The fibrotic scar due to excessive deposition of extracellular matrix(ECM)after spinal cord injury(SCI)remains one of formidable challenges to axonal regeneration.Previous therapeutic strategies mainly focus on elimin...The fibrotic scar due to excessive deposition of extracellular matrix(ECM)after spinal cord injury(SCI)remains one of formidable challenges to axonal regeneration.Previous therapeutic strategies mainly focus on eliminating fibrotic scars by blocking(Göritz et al.,2011)or inhibiting(Dias et al.,2018)the generation of scar-forming stromal cells,as well as inducing their migratory defect(Hellal et al.,2011;Ruschel et al.,2015).展开更多
目的:评价尼妥珠单抗联合吉西他滨(nimotuzumab plus gemcitabine,NG)一线治疗局部晚期或转移性K-Ras野生型胰腺癌患者的经济性,为相关卫生决策提供参考。方法:基于一项多中心、随机、开放标签的Ⅲ期临床试验(NCT02395016)数据构建分区...目的:评价尼妥珠单抗联合吉西他滨(nimotuzumab plus gemcitabine,NG)一线治疗局部晚期或转移性K-Ras野生型胰腺癌患者的经济性,为相关卫生决策提供参考。方法:基于一项多中心、随机、开放标签的Ⅲ期临床试验(NCT02395016)数据构建分区生存模型,模拟时限为5年,循环周期为28 d。比较NG方案和吉西他滨(gemcitabine,G)方案一线治疗局部晚期或转移性K-Ras野生型胰腺癌的经济性。以质量调整生命年(quality-adjusted life year,QALY)作为产出指标并计算增量成本-效果比(incremental cost-effectiveness ratio,ICER),采用单因素敏感性分析及概率敏感性分析评价模型参数变化对结果稳健性的影响。结果:基础分析结果显示,相较于G方案,NG方案人均成本增加304806.15元,人均效用增加0.16 QALYs,ICER为1865405.26元/QALY,高于本研究设定的268074.00元/QALY的意愿支付(willingness-to-pay,WTP)阈值。单因素敏感性分析结果表明,尼妥珠单抗的成本、肿瘤稳定状态效用和肿瘤进展状态效用对ICER的影响较大。概率敏感性分析结果显示,在WTP阈值为268074.00元/QALY时,NG方案具有经济性的概率为0。结论:与G方案相比,NG方案作为一线药物治疗局部晚期或转移性K-Ras野生型胰腺癌不具有经济性。展开更多
The cemented tailings backfill(CTB)with initial defects is more prone to destabilization damage under the influence of various unfavorable factors during the mining process.In order to investigate its influence on the...The cemented tailings backfill(CTB)with initial defects is more prone to destabilization damage under the influence of various unfavorable factors during the mining process.In order to investigate its influence on the stability of underground mining engineering,this paper simulates the generation of different degrees of initial defects inside the CTB by adding different contents of air-entraining agent(AEA),investigates the acoustic emission RA/AF eigenvalues of CTB with different contents of AEA under uniaxial compression,and adopts various denoising algorithms(e.g.,moving average smoothing,median filtering,and outlier detection)to improve the accuracy of the data.The variance and autocorrelation coefficients of RA/AF parameters were analyzed in conjunction with the critical slowing down(CSD)theory.The results show that the acoustic emission RA/AF values can be used to characterize the progressive damage evolution of CTB.The denoising algorithm processed the AE signals to reduce the effects of extraneous noise and anomalous spikes.Changes in the variance curves provide clear precursor information,while abrupt changes in the autocorrelation coefficient can be used as an auxiliary localization warning signal.The phenomenon of dramatic increase in the variance and autocorrelation coefficient curves during the compression-tightening stage,which is influenced by the initial defects,can lead to false warnings.As the initial defects of the CTB increase,its instability precursor time and instability time are prolonged,the peak stress decreases,and the time difference between the CTB and the instability damage is smaller.The results provide a new method for real-time monitoring and early warning of CTB instability damage.展开更多
