Association between handgrip strength and depressive symptoms in patients undergoing hemodialysis: a cross-sectional study from a single Chinese center.

BACKGROUND: The relationship between handgrip strength (HGS) and depression in patients undergoing hemodialysis (HD) was unknown. Therefore, we aimed to clarify this association in a cohort of patients. METHODS: HGS was used as a representative indicator of muscle strength and was measured with a handheld dynamometer. Depressive symptoms were assessed with the self-reported Patient Health Questionnaire-9. A multivariable logistic regression model and restricted cubic spline analysis were used to assess the relationship between HGS and depression. RESULTS: The prevalence of depression in our study was 34% in 568 Chinese patients undergoing HD. Compared with patients in the lowest tertiles of absolute and weighted HGS, patients in the highest tertiles of HGS had an approximately 59% lower [odds ratio (OR) = 0.41, 95% confidence interval (CI) = 0.24-0.68; OR = 0.41, 95%CI = (0.24-0.69)] prevalence of depressive symptoms after multivariate adjustments. Besides, the risk of depression in hemodialysis patients decreased by 33% (OR = 0.67, 95%CI = 0.53-0.85) and 32% (OR = 0.68, 95%CI = 0.54-0.85) for each standard deviation increase in absolute HGS and weighted HGS, respectively. The prevalence of depressive symptoms decreased with both increasing absolute HGS and weighted HGS after multivariate adjustments (p for trend < 0.05). Furthermore, a linear dose-response relationship was observed between absolute HGS and weighted HGS and the prevalence of depressive symptoms (pnonlinearity>0.05). CONCLUSIONS: This study suggests that lower handgrip strength, a simple and modifiable parameter, is associated with a higher prevalence of depression in Chinese patients undergoing HD. Considering that depression is often unrecognized or underdiagnosed in HD patients, lowered muscle strength should be an important indicator and incentive for medical staff to screen for depression.

Roxadustat alleviates the inflammatory status in patients receiving maintenance hemodialysis with erythropoiesis-stimulating agent resistance by increasing the short-chain fatty acids producing gut bacteria.

BACKGROUND: Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have improved the treatment of renal anemia, especially in patients resistant to erythropoiesis-stimulating agents (ESAs). HIF facilitates maintain gut microbiota homeostasis, which plays an important role in inflammation and iron metabolism, which are in turn key factors affecting ESA resistance. The current study aimed to investigate the effects of roxadustat on inflammation and iron metabolism and on the gut microbiota in patients with ESA resistance. METHODS: We conducted a self-controlled, single-center study including 30 patients with ESA resistance undergoing maintenance hemodialysis. All patients received roxadustat without iron agents for renal anemia. Hemoglobin and inflammatory factors were monitored. Fecal samples were collected before and after 3 months' administration and the gut microbiota were analyzed by 16S ribosomal RNA gene sequencing. RESULTS: Hemoglobin levels increased after treatment with roxadustat for 3 months (P < 0.05). Gut microbiota diversity and abundance also changed, with increases in short-chain fatty acid (SCFA)-producing bacteria (Acidaminococcaceae, Butyricicoccus, Ruminococcus bicirculans, Ruminococcus bromii, Bifidobacterium dentium, Eubacterium hallii) (P < 0.05). Serum SCFA levels also increased (P < 0.05). Inflammatory factors, including interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α, interferon-γ, and endotoxin gradually decreased (P < 0.05). Serum hepcidin, ferritin, and total and unsaturated iron-binding capacities decreased (P < 0.05), while soluble transferrin receptor levels increased at each time point (P < 0.05). There were no significant differences in serum iron and transferrin saturation at each time point. The abundance of Alistipes shahii was significantly negatively correlated with IL-6 and TNF-α (P < 0.05). CONCLUSIONS: Roxadustat alleviated renal anemia in patients with ESA resistance by decreasing inflammatory factors and hepcidin levels and improving iron utilization. These effects were at least partly mediated by improved diversity and abundance of SCFA-producing gut bacteria, probably via activation of HIF.

