Background:The heterogeneity of prognosis and treatment benefits among patients with gliomas is due to tumor microenvironment characteristics.However,biomarkers that reflect microenvironmental characteristics and predic...Background:The heterogeneity of prognosis and treatment benefits among patients with gliomas is due to tumor microenvironment characteristics.However,biomarkers that reflect microenvironmental characteristics and predict the prognosis of gliomas are limited.Therefore,we aimed to develop a model that can effectively predict prognosis,differentiate microenvironment signatures,and optimize drug selection for patients with glioma.Materials and Methods:The CIBERSORT algorithm,bulk sequencing analysis,and single-cell RNA(scRNA)analysis were employed to identify significant cross-talk genes between M2 macrophages and cancer cells in glioma tissues.A predictive model was constructed based on cross-talk gene expression,and its effect on prognosis,recurrence prediction,and microenvironment characteristics was validated in multiple cohorts.The effect of the predictive model on drug selection was evaluated using the OncoPredict algorithm and relevant cellular biology experiments.Results:A high abundance of M2 macrophages in glioma tissues indicates poor prognosis,and cross-talk between macrophages and cancer cells plays a crucial role in shaping the tumor microenvironment.Eight genes involved in the cross-talk between macrophages and cancer cells were identified.Among them,periostin(POSTN),chitinase 3 like 1(CHI3L1),serum amyloid A1(SAA1),and matrix metallopeptidase 9(MMP9)were selected to construct a predictive model.The developed model demonstrated significant efficacy in distinguishing patient prognosis,recurrent cases,and characteristics of high inflammation,hypoxia,and immunosuppression.Furthermore,this model can serve as a valuable tool for guiding the use of trametinib.Conclusions:In summary,this study provides a comprehensive understanding of the interplay between M2 macrophages and cancer cells in glioma;utilizes a cross-talk gene signature to develop a predictive model that can predict the differentiation of patient prognosis,recurrence instances,and microenvironment characteristics;and aids in optimizing the application of trametinib in glioma patients.展开更多
BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabet...BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.展开更多
Alveolar echinococcosis(AE)is a chronic zoonotic parasitic disease caused by infection with Echinococcus multilocularis.AE is associated with a high mortality rate and poses a significant threat to human health.The pr...Alveolar echinococcosis(AE)is a chronic zoonotic parasitic disease caused by infection with Echinococcus multilocularis.AE is associated with a high mortality rate and poses a significant threat to human health.The primary treatment for AE is surgical resection of the lesions;however,owing to its long incubation period and insidious disease progression,many patients are diagnosed only after the onset of complications such as liver cirrhosis,jaundice,and portal hypertension,which preclude curative surgical intervention.For patients who are unwilling or unable to undergo surgery,lifelong administration of anti-AE medications is necessary.Benzimidazole compounds,such as albendazole and mebendazole,are the current mainstays of treatment,offering good efficacy.Nevertheless,these medications primarily inhibit parasite proliferation rather than eradicate the infection,and their long-term use can lead to significant drug-related toxic effects.Consequently,there is an urgent need to develop new therapeutic strategies that convey better efficacy and reduce the adverse effects associated with current treatments.Recent advancements in AE therapy include novel synthetic compounds such as antiviral agents,antibiotics,antineoplastic agents,immunosuppressants,and antiangiogenic agents,as well as natural compounds derived from traditional Chinese and Tibetan medicine.These new drugs show promising clinical potential because they interfere with parasitic metabolic pathways and cellular structures.This review aims to discuss recent research on AE drug therapy,including mechanisms of action,dosing regimens,signalling pathways,and therapeutic outcomes,with a goal of providing new insights and directions for the development of anti-AE drugs and summarizing current advancements in AE pharmacotherapy.展开更多
At present,the commonly used treatment methods for chronic respiratory diseases are drug,oxygen,interventional and atomization therapy.Atomization therapy is the most widely used because of its characteristics of fast...At present,the commonly used treatment methods for chronic respiratory diseases are drug,oxygen,interventional and atomization therapy.Atomization therapy is the most widely used because of its characteristics of fast effect,high local drug concentration,less drug dosage,convenient application and few systemic adverse reactions.In this paper,the mechanism,characteristics,commonly used drugs and clinical application of atomization therapy are discussed.展开更多
