The impact of communication training on the clinical care of hypertension in general practice: a cluster randomized controlled trial in China.

BACKGROUND: Hypertension is one of the most common chronic diseases with a low control rate globally. The effect of communication skills training contributing to hypertension control remains uncertain. The aim of the present study was to assess the effectiveness of an educational intervention based on the Calgary-Cambridge guide in improving hypertensive management. METHODS: A cluster randomized controlled trial enrolled 27 general practitioners (GPs) and 540 uncontrolled hypertensive patients attending 6 community health centers in Chengdu, China. GPs allocated to the intervention group were trained by an online communication course and two face-to-face workshops based on Calgary-Cambridge guides. The primary outcome was blood pressure (BP) control rates and reductions in systolic and diastolic BP from baseline to 3 months. The secondary outcome was changes in GPs' communication skills after one month, patients' knowledge and satisfaction after 3 months. Bivariate analysis and the regression model assessed whether the health provider training improved outcomes. RESULTS: After the communication training, the BP control rate was significantly higher (57.2% vs. 37.4%, p < 0.001) in the intervention groups. Compared to the control group, there was a significant improvement in GP's communication skills (13.0 vs 17.5, p < 0.001), hypertensive patients' knowledge (18.0 vs 20.0, p < 0.001), and systolic blood pressure (139.1 vs 134.7, p < 0.001) after 3 months of follow-up. Random effects least squares regression models showed significant interactions between the intervention group and time period in the change of GP's communication skills (Parameter Estimated (PE): 0.612, CI:0.310,0.907, p = 0.006), hypertensive patient's knowledge (PE:0.233, CI: 0.098, 0.514, p < 0.001), satisfaction (PE:0.495, CI: 0.116, 0.706, p = 0.004), SBP (PE:-0.803, CI: -1.327, -0.389, p < 0.001) and DBP (PE:-0.918, CI: -1.694, -0.634, p < 0.001), from baseline to follow-up. CONCLUSION: Communication training based on the Calgary-Cambridge guide for GPs has shown to be an efficient way in the short term to improve patient-provider communication skills and hypertension outcomes among patients with uncontrolled BPs. TRIAL REGISTRATION: The trial was registered on Chinese Clinical Trials Registry on 2019-04-03. (ChiCTR1900022278).

Global epidemiological features and impact of osteosarcopenia: A comprehensive meta-analysis and systematic review.

Osteosarcopenia is defined as the concurrent occurrence of osteopenia/osteoporosis and sarcopenia. The aim of the current study was to perform a systematic review with meta-analysis to determine the global prevalence, risk factors and clinical outcomes of osteosarcopenia. This review was registered in PROSPERO (CRD42022351229). PubMed, Cochrane, Medline and Embase were searched from inception to February 2023 to retrieve eligible observational population-based studies. Pooled osteosarcopenia prevalence was calculated with 95% confidence interval (CI), and subgroup analyses were performed. The risk factor of osteosarcopenia and its association with clinical outcomes were expressed as odds ratio (OR) and hazard ratio (HR), respectively. Heterogeneity was estimated using the I2 test. Study quality was assessed using validated instruments matched to study designs. The search identified 55 158 studies, and 66 studies (64 404 participants, mean age from 46.6 to 93 years) were analysed in the final analysis, including 48 cross-sectional studies, 17 cohort studies and 1 case-control study. Overall, the pooled prevalence of osteosarcopenia was 18.5% (95% CI: 16.7-20.3, I2  = 98.7%), including 15.3% (95% CI: 13.2-17.4, I2  = 97.6%) in men and 19.4% (95% CI: 16.9-21.9, I2  = 98.5%) in women. The prevalence of osteosarcopenia diagnosed using sarcopenia plus osteopenia/osteoporosis was 20.7% (95% CI: 17.1-24.4, I2  = 98.55%), and the prevalence of using sarcopenia plus osteoporosis was 16.1% (95% CI: 13.3-18.9, I2  = 98.0%). The global osteosarcopenia prevalence varied in different regions with 22.9% in Oceania, 21.6% in Asia, 20.8% in South America, 15.7% in North America and 10.9% in Europe. A statistically significant difference was found in the subgroups of the study population between the hospital (24.7%) and community (12.9%) (P = 0.001). Frailty (OR = 4.72, 95% CI: 2.71-8.23, I2  = 61.1%), malnutrition (OR = 2.35, 95% CI: 1.62-3.40, I2  = 50.0%), female sex (OR = 5.07, 95% CI: 2.96-8.69, I2  = 73.0%) and higher age (OR = 1.10, 95% CI: 1.06-1.15, I2 ==86.0%) were significantly associated with a higher risk for osteosarcopenia. Meta-analysis of cohort studies showed that osteosarcopenia significantly increased the risk of fall (HR = 1.54, 95% CI: 1.20-1.97; I2  = 1.0%, three studies), fracture (HR = 2.13, 95% CI: 1.61-2.81; I2  = 67.8%, seven studies) and mortality (HR = 1.75, 95% CI: 1.34-2.28; I2  = 0.0%, five studies). Despite the heterogeneity arising from varied definitions and criteria, our findings highlight a significant global prevalence of osteosarcopenia and its negative impact on clinical health. Standardizing diagnostic criteria for osteosarcopenia would be advantageous in the future, and early detection and management should be emphasized in this patient population.

