One of the main causes of cancer-related morbidity and mortality globally is hepatocellular carcinoma(HCC).At every stage of the disease,HCC may now be treated using a variety of therapy techniques.Nevertheless,despit...One of the main causes of cancer-related morbidity and mortality globally is hepatocellular carcinoma(HCC).At every stage of the disease,HCC may now be treated using a variety of therapy techniques.Nevertheless,despite the abundance of effective therapeutic choices,the prognosis for patients with HCC is still typically dismal.Prognostic indicators are crucial when assessing prognosis and tracking tumor metastases or recurrence.There are many prognostic markers in HCC.We mainly focused on newly reported prognostic markers such as MEX3A,apolipoprotein B,alpha-fetoprotein,circulating tumor cells,SAMD13,Agrin,and Glypican-3 in the pathogenesis of HCC.Further,we highlighted how these prognostic markers correlated to clinical parameters such as tumor node metastasis,tumor diameter,differentiation,hepatocirrhosis,vascular invasion,and others in HCC.Therefore,identifying specific prognostic biomarkers of HCC helps to provide a great opportunity to improve the prognosis in patients with HCC and provide therapeutic targets.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
Atrial fibrillation(AF)is a prevalent cardiac arrhythmia characterized by irregular and frequently rapid electrical activity in the atria.Adipokines are bioactive molecules that are secreted by adipose tissue,and exer...Atrial fibrillation(AF)is a prevalent cardiac arrhythmia characterized by irregular and frequently rapid electrical activity in the atria.Adipokines are bioactive molecules that are secreted by adipose tissue,and exert diverse effects on health and disease.Obesity is a complex condition influenced by multiple interconnected factors,and the specific mechanisms linking obesity to AF may vary among individuals.Obesity contributes to the development of atrial arrhythmia.Moreover,obesity plays major roles in the pathophysiology of AF and its associated complications by inducing systemic changes,including altered hemodynamics,heightened sympathetic tone,and a persistent low-grade inflammatory state.Although the associations between overweight or obesity and elevated risk of AF have been established,the underlying mechanisms remain incompletely characterized.This article highlights the pathophysiological aspects of adipokines,such as Angiopoietin-like protein 2,Fibroblast growth factor 21,Lipocalin,Vaspin,Visfatin,and Nesfatin-1,in AF and concludes that adipokines play major roles in AF pathogenesis.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
Dear Editor,Obesity has nowadays become a global public health challenge due to its rapidly growing prevalence and interconnection with a wide spectrum of comorbidities.
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
Gastric polyps become a major clinical problem because of high prevalence and tendency to malignant transformation of some of them. The development of gastric hyperplastic polyps results from excessive proliferation o...Gastric polyps become a major clinical problem because of high prevalence and tendency to malignant transformation of some of them. The development of gastric hyperplastic polyps results from excessive proliferation of foveolar cells accompanied by their increased exfoliation, and they are macroscopically indistinguishable from other polyps with lower or higher malignant potential. Panendoscopy allows detection and differentiation of gastric polyps, usually after obtaining histopathological biopsy specimens. Unremoved gastric hyperplastic polyps may enlarge and sometimes spontaneously undergo a sequential progression to cancer. For this reason, gastric hyperplastic polyps larger than 5 mm in size should be removed in one piece. After excision of polyps with atypical focal lesion, endoscopic surveillance is suggested depending on histopathological diagnosis and possibility of confirming the completeness of endoscopic resection. Because of the risk of cancer development also in gastric mucosa outside the polyp, neighboring fragments of gastric mucosa should undergo microscopic investigations. This procedure allows for identification of patients who can benefit most from oncological endoscopic surveillance. If Helicobacter pylori(H. pylori) infection of the gastric mucosa is confirmed, treatment strategies should include eradication of bacteria, which may prevent progression of intestinal metaplasia. The efficacy of H. pylori eradication should be checked 3-6 mo later.展开更多
