BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression result...BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCFFBXW7,p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCFFBXW7,p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCFFBXW7(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCFFBXW7 and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCFFBXW7,thereby influencing the ubiquitination and degradation of cyclin E1.展开更多
In this study,ionosonde observations over Fuke(19.5°N,109.1°E),Wuhan(30.5°N,114.4°E),and Mohe(53.5°N,122.3°E)were analyzed to demonstrate the responses of the sporadic E()to the severe at...In this study,ionosonde observations over Fuke(19.5°N,109.1°E),Wuhan(30.5°N,114.4°E),and Mohe(53.5°N,122.3°E)were analyzed to demonstrate the responses of the sporadic E()to the severe atmospheric disturbances caused by the Tonga volcanic eruptions on January 15,2022.The most prominent signature was the disappearance of the layer after~10:00 UT over Wuhan and Fuke,which was attributed to the vertical drift caused by the eruptions.The occurred intermittently after 13:00 UT following the arrival of the tropospheric Lamb wave.To examine the causal mechanism for the intermittence,we also included data of horizontal winds in the mesosphere and lower thermosphere region recorded by the meteor radars at Wuhan and Mohe in this study.The wind disturbances with periods of~20 hours contributed to the formation of the layer in the nighttime on January 15.展开更多
In addition to being driven by tidal winds,the sporadic E(Es)layers are modulated by gravity waves(GWs),although the effects are not yet comprehensively understood.In this article,we discuss the effects of mesoscale G...In addition to being driven by tidal winds,the sporadic E(Es)layers are modulated by gravity waves(GWs),although the effects are not yet comprehensively understood.In this article,we discuss the effects of mesoscale GWs on the Es layers determined by using a newly developed model,MISE-1D(one-dimensional Model of Ionospheric Sporadic E),with low numerical dissipation and high resolution.Driven by the wind fields resolved by the high-resolution version of the Whole Atmosphere Community Climate Model with thermosphere and ionosphere extension(WACCM-X),the MISE-1D simulation revealed that GWs significantly influence the evolution of the Es layer above 100 km but have a very limited effect at lower altitudes.The effects of GWs are diverse and complex,generally including the generation of fluctuating wavelike structures on the Es layer with frequencies similar to those of the GWs.The mesoscale GWs can also cause increases in the density of Es layers,or they can disperse or diffuse the Es layers and increase their thickness.In addition,the presence of GWs is a key factor in sustaining the Es layers in some cases.展开更多
Sporadic E(Es)layers in the ionosphere are characterized by intense plasma irregularities in the E region at altitudes of 90-130 km.Because they can significantly influence radio communications and navigation systems,...Sporadic E(Es)layers in the ionosphere are characterized by intense plasma irregularities in the E region at altitudes of 90-130 km.Because they can significantly influence radio communications and navigation systems,accurate forecasting of Es layers is crucial for ensuring the precision and dependability of navigation satellite systems.In this study,we present Es predictions made by an empirical model and by a deep learning model,and analyze their differences comprehensively by comparing the model predictions to satellite RO measurements and ground-based ionosonde observations.The deep learning model exhibited significantly better performance,as indicated by its high coefficient of correlation(r=0.87)with RO observations and predictions,than did the empirical model(r=0.53).This study highlights the importance of integrating artificial intelligence technology into ionosphere modelling generally,and into predicting Es layer occurrences and characteristics,in particular.展开更多
