Although ipilimumab has been shown to improve survival in patients with metastatic melanoma and cause regression of metastatic renal cell carcinoma, the associated immune-related toxicities are of concern.The resultan...Although ipilimumab has been shown to improve survival in patients with metastatic melanoma and cause regression of metastatic renal cell carcinoma, the associated immune-related toxicities are of concern.The resultant T cell activation by this monoclonal antibody causes an increased immune response, which has been associated with many immune-regulated adverse effects.One of the most concerning effects is the development of colitis.Upwards to 8% of patients have been reported to develop colitis, with 5% being severe(Grades 3-4).While initial treatment of such adverse effects is generally comprised of supportive and symptomatic treatment, more severe cases warrant the use of high dose steroids.Furthermore, use of anti-TNF agents is usually reserved for those cases that prove to be refractory to steroids.We describe a systematic case review of seven patients who developed gastrointestinal symptoms following initiation of ipilimumab immunotherapy, and present the steps in their evaluation, treatment and outcomes at our institution.展开更多
Background:The medicinal material known as Os Draconis(Longgu)originates from fossilized remains of ancient mammals and is widely used in treating emotional and mental conditions.However,fossil resources are nonrenewa...Background:The medicinal material known as Os Draconis(Longgu)originates from fossilized remains of ancient mammals and is widely used in treating emotional and mental conditions.However,fossil resources are nonrenewable,and clinical demand is increasingly difficult to meet,leading to a proliferation of counterfeit products.During prolonged geological burial,static pressure from the surrounding strata severely compromises the microstructural integrity of osteons in Os Draconis,but Os Draconis still largely retains the structural features of mammalian bone.Methods:Using verified authentic Os Draconis samples over 10,000 years old as a baseline,this study summarizes the ultrastructural characteristics of genuine Os Draconis.Employing electron probe microanalysis and optical polarized light microscopy,we examined 28 batches of authentic Os Draconis and 31 batches of counterfeits to identify their ultrastructural differences.Key points for ultrastructural identification of Os Draconis were compiled,and a new identification approach was proposed based on these differences.Results:Authentic Os Draconis exhibited distinct ultrastructural markers:irregularly shaped osteons with traversing fissures,deformed/displaced Haversian canals,and secondary mineral infill(predominantly calcium carbonate).Counterfeits showed regular osteon arrangements,absent traversal fissures,and homogeneous hydroxyapatite composition.Lab-simulated samples lacked structural degradation features.EPMA confirmed calcium carbonate infill in fossilized Haversian canals,while elemental profiles differentiated lacunae types(void vs.mineral-packed).Conclusion:The study established ultrastructural criteria for authentic Os Draconis identification:osteon deformation,geological fissures penetrating bone units,and heterogenous mineral deposition.These features,unattainable in counterfeits or modern processed bones,provide a cost-effective,accurate identification method.This approach bridges gaps in TCM material standardization and supports quality control for clinical applications.展开更多
Background:Cyperi Rhizoma,derived from Cyperus rotundus L.,is a widely used medicinal herb in traditional Chinese medicine(TCM),with Shandong Province recognized as its geo-authentic habitat.However,the quality of Cyp...Background:Cyperi Rhizoma,derived from Cyperus rotundus L.,is a widely used medicinal herb in traditional Chinese medicine(TCM),with Shandong Province recognized as its geo-authentic habitat.However,the quality of Cyperi Rhizoma varies significantly across different regions,potentially influencing its therapeutic efficacy.This study investigates the influence of geographic origin on the chemical composition and overall quality of Cyperi Rhizoma.Methods:A comprehensive approach,including traditional quality assessment,GC-MS(g as c hromatography-m ass s pectrometry),RP-HPLC(r everse p hase h igh-p erformance l iquid c hromatography),and FT-IR(f ourier t ransform i nfrared s pectroscopy)techniques,was employed to analyze Cyperi Rhizoma samples from Shandong Province.These methods examined the physical appearance,chemical profile,and content variations,particularly focusing onα-cyperone.Results:Traditional quality assessments revealed noticeable differences in the external characteristics of the samples.GC-MS analysis identified a variety of unique chemical constituents,while RP-HPLC and FT-IR showed significant variations inα-cyperone content,with higher levels found in Shandong samples.Conclusion:These results demonstrate that geographic origin is a critical determinant of Cyperi Rhizoma quality,with Shandong specimens exhibiting superiorα-cyperone levels and characteristic phytochemical profiles.This validates the geo-authenticity concept in TCM and provides actionable data for developing evidence-based quality standards,suggesting that provenance should be prioritized in medicinal material selection and pharmacopeial specifications.展开更多