Association between serum ß2-microglobulin levels and the risk of all-cause and cardiovascular disease mortality in chinese patients undergoing maintenance hemodialysis.

BACKGROUND: The association between serum ß2-microglobulin (ß2M) levels and the risk of all-cause and cardiovascular disease (CVD) mortality and the incidence of cardiovascular events (CVEs) in patients undergoing maintenance hemodialysis (MHD) is inconclusive. Furthermore, no study has been performed in China on the significance of serum ß2M levels in MHD patients. Therefore, this study investigated the aforementioned association in MHD patients. METHODS: In this prospective cohort study, 521 MHD patients were followed at Dalian Municipal Central Hospital affiliated with Dalian University of Technology from December 2019 to December 2021. The serum ß2M levels were categorized into three tertiles, and the lowest tertile served as the reference group. Survival curves were calculated by the Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. Sensitivity analysis was performed by excluding patients with CVD at baseline. RESULTS: During the follow-up period of 21.4 ± 6.3 months, there were 106 all-cause deaths, of which 68 were caused by CVD. When excluding CVD patients at baseline, there were 66 incident CVEs. Kaplan-Meier analysis revealed that the risk of all-cause and CVD mortality in the highest tertile of serum ß2M levels was significantly higher than that in the lowest tertile (P < 0.05), but not for the CVEs (P > 0.05). After adjusting for potential confounders, serum ß2M levels were positively associated with the risk of all-cause (HR = 2.24, 95% CI = 1.21-4.17) and CVD (HR = 2.54, 95% CI = 1.19-5.43) mortality, and a linear trend was evident (P < 0.05). Besides, the results of sensitivity analysis were consistent with the main findings. However, we didn't observed the significant association between serum ß2M levels and CVEs (P > 0.05). CONCLUSION: The serum ß2M level may be a significant predictor of the risk of all-cause and CVD mortality in MHD patients. Further studies are needed to confirm this finding.

Association between corrected serum calcium levels after dialysis and post-dialysis fatigue risk: a hospital-based case-control study.

OBJECTIVE: Post-dialysis fatigue (PDF) is an important problem in patients undergoing maintenance hemodialysis (MHD); however, evidence of the association between serum calcium after dialysis and the risk of PDF is limited and controversial. We explored this association among patients receiving MHD. METHODS: We carried out a case-control study of patients in the dialysis unit of Dalian Municipal Central Hospital between December 2019 and January 2020, including 340 patients with PDF and 270 patients without PDF. PDF was assessed by a \validated self-administered questionnaire. Clinical variables were tested for multicollinearity using variance inflation factor analysis. Corrected serum calcium levels were categorized into three groups, with the lowest tertile used as the reference category. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for PDF risk were estimated using an unconditional logistic regression model. RESULT: After adjusting for potential confounders, corrected serum calcium levels showed a significant positive association with the risk of PDF (ORT3vs.T1 = 1.61, 95% CI = 1.01-2.58). Notably, after stratification by age, corrected serum calcium was also positively associated with the risk of PDF in patients aged ≥ 65 years (ORT3vs.T1 = 4.25, 95% CI 1.66-11.46). Furthermore, a significant linear trend and interaction were also observed (P < 0.05). DISCUSSION: Higher corrected serum calcium levels after dialysis might increase the risk of PDF among MHD patients. However, further studies are warranted to confirm these findings.

Association of dietary fiber with subjective sleep quality in hemodialysis patients: a cross-sectional study in China.

