Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,includi...Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,including cerebrospinal fluid,varies significantly(Figure 1Α;Yung et al.,2014).LPA actually corresponds to a variety of lipid species that include different stereoisomers with either saturated or unsaturated fatty acids bearing likely differentiated biological activities(Figure 1Α;Yung et al.,2014;Hernández-Araiza et al.,2018).展开更多
Tauopathies are a group of neurodegenerative diseases characterized by abnormal metabolism of the misfolded tau protein. Tau is encoded by the microtubule-associated protein tau gene(MAPT) and can be classified as eit...Tauopathies are a group of neurodegenerative diseases characterized by abnormal metabolism of the misfolded tau protein. Tau is encoded by the microtubule-associated protein tau gene(MAPT) and can be classified as either 3-repeat(3R) or 4-repeat(4R) based on the number of repeat domains from alternative splicing of exon 10 of the MAPT gene.展开更多
Endoscopic retrograde cholangiopancreatography is considered the gold standard for treating benign and malignant biliary obstructions.However,its use in complex biliary obstructions is limited.Over the past decades,th...Endoscopic retrograde cholangiopancreatography is considered the gold standard for treating benign and malignant biliary obstructions.However,its use in complex biliary obstructions is limited.Over the past decades,therapeutic endosonography(EUS)and emerging technologies such as lumen-apposing metal stents have enabled endoscopic treatment of conditions previously requiring nonendoscopic or surgical approaches.Studies show that EUS-guided choledochoduodenostomy is a reliable alternative to endoscopic retrograde cholangiopancreatography in the treatment of distal malignant biliary obstructions and can be considered a primary drainage modality in centers with adequate expertise.For malignant hilar biliary obstructions,draining at least 50%of viable liver tissue often requires combining different modalities.The treatment strategy in these patients should be individualized,depending on the Bismuth classification,patient physical status,and intended systemic therapy.Due to the lack of evidence,general recommendations cannot be made for EUS-guided hepaticoduodenostomy or combined procedures with transhepatic bridging stents.These novel techniques should be limited to selected palliative cases where conventional methods have failed and conducted within clinical trials to generate evidence before broader application.展开更多
Magnesium-based materials,including magnesium alloys,have emerged as a promising class of biodegradable materials with potential applications in cancer therapy due to their unique properties,including biocompatibility...Magnesium-based materials,including magnesium alloys,have emerged as a promising class of biodegradable materials with potential applications in cancer therapy due to their unique properties,including biocompatibility,biodegradability,and the ability to modulate the tumor microenvironment.The main degradation products of magnesium alloys are magnesium ions(Mg^(2+)),hydrogen(H_(2)),and magnesium hydroxide(Mg(OH)_(2)).Magnesium ions can regulate tumor growth and metastasis by mediating the inflammatory response and oxidative stress,maintaining genomic stability,and affecting the tumor microenvironment.Similarly,hydrogen can inhibit tumorigenesis through antioxidant and anti-inflammatory properties.Moreover,Mg(OH)_(2) can alter the pH of the microenvironment,impacting tumorigenesis.Biodegradable magnesium alloys serve various functions in clinical applications,including,but not limited to,bonefixation,coronary stents,and drug carriers.Nonetheless,the anti-tumor mechanism associated with magnesium-based materials has not been thoroughly investigated.This review provides a comprehensive overview of the current state of magnesium-based therapies for cancer.It highlights the mechanisms of action,identifies the challenges that must be addressed,and discusses prospects for oncological applications.展开更多
Objective:This study aimed to investigate the epidemiological characteristics and treatment regimens of non-Hodgkin lymphoma(NHL)in China through a retrospective analysis of 9,064 NHL cases.Methods:Clinical data of 9,...Objective:This study aimed to investigate the epidemiological characteristics and treatment regimens of non-Hodgkin lymphoma(NHL)in China through a retrospective analysis of 9,064 NHL cases.Methods:Clinical data of 9,064 patients were collected from 555 hospitals in 28 provinces of China.Results:Among 9,064 NHL patients,there were 5,241 males(57.8%)and 3,823 females(42.2%),with a male-to-female ratio of 1.37:1.Patients aged≥45 years accounted for 89.6%,with a mean age of 61.87±13.30 years.The predominant NHL subtypes were diffuse large B-cell lymphoma(DLBCL,45.2%),chronic lymphocytic leukemia/small lymphocytic lymphoma(CLL/SLL,19.8%),marginal zone lymphoma(MZL,13.9%),mantle cell lymphoma(MCL,9.7%),and central nervous system lymphoma(CNSL,4.3%).Combination therapy served as the primary treatment modality across all NHL subtypes.Conclusions:NHL in China demonstrates male predominance and primarily affects middle-aged and elderly populations,with combination chemotherapy remaining the mainstay therapeutic approach.展开更多
