ObjectiveTo reveal the active substances and mechanisms of modified Qing'e formula （MQEF） in delaying skin photoaging by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS），network pharmacology， and cell experiments. MethodsUPLC-Q-TOF-MS and a literature review were employed to analyze the transdermally absorbed components in mice after the topical application of MQEF. The potential targets of MQEF in treating skin photoaging were retrieved from databases.The compound-potential target network and protein-protein interaction network were constructed to screen the key components and core targets. A photoaging cell model was established by irradiating HaCaT cells with medium-wave ultraviolet B （UVB）. The safe doses of bakuchiol （BAK） and salvianolic acid B （SAB） for treating HaCaT cells and the effects of BAK and SAB on the viability of cells exposed to UVB irradiation were determined by the cell counting kit-8 （CCK-8） method.The reactive oxygen species （ROS） fluorescent probe was used to measure the ROS production in the cells treated with BAK and SAB.The expression levels of genes related to oxidative stress，inflammation，collagen metabolism，and circadian rhythm clock were measured by Real-time PCR. ResultsA total of 24 transdermally absorbed components of MQEF were identified，which acted on 367 potential targets，and 417 targets related to skin photoaging were screened out，among which 47 common targets were predicted as the targets of MQEF in treating skin photoaging. MQEF exerted the anti-photoaging effect via key components such as BAK and SAB，which acted on core proteins such as serine/threonine kinase 1 （Akt1） and mitogen-activated protein kinase 3 （MAPK3） and intervened in core pathways such as the tumor necrosis factor （TNF） and phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathways.Compared with the model group，the administration of BAK and SAB increased the survival rate of HaCaT cells （P<0.01），down-regulated the mRNA levels of cyclooxygenase-2 （COX-2），interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），matrix metalloproteinase-1 （MMP-1），and matrix metalloproteinase-9 （MMP-9） （P<0.01），and up-regulated the mRNA levels of heme oxygenase-1 （HO-1） and NAD（P）H quinone dehydrogenase 1 （NQO-1） （P<0.05，P<0.01） in photoaged HaCaT cells.In addition，it eliminated excess ROS production induced by UVB and up-regulated the mRNA levels of brain and muscle ARNT-like 1 （BMAL1） and circadian locomotor output cycles kaput （CLOCK） associated with circadian clock （P<0.05，P<0.01）. ConclusionMQEF delays skin photoaging through the coordinated effects of various components，multiple targets，and diverse pathways.The key components BAK and SAB in MQEF exhibit anti-photoaging properties，which involve inhibiting oxidative stress，preventing collagen degradation，mitigating inflammation，and maintaining normal skin circadian rhythms by regulating clock gene expression.

Peripheral artery disease(PAD),commonly encountered in vascular surgery,predominantly affects the lower limbs and presents with ischemic symptoms resulting from atherosclerosis.It carries risks of adverse limb events and cardiovascular events.Antithrombotic therapy remains a cornerstone in the management of PAD.This article reviews the evidence and research progress regarding dual-pathway antithrombotic therapy for PAD.Multiple clinical trials have demonstrated that,compared to single antiplatelet therapy,dual-pathway antithrombotic therapy significantly reduces the risks of major adverse limb events and major adverse cardiovascular events without a significant increase in bleeding risk.For high-risk patients,such as those with advanced age,multivessel disease,comorbid coronary artery disease,or those undergoing endovascular revascularization,the benefits of dual-pathway antithrombotic therapy are particularly pronounced.Current clinical guidelines have incorporated dual-pathway antithrombotic therapy into their recommendations,standardized criteria for identifying the most appropriate patient populations remain lacking.Despite its advantages in reducing adverse events,its long-term safety profile and optimal target populations warrant further investigation.

AIM To prepare the borneol-menthol eutectic mixture-loaded nanoemulsion gel of tetramethylpyrazine.METHODS The equilibrium solubilities of tetramethylpyrazine in different oil phases,emulsifiers and co-emulsifiers were determined,after which compatibility experiment was performed,and pseudo-ternary phase diagram was drawn.With Km value,oil phase proportion and water phase consumption as influencing factors,particle size,PDI and saturated drug loading as evaluation indices,the formulation was optimized by central composite design-response surface method.The drug-loaded nanoemulsion was dispersed into carbomer 940 gel matrix to prepare nanoemulsion gel,then the physicochemical properties,in vitro drug release and transdermal absorption properties were investigated.RESULTS The optimal formulation was determined to be 3.31∶6.16∶1.56∶88.97 for eutectic mixture-EL-40-1,2-propylene glycol-water ratio,the particle size,PDI and saturated drug loading were 37.85 nm,23.04 and 5.82 mg/g,respectively.The obtained white,semi-solid nanoemulsion gel demonstrated the average pH value and viscosity of 6.68±0.07 and(289.69±1.06)mPa·s,respectively,whose in vitro drug release accorded with Higuchi equation,and the accumulative permeability per unit area was(2 048.23±55.6)μg/cm2 within 24 h,which were 3.72 and 1.21 times higher than those of hydrogel and aqueous solution,respectively.CONCLUSION The borneol-menthol eutectic mixture-loaded nanoemulsion gel of tetramethylpyrazine meets preparation requirements,thus can achieve the effective transdermal delivery of raw medicine.