BACKGROUND Patients harboring gene mutations like KRAS,NRAS,and BRAF demonstrate highly variable responses to chemotherapy,posing challenges for treatment optimization.Multiparametric magnetic resonance imaging(MRI),w...BACKGROUND Patients harboring gene mutations like KRAS,NRAS,and BRAF demonstrate highly variable responses to chemotherapy,posing challenges for treatment optimization.Multiparametric magnetic resonance imaging(MRI),with its noninvasive capability to assess tumor characteristics in detail,has shown promise in evaluating treatment response and predicting therapeutic outcomes.This technology holds potential for guiding personalized treatment strategies tailored to individual patient profiles,enhancing the precision and effectiveness of colorectal cancer care.AIM To create a multiparametric MRI-based predictive model for assessing chemotherapy efficacy in colorectal cancer patients with gene mutations.METHODS This retrospective study was conducted in a tertiary hospital,analyzing 157 colorectal cancer patients with gene mutations treated between August 2022 and December 2023.Based on chemotherapy outcomes,the patients were categorized into favorable(n=60)and unfavorable(n=50)response groups.Univariate and multivariate logistic regression analyses were performed to identify independent predictors of chemotherapy efficacy.A predictive nomogram was constructed using significant variables,and its performance was assessed using the area under the receiver operating characteristic curve(AUC)in both training and validation sets.RESULTS Univariate analysis identified that tumor differentiation,T2 signal intensity ratio,tumor-to-anal margin distance,and MRI-detected lymph node metastasis as significantly associated with chemotherapy response(P<0.05).Multivariate Logistics regression confirmed these four parameters as independent predictors.The predictive model demonstrated strong discrimination,with an AUC of 0.938(sensitivity:86%;specificity:92%)in the training set,and 0.942(sensitivity:100%;specificity:83%)in the validation set.CONCLUSION We established and validated a multiparametric MRI-based model for predicting chemotherapy response in colorectal cancer patients with gene mutations.This model holds promise for guiding individualized treatment strategies.展开更多
Ras homolog enriched in brain(Rheb) is a small GTPase that activates mammalian target of rapamycin complex 1(mTORC1).Previous studies have shown that constitutively active Rheb can enhance the regeneration of sensory ...Ras homolog enriched in brain(Rheb) is a small GTPase that activates mammalian target of rapamycin complex 1(mTORC1).Previous studies have shown that constitutively active Rheb can enhance the regeneration of sensory axons after spinal cord injury by activating downstream effectors of mTOR.S6K1 and4E-BP1 are important downstream effectors of mTORC1.In this study,we investigated the role of Rheb/mTOR and its downstream effectors S6K1 and 4E-BP1in the protection of retinal ganglion cells.We transfected an optic nerve crush mouse model with adeno-associated viral 2-mediated constitutively active Rheb and observed the effects on retinal ganglion cell survival and axon regeneration.We found that overexpression of constitutively active Rheb promoted survival of retinal ganglion cells in the acute(14 days) and chronic(21 and 42 days) stages of injury.We also found that either co-expression of the dominant-negative S6K1mutant or the constitutively active 4E-BP1 mutant together with constitutively active Rheb markedly inhibited axon regeneration of retinal ganglion cells.This suggests that mTORC1-mediated S6K1 activation and 4E-BP1 inhibition were necessary components for constitutively active Rheb-induced axon regeneration.However,only S6K1 activation,but not 4E-BP1 knockdown,induced axon regeneration when applied alone.Furthermore,S6K1 activation promoted the survival of retinal ganglion cells at 14 days post-injury,whereas 4E-BP1 knockdown unexpectedly slightly decreased the survival of retinal ganglion cells at 14 days postinjury.Ove rexpression of constitutively active 4E-BP1 increased the survival of retinal ganglion