Lipid parameters, adipose tissue distribution and prognosis prediction in chronic kidney Disease patients.

BACKGROUND: Lipid management in clinic is critical to the prevention and treatment of Chronic kidney disease (CKD), while the manifestations of lipid indicators vary in types and have flexible association with CKD prognosis. PURPOSE: Explore the associations between the widely used indicators of lipid metabolism and their distribution in clinic and CKD prognosis; provide a reference for lipid management and inform treatment decisions for patients with non-dialysis CKD stage 3-5. METHODS: This is a retrospective cohort study utilizing the Self-Management Program for Patients with Chronic Kidney Disease Cohort (SMP-CKD) database of 794 individuals with CKD stages 3-5. It covers demographic data, clinical diagnosis and medical history collection, laboratory results, circulating lipid profiles and lipid distribution assessments. Primary endpoint was defined as a composite outcome(the initiation of chronic dialysis or renal transplantation, sustained decline of 40% or more in estimated glomerular filtration rate (eGFR), doubled of serum creatinine (SCr) from the baseline, eGFR less than 5 mL/min/1.73m2, or all-cause mortality). Exposure variables were circulating lipid profiles and lipid distribution measurements. Association were assessed using Relative risks (RRs) (95% confidence intervals (CIs)) computed by multivariate Poisson models combined with least absolute shrinkage and selection operator (LASSO) regression according to categories of lipid manifestations. The best model was selected via akaike information criterion (AIC), area under curve (AUC), receiver operating characteristic curve (ROC) and net reclassification index (NRI). Subgroup analysis and sensitivity analysis were performed to assess the interaction effects and robustness.. RESULTS: 255 individuals reached the composite outcome. Median follow-up duration was 2.03 [1.06, 3.19] years. Median age was 58.8 [48.7, 67.2] years with a median eGFR of 33.7 [17.6, 47.8] ml/min/1.73 m2. Five dataset were built after multiple imputation and five category-based Possion models were constructed for each dataset. Model 5 across five datasets had the best fitness with smallest AIC and largest AUC. The pooled results of Model 5 showed that total cholesterol (TC) (RR (95%CI) (per mmol/L) :1.143[1.023,1.278], P = 0.018) and percentage of body fat (PBF) (RR (95%CI) (per percentage):0.976[0.961,0.992], P = 0.003) were significant factors of composite outcome. The results indicated that comprehensive consideration of lipid metabolism and fat distribution is more critical in the prediction of CKD prognosis.. CONCLUSION: Comprehensive consideration of lipid manifestations is optimal in predicting the prognosis of individuals with non-dialysis CKD stages 3-5.

Expansin SlExp1 and endoglucanase SlCel2 synergistically promote fruit softening and cell wall disassembly in tomato.

Fruit softening, an irreversible process that occurs during fruit ripening, can lead to losses and waste during postharvest transportation and storage. Cell wall disassembly is the main factor leading to loss of fruit firmness, and several ripening-associated cell wall genes have been targeted for genetic modification, particularly pectin modifiers. However, individual knockdown of most cell wall-related genes has had minimal influence on cell wall integrity and fruit firmness, with the notable exception of pectate lyase. Compared to pectin disassembly, studies of the cell wall matrix, the xyloglucan-cellulose framework, and underlying mechanisms during fruit softening are limited. Here, a tomato (Solanum lycopersicum) fruit ripening-associated α-expansin (SlExpansin1/SlExp1) and an endoglucanase (SlCellulase2/SlCel2), which function in the cell wall matrix, were knocked out individually and together using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9-mediated genome editing. Simultaneous knockout of SlExp1 and SlCel2 enhanced fruit firmness, reduced depolymerization of homogalacturonan-type pectin and xyloglucan, and increased cell adhesion. In contrast, single knockouts of either SlExp1 or SlCel2 did not substantially change fruit firmness, while simultaneous overexpression of SlExp1 and SlCel2 promoted early fruit softening. Collectively, our results demonstrate that SlExp1 and SlCel2 synergistically regulate cell wall disassembly and fruit softening in tomato.

Impact of dialysis modality choice on the survival of end-stage renal disease patients with congestive heart failure in southern China: A retrospective cohort study.

