Chronic Disease Research Articles

Advancements in Research on Genetic Kidney Diseases Using Human-Induced Pluripotent Stem Cell-Derived Kidney Organoids

Genetic or hereditary kidney disease stands as a pivotal cause of chronic kidney disease (CKD). The proliferation and widespread utilization of DNA testing in clinical settings have notably eased the diagnosis of genetic kidney diseases, which were once elusive but are now increasingly identified in cases previously deemed CKD of unknown etiology. However, despite these diagnostic strides, research into disease pathogenesis and novel drug development faces significant hurdles, chiefly due to the dearth of appropriate animal models and the challenges posed by limited patient cohorts in clinical studies. Conversely, the advent and utilization of human-induced pluripotent stem cells (hiPSCs) offer a promising avenue for genetic kidney disease research. Particularly, the development of hiPSC-derived kidney organoid systems presents a novel platform for investigating various forms of genetic kidney diseases. Moreover, the integration of the CRISPR/Cas9 technique into this system holds immense potential for efficient research on genetic kidney diseases. This review aims to explore the applications of in vitro kidney organoids generated from hiPSCs in the study of diverse genetic kidney diseases. Additionally, it will delve into the limitations of this research platform and outline future perspectives for advancing research in this crucial area.

Lubricating adhesive hyaluronate patch promotes cartilage regeneration and functional restoration in osteoarthritis

Osteoarthritis (OA) is a common chronic degenerative joint disease characterized by gradual deterioration and pain. Viscosupplementation, involving hyaluronic acid (HA) injection into the affected joint, is a minimally invasive option to reduce pain by improving joint lubrication and potentially avoiding the need for replacement surgery. However, the low adhesion and rapid degradation of HA often lead to inadequate therapeutic effects. In this study, we present lubricating adhesive HA-based hydrogel patches designed to effectively treat OA. The HA patches, modified with pyrogallol, have high elastic and compressive moduli, delaying degradation when exposed to external stimuli. Furthermore, they securely adhere to cartilage tissue surfaces and efficiently lubricate damaged cartilage, leading to a reduced friction and wear. In addition to these benefits, our HA patches exhibit scavenging effect of reactive oxygen species and sustainably release an encapsulated anti-inflammatory drug (dexamethasone: Dex). These features further enhance their therapeutic potential for OA treatment. In a mouse OA model, the hydrogel patches loaded with Dex promote healing of damaged cartilage and restore its motor function. Overall, our bioinspired HA hydrogel patches present a promising treatment option for managing the debilitating joint disease by offering enhanced adhesion, lubrication for cartilage protection, antioxidant effect, and sustained drug release.

Role of serum complement C3 and C4 on kidney outcomes in IgA nephropathy

IgA Nephropathy (IgAN) is the most prevalent glomerular disease worldwide. Complement system activation is crucial in its pathogenesis. Few studies correlated serum C3 and C4 with disease activity and prognosis. This retrospective study investigated the prognostic value of serum complement at the time of diagnosis in patients with IgAN. Specifically we evaluated whether adding serum C3 and C4 levels to established predictive models-one based on variables related to chronic kidney disease (CKD) progression and another incorporating variables from the International IgA Prediction Tool (IntIgAPT)-enhances the accuracy of outcome prediction. A composite renal outcome was defined as 50% decline in eGFR or onset of kidney failure. 101 patients were stratified according to baseline C3 levels in three groups (Low, Medium and High). During a median follow-up of 54 months, the Low group exhibited higher incidence of primary outcome (16.3 events vs 2.9 and 1.7 events × 100 pts/year, p = 0.0026). Model-1 (M1), consisting of CKD progression variables, and Model-3 (M3), comprising IntIgANPT variables, were implemented with baseline C3 and C4 to create Model-2 (M2) and Model-4 (M4), respectively. M2 demonstrated better predictive performance over M1, showing higher discrimination (lower AIC and BIC, higher C-index and NR2). Similarly, M4 outperformed M3, showing enhanced outcome prediction when C3 and C4 levels were added. Implementation of serum C3 and C4 can enhance prediction accuracy of already-validated prognostic models in IgAN. Lower C3 and higher C4 levels were associated with poorer prognosis, highlighting a more 'Complement-Pathic' subset of patients.

