BACKGROUND:In clinical practice,some patients might not be able or unwilling to provide a thorough history of medication and poison exposure.The aim of this study was to use toxicological analysis to examine the clini...BACKGROUND:In clinical practice,some patients might not be able or unwilling to provide a thorough history of medication and poison exposure.The aim of this study was to use toxicological analysis to examine the clinical characteristics of patients with acute poisoning whose exposure history was uncertain from a toxicological analysis perspective.METHODS:This was a retrospective and descriptive study from an institute of poisoning.Patient registration information and test reports spanning the period from April 1,2020 to March 31,2022,were obtained.Patients with uncertain exposure histories and who underwent toxicological analysis were included.Clinical manifestations and categories of toxics were analyzed.RESULTS:Among the 195 patients with positive toxicological analysis results,the main causes of uncertain exposure history was disturbance of consciousness(62.6%),unawareness(23.6%)and unwillingness or lack of cooperation(13.8%).The predominant clinical manifestations were disturbed consciousness(62.6%),followed by vomiting and nausea(14.4%)and liver function abnormalities(8.7%).A comparison of clinical manifestations between patients with positive and negative(n=99)toxicological analyses results revealed significantly different proportions of disturbances in consciousness(63%vs.21%),dizziness(1.5%vs.5.1%),multi-organ failure(1.5%vs.7.1%),and local pain(0 vs 4%).The main categories of substances involved were psychiatric medications(23.1%),sedatives(20.5%),insecticides(13.8%),and herbicides(12.8%).CONCLUSION:The clinical manifestations of acute poisoning in patients with an uncertain exposure history are diverse and nonspecific,and toxicological analysis plays a pivotal role in the diagnosis and differential diagnosis of such patients.展开更多
Locomotion behaviors are susceptible to disruption by a broad spectrum of chemicals and environmental stresses. However, no systematic testing of locomotion behavior defects induced by metal exposure has been conducte...Locomotion behaviors are susceptible to disruption by a broad spectrum of chemicals and environmental stresses. However, no systematic testing of locomotion behavior defects induced by metal exposure has been conducted in the model organism of nematode Caenorhabditis elegans. In this study, the acute toxicity from heavy metal exposure on the locomotion behaviors was analyzed in nematodes. Endpoints of head thrash, body bend, forward turn, backward turn, and Omega/U turn were chosen to evaluate the locomotio...展开更多
Cold exposure is a pervasive stressor in the polar and subpolar regions,exerting both acute and chronic effects on individuals.This environmental factor is known to induce physiological stress,compromise immune respon...Cold exposure is a pervasive stressor in the polar and subpolar regions,exerting both acute and chronic effects on individuals.This environmental factor is known to induce physiological stress,compromise immune response efficacy,and increase susceptibility to various diseases.Chronic cold exposure,characterized by repetitive nonconsecutive exposure to suboptimal temperatures over an extended duration.展开更多
Hepatitis C virus(HCV) infection after biological accident(needlestick injury) is a rare event.This report describes the first case of acute HCV infection after a needlestick injury in a female nursing student at Padu...Hepatitis C virus(HCV) infection after biological accident(needlestick injury) is a rare event.This report describes the first case of acute HCV infection after a needlestick injury in a female nursing student at Padua University Hospital.The student nurse was injured on the second finger of the right hand when recapping a 23-gauge needle after taking a blood sample.The patient who was the source was a 72-year-old female with weakly positive anti-HCV test results.Three months after the injury,at the second step of followup,a relevant increase in transaminases with a low viral replication activity(350 IU/mL) was observed in the student,indicating HCV infection.The patient tested positive for the same genotype(1b) of HCV as the injured student.A rapid decline in transaminases,which was not accompanied by viral clearance,and persistently positive HCV-RNA was described 1 mo later.Six months after testing positive for HCV,the student was treated with pegylated interferon plus ribavirin for 24 wk.A rapid virological response was observed after 4 wk of treatment,and a sustained virological response(SVR) was evident 6 mo after therapy withdrawal,confirming that the patient was definitively cured.Despite the favourable IL28B gene(rs12979860) CC-polymorphism observed in the patient,which is usually predictive of a spontaneous clearance and SVR,spontaneous viral clearance did not take place;however,infection with this genotype was promising for a sustained virological response after therapy.展开更多