Diabetes is mainly a series of symptoms of glucose metabolism disorder caused by relative or absolute insufficiencies of insulin.Most patients are accompanied by protein,fat,water and electrolyte disorders,including d...Diabetes is mainly a series of symptoms of glucose metabolism disorder caused by relative or absolute insufficiencies of insulin.Most patients are accompanied by protein,fat,water and electrolyte disorders,including diabetes type 1 and diabetes type 2,of which diabetes type 2 accounts for more than 90%.The incidence rate of diabetes is high,the course of disease is long,and it is difficult to cure.Most patients need long-term medication.This study analyzed the clinical manifestations and predisposing factors of diabetes,and explored the progress of drug treatment of diabetes,which is summarized as follows.展开更多
Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with vene...Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.展开更多
Transdermal drug delivery offers a promising alternative to traditional cancer therapies by providing a non-invasive,controlled,and targeted delivery of therapeutic agents.This paper explores the advancements,benefits...Transdermal drug delivery offers a promising alternative to traditional cancer therapies by providing a non-invasive,controlled,and targeted delivery of therapeutic agents.This paper explores the advancements,benefits,and challenges associated with transdermal drug delivery systems(TDDS)in cancer treatment.It highlights the mechanisms of action,key technologies,and the potential impact on patient outcomes.By examining recent studies and clinical trials,this paper aims to provide a comprehensive overview of the efficacy,safety,and prospects of transdermal drug delivery in oncology.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
The emergence and spread of drug-recalcitrant Plasmodium falciparum parasites threaten to reverse the gains made in the fight against malaria.Urgent measures need to be taken to curb this impending challenge.The highe...The emergence and spread of drug-recalcitrant Plasmodium falciparum parasites threaten to reverse the gains made in the fight against malaria.Urgent measures need to be taken to curb this impending challenge.The higher plant-derived sesquiterpene,quinoline alkaloids,and naphthoquinone natural product classes of compounds have previously served as phenomenal chemical scaffolds from which integral antimalarial drugs were developed.Historical successes serve as an inspiration for the continued investigation of plant-derived natural products compounds in search of novel molecular templates from which new antimalarial drugs could be developed.The aim of this study was to identify potential chemical scaffolds for malaria drug discovery following analysis of historical data on phytochemicals screened in vitro against P.falciparum.To identify these novel scaffolds,we queried an in-house manually curated database of plant-derived natural product compounds and their in vitro biological data.Natural products were assigned to different structural classes using NPClassifier.To identify the most promising chemical scaffolds,we then correlated natural compound class with bioactivity and other data,namely(i)potency,(ii)resistance index,(iii)selectivity index and(iv)physicochemical properties.We used an unbiased scoring system to rank the different natural product classes based on the assessment of their bioactivity data.From this analysis we identified the top-ranked natural product pathway as the alkaloids.The top three ranked super classes identified were(i)pseudoalkaloids,(ii)naphthalenes and(iii)tyrosine alkaloids and the top five ranked classes(i)quassinoids(of super class triterpenoids),(ii)steroidal alkaloids(of super class pseudoalkaloids)(iii)cycloeudesmane sesquiterpenoids(of super class triterpenoids)(iv)isoquinoline alkaloids(of super class tyrosine alkaloids)and(v)naphthoquinones(of super class naphthalenes).Launched chemical space of these identified classes of compounds was,by and large,distinct from that of‘legacy’antimalarial drugs.Our study was able to identify chemical scaffolds with acceptable biological properties that are structurally different from current and previously used antimalarial drugs.These molecules have the potential to be developed into new antimalarial drugs.展开更多
Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted ...Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.展开更多
Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attrac...Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.展开更多
Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response ...Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.展开更多
Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory ca...Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory cancer cell populations.Focusing on how cancer cells develop resistance during the encounter with targeted drugs and the immune system,we propose a mathematical model for studying the dynamics of drug resistance in a conjoint heterogeneous tumor-immune setting.We analyze the local geometric properties of the equilibria of the model.Numerical simulations show that the selectively targeted removal of sensitive cancer cells may cause the initially heterogeneous population to become a more resistant population.Moreover,the decline of immune recruitment is a stronger determinant of cancer escape from immune surveillance or targeted therapy than the decay in immune predation strength.Sensitivity analysis of model parameters provides insight into the roles of the immune system combined with targeted therapy in determining treatment outcomes.展开更多
This review aims to summarize the currently viable vaccine strategies including the approved vaccines and the those in trials for next-generation malaria vaccines.Data on malaria vaccine development was collected thro...This review aims to summarize the currently viable vaccine strategies including the approved vaccines and the those in trials for next-generation malaria vaccines.Data on malaria vaccine development was collected through a comprehensive review.The literature search was performed using databases including Google Scholar,PubMed,NIH,and Web of Science.Various novel approaches of vaccination are being developed,including those based on radiation-attenuated strategies,monoclonal antibodies,targeted immunogenic peptides,RNA and DNA vaccines,nanoparticle-based vaccines,protein-based vaccination protocols,and whole organism-based vaccination strategies.Trials on RTS,S have entered phase Ⅲtesting,and those based on blood-stage vaccines and vaccines to interrupt malarial transmission have advanced to higher stages of trials.Mathematical modeling,combined drug and vaccine strategies,mass drug administration,polyvalent vaccine formulations,and targeted vaccination campaigns is playing an important role in malarial prevention.Furthermore,assessing coverage,accessibility,acceptability,deployment,compilation,and adherence to specific vaccination strategies in endemic regions is essential for vaccination drives against malaria.展开更多
India reports the highest number of malaria cases in Southeast Asia,of which Plasmodium falciparum contribute more than half of the cases every year.North eastern states of India contribute only 3.96%of country’s pop...India reports the highest number of malaria cases in Southeast Asia,of which Plasmodium falciparum contribute more than half of the cases every year.North eastern states of India contribute only 3.96%of country’s population but account for】10%of total reported malaria cases.11%of Plasmodium falciparum cases and 20%of malaria related deaths annually.In India,chloroquine resistance was reported for the first time from northeast region and since then chloroquine treatment failure is being reported from many parts of the region.Increased chloroquine treatment failure has led to change of the drug policy to artemisinin combination therapy as first line of malaria treatment in the region.However,replacing chloroquine to artemisinin combination therapy has not shown significant difference in the overall malaria incidence in the region,The present review addresses the current malaria situation of northeastern region of India in the light of antimalarials drug resistance.展开更多
Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer tre...Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, via exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.展开更多
Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeuti...Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.展开更多
Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none o...Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.展开更多
BACKGROUND Patient-derived organoids(PDOs)have been demonstrated to predict the response to drugs in multiple cancer types.However,it remains unclear about its application in cholangiocarcinoma.CASE SUMMARY A 59-year-...BACKGROUND Patient-derived organoids(PDOs)have been demonstrated to predict the response to drugs in multiple cancer types.However,it remains unclear about its application in cholangiocarcinoma.CASE SUMMARY A 59-year-old woman was admitted to the hospital due to upper abdominal pain for over 8 months.According to relevant examinations,she was diagnosed as perihilar cholangiocarcinoma(pCCA)with intrahepatic metastasis and perihilar lymphatic metastasis.After multidisciplinary team discussion,percutaneous transhepatic