Chronic heart failure (CHF) is a set of symptoms and physical manifestations caused by the inability of the heart to perform its normal contractile function and satisfy the blood needs of all organs. This dysfunction leads to a non-physiological adaptation of all body systems, including the skeletal muscles and the diaphragm. The myopathy found in patients brings symptoms such as fatigue and intolerance to exercise, with an entity not always attributable to cardiac function. Neuromuscular incoordination is one of the symptoms related to CHF, causing an increased risk of mortality and hospitalization. The article reviews diaphragmatic adaptation in the presence of CHF and seeks to emphasize the importance of the diaphragm in understanding skeletal muscle incoordination in patients. Myocardial infarction (MI) is the main presentation causing ischemic chronic heart failure (CHF) detection. In contrast, the most important causes leading to non-ischemic CHF are Myocardial infarction (MI), which is the main cause causing the due to metabolic dysfunction and hypertension . The preOsteoporosis is present in patients with cardiac dysfunction, with a high risk of bone fractures. A bone density decrease is an independent risk factor for developing CHF . The oveThe article reviews the non-physiological adaptation of the main respiratory muscle, highlighting some functions related to the neuromotor behavior of the patient. This information can help understand the patients needs better.Diaphragm adaptation in patients with CHFAfter an ischemic heart attack, before chronic dysfunction occurs, the diaphragm muscle on an animal model undergoes an alteration of the transcript of the ribonucleic acid (RNA) sequencing ,12. ThisThe importance of the diaphragm muscle in patients with CHF in neuromotor expressionWe know that patients with CHF suffer from neuromuscular incoordination. This condition leads to an increased risk of falls. Patients are approximately 43% more likely to fall than patients without CHF; muscle incoordination is a predictor of mortality and hospitalization . ApproxiApproximately 90% of the collected information will be carried to the NTS, while approximately 10% will be carried toward the spinal trigeminal nucleus. NTS will send the received afferents to the cerebellum and vestibular area. The cerebellum and the vestibular area will send back various information to the NTS, which, with the new directives acquired, will send afferents toward the limbic area and the M1 motor cortex ,20. The Future perspectiveConsidering that the non-physiological adaptation of the skeletal muscles and the diaphragm can be considered more important than the cardiac adaptation, the clinician should consider the patient's respiratory aspect . There iChronic heart failure (CHF) is a growing pathology, both due to the increase in the age of the population (aging) and thanks to the improvement of the clinical, pharmaceutical, and instrumental approaches. Many pathological systemic adaptations affect the patient with CHF, such as respiratory, metabolic, bone, and other dysfunctions. Among the non-physiological adaptations, the diaphragm muscle undergoes harmful alterations that cause further complexity to the patient's clinical picture, such as fatigue and neuromuscular incoordination. Each eupnoeic act stimulates a parasympathetic response which determines a more coordinated voluntary movement of the limbs and trunk. Considering that the diaphragm in patients with CHF undergoes different pathological alterations, we can assume that the increase in the patient's neuromotor incoordination can be traced back to the main respiratory muscle. Greater emphasis should be given to the diaphragm to understand the patient's clinical picture better.


Adverse systolic remodeling after ST-elevation myocardial infarction (STEMI) is associated with poor clinical outcomes. However, little is known about diastolic remodeling. The purpose of this study was to identify the factors leading to diastolic remodeling.Echocardiography was performed during hospitalization and at 4 months follow-up in 267 non-diabetic STEMI patients from the GIPS-III trial. As parameters of diastolic remodeling we used (1.) the E/e′ at 4 months adjusted for the E/e′ at hospitalization and (2.) the change in E/e′ between hospitalization and 4 months. Multivariable regression models correcting for age and sex were constructed to identify possible association of clinical and angiographic variables as well as biomarkers with diastolic remodeling.2:0.20). After adjustment for E/e′ during hospitalization only female gender, multivessel disease and higher glucose remained predictors of E/e′ at four months (R2:0.40). Lower myocardial blush grade, AST and NT-proBNP were independent predictors of a higher increase of E/e′ between hospitalization and at 4 months in a multivariable model (R2:0.08).Older age, female gender, hypertension, multi vessel disease, higher glucose and higher peak CK were independent predictors of higher E/e′ at 4 months in a multivariable model (ROur data supports the hypothesis that female gender, multivessel coronary artery disease, and microvascular damage are important predictors of adverse diastolic remodeling after STEMI. In addition, our data suggests that older age and hypertension prior to STEMI may have contributed to worse pre-existing diastolic function.Trial registration: NIH, NCT01217307. Prospectively registered on October 8th 2010, https://clinicaltrials.gov/ct2/show/NCT01217307.The online version contains supplementary material available at 10.1186/s12872-023-03064-7. Myocardial damage caused by myocardial infarction (MI) can lead to adverse cardiac remodeling which is associated with the development of heart failure and malignant arrhythmias . Heart fSeveral risk factors, notably hypertension and diabetes, have been identified as predictors of diastolic dysfunction in the general population , 10. HowThe current study is a predefined echocardiography sub-study of the GIPS-III trial. This randomized, double blind, placebo-controlled trial studied the effect of metformin on left ventricular ejection fraction (LVEF) in patients presenting with STEMI. Design of this study, baseline patient characteristics, primary outcomes and effect on diastolic function have been reported previously. In summary, between January 1, 2011 and May 26, 2013, patients presenting to the University Medical Center Groningen (UMCG) with STEMI who underwent successful PCI with implantation of at least 1 stent with a diameter of at least 3 mm were included. Important exclusion criteria were age younger than 18 years, previous myocardial infarction, known diabetes, inability to undergo magnetic resonance imaging and severe renal dysfunction. Patients were randomized to either metformin 500 mg twice daily or visually matching placebo twice daily, which started immediately after PCI. After 4 months of treatment patients underwent cardiac MRI to assess the primary endpoint, LVEF. Treatment duration of 4 months was chosen based on the presumption that the majority of myocardial remodeling occurs over the course of this critical period . Our resFor the current study, all patients from the GIPS-III study with reliable measurements of the ratio of transmitral early flow to early mitral annulus velocity (E/e′) were included.1c), total creatine kinase , myocardial band creatine kinase (CK-MB), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), high sensitive troponin T. Periprocedural angiographic assessments included: absence or presence of multi vessel disease, thrombolysis in myocardial infarction (TIMI) grade flow before reperfusion therapy, TIMI grade flow after reperfusion therapy and myocardial blush grade (MBG) after reperfusion therapy.Venous blood samples were taken at admission for standard blood analyses at the central laboratory of the UMCG. Blood analyses were repeated during hospitalization to determine enzymatic infarct size. The variables collected were age, gender, history of hypertension, history of hypercholesterolemia, smoking status, total ischemic time, heart rate, systolic blood pressure, diastolic blood pressure, hemoglobin, thrombocytes, leucocytes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, high-density lipoproteins, low-density lipoproteins, triglycerides, sodium, potassium, creatinin, ureum, glucose, glycated hemoglobin  were checked for correlation and when appropriate the variable with the weakest relation to the outcome was excluded from further analysis. Bootstrapping stepwise regression was used to narrow the remaining candidate set of variables that were associated with E/e′ at four-month follow-up. The bootstrap sample size was 266 (99.6% of the entire data set). Variables selected > 600 times were assumed to be accurate and included in the final multivariable model. The final multivariable predictive model for E/e′ at follow-up was adjusted for the E/e′ at hospitalization to identify variables that were associated with diastolic remodeling. All reported P values are two-sided, and a P value of < 0.05 was considered to indicate an independent association. All analyses were performed using Stata version 14.0 (StataCorp).Continuous variables are presented as mean ± standard deviation (SD) or median  for normally and non-normally distributed data, respectively. Non-normally distributed data was transformed using log-transformation. Outcome observations of median ± 5 times the standard deviation were considered extreme outliers and excluded from the cohort. Differences between groups were tested using two-tailed t test for normally distributed data and Wilcoxon rank-sum for non-normally distributed data. To identify possible association of clinical and angiographic variables as well as biomarkers with diastolic function at follow-up, multivariable regression models correcting for age and sex were constructed using our baseline parameters as well as LVEF during hospitalization. Linear regression was applied for outcome variables on a continuous scale and logistic regression was applied for binary outcome variables. The candidate sets of variables measured at baseline  patients underwent echocardiography both during hospitalization and at four months; 43 11%) of these patients only underwent echocardiography during hospitalization and 5 (1.3%) patients only at four months. E/e′ could be determined in 321 (85%) patients during hospitalization and in 319 (84%) patients at four months. 269 (71%) patients with measurements of E/e′ at both time points were eligible for the study analysis. Of these, 2 (1%) patients were recognized as extreme outliers and excluded from the cohort 267 (70%) patients with reliable measurement of E/e′ remained eligible for the final analysis . Patients with an E/e′ at 4 months above median were older, had a higher systolic blood pressure and were more likely to have a history of hypertension. Plasma level of glucose and NT-proBNP at baseline were also higher in patients with an E/e′ at 4 months above median. There were no differences in the prescription of cardiac medication at discharge between the two groups  years, 23% were females and 38% had an infarction of the left anterior descending artery. The baseline and hospitalization characteristics were compared between the patients with E/e′ at 4 months follow up above or below median . When adjusting this model for E/e′ measured during hospitalization, only gender, multivessel disease and glucose remained associated with E/e′ at 4 months (Table 2:0.40) suggesting that the effects of age, hypertension and infarct size might originate from prior to the measurements at hospitalization.Multivariable linear regression analyses of the baseline variables showed an age and gender independent positive correlation between E/e′ at 4 months with hypertension, multivessel disease, systolic blood pressure, glucose, NT-proBNP, peak CK-total and peak CK-MB, a negative correlation with potassium, and a positive trend with HbA1c and peak NT-proBNP Table . In a bo2:0.08).Analysis of the change in E/e′ between hospitalization and follow-up revealed an age and gender independent association of lower myocardial blush grade, AST, LDH, CK-total, CK-MB, NT-proBNP, and peak CK-MB with greater increase in E/e′, and a similar trend for peak CK-total Table . The mulTreatment allocation was not related to diastolic remodeling in either of the analyses.In this predefined echocardiographic sub study of the GIPS-III trial we found that female gender, multivessel disease, higher glucose, lower