Objective To examine if the variations at sea level would be able to predict subsequent susceptibility to acute altitude sickness in subjects upon a rapid ascent to high altitude.Methods One hundred and six Han nation...Objective To examine if the variations at sea level would be able to predict subsequent susceptibility to acute altitude sickness in subjects upon a rapid ascent to high altitude.Methods One hundred and six Han nationality male individuals were recruited to this research.Dynamic electrocardiogram,treadmill exercise test,echocardiography,routine blood examination and biochemical analysis were performed when subjects at sea level and entering the plateau respectively.Then multiple regression analysis was performed to construct a multiple linear regression equation using the Lake Louise Score as dependent variable to predict the risk factors at sea level related to acute mountain sickness(AMS).Results Approximately 49.05%of the individuals developed AMS.The tricuspid annular plane systolic excursion(22.0+2.66 vs.23.2+3.19 mm,t=l.998,P=0.048)was significantly lower in the AMS group at sea level,while count of eosinophil[(0.264+0.393)×109/L vs.(0.126+0.084)×109/L,t=-2.040,P—0.045],percentage of diflerences exceeding 50 ms between adjacent normal number of intervals(PNN50,9.66%±5.40%vs.6.98%±5.66%,t=-2.229,P=0.028)and heart rate variability triangle index(57.1+16.1 vs.50.6+12.7,t=-2.271,P=0.025)were significantly higher.After acute exposure to high altitude,C-reactive protein(0.098+0.103 vs.0.062+0.045 g/L,t=-2.132,P=0.037),aspartate aminotransferase(19.7+6.7275.17,3±3.95 U/L,t=-2.231,P=0.028)and creatinine(85.1±12.9 vs.77.7±11.2 mmol/L,t=3.162,P=0.002)were significantly higher in the AMS group,while alkaline phosphatase(71.7+18.2 vs.80.6+20.2 U/L,t=2.389,P=0.019),standard deviation of normal-to-normal RR intervals(126.5+35.9 vs.143.3+36.4 ms,t—2.320,P—0.022),ejection time(276.9+50.8 vs.313.8+48.9 ms,t—3.641,P—0.001)and heart rate variability triangle index(37.1+12.9 vs.41.9+11.1,t=2.O2O,P=0.047)were significantly lower.Using the Lake Louise Score as the dependent variable,prediction equation were established to estimate AMS:Lake Louise Score=3.783+0.281Xeosinophil-0.219Xalkaline phosphatase+O.O32XPNN50.Conclusions We elucidated the differences of pl^siological variables as well as noninvasive cardiovascular indicators for subjects after high altitude exposure compared with those at sea level.We also created an acute high altitude reaction early warning equation based on the physiological variables and noninvasive cardiovascular indicators at sea level.展开更多
Background: Alterations in hematology, especially erythroid changes, may be involved in acute mountain sickness(AMS) at high altitude. This study aimed to identify the relationship between excessive erythrocytosis and...Background: Alterations in hematology, especially erythroid changes, may be involved in acute mountain sickness(AMS) at high altitude. This study aimed to identify the relationship between excessive erythrocytosis and AMS following different durations of high-altitude exposure.Methods: A total of 692 healthy young Chinese men were recruited for the study in June and July of 2012 and were divided into the following five groups: I) the 24-h group(24 hours after arrival at Lhasa, 3,700 m, n=261); II) the 7-d group(exposed at Lhasa, 3,700 m for seven days, n=99); III) the re-exposure group(re-exposed at Yang Bajing, 4,400 m for seven days after 】1 year of acclimation at 3,700 m, n=94); IV) the acclimated group(】1 year of acclimation at 3,700 m, Lhasa, n=42); and V) the sea-level control(control group, Chengdu, n=196). Case report forms were used to record the subjects’ demographic information and AMS-related symptoms. All of the subjects