Acute pancreatitis(AP)is a common clinical condition with an incidence of about 300 or more patients per million annually.About 10%-15%of patients will develop severe acute pancreatitis(SAP)and of those, 10%-30%may di...Acute pancreatitis(AP)is a common clinical condition with an incidence of about 300 or more patients per million annually.About 10%-15%of patients will develop severe acute pancreatitis(SAP)and of those, 10%-30%may die due to SAP-associated complications.Despite the improvements done in the diagnosis and management of AP,the mortality rate has not significantly declined during the last decades.Toll-like receptors(TLRs)are pattern-recognition receptors that seem to play a major role in the development of numerous diseases,which make these molecules attractive as potential therapeutic targets.TLRs are involved in the development of the systemic inflammatory response syndrome,a potentially lethal complication in SAP.In the present review,we explore the current knowledge about the role of different TLRs that have been described associated with AP.The main candidate for targeting seems to be TLR4,which recognizes numerous damage-associated molecular patterns related to AP.TLR2 has also been linked with AP,but there are only limited studies that exclusively studied its role in AP.There is also data suggesting that TLR9 may play a role in AP.展开更多
Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammat...Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammatory process.NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling.However,NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction.Additionally,it plays a complex role in various physiological processes and mediates several diseases.Sivelestat,a specific NE inhibitor,has strong potential for clinical application,particularly in the treatment of coronavirus disease 2019(COVID-19).This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.展开更多
目的测定美罗培南在脓毒症和脓毒症休克患者中不同时间的血药浓度,求出不同最小抑菌浓度(minimal inhibitory comentration,MIC)值时%T>4MIC的值及达标概率(probability of target attainments,PTAs),探讨脓毒症及脓毒症休克患者病...目的测定美罗培南在脓毒症和脓毒症休克患者中不同时间的血药浓度,求出不同最小抑菌浓度(minimal inhibitory comentration,MIC)值时%T>4MIC的值及达标概率(probability of target attainments,PTAs),探讨脓毒症及脓毒症休克患者病理生理学的变化对美罗培南药代动力学(pharmacokinetics,PK)的影响。方法选自2012年9月至2013年3月呼吸重症监护病房(respiratory intensive care unit,RICU)中10例脓毒症和脓毒症休克患者,按美罗培南1.0g/2h延长输注法的点滴模型给药。采用高效液相色谱法(high performance liquid chromatography,HPLC)测定美罗培南给药前和给药后0.25、0.5、1、2、4、6、8h的血药浓度。按人口学资料中APACHEⅡ评分将10例患者分成轻度和重度脓毒症两组,将测得的时间-血药浓度数据输入药代动力学(PK)软件Winnonlin5.2求出各例患者的药代动力学参数。使用CrystalBall软件按PK/PD(药效学)模型进行蒙特卡罗模拟(monte carlo simulation,MCS)计算出美罗培南%T>4MIC的值及达标概率(PTAs)。结果当MIC分别为0.5、1、2、4、8μg/ml时,10例患者的平均%T>4MIC(%)值分别为124.04±39.02、99.83±32.01、73.26±24.67、46.97±16.87、14.85±8.31。轻度脓毒症组分别为172.19±11.51、138.88±8.79、105.57±7.41、71.70±5.59、36.93±4.37;重度脓毒症组分别为81.77±13.20、63.31±10.34、45.37±7.07、26.70±4.33、6.82±1.75。不同MIC值时总体组的达标概率分别为100%、99.7%、96.0%、62.5%、0.93%。轻度组达标概率分别为100%、100%、100%、100%、24.5%;重度组分别为100%、99.8%、75.7%、0.9%、0.0%。结论脓毒症和脓毒症休克患者病理生理的变化改变了抗生素的药代动力学和药效学,轻度组和重度组的药代动力学有明显差异,当MIC=4.0μg/ml时,重度组%T>4MIC的值仅为26.70±4.33,需要加大药物剂量或/和增加药物给药次数。当MIC=8.0μg/ml时无论轻、重组均不达标,需加大药物剂量或/和增加药物给药次数。展开更多
Objective： This review examines the evidence that： Diabetes is a state of DNA damage; pathophysiological factors in diabetes can cause DNA damage： DNA damage can cause mutations： and DNA mutation is linked to carc...Objective： This review examines the evidence that： Diabetes is a state of DNA damage; pathophysiological factors in diabetes can cause DNA damage： DNA damage can cause mutations： and DNA mutation is linked to carcinogenesis. Data Sources： We retrieved information from the PubMed database up to January, 2014, using various search terms and their combinations including DNA damage, diabetes, cancer, high glucose, hyperglycemia, free fatty acids, palmitic acid, advanced glycation end products, mutation and carcinogenesis. Study Selection： We included data from peer-reviewed journals and a textbook printed in English on relationships between DNA damage and diabetes as well as pathophysiological factors in diabetes. Publications on relationships among DNA damage, mutagenesis, and carcinogenesis, were also reviewed. We organized this information into a conceptual framework to explain the possible causal relationship between DNA damage and carcinogenesis in diabetes. Results： There are a large amount of data supporting the view that DNA mutation is a typical feature in carcinogenesis. Patients with type 2 diabetes have increased production of reactive oxygen species, reduced levels of antioxidant capacity, and increased levels of DNA damage. The pathophysiological factors and metabolic milieu in diabetes can cause DNA damage such as DNA strand break and base modification （i.e., oxidation）. Emerging experimental data suggest that signal pathways （i.e., Akt/tuberin） link diabetes to DNA damage. This collective evidence indicates that diabetes is a pathophysiological state of oxidative stress and DNA damage which can lead to various types of mutation to cause aberration in cells and thereby increased cancer risk. Conclusions： This review highlights the interrelationships amongst diabetes, DNA damage, DNA mutation and carcinogenesis, which suggests that DNA damage can be a biological link between diabetes and cancer.展开更多