blush-grade but also lower AST and lower NT-proBNP were independently associated with adverse diastolic remodeling after STEMI.Our data adds to our understanding of cardiac remodeling after STEMI. Several previous studies reported on the factors associated with the development of reduced systolic function and identified infarct size and inflammatory markers as major determinants of systolic function after STEMI , 23. WheIschemia related factors have previously been reported to increase left ventricular diastolic chamber stiffness with resulting increase of diastolic pressures . Plasma In our results we report that LVEDD during hospitalization was higher in patients with E/e′ below the median. However, there was no difference in LVEDV during hospitalization between patients with E/e′ above or below the median even though LVEDD and LVEDV both provide an indication of LV size. Similarly, we report LVESV at follow-up to be higher in patients with an E/e′ above the median, while no difference was found in LVESD. Though these results seem conflicting it must be stated that diameters are obtained from a single dimension while volumes are obtained from two dimensions. As a result of this difference in methodology diameters and volumes cannot be compared 1:1.We found that older age and hypertension were associated with worse diastolic function at 4 months but not with diastolic remodeling in a 4-month interval after STEMI. This suggests that the effects of age and hypertension might have already affected diastolic function parameters in the first measurement. In epidemiological studies in the general population, age and hypertension have previously been observed to be independent risk factors for deterioration of diastolic function , 10.A major strength of our study is that diastolic function was a predefined secondary endpoint of GIPS-III for the trial and echocardiography was focused on obtaining diastolic parameters which were evaluated by a blinded observer in a core laboratory. Furthermore, we previously suggested that the experimental metformin treatment had no beneficial effect on diastolic function . HoweverOur data supports the hypothesis that female gender and multivessel coronary artery disease are important predictors of adverse diastolic remodeling after STEMI. Furthermore, our results implicate microvascular damage of the coronary arteries as a possible contributing factor to adverse diastolic remodeling. In addition, our data suggests that older age and hypertension prior to STEMI contribute to worse pre-existing diastolic function. These findings may carry implications for our understanding of the development of heart failure with preserved ejection fraction (HFpEF) in patients after STEMI,Additional files 1: Table S1. Discharge medication of all patients, and stratified by E/e′ below and above median at 4 months after STEMI. E/e′: ratio of transmitral flow velocity (E) to early mitral annulus velocity (e′).


Chronic kidney disease (CKD) is a highly comorbid condition with significant effects on vascular health and remodeling. Upper extremity veins are important in end-stage kidney disease (ESKD) due to their potential use to create vascular accesses. However, unlike arteries, the contribution of CKD-associated factors to the chronic remodeling of veins has been barely studied.We measured morphometric parameters in 315 upper extremity veins, 131 (85% basilic) from stage 5 CKD/ESKD patients and 184 (89% basilic) from non-CKD organ donors. Associations of demographic and clinical characteristics with intimal hyperplasia (IH) and medial fibrosis were evaluated using multivariate regression models.The study cohort included 33% females, 30% blacks, 32% Hispanics, and 37% whites. Over 60% had hypertension, and 25% had diabetes independent of CKD status. Among kidney disease participants, 26% had stage 5 CKD, while 22 and 52% had ESKD with and without history of a previous arteriovenous fistula/graft (AVF/AVG), respectively. Intimal hyperplasia was associated with older age , dialysis vintage > 12 months , and previous AVF/AVG creation . Upper quartile values of IH were significantly associated with diabetes , which demonstrated an additive effect with previous AVF/AVG history and longer vintage in exacerbating IH. Medial fibrosis also increased as a function of age  and among patients with diabetes . Age was the predominant factor predicting upper quartile values of fibrosis  independent of other comorbidities.Age and diabetes are the most important risk factors for chronic development of venous IH and fibrosis independent of CKD status. Among kidney disease patients, longer dialysis vintage, and history of a previous AVF/AVG are strong predictors of IH. Upper extremity vessels are the preferred sites for creation of hemodialysis accesses. Traditional and non-traditional risk factors in chronic kidney disease (CKD) are thought to induce structural changes that lead to wall stiffness and impair vasoactivity, affecting the capacity of vessels to remodel and mature after vascular access creation . UnfortuIntimal hyperplasia (IH) and imbalanced extracellular matrix (ECM) remodeling are implicated in the origin and progression of vascular diseases, and in postoperative complications after vascular surgeries , 5–10. CIn the acute or postoperative scenarios, IH is the main pathophysiological feature in arterial restenosis and vein graft disease , 16. VasIn this work, we embarked on a comparative analysis of upper vein morphometry in 131 veins from stage 5 CKD and end-stage kidney disease (ESKD) patients and 184 from non-CKD organ donors with moderate prevalence of other chronic comorbidities. We studied the associations of clinical characteristics with venous morphometry, and the specific roles of CKD and hemodialysis on these vascular changes. To our knowledge, this is the first systematic study of upper extremity veins in more than 300 CKD and non-CKD patients. This information may be valuable for the understanding of mechanisms driving postoperative remodeling of veins after access creation and for the design of preventive treatments and lifestyle interventions to improve vascular health in CKD patients.The CKD cohort consisted of 131 patients, who were undergoing surgery for AVF creation and enrolled in prospective studies previously reported by us , 18. Of later  and stored at –80°C. A 1–5 mm cross-section was fixed in 10% neutral formalin  before paraffin embedding and sectioning.The non-CKD cohort included 184 organ donors whose tissues were donated for research purposes through a collaboration with the Life Alliance Recovery Agency. Cross-sectional samples of upper extremity veins , approximately 2 cm in length, were obtained post mortem following organ procurement procedures. All veins were collected in RNAVein sections were stained with Masson’s trichrome for gross histomorphometric analysis. Medial fibrosis (% area of collagen), intimal area, and medial area were quantified using ImageJ  and color thresholding methods. Intimal hyperplasia (IH) was calculated as the intima/media area ratio to normalize for vein size differences due to anatomy or tissue shrinkage during formalin fixation and dehydration. Images were acquired using a VisionTek DM01 digital microscope . Operators blinded to the clinical data performed image digital processing and morphometric measurements.t-test. When normality criteria were not met, data were expressed as median and interquartile range (IQR) and compared using the Mann-Whitney test or Kruskal-Wallis tests with post hoc comparisons. Categorical values were compared using the Fisher’s exact test. Associations between binary clinical covariates  and continuous morphometry data  were evaluated using multivariate general linear regression models adjusted for age, sex, ethnicity/race, comorbidities, and type of vein. In addition, we evaluated associations between clinical covariates and upper quartile morphometry values (Q3-maximum). Continuous data were converted to binary status  based on the upper quartile values of the overall study population and analyzed using multivariate logistic regression models adjusted for the above characteristics. To examine the additive effects of CKD/ESKD and diabetes on upper quartile morphometry status, we used logistic regression models controlling for age. Results were considered significant when p < 0.05.Statistical analyses were performed using XLSTAT 2020.1.1  and GraphPad Prism 8.4.0 . Normally distributed data were expressed as mean ± standard deviation (SD) and compared using the Student’s The overall cohort had a mean age of 49 years (± 15) and was composed of 33% females, 30% non-Hispanic blacks, 32% Hispanics, and 36% whites . Over 60As expected, the CKD/ESKD subgroup was significantly older than non-CKD participants  and had higher prevalence of hypertension (98 vs. 36%) and diabetes (47 vs. 10%). There was also a different ratio of black to white individuals between the CKD/ESKD and non-CKD groups . Among kp < 0.0001), including patients with CKD5 status, ESKD with and without a previous AVF/AVG, and ESKD with dialysis vintage > 12 months (p = 0.046) and CKD/ESKD , specifically with history of a previous AVF/AVG and vintage > 12 months  and diabetes  in multivariate general linear regression models   . Combine= 0.013) , suggestIntimal hyperplasia and imbalanced ECM remodeling are histopathological changes associated with poor venous health , 19, 20.Our analysis of > 300 CKD and non-CKD veins indicates that IH and medial fibrosis are not unique to CKD/ESKD, and that both groups present overlapping ranges of these morphometric parameters. Both IH and medial fibrosis increase over time as a function of age. The positive association of age with both cellular and ECM changes agrees with the concept of vascular aging that is thought to affect arteries and veins –24. Age-The association of ESKD with increased IH is not at all surprising, but finally puts to rest a presumed notion based on comparisons with small numbers of non-CKD veins  , 32–35. Despite the significant effects of dialysis vintage in IH, we failed to find a consistent association between CKD/ESKD stages and chronic venous fibrosis. The risk of high medial fibrosis was significantly higher in patients with diabetes and CKD5 only with respect to non-diabetic CKD5 or shorter vintage ESKD patients, but not compared to the rest of the models, suggesting differential effects of ESKD stages on the venous ECM. These results contrast the widely known association of kidney disease with increased fibrosis of kidneys, heart, arteries, and other organ systems , 37. HowImportantly, our study demonstrated a broad influence of diabetes in the detrimental chronic remodeling of veins by exacerbating IH and increasing medial fibrosis. This finding is of interest given the treatable nature of hyperglycemia and the potential benefits in improving vein health. A relationship between diabetes and arterial IH and fibrosis has been previously reported , 41–43, The limitations of the study include the retrospective nature of the analyses, the lack of information on the onset of comorbidities for the CKD cohort, and the limited clinical records for organ donors which prevented us from analyzing the effects of other clinical factors. While statistical models accounted for both clinical and demographics factors, differences in the latter between the CKD and non-CKD groups may be a confounding factor to consider in future studies. Despite these limitations, to our knowledge, this is the first systematic analysis of vein morphometry in CKD and non-CKD individuals. This work improves our understanding of vascular aging and dialysis effects in upper extremity veins and identifies diabetes as a critical and manageable factor in the development of venous IH and medial fibrosis.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the University of Miami Institutional Review Board. The patients/participants provided their written informed consent to participate in this study.LM and RV-P contributed to the idea and study design. AS and MT were responsible for tissue collection. XL, ZZ, AC, CM, KM-P, and AA were responsible for tissue processing and data acquisition. XL, LM, and YP performed data analysis. XL, LM, and RV-P drafted the manuscript. LM, MT, AS, and RV-P were responsible for supervision and mentorship. MT, LS, and XY contributed fruitful discussions and clinical insights. All authors took part in the interpretation of the results and approved the final version of the manuscript.