underwent routine blood tests.Results: The red blood cell(RBC) count fell slightly but was not significant upon acute exposure to high altitude, whereas the hemoglobin concentration([Hb]) increased significantly. After high-altitude re-exposure, both of the [Hb] and RBC count showed significant increases. The incidence of AMS was 65.1%, 26.3% and 51.1%, respectively in the 24-h, 7-d and re-exposure groups. The [Hb](P=0.024) and hematocrit(P=0.017) were greater in the AMS+ individuals than in the AMS– individuals in 7-d group. A correlation analysis revealed that the [Hb] and hematocrit were closely related with AMS score in 7-d and re-exposure groups, while the RBC showed a correlation with AMS score only in the re-exposure group. The AMS incidence was lowest when the [Hb] was between 140 and 160 g/L in the 24-h and 7-d groups.Conclusions: AMS is associated with both [Hb] and excessive erythrocytosis. Additionally, our findings indicate the existence of an optimal [Hb] for preventing AMS.展开更多
The oil spill impact analysis (OSIA) software system has been developed to supply a tool for comprehensive, quantitative environmental impact assessments resulting from oil spills. In the system, a biological componen...The oil spill impact analysis (OSIA) software system has been developed to supply a tool for comprehensive, quantitative environmental impact assessments resulting from oil spills. In the system, a biological component evaluates potential effects on exposed organisms based on results from a physico chemical fates component, including the extent and characteristics of the surface slick, and dissolved and total concentrations of hydrocarbons in the water column. The component includes a particle based exposure model for migratory adult fish populations, a particle based exposure model for spawning planktonic organisms (eggs and larvae), and an exposure model for wildlife species (sea birds or marine mammals). The exposure model for migratory adult fish populations simulates the migration behaviors of fish populations migrating to or staying in their feeding areas, over wintering areas or spawning areas, and determines the acute effects (mortality) and chronic accumulation (body burdens) from the dissolved contaminant. The exposure model for spawning planktonic organisms simulates the release of eggs and larvae, also as particles, from specific spawning areas during the spawning period, and determines their potential exposure to contaminants in the water or sediment. The exposure model for wild species calculates the exposure to surface oil of wildlife (bird and marine mammal) categories inhabiting the contaminated area. Compared with the earlier models in which all kinds of organisms are assumed evenly and randomly distributed, the updated biological exposure models can more realistically estimate potential effects on marine ecological system from oil spill pollution events.展开更多
Introduction: Chronic exposure to organic solvents may result in a variety of neurologic complications like dementia, cerebellar dysfunction, pyramidal syndrome, cranial nerve abnormalities, and neuropathy. Clinical P...Introduction: Chronic exposure to organic solvents may result in a variety of neurologic complications like dementia, cerebellar dysfunction, pyramidal syndrome, cranial nerve abnormalities, and neuropathy. Clinical Presentation: We report an unusual case of subacute chorea induced by occupational exposure. Brain magnetic resonance imaging showed diffuse white matter T2 hyperintensity. The screening of basic blood tests, and CSF studies to eliminate alternate diagnoses, were normal. The patient received 1000 mg/day of intravenous methylprednisolone for 3 days, with cessation of professional activity. We observed a regression of neurological symptoms after 3 months of follow-up. Conclusion: This case highlights the diversity of acute or chronic neurological complications of solvents.展开更多
