Antifungal resistance is the leading cause of antifungal treatment failure in invasive candidiasis.Metabolic rewiring could become a new insight to account for antifungal resistance as to find innovative clinical ther...Antifungal resistance is the leading cause of antifungal treatment failure in invasive candidiasis.Metabolic rewiring could become a new insight to account for antifungal resistance as to find innovative clinical therapies.Here,we show that dynamic surface-enhanced Raman spectroscopy is a promising tool to identify the metabolic differences between fluconazole(Diflucan)-resistant and fluconazole(Diflucan)-sensitive Candida albicans through the signatures of biochemical components and complemented with machine learning algorithms and two-dimensional correlation spectroscopy,an underlying resistance mechanism,that is,the change of purine metabolites induced the resistance of Candida albicans has been clarified yet never reported anywhere.We hope the integrated methodology introduced in this work could be beneficial for the interpretation of cellular regulation,propelling the development of targeted antifungal therapies and diagnostic tools for more efficient management of severe antifungal resistance.展开更多
·AIM:To evaluate the efficacy and safety of HLX04-O,an investigational ophthalmic formulation of HLX04(bevacizumab biosimilar)for intravitreal injection,as a treatment for wet age-related macular degeneration(wAM...·AIM:To evaluate the efficacy and safety of HLX04-O,an investigational ophthalmic formulation of HLX04(bevacizumab biosimilar)for intravitreal injection,as a treatment for wet age-related macular degeneration(wAMD)in a phase 1/2 clinical trial(NCT04993352).·METHODS:Eligible patients with wAMD were enrolled to receive HLX04-O intravitreal injections at a dose of1.25 mg/0.05 mL every four weeks.Efficacy and adverse events were evaluated every month during study visits.·RESULTS:A 76-year-old male with wAMD in his left eye participated in the trial and completed six cycles of HLX04-O intravitreal injections.Changes were observed in macular center point thickness(baseline vs last study visit,437 vs 255μm)and best-corrected visual acuity letter score(baseline vs last study visit,36 vs 77)of the affected eye,which indicated an improvement in wAMD over treatment.No adverse events were reported by the data cutoff date.·CONCLUSION:HLX04-O at 1.25 mg/0.05 mL every four weeks is well tolerated in this patient,demonstrating promising safety and efficacy in wAMD treatment.Largescale studies are required to confirm the outcomes.展开更多
The rise in the incidence of cancer globally has led to a heightened interest in targeted therapies as a form of anticancer treatment.Key oncogenic targets,including epidermal growth factor receptor(EGFR),vascular end...The rise in the incidence of cancer globally has led to a heightened interest in targeted therapies as a form of anticancer treatment.Key oncogenic targets,including epidermal growth factor receptor(EGFR),vascular endothelial growth factor(VEGF),and kirsten rat sarcoma viral oncogene homologue(KRAS),have emerged as focal points in the development of targeted agents.Research has investigated the impact of gut microbiota on the efficacy of various anticancer therapies,such as immunotherapy,chemotherapy,and radiotherapy.However,a notable gap exists in the literature regarding the relationship between gut microbiota and targeted agents.This review emphasizes how specific gut microbiota and gut microbiota metabolites,including butyrate,propionate,and ursodeoxycholic acid,interact with oncogenic pathways to modulate anti-tumor effects.Conversely,deoxycholic acid,lipopolysaccharide,and trimethylamine n-oxide may exert pro-tumor effects.Furthermore,modulation of the gut microbiota influences glucose and lipid metabolism,thereby enhancing the response to anti-KRAS agents and addressing diarrhea induced by tyrosine kinase inhibitors.By elucidating the connection between gut microbiota and the EGFR/VEGF/KRAS pathways,this review provides valuable insights for advancing targeted cancer therapy and optimizing treatment outcomes in clinical settings.展开更多
Lung cancer is a malignant tumor with high incidence and mortality rates in China and worldwide.Approximately 10%of these diseases are caused by multiple primary non-small cell lung cancers(NSCLC).Traditional antitumo...Lung cancer is a malignant tumor with high incidence and mortality rates in China and worldwide.Approximately 10%of these diseases are caused by multiple primary non-small cell lung cancers(NSCLC).Traditional antitumor therapies,such as chemotherapy,radiotherapy,and targeted therapy,have limited efficacy in the treatment of advanced synchronous multiple primary NSCLC.Immunotherapy is considered the standard of care for advanced or recurrent NSCLC,however,approximately 60%of patients develop primary or secondary resistance to treatment.There are no standard recommendations for overcoming immune resistance.We describe a case of simultaneous multiple primary NSCLC in a patient who received programmed death factor-1(PD-1)inhibitor monotherapy and developed brain metastases.After receiving second-line treatment with a combination of another PD-1 inhibitor,pemetrexed,and bevacizumab,the patient achieved complete remission,although they experienced grade 3 immune-related adverse reactions.Immune re-challenge is safe and feasible,and choosing a synergistic combination regimen is one of the options to overcome immune resistance.A larger sample size is needed to confirm the effectiveness and safety of this strategy in patients with NSCLC resistant to prior PD-1 inhibitors.展开更多
