF-α-mediated NF-κB signaling pathway. Animal studies demonstrated that 4MC [10 mg/(kg·day)] significantly lowered serum levels of IL-1β, IL-6, and TNF-α, and alleviated arthritis severity and bone destruction in CIA mice. CONCLUSION 4MC not only inhibits the migration of RA-FLS but also mitigates their inflammatory response by suppressing the NF-κB signaling pathway, thereby effectively exerting its anti-RA effects.
Synoviocytes/metabolism* ; Arthritis, Rheumatoid/metabolism* ; Animals ; Cell Movement/drug effects* ; Humans ; Catechols/therapeutic use* ; Fibroblasts/drug effects* ; Mice ; Tumor Necrosis Factor-alpha/pharmacology* ; Interleukin-1beta/metabolism* ; Interleukin-6/metabolism* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/cytology* ; Cells, Cultured ; Male ; Arthritis, Experimental ; Anti-Inflammatory Agents/pharmacology* ; NF-KappaB Inhibitor alpha ; Inflammation

BACKGROUND:Non-alcoholic fatty liver disease is one of the common chronic liver diseases in the world.Aerobic exercise is considered to be an important means for the treatment of non-alcoholic fatty liver disease.However,the mechanism of exercise to improve non-alcoholic fatty liver disease has not been fully clarified.OBJECTIVE:To investigate the effects of aerobic exercise on the protein kinase B/glycogen synthase kinase-3β pathway mediated by Canopy FGF signaling regulator 2(CNPY2)in the liver canopy of non-alcoholic fatty liver disease mice and its mechanism.METHODS:Thirty male CNPY2 knockout mice(ko)and thirty their litters of wild-type mice(wt)were fed adaptively for one week and randomly divided into control group,model group,and model exercise group,with 10 mice in each group.The control group was fed with ordinary diet.The model group and the model exercise group were fed with high-fat diet for 17 weeks.The model exercise group received continuous aerobic exercise intervention from week 10 until the end of the experiment at week 18.Liver histopathology was observed by hematoxylin-eosin and oil red O staining.The levels of serum lipids and liver function were detected by automatic biochemical analyzer.The expression levels of CNPY2,protein kinase B/glycogen synthase kinase-3β pathway,and Caspase-3 protein in liver tissues were detected by Western Blotting.The apoptosis rate of hepatocytes was detected by TUNEL staining.RESULTS AND CONCLUSION:(1)Compared with wt control group,CNPY2 expression in liver tissues of wt model group was increased(P＜0.05),while CNPY2 expression in wt model exercise group was decreased compared with wt model group(P＜0.05).Compared with control group,wt mice and ko mice in model group showed steatosis,increased lipid droplets,abnormal blood lipids and liver function,decreased protein kinase B/glycogen synthase kinase-3β expression(P＜0.05)and increased Caspase-3 expression(P＜0.05),and increased hepatocyte apoptosis rate in liver tissue(P＜0.05).(2)Compared with the model group,wt mice and ko mice showed improvement in the above indexes in model exercise group.(3)Compared with wt mice,the above indexes of ko mice were improved.(4)These findings indicate that CNPY2 gene deletion and aerobic exercise can effectively improve non-alcoholic fatty liver disease.The mechanism may be related to aerobic exercise reducing CNPY2 expression,activating protein kinase B/glycogen synthase kinase-3β signaling pathway,and thus inhibiting hepatocyte apoptosis.

