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
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
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
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
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
BACKGROUND Metastases from pancreas or ampullary malignancies are common,but the spread to testicle and paratesticular tissue is exceedingly rare.To the best of our knowledge,fewer than 30 cases have been reported in ...BACKGROUND Metastases from pancreas or ampullary malignancies are common,but the spread to testicle and paratesticular tissue is exceedingly rare.To the best of our knowledge,fewer than 30 cases have been reported in the literature.More rarely,metastasis to tunica vaginalis testis occurs without involvement of the testes and epididymis.CASE SUMMARY A 65-year-old male who complained of painless swelling of the left scrotum for over 1 wk was referred to the Department of Urology.Scrotal ultrasound showed left testicular hydrocele with paratesticular masses.Chest computed tomography revealed lung metastasis and enlarged left supraclavicular lymph node.The blood tumor markersalpha-fetoprotein,human chorionic gonadotropin,and serum lactate dehydrogenase were withinnormal limits.The preoperative diagnosis was left testicular tumor with lung metastasis.Then radical orchidectomy of the left testicle and high ligation of the spermatic cord were performed,and postoperative histopathology suggested metastatic tumors that was confirmed by an abdominal computed tomographic scan.The positive computed tomography findings,in conjunction with the expression of cytokeratin 7(CK7),CK20,CK5/6,and absence of expression of Wilms’tumor suppressor gene 1,calretinin,melanocyte,prostate-specific antigen,thyroid transcription factor-1,GATA binding protein 3,caudal type homeobox 2,and napsinA supported the diagnosis of pancreatic adenocarcinoma.The outcome of this patient was unsatisfactory,and he died 3 mo later.CONCLUSION This case suggests that pancreatic metastatic carcinoma must be considered in the differential diagnosis of scrotal enlargement.The advanced age of the patient wassuggestive of a secondary testicular tumor.In addition,careful physical examination and ultrasonography as well as radiological examination have become a standard modality.展开更多
Dear Editor,Severe fever with thrombocytopenia syndrome(SFTS),caused by SFTS virus(SFTSV)in the genus Banyangvirus of the family Phenuiviridae,is an emerging tick-borne viral zoonosis(Liu et al.2014).Typical clinical ...Dear Editor,Severe fever with thrombocytopenia syndrome(SFTS),caused by SFTS virus(SFTSV)in the genus Banyangvirus of the family Phenuiviridae,is an emerging tick-borne viral zoonosis(Liu et al.2014).Typical clinical symptoms of SFTS include fever,headache,thrombocytopenia,and leukocytopenia(Yu et al.2011).Since SFTSV was identified in 2009,it has been found in more than 20 provinces in China and is closely related to strains from Japan and South Korea(Kim et al.2013;Takahashi et al.2014).展开更多
Background The Global Leadership Initiative on Malnutrition(GLIM)recently developed a new set of diagnostic criteria for identifying patients with malnutrition.Because the GLIM criteria were only introduced a little o...Background The Global Leadership Initiative on Malnutrition(GLIM)recently developed a new set of diagnostic criteria for identifying patients with malnutrition.Because the GLIM criteria were only introduced a little over 3 years ago,additional validation and reliability testing are needed in a variety of populations.Methods We performed an observational,multicenter cohort study.From July 2013 to October 2018,lung cancer patients were recruited from the Daping Hospital of Army Medical University and the First Hospital of Jilin University as part of the INSCOC project.Previously-established cut-off values for the calf circumference(CC,male<30 cm,female<29.5 cm)were applied as the reduced muscal mass of phenotypic criteria to establish the GLIM diagnosis.Multivariate Cox regression analyses were performed to analyze the association between the GLIM criteria and survival.Results A total of 1219 patients with lung cancer were studied as subjects.Their age was 58.81±9.92 years old,and 820 were male and 399 were female.According to the GLIM diagnostic criteria using the CC as a muscle mass measurement,303 patients(24.9%)were categorized as malnourished,142 patients(23.1%)in the adult group(18≤age<60)and 161 patients(26.7%)in the older group(age≥60 years).The patients with malnutrition had a higher incidence of anemia than the nourished patients(P=0.012).The QLQ-C30 score and KPS score indicating that the malnourished patients had a consistently worse quality of life compared to the nourished group(all P<0.001).The median survival of the malnutrition group was 