Subthreshold Depression: A Systematic Review and Network Meta-Analysis of Non-Pharmacological Interventions.

Background: Subthreshold depression (StD) is considered to be the "precursor" stage of major depressive disorder (MDD), which could cause higher risk of suicide, disease burden and functional impairment. There have been various non-pharmacological interventions for StD. However, the comparison of their effectiveness still lacks sufficient evidence. We performed a systematic review and network meta-analysis to evaluate and rank the efficacy of multiple non-pharmacological interventions targeting StD. Methods: We conducted a thorough search across various databases including PubMed, Medline, Embase, Web of Science and PsycINFO from inception to December 2022. All included studies were randomized controlled trials (RCTs) of non-pharmacological interventions for patients with StD compared with control group (CG). Several universal scales for measuring depression severity were used as efficacy outcomes. The surface under the cumulative ranking curve (SUCRA) was used to separately rank each intervention using the "Stata 17.0" software. Results: A total of thirty-six trials were included, involving twenty-eight interventions and 7417 participants. The research found that most non-pharmacological interventions were superior to controls for StD. In each outcome evaluation by different scales for measuring depression, psychotherapy always ranked first in terms of treatment effectiveness, especially Problem-solving Therapy (PST), Behavioral Activation Therapy (BAT), Cognitive Behavioral Therapy (CBT)/Internet-based CBT (I-CBT)/Telephone-based CBT (T-CBT). Since different groups could not be directly compared, the total optimal intervention could not be determined. Conclusion: Here, we show that psychotherapy may be the better choice for the treatment of StD. This study provides some evidence on StD management selection for clinical workers. However, to establish its intervention effect more conclusively, the content, format and operators of psychotherapy still require extensive exploration to conduct more effective, convenient and cost-effective implementation in primary healthcare. Notably, further research is also urgently needed to find the biological and neural mechanisms of StD by examining whether psychotherapy alters neuroplasticity in patients with StD.

Nomogram for the prediction of crescent formation in IgA nephropathy patients: a retrospective study.

BACKGROUND: The 2017 Oxford classification of immunoglobulin A nephropathy (IgAN) recently reported that crescents could predict a worse renal outcome. Early prediction of crescent formation can help physicians determine the appropriate intervention, and thus, improve the outcomes. Therefore, we aimed to establish a nomogram model for the prediction of crescent formation in IgA nephropathy patients. METHODS: We retrospectively analyzed 200 cases of biopsy-proven IgAN patients. Least absolute shrinkage and selection operator(LASSO) regression and multivariate logistic regression was applied to screen for influencing factors of crescent formation in IgAN patients. The performance of the proposed nomogram was evaluated based on Harrell's concordance index (C-index), calibration plot, and decision curve analysis. RESULTS: Multivariate logistic analysis showed that urinary protein ≥ 1 g (OR = 3.129, 95%CI = 1.454-6.732), urinary red blood cell (URBC) counts ≥ 30/ul (OR = 3.190, 95%CI = 1.590-6.402), mALBU ≥ 1500 mg/L(OR = 2.330, 95%CI = 1.008-5.386), eGFR < 60ml/min/1.73m2(OR = 2.295, 95%CI = 1.016-5.187), Serum IgA/C3 ratio ≥ 2.59 (OR = 2.505, 95%CI = 1.241-5.057), were independent risk factors for crescent formation. Incorporating these factors, our model achieved well-fitted calibration curves and a good C-index of 0.776 (95%CI [0.711-0.840]) in predicting crescent formation. CONCLUSIONS: Our nomogram showed good calibration and was effective in predicting crescent formation risk in IgAN patients.

Development and Validation of Prediction Models for All-Cause Mortality and Cardiovascular Mortality in Patients on Hemodialysis: A Retrospective Cohort Study in China.