Liver fibrosis is a complex pathological process controlled by a variety of cells,mediators and signaling pathways.Hepatic stellate cells play a central role in the development of liver fibrosis.In chronic liver disea...Liver fibrosis is a complex pathological process controlled by a variety of cells,mediators and signaling pathways.Hepatic stellate cells play a central role in the development of liver fibrosis.In chronic liver disease,hepatic stellate cells undergo dramatic phenotypic activation and acquire fibrogenic properties.This review focuses on the pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis.They enter the cell cycle under the influence of various triggers.The“Initiation”phase of hepatic stellate cells activation overlaps and continues with the“Perpetuation”phase,which is characterized by a pronounced inflammatory and fibrogenic reaction.This is followed by a resolution phase if the injury subsides.Knowledge of these pathophysiological mechanisms paved the way for drugs aimed at preventing the development and progression of liver fibrosis.In this respect,impairments in intracellular signaling,epigenetic changes and cellular stress response can be the targets of therapy where the goal is to deactivate hepatic stellate cells.Potential antifibrotic therapy may focus on inducing hepatic stellate cells to return to an inactive state through cellular aging,apoptosis,and/or clearance by immune cells,and serve as potential antifibrotic therapy.It is especially important to prevent the formation of liver cirrhosis since the only radical approach to its treatment is liver transplantation which can be performed in only a limited number of countries.展开更多
Patients with autism spectrum disorders(ASD) present deficits in social interactions and communication, they also show limited and stereotypical patterns of behaviors and interests. The pathophysiological bases of ASD...Patients with autism spectrum disorders(ASD) present deficits in social interactions and communication, they also show limited and stereotypical patterns of behaviors and interests. The pathophysiological bases of ASD have not been defined yet. Many factors seem to be involved in the onset of this disorder. These include genetic and environmental factors, but autism is not linked to a single origin, only. Autism onset can be connected with various factors such as metabolic disorders: including carnitine deficiency. Carnitine is a derivative of two amino acid lysine and methionine. Carnitine is a cofactor for a large family of enzymes: the carnitine acyltransferases. Through their action these enzymes(and L-carnitine) are involved in energy production and metabolic homeostasis. Some people with autism(less than 20%) seem to have L-carnitine metabolism disorders and for these patients, a dietary supplementation with Lcarnitine is beneficial. This review summarizes the available information on this topic.展开更多
Pancreatic ductal adenocarcinoma(PDA)is a devastating disease with pronounced morbidity and a high mortality rate.Currently available treatments lack convincing cost-efficiency determinations and are in most cases not...Pancreatic ductal adenocarcinoma(PDA)is a devastating disease with pronounced morbidity and a high mortality rate.Currently available treatments lack convincing cost-efficiency determinations and are in most cases not associated with relevant success rate.Experimental stimulation of the immune system in murine PDA models has revealed some promising results.Tolllike receptors(TLRs)are pillars of the immune system that have been linked to several forms of malignancy,including lung,breast and colon cancer.In humans,TLRs are expressed in the pancreatic cancer tissue and in several cancer cell lines,whereas they are not expressed in the normal pancreas.In the present review,we explore the current knowledge concerning the role of different TLRs associated to PDA.Even if almost all known TLRs are expressed in the pancreatic cancer microenvironment,there are only five TLRs suggested as possible therapeutic targets.Most data points at TLR2 and TLR9 as effective tumor markers and agonists could potentially be used as e.g.future adjuvant therapies.The elucidation of the role of TLR3 in PDA is only in its initial phase.The inhibition/blockage of TLR4-related pathways has shown some promising effects,but there are still many steps left before TLR4 inhibitors can be considered as possible therapeutic agents.Finally,TLR7 antagonists seem to be potential candidates for therapy.Independent of their potential in immunotherapies,all existing data indicate that TLRs are strongly involved in the pathophysiology and development of PDA.展开更多
Gastroesophageal reflux disease(GERD)poses a substantial global health challenge,with prevalence rates exhibiting geographical variation.Despite its widespread recognition,the exact prevalence and associated risk fact...Gastroesophageal reflux disease(GERD)poses a substantial global health challenge,with prevalence rates exhibiting geographical variation.Despite its widespread recognition,the exact prevalence and associated risk factors remain elusive.This article comprehensively analyzed the global burden of GERD,shedding light on its risk factors,underlying pathophysiological mechanisms,current diagnostic modalities,evolving management strategies tailored to diverse patient profiles,and complex determinants contributing to treatment failures.A deeper comprehension of GERD is achieved by dissecting these intricate facets,paving the way for enhanced clinical management and improved patient outcomes.展开更多