AIM: To explore the approaches exerted by mesenchymal stem cells (MSCs) to improve Parkinson’s disease (PD) pathophysiology.METHODS: MSCs were harvested from bone marrow of femoral bones of male rats, grow...AIM: To explore the approaches exerted by mesenchymal stem cells (MSCs) to improve Parkinson’s disease (PD) pathophysiology.METHODS: MSCs were harvested from bone marrow of femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group (1) was control, Groups (2) and (3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group (2) was left untreated, while Group (3) was treated with single intravenous dose of bone marrow derived MSCs (BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1) and brain derived neurotrophic factor (BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase (TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1 (489.7 ± 13.0 vs 691.2 ± 8.0, P < 0.05) and MCP-1 (89.6 ± 2.0 vs 112.1 ± 1.9, P < 0.05) levels associated with significant increase in serum BDNF (3663 ± 17.8 vs 2905 ± 72.9, P < 0.05) and brain DA (874 ± 15.0 vs 599 ± 9.8, P < 0.05) levels as well as brain TH (1.18 ± 0.004 vs 0.54 ± 0.009, P < 0.05) and nestin (1.29 ± 0.005 vs 0.67 ± 0.006, P < 0.05) genes expression levels. In addition to, producing insignificant increase in the number of positive cells for survivin (293.2 ± 15.9 vs 271.5 ± 15.9, P > 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs.CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.展开更多
Obstructive jaundice(OJ)is a common problem in daily clinical practice.However,completely understanding the pathophysiological changes in OJ remains a challenge for planning current and future management.The effects o...Obstructive jaundice(OJ)is a common problem in daily clinical practice.However,completely understanding the pathophysiological changes in OJ remains a challenge for planning current and future management.The effects of OJ are widespread,affecting the biliary tree,hepatic cells,liver function,and causing systemic complications.The lack of bile in the intestine,destruction of the intestinal mucosal barrier,and increased absorption of endotoxins can lead to endotoxemia,production of proinflammatory cytokines,and induce systemic inflammatory response syndrome,ultimately leading to multiple organ dysfunction syndrome.Proper management of OJ includes adequate water supply and electrolyte replacement,nutritional support,preventive antibiotics,pain relief,and itching relief.The surgical treatment of OJ depends on the cause,location,and severity of the obstruction.Biliary drainage,surgery,and endoscopic intervention are potential treatment options depending on the patient's condition.In addition to modern medical treatments,Traditional Chinese medicine may offer therapeutic benefits for OJ.A comprehensive search was conducted on PubMed for relevant articles published up to August 1970.This review discusses in detail the pathophysiological changes associated with OJ and presents effective strategies for managing the condition.展开更多
AIM: To study the pathophysiological significance of gallbladder volume (GBV) and ejection fraction changes in gallstone patients.METHODS: The fasting GBV of gallstone patients with acute cholecystitis (n = 99), chron...AIM: To study the pathophysiological significance of gallbladder volume (GBV) and ejection fraction changes in gallstone patients.METHODS: The fasting GBV of gallstone patients with acute cholecystitis (n = 99), chronic cholecystitis (n = 85) and non-gallstone disease (n = 240) were measured by preoperative computed tomography. Direct saline injection measurements of GBV after cholecystectomy were also performed. The fasting and postprandial GBV of 65 patients with gallstones and chronic cholecystitis and 53 healthy subjects who received health examinations were measured by abdominal ultrasonography. Proper adjustments were made after the correction factors were calculated by comparing the preoperative and postoperative measurements. Pathological correlations between gallbladder changes in patients with acute calculous cholecystitis and the stages defined by the Tokyo International Consensus Meeting in 2007 were made. Unpaired Student's t tests were used. P < 0.05 was deemed statistically significant. RESULTS: The fasting GBV was larger in late stage than in early/second stage acute cholecystitis gallbladders (84.66 ± 26.32 cm 3 , n = 12, vs 53.19 ± 33.80 cm 3 , n = 87, P = 0.002). The fasting volume/ejection fraction of gallbladders in chronic cholecystitis were larger/lower than those of normal subjects (28.77 ± 15.00 cm 3 vs 6.77 ± 15.75 cm 3 , P < 0.0001)/(34.6% ± 10.6%, n = 65, vs 53.3% ± 24.9%, n = 53, P < 0.0001). CONCLUSION: GBV increases as acute cholecystitis progresses to gangrene and/or empyema. Gallstone formation is associated with poorer contractility and larger volume in gallbladders that contain stones.展开更多
