Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

Objective To explore the effect of different needle track management on Yttrium-90 microsphere selective internal radiation therapy (⁹⁰Y-SIRT) on liver cancer after liver biopsy. Methods A retrospective analysis was conducted on the clinical data of 21 patients with liver cancer who underwent Technetium-99m-macroaggregated albumin (^99mTc-MAA) evaluation and ⁹⁰Y-SIRT after liver biopsy from June 2023 to December 2024. The methods of needle track management, hepatic arteriovenous shunting, and lung shunt fraction (LSF) were recorded. The occurrence of hepatic arteriovenous fistula (HAVF), as well as the corresponding countermeasures were analyzed. Results Among the 21 liver cancer patients, 7 cases (medical glue group) underwent embolization of the needle tract with medical glue (N-butyl 2-cyanoacrylate [NBCA]) immediately after biopsy, and no significant HAVF was observed during the ^99mTc-MAA tests; 14 cases (non-medical glue group) were treated with delayed needle extraction or gelatin sponge particle blocking after biopsy, among which 7 cases developed significant HAVF, and the fistulas were treated with NBCA. The LSF of the medical glue group was significantly lower than that of the non-medical glue group ([7.06±2.33] % vs [12.43±7.73] %, P＝0.037). All 21 patients successfully completed ⁹⁰Y-SIRT. Conclusions Liver biopsy may affect ⁹⁰Y-SIRT by causing iatrogenic HAVF. Immediate NBCA-embolization of the needle tract after biopsy or timely NBCA-embolization of fistulas during ^99mTc-MAA tests may reduce the impact.

Objective:To establish a set of dynamic definition methods and key operational techniques for community pediatric services contents within the framework of an integrated children health services model.Methods:This was a cross-sectional study. From December 2023 to June 2024, a study was conducted at the Shanghai Gumei Community Health Service Center. The study was divided into three phases: identifying the health needs of community children (Phase A), developing the service content and methods for community children (Phase B), and establishing a community children service network (Phase C). A variety of methods, including questionnaires and focus group interviews, were comprehensively employed in each phase to develop the ABC demand network and its construction approach for community children, and to establish a networked service system.Results:A total of 512 questionnaires were distributed in Phase A, of which 499 were returned for an effective recovery rate of 97.5%. Of the parents, 488 (97.8%, 488/499) would actively seek information related to children′s health. Of those parents, 90.6% (452/499), 80.8% (403/499), and 71.9% (359/499) expressed concern about their children′s growth and development, mental health and social adaptation, and the prevention and treatment of common, frequently occurring diseases, respectively. The research clarified the health needs of children in the community and the health issues of children in different age groups. This included the mental health and social adaptation of community children, as well as common and frequently occurring diseases. The study also revealed a lack of mental health and social adaptation's services for children in the community. After sorting the community′s services into categories such as children′s growth and development detection, diagnosis and treatment of common diseases, and planned immunizations, and establishing corresponding service methods, it was found that Gumei community Health Service Center had strong diagnostic service capabilities for children aged 0-3 and 4-6, but need improved for children aged 7-12 and 13-15. At the same time, a service network consisting of five major categories, represented by medical alliances, has been established to address unmet needs in diagnosis and rehabilitation care for mental health and social adaptation, as well as major diseases.Conclusions:The study has developed an ABC demand network and its construction method for community children. It provides new ideas for defining the content of community pediatric services and establishing supporting methods, and it offers a practical basis for the constructing a community pediatric service system.

Objective:To evaluate the outcomes of minimally invasive therapy for aortic arch pathology after ascending aortic replacement.Methods:A retrospective analysis was conducted at the Department of Cardiovascular Surgery, West China Hospital of Sichuan University from 2016 to 2024. After multidisciplinary discussion, these included patients were evaluated to be at high risk for traditional open surgery. Various minimally invasive repair techniques were employed, including Ⅳb hybrid technique, physician-modified endograft and novel unibody endograft. The study outcomes were technical success, in-hospital and follow-up mortality, stroke, endoleak, and the patency of the supra-aortic vessels.Results:A total of 40 patients(32 males and 8 females) with a median age of 60 years old were included in this study. The technique success rate was 100%, with no deaths or strokes reported. The patency of the supra-aortic vessels was 100%. 10 patients underwent Type Ⅳb hybrid surgery without any endoleaks occurring. Among the 22 patients who received physician-modified endograft, endoleaks were observed in 2 cases. One of these type Ⅰc endoleaks persisted and underwent reintervention. One patient underwent femoral artery replacement due to vascular injury. For the 8 patients who received novel unibody endograft, one case required reintervention due to persistent type Ⅰc endoleaks.Conclusion:With the development of different endovascular techniques and novel branched endograft, patients with aortic arch pathology who are at high risk for redo open surgery can achieve favorable outcomes with various minimal invasive techniques. However, long-term and large-sample follow-up studies are needed for further evaluation.

