BACKGROUND:To investigate the most appropriate dual antiplatelet therapy(DAPT)duration for patients with acute coronary syndrome(ACS)after drug-eluting stent(DES)implantation in the largest cardiovascular center of Ch...BACKGROUND:To investigate the most appropriate dual antiplatelet therapy(DAPT)duration for patients with acute coronary syndrome(ACS)after drug-eluting stent(DES)implantation in the largest cardiovascular center of China.METHODS:We enrolled 5,187 consecutive patients with ACS who received DES from January to December 2013.Patients were divided into four groups based on DAPT duration:standard DAPT group(11-13 months,n=1,568)and prolonged DAPT groups(13-18 months[n=308],18-24 months[n=2,125],and>24 months[n=1,186]).Baseline characteristics and 5-year clinical outcomes were recorded.RESULTS:Baseline characteristics were similar across the four groups.Among the four groups,those with prolonged DAPT(18-24 months)had the lowest incidence of major adverse cardiovascular and cerebrovascular events(MACCEs)(14.1%vs.11.7%vs.9.6%vs.24.2%,P<0.001),all-cause death(4.8%vs.3.9%vs.2.1%vs.2.6%,P<0.001),cardiac death(3.1%vs.2.6%vs.1.4%vs.1.9%,P=0.004),and myocardial infarction(MI)(3.8%vs.4.2%vs.2.5%vs.5.8%,P<0.001).The incidence of bleeding was not different among the four groups(9.9%vs.9.4%vs.11.0%vs.9.4%,P=0.449).Cox multivariable analysis showed that prolonged DAPT(18-24 months)was an independent protective factor for MACCEs(hazard ratio[HR]0.802,95%confidence interval[CI]0.729-0.882,P<0.001),all-cause death(HR 0.660,95%CI 0.547-0.795,P<0.001),cardiac death(HR 0.663,95%CI 0.526-0.835,P<0.001),MI(HR 0.796,95%CI 0.662-0.957,P=0.015),and target vessel revascularization(HR 0.867,95%CI 0.755-0.996,P=0.044).Subgroup analysis for high bleeding risk showed that prolonged DAPT remained an independent protective factor for all-cause death and MACCEs.CONCLUSION:For patients with ACS after DES,appropriately prolonging the DAPT duration may be associated with a reduced risk of adverse ischemic events without increasing the bleeding risk.展开更多
Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk fac...Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.展开更多
BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE patients.AIM To improve overall understanding of this disease’s diagnosis an...BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE patients.AIM To improve overall understanding of this disease’s diagnosis and prognosis.METHODS We retrospectively analyzed the clinical,endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023,whose diagnosis was based on the 2007 diagnostic criteria.RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea.The common endoscopic manifestations were edema,villous blunting and mucosal hyperemia in the duodenum and ileum.Villous blunting(100%),deep crypt lymphocytic infiltration(67%),apoptotic bodies(50%),and mild intraepithelial lymphocytosis(69%)were observed in the duodenal biopsies.Moreover,there were other remarkable abnormalities,including reduced or absent goblet cells(duodenum 94%,ileum 62%),reduced or absent Paneth cells(duodenum 94%,ileum 69%)and neutrophil infiltration(duodenum 100%,ileum 69%).Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies.All patients received glucocorticoid therapy as the initial medication,of which 14/16 patients achieved a clinical response in 5(IQR:3-20)days.Immunosuppressants were administered to 9 patients with indications of steroid dependence(6/9),steroid refractory status(2/9),or intensified maintenance medication(1/9).During the median of 20.5 months of followup,2 patients died from multiple organ failure,and 1 was diagnosed with non-Hodgkin’s lymphoma.The cumulative relapse-free survival rates were 62.5%,55.6%and 37.0%at 6 months,12 months and 48 months,respectively.CONCLUSION Certain histopathological findings,including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies,might be potential diagnostic criteria for adult AIE.The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications,which highlights the need for early diagnosis and novel medications.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemis...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.展开更多
