BACKGROUND Effective health management for high-risk stroke populations is essential.The hospital-community-home(HCH)collaborative health management(CHM)model leverages resources from hospitals,communities,and familie...BACKGROUND Effective health management for high-risk stroke populations is essential.The hospital-community-home(HCH)collaborative health management(CHM)model leverages resources from hospitals,communities,and families.By integrating patient information across these three domains,it facilitates the delivery of tailored guidance,health risk assessments,and three-in-one health education.AIM To explore the effects of the HCH-CHM model on stroke risk reduction in highrisk populations.METHODS In total,110 high-risk stroke patients screened in the community from January 2019 to January 2023 were enrolled,with 52 patients in the control group receiving routine health education and 58 in the observation group receiving HCH-CHM model interventions based on routine health education.Stroke awareness scores,health behavior levels,medication adherence,blood pressure,serum biochemical markers(systolic/diastolic blood pressure,total cholesterol,and triglyceride),and psychological measures(self-rating anxiety/depression scale)were evaluated and compared between groups.RESULTS The observation group showed statistically significant improvements in stroke awareness scores and health behavior levels compared to the control group(P<0.05),with notable enhancements in lifestyle and dietary habits(P<0.05)and reductions in postintervention systolic blood pressure,diastolic blood pressure,total cholesterol,triglyceride,self-rating anxiety scale,and self-rating depression scale scores(P<0.05).CONCLUSION The HCH-CHM model had a significant positive effect on high-risk stroke populations,effectively increasing disease awareness,improving health behavior and medication adherence,and appropriately ameliorating blood pressure,serum biochemical marker levels,and negative psychological symptoms.展开更多
Objective:To explore the rehabilitation effect of pulmonary rehabilitation training in elderly patients with chronic obstructive pulmonary disease(COPD).Methods:Elderly COPD patients hospitalized from June 2024 to Dec...Objective:To explore the rehabilitation effect of pulmonary rehabilitation training in elderly patients with chronic obstructive pulmonary disease(COPD).Methods:Elderly COPD patients hospitalized from June 2024 to December 2024 were selected as subjects for a quasi-experimental study.The study randomly assigned patients into two equal groups of 50 each.One group served as the control and received standard treatment and nursing care,while the other group,the intervention group,was given additional pulmonary rehabilitation exercises alongside the conventional care.The lung function indexes[forced expiratory volume in the first second(FEV1),forced vital capacity(FVC),FEV1/FVC],6-minute walk distance(6MWD),Borg’s Category Scale for perceived exertion(BCSS),COPD Assessment Test(CAT),Barthel Index for activities of daily living,blood oxygen saturation,and Modified Medical Research Council(MMRC)dyspnea scale were compared between the two groups before and after intervention.Results:Following the intervention,the intervention group demonstrated improved lung function compared to the control group(P<0.05).However,no significant difference was observed in the 6-minute walk distance(6MWD)(P>0.05).The intervention group had lower Bronchitis Severity Scale(BCSS)scores(P<0.05)and better quality of life scores(P<0.05)than the control group.No notable differences were found in activities of daily living scores or blood oxygen saturation(P>0.05).Additionally,the intervention group exhibited a lower proportion of residual severe dyspnea(P<0.05).Conclusion:Pulmonary rehabilitation can enhance respiratory function in individuals with COPD,leading to beneficial therapeutic outcomes and ultimately improving their overall quality of life.展开更多
BACKGROUND Microsatellite stable(MSS)metastatic colorectal cancer(mCRC)is characterized by an immunosuppressive tumor microenvironment,leading to limited efficacy of immunotherapy in these patients.Clinical trial data...BACKGROUND Microsatellite stable(MSS)metastatic colorectal cancer(mCRC)is characterized by an immunosuppressive tumor microenvironment,leading to limited efficacy of immunotherapy in these patients.Clinical trial data suggest that chemotherapy and anti-angiogenic therapy may have the potential to enhance the response to immunotherapy in these patients.However,whether these research findings can be“replicated”in clinical practice still requires further validation through real-world studies.This study aims to evaluate the effectiveness and safety of chemo-therapy combined with bevacizumab with or without anti-programmed death 1(PD-1)immunotherapy as the first-line regimen for MSS mCRC in the real world.AIM To evaluate the effectiveness and safety of chemotherapy combined with beva-cizumab with or without anti-PD-1 immunotherapy as the first-line regimen for MSS mCRC in the real world.METHODS We conducted a retrospective analysis of patients with MSS mCRC diagnosed at Peking University First Hospital and Jilin Cancer Hospital between January 2020 and December 2024.Patients were stratified into two treatment groups:(1)An experimental group receiving first-line chemotherapy combined with bevaci-zumab and anti-PD-1 immunotherapy;and(2)A control group receiving chemo-therapy plus bevacizumab alone.Propensity score matching was employed to balance baseline characteristics,including age,gender,Eastern Cooperative Onco-logy Group performance status,number of metastatic sites,and primary tumor location.The primary endpoints were progression-free survival and overall survival,while secondary endpoints included disease control rate,objective response rate,and treatment-related adverse events.Survival outcomes were assessed using Kaplan-Meier analysis with log-rank testing.Additionally,inverse probability of treatment weighting was applied for sensitivity analysis to validate the robustness of our findings.RESULTS The propensity score matching analysis identified 103 well-balanced patient pairs with a median follow-up of 25.5 months.The experimental group demonstrated numerically higher objective response(36.00%vs 23.08%,P=0.309)and disease control rates(96.00%vs 91.03%,P=0.6759)compared to the control group,though these differences were not statistically significant.Similarly,no significant survival benefit was observed for either progression-free survival[hazard ratio(HR)=0.7076,95%confidence interval(CI):0.4069-1.23,P=0.22]or overall survival(HR=1.154,95%CI:0.4712-2.827,P=0.75).Multivariate analysis identified liver metastases as an independent poor prognostic factor(HR=3.36,95%CI:1.71-6.60,P<0.001),while subgroup analyses revealed potential benefits of the experimental regimen in male patients(HR=0.33,95%CI:0.14-0.81,P=0.025)and those with right-sided primary tumors(HR=0.40,95%CI:0.17-0.95,P=0.022).Safety profiles were comparable between groups,though elevated lactate dehydrogenase emerged as an independent risk factor for poorer outcomes in the experimental group(HR=4.11,95%CI:1.02-16.55,P=0.046).CONCLUSION Chemotherapy combined with bevacizumab and anti-PD-1 immunotherapy could not demonstrate promising efficacy in treating MSS mCRC compared to the standard first-line chemotherapy regimen with bevacizumab.Male patients or those with right-sided mCRC may derive benefits from immune-based combination therapy.Further research is needed to investigate specific clinical characteristics or biomarkers to identify patients who may derive benefit from combined immunotherapy approaches.展开更多
Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter rel...Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter release,and signal transmission,and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases.The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention,but their specific mechanisms remain to be fully understood.This review aims to explore how lipids regulate synaptic activity in the central nervous system,focusing on their roles in synapse formation,neurotransmitter release,and signal transmission.Additionally,it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation.This review shows that within the central nervous system,lipids are essential components of the cell membrane bilayer,playing critical roles in synaptic structure and function.They regulate presynaptic vesicular trafficking,postsynaptic signaling pathways,and glial-neuronal interactions.Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts.Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles.Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis.Fatty acids are vital for energy metabolism and the synthesis of signaling molecules.Abnormalities in lipid metabolism may lead to impairments in synaptic function,affecting information transmission between neurons and the overall health of the nervous system.Therapeutic strategies targeting lipid metabolism,particularly through cholesterol modulation,show promise for treating these conditions.In neurodegenerative diseases such as Alzheimer’s disease,Parkinson disease,and amyotrophic lateral sclerosis,dysregulation of lipid metabolism is closely linked to synaptic dysfunction.Therefore,lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs.Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.展开更多