Neurodegenerative diseases are a group of chronic progressive diseases characterized by inflammation,degenera-tion and apoptosis.Chronic neuroinflammation is gradually becoming a potential pathogenic and predisposing factor.As a widely expressed non-histone nucleoprotein,HMGB1 participates in inflammatory process of human body through receptors of advanced glycation end products and Toll-like receptors while maintaining chromosome homeostasis.As a key factor of neuroinflammation,HMGB1 is widely involved in development of neurodegenerative diseases and may become a biomarker and a potential therapeutic target of neurodegenerative diseases.This article reviews the role of HMGB1 in neurodegenerative diseases and tries to provide ground-work for basic research and clinical application for targeting HMGB1 in the treatment of neurodegenerative diseases.

Objective To investigate the effect of long non-coding RNA(lncRNA)potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1(KCNQ1OT1)on oxidative glucose deprivation/reoxygenation(OGD/R)-induced microglia injury through regulating the miR-145-5p/Rho-associated coiled-coil forming protein kinase 1(ROCK1)axis.Methods Microglia N9 were divided into the control group(normal culture),the OGD/R group(OGD/R-induced injury),the sh-NC group(transfected with sh-NC after OGD/R-induced injury),the sh-KCNQ1OT1 group(transfected with sh-KCNQ1OT1 after OGD/R-induced injury),the sh-KCNQ1OT1+inhibitor NC group(co-transfected with sh-KCNQ1OT1 and inhibitor NC after OGD/R-induced injury),and the sh-KCNQ1OT1+miR-145-5p inhibitor group(co-transfected with sh-KCNQ1OT1 and miR-145-5p inhibitor after OGD/R-induced injury).RT-qPCR was applied to detect the expression of lncRNA KCNQ1OT1,miR-145-5p,and ROCK1 mRNA in cells.The expression of ROCK1 protein was detected by Western blot.CCK-8 was applied to detect the cell proliferation.Flow cytometry was applied to detect cell apoptosis.ELISA was applied to detect the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in cells.The action sites of miR-145-5p with lncRNA KCNQ1OT1 and ROCK1 were predicted by bioinformatics website,and their targeting relationships were verified by dual-luciferase reporter assay.Results Compared with the control group,the expression of lncRNA KCNQ1OT1,the expression of ROCK1 mRNA and protein,the apoptosis rate,and the levels of IL-6,TNF-α,and IL-1β in cells were all increased,and the level of miR-145-5p and cell survival rate were all decreased in the OGD/R group(P<0.05).Compared with the OGD/R group and the sh-NC group,the expression of lncRNA KCNQ1OT1,the expression of ROCK1 mRNA and protein,the apoptosis rate,and the levels of IL-6,TNF-α,and IL-1β in cells were all decreased,and the level of miR-145-5p and cell survival rate were all increased in the sh-KCNQ1OT1 group,with significant differences(P<0.05).Compared with the sh-KCNQ1OT1+inhibitor NC group,the expression of ROCK1 mRNA and protein,the apoptosis rate,and the levels of IL-6,TNF-α,and IL-1β in cells were all increased,and the expression of miR-145-5p and cell survival rate were all decreased in the sh-KCNQ1OT1+miR-145-5p inhibitor group,with significant differences(P<0.05).Bioinformatics website showed that miR-145-5p had targeted action sites with lncRNA KCNQ1OT1 and ROCK1,and dual-luciferase reporter assay confirmed that miR-145-5p had targeting relationships with lncRNA KCNQ1OT1 and ROCK1(P<0.05).Conclusion Silencing lncRNA KCNQ1OT1 can alleviate OGD/R-induced microglia injury via upregulating the expression of miR-145-5p and targeting the down-regulation of ROCK1 expression.