The incidence of diabetes mellitus(DM) is increasing rapidly. DM is the leading cause of cardiovascular diseases, which can lead to varied cardiovascular complications by aggravated atherosclerosis in large arteries a...The incidence of diabetes mellitus(DM) is increasing rapidly. DM is the leading cause of cardiovascular diseases, which can lead to varied cardiovascular complications by aggravated atherosclerosis in large arteries and coronary atherosclerosis, thereby grows the risk for macro and microangiopathy such as myocardial infarction, stroke, limb loss and retinopathy. Moreover diabetes is one of the strongest and independent risk factor for cardiovascular morbidity and mortality, which associated frequently rhythm disorders such as atrial fibrillation(AF) and ventricular arrhythmias(VA). The present article provides a concise overview of the association between DM and rhythm disorders such as AF and VA with underlying pathophysiological mechanisms.展开更多
The introduction of laparoscopy in the surgeon’s armamentarium was in fact a “revolution in the history of surgery”. Since this technique involves insufflation of carbon dioxide it ...The introduction of laparoscopy in the surgeon’s armamentarium was in fact a “revolution in the history of surgery”. Since this technique involves insufflation of carbon dioxide it produces several pathophysiological changes which have to be understood by the anaesthesiologist who can modify the anaesthesia technique accordingly. Advantages of laparoscopy include reduced pain, small scars and early return to work. Certain complications specific to laparoscopic surgery are due to carboperitoneum and increased intra-abdominal pressure. Venous air embolism, although very rare, can be lethal if not managed promptly. Other complications include subcutaneous emphysema, haemodynamic compromise and arrhythmias. Although associated with minimal postoperative morbidity, postoperative pain, nausea and vomiting can be quite problematic. The limitations of laparoscopy have been overcome by the introduction of robotic surgery. There are important implications for the anaesthesiologist during robotic surgeries which have to be practiced accordingly. Robotic surgery has a learning curve for both the surgeon and the anaesthesiologist. The robot is bulky, and cannot be disengaged after docking. Therefore it is important that the anaesthetized patient remains immobile throughout surgery and anaesthesia is reversed only after the robot has been disengaged at the end of surgery. Advances in laparoscopy and robotic surgery have modified anaesthetic techniques too.展开更多
Paroxysmal kinesigenic dyskinesia(PKD),the most common type of paroxysmal movement disorder,is characterized by sudden and brief attacks of choreoathetosis or dystonia triggered by sudden voluntary movements.PKD is ma...Paroxysmal kinesigenic dyskinesia(PKD),the most common type of paroxysmal movement disorder,is characterized by sudden and brief attacks of choreoathetosis or dystonia triggered by sudden voluntary movements.PKD is mainly caused by mutations in the PRRT2 or TMEM151A gene.The exact pathophysiological mechanisms of PKD remain unclear,although the function of PRRT2 protein has been well characterized in the last decade.Based on abnormal ion channels and disturbed synaptic transmission in the absence of PRRT2,PKD may be channelopathy or synaptopathy,or both.In addition,the cerebellum is regarded as the key pathogenic area.Spreading depolarization in the cerebellum is tightly associated with dyskinetic episodes.Whereas,in PKD,other than the cerebellum,the role of the cerebrum including the cortex and thalamus needs to be further investigated.展开更多
BACKGROUND:Rhabdomyolysis may cause severe damage to the human body because of acute renal failure,fatal heart rhythm disturbances,hypovolemic shock,disturbances of electrolyte balance,metabolic acidosis,hyperthermia,...BACKGROUND:Rhabdomyolysis may cause severe damage to the human body because of acute renal failure,fatal heart rhythm disturbances,hypovolemic shock,disturbances of electrolyte balance,metabolic acidosis,hyperthermia,disseminated intravascular coagulation,etc.Drugs and toxins are the most common factors for the disease.This article aimed to review the prognosis of rhabdomyolysis.DATA SOURCES:Based on the reported studies of cell and molecular biology,we reviewed the clinical presentations,laboratory findings,and mechanisms of rhabdomyolysis in the Pubmed.RESULTS:The clinical symptoms of rhabdomyolysis were dependent on the severity of the condition and whether kidney failure develops.Since the necrosis and dissolution of muscle cells,entocytes such as myoglobin,creatine phosphokinase(CPK),electrolytes,proteins and non-protein substances were released into the plasma,the detection of the entocytes may contribute to the early diagnosis of rhabdomyolysis.CONCLUSION:Despite the etiology of the disease is multifactorial,the potential causes of rhabdomyolysis share the same pathophysiological pathway involving an increase in intracellular calcium.展开更多
