[Mechanism of Fushen Granules treat peritoneal dialysis-related peritonitis by regulating TLR4/NF-κB pathway:based on network pharmacology and animal experiments].

Network pharmacology was employed to probe into the mechanism of Fushen Granules in treating peritoneal dialysis-rela-ted peritonitis(PDRP) in rats. The main active components of Fushen Granules were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and their targets were predicted. PDRP-related targets were retrieved from DisGeNET and other databases. The common targets shared by the drug and the disease were identified by the online tool, and protein-protein interaction(PPI) network of the common targets. The obtained 276 common targets were imported into DAVID for GO function enrichment and KEGG pathway enrichment. The main signaling pathway of Fushen Granules in the treatment of PDRP was predicted as Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB. The rat model of uremia was induced by 5/6 nephrectomy. From two weeks after operation, the rat model of peritoneal dialysis(PD) was established by intraperitoneal injection of 20 mL dialysate with 1.25% glucose every day. The sham operation group and model group received 2 mL normal saline by gavage every day. The rats in Fushen Gra-nules groups were administrated with 2 mL solutions of low-(0.54 g·kg~(-1)), medium-(1.08 g·kg~(-1)) and high-dose(2.16 g·kg~(-1)) Fushen Granules every day. The bifico group received 2 mL(113.4 mg·kg~(-1)) of bifico solution every day. At the end of the 8th week, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in each group were measured. The serum levels of hypersensitive C reactive protein(hs-CRP), tumor necrosis factor(TNF)-α, and interleukin(IL)-6 were measured, and the pathological changes in the colon tissue were observed by hematoxylin-eosin(HE) staining. The serum levels of lipopolysaccharide(LPS) and lipopolysaccharide-binding protein(LBP) of rats were measured, and the expression levels of LBP, TLR4, NF-κB p65, inhibitor of κB kinase α(IκBα), TNF-α, and IL-1ß in the colon tissue were determined. Compared with sham operation group, the model group had abnormal structure of all layers of colon tissue, sparse and shorter intestinal villi, visible edema in mucosal layer, wider gap, obvious local inflammatory cell infiltration, significantly decreased body weight(P<0.01), and significantly increased kidney function index(Scr, BUN) content(P<0.01). Serum levels of inflammatory cytokines(hs-CRP, TNF-α, IL-6), LPS and LBP were significantly increased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß were significantly increased(P<0.01), and protein expressions of IκBα were significantly decreased(P<0.01). Compared with model group, intestinal villi damage in colonic tissue of rats in low-, medium-and high-dose Fushen Granules groups and bifico group were alleviated to different degrees, edema in submucosa was alleviated, space was narrowed, and inflammatory cell infiltration in lamina propria was reduced. The contents of renal function index(Scr, BUN) and serum inflammatory factors(hs-CRP, TNF-α, IL-6) were significantly decreased(P<0.05 or P<0.01) in medium-and high-dose Fushen Granules groups and bifico group(P<0.05 or P<0.01). Serum LPS and LBP contents in Fushen Granules group and bifico group were significantly decreased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß in Fushen Granules group were significantly decreased(P<0.05 or P<0.01), and protein expressions of IκBα were significantly increased(P<0.01). The expression of LBP protein in bifico group was significantly decreased(P<0.01). The results suggest that Fushen Granules can protect the residual renal function of PD rats, reduce the inflammatory response, and protect the colon tissue. Based on network pharmacology, TLR4/NF-κB pathway may be the main signaling pathway of Fushen granule in the treatment of PDRP. The results showed that Fushen Granules could improve intestinal inflammation and protect intestinal barrier to prevent PDRP by regulating the expression of key factors in TLR4/NF-κB pathway in colon of PD rats.

The potential mechanism of gut microbiota-microbial metabolites-mitochondrial axis in progression of diabetic kidney disease.

