BACKGROUND The pathophysiological characteristics of severe pneumonia complicated by respiratory failure comprise pulmonary parenchymal changes leading to ventilation imbalance,alveolar capillary injury,pulmonary edem...BACKGROUND The pathophysiological characteristics of severe pneumonia complicated by respiratory failure comprise pulmonary parenchymal changes leading to ventilation imbalance,alveolar capillary injury,pulmonary edema,refractory hypoxemia,and reduced lung compliance.Prolonged hypoxia can cause acid-base balance disorder,peripheral circulatory failure,blood-pressure reduction,arrhythmia,and other adverse consequences.AIM To investigate sequential mechanical ventilation’s effect on severe pneumonia complicated by respiratory failure.METHODS We selected 108 patients with severe pneumonia complicated by respiratory failure who underwent mechanical ventilation between January 2018 and September 2020 at the Luhe Hospital’s Intensive Care Unit and divided them into sequential and regular groups according to a randomized trial,with each group comprising 54 patients.The sequential group received invasive and non-invasive sequential mechanical ventilation,whereas the regular group received invasive mechanical ventilation.Blood-gas parameters,hemodynamic parameters,respiratory mechanical parameters,inflammatory factors,and treatment outcomes were compared between the two groups before and after mechanical-ventilation treatment.RESULTS The arterial oxygen partial pressure and stroke volume variation values of the sequential group at 24,48,and 72 h of treatment were higher than those of the conventional group(P<0.05).The carbon dioxide partial pressure value of the sequential group at 72 h of treatment and the Raw value of the treatment group at 24 and 48 h were lower than those of the conventional group(P<0.05).The pH value of the sequential group at 24 and 72 h of treatment,the central venous pressure value of the treatment at 24 h,and the Cst value of the treatment at 24 and 48 h were higher than those of the conventional group(P<0.05).The tidal volume in the sequential group at 24 h of treatment was higher than that in the conventional group(P<0.05),the measured values of interleukin-6 and tumor necrosis factor-αin the sequential group at 72 h of treatment were lower than those in the conventional group(P<0.05),and the total time of mechanical ventilation in the sequential group was shorter than that in the conventional group,with a statistically significant difference(P<0.05).CONCLUSION Treating severe pneumonia complicated by respiratory failure with sequential mechanical ventilation is more effective in improving respiratory system compliance,reducing inflammatory response,maintaining hemodynamic stability,and improving patient blood-gas levels;however,from this study’s perspective,it cannot reduce patient mortality.展开更多
Osteoporosis,a prevalent systemic degenerative disease,poses significant challenges to China’s national health,particularly due to complications such as fractures.Therapeutic interventions for osteoporosis primarily ...Osteoporosis,a prevalent systemic degenerative disease,poses significant challenges to China’s national health,particularly due to complications such as fractures.Therapeutic interventions for osteoporosis primarily involve bone resorption inhibitors(antiresorptive)and bone formation promoters(anabolic).Numerous studies underscore the importance of sequential and combination treatments using diverse drug types.Such approaches have shown considerable efficacy in increasing bone mineral density,reducing fracture risk,and preventing the progression of osteoporosis.This article aimed to consolidate various sequential treatment schemes,offering valuable insights for clinicians in their practice.展开更多
Objective:To investigate the overall survival of patients with KRAS wild-type metastatic colorectal cancer(mCRC)after sequentially receiving both bevacizumab and cetuximab during the course of treatment.Methods:Twenty...Objective:To investigate the overall survival of patients with KRAS wild-type metastatic colorectal cancer(mCRC)after sequentially receiving both bevacizumab and cetuximab during the course of treatment.Methods:Twenty-six mCRC patients who received both bevacizumab and cetuximab at the Sun Yat-sen University Gastrointestinal Hospital were retrospectively analyzed.Group A(n¼8)comprised patients who received bevacizumab first,and group B(n¼18)comprised those who received cetuximab first.The objective response rate,progression-free survival,and overall survival were compared.Results:Baseline characteristics between the two groups were statistically similar.The objective response in groups A and B patients was 62.5%and 66.6%,respectively(P¼0.132).The median progression-free survival for groups A and B patients was 13 and 10 months,respectively(P¼0.798).The median overall survival for the entire cohort was 42 months,44 months for group A and 39 months for group p B(P¼0.862)patients,respectively.Patients aged<40 years had worse survival than those aged40 years(22 vs 44 months;P¼0.029).Patients with synchronous metastasis had worse survival than those with metachronous metastasis(unreached and 36 months,respectively).In multivariate analyses,synchronous metastasis and age remained statistically significant.The hazard ratio for synchronous metastasis was 4.548,and the HR for patients aged40 years was 0.237.Conclusion:A longer median survival time was observed in patients regardless of the targeted therapy sequence,which warrants further investigation.展开更多