Inhibition of skeletal muscle differentiation by calciprotein particles in human primary myoblasts.

Sarcopenia is a common complication of chronic kidney disease (CKD) and has a detrimental effect on prognosis. Previous studies have explored the role of secondary calciprotein particles (CPP2) in determining the progression of complications and poor outcomes in patients with CKD. However, no study has demonstrated that CPP2 impairs skeletal myogenesis. Our study revealed that CPP2 exposure inhibits skeletal myogenesis by suppressing myotube formation and expression of skeletal muscle-specific myosin heavy chain and actin in human primary myoblasts. Moreover, CPP2 exposure altered the expression patterns of lineage-determinative transcription factors responsible for regulating myotube differentiation marker genes. This study first demonstrated that CPP2 interferes with myoblast differentiation and myotube formation in vitro.

The use of fosfomycin in infections caused by multidrug-resistant pathogens, especially pneumonia in children: a five-year retrospective single-centre experience.

Fosfomycin is gaining increasing attention for its activity against MDR or XDR pathogens. Currently, IV fosfomycin is a potential option for treating various infections, including urinary tract infections, pneumonia and skin infections when first-line treatments fail. To evaluate the demographic, clinical, microbiological and treatment modality of children received IV fosfomycin to treat infections caused by MDR pathogens since there are few data on the use of fosfomycin in children. This study was conducted retrospectively with patients under 18 years of age who were treated with IV fosfomycin for at least 72 h due to infections caused by MDR pathogens between January 2019 and October 2023 at Marmara University Pendik Training and Research Hospital, İstanbul, Türkiye. Data on demographic and clinical features, microbiological findings, treatment modalities and side effects were evaluated. Twenty-five children, for a total of 32 cases of infection episodes, with a mean age of 11.4 ± 3.92 years who received IV fosfomycin were included. The most frequent comorbidity was chronic pulmonary diseases, and the most common infection needed for IV fosfomycin was MDR Pseudomonas aeruginosa pneumonia. In all cases, fosfomycin was administered in combination with other antibiotics, mainly meropenem-colistin (68.7%) or meropenem (15.6%). Twenty-two (71.9%) cases had favourable clinical responses at the end of therapy. Our results suggest that IV fosfomycin may be an effective treatment option for MDR pathogens in the paediatric population. Nevertheless, careful stewardship is necessary to maintain efficacy and reduce antimicrobial resistance selection risk.

Successful A2 to O Simultaneous Liver and Kidney Transplantation in the Setting of Pre-operative Positive HLA Crossmatch: A Case Report

Simultaneous liver and kidney transplantation (SLKT) is possible for patients with high donor-specific HLA antibodies or with A2 donors to O recipients with high A2 titers. We report the first case of SLKT in a highly sensitized O recipient with organs from an A2 donor. The recipient is a 59-year-old woman with chronic kidney disease and liver failure due to autoimmune hepatitis and drug-induced liver injury. Immune work-up 8 days pre-transplant demonstrated a negative crossmatch and no HLA antibody (calculated panel reactive antibodies = 0%). Anti-A2 IgG levels were 512. The donor was a deceased 24-year-old man. One day before transplantation, serum from the recipient showed a significant increase in antibody reactivity (calculated panel reactive antibodies = 100%) attributable to blood product transfusion and memory response from previous pregnancies. Consequently, a crossmatch was positive for T and B cells with two newly detected HLA antibodies against the donor's antigens. On the day of surgery, the liver was transplanted first. Six hours and 37 minutes later, a repeat flow crossmatch was negative; donor-specific antibodies (DSAs) fell below the positive threshold, and anti-A2 IgG titer fell to 256. Thus, the kidney was transplanted after basiliximab induction therapy. Seven days post-transplant, non-donor-specific HLA antibodies were present but DSAs remain negative. The patient was discharged on postoperative day 57 with no signs of rejection at 4 months. This case illustrates a rapid and prolonged reduction in antibody titers (HLA and ABO) after SLKT. SLKT is feasible in patients with both DSA and high anti-A2 titer.