HA121-28,a promising multikinase inhibitor,mainly targets rearranged during transfection(RET)fusions and selectively targets vascular endothelial growth factor receptor-2,endothelial growth factor receptor,and fibrobl...HA121-28,a promising multikinase inhibitor,mainly targets rearranged during transfection(RET)fusions and selectively targets vascular endothelial growth factor receptor-2,endothelial growth factor receptor,and fibroblast growth factor receptor 1-3.The safety,pharmacokinetics,and efficacy of HA121-28 were assessed in advanced solid tumors(phase 1,ClinicalTrials.gov NCT03994484)and advanced RET fusion-positive non-small-cell lung cancer(RET-TKI naive NSCLC,phase 2,ClinicalTrials.gov NCT05117658).HA121-28 was administered orally in doses range from 25 to 800 mg under the 21-day on/7-day off scheme for a 28-day cycle in phase 1 trial.The recommended dose identified in phase 1(450 mg)was administered for patients during phase 2.The primary endpoints were the maximum tolerated dose(MTD)in phase 1 and the objective response rate(ORR)in phase 2.162 patients were enrolled in phase 1 and 48 in phase 2.A total of 600 mg once daily was set as MTD.Across 100-800 mg,the exposure of HA121-28 increased in a dose-dependent manner.Consistent between both trials,diarrhea,rash,and prolonged QTc interval,were the most reported treatment-emergent adverse events.40.0%(phase 1)and 62.5%(phase 2)patients experienced grade≥3 treatment-related adverse events,respectively.The overall ORR was 26.8%and the median progression-free survival(PFS)was 5.5 months among 97 NSCLC patients with advanced RET fusion receiving a dose at≥450 mg once daily.HA121-28 showed encouraging efficacy in advanced RET fusion NSCLC and its toxicity was tolerable in most patients.Nevertheless,cardiotoxicity is a notable concern that warrants careful attention.展开更多
BACKGROUND Esophageal cancer is a common malignant tumor of the digestive system.At present,surgery is the most important treatment strategy.After esophagectomy and gastric esophagoplasty,the patients are prone to reg...BACKGROUND Esophageal cancer is a common malignant tumor of the digestive system.At present,surgery is the most important treatment strategy.After esophagectomy and gastric esophagoplasty,the patients are prone to regurgitation.However,these patients currently do not receive much attention,especially from anesthesiologists.CASE SUMMARY A 55-year-old woman was scheduled for right lower lung lobectomy.The patient had undergone radical surgery for esophageal cancer under general anesthesia 6 mo prior.Although the patient had fasted for>17 h,unexpected aspiration still occurred during induction of general anesthesia.Throughout the operation,oxygen saturation was 98%-100%,but the airway pressure was high(35 cmH2O at double lung ventilation).The patient was sent to the intensive care unit after surgery.Bedside chest radiography was performed,which showed exudative lesions in both lungs compared with the preoperative image.After surgery,antibiotics were given to prevent lung infection.On day 2 in the intensive care unit,the patient was extubated and discharged on postoperative day 7 without complications related to aspiration pneumonia.CONCLUSION After esophagectomy,patients are prone to regurgitation.We recommend nasogastric tube placement followed by rapid sequence induction or conscious intubation.展开更多
BACKGROUND Endoscopic thyroidectomy has obvious advantages over conventional surgical techniques in terms of postoperative cosmetic outcome.Although the incidence of carbon dioxide embolism(CDE)during endoscopic thyro...BACKGROUND Endoscopic thyroidectomy has obvious advantages over conventional surgical techniques in terms of postoperative cosmetic outcome.Although the incidence of carbon dioxide embolism(CDE)during endoscopic thyroidectomy is very low,it is potentially fatal.The clinical manifestations of CDE vary,and more attention should be paid to this disorder.CASE SUMMARY A 27-year-old man was scheduled for thyroidectomy by the transoral vestibular approach.The patient had no other diseases or surgical history.During the operation,he developed a CDE following inadvertent injury of the anterior jugular vein.The clinical manifestation in this patient was a transient sharp rise in end-tidal carbon dioxide,and his remaining vital signs were stable.In addition,loud coarse systolic and diastolic murmurs were heard over the precordium.The patient was discharged on day 4 after surgery without complications.CONCLUSION A transient sharp rise in end-tidal carbon dioxide is considered a helpful early sign of CDE during endoscopic thyroidectomy.展开更多