This case report is designed to investigate sequential treatment principles,the appropri-ate timing for nephrostomy and radical nephrectomy,and the merits and demerits of la-paroscopic and open surgical procedures in ...This case report is designed to investigate sequential treatment principles,the appropri-ate timing for nephrostomy and radical nephrectomy,and the merits and demerits of la-paroscopic and open surgical procedures in the context of a duplex kidney accompanied by pyonephrosis.Through a meticulous analysis of two representative cases and a com-prehensive review of pertinent literature,the report offers a valuable reference for clinical practice.This enables the optimization of treatment strategies for patients afflicted with a duplex kidney and pyonephrosis,leading to enhanced treatment efficacy and a reduction in potential complications.展开更多
In the original publication of our paper,“Sequential treatment escalation improves survival in patients with Waldenstrom macroglobulinemia,”published on Blood Science,2024 Jan;6(1):e00179,we have identified several ...In the original publication of our paper,“Sequential treatment escalation improves survival in patients with Waldenstrom macroglobulinemia,”published on Blood Science,2024 Jan;6(1):e00179,we have identified several errors that require correction.展开更多
BACKGROUND Tetralogy of Fallot(TOF)is one of the most common congenital heart defects,and surgery is the primary treatment.There are no precise guidelines on the treatment protocol for tricuspid regurgitation(TR)as a ...BACKGROUND Tetralogy of Fallot(TOF)is one of the most common congenital heart defects,and surgery is the primary treatment.There are no precise guidelines on the treatment protocol for tricuspid regurgitation(TR)as a common complication of TOF repair.The timing for treatment in patients presenting with valve regurgitation after TOF repair is often difficult to determine.Here,we report the first case of sequential treatment of pulmonary and TR using interventional therapy.CASE SUMMARY We present the case of a 52-year-old female patient,who had a history of TOF repair at a young age.A few years later,the patient presented with pulmonary and tricuspid regurgitation.The symptoms persisted and TR worsened following percutaneous pulmonary valve implantation.Preoperative testing revealed that the patient’s disease had advanced to an intermediate to advanced stage and that her general health was precarious.Because open-heart surgery was not an option for the patient,transcatheter tricuspid valve replacement was suggested.This procedure was successful,and the patient recovered fully without any adverse effects.This case report may serve as a useful resource for planning future treatments.CONCLUSION Treatment of both valves should be considered in patients with tricuspid and pulmonary regurgitations following TOF repair.The interventional strategy could be an alternative for patients with poor general health.展开更多
Cellular senescence is characterized by a sustained and irreversible cessation of cell proliferation in response to diverse environmental stimuli.However,senescent cells exhibit strong metabolic activity and release a...Cellular senescence is characterized by a sustained and irreversible cessation of cell proliferation in response to diverse environmental stimuli.However,senescent cells exhibit strong metabolic activity and release a range of cytokines and inflammatory mediators into the tumor microenvironment,collectively referred to as the senescence-associated secretory phenotype(SASP).In recent years,to develop new therapies for cancers,researchers have conducted extensive studies on the mechanism of cancer cell senescence and revealed that induction of cancer cell senescence could effectively suppress cancer progression.However,it has been documented that cellular senescence not only inhibits cancer initiation but also contributes significantly to cancer progression in some cases.Hence,it is imperative to comprehend the correlation between cellular senescence and tumorigenesis,and discuss the potential utilization of cellular senescence mechanisms to suppress cancer progression,which lays a theoretical foundation for new drugs to treat cancers.In this review,we first provide an overview of the discovery of cellular senescence and its key milestone events.Meanwhile,this review examines the major stimulus for the induction of senescence,and provides an overview of the categorization of cellular senescence.Subsequently,an examination of the primary regulatory mechanisms of cellular senescence is discussed,followed by a summary of the control of the SASP expression and its dual biological roles in cancers.Additionally,we also provide an overview of common biomarkers utilized in the identification of cellular senescence.Finally,this review investigates the efficacy of the“One-Two punch”sequential treatment approach for cancers,and examines the emerging challenges of this novel approach.展开更多