Organoid technology,characterized by high fidelity in mimicking the in vivo microenvironment,preservation of tumor heterogeneity,and capacity for high-throughput operations,has emerged as a critical tool in head and n...Organoid technology,characterized by high fidelity in mimicking the in vivo microenvironment,preservation of tumor heterogeneity,and capacity for high-throughput operations,has emerged as a critical tool in head and neck cancer research.To address clinical challenges in head and neck cancer management—including marked tumor heterogeneity,therapeutic resistance,and significant prognostic variability—this review focuses on four key translational applications of organoid technology:In mechanistic studies,organoid models provide a reliable platform for investigating tumorigenesis,progression,and drug resistancemechanisms.In personalized therapy,organoid-based drug sensitivity testing enables data-driven clinical decision-making.For biomarker discovery,organoids facilitate the identification of novel diagnostic markers and therapeutic targets.With ongoing improvements and standardization of organoid culture systems,this technology holds substantial promise for advancing precision medicine in head and neck cancer,bridging the gap between basic research and clinical practice.展开更多
BACKGROUND Primary ciliary dyskinesia(PCD)is a rare genetic disorder caused by motile cilia dysfunction.Identifying pathogenic variants is essential for diagnosis and personalized care,especially in consanguineous pop...BACKGROUND Primary ciliary dyskinesia(PCD)is a rare genetic disorder caused by motile cilia dysfunction.Identifying pathogenic variants is essential for diagnosis and personalized care,especially in consanguineous populations like Saudi Arabia.CASE SUMMARY This report presents a Saudi pediatric patient diagnosed with PCD who exhibited persistent neonatal tachypnea,chronic productive cough,and recurrent otitis media.Whole-exome sequencing revealed a novel homozygous nonsense variant in the C3orf67 gene(NM_198463.2:c.508C>T),resulting in a truncated,nonfunctional protein.This mutation likely impairs ciliary motility due to the production of a truncated,non-functional protein.The clinical findings were supported by multiple positive sputum cultures and a significant family history of similar symptoms,suggesting a genetic etiology consistent with autosomal recessive inheritance.CONCLUSION This case highlights the importance of genetic studies in diagnosing PCD,particularly in communities with a high rate of consanguinity.The identification of a novel homozygous variant in the C3orf67 gene expands the known genetic landscape of the disease.Further research is essential to clarify the functional role of C3orf67 in ciliary biology and its contribution to PCD pathogenesis.展开更多
Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connect...Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connectivity of this structure has been studied extensively over the past century,mainly using a range of anterograde and retrograde anatomical tracers[3].展开更多
Background:With advancements in burn treatment and intensive care leading to decreased mortality rates,a growing cohort of burn survivors is emerging.These individuals may be susceptible to frailty,characterized by re...Background:With advancements in burn treatment and intensive care leading to decreased mortality rates,a growing cohort of burn survivors is emerging.These individuals may be susceptible to frailty,characterized by reduced physiological reserve and increased vulnerability to stressors commonly associated with aging,which significantly complicates their recovery process.To date,no study has investigated burns as a potential risk factor for frailty.This study aimed to determine the short-term prevalence of frailty among burn survivors’months after injury and compare it with that of the general population.Methods:A post hoc analysis was conducted on the Randomized Trial of Enteral Glutamine to Minimize the Effects of Burn Injury(RE-ENERGIZE)trial,an international randomized-controlled trial involving 1200 burn injury patients with partial-or full-thickness burns.Participants who did not complete the 36-Item Short Form Health Survey(SF-36)questionnaire were excluded.Data for the general population were obtained from the 2022 National Health Interview Survey(NHIS).Frailty was assessed using the FRAIL(Fatigue,Resistance,Ambulation,Illness,Loss of weight)scale.Due to lack of data on loss of weight,for the purposes of this study,malnutrition was used as the fifth variable.Illness and malnutrition were based on admission data,while fatigue,resistance,and ambulation were determined from post-discharge responses to the SF-36.The burn cohort and general population groups were matched using propensity score matching and compared in terms of frailty status.Within the burn group,patients were divided into different subgroups based on their frailty status,and the differences in