Diffuse large B-cell lymphoma(DLBCL)is a prevalent human malignancy,and understanding its biology will help identify problems in refractory patients and customize alternative therapies for them.We found that DLBCL can...Diffuse large B-cell lymphoma(DLBCL)is a prevalent human malignancy,and understanding its biology will help identify problems in refractory patients and customize alternative therapies for them.We found that DLBCL can be stratified into two independent subtypes with different clinical characteristics and outcomes by consensus clustering of expression of ferroptosis regulatory genes,which proves that ferroptosis is effective in treating refractory cases.In this work,we constructed a novel ferroptosis nanocarrier(PBPMn@PEG)by coating Prussian blue nanoparticles with manganese ions and encapsulating them with poly(ethyleneglycol).The low efficiency of the Fenton reaction of Prussian blue nanoparticles can be improved greatly by manganese coating,and can effectively generate hydroxyl radicals,and induce ferroptosis of lymphoma cells(SU-DHL-10 cells)by down-regulating ferroptosis suppressor genes and up-regulating ferroptosis driver genes.It also induces effective cell apoptosis,which is synergistic with ferroptosis for DLBCL therapy.In vivo experiments also prove that PBPMn@PEG achieved a better anti-tumor effect by up-regulating COX2,HO-1/hemeoxygenase-1(HMOX1),and NADPH oxidase-4(NOX4),and downregulating FSP1 and GPX4,with lower biotoxicity.As a novel and potential DLBCL drug carrier,our discovery served as a foundation for the treatment of the refractory DLBCL by inducing ferroptosis for DLBCL treatment in addition to the therapeutic effect of drugs.展开更多
Background:Metaplastic breast carcinoma(MBC)is a rare breast cancer subtype;most cases are triple‐negative breast cancers(TNBCs)and are poorly responsive to conventional systemic therapy.Few potential diagnostic and ...Background:Metaplastic breast carcinoma(MBC)is a rare breast cancer subtype;most cases are triple‐negative breast cancers(TNBCs)and are poorly responsive to conventional systemic therapy.Few potential diagnostic and prognostic markers for distinguishing between metaplastic TNBC and nonmetaplastic TNBC have been discovered.We performed bioinformatic analysis to explore the underlying mechanism by which metaplastic TNBC differs from nonmetaplastic TNBC and provides potential pathogenic genes of metaplastic TNBC.Methods:Differentially expressed genes(DEGs)in metaplastic tumors and nonmetaplastic tumors from TNBC patients were screened using GSE165407.The GSE76275 data set and The Cancer Genome Atlas(TCGA)database were used to screen DEGs in TNBC and non‐TNBC.Metascape and DAVID were used for the Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology(GO)analysis of DEGs.Online databases,including UALCAN,GEPIA,HPA,Breast Cancer Gene‐Expression Miner,and quantitative PCR and western blot,were used to examine KLK5 messenger RNA and protein expression in breast cancer.Analysis of KLK5‑associated genes was performed with TCGA data,and the LinkedOmics database was used to detect the genes co‐expressed with KLK5.STRING(Search Tool for the Retrieval of Interacting Genes)and Cytoscape were used to screen for hub genes.Kaplan‑Meier plotter was used for survival analysis.Results:KLK5 was identified among the DEGs in nonmetaplastic TNBC and metaplastic TNBC.The KLK5 gene was overexpressed in nonmetaplastic TNBC but downregulated in metaplastic TNBC.KEGG and GO analyses revealed that epithelial‐to‐mesenchymal transition was a pathogenic mechanism in metaplastic TNBC and an important pathway by which KLK5 and its associated genes DSG1and DSG3 influence metaplastic TNBC progression. Prognosis analysis showedthat only low expression of KLK5 in metaplastic TNBC had clinical significance.Conclusion: Our research indicated that KLK5 may be a pivotal moleculewith a key role in the mechanism of tumorigenesis in metaplastic TNBC.展开更多
Background and Aims:It is challenging to predict the 90-day outcomes of patients infected with hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)via prevailing predictive models.This study aimed to dev...Background and Aims:It is challenging to predict the 90-day outcomes of patients infected with hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)via prevailing predictive models.This study aimed to develop an innovative model to enhance the analytical efficacy of 90-day mortality in HBV-ACLF.Methods:In this study,149 HBV-ACLF patients were evaluated by constructing a death risk prediction nomogram.Bootstrap resampling and an independent validation cohort comprising 31 patients from June 2019 to February 2020 were assessed for model confirmation.Results:The nomogram was constructed by entering and identifying five factors age,total bilirubin,prothrombin activity(PTA),lymphocyte(L)%,and monocyte(M)%.Healthy refinement was achieved from the nomogram analysis,where the area under the receiver operating characteristic curve was 0.864 for the training cohort and 0.874 was achieved for the validation cohort.There was admirable concordance between the predicted and true results in the equilibrium curve.The decision curve assessment revealed the useful clinical application of the nomogram.Conclusions:We constructed an innovative nomogram and validated it for the prediction of 90-day HBV-ACLF patient outcomes.This model might help develop optimized treatment protocol recommendations for HBV-ACLF patients。展开更多