Background:Os Draconis is an important material in traditional Chinese medicine(TCM).However,its market is saturated with counterfeit products,and the limitations of current identification methods pose a serious threa...Background:Os Draconis is an important material in traditional Chinese medicine(TCM).However,its market is saturated with counterfeit products,and the limitations of current identification methods pose a serious threat to clinical effectiveness and drug safety.This study aims to establish a more accurate and comprehensive authentication system for Os Draconis.Methods:A comprehensive approach was employed to analyze authentic Os Draconis,fossilized Os Draconis,counterfeit products,and lab-prepared modern animal bones.The analytical techniques included ^(14)C dating,electron probe microanalysis(EPMA),polarized light microscopy,X-ray diffraction(XRD),inductively coupled plasma mass spectrometry(ICP-MS),and fourier-transform infrared spectroscopy(FTIR).The study focused on examining the microstructural features and micro-area elemental compositions to identify distinguishing characteristics.Results:Physical identification alone was insufficient to reliably distinguish authentic Os Draconis from its counterfeits.XRD analysis revealed that while hydroxyapatite is the main component in all samples,authentic Os Draconis also contains calcium carbonate and quartz,which were absent in counterfeit and lab-prepared samples.FTIR spectra identified the carbonate ion(CO_(3)^(2-))as a characteristic infrared marker for authentic Os Draconis.ICP-MS analysis showed that Ca and P are the major elements,with a notably high content of Lanthanum(La)among rare earth elements in authentic samples.The EPMA results demonstrated that the Ca/P ratio of authentic Os Draconis is distinct,falling between that of fossilized Os Draconis and counterfeit samples.Conclusion:This study successfully identified several precise markers,including the presence of calcium carbonate,the characteristic CO_(3)^(2-)infrared peak,a high La content,and a specific Ca/P ratio,for the accurate and rapid authentication of Os Draconis.Furthermore,the analysis of its natural porous structure,suitable pore size,and surface area suggests that Os Draconis has significant potential as a natural drug carrier.展开更多
BACKGROUND A major cause of mortality in the coronavirus disease 2019(COVID-19)pandemic was acute respiratory distress syndrome(ARDS).Currently,moderate to severe ARDS induced by COVID-19(COVID ARDS)and other viral an...BACKGROUND A major cause of mortality in the coronavirus disease 2019(COVID-19)pandemic was acute respiratory distress syndrome(ARDS).Currently,moderate to severe ARDS induced by COVID-19(COVID ARDS)and other viral and non-viral etiologies are treated by traditional ARDS protocols that recommend 12-16 hours of prone position ventilation(PPV)with neuromuscular blocking agents(NMBA)and a trial of inhaled vasodilators(IVd)if oxygenation does not improve.However,debate on the efficacy of adjuncts to PPV and low tidal volume ventilation persists and evidence about the benefits of IVd/NMBA in COVID ARDS is sparse.In our multi-center retrospective review,we evaluated the impact of PPV,IVd,and NMBA on outcomes and lung mechanics in COVID ARDS patients with moderate to severe ARDS.AIM To evaluate the impact of PPV used alone or in combination with pulmonary IVd and/or NMBA in mechanically ventilated patients with moderate to severe ARDS during the COVID-19 pandemic.METHODS A retrospective study at two tertiary academic medical centers compared outcomes between COVID ARDS patients receiving PPV and patients in the supine position.PPV patients were divided based on concurrent use of ARDS adjunct therapies resulting in four subgroups:(1)PPV alone;(2)PPV and IVd;(3)PPV and NMBA;and(4)PPV,IVd,and NMBA.Primary outcomes were hospital and intensive care unit(ICU)length of stay(LOS),mortality,and venovenous extracorporeal membrane oxygenation(VV-ECMO)status.Secondary outcomes included changes in lung mechanics at 24-hour intervals for 7 days.RESULTS Total 114 patients were included in this study.Baseline respiratory parameters and Sequential Organ Failure Assessment scores were significantly worse in the PPV group.ICU LOS and LOS were significantly