ShengqingJiangzhuo capsule ameliorates diabetic nephropathy by improving Keap1/Nrf2 signaling pathway.

Diabetic nephropathy (DN) is a major contributor to end-stage renal failure, and lacking effective treatment options. Shengqing Jiangzhuo capsule (SQJZJN), a traditional Chinese medicine prescription with known efficacy in chronic kidney disease, has not been thoroughly investigated for its potential in DN protection. Eight-week-old male C57BLKS/J db/db, C57BLKS/J db/m mice, and human glomerular mesangial cell (HMC) cells cultured with high glucose were used as experimental models in this study. The in vivo investigation showed that SQJZJN can significantly ameliorate renal pathological damage, reduce serum creatinine, and lower urinary microalbumin levels in db/db mice. In vitro, SQJZJN treatment mitigated advanced glycation end products (AGEs) and reactive oxygen species (ROS), leading to a reduction in renal cell apoptosis. Mechanistically, SQJZJN activated the Keap1/Nrf2/ARE pathway by promoting nuclear factor erythroid-derived 2-related factor 2 (Nrf2), γ-glutamylcysteine synthetase heavy subunit (γ-GCS), and Heme oxygenase-1 (HO-1) expressions, while decreasing Kelch-like ECH-associated protein 1 (KEAP1) expressions. These findings suggest that SQJZJN exerts a protective effect on DN, potentially through the activation of the Keap1/Nrf2/ARE pathway.

Midregional Proatrial Natriuretic Peptide (MRproANP) is associated with vertebral fractures and low bone density in patients with chronic obstructive pulmonary disease (COPD)

BackgroundPatients with COPD are often affected by loss of bone mineral density (BMD) and osteoporotic fractures. Natriuretic peptides (NP) are known as cardiac markers, but have also been linked to fragility-associated fractures in the elderly. As their functions include regulation of fluid and mineral balance, they also might affect bone metabolism, particularly in systemic disorders such as COPD.Research questionWe investigated the association between NP serum levels, vertebral fractures and BMD assessed by chest computed tomography (CT) in patients with COPD.MethodsParticipants of the COSYCONET cohort with CT scans were included. Mean vertebral bone density on CT (BMD-CT) as a risk factor for osteoporosis was assessed at the level of TH12 (AI-Rad Companion), and vertebral compression fractures were visually quantified by two readers. Their relationship with N-terminal pro-B-type natriuretic peptide (NT-proBNP), Mid-regional pro-atrial natriuretic peptide (MRproANP) and Midregional pro-adrenomedullin (MRproADM) was determined using group comparisons and multivariable analyses.ResultsAmong 418 participants (58% male, median age 64 years, FEV1 59.6% predicted), vertebral fractures in TH12 were found in 76 patients (18.1%). Compared to patients without fractures, these had elevated serum levels (p ≤ 0.005) of MRproANP and MRproADM. Using optimal cut-off values in multiple logistic regression analyses, MRproANP levels ≥ 65 nmol/l (OR 2.34; p = 0.011) and age (p = 0.009) were the only significant predictors of fractures after adjustment for sex, BMI, smoking status, FEV1% predicted, SGRQ Activity score, daily physical activity, oral corticosteroids, the diagnosis of cardiac disease, and renal impairment. Correspondingly, MRproANP (p < 0.001), age (p = 0.055), SGRQ Activity score (p = 0.061) and active smoking (p = 0.025) were associated with TH12 vertebral density.InterpretationMRproANP was a marker for osteoporotic vertebral fractures in our COPD patients from the COSYCONET cohort. Its association with reduced vertebral BMD on CT and its known modulating effects on fluid and ion balance are suggestive of direct effects on bone mineralization.Trial registrationClinicalTrials.gov NCT01245933, Date of registration: 18 November 2010.