Purpose: This study aimed to develop two predictive nomograms for the assessment of long-term survival status in hemodialysis (HD) patients by examining the prognostic factors for all-cause mortality and cardiovascular (CVD) event mortality. Patients and methods: A total of 551 HD patients with an average age of over 60 were included in this study. The patients' medical records were collected from our hospital and randomly allocated to two cohorts: the training cohort (n=385) and the validation cohort (n=166). We employed multivariate Cox assessments and fine-gray proportional hazards models to explore the predictive factors for both all-cause mortality and cardiovascular event mortality risk in HD patients. Two nomograms were established based on predictive factors to forecast patients' likelihood of survival for 3, 5, and 8 years. The performance of both models was evaluated using the area under the curve (AUC), calibration plots, and decision curve analysis. Results: The nomogram for all-cause mortality prediction included seven factors: age ≥ 60, sex (male), history of diabetes and coronary artery disease, diastolic blood pressure, total triglycerides (TG), and total cholesterol (TC). The nomogram for cardiovascular event mortality prediction included three factors: history of diabetes and coronary artery disease, and total cholesterol (TC). Both models demonstrated good discrimination, with AUC values of 0.716, 0.722 and 0.725 for all-cause mortality at 3, 5, and 8 years, respectively, and 0.702, 0.695, and 0.677 for cardiovascular event mortality, respectively. The calibration plots indicated a good agreement between the predictions and the decision curve analysis demonstrated a favorable clinical utility of the nomograms. Conclusion: Our nomograms were well-calibrated and exhibited significant estimation efficiency, providing a valuable predictive tool to forecast prognosis in HD patients.

Association of adverse childhood experiences and depression among medical students: the role of family functioning and insomnia.

Background: Few studies have explored the mechanisms linking adverse childhood experiences (ACEs) to depression in medical students. This study aimed to investigate the relationship between ACEs and depression through the serial mediation effect of family functioning and insomnia. Methods: A cross-sectional survey was conducted with 368 medical students from university in Chengdu in 2021. The participants were asked to complete four self-report questionnaires, including ACEs scale, the family APGAR index, the ISI and PHQ-9. Singe and serial mediation analyses were conducted using structural equation modeling by Mplus 8.3. Results: ACEs had a significant direct effect on depression (ß = 0.438, p < 0.001) and through three significantly indirect pathways: (1) through family functioning (ß = 0.026, 95% CI: 0.007-0.060), accounting for 5.9% of the total effect; (2) through insomnia (ß = 0.103, 95% CI: 0.011-0.187), accounting for 23.5% of the total effect; and (3) through the serial mediators involving in family functioning and insomnia (ß = 0.038, 95% CI: 0.015-0.078), accounting for 8.7% of the total effect. The total indirect effect was 38.1%. Limitations: This cross-sectional study prevented us from establishing causality. Conclusion: This study highlights the role of family functioning and insomnia as serial mediators of the relationship between ACEs and depression. Findings help to elucidate the mechanism that underlines the pathway between ACEs and depression in medical students. These findings may indicate developing measures to strengthen family functioning and improve insomnia aiming to reduce depression in medical students with ACEs.

Steroid hormone 20-hydroxyecdysone disturbs fat body lipid metabolism and negatively regulates gluconeogenesis in Hyphantria cunea larvae.

The steroid hormone 20-hydroxyecdysone (20E) has been described to regulate fat body lipid metabolism in insects, but its accurate regulatory mechanism, especially the crosstalk between 20E-induced lipid metabolism and gluconeogenesis remains largely unclear. Here, we specially investigated the effect of 20E on lipid metabolism and gluconeogenesis in the fat body of Hyphantria cunea larvae, a notorious pest in forestry. Lipidomics analysis showed that a total of 1 907 lipid species were identified in the fat body of H. cunea larvae assigned to 6 groups and 48 lipid classes. The differentially abundant lipids analysis showed a significant difference between 20E-treated and control samples, indicating that 20E caused a remarkable alteration of lipidomics profiles in the fat body of H. cunea larvae. Further studies demonstrated that 20E accelerated fatty acid ß-oxidation, inhibited lipid synthesis, and promoted lipolysis. Meanwhile, the activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase were dramatically suppressed by 20E in the fat body of H. cunea larvae. As well, the transcriptions of genes encoding these 4 rate-limiting gluconeogenic enzymes were significantly downregulated in the fat body of H. cunea larvae after treatment with 20E. Taken together, our results revealed that 20E disturbed fat body lipid homeostasis, accelerated fatty acid ß-oxidation and promoted lipolysis, but negatively regulated gluconeogenesis in H. cunea larvae. The findings might provide a new insight into hormonal regulation of glucose and lipid metabolism in insect fat body.

Association of depression with cognitive frailty: A systematic review and meta-analysis.