BACKGROUND Local mesenchymal stem cell(MSC)therapy for complex perianal fistulas(PFs)has shown considerable promise.But,the long-term safety and efficacy of MSC therapy in complex PFs remain unknown.AIM To explore the...BACKGROUND Local mesenchymal stem cell(MSC)therapy for complex perianal fistulas(PFs)has shown considerable promise.But,the long-term safety and efficacy of MSC therapy in complex PFs remain unknown.AIM To explore the long-term effectiveness and safety of local MSC therapy for complex PFs.METHODS Sources included the PubMed,EMBASE,and Cochrane Library databases.A standard meta-analysis was performed using RevMan 5.3.RESULTS After screening,6 studies met the inclusion criteria.MSC therapy was associated with an improved long-term healing rate(HR)compared with the control condition[odds ratio(OR)=2.13;95%confidence interval(95%CI):1.34 to 3.38;P=0.001].Compared with fibrin glue(FG)therapy alone,MSC plus FG therapy was associated with an improved long-term HR(OR=2.30;95%CI:1.21 to 4.36;P=0.01).When magnetic resonance imaging was used to evaluate fistula healing,MSC therapy was found to achieve a higher long-term HR than the control treatment(OR=2.79;95%CI:1.37 to 5.67;P=0.005).There were no significant differences in long-term safety(OR=0.77;95%CI:0.27 to 2.24;P=0.64).CONCLUSION Our study indicated that local MSC therapy promotes long-term and sustained healing of complex PFs and that this method is safe.展开更多
In this editorial we comment on the article published by Zhang et al in the recent issue of World Journal of Clinical Cases.We evaluate their claims on the benefit of use of Aspirin in the early management of patients...In this editorial we comment on the article published by Zhang et al in the recent issue of World Journal of Clinical Cases.We evaluate their claims on the benefit of use of Aspirin in the early management of patients with ischemic stroke.We also comment on their contention of using aspirin in the early management of patients with intracranial hemorrhage,a practice not seen in modern medicine.Large clinical trials such as the International Stroke Trial and the Chinese Acute Stroke Trial have shown the benefit of Aspirin use within 48 h of patients with Acute Ischemic Stroke.The findings were corroborated in the open-label trial performed by Zhang et al in a smaller sample group of 25 patients where they showed improvement in functional scores at 90 days without an increase in adverse events.As such,this intervention is also recommended by the American Heart Association stroke guidelines from 2021.With regard to Intracranial hemorrhage,traditional practice has been to discontinue or avoid antiplatelet therapy in these patient groups.However,no studies have been done to evaluate this management strategy that is more borne out of the mechanism behind Aspirin’s effect on the coagulation pathway.Zhang et al evaluate the benefits of Aspirin on patients with low-volume intracranial hemorrhage,i.e.,less than 30 mL on computed tomo-graphy imaging,and show no increase in mortality.The caveat of this finding is that all outcomes were pooled into one group for results,and the number of patients was low.While more studies with larger patient groups are required,the data from Zhang et al suggests that patients with small-volume intracranial hemorrhages may benefit from Aspirin administration in the acute phase of management.展开更多
Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM ...Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.展开更多
BACKGROUND Whether hyperbaric oxygen therapy(HBOT)can cause paradoxical herniation is still unclear.CASE SUMMARY A 65-year-old patient who was comatose due to brain trauma underwent decompressive craniotomy and gradua...BACKGROUND Whether hyperbaric oxygen therapy(HBOT)can cause paradoxical herniation is still unclear.CASE SUMMARY A 65-year-old patient who was comatose due to brain trauma underwent decompressive craniotomy and gradually regained consciousness after surgery.HBOT was administered 22 d after surgery due to speech impairment.Paradoxical herniation appeared on the second day after treatment,and the patient’s condition worsened after receiving mannitol treatment at the rehabilitation hospital.After timely skull repair,the paradoxical herniation was resolved,and the patient regained consciousness and had a good recovery as observed at the follow-up visit.CONCLUSION Paradoxical herniation is rare and may be caused by HBOT.However,the underlying mechanism is unknown,and the understanding of this phenomenon is insufficient.The use of mannitol may worsen this condition.Timely skull repair can treat paradoxical herniation and prevent serious complications.展开更多
Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic ...Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.展开更多
Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emerge...Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.展开更多
BACKGROUND Tardive dyskinesia(TD)is a serious and disabling movement disorder;it impairs social function and quality of life and increases the mortality rate.TD is usually induced by the use of antipsychotic drugs;how...BACKGROUND Tardive dyskinesia(TD)is a serious and disabling movement disorder;it impairs social function and quality of life and increases the mortality rate.TD is usually induced by the use of antipsychotic drugs;however,the underlying mechanism remains unclear.Pharmacotherapy of TD includes cholinergic drugs,benzodiazepines,ginkgo biloba extract(GBE),antioxidants,amantadine,propanolol,botulinum toxin,valbenazine,and deutetrabenazine,whereas the non-pharmacotherapy approach includes modified electroconvulsive therapy(MECT)and deep brain stimulation.We successfully treated a chronic schizophrenia patient with comorbid long-term severe TD using deutetrabenazine,clozapine,and MECT.CASE SUMMARY A 69-year-old woman who was diagnosed as having schizophrenia 16 years ago developed severe TD after 6-mo prescription of risperidone oral solution.Her TD symptoms did not resolve despite various treatments,such as GBE,vitamin E,trihexyphenidyl,promethazine,benzodiazepines,and switching to quetiapine and olanzapine.After admission,she was given deutetrabenazine 6 mg bid.Her buccal tremor was slightly resolved 3 d later;however,her tongue remained protruded and could not be retracted.Quetiapine was switched to clozapine on day 4,and the buccal tremor remarkably resolved,and the tongue could be retracted into the mouth from day 6 onward.After three sessions of MECT,the buccal tremor resolved further.Since then,she has been able to take a semifluid diet,and her quality of life improved remarkably during 6 mo of follow-up.CONCLUSION TD is a serious condition which could be caused by antipsychotic medications;however,the best strategy against TD is prevention and monitoring during using antipsychotics.For patients with TD caused by antipsychotic medication use,multiple measures should be considered like switching to clozapine,adjunction with deutetrabenazine,or even MECT.展开更多
The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarr...The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.展开更多
Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebr...Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.展开更多
The realization of real-time thermal feedback for monitoring photothermal therapy(PTT)under near-infrared(NIR)light irradiation is of great interest and challenge for antitumor therapy.Herein,by assembling highly effi...The realization of real-time thermal feedback for monitoring photothermal therapy(PTT)under near-infrared(NIR)light irradiation is of great interest and challenge for antitumor therapy.Herein,by assembling highly efficient photothermal conversion gold nanorods and a temperature-responsive probe((E)-4-(4-(diethylamino)styryl)-1-methylpyridin-1-ium,PyS)within MOF-199,an intelligent nanoplatform(AMPP)was fabricated for simultaneous chemodynamic therapy and NIR light-induced temperature-feedback PTT.The fluorescence intensity and temperature of the PyS probe are linearly related due to the restriction of the rotation of the characteristic monomethine bridge.Moreover,the copper ions resulting from the degradation of MOF-199 in an acidic microenvironment can convert H_(2)O_(2)into•OH,resulting in tumor ablation through a Fenton-like reaction,and this process can be accelerated by increasing the temperature.This study establishes a feasible platform for fabricating highly sensitive temperature sensors for efficient temperature-feedback PTT.展开更多
BACKGROUND The efficacy of Vonoprazan-amoxicillin dual therapy(VAT)in the treatment of Helicobacter pylori(H.pylori)is controversial.AIM To evaluate the efficacy of VAT in the Chinese population.METHODS This prospecti...BACKGROUND The efficacy of Vonoprazan-amoxicillin dual therapy(VAT)in the treatment of Helicobacter pylori(H.pylori)is controversial.AIM To evaluate the efficacy of VAT in the Chinese population.METHODS This prospective,multicenter,randomized,open-label,and two-stage study was conducted at 23 centers in Fujian,China(May 2021-April 2022).H.pylori-infected patients were randomized to bismuth quadruple therapy(BQT),BQT-Vonoprazan(BQT-V),seven-day VAT(VAT-7),ten-day VAT(VAT-10),and fourteen-day VAT(VAT-14)groups.The