Olive Oil Consumption, Risk Factors, and Diseases: An Umbrella Review.

Olive oil is a vegetable oil that provides health benefits, including a reduction in free radicals and total cholesterol and prevention of chronic diseases. The escalating incidence of chronic diseases presents a substantial challenge to public health, prompting numerous studies to assess these health-related effects. Despite several systematic reviews and meta-analyses summarizing the association between olive oil consumption and specific health outcomes, there is no summary of the accumulated evidence from these reviews. This umbrella review summarizes the evidence on olive oil consumption or intervention in adults and its association with multiple risk factors and diseases. We retrieved systematic reviews of randomized trials or observational studies on oral interventions or the consumption of olive oil. The systematic search encompassed databases including MEDLINE, Embase, Scopus, Web of Science, LILACS, and CENTRAL from inception to February 6, 2023. Two independent reviewers conducted data extraction and assessed methodological quality using the Joanna Briggs Institute tool. Overall, 17 systematic reviews of randomized trials and observational studies, covering outcomes such as cardiovascular diseases, cancer, type 2 diabetes, glucose metabolism, inflammatory and oxidative markers, and all-cause mortality, were included. The evidence suggests a beneficial association between olive oil consumption and cardiovascular diseases, cancer, type 2 diabetes, and all-cause mortality. However, the evidence was less definitive for inflammatory markers, oxidative stress, glucose metabolism, and blood lipid outcomes. Several meta-analyses revealed high heterogeneity and wide confidence intervals, along with a limited number of randomized clinical trials. Given the high heterogeneity and low quality of evidence, further studies involving randomized trials are imperative. Prioritizing an in-depth analysis of specific olive oil components and using a control group with distinct characteristics and different effects is strongly recommended. PROSPERO registration no. CRD42022357290.

Switching to e-cigarettes as harm reduction among individuals with chronic disease who currently smoke: Results of a pilot randomized controlled trial.

E-cigarettes (ECs) may be an effective harm reduction strategy for individuals with conditions like chronic obstructive pulmonary disease (COPD), asthma, coronary artery disease (CAD), and peripheral arterial disease (PAD) who smoke combustible cigarettes (CCs). Our aim was to examine how individuals with chronic conditions transition from CCs to ECs and its impact on health outcomes. In a pilot randomized controlled trial (RCT), patients with COPD, asthma, CAD/PAD who currently smoke CCs and have not used nicotine replacement therapy (NRT) or ECs in the past 14 days were randomized to receive ECs or combination NRT with behavioral counselling. Disease symptoms, acceptability/satisfaction (TSQM-9) and feasibility, and cigarettes per day (CPD), and/or EC use were collected at baseline, 3-, and 6-months. Descriptive statistics and a linear regression were conducted to explore changes in CPD and chronic condition-specific assessments (CAT, SAQ-7, ACT) that assess COPD, asthma, and CAD/PAD symptom change. At 3-months, the EC group (n=63, mean CPD=9±11) reduced their CPD by 54% vs. 60% in the NRT group (n=58, mean CPD=7±6), p=0.56. At 6-months, 17.5% had switched completely to ECs while 23% quit smoking in the NRT arm. CAT scores showed a significant 6-point reduction in the EC arm (p=0.03). Participants scored an average of 69±27 for EC effectiveness, 87±23 for convenience, and 75±27 for overall satisfaction. This pilot study suggests that ECs may be a safer alternative for chronic condition patients using CCs and warrants further research on expected smoking cessation/reduction among individuals who use ECs. The findings from this pilot RCT hold significant implications with chronic conditions such as COPD, asthma, CAD and PAD who smoke CCs. The observed reduction in cigarettes per day and improvement in respiratory symptoms suggest that switching to ECs appears feasible and acceptable among those with chronic diseases. These results suggest that ECs may offer an alternative for individuals struggling to quit CC smoking through existing pharmacotherapies. This study supports further exploration of switching to ECs as a harm reduction strategy among CC users who have been unsuccessful at quitting by other means.

