Background: At-home phototherapy devices for the treatment of acne have emerged as an appealing treatment option and as an effective adjunct treatment to existing modalities. The principal goal of the study was to det...Background: At-home phototherapy devices for the treatment of acne have emerged as an appealing treatment option and as an effective adjunct treatment to existing modalities. The principal goal of the study was to determine the changes in the number of inflammatory lesions in acne patients. Methods: Patients received instruction for daily at-home use of Silk’n Blue device for 12 weeks. Follow-up visits were conducted at 1 and 3 months to collect data. Results: Fifteen subjects with mild to severe cases experienced improvement over the course of the trial. The decrease in mean inflammatory acne counts (from 41.26 to 24.46) and mean percent reduction (41.8%) were statistically significant (p < 0.001). Some participants experienced percent reductions as great as 67%. No adverse events were recorded. Conclusions: The Silk’n Blue device is a safe and effective modality for at-home treatment of mild, moderate, and severe inflammatory acne vulgaris with proper use.展开更多
A proton therapy(PT)facility with multiple treatment rooms based on the superconducting cyclotron scheme is under development at Huazhong University of Science and Technology(HUST).This paper attempts to describe the ...A proton therapy(PT)facility with multiple treatment rooms based on the superconducting cyclotron scheme is under development at Huazhong University of Science and Technology(HUST).This paper attempts to describe the design considerations and implementation of the PT beamline from a systematic viewpoint.Design considerations covering beam optics and the influence of high-order aberrations,beam energy/intensity modulation,and beam orbit correction are described.In addition to the technical implementation of the main beamline components and subsystems,including the energy degrader,fast kicker,beamline magnets,beam diagnostic system,and beamline control system are introduced.展开更多
Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the und...Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.展开更多
BACKGROUND Sensory integration intervention is highly related to the child's effective interaction with the environment and the child's development.Currently,various sensory integration interventions are being...BACKGROUND Sensory integration intervention is highly related to the child's effective interaction with the environment and the child's development.Currently,various sensory integration interventions are being applied,but research methodological problems are arising due to unsystematic protocols.This study aims to present the optimal intervention protocol by presenting scientific standards for sensory integration intervention through meta-analysis.AIM To prove the effectiveness of sensory integration therapy,examine the latest trend of sensory integration studies in Korea,and provide clinical evidence for sensory integration therapies.METHODS The database of Korean search engines,including RISS,KISS,and DBpia,was used to search for related literature published from 2001 to October 2020.The keywords,“Children”,“Sensory integration”,“Integrated sensory”,“Sensorymotor”,and“Sensory stimulation”were used in this search.Then,a meta-analysis was conducted on 24 selected studiesRISS,KISS,and DBpia,was used to search for related literature published from 2001 to October 2020.The keywords,“Children”,“Sensory integration”,“Integrated sensory”,“Sensorymotor”,and“Sensory stimulation”were used in this search.Then,a meta-analysis was conducted on 24 selected studies.RESULTS Sensory integration intervention has been proven effective in children with cerebral palsy,autism spectrum disorder,attention deficit/hyperactivity disorder,developmental disorder,and intellectual disability in relation to the diagnosis of children.Regarding sensory integration therapies,1:1 individual treatment with a therapist or a therapy session lasting for 40 min was most effective.In terms of dependent variables,sensory integration therapy effectively promoted social skills,adaptive behavior,sensory processing,and gross motor and fine motor skills.CONCLUSION The results of this study may be used as therapeutic evidence for sensory integration intervention in the clinical field of occupational therapy for children,and can help to present standards for sensory integration intervention protocols.展开更多
The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over time.How-ever,this prolonged survival has also been associated with a highe...The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over time.How-ever,this prolonged survival has also been associated with a higher likelihood of cancer diagnoses among these patients including breast cancer.Breast cancer treatment typically involves surgery,radiation,and systemic therapies,with ap-proaches tailored to cancer type,stage,and patient preferences.However,renal replacement therapy complicates systemic therapy due to altered drug clearance and the necessity for dialysis sessions.This review emphasizes the need for opti-mized dosing and administration strategies for systemic breast cancer treatments in dialysis patients,aiming to ensure both efficacy and safety.Additionally,ch-allenges in breast cancer screening and diagnosis in this population,including soft-tissue calcifications,are highlighted.展开更多
This editorial contains comments on the article“Systematic sequential therapy for ex vivo liver resection and autotransplantation:A case report and review of li-terature”in the recent issue of World Journal of Gastr...This editorial contains comments on the article“Systematic sequential therapy for ex vivo liver resection and autotransplantation:A case report and review of li-terature”in the recent issue of World Journal of Gastrointestinal Surgery.It points out the actuality and importance of the article and focuses primarily on the role and place of ex vivo liver resection and autotransplantation(ELRAT)and systemic therapy,underlying molecular mechanisms for targeted therapy in perihilar cho-langiocarcinoma(pCCA)management.pCCA is a tough malignancy with a high proportion of advanced disease at the time of diagnosis.The only curative option is radical surgery.Surgical excision and reconstruction become extremely com-plicated and not always could be performed even in localized disease.On the other hand,ELRAT takes its place among surgical options for carefully selected pCCA patients.In advanced disease,systemic therapy