primary endpoint was the H.pylori eradication rate.The secondary endpoint was the frequency of adverse events.This study was registered with the Chinese Clinical Trial Registry,ChiCTR2100045778.RESULTS In the first stage,VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated.In the second stage,the eradication rates for BQT,VAT-10,and VA-14 were 80.2%[95%confidence interval(95%CI):71.4%-86.8%],93.2%(86.6%-96.7%),92.2%(85.3%-96.0%)in the intention-to-treat(ITT)analysis,and 80.9%(95%CI:71.7%-87.5%),94.0%(87.5%-97.2%),and 93.9%(87.4%-97.2%)in the per-protocol analysis.The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group(P=0.022 and P=0.046,respectively).The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group(25.27%and 13.73%vs 37.62%,respectively;P<0.001).CONCLUSION VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT,with a more tolerable safety profile in H.pylori-infected patients in Fujian.Huang XP et al.VAT for H.pylori eradication.展开更多
Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monocl...Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.展开更多
Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied fo...Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy ...BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.展开更多
Introduction: Music therapy is a practice for helping and supporting people with intellectual and relational difficulties. This study illustrated the benefits of music therapy for young people living with intellectual...Introduction: Music therapy is a practice for helping and supporting people with intellectual and relational difficulties. This study illustrated the benefits of music therapy for young people living with intellectual disabilities (YLID) in an African context. Methodology: This study investigated six young individuals with intellectual disabilities who had undergone three years of music therapy. They were participants in the inclusive non-academic training program at the National School of Arts in Dakar from 2017 to 2019. Data collection utilized individual interviews with the youths, evaluation grids from teachers and psychiatrists. Guardians provided informed consent along with the assent of the young participants. Results: The six young were aged between 18 and 30 years old, with an average age of 24.6 years. Four of the YLID were male. Three young people with intellectual disabilities had delayed psychomotor development. Observations revealed the beneficial influence of music therapy on the health and well-being of young individuals. Music played a role in alleviating stress and anxiety among youth with intellectual disabilities (YLID), enhancing their mood and mental health. It assisted in navigating challenging situations and heightened alertness among YLID. Additionally, music therapy contributed to improvements in dyslexia, fine and gross motor skills, and memory development among intellectually disabled youth, ultimately facilitating their integration into society. Conclusion: In light of our results, music therapy makes a major contribution to the empowerment of YLID. Engaging in musical activities helps young people connect with others through instrumental expression and a sense of accomplishment. By facilitating music therapy, it becomes possible to combat discrimination and stigmatization, thus promoting the social inclusion of intellectually disabled youth. Therefore, it is important to promote music therapy in Senegal to meet the needs of YLID.展开更多
Ischemic stroke(IS)causes severe disability and high mortality worldwide.Stem cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current treatments.SC’s cell homing,differentiation and par...Ischemic stroke(IS)causes severe disability and high mortality worldwide.Stem cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current treatments.SC’s cell homing,differentiation and paracrine abilities give hope for neuroprotection.Recent studies on SC modification have enhanced therapeutic effects for IS,including gene transfection,nanoparticle modification,biomaterial modification and pretreatment.Thesemethods improve survival rate,homing,neural differentiation,and paracrine abilities in ischemic areas.However,many problems must be resolved before SC therapy can be clinically applied.These issues include production quality and quantity,stability during transportation and storage,as well as usage regulations.Herein,we reviewed the brief pathogenesis of IS,the“multi-mechanism”advantages of SCs for treating IS,various SC modification methods,and SC therapy challenges.We aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.展开更多
