Intervertebral disc degeneration （IVDD） is the core cause of chronic low back pain， which severely impairs patients’ quality of life and imposes a heavy social and medical burden. The hypoxia-pyroptosis-inflammation cascade mediated by hypoxia-inducible factor-1α （HIF-1α） is the core pathological mechanism driving the initiation and progression of IVDD. Natural active ingredients derived from traditional Chinese medicine （TCM） have become a research hotspot in the field of IVDD prevention and treatment due to their advantages of multi-target effects， favorable efficacy， and low toxicity. This paper systematically reviews the mechanism of HIF-1α-mediated hypoxia-pyroptosis-inflammation cascade in degenerative nucleus pulposus tissue and the intervention of related active ingredients. It is found that natural active ingredients such as baicalein， curcumin and resveratrol can intervene in the HIF-1α-mediated pathological cascade through four core links to delay IVDD progression： targeting the HIF-1α oxygen sensing pathway to block the initiation of pyroptosis cascade， inhibiting NOD-like receptor protein 3 inflammasome activation to cut off the cascade amplification of inflammatory signals， intervening in the Gasdermin D-mediated pyroptosis execution stage to protect cell membrane integrity， and regulating extracellular matrix metabolism to reconstruct intervertebral disc homeostasis.

ObjectiveTo compare the differences between the ultrafiltration method and the dextran gel filtration method during the purification of Tfn-modified PCL micelles by using purification efficiency and micelle purity as indicators. MethodsCoumarin-6 （C6） was used as a fluorescent probe and was loaded into HOOC-PEG-PCL to form PCL micelles by the film-dispersion method. Tfn was then conjugated to the surface of PCL micelles via an amidation reaction， resulting in two types of micelles： Tfn/PCL_H and Tfn/PCL_L. The pharmaceutical properties of the two types of micelles were characterized. The micelles were then purified through ultrafiltration method and dextran gel method respectively， and the efficiency of the two methods， along with the purity of the final micelles， was compared. The density of Tfn on the surface of PCL micelles was also calculated. ResultsThe hydrated diameter of PCL micelles was approximately 73 nm， and the C6 loading efficiency was around 0.046%. The size increased to 134 nm and 158 nm for Tfn/PCL_L and Tfn/PCL_H， respectively. The micelle population was monodisperse. The purification results showed that， for the ultrafiltration method， after two and one rounds of purification， the Tfn/C6 ratio stabilized at 23.6 and 3.4 for Tfn/PCL_H and Tfn/PCL_L， respectively. For the dextran gel filtration method， the Tfn/C6 ratio reached 23.7 for the Tfn/PCL_H group after two rounds of purification. However， for the Tfn/PCL_L group， the Tfn/C6 ratio increased during four rounds of dextran gel purification， and a significant difference （P = 0.042 4） was observed between the first and last filtrations. The density of Tfn in the final micelles were calculated. For the ultrafiltration method， the Tfn density of Tfn/PCL_H and Tfn/PCL_L were 94.9% and 13.8%， respectively. For the dextran gel filtration method， the density of the two micelles were 95.6% and 14.4%， respectively. For Tfn/PCL_L group， the density results revealing a statistically significant difference （P=0.000 2）. ConclusionThe purification efficiency of the two methods is comparable. However， the purity of the final micelles shows a significant difference， with the dextran gel filtration method resulting in higher purity， particularly for the Tfn/PCL_L micelles.