Effective treatment methods for stroke,a common cerebrovascular disease with a high mortality rate,are still being sought.Exosome therapy,a form of acellular therapy,has demonstrated promising efficacy in various dise...Effective treatment methods for stroke,a common cerebrovascular disease with a high mortality rate,are still being sought.Exosome therapy,a form of acellular therapy,has demonstrated promising efficacy in various diseases in animal models;however,there is currently insufficient evidence to guide the clinical application of exosome in patients with stroke.This article reviews the progress of exosome applications in stroke treatment.It aims to elucidate the significant potential value of exosomes in stroke therapy and provide a reference for their clinical translation.At present,many studies on exosome-based therapies for stroke are actively underway.Regarding preclinical research,exosomes,as bioactive substances with diverse sources,currently favor stem cells as their origin.Due to their high plasticity,exosomes can be effectively modified through various physical,chemical,and genetic engineering methods to enhance their efficacy.In animal models of stroke,exosome therapy can reduce neuroinflammatory responses,alleviate oxidative stress damage,and inhibit programmed cell death.Additionally,exosomes can promote angiogenesis,repair and regenerate damaged white matter fiber bundles,and facilitate the migration and differentiation of neural stem cells,aiding the repair process.We also summarize new directions for the application of exosomes,specifically the exosome intervention through the ventricular-meningeal lymphatic system.The review findings suggest that the treatment paradigm for stroke is poised for transformation.展开更多
Dear Editor,Linear and whorled nevoid hypermelanosis(LWNH)is a rare,sporadic pigmentary disorder characterized by hyperpigmented macules arranged in linear streaks and whorls along Blaschko's lines,typically appea...Dear Editor,Linear and whorled nevoid hypermelanosis(LWNH)is a rare,sporadic pigmentary disorder characterized by hyperpigmented macules arranged in linear streaks and whorls along Blaschko's lines,typically appearing within the first few weeks of life[1],and remains a challenge to treat.Here,we report a case of LWNH and review the relevant literature to help clinicians better understand this disease.展开更多
Some patients with systemic lupus erythematosus experience neuropsychiatric symptoms.Although magnetic resonance imaging can detect abnormal signals in the white matter of the brain,conventional methods often struggle...Some patients with systemic lupus erythematosus experience neuropsychiatric symptoms.Although magnetic resonance imaging can detect abnormal signals in the white matter of the brain,conventional methods often struggle to accurately capture microstructural changes.Various diffusion models have been used to study white matter in systemic lupus erythematosus;however,comparative analyses of their sensitivity and specificity for detecting microstructural changes remain insufficient.To address this,our team designed a diagnostic trial that used multimodal diffusion imaging techniques to observe white matter microstructural changes in patients with systemic lupus erythematosus who had neuropsychiatric symptoms,with an aim to identify key diagnostic biomarkers for these patients.Patients with active lupus who received treatment at the Department of Rheumatology and Immunology,The First Affiliated Hospital of China Medical University,from September 2023 to March 2024 were recruited.According to the standards of the American College of Rheumatology,patients with systemic lupus erythematosus who had neuropsychiatric symptoms were assigned to the systemic lupus erythematosus group,whereas those without neuropsychiatric symptoms were assigned to the non-systemic lupus erythematosus group.Additionally,healthy volunteers matched by region,sex,and age were recruited as controls.All three groups underwent the same diffusion magnetic resonance imaging examination protocol to compare differences in diffusion parameters.Advanced diffusion imaging models were able to sensitively detect microstructural changes in the white matter fibers of patients with systemic lupus erythematosus who had neuropsychiatric symptoms,with specific diffusion parameters showing significant abnormalities in key brain regions.In the left superior longitudinal fasciculus subregion and the right thalamic radiations of patients with systemic lupus erythematosus who had neuropsychiatric symptoms,we also identified abnormal diffusion characteristics that were clearly correlated with disease activity,suggesting that microstructural changes in these areas may reflect the dynamic process of neuroinflammatory damage.The present study addresses critical challenges in the diagnosis of systemic lupus erythematosus by identifying specific white matter imaging biomarkers and elucidating the association between microstructural damage and clinical manifestations.The main contributions of our study include:1)establishing axial regression probability parameters from mean apparent propagator magnetic resonance imaging as sensitive biomarkers for systemic lupus erythematosus,particularly in the third subregion of the left superior longitudinal fasciculus;2)demonstrating that multimodal diffusion imaging may be superior to conventional diffusion tensor imaging for detecting white matter microstructural abnormalities in patients with systemic lupus erythematosus;and 3)integrating tract-based spatial statistics with clinically relevant analyses to link imaging findings to pathological mechanisms.展开更多
Radiofrequency ablation(RFA),particularly endoscopic ultrasound-guided RFA(EUS-RFA),has emerged as a promising minimally invasive approach for the treatment of pancreatic cancer,especially in patients with locally adv...Radiofrequency ablation(RFA),particularly endoscopic ultrasound-guided RFA(EUS-RFA),has emerged as a promising minimally invasive approach for the treatment of pancreatic cancer,especially in patients with locally advanced or unresectable disease.This review outlines recent technological developments in EUS-RFA,including innovations in energy delivery systems,probe design,and real-time thermal monitoring,which have improved the precision and safety of the procedure.Clinical studies combining EUS-RFA with chemotherapy have demonstrated encouraging outcomes,with improvements in overall survival,progression-free survival,tumor necrosis,and symptom control compared to chemotherapy alone.Additionally,RFA-induced tumor antigen release and modulation of the tumor microenvironment suggest a potential synergistic role with immunotherapy.Despite its promise,the widespread adoption of EUS-RFA is limited by a lack of large-scale randomized controlled trials and standardized treatment protocols.展开更多
Objectives:Gastric cancer(GC)is among the most prevalent malignancies worldwide,ranking as the fifth most common cancer and the fifth leading cause of cancer-related mortality.This study intends to investigate how Inh...Objectives:Gastric cancer(GC)is among the most prevalent malignancies worldwide,ranking as the fifth most common cancer and the fifth leading cause of cancer-related mortality.This study intends to investigate how Inhibin subunit beta A(INHBA)promotes the progression of GC by activating the mitogen-activated protein kinase(MAPK)signaling pathway via targeting Integrin alpha-6(ITGA6).Methods:Quantitative reverse transcription-Polymerase Chain Reaction(qRT-PCR)and Immunohistochemistry(IHC)were utilised to validate the expression levels of INHBA in GC,which were subsequently correlated with the clinicopathological factors and outcomes.Cellular and animal studies were conducted to ascertain the role of INHBA in GC.RNA-sequencing(RNA-seq)and bioinformatics analysis were used to screen for the downstream target and pathway of INHBA,with Co-immunoprecipitation(Co-IP),Co-Immunofluorescent(Co-IF),Western blot(WB)and Rescue experiments validating their mechanisms of action in GC.Results:IHC and qRT-PCR analysis confirmed that GC tissues exhibited higher INHBA expression than adjacent noncancerous tissues.This elevated INHBA expression was found to be significantly associated with the incidence of tumor lesions,lymph node metastasis,and progression to higher TNM stages.Functional experiments showed that INHBA promoted GC cell proliferation and enhanced their migration and invasion in vitro while inhibiting apoptosis.Animal studies results indicated that INHBA overexpression promoted tumor growth and increased tumor weight and volume.Through a series of experiments,including RNA-seq,Co-IP,Co-IF,WB,and rescue assays,this study demonstrated that INHBA promotes GC progression by targeting ITGA6 to regulate the MAPK signaling pathway.Conclusions:INHBA/ITGA6/MAPK axis can provide new insights into GC therapy.Targeted INHBA inhibition holds promise as a therapeutic approach for GC treatment.展开更多