Dear Editor,Circadian rhythms are physical,behavioral,and mental changes that follow a roughly 24-h cycle.Our prior researches have estab-lished a significant correlation between the disruption of the cir-cadian rhyth...Dear Editor,Circadian rhythms are physical,behavioral,and mental changes that follow a roughly 24-h cycle.Our prior researches have estab-lished a significant correlation between the disruption of the cir-cadian rhythm and the severity of experimental colitis,an animal model replicating inflammatory bowel disease(IBD)in humans[1,2].IBD is a chronic inflammatory disease of the gastrointesti-nal tract and is divided into ulcerative colitis and Crohn’s disease.Approximately 0.5%of the population in the Western world suf-fers from IBD[3].展开更多
Gastric cancer is a highly heterogeneous and aggressive malignancy,with conventional therapies often hampered by poor drug targeting and an immunosuppressive tumor microenvironment(TME).To address these limitations,we...Gastric cancer is a highly heterogeneous and aggressive malignancy,with conventional therapies often hampered by poor drug targeting and an immunosuppressive tumor microenvironment(TME).To address these limitations,we developed a biomimetic nanoplatform(PLGA-UA@MA)composed of poly(lactic-co-glycolic acid)(PLGA)nanoparticles encapsulating the natural antitumor agent ursolic acid(UA),further cloaked with homologous gastric cancer cell membranes doped with the immunoadjuvant monophosphoryl lipid A(MPLA).This engineered system synergistically combines tumor-specific targeting,immune modulation,and stimuliresponsive drug release,presenting a precision therapeutic strategy for gastric cancer.PLGA-UA@M-A exhibits selective homing to primary tumor sites,facilitated by membrane fusion-mediated enhanced cellular uptake.In vitro studies demonstrated potent inhibition of MFC gastric cancer cell proliferation,induction of apoptosis,and suppression of metastatic behavior,underscoring its enhanced antitumor efficacy.Moreover,the nanoplatform triggered immunogenic cell death(ICD),while MPLA acted as an immunostimulant to promote dendritic cell maturation and T-cell priming—effectively reprogramming the immunosuppressive TME.In vivo evaluations confirmed excellent tumor accumulation,robust antitumor activity,and negligible systemic toxicity,highlighting its favorable biosafety profile.Collectively,PLGA-UA@M-A represents a multifunctional biomimetic delivery system that integrates chemotherapy with immune activation,offering a promising therapeutic paradigm for gastric cancer treatment.展开更多
With the acceleration of China's aging society,elderly patients have become a high-risk group for malignant tumors and exhibit high prevalence of pain.For a long time,the diagnosis,treatment,and management of canc...With the acceleration of China's aging society,elderly patients have become a high-risk group for malignant tumors and exhibit high prevalence of pain.For a long time,the diagnosis,treatment,and management of cancer pain in elderly Chinese patients have been inadequate.This study used"Older adults,geriatric patients,cancer pain,pain assessment,pain management,elderly cancer,geriatric oncology,medication management,palliative care,interdisciplinary pain management,Analgesics,quality of life"as key words.We systematically searched PubMed,Web of Science,CNKI,and Wanfang databases from their inception to September 2024.The search primarily included phase I to III clinical trials,randomized controlled trials,meta-analyses,systematic reviews,and case reports.Elderly patients typically present with complex pain mechanisms,including both cancer-related and non-cancer pain,cognitive dysfunction,comorbidities,and polypharmacy,posing significant challenges for clinical diagnosis and treatment.Notable clinical differences exist between elderly and younger patients in the epidemiology,assessment,diagnosis,and treatment of cancer pain.Currently,the awareness of comprehensive management for elderly cancer pain patients is limited,and specific,implementable clinical guidelines are lacking.Therefore,developing a comprehensive,localized management model for elderly cancer pain patients in China—incorporating factors such as age-related impacts,organ function status,and comorbidities—has become an urgent necessity.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.22074015 and 82074428)Youth Talent Cultivation Initiation Fund of Zhongda Hospital,Southeast University(No.CZXM-GSP-RC110)to Hao Li+1 种基金Evidence-Based Capacity Building for TCM Specialty Therapies for Skin Diseases of National Administration of TCMInnovative Team Projects of Shanghai Municipal Commission of Health(No.2022CX011)to Fulun Li.
