BACKGROUND:Pyroptosis participate in the degradation of the extracellular matrix of chondrocytes,synovial inflammation and pain,and plays an important role in the prevention and treatment of osteoarthritis.In addition,exercise can inhibit the occurrence of pyroptosis to regulate the progression of osteoarthritis,which has become a research hot spot in the prevention and treatment of osteoarthritis. OBJECTIVE:To summarize the regulatory role of pyroptosis in osteoarthritis and the mechanism of exercise-mediated pyroptosis in osteoarthritis. METHODS:PubMed and CNKI databases were searched during 1992 to 2024 with the keywords"pyroptosis,osteoarthritis,chondrocyte pyroptosis,synovial cell pyroptosis,exercise"in English and Chinese,respectively.Finally,71 relevant articles were selected according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Osteoarthritis is a chronic degenerative joint disease characterized by the breakdown of cartilage extracellular matrix,synovial inflammation,and subchondral bone remodeling.This condition often leads to organic lesions,bone pain,and functional impairment.(2)Pyroptosis,a distinct programmed cell death mechanism,involves cell lysis and the release of inflammatory cytokines,triggering a robust inflammatory response,and is closely related to the development of osteoarthritis.Pyroptosis can result in the release of numerous inflammatory factors,thereby activate the nuclear factor kappa-B transcription and increase pyroptosis protein production,and in turn exacerbate the occurrence and development of osteoarthritis.Therefore,pyroptosis can be a new direction for the prevention and treatment of osteoarthritis.(3)Exercise has been shown to down-regulate the pyroptosis protein signaling pathway and inhibit the expression of related inflammatory factors,thereby playing a pivotal role in osteoarthritis prevention and treatment.Aerobic and anaerobic exercises can delay the pathological process of osteoarthritis by inhibiting the occurrence of pyroptosis.Moderate-intensity aerobic exercise is most effective in improving osteoarthritis by inhibiting pyroptosis signaling pathways,while anaerobic exercise can have beneficial effects on osteoarthritis by improving muscle mass.

Aim To explore the protective effect of PPARδ agonist GW501516 on neuro-vascular unit(NVU)injury induced by high glucose in vitro and its mechanism.Methods SD rat hippocampal neurons(Neu),astrocytes(Ast)and brain microvascular en-dothelial cells(BMEC)were isolated,purified and cultured in vitro,and NVU co-culture system was estab-lished.NVU co-culture system cells were divided into the control group,high glucose group(HG group),HG+GW501516 low,medium and high concentration groups(25,50 and 100 nmol·L-1)and HG+GW501516(100 nmol·L-1)+ANA12(TrkB inhibi-tor,5 μmol·L-1)group.NUV barrier function was e-valuated by transendothelial resistance(TEER)test and leakage test;the proliferative activity of Neu cells in co-culture system was detected by CCK-8 assay;the levels of inflammatory cytokines TNF-α,IL-6 and IL-1β in cell supernatant were detected by ELISA;the levels of SOD,MDA and NO in Neu cells were detected by chemical method;the apoptosis level was detected by flow cytometry;the protein expression levels of PPARδ,Bax,Bcl-2,cleaved caspase-3,and BDNF/TrkB pathway-related proteins BDNF,p-TrkB,and TrkB in Neu cells were detected by Western blot.Re-sults Compared with the control group,the TEER val-ue decreased and leakage value increased in HG group;the proliferation activity of Neu cells decreased,the levels of TNF-α,IL-6,IL-1β in supernatant and MDA and NO in Neu cells increased,and the SOD lev-el decreased;Neu cell apoptosis rate and expression levels of Bax and Cleaved caspase-3 increased,while the expression levels of PPARδ,Bcl-2,BDNF and p-TRKB/TrkB decreased(P＜0.05).Compared with the HG group,after treatment with different concentra-tions of GW501516,TEER value increased,leakage value decreased,proliferation activity of Neu cells in-creased,levels of TNF-α,IL-6,IL-1β in supernatant and MDA and NO in Neu cells decreased,and SOD level increased,and apoptosis rate of Neu cells and ex-pression levels of Bax and cleaved caspase-3 were de-creased,and expression levels of PPARδ,Bcl-2,BDNF and p-TRKB/TrkB increased(P＜0.05)in a dose-dependent manner.However,ANA12 intervention re-versed the effect of GW501516 on NVU damage under high glucose conditions.Conclusion PPARδ agonist GW501516 improves in vitro NVU injury induced by high glucose by activating BDNF/TrkB signaling path-way.

