Pulmonary artery stent thrombosis and symptomatic pulmonary hypertension following COVID-19 infection in Alagille patient:A case report

BACKGROUND Alagille syndrome is a multisystem disease that results in various vascular anomalies,commonly involving the cardiac and pulmonary systems.To the best of our knowledge,there is no literature regarding the cardiovascular outcomes of these patients in association with coronavirus disease 2019(COVID-19).CASE SUMMARY A 34-year-old woman with a history of Alagille syndrome who underwent successful atrial septal defect with partial anomalous pulmonary veins and patent ductus arteriosus repair,as well as left pulmonary artery catheterization and stenting in childhood due to pulmonary stenosis.The patient was without any respiratory symptoms and was a dancer prior to contracting COVID-19.Several weeks after her COVID-19 infection,she developed left pulmonary artery stent thrombosis and subsequent symptomatic pulmonary hypertension.A treatment strategy of anticoagulation alongside pharmacological agents for pulmonary hypertension for 3 months followed by balloon pulmonary artery angioplasty to reopen the stenosis was unsuccessful.CONCLUSION In the era of COVID-19,patients with pulmonary vascular malformations and endovascular stents are at an increased risk for chronic thromboembolic disease.Patients may benefit from prophylactic antiplatelet or anticoagulation therapy.Stent thrombosis is a devastating phenomenon and should be treated urgently and aggressively with balloon pulmonary angioplasty,and/or a thrombolytic agent.

Management of small hepatocellular carcinoma in cirrhosis:Focus on portal hypertension

The incidence of hepatocellular carcinoma(HCC) is rising worldwide being currently the fifth most common cancer and third cause of cancer-related mortality.Early detection of HCC through surveillance programs have enabled the identification of small nodules with higher frequency,and nowadays account for 10%-15% of patients diagnosed in the West and almost 30% in Japan.Patients with small HCC can be candidates for potential curative treatments:liver transplantation,surgical resection and percutaneous ablation,depending on the presence of portal hypertension and co-morbidities.This review will analyze recent advancements in the clinical management of these individuals,focusing on issues related to the role of portal hypertension,the debate between resection and ablative therapies and the future impact of molecular technologies.

Effects of telmisartan combined with nifedipine controlled release tablet on inflammatory factors, vascular endothelial function and left ventricular function in patients with coronary heart disease with mild to moderate hypertension

Objective: To investigate the effect of telmisartan combined with Nifedipine Controlled Release Tablet on inflammatory factors, vascular endothelial function and left ventricular function in patients with coronary heart disease with mild to moderate hypertension. Methods:A total of 92 cases of patients with coronary heart disease with mild to moderate hypertension were selected as the object of observation, according to the random data table, they were divided into the control group (n=46) and observation group (n=46), and patients in the control group were treated with Nifedipine Controlled Release Table therapy, on this basis, the observation group patients were given telmisartan treatment, two groups were treated for 6 months. The levels of the blood pressure, inflammatory factors, vascular endothelial function and left ventricular function compared between the two groups before and after treatment. Results: There were no significant differences in the levels of SBP, DBP, hs-CRP, TNF-α, NO, ET-1, LVEF, LVEDD and LVESD in the two groups before treatment. After treatment, two groups of SBP, DBP, hs-CRP, TNF-α, ET-1, LVEDD and LVESD levels were significantly lower than those in the same group before treatment, and after treatment, the levels of SBP, DBP, hs-CRP, TNF-α, ET-1 and LVESD in the observation group were significantly lower than those in the control group, while there were no significant difference in the level of LVEDD between the two groups after treatment;Compared with level in the group before treatment, the levels of NO and LVEF in the two groups were significantly increased, and the observation group [(82.13±19.01) μmol/L, (52.83±7.45)%] was significantly higher than the control group ((67.37±13.08) μmol/L, (49.47±6.96)%)Conclusion: Telmisartan combined with Nifedipine Controlled Release Table in treating coronary heart disease with mild to moderate hypertension, can effectively control blood pressure, reduce the inflammatory stress, improve vascular endothelial function and left ventricular function of patients, has an important clinical value.