This study examined a case of ventilator-associated pneumonia caused by Ralstonia mannitolilytica in a neonatal department in order to determine the source of infection and mode of transmission.Symptoms of infection b...This study examined a case of ventilator-associated pneumonia caused by Ralstonia mannitolilytica in a neonatal department in order to determine the source of infection and mode of transmission.Symptoms of infection began to appear on day 16 of admission,and both sputum and catheter tip cultures revealed R.mannitolilytica.The infection control department of the hospital later sampled and identified R.mannitolilytica in the ventilator tube that was used by the patient with the exact gene sequence as the infecting strain.These findings indicate that ventilator tubing is a significant contamination source of this pathogen,and hospitals need to enhance their disinfection methods of ventilator-related devices.展开更多
Objectives:Although standardized residency trainees are at high risk for depression,anxiety,and suicidal ideation,the psychological pathways connecting depression and anxiety to suicidal ideation,especially the modera...Objectives:Although standardized residency trainees are at high risk for depression,anxiety,and suicidal ideation,the psychological pathways connecting depression and anxiety to suicidal ideation,especially the moderating role of resilience,remain elusive.This study aimed to examine the associations between depression,anxiety,and suicidal ideation among physicians undergoing standardized residency training,and to investigate the moderating roles of different dimensions of individual resilience,namely tenacity,strength,and optimism.Methods:A convenience sampling method was adopted to recruit 133 resident physicians.Validated instruments assessing individual resilience,depressive symptoms,anxiety levels,and suicidal ideation were administered.Spearman correlation analysis was used to evaluate the relationships among the variables.Hierarchical regression analysis was conducted to assess the moderating roles of tenacity,strength,and optimism in the associations between depression,anxiety,and suicidal ideation.Results:Depressive symptoms and anxiety levels were both positively associated with suicidal ideation(p<0.001).All three resilience dimensions were negatively correlated with suicidal ideation(tenacity:r=−0.504,strength:r=−0.477,optimism:r=−0.440,all p<0.001).Tenacity,strength,and optimism significantly moderated the associations between depression and suicidal ideation(all p<0.05).When resilience levels in these dimensions were high,the associations between depression and suicidal ideation were weaker.Strength and optimism also moderated the associations between anxiety and suicidal ideation(strength:p=0.028,optimism:p=0.028).When the resiliences(strength and optimism)were high,the associations between anxiety and suicidal ideation were weaker.Conclusion:Individual resilience,particularly in the dimensions of tenacity,strength,and optimism,may serve as protective correlates for physicians in training,being associated with weaker relationships between depression,anxiety,and suicidal ideation.These findings highlight the potential value of resilience-enhancing strategies in clinical training settings,although causal inferences cannot be drawn due to the cross-sectional design.展开更多
Objectives This study aimed to compare the effectiveness of the semi-virtual simulation and traditional simulation teaching models based on the Standards of Best Practice(SOBP)according to the International Nursing As...Objectives This study aimed to compare the effectiveness of the semi-virtual simulation and traditional simulation teaching models based on the Standards of Best Practice(SOBP)according to the International Nursing Association for Clinical Simulation and Learning(INACSL)in the Adult Nursing course.Methods This study used a quasi-experimental design.A total of 94 third-year nursing students from a university in Beijing between November and December 2022 were recruited as participants.An innovative semi-virtual simulation teaching model was designed based on the SOBP established by the INACSL.In the Adult Nursing course,both the semi-virtual and traditional simulation teaching models were implemented.At the end of the simulation sessions,participants completed the Chinese version of the Simulation Effectiveness Tool-Modified(SET-M)to assess the effectiveness of the two teaching models.Results All nursing students completed the simulation sessions.There was no difference(t=−0.93,P=0.353)in the total scores between the semi-virtual simulation teaching model(50.87±5.30)and the traditional simulation teaching model(50.37±5.16).However,there was a statistically significant difference(t=−2.65,P=0.010)in the prebriefing section(semi-virtual simulation:5.60±0.71;traditional simulation:5.33±0.78).In contrast,no statistically significant differences were found for the scenario and debriefing sections(P>0.05).At the individual item level,statistical differences(P<0.05)between the two models were identified for items 1 and 9,but not for the remaining items(P>0.05).By analyzing the open-ended question,it was found that both simulation models were effective,and students’comments were similar.Conclusions The study demonstrated equivalent effectiveness between the semi-virtual and traditional simulation teaching models.Semi-virtual simulation teaching model could offer a more flexible and feasible approach to simulation teaching.展开更多
Silicosis is one of the most serious and prevalent occupational diseases globally,characterized by typical silicotic nodules and fibrosis.Recent studies suggest that the perinodular zone of the lung shares certain cha...Silicosis is one of the most serious and prevalent occupational diseases globally,characterized by typical silicotic nodules and fibrosis.Recent studies suggest that the perinodular zone of the lung shares certain characteristics with the nodules themselves.In this study,a silicotic rat model was established via a single intratracheal in-stillation of a 50 mg/mL silica suspension.Pulmonary anatomical and pathological examinations revealed that silica deposition induced severe alterations in both the nodular and perinodular tissues.Subsequently,pseudo-targeted metabolomics analysis revealed that abnormally elevated ornithine levels were closely associated with the progression of silicosis,from normal to perinodular and finally to nodular tissues.Immunofluorescent stain-ing demonstrated that,in addition to M2 macrophages,silica exposure increased the protein levels of ARG1 in epithelial cells,a finding further confirmed by in vitro experiments using A549 and BEAS-2B cells.Moreover,accumulated ornithine induced epithelial-mesenchymal transition in vitro,increased extracellular matrix expres-sion in NIH 3T3 fibroblasts,and enhanced TGF-β1 levels in RAW264.7 cells.Co-exposure to ornithine and silica significantly induced the aberrant expression of fibrosis-associated proteins compared to silica exposure alone,characterized by increased levels of FN and𝛼-SMA,as well as decreased E-cad expression.These findings sug-gest that silica exposure up-regulates ARG1 in various cells,leading to ornithine accumulation,which in turn accelerates the progression of fibrosis.展开更多