Sensitive skin is a clinical syndrome characterized by a hyper-reactive state of the skin,primarily on the face.It is accompanied by subjective symptoms such as burning,stinging,itching,and tightness when exposed to p...Sensitive skin is a clinical syndrome characterized by a hyper-reactive state of the skin,primarily on the face.It is accompanied by subjective symptoms such as burning,stinging,itching,and tightness when exposed to physical,chemical,or psychological stimuli.Objective signs,such as erythema,scales,and dilated blood vessels,may or may not be present.The discomfort associated with sensitive skin can be triggered by various endogenous and exogenous factors,which usually have no significant effect on the individual and do not induce irritant reactions.Sensitive skin often presents as a subjective state without clinical signs and exhibits diversity,posing challenges in sensitive skin research and care.This review summarizes the prevalence,key factors,pathophysiological mechanisms,diagnosis,and progress in daily care for sensitive skin.The aim is to provide a clearer and more systematic understanding of sensitive skin and offer guidance for sensitive skin care.展开更多
Recently,the substance P(SP)/neurokinin-1 receptor(NK-1R)system has been found to be involved in various human pathophysiological disorders including the symptoms of coronavirus disease 2019(COVID-19).Besides,studies ...Recently,the substance P(SP)/neurokinin-1 receptor(NK-1R)system has been found to be involved in various human pathophysiological disorders including the symptoms of coronavirus disease 2019(COVID-19).Besides,studies in the oncological field have demonstrated an intricate correlation between the upregulation of NK-1R and the activation of SP/NK-1R system with the progression of multiple carcinoma types and poor clinical prognosis.These findings indicate that the modulation of SP/NK-1R system with NK-1R antagonists can be a potential broad-spectrum antitumor strategy.This review updates the latest potential and applications of NK-1R antagonists in the treatment of human diseases and cancers,as well as the underlying mechanisms.Furthermore,the strategies to improve the bioavailability and efficacy of NK-1R antagonist drugs are summarized,such as solid dispersion systems,nanonization,and nanoencapsulation.As a radiopharmaceutical therapeutic,the NK-1R antagonist aprepitant was originally developed as radioligand receptor to target NK-1R-overexpressing tumors.However,combining NK-1R antagonists with other drugs can produce a synergistic effect,thereby enhancing the therapeutic effect,alleviating the symptoms,and improving patients’quality of life in several diseases and cancers.展开更多
The pathophysiological characteristics of Phlegm-stasis Cementation Syndrome in Coronary Heart Disease(CHD) has been summarized in this article. According to epidemiological investigations, phlegm-stasis cementation s...The pathophysiological characteristics of Phlegm-stasis Cementation Syndrome in Coronary Heart Disease(CHD) has been summarized in this article. According to epidemiological investigations, phlegm-stasis cementation syndrome has become a dominant syndrome in CHD along with the improvement in living and dietary condition. The interaction between blood stasis and phlegm turbidity that is called Phlegmstasis Cementation Syndrome exists in CHD and other diseases. The bridge linked blood stasis and phlegm turbidity lies in the adversely effects of lipid metabolism disorder on platelet activation, vascular function and hemorheology indexes. Lipid metabolism disorder also can induce persistent inflammation including monocyte/macrophage activation and oxidative stress. Inflammation also is an important stimulating factor for atherosclerosis and the biology that underlies the complications of CHD,which belonged to the concept of "toxin" in Traditional Chinese medicines(TCM). On the other hand, the important function of inflammatory process on abnormal hemorheology,platelet activation and vascular dysfunction can be used to elucidate the basic pathogenetic condition of the toxin inducing blood stasis in TCM. Therefore, it is this pathological process that can be used to address the basic pathogenetic theory of phlegm turbidity inducing the symptom of toxin and blood stasis, and subsequently phlegm-stasis cementation in TCM. We deduced that lipid metabolic disturbance,inflammation activation, vascular dyfunction and hemorheological disorders could be as pathophysiological characteristics of Phlegm-stasis cementation syndrome.展开更多
Tako-tsubo cardiomyopathy（TC） is a recently described acute cardiac syndrome, which the latest cardiomyopathy classification of the European Society of Cardiology describes as an unclassified cardiomyopathy. TC mimi...Tako-tsubo cardiomyopathy（TC） is a recently described acute cardiac syndrome, which the latest cardiomyopathy classification of the European Society of Cardiology describes as an unclassified cardiomyopathy. TC mimics acute myocardial infarction（AMI） and is characterised by ischaemic chest symptoms, an elevated electrocardiogram ST-segment, and moderately increased levels of cardiac disease markers. However, patients with TC have no coronary angiogram-detectable or non-obstructive coronary arterial disease（CAD）, and left ventriculography documents transient left apical and middle ventricular wall dysfunction. In this review, we describe TC and evaluate epidemiological, clinical and instrumental features, pathophysiological mechanisms, therapy and prognosis of this syndrome,with a view to raising awareness of the disease.展开更多