Objective:Chimeric antigen receptor T-cell(CAR-T)immunotherapy has made major breakthroughs in the treatment of blood tu-mors.However,current CAR-T therapies face several limitations:they require autologous cells,involve a lengthy and costly production pro-cess,and use lentiviral transduction that carry risk of insertional carcinogenesis due to random integration.Therefore,there is an urgent need to develop a universal cost-effective cancer immunotherapy method generating CAR-T cells for in vivo cancer immunotherapy.Meth-ods:This study successfully established an exosome-mediated,T-cell targeted delivery system,demonstrating both precise design and func-tional efficacy for biomedical applications.To optimize CAR-T cell generation the transfection dose was adjusted,and the kinetics of CAR-T cell percentage were recorded.The cytotoxicity of the resulting CAR-T cells was evaluated in vitro by calcein-AM release.To test the tumor-killing in vivo of engineered exosomes,human PBMCs were injected into NPG mice via the tail vein to establish humanized mice,followed by intravenous injection of tumor cells to induce cancer.Results:To overcome the limitations of conditional autologous CAR-T cells,we de-veloped a T cell-targeted exosome system capable of specifically targeting human CD3+,CD4+,and CD8+T cells.CAR-T production was dose-dependent,with transfection efficiency reaching upto 97.8%at 106 particles/cell.Both in vitro cytotoxicity assays and in vivo animal experi-ments demonstrated that exosome-incubated CAR-T cells effectively eliminated CD19-positive Raji cells,highlighting their specificity and therapeutic potential in antigen-directed applications.Conclusions:We successfully established a CD8-targeting exosome delivery system for CAR-T cell production capable of transforming CD8+T cells into functional CAR-T cells,which showed significant tumor-killing ability in vitro and in mice.Compared with the traditional lentiviral vector for the preparation of CAR-T cells in vitro,in vivo-reprogrammed CAR-T cells us-ing our CD8-targeted exosome delivery system,with higher transfection efficiency,shorter production period,lower cost,and eliminated the risk of insertion carcinogenesis.This strategy promises to bring a new era of universal CAR-T medicine,which can improve cancer immuno-therapy and may hold promise as a therapeutic platform to treat various diseases.

Objective To explore the establishment,implementation,and outcomes of an integrated physician-nurse team-based comprehensive management model for breast cancer chemotherapy outpatients,ai-ming to provide a reference for standardized patient care.Methods In January 2019,the Breast Surgery De-partment of Peking Union Medical College Hospital developed an integrated physician-nurse team and estab-lished a full-cycle management pathway covering the pre-chemotherapy,chemotherapy,and inter-cycle phases.This model featured appointment-based scheduling,time-segmented visits,and closed-loop patient management.Key performance indicators-including healthcare efficiency,chemotherapy safety,staffing ratios,and satisfaction levels among patients and healthcare providers-were compared between pre-implementation(2018)and post-imple-mentation(2019)periods.Results Before implementation,patient waited times ranged from 30 to 120(75.40±20.97)minutes,with an annual chemotherapy volume of 8 715 cases.Two ward nurses were routinely redeployed daily to support the chemotherapy clinic.Post-implementation,patients received timely chemotherapy per scheduled appointments without delays,annual chemotherapy volume in-creased to 10 101 cases,and staffing between two chemotherapy units became flexibly adjustable.Ward nurses transitioned from an on-call to a reserve role.Adverse events(chemotherapy-related,catheter-related,and nursing incidents)remained at 0,consistent with pre-implementation levels.Both patient and staff satisfaction scores significantly improved across all domains(all P＜0.05).Conclusions The integrated physician-nurse team-based chemotherapy management model enhances service efficiency,ensures treatment safety,optimizes workforce allocation,and improves satisfaction among patients and healthcare providers.

Extramedullary plasmacytoma(EMP)is a malignant neoplasm characterized by monoclonal plasma cell proliferation originating outside the bone marrow and hematopoietic tissues.The co-occurrence of multiple myeloma(MM)with mammary EMP is clinically rare.This case report describes the diagnostic and therapeutic management of a middle-aged female patient with MM and mammary EMP,accompanied by a litera-ture review.The patient presented with persistent fever and was found to have a right breast mass via PET/CT during routine follow-up for MM.The lesion was biopsy-confirmed as mammary EMP,and the patient subse-quently underwent chemotherapy.This case highlights the critical importance of differential diagnosis between breast cancer and rare hematologic metastatic tumors in early prevention of disease progression.