42(95%CI:34-50)months,which was much shorter than the 62(95%CI:57-66)months in the nourished group(P<0.001).In the adult group,the median survival decreased from 65(95%CI:55-72)months in nourished group to 34(95%CI:25-48)months in the patients with malnutrition(P<0.001).In the older group,it decreased from 61(95%CI:55-67)months to 48(95%CI:39-59)months(P=0.001).A Cox regression analysis showed that GLIM-diagnosed malnutrition was associated with an increased risk of death among adult group(HR=1.670,95%CI:1.29-2.16),older group(HR=1.332,95%CI:1.05-1.69)and overall(HR=1.453,95%CI:1.22-1.72).Conclusion All of these results demonstrate that GLIM-diagnosed malnutrition is associated with a poorer survival for all lung cancer patients,independent of age.展开更多
Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxid...Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.展开更多
BACKGROUND Extrahepatic cholangiocarcinoma sarcoma is extremely rare in clinical practice.These cells consist of both epithelial and mesenchymal cells.Patient-derived cell lines that maintain tumor characteristics are...BACKGROUND Extrahepatic cholangiocarcinoma sarcoma is extremely rare in clinical practice.These cells consist of both epithelial and mesenchymal cells.Patient-derived cell lines that maintain tumor characteristics are valuable tools for studying the molecular mechanisms associated with carcinosarcoma.However,cholangiocarcinoma sarcoma cell lines are not available in cell banks.AIM To establish and characterize a new extrahepatic cholangiocarcinoma sarcoma cell line,namely CBC2T-2.METHODS We conducted a short tandem repeat(STR)test to confirm the identity of the CBC2T-2 cell line.Furthermore,we assessed the migratory and invasive properties of the cells and performed clonogenicity assay to evaluate the ability of individual cells to form colonies.The tumorigenic potential of CBC2T-2 cells was tested in vivo using nonobese diabetic/severe combined immunodeficient(NOD/SCID)mice.The cells were injected subcutaneously and tumor formation was observed.In addition,immunohistochemical analysis was carried out to examine the expression of epithelial marker CK19 and mesenchymal marker vimentin in both CBC2T-2 cells and xenografts.The CBC2T-2 cell line was used to screen the potential therapeutic effects of various clinical agents in patients with cholangiocarcinoma sarcoma.Lastly,whole-exome sequencing was performed to identify genetic alterations and screen for somatic mutations in the CBC2T-2 cell line.RESULTS The STR test showed that there was no cross-contamination and the results were identical to those of the original tissue.The cells showed round or oval-shaped epithelioid cells and mesenchymal cells with spindle-shaped or elongated morphology.The cells exhibited a high proliferation ratio with a doubling time of 47.11 h.This cell line has migratory,invasive,and clonogenic abilities.The chromosomes in the CBC2T-2 cells were polyploidy,with numbers ranging from 69 to 79.The subcutaneous tumorigenic assay confirmed the in vivo tumorigenic ability of CBC2T-2 cells in NOD/SCID mice.CBC2T-2 cells and xenografts were positive for both the epithelial marker,CK19,and the mesenchymal marker,vimentin.These results suggest that CBC2T-2 cells may have both epithelial and mesenchymal characteristics.The cells were also used to screen clinical agents in patients with cholangiocarcinoma sarcoma,and a combination of paclitaxel and gemcitabine was found to be the most effective treatment option.CONCLUSION We established the first human cholangiocarcinoma sarcoma cell line,CBC2T-2,with stable biogenetic traits.This cell line,as a research model,has a high clinical value and would facilitate the understanding of the pathogenesis of cholangiocarcinoma sarcoma.展开更多
BACKGROUND The incidence and mortality rates of gastric cancer in China are the second-highest in the world,and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis.AIM To expl...BACKGROUND The incidence and mortality rates of gastric cancer in China are the second-highest in the world,and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis.AIM To explore the predictive potential of serum basic fibroblast growth factor and interleukin-1βlevels for the effect of first-line chemotherapy in patients with advanced gastric cancer.METHODS From the gastric cancer patients admitted to our hospital from May 2019 to April 2023,84 patients were selected and randomly and equally assigned to the experimental or control group.The FLOT group received the FLOT chemotherapy regimen(composed of oxaliplatin+calcium folinate+fluorouracil+paclitaxel),while the SOX group received the SOX chemotherapy regimen(composed of oxaliplatin+tiga capsules).The clinical efficacy,tumor marker levels,adverse reactions,and survival rates of the two groups were compared 7 days after the end of the