Diabetic kidney disease (DKD), has become the main cause of end-stage renal disease (ESRD) worldwide. Lately, it has been shown that the onset and advancement of DKD are linked to imbalances of gut microbiota and the abnormal generation of microbial metabolites. Similarly, a body of recent evidence revealed that biological alterations of mitochondria ranging from mitochondrial dysfunction and morphology can also exert significant effects on the occurrence of DKD. Based on the prevailing theory of endosymbiosis, it is believed that human mitochondria originated from microorganisms and share comparable biological characteristics with the microbiota found in the gut. Recent research has shown a strong correlation between the gut microbiome and mitochondrial function in the occurrence and development of metabolic disorders. The gut microbiome's metabolites may play a vital role in this communication. However, the relationship between the gut microbiome and mitochondrial function in the development of DKD is not yet fully understood, and the role of microbial metabolites is still unclear. Recent studies are highlighted in this review to examine the possible mechanism of the gut microbiota-microbial metabolites-mitochondrial axis in the progression of DKD and the new therapeutic approaches for preventing or reducing DKD based on this biological axis in the future.

Exogenous abscisic acid improves grain filling capacity under heat stress by enhancing antioxidative defense capability in rice.

BACKGROUND: Heat stress is a major restrictive factor that causes yield loss in rice. We previously reported the priming effect of abscisic acid (ABA) on rice for enhanced thermotolerance at the germination, seedling and heading stages. In the present study, we aimed to understand the priming effect and mechanism of ABA on grain filling capacity in rice under heat stress. RESULTS: Rice plants were pretreated with distilled water, 50 µM ABA and 10 µM fluridone by leaf spraying at 8 d or 15 d after initial heading (AIH) stage and then were subjected to heat stress conditions of 38 °C day/30 °C night for 7 days, respectively. Exogenous ABA pretreatment significantly super-activated the ABA signaling pathway and improved the SOD, POD, CAT and APX enzyme activity levels, as well as upregulated the ROS-scavenging genes; and decreased the heat stress-induced ROS content (O2- and H2O2) by 15.0-25.5% in rice grain under heat stress. ABA pretreatment also increased starch synthetase activities in rice grain under heat stress. Furthermore, ABA pretreatment significantly improved yield component indices and grain yield by 14.4-16.5% under heat stress. ABA pretreatment improved the milling quality and the quality of appearance and decreased the incidence of chalky kernels and chalkiness in rice grain and improved the rice grain cooking quality by improving starch content and gel consistence and decreasing the amylose percentage under heat stress. The application of paraquat caused overaccumulation of ROS, decreased starch synthetase activities and ultimately decreased starch content and grain yield. Exogenous antioxidants decreased ROS overaccumulation and increased starch content and grain yield under heat stress. CONCLUSION: Taken together, these results suggest that exogenous ABA has a potential priming effect for enhancing rice grain filling capacity under heat stress at grain filling stage mainly by inhibiting ROS overaccumulation and improving starch synthetase activities in rice grain.

In-center Automated Peritoneal Dialysis: Clinical Features, Practice Patterns, and Patient Survival From a 6-year Cohort Study in China.

INTRODUCTION: In-center automated peritoneal dialysis (APD) has been more frequently adopted in clinical practice for maintenance PD patients in China. For a better understanding of its clinical uptake, this retrospective study reviewed incident PD patients for a period of 6 years, investigating the practice pattern of in-center APD, factors associated with the use of in-center APD, and report on the patient survival compared to the non-users of APD among hospitalised PD patients. METHODS: This was a cohort study of all incident PD patients who met the inclusion criteria from 2013/01/01 to 2018/09/30, and were followed until death, cessation of PD, loss to follow-up, or 2018/12/31. Clinical characteristics, patient outcomes, and detailed data on APD sessions were recorded. We used time-dependent Cox model to estimate the variables associated with the initiation of in-center APD, and marginal structural model through inverse probability weighting to adjust for time-varying APD use on the causal pathway to all-cause mortality. RESULTS: A total of 651 subjects over 17501 patient-months were enrolled. Of these, 633 (97.2%) PD patients were hospitalised at least once during follow-up, and 369 (56.7%) received in-center APD at a certain point, and the timing of APD use during the first 3 months, first year and first 2 years since PD inception were 14.8%, 45.4% and 74.8%, respectively. A total of 12553 in-center APD sessions were recorded, where 85.9% used 4 bags of 5L-exchanges per prescription. Time-dependent Cox model showed that diabetes (hazard ratio [HR], 1.39, 95% confidence interval [CI], 1.09-1.76), urine output (HR 0.80, 95% CI 0.70-0.92), serum albumin (HR 0.84, 95%CI 0.72-0.99), hemoglobin (HR 0.88, 95%CI 0.77-0.99), and Ca×P (HR 1.19, 95%CI 1.06-1.35) were significantly associated with in-center APD use. Among all hospitalised PD patients, the estimated hazard ratio corresponding to the marginal causal effect of in-center APD use on all-cause mortality is 0.13 (95% CI 0.05-0.31, P<0.001). Significant survival benefit (adjusted-HR 0.56, 95%CI 0.33-0.95) associated with starting APD after the first PD year was observed among in-center APD users. CONCLUSIONS: In-center APD is used intensively during the first 2 years of PD and is associated with certain clinical features. Over all a significant survival benefit of in-center APD use was observed.