cholangiodrainage was performed to relieve biliary obstruction,and puncture biopsy was conducted to confirm the pathological diagnosis.Transarterial chemoembolization with nab-paclitaxel was used in combination with toripalimab and lenvatinib,but the levels of tumor markers including alpha fetal protein,carcinoembryonic antigen,carbohydrate antigen 15-3 and cancer antigen 125 were still raised.The PDO for drug screening showed sensitive to gemcitabine and cisplatin.Accordingly,the chemotherapy regimen was adjusted to gemcitabine and cisplatin in combination with toripalimab and lenvatinib.After 4 cycles of treatment,the tumor was assessed resectable,and radical surgical resection was performed successfully.One year after surgery,the patient was still alive,and no recurrence or occurred.CONCLUSION PDOs for drug sensitivity contribute to screening effective chemotherapy drugs for advanced pCCA,promoting conversion therapy and improving the prognosis.展开更多
BACKGROUND For primary liver cancer,the key to conversion therapy depends on the effectiveness of drug treatment.Patient-derived tumor organoids have been demonstrated to improve the efficacy of conversion therapy by ...BACKGROUND For primary liver cancer,the key to conversion therapy depends on the effectiveness of drug treatment.Patient-derived tumor organoids have been demonstrated to improve the efficacy of conversion therapy by identifying individualtargeted effective drugs,but their clinical effects in liver cancer remain unknown.CASE SUMMARY We described a patient with hepatocellular carcinoma(HCC)who achieved pathologic complete response(pCR)to conversion therapy guided by the patientderived organoid(PDO)drug sensitivity testing.Despite insufficiency of the remaining liver volume after hepatectomy,the patient obtained tumor reduction after treatment with the PDO-sensitive drugs and successfully underwent radical surgical resection.Postoperatively,pCR was observed.CONCLUSION PDOs contributes to screening sensitive drugs for HCC patients to realize the personalized treatment and improve the conversion therapy efficacy.展开更多
基金funded by the Scientific Research Project of the Higher Education Department of Guizhou Province[Qianjiaoji 2022(187)]Department of Education of Guizhou Province[Guizhou Teaching and Technology(2023)015]+1 种基金Guizhou Medical University National Natural Science Foundation Cultivation Project(22NSFCP45)China Postdoctoral Science Foundation Project(General Program No.2022M720929).
文摘Background:The heterogeneity of prognosis and treatment benefits among patients with gliomas is due to tumor microenvironment characteristics.However,biomarkers that reflect microenvironmental characteristics and predict the prognosis of gliomas are limited.Therefore,we aimed to develop a model that can effectively predict prognosis,differentiate microenvironment signatures,and optimize drug selection for patients with glioma.Materials and Methods:The CIBERSORT algorithm,bulk sequencing analysis,and single-cell RNA(scRNA)analysis were employed to identify significant cross-talk genes between M2 macrophages and cancer cells in glioma tissues.A predictive model was constructed based on cross-talk gene expression,and its effect on prognosis,recurrence prediction,and microenvironment characteristics was validated in multiple cohorts.The effect of the predictive model on drug selection was evaluated using the OncoPredict algorithm and relevant cellular biology experiments.Results:A high abundance of M2 macrophages in glioma tissues indicates poor prognosis,and cross-talk between macrophages and cancer cells plays a crucial role in shaping the tumor microenvironment.Eight genes involved in the cross-talk between macrophages and cancer cells were identified.Among them,periostin(POSTN),chitinase 3 like 1(CHI3L1),serum amyloid A1(SAA1),and matrix metallopeptidase 9(MMP9)were selected to construct a predictive model.The developed model demonstrated significant efficacy in distinguishing patient prognosis,recurrent cases,and characteristics of high inflammation,hypoxia,and immunosuppression.Furthermore,this model can serve as a valuable tool for guiding the use of trametinib.Conclusions:In summary,this study provides a comprehensive understanding of the interplay between M2 macrophages and cancer cells in glioma;utilizes a cross-talk gene signature to develop a predictive model that can predict the differentiation of patient prognosis,recurrence instances,and microenvironment characteristics;and aids in optimizing the application of trametinib in glioma patients.
基金Supported by The National Key R and D Program of China,No.2018YFC1314103The National Natural Science Foundation of China,No.81870563 and No.82270838.
文摘BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.
基金Supported by the Guiding Program Project of Qinghai Provincial Health Commission,No.2020-wjzdx-27.