文摘Antifungal resistance is the leading cause of antifungal treatment failure in invasive candidiasis.Metabolic rewiring could become a new insight to account for antifungal resistance as to find innovative clinical therapies.Here,we show that dynamic surface-enhanced Raman spectroscopy is a promising tool to identify the metabolic differences between fluconazole(Diflucan)-resistant and fluconazole(Diflucan)-sensitive Candida albicans through the signatures of biochemical components and complemented with machine learning algorithms and two-dimensional correlation spectroscopy,an underlying resistance mechanism,that is,the change of purine metabolites induced the resistance of Candida albicans has been clarified yet never reported anywhere.We hope the integrated methodology introduced in this work could be beneficial for the interpretation of cellular regulation,propelling the development of targeted antifungal therapies and diagnostic tools for more efficient management of severe antifungal resistance.
文摘·AIM:To evaluate the efficacy and safety of HLX04-O,an investigational ophthalmic formulation of HLX04(bevacizumab biosimilar)for intravitreal injection,as a treatment for wet age-related macular degeneration(wAMD)in a phase 1/2 clinical trial(NCT04993352).·METHODS:Eligible patients with wAMD were enrolled to receive HLX04-O intravitreal injections at a dose of1.25 mg/0.05 mL every four weeks.Efficacy and adverse events were evaluated every month during study visits.·RESULTS:A 76-year-old male with wAMD in his left eye participated in the trial and completed six cycles of HLX04-O intravitreal injections.Changes were observed in macular center point thickness(baseline vs last study visit,437 vs 255μm)and best-corrected visual acuity letter score(baseline vs last study visit,36 vs 77)of the affected eye,which indicated an improvement in wAMD over treatment.No adverse events were reported by the data cutoff date.·CONCLUSION:HLX04-O at 1.25 mg/0.05 mL every four weeks is well tolerated in this patient,demonstrating promising safety and efficacy in wAMD treatment.Largescale studies are required to confirm the outcomes.
基金supported by the Major International(Regional)Joint Research Program of the National Natural Science Foundation of China(Grant No.81920108027)National Outstanding Youth Reserve Talent Training Project,Research Capacity Enhancement Project of Chongqing University Cancer Hospital(Grant No.Y121)Funding for Chongqing Young and Middle-Aged Medical Excellence Team.
文摘The rise in the incidence of cancer globally has led to a heightened interest in targeted therapies as a form of anticancer treatment.Key oncogenic targets,including epidermal growth factor receptor(EGFR),vascular endothelial growth factor(VEGF),and kirsten rat sarcoma viral oncogene homologue(KRAS),have emerged as focal points in the development of targeted agents.Research has investigated the impact of gut microbiota on the efficacy of various anticancer therapies,such as immunotherapy,chemotherapy,and radiotherapy.However,a notable gap exists in the literature regarding the relationship between gut microbiota and targeted agents.This review emphasizes how specific gut microbiota and gut microbiota metabolites,including butyrate,propionate,and ursodeoxycholic acid,interact with oncogenic pathways to modulate anti-tumor effects.Conversely,deoxycholic acid,lipopolysaccharide,and trimethylamine n-oxide may exert pro-tumor effects.Furthermore,modulation of the gut microbiota influences glucose and lipid metabolism,thereby enhancing the response to anti-KRAS agents and addressing diarrhea induced by tyrosine kinase inhibitors.By elucidating the connection between gut microbiota and the EGFR/VEGF/KRAS pathways,this review provides valuable insights for advancing targeted cancer therapy and optimizing treatment outcomes in clinical settings.
文摘Lung cancer is a malignant tumor with high incidence and mortality rates in China and worldwide.Approximately 10%of these diseases are caused by multiple primary non-small cell lung cancers(NSCLC).Traditional antitumor therapies,such as chemotherapy,radiotherapy,and targeted therapy,have limited efficacy in the treatment of advanced synchronous multiple primary NSCLC.Immunotherapy is considered the standard of care for advanced or recurrent NSCLC,however,approximately 60%of patients develop primary or secondary resistance to treatment.There are no standard recommendations for overcoming immune resistance.We describe a case of simultaneous multiple primary NSCLC in a patient who received programmed death factor-1(PD-1)inhibitor monotherapy and developed brain metastases.After receiving second-line treatment with a combination of another PD-1 inhibitor,pemetrexed,and bevacizumab,the patient achieved complete remission,although they experienced grade 3 immune-related adverse reactions.Immune re-challenge is safe and feasible,and choosing a synergistic combination regimen is one of the options to overcome immune resistance.A larger sample size is needed to confirm the effectiveness and safety of this strategy in patients with NSCLC resistant to prior PD-1 inhibitors.