relevant treatments.RESULTS The target effective rate of the FLOT group was 54.76%,which was much higher than that of the SOX group(33.33%;P<0.05).After treatment,both the groups demonstrated lower levels of cancer antigen(CEA),carbohydrate antigen 199(CA199),and peptide tissue antigen(TPS).For several patients before treatment(P<0.05).Third and fourth grades.In terms of adverse reactions,the level of white blood cells in both the groups was lower.Moreover,the incidence of hand-foot skin reactions in these two study groups was lower(P<0.05),while those of peripheral neuritis,vomiting,diarrhea,and abnormal liver function were significant(P<0.05).No statistically significant difference was noted between the two groups(P<0.05).The 1-year survival rate was higher in the FLOT group(P<0.05).CONCLUSION The FLOT regimen was effective in reducing the serum CEA,CA199,and TPS levels as well as in improving the 1-year survival rate of patients with good tolerability,making it worthy of clinical promotion and application.展开更多
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
Brain-computer interfaces(BCIs)represent an emerging technology that facilitates direct communication between the brain and external devices.In recent years,numerous review articles have explored various aspects of BC...Brain-computer interfaces(BCIs)represent an emerging technology that facilitates direct communication between the brain and external devices.In recent years,numerous review articles have explored various aspects of BCIs,including their fundamental principles,technical advancements,and applications in specific domains.However,these reviews often focus on signal processing,hardware development,or limited applications such as motor rehabilitation or communication.This paper aims to offer a comprehensive review of recent electroencephalogram(EEG)-based BCI applications in the medical field across 8 critical areas,encompassing rehabilitation,daily communication,epilepsy,cerebral resuscitation,sleep,neurodegenerative diseases,anesthesiology,and emotion recognition.Moreover,the current challenges and future trends of BCIs were also discussed,including personal privacy and ethical concerns,network security vulnerabilities,safety issues,and biocompatibility.展开更多
Background: Otitis media (OM) is highly prevalent and is one of the most important causes of preventable hearing loss in developing countries and it may have long-term impacts on the children. Several hospital-based c...Background: Otitis media (OM) is highly prevalent and is one of the most important causes of preventable hearing loss in developing countries and it may have long-term impacts on the children. Several hospital-based cross-sectional studies have been conducted in East African countries to assess the prevalence of OM;however, no similar studies have been conducted in Somalia. Therefore, we conducted a hospital-based cross-sectional study to identify the prevalence and the underlying risk factors of OM among children under the age of five in Mogadishu, Somalia. Methodology: A hospital-based cross-sectional study was conducted from July 2022 to November 2022 at three main hospitals in Mogadishu, Somalia. A total of 384 children aged less than 5 years were included. Parents of these children were interviewed with a questionnaire and a clinical examination was performed for each child. The Statistical Package for Social Sciences, SPSS (Version 22, IBM, Inc.), was used for the statistical analysis. Result: The prevalence of otitis media among the 384 children recruited was 31.25% (120/384). Otitis media was significantly associated with age less than one year (P = 0.006), malnutrition (P Conclusion: In summary, the present study found that otitis media was highly prevalent (31.25%) in Mogadishu, Somalia. The majority of the affected children were younger than one year. Age of the child, malnutrition, upper respiratory tract infections, feeding in lying position, and dripping something into a child’s ear were found to significantly increase the risk of developing otitis media in children. In contrast, breastfeeding for more than one year has been found to reduce the risk of developing otitis media in children.展开更多