becomes a viable option to prolong survival.This editorial describes current possibilities in chemotherapy and reveals underlying mechanisms and projections in targeted therapy with ki-nase inhibitors and immunotherapy in both palliative and adjuvant settings.Fi-broblast grow factor and fibroblast grow factor receptor,human epidermal grow-th factor receptor 2,isocitrate dehydrogenase,and protein kinase cAMP activated catalytic subunit alpha(PRKACA)and beta(PRKACB)pathways have been ac-tively investigated in CCA in last years.Several agents were introduced and approved by the Food and Drug Administration.They all demonstrated mean-ingful activity in CCA patients with no global change in outcomes.That is why every successfully treated patient counts,especially those with advanced disease.In conclusion,pCCA is still hard to treat due to late diagnosis and extremely complicated surgical options.ELRAT also brings some hope,but it could be performed in very carefully selected patients.Advanced disease requires systemic anticancer treatment,which is supposed to be individualized according to the genetic and molecular features of cancer cells.Targeted therapy in combination with chemo-immunotherapy could be effective in susceptible patients.展开更多
BACKGROUND The association between tumor-infiltrating lymphocyte(TIL)levels and the res-ponse to neoadjuvant therapy(NAT)in patients with triple-negative breast cancer(TNBC)remains unclear.AIM To investigate the predi...BACKGROUND The association between tumor-infiltrating lymphocyte(TIL)levels and the res-ponse to neoadjuvant therapy(NAT)in patients with triple-negative breast cancer(TNBC)remains unclear.AIM To investigate the predictive potential of TIL levels for the response to NAT in TNBC patients.METHODS A systematic search of the National Center for Biotechnology Information PubMed database was performed to collect relevant published literature prior to August 31,2023.The correlation between TIL levels and the NAT pathologic com-plete response(pCR)in TNBC patients was assessed using a systematic review and meta-analysis.Subgroup analysis,sensitivity analysis,and publication bias analysis were also conducted.RESULTS A total of 32 studies were included in this meta-analysis.The overall meta-ana-lysis results indicated that the pCR rate after NAT treatment in TNBC patients in the high TIL subgroup was significantly greater than that in patients in the low TIL subgroup(48.0%vs 27.7%)(risk ratio 2.01;95%confidence interval 1.77-2.29;P<0.001,I2=56%).Subgroup analysis revealed that the between-study hetero-geneity originated from differences in study design,TIL level cutoffs,and study populations.Publication bias could have existed in the included studies.The meta-analysis based on different NAT protocols revealed that all TNBC patients with high levels of TILs had a greater rate of pCR after NAT treatment in all protocols(all P≤0.01),and there was no significant between-protocol difference in the statistics among the different NAT protocols(P=0.29).Additionally,sensitivity analysis demonstrated that the overall results of the meta-analysis remained consistent when the included studies were individually excluded.CONCLUSION TILs can serve as a predictor of the response to NAT treatment in TNBC patients.TNBC patients with high levels of TILs exhibit a greater NAT pCR rate than those with low levels of TILs,and this predictive capability is con-sistent across different NAT regimens.展开更多
The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trial...The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC(J Clin Oncol 2019;37:3223-3233),NCT04165772(N Engl J Med 2022;386:2363-2376),and PROSPECT(N Engl J Med 2023;389:322-334).In this review,we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.展开更多
Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-der...Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.展开更多
Introduction: In hyperthyroidism, selective irradiation of the thyroid gland with radioactive iodine is a radical treatment and an alternative to surgery. The aim of this review is to assess the medium-term efficacy o...Introduction: In hyperthyroidism, selective irradiation of the thyroid gland with radioactive iodine is a radical treatment and an alternative to surgery. The aim of this review is to assess the medium-term efficacy of outpatient treatment of hyperthyroidism with iodine-131 in Africa. Methods: We identified the studies carried out in Africa on outpatient radiation therapy between 2016 and 2020. For each article included, we noted the country concerned and the year of publication, the numbers studied, the socio-demographic characteristics of the patients, the indications for radio iodine therapy, the dose administered, the results of the hormonal dosage 6 months after radiation. Results: 13 retrospective studies were included to constitute a total population of 925 patients. The average age was 40.77 years, the sex ratio of 1/5.4 with a clear female predominance. The 3 main etiologies of hyperthyroidism justifying outpatient radio iodine therapy were Graves’ disease (55.89%), toxic multinodular goiter (22.70%) and toxic adenoma (21.40%). The average dose of iodine 131 administered per course is 13.7 mCi. No short-and medium-term complications were reported. The radio iodine therapy was effective in 86.08% (n = 796) of the patients with extremes of 72% and 100%. Conclusion: Radio iodine therapy is effective in Africa. It is simple, inexpensive on an outpatient basis and well tolerated. The introduction of outpatient radio iodine therapy could improve the management of patients with hyperthyroidism in Burkina Faso.展开更多
