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 elucidate the molecular mechanisms through which high-dose dexamethasone exerts long-term effects on bone marrow mesenchymal stem cells (BMSCs), specifically its role in suppressing osteogenic differentiation, accelerating cellular senescence, triggering the senescence-associated secretory phenotype (SASP), and inducing apoptosis.Methods:Primary rat BMSCs were isolated and treated with high-dose dexamethasone (1×10 -4 mol/L) to establish the experimental group, while untreated cells served as the control. The gene and protein expression levels of osteogenic markers, bone alkaline phosphatase (bALP) and Runt-related transcription factor 2 (Runx2), were analyzed in both groups. Cellular senescence was evaluated using senescence-associated β-galactosidase (SA-β-gal) staining. The expression of senescence-related markers (P16 and P21), components of the senescence-associated secretory phenotype (SASP), including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-γ, as well as apoptosis-related proteins (Bcl-2, Bax, and Cleaved-Caspase-3), and key factors of the Nrf2/HO-1 signaling pathway were assessed at both transcriptional and protein levels using qRT-PCR, immunofluorescence, and Western-blot analyses. These comprehensive evaluations aimed to determine the senescent state, apoptotic features, and alterations in osteogenic differentiation of BMSCs. Results:Following treatment with dexamethasone and subsequent withdrawal, both qRT-PCR and Western blot analyses indicated a significant reduction in the expression of the osteogenic markers bALP and Runx2 at both mRNA and protein levels. The proportion of SA-β-gal positive cells was markedly higher in the dexamethasone group (74.33%±6.89%) than in the control group (20.30%±1.57%, t=17.300, P<0.001). qRT-PCR analysis revealed upregulated mRNA expression of the senescence-related genes P16 and P21 after dexamethasone treatment, which was further supported at the protein level by immunofluorescence showing increased P21 expression. Western-blot results confirmed that protein expression levels of P16 and P21 were significantly elevated in the dexamethasone group (7.025±0.255 and 6.362±0.456, respectively) compared with the control group (1.016±0.115 and 0.816±0.172; both P<0.05). Furthermore, gene expression levels of the senescence-associated secretory phenotype (SASP) factors TNF-α and IL-1β were significantly increased (TNF-α: 3.539±0.599 vs. 0.742±0.095; IL-1β: 4.469±0.331 vs. 0.799±0.175; both P<0.05), and their protein expression was consistently upregulated as validated by Western-blot. Additionally, protein expression levels of TNF-α, IL-1β, and IFN-γ were significantly higher in the dexamethasone-treated group (3.476±0.932 vs. 0.945±0.095; 4.111±0.220 vs. 0.762±0.105; 2.155±0.240 vs. 0.656±0.104; all P<0.05).Western-blot analysis also demonstrated that protein expression of Nrf2 and HO-1 was significantly suppressed in the dexamethasone group (0.21±0.07 and 0.19±0.06, respectively) compared with the control group (1.13±0.15 and 0.92±0.21; P<0.05). Moreover, Western-blot analysis revealed that the expression levels of the pro-apoptotic proteins Bax and Cleaved-Caspase-3 were significantly up, regulated in the dexamethasone, treated BMSCs (Bax: 3.673±0.397 vs. 0.453±0.111; Cleaved-Caspase-3: 3.863±0.399 vs. 0.465±0.057), while the expression of the anti-apoptotic protein Bcl-2 was markedly down, regulated (0.959±0.073 vs. 2.126±0.195), with all differences being statistically significant ( P<0.05). Conclusions:High-dose dexamethasone treatment of BMSCs, followed by withdrawal of dexamethasone, induces cellular senescence and enhances the expression of the senescence-associated secretory phenotype (SASP) through suppression of the Nrf2/HO-1 signaling pathway. Concurrently, it promotes apoptosis by activating the mitochondrial apoptotic pathway, collectively leading to impaired osteogenic differentiation of BMSCs.

Objective:This study analyzed the epidemiological characteristics of the clustered cases of severe fever with thrombocytopenia syndrome (SFTS) in Jiangsu province, so as to provide a scientific basis for prevention and control efforts.Methods:In this study we searched for cases related to clustered outbreaks and conducted epidemiological investigations of the cases, their co-exposed individuals, and close contacts. The basic information of the cases and their disease progression were collected and documented. The source of infection and transmission routes were analyzed. Fisher’s exact probability test and independent samples t-test were used to compare the differences between index and secondary cases. Results:From 2018 and 2024, a total of nine cluster outbreaks were reported in Jiangsu province, involving 32 cases of SFTS with 12 fatalities. Seven clustered outbreaks occurred in rural communities, while two occurred in medical institutions. The primary cause of these outbreaks was direct contact with confirmed cases.Conclusions:In recent years, Jiangsu province has experienced multiple clustered outbreaks of SFTS. Targeted health education should be implemented in high-risk areas to increase awareness of personal protective measures. Medical institutions should standardize the management of confirmed cases, educate patients′ families about prevention and control measures, and strengthen training for healthcare workers to ensure effective infection control within hospitals.

