Objective To investigate the effect of ubiquitin specific peptidase 22 (USP22) on the occurrence and development of esophageal squamous cell carcinoma (ESCC) under hypoxic conditions, and its regulatory relationship with hypoxia-inducible factor-1α (HIF-1α). Methods Western blotting and quantitative polymerase chain reaction were used to detect the differences in USP22 protein and mRNA expression between normal esophageal epithelial cells HEEC and ESCC cell lines KYSE30, KYSE150, EC9706, and TE-1 under normoxic (5% CO2, 20% O2, 75% N2) and hypoxic (5% CO2, 1% O2, 94% N2) conditions. By transfecting USP22 plasmid or siUSP22, ESCC cells were divided into a normoxia control group, a normoxia+USP22 group, a normoxia+siUSP22 group, a hypoxia control group, a hypoxia+USP22 group, and a hypoxia+siUSP22 group. The proliferation and migration abilities of cells in each group were detected. The expression of USP22 and HIF-1α under hypoxic conditions after up-regulating or down-regulating USP22 was detected, and their regulatory relationship was verified. The interaction between USP22 and HIF-1α was verified by co-immunoprecipitation (Co-IP) technique. Results Compared with HEEC cells, the expression of USP22 in ESCC cells was significantly increased (P<0.05). Up-regulation of USP22 expression promoted the proliferation and migration of ESCC cells, while silencing USP22 inhibited the proliferation and migration of ESCC cells (P<0.05). Under hypoxic conditions, the expression of USP22 and HIF-1α increased, and with the up-regulation of USP22 expression, the expression of HIF-1α also significantly increased (P<0.05). Co-IP experiment confirmed the binding between USP22 and HIF-1α. Conclusion Up-regulation of USP22 expression promotes the proliferation and migration of ESCC cells. Hypoxia microenvironment can induce the increase of USP22 expression in ESCC. USP22 may participate in the regulation of the occurrence and development of ESCC by directly binding to HIF-1α.

ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

Objectives: This study aimed to achieve expert consensus on menopause management in the Asia-Pacific region, taking into account patient diversity, the latest evidence, and current treatment options. Methods: A focused literature search was performed to identify clinical practice statements on menopause management. Menopause experts were nominated by members of the Asia-Pacific Menopause Federation (APMF) society. A modified Delphi methodology, involving iterative rounds of anonymous surveys, was employed until consensus was reached for each statement. Consensus was defined as ≥ 70% of experts voting ‘agree’ or ‘strongly agree’ for a given clinical practice statement. Results: A total of 39 participants from 14 different APMF member societies were involved. Eighty-five clinical practice statements reached a consensus. Based on the clinical practice statements, an algorithm was created as a tool to guide clinicians on menopause management. APMF experts agreed that, in addition to vasomotor symptoms, Asian women experiencing somatic or psychological symptoms may also benefit from treatment with menopausal hormone therapy (MHT). MHT should also be considered for the prevention of osteoporosis in asymptomatic peri- and postmenopausal women. Conclusions This APMF consensus statement supersedes the previous one published in 2008. It provides guidance to gynecologists, endocrinologists, family physicians, and other healthcare professionals in delivering optimal care to menopausal women in the ethnically and culturally diverse Asia-Pacific region.

Parkinson's disease(PD)is a neurodegenerative disorder whose core pathological feature is the abnormal accumulation of pathological α-synuclein(α-syn)in the brain,but there are rare clinical therapeutic modalities that target this.As a hot research topic in recent years,meningeal lymphatic vessels(MLVs)play an important role in central nervous system fluid(CNS)drainage,and can promote the exocytosis and clearance of metabolic wastes such as α-syn from the brain.Regulating the morphology and function of MLVs to promote α-syn exocytosis is likely to become an influential direction for future intervention in PD research and provide new approaches for the clinical therapy of PD.In this article,we will overview 3 aspects of the structure and function of MLVs,the role of MLVs in PD,and the strategy of targeting MLVs to treat PD.