BACKGROUND Due to increasing resistance rates of Helicobacter pylori(H.pylori)to different antibiotics,failures in eradication therapies are becoming more frequent.Even though eradication criteria and treatment algori...BACKGROUND Due to increasing resistance rates of Helicobacter pylori(H.pylori)to different antibiotics,failures in eradication therapies are becoming more frequent.Even though eradication criteria and treatment algorithms for first-line and second-line therapy against H.pylori infection are well-established,there is no clear recommendation for third-line and rescue therapy in refractory H.pylori infection.AIM To perform a systematic review evaluating the efficacy and safety of rescue therapies against refractory H.pylori infection.METHODS A systematic search of available rescue treatments for refractory H.pylori infection was conducted on the National Library of Medicine’s PubMed search platform based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Randomized or non-randomized clinical trials and observational studies evaluating the effectiveness of H.pylori infection rescue therapies were included.RESULTS Twenty-eight studies were included in the analysis of mean eradication rates as rescue therapy,and 21 of these were selected for analysis of mean eradication rate as third-line treatment.For rifabutin-,sitafloxacin-,levofloxacin-,or metronidazole-based triple-therapy as third-line treatment,mean eradication rates of 81.6%and 84.4%,79.4%and 81.5%,55.7%and 60.6%,and 62.0%and 63.0%were found in intention-to-treat(ITT)and per-protocol(PP)analysis,respectively.For third-line quadruple therapy,mean eradication rates of 69.2%and 72.1%were found for bismuth quadruple therapy(BQT),88.9%and 90.9%for bismuth quadruple therapy,three-in-one,Pylera®(BQT-Pylera),and 61.3%and 64.2%for non-BQT)in ITT and PP analysis,respectively.For rifabutin-,sitafloxacin-,levofloxacin-,or metronidazole-based triple therapy as rescue therapy,mean eradication rates of 75.4%and 78.8%,79.4 and 81.5%,55.7%and 60.6%,and 62.0%and 63.0%were found in ITT and PP analysis,respectively.For quadruple therapy as rescue treatment,mean eradication rates of 76.7%and 79.2%for BQT,84.9%and 87.8%for BQT-Pylera,and 61.3%and 64.2%for non-BQT were found in ITT and PP analysis,respectively.For susceptibility-guided therapy,mean eradication rates as third-line and rescue treatment were 75.0%in ITT and 79.2%in PP analysis.CONCLUSION We recommend sitafloxacin-based triple therapy containing vonoprazan in regions with low macrolide resistance profile.In regions with known resistance to macrolides or unavailability of bismuth,rifabutin-based triple therapy is recommended.展开更多
Objective: The aim of this study was to investigate the factors influencing pathological complete response(pCR)rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab(H) + pertuzumab(P)] th...Objective: The aim of this study was to investigate the factors influencing pathological complete response(pCR)rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab(H) + pertuzumab(P)] therapy combined with chemotherapy. Additionally, the consistency of the Miller-Payne and residual cancer burden(RCB)systems in evaluating the efficacy of neoadjuvant therapy for early human epidermal growth factor receptor-2(HER2)+ breast cancer was analyzed.Methods: The clinicopathological data of female patients with early-stage HER2+ breast cancer who received dual-target neoadjuvant therapy at 26 hospitals of the Chinese Society of Breast Surgery(CSBrS) from March 2019 to December 2021 were collected. Patients were allocated to four groups: the HER2 immunohistochemistry(IHC)3+/hormone receptor(HR)-, IHC3+/HR+, IHC2+ in situ hybridization(ISH)+/HR-and IHC2+ ISH+/HR+groups. The overall pCR rate for patients, the pCR rate in each group and the factors affecting the pCR rate were analyzed. The consistency between the Miller-Payne and RCB systems in assessing the efficacy of neoadjuvant therapy was analyzed.Results: From March 1, 2019, to December 31, 2021, 77,376 female patients with early-stage breast cancer were treated at 26 hospitals;18,853(24.4%) of these patients were HER2+. After exclusion of unqualified patients, 2,395 patients who received neoadjuvant dual-target(H+P) therapy combined with chemotherapy were included in this study. The overall pCR rate was 53.0%, and the patients' HR statuses and different HER2+ statuses were significantly correlated with the pCR rate(P<0.05). The consistency of the pathological efficacy assessed by the Miller-Payne and RCB systems was 88.0%(κ=0.717, P<0.001).Conclusions: Different HER2 expression statuses and HR expression statuses are correlated with the pCR rate after dual-target neoadjuvant therapy in HER2+ breast cancer patients. There is a relatively good consistency between Miller-Payne and RCB systems in evaluating the pathologic efficacy of neoadjuvant therapy for HER2+breast cancer.展开更多
Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective deli...Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.展开更多
BACKGROUND Chemotherapy is the primary treatment for patients with advanced gastrointestinal cancer,but it has many adverse reactions,particularly nausea and vomiting.Music therapy can reduce anxiety symptoms,avoid th...BACKGROUND Chemotherapy is the primary treatment for patients with advanced gastrointestinal cancer,but it has many adverse reactions,particularly nausea and vomiting.Music therapy can reduce anxiety symptoms,avoid the response to the human body under various stress conditions through psychological adjustment,and improve the adverse reactions of chemotherapy.AIM To investigate the impact of music therapy on relieving gastrointestinal adverse reactions in chemotherapy for patients with digestive tract cancer by metaanalysis.METHODS EMBASE,PubMed,OVID,WoS,CNKI,CBM,and VIP database were all used for searching relevant literature,and the efficacy after treatment was combined for analysis and evaluation.RESULTS This study included seven articles.The results of meta-analysis indicated that music therapy could reduce the nausea symptom score of patients after chemotherapy[mean difference(MD)=-3.15,95%confidence interval(CI):-4.62 to-1.68,Z=-4.20,P<0.0001].Music therapy could reduce the vomiting symptom score of patients after chemotherapy(MD=-2.28,95%CI:-2.46 to-2.11,Z=-25.15,P<0.0001).Furthermore,music therapy could minimize the incidence of grade I and above nausea or vomiting in patients after chemotherapy(odds ratio=0.38,95%CI:0.26-0.56,Z=-4.88,P<0.0001).Meta-regression analysis found that publication year was not a specific factor affecting the combined results.There was no significant publication bias(P>0.05).CONCLUSION Music therapy can significantly improve the scores of nausea and vomiting symptoms in patients with digestive system cancer during chemotherapy and reduce the incidence of grade I and above nausea and vomiting after chemotherapy,making it an effective psychological intervention method worthy of clinical promotion.展开更多