their(instrumental)activities of daily living(iADL and ADL)were compared.A multivariable analysis was performed within the burn cohort to identify factors predisposing to frailty as well as compromised iADL and ADL.Results:Out of the 1200 burn patients involved in the study,600 completed the required questionnaires[follow-up time:(5.5±2.3)months]and were matched to 1200 adults from the general population in the U.S.In comparison to the general population,burn patients exhibited a significantly higher likelihood of being pre-frail(42.3%vs.19.8%,P<0.0001),or frail(13.0%vs.1.0%,P<0.0001).When focusing on specific components,burn patients were more prone to experiencing fatigue(25.8%vs.13.5%,P<0.0001),limited resistance(34.0%vs.2.7%,P<0.0001),and restricted ambulation(41.8%vs.3.8%,P<0.0001).Conversely,the incidence rate of illness was observed to be higher in the general population(1.2%vs.2.8%,P=0.03),while no significant difference was detected regarding malnutrition(2.3%vs.2.6%,P=0.75).Furthermore,in comparison with robust burn patients,it was significantly more likely for pre-frail and frail patients to disclose compromise in ADL and iADL.The frail cohort reported the most pronounced limitation.Conclusions:Our findings suggest a higher incidence of post-discharge frailty among burn survivors in the short-term following injury.Burn survivors experience compromised fatigue,resistance,and ambulation,while rates of illness and malnutrition were lower or unchanged,respectively.These results underscore the critical need for early identification of frailty after a burn injury,with timely and comprehensive involvement of a multidisciplinary team including burn and pain specialists,community physicians,physiotherapists,nutritionists,and social workers.This collaborative effort can ensure holistic care to address and mitigate frailty in this patient population.展开更多
Low birth-weight is now known to be associated with increased rates of hypertension in later life. The renin-angiotensin system (RAS) is mainly involved in the regulation of blood pressure. In animal models, alteratio...Low birth-weight is now known to be associated with increased rates of hypertension in later life. The renin-angiotensin system (RAS) is mainly involved in the regulation of blood pressure. In animal models, alterations of RAS induced by fetal insults such as gestational protein restriction and placental insufficiency may serve as a potential mechanism critical to the fetal programming of hypertension. Blockade of RAS during the nephrogenic period in rats leads to a marked reduction in nephron numbers as well as low birth-weight. The renal RAS suppression during a critical window of nephrogenesis may be a key component in this programming cascade. This article summarizes the potential mechanisms involved in fetal programming of RAS critical to the development of adult hypertension.展开更多
基金supported by the Hellenic Foundation for Research and Innovation,HFRI,“2nd Call for HFRI Research Projects to support Faculty Members&Researchers”Project 02667 to GL.
文摘Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,including cerebrospinal fluid,varies significantly(Figure 1Α;Yung et al.,2014).LPA actually corresponds to a variety of lipid species that include different stereoisomers with either saturated or unsaturated fatty acids bearing likely differentiated biological activities(Figure 1Α;Yung et al.,2014;Hernández-Araiza et al.,2018).
基金supported by the Rainwater Charitable Foundation。
文摘Tauopathies are a group of neurodegenerative diseases characterized by abnormal metabolism of the misfolded tau protein. Tau is encoded by the microtubule-associated protein tau gene(MAPT) and can be classified as either 3-repeat(3R) or 4-repeat(4R) based on the number of repeat domains from alternative splicing of exon 10 of the MAPT gene.
文摘Endoscopic retrograde cholangiopancreatography is considered the gold standard for treating benign and malignant biliary obstructions.However,its use in complex biliary obstructions is limited.Over the past decades,therapeutic endosonography(EUS)and emerging technologies such as lumen-apposing metal stents have enabled endoscopic treatment of conditions previously requiring nonendoscopic or surgical approaches.Studies show that EUS-guided choledochoduodenostomy is a reliable alternative to endoscopic retrograde cholangiopancreatography in the treatment of distal malignant biliary obstructions and can be considered a primary drainage modality in centers with adequate expertise.For malignant hilar biliary obstructions,draining at least 50%of viable liver tissue often requires combining different modalities.The treatment strategy in these patients should be individualized,depending on the Bismuth classification,patient physical status,and intended systemic therapy.Due to the lack of evidence,general recommendations cannot be made for EUS-guided hepaticoduodenostomy or combined procedures with transhepatic bridging stents.These novel techniques should be limited to selected palliative cases where conventional methods have failed and conducted within clinical trials to generate evidence before broader application.