Whether Mineralocorticoid receptor antagonists (MRA) reduce mortality and cardiovascular effects of dialysis patients remains unclear. A meta-analysis was designed to investigate whether MRA reduce mortality and cardiovascular effects of dialysis patients, with a registration in INPLASY (INPLASY2020120143). The meta-analysis revealed that MRA significantly reduced all-cause mortality (ACM) and cardiovascular mortality (CVM). Patients receiving MRA presented improved left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF), decreased systolic blood pressure (SBP) and diastolic blood pressure (DBP). There was no significant difference in the serum potassium level between the MRA group and the placebo group. MRA vs. control exerts definite survival and cardiovascular benefits in dialysis patients, including reducing all-cause mortality and cardiovascular mortality, LVMI, and arterial blood pressure, and improving LVEF. In terms of safety, MRA did not increase serum potassium levels for dialysis patients with safety.Systematic Review Registration: (https://inplasy.com/inplasy-protocol-1239-2/), identifier (INPLASY2020120143). Worldwide, approximately 2 million people receive dialysis for end-stage renal disease . End-staAt present, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are used in clinic to slow the maintain of RRF of patients. Although ACEIs are effective, the long-term application of these drugs may lead to aldosterone escape, and thus, they may not be able to completely inhibit the production of aldosterone . As a reDOI: 10.3776/inplasy2020.12.0143).This article is conducted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline  and regiTwo researchers (Zhang and Tuo) independently searched the PubMed, EMBASE and China National Knowledge Internet (CNKI) databases from inception to May 2020 by using medical subject headings (MeSH), Emtree, and text word with no language limitations.The following keywords were used for search strategy: “mineralocorticoid receptor antagonists”, “MRA”, “spironolactone”, “eplerenone”, “haemodialysis”, “ESRD”, “dialysis” and “hemodialysis” . ReferenTwo authors (ZY and Wb) independently carried out the primary review to search for trials that met the inclusion criteria . The folTwo reviewers (Li and Jiang) independently extracted data from the same set of publications. The following information were extracted: author, year, sample size, study design, dialysis solution, intervention, control group, follow-up and main results.p < 0.05 cutoff (Odds ratios (OR) with 95% confidence intervals (CIs) were used as the effect size measures of dichotomous data. Mean differences (MD) with 95% CIs were computed for continuous data. The weight of enrolled studies accounted for by taking into account of the size of treatment group, control group, and total sample size. Z-test was calculated and therapeutic efficacy was deemed significant with a 5 cutoff .The quality of all trials was evaluated independently by two authors (Zhang and Li) according to the Cochrane quality criteria (Fi1 S1). Any disagreement between the authors was settled by discussion with a third author (Tuo).2 and χ2 statistics. If there was significant heterogeneity, a sensitivity analysis was conducted to evaluate the consistency and quality of the results. Publication bias was evaluated using Begg’s and Egger’s tests.STATA 16.0  was used to perform statistical analyses. Labbe plot and meta-regression were used for intuitive judgment of heterogeneity. For remaining circumstances, a random effect model was used for pooling the effect size to calculate for statistical heterogeneity. Heterogeneity was analyzed by IA total of 321 literature were identified during the initial search, after excluding duplicate records (n = 35). Thirty-three articles were retained after title/abstract curation (excluding 288 records). Thereafter, we read the full text and enrolled 16 RCTs involving a total of 1,630 patients for quantitative synthesis . The maip < 0.01, 2 = 0%, Pooled analysis of 8 studies  demonstrates that treatment with MRA  may sign2 = 0%, p = 0.116, p = 0.039, The meta-regression by Bubble plot reveals no significant heterogeneity of the study size (Ip < 0.01)  demonstrates that the MRA treatment  may sign < 0.01) . No sign 2 = 0%, . The cho 2 = 0%, . Overall 2 = 0%, . Subgrou 2 = 0%, .2 = 0%, p = 0.134, p = 0.446, The meta-regression by Bubble plot reveals no significant heterogeneity of the study size (Ip = 0.01). No significant heterogeneity was observed . No significant heterogeneity was observed    and serum potassium were assessed. Our meta-analysis found that MRA vs. control exerts definite cardiovascular effects in dialysis patients, including reducing mortality and cardiovascular mortality, LVMI, and arterial blood pressure, and improving LVEF. And MRA for dialysis patients is with safety that did not increase serum potassium levels.It was once believed that aldosterone was secreted by adrenal cortical globular zone cells and that its regulation depended on the classic RAAS pathway . HoweverIn 2016, Quach  etc. fouMRAs are one of the cornerstones of therapy in HFrEF . HoweverOur analysis included a total of 1,630 patients across 16 RCTs. In our study, the results showed that a low dose of spironolactone (12.5–50 mg daily) could significantly improve the LVMI and LVEF of hemodialysis patients, reduce arterial blood pressure and improve the long-term survival rate without significantly increasing the serum potassium level. However, we also noticed that hyperkalemia occurs more frequently as the dosage increases to 50 mg daily. It seems that 25 mg daily is likely to be the best choice to strike a balance between the effects of the drug and its side effects, consistent with the findings of Zannad et al. . In addiHypertension is an important risk factor for cardiovascular disease and is very common in ESRD patients. In a cohort study with a large sample size, the prevalence of hypertension was found to be higher than 80% among patients with ESRD, and only approximately 30% of these patients had good blood pressure control . CurrentPrevious studies have shown that approximately 75% of maintenance hemodialysis patients have left ventricular hypertrophy and 40% have left ventricular insufficiency, and the incidence of cardiovascular and cerebrovascular events is significantly higher than that of normal left ventricular hemodialysis patients . The recWe used the LVMI and LVEF as evaluation criteria for left ventricular hypertrophy and left ventricular systolic function, respectively. Our meta-analysis found that spironolactone can reverse left ventricular hypertrophy and improve LVEF in patients with hemodialysis. In addition to the protective cardiovascular effects of lowering blood pressure and preventing heart remodeling, spironolactone also has unexpected benefits. Currently, it is generally believed that an increase in CIMT is an early manifestation of atherosclerosis, the degree of atherosclerosis can be evaluated early by detecting CIMT with ultrasound, and the risk of adverse cardiovascular and cerebrovascular events can be predicted. Vukusich et al.  found thWe noticed that previous published meta-analyses omitted important trials , Zhao’sStrikingly, the conclusion seems to be opposed to previous publications . Based o.More importantly, our results show that MRA significantly reduce ACM and cardiovascular mortality in hemodialysis patients. As mentioned above, spironolactone has multiple protective cardiovascular effects in patients with hemodialysis, and the possible mechanisms for its beneficial effects on long-term prognosis include diuretic and non-diuretic hypotension, the reversal of left ventricular hypertrophy, the improvement of cardiac systolic function, anti-atherosclerosis and the improvement of heart rate variability in patients undergoing hemodialysis .Firstly, our meta-analysis was performed by a Cochrane Member and supervised by strict quality control evaluated by Cohen’s kappa coefficient , which showed a high degree of agreement. Secondly, our study included 16 RCTs with more than 1,630 participants and conducted a comprehensive and thorough assessment of the risks of publication bias, sensitivity analyses, subgroup analyses, Begg’s plot, Egger’s test and meta-regression to ensure that the results were reliable. we attempted to be as inclusive and transparent in this manuscript in terms of our methods including all origin of software and websites. Thirdly, we refined our analyses strictly in accordance to the PICOS principle. Specifically, we conducted 5 subgroup analysis perform the effects of different dialysis methods, different MRA drug types and different countries, and refined the outcomes into 10 types.However, several limitations of our meta-analysis shall be considered. First, the true event rates of participants lost to follow-up are unpredictable and unlikely to be at either extreme of our assumptions. Second, the quality of several trials was not high, follow-up times were different, and the treatment doses were variable, which could have affected our conclusions. Third, the concomitant diseases of patients included in various institutes were different, which may lead to a risk of bias. Fourth, this meta-analysis did not include a particularly large number of RCTs and could have affected our conclusions. Despite statistical significance, the results should be interpreted cautiously, and further studies are needed to substantiate or refute these results before any changes to clinical practice or guidelines are made.Our meta-analysis demonstrated that MRA can effectively improve the dialysis patient’s heart function, reduce incidence of cardiovascular morbidity and mortality, including reducing mortality and cardio mortality, LVMI, and arterial blood pressure, and improving LVEF. and does not significant affect the potassium level. We hope that the results of our study will provide some reference for the prevention and treatment of cardiovascular diseases in dialysis patients.