The development of substitutable meniscus implants that can effectively protect articular cartilage remains a great challenge.Herein,a polyurethane with chemical crosslinking and sulfobetaine extenders containing hydr...The development of substitutable meniscus implants that can effectively protect articular cartilage remains a great challenge.Herein,a polyurethane with chemical crosslinking and sulfobetaine extenders containing hydrophobic chains(PU-CL-hSB)is developed,which could improve comprehensive properties and long-term stability simultaneously.By regulating the mole ratio of functional groups,PU-CL-hSB with appropriate mechanical properties,excellent tribological properties,and good fatigue resistance is used to prepare substitutable meniscus implant by hot-pressing.Due to the synergistic effect of functional groups,PU-CL-hSB meniscus implant presents comparable or even superior properties to native meniscus.It withstands a maximum force of 26.08 N versus 25.14 N for native meniscus,an energy dissipation from 45.93 to 39.17 N mm compared to 28.83 to 19.11 N mm for native meniscus over 300 cycles,and a friction coefficient from 0.08 to 0.19 compared to 0.11 to 0.26 for native meniscus.This PU-CL-hSB meniscus implant is further implanted into live rabbit knee joints for 8 and 25 weeks by a new approach,and in vivo data indicate that PU-CL-hSB meniscus implant not only protects articular cartilage from severe damage without eliciting inflammatory responses,but also can maintain normal physiological activities in the native state.Our findings present a substitutable meniscus implant that could be applied in vivo and propose evaluation methodologies for meniscus implants.展开更多
Over the past few decades,the Sonic Hedgehog protein has become a pivotal player in many biological processes,including tumourigenesis,embryonic development,and protective mechanisms after cerebral damage.The Sonic He...Over the past few decades,the Sonic Hedgehog protein has become a pivotal player in many biological processes,including tumourigenesis,embryonic development,and protective mechanisms after cerebral damage.The Sonic Hedgehog signaling pathway is crucial in the central nervous system,with implications in a diverse range of diseases,including Parkinson's disease,Alzheimer's disease,spinal cord injury,traumatic brain injury,depression,Sonic Hedgehog medulloblastoma,and stroke.In this comprehensive review,we examined Sonic Hedgehog from the perspective of canonical and non-canonical pathways,elucidating their complex connections to the central nervous system.Subsequently,we summarize the latest advancements in drug therapies that offer novel strategies for treating neurological diseases by modulating the Sonic Hedgehog protein.Finally,we summarize and extend the technologies and tools for studying the Sonic Hedgehog signaling field,with the aim of providing new research ideas and methods.展开更多
Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis....Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis.Herein,the targeted theranostic platform of cysteine-modified gold nanodots-sulfhydrated luteinizing hormone releasing hormone(CGN-SLR)nanosystem was designed for target recognition and precise dual-mode imaging-guided photothermal therapy(PTT)against TNBC.On the one hand,the CGN-SLR nanosystem can serve as an ideal targeting fluorescent probe and computed tomography(CT)enhancer to facilitate the accurate diagnosis and surgical guidance of TNBC.On the other hand,the CGN-SLR nanosystem with great targeting and PTT ability can significantly inhibit the growth of TNBC,without causing harm to normal tissues and healthy organs.It provides an effective strategy for the diagnosis and treatment of TNBC through the rational design of multifunctional nanoplatform with target recognition,multiple imaging guidance/monitoring,and high-efficiency PTT.展开更多
The meniscus plays an important role in the biomechanical function of the knee joint,but knee osteoarthritis(OA)deteriorates the mechanical properties of the meniscus.Thus understanding the mechanical behaviour of the...The meniscus plays an important role in the biomechanical function of the knee joint,but knee osteoarthritis(OA)deteriorates the mechanical properties of the meniscus.Thus understanding the mechanical behaviour of the OA meniscus is very important.This study aimed to assess the quasi-static nonlinear mechanical behaviours of the three zones of the OA meniscus by a proposed meso-indentation method,and further to investigate its nonlinear mechanical responses under the stance.Four pairs of menisci were harvested from OA patients during total knee arthroplasty.One pair of the menisci was first used for the histological analysis.Binocular fringe projection technology was then employed to reconstruct the morphology of the other three pairs of the menisci.Subsequently,a meso-indentation method was proposed to characterize the nonlinear behaviors of the meniscus zones,moreover,the hyperelastic model(HEM)together with the Hertz’s elastic model(EM)was used to fit the indentation force-depth curves of the meniscus zones.Furthermore,the fitted HEM and EM materials parameters were used to simulate the mechanical response of the meniscus in the stance by two simplified meniscus models.The results showed that the type III collagen widely existed in the OA menisci,and the red-white zone exhibited the best mechanical performance,and the 3-term Mooney-Rivlin model was the best descriptor for the nonlinear mechanical characterization of the three zones.Moreover,the stress or strain distributions of the simplified meniscus models differed significantly between the HEM and EM under the stance,and the EM underestimated the mechanical behaviours of the meniscus.The current work generally provides a novel testing method to study the nonlinear mechanical behaviour of soft biological materials,and is specifically helpful to understand the nonlinear mechanical behaviour of the OA meniscus for which the HEM should be used in the meniscus-related biomechanical studies.展开更多
BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically...BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically experience a poor prognosis,highlighting an urgent need to explore novel treatment approaches.This study evaluated the overall efficacy and safety of CMT vs CMT combined with immune checkpoint inhibitors(ICIs)in the treatment of EC patients with liver metastases.Furthermore,prognostic factors influencing outcomes in this patient population were identified.AIM To evaluate the efficacy and safety of first-line chemoimmunotherapy for EC patients with liver metastases and to analyze prognostic factors.METHODS This retrospective study included 126 EC patients with liver metastases at Zhejiang Cancer Hospital between 2014 and 2024.Patients receiving CMT were compared with those receiving CMT+ICI.Analyzed variables included clinicopathological features,treatment history,characteristics of metastasis,systemic and local treatments,overall survival(OS),and treatment-related adverse events(TRAEs).Prognostic factors were evaluated using univariate and multivariate Cox proportional-hazards regression models.Finally,efficacy outcomes and TRAE profiles were compared between the two groups.RESULTS A significant difference in median OS was identified between the two groups(10.8 months in the CMT group vs 20.8 months in the CMT+ICI group,P=0.004).The CMT+ICI group also demonstrated a significantly longer median progression-free survival of 11.7 months(P<0.001).Patients receiving combination therapy exhibited significantly improved systemic objective response rate and disease control rate.Multivariate analysis identified key factors significantly influencing OS in EC patients with liver metastases:Karnofsky Performance Status score≥70,receipt of local therapy for liver metastases,and the number of cycles of CMT and immunotherapy received.Furthermore,the incidence of TRAEs did not significantly differ between the CMT+ICI and CMT groups.CONCLUSION For EC patients with liver metastases,the combination of CMT and ICIs demonstrates significantly superior efficacy compared with CMT alone,while maintaining manageable TRAEs.展开更多
Acute myocardial infarction （AMI） has a high mortality rate and poor prognosis for patients. The primary causes of death are arrhythmia and heart failure. For patients admitted because of myocardial infarction, vari...Acute myocardial infarction （AMI） has a high mortality rate and poor prognosis for patients. The primary causes of death are arrhythmia and heart failure. For patients admitted because of myocardial infarction, various risk evaluations are initiated to foresee possible complications. The thrombolysis in myocardial infarction （TIMI） risk score, which can be used to predict the prognosis and the need for revas-cularisation, is the most convenient and commonly used system, but is inadequate for AMI patients on admittance. Fragmented QRS （fQRS） has been shown to be a valuable electrocardiographic （ECG） index for predicting the prognosis of patients with coronary heart disease （Das et al., 2006, 2007）.展开更多
基金Supported by Guiding Project of Hebei Provincial Health Commission,No.20201190 and 20180220.