Acute myocardial infarction is a deadly disease, and in the Indian context, it occurs at a younger age, even below the age of 40 years, and sometimes even below 30 years. These young MI patients have high mortality ra...Acute myocardial infarction is a deadly disease, and in the Indian context, it occurs at a younger age, even below the age of 40 years, and sometimes even below 30 years. These young MI patients have high mortality rates, and many of them are not able to reach the hospital. The pathophysiology of AMI is very well understood. AMI is a multifactorial disease and has several risk factors, like dyslipidemia, diabetes, hypertension, smoking, diet, etc. However, low-density lipoprotein cholesterol (LDL-C) has a very strong causal relationship with atherosclerosis. Reducing LDL-C to <70 results in the arrest of the progression of atherosclerosis, and slashing its level to below 50 produces the regression of atherosclerosis. The cumulative exposure of LDL-C to the arterial wall is a very strong determinant of atherosclerosis and the development of AMI. The coronary heart disease (CHD) threshold target of LDL-C for the development of AMI is roughly 7000 mg/year. If LDL-C is 100 mg/dL from an early age, the CHD threshold target for the development of AMI will reach 70 years of age. However, if LDL-C target is <70 mg/dL from an early age, the patients will reach the CHD threshold of LDL-C at the age of 100 years. Based on the current science, this is an emerging concept to postpone AMI by several years, even up to 100 years. The goal of LDL-C <70 mg/dL can be achieved by available oral or injectable drugs. Gene editing with CRISPR technology is emerging as a very exciting modality for lowering LDL-C to a very low level for the rest of life.展开更多
Brown adipose tissue (BAT) plays an essential role in non-shivering thermogenesis. The phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) is identified as a lipid transporter that reciprocally transfers ph...Brown adipose tissue (BAT) plays an essential role in non-shivering thermogenesis. The phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) is identified as a lipid transporter that reciprocally transfers phospholipids between intracellular membrane structures. However, the physiological significance of PITPNC1 and its regulatory mechanism remain unclear. Here, we demonstrate that PITPNC1 is a key player in thermogenesis of BAT. While Pitpnc1^(−/−) mice do not differ with wildtype mice in body weight and insulin sensitivity on either chow or high-fat diet, they develop hypothermia when subjected to acute cold exposure at 4℃. The Pitpnc1^(−/−) brown adipocytes exhibit defective β-oxidation and abnormal thermogenesis-related metabolism pathways in mitochondria. The deficiency of lipid mobilization in Pitpnc1^(−/−) brown adipocytes might be the result of excessive accumulation of phosphatidylcholine and a reduction of phosphatidic acid. Our findings have uncovered significant roles of PITPNC1 in mitochondrial phospholipid homeostasis and BAT thermogenesis.展开更多
基金supported by National Natural Science Foundation of China(82172184)。
文摘BACKGROUND:In clinical practice,some patients might not be able or unwilling to provide a thorough history of medication and poison exposure.The aim of this study was to use toxicological analysis to examine the clinical characteristics of patients with acute poisoning whose exposure history was uncertain from a toxicological analysis perspective.METHODS:This was a retrospective and descriptive study from an institute of poisoning.Patient registration information and test reports spanning the period from April 1,2020 to March 31,2022,were obtained.Patients with uncertain exposure histories and who underwent toxicological analysis were included.Clinical manifestations and categories of toxics were analyzed.RESULTS:Among the 195 patients with positive toxicological analysis results,the main causes of uncertain exposure history was disturbance of consciousness(62.6%),unawareness(23.6%)and unwillingness or lack of cooperation(13.8%).The predominant clinical manifestations were disturbed consciousness(62.6%),followed by vomiting and nausea(14.4%)and liver function abnormalities(8.7%).A comparison of clinical manifestations between patients with positive and negative(n=99)toxicological analyses results revealed significantly different proportions of disturbances in consciousness(63%vs.21%),dizziness(1.5%vs.5.1%),multi-organ failure(1.5%vs.7.1%),and local pain(0 vs 4%).The main categories of substances involved were psychiatric medications(23.1%),sedatives(20.5%),insecticides(13.8%),and herbicides(12.8%).CONCLUSION:The clinical manifestations of acute poisoning in patients with an uncertain exposure history are diverse and nonspecific,and toxicological analysis plays a pivotal role in the diagnosis and differential diagnosis of such patients.