A comparison of the area under the curve (AUC) profiles on multiple receiver operating characteristic curves of the DEGs in DKD and other renal diseases revealed that REG1A and RUNX3 had the highest specificity for DKD diagnosis. The AUCs of the combined expression of REG1A and RUNX3 in kidney (AUC = 0.929) and blood samples (AUC = 0.917) of DKD patients were similar to each other. The AUC of blood samples from DKD patients and healthy individuals obtained for external validation further demonstrated that REG1A combined with RUNX3 had significant diagnostic efficacy (AUC=0.948). REG1A and RUNX3 expression levels were found to be positively and negatively correlated with urinary albumin creatinine ratio and estimated glomerular filtration rate, respectively. Kaplan-Meier curves also revealed the potential of REG1A and RUNX3 for predicting the risk of DKD. In conclusion, REG1A and RUNX3 may serve as biomarkers for predicting the risk of developing DKD.Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Clinical features are traditionally used to predict DKD, yet with low diagnostic efficacy. Most of the recent biomarkers used to predict DKD are based on transcriptomics and metabolomics; however, they also should be used in combination with many other predictive indicators. The purpose of this study was thus to identify a simplified class of blood biomarkers capable of predicting the risk of developing DKD. The Gene Expression Omnibus database was screened for DKD biomarkers, and differentially expressed genes (DEGs) in human blood and kidney were identified  Approxi studies . Several studies . The sur studies . AlthougGenome-wide transcriptome analysis has been widely used in the field of DKD to help gain insight into disease pathogenesis, molecular classification and identification of biomarkers . These ghttps://www.ncbi.nlm.nih.gov/geo/), and performed gene ID and symbol conversions via Perl scripts  was used for data analysis and plotting. The “limma” R package  method, as implemented in the “glmnet” software package, was used for reduction of data dimensionality and selection of predictive features for DKD patients , 19. TheThe “ggstatsplot” package was used to perform Spearman correlation analysis of diagnostic markers and clinical features , and theKaplan-Meier (KM) curves were constructed using “survival” and “survminer” software packages to assess the probability of DKD occurring at specific time periods, and log-rank tests were used to determine differences between groups . The proA total of 141 human blood samples from patients with DKD, DM (without DKD), and healthy individuals, were collected from the biospecimen bank of Shenzhen People’s Hospital. The study was approved by the Ethics Committee of Shenzhen People’s Hospital. Data are expressed as mean plus/minus standard deviation (SD) or median and interquartile range for continuous variables and as percentages for categorical variables. The Mann-Whitney U-test or t-test was performed to compare the differences between the two groups depending on whether the data conformed to a normal distribution. Chi-square test was applied to compare frequencies. This work was approved by the Institutional Review Board and the Ethics Committee of the Shenzhen People’s Hospital (No. LL-KT-2018338) and informed written consent was obtained from all participants.△△Ct for gene expression. Gene-specific PCR primers are listed in Trizol (Invitrogen) was used to extract total RNA from peripheral blood mononuclear cells (PBMC) according to manufacturer’s instructions. Reverse transcription of RNA was performed using the RevertAid RT Reverse Transcription Kit (Thermo Fisher Scientific). Quantitative PCR was performed using PowerUp SYBR Green Master Mix (Thermo Scientific). The results were standardized using GAPDH. qPCR was conducted using an ABI 7500 real-time PCR system . Fold-change was determined as 2-ADRA2A), C-C motif chemokine 5 (CCL5), cholesterol 25-hydroxylase (CH25H), C-X-C chemokine receptor type 4 (CXCR4), hemoglobin subunit delta (HBD), hydroxycarboxylic acid receptor 3 (HCAR3), lysophosphatidylcholine acyltransferase 1 (LPCAT1), Lithostathine-1-alpha (REG1A), and Runt-related transcription factor 3 (RUNX3). The distribution of the expression profiles of these DEGs in the blood and kidney of DKD patients . A total of 16 DEGs were identified as diagnostic DKD markers  were found to have high diagnostic efficiency in blood samples (AUC > 0.70), except for CH25H (AUC =0.67)  and HC (n = 41) groups were included in the validation set , C-peptide (C-P), HbA1C, fasting blood glucose (FBG), and urinary albumin creatinine ratio (UACR) and negatively correlated with eGFR level (RUNX3 was positively correlated with UACR and SCr and negatively correlated with eGFR level (REG1A and RUNX3 expression levels were found to be positively correlated as well (r=0.3) (The DKD (n=50) and DM (without DKD) groups (n=50) in the validation set were used to analyze correlation between expression levels of diagnostic DEGs and clinical characteristics Table 3.REG1A, RUNX3, total cholesterol (TC), FBG, SCr, body mass index (BMI), and UACR, whereas elevated levels of high-density lipoprotein cholesterol (HDL-C), age, and eGFR indicated a positive prognosis   Figure 8In the present study, we found that serum RUNX3 and REG1A have potential as diagnostic markers for DKD. Patients with DM who have elevated expression of both RUNX3 and REG1A will have a much higher risk of developing DKD at about 10 years into the disease. Compared to existing studies of diagnostic markers for DKD , 27, we RUNX3 plays a downstream role in the TGF-β signalling pathway , insufficient sample size may have led to unreliable results. We plan to continue collecting blood from patients with chronic kidney disease in subsequent studies to determine the specificity of REG1A and RUNX3 were found to have high diagnostic efficacy for DK, which was proven through external validation. REG1A and RUNX3 levels were positively and negatively correlated with UACR and eGFR levels, respectively. Thus, the transcription levels of REG1A and RUNX3 in blood samples have potential to predict DKD risk.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Shenzhen people’s hospital. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.XW, HW and GY contributed equally to this work. XW, GY, HW and JX contributed to the acquisition of data, analysis and interpretation of data. SY and XW drafted the work or revised it critically for important intellectual content. LX, LZ, TL, and XZ, and LK analyzed the data and revised the article critically for important intellectual content. ZL and SY contributed to the conception and the study design. All authors gave their approval of the version to be published. All authors contributed to the article and approved the submitted version.This work was supported by grants from the National Key Research and Development Program of China (2018YFC2001100); the National Natural Science Foundation of China .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This study was aimed to examine the effectiveness of App-assisted self-care in a Beijing community based on intelligent family physician-optimised collaborative model (IFOCM) program. We conducted a survey of 12,050 hypertensive patients between Jan 2014 and Dec 2021. Generalized linear model was used to analyze the covariates that associated with blood pressure (BP) control. Decision tree and random forest algorithm was used to extract the important factors of BP outcome.The study included 5937 patients, mean age 66.2 ± 10.8, with hypertension in the baseline; 3108(52.4) were female. The community management resulted in mean systolic BP and diastolic BP reductions of 4.6 mmHg and 3.8 mmHg at follow-up. There were 3661 (61.6%) hypertension patients with BP control, increasing from 55.0% in 2014 to 75.0% in 2021. After adjusted for covariates, antihypertensive medication adherence, diabetes, and APP-assisted self-care were common predictors associated with BP control in GLM model and machine learning algorithm.Community management based on IFOCM program significantly improved BP control in hypertensive patients. APP-assisted self-care would be beneficial for the management of chronic disease.The online version contains supplementary material available at 10.1186/s12875-023-01965-2. Hypertension has become one of the most important causes of disease burden in the world . It is tSelf-management of blood pressure (BP), where patients management their own BP usually in a home environment, is an increasingly strategy of hypertension management , 10, whiWhen facing such large number of hypertensive patients, Chinese government launched the Basic Public Health Service Program in 2009 and Family Physician Program in 2016. Beijing was the earliest pilot city implementing the intelligent family physician-optimised coordination model (IFOCM) program in China . With thThis study was a community-based survey for patients with hypertension, performed by our community healthcare from Jan 2014 to December 2021. All patients having baseline record in the database of Beijing Primary Medical and Public Health Information System were initially considered for inclusion. Patients were included if they: (1) 18 years or older and diagnosed as having hypertension in the baseline; (2) had at least one follow-up record documented in the database; and (3) were not involved in other public health intervention program. Patients were excluded if they had severe neurological or psychiatric disorders; physical disability; and pregnancy hypertension. Informed consent from all subjects and/or their legal guardian was signed in the community health service center, and analysis was performed using deidentified data. The study was approved by the ethics committee of our community health service center. Deidentified data were extracted from the database, which included all patients with chronic diseases managed by community health service center. All individuals participated in baseline survey, physical examination, blood tests. The survey investigated the demographic characteristic, comorbidities such as hypertension, diabetes mellitus, coronary artery disease, and stroke. Physical examination included blood pressure, body weight, body height, waist girth, and hip girth. Blood tests assessed fasting blood-glucose and total cholesterol level. For residents participated IFOCM program, follow-up was conducted by team member