Immunotherapy has become a promising research“hotspot”in cancer treatment.“Soldier”immune cells are not uniform throughout the body;they accumulate mostly in the immune organs such as the spleen and lymph nodes(LN...Immunotherapy has become a promising research“hotspot”in cancer treatment.“Soldier”immune cells are not uniform throughout the body;they accumulate mostly in the immune organs such as the spleen and lymph nodes(LNs),etc.The unique structure of LNs provides the microenvironment suitable for the survival,activation,and proliferation of multiple types of immune cells.LNs play an important role in both the initiation of adaptive immunity and the generation of durable anti-tumor responses.Antigens taken up by antigen-presenting cells in peripheral tissues need to migrate with lymphatic fluid to LNs to activate the lymphocytes therein.Meanwhile,the accumulation and retaining of many immune functional compounds in LNs enhance their efficacy significantly.Therefore,LNs have become a key target for tumor immunotherapy.Unfortunately,the nonspecific distribution of the immune drugs in vivo greatly limits the activation and proliferation of immune cells,which leads to unsatisfactory anti-tumor effects.The efficient nano-delivery system to LNs is an effective strategy to maximize the efficacy of immune drugs.Nano-delivery systems have shown beneficial in improving biodistribution and enhancing accumulation in lymphoid tissues,exhibiting powerful and promising prospects for achieving effective delivery to LNs.Herein,the physiological structure and the delivery barriers of LNs were summarized and the factors affecting LNs accumulation were discussed thoroughly.Moreover,developments in nano-delivery systems were reviewed and the transformation prospects of LNs targeting nanocarriers were summarized and discussed.展开更多
BACKGROUND Perihilar cholangiocarcinoma(pCCA)is a highly malignant tumor arising from the biliary tree.Radical surgery is the only treatment offering a chance of long-term survival.However,limited by the tumor’s anat...BACKGROUND Perihilar cholangiocarcinoma(pCCA)is a highly malignant tumor arising from the biliary tree.Radical surgery is the only treatment offering a chance of long-term survival.However,limited by the tumor’s anatomic location and peri-vascular invasion,most patients lose the chance for curative treatment.Therefore,more methods to increase the resectability of tumors as well as to improve outcomes are needed.CASE SUMMARY A 68-year-old female patient had a hepatic hilar mass without obvious symptoms.Laboratory results showed hepatitis B positivity.Magnetic resonance imaging indicated that the mass(maximum diameter:41 mm)invaded the left and right branches of the main portal vein,as well as the middle,left and right hepatic veins;enlarged lymph nodes were also detected in the hilum.The patient was diagnosed with pCCA,and the clinical stage was determined to be T4N1M0(stage IIIC).Considering the tumor’s anatomic location and vascular invasion,systematic conversion therapy followed by ex vivo liver resection and autotrans-plantation(ELRA)was determined as personalized treatment for this patient.Our original systemic sequential therapeutic strategy(lenvatinib and tislelizumab in combination with gemcitabine and cisplatin)was successfully adopted as conversion therapy because she achieved partial response after three cycles of treatment,without severe toxicity.ELRA,anastomotic reconstruction of the middle hepatic vein,right hepatic vein,root of portal vein,inferior vena cava and right hepatic artery,and lymph node dissection were performed at one month after systemic therapy.Pathological and immunohistochemical examination confirmed the diagnosis of pCCA with lymph node metastasis.Although the middle hepatic vein was partially obstructed four months later,hepatic vein stent implantation successfully addressed this problem.The patient has survived for 22 mo after the diagnosis,with no evidence of recurrence or metastasis.CONCLUSION An effective therapeutic strategy for conversion therapy greatly increases the feasibility and efficiency of ELRA.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
Objective:Neoadjuvant therapy(NAT)has been widely implemented as an essential treatment to improve therapeutic efficacy in patients with locally-advanced cancer to reduce tumor burden and prolong survival,particularly...Objective:Neoadjuvant therapy(NAT)has been widely implemented as an essential treatment to improve therapeutic efficacy in patients with locally-advanced cancer to reduce tumor burden and prolong survival,particularly for human epidermal growth receptor 2-positive and triple-negative breast cancer.The role of peripheral immune components in predicting therapeutic responses has received limited attention.Herein we determined the relationship between dynamic changes in peripheral immune indices and therapeutic responses during NAT administration.Methods:Peripheral immune index data were collected from 134 patients before and after NAT.Logistic regression and machine learning algorithms were applied to the feature selection and model construction processes,respectively.Results:Peripheral immune status with a greater number of CD3^(+)T cells before and after NAT,and a greater number of CD8^(+)T cells,fewer CD4^(+)T cells,and fewer NK cells after NAT was significantly related to a pathological complete response(P<0.05).The post-NAT NK cell-to-pre-NAT NK cell ratio was negatively correlated with the response to NAT(HR=0.13,P=0.008).Based on the results of logistic regression,14 reliable features(P<0.05)were selected to construct the machine learning model.The random forest model exhibited the best power to predict efficacy of NAT among 10 machine learning model approaches(AUC=0.733).Conclusions:Statistically significant relationships between several specific immune indices and the efficacy of NAT were revealed.A random forest model based on dynamic changes in peripheral immune indices showed robust performance in predicting NAT efficacy.展开更多
Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the sci...Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.展开更多
文摘Background: At-home phototherapy devices for the treatment of acne have emerged as an appealing treatment option and as an effective adjunct treatment to existing modalities. The principal goal of the study was to determine the changes in the number of inflammatory lesions in acne patients. Methods: Patients received instruction for daily at-home use of Silk’n Blue device for 12 weeks. Follow-up visits were conducted at 1 and 3 months to collect data. Results: Fifteen subjects with mild to severe cases experienced improvement over the course of the trial. The decrease in mean inflammatory acne counts (from 41.26 to 24.46) and mean percent reduction (41.8%) were statistically significant (p < 0.001). Some participants experienced percent reductions as great as 67%. No adverse events were recorded. Conclusions: The Silk’n Blue device is a safe and effective modality for at-home treatment of mild, moderate, and severe inflammatory acne vulgaris with proper use.