Objective:To systematically evaluate the care experience of family caregivers for amyotrophic lateral sclerosis (ALS) patients, providing guidance for home care of ALS patients.Methods:Qualitative studies on the care experience of family caregivers for ALS patients were retrieved from PubMed, American Psychological Association Psychnet, CINAHL, Web of Science, Medline, Cochrane Library, Embase, China Biology Medicine disc, WanFang Data, VIP, and China National Knowledge Infrastructure. The search period was from database establishment to October 30, 2022. The quality of literature was evaluated using the quality evaluation criteria for qualitative research of the Australia Joanna Briggs Institute Evidence-Based Health Care Center (2016 edition). The aggregative integration method was used to integrate the results using NVivo 11 software.Results:A total of 11 studies were included. A total of 22 complete and clear results were extracted and combined to form eight new categories, which were integrated into three results, namely, family caregivers facing personal development limitations and various family difficulties, experiencing complex and chaotic emotional experiences, and craving for diversified care support.Conclusions:Nursing staff should pay attention to the impact of ALS on their patient's family caregivers, provide caregiver knowledge and skill guidance, promote positive emotional experiences, and offer diversified care support to improve the quality of life of patients and family caregivers.

In order to mine candidate vaccine antigens against ticks and to control ticks safely and effectively,the aim of this study was to immunize rabbits with purified aquaporins(AQPs)rD-mAQP1,rDmAQP2 and rDmAQP3 of Dermacentor marginatus.Blood collections for Western blot and ELISA tests were performed.The anti-tick challenge was conducted.The optimal expression conditions of rDmAQP1,rDmAQP2 and rDmAQP3 were screened by SDS-PAGE gel electrophore-sis.The three recombinant proteins were purified by HisSepNi-NTA6FF purification column.Rab-bits were divided into four groups of three rabbits each,including a control group and three immu-nized groups.The three purified recombinant proteins were separately immunized to three groups of rabbits,and the rabbits were immunized once on the 0th,14th and 21st day.Blood samples were collected every 7 days to prepare polyclonal antibodies.The reactivity was detected by Western blot and the antibody titer was detected by ELISA.Tick challenge test was carried out after the anti-body titer increased.The results showed that the optimal expression conditions for rDmAQP1 were induced for 8 h at IPTG concentration of 1.0 mmol/L and 37 ℃;the optimal expression conditions for rDmAQP2 were induced for 7 h at IPTG concentration of 1.0 mmol/L and 37 ℃;and the opti-mal expression conditions for rDmAQP3 were induced for 5 h at IPTG concentration of 1.0 mmol/L and 37 ℃.Western blot results showed that rDmAQP1,rDmAQP2 and rDmAQP3 all had certain reactivity.The ELISA results showed that the antibody titers of rabbits immunized with rD-mAQP1,rDmAQP2 and rDmAQP3 were as follows:the total anti-tick effect of rDmAQP1 protein was 79.74％,and the inhibition rates on average full-blooded tick weight,average egg weight and average egg hatching rate were 9.43％,25.17％and 63.81％,respectively.The total anti-tick effect of rDmAQP2 protein was 78.78％,and the inhibition rates of average full-blooded tick weight,av-erage egg weight and average egg hatching rate of Dermacentor marginatus were 8.30％,20.14％and 68.26％,respectively.The total anti-tick effect of rDmAQP3 protein was 87.91％,and the inhi-bition rates of average full-blooded tick weight,average egg weight and average egg hatching rate were 3.23％,22.47％and 80.5％,respectively.Through serological test and anti-tick test,it has been found that rDmAQP1,rDmAQP2 and rDmAQP3 all have the potential of candidate antigens against ticks,among which rDmAQP3 has the best immune effect,which lays a foundation for the study of the function of rDmAQP1,rDmAQP2 and rDmAQP3.