ObjectiveTo analyze the epidemiological characteristics of a local dengue fever cluster outbreak in Qingpu District of Shanghai in 2024, and to provide a reference for subsequent dengue fever prevention and control. MethodsSeven confirmed local dengue fever cases reported through the National Notifiable Infectious Diseases Surveillance System in Qingpu District of Shanghai in 2024 were selected as the research subjects. Descriptive epidemiological methods were used to conduct investigation and analysis from the aspects of onset, medical treatment and reporting, clinical symptoms, travel and contact history within 15 days before onset, and activity trajectories. ResultsA total of 7 cases were identified in this outbreak. None of the cases had a travel history to dengue-endemic areas within 15 days prior to onset, while all had shared exposure environments and mosquito bite histories, indicating a local clustered transmission pattern. The main clinical manifestations included fever (100.00%) and myalgia (42.86%). All 7 cases were positive for dengue virus serotype 2 (DENV-2) by nucleic acid testing. Genetic sequencing showed that the virus strains belonged to the Cosmopolitan genotype and were most closely related to the epidemic DENV strains circulating in southern China in recent years. ConclusionThis outbreak might be a local secondary infection caused by the short-term stay of dengue fever-infected individuals, and the possible source of importation was dengue fever endemic areas in southern China.

Fang Yizhi broke through the bondage of"Taoism"of Song Confucianism and creatively put his"circle ∴"thought into the study of Gewu-zhizhi which is the core topic of Neo-Confucianism in the Song and Ming Dynasties.Thus,a unique study of"Gewu-zhizhi"is constructed.It has formed a unique academic system which covered knowledge and morality,metaphysics and physics.On this basis,two research fields of"Zhice"and"Tongji"are proposed.There have two inspirations for the inheritance and development of TCM:firstly,facing the strong impact of Western medicine,we should rationally learn from the advantages of Western medicine in the field of"Zhice"and promote the inheritance and reform of contemporary TCM;Secondly,facing the medical crisis of Western medicine,TCM should actively develop its advantages in the field of"Tongji"and contribute to the current transformation of Western medical model.

Objective To compare the impact of different primary tumor sites on the survival of patients with metastatic urothelial carcinoma(mUC)before and after the approval of immune checkpoints inhibitors(ICIs)based on data from Surveillance,Epidemiology,and End Results(SEER).Methods The mUC cases during 2013 and 2017 in the SEER database were enrolled.Cohorts were defined by primary tumor sites(renal pelvis,ureter,bladder)and then stratified by ICIs availability into non-ICIs era(2013)and ICIs era(2017).The survival differences in each cohort between the two eras were compared,and stratified analysis was performed.The 2-year overall survival(OS)was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards analysis.Results A total of 1750 mUC cases were enrolled,with 785 cases in the non-ICIs era and 965 in the ICIs era.No significant differences existed across different anatomical sites in the non-ICIs era,whether in the whole urinary system or inside bladder.The 2-year survival rates were 23.5％for ureteral cancer,18.0％for renal pelvic cancer,and 15.9％for bladder cancer.Significant prognostic disparities emerged among patients based on primary tumor sites in ICIs era(P＜0.05).The 2-year survival rates were 37.7％for ureteral cancer,25.5％for renal pelvic cancer,and 25.7％for bladder cancer.Further analysis revealed that the OS of the lesions originating from the bladder dome was significantly longer than that of the other bladder subgroups(P＜0.05),while the OS of the lesions in bladder bottom was the shortest.The 2-year survival rates were 52.0％for the bladder dome,13.0％for the bladder body,and 10.7％for the bladder bottom.Conclusion Our study indicates that in the non-ICIs era,there was no significant difference in the prognosis among mUC patients with lesions from different primary sites.In the ICIs era,the OS of ureteral cancer was significantly longer than that of bladder cancer and renal pelvis cancer.As for patients with metastatic bladder cancer,those with tumor located at the top of the bladder had a significantly better prognosis than those with tumors at other sites.