cells at 14 days post-injury.Likewise,co-expressing constitutively active Rheb and constitutively active 4E-BP1 markedly increased the survival of retinal ganglion cells compared with overexpression of constitutively active Rheb alone at 14 days post-injury.These findings indicate that functional 4E-BP1 and S6K1 are neuroprotective and that 4E-BP1 may exert protective effects through a pathway at least partially independent of Rhe b/mTOR.Together,our results show that constitutively active Rheb promotes the survival of retinal ganglion cells and axon regeneration through modulating S6K1 and 4E-BP1 activity.Phosphorylated S6K1 and 4E-BP1 promote axon regeneration but play an antagonistic role in the survival of retinal ganglion cells.展开更多
The regulating effects of TCM treatments including clearing away heat and toxic materials,promoting blood circulation and removing blood stasis,and strengthening the spleen and regulating qi on the oncogene transcript...The regulating effects of TCM treatments including clearing away heat and toxic materials,promoting blood circulation and removing blood stasis,and strengthening the spleen and regulating qi on the oncogene transcription were observed in the liver cancer model rats.The preliminary results indicated that the mRNA levels of H-ras N-ras and K-ras,and signal molecules correlated with the ras/MAPK signal transduction pathway were down-regulated by the different TCM treatments in varying degrees.Also,the regulating effects of the treatments on differently-displayed genes were discrepant.It is suggested that the molecular mechanisms of the TCM treatments for liver cancer was complex with different target genes.展开更多
This editorial comments on the study by Yang et al,emphasizing the Ras homolog enriched in brain 1(Rheb1)core function in restoring functionalβ-cell mass in diabetes,as crucial forβ-cell proliferation and survival.I...This editorial comments on the study by Yang et al,emphasizing the Ras homolog enriched in brain 1(Rheb1)core function in restoring functionalβ-cell mass in diabetes,as crucial forβ-cell proliferation and survival.It has been revealed that Rheb1 promotesβ-cell regeneration through a dual pathway,activating mammalian target of rapamycin complex 1 and simultaneously inhibiting AMP-activated protein kinase(AMPK).Blocking mammalian target of rapamycin complex 1 while stimulating AMPK was necessary to haltβ-cell expansion,challenging traditional single-target approaches.Rheb1 also supportedβ-cell identity by triggering neurogenic locus notch homolog protein 1 signaling and interacting with hepatocyte nuclear factor 4 alpha,linked to maturity-onset diabetes of the young 1.An age-related decline of Rheb1 in human islets suggests its role in diminished regenerative capacity in adulthood.These findings make Rheb1 a promising therapeutic target for rejuvenatingβ-cells by linking nutrient sensing and energy regulation.Focusing on Rheb1 could alter diabetes treatment,merging proliferation with identity preservation for next-generation therapies.The gaps and translational opportunities,from Rheb1 modulators to biomarkers,were emphasized,advocating for interdisciplinary collaboration to maximize this pathway for positive clinical outcomes.Additional studies are needed to thoroughly investigate AMPK’s involvement in the Rheb1 metabolic biomarker associated with brain health and its possible therapeutic benefits.展开更多
