The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,ta...Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.展开更多
Pancreatic cancer remains one of the most challenging malignancies to treat,with a poor prognosis and limited therapeutic options.Despite the success of immunotherapy and targeted therapies for other cancers,these app...Pancreatic cancer remains one of the most challenging malignancies to treat,with a poor prognosis and limited therapeutic options.Despite the success of immunotherapy and targeted therapies for other cancers,these approaches have not yet transformed the treatment landscape for pancreatic cancer.The unique tumor microenvironment(TME)of pancreatic cancer,characterized by dense fibrotic stroma and immunosuppressive myeloid cells,poses significant barriers to effective immunotherapy.Current research highlights the need for an in-depth understanding of the TME and the development of strategies to overcome its immunosuppressive properties.Recent studies have explored various immunotherapeutic approaches,including immune checkpoint inhibitors,cancer vaccines,and adoptive cell therapies,some of which have shown promising results in preclinical and early clinical trials.Furthermore,combining immunotherapy with traditional treatments,such as chemotherapy and radiotherapy,has shown potential for enhancing antitumor efficacy,although targeted therapies for pancreatic cancer are still in their early stages and are being investigated for their ability to disrupt specific molecular pathways involved in tumor growth and survival.This review provides a comprehensive overview of the advances in immunotherapy and targeted therapies for pancreatic cancer,discussing the current state of research,clinical outcomes,and future directions for improving patient prognosis.展开更多
Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are des...Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal cells.These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs simultaneously.Despite these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle therapies.Cell-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer cells.This review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer research.It covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer cells.By detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.展开更多
Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due...Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due to the complex pathogenesis.Although OA mechanisms have been investigated on a large scale over the past decade,the OA pathology correlated with aging-associated changes is still largely unrevealed.Therefore,in-depth analysis of the aging microenvironment and aging-related molecular mechanisms in OA may offer additional strategies for clinical prevention and treatment.In this review,we discuss the potential pathogenesis of OA in light of aging-associated changes and summarize three main components of the aging microenvironment of the OA joint:immune homeostatic imbalance,cellular senescence,and stem cell exhaustion,which could be induced by aging and further exacerbate OA progression.Additionally,it is emphasized that immune homeostatic imbalance appears before established OA,which occurs in the early stage and is the therapeutic window of opportunity for better clinical outcomes.Importantly,we evaluate recent therapeutic targets and promising interventions against these components,as well as the challenges and prospects for precise and individualized therapies of OA patients,which we believe would guide the construction of novel combined strategies targeting aging-related factors against OA for better treatments in the future.展开更多
This article provides a comprehensive review of various approaches to targeted drug delivery for liver cancer, an area of significant need due to the limited effectiveness of current treatments. The article begins by ...This article provides a comprehensive review of various approaches to targeted drug delivery for liver cancer, an area of significant need due to the limited effectiveness of current treatments. The article begins by highlighting the role of the liver in metabolism and discusses the high mortality associated with hepatocellular carcinoma (HCC). The shortcomings of traditional chemotherapy, such as multidrug resistance and off-target effects, necessitate the exploration of novel therapeutic strategies, with a focus on targeted approaches. The review details both passive and active targeting strategies. Passive targeting leverages the enhanced permeability and retention (EPR) effect and unique features of the tumor microenvironment, while active targeting employs specific ligands, such as peptides, antibodies, and proteins, to bind to overexpressed receptors on liver and tumor cells. The article further details many examples of active targeting using the asialoglycoprotein receptor (ASGPR), glycyrrhetinic acid (GA), transferrin receptor (TfR), and folate receptor (FR) on hepatocytes and tumor cells, demonstrating that there has been significant research effort put into this field. The importance of non-parenchymal cells in the liver is also discussed, and the article examines methods of targeting Kupffer cells, sinusoidal endothelial cells, and hepatic stellate cells for therapeutic benefit. The review goes on to cover the emerging field of subcellular targeting, including specific strategies to target the nucleus, mitochondria, and the endoplasmic reticulum/Golgi apparatus, noting that although there has been some progress, further research is needed in this area. The text finishes with a summary which acknowledges that while targeted therapies, including enzyme-activated prodrugs, such as Pradefovir, and other novel methods for drug delivery have shown significant promise, challenges remain in translating these therapies into clinical use due to limitations in understanding the sequential transport and the mechanisms of action. Ultimately, the article emphasizes the need for in-depth research to fully realize the potential of precision cancer therapies for liver cancer.展开更多
Conventional nutritional supplements frequently demonstrate limited clinical effectiveness due to the harsh milieu of the gastrointestinal tract,inefficient transepithelial transport,and rapid systemic clearance.Nanol...Conventional nutritional supplements frequently demonstrate limited clinical effectiveness due to the harsh milieu of the gastrointestinal tract,inefficient transepithelial transport,and rapid systemic clearance.Nanoliposomal delivery platforms-lipid bilayer vesicles on the nanometer scale-have attracted attention as an adaptive strategy to shield sensitive nutrients,navigate biological barriers,and deliver payloads directly to target tissues or even sub-cellular organelles.Despite a growing body of literature,a consolidated appraisal of design principles,targeting modalities,and translational hurdles is still needed to guide future nutraceutical innovation.We aim to:(1)Summarize the physicochemical foundations of nanoliposomal nutrient carriers;(2)Delineate state-of-the-art approaches for organ-specific and organelle-specific targeting,with particular emphasis on renal and mitochondrial delivery;(3)Evaluate current evidence supporting therapeutic benefits in cardiometabolic,neuroprotective,and renal-repair contexts;and(4)Map unresolved challenges-including manufacturing scale-up,cost,and regulatory oversight-to inform a roadmap