基金the National Key Research and Development Program of China(No.2016YFC0105305)the National Natural Science Foundation of China(11975107)the Program for HUST Academic Frontier Youth Team.
文摘A proton therapy(PT)facility with multiple treatment rooms based on the superconducting cyclotron scheme is under development at Huazhong University of Science and Technology(HUST).This paper attempts to describe the design considerations and implementation of the PT beamline from a systematic viewpoint.Design considerations covering beam optics and the influence of high-order aberrations,beam energy/intensity modulation,and beam orbit correction are described.In addition to the technical implementation of the main beamline components and subsystems,including the energy degrader,fast kicker,beamline magnets,beam diagnostic system,and beamline control system are introduced.
基金funded by the Spanish Ministry of Economy and Competitiveness,No.PID(2019)-106498GB-100 (to MVS)by the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional"Una manera de hacer Europa",No.PI19/00071 (to MAB)+2 种基金the RETICS subprograms of Spanish Networks OftoRed,Nos.RD16/0008/0026 (to DGB) and RD16/0008/0016 (to DGB)RICORS Terav,No.RD16/0011/0001 (to DGB)from Instituto de Salud CarlosⅢby the Fundacion Seneca,Agencia de Cienciay Tecnologia Región de Murcia,No.19881/GERM/15 (all to MVS)
文摘Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.
文摘BACKGROUND Sensory integration intervention is highly related to the child's effective interaction with the environment and the child's development.Currently,various sensory integration interventions are being applied,but research methodological problems are arising due to unsystematic protocols.This study aims to present the optimal intervention protocol by presenting scientific standards for sensory integration intervention through meta-analysis.AIM To prove the effectiveness of sensory integration therapy,examine the latest trend of sensory integration studies in Korea,and provide clinical evidence for sensory integration therapies.METHODS The database of Korean search engines,including RISS,KISS,and DBpia,was used to search for related literature published from 2001 to October 2020.The keywords,“Children”,“Sensory integration”,“Integrated sensory”,“Sensorymotor”,and“Sensory stimulation”were used in this search.Then,a meta-analysis was conducted on 24 selected studiesRISS,KISS,and DBpia,was used to search for related literature published from 2001 to October 2020.The keywords,“Children”,“Sensory integration”,“Integrated sensory”,“Sensorymotor”,and“Sensory stimulation”were used in this search.Then,a meta-analysis was conducted on 24 selected studies.RESULTS Sensory integration intervention has been proven effective in children with cerebral palsy,autism spectrum disorder,attention deficit/hyperactivity disorder,developmental disorder,and intellectual disability in relation to the diagnosis of children.Regarding sensory integration therapies,1:1 individual treatment with a therapist or a therapy session lasting for 40 min was most effective.In terms of dependent variables,sensory integration therapy effectively promoted social skills,adaptive behavior,sensory processing,and gross motor and fine motor skills.CONCLUSION The results of this study may be used as therapeutic evidence for sensory integration intervention in the clinical field of occupational therapy for children,and can help to present standards for sensory integration intervention protocols.
文摘The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over time.How-ever,this prolonged survival has also been associated with a higher likelihood of cancer diagnoses among these patients including breast cancer.Breast cancer treatment typically involves surgery,radiation,and systemic therapies,with ap-proaches tailored to cancer type,stage,and patient preferences.However,renal replacement therapy complicates systemic therapy due to altered drug clearance and the necessity for dialysis sessions.This review emphasizes the need for opti-mized dosing and administration strategies for systemic breast cancer treatments in dialysis patients,aiming to ensure both efficacy and safety.Additionally,ch-allenges in breast cancer screening and diagnosis in this population,including soft-tissue calcifications,are highlighted.