Objective To analyze the value of abnormal expression of platelet membrane P-selectin(CD62p)and zonula occluden-1 in predicting the instability of carotid atherosclerotic plaques in elderly patients with cerebral infarction.Methods A total of 203 elderly patients with cerebral in-farction admitted to our department from March 2021 to July 2023 were enrolled,and based on their status of carotid plaques,they were divided into a unstable plaque group(45 cases),a stable plaque group(89 cases),a no-plaque group(69 cases).General information was collected,and the serum levels of CD62p and zonula occluden-1 were measured.The risk factors for carotid athero-sclerotic plaque instability and their predictive value were analyzed.Results Statistical differences were observed in the levels of low-density lipoprotein,homocysteine(Hcy),C-reactive protein,IL-6,fibrinogen,and intercellular adhesion molecule-1(ICAM-1)among the three groups(P＜0.05,P＜0.01),so were in the serum levels of CD62p and zonula occluden-1(P＜0.05).In the un-stable plaque group,the serum levels of CD62p and zonula occluden-1 were positively correlated with the levels of low-density lipoprotein,Hcy,C-reactive protein,IL-6,fibrinogen,and ICAM-1(P＜0.05,P＜0.01).In the stable plaque group,the serum levels of CD62p and zonula occluden-1 were positively correlated with the levels of low-density lipoprotein,Hcy,C-reactive protein,IL-6 and ICAM-1(P＜0.05,P＜0.01).Logistic regress analysis showed that the serum levels of low-density lipoprotein,Hey,C-reactive protein,IL-6,fibrinogen,ICAM-1,CD62p and zonula occlu-den-1 were risk factors for plaque instability(P＜0.01).ROC curve analysis indicated that the AUC value of CD62p and zonula occluden-1 in predicting plaque instability was 0.850 and 0.838,respectively(P＜0.01).Conclusion Abnormal expression of serum CD62p and zonula occluden-1 can effectively predict the instability of carotid atherosclerotic plaques in elderly patients with cer-ebral infarction.

Objective To compare the impact of different primary tumor sites on the survival of patients with metastatic urothelial carcinoma(mUC)before and after the approval of immune checkpoints inhibitors(ICIs)based on data from Surveillance,Epidemiology,and End Results(SEER).Methods The mUC cases during 2013 and 2017 in the SEER database were enrolled.Cohorts were defined by primary tumor sites(renal pelvis,ureter,bladder)and then stratified by ICIs availability into non-ICIs era(2013)and ICIs era(2017).The survival differences in each cohort between the two eras were compared,and stratified analysis was performed.The 2-year overall survival(OS)was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards analysis.Results A total of 1750 mUC cases were enrolled,with 785 cases in the non-ICIs era and 965 in the ICIs era.No significant differences existed across different anatomical sites in the non-ICIs era,whether in the whole urinary system or inside bladder.The 2-year survival rates were 23.5％for ureteral cancer,18.0％for renal pelvic cancer,and 15.9％for bladder cancer.Significant prognostic disparities emerged among patients based on primary tumor sites in ICIs era(P＜0.05).The 2-year survival rates were 37.7％for ureteral cancer,25.5％for renal pelvic cancer,and 25.7％for bladder cancer.Further analysis revealed that the OS of the lesions originating from the bladder dome was significantly longer than that of the other bladder subgroups(P＜0.05),while the OS of the lesions in bladder bottom was the shortest.The 2-year survival rates were 52.0％for the bladder dome,13.0％for the bladder body,and 10.7％for the bladder bottom.Conclusion Our study indicates that in the non-ICIs era,there was no significant difference in the prognosis among mUC patients with lesions from different primary sites.In the ICIs era,the OS of ureteral cancer was significantly longer than that of bladder cancer and renal pelvis cancer.As for patients with metastatic bladder cancer,those with tumor located at the top of the bladder had a significantly better prognosis than those with tumors at other sites.