Recent Understanding and Future Directions in the Application of MMP-2 in Encapsulating Peritoneal Sclerosis Clinical Practice.

Encapsulating peritoneal sclerosis (EPS) is an uncommon and harmful complication which may cause destructive outcomes. Matrix metalloproteinase-2 (MMP-2) as a protease can reduce constituents of the extracellular matrix and play a crucial role in the progression of EPS. As a new biomarker, MMP-2 may improve the detection rate of EPS patients in clinical work. In this review, we summarize the recent study of MMP-2 in different etiologies and the assessment of its application value and draw attention to its future directions.

Preliminary Design and On-Site Testing Methodology of Roof-Cutting for Entry Retaining in Underground Coal Mine.

Entry retaining via roof cutting is a new longwall mining method that has emerged in recent years, and is characterized by high resource utilization and environmental friendliness. Due to the complexity of this method, a field study is commonly employed for process optimization. Roof blasting is a key operation for retaining the entry, and the current practice involves dynamically adjusting blasting parameters through on-site testing and postblasting monitoring. However, the existing literature lacks detailed descriptions of blasting operations, making it difficult for field engineers to replicate the results. In this study, based on a roof cutting project for entry retaining, a preliminary design of blasting parameters is made based on theories and on-site geological conditions. The on-site test methods and equipment for roof-cutting blasting are described in detail, and the fractural patterns under different blasting parameters are analyzed. After the retreat of the working face, the state of roof caving in the goaf is analyzed based on monitoring data, and the effectiveness of top cutting is evaluated through reverse analysis, leading to dynamic adjustments of the blasting parameters. This research provides a reproducible construction method for roof-cutting operations and establishes the relationship between blasting parameters and post-mining monitoring data. It contributes to the development of fundamental theories and systematic technical systems for entry retaining via roof cutting, offering high-quality case studies for similar geological engineering projects.

A metabolic biomarker panel of restless legs syndrome in peritoneal dialysis patients.

BACKGROUND: Restless legs syndrome (RLS) is a neuromotor disorder, and dialysis patients are more likely to develop RLS. RLS often causes sleep disorders, anxiety and depression in patients. It will increase the risk of death and severely affect the life of patients. At present, RLS has not received enough recognition and attention, and the misdiagnosis rate can reach more than 10%. METHODS: The discovery set selected 30 peritoneal dialysis (PD) patients and 27 peritoneal dialysis patients with RLS (PD-RLS). A metabolomics method based on ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometric method (UPLC-Q-TOF/MS) was used to analyze the differential metabolites of the two groups. 51 PD patients and 51 PD-RLS patients were included in the validation set. The receiver operating characteristic (ROC) analysis was used to evaluate the early diagnostic biomarkers, and the correlation between the differential metabolites and laboratory test indexes was analyzed to explore the biological function of the differential metabolites. RESULTS: Through the integrated analysis, four metabolites can be used as markers for the diagnosis of PD-RLS, including Hippuric acid, Phenylacetylglutamine, N,N,N-Trimethyl-L-alanyl-L-proline betaine and Threonic acid. Through ROC analysis, it is found that they can be used as a metabolic biomarker panel, and the area under the curve of this combination is more than 0.9, indicating that the panel has good diagnostic and predictive ability. CONCLUSION: Metabolomics based on UPLC-Q-TOF/MS technology can effectively identify the potential biomarkers, and provide a theoretical basis for the early diagnosis, prevention and treatment on PD-RLS.