Objective To investigate the effect of miR-7975 on the malignant phenotype of oral squamous cell carcinoma(OSCC)and its potential mechanisms.Methods This study compared the expression levels of miR-7975 in different oral cell lines by qRT-PCR.miR-7975 mimic and miR-7975 inhibitor were transfected into OSCC cell lines HSC3 and HN4 respectively.Colony formation as-say,CCK8 assay,Transwell assay,and wound healing assay were conducted to evaluate the effects of miR-7975 on the malignant phe-notype of OSCC cells.Western blot was employed to analyze changes in the expression of EMT related proteins and proteins associated with the RAS/ERK signaling pathway.Subcutaneous tumor model of nude mice was used to further validate the tumorigenic effect of miR-7975 in vivo.Results The expression of miR-7975 was downregulated in OSCC cells.Overexpression of miR-7975 reduced the proliferation,migration,and invasion abilities of OSCC cells,whereas downregulation of miR-7975 enhanced these abilities.After miR-7975 overexpression,the expression of the EMT-related protein E-cadherin was upregulated,while N-cadherin,Vimentin,β-catenin,Snail,and Slug were downregulated.Additionally,the expression of proteins related to the RAS/ERK signaling pathway increased.Conversely,the expression of EMT and RAS/ERK signaling pathway-related proteins showed opposite changes when miR-7975 was downregulated.Compared to the control group,the volume and weight of tumors formed in nude mice were significantly smaller after miR-7975 overexpression,while they were significantly larger when miR-7975 expression was reduced.Conclusion miR-7975 exerts its tumor-suppressive effects by inhibiting the proliferation,migration,and invasion of OSCC through the regulation of EMT and the RAS/ERK signaling pathway.

Objective To explore the effect of low-frequency repetitive transcranial magnetic stimulation(rTMS)combined with unilateral upper limb mirror training on contralateral limb strength in patients with hemiplegia after ischemic stroke.Methods A total of 196 patients with hemiplegia after ischemic stroke were selected.All patients were divided into study group and control group via a random number table method,with 98 patients in each group.The control group received mirror training,while the study group received low-frequency rTMS treatment in addition to the control group.The neuroelectrophysiology,neurological function,limb motor function,and clinical efficacy of all patients were observed before and after treatment,and all patients were performed the resting-state functional MRI examination.A generalized estimating equation(GEE)model were used to analyze the improvement of contralateral limb strength.Results After treatment,the seed points in the study group showed a significant enhancement in connectivity with the whole brain function.The overall efficiency of the study group was significantly better than that of the control group.After treatment,the central motor conduction time(CMCT),neuron specific enolase(NSE),cortical latency(CL),and S100β of the two groups of patients were significantly reduced compared with before treatment,while the neurotrophin-3(NT-3),nerve growth factor(NGF),Fugl-Meyer assessment upper extremities(FMA-UE),Wolf motor function test(WMFT),modified Barthel index(MBI),and Berg balance scale(BBS)scores were significantly increased.Moreover,the study group showed a more significant improvement compared to the control group(P＜0.05).The GEE model analysis results showed that the improvement of contralateral limb strength in the study group was significantly better than that in the control group.Conclusion Low-frequency rTMS combined with unilateral upper limb mirror training can improve cortical excitability and upper limb motor function in hemiplegic patients after ischemic stroke,with good therapeutic effects.

AIM:To investigate whether Xibining Ⅱ(XBN Ⅱ)attenuates cartilage damage in rats with knee osteoarthritis(KOA)by modulating glycolysis via the AMP-activated protein kinase(AMPK)/peroxisome proliferator-acti-vated receptor γ coactivator 1α(PGC1α)signaling pathway.METHODS:Thirty-two SD rats were randomly divided into sham group,KOA group,XBN Ⅱ group and metformin(AMPK activator)group,with 8 rats in each group.The rats in KOA group were subjected to the anterior cruciate ligament transection procedure to establish the KOA model.Starting from the 14th day after modeling,the rats in XBN Ⅱ group received a daily dose of XBN Ⅱ via gavage once a day,and those in metformin group were administered metformin via intraperitoneal injection once a day for 4 weeks.Subsequently,the histopathological changes of the cartilage were examined by HE and safranin O-fast green staining with matching Mankin and OARSI scores.The protein levels of phosphorylated AMPK(p-AMPK)and PGC1α in cartilage were quanti-fied through immunohistochemistry.In addition,RT-qPCR and Western blot were conducted to measure the mRNA and protein expression levels of glycolysis-related factors,including glucose transporter 1,hexokinase 2 and lactate dehydroge-nase A,biomarkers related to cartilage synthesis and catabolism,such as collagen type Ⅱ,aggrecan,matrix metallopro-teinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs 5,and AMPK/PGC1α signaling pathway-re-lated indicators.RESULTS:Lactate levels in cartilage and serum were higher in KOA group compared with sham group(P<0.05).Similarly,the cartilage in KOA group exhibited significant surface abrasion and structural damage,with faint-stained matrix and significantly higher Mankin and OARSI scores compared with sham group(P<0.05).Further analysis revealed significant decreases in the mRNA and protein expression levels of factors related to cartilage anabolism and AMPK/PGC1α signaling pathway in KOA group compared with sham group(P<0.05).In contrast,there were marked in-creases in the mRNA and protein expression levels of factors related to cartilage catabolism and glycolysis(P<0.05).No-tably,XBN Ⅱ and metformin treatments significantly improved the cartilage morphology,reduced Mankin and OARSI scores,and reversed the changes in mRNA and protein levels of the aforementioned indexes(P<0.05).CONCLU-SION:Treatment with XBN Ⅱ can alleviate cartilage damage in KOA rats by inhibiting glycolysis,through a mechanism involving activation of the AMPK/PGC1α signaling pathway.