Analysis of Cardiovascular Risk Factors in Newly Defined Stage 1 Hypertension among Chinese on the Basis of the 2017 ACC/AHA Hypertension Guidelines

In 2017,American College of Cardiology(ACC)/American Heart Association(AHA)et al.jointly released the latest guidelines for adult hypertension,exactly including prevention,diagnosis,assess and treatment,in which blood pressure levels greater than 130/80 mm Hg were defined as hypertension[1].Based on these modified guidelines,the morbidity of hypertension in US increased from 32%to 46%.

Cognitive impairment in cerebral small vessel disease induced by hypertension

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

Treatment of ectopic varices with portal hypertension

Ectopic varices are unusual with portal hypertension and can involve any site along the digestive tract outside the gastroesophageal region. Hemorrhage from ectopic varices generally are massive and life threatening.Diagnosis of ectopic varices is difficult and subsequent treatment is also difficult; the optimal treatment has not been established. Recently, interventional radiology and endoscopic treatments have been carried out successfully for hemorrhage from ectopic varices.

Spleen stiffness mirrors changes in portal hypertension after successful interferon-free therapy in chronic-hepatitis C virus patients

AIM To investigate changes in spleen stiffness measurements(SSMs) and other non-invasive tests(NITs) after treatment with direct-acting antivirals(DAAs) and identify predictors of SSM change after sustainedvirological response(SVR). METHODS We retrospectively analysed 146 advanced-chronic liver disease(ACLD) patients treated with DAA with available paired SSM at baseline and SVR24. Liver stiffness(LSM), spleen diameter(SD), platelet count(PLT) and liver stiffness-spleen diameter to platelet ratio score(LSPS) were also investigated. LSM ≥ 21 k Pa was used as a cut-off to rule-in clinically significant portal hypertension(CSPH). SSM reduction > 20% from baseline was defined as significant.RESULTS SSM significantly decreased at SVR24, in both patients with and without CSPH; in 44.8% of cases, SSM reduction was > 20%. LSPS significantly improved in the entire cohort at SVR24; SD and PLT changed significantly only in patients without CSPH. LSM significantly decreased in 65.7% of patients and also in 2/3 patients in whom SSM did not decrease. The independent predictor of decreased SSM was median relative change of LSM. CSPH persisted in 54.4% patients after SVR. Delta LSM and baseline SSM were independent factors associated with CSPH persistence.CONCLUSION SSM and other NITs significantly decrease after SVR, although differently according to the patient's clinical condition. SSM faithfully reflects changes in portal hypertension and could represent a useful NIT for the follow-up of these patients.

Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension

AIM To investigate the potential effect of inhibitors of phosphodiesterase-5(PDE-5) for therapy of portal hypertension in liver cirrhosis.METHODS In the rat model of thioacetamide-induced liver fibrosis/cirrhosis the nitric oxide-cyclic guanosine monophosphate(NO-cGMP) pathway was investigated. Expression and localization of PDE-5, the enzyme that converts vasodilating cGMP into inactive 5'-GMP, was in the focus of the study. Hepatic gene expression of key components of the NO-cGMP pathway was determined by qRT-PCR: Endothelial NO synthase(eNOS), inducible NO synthase(iNOS), soluble guanylate cyclase subunits α1 and β1(sGCa1, sGCb1), and PDE-5. Hepatic PDE-5 protein expression and localization were detected by immunohistochemistry. Serum cGMP concentrations were measured using ELISA. Acute effects of the PDE-5 inhibitor Sildenafil(0.1 mg/kg or 1.0 mg/kg) on portal and systemic hemodynamics were investigated using pressure transducers.RESULTS Hepatic gene expression of eNOS(2.2-fold; P = 0.003), sGCa1(1.7-fold; P = 0.003), sGCb1(3.0-fold; P = 0.003), and PDE-5(11-fold; P = 0.003) was increased in cirrhotic livers compared to healthy livers. Overexpression of PDE-5(7.7-fold; P = 0.006) was less pronounced in fibrotic livers. iNOS expression was only detected in fibrotic and cirrhotic livers. In healthy liver, PDE-5 protein was localized primarily in zone 3 hepatocytes and to a lesser extent in perisinusoidal cells. This zonation was disturbed in cirrhosis: PDE-5 protein expression in perisinusoidal cells was induced approximately 8-fold. In addition, PDE-5-expressing cells were also found in fibrous septa. Serum cGMP concentrations were reduced in rats with cirrhotic livers by approximately 40%. Inhibition of PDE-5 by Sildenafil caused a significant increase in serum cGMP concentrations [+ 64% in healthy rats(P = 0.024), + 85% in cirrhotic rats(P = 0.018)]. Concomitantly, the portal venous pressure was reduced by 19% in rats with liver cirrhosis. CONCLUSION Overexpression and abrogated zonation of PDE-5 likely contribute to the pathogenesis of cirrhotic portal hypertension. PDE-5 inhibition may therefore be a reasonable therapeutic approach for portal hypertension.

Arterial hypertension and electrocardiographic diagnosis of left ventricular hypertension in the group of geriatric patients with coronary heart disease living in the far north

As a result of research, high prevalence of arterial hypertension has been identified in the group of patients with coronary heart disease aged 60 and older. Most often, occurring form of arterial hypertension among geriatric patients is isolated systolic arterial hypertension (ISAH). The comparison of two ethnic groups of the population has showed higher levels of systolic and diastolic blood pressure (SBP and DBP) in the group of patients of non-indigenous nationality, rather than Yakut patients. Correlation was recorded in the group of non-indigenous patients as they age. Significant increase in the level of SBP was identified in the group of senile and long-livers than in the elderly. Detection of ECG signs of LVH showed the lowest specificity of Cornell voltage criterion comparing to Sokolow-Lyon criterion with its more often occurrence. ECG-signs of left ventricle hypertrophy are significantly more often established by Sokolow-Lyon criterion for men, Cornell voltage—for women. Correlation has been found between the presence of LVH and combination of Cornell voltage criterion with both Gubner-Ungerleider and Sokolow-Lyon criteria.

Gut microbiota shifts in hepatitis B-related portal hypertension after transjugular intrahepatic portosystemic shunt:Mechanistic and clinical implications

In this article,we provide commentary on the recent article by Zhao et al.We focus on the shifts in the gut microbiota of patients with hepatitis B virus(HBV)-associated cirrhosis/portal hypertension(PH)following transjugular intrahepatic portosystemic shunt(TIPS)and the implications for understanding the mechanisms,diagnosis,and treatment.By comparing the gut microbiota composition and dynamic changes before and after TIPS in patients with and without hepatic encephalopathy,the authors found an increase in non-probiotic bacteria in those who developed hepatic encephalopathy post-TIPS,with Morganella species present only in the hepatic encephalopathy group.The gut microbiota changes post-TIPS among patients without the occurrence of hepatic encephalopathy suggest potential therapeutic benefits through prophylactic microbiome therapies.Furthermore,the specific gut microbiota alterations may hold promise to predict the risk of hepatic encephalopathy in individuals undergoing TIPS for HBVrelated PH.Despite these promising findings,future studies are needed to address limitations,including a small sample size,a relatively short evaluation period for gut microbiota alterations,the absence of data on dynamic alterations in gut microbiota post-TIPS and their correlation with blood ammonia levels,and the lack of validation in animal models.In conclusion,Zhao et al's study has shed new light on the link of gut microbiota with post-TIPS hepatic encephalopathy,potentially through the intricate gut-liver axis,and has important clinical implications for improving the management of patients with HBV-related PH.