longer for patients who were proned,but no mortality benefit or difference in VV-ECMO status was found.Among the subgroups,no difference in primary outcomes were found.In the secondary analysis,PPV was associated with a significant improvement in arterial oxygen partial pressure(PaO_(2))/fractional inspired oxygen(FiO_(2))(P/F)ratio from day 1 to day 4(P<0.05)and higher driving pressures day 5 to day 7(P<0.05).The combination of PPV and IVd together resulted in improvements in P/F ratio from day 1 to day 7 and plateau pressure on day 4 and day 6(P<0.05).PPV with NMBA was not associated with improvements in any of the secondary outcomes.The use of all three rescue therapies together resulted in improvements in lung compliance on day 2(P<0.05)but no other improvements.CONCLUSION In mechanically ventilated patients diagnosed with moderate to severe COVID ARDS,PPV and PPV with the addition of IVd produced a significant and sustained increase in P/F ratio.The combination of PPV,IVd and NMBA improved compliance however this did not reach significance.Mortality and LOS did not improve with adjunct therapies.Further research is warranted to determine the efficacy of these therapies alone and in combination in the treatment of COVID ARDS.展开更多
BACKGROUND Persistent sinus tachycardia affects up to 40%of patients after heart transplantation and is linked with graft dysfunction,impaired diastolic filling,and increased morbidity.Conventional rate-limiting thera...BACKGROUND Persistent sinus tachycardia affects up to 40%of patients after heart transplantation and is linked with graft dysfunction,impaired diastolic filling,and increased morbidity.Conventional rate-limiting therapies such as betablockers and calcium channel blockers are quite often contraindicated due to risks of bradyarrhythmia or hypotension.Ivabradine,a selective I(f)channel inhibitor,reduces heart rate(HR)without negative inotropic or hypotensive effects.AIM To evaluate the efficacy and safety of ivabradine in heart transplant recipients.METHODS A comprehensive search of PubMed,EMBASE,Scopus,Cochrane Library,and Google Scholar was conducted from inception to April 15,2025.Eligible studies evaluated ivabradine in heart transplant recipient vs placebo or metoprolol,reporting HR,mortality,left ventricular mass(LVM),or safety.Data were independently extracted by two reviewers,and quality was assessed.Review Manager 5.4 performed pooled analyses using random-effects models.Mean differences(MD)or standardized MD(SMD)were calculated for continuous outcomes,and risk ratios for dichotomous outcomes.RESULTS Of 415 records identified,four studies comprising 264 patients(126 ivabradine,138 control)met the inclusion criteria.Ivabradine significantly reduced resting HR compared with controls(MD=-11.06 beats per minute;95%CI:-19.50 to-2.62;P<0.00001;I^(2)=93%).Sensitivity analysis demonstrated consistent findings(SMD=-6.74;95%CI:-9.23 to-4.24;I^(2)=0%).No significant difference in all-cause mortality was observed(MD=0.52;95%CI:0.17-1.64;P=0.27;I^(2)=85%).Pooled analysis of LVM revealed no significant effect of ivabradine(MD=-3.57 g;95%CI:-29.21 to 22.08;P=0.79;I^(2)=73%),with sensitivity analysis confirming neutrality.Adverse events were rare and mostly comparable between groups.CONCLUSION Ivabradine reduces HR effectively in heart transplant recipients without added adverse outcomes,supporting its use as safe and well-tolerated alternative when conventional agents are unsuitable.Despite potential clinical benefit,small sample size and heterogeneity the need for larger randomized trials to confirm long-term outcomes and establish ivabradine’s role in post-transplant care.展开更多
Traditional Medicine(TM),particularly Traditional Chinese Medicine(TCM),is an indispensable component of the global healthcare system,offering unique insights to modern medical science.Clinical efficacy is the bedrock...Traditional Medicine(TM),particularly Traditional Chinese Medicine(TCM),is an indispensable component of the global healthcare system,offering unique insights to modern medical science.Clinical efficacy is the bedrock for the inheritance and development of TM.To meet the growing demand for high-quality healthcare,it is imperative to integrate TM with modern technology to address the issue of insufficient evidence for the efficacy of TM.展开更多
基金Supported by Med Star Georgetown University Hospital,Washington,DC,United States