for clinical translation.A systematic literature search was performed across PubMed,Web of Science,and Scopus through May 2025 using Boolean combinations of“nanoliposome”,“nutrient”,“targeted delivery”,“bioavailability”,and organ-specific terms(e.g.,“kidney”,“mitochondria”).Primary research articles,systematic reviews,and relevant meta-analyses written in English were included.Data were extracted on liposomal composition,particle size,surface modifications(e.g.,polyethylene glycol,ligand conjugation),in vitro and in vivo bio-distribution,efficacy outcomes,and safety profiles.Key design variables were mapped against reported biological performance to identify convergent principles.Sixty-four original studies and twenty-one reviews met inclusion criteria.Encapsulation within phosphatidylcholine-rich bilayers consistently enhanced nutrient stability in simulated gastric fluid and improved Caco-2 trans-epithelial transport two-fold to ten-fold compared with free compound controls.Ligand-mediated strategies-such as folate,lactoferrin,or peptide conjugation-achieved organ-specific accumulation,with kidney-directed liposomes demonstrating up to a four-fold increase in renal cortex uptake.Mitochondrial targeting using amphipathic peptides(e.g.,SS-31)or triphenylphosphonium moieties delivered antioxidant nutrients to the organelle,restoring mitochondrial membrane potential and reducing reactive oxygen species(ROS)in preclinical cardiomyopathy and neurodegeneration models.Endosomal escape was most effectively triggered by fusogenic lipids(e.g.,dioleoylphosphatidylethanolamine)or pH-responsive polymers.PEGylation prolonged circulation half-life by 3-6 hours but elicited anti-polyethylene glycol antibodies in approximately one-quarter of recipients;emerging natural sterol-mimetic or collagen-mimetic coatings showed comparable stealth behavior with superior biodegradability.Scalability remains limited:Only three studies reported pilot-scale(>10 L)batches with Good Manufacturing Practice-compliant reproducibility.Targeted nanoliposomal systems substantially improve nutrient stability,absorption,and tissue specificity,offering a credible route to transform supplement efficacy for cardiometabolic,renal,and neuroprotective indications.Optimization of lipid composition,escape mechanisms,and biocompatible surface chemistries can further enhance therapeutic indices.Nonetheless,industrial-scale manufacturing,cost containment,and immunogenicity mitigation remain critical obstacles.Addressing these gaps through standardized characterization protocols,head-to-head clinical trials,and biomaterial innovation will be essential to unlock the full potential of nanoliposomal nutraceuticals in routine healthcare practice.展开更多
BACKGROUND Doctoral students often encounter mental health challenges,including stress,anxiety,depression,and sleep disorders.It is important to explore effective intervention methods to enhance their overall physical...BACKGROUND Doctoral students often encounter mental health challenges,including stress,anxiety,depression,and sleep disorders.It is important to explore effective intervention methods to enhance their overall physical and mental well-being.It is anticipated that targeted exercise will lead to a significant reduction in stress,anxiety,and depression levels as well as an improvement in sleep quality.AIM To assess the feasibility and potential benefits of both intervention models in enhancing the sleep quality of doctoral students while alleviating stress,anxiety,and depression.METHODS A retrospective analysis of health data from 64 doctoral students across three universities in Shenyang during the 2024-2025 academic year was conducted.The participants were divided into a targeted exercise group and a Tai Chi group.The study employed the Epworth Sleepiness Scale,Insomnia Severity Index,Pittsburgh Sleep Quality Index,Perceived Stress Scale-10,Generalized Anxiety Disorder Scale-7,and Patient Health Questionnaire-9 to evaluate the impact of the two interventions on reducing stress,anxiety,depression,and sleep disorders.RESULTS The primary results of the study indicated that targeted exercise interventions are significantly effective in alleviating symptoms of anxiety,stress,and depression,as well as in improving sleep quality.Compared to Tai Chi interventions,this approach demonstrates greater durability of effects.Although the efficacy of targeted interventions may gradually diminish over time,the overall research findings suggest that targeted exercise remains a more effective therapeutic approach than Tai Chi interventions.CONCLUSION The impact of targeted exercise on stress,anxiety,depression,and sleep disorders was greater than that of Tai Chi,confirming the potential benefits for psychological health intervention for doctoral students.展开更多
BACKGROUND Rhabdomyosarcoma of the uterine cervix is a rare form of soft-tissue sarcoma predominantly affecting young women,with no established standard treatment protocol.CASE SUMMARY This report presents a case of a...BACKGROUND Rhabdomyosarcoma of the uterine cervix is a rare form of soft-tissue sarcoma predominantly affecting young women,with no established standard treatment protocol.CASE SUMMARY This report presents a case of a 17-year-old female patient presenting with in-termittent,non-cyclical vaginal bleeding and associated lower abdominal pain.Pelvic magnetic resonance imaging and additional examinations led to the dia-gnosis of cervical rhabdomyosarcoma.The primary treatment options for uterine cervical rhabdomyosarcoma include surgery,with or without adjuvant chemo-therapy and radiotherapy.This patient underwent surgery followed by a posto-perative chemotherapy regimen of gemcitabine combined with docetaxel and bevacizumab.After 19 months of follow-up,the patient showed no signs of re-currence and maintained good overall health.Given the rarity of cervix rhab-domyosarcoma,this case is presented to provide insights into the diagnosis and treatment of this condition.CONCLUSION This suggests that bevacizumab may demonstrate potential efficacy in the treat-ment of cervical rhabdomyosarcoma.In the future,targeted therapy is expected to play an increasingly significant role in the management of rhabdomyosarcoma.展开更多
Collecting duct carcinoma (CDC), or Bellini duct carcinoma, is a rare and aggressive subtype of renal cell carcinoma, accounting for 0.2% - 1% of cases. It often presents at an advanced stage with nonspecific symptoms...Collecting duct carcinoma (CDC), or Bellini duct carcinoma, is a rare and aggressive subtype of renal cell carcinoma, accounting for 0.2% - 1% of cases. It often presents at an advanced stage with nonspecific symptoms, requiring histopathology for diagnosis. Surgery remains the standard of care for localized disease, serving both diagnostic and therapeutic purposes, though adjuvant chemotherapy has shown limited efficacy. In metastatic CDC, the gemcitabine-cisplatin regimen is commonly used due to its resemblance to urothelial cancer and supportive data from prospective studies. Newer therapies offer promise in advanced cases. Immune checkpoint inhibitors, such as nivolumab alone or with ipilimumab, have shown benefits in patients with high PD-L1 expression. Targeted therapies like cabozantinib demonstrated efficacy and safety as first-line treatments in phase II trials, while sunitinib and sorafenib have shown responses in various case reports and cohorts. However, combining chemotherapy with bevacizumab did not improve outcomes in phase II trials. Despite therapeutic advances in urothelial cancers and clear cell renal tumors, the CDC entity remains a challenging malignancy, emphasizing the need for continued research to understand the true efficacy of treatment and to prolong survival in advanced disease.展开更多
Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantati...Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantation are the gold standard for the radical treatment of HCC.However,due to the heterogeneity and high invasiveness of HCC,the rates of local and distant recurrence are extremely high,with over 70%of patients experiencing recurrence within 5 years after treatment,significantly impacting the long-term quality of life.Therefore,researchers are exploring other treatment methods to reduce tumor recurrence and improve patient survival.To date,extensive research has concentrated on new alternative therapies,including radiotherapy(e.g.,selective internal radiotherapy),targeted drug therapy(e.g.,sorafenib and lenvatinib),and immunotherapy(e.g.,immune checkpoint inhibitors),which have played an integral role in the comprehensive treatment of HCC.This review mainly focuses on the cutting-edge advancements in these treatment methods for HCC and their potential role in reducing HCC recurrence.展开更多
Melanoma is an aggressive type of skin cancer notorious for its resistance to chemotherapy,radiotherapy and immunotherapy,which greatly impacts its lethality.The hedgehog(HH)signaling cascade,originally known for its ...Melanoma is an aggressive type of skin cancer notorious for its resistance to chemotherapy,radiotherapy and immunotherapy,which greatly impacts its lethality.The hedgehog(HH)signaling cascade,originally known for its roles in embryonic development,regulates growth,proliferation and cancer stem cell(CSC)self-renewal.The glioma-associated oncogene homolog(GLI)transcription factors play crucial roles in melanoma.However,oncogenic B-Raf proto-oncogene,serine/threonine kinase(BRAF)steals the spotlight by driving the aberrant activation of HH-GLI1/2 signaling.Oncogenic BRAF-driven HH-GLI1/2 signaling imparts invasive phenotype to melanoma cells and sustains CSC self-renewal.Interestingly,the transcriptional activities of GLI1 and GLI2 are suppressed by acetylation,a process that is counteracted by the deacetylating actions of histone deacetylase(HDAC)1/2.Therefore,inhibiting HDAC1/2 might keep GLI proteins in inactive acetylated form,thus representing an attractive druggable target.Notably,both HDAC1 and HDAC2 are induced by HH signaling,creating a positive feedback loop where HH signaling upregulates the expression of both HDAC1 and HDAC2.Selective inhibition of BRAF/HH/HDAC/GLI signaling axis is likely to unravel new therapeutic opportunities in melanoma.However,the precise contribution of oncogenic BRAF-driven HH signaling to therapy resistance and CSC renewal remains unclear and requires thorough investigation.In this article,we endeavored to explore the crosstalk between oncogenic BRAF and HH signaling,and the pivotal role this interaction plays in the self-renewal of melanoma stem cells.A better understanding of the molecular mechanisms governing these interactions is essential for improving melanoma treatment strategies and identifying new therapeutic targets.展开更多
In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2...In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95%of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.展开更多
Mesothelioma is a rare and aggressive cancer with a poor prognosis and limited therapeutic options.Despite recent advances,conventional treatment approaches remain largely ineffective due to late diagnosis,chemore-sis...Mesothelioma is a rare and aggressive cancer with a poor prognosis and limited therapeutic options.Despite recent advances,conventional treatment approaches remain largely ineffective due to late diagnosis,chemore-sistance and immunosuppressive tumor microenvironment.This review reports the latest studies on combination therapies for mesothelioma,focusing on the potential of integrating chemotherapeutic agents,molecularly targeted agents,vaccines and natural bioactive compounds such as polyphenols.Clinical and preclinical studies demonstrate that integrating immune-modulating drugs or molecular inhibitors with chemotherapy can improve survival and reduce tumor progression in mesothelioma models and patients.Vaccine-based strategies show potential for inducing host-persistent immune responses when combined with conventional treatments.Moreover,natural compounds such as polyphenols show synergistic effects with chemotherapeutics and targeted agents by modulating several signaling pathways involved in cancer cell growth and progression and by overcoming drug resistance.While several combination strategies are under clinical investigation,further studies are needed to develop more effective and personalized therapeutic approaches that could be translated into standardized treatment protocols.展开更多
There remain several intractable challenges for chemotherapy in glioma treatment,including the blood-brain barrier(BBB),blood-brain tumor barrier(BBTB),and tumor heterogeneity caused by cancer stem cells(CSCs),which a...There remain several intractable challenges for chemotherapy in glioma treatment,including the blood-brain barrier(BBB),blood-brain tumor barrier(BBTB),and tumor heterogeneity caused by cancer stem cells(CSCs),which are resistant to conventional chemotherapy.Here,we established a nano strategy to kill glioma cells and CSCs,combining carfilzomib and bis(diethyldithiocarbamate)copper.The synergistic drug combination disturbed cell protein metabolism at different stages and induced apoptosis and cuproptosis.The Y-shaped targeting ligand pHA-VAP-modified nanodiscs were designed to help the chemotherapeutic agents cross the BBB/BBTB and finally accumulate in tumor site.This all-stage targeting and all-stage treatment nanomedicine significantly prolonged the survival in glioma-bearing mice and might inspire the rational design of advanced drug delivery platforms.展开更多
Colorectal cancer(CRC)with liver metastasis remains a significant therapeutic challenge,particularly in cases of postoperative recurrence.While transarterial chemoembolization(TACE)and targeted therapies have shown pr...Colorectal cancer(CRC)with liver metastasis remains a significant therapeutic challenge,particularly in cases of postoperative recurrence.While transarterial chemoembolization(TACE)and targeted therapies have shown promise individually,the efficacy combining these for treating postoperative recurrent CRC with liver metastasis requires further investigation.AIM To evaluate the efficacy and safety of TACE combined with targeted therapies for postoperative recurrent CRC with liver metastasis.METHODS This observational study enrolled 75 patients with postoperative recurrent CRC accompanied by liver metastasis between January 2020 and December 2023.All patients received combined treatment with TACE and targeted therapy:Bevacizumab(40 patients,53.3%),cetuximab(25 patients,33.3%),or panitumumab(10 patients,13.3%).Treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors 1.1 criteria,with overall survival(OS)and progression-free survival as the primary endpoints.Quality of life was assessed using the European Organization for Research and Treatment of Cancer quality of life questionnaire at baseline and after six months of treatment.RESULTS The median OS was 28 months(95%confidence interval:24-32 months),and the median progression-free survival was 12 months(95%confidence interval:10-14 months).Patients treated with bevacizumab showed significantly better survival outcomes than those treated with cetuximab/panitumumab(median OS,30 vs 24 months,P=0.015).The overall response rate was 58.7%,with a disease control rate of 86.7%.Quality of life scores improved significantly across all domains,with greater improvements observed in the bevacizumab group.Treatment-related adverse events were manageable,with grade 3-4 events occurring in 13.3%of the patients and no treatment-related mortality.CONCLUSION The combination of TACE with targeted therapy,particularly bevacizumab,has demonstrated promising efficacy and acceptable safety for the treatment of postoperative recurrent CRC with liver metastasis.This multimodal approach not only improved survival outcomes but also enhanced the patients’quality of life,suggesting its potential as a valuable treatment strategy for this challenging condition.展开更多