in community. Follow-up information, such as systolic blood pressure (SBP), diastolic blood pressure (DBP), blood-glucose, blood lipid level, antihypertensive medication adherence, adverse drug reaction and follow-up date was recorded.2) was calculated as the weight (kg) divided by squared height (m), and obesity was defined as BMI ≥ 27 at follow-up. Waist-hip ratio was calculated as the waist girth divided by hip girth, the ratio ≥ 0.9 was defined as increased level. The follow-up time was calculated as the last recorded visit date subtract baseline date.Hypertension was diagnosed as a maintained SBP/DBP ≥ 140/90 mmHg, or receiving antihypertensive medications. Baseline and follow-up body mass index  and BP control rates . When treated BP as categorical outcome, we assessed the rates of patients with hypertension in control, which was according to the following definitions based on Chinese guideline . For hypWe used the random forest (RF) algorithm for the prediction of poor BP control of hypertension patients. RF is a machine learning algorithm that aggregates many predictions to reduce the variance and improve the robustness and precision of outputs . A remarThe statistical analysis was performed by Stata (v.16.0) and R software (v.3.6.3). For normally distributed continuous variables, the values are expressed as mean ± standard deviation (SD) and compared using a 2-sided t-test. The categorical variables are expressed as frequencies, and comparisons are made using the Chi-squared test or Fisher’s exact test when appropriate.To analyze the outcome of BP control levels, we estimated covariates that affect the values of SBP and DBP, a generalized linear model (GLM) was used to adjust for covariates including demographic characteristic, comorbidity, BMI, waist-hip ratio, baseline blood pressure, blood-glucose and total cholesterol level. Decreases in SBP and DBP in follow-up compared with baseline were considered dependent variables, whereas other covariates were considered independent variables. To analyze the outcome of BP control rates, we estimated covariates that associated with BP control in the GLM, poor BP control was considered dependent variable, and other similar covariates considered as independent variables were adjusted. Predictors of poor BP control manifested a statistical significance of P < 0.05 were subsequently utilized for different machine learning algorithm. Mean Decrease Gini (MDG) involved in RF algorithm with cross-validation was used to rank the important covariates with poor BP control.P = 0.004), BMI , waist  and hip ; with significantly lower baseline SBP  and DBP . APP-assisted self-care patients were more likely to be female , unmarried , native resident , urban citizen . Patients with APP-assisted also had more chronic diseases, including diabetes , coronary heart disease , and stroke  than those patients without.A total of 44,039 community residents were recorded in the database at the baseline. The community center has 12,050 hypertensive patients, accounting for 27.3% of the population , increased waist-hip ratio , diabetes , stroke , baseline date , APP-assisted self-care , antihypertensive medication adherence  and follow-up time  was associated with decreases in SBP level; increased waist-hip ratio , diabetes , baseline date , APP-assisted self-care , antihypertensive medication adherence  and follow-up time  was associated with decreases in DBP level.Univariate GLM analysis using the difference in SBP or DBP level between baseline and follow-up as the dependent variable reveled that age  and DBP reduction  compared to those without diabetic. Later baseline date was associated with significant lower SBP reduction  and DBP reduction . In those patients with APP-assisted self-care, the results suggested a significant reduction both in SBP level  and in DBP level . Similarly, for patients with antihypertensive medication adherence, significant reduction was also found in SBP level  and in DBP level .After adjusted covariates in the multivariable GLM analysis, the results revealed that patients with diabetic exhibited a significant SBP reduction , diabetes (P < 0.001), coronary artery disease (P < 0.001), stroke (P = 0.001), baseline date (P < 0.001), APP-assisted self-care (P < 0.001), antihypertensive medication adherence (P < 0.001), and follow-up time (P < 0.001) are important factors associated with poor BP control. After adjusted covariates in the multivariable GLM analysis, the results revealed that native resident , diabetes , coronary artery disease , stroke , baseline date , APP-assisted self-care , antihypertensive medication adherence  and follow-up time  are predictors for BP control.There were 3661(61.6%) hypertension patients with BP control, which increased from 55.0% in 2014 to 75.0% in 2021 .


Chronic hepatitis B cirrhosis is often accompanied by glucose metabolism disorder, and intestinal microbiota was closely related to both cirrhosis and diabetes. There are few studies on the role of intestinal microbiota in hepatitis B liver cirrhosis and diabetes mellitus (LCDM). The purpose of this study was to investigate the characteristics of intestinal microbiota in patients with LCDM and to evaluate the relationship between the severity of intestinal microbiota imbalance and clinical significance. α-diversity, β-diversity, and linear discriminant analysis (LDA) effect size (LEfSe) was performed; and the correlation between bacteria and clinical indexes was analyzed.  A case-controlled study was conducted. People who met the inclusion and exclusion criteria of chronic HBV-related liver cirrhosis (LC), LCDM, and healthy controls (HC) were enrolled in, and their fecal and blood samples were collected. The V3-V4 region of 16s rDNA gene of fecal microbiota was sequenced; the bioinformatics analysis including α diversity of intestinal microbiota in the LCDM decreased than that in the HC. The abundance of Proteobacteria, Streptococcus, Escherichia-Shigella, and Lactobacillus increased, while the abundance of Bacteroidota, Bacteroides, Prevotella, Faecalibacterium, and Lachnospira decreased in the LCDM compared with the HC. The abundance of Lactobacillus, Roseburia, and Veillonella and the degree of hepatitis B cirrhosis dysbiosis indicator (HBCDI) increased in the LCDM than in the LC. The abundance of Escherichia-Shigella, Veillonella, and Lactobacillus positively correlated with liver injury and fasting blood glucose (FBG) level. The abundance of Escherichia-Shigella, Veillonella, Streptococcus, and Lactobacillus increased more significantly when FBG and glycosylated hemoglobin level increased.  A total of 70 participants completed fecal and blood tests, including 20 HC, 20 LCDM, and 30 LC. The  Intestinal microbiota of patients with LCDM was significantly disordered, and the degree was more serious than that cirrhosis patients without diabetes. Hepatitis B virus (HBV) infection is a global health problem, and HBV-associated cirrhosis is one of the major causes of death worldwide . The livEscherichia coli and Veillonella positively correlated with the Child–Turcotte–Pugh (CTP) score, while the decrease in the abundance of Bacteroides negatively correlated with the CTP score [Recent studies found that the intestinal microbiota was closely related to chronic hepatitis B cirrhosis and DM –11. In hTP score . The chaTP score . In DM, TP score . TherefoThis was a case-controlled study approved by the Medical Ethics Committee of Beijing Ditan Hospital, Capital Medical University (DT-IRB-2018-04001). All participants were required to sign the informed consent to participate in the study. The study was executed following the standards recommended by the Good Clinical Practice (GCP) guidelines.They were over 18 years oldTheir HBsAg positive and/or HBV-DNA positive were more than 6 monthsTheir imaging examination suggested cirrhosis, portal hypertension, esophageal varices, splenomegaly, with or without ascites, without infection, hepatic encephalopathy, and gastrointestinal bleedingPatients with a diagnosis of hepatitis B cirrhosis were eligible for the study if they met the following criteria:They met the aforementioned diagnostic criteria for hepatitis B cirrhosisThey were previously diagnosed with type 2 diabetes or had more than two random blood glucose ≥ 11.1 mmol/L or fasting blood glucose (FBG) ≥ 7.0 mmol/L at different timesPatients with a diagnosis of LCDM were eligible for the study if they met the following criteria:The exclusion criteria were as follows: patients complicated by liver diseases such as alcoholic liver disease, autoimmune liver disease, fatty liver disease, and other viral liver diseases; patients who had systematically used antibiotics, probiotics, and proton pump inhibitors within 1 month before enrollment; and pregnant and lactating women.In addition, patients whose results of physical examination, blood routine, urine routine, liver function, kidney function, serological markers of HBV, and abdominal ultrasound were within the normal range, and those without heart, brain, kidney, and lung diseases, were selected as healthy controls (HC).All participants eligible for inclusion were required to provide demographic information and previous health status and record the eating habits for 1 month earlier. The fasting peripheral venous blood was collected on the day of enrollment. Also, fresh fecal samples were collected in a sterile stool retention box and transferred to a –80°C refrigerator for storage within half an hour.All blood samples were tested in the laboratory of Beijing Ditan Hospital, Capital Medical University, on the day of collection. The liver functions, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), total bilirubin (TBil), renal function (creatinine), and FBG, were examined using an automatic biochemical analyzer . The blood routine, such as white blood cells (WBC), red blood cells (RBC), blood platelets (PLT), and hemoglobin (HGB), was examined using an automatic blood cell analyzer . The prothrombin time was examined using an automatic blood coagulation analyzer . The serum markers of HBV  were analyzed using an automatic chemiluminescence analyzer . The HBV DNA load was examined using a gene amplification instrument and its supporting reagent .Total genomic DNA was extracted from the fecal samples by the cetyltrimethylammonium bromide method. According to the selection of the sequencing region (the 16S V3–V4 region), the barcode-specific primers  were used for polymerase chain reaction amplification. The PCR products were purified by agarose gel electrophoresis with a concentration of 2%, and the sequences with the main strip of 400–450 bp were chosen for further experiments. The sequencing libraries were generated using an Illumina TruSeq DNA PCR-Free Library Preparation Kit . The library quality was assessed with a Qubit@ 2.0 Fluorometer (Thermo Scientific) and an Agilent Bioanalyzer 2100 system. At last, the library was sequenced on an Illumina NovaSeq platform.