BACKGROUND AND AIM: The relationship between cognitive frailty and depression is unclear and quantitative analyses are lacking. We conducted a systematic review and meta-analysis to investigate the relationship between cognitive frailty and depression. METHODS: We systematically searched Embase, PubMed, Medline (Ovid), Web of Science, and APA PsycInfo (American Psychological Association PsycInfo) databases until April 2022. Meta-analysis was performed using the Stata software. The prevalence between cognitive frailty and depression them was estimated by extracting the proportion of cognitive frailty and depression in the total number of patients. We extracted odds ratios (ORs) and 95 % confidence intervals (CI) to estimate the relationship between cognitive frailty and depression. RESULTS: A meta-analysis of 15 studies revealed that cognitive frailty in older adults was associated with a higher risk of depression (OR = 2.06, 95 % CI = 1.72-2.48, p = 0.001). Eight studies involved the prevalence of cognitive frailty and depression, with an overall prevalence of depression of 46 % (95 % CI, 30 % -62 %; p < 0.0001) in cognitively frail patients. LIMITATION: Differences in definitions and assessment methods for cognitive frailty across studies. CONCLUSION: The prevalence of cognitive frailty combined with depression in the elderly is high wherein both are mutually affected. More prospective studies are needed to investigate the relationship between cognitive frailty and depression and to propose targeted treatment options and preventive measures to improve the quality of life of the elderly population.

Metagenomics-based systematic analysis reveals that gut microbiota Gd-IgA1-associated enzymes may play a key role in IgA nephropathy.

Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. The objective of this study was to explore whether specific gut microbiota and associated enzymes affect Gd-IgA1 in IgAN. Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. Differences analysis in gut microbiota was performed to determine the overall microbiota composition, the representative enterotypes, and the microbiota abundance. Correlations between gut microbiota and clinical indicators were assessed by Spearman's analysis. Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively. Results: Bacteroides plebeius and Bacteroides vulgatus levels were higher, while Prevotella copri and Alistipes putredinis levels were lower in the IgAN group compared to HCs group. Enterotype I characterized by Bacteroides was closely related to the IgAN patients. Moreover, Bacteroides fragilis, Flavonifractor plautii and Ruminococcus gnavus were characteristic bacteria enriched in IgAN patients. Spearman's correlation analysis found that Eggerthella lenta and Ruminococcus bromii were positively correlated with urine protein-creatinine ratio, while Ruminococcus gnavus showed a direct association with red blood cells in urine, and Bacteroides vulgatus and Ruminococcus gnavus were positively correlated with eGFR. These results indicated that intestinal dysbacteriosis occurred in IgAN patients and was associated with clinical and biochemical features. In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii were enriched in IgAN patients. Conclusion: These findings suggested that α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii might be related to the production of Gd-IgA1, indicating that enzymes originated from abnormal intestinal microbiota may contribute to the production of Gd-IgA1 and play an important role in the pathogenesis of IgAN.

Comparison between outcomes of IgA nephropathy with nephrotic-range proteinuria and nephrotic syndrome: do podocytes play a role?

BACKGROUND: Nephrotic syndrome (NS) and nephrotic-range proteinuria (NRP) are uncommon in IgA nephropathy (IgAN), and their clinicopathology and prognosis have not been discussed. Podocytes may play an important role in both clinical phenotypes. METHODS: We investigated 119 biopsy-proven IgAN patients with proteinuria over 2 g/d. The patients were divided into three groups according to proteinuria level: the overt proteinuria (OP) group, NS group, and NRP group. In addition, according to the severity of foot process effacement (FPE), the patients were divided into three groups: the segmental FPE (SFPE) group, moderate FPE (MFPE) group, and diffuse FPE (DFPE) group. The outcome was survival from a combined event defined by a doubling of the baseline serum creatinine and a 50% reduction in eGFR or ESRD. RESULTS: Compared with the NRP group, patients in the NS group had more severe microscopic hematuria, presented with more severe endocapillary hypercellularity and had a higher percentage of DFPE. The Kaplan-Meier curve showed that MFPE patients had a better outcome in the NRP group <50% of tubular atrophy/interstitial fibrosis. In the multivariate model, the NRP group (HR = 17.098, 95% CI = 3.835-76.224) was associated with an increased risk of the combined event, while MFPE (HR = 0.260, 95% CI = 0.078-0.864; p = 0.028) was associated with a reduced risk of the combined event. After the addition of renin-angiotensin system inhibitors (RASi), the incidence of the combined event in the MFPE group (HR = 0.179, 95% CI = 0.047-0.689; p = 0.012) was further reduced. CONCLUSIONS: NS presented more active lesions and more severe FPE in IgAN. NRP was an independent risk factor for progression to the renal endpoint, while MFPE indicated a better prognosis in NRP without obvious chronic renal lesions, which may benefit from RASi.