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.

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:To observe the effect of different degrees of decentration and tilt on the optical quality of the intraocular lenses (IOLs) with different focus designs.Methods:The UV 3300 PC UV-visible spectrophotometer was employed to measure the spectral transmittance of the monofocal IOL CT ASPHINA 509M (509M), bifocal IOL AT LISA 809M (809M), and trifocal IOL AT LISA Tri 839MP (839MP) within Zeiss MICS platform with a refractive power of + 20 D. The modulation transfer function (MTF) values at a spatial frequency of 50 lp/mm along with MTF curves and United States Air Force (USAF) resolution test charts for each IOL at the focal point were measured at apertures of 3.0 mm and 4.5 mm using the in vitro optical quality testing system OptiSpheric IOL R&D under centered, decentered (0.3, 0.5, 0.7, 0.9 and 1.1 mm) and tilted (3°, 5°, 7°, 9° and 11°) conditions. Results:All three IOLs filtrated the ultraviolet (UV) spectrum below 400 nm.When each IOL was in the centered position, at the 3.0 mm aperture, the MTF values were 0.772 at the far focus of the monofocal IOL 509M, 0.467 and 0.282 at the far and near focus of the bifocal IOL 809M, and 0.416, 0.147, and 0.229 at the far, intermediate, and near focus of the trifocal IOL 839MP, respectively.Whereas at the 4.5 mm aperture, the monofocal IOL 509M MTF value at the far focus was 0.664, the bifocal IOL 809M MTF values at the far and near focus were 0.506 and 0.264, and the trifocal IOL 839MP MTF values at the far, intermediate, and near focus were 0.392, 0.107, and 0.210, respectively.Among the three centered IOLs, the 509M demonstrated the highest MTF value at the far focus, followed by the 809M and then the 839MP; at the near focus, the MTF value of the 809M surpassed that of the 839MP.For decentration and tilt, the difference in MTF values of the three IOLs at the far and near focus was consistent with the differences observed when they were centered.At the same degree of decentration and tilt, all three IOLs exhibited superior optical quality at the 3.0 mm aperture compared to the 4.5 mm aperture.The optical quality of all three IOLs exhibited an overall decline as decentration and tilt increased.All three IOLs demonstrated a decrease in optical quality at the decentration of 0.3 mm or the tilt of 5°.Conclusions:The IOLs within the Zeiss MICS platform design exhibits identical spectral transmittance and UV filtering properties.Among the three IOLs, when centered, the 509M, the 839MP, and the 809M exhibit superior optical quality at the far, intermediate, and near focal points, respectively.Under decentered and tilted conditions, the 509M and the 809M demonstrate better resistance against decentration and tilt, respectively, at both far and near focuses.Additionally, all three IOLs demonstrate better optical quality at smaller apertures, given equivalent degrees of decentration or tilt.However, the optical quality at each focal point of the three IOLs decreases compared to the centered position when subjected to a decentration of 0.3 mm or a tilt of 5°.

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.

The treatment process of multiple fertilization failure and salvage fertilization in a male infertile patient was retrospectively analyzed. The patient underwent in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in another hospital for 3 cycles, all of which had fertilization abnormalities. The complex heterozygous mutation of PLCZ1 gene was detected by infertility gene paneland confirmed by Sanger sequencing in the Reproductive Medicine Center of Renmin Hospital, Hubei University of Medicine, and the gene mutation was derived from both parents. No abnormal mutations were found in the woman's genetic testing. The woman underwent progestin-primed ovarian stimulation, resulting in the retrieval of 9 oocytes. ICSI combined with 10 μmol/L ionomycin assisted oocyte activation (AOA) was applied to all mature eggs,resulting in 7 normal fertilized oocytes and 7 cleavage embryos, 2 high-quality cleavage embryos were frozen. Two months later, the woman underwent frozen-thawed embryo transfer to obtain biochemical pregnancy. Simultaneously, we reviewed the literature on PLCZ1 gene mutations and AOA related literature at home and abroad. From this case we can draw the following conclusions: 1) When no fertilization or polyspermia occurs in an IVF cycle and total fertilization fails in ICSI, genetic testing of both spouses is required to find genetic factors. 2) The mutation of PLCZ1 gene mainly leads to fertilization failure. ICSI combined with AOA is an effective method to rescue fertilization failure. Ionomycin has a significant effect on oocyte activation, and has no effect on embryo formation. However, we still need to accumulate case data to verify the safety of ionomycin AOA.

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.