文摘Alveolar echinococcosis(AE)is a chronic zoonotic parasitic disease caused by infection with Echinococcus multilocularis.AE is associated with a high mortality rate and poses a significant threat to human health.The primary treatment for AE is surgical resection of the lesions;however,owing to its long incubation period and insidious disease progression,many patients are diagnosed only after the onset of complications such as liver cirrhosis,jaundice,and portal hypertension,which preclude curative surgical intervention.For patients who are unwilling or unable to undergo surgery,lifelong administration of anti-AE medications is necessary.Benzimidazole compounds,such as albendazole and mebendazole,are the current mainstays of treatment,offering good efficacy.Nevertheless,these medications primarily inhibit parasite proliferation rather than eradicate the infection,and their long-term use can lead to significant drug-related toxic effects.Consequently,there is an urgent need to develop new therapeutic strategies that convey better efficacy and reduce the adverse effects associated with current treatments.Recent advancements in AE therapy include novel synthetic compounds such as antiviral agents,antibiotics,antineoplastic agents,immunosuppressants,and antiangiogenic agents,as well as natural compounds derived from traditional Chinese and Tibetan medicine.These new drugs show promising clinical potential because they interfere with parasitic metabolic pathways and cellular structures.This review aims to discuss recent research on AE drug therapy,including mechanisms of action,dosing regimens,signalling pathways,and therapeutic outcomes,with a goal of providing new insights and directions for the development of anti-AE drugs and summarizing current advancements in AE pharmacotherapy.
基金the Project for the Development,Promotion and Application of Medical and Health Appropriate Technology in Guangxi(S2022153)Project for the Improvement of Basic Research Ability of Young and Middle-aged Teachers in Colleges and Universities in Guangxi(2024KY0499)+1 种基金Self-funded Research Project of Health Commission of Guangxi Zhuang Autonomous Region(Z-C20231971)Innovation and Entrepreneurship Training Planning Project for College Students(202310601058X,202310601057X).
文摘At present,the commonly used treatment methods for chronic respiratory diseases are drug,oxygen,interventional and atomization therapy.Atomization therapy is the most widely used because of its characteristics of fast effect,high local drug concentration,less drug dosage,convenient application and few systemic adverse reactions.In this paper,the mechanism,characteristics,commonly used drugs and clinical application of atomization therapy are discussed.
文摘Diabetes is mainly a series of symptoms of glucose metabolism disorder caused by relative or absolute insufficiencies of insulin.Most patients are accompanied by protein,fat,water and electrolyte disorders,including diabetes type 1 and diabetes type 2,of which diabetes type 2 accounts for more than 90%.The incidence rate of diabetes is high,the course of disease is long,and it is difficult to cure.Most patients need long-term medication.This study analyzed the clinical manifestations and predisposing factors of diabetes,and explored the progress of drug treatment of diabetes,which is summarized as follows.
文摘Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.
文摘Transdermal drug delivery offers a promising alternative to traditional cancer therapies by providing a non-invasive,controlled,and targeted delivery of therapeutic agents.This paper explores the advancements,benefits,and challenges associated with transdermal drug delivery systems(TDDS)in cancer treatment.It highlights the mechanisms of action,key technologies,and the potential impact on patient outcomes.By examining recent studies and clinical trials,this paper aims to provide a comprehensive overview of the efficacy,safety,and prospects of transdermal drug delivery in oncology.