BACKGROUND: Poor sleep quality is a common problem among hemodialysis (HD) patients. Dietary fiber is a key component of a healthy diet and is beneficial for a variety of health outcomes; however, evidence of an association between dietary fiber consumption and subjective sleep quality has not been established among HD patients. Therefore, we determined the association between dietary fiber consumption and the subjective sleep quality in Chinese maintenance HD patients, taking into account fiber type and source. METHODS: Dietary intake was assessed with a validated food frequency questionnaire in a cross-sectional study including 741 maintenance HD patients between December 2021 and January 2022. The daily intake of dietary fiber was categorized into three groups. The lowest tertile was used as the reference category. Sleep quality of patients was accurately calculated using the Pittsburgh sleep quality index standard questionnaire. Multivariable logistic regression model and restricted cubic spline analysis were performed to assess the relationship between dietary fiber consumption and poor sleep quality. RESULTS: Compared with the lowest tertile group of dietary fiber intake, the highest tertile group had a lower prevalence of poor sleep quality. After adjustment for potential confounders, a higher intake of total dietary fiber (ORtertile 3 (T3) to tertile 1 (T1)= 0.51, 95% CI: 0.31-0.85), total insoluble dietary fiber (ORT3 to T1 =0.54, 95% CI: 0.33-0.89), and soluble dietary fiber in vegetables (ORT3 to T1 =0.61, 95% CI: 0.40-0.93) were associated with a lower prevalence of poor sleep quality. Furthermore, significant linear trends were also observed (p < 0.05). No significant interactions were observed in subgroup analyses. CONCLUSION: A higher intake of dietary fiber was inversely associated with the poor sleep quality. These findings support the current recommendations that dietary fiber is essential for health and well-being.Key messagesThis study was conducted because there was not prior evidence connecting sleep quality and dietary fiber consumption in hemodialysis patients.In the present study a cross-sectional design was used to assess the association between dietary fiber consumption and poor sleep quality.Intake of total dietary fiber, total insoluble dietary fiber, and soluble dietary fiber in vegetables were negatively associated with poor sleep quality among maintenance hemodialysis patients.

RBM4 regulates cellular senescence via miR1244/SERPINE1 axis.

Cellular senescence serves as a powerful tumor suppressing mechanism that inhibits the proliferation of cancer cells bearing oncogenic mutations at the initial stage of cancer development. RNA-binding proteins (RBPs) play important roles in cancer progression and treatment through distinct functions. However, functions and mechanisms of RNA binding proteins in regulating senescence remain elusive. Here we reported that the RNA binding protein RBM4 contributed to cellular senescence. Depletion of RBM4 induced senescence in different types of cells, including multiple cancer cells. Meanwhile, RBM4 ablation inhibited cancer cell progression both in vitro and in vivo. Specifically, knockdown of RBM4 significantly increased the level of SERPINE1, a known promoter of senescence, thereby inducing the senescence of lung cancer cells. Mechanistically, miR-1244 bound to the 3'-UTR of SERPINE1 to suppress its expression, whereas depletion of RBM4 reduced the level of miR-1244 by promoting the degradation of primary miR-1244 transcripts (pri-miR1244), thus increasing the expression of SERPINE1 and inducing subsequent senescence. Moreover, either SERPINE1 inhibitor or miR-1244 mimics attenuated the RBM4 depletion-induced senescence. Altogether, our study revealed a novel mechanism of RBM4 in the regulation of cancer progression through controlling senescence, providing a new avenue for targeting RBM4 in cancer therapeutics.

Dialysis adequacy and hemoglobin levels predict cerebral atrophy in maintenance-hemodialysis patients.

The pathogenesis of cerebral atrophy (CA) is not clear. Previous studies show a high incidence of preterm CA in hemodialysis patients. This study aims to investigate the factors influencing CA and to derive a CA prediction nomogram in maintenance-hemodialysis patients. First, brain volumes of hemodialysis patients (≤55 years) were compared against age- and sex-matched healthy controls, and differences were revealed in bilateral insular cisterns width, maximum cerebral sulci width, Evans index, ventricular-brain ratio, frontal atrophy index, and temporal lobe ratio. Then, the patients were divided equally into "no or mild" or "severe" CA groups. Potential factors influencing CA were screened. Kt/V (urea removal index) and hemoglobin levels negatively correlated with CA degree, and were used to establish a nomogram within randomly assigned training and validation patient groups. The areas under the receiver operating characteristic curves (AUROC) for training and validation groups were 0.703 and 0.744, respectively. When potassium and calcium were added to the nomogram, the AUROC for training/validation group increased to 0.748/0.806. The nomogram had optimal AUROC for training (0.759) and validation (0.804) groups when albumin was also included. Hemodialysis patients showed reduced anterior brain volumes and the nomogram established herein may have predictive value for developing CA.