Background and object: Heart failure is one of the common complications in patients with end-stage renal disease (ESRD) and a major cause of death in these patients. The choice of dialysis modality for ESRD patients with congestive heart failure (CHF) is still inconclusive. The purpose of this study was to compare the prognosis of hemodialysis (HD) and peritoneal dialysis (PD) among ESRD patients with CHF and provide a basis for clinical decision-making. Materials and methods: This was a retrospective study conducted at Guangdong Provincial Hospital of Traditional Chinese Medicine that included patients with CHF requiring long-term renal replacement therapy between January 1, 2012 and December 31, 2017. The end of follow-up was December 31, 2020. All patients were divided into HD and PD groups and sub grouped by age, and we used univariate and multifactorial Cox regression analyses to calculate the relative hazard ratios (HR) of the different dialysis types and adjusted for differences in baseline data using propensity score matching (PSM). Result: A total of 121 patients with PD and 156 patients with HD were included in this study. Among younger ESRD patients (≤65 years of age) with CHF, the prognosis of HD was worse than that of PD [HR = 1.84, 95% confidence interval (CI) = 1.01-3.34], and this disadvantage remained significant in the fully adjusted model [sex, age at dialysis initiation, Charlson comorbidities index, body mass index, prealbumin, hemoglobin, and left ventricular ejection fraction (LVEF)] and after PSM. In the older group (>65 years of age), the prognosis of HD was better than that of PD (HR = 0.46, 95% CI = 0.25-0.85), and the protective effect remained in the fully adjusted model and after PSM. The aforementioned survival differences across the cohort were maintained in patients with preserved LVEF (>55%), but could not be reproduced in patients with reduced LVEF (≤55%). Conclusion: In southern China, PD is a better choice for younger patients with ESRD, CHF and preserved LVEF, and HD is the better option for older patients.

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.

Propensity-matched comparison of mortality between peritoneal dialysis and hemodialysis in patients with type 2 diabetes.

BACKGROUND: The optimal choice of dialysis modality for diabetic patients remains controversial. This study aimed to compare mortality between peritoneal dialysis (PD) and hemodialysis (HD) in end-stage renal disease (ESRD) patients with type 2 diabetes (T2D). METHODS: Our observational, longitudinal cohort consisted of all incident ESRD patients with T2D who received either PD or HD in our center from January 2012 to December 2017 and were followed until December 2019. Propensity scores were used to select a 1:1 matched cohort. Mortality was compared between dialysis modalities using Kaplan-Meier survival analysis, and risk factors for mortality were estimated using multivariate Cox regression analyses. RESULTS: The median follow-up times were 35.5 months in the PD group (n = 134) and 41.6 months in the HD group (n = 134, p = 0.0381). The 1-, 2-, 3-, 5-, and 7-year patient survival rates were 98%, 91%, 77%, 61%, and 35% for diabetic PD patients and 96%, 88%, 81%, 60%, and 57% for diabetic HD patients. Kaplan-Meier survival analysis showed that overall mortality did not significantly differ between modalities (log-rank = 0.9473, p = 0.6575). Using a multivariate Cox regression model, advanced age and increased cholesterol at the initiation of PD treatment were independent risk factors associated with mortality, whereas under HD therapy, the risk factors associated with mortality were lower BMI and higher HbA1c. CONCLUSIONS: These results suggest that in patients with T2D, mortality is comparable between PD and HD irrespective of whether there are the first 2 years or over the 2-year period, and that different mortality predictor patterns exist between patients treated with PD versus HD.

Effects of dialysis modality choice on the survival of end-stage renal disease patients in southern China: a retrospective cohort study.

BACKGROUND: The optimal choice of treatment, with hemodialysis (HD) or peritoneal dialysis (PD), for end-stage renal disease (ESRD) patients, is still controversial. Only a few studies comparing HD and PD have been conducted in China, which has the largest number of dialysis patients in the world. METHODS: A retrospective cohort study was conducted on ESRD patients who began renal replacement treatment from January 1, 2012 to December 31, 2017 in Guangdong Provincial Hospital of Chinese Medicine. Propensity scoring match was applied to balance the baseline conditions and multivariate Cox regression analysis to compare the mortality between HD and PD patients, and evaluated the correlation between mortality and various baseline characteristics. RESULTS: A total of 436 HD patients and 501 PD patients were included in this study, and PD patients had better survival than HD patients, but the difference was not statistically significant. For younger ESRD patients (≤60-year-old), the overall survival of PD was better than that of HD, but HD was associated with a lower risk of death in older patients (> 70-year-old). This difference was still significant after adjustment for a variety of confounding factors. Female gender, age at dialysis initiation, cardiovascular disease, cholesterol, and HD were risk factors of all-cause mortality in the younger subgroup, while PD was risk factor in the older subgroup. CONCLUSION: PD may be a better choice for younger ESRD patients, and HD for the older patients.