Assessment of the quality of life of patients suffering from chronic kidney disease depending on the clinical variability of the disease

This article describes in detail: features of the clinical course of the disease, assessment of quality of life, diagnostic criteria and modern classification of chronic kidney disease. Various pathogenesis of chronic kidney disease is revealed, taking into account the correspondence of the stages of chronic kidney disease to the ICD-10 coding. The article also details the modern methods of antihypertensive therapy in patients with chronic kidney disease, taking into account the latest clinical recommendations. Various modern studies of assessing the quality of life of patients using the SF-36 questionnaire are described, which includes 8 scales, namely: physical functioning (PF), role functioning due to physical condition (RFPC), pain intensity (PI), general health status (GHS), vital activity (VA), social functioning (SF), role functioning due to emotional state (RFES) and mental health (MH).

Zinc Protects against Swine Barn Dust-Induced Cilia Slowing

Agricultural workers exposed to organic dust from swine concentrated animal feeding operations (CAFOs) have increased chances of contracting chronic lung disease. Mucociliary clearance represents a first line of defense against inhaled dusts, but organic dust extracts (ODEs) from swine barns cause cilia slowing, leading to decreased bacterial clearance and increased lung inflammation. Because nutritional zinc deficiency is associated with chronic lung disease, we examined the role of zinc supplementation in ODE-mediated cilia slowing. Ciliated mouse tracheal epithelial cells were pretreated with 0–10 µg/mL ZinProTM for 1 h, followed by treatment with 5% ODE for 24 h. Cilia beat frequency (CBF) and protein kinase C epsilon (PKCε) activity were assayed. ODE treatment resulted in cilia slowing after 24 h, which was reversed with 0.5 and 1.0 µg/mL ZinPro pre-treatment. No zinc protection was observed at 50 ng/mL, and ciliated cells detached at high concentrations (100 µg/mL). ZinPro alone produced no changes in the baseline CBF and showed no toxicity to the cells at concentrations of up to 10 µg/mL. Pre-treatment with ZinPro inhibited ODE-stimulated PKCε activation in a dose-dependent manner. Based on ZinPro’s superior cell permeability compared to zinc salts, it may be therapeutically more effective at reversing ODE-mediated cilia slowing through a PKCε pathway. These data demonstrate that zinc supplementation may support the mucociliary transport apparatus in the protection of CAFO workers against dust-mediated chronic lung disease.

Unobvious long-term effects of COVID-19 for kidneys. The literature review

The impact of COVID-19 on the course of chronic kidney disease (CKD) has already been confirmed by researchers around the world. Basically, studying kidney damage in COVID-19, the authors pay attention to the new coronavirus infection in terms of the development of acute kidney injury (AKI) or mortality from it in patients with existing CKD, especially patients receiving hemodialysis or having a transplanted kidney, providing an analysis of mortality, risks and forecasts. However, there is still no published description of how this infection can affect the function of kidneys that did not have signs of CKD before COVID-19. Currently, studies devoted to the analysis of long-term results of observation and treatment of such patients are especially scarce. The review examines foreign and domestic studies concerning both the influence of chronic kidney disease on the severity of coronavirus infection and the risks of developing kidney disease after COVID-19, including the development of acute kidney injury and in the long term. This approach can highlight the relevance of timely identification of patients with developing CKD in the early stages among patients with COVID-19 for the purpose of their further follow-up and timely prescription of nephroprotective therapy. The search for literature sources was carried out using PubMed, Science Direct, eLibrary using the keywords “coronavirus”, “COVID-19”, “SARS-CoV-2”, “acute kidney injury”, “chronic kidney disease” and their combinations covering publications from 2019 to 2023 in Russian and English.