Objective To develop a tool for assessing the needs for care services for adults with disabilities in welfare institutions,and formulate criteria for classifying care needs.Methods Based on the theory of the International Classification of Functioning,Disability and Health,the core contents of domestic and international care service assessment standards were analysed,and the first draft of the assess-ment tool was formed integrating with the current practice of welfare institutions.A total of eleven experts in the field of care services validated the first draft,and the assessment tool was revised according to the experts'opin-ions.From May to June,2024,340 adults with disabilities from Second Social Welfare Institute of Shanghai were graded to analyze the reliability and validity of the assessment tool.And then,1 046 subjects from Second Social Welfare Institute of Shanghai were graded using the assessment tool,and the scoring intervals for the five levels of care were determined using cluster analysis.Results The assessment tool included four first-level dimensions,eleven second-level dimensions,39 third-level dimen-sions and 43 indicators.The coefficients of variation of each dimension and indicator were less than 0.25 for ex-pert validation,while the average score of the importance of each indicator was above 4.63,with a full score rate more than 0.86.The overall Cronbach's α coefficient was 0.956,the test-retest reliability was 0.997,and the con-tent validity index of each indicator was 0.83 to 1.00.The exploratory factor analysis extracted four common fac-tors,with a cumulative variance contribution of 86.679%;the loading coefficients of indicators were 0.675 to 0.878,and the correlation coefficients among the dimensions were 0.325 to 0.476.Cluster analysis determined the level of institutional care needs as level 1(severe),level 2(medium-heavy),level 3(medium),level 4(light-moderate),and level 5(light).Conclusion The needs assessment tool for care services for adults with disabilities in welfare institutions developed in this study is good in reliability and validity,and can be used in guiding the care services provided for people with disabilities more efficient and targeted.

Parkinson's disease(PD)is a neurodegenerative disorder whose core pathological feature is the abnormal accumulation of pathological α-synuclein(α-syn)in the brain,but there are rare clinical therapeutic modalities that target this.As a hot research topic in recent years,meningeal lymphatic vessels(MLVs)play an important role in central nervous system fluid(CNS)drainage,and can promote the exocytosis and clearance of metabolic wastes such as α-syn from the brain.Regulating the morphology and function of MLVs to promote α-syn exocytosis is likely to become an influential direction for future intervention in PD research and provide new approaches for the clinical therapy of PD.In this article,we will overview 3 aspects of the structure and function of MLVs,the role of MLVs in PD,and the strategy of targeting MLVs to treat PD.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Objective To investigate the role of Toll-like receptor 4(TLR4)in the regulation of homocys-teine(Hcy)-induced ferroptosis in macrophages.Methods Mouse macrophage cells RAW264.7 were cultured and divided into control group,Hcy intervention group(Hcy group),and Hcy plus ferroptosis inhibitor group(Hcy+Fer-1 group).After transfection with interference fragments,macrophages were treated with Hcy,and then divided into control group,Hcy intervention group(Hcy group),TLR4 interference negative control plus Hcy intervention group(si-NC+Hcy group),and TLR4 interference plus Hcy intervention group(si-TLR4+Hcy group).Macrophages were transfected with overexpression lentivirus and treated with Hcy,then were divided into control group,Hcy intervention group(Hcy group),a TLR4 overexpression negative control plus Hcy intervention group(OE-NC+Hcy group),and a TLR4 overexpression plus Hcy intervention group(OE-TLR4+Hcy group).After 48 hours of intervention,real-time fluorescent quantitative PCR and western blot were used to detect the expression levels of TLR4 in macrophages treated with Hcy;western blot was used to detect the expression levels of ferroptosis-related proteins ACSL4,GPX4,and FTH1 in macrophages,and ferrous ion assay kit to detect the concentration of Fe2+in macrophages;reactive oxygen species(ROS)assay kit and laser confocal microscopy were used to detect the content of intracellular reactive oxygen species.Results Compared with those in the control group,the expression level of the pro-ferroptosis protein ACSL4 was increased in the Hcy group(P<0.05),while the expression levels of anti-ferroptosis proteins GPX4 and FTH1 were decreased(P<0.05);the concentration of Fe2+was increased(P<0.05),and the content of ROS was increased.Meanwhile,the protein and mRNA expres-sion levels of TLR4 were both increased in the Hcy group(P<0.05).After macrophages were transfected with TLR4 interference fragments,compared with those in the si-NC+Hcy group,the expression levels of GPX4 and FTH1 were increased(P<0.05);the expression level of ACSL4 was decreased(P<0.05);the concentration of Fe2+was decreased(P<0.05),and the content of ROS was reduced in the si-TLR4+Hcy group.After macro-phages were transfected with TLR4 overexpression lentivirus,compared with those in the OE-NC+Hcy group,the expression levels of GPX4 and FTH1 were decreased(P<0.05),and the expression level of ACSL4 was increased(P<0.05)in the OE-TLR4+Hcy group.Conclusion Hcy induces the occurrence of ferroptosis in macrophages,and Toll-like receptor 4 has a positive feedback regulatory effect on ferroptosis in macrophages.