Background:Adult patients with T-cell lymphoblastic lymphoma(T-LBL)are treated with high-intensity chemotherapy regimens,but the response rate is still unsatisfactory because of frequent drug resistance.We aimed to in...Background:Adult patients with T-cell lymphoblastic lymphoma(T-LBL)are treated with high-intensity chemotherapy regimens,but the response rate is still unsatisfactory because of frequent drug resistance.We aimed to investigate the potential mechanisms of drug resistance in adults with T-LBL.Methods:Gene expression microarray was used to identify differential mRNA expression profiles between chemotherapy-resistant and chemotherapy-sensitive adult T-LBL tissues.Real-time PCR and immunohistochemistry were performed to detect the expression of bromodomain-containing protein 2(BRD2)and c-Myc in fresh-frozen T-LBL tissues from 85 adult patients.The Ras pull-down assay was performed to monitor Ras activation.Chromatin immunoprecipitation assays were used to analyze the binding of E2F transcription factor 1(E2F1)/BRD2 to the RAS guanyl releasing protein 1(RasGRP1)promoter region.The drug resistance effect and mechanism of BRD2 were determined by both in vivo and in vitro studies.Results:A total of 86 chemotherapy resistance-related genes in adult T-LBL were identified by gene expression microarray.Among them,BRD2 was upregulated in chemotherapy-resistant adult T-LBL tissues and associated with worse progressionfree survival and overall survival of 85 adult T-LBL patients.Furthermore,BRD2 suppressed doxorubicin(Dox)-induced cell apoptosis both in vitro and in vivo.The activation of RasGRP1/Ras/ERK signaling might contribute to the Dox resistance effect of BRD2.Besides,OTX015,a bromodomain and extra-terminal(BET)inhibitor,reversed the Dox resistance effect of BRD2.Patient-derived tumor xenograft demonstrated that the sequential use of OTX015 after Dox showed superior therapeutic effects.Conclusions:Our data showed that BRD2 promotes drug resistance in adult T-LBL through the RasGRP1/Ras/ERK signaling pathway.Targeting BRD2 may be a novel strategy to improve the therapeutic efficacy and prolong survival of adults with TLBL.展开更多
文摘BACKGROUND The pathophysiological characteristics of severe pneumonia complicated by respiratory failure comprise pulmonary parenchymal changes leading to ventilation imbalance,alveolar capillary injury,pulmonary edema,refractory hypoxemia,and reduced lung compliance.Prolonged hypoxia can cause acid-base balance disorder,peripheral circulatory failure,blood-pressure reduction,arrhythmia,and other adverse consequences.AIM To investigate sequential mechanical ventilation’s effect on severe pneumonia complicated by respiratory failure.METHODS We selected 108 patients with severe pneumonia complicated by respiratory failure who underwent mechanical ventilation between January 2018 and September 2020 at the Luhe Hospital’s Intensive Care Unit and divided them into sequential and regular groups according to a randomized trial,with each group comprising 54 patients.The sequential group received invasive and non-invasive sequential mechanical ventilation,whereas the regular group received invasive mechanical ventilation.Blood-gas parameters,hemodynamic parameters,respiratory mechanical parameters,inflammatory factors,and treatment outcomes were compared between the two groups before and after mechanical-ventilation treatment.RESULTS The arterial oxygen partial pressure and stroke volume variation values of the sequential group at 24,48,and 72 h of treatment were higher than those of the conventional group(P<0.05).The carbon dioxide partial pressure value of the sequential group at 72 h of treatment and the Raw value of the treatment group at 24 and 48 h were lower than those of the conventional group(P<0.05).The pH value of the sequential group at 24 and 72 h of treatment,the central venous pressure value of the treatment at 24 h,and the Cst value of the treatment at 24 and 48 h were higher than those of the conventional group(P<0.05).The tidal volume in the sequential group at 24 h of treatment was higher than that in the conventional group(P<0.05),the measured values of interleukin-6 and tumor necrosis factor-αin the sequential group at 72 h of treatment were lower than those in the conventional group(P<0.05),and the total time of mechanical ventilation in the sequential group was shorter than that in the conventional group,with a statistically significant difference(P<0.05).CONCLUSION Treating severe pneumonia complicated by respiratory failure with sequential mechanical ventilation is more effective in improving respiratory system compliance,reducing inflammatory response,maintaining hemodynamic stability,and improving patient blood-gas levels;however,from this study’s perspective,it cannot reduce patient mortality.