Adaptive optics(AO)is a technology designed to enhance the performance of optical systems through real-time measurement and correction of optical aberrations. With continuous advancements in refractive surgery techniques and rising patient expectations for surgical outcomes, the precise implementation of personalized refractive corrections has become a critical focus. The integration of AO technology into refractive surgery provides novel technical support. Specifically, the adaptive optics vision simulator(VAO)facilitates accurate preoperative objective and subjective refraction by dynamically measuring and correcting ocular wavefront aberrations, thereby improving refractive efficiency. Additionally, it enables effective prediction of postoperative aberrations for personalized procedures, assists clinicians in making data-driven preoperative decisions, facilitates comparative analysis of different surgical techniques, and allows intuitive evaluation of postoperative visual quality. This review comprehensively examines the advances in VAO applications for refractive surgery and analyzes both its clinical advantages and technical limitations.

Ischemic stroke is a disease resulting from the cerebral ischemia and hypoxia caused by the blockage of brain vessels in the brain,and is characterized by the focal neurological signs.Pathologically,neuronal necrosis in the infarcted area and the neuronal degeneration or delayed death of neurons in the ischemic penumbra,contribute to the morphological basis of the disease.Ischemic stroke is regulated by multiple processes,including ferroptosis,apoptosis,and autophagy.Ferroptosis,a type of iron-dependent cell death,is closely associated with ischemic stroke.Nuclear factor erythroid 2-related factor 2(Nrf2),a key transcription factor,plays a critical role in maintaining cellular redox balance and regulating inflammatory responses.Nrf2 promotes the expression of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),thereby activating the Nrf2 signaling pathway to counteract ferroptosis and protect cells from damage.This article reviews and analyzes recent experimental studies on traditional Chinese medicine(TCM)therapy targeting the Nrf2/SLC7A11/GPX4 pathway to suppress ferroptosis.The studies have found that TCM therapy with herbal compounds,Chinese patent medicines,single herbal components and their active ingredients,and acupuncture and moxibustion can inhibit ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway,which will provide novel strategies for the TCM intervention of ischemic stroke.

Osteoporotic vertebral compression fractures(OVCFs)are common orthopedic conditions that can lead to spinal pain and deformity,which greatly affects the quality of life of patients.Currently,there are various treatment methods for OVCFs,but there is still a lack of standards for optimal treatment modalities.Therefore,this article introduces the current treatment methods and character-istics of epidemiology for OVCFs,in order to improve the awareness of this disease among clinicians and provide a reference for select-ing more appropriate treatment regimens.Conservative treatment measures,such as bracing and analgesia,are the basic treatment mea-sures for OVCFs,and anti-osteoporosis drugs play a crucial role in management.Minimally invasive procedures,including percutane-ous vertebroplasty and percutaneous balloon kyphoplasty,remain the primary surgical interventions,and traditional open surgeries are also an important part of treatment,such as anterior spinal fusion,combined anterior and posterior spinal fusion,posterior spinal fusion with three-column osteotomy,and posterior spinal fusion with vertebroplasty.Furthermore,surgeons should focus on the accumulation of related surgical techniques and skills during surgery to effectively address the challenges and complications associated with surgical interventions.Finally,scientific and appropriate treatment methods should be selected for patients,in order to improve long-term treat-ment outcomes and increase the degree of satisfaction among pa-tients.