Association between red blood cell distribution width and non-valvular atrial fibrillation in hemodialysis patients: a single-center Chinese population study.

BACKGROUND: Red blood cell distribution width (RDW) has emerged as a prognostic marker of atrial fibrillation (AF) in various clinical settings. However, the relationship by which RDW was linked to AF in hemodialysis (HD) patients was not clear. We sought to reveal the relationship between RDW and AF occurrence in HD patients. METHODS: We enrolled 170 consecutive maintenance HD patients, including 86 AF patients and 84 non-AF patients. All participants' medical history and detailed clinical workup were recorded before the first dialysis session of the week. Electrocardiography, laboratory and transthoracic echocardiography examination indices were compared between the AF group and non-AF group. Multivariable logistic regression analysis was performed to identify the independent predictors of AF occurrence in HD patients. RESULTS: There were all paroxysmal AF patients in AF group. Compared to the non-AF group, patients with AF group had a significantly older age (61.0 ± 1.48 vs. 49.71 ± 1.79, p < 0.001), lower BMI (24.3 ± 4.11 vs. 25.8 ± 3.87, p < 0.05), higher RDW (15.10 ± 0.96 vs. 14.26 ± 0.82, p < 0.001) and larger LAD (39.87 ± 3.66 vs. 37.68 ± 5.08, p < 0.05). Multivariable logistic regression analyses demonstrated that values of age (OR: 1.030, 95%CI: 1.004-1.057, per one- year increase), BMI (OR: 0.863, 95%CI: 0.782-0.952, per 1 kg/m2 increase), RDW (OR: 2.917, 95%CI: 1.805-4.715, per 1% increase) and LAD (OR: 1.097, 95%CI: 1.004-1.199, per 1 mm increase) were independently associated with AF occurrence (p < 0.05, respectively). The best cutoff value of RDW to predict AF occurrence was 14.65% with a sensitivity of 68.6% and a specificity of 72.6%. CONCLUSIONS: The increased RDW was significantly associated with the paroxysmal AF occurrence in HD patients.

Involvement of CB2 signalling pathway in the development of osteoporosis by regulating the proliferation and differentiation of hBMSCs.

The aim of the present study was to explore the potential mechanism underlying the involvement of CB2 in osteoporosis. Micro-CT was utilized to examine femur bone architecture. Also, real-time PCR and Western blot analysis were utilized to detect the effect of 2-AG on the expression of CB2 and Notch, or the interaction between CB2 and Notch 2. 2-AG treatment up-regulated BMD, Tb.Sp and SMI in OVX mice, whereas proportion of bone volume in total volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and bone mineral density (BMD) were decreased in 2-AG-treated OVX mice. Accordingly, 2-AG administration up-regulated Notch 1 expression in OVX mice but had no effect on CB2 and Notch 2 expression. Meanwhile, 2-AG administration promoted the differentiation of hBMSCs in OVX mice, while exhibiting no effect on the proliferation of hBMSCs. Furthermore, in the cellular models, 2-AG treatment also up-regulated Notch 1 expression but had no effect on CB2 and Notch 2 expression, while Notch 1 shRNA had no effect on CB2 and Notch 2 expression. 2-AG promoted cell proliferation and differentiation, which were inhibited by Notch 1 shRNA. NICD had no effect on CB2 level but increased Notch 1 expression, and CB2 shRNA decreased CB2 and Notch 1 expression. Finally, CB2 shRNA inhibited cell proliferation and differentiation, whereas NICD promoted proliferation and differentiation of hBMSCs. Our results provided further evidence for the association of CB2 gene with BMD and osteoporosis, and identified CB2 as a promising target for the treatment of osteoporosis.