The liver is a primary site for xenobiotics detoxification, and its metabolism is readily altered by toxicity. The kidney is a common target for toxic xenobiotics due to its capacity to extract and concentrate toxic s...The liver is a primary site for xenobiotics detoxification, and its metabolism is readily altered by toxicity. The kidney is a common target for toxic xenobiotics due to its capacity to extract and concentrate toxic substances by highly specialized cells. So, they are the target organs of sodium fluoride toxicity. The aim of this review is to highlight on hepatorenal oxidative stress and pathophysiological changes induced by treatment of experimental animals with sodium fluoride. Our review shows fluoride toxicosis caused an elevation in the serum activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, acid phosphatase, and the level of total bilirubin, and reduction in the serum levels of total protein, albumin, and globulins, and serious histopathological changes in the hepaic tissues. Also, NaF administration caused increases in serum urea, creatinine, uric acid, sodium ions, and chloride ions levels and serious histopathological changes in the kidney tissues. Treatment of experimental animals with NaF induced oxidative stress in hepatic and renal tissues. It can be concluded that administration of sodium fluoride to experimental animals induced oxidative stress, serious hepatorenal histopathological changes, and disturbance in liver and kidney functions. So, human should be advised to decrease exposure to sodium fluoride to decrease the harmful effects of NaF on liver and kidney.展开更多
文摘Acute pancreatitis(AP)is a common clinical condition with an incidence of about 300 or more patients per million annually.About 10%-15%of patients will develop severe acute pancreatitis(SAP)and of those, 10%-30%may die due to SAP-associated complications.Despite the improvements done in the diagnosis and management of AP,the mortality rate has not significantly declined during the last decades.Toll-like receptors(TLRs)are pattern-recognition receptors that seem to play a major role in the development of numerous diseases,which make these molecules attractive as potential therapeutic targets.TLRs are involved in the development of the systemic inflammatory response syndrome,a potentially lethal complication in SAP.In the present review,we explore the current knowledge about the role of different TLRs that have been described associated with AP.The main candidate for targeting seems to be TLR4,which recognizes numerous damage-associated molecular patterns related to AP.TLR2 has also been linked with AP,but there are only limited studies that exclusively studied its role in AP.There is also data suggesting that TLR9 may play a role in AP.
基金This work has been supported by the Liaoning Province Natural Science Foundation(Grant Nos.:2020-ZLLH-47,2020-MS-065,2021-YGJC-02,and 2017225054).Figures in the paper were drawn using Figdraw,and we sincerely thank the free drawing support provided by the Figdraw platform(www.fgdraw.com).We also would like to thank Editage(www.editage.cn)for English language editing.
文摘Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammatory process.NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling.However,NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction.Additionally,it plays a complex role in various physiological processes and mediates several diseases.Sivelestat,a specific NE inhibitor,has strong potential for clinical application,particularly in the treatment of coronavirus disease 2019(COVID-19).This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.
文摘目的测定美罗培南在脓毒症和脓毒症休克患者中不同时间的血药浓度,求出不同最小抑菌浓度(minimal inhibitory comentration,MIC)值时%T>4MIC的值及达标概率(probability of target attainments,PTAs),探讨脓毒症及脓毒症休克患者病理生理学的变化对美罗培南药代动力学(pharmacokinetics,PK)的影响。方法选自2012年9月至2013年3月呼吸重症监护病房(respiratory intensive care unit,RICU)中10例脓毒症和脓毒症休克患者,按美罗培南1.0g/2h延长输注法的点滴模型给药。采用高效液相色谱法(high performance liquid chromatography,HPLC)测定美罗培南给药前和给药后0.25、0.5、1、2、4、6、8h的血药浓度。按人口学资料中APACHEⅡ评分将10例患者分成轻度和重度脓毒症两组,将测得的时间-血药浓度数据输入药代动力学(PK)软件Winnonlin5.2求出各例患者的药代动力学参数。使用CrystalBall软件按PK/PD(药效学)模型进行蒙特卡罗模拟(monte carlo simulation,MCS)计算出美罗培南%T>4MIC的值及达标概率(PTAs)。结果当MIC分别为0.5、1、2、4、8μg/ml时,10例患者的平均%T>4MIC(%)值分别为124.04±39.02、99.83±32.01、73.26±24.67、46.97±16.87、14.85±8.31。轻度脓毒症组分别为172.19±11.51、138.88±8.79、105.57±7.41、71.70±5.59、36.93±4.37;重度脓毒症组分别为81.77±13.20、63.31±10.34、45.37±7.07、26.70±4.33、6.82±1.75。不同MIC值时总体组的达标概率分别为100%、99.7%、96.0%、62.5%、0.93%。轻度组达标概率分别为100%、100%、100%、100%、24.5%;重度组分别为100%、99.8%、75.7%、0.9%、0.0%。结论脓毒症和脓毒症休克患者病理生理的变化改变了抗生素的药代动力学和药效学,轻度组和重度组的药代动力学有明显差异,当MIC=4.0μg/ml时,重度组%T>4MIC的值仅为26.70±4.33,需要加大药物剂量或/和增加药物给药次数。当MIC=8.0μg/ml时无论轻、重组均不达标,需加大药物剂量或/和增加药物给药次数。