Apart from avoiding exposure, allergen immunotherapy (AI) is the only causal method of treating allergic diseases. The results of numerous studies have been published concerning the safety and effectiveness of the AI ...Apart from avoiding exposure, allergen immunotherapy (AI) is the only causal method of treating allergic diseases. The results of numerous studies have been published concerning the safety and effectiveness of the AI in treating allergic rhinitis, asthma or allergy to the venom of Hymenoptera insects. It has also been proven that administration of increasing preparation doses of allergen extractions alleviates the symptoms in patients after the exposure to some sensitizing allergens. The effect of the AI remains visible many years after completion of the therapy. Studies have been done in an attempt to employ specific immunotherapy in patients with food allergy symptoms. They have been mostly concerned with populations of patients suffering from allergy to the protein found in cow’s milk and hen eggs. It appears that a need arises to create a new therapeutic method for successful treatment of food allergies and specific allergen immunotherapy seems to be a promising step. Although still in its experimental phase, in many well documented cases the method allows for building patient’s tolerance towards small doses of sensitizing allergen and seems conducive to protecting the patient from anaphylactic reactions after incidental allergen consumption.展开更多
Migraine is a highly prevalent neurological disorder and has been the second leading cause of disability worldwide for many years.The pathophysiology of migraines is complicated,and most available medications have unp...Migraine is a highly prevalent neurological disorder and has been the second leading cause of disability worldwide for many years.The pathophysiology of migraines is complicated,and most available medications have unpleasant side effects.Therefore,it is essential to understand the mechanism of migraine to develop potential preventive and therapeutic agents.Studies have confirmed that traditional Chinese medicine(TCM)can alleviate migraine by reducing neuroinflammation,oxidative stress,and apoptosis and regulating neurotransmitters and vascular function.Starting from the pathophysiological process of migraine,this review summarizes the mechanisms by which TCM improves neurovascular function after migraine to provide clues and a reference for the clinical application of TCM in the prevention and treatment of migraine and guide further research and development of new drugs.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
Ischemic stroke is a serious medical event that cannot be predicted in advance and can have longlasting effects on patients,families,and communities.A deeper understanding of the changes in gene expression and the fun...Ischemic stroke is a serious medical event that cannot be predicted in advance and can have longlasting effects on patients,families,and communities.A deeper understanding of the changes in gene expression and the fundamental molecular mechanisms involved could help address this critical issue.In recent years,research into regulatory long non-coding(lnc)RNAs,a diverse group of RNA molecules with regulatory functions,has emerged as a promising direction in the study of cerebral infarction.This review paper aims to provide a comprehensive exploration of the roles of regulatory lncRNAs in cerebral infarction,as well as potential strategies for their application in clinical settings.LncRNAs have the potential to act as“sponges”that attract specific microRNAs,thereby regulating the expression of microRNA target genes.These interactions influence various aspects of ischemic stroke,including reperfusion-induced damage,cell death,immune responses,autophagy,angiogenesis,and the generation of reactive oxygen species.We highlight several regulatory lncRNAs that have been utilized in animal model treatments,including lncRNA NKILA,lncRNA Meg8,and lncRNA H19.Additionally,we discuss lncRNAs that have been used as biomarkers for the diagnosis and prognosis of cerebral infarction,such as lncRNA FOXO3,lncRNA XIST,and lncRNA RMST.The lncRNAs hold potential for genetic-level treatments in patients.However,numerous challenges,including inefficiency,low targeting accuracy,and side effects observed in preliminary studies,indicate the need for thorough investigation.The application of lncRNAs in ischemic stroke presents challenges that require careful and extensive validation.展开更多
The BRASH syndrome,an acronym for bradycardia,renal failure,atrioventricular(AV)nodal blockade,shock,and hyperkalemia,was first described as a distinct clinical entity in 2016 by Josh Farkas.[1]He proposed a vicious p...The BRASH syndrome,an acronym for bradycardia,renal failure,atrioventricular(AV)nodal blockade,shock,and hyperkalemia,was first described as a distinct clinical entity in 2016 by Josh Farkas.[1]He proposed a vicious pathophysiological cycle driven by the synergy between AV nodal blockade and hyperkalemia.展开更多