文摘BACKGROUND Effective health management for high-risk stroke populations is essential.The hospital-community-home(HCH)collaborative health management(CHM)model leverages resources from hospitals,communities,and families.By integrating patient information across these three domains,it facilitates the delivery of tailored guidance,health risk assessments,and three-in-one health education.AIM To explore the effects of the HCH-CHM model on stroke risk reduction in highrisk populations.METHODS In total,110 high-risk stroke patients screened in the community from January 2019 to January 2023 were enrolled,with 52 patients in the control group receiving routine health education and 58 in the observation group receiving HCH-CHM model interventions based on routine health education.Stroke awareness scores,health behavior levels,medication adherence,blood pressure,serum biochemical markers(systolic/diastolic blood pressure,total cholesterol,and triglyceride),and psychological measures(self-rating anxiety/depression scale)were evaluated and compared between groups.RESULTS The observation group showed statistically significant improvements in stroke awareness scores and health behavior levels compared to the control group(P<0.05),with notable enhancements in lifestyle and dietary habits(P<0.05)and reductions in postintervention systolic blood pressure,diastolic blood pressure,total cholesterol,triglyceride,self-rating anxiety scale,and self-rating depression scale scores(P<0.05).CONCLUSION The HCH-CHM model had a significant positive effect on high-risk stroke populations,effectively increasing disease awareness,improving health behavior and medication adherence,and appropriately ameliorating blood pressure,serum biochemical marker levels,and negative psychological symptoms.
基金Hohhot Health Science and Technology Program Project(Project No.:2024-HHWK-041)。
文摘Objective:To explore the rehabilitation effect of pulmonary rehabilitation training in elderly patients with chronic obstructive pulmonary disease(COPD).Methods:Elderly COPD patients hospitalized from June 2024 to December 2024 were selected as subjects for a quasi-experimental study.The study randomly assigned patients into two equal groups of 50 each.One group served as the control and received standard treatment and nursing care,while the other group,the intervention group,was given additional pulmonary rehabilitation exercises alongside the conventional care.The lung function indexes[forced expiratory volume in the first second(FEV1),forced vital capacity(FVC),FEV1/FVC],6-minute walk distance(6MWD),Borg’s Category Scale for perceived exertion(BCSS),COPD Assessment Test(CAT),Barthel Index for activities of daily living,blood oxygen saturation,and Modified Medical Research Council(MMRC)dyspnea scale were compared between the two groups before and after intervention.Results:Following the intervention,the intervention group demonstrated improved lung function compared to the control group(P<0.05).However,no significant difference was observed in the 6-minute walk distance(6MWD)(P>0.05).The intervention group had lower Bronchitis Severity Scale(BCSS)scores(P<0.05)and better quality of life scores(P<0.05)than the control group.No notable differences were found in activities of daily living scores or blood oxygen saturation(P>0.05).Additionally,the intervention group exhibited a lower proportion of residual severe dyspnea(P<0.05).Conclusion:Pulmonary rehabilitation can enhance respiratory function in individuals with COPD,leading to beneficial therapeutic outcomes and ultimately improving their overall quality of life.
基金Supported by the National High Level Hospital Clinical Research Funding(Multi-Center Clinical Research Project of Peking University First Hospital),No.2022CR65.
文摘BACKGROUND Microsatellite stable(MSS)metastatic colorectal cancer(mCRC)is characterized by an immunosuppressive tumor microenvironment,leading to limited efficacy of immunotherapy in these patients.Clinical trial data suggest that chemotherapy and anti-angiogenic therapy may have the potential to enhance the response to immunotherapy in these patients.However,whether these research findings can be“replicated”in clinical practice still requires further validation through real-world studies.This study aims to evaluate the effectiveness and safety of chemo-therapy combined with bevacizumab with or without anti-programmed death 1(PD-1)immunotherapy as the first-line regimen for MSS mCRC in the real world.AIM To evaluate the effectiveness and safety of chemotherapy combined with beva-cizumab with or without anti-PD-1 immunotherapy as the first-line regimen for MSS mCRC in the real world.METHODS We conducted a retrospective analysis of patients with MSS mCRC diagnosed at Peking University First Hospital and Jilin Cancer Hospital between January 2020 and December 2024.Patients were stratified into two treatment groups:(1)An experimental group receiving first-line chemotherapy combined with bevaci-zumab and anti-PD-1 immunotherapy;and(2)A control group receiving chemo-therapy plus bevacizumab alone.Propensity score matching was employed to balance baseline characteristics,including age,gender,Eastern Cooperative Onco-logy Group performance status,number of metastatic sites,and primary tumor location.The primary endpoints were progression-free survival and overall survival,while secondary endpoints included disease control rate,objective response rate,and treatment-related adverse events.Survival outcomes were assessed using Kaplan-Meier analysis with log-rank testing.Additionally,inverse probability of treatment weighting was applied for sensitivity analysis to validate the robustness of our findings.RESULTS The propensity score matching analysis identified 103 well-balanced patient pairs with a median follow-up of 25.5 months.The experimental group demonstrated numerically higher objective response(36.00%vs 23.08%,P=0.309)and disease control rates(96.00%vs 91.03%,P=0.6759)compared to the control group,though these differences were not statistically significant.Similarly,no significant survival benefit was observed for either progression-free survival[hazard ratio(HR)=0.7076,95%confidence interval(CI):0.4069-1.23,P=0.22]or overall survival(HR=1.154,95%CI:0.4712-2.827,P=0.75).Multivariate analysis identified liver metastases as an independent poor prognostic factor(HR=3.36,95%CI:1.71-6.60,P<0.001),while subgroup analyses revealed potential benefits of the experimental regimen in male patients(HR=0.33,95%CI:0.14-0.81,P=0.025)and those with right-sided primary tumors(HR=0.40,95%CI:0.17-0.95,P=0.022).Safety profiles were comparable between groups,though elevated lactate dehydrogenase emerged as an independent risk factor for poorer outcomes in the experimental group(HR=4.11,95%CI:1.02-16.55,P=0.046).CONCLUSION Chemotherapy combined with bevacizumab and anti-PD-1 immunotherapy could not demonstrate promising efficacy in treating MSS mCRC compared to the standard first-line chemotherapy regimen with bevacizumab.Male patients or those with right-sided mCRC may derive benefits from immune-based combination therapy.Further research is needed to investigate specific clinical characteristics or biomarkers to identify patients who may derive benefit from combined immunotherapy approaches.
基金supported by the National Natural Science Foundation of China,No.82201568(to QQ)Capital’s Funds for Health Improvement and Research,No.2024-2-1031(to QQ)Beijing Nova Program,No.20240484566(to QQ).
文摘Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter release,and signal transmission,and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases.The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention,but their specific mechanisms remain to be fully understood.This review aims to explore how lipids regulate synaptic activity in the central nervous system,focusing on their roles in synapse formation,neurotransmitter release,and signal transmission.Additionally,it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation.This review shows that within the central nervous system,lipids are essential components of the cell membrane bilayer,playing critical roles in synaptic structure and function.They regulate presynaptic vesicular trafficking,postsynaptic signaling pathways,and glial-neuronal interactions.Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts.Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles.Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis.Fatty acids are vital for energy metabolism and the synthesis of signaling molecules.Abnormalities in lipid metabolism may lead to impairments in synaptic function,affecting information transmission between neurons and the overall health of the nervous system.Therapeutic strategies targeting lipid metabolism,particularly through cholesterol modulation,show promise for treating these conditions.In neurodegenerative diseases such as Alzheimer’s disease,Parkinson disease,and amyotrophic lateral sclerosis,dysregulation of lipid metabolism is closely linked to synaptic dysfunction.Therefore,lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs.Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.