BACKGROUND Many studies have found that sarcopenia is related to the survival of patients with liver cancer,which may lead to worse prognosis.AIM To investigate the relationship between skeletal muscle mass and progno...BACKGROUND Many studies have found that sarcopenia is related to the survival of patients with liver cancer,which may lead to worse prognosis.AIM To investigate the relationship between skeletal muscle mass and prognosis in patients with liver cancer receiving targeted therapy by meta-analysis.METHODS PubMed,Embase,Cochrane Library,and Web of Science were searched for clinical studies on the relationship between skeletal muscle index(SMI)and the prognosis of patients with liver cancer receiving targeted therapy from inception to March 1,2022.Meta-analysis and sensitivity analysis of the data were performed using Stata 16.0 software.RESULTS A total of 6877 studies were searched,and finally 12 articles with 1715 cases were included.Meta-analysis result of 8 articles showed that compared with non-low SMI group,the overall survival(OS)of patients with liver cancer in the low SMI group was significantly shorter(hazard ratio=1.60,95%confidence interval:1.44-1.77,P=0.000).Meta-analysis result of 4 articles showed that,compared with low SMI group,patients in the nonlow SMI group had longer OS(hazard ratio=0.59,95%confidence interval:0.38-0.91,P=0.018).CONCLUSION Skeletal muscle mass is positively correlated with OS in patients with liver cancer receiving targeted therapy.展开更多
The tumor microenvironment(TME)is a complex network composed of non-tumor cells,extracellular matrix,blood vessels,and various molecular signals that surround and profoundly influence tumor progression.As one of the k...The tumor microenvironment(TME)is a complex network composed of non-tumor cells,extracellular matrix,blood vessels,and various molecular signals that surround and profoundly influence tumor progression.As one of the key immune effector cells within the TME,mast cells(MCs)exhibit functional complexity,and their specific roles remain widely debated.Depending on the cancer type,spatial distribution,and interactions with other TME components,MCs can demonstrate dual regulatory capabilities—either promoting or inhibiting tumor growth.This characteristic has made them an important focus in current tumor immunology research.This review aims to systematically review the current understanding of MCs in the TME,with emphasis on their characteristics and functional differences across various tumor types,pathological status,and species.In recent years,advances in the understanding of MC markers,activation mechanisms,and biological functions have made targeting specific MC subsets an emerging therapeutic strategy.By comprehensively examining the origin,activation mechanisms,cellular interactions,and therapeutic regulation ofMCs,this review provides new perspectives and a basis for future directions in tumor research and treatment.展开更多
Background:Diabetic peripheral neuropathy(DPN)is a prevalent and debilitating complication of diabetes mellitus,lacking effective treatment options.Despite unclear underlying mechanisms,electroacupuncture(EA)shows pro...Background:Diabetic peripheral neuropathy(DPN)is a prevalent and debilitating complication of diabetes mellitus,lacking effective treatment options.Despite unclear underlying mechanisms,electroacupuncture(EA)shows promise in relieving DPN symptoms.Neurotransmitter dysregulation is central to DPN pathophysiology.This study aimed to investigate EA’s effects on DPN via targeted neurotransmitter metabolomics.Methods:A streptozotocin-induced mouse model of DPN was developed,and EA treatment was administered for two weeks to assess the therapeutic potential of EA.Following the collection of sciatic nerve samples,LC-MS-based targeted metabolomics analyses investigations were performed to examine alterations in DPN-associated neurotransmitter metabolism brought on by EA therapy.Multivariate statistical analyses were employed to assess metabolite expression patterns,using cluster heatmaps to display neurotransmitter expression results.KEGG pathway analyses were also used to explore the functional classifications of these neurotransmitters and associated metabolic pathways.Results:Targeted neurotransmitter-focused metabolomics analyses led to the identification of 34 putative biomarkers associated with EA treatment,of which 5 showed significant changes,such as beta-alanine(increased by 80.37%,P=0.0004)and kynurenine(decreased by 29.36%,P=0.0163).KEGG pathway analysis indicated that changes in the abundance of these metabolites were associated with the cAMP signaling pathway,neuroactive ligand-receptor interactions,the synaptic vesicle cycle,and other pathways.Conclusion:The results indicate that EA can efficiently regulate neurotransmitter metabolism and restore peripheral nerve function,suggesting a feasible non-pharmacological strategy for DPN treatment and warranting clinical translation.展开更多
TEM and SHV are among the most prevalentβ-lactamases contributing toβ-lactam antibiotic resistance in clinical settings,leading to treatment challenges and increased mortality rates.Except for penicillin and early c...TEM and SHV are among the most prevalentβ-lactamases contributing toβ-lactam antibiotic resistance in clinical settings,leading to treatment challenges and increased mortality rates.Except for penicillin and early cephalosporins,TEM and SHV variants have evolved with the ability to hydrolyze the second-and third-generation cephalosporins,monobactams,and evenβ-lactamase inhibitors.Accurate detection ofβ-lactamases is of paramount importance for optimizing antibiotic use and combating antimicrobial resistance(AMR).While genetic detection methods,such as polymerase chain reaction(PCR),are widely employed,their positive results may lack phenotypic correlation due to the low or absent expression of blaSHV and blaTEM in many strains[1].Therefore,a direct protein-level detection method such as targeted proteomics is more precise and clinically relevant.This study highlights the development of a rapid detection method using targeted proteomics with high-resolution accurate mass(HRAM)Orbitrap MS for the direct detection of TEM and SHV in Enterobacteriaceae strains,which offers greater clinical relevance compared to conventional genetic approaches.展开更多
基金partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
文摘Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.