Schizophrenia is characterized by psychotic symptoms,negative symptoms,and cognitive deficits,profoundly affecting individuals and their families.The etiology is multifactorial,involving genetic,endocrine,and immunolo...Schizophrenia is characterized by psychotic symptoms,negative symptoms,and cognitive deficits,profoundly affecting individuals and their families.The etiology is multifactorial,involving genetic,endocrine,and immunological risk factors.It is thought that schizophrenia is exclusively linked to alterations in brain structure and function,while the relationship between the brain and many organs may lack sufficient attention.Increasing evidence indicates abnormalities of the interactions between the brain and many organs in patients with schizophrenia.Inter-organ crosstalk affects the onset,course,and management of schizophrenia.Besides,the complex relationship between autonomic nervous system,endocrine system,and immune system further facilitates the development of schizophrenia.The present review summarizes the relationships between the brain and multiple organ systems in schizophrenia,providing new perspectives on the underlying pathophysiological mechanisms of schizophrenia.展开更多
Transjugular intrahepatic portosystemic shunts(TIPSs)are generally used for the management of complications of portal hypertension in patients with decompensated cirrhosis.However,hepatic encephalopathy(HE),which impa...Transjugular intrahepatic portosystemic shunts(TIPSs)are generally used for the management of complications of portal hypertension in patients with decompensated cirrhosis.However,hepatic encephalopathy(HE),which impairs neuropsychiatric function and motor control,remains the primary adverse effect of TIPS,limiting its utility.Prompt prevention and treatment of post-TIPS HE are critical,as they are strongly associated with readmission rates and poor quality of life.This review focuses on the main pathophysiological mechanisms underlying post-TIPS HE,explores advanced biomarkers and predictive tools,and discusses current management strategies and future directions to prevent or reverse HE following TIPS.These strategies include preoperative patient assessment,individualized shunt diameter optimization,spontaneous portosystemic shunt embolization during the TIPS procedure,postoperative preventive and therapeutic measures such as nutrition management,medical therapy,fecal microbiota transplantation,and stent reduction.展开更多
Exertional heat stroke (EHS) is a life-threatening condition characterized by profound central nervous system (CNS)dysfunction and core temperature typically>40°C.^([1])This condition involves complex pathophy...Exertional heat stroke (EHS) is a life-threatening condition characterized by profound central nervous system (CNS)dysfunction and core temperature typically>40°C.^([1])This condition involves complex pathophysiological processes in which heat triggers a cascade of dysregulated inflammatory responses,endothelial dysfunction,coagulation abnormalities,and muscle damage.These processes can lead to multiorgan failure,significantly increasing the risk of mortality.^([2])Given the severity of EHS,early identification and timely intervention are crucial.However,there are no specific diagnostic markers for EHS,^([1])highlighting the need to identify reliable clinical parameters that can assist early decision-making.展开更多
This editorial underscores the importance of Maranhão et al’s study,which investigates pleural adenosine deaminase(P-ADA)as a biomarker for inflammatory pleural effusions.Despite advances in imaging,distinguishi...This editorial underscores the importance of Maranhão et al’s study,which investigates pleural adenosine deaminase(P-ADA)as a biomarker for inflammatory pleural effusions.Despite advances in imaging,distinguishing between inflammatory and non-inflammatory causes of pleural effusion remains a diagnostic challenge.The authors conducted a rigorous retrospective cohort analysis of 157 patients(124 with inflammatory exudates and 33 with non-inflammatory transudates),establishing a robust cutoff value of P-ADA≥9.00 U/L for diagnosing inflammatory diseases using receiver operating characteristic curve analysis and internal statistical calibration.This is the first study to define a standardized PADA threshold in a Brazilian cohort,addressing previous inconsistencies in cutoff values.Furthermore,the authors delved into the pathophysiological mechanisms underlying elevated P-ADA,linking it to purinergic signaling pathways and immune cell activation,particularly emphasizing the role of ADA2 isoforms in macrophages and lymphocytes.Their findings support P-ADA as a non-invasive,cost-effective biomarker for early diagnosis,treatment stratification,and minimizing the need for invasive procedures such as thoracentesis.This has particular relevance in resource-limited settings,where streamlined diagnostics can reduce healthcare costs and improve patient outcomes.Future studies must prioritize global validation,explore the integration of adenosine deaminase with additional biomarkers(e.g.,interleukin 6,C-reactive protein),and support the development of point-of-care technologies.展开更多