Background and Objective:Idiopathic intracranial hypertension(IIH)is a disorder of raised intracranial pressure(ICP)associated with overweight and obesity,with weight loss being the mainstay of management.Diet and lif...Background and Objective:Idiopathic intracranial hypertension(IIH)is a disorder of raised intracranial pressure(ICP)associated with overweight and obesity,with weight loss being the mainstay of management.Diet and lifestyle changes alone are often unsuccessful at achieving meaningful or sustained weight loss.Glucagon-like peptide-1 receptor agonists(GLP-1RA)are a class of medications developed for the treatment of diabetes but are also highly effective for weight reduction.The objective of this narrative review is to present the current evidence for GLP-1RAs in the management of IIH.Methods:Articles were searched for inclusion through OVID using the following terms:[papilledema OR intracranial hypertension OR idiopathic intracranial hypertension OR brain pseudotumor]and[glucagon like peptide 1 OR glucagon like peptide 1 receptor agonist OR semaglutide OR exendin 4 OR liraglutide OR tirzepatide].Titles and abstracts were screened manually for relevance.There were no exclusion criteria for time frame,language,population or article type,although conference abstracts were not included.An illustrative case of a patient with IIH treated with tirzepatide and semaglutide is also presented.Key Content and Findings:GLP-1RAs have demonstrated the potential for significantly greater weight loss in patients with IIH,with a reduced requirement for IIH medications and improved symptoms,compared to conventional weight management.Treatment with GLP-1RAs has also been shown to result in a rapid and persistent reduction in ICP in both rat and human studies.The side effects of GLP-1RAs are generally well-tolerated,with low rates of discontinuation in clinical trials.However,continuous treatment is likely required to avoid weight rebound and symptom recurrence after cessation.Conclusions:Despite highly promising preliminary evidence,further clinical trials are needed to determine the most effective GLP-1RA medications within this class,appropriate dosing regimens and treatment duration.展开更多
BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metasta...BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metastatic colorectal cancer(mCRC).Several studies have also demonstrated the benefit of anti-EGFR therapy in sub-sequent line settings for this patient population.However,direct evidence com-paring the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited,leaving a crucial gap in guiding optimal treatment strategies.AIM To compare overall survival(OS)between frontline and subsequent anti-EGFR treatment in patients with unresectable,RAS and BRAF wild-type,left-sided mCRC.METHODS We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital,Thailand,between January 2013 and April 2023.Patients were classified into two groups based on the sequence of their anti-EGFR treatment.The primary endpoint was OS.RESULTS Among 222 patients with a median follow-up of 29 months,no significant difference in OS was observed between the frontline and subsequent-line groups(HR 1.03,95%CI:0.73-1.46,P=0.878).The median OS was 35.53 months(95%CI:26.59-44.47)for the frontline group and 31.60 months(95%CI:27.83-35.37)for the subsequent-line group.In the subsequent-line group,71 patients(32.4%)who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months(95%CI:12.87-26.53).CONCLUSION Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable,RAS/BRAF wild-type,left-sided mCRC patients,but early exposure is vital for those unlikely to receive subsequent therapy.展开更多
文摘The fibrotic scar due to excessive deposition of extracellular matrix(ECM)after spinal cord injury(SCI)remains one of formidable challenges to axonal regeneration.Previous therapeutic strategies mainly focus on eliminating fibrotic scars by blocking(Göritz et al.,2011)or inhibiting(Dias et al.,2018)the generation of scar-forming stromal cells,as well as inducing their migratory defect(Hellal et al.,2011;Ruschel et al.,2015).