With the sustained growth of the economy and significant changes in social demographics,the issue of elderly-related diseases has increasingly drawn attention,particularly.Alzheimer’s disease(AD),as a representative ...With the sustained growth of the economy and significant changes in social demographics,the issue of elderly-related diseases has increasingly drawn attention,particularly.Alzheimer’s disease(AD),as a representative disease of neurodegenerative diseases,has become a major challenge,affecting the health and quality of life of the elderly population severely.In recent years,the incidence,prevalence and mortality rates of AD have increased in China,imposing substantial economic burdens on families,society and the entire healthcare system.To proactively address this challenge and respond to the national‘Healthy China Action’initiative,leading experts from authoritative institutions jointly authored the China Alzheimer Report 2025.Building on previous editions,this report updates epidemiological data on AD in China,thoroughly analyses the latest economic burdens of the disease and comprehensively evaluates the current status of AD diagnosis and treatment services,as well as the allocation of public health resources in our country.Its release reflects China’s progress in AD research and prevention,underscores societal concern for elderly health and aims to provide scientific guidance and data support for AD prevention,diagnosis and treatment.It also facilitates academic exchanges and cooperation,enhancing public awareness and promoting active participation in elderly healthcare,towards achieving‘healthy ageing’in China.展开更多
Given customizable crystal structure and intriguing optical properties,lanthanide titanium-oxygen clusters(LTOCs)with atomic-level accuracy have gained a lot of interest.In this study,we prepared[Ln_(9)Ti_(2)(μ4-O)(...Given customizable crystal structure and intriguing optical properties,lanthanide titanium-oxygen clusters(LTOCs)with atomic-level accuracy have gained a lot of interest.In this study,we prepared[Ln_(9)Ti_(2)(μ4-O)(μ3-OH)_(14)(acac)_(17)(CH_(3)O)_(2)(CH_(3)OH)_(3)](Ln=Tb_(x)Eu_(9−x)(x=0,4,6,7,8,9),Hacac=acetylacetone),Tb^(3+)and Eu^(3+)co-doped LTOCs,to modify the optical properties for the luminescence thermometer.In detail,the serial LTOCs display dual characteristic emission peaks of ^(5)D_(4)→^(7)F_(5) for Tb^(3+)and^(5)D_(0)→^(7)F_(2) for Eu^(3+)at 548 and 616 nm,respectively,under 330 nm excitation.Effective energy transfer(ET)between Tb^(3+)ions and Eu^(3+)ions was revealed in terms of both emission spectra and luminescence lifetime.The ^(5)D_(0)→^(7)F_(2) emission intensity of Eu^(3+)ions at 616 nm is maximally enhanced(by a factor of 11.2)with a change in the relative molar ratio of Tb^(3+)to Eu^(3+),along with a change in the ET efficiency of Tb^(3+)→Eu^(3+).In addition,the luminescent color changes from red,orange,yellow,to green.This precise control of the ET process between rare-earth ions allows{Tb_(6)Eu_(3)Ti_(2)}to reach a maximum relative sensitivity of 1.241 K^(−1) at 355 K,which is an enhancement of up to 4.6-fold with respect to the previously reported homonuclear emission,holding great potential in the optical thermometers.展开更多
Yttrium-90(Y-90)microsphere therapy,known as radioembolization,has emerged as a pivotal treatment modality for hepatocellular carcinoma(HCC),delivering targeted radiation with minimal collateral damage to healthy live...Yttrium-90(Y-90)microsphere therapy,known as radioembolization,has emerged as a pivotal treatment modality for hepatocellular carcinoma(HCC),delivering targeted radiation with minimal collateral damage to healthy liver tissues.This review meticulously synthesizes current evidence regarding the clinical efficacy,underlying therapeutic mechanisms,patient selection criteria,and comparative advantages of Y-90 therapy.Clinical studies consistently demonstrate significant improvements in overall survival and progression-free survival,coupled with robust tumor response rates and manageable adverse events.The therapy’s efficacy is substantially enhanced by advanced dosimetric techniques,enabling precise radiation delivery tailored to individual tumor profiles.Comparative analyses reveal that Y-90 therapy provides superior local tumor control and a preferable safety profile compared to conventional treatments such as transarterial chemoembolization and external beam radiation therapy.Additionally,its clinical outcomes are comparable to those achieved with contemporary systemic therapies.Ongoing research into combination treatments incorporating Y-90 with systemic therapies,including targeted agents and immune checkpoint inhibitors,suggests promising advancements in comprehensive HCC management.Future directions highlight the necessity for continued refinement of dosimetry and patient stratification approaches,aiming to further optimize therapeutic outcomes.展开更多
In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B ...In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.展开更多
Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-i...Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.展开更多
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.
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.
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.
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 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National Natural Science Foundation of China,No.81901534.