BACKGROUND Although breast milk is ideal for newborns,in some cases,it is replaced with cow’s milk,which contains proteins that increase the risk of cow’s milk protein allergy(CMPA).AIM To evaluate CMPA prevalence i...BACKGROUND Although breast milk is ideal for newborns,in some cases,it is replaced with cow’s milk,which contains proteins that increase the risk of cow’s milk protein allergy(CMPA).AIM To evaluate CMPA prevalence in Bahrain and compare clinical characteristics of children with immunoglobulin E(IgE)-and non-IgE-mediated CMPA.METHODS This retrospective cohort study examined children with CMPA diagnosed at the pediatric gastroenterology outpatient clinic of the Salmaniya Medical Complex,Bahrain,between 2014 and 2022,and assessed CMPA prevalence.Clinical presentations,laboratory findings,dietary modifications,and outcomes were compared between children with IgE-mediated and non-IgE-mediated CMPA.Categorical variables were compared using Fisher’s exact test or Pearson’sχ2 test,whereas continuous variables were compared using Student’s t-test or the Mann-Whitney U test.RESULTS Of 8332 patients,6022(72.3%)adhered to their appointment.Of them,618(10.3%)were suggested of having CMPA and 595(96.3%)were included;CMPA prevalence was 2%.Most patients were Bahraini(93.8%)and males(55.3%).Non-IgE-mediated type accounted for 77.3%cases and IgE-mediated type,22.7%.IgE-mediated CMPA presented more in boys(P=0.030),and later in life(5.1 months±4.5 months vs 4.2 months±4.2 months,P=0.016,95%CI:0.08-1.73),had more associated diseases(P<0.001);and presented with more cutaneous(P=0.024)and respiratory(P=0.003)manifestations,severe symptoms[rash/dry skin(P=0.031),facial swelling/angioedema(P=0.003),failure to thrive(P=0.013),apparent life-threatening event(P<0.001)],and positive physical findings(P=0.002)than non-IgE-mediated CMPA.Most patients were exclusively fed cow milk formula(50.3%).The amino acid-based formula(AAF)was most prescribed(60.5%)with no difference between the two types(P=0.173).Although breastfeeding was recommended to 49.6%,only 8.2%were exclusively breastfed.IgE-mediated CMPA was associated with a longer follow-up duration than non-IgE-mediated CMPA(17.3 months±14.0 months vs 13.5 months±13.4 months,P=0.005,95%CI:1.1-6.3).CONCLUSION This study revealed a high CMPA prevalence with clinical differences between both types that can influence treatment.AAF was most prescribed,while breastfeeding with dietary modification is rarely applied.展开更多
BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohor...BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal cancer.Therefore,we further explored the survival benefits in the population with BRAF V600E mutant mCRC.AIM To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal cancer.METHODS A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December 2022.The patients were divided into two cohorts.RESULTS A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,respectively.Subgroup analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.展开更多
Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primar...Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.展开更多
BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among adults.However,recently a paradigm shift has been observed in the epidemiology of HA...BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among adults.However,recently a paradigm shift has been observed in the epidemiology of HAV,as evident by cases of acute hepatitis due to HAV among adults.AIM To estimate frequency of HAV in acute viral hepatitis and compare characteristics in HAV and hepatitis E virus(HEV)infection.METHODS This was a trend analysis conducted at Aga Khan University Hospital Karachi(Sindh,Pakistan)from February 2024 to May 2024.Individuals aged 18 years and older diagnosed with acute viral hepatitis attributed to hepatotropic viruses in 2024 were reviewed.To compare the trend patients admitted with acute hepatitis during 2019-2023 were also reviewed.Data regarding clinical and laboratory parameters were recorded.The yearly trend of acute hepatitis due to HAV and HEV was analyzed,and comparative analysis was done between HAV and HEV cases among adults.RESULTS A total of 396 patients were found to have acute hepatitis during our study duration.HAV was diagnosed in 234 patients(59%)while 157 patients(39.6%)were found to have acute HEV infection.Additionally,acute hepatitis B virus infection was identified in 3 patients(0.7%),whereas