基金the Southeast Uni-versity Foundation for Excellent Young Scholars (No.4023001013)the NIH,National Center for Foundation from Research Resource,USA
文摘Locomotion behaviors are susceptible to disruption by a broad spectrum of chemicals and environmental stresses. However, no systematic testing of locomotion behavior defects induced by metal exposure has been conducted in the model organism of nematode Caenorhabditis elegans. In this study, the acute toxicity from heavy metal exposure on the locomotion behaviors was analyzed in nematodes. Endpoints of head thrash, body bend, forward turn, backward turn, and Omega/U turn were chosen to evaluate the locomotio...
基金funded by the National Natural Science Foundation of China(Grant No.32172817)the Natural Science Foundation of Heilongjiang Province Grant(Grant No.LH2022C071)the Heilongjiang Bayi Agricultural University for San Heng San Zong(Grant No.ZRCQC202003).
文摘Cold exposure is a pervasive stressor in the polar and subpolar regions,exerting both acute and chronic effects on individuals.This environmental factor is known to induce physiological stress,compromise immune response efficacy,and increase susceptibility to various diseases.Chronic cold exposure,characterized by repetitive nonconsecutive exposure to suboptimal temperatures over an extended duration.
文摘Hepatitis C virus(HCV) infection after biological accident(needlestick injury) is a rare event.This report describes the first case of acute HCV infection after a needlestick injury in a female nursing student at Padua University Hospital.The student nurse was injured on the second finger of the right hand when recapping a 23-gauge needle after taking a blood sample.The patient who was the source was a 72-year-old female with weakly positive anti-HCV test results.Three months after the injury,at the second step of followup,a relevant increase in transaminases with a low viral replication activity(350 IU/mL) was observed in the student,indicating HCV infection.The patient tested positive for the same genotype(1b) of HCV as the injured student.A rapid decline in transaminases,which was not accompanied by viral clearance,and persistently positive HCV-RNA was described 1 mo later.Six months after testing positive for HCV,the student was treated with pegylated interferon plus ribavirin for 24 wk.A rapid virological response was observed after 4 wk of treatment,and a sustained virological response(SVR) was evident 6 mo after therapy withdrawal,confirming that the patient was definitively cured.Despite the favourable IL28B gene(rs12979860) CC-polymorphism observed in the patient,which is usually predictive of a spontaneous clearance and SVR,spontaneous viral clearance did not take place;however,infection with this genotype was promising for a sustained virological response after therapy.
基金National Science and Technology Major Projects for Major New Drugs Innovation and Development(2014ZX09J14102-02A)Special Topic on Military Health Care(17bjz41)National Natural Science Foundation of China(81170249 and 30700305).
文摘Objective To examine if the variations at sea level would be able to predict subsequent susceptibility to acute altitude sickness in subjects upon a rapid ascent to high altitude.Methods One hundred and six Han nationality male individuals were recruited to this research.Dynamic electrocardiogram,treadmill exercise test,echocardiography,routine blood examination and biochemical analysis were performed when subjects at sea level and entering the plateau respectively.Then multiple regression analysis was performed to construct a multiple linear regression equation using the Lake Louise Score as dependent variable to predict the risk factors at sea level related to acute mountain sickness(AMS).Results Approximately 49.05%of the individuals developed AMS.The tricuspid annular plane systolic excursion(22.0+2.66 vs.23.2+3.19 mm,t=l.998,P=0.048)was significantly lower in the AMS group at sea level,while count of eosinophil[(0.264+0.393)×109/L vs.(0.126+0.084)×109/L,t=-2.040,P—0.045],percentage of diflerences exceeding 50 ms between adjacent normal number of intervals(PNN50,9.66%±5.40%vs.6.98%±5.66%,t=-2.229,P=0.028)and heart rate variability triangle index(57.1+16.1 vs.50.6+12.7,t=-2.271,P=0.025)were significantly higher.After acute exposure to high altitude,C-reactive protein(0.098+0.103 vs.0.062+0.045 g/L,t=-2.132,P=0.037),aspartate aminotransferase(19.7+6.7275.17,3±3.95 U/L,t=-2.231,P=0.028)and creatinine(85.1±12.9 vs.77.7±11.2 mmol/L,t=3.162,P=0.002)were significantly higher in the AMS group,while alkaline phosphatase(71.7+18.2 vs.80.6+20.2 U/L,t=2.389,P=0.019),standard deviation of normal-to-normal RR intervals(126.5+35.9 vs.143.3+36.4 ms,t—2.320,P—0.022),ejection time(276.9+50.8 vs.313.8+48.9 ms,t—3.641,P—0.001)and heart rate variability triangle index(37.1+12.9 vs.41.9+11.1,t=2.O2O,P=0.047)were significantly lower.Using the Lake Louise Score as the dependent variable,prediction equation were established to estimate AMS:Lake Louise Score=3.783+0.281Xeosinophil-0.219Xalkaline phosphatase+O.O32XPNN50.Conclusions We elucidated the differences of pl^siological variables as well as noninvasive cardiovascular indicators for subjects after high altitude exposure compared with those at sea level.We also created an acute high altitude reaction early warning equation based on the physiological variables and noninvasive cardiovascular indicators at sea level.