Objective This study aimed to examine the risk factors and prognostic factors of brucellar spondylitis for early prevention and treatment of the disease,and improving the outcomes of patients.Methods A retrospective case-control study was conducted on the patients with brucellosis who were hospitalized in the Third Hospital of Hebei Medical University from June 2020 to June 2022.Patients were assigned to brucellosis without spondylitis group or brucellar spondylitis group according to the presence of spondylitis.The patients in brucellar spondylitis group were followed for 1 year.Then they were stratified into a subgroup of good or poor prognosis according to clinical outcomes.The dataset for the demographic and clinical variables of patients were analyzed using SPSS 26.0 software.Results A total of 300 patients with brucellosis were enrolled,including 113 cases of brucellosis without spondylitis and 187 cases of brucellar spondylitis.Multivariate analysis showed that age,time from onset to diagnosis,low back pain,and erythrocyte sedimentation rate were independent risk factors for brucellar spondylitis(P＜0.05).Of the 154 cases of brucellar spondylitis with known outcomes,121 cases showed good prognosis and 33 cases had poor prognosis.COX regression analysis showed that the time from onset to diagnosis,diabetes mellitus,paravertebral abscess,and neurological impairment were independent risk factors for poor prognosis in patients with brucellar spondylitis(P＜0.05).Conclusions Old age,prolonged time from onset to diagnosis,low back pain,and increased erythrocyte sedimentation rate are independent risk factors for spondylitis in patients with brucellosis.Prolonged time from onset to diagnosis,diabetes mellitus,paravertebral abscess,and neurological impairment are independent risk factors for poor prognosis of brucellar spondylitis.

Objective To investigate the effects of exosomes derived from hypoxia-treated mesenchymal stem cells on chondrocyte injury.Methods After mesenchymal stem cells were subjected to hypoxic treatment,the secreted exosomes were collected and co-cultured with IL-1β-stimulated chondrocytes.Cell viability was assessed using the CCK-8 assay,while apoptosis was evaluated by flow cytometry and the measurement of Caspase-3 and PARP activities.Intracellular levels of ROS,Fe2+,and MDA were quantified using commercial assay kits.The expression of GPX4,SLC7A11,and ACSL4 was analyzed at both mRNA and protein levels via qRT-PCR and Western blot,respectively.Additionally,the secretion of COL2A1,MMP13,ADAMTS5,TNF-α,IL-6,and PGE2 was determined by ELISA.Results Chondrocyte viability was significantly enhanced following the uptake of exosomes derived from hypoxia-treated mesenchymal stem cells(H-Exo)(P<0.05).IL-1β treatment reduced chondrocyte viability,increased Caspase-3 and PARP activities,and promoted apoptosis(P<0.05);however,H-Exo effectively reversed IL-1 β-induced apoptotic effects.Furthermore,IL-1 β markedly down-regulated the expression of GPX4 and SLC7A11,up-regulated ACSL4 expression,and elevated intracellular levels of ROS,Fe2+,and MDA(P<0.05),indicating the induction of ferroptosis.Both the ferroptosis inhibitor and H-Exo significantly attenuated IL-1β-triggered ferroptosis,and H-Exo counteracted the detrimental effects of IL-1β as well as those induced by a ferroptosis inducer.Additionally,IL-1β suppressed the expression of the chondrogenic marker COL2A1,up-regulated the catabolic enzymes MMP13 and ADAMTS5,and enhanced the secretion of pro-inflammatory cyto-kines TNF-α,IL-6,and PGE2(P<0.05).Notably,H-Exo alleviated IL-1β-mediated inflammation and restored the balance between chondrogenic anabolism and catabolism.Conclusions Exosomes secreted by mesenchymal stem cells under hypoxic conditions can effectively inhibit chondrocyte apoptosis and ferroptosis,thereby alleviating cellular injury.These findings suggest that such exosomes exert a protective effect on chondrocytes and hold prom-ise as a novel therapeutic strategy for cartilage repair.

With population aging worldwide,Alzheimer's disease(AD)has become a serious human health issue.Owing in part to the complexity of the pathogenesis of AD,effective therapeutic options are lacking.Mesenchymal stem cell-derived exosomes(MSC-Exos)have powerful regenerative properties and repair functions,providing a new direction for treatment.They are donor-derived,easily stored,natural carriers,with low immunogenicity and a low risk of tumor formation.They have shown great potential in the treatment of AD and post-treatment rehabilitation.This article introduces the pathological mechanisms of AD and characteristics of MSC-Exos,provides a detailed review of the roles of MSC-Exos in the treatment of AD,including anti-inflammatory effects,immunomodulatory effects,and related signaling pathway modulation,and summarizes recent research progress,with the aim of providing a basis for the development of novel therapeutic approaches to AD.