文摘BACKGROUND Metastases from pancreas or ampullary malignancies are common,but the spread to testicle and paratesticular tissue is exceedingly rare.To the best of our knowledge,fewer than 30 cases have been reported in the literature.More rarely,metastasis to tunica vaginalis testis occurs without involvement of the testes and epididymis.CASE SUMMARY A 65-year-old male who complained of painless swelling of the left scrotum for over 1 wk was referred to the Department of Urology.Scrotal ultrasound showed left testicular hydrocele with paratesticular masses.Chest computed tomography revealed lung metastasis and enlarged left supraclavicular lymph node.The blood tumor markersalpha-fetoprotein,human chorionic gonadotropin,and serum lactate dehydrogenase were withinnormal limits.The preoperative diagnosis was left testicular tumor with lung metastasis.Then radical orchidectomy of the left testicle and high ligation of the spermatic cord were performed,and postoperative histopathology suggested metastatic tumors that was confirmed by an abdominal computed tomographic scan.The positive computed tomography findings,in conjunction with the expression of cytokeratin 7(CK7),CK20,CK5/6,and absence of expression of Wilms’tumor suppressor gene 1,calretinin,melanocyte,prostate-specific antigen,thyroid transcription factor-1,GATA binding protein 3,caudal type homeobox 2,and napsinA supported the diagnosis of pancreatic adenocarcinoma.The outcome of this patient was unsatisfactory,and he died 3 mo later.CONCLUSION This case suggests that pancreatic metastatic carcinoma must be considered in the differential diagnosis of scrotal enlargement.The advanced age of the patient wassuggestive of a secondary testicular tumor.In addition,careful physical examination and ultrasonography as well as radiological examination have become a standard modality.
基金supported by the National Key Research and Development Program of China(2017YFD0501702,and 2017YFD0500104)the National Natural Science Foundation of China(31672542 and 31372430)。
文摘Dear Editor,Severe fever with thrombocytopenia syndrome(SFTS),caused by SFTS virus(SFTSV)in the genus Banyangvirus of the family Phenuiviridae,is an emerging tick-borne viral zoonosis(Liu et al.2014).Typical clinical symptoms of SFTS include fever,headache,thrombocytopenia,and leukocytopenia(Yu et al.2011).Since SFTSV was identified in 2009,it has been found in more than 20 provinces in China and is closely related to strains from Japan and South Korea(Kim et al.2013;Takahashi et al.2014).
基金supported by the National Natural Science Foundation of China(No.81673167 to Hongxia Xu)the Chongqing Technology Innovation and Application Demonstration Project for Social Livelihood(cstc2018jscx-msybX0094 to Jie Liu).
文摘Background The Global Leadership Initiative on Malnutrition(GLIM)recently developed a new set of diagnostic criteria for identifying patients with malnutrition.Because the GLIM criteria were only introduced a little over 3 years ago,additional validation and reliability testing are needed in a variety of populations.Methods We performed an observational,multicenter cohort study.From July 2013 to October 2018,lung cancer patients were recruited from the Daping Hospital of Army Medical University and the First Hospital of Jilin University as part of the INSCOC project.Previously-established cut-off values for the calf circumference(CC,male<30 cm,female<29.5 cm)were applied as the reduced muscal mass of phenotypic criteria to establish the GLIM diagnosis.Multivariate Cox regression analyses were performed to analyze the association between the GLIM criteria and survival.Results A total of 1219 patients with lung cancer were studied as subjects.Their age was 58.81±9.92 years old,and 820 were male and 399 were female.According to the GLIM diagnostic criteria using the CC as a muscle mass measurement,303 patients(24.9%)were categorized as malnourished,142 patients(23.1%)in the adult group(18≤age<60)and 161 patients(26.7%)in the older group(age≥60 years).The patients with malnutrition had a higher incidence of anemia than the nourished patients(P=0.012).The QLQ-C30 score and KPS score indicating that the malnourished patients had a consistently worse quality of life compared to the nourished group(all P<0.001).The median survival of the malnutrition group was 42(95%CI:34-50)months,which was much shorter than the 62(95%CI:57-66)months in the nourished group(P<0.001).In the adult group,the median survival decreased from 65(95%CI:55-72)months in nourished group to 34(95%CI:25-48)months in the patients with malnutrition(P<0.001).In the older group,it decreased from 61(95%CI:55-67)months to 48(95%CI:39-59)months(P=0.001).A Cox regression analysis showed that GLIM-diagnosed malnutrition was associated with an increased risk of death among adult group(HR=1.670,95%CI:1.29-2.16),older group(HR=1.332,95%CI:1.05-1.69)and overall(HR=1.453,95%CI:1.22-1.72).Conclusion All of these results demonstrate that GLIM-diagnosed malnutrition is associated with a poorer survival for all lung cancer patients,independent of age.