A methodologic survey on use of the GRADE approach in evidence syntheses published in high-impact factor urology and nephrology journals.

BACKGROUND: To identify and describe the use of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for rating the certainty of systematic reviews (SRs) evidence published in urology and nephrology journals. METHODS: SRs that were published in the top ten "urology and nephrology" journals with the highest impact factor according to the 2020 Journal Citation Reports (covering 2016-2020) were systematically searched and evaluated using the GRADE approach. RESULTS: A total of 445 SRs were researched. Sixty SRs of randomized control trials (RCTs) and/or non-randomized studies (NRSs) were evaluated using the GRADE approach. Forty-nine SRs (11%) rated the outcome-specific certainty of evidence (n = 29 in 2019-2020). We identified 811 certainty of evidence outcome ratings (n = 544 RCT ratings) as follows: very low (33.0%); low (32.1%); moderate (24.5%); and high (10.4%). Very low and high certainty of evidence ratings accounted for 55.0% and 0.4% of ratings in SRs of NRSs compared to 23.0% and 15.3% in SRs of RCTs. The certainty of evidence for RCTs and NRSs was downgraded most often for risk of bias and imprecision. CONCLUSIONS: We recommend increased emphasis on acceptance of the GRADE approach, as well as optimal use of the GRADE approach, in the synthesis of urinary tract evidence.

The association between dose of hemodialysis and patients mortality in a prospective cohort study.

Dialysis adequacy is a known risk factor for mortality in maintenance hemodialysis (MHD) patients. However, the optimal dialysis dose remains controversial. Therefore, we aimed to explore the relationship between dialysis dose and all-cause and cardiovascular disease (CVD) mortality among MHD. We examined the associations of dialysis dose with mortality in a cohort (n = 558) of MHD patients from 31 December 2015 to 31 December 2020. Dialysis adequacy was assessed using baseline Single-pool Kt/Vurea (spKt/V), which was categorized into three groups, and the lowest dose group was used as the reference category. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. A total of 214 patients died (64.5% for CVD). Compared with the low-dose group, high-dose group could reduce the risk of all-cause mortality by 33% (HR = 0.67, 95% CI: 0.47-0.98). Of note, when stratification by age, high-dose group was associated with both lower all-cause (HR = 0.46, 95% CI: 0.26-0.81) and CVD mortality (HR = 0.42, 95% CI: 0.20-0.88) among patients with age below 65 years. When stratification by dialysis age, high-dose group was associated with decreased risk of CVD mortality (HR = 0.43, 95% CI: 0.20-0.91) among patients with dialysis age over 60 months. spKt/V is a simple index of hemodialysis dose used in clinical practice and a useful modifiable factor in predicting the risk of death, especially in MHD patients under 65 years old or dialysis age more than 60 months.

Serum total indoxyl sulfate levels and all-cause and cardiovascular mortality in maintenance hemodialysis patients: a prospective cohort study.