Objective: To assess the role of dynamic contrast-enhanced (DCE)-MRI of the extraocular muscles (EOMs) for determining the activity of thyroid-associated ophthalmopathy (TAO) and treatment response to glucocorticoids (GCs). Materials and Methods: We prospectively enrolled 65 patients with TAO (41 active, 82 eyes; 24 inactive, 48 eyes). Twenty-two active patients completed the GC treatment and follow-up assessment, including 15 patients (30 eyes) and 7 patients (14 eyes), defined as responsive and unresponsive, respectively. Model-free (time to peak [TTP], area under the curve [AUC], and Slope max) and model-based (Ktrans , Kep, and Ve) parameters of EOMs in embedded simplified histogram analyses were calculated and compared between groups. Multivariable logistic regression analysis was used to identify the independent predictors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. Results: Active patients exhibited significantly higher TTP at the 10th percentile (-10th), TTP-mean, and TTP at the 90th percentile (-90th); AUC-10th, AUC-mean, AUC-90th, and AUC-max; Ktrans -10th and Ktrans -mean; and Ve-10th, Ve-mean, Ve-90th, and Ve-max than inactive patients (P < 0.05). Responsive patients exhibited significantly lower TTP-min; higher Ktrans -mean and Ktrans -max; and higher Kep-10th, Kep-mean, and Kep-max than unresponsive patients (P < 0.05). TTP-mean and Ve-mean were independent variables for determining disease activity (P = 0.017 and 0.022, respectively). A combination of the two parameters could determine active TAO with moderate performance (AUROC = 0.687). TTP-min and Ktrans -mean were independent predictors of the response to GCs (P = 0.023 and 0.004, respectively), uniting which could determine the response to GCs with decent performance (AUROC = 0.821). Conclusion DCE-MRI-derived model-free and model-based parameters of EOMs can assist in the evaluation of TAO. In particular, TTP-mean and Ve-mean could be useful for determining the activity of TAO, whereas TTP-min and K trans -mean could be promising biomarkers for determining the response to GCs.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Objective:To evaluate the risk factors for the complexity and surgical prognosis in patients with proliferative diabetic retinopathy (PDR).Methods:A historical cohort study of the CONCEPT trial, including 97 patients (97 eyes) who were diagnosed with PDR and requiring three-channel 23-gauge transconjunctival pars plana vitrectomy (PPV) from June 2017 to January 2018 at the First Affiliated Hospital of Nanjing Medical University.All patients received preoperative intravitreal injection of 0.5 mg conbercpet.Based on the PDR complexity score, patients were divided into >3 group or ≤3 group, and the systematic risk factors were compared between the two groups.The influence of sex, age, hypertension, renal insufficiency, duration of diabetes mellitus, and hemoglobin A1c level on the PDR complexity score was evaluated by multivariate logistic regression analysis.Based on age, patients were divided into <45 years group, 45-<60 years group, and ≥60 years group, and the differences in mean operative time, incidence of intraoperative hemorrhage, surgically induced lacrimation and silicone oil filling, and incidence of hemorrhage on color fundus photos and macular edema by optical coherence tomography at postoperative months 1 and 6 were analyzed among different age groups.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (No.2017-SR-283).Written informed consent was obtained from each subject.Results:The age of patients with PDR complexity score >3 was 46.5(36.0, 51.8) years, which was less than 54.0(45.5, 61.5) years for PDR complexity score ≤3, and the difference was statistically significant ( Z=1.835, P=0.002).Among the factors predicting PDR complexity score >3, logistic regression analysis indicated that only age was statistically significant ( P=0.005).For each 1-year increase in age, the risk of PDR complexity score >3 would increase by 7.4%( OR: 0.929, 95% CI: 0.883-0.977).Among the systemic factors, there were significant differences in age, history of diabetes, proportion of patients with hypertension and renal insufficiency among the three age groups (all at P<0.05).Among the ocular factors, there were significant differences in the proportion of patients with history of retinal laser treatment, fibrovascular membrane and complexity score >3 among the three groups (all at P<0.05).The proportion of patients with fibrovascular membrane and complexity score >3 in the <45 years group was significantly higher than that in the 45-<60 and ≥60 years groups (all at P<0.05).There were significant differences in the proportion of patients with intraoperative bleeding and silicone oil filling in the three age groups (all at P<0.017).The proportion of intraoperative bleeding and silicone oil filling in <45 years group was significantly higher than that in 45-<60 and ≥60 years groups (all at P<0.05).The macular edema on postoperative month 1 in the <45 years old group was significantly higher than that in the 45-<60 and ≥60 years groups (both at P<0.05). Conclusions:Among systemic factors, age has a significant impact on the increased PDR complexity and contributes to the poor prognosis of patients.There is a higher percentage of intraoperative complications and early postoperative macular edema in patients in the younger age group compared to the older age group.

Objective: To assess the role of dynamic contrast-enhanced (DCE)-MRI of the extraocular muscles (EOMs) for determining the activity of thyroid-associated ophthalmopathy (TAO) and treatment response to glucocorticoids (GCs). Materials and Methods: We prospectively enrolled 65 patients with TAO (41 active, 82 eyes; 24 inactive, 48 eyes). Twenty-two active patients completed the GC treatment and follow-up assessment, including 15 patients (30 eyes) and 7 patients (14 eyes), defined as responsive and unresponsive, respectively. Model-free (time to peak [TTP], area under the curve [AUC], and Slope max) and model-based (Ktrans , Kep, and Ve) parameters of EOMs in embedded simplified histogram analyses were calculated and compared between groups. Multivariable logistic regression analysis was used to identify the independent predictors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. Results: Active patients exhibited significantly higher TTP at the 10th percentile (-10th), TTP-mean, and TTP at the 90th percentile (-90th); AUC-10th, AUC-mean, AUC-90th, and AUC-max; Ktrans -10th and Ktrans -mean; and Ve-10th, Ve-mean, Ve-90th, and Ve-max than inactive patients (P < 0.05). Responsive patients exhibited significantly lower TTP-min; higher Ktrans -mean and Ktrans -max; and higher Kep-10th, Kep-mean, and Kep-max than unresponsive patients (P < 0.05). TTP-mean and Ve-mean were independent variables for determining disease activity (P = 0.017 and 0.022, respectively). A combination of the two parameters could determine active TAO with moderate performance (AUROC = 0.687). TTP-min and Ktrans -mean were independent predictors of the response to GCs (P = 0.023 and 0.004, respectively), uniting which could determine the response to GCs with decent performance (AUROC = 0.821). Conclusion DCE-MRI-derived model-free and model-based parameters of EOMs can assist in the evaluation of TAO. In particular, TTP-mean and Ve-mean could be useful for determining the activity of TAO, whereas TTP-min and K trans -mean could be promising biomarkers for determining the response to GCs.