BACKGROUND:Remyelination in the central nervous system is a basic repair process triggered by demyelinating events,mainly through the proliferation,migration,and differentiation of oligodendrocyte precursor cells into oligodendrocytes.The process of remyelination is affected by many factors such as astrocytes,myelin debris,microglia,macrophages,endothelial cells,pericytes,T cells,and age.OBJECTIVE:Astrocytes play an important role in regulating synaptic activity,nutritional support,and tissue repair in the central nervous system.This review aims to provide potential therapeutic targets for demyelinating diseases of central nervous system by reviewing the role of astrocytes in remyelination.METHODS:A search was conducted on relevant literature collected from CNKI,PubMed,and Web of Science from 2014 tO 2024.The search terms were"astrocytes,oligodendrocyte precursor cells,remyelination"in both Chinese and English.Finally,66 articles were included after screening and summarized.RESULTS AND CONCLUSION:(1)The treatment of demyelinating diseases,such as multiple sclerosis,is limited to disease-modifying therapies,and there is no available method to overcome the failure of remyelination.Therefore,it is necessary to explore targets related to remyelination to promote myelin repair.(2)Remyelination is a process in which oligodendrocyte precursor cells proliferate,migrate,differentiate,and mature into oligodendrocytes,and the latter produce myelin to wrap axons to form myelin sheath.(3)Astrocytes regulate remyelination by phagocytosis of myelin debris,participating in inflammatory response,transforming into oligodendrocyte lineage cells,providing energy supply for oligodendrocyte lineage cells,releasing neurotrophic factors,and secreting extracellular matrix components.(4)The drugs screened in this paper use astrocytes and their derived factors as intervention targets to regulate the remyelination.Some drugs have satisfactory effects,but their effectiveness and safety still need more basic research and clinical trials to verify.(5)The mechanism of action of astrocytes in remyelination has not been fully elucidated,and the related molecular targets and signaling pathways can be further studied.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Organ transplantation is an effective treatment for end-stage organ failure, but postoperative infections and rejection reactions are key factors affecting the survival of the patients. Recently, the incidence of human parvovirus B19 (B19V) infection following transplantation has increased. B19V is a non-enveloped virus that primarily infects the upper respiratory tract and exhibits significant tropism for erythroid progenitor cells in the bone marrow, leading to the lysis of erythrocytes and hematological abnormalities. After B19V viremia, it may further infect other cells, triggering inflammatory responses and tissue damage. B19V infection may lead to chronic anemia in organ transplant patients, thereby affecting the success of the transplant and the survival of the patients. Therefore, it is essential to diagnose and monitor B19V infection post-transplantation. Due to the immunosuppressive therapy following transplantation, traditional serological detection methods, such as IgM and IgG antibody tests, are often unreliable. In contrast, molecular biological detection, especially real-time fluorescent quantitative PCR technology, provides more accurate results. However, the diversity of B19V genotypes may lead to the missed detection of some genotypes. Thus, it is necessary to use different detection techniques to improve the diagnostic accuracy of B19 virus infections. Additionally, there is a need to explore more precise diagnostic methods to enhance the early identification and management of B19V infection, further improving the survival and life quality of the patients.

Objective:To study the relationship between the levels of multiple elements in urine and the risk of arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region (Inner Mongolia).Methods:From April 2023 to January 2024, a case-control study method was used to select 128 individuals with a residence time of ≥10 years in drinking water arsenic exposed areas in Inner Mongolia as study subjects. Eighty-one individuals diagnosed with arsenic poisoning were selected as the case group, and 47 healthy individuals were selected as the control group for urine sample collection and questionnaire survey. Inductively coupled plasma mass spectrometry was employed to determine the levels of 10 elements (chromium, manganese, cobalt, nickel, copper, zinc, arsenic, molybdenum, cadmium and lead) in urine. The levels of each element in urine were divided into four groups ( Q1, Q2, Q3, and Q4 groups) based on quartiles. The associations between the levels of various elements in urine and the risk of arsenic poisoning were studied using binary logistic regression model and restricted cubic spline (RCS). Results:The age of the control group and the case group [ M ( Q1, Q3)] were 61 (53, 69) and 61 (56, 67) years old, respectively. There were 19 and 43 males, and 28 and 38 females, respectively. There was no statistically significant differences in age and and gender composition between the two groups ( Z = - 0.39, P = 0.700; χ 2 = 1.91, P = 0.167). The levels of urinary copper and cadmium of the case group were higher than those of the control group, and the differences were statistically significant ( Z = - 2.66, - 2.16, P < 0.05). The results of univariate logistic regression analysis showed that urinary copper was an influencing factor for arsenic poisoning ( P = 0.017). The results of multivariate logistic regression analysis revealed that after adjusting for covariates, urinary copper and arsenic were independent influencing factors of arsenic poisoning ( P < 0.05). Taking Q1 group as a reference, urinary copper in Q3 group [ OR (95% CI) = 8.23 (1.81, 37.39), P = 0.006] increased the risk of arsenic poisoning, while urinary arsenic in Q2, Q3, and Q4 groups [ OR (95% CI) = 0.24 (0.06, 0.92), 0.12 (0.03, 0.53), 0.15 (0.04, 0.63), P < 0.05] decreased the risk of arsenic poisoning. After adjusting for covariates, RCS did not show a dose-response relationship between urinary copper, urinary arsenic, and arsenic poisoning ( P > 0.05). Conclusion:Urinary arsenic and copper are associated with the risk of arsenic poisoning in the drinking water arsenic exposed areas of Inner Mongolia, copper exposure may contribute significantly to arsenic poisoning.

Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.