Antibacterial and antibiofilm effects of flufenamic acid against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are one of the most serious surgery complications, and their prevention is of utmost importance. Flufenamic acid is a non-steroid anti-inflammatory drug approved for clinical use to relieve inflammation and pain in rheumatoid arthritis patients. In this study, we explored the antibacterial efficacy of flufenamic acid and the mechanisms underlying this effect. By using minimal inhibitory concentration (MIC), time-kill, resistance induction assays, and the antibiotic synergy test, we demonstrated that flufenamic acid inhibited the growth of methicillin-resistant staphylococci and did not induce resistance when it was used at the MIC. Furthermore, flufenamic acid acted synergistically with the beta-lactam antibiotic oxacillin and did not show significant toxicity toward mammalian cells. The biofilm inhibition assay revealed that flufenamic acid could prevent biofilm formation on medical implants and destroy the ultrastructure of the bacterial cell wall. RNA sequencing and quantitative RT-PCR indicated that flufenamic acid inhibited the expression of genes associated with peptidoglycan biosynthesis, beta-lactam resistance, quorum sensing, and biofilm formation. Furthermore, flufenamic acid efficiently ameliorated a local infection caused by MRSA in mice. In conclusion, flufenamic acid may be a potent therapeutic compound against MRSA infections and a promising candidate for antimicrobial coating of implants and surgical devices.

Importance of non-medical reasons for dropout in patients on peritoneal dialysis.

BACKGROUND: To describe the associated factors for non-medical reasons for dropout in peritoneal dialysis (PD) patients. METHODS: A retrospective cohort study was performed using registry data of adult patients commencing PD as their initial renal replacement therapy in one hospital-facilitated PD center in Taiwan between 2014 and 2018. The collected data included socio-demographics and relevant medical and PD-related parameters. Kaplan-Meier analysis was used to determine the impact of non-medical reasons and medical reasons on PD dropout. RESULTS: The analysis included 224 PD patients, of whom 37 dropped out for non-medical reasons and 187 for medical reasons during the study period. There was significant difference between the two cohorts in age (62.3 years vs. 56.1 years, P = 0.010) and PD vintage (median 3.4 years vs. 4.8 years, P = 0.001). Diabetes was more predominant in the cohort for non-medical reasons than in the one for medical reasons (54.1% vs. 27.3% respectively, P = 0.001). In non-medical reason cohort, two leading reasons given for dropping out were lacking of caregivers (n = 12) and losing confidence (n = 10), whereas PD-related peritonitis (n = 101) was the main medical reason for PD dropout. Using Kaplan-Meier curve analysis, patients in the non-medical reason cohort demonstrated higher cumulative dropout rate compared to patients in the medical reason cohort during a 10-year period (P < 0.001). CONCLUSIONS: The main characteristics of PD dropout patients for non-medical reasons are age, diabetes, patients' perception and caregiver support.

Efficacy and safety of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker therapy for IgA nephropathy: A meta-analysis of randomized controlled trials.