基金supported by the National High Level Hospital Clinical Research Funding(2022-GSP-QN-1)the National Clinical Research Center for Cardiovascular Diseases,Fuwai Hospital,Chinese Academy of Medical Sciences(NCRC2020013)+1 种基金the National Natural Science Foundation of China(81900323)China International Exchange and Promotion Association for Medical and Healthcare Investigator Sponsored Study(CN174125,DIREGL08735-DAPT)。
文摘BACKGROUND:To investigate the most appropriate dual antiplatelet therapy(DAPT)duration for patients with acute coronary syndrome(ACS)after drug-eluting stent(DES)implantation in the largest cardiovascular center of China.METHODS:We enrolled 5,187 consecutive patients with ACS who received DES from January to December 2013.Patients were divided into four groups based on DAPT duration:standard DAPT group(11-13 months,n=1,568)and prolonged DAPT groups(13-18 months[n=308],18-24 months[n=2,125],and>24 months[n=1,186]).Baseline characteristics and 5-year clinical outcomes were recorded.RESULTS:Baseline characteristics were similar across the four groups.Among the four groups,those with prolonged DAPT(18-24 months)had the lowest incidence of major adverse cardiovascular and cerebrovascular events(MACCEs)(14.1%vs.11.7%vs.9.6%vs.24.2%,P<0.001),all-cause death(4.8%vs.3.9%vs.2.1%vs.2.6%,P<0.001),cardiac death(3.1%vs.2.6%vs.1.4%vs.1.9%,P=0.004),and myocardial infarction(MI)(3.8%vs.4.2%vs.2.5%vs.5.8%,P<0.001).The incidence of bleeding was not different among the four groups(9.9%vs.9.4%vs.11.0%vs.9.4%,P=0.449).Cox multivariable analysis showed that prolonged DAPT(18-24 months)was an independent protective factor for MACCEs(hazard ratio[HR]0.802,95%confidence interval[CI]0.729-0.882,P<0.001),all-cause death(HR 0.660,95%CI 0.547-0.795,P<0.001),cardiac death(HR 0.663,95%CI 0.526-0.835,P<0.001),MI(HR 0.796,95%CI 0.662-0.957,P=0.015),and target vessel revascularization(HR 0.867,95%CI 0.755-0.996,P=0.044).Subgroup analysis for high bleeding risk showed that prolonged DAPT remained an independent protective factor for all-cause death and MACCEs.CONCLUSION:For patients with ACS after DES,appropriately prolonging the DAPT duration may be associated with a reduced risk of adverse ischemic events without increasing the bleeding risk.
文摘Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.
基金Supported by National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-022 and No.2022-PUMCH-D-002CAMS Innovation Fund for Medical Sciences,No.2021-1-I2M-003+1 种基金Undergraduate Innovation Program,No.2023-zglc-06034National Key Clinical Specialty Construction Project,No.ZK108000。
文摘BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE patients.AIM To improve overall understanding of this disease’s diagnosis and prognosis.METHODS We retrospectively analyzed the clinical,endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023,whose diagnosis was based on the 2007 diagnostic criteria.RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea.The common endoscopic manifestations were edema,villous blunting and mucosal hyperemia in the duodenum and ileum.Villous blunting(100%),deep crypt lymphocytic infiltration(67%),apoptotic bodies(50%),and mild intraepithelial lymphocytosis(69%)were observed in the duodenal biopsies.Moreover,there were other remarkable abnormalities,including reduced or absent goblet cells(duodenum 94%,ileum 62%),reduced or absent Paneth cells(duodenum 94%,ileum 69%)and neutrophil infiltration(duodenum 100%,ileum 69%).Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies.All patients received glucocorticoid therapy as the initial medication,of which 14/16 patients achieved a clinical response in 5(IQR:3-20)days.Immunosuppressants were administered to 9 patients with indications of steroid dependence(6/9),steroid refractory status(2/9),or intensified maintenance medication(1/9).During the median of 20.5 months of followup,2 patients died from multiple organ failure,and 1 was diagnosed with non-Hodgkin’s lymphoma.The cumulative relapse-free survival rates were 62.5%,55.6%and 37.0%at 6 months,12 months and 48 months,respectively.CONCLUSION Certain histopathological findings,including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies,might be potential diagnostic criteria for adult AIE.The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications,which highlights the need for early diagnosis and novel medications.