文摘Pancreatic cancer remains one of the most challenging malignancies to treat,with a poor prognosis and limited therapeutic options.Despite the success of immunotherapy and targeted therapies for other cancers,these approaches have not yet transformed the treatment landscape for pancreatic cancer.The unique tumor microenvironment(TME)of pancreatic cancer,characterized by dense fibrotic stroma and immunosuppressive myeloid cells,poses significant barriers to effective immunotherapy.Current research highlights the need for an in-depth understanding of the TME and the development of strategies to overcome its immunosuppressive properties.Recent studies have explored various immunotherapeutic approaches,including immune checkpoint inhibitors,cancer vaccines,and adoptive cell therapies,some of which have shown promising results in preclinical and early clinical trials.Furthermore,combining immunotherapy with traditional treatments,such as chemotherapy and radiotherapy,has shown potential for enhancing antitumor efficacy,although targeted therapies for pancreatic cancer are still in their early stages and are being investigated for their ability to disrupt specific molecular pathways involved in tumor growth and survival.This review provides a comprehensive overview of the advances in immunotherapy and targeted therapies for pancreatic cancer,discussing the current state of research,clinical outcomes,and future directions for improving patient prognosis.
文摘Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal cells.These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs simultaneously.Despite these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle therapies.Cell-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer cells.This review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer research.It covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer cells.By detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.
基金supported by grants from National Natural Science Foundation of China(32370892)Science and Technology Commission of Shanghai Municipality(23141901200)+3 种基金Shanghai Natural Science Foundation(24ZR1450100)Health Commission of Shanghai Municipality(2022JC029)Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiaotong University School of Medicine(2022LHA11)Talent-Introduction Program of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine(2022YJRC05).
文摘Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due to the complex pathogenesis.Although OA mechanisms have been investigated on a large scale over the past decade,the OA pathology correlated with aging-associated changes is still largely unrevealed.Therefore,in-depth analysis of the aging microenvironment and aging-related molecular mechanisms in OA may offer additional strategies for clinical prevention and treatment.In this review,we discuss the potential pathogenesis of OA in light of aging-associated changes and summarize three main components of the aging microenvironment of the OA joint:immune homeostatic imbalance,cellular senescence,and stem cell exhaustion,which could be induced by aging and further exacerbate OA progression.Additionally,it is emphasized that immune homeostatic imbalance appears before established OA,which occurs in the early stage and is the therapeutic window of opportunity for better clinical outcomes.Importantly,we evaluate recent therapeutic targets and promising interventions against these components,as well as the challenges and prospects for precise and individualized therapies of OA patients,which we believe would guide the construction of novel combined strategies targeting aging-related factors against OA for better treatments in the future.
文摘This article provides a comprehensive review of various approaches to targeted drug delivery for liver cancer, an area of significant need due to the limited effectiveness of current treatments. The article begins by highlighting the role of the liver in metabolism and discusses the high mortality associated with hepatocellular carcinoma (HCC). The shortcomings of traditional chemotherapy, such as multidrug resistance and off-target effects, necessitate the exploration of novel therapeutic strategies, with a focus on targeted approaches. The review details both passive and active targeting strategies. Passive targeting leverages the enhanced permeability and retention (EPR) effect and unique features of the tumor microenvironment, while active targeting employs specific ligands, such as peptides, antibodies, and proteins, to bind to overexpressed receptors on liver and tumor cells. The article further details many examples of active targeting using the asialoglycoprotein receptor (ASGPR), glycyrrhetinic acid (GA), transferrin receptor (TfR), and folate receptor (FR) on hepatocytes and tumor cells, demonstrating that there has been significant research effort put into this field. The importance of non-parenchymal cells in the liver is also discussed, and the article examines methods of targeting Kupffer cells, sinusoidal endothelial cells, and hepatic stellate cells for therapeutic benefit. The review goes on to cover the emerging field of subcellular targeting, including specific strategies to target the nucleus, mitochondria, and the endoplasmic reticulum/Golgi apparatus, noting that although there has been some progress, further research is needed in this area. The text finishes with a summary which acknowledges that while targeted therapies, including enzyme-activated prodrugs, such as Pradefovir, and other novel methods for drug delivery have shown significant promise, challenges remain in translating these therapies into clinical use due to limitations in understanding the sequential transport and the mechanisms of action. Ultimately, the article emphasizes the need for in-depth research to fully realize the potential of precision cancer therapies for liver cancer.
文摘Conventional nutritional supplements frequently demonstrate limited clinical effectiveness due to the harsh milieu of the gastrointestinal tract,inefficient transepithelial transport,and rapid systemic clearance.Nanoliposomal delivery platforms-lipid bilayer vesicles on the nanometer scale-have attracted attention as an adaptive strategy to shield sensitive nutrients,navigate biological barriers,and deliver payloads directly to target tissues or even sub-cellular organelles.Despite a growing body of literature,a consolidated appraisal of design principles,targeting modalities,and translational hurdles is still needed to guide future nutraceutical innovation.We aim to:(1)Summarize the physicochemical foundations of nanoliposomal nutrient carriers;(2)Delineate state-of-the-art approaches for organ-specific and organelle-specific targeting,with particular emphasis on renal and mitochondrial delivery;(3)Evaluate current evidence supporting therapeutic benefits in cardiometabolic,neuroprotective,and renal-repair contexts;and(4)Map unresolved challenges-including manufacturing scale-up,cost,and regulatory oversight-to inform a roadmap for clinical translation.A systematic literature search was performed across PubMed,Web of Science,and Scopus through May 2025 using Boolean combinations of“nanoliposome”,“nutrient”,“targeted delivery”,“bioavailability”,and organ-specific terms(e.g.,“kidney”,“mitochondria”).Primary research articles,systematic reviews,and relevant meta-analyses written in English were included.Data were extracted on liposomal composition,particle size,surface modifications(e.g.,polyethylene glycol,ligand conjugation),in vitro and in vivo bio-distribution,efficacy outcomes,and safety profiles.Key design variables were mapped against reported biological performance to identify convergent principles.Sixty-four original studies and twenty-one reviews met inclusion criteria.Encapsulation within phosphatidylcholine-rich bilayers consistently enhanced nutrient stability in simulated gastric fluid and improved Caco-2 trans-epithelial transport two-fold to ten-fold compared with free compound controls.Ligand-mediated strategies-such as folate,lactoferrin,or peptide conjugation-achieved organ-specific accumulation,with kidney-directed liposomes demonstrating up to a four-fold increase in renal cortex uptake.Mitochondrial targeting using amphipathic peptides(e.g.,SS-31)or triphenylphosphonium moieties delivered antioxidant nutrients to the organelle,restoring mitochondrial membrane potential and reducing reactive oxygen species(ROS)in preclinical cardiomyopathy and neurodegeneration models.Endosomal escape was most effectively triggered by fusogenic lipids(e.g.,dioleoylphosphatidylethanolamine)or pH-responsive polymers.PEGylation prolonged circulation half-life by 3-6 hours but elicited anti-polyethylene glycol antibodies in approximately one-quarter of recipients;emerging natural sterol-mimetic or collagen-mimetic coatings showed comparable stealth behavior with superior biodegradability.Scalability remains limited:Only three studies reported pilot-scale(>10 L)batches with Good Manufacturing Practice-compliant reproducibility.Targeted nanoliposomal systems substantially improve nutrient stability,absorption,and tissue specificity,offering a credible route to transform supplement efficacy for cardiometabolic,renal,and neuroprotective indications.Optimization of lipid composition,escape mechanisms,and biocompatible surface chemistries can further enhance therapeutic indices.Nonetheless,industrial-scale manufacturing,cost containment,and immunogenicity mitigation remain critical obstacles.Addressing these gaps through standardized characterization protocols,head-to-head clinical trials,and biomaterial innovation will be essential to unlock the full potential of nanoliposomal nutraceuticals in routine healthcare practice.