基金supported by the Natural Science Foundation of Chongqing,No.CSTB2023NSCQ-mSX0561(to WL).
文摘Effective treatment methods for stroke,a common cerebrovascular disease with a high mortality rate,are still being sought.Exosome therapy,a form of acellular therapy,has demonstrated promising efficacy in various diseases in animal models;however,there is currently insufficient evidence to guide the clinical application of exosome in patients with stroke.This article reviews the progress of exosome applications in stroke treatment.It aims to elucidate the significant potential value of exosomes in stroke therapy and provide a reference for their clinical translation.At present,many studies on exosome-based therapies for stroke are actively underway.Regarding preclinical research,exosomes,as bioactive substances with diverse sources,currently favor stem cells as their origin.Due to their high plasticity,exosomes can be effectively modified through various physical,chemical,and genetic engineering methods to enhance their efficacy.In animal models of stroke,exosome therapy can reduce neuroinflammatory responses,alleviate oxidative stress damage,and inhibit programmed cell death.Additionally,exosomes can promote angiogenesis,repair and regenerate damaged white matter fiber bundles,and facilitate the migration and differentiation of neural stem cells,aiding the repair process.We also summarize new directions for the application of exosomes,specifically the exosome intervention through the ventricular-meningeal lymphatic system.The review findings suggest that the treatment paradigm for stroke is poised for transformation.
文摘Dear Editor,Linear and whorled nevoid hypermelanosis(LWNH)is a rare,sporadic pigmentary disorder characterized by hyperpigmented macules arranged in linear streaks and whorls along Blaschko's lines,typically appearing within the first few weeks of life[1],and remains a challenge to treat.Here,we report a case of LWNH and review the relevant literature to help clinicians better understand this disease.
基金supported by the National Natural Science Foundation Joint Fund,No.U22A20309(to PY)the Natural Science Foundation of LiaoningProvince,No.2023-MS-07(to HuL)the Unveiling Key Scientific and Technological Projects of Liaoning Province,No.2021JH1/10400051(to HuL).
文摘Some patients with systemic lupus erythematosus experience neuropsychiatric symptoms.Although magnetic resonance imaging can detect abnormal signals in the white matter of the brain,conventional methods often struggle to accurately capture microstructural changes.Various diffusion models have been used to study white matter in systemic lupus erythematosus;however,comparative analyses of their sensitivity and specificity for detecting microstructural changes remain insufficient.To address this,our team designed a diagnostic trial that used multimodal diffusion imaging techniques to observe white matter microstructural changes in patients with systemic lupus erythematosus who had neuropsychiatric symptoms,with an aim to identify key diagnostic biomarkers for these patients.Patients with active lupus who received treatment at the Department of Rheumatology and Immunology,The First Affiliated Hospital of China Medical University,from September 2023 to March 2024 were recruited.According to the standards of the American College of Rheumatology,patients with systemic lupus erythematosus who had neuropsychiatric symptoms were assigned to the systemic lupus erythematosus group,whereas those without neuropsychiatric symptoms were assigned to the non-systemic lupus erythematosus group.Additionally,healthy volunteers matched by region,sex,and age were recruited as controls.All three groups underwent the same diffusion magnetic resonance imaging examination protocol to compare differences in diffusion parameters.Advanced diffusion imaging models were able to sensitively detect microstructural changes in the white matter fibers of patients with systemic lupus erythematosus who had neuropsychiatric symptoms,with specific diffusion parameters showing significant abnormalities in key brain regions.In the left superior longitudinal fasciculus subregion and the right thalamic radiations of patients with systemic lupus erythematosus who had neuropsychiatric symptoms,we also identified abnormal diffusion characteristics that were clearly correlated with disease activity,suggesting that microstructural changes in these areas may reflect the dynamic process of neuroinflammatory damage.The present study addresses critical challenges in the diagnosis of systemic lupus erythematosus by identifying specific white matter imaging biomarkers and elucidating the association between microstructural damage and clinical manifestations.The main contributions of our study include:1)establishing axial regression probability parameters from mean apparent propagator magnetic resonance imaging as sensitive biomarkers for systemic lupus erythematosus,particularly in the third subregion of the left superior longitudinal fasciculus;2)demonstrating that multimodal diffusion imaging may be superior to conventional diffusion tensor imaging for detecting white matter microstructural abnormalities in patients with systemic lupus erythematosus;and 3)integrating tract-based spatial statistics with clinically relevant analyses to link imaging findings to pathological mechanisms.
文摘Radiofrequency ablation(RFA),particularly endoscopic ultrasound-guided RFA(EUS-RFA),has emerged as a promising minimally invasive approach for the treatment of pancreatic cancer,especially in patients with locally advanced or unresectable disease.This review outlines recent technological developments in EUS-RFA,including innovations in energy delivery systems,probe design,and real-time thermal monitoring,which have improved the precision and safety of the procedure.Clinical studies combining EUS-RFA with chemotherapy have demonstrated encouraging outcomes,with improvements in overall survival,progression-free survival,tumor necrosis,and symptom control compared to chemotherapy alone.Additionally,RFA-induced tumor antigen release and modulation of the tumor microenvironment suggest a potential synergistic role with immunotherapy.Despite its promise,the widespread adoption of EUS-RFA is limited by a lack of large-scale randomized controlled trials and standardized treatment protocols.
基金funded by Medical Science Foundation of Hebei University 2024B03Hebei Provincial Government-funded Provincial Medical Excellent Talent Project ZF2023025,ZF2024134,ZF2025045,ZF2025048,and ZF2025051+3 种基金Hebei Natural Science Foundation H2022206292,H2024206140Key R&D Program of Hebei Province 223777103D and 223777113DHebei Province County General Hospital Appropriate Health Technology Promotion Project 20220018other projects of Hebei Province SGH201501.
文摘Objectives:Gastric cancer(GC)is among the most prevalent malignancies worldwide,ranking as the fifth most common cancer and the fifth leading cause of cancer-related mortality.This study intends to investigate how Inhibin subunit beta A(INHBA)promotes the progression of GC by activating the mitogen-activated protein kinase(MAPK)signaling pathway via targeting Integrin alpha-6(ITGA6).Methods:Quantitative reverse transcription-Polymerase Chain Reaction(qRT-PCR)and Immunohistochemistry(IHC)were utilised to validate the expression levels of INHBA in GC,which were subsequently correlated with the clinicopathological factors and outcomes.Cellular and animal studies were conducted to ascertain the role of INHBA in GC.RNA-sequencing(RNA-seq)and bioinformatics analysis were used to screen for the downstream target and pathway of INHBA,with Co-immunoprecipitation(Co-IP),Co-Immunofluorescent(Co-IF),Western blot(WB)and Rescue experiments validating their mechanisms of action in GC.Results:IHC and qRT-PCR analysis confirmed that GC tissues exhibited higher INHBA expression than adjacent noncancerous tissues.This elevated INHBA expression was found to be significantly associated with the incidence of tumor lesions,lymph node metastasis,and progression to higher TNM stages.Functional experiments showed that INHBA promoted GC cell proliferation and enhanced their migration and invasion in vitro while inhibiting apoptosis.Animal studies results indicated that INHBA overexpression promoted tumor growth and increased tumor weight and volume.Through a series of experiments,including RNA-seq,Co-IP,Co-IF,WB,and rescue assays,this study demonstrated that INHBA promotes GC progression by targeting ITGA6 to regulate the MAPK signaling pathway.Conclusions:INHBA/ITGA6/MAPK axis can provide new insights into GC therapy.Targeted INHBA inhibition holds promise as a therapeutic approach for GC treatment.