Portal hypertension and gastrointestinal bleeding:Diagnosis,prevention and management

Bleeding from esophageal varices is a life threatening complication of portal hypertension.Primary prevention of bleeding in patients at risk for a first bleeding episode is therefore a major goal.Medical prophylaxis consists of non-selective beta-blockers like propranolol or carvedilol.Variceal endoscopic band ligation is equally effective but procedure related morbidity is a drawback of the method.Therapy of acute bleeding is based on three strategies:vasopressor drugs like terlipressin,antibiotics and endoscopic therapy.In refractory bleeding,self-expandable stents offer an option for bridging to definite treatments like transjugular intrahepatic portosystemic shunt(TIPS).Treatment of bleeding from gastric varices depends on vasopressor drugs and on injection of varices with cyanoacrylate.Strategies for primary or secondary prevention are based on non-selective beta-blockers but data from large clinical trials is lacking.Therapy of refractory bleeding relies on shuntprocedures like TIPS.Bleeding from ectopic varices,portal hypertensive gastropathy and gastric antral vascular ectasia-syndrome is less common.Possible medical and endoscopic treatment options are discussed.

Influence of folic acid and vitamin B12 combined therapy on plasma Hcy, inflammatory factor levels and blood vessels endothelial function in patients with vascular dementia and type H hypertension

Objective:To investigate influence of folic acid and vitamin B12 combined therapy on plasma homocysteine (Hcy) level, blood vessels endothelial function and inflammatory factors in patients with vascular dementia and type H hypertension.Methods:100 cases of patients with vascular dementia and type H hypertension accorded with the inclusion criteria were selected as research objects. They were randomly divided as the control group and the therapeutic group, 50 cases each. For control group, Enalapril tablets were administered by mouth for treatment. For therapeutic group, folic acid and vitamin B12 treatment were provided on the basis of treatment for control group. Treatments were continued for 12 weeks. Plasma Hcy levels, inflammatory factors [(interleukin-6 (IL-6), interleukin-8 (IL-8) and hypersensitive C reaction protein (hs-CRP)], blood vessels endothelial function indexes variation in patients before and after treatment were observed and detected.Results:Plasma Hcy, IL-6, IL-8 and hs-CRP levels in two groups of patients after treatment were significantly decreased comparing with the same group before treatment, and the above index levels in therapeutic group after treatment were significantly lower than control group (P<0.05);For comparison of blood vessels endothelial function indexes in the patients, NO levels in two groups after treatment were increased in various degrees, and endothelin-1 (ET-1) were decreased. The differences between levels of the two indexes in therapeutic group before and after treatment were significant, and levels after treatment in therapeutic group were significantly better than in control group (P<0.05). While variations of the differences in control group before and after treatment were not significant (P>0.05);After treatment, diastolic pressure and systolic pressure in the two groups of patients were significantly improved comparing with before treatment (P<0.05). However, after treatment, the differences of levels between therapeutic group and control group were not significant (P>0.05). MMSE score in therapeutic group after treatment was significantly higher than before treatment, and significantly higher than in control group (P<0.05).Conclusions: Combined therapy of folic acid and vitamin B12 for treating vascular dementia with type H hypertension could effectively decrease plasma Hcy and inflammatory factor levels, and improve blood vessels endothelial function and dementia degree on patients. It has certain clinical value which deserves to be promoted.