基金Supported by the Key Think Tank Research Project of the Shaanxi Federation of Social Sciences,No.2023ZD1080。
文摘BACKGROUND Doctoral students often encounter mental health challenges,including stress,anxiety,depression,and sleep disorders.It is important to explore effective intervention methods to enhance their overall physical and mental well-being.It is anticipated that targeted exercise will lead to a significant reduction in stress,anxiety,and depression levels as well as an improvement in sleep quality.AIM To assess the feasibility and potential benefits of both intervention models in enhancing the sleep quality of doctoral students while alleviating stress,anxiety,and depression.METHODS A retrospective analysis of health data from 64 doctoral students across three universities in Shenyang during the 2024-2025 academic year was conducted.The participants were divided into a targeted exercise group and a Tai Chi group.The study employed the Epworth Sleepiness Scale,Insomnia Severity Index,Pittsburgh Sleep Quality Index,Perceived Stress Scale-10,Generalized Anxiety Disorder Scale-7,and Patient Health Questionnaire-9 to evaluate the impact of the two interventions on reducing stress,anxiety,depression,and sleep disorders.RESULTS The primary results of the study indicated that targeted exercise interventions are significantly effective in alleviating symptoms of anxiety,stress,and depression,as well as in improving sleep quality.Compared to Tai Chi interventions,this approach demonstrates greater durability of effects.Although the efficacy of targeted interventions may gradually diminish over time,the overall research findings suggest that targeted exercise remains a more effective therapeutic approach than Tai Chi interventions.CONCLUSION The impact of targeted exercise on stress,anxiety,depression,and sleep disorders was greater than that of Tai Chi,confirming the potential benefits for psychological health intervention for doctoral students.
文摘BACKGROUND Rhabdomyosarcoma of the uterine cervix is a rare form of soft-tissue sarcoma predominantly affecting young women,with no established standard treatment protocol.CASE SUMMARY This report presents a case of a 17-year-old female patient presenting with in-termittent,non-cyclical vaginal bleeding and associated lower abdominal pain.Pelvic magnetic resonance imaging and additional examinations led to the dia-gnosis of cervical rhabdomyosarcoma.The primary treatment options for uterine cervical rhabdomyosarcoma include surgery,with or without adjuvant chemo-therapy and radiotherapy.This patient underwent surgery followed by a posto-perative chemotherapy regimen of gemcitabine combined with docetaxel and bevacizumab.After 19 months of follow-up,the patient showed no signs of re-currence and maintained good overall health.Given the rarity of cervix rhab-domyosarcoma,this case is presented to provide insights into the diagnosis and treatment of this condition.CONCLUSION This suggests that bevacizumab may demonstrate potential efficacy in the treat-ment of cervical rhabdomyosarcoma.In the future,targeted therapy is expected to play an increasingly significant role in the management of rhabdomyosarcoma.
文摘Collecting duct carcinoma (CDC), or Bellini duct carcinoma, is a rare and aggressive subtype of renal cell carcinoma, accounting for 0.2% - 1% of cases. It often presents at an advanced stage with nonspecific symptoms, requiring histopathology for diagnosis. Surgery remains the standard of care for localized disease, serving both diagnostic and therapeutic purposes, though adjuvant chemotherapy has shown limited efficacy. In metastatic CDC, the gemcitabine-cisplatin regimen is commonly used due to its resemblance to urothelial cancer and supportive data from prospective studies. Newer therapies offer promise in advanced cases. Immune checkpoint inhibitors, such as nivolumab alone or with ipilimumab, have shown benefits in patients with high PD-L1 expression. Targeted therapies like cabozantinib demonstrated efficacy and safety as first-line treatments in phase II trials, while sunitinib and sorafenib have shown responses in various case reports and cohorts. However, combining chemotherapy with bevacizumab did not improve outcomes in phase II trials. Despite therapeutic advances in urothelial cancers and clear cell renal tumors, the CDC entity remains a challenging malignancy, emphasizing the need for continued research to understand the true efficacy of treatment and to prolong survival in advanced disease.
基金Supported by the National Natural Science Foundation of China,No.82270634Third Affiliated Hospital of Naval Medical University,No.tf2024yzyy01.
文摘Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantation are the gold standard for the radical treatment of HCC.However,due to the heterogeneity and high invasiveness of HCC,the rates of local and distant recurrence are extremely high,with over 70%of patients experiencing recurrence within 5 years after treatment,significantly impacting the long-term quality of life.Therefore,researchers are exploring other treatment methods to reduce tumor recurrence and improve patient survival.To date,extensive research has concentrated on new alternative therapies,including radiotherapy(e.g.,selective internal radiotherapy),targeted drug therapy(e.g.,sorafenib and lenvatinib),and immunotherapy(e.g.,immune checkpoint inhibitors),which have played an integral role in the comprehensive treatment of HCC.This review mainly focuses on the cutting-edge advancements in these treatment methods for HCC and their potential role in reducing HCC recurrence.