文摘This editorial contains comments on the article“Systematic sequential therapy for ex vivo liver resection and autotransplantation:A case report and review of li-terature”in the recent issue of World Journal of Gastrointestinal Surgery.It points out the actuality and importance of the article and focuses primarily on the role and place of ex vivo liver resection and autotransplantation(ELRAT)and systemic therapy,underlying molecular mechanisms for targeted therapy in perihilar cho-langiocarcinoma(pCCA)management.pCCA is a tough malignancy with a high proportion of advanced disease at the time of diagnosis.The only curative option is radical surgery.Surgical excision and reconstruction become extremely com-plicated and not always could be performed even in localized disease.On the other hand,ELRAT takes its place among surgical options for carefully selected pCCA patients.In advanced disease,systemic therapy becomes a viable option to prolong survival.This editorial describes current possibilities in chemotherapy and reveals underlying mechanisms and projections in targeted therapy with ki-nase inhibitors and immunotherapy in both palliative and adjuvant settings.Fi-broblast grow factor and fibroblast grow factor receptor,human epidermal grow-th factor receptor 2,isocitrate dehydrogenase,and protein kinase cAMP activated catalytic subunit alpha(PRKACA)and beta(PRKACB)pathways have been ac-tively investigated in CCA in last years.Several agents were introduced and approved by the Food and Drug Administration.They all demonstrated mean-ingful activity in CCA patients with no global change in outcomes.That is why every successfully treated patient counts,especially those with advanced disease.In conclusion,pCCA is still hard to treat due to late diagnosis and extremely complicated surgical options.ELRAT also brings some hope,but it could be performed in very carefully selected patients.Advanced disease requires systemic anticancer treatment,which is supposed to be individualized according to the genetic and molecular features of cancer cells.Targeted therapy in combination with chemo-immunotherapy could be effective in susceptible patients.
基金Supported by Henan Province Medical Science and Technology Tackling Plan Joint Construction Project,No.LHGJ20220684.
文摘BACKGROUND The association between tumor-infiltrating lymphocyte(TIL)levels and the res-ponse to neoadjuvant therapy(NAT)in patients with triple-negative breast cancer(TNBC)remains unclear.AIM To investigate the predictive potential of TIL levels for the response to NAT in TNBC patients.METHODS A systematic search of the National Center for Biotechnology Information PubMed database was performed to collect relevant published literature prior to August 31,2023.The correlation between TIL levels and the NAT pathologic com-plete response(pCR)in TNBC patients was assessed using a systematic review and meta-analysis.Subgroup analysis,sensitivity analysis,and publication bias analysis were also conducted.RESULTS A total of 32 studies were included in this meta-analysis.The overall meta-ana-lysis results indicated that the pCR rate after NAT treatment in TNBC patients in the high TIL subgroup was significantly greater than that in patients in the low TIL subgroup(48.0%vs 27.7%)(risk ratio 2.01;95%confidence interval 1.77-2.29;P<0.001,I2=56%).Subgroup analysis revealed that the between-study hetero-geneity originated from differences in study design,TIL level cutoffs,and study populations.Publication bias could have existed in the included studies.The meta-analysis based on different NAT protocols revealed that all TNBC patients with high levels of TILs had a greater rate of pCR after NAT treatment in all protocols(all P≤0.01),and there was no significant between-protocol difference in the statistics among the different NAT protocols(P=0.29).Additionally,sensitivity analysis demonstrated that the overall results of the meta-analysis remained consistent when the included studies were individually excluded.CONCLUSION TILs can serve as a predictor of the response to NAT treatment in TNBC patients.TNBC patients with high levels of TILs exhibit a greater NAT pCR rate than those with low levels of TILs,and this predictive capability is con-sistent across different NAT regimens.
基金National Science and Technology Council,No.NSTC 112-2314-B-039-048.
文摘The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC(J Clin Oncol 2019;37:3223-3233),NCT04165772(N Engl J Med 2022;386:2363-2376),and PROSPECT(N Engl J Med 2023;389:322-334).In this review,we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.
基金supported by Quzhou City Jiang District Life Oasis Public Welfare Service Center,Health and Health Development Promotion Project(Oncology Research Special Project,no:BJHA-CRP-027).
文摘Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.
文摘Introduction: In hyperthyroidism, selective irradiation of the thyroid gland with radioactive iodine is a radical treatment and an alternative to surgery. The aim of this review is to assess the medium-term efficacy of outpatient treatment of hyperthyroidism with iodine-131 in Africa. Methods: We identified the studies carried out in Africa on outpatient radiation therapy between 2016 and 2020. For each article included, we noted the country concerned and the year of publication, the numbers studied, the socio-demographic characteristics of the patients, the indications for radio iodine therapy, the dose administered, the results of the hormonal dosage 6 months after radiation. Results: 13 retrospective studies were included to constitute a total population of 925 patients. The average age was 40.77 years, the sex ratio of 1/5.4 with a clear female predominance. The 3 main etiologies of hyperthyroidism justifying outpatient radio iodine therapy were Graves’ disease (55.89%), toxic multinodular goiter (22.70%) and toxic adenoma (21.40%). The average dose of iodine 131 administered per course is 13.7 mCi. No short-and medium-term complications were reported. The radio iodine therapy was effective in 86.08% (n = 796) of the patients with extremes of 72% and 100%. Conclusion: Radio iodine therapy is effective in Africa. It is simple, inexpensive on an outpatient basis and well tolerated. The introduction of outpatient radio iodine therapy could improve the management of patients with hyperthyroidism in Burkina Faso.