Identifying Frail Patients by Using Electronic Health Records in Primary Care: Current Status and Future Directions.

With the rapidly aging population, frailty, characterized by an increased risk of adverse outcomes, has become a major public health problem globally. Several frailty guidelines or consensuses recommend screening for frailty, especially in primary care settings. However, most of the frailty assessment tools are based on questionnaires or physical examinations, adding to the clinical workload, which is the major obstacle to converting frailty research into clinical practice. Medical data naturally generated by routine clinical work containing frailty indicators are stored in electronic health records (EHRs) (also called electronic health record (EHR) data), which provide resources and possibilities for frailty assessment. We reviewed several frailty assessment tools based on primary care EHRs and summarized the features and novel usage of these tools, as well as challenges and trends. Further research is needed to develop and validate frailty assessment tools based on EHRs in primary care in other parts of the world.

Auricular Acupressure for Hemodialysis Patients with Insomnia: A Multicenter Double-Blind Randomized Sham-Controlled Trial.

Background and objectives: The effect of auricular acupressure (AA) for maintenance hemodialysis (MHD) patients with insomnia has been controversial. This study assessed the efficacy and safety of AA for MHD patients with chronic insomnia. Design, setting, participants, and measurements: This was a multicenter, double-blind (participant and assessor), randomized sham-controlled trial. A total of 133 subjects were randomized to receive AA on active points (AA group, n = 64) or on sham auricular acupressure (SAA) points (SAA group, n = 69) for 8 weeks and followed up for 12 weeks. AA was provided by assigned qualified nurses who were not involved in assessment. The primary outcome was the clinical response rate, which was defined as the percentage of participants who reached a reduction of Pittsburgh Sleep Quality Index (PSQI) global score ≥3 in each group. Secondary outcomes included changes in PSQI scores over time, PSQI scores and hypnotics use at each visit, and changes in the weekly dose of hypnotics for drug-dependent subjects. Results: At week 8, the AA group yielded a higher clinical response rate than the SAA group (AA: 55% vs. SAA: 36%, odds ratio: 1.5, 95% confidence interval: 1.0-2.2, p = 0.033). Both groups showed a reduction in PSQI global scores during treatment and follow-up, compared with the baseline, respectively. A significant change of PSQI global score was observed over time (F = 28.387, p < 0.001). PSQI global score of the AA group was relatively lower than that of the SAA group at each visit (p < 0.05 at week 16 and 20). For those depending on hypnotics, AA reduced their consumption of hypnotics. The intervention was safe, and its adherence was satisfactory. Conclusion: AA could serve as a complementary or alternative therapy for MHD patients with insomnia by improving their sleep quality and reducing their use of hypnotics. Clinical trial registration: Clinicaltrials.gov, Identifier: NCT03015766.

Prediction of prognosis in immunoglobulin a nephropathy patients with focal crescent by machine learning.

BACKGROUND AND OBJECTIVES: Immunoglobulin a nephropathy (IgAN) is the most common primary glomerular disease in the world, with different clinical manifestations, varying severity of pathological changes, common complications of crescent formation in different proportions, and great individual heterogeneous in clinical outcomes. Therefore, we aim to develop a machine learning (ML) based predictive model for predicting the prognosis of IgAN with focal crescent formation and without obvious chronic renal lesions (glomerulosclerosis <25%). MATERIALS: We retrospectively reviewed biopsy-proven IgAN patients in our hospital and cooperative hospital from 2005 to 2017. The method of feature importance of random forest (RF) was applied to conduct feature exploration of feature variables to establish the characteristic variables that are closely related to the prognosis of focal crescent IgAN. Multiple ML algorithms were attempted to establish the prediction models. The area under the precision-recall curve (AUPRC) and the area under the receiver operating characteristic curve (AUROC) were applied to evaluate the predictive performance via three-fold cross validation (namely 2 training sets and 1 validation set). RESULTS: RF was used to screen the important features, the top three of which were baseline estimated glomerular filtration rate (eGFR), serum creatine and triglyceride. Ten important features were selected as important predictors for modeling on the basis of data-driven and medical selection, predictors include: age, baseline eGFR, serum creatine, serum triglycerides, complement 3(C3), proteinuria, mean arterial pressure (MAP) and Hematuria, crescents proportion of glomeruli, Global crescent proportion of glomeruli. In a variety of ML algorithms, the support vector machine (SVM) algorithm displayed better predictive performance, with Precision of 0.77, Recall of 0.77, F1-score of 0.73, accuracy of 0.77, AUROC of 79.57%, and AUPRC of 76.5%. CONCLUSIONS: The SVM model is potentially useful for predicting the prognosis of IgAN patients with focal crescent shape and without obvious chronic renal lesions.