文摘This study examined a case of ventilator-associated pneumonia caused by Ralstonia mannitolilytica in a neonatal department in order to determine the source of infection and mode of transmission.Symptoms of infection began to appear on day 16 of admission,and both sputum and catheter tip cultures revealed R.mannitolilytica.The infection control department of the hospital later sampled and identified R.mannitolilytica in the ventilator tube that was used by the patient with the exact gene sequence as the infecting strain.These findings indicate that ventilator tubing is a significant contamination source of this pathogen,and hospitals need to enhance their disinfection methods of ventilator-related devices.
基金supported by Jiangsu Cancer Hospital Science and Technology Development Fund Project(NO.XHMS202404)Nanjing Medical Science and Technology Development Fund Project(GBX22289).
文摘Objectives:Although standardized residency trainees are at high risk for depression,anxiety,and suicidal ideation,the psychological pathways connecting depression and anxiety to suicidal ideation,especially the moderating role of resilience,remain elusive.This study aimed to examine the associations between depression,anxiety,and suicidal ideation among physicians undergoing standardized residency training,and to investigate the moderating roles of different dimensions of individual resilience,namely tenacity,strength,and optimism.Methods:A convenience sampling method was adopted to recruit 133 resident physicians.Validated instruments assessing individual resilience,depressive symptoms,anxiety levels,and suicidal ideation were administered.Spearman correlation analysis was used to evaluate the relationships among the variables.Hierarchical regression analysis was conducted to assess the moderating roles of tenacity,strength,and optimism in the associations between depression,anxiety,and suicidal ideation.Results:Depressive symptoms and anxiety levels were both positively associated with suicidal ideation(p<0.001).All three resilience dimensions were negatively correlated with suicidal ideation(tenacity:r=−0.504,strength:r=−0.477,optimism:r=−0.440,all p<0.001).Tenacity,strength,and optimism significantly moderated the associations between depression and suicidal ideation(all p<0.05).When resilience levels in these dimensions were high,the associations between depression and suicidal ideation were weaker.Strength and optimism also moderated the associations between anxiety and suicidal ideation(strength:p=0.028,optimism:p=0.028).When the resiliences(strength and optimism)were high,the associations between anxiety and suicidal ideation were weaker.Conclusion:Individual resilience,particularly in the dimensions of tenacity,strength,and optimism,may serve as protective correlates for physicians in training,being associated with weaker relationships between depression,anxiety,and suicidal ideation.These findings highlight the potential value of resilience-enhancing strategies in clinical training settings,although causal inferences cannot be drawn due to the cross-sectional design.
文摘Objectives This study aimed to compare the effectiveness of the semi-virtual simulation and traditional simulation teaching models based on the Standards of Best Practice(SOBP)according to the International Nursing Association for Clinical Simulation and Learning(INACSL)in the Adult Nursing course.Methods This study used a quasi-experimental design.A total of 94 third-year nursing students from a university in Beijing between November and December 2022 were recruited as participants.An innovative semi-virtual simulation teaching model was designed based on the SOBP established by the INACSL.In the Adult Nursing course,both the semi-virtual and traditional simulation teaching models were implemented.At the end of the simulation sessions,participants completed the Chinese version of the Simulation Effectiveness Tool-Modified(SET-M)to assess the effectiveness of the two teaching models.Results All nursing students completed the simulation sessions.There was no difference(t=−0.93,P=0.353)in the total scores between the semi-virtual simulation teaching model(50.87±5.30)and the traditional simulation teaching model(50.37±5.16).However,there was a statistically significant difference(t=−2.65,P=0.010)in the prebriefing section(semi-virtual simulation:5.60±0.71;traditional simulation:5.33±0.78).In contrast,no statistically significant differences were found for the scenario and debriefing sections(P>0.05).At the individual item level,statistical differences(P<0.05)between the two models were identified for items 1 and 9,but not for the remaining items(P>0.05).By analyzing the open-ended question,it was found that both simulation models were effective,and students’comments were similar.Conclusions The study demonstrated equivalent effectiveness between the semi-virtual and traditional simulation teaching models.Semi-virtual simulation teaching model could offer a more flexible and feasible approach to simulation teaching.
基金supported by the National Natural Science Foundation of China(No.81973466)the National Administration of Traditional Chinese Medicine Youth Qihuang Scholars Support Project,and the Program of Graduate Innovation Research in Shanxi Province(No.2023KY019).
文摘Silicosis is one of the most serious and prevalent occupational diseases globally,characterized by typical silicotic nodules and fibrosis.Recent studies suggest that the perinodular zone of the lung shares certain characteristics with the nodules themselves.In this study,a silicotic rat model was established via a single intratracheal in-stillation of a 50 mg/mL silica suspension.Pulmonary anatomical and pathological examinations revealed that silica deposition induced severe alterations in both the nodular and perinodular tissues.Subsequently,pseudo-targeted metabolomics analysis revealed that abnormally elevated ornithine levels were closely associated with the progression of silicosis,from normal to perinodular and finally to nodular tissues.Immunofluorescent stain-ing demonstrated that,in addition to M2 macrophages,silica exposure increased the protein levels of ARG1 in epithelial cells,a finding further confirmed by in vitro experiments using A549 and BEAS-2B cells.Moreover,accumulated ornithine induced epithelial-mesenchymal transition in vitro,increased extracellular matrix expres-sion in NIH 3T3 fibroblasts,and enhanced TGF-β1 levels in RAW264.7 cells.Co-exposure to ornithine and silica significantly induced the aberrant expression of fibrosis-associated proteins compared to silica exposure alone,characterized by increased levels of FN and𝛼-SMA,as well as decreased E-cad expression.These findings sug-gest that silica exposure up-regulates ARG1 in various cells,leading to ornithine accumulation,which in turn accelerates the progression of fibrosis.
基金supported by the Special Project for High-tech Industrialization of Science and Technology Cooperation between Jilin Province and Chinese Academy of Sciences(2023SYHZ0042)。
文摘The development of substitutable meniscus implants that can effectively protect articular cartilage remains a great challenge.Herein,a polyurethane with chemical crosslinking and sulfobetaine extenders containing hydrophobic chains(PU-CL-hSB)is developed,which could improve comprehensive properties and long-term stability simultaneously.By regulating the mole ratio of functional groups,PU-CL-hSB with appropriate mechanical properties,excellent tribological properties,and good fatigue resistance is used to prepare substitutable meniscus implant by hot-pressing.Due to the synergistic effect of functional groups,PU-CL-hSB meniscus implant presents comparable or even superior properties to native meniscus.It withstands a maximum force of 26.08 N versus 25.14 N for native meniscus,an energy dissipation from 45.93 to 39.17 N mm compared to 28.83 to 19.11 N mm for native meniscus over 300 cycles,and a friction coefficient from 0.08 to 0.19 compared to 0.11 to 0.26 for native meniscus.This PU-CL-hSB meniscus implant is further implanted into live rabbit knee joints for 8 and 25 weeks by a new approach,and in vivo data indicate that PU-CL-hSB meniscus implant not only protects articular cartilage from severe damage without eliciting inflammatory responses,but also can maintain normal physiological activities in the native state.Our findings present a substitutable meniscus implant that could be applied in vivo and propose evaluation methodologies for meniscus implants.