文摘Although ipilimumab has been shown to improve survival in patients with metastatic melanoma and cause regression of metastatic renal cell carcinoma, the associated immune-related toxicities are of concern.The resultant T cell activation by this monoclonal antibody causes an increased immune response, which has been associated with many immune-regulated adverse effects.One of the most concerning effects is the development of colitis.Upwards to 8% of patients have been reported to develop colitis, with 5% being severe(Grades 3-4).While initial treatment of such adverse effects is generally comprised of supportive and symptomatic treatment, more severe cases warrant the use of high dose steroids.Furthermore, use of anti-TNF agents is usually reserved for those cases that prove to be refractory to steroids.We describe a systematic case review of seven patients who developed gastrointestinal symptoms following initiation of ipilimumab immunotherapy, and present the steps in their evaluation, treatment and outcomes at our institution.
基金supported by the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences(CI2021A04013)the National Natural Science Foundation of China(82204610)+1 种基金the Qihang Talent Program(L2022046)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ15-YQ-041 and L2021029).
文摘Background:The medicinal material known as Os Draconis(Longgu)originates from fossilized remains of ancient mammals and is widely used in treating emotional and mental conditions.However,fossil resources are nonrenewable,and clinical demand is increasingly difficult to meet,leading to a proliferation of counterfeit products.During prolonged geological burial,static pressure from the surrounding strata severely compromises the microstructural integrity of osteons in Os Draconis,but Os Draconis still largely retains the structural features of mammalian bone.Methods:Using verified authentic Os Draconis samples over 10,000 years old as a baseline,this study summarizes the ultrastructural characteristics of genuine Os Draconis.Employing electron probe microanalysis and optical polarized light microscopy,we examined 28 batches of authentic Os Draconis and 31 batches of counterfeits to identify their ultrastructural differences.Key points for ultrastructural identification of Os Draconis were compiled,and a new identification approach was proposed based on these differences.Results:Authentic Os Draconis exhibited distinct ultrastructural markers:irregularly shaped osteons with traversing fissures,deformed/displaced Haversian canals,and secondary mineral infill(predominantly calcium carbonate).Counterfeits showed regular osteon arrangements,absent traversal fissures,and homogeneous hydroxyapatite composition.Lab-simulated samples lacked structural degradation features.EPMA confirmed calcium carbonate infill in fossilized Haversian canals,while elemental profiles differentiated lacunae types(void vs.mineral-packed).Conclusion:The study established ultrastructural criteria for authentic Os Draconis identification:osteon deformation,geological fissures penetrating bone units,and heterogenous mineral deposition.These features,unattainable in counterfeits or modern processed bones,provide a cost-effective,accurate identification method.This approach bridges gaps in TCM material standardization and supports quality control for clinical applications.
基金supported by the National Natural Science Foundation of China(No.82204610)Qihang Talent Program(L2022046)+1 种基金the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(CI2021A04013)Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ15-YQ-041 and L2021029).
文摘Background:Cyperi Rhizoma,derived from Cyperus rotundus L.,is a widely used medicinal herb in traditional Chinese medicine(TCM),with Shandong Province recognized as its geo-authentic habitat.However,the quality of Cyperi Rhizoma varies significantly across different regions,potentially influencing its therapeutic efficacy.This study investigates the influence of geographic origin on the chemical composition and overall quality of Cyperi Rhizoma.Methods:A comprehensive approach,including traditional quality assessment,GC-MS(g as c hromatography-m ass s pectrometry),RP-HPLC(r everse p hase h igh-p erformance l iquid c hromatography),and FT-IR(f ourier t ransform i nfrared s pectroscopy)techniques,was employed to analyze Cyperi Rhizoma samples from Shandong Province.These methods examined the physical appearance,chemical profile,and content variations,particularly focusing onα-cyperone.Results:Traditional quality assessments revealed noticeable differences in the external characteristics of the samples.GC-MS analysis identified a variety of unique chemical constituents,while RP-HPLC and FT-IR showed significant variations inα-cyperone content,with higher levels found in Shandong samples.Conclusion:These results demonstrate that geographic origin is a critical determinant of Cyperi Rhizoma quality,with Shandong specimens exhibiting superiorα-cyperone levels and characteristic phytochemical profiles.This validates the geo-authenticity concept in TCM and provides actionable data for developing evidence-based quality standards,suggesting that provenance should be prioritized in medicinal material selection and pharmacopeial specifications.