Efficacy and safety analysis of sodium zirconium cyclosilicate and calcium polystyrene sulfonate on rapid reduction of potassium in moderate to severe hyperkalemia patients with chronic kidney disease without dialysis.

Hyperkalemia is a common complication of chronic kidney disease (CKD). This study aims to investigate the efficacy and safety of sodium zirconium cyclosilicate and calcium polystyrene sulfonate in reducing potassium in patients with acute and severe hyperkalemia in CKD who are not undergoing dialysis. A retrospective real-world study was conducted among 73 patients with non-dialysis chronic kidney disease who were hospitalized in the First Affiliated Hospital of Chengdu Medical College from June 2020 to June 2022. 33 patients treated with sodium zirconium cyclosilicate were categorized as SZC group, and the other 40 patients treated with calcium polystyrene sulfonate were categorized as CPS group. Serum potassium, serum sodium, magnesium, calcium, and phosphorus levels were examined. Adverse reactions were recorded during medication. Significantly decreased serum potassium was observed in both groups, whereas the potassium reduction was higher in the SZC group than in the CPS group at 2, 4, 24, and 48 hours after medication while there was no statistically significant difference in the serum potassium level between the two groups at 72 hours. For those people whose initial potassium exceeded 6 mmol/L, the potassium reduction was more obvious in the SZC group than in the CPS group at 2 and 4 hours after medication. The control rate of hyperkalemia in the SZC group was significantly higher than in the CPS group at 4, 24, and 48 hours. No distinct change was observed in serum sodium, calcium, magnesium, and phosphorus before and 72 hours after medication. No severe adverse reactions occurred. Sodium zirconium cyclosilicate has a more obvious effect on reducing potassium particularly for those patients with moderate to severe hyperkalemia who need rapid potassium reduction.

7-Phenylheptanoic Acid-Hydroxypropyl β-Cyclodextrin Complex Slows the Progression of Renal Failure in Adenine-Induced Chronic Kidney Disease Mice

The characteristic accumulation of circulating uremic toxins, such as indoxyl sulfate (IS), in chronic kidney disease (CKD) further exacerbates the disease progression. The gut microbiota, particularly gut bacterial-specific enzymes, represents a selective and attractive target for suppressing uremic toxin production and slowing the progression of renal failure. This study investigates the role of 4-phenylbutyrate (PB) and structurally related compounds, which are speculated to possess renoprotective properties in suppressing IS production and slowing or reversing renal failure in CKD. In vitro enzyme kinetic studies showed that 7-phenylheptanoic acid (PH), a PB homologue, suppresses the tryptophan indole lyase (TIL)-catalyzed decomposition of tryptophan to indole, the precursor of IS. A hydroxypropyl β-cyclodextrin (HPβCD) inclusion complex formulation of PH was prepared to enhance its biopharmaceutical properties and to facilitate in vivo evaluation. Prophylactic oral administration of the PH-HPβCD complex formulation reduced circulating IS and attenuated the deterioration of renal function and tubulointerstitial fibrosis in adenine-induced CKD mice. Additionally, treatment of moderately advanced adenine-induced CKD mice with the formulation ameliorated renal failure, although tissue fibrosis was not improved. These findings suggest that PH-HPβCD can slow the progression of renal failure and may have implications for preventing or managing CKD, particularly in early-stage disease.

The Association between Dyslipidemia and Pulmonary Diseases.