基金supported by the National Natural Science Foundation of China,No.82071442 (to LS)a grant from the Jilin Provincial Department of Finance,No.JLSWSRCZX2021-004 (to LS)。
文摘Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.
基金the National Natural Science Foundation of China,No.82060551and Lanzhou Chengguan District Science and Technology Planning Project,No.2019JSCX0092.
文摘BACKGROUND Extrahepatic cholangiocarcinoma sarcoma is extremely rare in clinical practice.These cells consist of both epithelial and mesenchymal cells.Patient-derived cell lines that maintain tumor characteristics are valuable tools for studying the molecular mechanisms associated with carcinosarcoma.However,cholangiocarcinoma sarcoma cell lines are not available in cell banks.AIM To establish and characterize a new extrahepatic cholangiocarcinoma sarcoma cell line,namely CBC2T-2.METHODS We conducted a short tandem repeat(STR)test to confirm the identity of the CBC2T-2 cell line.Furthermore,we assessed the migratory and invasive properties of the cells and performed clonogenicity assay to evaluate the ability of individual cells to form colonies.The tumorigenic potential of CBC2T-2 cells was tested in vivo using nonobese diabetic/severe combined immunodeficient(NOD/SCID)mice.The cells were injected subcutaneously and tumor formation was observed.In addition,immunohistochemical analysis was carried out to examine the expression of epithelial marker CK19 and mesenchymal marker vimentin in both CBC2T-2 cells and xenografts.The CBC2T-2 cell line was used to screen the potential therapeutic effects of various clinical agents in patients with cholangiocarcinoma sarcoma.Lastly,whole-exome sequencing was performed to identify genetic alterations and screen for somatic mutations in the CBC2T-2 cell line.RESULTS The STR test showed that there was no cross-contamination and the results were identical to those of the original tissue.The cells showed round or oval-shaped epithelioid cells and mesenchymal cells with spindle-shaped or elongated morphology.The cells exhibited a high proliferation ratio with a doubling time of 47.11 h.This cell line has migratory,invasive,and clonogenic abilities.The chromosomes in the CBC2T-2 cells were polyploidy,with numbers ranging from 69 to 79.The subcutaneous tumorigenic assay confirmed the in vivo tumorigenic ability of CBC2T-2 cells in NOD/SCID mice.CBC2T-2 cells and xenografts were positive for both the epithelial marker,CK19,and the mesenchymal marker,vimentin.These results suggest that CBC2T-2 cells may have both epithelial and mesenchymal characteristics.The cells were also used to screen clinical agents in patients with cholangiocarcinoma sarcoma,and a combination of paclitaxel and gemcitabine was found to be the most effective treatment option.CONCLUSION We established the first human cholangiocarcinoma sarcoma cell line,CBC2T-2,with stable biogenetic traits.This cell line,as a research model,has a high clinical value and would facilitate the understanding of the pathogenesis of cholangiocarcinoma sarcoma.
基金Jiangxi Province Major Discipline Academic and Technical Leaders Project,No.812178084229.