acute hepatitis C virus infection was found in 2(0.5%)cases of acute hepatitis.Yearly trends showed increasing occurrence of HAV infection among adults over last 5 years.The patients with acute HAV were younger than patients with HEV(28 years±8 years vs 30 years±8 years;P<0.01).Higher levels of total bilirubin were seen in HEV infection,while higher levels of alanine transaminase were seen in HAV infection.However,a higher proportion of acute liver failure(ALF),coagulopathy,and mortality were observed in HEV.CONCLUSION An increase in acute hepatitis A cases among adults shows less severity than hepatitis E,highlighting the need for better sanitation,hygiene,and adult hepatitis A vaccination programs.展开更多
目的:建立天南星中化学成分快速表征的分析方法,并用于该药材的质量控制。方法:采用超高效液相色谱联用四级杆串联飞行时间质谱(UPLC-Q-TOF/MS)结合UNIFI质谱数据分析平台,选择Waters Acquity UPLC HSS T 3 C 18色谱柱,以0.1%甲酸水和0...目的:建立天南星中化学成分快速表征的分析方法,并用于该药材的质量控制。方法:采用超高效液相色谱联用四级杆串联飞行时间质谱(UPLC-Q-TOF/MS)结合UNIFI质谱数据分析平台,选择Waters Acquity UPLC HSS T 3 C 18色谱柱,以0.1%甲酸水和0.1%甲酸乙腈为流动相进行梯度洗脱,流速为0.35 mL/min,进样量5μL;选择电喷雾离子源,以MS^(E)模式采集正、负离子下天南星化学成分的质谱数据;通过UNIFI平台自带数据库结合文献检索建立天南星化学成分数据库,并根据化合物的精准分子质量、二级碎片离子信息及与对照品和文献数据等比对进化学成分的鉴定。结果:在正离子模式下鉴定出49个化合物,负离子模式下鉴定16个化合物,主要以有机酸、氨基酸及黄酮苷类化合物为主。其中,35个化合物可能首次从天南星中发现。结论:采用UPLC-Q-TOF/MS结合UNIFI平台的分析方法可快速鉴定天南星的化学成分,该研究结果可为天南星药效物质基础的研究以及质量控制体系建立和产品开发等提供科学依据。展开更多
基金Supported by Innovative Practice Platform for Undergraduate Students,School of Public Health Xiamen University,No.2021001.
文摘BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCFFBXW7,p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCFFBXW7,p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCFFBXW7(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCFFBXW7 and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCFFBXW7,thereby influencing the ubiquitination and degradation of cyclin E1.
基金the Funds of the National Natural Science Foundation of China(NSFC),grant numbers 42174211,42230207,and U2039205.
文摘In this study,ionosonde observations over Fuke(19.5°N,109.1°E),Wuhan(30.5°N,114.4°E),and Mohe(53.5°N,122.3°E)were analyzed to demonstrate the responses of the sporadic E()to the severe atmospheric disturbances caused by the Tonga volcanic eruptions on January 15,2022.The most prominent signature was the disappearance of the layer after~10:00 UT over Wuhan and Fuke,which was attributed to the vertical drift caused by the eruptions.The occurred intermittently after 13:00 UT following the arrival of the tropospheric Lamb wave.To examine the causal mechanism for the intermittence,we also included data of horizontal winds in the mesosphere and lower thermosphere region recorded by the meteor radars at Wuhan and Mohe in this study.The wind disturbances with periods of~20 hours contributed to the formation of the layer in the nighttime on January 15.
基金supported by the Project of Stable Support for Youth Teams in Basic Research Field,Chinese Academy of Sciences(CASGrant No.YSBR-018)+2 种基金the B-type Strategic Priority Program of CAS(Grant No.XDB41000000)the National Natural Science Foundation of China(Grant No.42204165)the National Key Research and Development Program(Grant No.2022YFF0504400).
文摘In addition to being driven by tidal winds,the sporadic E(Es)layers are modulated by gravity waves(GWs),although the effects are not yet comprehensively understood.In this article,we discuss the effects of mesoscale GWs on the Es layers determined by using a newly developed model,MISE-1D(one-dimensional Model of Ionospheric Sporadic E),with low numerical dissipation and high resolution.Driven by the wind fields resolved by the high-resolution version of the Whole Atmosphere Community Climate Model with thermosphere and ionosphere extension(WACCM-X),the MISE-1D simulation revealed that GWs significantly influence the evolution of the Es layer above 100 km but have a very limited effect at lower altitudes.The effects of GWs are diverse and complex,generally including the generation of fluctuating wavelike structures on the Es layer with frequencies similar to those of the GWs.The mesoscale GWs can also cause increases in the density of Es layers,or they can disperse or diffuse the Es layers and increase their thickness.In addition,the presence of GWs is a key factor in sustaining the Es layers in some cases.