Dyslipidemia is one of the most common diseases worldwide. As a component of metabolic syndrome, the prevalence and mechanism by which dyslipidemia promotes cardiovascular diseases has been well studied, although the relationship between pulmonary diseases is not well understood. Because the lung is a respiratory organ with a large surface area and is exposed to the environment outside the body, it continuously inhales various substances. As a result, pulmonary diseases have a vast diversity, including chronic inflammatory diseases, allergic diseases, cancers, and infectious diseases. Recently, growing evidence has suggested that dyslipidemia plays a role in the pathogenesis and prognosis of various pulmonary diseases. We herein review the current understanding of the relationship between dyslipidemia and pulmonary diseases, including chronic obstructive pulmonary diseases, asthma, and lung cancer, and infectious pulmonary diseases, including community-acquired pneumonia, tuberculosis, nontuberculous mycobacterial pulmonary disease, and COVID-19. In addition, we focus on recent evidence of the utility of statins, specifically 3-hydroxy-3-methylglutaryl-coA reductase inhibitors, in the prevention and treatment of the various pulmonary diseases described above.

Issues in the diagnosis and evaluation of pulmonary aspergillosis in patients with chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease (COPD) may present with various forms of pulmonary aspergillosis, including invasive pulmonary aspergillosis (IPA), chronic cavitary pulmonary aspergillosis, and allergic bronchopulmonary aspergillosis. Accurate diagnosis and disease evaluation are essential for tailoring individualized treatment strategies. Key aspects include: (1) Comprehensive assessment of IPA risk factors, with enhanced monitoring for critically ill patients; (2) Understanding the clinical manifestations and radiological features of different forms of pulmonary aspergillosis and emphasizing the importance of bronchoscopic examination; (3) Obtaining microbiological evidence whenever possible; (4) Differentiating colonization from infection to avoid overdiagnosis; (5) Vigilance for co-existing sensitization to Aspergillus. During treatment and long-term disease management, the use of inhaled or systemic corticosteroids and antifungal agents should be dynamically adjusted according to the patient's condition.

Clinical and pathogenetic features of the development of endothelial dysfunction in patients with chronic kidney disease and its contribution to the development of cognitive impairments

THE AIM: to study the clinical and pathogenetic features of the development of endothelial dysfunction (ED) in patients with chronic kidney disease stages 3A-5D and its contribution to the development of cognitive impairment.PATIENTS AND METHODS: The study included 80 patients with CKD stages 3A-5D aged from 26 to 79 years (average age 58.9 ± 1.4 years): 43 women (average age 60.1 ± 1.9 years) and 37 men (average age 57.4±2.3 years). The patients were divided into 2 groups: group 1 included 40 patients with CKD 3A-5 (average age 59.9 ± 2.1 years), group 2 included 40 patients with CKD 5D (average age 58.1 ± 2 years). All patients underwent common and biochemical blood tests, the levels of endothelial nitric oxide synthase 3 (eNOS-3) and endothelin-1 (END-1) were determined, an endothelium-dependent vasodilation test (EDVD) was performed, testing for the presence and severity of cognitive disorders using the Montreal Cognitive Assessment Scale (MoCA) and the Mini Mental State Examination (MMSE).RESULTS: The prevalence of ED in the overall cohort of patients based on the results of a positive test with EDVD was 55 % of cases. ED was statistically significantly more often detected in the group of patients receiving hemodialysis treatment compared to patients in group 1: 70 % versus 40 %, respectively (p=0.007). The level of eNOS-3 in group 1 was higher compared to group 2 and amounted to 1.01±0.5 ng/ml versus 0.76±0.3 ng/ml (p=0.008). While the level of END-1 was statistically significantly lower in patients of group 1 compared to group 2 and amounted to 45.4±9.1 pg/ml versus 54.9±4.7 pg/ml (p&lt;0.001). Cognitive impairments were identified in the general cohort: according to MMSE – in 67.5 % of cases, according to MoCA – in 71.3 %, and were more common in group 2. There were no statistically significant relationships between the results of the EDVD test and testing on the MoCA and MMSE scales. The level of eNOS-3 was lower in the subgroup of patients with cognitive impairment according to MoCA compared to the subgroup without it: 0.73±0.1 ng/ ml versus 0.94±0.2 ng/ml (p=0.127). The content of END-1 was statistically significantly higher in the subgroup of patients with cognitive impairment according to MoCA – 52.98±1.2 pg/ml compared to the subgroup without it – 47.67±1.5 pg/ml (p=0.043). When assessing the relationship between the levels of eNOS-3 and END-1 and the results of the EDVD test, it was found that in patients with a positive test in group 1, the level of eNOS-3 was statistically significantly higher compared to group 2 (p=0.01). An inverse relationship was observed for END-1; its level was lower in patients of group 1 compared to group 2 (p&lt;0.01).CONCLUSION. Thus, the study revealed a high prevalence of endothelial dysfunction in patients with CKD stages 3A-5D. Progressive loss of renal function leads to dysregulation of the molecular mechanisms controlling vascular tone and the development of ED. eNOS-3 and END-1 have demonstrated high sensitivity for ED verification, and their detection improves the quality of the EDVD test. The development and progression of ED in patients with CKD is a multifactorial process that leads to hemodynamic disturbances in various organs and tissues, their damage and has a negative impact on the patient’s quality of life, his cognitive status and life expectancy.