文摘Magnesium-based materials,including magnesium alloys,have emerged as a promising class of biodegradable materials with potential applications in cancer therapy due to their unique properties,including biocompatibility,biodegradability,and the ability to modulate the tumor microenvironment.The main degradation products of magnesium alloys are magnesium ions(Mg^(2+)),hydrogen(H_(2)),and magnesium hydroxide(Mg(OH)_(2)).Magnesium ions can regulate tumor growth and metastasis by mediating the inflammatory response and oxidative stress,maintaining genomic stability,and affecting the tumor microenvironment.Similarly,hydrogen can inhibit tumorigenesis through antioxidant and anti-inflammatory properties.Moreover,Mg(OH)_(2) can alter the pH of the microenvironment,impacting tumorigenesis.Biodegradable magnesium alloys serve various functions in clinical applications,including,but not limited to,bonefixation,coronary stents,and drug carriers.Nonetheless,the anti-tumor mechanism associated with magnesium-based materials has not been thoroughly investigated.This review provides a comprehensive overview of the current state of magnesium-based therapies for cancer.It highlights the mechanisms of action,identifies the challenges that must be addressed,and discusses prospects for oncological applications.
文摘Objective:This study aimed to investigate the epidemiological characteristics and treatment regimens of non-Hodgkin lymphoma(NHL)in China through a retrospective analysis of 9,064 NHL cases.Methods:Clinical data of 9,064 patients were collected from 555 hospitals in 28 provinces of China.Results:Among 9,064 NHL patients,there were 5,241 males(57.8%)and 3,823 females(42.2%),with a male-to-female ratio of 1.37:1.Patients aged≥45 years accounted for 89.6%,with a mean age of 61.87±13.30 years.The predominant NHL subtypes were diffuse large B-cell lymphoma(DLBCL,45.2%),chronic lymphocytic leukemia/small lymphocytic lymphoma(CLL/SLL,19.8%),marginal zone lymphoma(MZL,13.9%),mantle cell lymphoma(MCL,9.7%),and central nervous system lymphoma(CNSL,4.3%).Combination therapy served as the primary treatment modality across all NHL subtypes.Conclusions:NHL in China demonstrates male predominance and primarily affects middle-aged and elderly populations,with combination chemotherapy remaining the mainstay therapeutic approach.
基金supported by the National Natural Science Foundation of China(Grant No.82072997)the BeijingMunicipal Science&Technology Commission(No.Z221100007422045)BeijingMunicipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(Code:ZLRK202304).
文摘Organoid technology,characterized by high fidelity in mimicking the in vivo microenvironment,preservation of tumor heterogeneity,and capacity for high-throughput operations,has emerged as a critical tool in head and neck cancer research.To address clinical challenges in head and neck cancer management—including marked tumor heterogeneity,therapeutic resistance,and significant prognostic variability—this review focuses on four key translational applications of organoid technology:In mechanistic studies,organoid models provide a reliable platform for investigating tumorigenesis,progression,and drug resistancemechanisms.In personalized therapy,organoid-based drug sensitivity testing enables data-driven clinical decision-making.For biomarker discovery,organoids facilitate the identification of novel diagnostic markers and therapeutic targets.With ongoing improvements and standardization of organoid culture systems,this technology holds substantial promise for advancing precision medicine in head and neck cancer,bridging the gap between basic research and clinical practice.
文摘BACKGROUND Primary ciliary dyskinesia(PCD)is a rare genetic disorder caused by motile cilia dysfunction.Identifying pathogenic variants is essential for diagnosis and personalized care,especially in consanguineous populations like Saudi Arabia.CASE SUMMARY This report presents a Saudi pediatric patient diagnosed with PCD who exhibited persistent neonatal tachypnea,chronic productive cough,and recurrent otitis media.Whole-exome sequencing revealed a novel homozygous nonsense variant in the C3orf67 gene(NM_198463.2:c.508C>T),resulting in a truncated,nonfunctional protein.This mutation likely impairs ciliary motility due to the production of a truncated,non-functional protein.The clinical findings were supported by multiple positive sputum cultures and a significant family history of similar symptoms,suggesting a genetic etiology consistent with autosomal recessive inheritance.CONCLUSION This case highlights the importance of genetic studies in diagnosing PCD,particularly in communities with a high rate of consanguinity.The identification of a novel homozygous variant in the C3orf67 gene expands the known genetic landscape of the disease.Further research is essential to clarify the functional role of C3orf67 in ciliary biology and its contribution to PCD pathogenesis.