文摘目的:评价尼妥珠单抗联合吉西他滨(nimotuzumab plus gemcitabine,NG)一线治疗局部晚期或转移性K-Ras野生型胰腺癌患者的经济性,为相关卫生决策提供参考。方法:基于一项多中心、随机、开放标签的Ⅲ期临床试验(NCT02395016)数据构建分区生存模型,模拟时限为5年,循环周期为28 d。比较NG方案和吉西他滨(gemcitabine,G)方案一线治疗局部晚期或转移性K-Ras野生型胰腺癌的经济性。以质量调整生命年(quality-adjusted life year,QALY)作为产出指标并计算增量成本-效果比(incremental cost-effectiveness ratio,ICER),采用单因素敏感性分析及概率敏感性分析评价模型参数变化对结果稳健性的影响。结果:基础分析结果显示,相较于G方案,NG方案人均成本增加304806.15元,人均效用增加0.16 QALYs,ICER为1865405.26元/QALY,高于本研究设定的268074.00元/QALY的意愿支付(willingness-to-pay,WTP)阈值。单因素敏感性分析结果表明,尼妥珠单抗的成本、肿瘤稳定状态效用和肿瘤进展状态效用对ICER的影响较大。概率敏感性分析结果显示,在WTP阈值为268074.00元/QALY时,NG方案具有经济性的概率为0。结论:与G方案相比,NG方案作为一线药物治疗局部晚期或转移性K-Ras野生型胰腺癌不具有经济性。
基金Projects(52374138,51764013)supported by the National Natural Science Foundation of ChinaProject(20204BCJ22005)supported by the Training Plan for Academic and Technical Leaders of Major Disciplines of Jiangxi Province,China+1 种基金Project(2019M652277)supported by the China Postdoctoral Science FoundationProject(20192ACBL21014)supported by the Natural Science Youth Foundation Key Projects of Jiangxi Province,China。
文摘The cemented tailings backfill(CTB)with initial defects is more prone to destabilization damage under the influence of various unfavorable factors during the mining process.In order to investigate its influence on the stability of underground mining engineering,this paper simulates the generation of different degrees of initial defects inside the CTB by adding different contents of air-entraining agent(AEA),investigates the acoustic emission RA/AF eigenvalues of CTB with different contents of AEA under uniaxial compression,and adopts various denoising algorithms(e.g.,moving average smoothing,median filtering,and outlier detection)to improve the accuracy of the data.The variance and autocorrelation coefficients of RA/AF parameters were analyzed in conjunction with the critical slowing down(CSD)theory.The results show that the acoustic emission RA/AF values can be used to characterize the progressive damage evolution of CTB.The denoising algorithm processed the AE signals to reduce the effects of extraneous noise and anomalous spikes.Changes in the variance curves provide clear precursor information,while abrupt changes in the autocorrelation coefficient can be used as an auxiliary localization warning signal.The phenomenon of dramatic increase in the variance and autocorrelation coefficient curves during the compression-tightening stage,which is influenced by the initial defects,can lead to false warnings.As the initial defects of the CTB increase,its instability precursor time and instability time are prolonged,the peak stress decreases,and the time difference between the CTB and the instability damage is smaller.The results provide a new method for real-time monitoring and early warning of CTB instability damage.
基金Supported by Shenzhen High-level Hospital Construction Fund.
文摘BACKGROUND Patients harboring gene mutations like KRAS,NRAS,and BRAF demonstrate highly variable responses to chemotherapy,posing challenges for treatment optimization.Multiparametric magnetic resonance imaging(MRI),with its noninvasive capability to assess tumor characteristics in detail,has shown promise in evaluating treatment response and predicting therapeutic outcomes.This technology holds potential for guiding personalized treatment strategies tailored to individual patient profiles,enhancing the precision and effectiveness of colorectal cancer care.AIM To create a multiparametric MRI-based predictive model for assessing chemotherapy efficacy in colorectal cancer patients with gene mutations.METHODS This retrospective study was conducted in a tertiary hospital,analyzing 157 colorectal cancer patients with gene mutations treated between August 2022 and December 2023.Based on chemotherapy outcomes,the patients were categorized into favorable(n=60)and unfavorable(n=50)response groups.Univariate and multivariate logistic regression analyses were performed to identify independent predictors of chemotherapy efficacy.A predictive nomogram was constructed using significant variables,and its performance was assessed using the area under the receiver operating characteristic curve(AUC)in both training and validation sets.RESULTS Univariate analysis identified that tumor differentiation,T2 signal intensity ratio,tumor-to-anal margin distance,and MRI-detected lymph node metastasis as significantly associated with chemotherapy response(P<0.05).Multivariate Logistics regression confirmed these four parameters as independent predictors.The predictive model demonstrated strong discrimination,with an AUC of 0.938(sensitivity:86%;specificity:92%)in the training set,and 0.942(sensitivity:100%;specificity:83%)in the validation set.CONCLUSION We established and validated a multiparametric MRI-based model for predicting chemotherapy response in colorectal cancer patients with gene mutations.This model holds promise for guiding individualized treatment strategies.