A Multi-State Model Study of the Disability-Free Life Expectancy Among Older Adults with Chronic Multimorbidity Based on CHARLS - China, 2011-2020.

Chronic disease multimorbidity is prevalent among older Chinese people, seriously affecting their well-being and quality of life. This study estimated the impact of multimorbidity on the risk of health state transitions and health expectancy among older adults in China. It used population-representative, long-term longitudinal data and multi-state Markov modeling along with microsimulation methods. The study results suggest that the Chinese government should strengthen the prevention and management of multimorbidity and accelerate the transition from chronic disease management to multimorbidity management.

GP’s GP, general practitioner’s health and willingness to contract family doctors in China: a national cross-sectional study

ObjectivesGeneral practitioners are trained to care for patients with a high level of responsibility and professional competency. However, there are few reports on the physical and mental health status of general practitioners (GPs) in China, particularly regarding help seeking and self-treatment. The primary aims of this study were to explore GPs’ expectations of their own family doctors and their reflection on role positioning, and to explore the objective factors that hinder the system of family doctors.Study designCross-sectional study.MethodsWe conducted an online survey of Chinese GPs. Descriptive statistics were used to summarize the findings.ResultsMore than half of the participants (57.20%) reported that their health was normal over the past year. A total of 420 participants (23.35%) reported having chronic diseases. For sleep duration, 1205 participants (66.98%) reported sleeping 6–8 h per day; 473 participants (26.29%) reported chronic insomnia. Two hundred thirty-one participants (12.84%) had possible depression. A total of 595 (33.07%) participants reported that they had contracted a fixed family doctor. In terms of preventing themselves from contracting for a family doctor, the following factors were identified: lack of sufficient time (54.81%), could solve obstacles themselves (50.97%), and embarrassment (24.24%). The proportion of the contract group (12.44%) taking personal relationship as a consideration was higher than that of the non-contract group (7.64%) (χ2 = 10.934 P = 0.01). Most participants (79.90%) in the non-signed group reported never having seen a family doctor. In terms of obstacles, more than half of the signed group thought that they could solve obstacles themselves, while the non-signed group (39.20%) was less confident in the ability of family doctors than the signed group (29.75%) (χ2 = 15.436, P < 0.01).ConclusionsGPs work under great pressure and lack of self-care awareness, resulting in an increased prevalence of health conditions. Most GPs did not have a regular family doctor. Having a family doctor with a fixed contract is more conducive to the scientific management of their health and provides a reasonable solution to health problems. The main factors hindering GPs from choosing a family doctor were time consumption, abilities to solve obstacles themselves, and trust in the abilities of GPs. Therefore, simplifying the process of family doctor visits, Changing the GPs' medical cognition, and strengthening the policy of GP training would be conducive to promoting a family doctor system that enhances hierarchical diagnosis and treatment. International collaboration could integrate GP health support into global healthcare system.