基金funded by Sun Yat-sen University clinical research 5010 program(84000-31630002)Cancer Innovative Research Program of Sun Yat-sen University Cancer Center(CIRP-SYSUCC-0004)+4 种基金the National Natural Science Foundation of China(82073396)CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-036)the Guangdong Basic and Applied Basic Research Foundation(2021A1515110697)the Guangzhou Key Research and Development Plan(202206010141)CSPC ZhongQi Pharmaceutical Technology(Shijiazhuang)Co.
文摘HA121-28,a promising multikinase inhibitor,mainly targets rearranged during transfection(RET)fusions and selectively targets vascular endothelial growth factor receptor-2,endothelial growth factor receptor,and fibroblast growth factor receptor 1-3.The safety,pharmacokinetics,and efficacy of HA121-28 were assessed in advanced solid tumors(phase 1,ClinicalTrials.gov NCT03994484)and advanced RET fusion-positive non-small-cell lung cancer(RET-TKI naive NSCLC,phase 2,ClinicalTrials.gov NCT05117658).HA121-28 was administered orally in doses range from 25 to 800 mg under the 21-day on/7-day off scheme for a 28-day cycle in phase 1 trial.The recommended dose identified in phase 1(450 mg)was administered for patients during phase 2.The primary endpoints were the maximum tolerated dose(MTD)in phase 1 and the objective response rate(ORR)in phase 2.162 patients were enrolled in phase 1 and 48 in phase 2.A total of 600 mg once daily was set as MTD.Across 100-800 mg,the exposure of HA121-28 increased in a dose-dependent manner.Consistent between both trials,diarrhea,rash,and prolonged QTc interval,were the most reported treatment-emergent adverse events.40.0%(phase 1)and 62.5%(phase 2)patients experienced grade≥3 treatment-related adverse events,respectively.The overall ORR was 26.8%and the median progression-free survival(PFS)was 5.5 months among 97 NSCLC patients with advanced RET fusion receiving a dose at≥450 mg once daily.HA121-28 showed encouraging efficacy in advanced RET fusion NSCLC and its toxicity was tolerable in most patients.Nevertheless,cardiotoxicity is a notable concern that warrants careful attention.
基金Supported by Natural Science Foundation of Chongqing,China,No.CSTC2019JCYJ-MSXMX0623。
文摘BACKGROUND Esophageal cancer is a common malignant tumor of the digestive system.At present,surgery is the most important treatment strategy.After esophagectomy and gastric esophagoplasty,the patients are prone to regurgitation.However,these patients currently do not receive much attention,especially from anesthesiologists.CASE SUMMARY A 55-year-old woman was scheduled for right lower lung lobectomy.The patient had undergone radical surgery for esophageal cancer under general anesthesia 6 mo prior.Although the patient had fasted for>17 h,unexpected aspiration still occurred during induction of general anesthesia.Throughout the operation,oxygen saturation was 98%-100%,but the airway pressure was high(35 cmH2O at double lung ventilation).The patient was sent to the intensive care unit after surgery.Bedside chest radiography was performed,which showed exudative lesions in both lungs compared with the preoperative image.After surgery,antibiotics were given to prevent lung infection.On day 2 in the intensive care unit,the patient was extubated and discharged on postoperative day 7 without complications related to aspiration pneumonia.CONCLUSION After esophagectomy,patients are prone to regurgitation.We recommend nasogastric tube placement followed by rapid sequence induction or conscious intubation.
基金Science and Technology Bureau of Shapingba District,Chongqing,China,No.JCD202041and Science and Technology Bureau of Chongqing,China,No.CSTC2019JXJL130029.
文摘BACKGROUND Endoscopic thyroidectomy has obvious advantages over conventional surgical techniques in terms of postoperative cosmetic outcome.Although the incidence of carbon dioxide embolism(CDE)during endoscopic thyroidectomy is very low,it is potentially fatal.The clinical manifestations of CDE vary,and more attention should be paid to this disorder.CASE SUMMARY A 27-year-old man was scheduled for thyroidectomy by the transoral vestibular approach.The patient had no other diseases or surgical history.During the operation,he developed a CDE following inadvertent injury of the anterior jugular vein.The clinical manifestation in this patient was a transient sharp rise in end-tidal carbon dioxide,and his remaining vital signs were stable.In addition,loud coarse systolic and diastolic murmurs were heard over the precordium.The patient was discharged on day 4 after surgery without complications.CONCLUSION A transient sharp rise in end-tidal carbon dioxide is considered a helpful early sign of CDE during endoscopic thyroidectomy.