基金supported by the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences(CI2021A04013)the National Natural Science Foundation of China(82204610)+1 种基金the Qihang Talent Program(L2022046)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ15-YQ-041 and L2021029).
文摘Background:Os Draconis is an important material in traditional Chinese medicine(TCM).However,its market is saturated with counterfeit products,and the limitations of current identification methods pose a serious threat to clinical effectiveness and drug safety.This study aims to establish a more accurate and comprehensive authentication system for Os Draconis.Methods:A comprehensive approach was employed to analyze authentic Os Draconis,fossilized Os Draconis,counterfeit products,and lab-prepared modern animal bones.The analytical techniques included ^(14)C dating,electron probe microanalysis(EPMA),polarized light microscopy,X-ray diffraction(XRD),inductively coupled plasma mass spectrometry(ICP-MS),and fourier-transform infrared spectroscopy(FTIR).The study focused on examining the microstructural features and micro-area elemental compositions to identify distinguishing characteristics.Results:Physical identification alone was insufficient to reliably distinguish authentic Os Draconis from its counterfeits.XRD analysis revealed that while hydroxyapatite is the main component in all samples,authentic Os Draconis also contains calcium carbonate and quartz,which were absent in counterfeit and lab-prepared samples.FTIR spectra identified the carbonate ion(CO_(3)^(2-))as a characteristic infrared marker for authentic Os Draconis.ICP-MS analysis showed that Ca and P are the major elements,with a notably high content of Lanthanum(La)among rare earth elements in authentic samples.The EPMA results demonstrated that the Ca/P ratio of authentic Os Draconis is distinct,falling between that of fossilized Os Draconis and counterfeit samples.Conclusion:This study successfully identified several precise markers,including the presence of calcium carbonate,the characteristic CO_(3)^(2-)infrared peak,a high La content,and a specific Ca/P ratio,for the accurate and rapid authentication of Os Draconis.Furthermore,the analysis of its natural porous structure,suitable pore size,and surface area suggests that Os Draconis has significant potential as a natural drug carrier.
文摘BACKGROUND A major cause of mortality in the coronavirus disease 2019(COVID-19)pandemic was acute respiratory distress syndrome(ARDS).Currently,moderate to severe ARDS induced by COVID-19(COVID ARDS)and other viral and non-viral etiologies are treated by traditional ARDS protocols that recommend 12-16 hours of prone position ventilation(PPV)with neuromuscular blocking agents(NMBA)and a trial of inhaled vasodilators(IVd)if oxygenation does not improve.However,debate on the efficacy of adjuncts to PPV and low tidal volume ventilation persists and evidence about the benefits of IVd/NMBA in COVID ARDS is sparse.In our multi-center retrospective review,we evaluated the impact of PPV,IVd,and NMBA on outcomes and lung mechanics in COVID ARDS patients with moderate to severe ARDS.AIM To evaluate the impact of PPV used alone or in combination with pulmonary IVd and/or NMBA in mechanically ventilated patients with moderate to severe ARDS during the COVID-19 pandemic.METHODS A retrospective study at two tertiary academic medical centers compared outcomes between COVID ARDS patients receiving PPV and patients in the supine position.PPV patients were divided based on concurrent use of ARDS adjunct therapies resulting in four subgroups:(1)PPV alone;(2)PPV and IVd;(3)PPV and NMBA;and(4)PPV,IVd,and NMBA.Primary outcomes were hospital and intensive care unit(ICU)length of stay(LOS),mortality,and venovenous extracorporeal membrane oxygenation(VV-ECMO)status.Secondary outcomes included changes in lung mechanics at 24-hour intervals for 7 days.RESULTS Total 114 patients were included in this study.Baseline respiratory parameters and Sequential