基金supported by the National Natural Science Foundation of China,No.82474468the Science and Technology Innovation Program of Hunan Province,No.2024RC3200+3 种基金the Health Commission Talent Project of Hunan Province,No.20240304118the Scientific Research Project of Hunan Department of Education,No.23A0281the Open Fund for Chinese Medicine Powder and Innovative Drugs in the Cultivation Base of the Provincial-Ministry Jointly Established State Key Laboratory of Chinese Medicine,No.23PTKF1013the Training Plan of Outstanding Innovative Youth of Changsha,No.kq2009018(all to PM)。
文摘Over the past few decades,the Sonic Hedgehog protein has become a pivotal player in many biological processes,including tumourigenesis,embryonic development,and protective mechanisms after cerebral damage.The Sonic Hedgehog signaling pathway is crucial in the central nervous system,with implications in a diverse range of diseases,including Parkinson's disease,Alzheimer's disease,spinal cord injury,traumatic brain injury,depression,Sonic Hedgehog medulloblastoma,and stroke.In this comprehensive review,we examined Sonic Hedgehog from the perspective of canonical and non-canonical pathways,elucidating their complex connections to the central nervous system.Subsequently,we summarize the latest advancements in drug therapies that offer novel strategies for treating neurological diseases by modulating the Sonic Hedgehog protein.Finally,we summarize and extend the technologies and tools for studying the Sonic Hedgehog signaling field,with the aim of providing new research ideas and methods.
基金supported by the Natural Science Foundation of Jilin Province(No.SKL202302002).
文摘Triple-negative breast cancer(TNBC)presents significant diagnostic and therapeutic challenges due to the lack of targeted treatments,rapid progression,high recurrence and metastasis rates,and overall poorer prognosis.Herein,the targeted theranostic platform of cysteine-modified gold nanodots-sulfhydrated luteinizing hormone releasing hormone(CGN-SLR)nanosystem was designed for target recognition and precise dual-mode imaging-guided photothermal therapy(PTT)against TNBC.On the one hand,the CGN-SLR nanosystem can serve as an ideal targeting fluorescent probe and computed tomography(CT)enhancer to facilitate the accurate diagnosis and surgical guidance of TNBC.On the other hand,the CGN-SLR nanosystem with great targeting and PTT ability can significantly inhibit the growth of TNBC,without causing harm to normal tissues and healthy organs.It provides an effective strategy for the diagnosis and treatment of TNBC through the rational design of multifunctional nanoplatform with target recognition,multiple imaging guidance/monitoring,and high-efficiency PTT.
基金supported by the National Nature Science Foundation of China(Grant Nos.32171307,12372307,12172089,61821002 and 82102567)the Basic Research Plan Natural Science Foundation of Jiangsu Province(Grant No.BK20232023)+1 种基金the Nature Science Foundation of Jiangsu Province(Grant No.BK20200144)the Postgraduate Research and Practice Innovation Program of Jiangsu Province(Grant No.5007032303).
文摘The meniscus plays an important role in the biomechanical function of the knee joint,but knee osteoarthritis(OA)deteriorates the mechanical properties of the meniscus.Thus understanding the mechanical behaviour of the OA meniscus is very important.This study aimed to assess the quasi-static nonlinear mechanical behaviours of the three zones of the OA meniscus by a proposed meso-indentation method,and further to investigate its nonlinear mechanical responses under the stance.Four pairs of menisci were harvested from OA patients during total knee arthroplasty.One pair of the menisci was first used for the histological analysis.Binocular fringe projection technology was then employed to reconstruct the morphology of the other three pairs of the menisci.Subsequently,a meso-indentation method was proposed to characterize the nonlinear behaviors of the meniscus zones,moreover,the hyperelastic model(HEM)together with the Hertz’s elastic model(EM)was used to fit the indentation force-depth curves of the meniscus zones.Furthermore,the fitted HEM and EM materials parameters were used to simulate the mechanical response of the meniscus in the stance by two simplified meniscus models.The results showed that the type III collagen widely existed in the OA menisci,and the red-white zone exhibited the best mechanical performance,and the 3-term Mooney-Rivlin model was the best descriptor for the nonlinear mechanical characterization of the three zones.Moreover,the stress or strain distributions of the simplified meniscus models differed significantly between the HEM and EM under the stance,and the EM underestimated the mechanical behaviours of the meniscus.The current work generally provides a novel testing method to study the nonlinear mechanical behaviour of soft biological materials,and is specifically helpful to understand the nonlinear mechanical behaviour of the OA meniscus for which the HEM should be used in the meniscus-related biomechanical studies.
基金Supported by National Natural Science Foundation of China,No.82303672Zhejiang Provincial Health Commission and Zhejiang Provincial Administration of Traditional Chinese Medicine through the Targeted Project for Medical and Health Research,No.2025ZL017and China Primary Health Care Foundation,No.ZLMY20240311001ZJ.
文摘BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically experience a poor prognosis,highlighting an urgent need to explore novel treatment approaches.This study evaluated the overall efficacy and safety of CMT vs CMT combined with immune checkpoint inhibitors(ICIs)in the treatment of EC patients with liver metastases.Furthermore,prognostic factors influencing outcomes in this patient population were identified.AIM To evaluate the efficacy and safety of first-line chemoimmunotherapy for EC patients with liver metastases and to analyze prognostic factors.METHODS This retrospective study included 126 EC patients with liver metastases at Zhejiang Cancer Hospital between 2014 and 2024.Patients receiving CMT were compared with those receiving CMT+ICI.Analyzed variables included clinicopathological features,treatment history,characteristics of metastasis,systemic and local treatments,overall survival(OS),and treatment-related adverse events(TRAEs).Prognostic factors were evaluated using univariate and multivariate Cox proportional-hazards regression models.Finally,efficacy outcomes and TRAE profiles were compared between the two groups.RESULTS A significant difference in median OS was identified between the two groups(10.8 months in the CMT group vs 20.8 months in the CMT+ICI group,P=0.004).The CMT+ICI group also demonstrated a significantly longer median progression-free survival of 11.7 months(P<0.001).Patients receiving combination therapy exhibited significantly improved systemic objective response rate and disease control rate.Multivariate analysis identified key factors significantly influencing OS in EC patients with liver metastases:Karnofsky Performance Status score≥70,receipt of local therapy for liver metastases,and the number of cycles of CMT and immunotherapy received.Furthermore,the incidence of TRAEs did not significantly differ between the CMT+ICI and CMT groups.CONCLUSION For EC patients with liver metastases,the combination of CMT and ICIs demonstrates significantly superior efficacy compared with CMT alone,while maintaining manageable TRAEs.
基金Project supported by the National Key Technology R&D Program of China(No.2011BAI11B06)
文摘Acute myocardial infarction （AMI） has a high mortality rate and poor prognosis for patients. The primary causes of death are arrhythmia and heart failure. For patients admitted because of myocardial infarction, various risk evaluations are initiated to foresee possible complications. The thrombolysis in myocardial infarction （TIMI） risk score, which can be used to predict the prognosis and the need for revas-cularisation, is the most convenient and commonly used system, but is inadequate for AMI patients on admittance. Fragmented QRS （fQRS） has been shown to be a valuable electrocardiographic （ECG） index for predicting the prognosis of patients with coronary heart disease （Das et al., 2006, 2007）.