Objective: To assess the role of dynamic contrast-enhanced (DCE)-MRI of the extraocular muscles (EOMs) for determining the activity of thyroid-associated ophthalmopathy (TAO) and treatment response to glucocorticoids (GCs). Materials and Methods: We prospectively enrolled 65 patients with TAO (41 active, 82 eyes; 24 inactive, 48 eyes). Twenty-two active patients completed the GC treatment and follow-up assessment, including 15 patients (30 eyes) and 7 patients (14 eyes), defined as responsive and unresponsive, respectively. Model-free (time to peak [TTP], area under the curve [AUC], and Slope max) and model-based (Ktrans , Kep, and Ve) parameters of EOMs in embedded simplified histogram analyses were calculated and compared between groups. Multivariable logistic regression analysis was used to identify the independent predictors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. Results: Active patients exhibited significantly higher TTP at the 10th percentile (-10th), TTP-mean, and TTP at the 90th percentile (-90th); AUC-10th, AUC-mean, AUC-90th, and AUC-max; Ktrans -10th and Ktrans -mean; and Ve-10th, Ve-mean, Ve-90th, and Ve-max than inactive patients (P < 0.05). Responsive patients exhibited significantly lower TTP-min; higher Ktrans -mean and Ktrans -max; and higher Kep-10th, Kep-mean, and Kep-max than unresponsive patients (P < 0.05). TTP-mean and Ve-mean were independent variables for determining disease activity (P = 0.017 and 0.022, respectively). A combination of the two parameters could determine active TAO with moderate performance (AUROC = 0.687). TTP-min and Ktrans -mean were independent predictors of the response to GCs (P = 0.023 and 0.004, respectively), uniting which could determine the response to GCs with decent performance (AUROC = 0.821). Conclusion DCE-MRI-derived model-free and model-based parameters of EOMs can assist in the evaluation of TAO. In particular, TTP-mean and Ve-mean could be useful for determining the activity of TAO, whereas TTP-min and K trans -mean could be promising biomarkers for determining the response to GCs.

Deficient mismatch repair(dMMR)is currently recognized as a biomarker for predicting the efficacy of immune checkpoint inhib-itors(ICIs),and domestic and foreign guidelines recommend first-line immunotherapy for patients with solid dMMR tumors.For rectal can-cer,only 5%of patients are classified as dMMR/microsatellite instability-high(MSI-H),and most have"immune desert type"or mismatch re-pair proficient(pMMR)/microsatellite stabilization(MSS)diseases,which respond poorly to ICIs.Therefore,recently,the synergistic effect of immune drugs and neoadjuvant chemoradiotherapy has been the focus of basic and clinical research.An increasing number of clinical trials of phase Ⅱ/Ⅲ immuno-total neoadjuvant therapy(iTNT)have emerged,and the management of locally advanced rectal cancer(LARC)has begun to enter the non-operative treatment era.Furthermore,an increasing number of studies support the efficacy of neoadjuvant immun-otherapy in patients with dMMR/MSI-H LARC,which exempts such patients from surgery and chemoradiotherapy as follow-up treatment and results in a pivot in the treatment paradigm of a watch-and-wait strategy.Regarding the LARC with pMMR/MSS,the preliminary iTNT findings support ICIs as a shift from an initial posterior-line palliative scheme to a first-line selection strategy and the continuation of large-scale clinical trials.However,no definitive conclusion has been reached regarding the best iTNT application for LARC.Recent studies have shown that short-course radiotherapy and sequential neoadjuvant chemotherapy,combined with immunotherapy,can achieve good short-term outcomes.Finally,identifying other new biomarkers may facilitate the identification of patients with pMMR/MSS who are sensitive to immune drugs(especially for low rectal cancer).In the future,the treatment strategy of LARC should be combined with the stratification of clinical recurrence risk and patient willingness for organ retention to achieve stratified and accurate treatment.This article will review the re-lated research background,basic and clinical research progress and existing problems of iTNT in LARC.