Achieving control of resistant hypertension:Not just the number of blood pressure medications

Resistant hypertension(RH) has a prevalence of around 12% and is associated with an increased risk of cardiovascular disease, progression to end-stage renal disease, and even mortality. In 2017, the American College of Cardiology and American Heart Association released updated guidelines that detail steps to ensure proper diagnosis of RH, including the exclusion of pseudoresistance.Lifestyle modifications, such as low salt diet and physical exercise, remain at the forefront of optimizing blood pressure control. Secondary causes of RH also need to be investigated, including screening for obstructive sleep apnea. Notably, the guidelines demonstrate a major change in medication management recommendations to include mineralocorticoid receptor antagonists. In addition to advances in medication optimization, there are several device-based therapies that have been showing efficacy in the treatment of RH. Renal denervation therapy has struggled to show efficacy for blood pressure control, but with a redesigned catheter device, it is once again being tested in clinical trials. Carotid baroreceptor activation therapy(BAT) via an implantable pulse generator has been shown to be effective in lowering blood pressure both acutely and in longterm follow up data, but there is some concern about the safety profile. Both a second-generation pulse generator and an endovascular implant are being tested in new clinical trials with hopes for improved safety profiles while maintaining therapeutic efficacy. Both renal denervation and carotid BAT need continued study before widespread clinical implementation. Central arteriovenous anastomosis has emerged as another possible therapy and is being actively explored. The ongoing pursuit of blood pressure control is a vital part of minimizing adverse patient outcomes. The future landscape appears hopeful for helping patients achieve blood pressure goals not only through the optimization of antihypertensive medications but also through device-based therapies in select individuals.

Hypertension, Autonomic Storm, Increased Counter Regulatory Hormones and Suppressed Insulin in Acute Myocarditis in Scorpion Envenoming Syndrome

Death due to scorpion envenoming syndrome is a common event in many of the tropical and non-tropical counties. Initial transient hypertension is commonly observed in scorpion sting victims. Scorpion envenoming causes autonomic storm resulting in initial transient hypertension followed by hypotension, cold clammy skin, hypothermia, cardiovascular disturbances, acute myocarditis, sarcolemmal defects, pulmonary oedema, acute pancreatitis, disseminated intravascular coagulation (DIC), Adult respiratory distress syndrome (ARDS), and many other clinical manifestations. All these manifestations could be due to sudden increase in catecholamines, angiotensin II, glucagon, Cortisol and either due to suppressed insulin secretion or insulin resistance and death. The sudden increase of metabolic A in counter-regulatory hormones along with either suppressed insulin secretion/or insulin resistance results in glycogenolysis in liver, cardiac and skeletal muscles causing hyperglycemia and a sudden increase in free fatty acid levels. Free Fatty Acids increase the susceptibility of the ventricles to the disorganized electrical behavior, inhibit cardiac sarcolemmal Na+-K+ ATPase activity, increase the tendency to intravascular thrombus, increase myocardial oxygen consumption, interfere with tropomyosin-troponin activation of Actin-Myosin coupling, show detergent effects on cell membranes and they could alter the stabilization of lysosomal membranes and probably become toxic to the myocardium. Based on our animal experiments in which insulin administration reversed the metabolic and ECG changes induced by scorpion envenoming and treating the poisonous scorpion sting victims with insulin, we consider that insulin has a primary metabolic role in preventing, counter-acting and reversing all the deleterious effects of FFA by inhibiting the catecholamine induced by lipolysis, and increasing intra-cellular K+, facilitating glucose transport to the myocardium and glucose metabolism through different pathways. Administration of insulin-glucose infusion to scorpion sting victims appears to be the physiological basis for the control of the metabolic response when that has become a determinant to survival. Treatment using continuous infusion of regular crystalline insulin should be given at the rate of 0.3 U/g glucose and glucose at the rate of 0.1 g/kg body weight/hour, for 48 - 72 hours, with supplementation of potassium as needed and maintenance of fluid, electrolytes and acid-base balance.

