Parkinson's disease(PD)is one of the most common neurodegenerative disorders.Recent evidence implicates pyroptosis as one of the pathogenic mechanisms in central nervous system disorders,although its specific mechanisms remain unclear.In this study,SH-SY5Y cells were transfected with py-roptosis-related proteins GSDME full-length(GSDME-F)or GSDME-N terminal(GSDME-N)plasmids revealed that GSDME-N significantly reduced mitochondrial membrane potential(P＜0.0001).To inves-tigate the mechanism by which GSDME mediates mitochondrial dysfunction,Western blotting analysis demonstrated that transfection with GSDME-N plasmids significantly increased BAX expression and en-hanced its translocation to mitochondria in both HEK 293T and SH-SY5Y cells(P＜0.05).SH-SY5Y cells treated with varying concentrations of rotenone(ROT)exhibited GSDME cleavage,elevated BAX expression(P＜0.05),increased mitochondrial BAX aggregation(P＜0.05),and reduced mitochondrial membrane potential(P＜0.01),as confirmed by Western blotting and JC-1 staining.Concurrently,MTT assays assessing cell viability and lactate dehydrogenase(LDH)release assays indicated that ROT in-duced these processes prior to pyroptosis.Furthermore,in a ROT-induced mouse PD model,ROT trig-gered GSDME cleavage,enhanced BAX expression,caused dopaminergic neuronal damage,and induced motor deficits.In summary,this study demonstrates that GSDME-N exacerbates mitochondrial damage and increases cytotoxicity by upregulating BAX expression and facilitating its mitochondrial translocation.This study provides novel insights into the role of GSDME in PD pathogenesis and suggests potential avenues for therapeutic intervention.

Aim To investigate the anti-Zika virus(ZIKV)mechanism of diterpenoid compound 9 from Euphorbia helioscopia in vitro.Methods The cytotox-icity of compound 9 was evaluated using the CCK-8 as-say.A ZIKV-infected Vero cell model was established,and the antiviral activity was assessed through RT-qPCR,plaque assay,Western blot,and immunofluores-cence.Furthermore,the mechanism of action was elu-cidated using multi-cell line validation,nanoparticle tracking analysis,cellular thermal shift assay,and mo-lecular docking.Results In Vero cells,compound 9 exhibited an EC50 of(3.95±0.15)μmol·L-1 and a CC50 of(272.12±8.56)μmol·L-1,demonstrating significantly higher antiviral efficacy than the positive control drug ribavirin(RBV).Its virus inactivation effect was time-dependent and could significantly re-duce viral load and plaque formation.Studies revealed that compound 9 altered the physicochemical properties of ZIKV particles,including reducing surface charge and increasing particle size distribution.Additionally,it significantly enhanced the thermal stability of the prM protein.Molecular docking analysis indicated that compound 9 formed a high-affinity interaction with the prM protein(binding energy:-38.52 kJ·mol-1)and stabilized its structure through hydrophobic interac-tions.Conclusion Compound 9 exerts in vitro anti-ZIKV activity by directly inactivating the virus,disrup-ting viral particle integrity,and targeting the prM pro-tein.

Parkinson's disease(PD)is one of the most common neurodegenerative disorders.Recent evidence implicates pyroptosis as one of the pathogenic mechanisms in central nervous system disorders,although its specific mechanisms remain unclear.In this study,SH-SY5Y cells were transfected with py-roptosis-related proteins GSDME full-length(GSDME-F)or GSDME-N terminal(GSDME-N)plasmids revealed that GSDME-N significantly reduced mitochondrial membrane potential(P＜0.0001).To inves-tigate the mechanism by which GSDME mediates mitochondrial dysfunction,Western blotting analysis demonstrated that transfection with GSDME-N plasmids significantly increased BAX expression and en-hanced its translocation to mitochondria in both HEK 293T and SH-SY5Y cells(P＜0.05).SH-SY5Y cells treated with varying concentrations of rotenone(ROT)exhibited GSDME cleavage,elevated BAX expression(P＜0.05),increased mitochondrial BAX aggregation(P＜0.05),and reduced mitochondrial membrane potential(P＜0.01),as confirmed by Western blotting and JC-1 staining.Concurrently,MTT assays assessing cell viability and lactate dehydrogenase(LDH)release assays indicated that ROT in-duced these processes prior to pyroptosis.Furthermore,in a ROT-induced mouse PD model,ROT trig-gered GSDME cleavage,enhanced BAX expression,caused dopaminergic neuronal damage,and induced motor deficits.In summary,this study demonstrates that GSDME-N exacerbates mitochondrial damage and increases cytotoxicity by upregulating BAX expression and facilitating its mitochondrial translocation.This study provides novel insights into the role of GSDME in PD pathogenesis and suggests potential avenues for therapeutic intervention.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Aim To investigate the anti-Zika virus(ZIKV)mechanism of diterpenoid compound 9 from Euphorbia helioscopia in vitro.Methods The cytotox-icity of compound 9 was evaluated using the CCK-8 as-say.A ZIKV-infected Vero cell model was established,and the antiviral activity was assessed through RT-qPCR,plaque assay,Western blot,and immunofluores-cence.Furthermore,the mechanism of action was elu-cidated using multi-cell line validation,nanoparticle tracking analysis,cellular thermal shift assay,and mo-lecular docking.Results In Vero cells,compound 9 exhibited an EC50 of(3.95±0.15)μmol·L-1 and a CC50 of(272.12±8.56)μmol·L-1,demonstrating significantly higher antiviral efficacy than the positive control drug ribavirin(RBV).Its virus inactivation effect was time-dependent and could significantly re-duce viral load and plaque formation.Studies revealed that compound 9 altered the physicochemical properties of ZIKV particles,including reducing surface charge and increasing particle size distribution.Additionally,it significantly enhanced the thermal stability of the prM protein.Molecular docking analysis indicated that compound 9 formed a high-affinity interaction with the prM protein(binding energy:-38.52 kJ·mol-1)and stabilized its structure through hydrophobic interac-tions.Conclusion Compound 9 exerts in vitro anti-ZIKV activity by directly inactivating the virus,disrup-ting viral particle integrity,and targeting the prM pro-tein.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Objective:To analyze the prognostic value of del(1p32)in patients with newly diagnosed multiple myeloma(MM).Methods:The clinical data of 341 newly diagnosed MM attended in Jiangsu Province Hospital were retrospective analyzed.Clinical characteristic combined with genetic features,especially del(1p32),were analyzed for survival and prognostic of patients.Results:Among the 341 patients with newly diagnosed MM,24(7.0％)patients were del(1p32)positive.The progression-free survival(PFS)and overall survival(OS)were significantly shorter in MM patients with del(1p3 2)than those without de1(1p32)(PFS:P＜0.001;OS:P＜0.001).The COX proportional-hazards model showed that del(1 p32)was an independent risk factor for PFS and OS of patients with MM.The patients with both 1q21 gain/amplification and del(1p32),as"double-hit chromosome 1",have worse prognosis than those with only 1q21 gain/amplification or only del(1 p32)(PFS:P＜0.001;OS:P＜0.001).Conclusion:Del(1p32)is an independent risk factor for PFS and OS of patients with MM.Del(1p32)detection should be widely used in the prognostic analysis for newly diagnosed MM patients.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.