In order to establish a competitive chemiluminescent enzyme-linked immunoassay for rapid and quantitative detection of Senecavirus A antibodies,the polystyrene plate was coated with inactivated Senecavirus A antigen,and the monoclonal antibodies against Senecavirus A VP2 and VP3 proteins labeled by horseradish peroxidase(HRP)were used as the competitive enzymic anti-bodies of the antibodies in the serum samples.The standard curve of the calibrator prepared by di-lution of positive serum was drawn to achieve quantitative detection.The successfully established SVA competitive CLEIA reported the result within 45 minutes.The maximum dilution of 1∶2 048 for calibrator serum was still detectable with no cross-reaction with the standard positive serum of other five kinds of virus antigens such as foot-and-mouth disease.The coefficient of variation within batches was less than 10％,and the coefficient of variation between batches was less than 15％,which showed good repeatability and stability.The positive and negative coincidence rates were 95.30％and 97.57％,respectively,and the total coincidence rate was 96.88％,showing high consistency.The SVA competitive CLEIA assay established in this study can be used for the rapid quantitative detection of Senecavirus A antibodies,filling the gap in the domestic rapid quantitative detection of SVA antibodies.

Objective To investigate the effect of miR-7975 on the malignant phenotype of oral squamous cell carcinoma(OSCC)and its potential mechanisms.Methods This study compared the expression levels of miR-7975 in different oral cell lines by qRT-PCR.miR-7975 mimic and miR-7975 inhibitor were transfected into OSCC cell lines HSC3 and HN4 respectively.Colony formation as-say,CCK8 assay,Transwell assay,and wound healing assay were conducted to evaluate the effects of miR-7975 on the malignant phe-notype of OSCC cells.Western blot was employed to analyze changes in the expression of EMT related proteins and proteins associated with the RAS/ERK signaling pathway.Subcutaneous tumor model of nude mice was used to further validate the tumorigenic effect of miR-7975 in vivo.Results The expression of miR-7975 was downregulated in OSCC cells.Overexpression of miR-7975 reduced the proliferation,migration,and invasion abilities of OSCC cells,whereas downregulation of miR-7975 enhanced these abilities.After miR-7975 overexpression,the expression of the EMT-related protein E-cadherin was upregulated,while N-cadherin,Vimentin,β-catenin,Snail,and Slug were downregulated.Additionally,the expression of proteins related to the RAS/ERK signaling pathway increased.Conversely,the expression of EMT and RAS/ERK signaling pathway-related proteins showed opposite changes when miR-7975 was downregulated.Compared to the control group,the volume and weight of tumors formed in nude mice were significantly smaller after miR-7975 overexpression,while they were significantly larger when miR-7975 expression was reduced.Conclusion miR-7975 exerts its tumor-suppressive effects by inhibiting the proliferation,migration,and invasion of OSCC through the regulation of EMT and the RAS/ERK signaling pathway.

Objective To explore the effect of low-frequency repetitive transcranial magnetic stimulation(rTMS)combined with unilateral upper limb mirror training on contralateral limb strength in patients with hemiplegia after ischemic stroke.Methods A total of 196 patients with hemiplegia after ischemic stroke were selected.All patients were divided into study group and control group via a random number table method,with 98 patients in each group.The control group received mirror training,while the study group received low-frequency rTMS treatment in addition to the control group.The neuroelectrophysiology,neurological function,limb motor function,and clinical efficacy of all patients were observed before and after treatment,and all patients were performed the resting-state functional MRI examination.A generalized estimating equation(GEE)model were used to analyze the improvement of contralateral limb strength.Results After treatment,the seed points in the study group showed a significant enhancement in connectivity with the whole brain function.The overall efficiency of the study group was significantly better than that of the control group.After treatment,the central motor conduction time(CMCT),neuron specific enolase(NSE),cortical latency(CL),and S100β of the two groups of patients were significantly reduced compared with before treatment,while the neurotrophin-3(NT-3),nerve growth factor(NGF),Fugl-Meyer assessment upper extremities(FMA-UE),Wolf motor function test(WMFT),modified Barthel index(MBI),and Berg balance scale(BBS)scores were significantly increased.Moreover,the study group showed a more significant improvement compared to the control group(P＜0.05).The GEE model analysis results showed that the improvement of contralateral limb strength in the study group was significantly better than that in the control group.Conclusion Low-frequency rTMS combined with unilateral upper limb mirror training can improve cortical excitability and upper limb motor function in hemiplegic patients after ischemic stroke,with good therapeutic effects.