基金supported by the National Natural Science Foundation of China(Nos.32071334,51825302,and 21734002)Natural Science Foundation of Chongqing(Nos.cstc2021jcyj-cxttX0002 and cstc2019jscx-msxmX0160).
文摘Diffuse large B-cell lymphoma(DLBCL)is a prevalent human malignancy,and understanding its biology will help identify problems in refractory patients and customize alternative therapies for them.We found that DLBCL can be stratified into two independent subtypes with different clinical characteristics and outcomes by consensus clustering of expression of ferroptosis regulatory genes,which proves that ferroptosis is effective in treating refractory cases.In this work,we constructed a novel ferroptosis nanocarrier(PBPMn@PEG)by coating Prussian blue nanoparticles with manganese ions and encapsulating them with poly(ethyleneglycol).The low efficiency of the Fenton reaction of Prussian blue nanoparticles can be improved greatly by manganese coating,and can effectively generate hydroxyl radicals,and induce ferroptosis of lymphoma cells(SU-DHL-10 cells)by down-regulating ferroptosis suppressor genes and up-regulating ferroptosis driver genes.It also induces effective cell apoptosis,which is synergistic with ferroptosis for DLBCL therapy.In vivo experiments also prove that PBPMn@PEG achieved a better anti-tumor effect by up-regulating COX2,HO-1/hemeoxygenase-1(HMOX1),and NADPH oxidase-4(NOX4),and downregulating FSP1 and GPX4,with lower biotoxicity.As a novel and potential DLBCL drug carrier,our discovery served as a foundation for the treatment of the refractory DLBCL by inducing ferroptosis for DLBCL treatment in addition to the therapeutic effect of drugs.
基金National Natural Science Foundation of China,Grant/Award Number:82002816。
文摘Background:Metaplastic breast carcinoma(MBC)is a rare breast cancer subtype;most cases are triple‐negative breast cancers(TNBCs)and are poorly responsive to conventional systemic therapy.Few potential diagnostic and prognostic markers for distinguishing between metaplastic TNBC and nonmetaplastic TNBC have been discovered.We performed bioinformatic analysis to explore the underlying mechanism by which metaplastic TNBC differs from nonmetaplastic TNBC and provides potential pathogenic genes of metaplastic TNBC.Methods:Differentially expressed genes(DEGs)in metaplastic tumors and nonmetaplastic tumors from TNBC patients were screened using GSE165407.The GSE76275 data set and The Cancer Genome Atlas(TCGA)database were used to screen DEGs in TNBC and non‐TNBC.Metascape and DAVID were used for the Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology(GO)analysis of DEGs.Online databases,including UALCAN,GEPIA,HPA,Breast Cancer Gene‐Expression Miner,and quantitative PCR and western blot,were used to examine KLK5 messenger RNA and protein expression in breast cancer.Analysis of KLK5‑associated genes was performed with TCGA data,and the LinkedOmics database was used to detect the genes co‐expressed with KLK5.STRING(Search Tool for the Retrieval of Interacting Genes)and Cytoscape were used to screen for hub genes.Kaplan‑Meier plotter was used for survival analysis.Results:KLK5 was identified among the DEGs in nonmetaplastic TNBC and metaplastic TNBC.The KLK5 gene was overexpressed in nonmetaplastic TNBC but downregulated in metaplastic TNBC.KEGG and GO analyses revealed that epithelial‐to‐mesenchymal transition was a pathogenic mechanism in metaplastic TNBC and an important pathway by which KLK5 and its associated genes DSG1and DSG3 influence metaplastic TNBC progression. Prognosis analysis showedthat only low expression of KLK5 in metaplastic TNBC had clinical significance.Conclusion: Our research indicated that KLK5 may be a pivotal moleculewith a key role in the mechanism of tumorigenesis in metaplastic TNBC.
基金supported by the Municipal Natural Science Foundation of Beijing,China(No.7192085)National Science and Technology Major Project of China(No.2018ZX10302206-003-007)+2 种基金National Natural Science Foundation of China(No.82002461)Medjaden Academy and Research Foundation for Young Scientists(MJR20211110)as well as the Fund for Fostering Young Scholars of Peking University Health Science Center(BMU2021PY010).