Association of Kidney Function with Infections by Multidrug-Resistant Organisms: An Electronic Medical Record Analysis.

Antibiotic resistance is a major global health threat. High prevalences of colonization and infection with multi-drug resistance organisms (MDROs) have been reported in patients undergoing dialysis. It is unknown if this finding extends to patients with mild and moderate/severe kidney disease. An observational study included all adult incident patients hospitalized with a discharge diagnosis of infection in four hospitals from Guangzhou, China. INCLUSION CRITERIA: Serum creatinine measurement at admission together with microbial culture confirmed infections. Exclusion criterion: Undergoing renal replacement therapy. Four categories of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) were compared: eGFR ≥ 105, 60-104 (reference), 30-59, and <30 ml/min/1.73 m2. The odds ratio of MDROs, defined as specific pathogens (Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp.) resistant to three or more antibiotic classes, were calculated using a multivariable logistic regression model across eGFR strata. Of 94,445 total microbial culture records, 7,288 first positive cultures matched to infection diagnosis were selected. Among them, 5,028 (68.9%) were potential MDROs. The odds of infections by MDROs was 19% and 41% higher in those with eGFR between 30-59 ml/min/1.73 m2 (Adjusted odds ratio, AOR): 1.19, 95% CI:1.02-1.38, P = 0.022) and eGFR < 30 ml/min/1.73 m2 (AOR: 1.41, 95% CI:1.12-1.78, P = 0.004), respectively. Patients with impaired renal function have a higher risk of infections by MDROs. Kidney dysfunction at admission may be an indicator for need of closer attention to microbial culture results requiring subsequent change of antibiotics.

Auricular acupressure for insomnia in hemodialysis patients: study protocol for a randomized controlled trial.

BACKGROUND: Patients on maintenance hemodialysis (MHD) frequently complain of insomnia. Poor sleep quality impairs their quality of life and adversely affects long-term outcome. Previously we applied auricular acupressure therapy (AAT) for MHD patients with insomnia and yielded favorable results. AAT probably improves sleep quality by stimulating the vagus nerve and inhibiting sympathetic overactivity. However, the efficacy of AAT for insomnia in this population is still lacking. The proposed randomized controlled trial (RCT) will evaluate the efficacy and safety of AAT for improvement of sleep quality in MHD patients with insomnia. METHODS/DESIGN: The proposed study is a multi-center, double-blind (participants and assessors), parallel-group RCT. A total of 112 participants with insomnia will be recruited from six hemodialysis centers in Guangzhou, China, and randomly allocated in a 1:1 ratio to receive auricular acupressure on either active points (AA group) or control points (points irrelevant to insomnia management, SAA group). The treatment will last for 8 weeks prior to a follow-up period of 12 weeks. Evaluation by blinded assessors at baseline, at 8 weeks (end of treatment) as well as at 4-week, 8-week and 12-week follow-ups (after intervention) will include Pittsburgh Sleep Quality Index (PSQI) scores and average weekly dose of hypnotics. The primary endpoint is clinical response rate (percentage of participants who reach a reduction of PSQI global score ≥ 3 in each group) at 8 weeks from baseline. Secondary endpoints include the changes in PSQI scores over time from baseline, as well as the changes in weekly dose of hypnotics. DISCUSSION: This paper describes the rationale and design of a double-blind RCT that aims to determine the efficacy and safety of AAT for insomnia of hemodialysis patients. If successful, this project will provide evidence of the efficacy and safety of AAT for insomnia of hemodialysis patients. TRIAL REGISTRATION: ClinicalTrials.gov , Identifier: NCT03015766 . Registered on 22 December 2016.

Syndrome Differentiation of IgA Nephropathy Based on Clinicopathological Parameters: A Decision Tree Model.