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The emergence and spread of drug-recalcitrant Plasmodium falciparum parasites threaten to reverse the gains made in the fight against malaria.Urgent measures need to be taken to curb this impending challenge.The higher plant-derived sesquiterpene,quinoline alkaloids,and naphthoquinone natural product classes of compounds have previously served as phenomenal chemical scaffolds from which integral antimalarial drugs were developed.Historical successes serve as an inspiration for the continued investigation of plant-derived natural products compounds in search of novel molecular templates from which new antimalarial drugs could be developed.The aim of this study was to identify potential chemical scaffolds for malaria drug discovery following analysis of historical data on phytochemicals screened in vitro against P.falciparum.To identify these novel scaffolds,we queried an in-house manually curated database of plant-derived natural product compounds and their in vitro biological data.Natural products were assigned to different structural classes using NPClassifier.To identify the most promising chemical scaffolds,we then correlated natural compound class with bioactivity and other data,namely(i)potency,(ii)resistance index,(iii)selectivity index and(iv)physicochemical properties.We used an unbiased scoring system to rank the different natural product classes based on the assessment of their bioactivity data.From this analysis we identified the top-ranked natural product pathway as the alkaloids.The top three ranked super classes identified were(i)pseudoalkaloids,(ii)naphthalenes and(iii)tyrosine alkaloids and the top five ranked classes(i)quassinoids(of super class triterpenoids),(ii)steroidal alkaloids(of super class pseudoalkaloids)(iii)cycloeudesmane sesquiterpenoids(of super class triterpenoids)(iv)isoquinoline alkaloids(of super class tyrosine alkaloids)and(v)naphthoquinones(of super class naphthalenes).Launched chemical space of these identified classes of compounds was,by and large,distinct from that of‘legacy’antimalarial drugs.Our study was able to identify chemical scaffolds with acceptable biological properties that are structurally different from current and previously used antimalarial drugs.These molecules have the potential to be developed into new antimalarial drugs.
基金supported by grants from the 2021 Graduate Education Innovation Program Project of Guangxi Zhuang Autonomous Region [YCBZ2021041]the National innovative training program for college students [202100001580]grants from the National Natural Science Foundation of China [NSFC,31860040]。
文摘Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.
基金the National Natural Science Foundation of China(Grant No.:51803120).
文摘Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.
基金supported by grants from Sanming Project of Medicine in Shenzhen(No.SZSM202211030)the Science and Technology Department Basic Research Project of Shanxi(No.202203021221284)。
文摘Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.
基金supported by the National Natural Science Foundation of China(11871238,11931019,12371486)。
文摘Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory cancer cell populations.Focusing on how cancer cells develop resistance during the encounter with targeted drugs and the immune system,we propose a mathematical model for studying the dynamics of drug resistance in a conjoint heterogeneous tumor-immune setting.We analyze the local geometric properties of the equilibria of the model.Numerical simulations show that the selectively targeted removal of sensitive cancer cells may cause the initially heterogeneous population to become a more resistant population.Moreover,the decline of immune recruitment is a stronger determinant of cancer escape from immune surveillance or targeted therapy than the decay in immune predation strength.Sensitivity analysis of model parameters provides insight into the roles of the immune system combined with targeted therapy in determining treatment outcomes.
文摘This review aims to summarize the currently viable vaccine strategies including the approved vaccines and the those in trials for next-generation malaria vaccines.Data on malaria vaccine development was collected through a comprehensive review.The literature search was performed using databases including Google Scholar,PubMed,NIH,and Web of Science.Various novel approaches of vaccination are being developed,including those based on radiation-attenuated strategies,monoclonal antibodies,targeted immunogenic peptides,RNA and DNA vaccines,nanoparticle-based vaccines,protein-based vaccination protocols,and whole organism-based vaccination strategies.Trials on RTS,S have entered phase Ⅲtesting,and those based on blood-stage vaccines and vaccines to interrupt malarial transmission have advanced to higher stages of trials.Mathematical modeling,combined drug and vaccine strategies,mass drug administration,polyvalent vaccine formulations,and targeted vaccination campaigns is playing an important role in malarial prevention.Furthermore,assessing coverage,accessibility,acceptability,deployment,compilation,and adherence to specific vaccination strategies in endemic regions is essential for vaccination drives against malaria.