基金supported by the Project of Stable Support for Youth Team in Basic Research Field,CAS(grant No.YSBR-018)the National Natural Science Foundation of China(grant Nos.42188101,42130204)+4 种基金the B-type Strategic Priority Program of CAS(grant no.XDB41000000)the National Natural Science Foundation of China(NSFC)Distinguished Overseas Young Talents Program,Innovation Program for Quantum Science and Technology(2021ZD0300301)the Open Research Project of Large Research Infrastructures of CAS-“Study on the interaction between low/mid-latitude atmosphere and ionosphere based on the Chinese Meridian Project”.The project was supported also by the National Key Laboratory of Deep Space Exploration(Grant No.NKLDSE2023A002)the Open Fund of Anhui Provincial Key Laboratory of Intelligent Underground Detection(Grant No.APKLIUD23KF01)the China National Space Administration(CNSA)pre-research Project on Civil Aerospace Technologies No.D010305,D010301.
文摘Sporadic E(Es)layers in the ionosphere are characterized by intense plasma irregularities in the E region at altitudes of 90-130 km.Because they can significantly influence radio communications and navigation systems,accurate forecasting of Es layers is crucial for ensuring the precision and dependability of navigation satellite systems.In this study,we present Es predictions made by an empirical model and by a deep learning model,and analyze their differences comprehensively by comparing the model predictions to satellite RO measurements and ground-based ionosonde observations.The deep learning model exhibited significantly better performance,as indicated by its high coefficient of correlation(r=0.87)with RO observations and predictions,than did the empirical model(r=0.53).This study highlights the importance of integrating artificial intelligence technology into ionosphere modelling generally,and into predicting Es layer occurrences and characteristics,in particular.
文摘BACKGROUND Although breast milk is ideal for newborns,in some cases,it is replaced with cow’s milk,which contains proteins that increase the risk of cow’s milk protein allergy(CMPA).AIM To evaluate CMPA prevalence in Bahrain and compare clinical characteristics of children with immunoglobulin E(IgE)-and non-IgE-mediated CMPA.METHODS This retrospective cohort study examined children with CMPA diagnosed at the pediatric gastroenterology outpatient clinic of the Salmaniya Medical Complex,Bahrain,between 2014 and 2022,and assessed CMPA prevalence.Clinical presentations,laboratory findings,dietary modifications,and outcomes were compared between children with IgE-mediated and non-IgE-mediated CMPA.Categorical variables were compared using Fisher’s exact test or Pearson’sχ2 test,whereas continuous variables were compared using Student’s t-test or the Mann-Whitney U test.RESULTS Of 8332 patients,6022(72.3%)adhered to their appointment.Of them,618(10.3%)were suggested of having CMPA and 595(96.3%)were included;CMPA prevalence was 2%.Most patients were Bahraini(93.8%)and males(55.3%).Non-IgE-mediated type accounted for 77.3%cases and IgE-mediated type,22.7%.IgE-mediated CMPA presented more in boys(P=0.030),and later in life(5.1 months±4.5 months vs 4.2 months±4.2 months,P=0.016,95%CI:0.08-1.73),had more associated diseases(P<0.001);and presented with more cutaneous(P=0.024)and respiratory(P=0.003)manifestations,severe symptoms[rash/dry skin(P=0.031),facial swelling/angioedema(P=0.003),failure to thrive(P=0.013),apparent life-threatening event(P<0.001)],and positive physical findings(P=0.002)than non-IgE-mediated CMPA.Most patients were exclusively fed cow milk formula(50.3%).The amino acid-based formula(AAF)was most prescribed(60.5%)with no difference between the two types(P=0.173).Although breastfeeding was recommended to 49.6%,only 8.2%were exclusively breastfed.IgE-mediated CMPA was associated with a longer follow-up duration than non-IgE-mediated CMPA(17.3 months±14.0 months vs 13.5 months±13.4 months,P=0.005,95%CI:1.1-6.3).CONCLUSION This study revealed a high CMPA prevalence with clinical differences between both types that can influence treatment.AAF was most prescribed,while breastfeeding with dietary modification is rarely applied.