文摘BACKGROUND Due to increasing resistance rates of Helicobacter pylori(H.pylori)to different antibiotics,failures in eradication therapies are becoming more frequent.Even though eradication criteria and treatment algorithms for first-line and second-line therapy against H.pylori infection are well-established,there is no clear recommendation for third-line and rescue therapy in refractory H.pylori infection.AIM To perform a systematic review evaluating the efficacy and safety of rescue therapies against refractory H.pylori infection.METHODS A systematic search of available rescue treatments for refractory H.pylori infection was conducted on the National Library of Medicine’s PubMed search platform based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Randomized or non-randomized clinical trials and observational studies evaluating the effectiveness of H.pylori infection rescue therapies were included.RESULTS Twenty-eight studies were included in the analysis of mean eradication rates as rescue therapy,and 21 of these were selected for analysis of mean eradication rate as third-line treatment.For rifabutin-,sitafloxacin-,levofloxacin-,or metronidazole-based triple-therapy as third-line treatment,mean eradication rates of 81.6%and 84.4%,79.4%and 81.5%,55.7%and 60.6%,and 62.0%and 63.0%were found in intention-to-treat(ITT)and per-protocol(PP)analysis,respectively.For third-line quadruple therapy,mean eradication rates of 69.2%and 72.1%were found for bismuth quadruple therapy(BQT),88.9%and 90.9%for bismuth quadruple therapy,three-in-one,Pylera®(BQT-Pylera),and 61.3%and 64.2%for non-BQT)in ITT and PP analysis,respectively.For rifabutin-,sitafloxacin-,levofloxacin-,or metronidazole-based triple therapy as rescue therapy,mean eradication rates of 75.4%and 78.8%,79.4 and 81.5%,55.7%and 60.6%,and 62.0%and 63.0%were found in ITT and PP analysis,respectively.For quadruple therapy as rescue treatment,mean eradication rates of 76.7%and 79.2%for BQT,84.9%and 87.8%for BQT-Pylera,and 61.3%and 64.2%for non-BQT were found in ITT and PP analysis,respectively.For susceptibility-guided therapy,mean eradication rates as third-line and rescue treatment were 75.0%in ITT and 79.2%in PP analysis.CONCLUSION We recommend sitafloxacin-based triple therapy containing vonoprazan in regions with low macrolide resistance profile.In regions with known resistance to macrolides or unavailability of bismuth,rifabutin-based triple therapy is recommended.
基金supported by Beijing Science and Technology Innovation Medical Development Foundation (No. KC2021-JF-0167-01 and No. KC2021-JF-0167-24)。
文摘Objective: The aim of this study was to investigate the factors influencing pathological complete response(pCR)rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab(H) + pertuzumab(P)] therapy combined with chemotherapy. Additionally, the consistency of the Miller-Payne and residual cancer burden(RCB)systems in evaluating the efficacy of neoadjuvant therapy for early human epidermal growth factor receptor-2(HER2)+ breast cancer was analyzed.Methods: The clinicopathological data of female patients with early-stage HER2+ breast cancer who received dual-target neoadjuvant therapy at 26 hospitals of the Chinese Society of Breast Surgery(CSBrS) from March 2019 to December 2021 were collected. Patients were allocated to four groups: the HER2 immunohistochemistry(IHC)3+/hormone receptor(HR)-, IHC3+/HR+, IHC2+ in situ hybridization(ISH)+/HR-and IHC2+ ISH+/HR+groups. The overall pCR rate for patients, the pCR rate in each group and the factors affecting the pCR rate were analyzed. The consistency between the Miller-Payne and RCB systems in assessing the efficacy of neoadjuvant therapy was analyzed.Results: From March 1, 2019, to December 31, 2021, 77,376 female patients with early-stage breast cancer were treated at 26 hospitals;18,853(24.4%) of these patients were HER2+. After exclusion of unqualified patients, 2,395 patients who received neoadjuvant dual-target(H+P) therapy combined with chemotherapy were included in this study. The overall pCR rate was 53.0%, and the patients' HR statuses and different HER2+ statuses were significantly correlated with the pCR rate(P<0.05). The consistency of the pathological efficacy assessed by the Miller-Payne and RCB systems was 88.0%(κ=0.717, P<0.001).Conclusions: Different HER2 expression statuses and HR expression statuses are correlated with the pCR rate after dual-target neoadjuvant therapy in HER2+ breast cancer patients. There is a relatively good consistency between Miller-Payne and RCB systems in evaluating the pathologic efficacy of neoadjuvant therapy for HER2+breast cancer.
文摘Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.
文摘BACKGROUND Chemotherapy is the primary treatment for patients with advanced gastrointestinal cancer,but it has many adverse reactions,particularly nausea and vomiting.Music therapy can reduce anxiety symptoms,avoid the response to the human body under various stress conditions through psychological adjustment,and improve the adverse reactions of chemotherapy.AIM To investigate the impact of music therapy on relieving gastrointestinal adverse reactions in chemotherapy for patients with digestive tract cancer by metaanalysis.METHODS EMBASE,PubMed,OVID,WoS,CNKI,CBM,and VIP database were all used for searching relevant literature,and the efficacy after treatment was combined for analysis and evaluation.RESULTS This study included seven articles.The results of meta-analysis indicated that music therapy could reduce the nausea symptom score of patients after chemotherapy[mean difference(MD)=-3.15,95%confidence interval(CI):-4.62 to-1.68,Z=-4.20,P<0.0001].Music therapy could reduce the vomiting symptom score of patients after chemotherapy(MD=-2.28,95%CI:-2.46 to-2.11,Z=-25.15,P<0.0001).Furthermore,music therapy could minimize the incidence of grade I and above nausea or vomiting in patients after chemotherapy(odds ratio=0.38,95%CI:0.26-0.56,Z=-4.88,P<0.0001).Meta-regression analysis found that publication year was not a specific factor affecting the combined results.There was no significant publication bias(P>0.05).CONCLUSION Music therapy can significantly improve the scores of nausea and vomiting symptoms in patients with digestive system cancer during chemotherapy and reduce the incidence of grade I and above nausea and vomiting after chemotherapy,making it an effective psychological intervention method worthy of clinical promotion.