Meta-analysis of Integrated Traditional Chinese and Western Medicine in Treating H Type Hypertension

Objective: The aim of this study was to compare the clinical emcacy of integration of traditional Chinese medicine (TCM) and we stern medicine, and the western medicine therapy for H type hypertension. Methods: The randomized contmlled trials were collected via searching the internet. The literatures were screened according to inclusion and exclusion criteria. All the assignments were performed by two researchers. If there was disagreement between the two researchers, we would ask evidence based medicine expert for advice, to get an optimal result. The database included the ChianInfo (1978—2015), the Superstar database (1955—2017), the CBM(1985—2017), CNKI(1984—2017), PubMed(1966—2017). Accordingto Meta analysis, the RevMan 5.2 software was used to recover and analyze the literatures, and make the assessment of the integration of TCM and westem medicine in treating H Type Hypertension. Results: In the study, 12 trials were included. The total number of cases is 1139. The Meta analysis results showed that: Compared with western medicine the integration of TCM and western medicine would improve the antihypertensive efficacy [OR=0.39, 95%CI (0.25, 0.59), Z=4.38(P< 0.0001)],lower Hcy levels [WMD=-1.93, 95%CI (-2.27, 0.21), Z=4.38 (P< 0.0001)]. Conclusion: The combination therapy can effectively reduce Hcy levels, control blood pressure, better than Western medicine.

Women with overweight, mixed hyperlipidemia, intolerance to glucose and diastolic hypertension

Primarily healthy women who attended a practice of General Medicine were examined and coded data were evaluated using two statistical methods (n = 248, aged 36 ± 14 years). It was found that participants with LDL-related (mixed) hyperlipidemia showed higher blood pressure, a higher proportion of alcohol problems and/or smoking compared to normolipidemic women (p ≤ 0.05). These hyperlipidemic women who reported alcohol problems and/or smoking more often showed proteinuria and/or hematuria, rise of LDL/HDL, critical fasting blood glucose and lower HDL-cholesterol compared to hyperlipidemic women reporting healthy lifestyle (p ≤ 0.05). Likewise, high triglycerides were associated with rise of blood pressure and intolerance to glucose (p ≤ 0.05) and also with elevated total cholesterol. Alcohol-related hypertriglyceridemia overlapped with diastolic hypertension, rise of body weight and urine pathology, lowering of HDL-cholesterol and critical fasting blood glucose. The motivating message was that women with mixed hyperlipidemia and healthy lifestyle had functionally renal endothelium and healthy HDL-related baseline measures. Altogether, LDL-related hyperlipidemia and/or high triglycerides were correlated with diastolic hypertension whereby critical alcohol consumption declined renal endothelium and lowered HDL-cholesterol implicating baseline strategies to neutralize early risk factors.

Novel contributions of multimodality imaging in hypertension:A narrative review

Hypertension is currently one of the most prevalent il nesses worldwide,and is the second most common cause of heart failure,only behind ischemic cardiomyopathy.The development of novel multimodality imaging techniques in recent years has broadened the diagnostic methods,risk stratification and monitoring of treatment of cardiovascular diseases available for clinicians.Cardiovascular magnetic resonance(CMR) has a great capacity to evaluate cardiac dimensions and ventricular function,is extremely useful in ruling-out ischemic cardiomyopathy,the evaluation of the vascular system,in making the differential diagnosis for resistant hypertension and risk stratification for hypertensive cardiomyopathy and constitutes today,the method of choice to evaluate left ventricular systolic function.Computed tomography(CT) is the method of choice for the evaluation of vascular anatomy,including coronary arteries,and is also able to provide both functional and structural information.Finally,nuclear cardiology studies have been traditionally used to evaluate myocardial ischemia,along with offering the capacity to evaluate ventricular,endothelial and cardiac innervation function;information that is key in directing the treatment of the patient.In this narrative review,the most recent contributions of multimodality imaging to the patient with hypertension(CMR,CT and nuclear cardiology) will be reviewed.