Total or severe teratospermia affects the prognosis of fertility and causes serious problems for patients undergoing assisted reproduction[1].The pathophysiological mechanism of teratospermia is unclear.It has been sh...Total or severe teratospermia affects the prognosis of fertility and causes serious problems for patients undergoing assisted reproduction[1].The pathophysiological mechanism of teratospermia is unclear.It has been shown that patients with sperm parameters abnormalities and abnormal morphology have a high rate of fragmentation and sperm DNA decondensation[2,3],and that sperm DNA fragmentation analysis could be used as a predictor factor of fertility potential[4].展开更多
文摘One of the main causes of cancer-related morbidity and mortality globally is hepatocellular carcinoma(HCC).At every stage of the disease,HCC may now be treated using a variety of therapy techniques.Nevertheless,despite the abundance of effective therapeutic choices,the prognosis for patients with HCC is still typically dismal.Prognostic indicators are crucial when assessing prognosis and tracking tumor metastases or recurrence.There are many prognostic markers in HCC.We mainly focused on newly reported prognostic markers such as MEX3A,apolipoprotein B,alpha-fetoprotein,circulating tumor cells,SAMD13,Agrin,and Glypican-3 in the pathogenesis of HCC.Further,we highlighted how these prognostic markers correlated to clinical parameters such as tumor node metastasis,tumor diameter,differentiation,hepatocirrhosis,vascular invasion,and others in HCC.Therefore,identifying specific prognostic biomarkers of HCC helps to provide a great opportunity to improve the prognosis in patients with HCC and provide therapeutic targets.
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Atrial fibrillation(AF)is a prevalent cardiac arrhythmia characterized by irregular and frequently rapid electrical activity in the atria.Adipokines are bioactive molecules that are secreted by adipose tissue,and exert diverse effects on health and disease.Obesity is a complex condition influenced by multiple interconnected factors,and the specific mechanisms linking obesity to AF may vary among individuals.Obesity contributes to the development of atrial arrhythmia.Moreover,obesity plays major roles in the pathophysiology of AF and its associated complications by inducing systemic changes,including altered hemodynamics,heightened sympathetic tone,and a persistent low-grade inflammatory state.Although the associations between overweight or obesity and elevated risk of AF have been established,the underlying mechanisms remain incompletely characterized.This article highlights the pathophysiological aspects of adipokines,such as Angiopoietin-like protein 2,Fibroblast growth factor 21,Lipocalin,Vaspin,Visfatin,and Nesfatin-1,in AF and concludes that adipokines play major roles in AF pathogenesis.
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Dear Editor,Obesity has nowadays become a global public health challenge due to its rapidly growing prevalence and interconnection with a wide spectrum of comorbidities.
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.
文摘Gastric polyps become a major clinical problem because of high prevalence and tendency to malignant transformation of some of them. The development of gastric hyperplastic polyps results from excessive proliferation of foveolar cells accompanied by their increased exfoliation, and they are macroscopically indistinguishable from other polyps with lower or higher malignant potential. Panendoscopy allows detection and differentiation of gastric polyps, usually after obtaining histopathological biopsy specimens. Unremoved gastric hyperplastic polyps may enlarge and sometimes spontaneously undergo a sequential progression to cancer. For this reason, gastric hyperplastic polyps larger than 5 mm in size should be removed in one piece. After excision of polyps with atypical focal lesion, endoscopic surveillance is suggested depending on histopathological diagnosis and possibility of confirming the completeness of endoscopic resection. Because of the risk of cancer development also in gastric mucosa outside the polyp, neighboring fragments of gastric mucosa should undergo microscopic investigations. This procedure allows for identification of patients who can benefit most from oncological endoscopic surveillance. If Helicobacter pylori(H. pylori) infection of the gastric mucosa is confirmed, treatment strategies should include eradication of bacteria, which may prevent progression of intestinal metaplasia. The efficacy of H. pylori eradication should be checked 3-6 mo later.