基金supported by National Natural Science Foundation of China(No.82173757,No.82173756)Scientists Fund of National Natural Science Foundation of China(82003682)+1 种基金Medical Science and Technolpgy Program of Henan Province(Joint construction project,LHGJ20200026)Shandong Excellent Youth Fund(ZR2022YQ76).
文摘Immunotherapy has become a promising research“hotspot”in cancer treatment.“Soldier”immune cells are not uniform throughout the body;they accumulate mostly in the immune organs such as the spleen and lymph nodes(LNs),etc.The unique structure of LNs provides the microenvironment suitable for the survival,activation,and proliferation of multiple types of immune cells.LNs play an important role in both the initiation of adaptive immunity and the generation of durable anti-tumor responses.Antigens taken up by antigen-presenting cells in peripheral tissues need to migrate with lymphatic fluid to LNs to activate the lymphocytes therein.Meanwhile,the accumulation and retaining of many immune functional compounds in LNs enhance their efficacy significantly.Therefore,LNs have become a key target for tumor immunotherapy.Unfortunately,the nonspecific distribution of the immune drugs in vivo greatly limits the activation and proliferation of immune cells,which leads to unsatisfactory anti-tumor effects.The efficient nano-delivery system to LNs is an effective strategy to maximize the efficacy of immune drugs.Nano-delivery systems have shown beneficial in improving biodistribution and enhancing accumulation in lymphoid tissues,exhibiting powerful and promising prospects for achieving effective delivery to LNs.Herein,the physiological structure and the delivery barriers of LNs were summarized and the factors affecting LNs accumulation were discussed thoroughly.Moreover,developments in nano-delivery systems were reviewed and the transformation prospects of LNs targeting nanocarriers were summarized and discussed.
文摘BACKGROUND Perihilar cholangiocarcinoma(pCCA)is a highly malignant tumor arising from the biliary tree.Radical surgery is the only treatment offering a chance of long-term survival.However,limited by the tumor’s anatomic location and peri-vascular invasion,most patients lose the chance for curative treatment.Therefore,more methods to increase the resectability of tumors as well as to improve outcomes are needed.CASE SUMMARY A 68-year-old female patient had a hepatic hilar mass without obvious symptoms.Laboratory results showed hepatitis B positivity.Magnetic resonance imaging indicated that the mass(maximum diameter:41 mm)invaded the left and right branches of the main portal vein,as well as the middle,left and right hepatic veins;enlarged lymph nodes were also detected in the hilum.The patient was diagnosed with pCCA,and the clinical stage was determined to be T4N1M0(stage IIIC).Considering the tumor’s anatomic location and vascular invasion,systematic conversion therapy followed by ex vivo liver resection and autotrans-plantation(ELRA)was determined as personalized treatment for this patient.Our original systemic sequential therapeutic strategy(lenvatinib and tislelizumab in combination with gemcitabine and cisplatin)was successfully adopted as conversion therapy because she achieved partial response after three cycles of treatment,without severe toxicity.ELRA,anastomotic reconstruction of the middle hepatic vein,right hepatic vein,root of portal vein,inferior vena cava and right hepatic artery,and lymph node dissection were performed at one month after systemic therapy.Pathological and immunohistochemical examination confirmed the diagnosis of pCCA with lymph node metastasis.Although the middle hepatic vein was partially obstructed four months later,hepatic vein stent implantation successfully addressed this problem.The patient has survived for 22 mo after the diagnosis,with no evidence of recurrence or metastasis.CONCLUSION An effective therapeutic strategy for conversion therapy greatly increases the feasibility and efficiency of ELRA.
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supported by the National Natural Science Foundation of China(Grant No.82203786)the Natural Science Foundation of Liaoning Province of China(Grant No.2022-YGJC-68)Chinese Young Breast Experts Research project(Grant No.CYBER-2021-A02)。
文摘Objective:Neoadjuvant therapy(NAT)has been widely implemented as an essential treatment to improve therapeutic efficacy in patients with locally-advanced cancer to reduce tumor burden and prolong survival,particularly for human epidermal growth receptor 2-positive and triple-negative breast cancer.The role of peripheral immune components in predicting therapeutic responses has received limited attention.Herein we determined the relationship between dynamic changes in peripheral immune indices and therapeutic responses during NAT administration.Methods:Peripheral immune index data were collected from 134 patients before and after NAT.Logistic regression and machine learning algorithms were applied to the feature selection and model construction processes,respectively.Results:Peripheral immune status with a greater number of CD3^(+)T cells before and after NAT,and a greater number of CD8^(+)T cells,fewer CD4^(+)T cells,and fewer NK cells after NAT was significantly related to a pathological complete response(P<0.05).The post-NAT NK cell-to-pre-NAT NK cell ratio was negatively correlated with the response to NAT(HR=0.13,P=0.008).Based on the results of logistic regression,14 reliable features(P<0.05)were selected to construct the machine learning model.The random forest model exhibited the best power to predict efficacy of NAT among 10 machine learning model approaches(AUC=0.733).Conclusions:Statistically significant relationships between several specific immune indices and the efficacy of NAT were revealed.A random forest model based on dynamic changes in peripheral immune indices showed robust performance in predicting NAT efficacy.
基金This work is supported by the United Arab Emirates University UPAR(Grant No.G3458).
文摘Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.