BACKGROUND: The association between serum total indoxyl sulfate (tIS), and cardiovascular disease (CVD) and all-cause mortality is a matter of debate. In the current study we sought to determine the association, if any, between serum tIS, and all-cause and CVD-associated mortality in patients on maintenance hemodialysis (MHD). METHODS: A prospective cohort study was conducted involving 500 MHD patients at Dalian Municipal Central Hospital from 31 December 2014 to 31 December 2020. Serum tIS levels were measured at baseline and classified as high (≥44.16 ng/ml) or low (< 44.16 ng/ml) according to the "X-tile" program. Besides, the associations between continuous serum tIS and outcomes were also explored. Predictors were tested for colinearity using variance inflation factor analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Restricted cubic spline model was performed to assess dose-response relationships between tIS concentration and all-cause and CVD mortality. RESULTS: During a 58-month median follow-up period, 224 deaths (132 CVD deaths) were documented. After adjustment for potential confounders, the serum tIS level was positively associated with all-cause mortality (HR = 1.02, 95% = 1.01-1.03); however, we did not detect a significant association when tIS was a dichotomous variable. Compared with the MHD population with a serum tIS level < 44.16 ng/ml, the adjusted HR for CVD mortality among those with a serum tIS level ≥ 44.16 ng/ml was 1.76 (95% = 1.10-2.82). Furthermore, we also noted the same association when the serum tIS level was a continuous variable. CONCLUSION: The serum tIS level was associated with higher risk of all-cause and CVD mortality among MHD patients. Further prospective large-scale studies are required to confirm this finding.

Molecular cloning and functional analysis of nine cinnamyl alcohol dehydrogenase family members in Populus tomentosa.

MAIN CONCLUSION: Nine CAD/CAD-like genes in P. tomentosa were classified into four classes based on expression patterns, phylogenetic analysis and biochemical properties with modification for the previous claim of SAD. Cinnamyl alcohol dehydrogenase (CAD) functions in monolignol biosynthesis and plays a critical role in wood development and defense. In this study, we isolated and cloned nine CAD/CAD-like genes in the Populus tomentosa genome. We investigated differential expression using microarray chips and found that PtoCAD1 was highly expressed in bud, root and vascular tissues (xylem and phloem) with the greatest expression in the root. Differential expression in tissues was demonstrated for PtoCAD3, PtoCAD6 and PtoCAD9. Biochemical analysis of purified PtoCADs in vitro indicated PtoCAD1, PtoCAD2 and PtoCAD8 had detectable activity against both coniferaldehyde and sinapaldehyde. PtoCAD1 used both substrates with high efficiency. PtoCAD2 showed no specific requirement for sinapaldehyde in spite of its high identity with so-called PtrSAD (sinapyl alcohol dehydrogenase). In addition, the enzymatic activity of PtoCAD1 and PtoCAD2 was affected by temperature. We classified these nine CAD/CAD-like genes into four classes: class I included PtoCAD1, which was a bone fide CAD with the highest activity; class II included PtoCAD2, -5, -7, -8, which might function in monolignol biosynthesis and defense; class III genes included PtoCAD3, -6, -9, which have a distinct expression pattern; class IV included PtoCAD12, which has a distinct structure. These data suggest divergence of the PtoCADs and its homologs, related to their functions. We propose genes in class II are a subset of CAD genes that evolved before angiosperms appeared. These results suggest CAD/CAD-like genes in classes I and II play a role in monolignol biosynthesis and contribute to our knowledge of lignin biosynthesis in P. tomentosa.

Electrochemical performance of La2O3/Li2O/TiO2 nano-particle coated cathode material LiFePO4.

Cathode material, LiFePO4 was modified by coating with a thin layer of La2O3/Li2O/TiO2 nano-particles for improving its performance for lithium ion batteries. The morphology and structure of the modified cathode material were characterized by powder X-ray diffraction, scanning electron microcopy and AES. The performance of the battery with the modified cathode material, including cycling stability, C-rate discharge was examined. The results show that the battery composed of the coated cathode materials can discharge at a large current density and show stable cycling performance in the range from 2.5 to 4.0 V. The rate of Li ion diffusion increases in the battery with the La2O3/Li2O/TiO2-coated LiFePO4 as a cathode and the coating layer may acts as a faster ion conductor (La(2/3-x)Li(3x)TiO3).

Characteristics and influence factors of pathologic transformation in the subclasses of class IV lupus nephritis.