文摘AIM: To explore the approaches exerted by mesenchymal stem cells (MSCs) to improve Parkinson’s disease (PD) pathophysiology.METHODS: MSCs were harvested from bone marrow of femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group (1) was control, Groups (2) and (3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group (2) was left untreated, while Group (3) was treated with single intravenous dose of bone marrow derived MSCs (BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1) and brain derived neurotrophic factor (BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase (TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1 (489.7 ± 13.0 vs 691.2 ± 8.0, P < 0.05) and MCP-1 (89.6 ± 2.0 vs 112.1 ± 1.9, P < 0.05) levels associated with significant increase in serum BDNF (3663 ± 17.8 vs 2905 ± 72.9, P < 0.05) and brain DA (874 ± 15.0 vs 599 ± 9.8, P < 0.05) levels as well as brain TH (1.18 ± 0.004 vs 0.54 ± 0.009, P < 0.05) and nestin (1.29 ± 0.005 vs 0.67 ± 0.006, P < 0.05) genes expression levels. In addition to, producing insignificant increase in the number of positive cells for survivin (293.2 ± 15.9 vs 271.5 ± 15.9, P > 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs.CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.
基金Tianjin Municipal Education Commission Scientific Research Program,China,No.2022KJ271。
文摘Obstructive jaundice(OJ)is a common problem in daily clinical practice.However,completely understanding the pathophysiological changes in OJ remains a challenge for planning current and future management.The effects of OJ are widespread,affecting the biliary tree,hepatic cells,liver function,and causing systemic complications.The lack of bile in the intestine,destruction of the intestinal mucosal barrier,and increased absorption of endotoxins can lead to endotoxemia,production of proinflammatory cytokines,and induce systemic inflammatory response syndrome,ultimately leading to multiple organ dysfunction syndrome.Proper management of OJ includes adequate water supply and electrolyte replacement,nutritional support,preventive antibiotics,pain relief,and itching relief.The surgical treatment of OJ depends on the cause,location,and severity of the obstruction.Biliary drainage,surgery,and endoscopic intervention are potential treatment options depending on the patient's condition.In addition to modern medical treatments,Traditional Chinese medicine may offer therapeutic benefits for OJ.A comprehensive search was conducted on PubMed for relevant articles published up to August 1970.This review discusses in detail the pathophysiological changes associated with OJ and presents effective strategies for managing the condition.
基金Supported by Grants from Chung Shan Medical University with Grant Numbers CSMUTTM-097-001 and CSMU-TTM-098-002
文摘AIM: To study the pathophysiological significance of gallbladder volume (GBV) and ejection fraction changes in gallstone patients.METHODS: The fasting GBV of gallstone patients with acute cholecystitis (n = 99), chronic cholecystitis (n = 85) and non-gallstone disease (n = 240) were measured by preoperative computed tomography. Direct saline injection measurements of GBV after cholecystectomy were also performed. The fasting and postprandial GBV of 65 patients with gallstones and chronic cholecystitis and 53 healthy subjects who received health examinations were measured by abdominal ultrasonography. Proper adjustments were made after the correction factors were calculated by comparing the preoperative and postoperative measurements. Pathological correlations between gallbladder changes in patients with acute calculous cholecystitis and the stages defined by the Tokyo International Consensus Meeting in 2007 were made. Unpaired Student's t tests were used. P < 0.05 was deemed statistically significant. RESULTS: The fasting GBV was larger in late stage than in early/second stage acute cholecystitis gallbladders (84.66 ± 26.32 cm 3 , n = 12, vs 53.19 ± 33.80 cm 3 , n = 87, P = 0.002). The fasting volume/ejection fraction of gallbladders in chronic cholecystitis were larger/lower than those of normal subjects (28.77 ± 15.00 cm 3 vs 6.77 ± 15.75 cm 3 , P < 0.0001)/(34.6% ± 10.6%, n = 65, vs 53.3% ± 24.9%, n = 53, P < 0.0001). CONCLUSION: GBV increases as acute cholecystitis progresses to gangrene and/or empyema. Gallstone formation is associated with poorer contractility and larger volume in gallbladders that contain stones.