基金The Undergraduate Research Innovation Program of Capital Medical University(Grant No.XSKY2021387).
文摘Osteoporosis,a prevalent systemic degenerative disease,poses significant challenges to China’s national health,particularly due to complications such as fractures.Therapeutic interventions for osteoporosis primarily involve bone resorption inhibitors(antiresorptive)and bone formation promoters(anabolic).Numerous studies underscore the importance of sequential and combination treatments using diverse drug types.Such approaches have shown considerable efficacy in increasing bone mineral density,reducing fracture risk,and preventing the progression of osteoporosis.This article aimed to consolidate various sequential treatment schemes,offering valuable insights for clinicians in their practice.
基金supported by the China National Natural Science Foundation(No.81472249)。
文摘Objective:To investigate the overall survival of patients with KRAS wild-type metastatic colorectal cancer(mCRC)after sequentially receiving both bevacizumab and cetuximab during the course of treatment.Methods:Twenty-six mCRC patients who received both bevacizumab and cetuximab at the Sun Yat-sen University Gastrointestinal Hospital were retrospectively analyzed.Group A(n¼8)comprised patients who received bevacizumab first,and group B(n¼18)comprised those who received cetuximab first.The objective response rate,progression-free survival,and overall survival were compared.Results:Baseline characteristics between the two groups were statistically similar.The objective response in groups A and B patients was 62.5%and 66.6%,respectively(P¼0.132).The median progression-free survival for groups A and B patients was 13 and 10 months,respectively(P¼0.798).The median overall survival for the entire cohort was 42 months,44 months for group A and 39 months for group p B(P¼0.862)patients,respectively.Patients aged<40 years had worse survival than those aged40 years(22 vs 44 months;P¼0.029).Patients with synchronous metastasis had worse survival than those with metachronous metastasis(unreached and 36 months,respectively).In multivariate analyses,synchronous metastasis and age remained statistically significant.The hazard ratio for synchronous metastasis was 4.548,and the HR for patients aged40 years was 0.237.Conclusion:A longer median survival time was observed in patients regardless of the targeted therapy sequence,which warrants further investigation.
文摘This case report is designed to investigate sequential treatment principles,the appropri-ate timing for nephrostomy and radical nephrectomy,and the merits and demerits of la-paroscopic and open surgical procedures in the context of a duplex kidney accompanied by pyonephrosis.Through a meticulous analysis of two representative cases and a com-prehensive review of pertinent literature,the report offers a valuable reference for clinical practice.This enables the optimization of treatment strategies for patients afflicted with a duplex kidney and pyonephrosis,leading to enhanced treatment efficacy and a reduction in potential complications.
文摘In the original publication of our paper,“Sequential treatment escalation improves survival in patients with Waldenstrom macroglobulinemia,”published on Blood Science,2024 Jan;6(1):e00179,we have identified several errors that require correction.
文摘BACKGROUND Tetralogy of Fallot(TOF)is one of the most common congenital heart defects,and surgery is the primary treatment.There are no precise guidelines on the treatment protocol for tricuspid regurgitation(TR)as a common complication of TOF repair.The timing for treatment in patients presenting with valve regurgitation after TOF repair is often difficult to determine.Here,we report the first case of sequential treatment of pulmonary and TR using interventional therapy.CASE SUMMARY We present the case of a 52-year-old female patient,who had a history of TOF repair at a young age.A few years later,the patient presented with pulmonary and tricuspid regurgitation.The symptoms persisted and TR worsened following percutaneous pulmonary valve implantation.Preoperative testing revealed that the patient’s disease had advanced to an intermediate to advanced stage and that her general health was precarious.Because open-heart surgery was not an option for the patient,transcatheter tricuspid valve replacement was suggested.This procedure was successful,and the patient recovered fully without any adverse effects.This case report may serve as a useful resource for planning future treatments.CONCLUSION Treatment of both valves should be considered in patients with tricuspid and pulmonary regurgitations following TOF repair.The interventional strategy could be an alternative for patients with poor general health.
