Association of blood pressure variability with target organ damage in older patients with essential hypertension

Background:Although multiple measures of blood pressure variability(BPV)have been proposed,whether they are better than mean blood pressure in predicting target organs is unclear.We aimed to determine the relationship between short term BPV and target organ injury.Methods:This study was a retrospective study,and 635 inpatients in the Department of Cardiology from 2015 to 2020 were selected.We divided participants into four groups on the basis of the quartiles of BPV.One-way analysis of variance was used to compare the differences between the groups,and linear regression was used to analyze the relationship between BPV and target organ damage.Results:The average age of 635 patients was 74.36±6.50 years old.Among them,354 of 627 patients had diminished renal function(56.5%),221of 604 patients had associated left ventricular hypertrophy(36.6%),and 227 of 231 patients had carotid plaque formation(98.3%).The baseline data indicated significant differences in fasting glucose,total cholesterol,low-density lipoprotein,creatinine,glomerular filtration rate,sex,calcium channel blocker use,and the rate of diminished renal function.Multiple linear regression analysis showed that BPV was negatively correlated with renal injury(creatinine:r=0.306,p<0.01;estimated glomerular filtration rate:r=0.058,p<0.01),and BPV is positively correlated with cardiac injury(r=0.083,p<0.01).Elevated BPV was not found to be associated with vascularinjury.Conclusion:Renal function decreases with increasing BPV and left ventricular mass increases with increasing BPV.

Effects of enteral nutrition with different energy supplies on metabolic changes and organ damage in burned rats

Background:Enteral nutrition(EN)is an important treatment for burn patients.However,severe gastrointestinal damage caused by major burns often leads to EN intolerance.Trophic EN solves this problem basically,but how to transition from trophic EN to standard EN smoothly is still a challenge in burn clinical nutrition.The aim of this study is to investigate the effects of EN with different energy supplies on metabolic changes,organ damage and prognosis in burned rats.Methods:Different feeding regimens were designed based on the continuous monitoring of resting energy expenditure in rats.Thirty-two Sprague-Dawley rats were randomly divided into a normal control group,burn+50%REE group,burn+75%REE group and burn+100%REE group.At the end of a nutritional treatment cycle(14th day),nuclear magnetic resonance spectroscopy,blood biochemistry analysis and quantification of subscab bacteria were performed to explore the differences in metabolic changes,degrees of organ damage and prognoses between the groups.Results:Sixteen metabolites involving seven metabolic pathways were identified from the different energy supply groups.After burn injury,resting energy consumption and body weight loss increased obviously.Meanwhile,weight loss was inversely related to energy supply.The greatest changes in the degree of organ damage,the level of plasma proteins,lipids and endotoxins,as well as the quantification of subscab bacteria were observed in the 50%REE group,followed by the 75 and 100%groups.Conclusions:Achieving an early balance between energy supply and expenditure is conducive to mitigating metabolic disorders and improving prognosis after burn injury.

End-organ protection in hypertension by the novel and selective Rho-kinase inhibitor, SAR407899

AIM: To compare the therapeutic efficacy of SAR407899 with the current standard treatment for hypertension [an angiotensin converting enzyme(ACE)-inhibitor and a calcium channel blocker] and compare the frequency and severity of the hypertension-related end-organ damage. METHODS: Long-term pharmacological characterization of SAR407899 has been performed in two animal models of hypertension, of which one is sensitive to ACE-inhibition and the other is insensitive [deoxycorticosterone acetate(DOCA)]. SAR407899 efficiently lowered high blood pressure and significantly reduced late-stage end organ damage as indicated by improved heart, kidney and endothelial function and reduced heart and kidney fibrosis in both models of chronic hypertension. RESULTS: Long term treatment with SAR407899 has been well tolerated and dose-dependently reduced elevated blood pressure in both models with no signs of tachyphylaxia. Blood pressure lowering effects and protective effects on hypertension related end organ damage of SAR407899 were superior to ramipril and amlodipine in the DOCA rat. Typical end-organ damage was significantly reduced in the SAR407899-treated animals. Chronic administration of SAR407899 significantly reduced albuminuria in both models. The beneficial effect of SAR407899 was associated with a reduction in leukocyte/macrophage tissue infiltration. The overall protective effect of SAR407899 was superior or comparable to that of ACE-inhibition or calciumchannel blockade. Chronic application of SAR407899 protects against hypertension and hypertension-induced end organ damage, regardless of the pathophysiological mechanism of hypertension. CONCLUSION: Rho-kinases-inhibition by the SAR407899 represents a new therapeutic option for the treatment of hypertension and its complications.

Multi-Organ Pathogenesis and Therapeutic Strategies for Cystic Fibrosis

Cystic Fibrosis (CF) is the most common lethal autosomal inherited disorder that affects all races and ethnicities in the United States. However, it is mostly predominant in the Caucasian populace accounting for about 80% of all CF cases. CF most severe complication can be referred to as pulmonary bronchiectasis and infections of the airways, nonetheless, the devastating effects of the disease have far-reaching consequences beyond lung damage. CF is a heterogeneous disease that is caused by mutations in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. The impairment or absence of this gene can affect multiple organs and systems and is characterized not only by chronic lung blockage, infections, and inflammation but also by exocrine gland dysfunction, intestinal obstruction, liver pathology, elevated sweat chloride concentration, and in males, infertility due to the congenital bilateral absence of the vas deferens. To this end, we briefly explore the pathological effects of CF and how CF mediates the destruction of several critical organs in the body and some of the gene therapeutical approaches such as gene editing and viral-based strategies available for the treatment of this multi-organ disease.

Biomarkers of graft-vs-host disease:Understanding and applications for the future

Hematopoietic stem cell transplantation(HSCT)is widely performed as a treatment for malignant blood disorders,such as leukemia.To achieve good clinical outcomes in HSCT,it is necessary to minimize the unfavorable effects of acute graft-vs-host disease(GVHD)and induce the more tolerable,chronic form of the disease.For better management of GVHD,sensitive and specific biomarkers that predict the severity and prognosis of the disease have been intensively investigated using proteomics,transcriptomics,genomics,cytomics,and tandem mass spectrometry methods.Here,I will briefly review the current understanding of GVHD biomarkers and future prospects.

Nanomaterials disrupting cell-cell junctions towards various diseases

As the continuous development of the industrial revolution,nanomaterials with excellent characteristics have been widely applied in various fields,greatly increasing the probability of human exposure to nanomaterials and the concerns about the potential nanotoxicity.Existing studies have shown that the toxicity of nanomaterials may be closely related to oxidative stress,inflammatory response,phagocytosis dysfunction,DNA damage,etc.Based on our focus,nanomaterials may cross the human barrier through various channels and disrupt various cell-cell junctions,while the integrity of cellular barrier is a necessary for the normal physiological function of various organs.However,until now,there is still a lack of systematic discussion in this field.This review illustrates the importance of cell-cell junctions in maintaining various organ functions and highlights the mechanism of various nanomaterials disrupt cell-cell junctions,as well as the possible damage to various organs,such as brain,eye,lung,breast,intestine,placenta,testis,heart,liver,kidney,skin,etc.Awareness of the potential negative effects of nanomaterials will help scientists deeply understand the limitations of nanotechnology,inspiring them to develop safer and more efficient nanomaterials for future personalized nanomedicine.