基金supported by grants from the Special Health Research Project,Ministry of Health of China(201002012)
文摘Background: Alterations in hematology, especially erythroid changes, may be involved in acute mountain sickness(AMS) at high altitude. This study aimed to identify the relationship between excessive erythrocytosis and AMS following different durations of high-altitude exposure.Methods: A total of 692 healthy young Chinese men were recruited for the study in June and July of 2012 and were divided into the following five groups: I) the 24-h group(24 hours after arrival at Lhasa, 3,700 m, n=261); II) the 7-d group(exposed at Lhasa, 3,700 m for seven days, n=99); III) the re-exposure group(re-exposed at Yang Bajing, 4,400 m for seven days after 】1 year of acclimation at 3,700 m, n=94); IV) the acclimated group(】1 year of acclimation at 3,700 m, Lhasa, n=42); and V) the sea-level control(control group, Chengdu, n=196). Case report forms were used to record the subjects’ demographic information and AMS-related symptoms. All of the subjects underwent routine blood tests.Results: The red blood cell(RBC) count fell slightly but was not significant upon acute exposure to high altitude, whereas the hemoglobin concentration([Hb]) increased significantly. After high-altitude re-exposure, both of the [Hb] and RBC count showed significant increases. The incidence of AMS was 65.1%, 26.3% and 51.1%, respectively in the 24-h, 7-d and re-exposure groups. The [Hb](P=0.024) and hematocrit(P=0.017) were greater in the AMS+ individuals than in the AMS– individuals in 7-d group. A correlation analysis revealed that the [Hb] and hematocrit were closely related with AMS score in 7-d and re-exposure groups, while the RBC showed a correlation with AMS score only in the re-exposure group. The AMS incidence was lowest when the [Hb] was between 140 and 160 g/L in the 24-h and 7-d groups.Conclusions: AMS is associated with both [Hb] and excessive erythrocytosis. Additionally, our findings indicate the existence of an optimal [Hb] for preventing AMS.
基金theChinaScholarshipCouncil (CSC)andOceanographicScientificFundsforYouthfromtheStateOceanographicAdministration (No .96 80 1)
文摘The oil spill impact analysis (OSIA) software system has been developed to supply a tool for comprehensive, quantitative environmental impact assessments resulting from oil spills. In the system, a biological component evaluates potential effects on exposed organisms based on results from a physico chemical fates component, including the extent and characteristics of the surface slick, and dissolved and total concentrations of hydrocarbons in the water column. The component includes a particle based exposure model for migratory adult fish populations, a particle based exposure model for spawning planktonic organisms (eggs and larvae), and an exposure model for wildlife species (sea birds or marine mammals). The exposure model for migratory adult fish populations simulates the migration behaviors of fish populations migrating to or staying in their feeding areas, over wintering areas or spawning areas, and determines the acute effects (mortality) and chronic accumulation (body burdens) from the dissolved contaminant. The exposure model for spawning planktonic organisms simulates the release of eggs and larvae, also as particles, from specific spawning areas during the spawning period, and determines their potential exposure to contaminants in the water or sediment. The exposure model for wild species calculates the exposure to surface oil of wildlife (bird and marine mammal) categories inhabiting the contaminated area. Compared with the earlier models in which all kinds of organisms are assumed evenly and randomly distributed, the updated biological exposure models can more realistically estimate potential effects on marine ecological system from oil spill pollution events.