Organ Failure Assessment scores were significantly worse in the PPV group.ICU LOS and LOS were significantly longer for patients who were proned,but no mortality benefit or difference in VV-ECMO status was found.Among the subgroups,no difference in primary outcomes were found.In the secondary analysis,PPV was associated with a significant improvement in arterial oxygen partial pressure(PaO_(2))/fractional inspired oxygen(FiO_(2))(P/F)ratio from day 1 to day 4(P<0.05)and higher driving pressures day 5 to day 7(P<0.05).The combination of PPV and IVd together resulted in improvements in P/F ratio from day 1 to day 7 and plateau pressure on day 4 and day 6(P<0.05).PPV with NMBA was not associated with improvements in any of the secondary outcomes.The use of all three rescue therapies together resulted in improvements in lung compliance on day 2(P<0.05)but no other improvements.CONCLUSION In mechanically ventilated patients diagnosed with moderate to severe COVID ARDS,PPV and PPV with the addition of IVd produced a significant and sustained increase in P/F ratio.The combination of PPV,IVd and NMBA improved compliance however this did not reach significance.Mortality and LOS did not improve with adjunct therapies.Further research is warranted to determine the efficacy of these therapies alone and in combination in the treatment of COVID ARDS.
文摘BACKGROUND Persistent sinus tachycardia affects up to 40%of patients after heart transplantation and is linked with graft dysfunction,impaired diastolic filling,and increased morbidity.Conventional rate-limiting therapies such as betablockers and calcium channel blockers are quite often contraindicated due to risks of bradyarrhythmia or hypotension.Ivabradine,a selective I(f)channel inhibitor,reduces heart rate(HR)without negative inotropic or hypotensive effects.AIM To evaluate the efficacy and safety of ivabradine in heart transplant recipients.METHODS A comprehensive search of PubMed,EMBASE,Scopus,Cochrane Library,and Google Scholar was conducted from inception to April 15,2025.Eligible studies evaluated ivabradine in heart transplant recipient vs placebo or metoprolol,reporting HR,mortality,left ventricular mass(LVM),or safety.Data were independently extracted by two reviewers,and quality was assessed.Review Manager 5.4 performed pooled analyses using random-effects models.Mean differences(MD)or standardized MD(SMD)were calculated for continuous outcomes,and risk ratios for dichotomous outcomes.RESULTS Of 415 records identified,four studies comprising 264 patients(126 ivabradine,138 control)met the inclusion criteria.Ivabradine significantly reduced resting HR compared with controls(MD=-11.06 beats per minute;95%CI:-19.50 to-2.62;P<0.00001;I^(2)=93%).Sensitivity analysis demonstrated consistent findings(SMD=-6.74;95%CI:-9.23 to-4.24;I^(2)=0%).No significant difference in all-cause mortality was observed(MD=0.52;95%CI:0.17-1.64;P=0.27;I^(2)=85%).Pooled analysis of LVM revealed no significant effect of ivabradine(MD=-3.57 g;95%CI:-29.21 to 22.08;P=0.79;I^(2)=73%),with sensitivity analysis confirming neutrality.Adverse events were rare and mostly comparable between groups.CONCLUSION Ivabradine reduces HR effectively in heart transplant recipients without added adverse outcomes,supporting its use as safe and well-tolerated alternative when conventional agents are unsuitable.Despite potential clinical benefit,small sample size and heterogeneity the need for larger randomized trials to confirm long-term outcomes and establish ivabradine’s role in post-transplant care.
文摘Traditional Medicine(TM),particularly Traditional Chinese Medicine(TCM),is an indispensable component of the global healthcare system,offering unique insights to modern medical science.Clinical efficacy is the bedrock for the inheritance and development of TM.To meet the growing demand for high-quality healthcare,it is imperative to integrate TM with modern technology to address the issue of insufficient evidence for the efficacy of TM.