α diversity index (Chao1 index and ACE index) was calculated using the QIIME software (version 1.9.1). The β diversity was used binary Jaccard distance principal coordinate analysis to evaluate the microbial structure and distribution. Venn diagram was drawn using the R software (version 2.15.3). The linear discriminant analysis (LDA) effect size (LEfSe) was used to screen different species between different groups. A log LDA score > 2 was the threshold of differential taxa.The t-test were used to compare the categorical variables and continuous variables between the groups. A P value < 0.05 indicated a statistically significant difference.The chi-square test, nonparametric test, and Student P = 0.966). In LC and LCDM, 22 patients (73.3%) and 14 patients (70%) received antiviral treatment for more than one year, and 8 patients (26.7%) and 6 patients (30%) received antiviral treatment for less than one year, respectively. There is no significant difference in antiviral treatment of LC and LCDM (P = 0.797). In LCDM, five patients (25%) were treated with insulin, four (20%) were treated with acarbose, one (5%) was treated with insulin combined with acarbose, one (5%) was treated with metformin, and nine (45%) controlled blood glucose through diet and exercise. The blood glucose levels at the time of enrollment are shown in P > 0.05). The FBG level in the LCDM group was significantly higher than that in the LC and HC groups (P < 0.05). Also, no significant differences were observed in the levels of AST and ALB, WBC counts, RBC counts, HGB level, PLT counts, and HBeAg between the LCDM and LC groups (P > 0.05). Although not all patients had HBV DNA load lower than the lowest detection limit, there was no significant difference in viral load between LC and LCDM group. Therefore, it indicated that the intestinal microbiota difference between the two groups was mainly due to the presence or absence of diabetes.A total of 79 samples were screened out, of which 5 complicated with other diseases and 4 with missing information were excluded. Finally, 70 enrolled participants completed the detection of 16SrDNA in blood and feces, including 20 cases of HC, 30 cases of LC, and 20 cases of LCDM . No infeα diversity of intestinal microbiota (Chao1 index and ACE index) decreased in the LC and LCDM groups compared with the HC group, but no significant differences were found between the LC and LCDM groups , Escherichia-Shigella , Lactobacillus , Blautia , and Akkermansia  increased, while the relative abundance of Bacteroidota, Bacteroides, Faecalibacterium, Prevotella, and Lachnospira decreased in the LCDM group , Roseburia , Veillonella , and Lactonifactor  increased while the relative abundance of Megasphaera decreased in the LCDM group compared with the LC group  and negatively correlated with PLT, ALB level, RBC count, and HGB . The abundance of Escherichia-Shigella, Veillonella, Lactobacillus, and Megasphaera also positively correlated with the FBG level . It indicated that the abundance of Escherichia-Shigella, Veillonella, and Lactobacillus correlated with not only liver injury indicators but also the FBG level   .n = 5) and the elevated blood glucose group . From the HC, the NG, to the EG group, the abundance of Bacteroidota tended to decrease, while the abundance of Verrucomicrobiota and Proteobacteria tended to increase  and an elevated glycosylated hemoglobin group . From the HC, the NH, to the EH group, the abundance of Verrucomicrobiota, Proteobacteria /(Ruminococcus + Prevotella + Bacteroides) [P < 0.001), indicating that the imbalance of intestinal microbiota increased in patients with LCDM.The degree of intestinal microbiota imbalance in patients with LCDM was evaluated using the HBCDI. HBCDI = (eroides) . The medA large number of bacteria are present in the human intestine; it is estimated that the gene of intestinal bacteria in the human body is 150 times that of the host gene , 17. TheFaecalibacterium, Bacteroides, Prevotella, and Lachnospira decreased in the LCDM group, all of which were butyric acid–producing bacteria [Escherichia coli, Streptococcus, and Lactobacillus increased in prediabetes and diabetes mellitus [Escherichia-Shigella, Streptococcus, and Lactobacillus increased in the LCDM group; the abundance of these bacteria positively correlated with the liver injury index. The abundance of Escherichia-Shigella and Lactobacillus also positively correlated with the FBG level. A recent study has shown that Escherichia coli-derived LPS can promote blood glucose disorder and adipose inflammation, delay intestinal glucose absorption, and increase the secretion of insulin and glucagon-like peptide [Roseburia and Akkermansia reduced in diabetes. However, in our study, the abundance of these two bacteria increased in the LCDM group. Some studies suggested that metformin treatment of diabetes increased the relative abundance of Akkermansia [Roseburia and Akkermansia.Compared with the HC group, the diversity and the relative abundance of bacteria , 21, whibacteria , 23. In mellitus . In this peptide . The proermansia . We analLactobacillus, Roseburia, and Veillonella increased in the LCDM group compared with the LC group. This was consistent with the findings of Ke et al. [Roseburia and Veillonella significantly correlated with hepatitis B-related liver cancer. Veillonella could decompose lactic acid to produce a short-chain fatty acid propionic acid [Roseburia is a butyric acid–producing bacterium [Another interesting finding of our study was that despite no difference in the diversity, still, some differences existed in the composition of intestinal microbiota between the LC and LCDM groups. The relative abundance of e et al. . In our nic acid  and alsonic acid , thus tracterium . Usuallyacterium . DiabeteIn our previous study, we constructed HBCDI, an index reflecting the degree of intestinal microbiota imbalance in patients with hepatitis B cirrhosis, to assess the severity of the liver disease. In this study, the HBCDI was used to evaluate the degree of intestinal microbiota imbalance. The study found that the intestinal microbiota in patients with LCDM caused more serious injury than that in patients with LC, which indicated an increase in the total number of potential pathogens. Therefore, we should pay more attention to the microbiota of patients with LCDM. Probiotics may be beneficial to blood glucose homeostasis, reduce pathological bacterial translocation in liver cirrhosis , and imp


Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most common complications of cardiac surgery procedures. In this study, the authors attempt to provide new data regarding the application of novel kidney injury biomarkers in the early diagnostics of CSA-AKI. 128 adult patients undergoing elective cardiac surgery procedures with the use of cardiopulmonary by-pass (CPB) were enrolled in this study. Novel kidney injury biomarkers were marked in the plasma and urine 6 h after weaning from the CPB. A significant difference in the postoperative biomarkers’ concentration between the AKI and no-AKI group was found, regarding plasma IL-8, plasma TNF-α and urine NGAL, normalized for creatinine excretion (NGAL/Cr). These were also independent predictors of CSA-AKI. An independent risk factor for CSA-AKI proved to be preoperative CKD. Plasma IL-8 and TNF-α, as well as urine NGAL/Cr, are independent early indicators of CSA-AKI and pose a promising alternative for creatinine measurements. The cut-off points for these biomarkers proposed in this investigation should be confronted with more data and revised to achieve a suitable diagnostic value. Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most common complications of cardiac surgery procedures, affecting approximately 25–30% of patients ,2. The KThe main issue concerning CSA-AKI diagnostics with serum creatinine is the massive fluid transfusion, mainly during cardiopulmonary by-pass. This involves a priming fluid of approximately 1500 mL, at least 500 mL of cardioplegic solution (assuming the use of lower volume blood cardioplegia) and intravenous fluids from anesthesia, which rarely account for less than 500 mL. This sums to at least 2500 mL of fluids administered to the patient during the operation. Additionally, there are fluids administered in the postoperative period. As a result of this considerable fluid intake, serum metabolites (including creatinine) become diluted. For this reason, it usually takes about 24 h for the serum creatinine to accumulate and meet the AKI criteria ,10. StudIL-6 is produced by myeloid cells together with interleukin 1 beta (IL-1 β) and TNF-α, which leads to an increase in IL-6 production through a positive feedback mechanism. This mechanism is so potent that the IL-6 level can increase as much as six orders of magnitude. This makes IL-6 a sensitive indicator of inflammation, infection and neoplasia growth ,19,20.IL-8 is another proinflammatory cytokine produced by mononuclear macrophages in systemic infections. Its increase is associated with higher mortality in patients with sepsis . It is aOne of the main pathophysiological mechanisms underlying AKI is renal ischemia followed by reperfusion (ischemia–reperfusion injury—IRI). The most important cytokine in this process is TNF-α, which acts by activating cyclooxygenase 2 (COX-2) . The majNGAL is secreted by the cells of the proximal kidney tubule, the ascending limb of the Henle loop and the collecting duct. NGAL, present in urine, is produced in the lungs, liver and leukocytes (including leukocytes that infiltrate kidneys) as a response to the inflammation process , which iKIM-1 is an orphan transmembrane receptor produced in substantial amounts in the proximal tubule subsequent to an injury . It can MMP-9 is dynamically expressed and activated in inflamed tissues, degrading the extracellular matrix proteins and taking part in tissue remodeling secondary to injury ,29. MMP-IL-18 is produced as an inactive precursor