Rhubarb Enema Increasing Short-Chain Fatty Acids that Improves the Intestinal Barrier Disruption in CKD May Be Related to the Regulation of Gut Dysbiosis.

The incidence of CKD seriously endangers people's health. Researchers have proposed that improving the intestinal barrier damage in CKD may be an effective target for delaying the progression of CKD. Rhubarb can effectively improve the intestinal barrier and renal fibrosis, which may be related to the regulation of gut dysbiosis, but the mechanism needs to be further studied. Short-chain fatty acids (SCFAs) are important metabolites of the gut microbiota and play an important role in maintaining the intestinal barrier. The purpose of this study was to investigate whether rhubarb enema regulates the production of short-chain fatty acid-related gut microbiota and improves the intestinal barrier damage of CKD. 5/6 nephrectomy rats were used as the animal model, sevelamer was used as the positive control group, and the sham operation rats were used as the control group. After 4 weeks of enema treatment, the general clinical indicators, short-chain fatty acid levels, renal pathology, intestinal tissue pathology, intestinal tight junction protein, and changes in gut microbiota were detected. The results showed that rhubarb enema can increase the level of short-chain fatty acids in the 5/6 nephrectomy model rats, improve the intestinal barrier damage, inhibit the decrease of intestinal tight junction proteins, reduce inflammation levels, improve kidney pathology, reduce blood creatinine levels, and regulate the intestinal tract, the abundance, and composition of the flora. Further correlation analysis showed that rhubarb enema increased the level of short-chain fatty acids in 5/6 nephrectomy model rats, which may be related to the 7 strains that may regulate the production of short-chain fatty acids. This study indicated that rhubarb enema can improve the intestinal barrier damage of 5/6 nephrectomy model rats and improve CKD, which may be related to the regulation of short-chain fatty acid-producing gut microbiota.

Plaque control alleviated renal damage that was aggravated by experimental periodontitis in obese rats.

OBJECTIVE: This study aimed to evaluate the influence of experimental periodontitis on renal damage in obese rats. MATERIALS AND METHODS: Thirty-two male Sprague Dawley rats were randomly allocated into 4 groups with 8 animals each: obese rats (obese group), obese rats with periodontitis (periodontitis obese group), obese rats with periodontitis that underwent plaque control (plaque-control obese group), and healthy rats (healthy group). Rats were fed a high-fat diet to establish an obesity model. Experimental periodontitis was induced by local ligation with silk around the bilateral maxillary second molars. The plaque control was accomplished by removing ligations and local wiping with an antiseptic rinse. Histology was used to observe the gingival inflammation and clinical attachment level (CAL) to further assess bone loss and to also observe renal structure. Serum creatinine, urea nitrogen, and kidney injury molecule-1 (KIM-1) levels were measured to evaluate renal function. Renal Toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), serum C-reactive protein (CRP), lipopolysaccharides (LPS), and interleukin-1ß (IL-1ß) were measured to evaluate renal and systemic inflammation. RESULTS: Periodontal histology showed that in the periodontitis obese group, the epithelial barrier was considerably eroded by inflammatory cells, which infiltrated into the subepithelial connective tissue and lamina propria. A periodontal pocket was forming accompanied by the loss of attachment. The extent of infiltration of inflammatory cells and the CAL were significantly higher than those of the obese group (p < .001). In the plaque-control obese group, although the inflammatory condition was significantly improved than in the periodontitis obese group, the clinical attachment level with the presence of fiber hyperplasia could not be restored. Renal histology showed that renal tubular structural damage was aggravated in the periodontitis obese group, including vacuolar degeneration, exfoliation of the proximal tubular epithelial cell lining, multifocal loss of the brush border, and movement of several nuclei from the basement membrane to the lumen. These alterations were improved in the plaque-control obese group. Kidney TLR4 and NF-κB mRNA levels increased significantly in the periodontitis obese group compared to the obese group (p = .015 and p = .015, respectively) and decreased significantly in the plaque-control obese group (p = .028 and p = .021, respectively). Kidney TLR4 and NF-κB protein expression in the plaque-control obese group were significantly lower than those in the periodontitis obese group (p < .001 and p = .043, respectively). Serum creatinine and KIM-1 levels significantly decreased in the plaque-control obese group compared to the periodontitis obese group (p = .001 and p = .002, respectively). At 21 weeks (1 week after periodontal ligation), serum CRP levels in the periodontitis obese group were significantly higher than that in the healthy group (p = .017). Other serum inflammatory markers (LPS and IL-1ß) did not change significantly. CONCLUSION: Experimental periodontitis induced dysfunction and structural destruction of the kidney in obese rats. Plaque control relieved renal damage.