基金the Suzhou Medical Center,No.Szlcyxzx202103the National Natural Science Foundation of China,No.82171828+9 种基金the Key R&D Plan of Jiangsu Province(Social Development),No.BE2021652the Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011Wu Jieping Medical Foundation,No.320.6750.2021-01-12the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113Beijing Bethune Charitable Foundation,No.STLKY0016Research Projects of China Baoyuan Investment Co.,No.270004Suzhou Gusu Health Talent Program,No.GSWS2022028Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
文摘BACKGROUND Local mesenchymal stem cell(MSC)therapy for complex perianal fistulas(PFs)has shown considerable promise.But,the long-term safety and efficacy of MSC therapy in complex PFs remain unknown.AIM To explore the long-term effectiveness and safety of local MSC therapy for complex PFs.METHODS Sources included the PubMed,EMBASE,and Cochrane Library databases.A standard meta-analysis was performed using RevMan 5.3.RESULTS After screening,6 studies met the inclusion criteria.MSC therapy was associated with an improved long-term healing rate(HR)compared with the control condition[odds ratio(OR)=2.13;95%confidence interval(95%CI):1.34 to 3.38;P=0.001].Compared with fibrin glue(FG)therapy alone,MSC plus FG therapy was associated with an improved long-term HR(OR=2.30;95%CI:1.21 to 4.36;P=0.01).When magnetic resonance imaging was used to evaluate fistula healing,MSC therapy was found to achieve a higher long-term HR than the control treatment(OR=2.79;95%CI:1.37 to 5.67;P=0.005).There were no significant differences in long-term safety(OR=0.77;95%CI:0.27 to 2.24;P=0.64).CONCLUSION Our study indicated that local MSC therapy promotes long-term and sustained healing of complex PFs and that this method is safe.
文摘In this editorial we comment on the article published by Zhang et al in the recent issue of World Journal of Clinical Cases.We evaluate their claims on the benefit of use of Aspirin in the early management of patients with ischemic stroke.We also comment on their contention of using aspirin in the early management of patients with intracranial hemorrhage,a practice not seen in modern medicine.Large clinical trials such as the International Stroke Trial and the Chinese Acute Stroke Trial have shown the benefit of Aspirin use within 48 h of patients with Acute Ischemic Stroke.The findings were corroborated in the open-label trial performed by Zhang et al in a smaller sample group of 25 patients where they showed improvement in functional scores at 90 days without an increase in adverse events.As such,this intervention is also recommended by the American Heart Association stroke guidelines from 2021.With regard to Intracranial hemorrhage,traditional practice has been to discontinue or avoid antiplatelet therapy in these patient groups.However,no studies have been done to evaluate this management strategy that is more borne out of the mechanism behind Aspirin’s effect on the coagulation pathway.Zhang et al evaluate the benefits of Aspirin on patients with low-volume intracranial hemorrhage,i.e.,less than 30 mL on computed tomo-graphy imaging,and show no increase in mortality.The caveat of this finding is that all outcomes were pooled into one group for results,and the number of patients was low.While more studies with larger patient groups are required,the data from Zhang et al suggests that patients with small-volume intracranial hemorrhages may benefit from Aspirin administration in the acute phase of management.
基金from CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-002)National Key Clinical Specialty Construction Project(ZK108000)+1 种基金National High-Level Hospital Clinical Research Funding(2022-PUMCH-B-024)National Natural Science Foundation of China,Joint Fund Project(U20A600).
文摘Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.
文摘BACKGROUND Whether hyperbaric oxygen therapy(HBOT)can cause paradoxical herniation is still unclear.CASE SUMMARY A 65-year-old patient who was comatose due to brain trauma underwent decompressive craniotomy and gradually regained consciousness after surgery.HBOT was administered 22 d after surgery due to speech impairment.Paradoxical herniation appeared on the second day after treatment,and the patient’s condition worsened after receiving mannitol treatment at the rehabilitation hospital.After timely skull repair,the paradoxical herniation was resolved,and the patient regained consciousness and had a good recovery as observed at the follow-up visit.CONCLUSION Paradoxical herniation is rare and may be caused by HBOT.However,the underlying mechanism is unknown,and the understanding of this phenomenon is insufficient.The use of mannitol may worsen this condition.Timely skull repair can treat paradoxical herniation and prevent serious complications.