by macrophages, dendritic cells, epithelial cells, keratinocytes, chondrocytes and fibroblasts. In the kidneys, its primary sources are tubule epithelial cells ,32,33. AThe above-described biomarkers were incorporated into this investigation, as they have dynamic serum kinetics  or are secreted with urine , which makes them a noninvasive alternative to serum creatinine measurements. All of them were also proved to be reliable kidney injury indicators. An early diagnosis is vital for the rapid treatment of CSA-AKI and, as a consequence, for reducing morbidity and mortality due to postoperative renal failure ,38,39,40The overall prevalence of CSA-AKI in this study population was 32%. Most AKI cases were diagnosed 24 h after the operation (63.41%). After the 24th postoperative hour, the number of newly diagnosed AKI gradually decreased: 17.07% on the 2nd postoperative day, 12.2% on the 3rd and 7.32% in the next 48 h.The preoperative characteristics of the study population with regard to AKI occurrence are included in The overall preoperative incidence of chronic kidney disease (CKD) in this study population was 17.19%, out of which 68.18% was KDIGO 3a stage, and the remaining 31.82% was KDIGO 3b stage.p = 0.034). The percentage of patients who underwent isolated coronary artery by-pass grafting and isolated valvular surgeries did not differ significantly between the groups . There was no difference between the total CPB time and aortic cross-clamp time between the AKI and no-AKI group .In the AKI group, there was a higher percentage of patients who underwent complex procedures : 26.83% ; A positive correlation was observed between the patients’ age and some biomarker concentrations. Additionally, a negative correlation existed between some of the biomarkers and preoperative kidney function, as well as the mean hematocrit value during CPB—Multivariable logistic regression was applied to adjust the analysis for potentially confounding factors . According to this analysis, the independent predictors of CSA-AKI were high plasma TNF-α, high plasma IL-8 and high urine NGAL/Cr. An independent risk factor for CSA-AKI proved to be preoperative CKD. There was a positive correlation between plasma IL-8 and plasma TNF-α, hence the loss of statistical significance for these biomarkers when incorporating them into one logistic regression model. For this reason, two different logistic regression models were calculated, as presented in p-value < 0.001). The results of the analysis are presented in Receiver operating characteristic (ROC) analysis was conducted to assess the biomarkers’ potential to serve as a diagnostic tool. Plasma IL-8, plasma TNF-α and urine NGAL/Cr proved to be the most suitable AKI indicators  ,42. ConsNumerous studies report elevated levels of novel kidney injury biomarkers in patients with postoperative AKI ,44,45,46In this study, the authors wanted to provide transparent, up-to-date data concerning adult post-cardiac surgery patients, and so, all the current standards in this field of investigation were kept .® technology used in this investigation was proven to have high reliability in the field of kidney injury research [Despite a modest sample size, the authors provided cut-off points for the most promising biomarkers as a step toward the clinical application of this research. The Luminexresearch . It is, As demonstrated by Youden’s index , the results of this study cannot be yet introduced to clinical practice. A larger patient cohort is required to improve the sensitivity and specificity of these tests. However, considering the favorable kinetics of these biomarkers and less invasive testing methods compared to serum creatinine (regarding NGAL), further endeavors in this field are highly recommended. In more than half of this study population, AKI could have been diagnosed up to four times faster if biomarkers were used instead of creatinine measurements. In the rest of the patients, the diagnosis could have been made even so much as days earlier. This lost time is a severe handicap for the kidneys striving to regenerate from injury, as it delays introducing a proper treatment.Two essential issues concerning introducing novel biomarkers to routine diagnostics are poor testing standardization and high cost. Nonetheless, these obstacles can be overcome if sufficient data are gathered and the testing becomes more widespread.While the main objective of this study was to provide new data regarding novel kidney injury biomarkers, other observations were made during this research. Older age, lower intraoperative hematocrit value and poorer preoperative kidney function are all known risk factors for CSA-AKI. In this study the authors demonstrated that they also directly correlate with the postoperative biomarkers’ concentrations. This suggests that these factors enhance kidney damage during cardiac surgery and should not be underestimated even in the absence of clinically evident AKI.A cohort of 128 adult patients undergoing elective cardiac surgery procedures with the use of CPB were enrolled in this study over a 24-month period. Regional Bioethical Committee approved the study protocol and conditions (document’s signature: KB-0012/45/2021). Informed consent was obtained from each patient prior to the enrollment.Qualification for an elective cardiac surgery procedure with the use of CPB;Written consent for study enrolment.Inclusion criteria:2);End-stage renal disease  within 6 h after the procedure.Exclusion criteria:Blood and urine samples were collected from the patients 6 h after weaning from CPB. Blood was collected from the radial artery using S-Monovette 3.4 mL sterile containers . Urine was collected directly from the Foley catheter using standard non-sterile urine containers. After the collection, blood and urine samples were stored at 5 °C for no longer than 4 h and subsequently centrifuged . After centrifugation, 1 mL of supernatant was taken and stored at −70 °C for no longer than six months.® Bead Washing device was used to wash the samples. The microplates were placed on the separator for 1 min, after which the remains not attached to the magnet were removed. Subsequently, 100 μL of the wash buffer was added to each well and incubated for 1 min, after which the remains not attached to the magnet were once again removed. This last step was repeated three times.Quantitative assessment of IL-6, IL-8 and TNF-α (in plasma), as well as NGAL, KIM-1, IL-18 and MMP-9 (in urine) levels in patients enrolled in this study was performed using Luminex xMAP technology . The first measurements using urine samples were carried out on the native urine form, and the results obtained exceeded the upper detection limit for this assay. Due to that, an optimization process was conducted in order to determine the optimal dilution for all samples. The following dilutions were selected as optimal: 1:2 (for NGAL and KIM-1) and 1:10 (for IL-18 and MMP-9). Plasma samples were tested in their native form. Thawed samples were centrifuged  immediately before use. The analysis was conducted according to manuals provided with the multiplex reagent kit  using the Luminex 100 analyzer and Xponent 4.2 Build software. On a microplate, 50 μL of samples were incubated in each well with a 50 μL diluted microparticle cocktail for 2 h at room temperature on a horizontal orbital microplate shaker (0.12” orbit) set at 800 ± 50 RPM. A magnetic Manual MagPlex® standards. Concentrations of the analyzed biomarkers were calculated based on a standard 6-point curve.In this step, 50 μL of a diluted Biotin-Antibody Cocktail were then added to the wells and incubated for 1 h at room temperature on the shaker (800 ± 50 RPM). Microplates were washed again. In this step, 50 μL of diluted Streptavidin-PE were added and incubated for 30 min at room temperature on the shaker (800 ± 50 RPM). Microplates were washed again. The microparticles were then resuspended by adding 100 μL of the wash buffer and incubated for 2 min on the shaker (800 ± 50 RPM). The microplates were read within 90 min using the LuminexCreatinine concentration was also determined in the urine samples to normalize the urinary biomarkers’ concentrations to creatinine excretion. Creatinine was measured in the defrosted urine samples after 12 h of storage in a dark and cooled compartment (5 °C). A kinetic colorimetric test based on Jaffe’s method was used to measure the creatinine concentration in urine .A quantitative assessment of the protein level in the urine samples was not conducted as there was, at most, a trace amount of protein present in the samples. Such an amount of protein was deemed insignificant as it does not interfere with the biomarker’s level measurement. Postoperative AKI was diagnosed according to the KDIGO criteria (≥0.3 mg or 50% increase in serum creatinine within 48 h or diuresis < 0.5 mL/kg/h for at least 6 h) until the 5th postoperative day. Serum creatinine was measured on the day preceding the operation, on the 1st postoperative day and, subsequently, every 48 h.p < 0.05 were considered statistically significant. Calculations were performed with Statistica 13 program.Fisher’s exact test was used to compare qualitative variables between the groups. Since most quantitative variables were non-normally distributed, they were presented as median (M) and interquartile range (Q1–Q3). Following, non-parametric tests were used: Mann–Whitney test for differences between the groups and Spearman’s rank correlation coefficient for correlations between the parameters. Multivariable logistic regression was used to find independent predictors of AKI with normalizing logarithmic transformation of biomarker concentrations. Receiver operating characteristic (ROC) analysis was conducted to estimate the diagnostic value of the biomarkers in relation to AKI prognosis. The suggested cut-off points were based on the maximization of Youden’s index. Associations with The objective of this study was to assess the utility of novel kidney injury biomarkers in the early diagnostics of CSA-AKI.Plasma IL-8 and TNF-α, as well as urine NGAL/Cr, are independent early indicators of CSA-AKI and pose a promising alternative for creatinine measurements. Cut-off points for these biomarkers proposed in this investigation should be confronted with more data and revised to achieve a suitable diagnostic value. Future investigations in this area should focus on providing specific data to improve these biomarkers’ clinical performance.