文摘Objective： This review examines the evidence that： Diabetes is a state of DNA damage; pathophysiological factors in diabetes can cause DNA damage： DNA damage can cause mutations： and DNA mutation is linked to carcinogenesis. Data Sources： We retrieved information from the PubMed database up to January, 2014, using various search terms and their combinations including DNA damage, diabetes, cancer, high glucose, hyperglycemia, free fatty acids, palmitic acid, advanced glycation end products, mutation and carcinogenesis. Study Selection： We included data from peer-reviewed journals and a textbook printed in English on relationships between DNA damage and diabetes as well as pathophysiological factors in diabetes. Publications on relationships among DNA damage, mutagenesis, and carcinogenesis, were also reviewed. We organized this information into a conceptual framework to explain the possible causal relationship between DNA damage and carcinogenesis in diabetes. Results： There are a large amount of data supporting the view that DNA mutation is a typical feature in carcinogenesis. Patients with type 2 diabetes have increased production of reactive oxygen species, reduced levels of antioxidant capacity, and increased levels of DNA damage. The pathophysiological factors and metabolic milieu in diabetes can cause DNA damage such as DNA strand break and base modification （i.e., oxidation）. Emerging experimental data suggest that signal pathways （i.e., Akt/tuberin） link diabetes to DNA damage. This collective evidence indicates that diabetes is a pathophysiological state of oxidative stress and DNA damage which can lead to various types of mutation to cause aberration in cells and thereby increased cancer risk. Conclusions： This review highlights the interrelationships amongst diabetes, DNA damage, DNA mutation and carcinogenesis, which suggests that DNA damage can be a biological link between diabetes and cancer.
文摘Liver fibrosis is a complex pathological process controlled by a variety of cells,mediators and signaling pathways.Hepatic stellate cells play a central role in the development of liver fibrosis.In chronic liver disease,hepatic stellate cells undergo dramatic phenotypic activation and acquire fibrogenic properties.This review focuses on the pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis.They enter the cell cycle under the influence of various triggers.The“Initiation”phase of hepatic stellate cells activation overlaps and continues with the“Perpetuation”phase,which is characterized by a pronounced inflammatory and fibrogenic reaction.This is followed by a resolution phase if the injury subsides.Knowledge of these pathophysiological mechanisms paved the way for drugs aimed at preventing the development and progression of liver fibrosis.In this respect,impairments in intracellular signaling,epigenetic changes and cellular stress response can be the targets of therapy where the goal is to deactivate hepatic stellate cells.Potential antifibrotic therapy may focus on inducing hepatic stellate cells to return to an inactive state through cellular aging,apoptosis,and/or clearance by immune cells,and serve as potential antifibrotic therapy.It is especially important to prevent the formation of liver cirrhosis since the only radical approach to its treatment is liver transplantation which can be performed in only a limited number of countries.
文摘Patients with autism spectrum disorders(ASD) present deficits in social interactions and communication, they also show limited and stereotypical patterns of behaviors and interests. The pathophysiological bases of ASD have not been defined yet. Many factors seem to be involved in the onset of this disorder. These include genetic and environmental factors, but autism is not linked to a single origin, only. Autism onset can be connected with various factors such as metabolic disorders: including carnitine deficiency. Carnitine is a derivative of two amino acid lysine and methionine. Carnitine is a cofactor for a large family of enzymes: the carnitine acyltransferases. Through their action these enzymes(and L-carnitine) are involved in energy production and metabolic homeostasis. Some people with autism(less than 20%) seem to have L-carnitine metabolism disorders and for these patients, a dietary supplementation with Lcarnitine is beneficial. This review summarizes the available information on this topic.
文摘Pancreatic ductal adenocarcinoma(PDA)is a devastating disease with pronounced morbidity and a high mortality rate.Currently available treatments lack convincing cost-efficiency determinations and are in most cases not associated with relevant success rate.Experimental stimulation of the immune system in murine PDA models has revealed some promising results.Tolllike receptors(TLRs)are pillars of the immune system that have been linked to several forms of malignancy,including lung,breast and colon cancer.In humans,TLRs are expressed in the pancreatic cancer tissue and in several cancer cell lines,whereas they are not expressed in the normal pancreas.In the present review,we explore the current knowledge concerning the role of different TLRs associated to PDA.Even if almost all known TLRs are expressed in the pancreatic cancer microenvironment,there are only five TLRs suggested as possible therapeutic targets.Most data points at TLR2 and TLR9 as effective tumor markers and agonists could potentially be used as e.g.future adjuvant therapies.The elucidation of the role of TLR3 in PDA is only in its initial phase.The inhibition/blockage of TLR4-related pathways has shown some promising effects,but there are still many steps left before TLR4 inhibitors can be considered as possible therapeutic agents.Finally,TLR7 antagonists seem to be potential candidates for therapy.Independent of their potential in immunotherapies,all existing data indicate that TLRs are strongly involved in the pathophysiology and development of PDA.