Objectives: This study aimed to achieve expert consensus on menopause management in the Asia-Pacific region, taking into account patient diversity, the latest evidence, and current treatment options. Methods: A focused literature search was performed to identify clinical practice statements on menopause management. Menopause experts were nominated by members of the Asia-Pacific Menopause Federation (APMF) society. A modified Delphi methodology, involving iterative rounds of anonymous surveys, was employed until consensus was reached for each statement. Consensus was defined as ≥ 70% of experts voting ‘agree’ or ‘strongly agree’ for a given clinical practice statement. Results: A total of 39 participants from 14 different APMF member societies were involved. Eighty-five clinical practice statements reached a consensus. Based on the clinical practice statements, an algorithm was created as a tool to guide clinicians on menopause management. APMF experts agreed that, in addition to vasomotor symptoms, Asian women experiencing somatic or psychological symptoms may also benefit from treatment with menopausal hormone therapy (MHT). MHT should also be considered for the prevention of osteoporosis in asymptomatic peri- and postmenopausal women. Conclusions This APMF consensus statement supersedes the previous one published in 2008. It provides guidance to gynecologists, endocrinologists, family physicians, and other healthcare professionals in delivering optimal care to menopausal women in the ethnically and culturally diverse Asia-Pacific region.

We propose a strategy to reduce unnecessary prostate biopsies in Chinese patients with total prostate-specific antigen (tPSA) >10 ng ml -1 and Prostate Imaging Reporting and Data System (PI-RADS) scores between 1 and 3. Clinical data derived from 517 patients of The First Affiliated Hospital of USTC (Hefei, China) from January 2020 to December 2023 who met the screening criteria for the study were retrospectively collected. Independent predictors were identified via univariate and multivariate logistic regression analysis. The diagnostic capacity of clinical variables was evaluated using the receiver operating characteristic (ROC) curves and area under the curve (AUC). A prostate biopsy strategy was developed via risk stratification. Of the 517 patients, 17/348 (4.9%) with PI-RADS 1-2 were diagnosed with clinically significant prostate cancer (csPCa), and 27/169 (16.0%) patients with PI-RADS 3 were diagnosed with csPCa. The appropriate prostate-specific antigen density (PSAD) cut-off values were 0.45 ng ml -2 for PI-RADS 1-2 patients and 0.3 ng ml -2 for PI-RADS 3 patients. The appropriate prostate volume (PV) cut-off values were 40 ml for PI-RADS 1-2 patients and 50 ml for PI-RADS 3 patients. The prostate biopsy strategy based on PSAD and PV developed in this study can reduce unnecessary prostate biopsies in patients with tPSA >10 ng ml -1 and PI-RADS 1-3. In the study, 66.5% (344/517) patients did not need to undergo prostate biopsy, at the expense of missing only 1.7% (6/344) patients with csPCa.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged ; Retrospective Studies ; Prostate/diagnostic imaging* ; Unnecessary Procedures/statistics & numerical data* ; Biopsy/statistics & numerical data* ; China ; ROC Curve