文摘BACKGROUND The incidence and mortality rates of gastric cancer in China are the second-highest in the world,and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis.AIM To explore the predictive potential of serum basic fibroblast growth factor and interleukin-1βlevels for the effect of first-line chemotherapy in patients with advanced gastric cancer.METHODS From the gastric cancer patients admitted to our hospital from May 2019 to April 2023,84 patients were selected and randomly and equally assigned to the experimental or control group.The FLOT group received the FLOT chemotherapy regimen(composed of oxaliplatin+calcium folinate+fluorouracil+paclitaxel),while the SOX group received the SOX chemotherapy regimen(composed of oxaliplatin+tiga capsules).The clinical efficacy,tumor marker levels,adverse reactions,and survival rates of the two groups were compared 7 days after the end of the relevant treatments.RESULTS The target effective rate of the FLOT group was 54.76%,which was much higher than that of the SOX group(33.33%;P<0.05).After treatment,both the groups demonstrated lower levels of cancer antigen(CEA),carbohydrate antigen 199(CA199),and peptide tissue antigen(TPS).For several patients before treatment(P<0.05).Third and fourth grades.In terms of adverse reactions,the level of white blood cells in both the groups was lower.Moreover,the incidence of hand-foot skin reactions in these two study groups was lower(P<0.05),while those of peripheral neuritis,vomiting,diarrhea,and abnormal liver function were significant(P<0.05).No statistically significant difference was noted between the two groups(P<0.05).The 1-year survival rate was higher in the FLOT group(P<0.05).CONCLUSION The FLOT regimen was effective in reducing the serum CEA,CA199,and TPS levels as well as in improving the 1-year survival rate of patients with good tolerability,making it worthy of clinical promotion and application.
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supported by the National Key R&D Program of China(2021YFF1200602)the National Science Fund for Excellent Overseas Scholars(0401260011)+3 种基金the National Defense Science and Technology Innovation Fund of Chinese Academy of Sciences(c02022088)the Tianjin Science and Technology Program(20JCZDJC00810)the National Natural Science Foundation of China(82202798)the Shanghai Sailing Program(22YF1404200).
文摘Brain-computer interfaces(BCIs)represent an emerging technology that facilitates direct communication between the brain and external devices.In recent years,numerous review articles have explored various aspects of BCIs,including their fundamental principles,technical advancements,and applications in specific domains.However,these reviews often focus on signal processing,hardware development,or limited applications such as motor rehabilitation or communication.This paper aims to offer a comprehensive review of recent electroencephalogram(EEG)-based BCI applications in the medical field across 8 critical areas,encompassing rehabilitation,daily communication,epilepsy,cerebral resuscitation,sleep,neurodegenerative diseases,anesthesiology,and emotion recognition.Moreover,the current challenges and future trends of BCIs were also discussed,including personal privacy and ethical concerns,network security vulnerabilities,safety issues,and biocompatibility.
文摘Background: Otitis media (OM) is highly prevalent and is one of the most important causes of preventable hearing loss in developing countries and it may have long-term impacts on the children. Several hospital-based cross-sectional studies have been conducted in East African countries to assess the prevalence of OM;however, no similar studies have been conducted in Somalia. Therefore, we conducted a hospital-based cross-sectional study to identify the prevalence and the underlying risk factors of OM among children under the age of five in Mogadishu, Somalia. Methodology: A hospital-based cross-sectional study was conducted from July 2022 to November 2022 at three main hospitals in Mogadishu, Somalia. A total of 384 children aged less than 5 years were included. Parents of these children were interviewed with a questionnaire and a clinical examination was performed for each child. The Statistical Package for Social Sciences, SPSS (Version 22, IBM, Inc.), was used for the statistical analysis. Result: The prevalence of otitis media among the 384 children recruited was 31.25% (120/384). Otitis media was significantly associated with age less than one year (P = 0.006), malnutrition (P Conclusion: In summary, the present study found that otitis media was highly prevalent (31.25%) in Mogadishu, Somalia. The majority of the affected children were younger than one year. Age of the child, malnutrition, upper respiratory tract infections, feeding in lying position, and dripping something into a child’s ear were found to significantly increase the risk of developing otitis media in children. In contrast, breastfeeding for more than one year has been found to reduce the risk of developing otitis media in children.
基金supported by a grant from Brain Science and BrainLike Intelligence Technology of the Ministry of Science and Technology of China(2021ZD0201804).
文摘With the sustained growth of the economy and significant changes in social demographics,the issue of elderly-related diseases has increasingly drawn attention,particularly.Alzheimer’s disease(AD),as a representative disease of neurodegenerative diseases,has become a major challenge,affecting the health and quality of life of the elderly population severely.In recent years,the incidence,prevalence and mortality rates of AD have increased in China,imposing substantial economic burdens on families,society and the entire healthcare system.To proactively address this challenge and respond to the national‘Healthy China Action’initiative,leading experts from authoritative institutions jointly authored the China Alzheimer Report 2025.Building on previous editions,this report updates epidemiological data on AD in China,thoroughly analyses the latest economic burdens of the disease and comprehensively evaluates the current status of AD diagnosis and treatment services,as well as the allocation of public health resources in our country.Its release reflects China’s progress in AD research and prevention,underscores societal concern for elderly health and aims to provide scientific guidance and data support for AD prevention,diagnosis and treatment.It also facilitates academic exchanges and cooperation,enhancing public awareness and promoting active participation in elderly healthcare,towards achieving‘healthy ageing’in China.