基金Supported by the Science and Engineering Research Board,No.PDF/2016/002730.
文摘Melanoma is an aggressive type of skin cancer notorious for its resistance to chemotherapy,radiotherapy and immunotherapy,which greatly impacts its lethality.The hedgehog(HH)signaling cascade,originally known for its roles in embryonic development,regulates growth,proliferation and cancer stem cell(CSC)self-renewal.The glioma-associated oncogene homolog(GLI)transcription factors play crucial roles in melanoma.However,oncogenic B-Raf proto-oncogene,serine/threonine kinase(BRAF)steals the spotlight by driving the aberrant activation of HH-GLI1/2 signaling.Oncogenic BRAF-driven HH-GLI1/2 signaling imparts invasive phenotype to melanoma cells and sustains CSC self-renewal.Interestingly,the transcriptional activities of GLI1 and GLI2 are suppressed by acetylation,a process that is counteracted by the deacetylating actions of histone deacetylase(HDAC)1/2.Therefore,inhibiting HDAC1/2 might keep GLI proteins in inactive acetylated form,thus representing an attractive druggable target.Notably,both HDAC1 and HDAC2 are induced by HH signaling,creating a positive feedback loop where HH signaling upregulates the expression of both HDAC1 and HDAC2.Selective inhibition of BRAF/HH/HDAC/GLI signaling axis is likely to unravel new therapeutic opportunities in melanoma.However,the precise contribution of oncogenic BRAF-driven HH signaling to therapy resistance and CSC renewal remains unclear and requires thorough investigation.In this article,we endeavored to explore the crosstalk between oncogenic BRAF and HH signaling,and the pivotal role this interaction plays in the self-renewal of melanoma stem cells.A better understanding of the molecular mechanisms governing these interactions is essential for improving melanoma treatment strategies and identifying new therapeutic targets.
基金support from the Science Research Program Project for Drug Regulation,Jiangsu Medical Products Administration,China(Grant No.:202207)the National Drug Standards Revision Project,China(Grant No.:2023Y41)+1 种基金the National Natural Science Foundation of China(Grant No.:22276080)the Foreign Expert Project,China(Grant No.:G2022014096L).
文摘In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95%of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.
基金funded by a grant fromtheMinistero dell’Universita e della Ricerca,PRIN 2022 PNRR grant(Prot.P2022LZXNWto R.B.).
文摘Mesothelioma is a rare and aggressive cancer with a poor prognosis and limited therapeutic options.Despite recent advances,conventional treatment approaches remain largely ineffective due to late diagnosis,chemore-sistance and immunosuppressive tumor microenvironment.This review reports the latest studies on combination therapies for mesothelioma,focusing on the potential of integrating chemotherapeutic agents,molecularly targeted agents,vaccines and natural bioactive compounds such as polyphenols.Clinical and preclinical studies demonstrate that integrating immune-modulating drugs or molecular inhibitors with chemotherapy can improve survival and reduce tumor progression in mesothelioma models and patients.Vaccine-based strategies show potential for inducing host-persistent immune responses when combined with conventional treatments.Moreover,natural compounds such as polyphenols show synergistic effects with chemotherapeutics and targeted agents by modulating several signaling pathways involved in cancer cell growth and progression and by overcoming drug resistance.While several combination strategies are under clinical investigation,further studies are needed to develop more effective and personalized therapeutic approaches that could be translated into standardized treatment protocols.
基金sponsored by Shanghai Education Commission Major Project(2017-01-07-00-07-E00052)National Natural Science Foundation of China(No.81773657)+1 种基金Shanghai Sailing Program(No.20YF1404500)Scientific Research Foundation of Huashan Hospital,Fudan University(No.2019QD012).
文摘There remain several intractable challenges for chemotherapy in glioma treatment,including the blood-brain barrier(BBB),blood-brain tumor barrier(BBTB),and tumor heterogeneity caused by cancer stem cells(CSCs),which are resistant to conventional chemotherapy.Here,we established a nano strategy to kill glioma cells and CSCs,combining carfilzomib and bis(diethyldithiocarbamate)copper.The synergistic drug combination disturbed cell protein metabolism at different stages and induced apoptosis and cuproptosis.The Y-shaped targeting ligand pHA-VAP-modified nanodiscs were designed to help the chemotherapeutic agents cross the BBB/BBTB and finally accumulate in tumor site.This all-stage targeting and all-stage treatment nanomedicine significantly prolonged the survival in glioma-bearing mice and might inspire the rational design of advanced drug delivery platforms.
基金Supported by 2023 Hebei Provincial Medical Scientific Research Project Plan,No.20231304.
文摘Colorectal cancer(CRC)with liver metastasis remains a significant therapeutic challenge,particularly in cases of postoperative recurrence.While transarterial chemoembolization(TACE)and targeted therapies have shown promise individually,the efficacy combining these for treating postoperative recurrent CRC with liver metastasis requires further investigation.AIM To evaluate the efficacy and safety of TACE combined with targeted therapies for postoperative recurrent CRC with liver metastasis.METHODS This observational study enrolled 75 patients with postoperative recurrent CRC accompanied by liver metastasis between January 2020 and December 2023.All patients received combined treatment with TACE and targeted therapy:Bevacizumab(40 patients,53.3%),cetuximab(25 patients,33.3%),or panitumumab(10 patients,13.3%).Treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors 1.1 criteria,with overall survival(OS)and progression-free survival as the primary endpoints.Quality of life was assessed using the European Organization for Research and Treatment of Cancer quality of life questionnaire at baseline and after six months of treatment.RESULTS The median OS was 28 months(95%confidence interval:24-32 months),and the median progression-free survival was 12 months(95%confidence interval:10-14 months).Patients treated with bevacizumab showed significantly better survival outcomes than those treated with cetuximab/panitumumab(median OS,30 vs 24 months,P=0.015).The overall response rate was 58.7%,with a disease control rate of 86.7%.Quality of life scores improved significantly across all domains,with greater improvements observed in the bevacizumab group.Treatment-related adverse events were manageable,with grade 3-4 events occurring in 13.3%of the patients and no treatment-related mortality.CONCLUSION The combination of TACE with targeted therapy,particularly bevacizumab,has demonstrated promising efficacy and acceptable safety for the treatment of postoperative recurrent CRC with liver metastasis.This multimodal approach not only improved survival outcomes but also enhanced the patients’quality of life,suggesting its potential as a valuable treatment strategy for this challenging condition.