BACKGROUND: Published reports evaluating whether angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (ACEI/ARB) therapy could bring improvements to the prognosis of immunoglobulin A nephropathy (IgAN) have yielded confusing results, which entails a systematic review of those reports. In this study, we summarized currently available evidence from randomized controlled trials (RCTs) that evaluated the effect of ACEI/ARB therapy of IgAN. METHODS: PubMed, International comprehensive biomedical information bibliographic database produced by the National Library of Medicine (MEDLINE), Excerpt Medica Database (EMBASE), and Cochrane Library and article reference lists were searched for RCTs that compared ACEI/ARB with placebo and any other nonimmunosuppressive agents except RAAS agents for treating IgAN. The quality of the studies was evaluated with the performance of explicit eligibility criteria and the revised Jadad scale. Meta-analyses were completed on the outcomes of proteinuria, serum creatinine (SCr), blood pressure and glomerular filtration rate (GFR) in patients with IgAN. RESULTS: Five RCTs involving 295 patients were included in this review. ACEI/ARB agents had statistically significant effects on reduction proteinuria (standardized mean differences [SMD], -0.46; 95% confidence interval [CI], -0.64 to -0.27; P < 0.00001; heterogeneity I 2 = 35%; P = 0.20) and blood pressure, but no significant difference was found on SCr (SMD, -3.51; 95% CI, -16.55 to 9.54; P = 0.60; heterogeneity I 2 = 0%; P = 0.74) and GFR (SMD, 2.59; 95% CI, -7.14 to 12.33; P = 0.60; heterogeneity I 2 = 57%; P = 0.10). CONCLUSION: ACEI/ARB agents had statistically significant effects on reducing proteinuria. As proteinuria is a major pathology of IgAN, which was significantly improved by ACEI/ARB, we proposed that ACEI/ARB agents were a promising therapy. Because the studies under review did not perform blind method, used a variety of doses and types of ACEI/ARB agents and lacked follow-up to evaluate the long-term effect of the agents on IgAN patients.

Fungal peritonitis in peritoneal dialysis: 5-year review from a North China center.

PURPOSE: Fungal peritonitis (FP) is a rare but devastating complication in peritoneal dialysis (PD), accounting for high rates of technique failure, morbidity and mortality. This study was conducted to investigate FPs with regard to peritonitis rate, microbiology testing, patient characteristics, clinical features, antifungal treatments, and clinical outcomes in patients on PD. METHODS: This single-center study retrospectively reviewed all FP episodes diagnosed from June 1, 2012 to June, 2017. All FPs were matched in a 1:5 ratio with PD patients diagnosed with bacterial peritonitis. Clinical, biochemical characteristics and detailed data on peritonitis episodes were recorded. RESULTS: Eleven fungal peritonitis episodes (rate of 0.0067 episodes per patient-year on dialysis) were identified. All FPs were caused by Candida species (identification and antifungal susceptibility testing were performed with VITEK 2® compact system), including C. albicans (6/11), C. parapsilosis (4/11) and C. krusei (1/11). Except C. krusei, no Candida resistance to fluconazole was detected. Compared to bacterial peritonitis (matched cases, n = 55), FP group showed higher rate of previous antibiotic use (p = 0.002), higher total effluent cell count (p = 0.007), and lower serum albumin (p = 0.01), higher rate of infection-related surgery (p < 0.001), HD transfer (p = 0.001), and all-cause death (p = 0.006). High prevalence (≥ 50%) of female gender, anuria, CCI ≥ 4, hypoalbuminemia, anemia, and hypokalemia were also observed in FP patients. More than half of the FP patients presented gastrointestinal symptoms (7/11) and extraperitoneal infection (6/11). Eight (72.7%) patients had catheter surgically removed with a median 5.5 lag days, four (36.4%) patients died within 3 months and six (54.5%) cases led to technique failure. CONCLUSIONS: FP results in high rates of catheter loss and all-cause mortality in 3 months of follow-up, candida species were the commonest pathogens in our center. Variations of clinical features and susceptibility patterns were observed. Gastrointestinal disorders maybe a potential risk factor for FP.

Comparison of Solute Clearance, Hospitalization Rate, and Aortic Arch Calcification between Online Hemodiafiltration and High-Flux Hemodialysis: A 6-Year Observational Study.

BACKGROUND/AIMS: Studies on the long-term clinical benefits of hemodiafiltration (HDF) and high-flux hemodialysis (HFHD) are very limited. This study aimed to investigate the hospitalization rate and aortic arch calcification (AAC) of these two dialysis modalities over 6 years. METHODS: Participants who received regular HDF and HFHD in one hospital-facilitated hemodialysis center were prospectively enrolled after matching for age, sex, and diabetes between January 2009 and December 2014. Medical records were reviewed retrospectively on demographics, laboratory variables, calcified scores in aortic arch measured by chest radiography, and rates of hospital admission. Cox proportional hazard regression and linear regression were used to obtain the outcome results. RESULTS: The HDF and HFHD groups consisted of 108 and 102 participants, respectively. Levels of laboratory variables including small soluble solutes and Kt/V were not statistically different over the 6-year period between the HDF and HFHD groups. Calcified scores of the aortic arch increased over 6 years in both groups. The changes in the mean calcified scores were significant when compared between the two groups (0.44-1.82 in HFHD, 0.79-1.8 in HDF, respectively, p = 0.008). Hospitalization rates were 735 per 1,000 patients in the HDF group and 852 per 1,000 patients in the HFHD group, respectively. No significant difference was observed in frequency and days of hospitalization between HDF and HFHD. CONCLUSION: Hospitalization rates and AAC were observed to be equal for HDF and HFHD.