基金supported by the National Natural Science Foundation of China,No.31960120Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(both to ZW).
文摘Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.
文摘Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.
基金Science and Technology Program of Huzhou City,No.2023GYB32.
文摘BACKGROUND Tardive dyskinesia(TD)is a serious and disabling movement disorder;it impairs social function and quality of life and increases the mortality rate.TD is usually induced by the use of antipsychotic drugs;however,the underlying mechanism remains unclear.Pharmacotherapy of TD includes cholinergic drugs,benzodiazepines,ginkgo biloba extract(GBE),antioxidants,amantadine,propanolol,botulinum toxin,valbenazine,and deutetrabenazine,whereas the non-pharmacotherapy approach includes modified electroconvulsive therapy(MECT)and deep brain stimulation.We successfully treated a chronic schizophrenia patient with comorbid long-term severe TD using deutetrabenazine,clozapine,and MECT.CASE SUMMARY A 69-year-old woman who was diagnosed as having schizophrenia 16 years ago developed severe TD after 6-mo prescription of risperidone oral solution.Her TD symptoms did not resolve despite various treatments,such as GBE,vitamin E,trihexyphenidyl,promethazine,benzodiazepines,and switching to quetiapine and olanzapine.After admission,she was given deutetrabenazine 6 mg bid.Her buccal tremor was slightly resolved 3 d later;however,her tongue remained protruded and could not be retracted.Quetiapine was switched to clozapine on day 4,and the buccal tremor remarkably resolved,and the tongue could be retracted into the mouth from day 6 onward.After three sessions of MECT,the buccal tremor resolved further.Since then,she has been able to take a semifluid diet,and her quality of life improved remarkably during 6 mo of follow-up.CONCLUSION TD is a serious condition which could be caused by antipsychotic medications;however,the best strategy against TD is prevention and monitoring during using antipsychotics.For patients with TD caused by antipsychotic medication use,multiple measures should be considered like switching to clozapine,adjunction with deutetrabenazine,or even MECT.
基金supported by Zanjan University of Medical Sciences,Zanjan,Iran(Grant Number:A-12-1244-16&Ethical Code:IR.ZUMS.REC.1399.316).
文摘The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.
文摘Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.
基金supported by the National Natural Science Foundation of China(22171001,22305001,51972001,52372073)the Natural Science Foundation of Anhui Province of China(2108085MB49).
文摘The realization of real-time thermal feedback for monitoring photothermal therapy(PTT)under near-infrared(NIR)light irradiation is of great interest and challenge for antitumor therapy.Herein,by assembling highly efficient photothermal conversion gold nanorods and a temperature-responsive probe((E)-4-(4-(diethylamino)styryl)-1-methylpyridin-1-ium,PyS)within MOF-199,an intelligent nanoplatform(AMPP)was fabricated for simultaneous chemodynamic therapy and NIR light-induced temperature-feedback PTT.The fluorescence intensity and temperature of the PyS probe are linearly related due to the restriction of the rotation of the characteristic monomethine bridge.Moreover,the copper ions resulting from the degradation of MOF-199 in an acidic microenvironment can convert H_(2)O_(2)into•OH,resulting in tumor ablation through a Fenton-like reaction,and this process can be accelerated by increasing the temperature.This study establishes a feasible platform for fabricating highly sensitive temperature sensors for efficient temperature-feedback PTT.
基金Supported by the Natural Science Foundation of Fujian Province,No.2020J011087 and No.2022J011025Medical Innovation Project of Fujian Provincial Health Commission,No.2020CXA006Zhuhai Science and Technology Project,No.20181117E030040.