Purpose: The study aimed to evaluate the effect of intraocular pressure (IOP) reduction on macular and peripapillary microcirculation in patients with Posner–Schlossman syndrome (PSS) by optical coherence tomography angiography (OCTA).Methods: A prospective comparative study was conducted. Patients diagnosed with PSS at the Eye Center of Xiangya Hospital, Central South University, from February 2020 to November 2021 were consecutively included. OCTA was used for the macular and peripapillary microcirculation measurements, and optical coherence tomography (OCT) was employed for the retinal nerve fiber layer (RNFL) and lamina cribrosa depth (LCD) measurements. The patients received OCT and OCTA examinations at baseline and 1 week post-treatment when the IOP was under control. Changes in macular and peripapillary microcirculation, RNFL, and LCD were calculated for all the analyzed areas.Results: Twenty-one eyes from 21 patients were included in the study. Pre-treatment and post-treatment IOP were 43.17 ± 10.36 mm Hg  and 17.17 ± 2.85 mm Hg , respectively. No statistically significant changes were detected in RNFL, LCD, or macular and peripapillary microcirculation after significant IOP reduction.Conclusion: The results suggested that a large IOP reduction may not result in a significant increase in peripapillary and macular capillary perfusion in patients with PSS. Up until now, how the changes in intraocular pressure (IOP) affect the retinal blood flow has not been completely demonstrated.2. IOP reduction might not result in a significant increase in peripapillary and macular capillary perfusion in patients with Posner–Schlossman syndrome (PSS).3. The defects in the neural structure of the patients, such as lamina cribrosa (LC) displacement and retinal nerve fiber layer (RNFL) thinning, but not changes in IOP itself, may be more responsible for the changes in the retinal blood flow.Elevated intraocular pressure (IOP) is the major risk factor for glaucoma, and IOP reduction is the only proven way to slow down the disease progression  Heijl e. In addiObservation of hemodynamic changes in macular and peripapillary circulation in response to changes in IOP may provide some clues to understanding the pathogenesis of glaucoma. Since its introduction in 2012, optical coherence tomography angiography (OCTA) has shown better performance in the quantitative assessment of retinal vasculature than conventional angiography. It can provide noninvasive, rapid, detailed, reproducible, quantitative information about the microcirculation of ONH and retina . TherefoCurrently, the scleral suction cup , darkrooPSS is a special type of glaucoma that is characterized by recurrent, acute attacks of mild, unilateral, nongranulomatous anterior uveitis accompanied by markedly elevated IOP. During the acute attacks, IOP is always markedly high (the mean IOP in published studies varies from 42.77 to 49.2 mm Hg), and the high IOP can remain for several days . ContinuA prospective comparative study was conducted at the Eye Center of Xiangya Hospital, Central South University, from February 2020 to November 2021. The clinical study registration number was ChiCTR2100050912. A total of 21 patients diagnosed with PSS were consecutively included. The diagnostic criteria for PSS were as follows: 1) transient episode of elevated IOP; 2) mild anterior chamber inflammation and/or a few small-to-medium, discrete, round, white keratic precipitates (KP), accumulating in the lower half of the cornea, without iris posterior synechiae ; 3) deepAt the initial visit, all of the subjects underwent a comprehensive ophthalmologic examination, including best corrected visual acuity (BCVA), slit-lamp examination, gonioscopy, IOP measured by Goldmann applanation tonometry, fundus examination, axial length measurement , VF test , spectral domain (SD)-OCT , and blood pressure examination. A history of smoking, diabetes, hypertension, and the use of systemic and ocular medications were recorded. After the initial evaluation, 0.01% prednisolone (four times a day), 0.5% timolol (twice a day), and 0.2% brimonidine eye drops (twice a day) were given to control the IOP. At 1-week follow-up, BCVA, slit-lamp examination, fundus examination, IOP measurement, VF test, OCT, and OCTA examination were performed. The blood pressure was measured right before the OCTA examination.LCD was measured with SD-OCT  at the initial visit and at the 1-week follow-up. To determine LCD, five B-scans were selected from the three-dimensional image dataset of SD-OCT . The fivAll of the subjects underwent SD-OCTA examinations using CIRRUS AngioPlex 5000 equipment . Two OCTA scans of the macula and papilla were performed consecutively with a 1 min interval between the tests. These examinations were performed by a trained ophthalmologist (J.Y.) in a masked manner without knowledge of the results of the other examinations.TM (software version 10.0.0.14618) were the macular vascular length density  and vessel perfusion density .At the macula, a 6 mm × 6 mm volumetric macular superficial retinal vessel image that consisted of vessels from the layer of the inner limiting membrane (ILM) to the inner plexiform layer (IPL) was obtained. The system software divided macular images into three regions, namely, a central circle (1 mm radius from the fovea), an inner circle (1–3 mm radius from the fovea), and an external circle (3–6 mm radius from the fovea) . The parTM automatically segmented a ring  limited by an internal and external radius of 2.0 and 4.5 mm, respectively, which was, in turn, subdivided into four quadrants   . For thiPoor quality scans with signal strength index (SSI) values of less than 8 were excluded from the study.t-test. Differences were considered to be significant if p values were lower than 0.05.Statistical analyses were performed in SPSS software . Data were represented as mean ± standard deviation. Measurements obtained before and after treatment were compared using the paired p < 0.001), and the mean reduction of IOP was 26.05 ± 7.91 mm Hg (60.3%). The number of KP reduced, and BCVA improved significantly (p < 0.001), but the RNFL thickness, VF, LCD, and blood pressure did not change significantly   , 2.In this study, we investigated macular and peripapillary OCTA parameters in PSS patients. Our data showed that although the reduction in IOP was 26.05 ± 7.9 mm Hg (60.3%), neither the papillary nor the macular vessel density measured by OCTA displayed any changes. These findings indicate that patients with PSS might have strong retinal autoregulation to maintain the blood flow in the ONH and macula under remarkably elevated IOP for several days. To our knowledge, this is the first study to investigate the effect of IOP reduction on the retinal microcirculation in patients with PSS.The autoregulation of blood flow in the eye is the ability to maintain ocular blood flow at a constant level despite alterations in ocular perfusion pressure. Autoregulation of the ocular blood flow in response to the changes in IOP has been investigated in many studies, and most of them have shown that the blood supply to the retina and ONH is well autoregulated. Wang et al. found that the ONH blood flow remained at a constant level within a range of ocular perfusion pressure of 41 mm Hg and above in normal and experimental glaucoma monkeys . Riva anNevertheless, some studies have shown a significant increase in the retinal vessel density after a mild-to-moderate IOP decrease in glaucoma patients as quantified by OCTA. Two studies have shown a significant increase in the peripapillary vessel density 3 months after trabeculectomy, with an average IOP decrease of 14 and 18 mm Hg . Hollo sAn interesting study carried out by Recently, multiple studies have suggested that the vessel density loss occurs later than neural structural changes in glaucoma patients and may be a consequence of a neural structure defect . Si Bum A limitation in our study was that the selected PSS patients displayed no damage in their visual field and the thickness of RNFL. Since some patients with PSS may have optic nerve injury after several high IOP attacks , we shouIn conclusion, patients with PSS did not show significant changes in the peripapillary and macular capillary vessel density after a marked IOP reduction. The results indicated that elevated IOP is not the key factor that directly influences retinal perfusion in patients with PSS. The defects in the neural structure of these patients, such as LC displacement and RNFL thinning, but not changes in IOP itself, may be responsible for the changes in the retinal blood flow.