Background. IgA nephropathy is the most common cause of primary glomerulonephritis in China, and Traditional Chinese Medicine (TCM) is a vital treatment strategy. However, not all doctors prescribing TCM medicine have adequate knowledge to classify the syndrome accurately. Aim. To explore the feasibility of differentiation of TCM syndrome types among IgA nephropathy patients based on clinicopathological parameters. Materials and Methods. The cross-sectional study enrolled 464 biopsy-proven IgA nephropathy adult patients from 2010 to 2016. The demographic data, clinicopathological features, and TCM syndrome types were collected, and the decision tree models based on classification and regression tree were built to differentiate between the syndrome types. Results. 370 patients of training dataset were 32 years old with serum creatinine of 79 µmol/L, estimated glomerular filtration rate (eGFR) of 97.2 mL/min/1.73 m2, and proteinuria of 1.0 g/day. The scores of Oxford classifications were as follows: M1 = 97.6%, E1 = 14.6%, S1 = 50.0%, and T1 = 52.2%/T2 = 18.4%. The decision trees without or with MEST scores achieved equal precision in training data. However, the tree with MEST scores performed better in validation dataset, especially in classifying the syndrome of qi deficiency of spleen and kidney. Conclusion. A feasible method to deduce TCM syndromes of IgA nephropathy patients by common parameters in routine clinical practice was proposed. The MEST scores helped in the differentiation of TCM syndromes with clinical data.

Graphene Nanopores for Protein Sequencing.

An inexpensive, reliable method for protein sequencing is essential to unraveling the biological mechanisms governing cellular behavior and disease. Current protein sequencing methods suffer from limitations associated with the size of proteins that can be sequenced, the time, and the cost of the sequencing procedures. Here, we report the results of all-atom molecular dynamics simulations that investigated the feasibility of using graphene nanopores for protein sequencing. We focus our study on the biologically significant phenylalanine-glycine repeat peptides (FG-nups)-parts of the nuclear pore transport machinery. Surprisingly, we found FG-nups to behave similarly to single stranded DNA: the peptides adhere to graphene and exhibit step-wise translocation when subject to a transmembrane bias or a hydrostatic pressure gradient. Reducing the peptide's charge density or increasing the peptide's hydrophobicity was found to decrease the translocation speed. Yet, unidirectional and stepwise translocation driven by a transmembrane bias was observed even when the ratio of charged to hydrophobic amino acids was as low as 1:8. The nanopore transport of the peptides was found to produce stepwise modulations of the nanopore ionic current correlated with the type of amino acids present in the nanopore, suggesting that protein sequencing by measuring ionic current blockades may be possible.

Shenfu injection for intradialytic hypotension: a systematic review and meta-analysis.

Objective. To evaluate the effectiveness and safety of Shenfu injection (SFI) for intradialytic hypotension (IDH). Methods. A systematic review of data sources published as of April 2014 was conducted. These included the Cochrane Central Register of Controlled Trials (2014 issue 4), Pubmed, Embase, CBM, CNKI, VIP, and Wangfang Data. Randomized controlled trials (RCTs) involving SFI for treatment and prevention of IDH were identified. Two researchers independently selected articles, extracted data, assessed quality, and cross checked the results. Revman 5.2 was used to analyze the results. Results. Eight RCTs were included. The meta-analysis indicated that compared with conventional therapies alone, SFI could elevate systolic blood pressure (SBP), increase the clinical effective rate, decrease the incidence of hypotension, increase serum albumin (ALB) levels, and reduce C-reactive protein (CRP) levels without serious adverse effects. GRADE Quality of Evidence. the quality of SBP, the effective rate, ALB, and CRP were low, and hypotension incidence and DBP were very low. Conclusions. SFI is more effective than conventional therapies for prevention and treatment of IDH. However, a clinical recommendation is not warranted due to the small number of studies included and low methodology quality. Multi-center and high-quality RCTs with large sample sizes are needed to provide stronger evidence.

ZD1839 and cisplatin alone or in combination for treatment of a nasopharyngeal carcinoma cell line and Xenografts.

This study evaluated the effects of ZD1839, an orally active, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, on nasopharyngeal carcinoma (NPC) both in vitro and in vivo. Influence of ZD1839 alone or combined with cisplatin on the NPC cell line CNE2 was detected by MTT assay with flow cytometry assessment of cell cycle distribution and apoptosis rates. Nude mice NPC xenografts were also used to evaluate the effects of ZD1839 alone or combined with cisplatin. The Student's t test evaluated statistical significance. ZD1839 alone or combined with cisplatin inhibited CNE2 cell line proliferation. ZD1839 induced CNE2 cell cycle arrest in the G1 phase, and higher concentrations induced apoptosis. Xenograft tumors were significantly smaller when treated with 200 mg/kg ZD1839, cisplatin, or cisplatin combined with 100 mg/kg ZD1839 than untreated controls. ZD1839 (200 mg/kg) alone showed good tumor inhibition effects, reduction of tumor weights, and smaller tumor volume without loss of body weight. ZD1839 (200 mg/kg) might provide a good and effective therapeutic reagent for NPC.