The role of urine IgG in the progression of IgA nephropathy with a high proportion of global glomerulosclerosis.

BACKGROUND: IgA nephropathy (IgAN), the most common glomerulonephritis in the world, is an important cause of end-stage renal disease (ESRD). It is necessary to explore new prognostic markers for predicting the activity and progress of IgAN. There are few studies on new prognostic markers in IgAN patients with high proportion of glomerulosclerosis. This study aims to explore the value of urine IgG in predicting the prognosis of IgAN patients. METHODS: The primary end point of this retrospective study was a composite event with a reduction in estimated glomerular filtration rate (eGFR) of ≥ 50% or ESRD or death. This study assessed the association between urinary IgG and clinicopathological parameters, as well as the prognosis of a high proportion of patients with global glomerulosclerotic IgAN. RESULTS: This study included 105 IgAN patients with high proportion of global glomerulosclerotic. The level of urinary protein IgG was significantly correlated with clinical prognostic factors. The level of urinary protein IgG was positively correlated with urinary protein excretion (rs = 0.834, P < 0.001), CRP (rs = 0.375, P < 0.001), and C4 (rs = 0.228, P = 0.019), and negatively correlated with eGFR (rs = - 0.307, P = 0.001). In addition, the level of urinary IgG increased with the increase of tubulointerstitial injury rate, which was positively correlated with endothelial cell proliferation and crescent (all P < 0.05). Prognostic analysis using the Cox proportional hazard regression model and Kaplan-Meier survival curve further determined that urine IgG is an independent risk factor for the prognosis of IgAN with high proportion of global glomerulosclerosis. CONCLUSIONS: This study determined that urine IgG can be used as a useful predictor of the prognosis of IgAN patients with high proportion global glomerulosclerosis. The mechanism of urine IgG trends in IgAN with high proportion of glomerulosclerosis needs further study.

Rhubarb Enema Decreases Circulating Trimethylamine N-Oxide Level and Improves Renal Fibrosis Accompanied With Gut Microbiota Change in Chronic Kidney Disease Rats.

Objectives: Trimethylamine N-oxide (TMAO), a metabolic product of gut flora, is increased in chronic kidney disease (CKD) subjects and is recognized as one type of uremic toxins which is associated with poor cardiovascular outcomes and kidney function loss. Previous studies have suggested that rhubarb enema could reduce circulating uremic toxins such as urea, creatinine, and indoxyl sulfate and also regulate the intestinal microbiota. However, whether rhubarb enema retards kidney dysfunction by reducing circulating TMAO and its underlying mechanism, are still unclear. The present study aims to investigate the impact of rhubarb enema on TMAO and its precursors, as well as on the intestinal microbiota in 5/6 nephrectomized (5/6Nx) CKD rats. Design: Rats in the treatment groups were given rhubarb enema after modeling. At the end of the study, blood, feces, and kidney tissues were collected and processed for biochemical analyses, histological and western blot analyses, 16S rRNA sequence and untargeted metabolomic analyses. Results: Rhubarb enema reduced serum TMAO and trimethylamine (TMA) levels, inhibited the expression of inflammatory markers (interleukin-6, tumor necrosis factor α and Interferon-γ) and alleviated tubular atrophy, monocyte infiltration and interstitial fibrosis in 5/6Nx CKD rats. Moreover, rhubarb enema significantly increased the abundance of some symbiotic bacteria and probiotics, while reduced the abundance of some potential pathogens at the genus level. In addition, Spearman's correlation analysis revealed that lachnospiraceae and romboutsia were positively correlated with TMAO. Conclusion: Rhubarb enema decreases circulating TMAO level and improves renal fibrosis in 5/6Nx CKD rats, which may be related to the regulation of intestinal microbial community.

Volume of Crescents Affects Prognosis of IgA Nephropathy in Patients without Obvious Chronic Renal Pathology.