文摘Apart from avoiding exposure, allergen immunotherapy (AI) is the only causal method of treating allergic diseases. The results of numerous studies have been published concerning the safety and effectiveness of the AI in treating allergic rhinitis, asthma or allergy to the venom of Hymenoptera insects. It has also been proven that administration of increasing preparation doses of allergen extractions alleviates the symptoms in patients after the exposure to some sensitizing allergens. The effect of the AI remains visible many years after completion of the therapy. Studies have been done in an attempt to employ specific immunotherapy in patients with food allergy symptoms. They have been mostly concerned with populations of patients suffering from allergy to the protein found in cow’s milk and hen eggs. It appears that a need arises to create a new therapeutic method for successful treatment of food allergies and specific allergen immunotherapy seems to be a promising step. Although still in its experimental phase, in many well documented cases the method allows for building patient’s tolerance towards small doses of sensitizing allergen and seems conducive to protecting the patient from anaphylactic reactions after incidental allergen consumption.
基金supported by the National Natural Science Foundation of China(Grant No.82004331)Key Research and Development Program of Hu Bei Province of China(2021ACA004-03 and 2022ACA003-02-002)。
文摘Migraine is a highly prevalent neurological disorder and has been the second leading cause of disability worldwide for many years.The pathophysiology of migraines is complicated,and most available medications have unpleasant side effects.Therefore,it is essential to understand the mechanism of migraine to develop potential preventive and therapeutic agents.Studies have confirmed that traditional Chinese medicine(TCM)can alleviate migraine by reducing neuroinflammation,oxidative stress,and apoptosis and regulating neurotransmitters and vascular function.Starting from the pathophysiological process of migraine,this review summarizes the mechanisms by which TCM improves neurovascular function after migraine to provide clues and a reference for the clinical application of TCM in the prevention and treatment of migraine and guide further research and development of new drugs.
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.
基金supported by the China Postdoctoral Science Foundation,No.2022M712689the Natural Science Foundation of the Jiangsu Higher Education Institutions of China,No.22KJB1800029+1 种基金The University Student Innovation Project of Yangzhou University,No.XCX20240856The Jiangsu Provincial Science and Technology Talent Project,No.FZ20240964(all to TX).
文摘Ischemic stroke is a serious medical event that cannot be predicted in advance and can have longlasting effects on patients,families,and communities.A deeper understanding of the changes in gene expression and the fundamental molecular mechanisms involved could help address this critical issue.In recent years,research into regulatory long non-coding(lnc)RNAs,a diverse group of RNA molecules with regulatory functions,has emerged as a promising direction in the study of cerebral infarction.This review paper aims to provide a comprehensive exploration of the roles of regulatory lncRNAs in cerebral infarction,as well as potential strategies for their application in clinical settings.LncRNAs have the potential to act as“sponges”that attract specific microRNAs,thereby regulating the expression of microRNA target genes.These interactions influence various aspects of ischemic stroke,including reperfusion-induced damage,cell death,immune responses,autophagy,angiogenesis,and the generation of reactive oxygen species.We highlight several regulatory lncRNAs that have been utilized in animal model treatments,including lncRNA NKILA,lncRNA Meg8,and lncRNA H19.Additionally,we discuss lncRNAs that have been used as biomarkers for the diagnosis and prognosis of cerebral infarction,such as lncRNA FOXO3,lncRNA XIST,and lncRNA RMST.The lncRNAs hold potential for genetic-level treatments in patients.However,numerous challenges,including inefficiency,low targeting accuracy,and side effects observed in preliminary studies,indicate the need for thorough investigation.The application of lncRNAs in ischemic stroke presents challenges that require careful and extensive validation.
文摘The BRASH syndrome,an acronym for bradycardia,renal failure,atrioventricular(AV)nodal blockade,shock,and hyperkalemia,was first described as a distinct clinical entity in 2016 by Josh Farkas.[1]He proposed a vicious pathophysiological cycle driven by the synergy between AV nodal blockade and hyperkalemia.
基金Supported by Beijing Traditional Chinese Medicine Scientific and Technological Development Fund Project,No.BJZYYB-2023-66Beijing Natural Science Foundation,No.7212050the Capital’s Funds for Health Improvement and Research,No.2020-4-2126.