文摘BACKGROUND The efficacy of Vonoprazan-amoxicillin dual therapy(VAT)in the treatment of Helicobacter pylori(H.pylori)is controversial.AIM To evaluate the efficacy of VAT in the Chinese population.METHODS This prospective,multicenter,randomized,open-label,and two-stage study was conducted at 23 centers in Fujian,China(May 2021-April 2022).H.pylori-infected patients were randomized to bismuth quadruple therapy(BQT),BQT-Vonoprazan(BQT-V),seven-day VAT(VAT-7),ten-day VAT(VAT-10),and fourteen-day VAT(VAT-14)groups.The primary endpoint was the H.pylori eradication rate.The secondary endpoint was the frequency of adverse events.This study was registered with the Chinese Clinical Trial Registry,ChiCTR2100045778.RESULTS In the first stage,VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated.In the second stage,the eradication rates for BQT,VAT-10,and VA-14 were 80.2%[95%confidence interval(95%CI):71.4%-86.8%],93.2%(86.6%-96.7%),92.2%(85.3%-96.0%)in the intention-to-treat(ITT)analysis,and 80.9%(95%CI:71.7%-87.5%),94.0%(87.5%-97.2%),and 93.9%(87.4%-97.2%)in the per-protocol analysis.The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group(P=0.022 and P=0.046,respectively).The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group(25.27%and 13.73%vs 37.62%,respectively;P<0.001).CONCLUSION VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT,with a more tolerable safety profile in H.pylori-infected patients in Fujian.Huang XP et al.VAT for H.pylori eradication.
文摘Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.
文摘Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.
基金Supported by Shanghai Hospital Development Center Foundation,No.SHDC2022CRS033.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.
文摘Introduction: Music therapy is a practice for helping and supporting people with intellectual and relational difficulties. This study illustrated the benefits of music therapy for young people living with intellectual disabilities (YLID) in an African context. Methodology: This study investigated six young individuals with intellectual disabilities who had undergone three years of music therapy. They were participants in the inclusive non-academic training program at the National School of Arts in Dakar from 2017 to 2019. Data collection utilized individual interviews with the youths, evaluation grids from teachers and psychiatrists. Guardians provided informed consent along with the assent of the young participants. Results: The six young were aged between 18 and 30 years old, with an average age of 24.6 years. Four of the YLID were male. Three young people with intellectual disabilities had delayed psychomotor development. Observations revealed the beneficial influence of music therapy on the health and well-being of young individuals. Music played a role in alleviating stress and anxiety among youth with intellectual disabilities (YLID), enhancing their mood and mental health. It assisted in navigating challenging situations and heightened alertness among YLID. Additionally, music therapy contributed to improvements in dyslexia, fine and gross motor skills, and memory development among intellectually disabled youth, ultimately facilitating their integration into society. Conclusion: In light of our results, music therapy makes a major contribution to the empowerment of YLID. Engaging in musical activities helps young people connect with others through instrumental expression and a sense of accomplishment. By facilitating music therapy, it becomes possible to combat discrimination and stigmatization, thus promoting the social inclusion of intellectually disabled youth. Therefore, it is important to promote music therapy in Senegal to meet the needs of YLID.
基金supported by the National Natural Science Foundation of China(U22A20383,82003668)the Natural Science Foundation of Zhejiang Province(LD22H300002,LQ21H300002)Ningbo Technology Innovation 2025 Major Special Project(2022Z150).
文摘Ischemic stroke(IS)causes severe disability and high mortality worldwide.Stem cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current treatments.SC’s cell homing,differentiation and paracrine abilities give hope for neuroprotection.Recent studies on SC modification have enhanced therapeutic effects for IS,including gene transfection,nanoparticle modification,biomaterial modification and pretreatment.Thesemethods improve survival rate,homing,neural differentiation,and paracrine abilities in ischemic areas.However,many problems must be resolved before SC therapy can be clinically applied.These issues include production quality and quantity,stability during transportation and storage,as well as usage regulations.Herein,we reviewed the brief pathogenesis of IS,the“multi-mechanism”advantages of SCs for treating IS,various SC modification methods,and SC therapy challenges.We aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.