文摘Introduction: Chronic exposure to organic solvents may result in a variety of neurologic complications like dementia, cerebellar dysfunction, pyramidal syndrome, cranial nerve abnormalities, and neuropathy. Clinical Presentation: We report an unusual case of subacute chorea induced by occupational exposure. Brain magnetic resonance imaging showed diffuse white matter T2 hyperintensity. The screening of basic blood tests, and CSF studies to eliminate alternate diagnoses, were normal. The patient received 1000 mg/day of intravenous methylprednisolone for 3 days, with cessation of professional activity. We observed a regression of neurological symptoms after 3 months of follow-up. Conclusion: This case highlights the diversity of acute or chronic neurological complications of solvents.
文摘Acute myocardial infarction is a deadly disease, and in the Indian context, it occurs at a younger age, even below the age of 40 years, and sometimes even below 30 years. These young MI patients have high mortality rates, and many of them are not able to reach the hospital. The pathophysiology of AMI is very well understood. AMI is a multifactorial disease and has several risk factors, like dyslipidemia, diabetes, hypertension, smoking, diet, etc. However, low-density lipoprotein cholesterol (LDL-C) has a very strong causal relationship with atherosclerosis. Reducing LDL-C to <70 results in the arrest of the progression of atherosclerosis, and slashing its level to below 50 produces the regression of atherosclerosis. The cumulative exposure of LDL-C to the arterial wall is a very strong determinant of atherosclerosis and the development of AMI. The coronary heart disease (CHD) threshold target of LDL-C for the development of AMI is roughly 7000 mg/year. If LDL-C is 100 mg/dL from an early age, the CHD threshold target for the development of AMI will reach 70 years of age. However, if LDL-C target is <70 mg/dL from an early age, the patients will reach the CHD threshold of LDL-C at the age of 100 years. Based on the current science, this is an emerging concept to postpone AMI by several years, even up to 100 years. The goal of LDL-C <70 mg/dL can be achieved by available oral or injectable drugs. Gene editing with CRISPR technology is emerging as a very exciting modality for lowering LDL-C to a very low level for the rest of life.
基金the National Key R&D Program of China(2018YFA0506900)the National Key R&D Program of China(2018YFA0800301)+3 种基金the National Natural Science Foundation of China(91857103)Shanghai Basic Research Field Project“Science and Technology Innovation Action Plan”(21JC1400400)the Lingang Laboratory(LG-QS-202204-06)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)。
文摘Brown adipose tissue (BAT) plays an essential role in non-shivering thermogenesis. The phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) is identified as a lipid transporter that reciprocally transfers phospholipids between intracellular membrane structures. However, the physiological significance of PITPNC1 and its regulatory mechanism remain unclear. Here, we demonstrate that PITPNC1 is a key player in thermogenesis of BAT. While Pitpnc1^(−/−) mice do not differ with wildtype mice in body weight and insulin sensitivity on either chow or high-fat diet, they develop hypothermia when subjected to acute cold exposure at 4℃. The Pitpnc1^(−/−) brown adipocytes exhibit defective β-oxidation and abnormal thermogenesis-related metabolism pathways in mitochondria. The deficiency of lipid mobilization in Pitpnc1^(−/−) brown adipocytes might be the result of excessive accumulation of phosphatidylcholine and a reduction of phosphatidic acid. Our findings have uncovered significant roles of PITPNC1 in mitochondrial phospholipid homeostasis and BAT thermogenesis.