文摘Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connectivity of this structure has been studied extensively over the past century,mainly using a range of anterograde and retrograde anatomical tracers[3].
基金supported by the U.S.Department of Defense(W81XWH-09-2-0194 for the pilot phase)the Canadian Institutes of Health Research(MCT-94834 for the pilot phase and 14238 for the definitive phase).
文摘Background:With advancements in burn treatment and intensive care leading to decreased mortality rates,a growing cohort of burn survivors is emerging.These individuals may be susceptible to frailty,characterized by reduced physiological reserve and increased vulnerability to stressors commonly associated with aging,which significantly complicates their recovery process.To date,no study has investigated burns as a potential risk factor for frailty.This study aimed to determine the short-term prevalence of frailty among burn survivors’months after injury and compare it with that of the general population.Methods:A post hoc analysis was conducted on the Randomized Trial of Enteral Glutamine to Minimize the Effects of Burn Injury(RE-ENERGIZE)trial,an international randomized-controlled trial involving 1200 burn injury patients with partial-or full-thickness burns.Participants who did not complete the 36-Item Short Form Health Survey(SF-36)questionnaire were excluded.Data for the general population were obtained from the 2022 National Health Interview Survey(NHIS).Frailty was assessed using the FRAIL(Fatigue,Resistance,Ambulation,Illness,Loss of weight)scale.Due to lack of data on loss of weight,for the purposes of this study,malnutrition was used as the fifth variable.Illness and malnutrition were based on admission data,while fatigue,resistance,and ambulation were determined from post-discharge responses to the SF-36.The burn cohort and general population groups were matched using propensity score matching and compared in terms of frailty status.Within the burn group,patients were divided into different subgroups based on their frailty status,and the differences in their(instrumental)activities of daily living(iADL and ADL)were compared.A multivariable analysis was performed within the burn cohort to identify factors predisposing to frailty as well as compromised iADL and ADL.Results:Out of the 1200 burn patients involved in the study,600 completed the required questionnaires[follow-up time:(5.5±2.3)months]and were matched to 1200 adults from the general population in the U.S.In comparison to the general population,burn patients exhibited a significantly higher likelihood of being pre-frail(42.3%vs.19.8%,P<0.0001),or frail(13.0%vs.1.0%,P<0.0001).When focusing on specific components,burn patients were more prone to experiencing fatigue(25.8%vs.13.5%,P<0.0001),limited resistance(34.0%vs.2.7%,P<0.0001),and restricted ambulation(41.8%vs.3.8%,P<0.0001).Conversely,the incidence rate of illness was observed to be higher in the general population(1.2%vs.2.8%,P=0.03),while no significant difference was detected regarding malnutrition(2.3%vs.2.6%,P=0.75).Furthermore,in comparison with robust burn patients,it was significantly more likely for pre-frail and frail patients to disclose compromise in ADL and iADL.The frail cohort reported the most pronounced limitation.Conclusions:Our findings suggest a higher incidence of post-discharge frailty among burn survivors in the short-term following injury.Burn survivors experience compromised fatigue,resistance,and ambulation,while rates of illness and malnutrition were lower or unchanged,respectively.These results underscore the critical need for early identification of frailty after a burn injury,with timely and comprehensive involvement of a multidisciplinary team including burn and pain specialists,community physicians,physiotherapists,nutritionists,and social workers.This collaborative effort can ensure holistic care to address and mitigate frailty in this patient population.
文摘Low birth-weight is now known to be associated with increased rates of hypertension in later life. The renin-angiotensin system (RAS) is mainly involved in the regulation of blood pressure. In animal models, alterations of RAS induced by fetal insults such as gestational protein restriction and placental insufficiency may serve as a potential mechanism critical to the fetal programming of hypertension. Blockade of RAS during the nephrogenic period in rats leads to a marked reduction in nephron numbers as well as low birth-weight. The renal RAS suppression during a critical window of nephrogenesis may be a key component in this programming cascade. This article summarizes the potential mechanisms involved in fetal programming of RAS critical to the development of adult hypertension.