基金Supported by National Natural Science Foundation of China,No.82174461Hospital Capability Enhancement Project of Xiyuan Hospital,CACMS,No.XYZX0201-22Technology Innovation Project of China Academy of Chinese Medical Sciences,No.CI2021A01811.
文摘BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal cancer.Therefore,we further explored the survival benefits in the population with BRAF V600E mutant mCRC.AIM To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal cancer.METHODS A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December 2022.The patients were divided into two cohorts.RESULTS A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,respectively.Subgroup analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.
基金financially supported by the Science and Technology Innovation Program of Hunan Province,No.2022RC1220(to WP)China Postdoctoral Science Foundation,No.2022M711733(to ZZ)+2 种基金the National Natural Science Foundation of China,No.82160920(to ZZ)Hebei Postdoctoral Scientific Research Project,No.B2022003040(to ZZ)Hunan Flagship Department of Integrated Traditional Chinese and Western Medicine(to WP)。
文摘Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.
文摘BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among adults.However,recently a paradigm shift has been observed in the epidemiology of HAV,as evident by cases of acute hepatitis due to HAV among adults.AIM To estimate frequency of HAV in acute viral hepatitis and compare characteristics in HAV and hepatitis E virus(HEV)infection.METHODS This was a trend analysis conducted at Aga Khan University Hospital Karachi(Sindh,Pakistan)from February 2024 to May 2024.Individuals aged 18 years and older diagnosed with acute viral hepatitis attributed to hepatotropic viruses in 2024 were reviewed.To compare the trend patients admitted with acute hepatitis during 2019-2023 were also reviewed.Data regarding clinical and laboratory parameters were recorded.The yearly trend of acute hepatitis due to HAV and HEV was analyzed,and comparative analysis was done between HAV and HEV cases among adults.RESULTS A total of 396 patients were found to have acute hepatitis during our study duration.HAV was diagnosed in 234 patients(59%)while 157 patients(39.6%)were found to have acute HEV infection.Additionally,acute hepatitis B virus infection was identified in 3 patients(0.7%),whereas acute hepatitis C virus infection was found in 2(0.5%)cases of acute hepatitis.Yearly trends showed increasing occurrence of HAV infection among adults over last 5 years.The patients with acute HAV were younger than patients with HEV(28 years±8 years vs 30 years±8 years;P<0.01).Higher levels of total bilirubin were seen in HEV infection,while higher levels of alanine transaminase were seen in HAV infection.However,a higher proportion of acute liver failure(ALF),coagulopathy,and mortality were observed in HEV.CONCLUSION An increase in acute hepatitis A cases among adults shows less severity than hepatitis E,highlighting the need for better sanitation,hygiene,and adult hepatitis A vaccination programs.
文摘目的:建立天南星中化学成分快速表征的分析方法,并用于该药材的质量控制。方法:采用超高效液相色谱联用四级杆串联飞行时间质谱(UPLC-Q-TOF/MS)结合UNIFI质谱数据分析平台,选择Waters Acquity UPLC HSS T 3 C 18色谱柱,以0.1%甲酸水和0.1%甲酸乙腈为流动相进行梯度洗脱,流速为0.35 mL/min,进样量5μL;选择电喷雾离子源,以MS^(E)模式采集正、负离子下天南星化学成分的质谱数据;通过UNIFI平台自带数据库结合文献检索建立天南星化学成分数据库,并根据化合物的精准分子质量、二级碎片离子信息及与对照品和文献数据等比对进化学成分的鉴定。结果:在正离子模式下鉴定出49个化合物,负离子模式下鉴定16个化合物,主要以有机酸、氨基酸及黄酮苷类化合物为主。其中,35个化合物可能首次从天南星中发现。结论:采用UPLC-Q-TOF/MS结合UNIFI平台的分析方法可快速鉴定天南星的化学成分,该研究结果可为天南星药效物质基础的研究以及质量控制体系建立和产品开发等提供科学依据。