文摘Gastroesophageal reflux disease(GERD)poses a substantial global health challenge,with prevalence rates exhibiting geographical variation.Despite its widespread recognition,the exact prevalence and associated risk factors remain elusive.This article comprehensively analyzed the global burden of GERD,shedding light on its risk factors,underlying pathophysiological mechanisms,current diagnostic modalities,evolving management strategies tailored to diverse patient profiles,and complex determinants contributing to treatment failures.A deeper comprehension of GERD is achieved by dissecting these intricate facets,paving the way for enhanced clinical management and improved patient outcomes.
文摘The incidence of diabetes mellitus(DM) is increasing rapidly. DM is the leading cause of cardiovascular diseases, which can lead to varied cardiovascular complications by aggravated atherosclerosis in large arteries and coronary atherosclerosis, thereby grows the risk for macro and microangiopathy such as myocardial infarction, stroke, limb loss and retinopathy. Moreover diabetes is one of the strongest and independent risk factor for cardiovascular morbidity and mortality, which associated frequently rhythm disorders such as atrial fibrillation(AF) and ventricular arrhythmias(VA). The present article provides a concise overview of the association between DM and rhythm disorders such as AF and VA with underlying pathophysiological mechanisms.
文摘The introduction of laparoscopy in the surgeon’s armamentarium was in fact a “revolution in the history of surgery”. Since this technique involves insufflation of carbon dioxide it produces several pathophysiological changes which have to be understood by the anaesthesiologist who can modify the anaesthesia technique accordingly. Advantages of laparoscopy include reduced pain, small scars and early return to work. Certain complications specific to laparoscopic surgery are due to carboperitoneum and increased intra-abdominal pressure. Venous air embolism, although very rare, can be lethal if not managed promptly. Other complications include subcutaneous emphysema, haemodynamic compromise and arrhythmias. Although associated with minimal postoperative morbidity, postoperative pain, nausea and vomiting can be quite problematic. The limitations of laparoscopy have been overcome by the introduction of robotic surgery. There are important implications for the anaesthesiologist during robotic surgeries which have to be practiced accordingly. Robotic surgery has a learning curve for both the surgeon and the anaesthesiologist. The robot is bulky, and cannot be disengaged after docking. Therefore it is important that the anaesthetized patient remains immobile throughout surgery and anaesthesia is reversed only after the robot has been disengaged at the end of surgery. Advances in laparoscopy and robotic surgery have modified anaesthetic techniques too.
基金supported by grants from the National Natural Science Foundation(81330025).
文摘Paroxysmal kinesigenic dyskinesia(PKD),the most common type of paroxysmal movement disorder,is characterized by sudden and brief attacks of choreoathetosis or dystonia triggered by sudden voluntary movements.PKD is mainly caused by mutations in the PRRT2 or TMEM151A gene.The exact pathophysiological mechanisms of PKD remain unclear,although the function of PRRT2 protein has been well characterized in the last decade.Based on abnormal ion channels and disturbed synaptic transmission in the absence of PRRT2,PKD may be channelopathy or synaptopathy,or both.In addition,the cerebellum is regarded as the key pathogenic area.Spreading depolarization in the cerebellum is tightly associated with dyskinetic episodes.Whereas,in PKD,other than the cerebellum,the role of the cerebrum including the cortex and thalamus needs to be further investigated.
文摘BACKGROUND:Rhabdomyolysis may cause severe damage to the human body because of acute renal failure,fatal heart rhythm disturbances,hypovolemic shock,disturbances of electrolyte balance,metabolic acidosis,hyperthermia,disseminated intravascular coagulation,etc.Drugs and toxins are the most common factors for the disease.This article aimed to review the prognosis of rhabdomyolysis.DATA SOURCES:Based on the reported studies of cell and molecular biology,we reviewed the clinical presentations,laboratory findings,and mechanisms of rhabdomyolysis in the Pubmed.RESULTS:The clinical symptoms of rhabdomyolysis were dependent on the severity of the condition and whether kidney failure develops.Since the necrosis and dissolution of muscle cells,entocytes such as myoglobin,creatine phosphokinase(CPK),electrolytes,proteins and non-protein substances were released into the plasma,the detection of the entocytes may contribute to the early diagnosis of rhabdomyolysis.CONCLUSION:Despite the etiology of the disease is multifactorial,the potential causes of rhabdomyolysis share the same pathophysiological pathway involving an increase in intracellular calcium.
基金supported by the Key-Area Research and Development Program of Guangdong Province[grant numbers 21202107201900005,21202107201900003].
文摘Sensitive skin is a clinical syndrome characterized by a hyper-reactive state of the skin,primarily on the face.It is accompanied by subjective symptoms such as burning,stinging,itching,and tightness when exposed to physical,chemical,or psychological stimuli.Objective signs,such as erythema,scales,and dilated blood vessels,may or may not be present.The discomfort associated with sensitive skin can be triggered by various endogenous and exogenous factors,which usually have no significant effect on the individual and do not induce irritant reactions.Sensitive skin often presents as a subjective state without clinical signs and exhibits diversity,posing challenges in sensitive skin research and care.This review summarizes the prevalence,key factors,pathophysiological mechanisms,diagnosis,and progress in daily care for sensitive skin.The aim is to provide a clearer and more systematic understanding of sensitive skin and offer guidance for sensitive skin care.