文摘Background and Aims:It is challenging to predict the 90-day outcomes of patients infected with hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)via prevailing predictive models.This study aimed to develop an innovative model to enhance the analytical efficacy of 90-day mortality in HBV-ACLF.Methods:In this study,149 HBV-ACLF patients were evaluated by constructing a death risk prediction nomogram.Bootstrap resampling and an independent validation cohort comprising 31 patients from June 2019 to February 2020 were assessed for model confirmation.Results:The nomogram was constructed by entering and identifying five factors age,total bilirubin,prothrombin activity(PTA),lymphocyte(L)%,and monocyte(M)%.Healthy refinement was achieved from the nomogram analysis,where the area under the receiver operating characteristic curve was 0.864 for the training cohort and 0.874 was achieved for the validation cohort.There was admirable concordance between the predicted and true results in the equilibrium curve.The decision curve assessment revealed the useful clinical application of the nomogram.Conclusions:We constructed an innovative nomogram and validated it for the prediction of 90-day HBV-ACLF patient outcomes.This model might help develop optimized treatment protocol recommendations for HBV-ACLF patients。
基金This work was supported by the National Natural Science Foundation of China(82104238&82373940)Guangdong Basic and Applied Basic Research Foundation(2020A1515110732)the Science and Technology Planning Project of Guangzhou(202201020349).
文摘Dear Editor,Circadian rhythms are physical,behavioral,and mental changes that follow a roughly 24-h cycle.Our prior researches have estab-lished a significant correlation between the disruption of the cir-cadian rhythm and the severity of experimental colitis,an animal model replicating inflammatory bowel disease(IBD)in humans[1,2].IBD is a chronic inflammatory disease of the gastrointesti-nal tract and is divided into ulcerative colitis and Crohn’s disease.Approximately 0.5%of the population in the Western world suf-fers from IBD[3].
基金supported by the National Natural Science Foundation of China(No.82360498)Gansu Joint Scientific Research Fund Major Project(No.23JRRA1537)+5 种基金the 2025 Central-Guided Local Science and Technology Development Found(No.25ZYJA003)Gansu Provincial Health Industry Science and Technology Innovation Major Project(No.GSWSZD2024-01)Gansu Province Key Talent Project(No.2025RCXM067)2024 Gansu Provincial Hospital Special Fund of NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor(No.23GSSYA-10)the 2021 Central-Guided Local Science and Technology Development Found(No.ZYYDDFFZZJ-1)Zhejiang Provincial Natural Science Foundation of China(No.LTGY23H160032).
文摘Gastric cancer is a highly heterogeneous and aggressive malignancy,with conventional therapies often hampered by poor drug targeting and an immunosuppressive tumor microenvironment(TME).To address these limitations,we developed a biomimetic nanoplatform(PLGA-UA@MA)composed of poly(lactic-co-glycolic acid)(PLGA)nanoparticles encapsulating the natural antitumor agent ursolic acid(UA),further cloaked with homologous gastric cancer cell membranes doped with the immunoadjuvant monophosphoryl lipid A(MPLA).This engineered system synergistically combines tumor-specific targeting,immune modulation,and stimuliresponsive drug release,presenting a precision therapeutic strategy for gastric cancer.PLGA-UA@M-A exhibits selective homing to primary tumor sites,facilitated by membrane fusion-mediated enhanced cellular uptake.In vitro studies demonstrated potent inhibition of MFC gastric cancer cell proliferation,induction of apoptosis,and suppression of metastatic behavior,underscoring its enhanced antitumor efficacy.Moreover,the nanoplatform triggered immunogenic cell death(ICD),while MPLA acted as an immunostimulant to promote dendritic cell maturation and T-cell priming—effectively reprogramming the immunosuppressive TME.In vivo evaluations confirmed excellent tumor accumulation,robust antitumor activity,and negligible systemic toxicity,highlighting its favorable biosafety profile.Collectively,PLGA-UA@M-A represents a multifunctional biomimetic delivery system that integrates chemotherapy with immune activation,offering a promising therapeutic paradigm for gastric cancer treatment.
文摘With the acceleration of China's aging society,elderly patients have become a high-risk group for malignant tumors and exhibit high prevalence of pain.For a long time,the diagnosis,treatment,and management of cancer pain in elderly Chinese patients have been inadequate.This study used"Older adults,geriatric patients,cancer pain,pain assessment,pain management,elderly cancer,geriatric oncology,medication management,palliative care,interdisciplinary pain management,Analgesics,quality of life"as key words.We systematically searched PubMed,Web of Science,CNKI,and Wanfang databases from their inception to September 2024.The search primarily included phase I to III clinical trials,randomized controlled trials,meta-analyses,systematic reviews,and case reports.Elderly patients typically present with complex pain mechanisms,including both cancer-related and non-cancer pain,cognitive dysfunction,comorbidities,and polypharmacy,posing significant challenges for clinical diagnosis and treatment.Notable clinical differences exist between elderly and younger patients in the epidemiology,assessment,diagnosis,and treatment of cancer pain.Currently,the awareness of comprehensive management for elderly cancer pain patients is limited,and specific,implementable clinical guidelines are lacking.Therefore,developing a comprehensive,localized management model for elderly cancer pain patients in China—incorporating factors such as age-related impacts,organ function status,and comorbidities—has become an urgent necessity.