Objective To report the diagnosis of a canine distemper virus outbreak among a colony of cynomolgus monkeys at an experimental monkey farm in 2019. MethodsA total of 46 samples were collected from 21 diseased cynomolgus monkeys (exhibiting symptoms such as facial rash, skin scurf, runny nose, and diarrhea) and from one deceased monkey at an experimental monkey breeding farm in South China in late 2019, including serum, skin rash swabs, and anticoagulated whole blood, liver, lung, and skin tissues were submitted for testing. All submitted samples were tested for canine distemper virus gene fragments using real-time quantitative PCR, while immunohistochemical staining was performed to detect canine distemper virus nucleoprotein in lung tissues. The skin tissue of the deceased monkey was ground and sieved. The filtrate was inoculated into a monolayer MDCK cell line for virus isolation. Then, whole-genome sequencing was performed to identify the isolated virus. The Clustal Omega tool was used to align and analyze the homology of different Asian canine distemper virus isolates. A phylogenetic tree was constructed, followed by genetic evolutionary analysis. ResultsClinical retrospective analysis revealed that the diseased cynomolgus monkeys exhibited symptoms similar to those observed in cynomolgus monkeys infected with measles virus. Necropsy findings showed red lesions in the lungs and significant hemorrhage in the colonic mucosa. Real-time quantitative PCR detected canine distemper virus nucleic acid in the serum, skin rash swabs of the infected monkeys, and various tissue samples of the deceased monkey, all of which tested positive. Calculation based on the standard curve formula indicated the viral load was highest in the skin tissue. Immunohistochemical staining of the deceased monkey's lung tissue demonstrated aggregation of CDV nucleoprotein in alveolar epithelial cells, bronchi, and bronchioles. A CDV strain was isolated from the skin tissue of the deceased monkey. Phylogenetic analysis indicated that this strain shares the closest relationship (98.86%) with the Asian-1 type canine distemper virus strain CDV/dog/HCM/33/140816, previously identified in dogs in Vietnam. ConclusionBased on comprehensive analysis of clinical symptoms, nucleic acid detection, viral protein immunohistochemistry, and whole-genome sequencing results, the diagnosis confirms that the cynomolgus monkeys in this facility are infected with canine distemper virus. It is recommended to include canine distemper virus as a routine surveillance target in captive monkey populations. Additionally, this study provides a foundation for further research on the molecular biological characteristics of canine distemper virus.

Objective To report the diagnosis of a canine distemper virus outbreak among a colony of cynomolgus monkeys at an experimental monkey farm in 2019. MethodsA total of 46 samples were collected from 21 diseased cynomolgus monkeys (exhibiting symptoms such as facial rash, skin scurf, runny nose, and diarrhea) and from one deceased monkey at an experimental monkey breeding farm in South China in late 2019, including serum, skin rash swabs, and anticoagulated whole blood, liver, lung, and skin tissues were submitted for testing. All submitted samples were tested for canine distemper virus gene fragments using real-time quantitative PCR, while immunohistochemical staining was performed to detect canine distemper virus nucleoprotein in lung tissues. The skin tissue of the deceased monkey was ground and sieved. The filtrate was inoculated into a monolayer MDCK cell line for virus isolation. Then, whole-genome sequencing was performed to identify the isolated virus. The Clustal Omega tool was used to align and analyze the homology of different Asian canine distemper virus isolates. A phylogenetic tree was constructed, followed by genetic evolutionary analysis. ResultsClinical retrospective analysis revealed that the diseased cynomolgus monkeys exhibited symptoms similar to those observed in cynomolgus monkeys infected with measles virus. Necropsy findings showed red lesions in the lungs and significant hemorrhage in the colonic mucosa. Real-time quantitative PCR detected canine distemper virus nucleic acid in the serum, skin rash swabs of the infected monkeys, and various tissue samples of the deceased monkey, all of which tested positive. Calculation based on the standard curve formula indicated the viral load was highest in the skin tissue. Immunohistochemical staining of the deceased monkey's lung tissue demonstrated aggregation of CDV nucleoprotein in alveolar epithelial cells, bronchi, and bronchioles. A CDV strain was isolated from the skin tissue of the deceased monkey. Phylogenetic analysis indicated that this strain shares the closest relationship (98.86%) with the Asian-1 type canine distemper virus strain CDV/dog/HCM/33/140816, previously identified in dogs in Vietnam. ConclusionBased on comprehensive analysis of clinical symptoms, nucleic acid detection, viral protein immunohistochemistry, and whole-genome sequencing results, the diagnosis confirms that the cynomolgus monkeys in this facility are infected with canine distemper virus. It is recommended to include canine distemper virus as a routine surveillance target in captive monkey populations. Additionally, this study provides a foundation for further research on the molecular biological characteristics of canine distemper virus.