文摘India reports the highest number of malaria cases in Southeast Asia,of which Plasmodium falciparum contribute more than half of the cases every year.North eastern states of India contribute only 3.96%of country’s population but account for】10%of total reported malaria cases.11%of Plasmodium falciparum cases and 20%of malaria related deaths annually.In India,chloroquine resistance was reported for the first time from northeast region and since then chloroquine treatment failure is being reported from many parts of the region.Increased chloroquine treatment failure has led to change of the drug policy to artemisinin combination therapy as first line of malaria treatment in the region.However,replacing chloroquine to artemisinin combination therapy has not shown significant difference in the overall malaria incidence in the region,The present review addresses the current malaria situation of northeastern region of India in the light of antimalarials drug resistance.
基金supported by the National Natural Science Foundation of China (Grant No. 81973861)Zhejiang Provincial Ministry Medical and Health Co-construction Major Project (Grant No. 20214355173)+2 种基金Zhejiang Science and Technology Department“Vanguard”“Leading Goose”research (Grant No. 2023C03044)Zhejiang Provincial Health“Leading Talents”ProjectZhejiang Medical and Health Science and Technology Project (Grant No. 2022KY558)。
文摘Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, via exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.
基金National Natural Science Foundation of China(Grant No.81273297)Shenyang Science and Technology Plan.Public Health R&D Special Project(21-173-9-67).
文摘Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.
基金supported by the 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant,No.2020LKSFG02C(to Qiang Fang and SG)the National Natural Science Foundation of China,No.82201511(to SG)+1 种基金the Guangdong Basic and Applied Basic Research Foundation,Nos.2021A1515110873(to SG),2022A1515110139(to TW)the Medical Scientific Research Foundation of Guangdong Province,No.A2022077(to SG)。
文摘Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.
基金Supported by the Chongqing Natural Science Foundation Project,No.CSTB2022NSCQ-MSX0172.
文摘BACKGROUND Patient-derived organoids(PDOs)have been demonstrated to predict the response to drugs in multiple cancer types.However,it remains unclear about its application in cholangiocarcinoma.CASE SUMMARY A 59-year-old woman was admitted to the hospital due to upper abdominal pain for over 8 months.According to relevant examinations,she was diagnosed as perihilar cholangiocarcinoma(pCCA)with intrahepatic metastasis and perihilar lymphatic metastasis.After multidisciplinary team discussion,percutaneous transhepatic cholangiodrainage was performed to relieve biliary obstruction,and puncture biopsy was conducted to confirm the pathological diagnosis.Transarterial chemoembolization with nab-paclitaxel was used in combination with toripalimab and lenvatinib,but the levels of tumor markers including alpha fetal protein,carcinoembryonic antigen,carbohydrate antigen 15-3 and cancer antigen 125 were still raised.The PDO for drug screening showed sensitive to gemcitabine and cisplatin.Accordingly,the chemotherapy regimen was adjusted to gemcitabine and cisplatin in combination with toripalimab and lenvatinib.After 4 cycles of treatment,the tumor was assessed resectable,and radical surgical resection was performed successfully.One year after surgery,the patient was still alive,and no recurrence or occurred.CONCLUSION PDOs for drug sensitivity contribute to screening effective chemotherapy drugs for advanced pCCA,promoting conversion therapy and improving the prognosis.
基金Chongqing Natural Science Foundation Project,No.CSTB2022NSCQ-MSX0172and Incubation Project for Talented Young People,No.2022YQB031.
文摘BACKGROUND For primary liver cancer,the key to conversion therapy depends on the effectiveness of drug treatment.Patient-derived tumor organoids have been demonstrated to improve the efficacy of conversion therapy by identifying individualtargeted effective drugs,but their clinical effects in liver cancer remain unknown.CASE SUMMARY We described a patient with hepatocellular carcinoma(HCC)who achieved pathologic complete response(pCR)to conversion therapy guided by the patientderived organoid(PDO)drug sensitivity testing.Despite insufficiency of the remaining liver volume after hepatectomy,the patient obtained tumor reduction after treatment with the PDO-sensitive drugs and successfully underwent radical surgical resection.Postoperatively,pCR was observed.CONCLUSION PDOs contributes to screening sensitive drugs for HCC patients to realize the personalized treatment and improve the conversion therapy efficacy.