基金Supported by Chongqing Young and Middle-aged Medical High-end Talents,No.YXGD202405Chongqing District and County Head Goose Talents,Chongqing Science and Technology and Health Joint Scientific Research Project on Traditional Chinese Medicine,No.2024ZYYB036Chongqing Banan District Science and Technology and Health Joint Scientific Research Project on Traditional Chinese Medicine,No.BNWJ202300112.
文摘BACKGROUND Many studies have found that sarcopenia is related to the survival of patients with liver cancer,which may lead to worse prognosis.AIM To investigate the relationship between skeletal muscle mass and prognosis in patients with liver cancer receiving targeted therapy by meta-analysis.METHODS PubMed,Embase,Cochrane Library,and Web of Science were searched for clinical studies on the relationship between skeletal muscle index(SMI)and the prognosis of patients with liver cancer receiving targeted therapy from inception to March 1,2022.Meta-analysis and sensitivity analysis of the data were performed using Stata 16.0 software.RESULTS A total of 6877 studies were searched,and finally 12 articles with 1715 cases were included.Meta-analysis result of 8 articles showed that compared with non-low SMI group,the overall survival(OS)of patients with liver cancer in the low SMI group was significantly shorter(hazard ratio=1.60,95%confidence interval:1.44-1.77,P=0.000).Meta-analysis result of 4 articles showed that,compared with low SMI group,patients in the nonlow SMI group had longer OS(hazard ratio=0.59,95%confidence interval:0.38-0.91,P=0.018).CONCLUSION Skeletal muscle mass is positively correlated with OS in patients with liver cancer receiving targeted therapy.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(2022A1515220184,Lewei Zhu)Hebei Natural Science Foundation(H2024105019).
文摘The tumor microenvironment(TME)is a complex network composed of non-tumor cells,extracellular matrix,blood vessels,and various molecular signals that surround and profoundly influence tumor progression.As one of the key immune effector cells within the TME,mast cells(MCs)exhibit functional complexity,and their specific roles remain widely debated.Depending on the cancer type,spatial distribution,and interactions with other TME components,MCs can demonstrate dual regulatory capabilities—either promoting or inhibiting tumor growth.This characteristic has made them an important focus in current tumor immunology research.This review aims to systematically review the current understanding of MCs in the TME,with emphasis on their characteristics and functional differences across various tumor types,pathological status,and species.In recent years,advances in the understanding of MC markers,activation mechanisms,and biological functions have made targeting specific MC subsets an emerging therapeutic strategy.By comprehensively examining the origin,activation mechanisms,cellular interactions,and therapeutic regulation ofMCs,this review provides new perspectives and a basis for future directions in tumor research and treatment.
基金supported by Pudong New Area Science and Technology Development Fund Special Research Project on the Livelihood of Institutions(No.PKJ2023-Y03)Pudong New Area Chinese Medicine Senior Teacher Training Program(No.PDZY-2023-0801)Talents Training Program of the Seventh People’s Hospital,Shanghai University of Traditional Chinese Medicine(No.JY2024-08).
文摘Background:Diabetic peripheral neuropathy(DPN)is a prevalent and debilitating complication of diabetes mellitus,lacking effective treatment options.Despite unclear underlying mechanisms,electroacupuncture(EA)shows promise in relieving DPN symptoms.Neurotransmitter dysregulation is central to DPN pathophysiology.This study aimed to investigate EA’s effects on DPN via targeted neurotransmitter metabolomics.Methods:A streptozotocin-induced mouse model of DPN was developed,and EA treatment was administered for two weeks to assess the therapeutic potential of EA.Following the collection of sciatic nerve samples,LC-MS-based targeted metabolomics analyses investigations were performed to examine alterations in DPN-associated neurotransmitter metabolism brought on by EA therapy.Multivariate statistical analyses were employed to assess metabolite expression patterns,using cluster heatmaps to display neurotransmitter expression results.KEGG pathway analyses were also used to explore the functional classifications of these neurotransmitters and associated metabolic pathways.Results:Targeted neurotransmitter-focused metabolomics analyses led to the identification of 34 putative biomarkers associated with EA treatment,of which 5 showed significant changes,such as beta-alanine(increased by 80.37%,P=0.0004)and kynurenine(decreased by 29.36%,P=0.0163).KEGG pathway analysis indicated that changes in the abundance of these metabolites were associated with the cAMP signaling pathway,neuroactive ligand-receptor interactions,the synaptic vesicle cycle,and other pathways.Conclusion:The results indicate that EA can efficiently regulate neurotransmitter metabolism and restore peripheral nerve function,suggesting a feasible non-pharmacological strategy for DPN treatment and warranting clinical translation.
基金supported by the National Natural Science Foundation of China(Grant Nos.:32141003,82330110,and 81803593)the CAMS Innovation Fund for Medical Sciences(CIFMS),China(Grant Nos.:2021-I2M-1-030,and 2021-I2M-1-039)+1 种基金the Fundamental Research Funds for the Central Universities,China(Grant No.:3332018094)the National Science and Technology Infrastructure of China(Project No.:National Pathogen Resource Center-NPRC-32).
文摘TEM and SHV are among the most prevalentβ-lactamases contributing toβ-lactam antibiotic resistance in clinical settings,leading to treatment challenges and increased mortality rates.Except for penicillin and early cephalosporins,TEM and SHV variants have evolved with the ability to hydrolyze the second-and third-generation cephalosporins,monobactams,and evenβ-lactamase inhibitors.Accurate detection ofβ-lactamases is of paramount importance for optimizing antibiotic use and combating antimicrobial resistance(AMR).While genetic detection methods,such as polymerase chain reaction(PCR),are widely employed,their positive results may lack phenotypic correlation due to the low or absent expression of blaSHV and blaTEM in many strains[1].Therefore,a direct protein-level detection method such as targeted proteomics is more precise and clinically relevant.This study highlights the development of a rapid detection method using targeted proteomics with high-resolution accurate mass(HRAM)Orbitrap MS for the direct detection of TEM and SHV in Enterobacteriaceae strains,which offers greater clinical relevance compared to conventional genetic approaches.