Change of hs-CRP,sVCAM-1,NT-proBNP levels in patients with pregnancy-induced hypertension after therapy with magnesium sulfate and nifudipine

Objective:To investigate the change of the hs-CRP,sVC AM-1,NT-proBNP levels of the patients with pregnancy-induced hypertension(PIH) syndrome.Methods:A total of 200 patients with PIH were divided into mild,moderate and severe group,and 50 healthy pregnancy patients served as the control group.The serum sVCAM-1 levels were detected by enzyme-linked immunosorbent assay,hs-CRP were detected by immunity transmission turbidity,and NT-proBNP levels were determined by the colloidal gold method.Patients were treated with magnesium sulfate and nifudipine and the contrastive analysis was performed before and after treatment.And the pathological changes in placental of PIH patients were delected by hematoxylin-eosin staining at the same time.Results:The hs-CRP,sVCAM-l,NT-proBNP levels of patients in the mild, moderate and severe PHI group were significantly higher than that in the control group(P<0.05). The hs-CKP,sVCAM-l,NT-proBNP levels in the severe group were significantly higher than the mild group and the moderate group,the difference was statistically significant(P<0.05).The hsCRP,sVCAM-l,NT-proBNP of the moderate group were significantly higher than the mild group(P<0.05).There was a positive correlation between hs-CRP,sVCAM-1,NT-proBNP expression levels and the degree of the PIH.The expression of hs-CRP,sVCAM-1,NT-proBNP levels of the moderate and the severe group were significantly decreased(P<0.05).The number of placental villi and interstitial blood vessel in the moderate and severe PIH group were significantly less than the control group(P<0.05).Conclusions:The increased levels of serum hs-CRP,sVCAM-1, NT-proBNP may be involved in the process of vascular endothelial cell injury of the PIH,and the hs-CRP,sVCAM-1,NT-proBNP can be used as the auxiliary index for diagnosis of PIH and determination of PIH severity.

Glycyrrhizinate reduces portal hypertension in isolated perfused rat livers with chronic hepatitis

AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was replicated with CCl4 in rats for 84 d.Model was identified by measuring the ascetic amounts,hepatic function,portal pressure in vivo,splenic index,and pathological alterations.Inducible nitric oxide synthase(iNOS)in liver was assessed by immunohistochemistry.IPPRLs were performed at d0,d28,d56,and d84.After phenylephrine-induced constriction,Gly was geometrically used to reduce PHT.Gly action was expressed as median effective concentration(EC50)and area under the curve(AUC).Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads.RESULTS:PHT model was confirmed with ascites,splenomegaly,serum biomarkers of hepatic injury,and elevated portal pressure.Pathological findings had shown normal hepatic structure at d0,degenerations at d28,fibrosis at d56,cirrhosis at d84in PHT rats.Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development.Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis.Gly potencies were increased gradually along with PHT development,characterized with its EC50at 2.80×10-10,3.03×10-11,3.77×10-11and 4.65×10-11mol/L at d0,d28,d56and d84,respectively.Existed iNOS was located at hepatocyte at d0,stellate cells at d28,stellate cells and macrophages at d56,and macrophages in portal triads at d84.Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development.AUC values of Gly were positively correlated with existed iNOS levels in portal triads.CONCLUSION:Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis.The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.

Role of ROS/Kv/HIF Axis in the Development of Hypoxia-Induced Pulmonary Hypertension

Hypoxic pulmonary hypertension (HPH) is a common complication in patients with chronic obstructive pulmonary disease (COPD), sleep-disordered breathing, or dwellers in high altitude. The exact mechanisms underlying the development of HPH still remain unclear. Reactive oxygen species (ROS),hypoxia inducible factors (HIF), and potassium channels (KV) are believed as the main factors during the development of HPH. We propose that the “ROS/Kv/HIF axis” may play an important initiating role in the development of HPH. Being formed under a hypoxic condition, ROS affects the expression and function of HIFs or KV, and consequently triggers multiple downstream signaling pathways and genes expression that participate in promoting pulmonary vasoconstriction and arterial remodeling. Thus, further study determining the initiating role of “ROS/Kv/HIF axis” in the development of HPH could provide theoretic evidences to better understand the underlying mechanisms of HPH, and help identify new potential targets in the treatment of HPH.