The study explored the characteristics and correlation factors of transformation in subclasses of class IV lupus nephritis. Patients with class IV lupus nephritis were subjected to repeat biopsies after 6 months of induction treatment. Transformation rate between two subclasses, class IV-S and class IV-G, was compared. Influence Factors of transformation were evaluated. Class IV-G had more severe hypertension and higher score of immunofluorescence index, glomerular active lesions, tubular and vascular lesions. Class IV-S had a higher percentage of glomerular fibrinoid necrosis. Class IV-S appeared a higher rate of transformation to class II than class IV-G (57% vs. 27%). In each subclass, active lesion also showed a higher rate of transformation to class II than active/chronic lesion (IV-G: 41.2% vs. 12.5%; IV-S: 71.4% vs. 42.8%). Patients who maintained class IV had higher blood pressure, obvious proteinuria, declined kidney function, and lower C3 level. Immunosuppressive therapy, urine protein, and vascular lesions were independent risk factors for the pathologic transformation. The rate of transformation in class IV-S was higher than that in class IV-G. The transformation is most likely to benefit from immunosuppressive therapy. Urine protein and vascular lesions are correlated with the transformation in class IV lupus nephritis.

[Effects of hypoxia on iron metabolism of rat L6 skeletal muscle cells].

The present study was aimed to investigate the effects of hypoxia on iron metabolism of skeletal muscle. Rat L6 skeletal muscle cells were randomly divided into three groups which were exposed to hypoxia (1% O(2)) for 0, 12, 24 h, respectively. Iron isotope tracing method was used to determine iron uptake and release. Iron content of labile iron pool (LIP) was investigated by flow cytometry, and the expressions of transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1), hypoxia-inducible transcription factor-1 (HIF-1) in L6 cells were observed by Western blot. The results showed that, compared with 0-hour hypoxia group, 12-hour hypoxia group exhibited significantly increased iron uptake and LIP (P < 0.05), as well as decreased iron release (P < 0.01). Not only iron uptake and release, but also LIP in 24-hour hypoxia group were significantly decreased, compared with those in 0- and 12-hour hypoxia groups (P < 0.01). The expressions of HIF-1, DMT1 (IRE), DMT1 (non-IRE) and TfR1 in 12-hour hypoxia group were significantly increased compared with those in 0-hour hypoxia group (P < 0.01). On the contrary, the expressions of DMT1 (IRE), DMT1 (non-IRE) and FPN1 in 24-hour hypoxia group were significantly decreased compared with those in the other two groups. However, TfR1 expression in 24-hour hypoxia was higher than those in 0- and 12-hour hypoxia groups (P < 0.05 or P < 0.01). These results suggest hypoxia plays an important role in iron metabolism of skeletal muscle cells. Moderate hypoxia can increase iron uptake and decrease iron release, resulting in higher LIP, but a prolonged hypoxia induces a disordered iron metabolism of skeletal cells.

[Different sensitivity of 23 common crop species to cadmium toxicity].

Cadmium toxicity to 23 kinds of commonly cultivated crops of 9 families was studied by solution culture with different cadmium concentrations. Most of the studied crop seedlings showed cadmium toxicity symptoms with 0.1-0.25 mg x L(-1). The toxic effects of cadmium on the crops were quite different. The effect of Cd on shoot biomass was more obvious and stable than the other parameters at low Cd concentrations (0.1-0.5 mg x L(-1)), Therefore, shoot fresh weight was selected to be the indicator of plant sensitivity to Cd. The EC20 (effective concentration causing a 20% inhibition of shoot biomass) values of Cd for the studied crops ranged from 0.03 to 24.67 mg x L(-1). The Cd sensitivity of the crops is classified according to the response endpoint of apparent symptoms and the EC20 values. Chinese cabbage, brassica napus, youmai lettuce, mustard and pakchoi are sensitive species to Cd toxicity that can be used as ecological receptors to determine the critical value of the toxicity of soil Cd to crops or as monitoring crop species of soil Cd pollution. Cucumber is most tolerant to Cd toxicity among the studies crops.