文摘Schizophrenia is characterized by psychotic symptoms,negative symptoms,and cognitive deficits,profoundly affecting individuals and their families.The etiology is multifactorial,involving genetic,endocrine,and immunological risk factors.It is thought that schizophrenia is exclusively linked to alterations in brain structure and function,while the relationship between the brain and many organs may lack sufficient attention.Increasing evidence indicates abnormalities of the interactions between the brain and many organs in patients with schizophrenia.Inter-organ crosstalk affects the onset,course,and management of schizophrenia.Besides,the complex relationship between autonomic nervous system,endocrine system,and immune system further facilitates the development of schizophrenia.The present review summarizes the relationships between the brain and multiple organ systems in schizophrenia,providing new perspectives on the underlying pathophysiological mechanisms of schizophrenia.
基金Supported by the National Natural Science Foundation of China,No.82270649.
文摘Transjugular intrahepatic portosystemic shunts(TIPSs)are generally used for the management of complications of portal hypertension in patients with decompensated cirrhosis.However,hepatic encephalopathy(HE),which impairs neuropsychiatric function and motor control,remains the primary adverse effect of TIPS,limiting its utility.Prompt prevention and treatment of post-TIPS HE are critical,as they are strongly associated with readmission rates and poor quality of life.This review focuses on the main pathophysiological mechanisms underlying post-TIPS HE,explores advanced biomarkers and predictive tools,and discusses current management strategies and future directions to prevent or reverse HE following TIPS.These strategies include preoperative patient assessment,individualized shunt diameter optimization,spontaneous portosystemic shunt embolization during the TIPS procedure,postoperative preventive and therapeutic measures such as nutrition management,medical therapy,fecal microbiota transplantation,and stent reduction.
基金funded by Research Fund of Zhejiang Provincial Health Commission (2025KY8662025)。
文摘Exertional heat stroke (EHS) is a life-threatening condition characterized by profound central nervous system (CNS)dysfunction and core temperature typically>40°C.^([1])This condition involves complex pathophysiological processes in which heat triggers a cascade of dysregulated inflammatory responses,endothelial dysfunction,coagulation abnormalities,and muscle damage.These processes can lead to multiorgan failure,significantly increasing the risk of mortality.^([2])Given the severity of EHS,early identification and timely intervention are crucial.However,there are no specific diagnostic markers for EHS,^([1])highlighting the need to identify reliable clinical parameters that can assist early decision-making.
文摘This editorial underscores the importance of Maranhão et al’s study,which investigates pleural adenosine deaminase(P-ADA)as a biomarker for inflammatory pleural effusions.Despite advances in imaging,distinguishing between inflammatory and non-inflammatory causes of pleural effusion remains a diagnostic challenge.The authors conducted a rigorous retrospective cohort analysis of 157 patients(124 with inflammatory exudates and 33 with non-inflammatory transudates),establishing a robust cutoff value of P-ADA≥9.00 U/L for diagnosing inflammatory diseases using receiver operating characteristic curve analysis and internal statistical calibration.This is the first study to define a standardized PADA threshold in a Brazilian cohort,addressing previous inconsistencies in cutoff values.Furthermore,the authors delved into the pathophysiological mechanisms underlying elevated P-ADA,linking it to purinergic signaling pathways and immune cell activation,particularly emphasizing the role of ADA2 isoforms in macrophages and lymphocytes.Their findings support P-ADA as a non-invasive,cost-effective biomarker for early diagnosis,treatment stratification,and minimizing the need for invasive procedures such as thoracentesis.This has particular relevance in resource-limited settings,where streamlined diagnostics can reduce healthcare costs and improve patient outcomes.Future studies must prioritize global validation,explore the integration of adenosine deaminase with additional biomarkers(e.g.,interleukin 6,C-reactive protein),and support the development of point-of-care technologies.
文摘Total or severe teratospermia affects the prognosis of fertility and causes serious problems for patients undergoing assisted reproduction[1].The pathophysiological mechanism of teratospermia is unclear.It has been shown that patients with sperm parameters abnormalities and abnormal morphology have a high rate of fragmentation and sperm DNA decondensation[2,3],and that sperm DNA fragmentation analysis could be used as a predictor factor of fertility potential[4].