基金This work was supported by the Zhejiang Provincial Natural Science Foundation of China(No.LD22H310004)the“Pioneer”and“Leading Goose”R&D Program of Zhejiang(No.2022C03005),China.
文摘Recently,the substance P(SP)/neurokinin-1 receptor(NK-1R)system has been found to be involved in various human pathophysiological disorders including the symptoms of coronavirus disease 2019(COVID-19).Besides,studies in the oncological field have demonstrated an intricate correlation between the upregulation of NK-1R and the activation of SP/NK-1R system with the progression of multiple carcinoma types and poor clinical prognosis.These findings indicate that the modulation of SP/NK-1R system with NK-1R antagonists can be a potential broad-spectrum antitumor strategy.This review updates the latest potential and applications of NK-1R antagonists in the treatment of human diseases and cancers,as well as the underlying mechanisms.Furthermore,the strategies to improve the bioavailability and efficacy of NK-1R antagonist drugs are summarized,such as solid dispersion systems,nanonization,and nanoencapsulation.As a radiopharmaceutical therapeutic,the NK-1R antagonist aprepitant was originally developed as radioligand receptor to target NK-1R-overexpressing tumors.However,combining NK-1R antagonists with other drugs can produce a synergistic effect,thereby enhancing the therapeutic effect,alleviating the symptoms,and improving patients’quality of life in several diseases and cancers.
基金supported by a National 973 Project(No.2015CB554405)
文摘The pathophysiological characteristics of Phlegm-stasis Cementation Syndrome in Coronary Heart Disease(CHD) has been summarized in this article. According to epidemiological investigations, phlegm-stasis cementation syndrome has become a dominant syndrome in CHD along with the improvement in living and dietary condition. The interaction between blood stasis and phlegm turbidity that is called Phlegmstasis Cementation Syndrome exists in CHD and other diseases. The bridge linked blood stasis and phlegm turbidity lies in the adversely effects of lipid metabolism disorder on platelet activation, vascular function and hemorheology indexes. Lipid metabolism disorder also can induce persistent inflammation including monocyte/macrophage activation and oxidative stress. Inflammation also is an important stimulating factor for atherosclerosis and the biology that underlies the complications of CHD,which belonged to the concept of "toxin" in Traditional Chinese medicines(TCM). On the other hand, the important function of inflammatory process on abnormal hemorheology,platelet activation and vascular dysfunction can be used to elucidate the basic pathogenetic condition of the toxin inducing blood stasis in TCM. Therefore, it is this pathological process that can be used to address the basic pathogenetic theory of phlegm turbidity inducing the symptom of toxin and blood stasis, and subsequently phlegm-stasis cementation in TCM. We deduced that lipid metabolic disturbance,inflammation activation, vascular dyfunction and hemorheological disorders could be as pathophysiological characteristics of Phlegm-stasis cementation syndrome.
文摘Tako-tsubo cardiomyopathy（TC） is a recently described acute cardiac syndrome, which the latest cardiomyopathy classification of the European Society of Cardiology describes as an unclassified cardiomyopathy. TC mimics acute myocardial infarction（AMI） and is characterised by ischaemic chest symptoms, an elevated electrocardiogram ST-segment, and moderately increased levels of cardiac disease markers. However, patients with TC have no coronary angiogram-detectable or non-obstructive coronary arterial disease（CAD）, and left ventriculography documents transient left apical and middle ventricular wall dysfunction. In this review, we describe TC and evaluate epidemiological, clinical and instrumental features, pathophysiological mechanisms, therapy and prognosis of this syndrome,with a view to raising awareness of the disease.
文摘The liver is a primary site for xenobiotics detoxification, and its metabolism is readily altered by toxicity. The kidney is a common target for toxic xenobiotics due to its capacity to extract and concentrate toxic substances by highly specialized cells. So, they are the target organs of sodium fluoride toxicity. The aim of this review is to highlight on hepatorenal oxidative stress and pathophysiological changes induced by treatment of experimental animals with sodium fluoride. Our review shows fluoride toxicosis caused an elevation in the serum activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, acid phosphatase, and the level of total bilirubin, and reduction in the serum levels of total protein, albumin, and globulins, and serious histopathological changes in the hepaic tissues. Also, NaF administration caused increases in serum urea, creatinine, uric acid, sodium ions, and chloride ions levels and serious histopathological changes in the kidney tissues. Treatment of experimental animals with NaF induced oxidative stress in hepatic and renal tissues. It can be concluded that administration of sodium fluoride to experimental animals induced oxidative stress, serious hepatorenal histopathological changes, and disturbance in liver and kidney functions. So, human should be advised to decrease exposure to sodium fluoride to decrease the harmful effects of NaF on liver and kidney.