基金Basic and Applied Basic Research Foundation of Guangdong Province,Grant/Award Number:2023A15111129the President Foundation of Nanfang Hospital,Southern Medical University,Grant/Award Number:2022A018Science and Technology Projects in Guangzhou,Grant/Award Number:2024A04J5111。
文摘Cellular senescence is characterized by a sustained and irreversible cessation of cell proliferation in response to diverse environmental stimuli.However,senescent cells exhibit strong metabolic activity and release a range of cytokines and inflammatory mediators into the tumor microenvironment,collectively referred to as the senescence-associated secretory phenotype(SASP).In recent years,to develop new therapies for cancers,researchers have conducted extensive studies on the mechanism of cancer cell senescence and revealed that induction of cancer cell senescence could effectively suppress cancer progression.However,it has been documented that cellular senescence not only inhibits cancer initiation but also contributes significantly to cancer progression in some cases.Hence,it is imperative to comprehend the correlation between cellular senescence and tumorigenesis,and discuss the potential utilization of cellular senescence mechanisms to suppress cancer progression,which lays a theoretical foundation for new drugs to treat cancers.In this review,we first provide an overview of the discovery of cellular senescence and its key milestone events.Meanwhile,this review examines the major stimulus for the induction of senescence,and provides an overview of the categorization of cellular senescence.Subsequently,an examination of the primary regulatory mechanisms of cellular senescence is discussed,followed by a summary of the control of the SASP expression and its dual biological roles in cancers.Additionally,we also provide an overview of common biomarkers utilized in the identification of cellular senescence.Finally,this review investigates the efficacy of the“One-Two punch”sequential treatment approach for cancers,and examines the emerging challenges of this novel approach.
基金supported by the grants from National Key R&D Program of China(2017YFC1309001 and 2016YFC1302305)National Natural Science Foundation of China(81603137,81672686,and 81973384)Special Support Program of Sun Yat-sen University Cancer Center(PT19020401).
文摘Background:Adult patients with T-cell lymphoblastic lymphoma(T-LBL)are treated with high-intensity chemotherapy regimens,but the response rate is still unsatisfactory because of frequent drug resistance.We aimed to investigate the potential mechanisms of drug resistance in adults with T-LBL.Methods:Gene expression microarray was used to identify differential mRNA expression profiles between chemotherapy-resistant and chemotherapy-sensitive adult T-LBL tissues.Real-time PCR and immunohistochemistry were performed to detect the expression of bromodomain-containing protein 2(BRD2)and c-Myc in fresh-frozen T-LBL tissues from 85 adult patients.The Ras pull-down assay was performed to monitor Ras activation.Chromatin immunoprecipitation assays were used to analyze the binding of E2F transcription factor 1(E2F1)/BRD2 to the RAS guanyl releasing protein 1(RasGRP1)promoter region.The drug resistance effect and mechanism of BRD2 were determined by both in vivo and in vitro studies.Results:A total of 86 chemotherapy resistance-related genes in adult T-LBL were identified by gene expression microarray.Among them,BRD2 was upregulated in chemotherapy-resistant adult T-LBL tissues and associated with worse progressionfree survival and overall survival of 85 adult T-LBL patients.Furthermore,BRD2 suppressed doxorubicin(Dox)-induced cell apoptosis both in vitro and in vivo.The activation of RasGRP1/Ras/ERK signaling might contribute to the Dox resistance effect of BRD2.Besides,OTX015,a bromodomain and extra-terminal(BET)inhibitor,reversed the Dox resistance effect of BRD2.Patient-derived tumor xenograft demonstrated that the sequential use of OTX015 after Dox showed superior therapeutic effects.Conclusions:Our data showed that BRD2 promotes drug resistance in adult T-LBL through the RasGRP1/Ras/ERK signaling pathway.Targeting BRD2 may be a novel strategy to improve the therapeutic efficacy and prolong survival of adults with TLBL.