基金National Natural Science Foundation of China,Nos.82070967,81770930the Natural Science Foundation of Hunan Province,No.2020jj4788 (all to BJ)。
文摘Ras homolog enriched in brain(Rheb) is a small GTPase that activates mammalian target of rapamycin complex 1(mTORC1).Previous studies have shown that constitutively active Rheb can enhance the regeneration of sensory axons after spinal cord injury by activating downstream effectors of mTOR.S6K1 and4E-BP1 are important downstream effectors of mTORC1.In this study,we investigated the role of Rheb/mTOR and its downstream effectors S6K1 and 4E-BP1in the protection of retinal ganglion cells.We transfected an optic nerve crush mouse model with adeno-associated viral 2-mediated constitutively active Rheb and observed the effects on retinal ganglion cell survival and axon regeneration.We found that overexpression of constitutively active Rheb promoted survival of retinal ganglion cells in the acute(14 days) and chronic(21 and 42 days) stages of injury.We also found that either co-expression of the dominant-negative S6K1mutant or the constitutively active 4E-BP1 mutant together with constitutively active Rheb markedly inhibited axon regeneration of retinal ganglion cells.This suggests that mTORC1-mediated S6K1 activation and 4E-BP1 inhibition were necessary components for constitutively active Rheb-induced axon regeneration.However,only S6K1 activation,but not 4E-BP1 knockdown,induced axon regeneration when applied alone.Furthermore,S6K1 activation promoted the survival of retinal ganglion cells at 14 days post-injury,whereas 4E-BP1 knockdown unexpectedly slightly decreased the survival of retinal ganglion cells at 14 days postinjury.Ove rexpression of constitutively active 4E-BP1 increased the survival of retinal ganglion cells at 14 days post-injury.Likewise,co-expressing constitutively active Rheb and constitutively active 4E-BP1 markedly increased the survival of retinal ganglion cells compared with overexpression of constitutively active Rheb alone at 14 days post-injury.These findings indicate that functional 4E-BP1 and S6K1 are neuroprotective and that 4E-BP1 may exert protective effects through a pathway at least partially independent of Rhe b/mTOR.Together,our results show that constitutively active Rheb promotes the survival of retinal ganglion cells and axon regeneration through modulating S6K1 and 4E-BP1 activity.Phosphorylated S6K1 and 4E-BP1 promote axon regeneration but play an antagonistic role in the survival of retinal ganglion cells.
文摘The regulating effects of TCM treatments including clearing away heat and toxic materials,promoting blood circulation and removing blood stasis,and strengthening the spleen and regulating qi on the oncogene transcription were observed in the liver cancer model rats.The preliminary results indicated that the mRNA levels of H-ras N-ras and K-ras,and signal molecules correlated with the ras/MAPK signal transduction pathway were down-regulated by the different TCM treatments in varying degrees.Also,the regulating effects of the treatments on differently-displayed genes were discrepant.It is suggested that the molecular mechanisms of the TCM treatments for liver cancer was complex with different target genes.
基金Supported by Zhejiang University Global Partnership Fund,No.BIO-0322023.