INTRODUCTION: A working group on the Oxford classification of IgA nephropathy (IgAN) recently reported that crescents detected in the kidney tissue predicted a worse renal outcome. However, the effect of C1 lesion (crescents in <1/4th of all glomeruli) and their volume on the prognosis of IgAN is still unclear. We explored the association of C1 lesion with the renal prognosis in IgAN patients without obvious chronic renal lesions (glomerulosclerosis <25%, T score <2). METHODS: We investigated 305 biopsy-proven IgAN patients without obvious chronic renal lesions. Clinicopathologic features and treatment modalities were recorded. The patients were divided into several groups according to the presence or absence of a global crescent: no crescent (NC) group, only segmental crescent (SC) group, and global crescent (GC) group. The outcome was the survival from a combined event defined by a ≥15% decline in the estimated glomerular filtration rate (eGFR) after 1 year or ≥30% decline in the eGFR after 2 years. RESULTS: Among all patients, 75.7% were in the NC group, 14.8% were in the SC group, and 9.5% were in the GC group. Compared with the NC group, patients in the SC group and the GC group had more urine protein, lower eGFR, and presented with more severe pathological change. During a median follow-up of 34.8 (26.16-57.95) months, the combined event occurred in 34 individuals (11.1%). In a multivariate model, the GC group (HR = 2.756, 95% CI = 1.068-7.109) was associated with an increased risk of the combined event. CONCLUSIONS: In IgAN patients without obvious chronic renal lesions, the GC group had more severe clinical and pathological manifestations than in the NC group. GC is an independent risk factor for the progression of IgAN renal function.

Microbiome-Metabolomics Analysis Reveals the Protection Mechanism of α-Ketoacid on Adenine-Induced Chronic Kidney Disease in Rats.

Objectives: As nitrogen-free precursors of corresponding essential amino, α-ketoacid have been widely prescribed to end-stage renal disease patients together with a low protein diet However, the impact of α-ketoacid on intestinal microbiota in chronic kidney disease (CKD) individuals is unknown. The study aims at investigating the variation in the intestinal microbiota and metabolic profile in response to α-ketoacid treatment in an adenine-induced CKD rat model. Design: Rats in the treatment groups were given solution of compound α-ketoacid tablets. At the end of the study, blood, feces, colon tissues and kidney tissues were collected and processed for biochemical analyses, histological and western blot analyses, 16S rRNA sequence and untargeted metabolomic analyses. Results: α-Ketoacid treatment reduced serum creatinine, blood urea nitrogen and 24 h urine protein, and alleviated tubular atrophy, glomerulosclerosis and interstitial fibrosis in adenine-induced CKD rats. Moreover, α-ketoacid significantly improved intestinal barrier and increased the abundance of Methanobrevibacter, Akkermansia, Blautia and Anaerositipes while reduced the abundance of Anaerovorax and Coprococcus_3 at the genus level. In addition, our results also demonstrated that α-ketoacid significantly reduced the concentrations of indoxyl sulfate, betaine, choline and cholesterol. Spearman's correlation analysis revealed that the abundance of Coprococcus_3 was positively correlated with serum level of betaine, trimethylamine N-oxide, indoxyl sulfate, cholic acid and deoxycholic acid. Conclusion: α-Ketoacid has a reno-protective effect against adenine-induced CKD, which may be mediated regulation of serum metabolic profiles via affecting intestinal microbial community.

Psychological Distress Reported by Primary Care Physicians in China During the COVID-19 Pandemic.

OBJECTIVE: Primary care physicians (PCPs) play a key role in responding to the COVID-19 epidemic. The objective of this study was to explore the influencing factors associated with self-reported psychological distress among a sample of PCPs in China in relation to COVID-19. METHODS: An online survey was distributed to a sample of PCPs in Chengdu city between February 10 and February 13, 2020. The survey consisted of three sections: demographic characteristics, COVID-19-related questions, and the General Health Questionnaire-12 (GHQ-12). After 5 months, a follow-up survey investigating the change of the GHQ-12 was conducted. RESULTS: A total of 712 PCPs completed the baseline survey (11.8% of those invited), 55.6% were female and 74.4% were aged between 30 and 49 years. High levels of psychological distress (GHQ-12 ≥3) were observed in 29.2% and were associated with low preparedness, high work impact, working with infected residents, personal life impact, and concerns, as well as older age and being married (p values < .05). Logistic regression analysis showed that psychological distress was associated with low preparedness (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.87-0.96), high work impact (OR = 1.11, 95% CI = 1.03-1.20), personal life impact (OR = 1.12, 95% CI = 1.07-1.17), and safety-related concerns (OR = 1.09, 95% CI = 1.02-1.16). At the 5-month assessment point, high psychological distress was less frequent (21.8%). CONCLUSIONS: COVID-19 has resulted in high levels of distress in approximately 30% of PCPs in China. Factors associated with high psychological distress levels include low preparedness and high levels of work impact, personal life impact, and concerns. These findings highlight the importance of enhancing psychological health throughout the course of infectious pandemics.