基金supported by the National Natural Science Foundation of China(Nos.12174151 and 12304448)the Specific Research Fund of the Innovation Platform for Academicians of Hainan Province(No.YSPTZX202208)+3 种基金Hainan Province Clinical Medical Center(No.QWYH_(2)022341)the Key Laboratory of New Energy and Rare Earth Resource Utilization of the State People’s Committee of China(No.NERE202206)the Department of Science and Technology of Jilin Province(No.20220101059JC)the Key Laboratory of the Ministry of Education for First Aid and Trauma Research(No.KLET-202218).
文摘Given customizable crystal structure and intriguing optical properties,lanthanide titanium-oxygen clusters(LTOCs)with atomic-level accuracy have gained a lot of interest.In this study,we prepared[Ln_(9)Ti_(2)(μ4-O)(μ3-OH)_(14)(acac)_(17)(CH_(3)O)_(2)(CH_(3)OH)_(3)](Ln=Tb_(x)Eu_(9−x)(x=0,4,6,7,8,9),Hacac=acetylacetone),Tb^(3+)and Eu^(3+)co-doped LTOCs,to modify the optical properties for the luminescence thermometer.In detail,the serial LTOCs display dual characteristic emission peaks of ^(5)D_(4)→^(7)F_(5) for Tb^(3+)and^(5)D_(0)→^(7)F_(2) for Eu^(3+)at 548 and 616 nm,respectively,under 330 nm excitation.Effective energy transfer(ET)between Tb^(3+)ions and Eu^(3+)ions was revealed in terms of both emission spectra and luminescence lifetime.The ^(5)D_(0)→^(7)F_(2) emission intensity of Eu^(3+)ions at 616 nm is maximally enhanced(by a factor of 11.2)with a change in the relative molar ratio of Tb^(3+)to Eu^(3+),along with a change in the ET efficiency of Tb^(3+)→Eu^(3+).In addition,the luminescent color changes from red,orange,yellow,to green.This precise control of the ET process between rare-earth ions allows{Tb_(6)Eu_(3)Ti_(2)}to reach a maximum relative sensitivity of 1.241 K^(−1) at 355 K,which is an enhancement of up to 4.6-fold with respect to the previously reported homonuclear emission,holding great potential in the optical thermometers.
文摘Yttrium-90(Y-90)microsphere therapy,known as radioembolization,has emerged as a pivotal treatment modality for hepatocellular carcinoma(HCC),delivering targeted radiation with minimal collateral damage to healthy liver tissues.This review meticulously synthesizes current evidence regarding the clinical efficacy,underlying therapeutic mechanisms,patient selection criteria,and comparative advantages of Y-90 therapy.Clinical studies consistently demonstrate significant improvements in overall survival and progression-free survival,coupled with robust tumor response rates and manageable adverse events.The therapy’s efficacy is substantially enhanced by advanced dosimetric techniques,enabling precise radiation delivery tailored to individual tumor profiles.Comparative analyses reveal that Y-90 therapy provides superior local tumor control and a preferable safety profile compared to conventional treatments such as transarterial chemoembolization and external beam radiation therapy.Additionally,its clinical outcomes are comparable to those achieved with contemporary systemic therapies.Ongoing research into combination treatments incorporating Y-90 with systemic therapies,including targeted agents and immune checkpoint inhibitors,suggests promising advancements in comprehensive HCC management.Future directions highlight the necessity for continued refinement of dosimetry and patient stratification approaches,aiming to further optimize therapeutic outcomes.
基金Supported by the Natural Science Foundation of China,No.81970529the Natural Science Foundation of Jilin Province,No.20230508074RC and No.YDZJ202401218ZYTS.
文摘In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.
基金supported by research grants from the Ningbo Science and Technology Plan Project,No.2022Z143hezuo(to BL)the National Natural Science Foundation of China,No.82201520(to XD)。
文摘Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.