文摘This editorial comments on the study by Yang et al,emphasizing the Ras homolog enriched in brain 1(Rheb1)core function in restoring functionalβ-cell mass in diabetes,as crucial forβ-cell proliferation and survival.It has been revealed that Rheb1 promotesβ-cell regeneration through a dual pathway,activating mammalian target of rapamycin complex 1 and simultaneously inhibiting AMP-activated protein kinase(AMPK).Blocking mammalian target of rapamycin complex 1 while stimulating AMPK was necessary to haltβ-cell expansion,challenging traditional single-target approaches.Rheb1 also supportedβ-cell identity by triggering neurogenic locus notch homolog protein 1 signaling and interacting with hepatocyte nuclear factor 4 alpha,linked to maturity-onset diabetes of the young 1.An age-related decline of Rheb1 in human islets suggests its role in diminished regenerative capacity in adulthood.These findings make Rheb1 a promising therapeutic target for rejuvenatingβ-cells by linking nutrient sensing and energy regulation.Focusing on Rheb1 could alter diabetes treatment,merging proliferation with identity preservation for next-generation therapies.The gaps and translational opportunities,from Rheb1 modulators to biomarkers,were emphasized,advocating for interdisciplinary collaboration to maximize this pathway for positive clinical outcomes.Additional studies are needed to thoroughly investigate AMPK’s involvement in the Rheb1 metabolic biomarker associated with brain health and its possible therapeutic benefits.
文摘Background and Objective:Idiopathic intracranial hypertension(IIH)is a disorder of raised intracranial pressure(ICP)associated with overweight and obesity,with weight loss being the mainstay of management.Diet and lifestyle changes alone are often unsuccessful at achieving meaningful or sustained weight loss.Glucagon-like peptide-1 receptor agonists(GLP-1RA)are a class of medications developed for the treatment of diabetes but are also highly effective for weight reduction.The objective of this narrative review is to present the current evidence for GLP-1RAs in the management of IIH.Methods:Articles were searched for inclusion through OVID using the following terms:[papilledema OR intracranial hypertension OR idiopathic intracranial hypertension OR brain pseudotumor]and[glucagon like peptide 1 OR glucagon like peptide 1 receptor agonist OR semaglutide OR exendin 4 OR liraglutide OR tirzepatide].Titles and abstracts were screened manually for relevance.There were no exclusion criteria for time frame,language,population or article type,although conference abstracts were not included.An illustrative case of a patient with IIH treated with tirzepatide and semaglutide is also presented.Key Content and Findings:GLP-1RAs have demonstrated the potential for significantly greater weight loss in patients with IIH,with a reduced requirement for IIH medications and improved symptoms,compared to conventional weight management.Treatment with GLP-1RAs has also been shown to result in a rapid and persistent reduction in ICP in both rat and human studies.The side effects of GLP-1RAs are generally well-tolerated,with low rates of discontinuation in clinical trials.However,continuous treatment is likely required to avoid weight rebound and symptom recurrence after cessation.Conclusions:Despite highly promising preliminary evidence,further clinical trials are needed to determine the most effective GLP-1RA medications within this class,appropriate dosing regimens and treatment duration.
文摘BACKGROUND The combination of anti-epidermal growth factor receptor(EGFR)therapy and chemotherapy is currently a preferred first-line treatment for patients with unre-sectable,RAS and BRAF wild-type,left-sided metastatic colorectal cancer(mCRC).Several studies have also demonstrated the benefit of anti-EGFR therapy in sub-sequent line settings for this patient population.However,direct evidence com-paring the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited,leaving a crucial gap in guiding optimal treatment strategies.AIM To compare overall survival(OS)between frontline and subsequent anti-EGFR treatment in patients with unresectable,RAS and BRAF wild-type,left-sided mCRC.METHODS We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital,Thailand,between January 2013 and April 2023.Patients were classified into two groups based on the sequence of their anti-EGFR treatment.The primary endpoint was OS.RESULTS Among 222 patients with a median follow-up of 29 months,no significant difference in OS was observed between the frontline and subsequent-line groups(HR 1.03,95%CI:0.73-1.46,P=0.878).The median OS was 35.53 months(95%CI:26.59-44.47)for the frontline group and 31.60 months(95%CI:27.83-35.37)for the subsequent-line group.In the subsequent-line group,71 patients(32.4%)who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months(95%CI:12.87-26.53).CONCLUSION Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable,RAS/BRAF wild-type,left-sided mCRC patients,but early exposure is vital for those unlikely to receive subsequent therapy.