Robust and flexible method for calibrating the focal length of on-orbit space zoom camera.

For the on-orbit space zoom camera, the camera focal length is in a constant process of change; accordingly, compared with calibrating other camera intrinsic parameters, calibrating the focal length has a practical significance for the space zoom camera. With the vanishing points obtained from the solar panel of human-made space satellites, this paper introduces a focal length self-calibration method for the on-orbit space zoom camera. First, the geometrical relationship and infinite homography of vanishing points at various camera positions are used to derive the method. To improve the accuracy and robustness performance of this approach, an optimization method is then proposed to nonlinearly optimize the camera focal length. Finally, simulation and real physical experiments demonstrate that the proposed method is flexible and accurate with good anti-noise interference and real-time capacity. The method proposed in this paper makes more realistic sense for a number of important space tasks.

Time-varying serum albumin levels and all-cause mortality in prevalent peritoneal dialysis patients: a 5-year observational study.

BACKGROUND: In this study, we investigated the association of time-varying serum albumin levels with mortality over a 5-year period in one cohort of patients undergoing long-term peritoneal dialysis (PD) therapy. METHODS: The participants in this study enrolled 302 patients who underwent long-term PD at a single PD center in Taiwan. We reviewed medical records from 2011 to 2015 retrospectively. Time-averaged albumin level and serum albumin reach rate (defined as the percentage of serum albumin measurements that reached ≥3.5 g/dL) were applied as the predictor variables in the first 2 years (2011-2012). All-cause mortality was used as the outcome variable in the subsequent 3 years (2013-2015). Hazard function of all-cause mortality in the study participants was examined by using Cox proportional hazard regression models . RESULTS: Patients with different albumin reach rates (75-< 100%, 50-< 75%, 1-< 50%) did not exhibit a significantly increased risk for all-cause mortality. Patients with a 0% albumin reach rate exhibited a significantly increased risk for all-cause mortality (hazard ratio [HR] 7.59, 95% confidence interval [CI], 2.38-24.21) by fully adjusted analysis. Patients with time-averaged albumin levels of < 3.5 g/dL (HR 15.49, 95% CI 1.74-137.72) exhibited a higher risk for all-cause mortality than those with serum albumin levels ≥4.0 g/dL. CONCLUSIONS: This study demonstrated that higher serum albumin reach rates and higher time-averaged serum albumin levels are associated with a lower mortality rate over a 5-year period among patients undergoing long-term PD.

Peritonitis: Episode Sequence, Microbiological Variation, Risk Factors and Clinical Outcomes in a North China Peritoneal Dialysis Center.

BACKGROUND/AIMS: This study investigated peritonitis episodes with regard to time sequence, microbiological variation, factors associated with peritonitis and clinical outcomes in peritoneal dialysis (PD) patients. METHODS: This single-center cohort study enrolled all incident patients who met the inclusion criteria at our center from June 1, 2012 to June 30, 2015 and who were followed until June, 2017. Clinical, biochemical characteristics and detailed data on peritonitis episodes, and hospitalizations were recorded. RESULTS: A total of 218 episodes of peritonitis corresponding to a rate of 0.27 episode per patient-year were recorded. Gram positive bacteria, identified in 115 (52.8%) episodes, were the most common pathogens. The occurrence of enterococcus peritonitis increased from 15.1% of the first to 27.3% of the later episodes. Multivariate logistic regression showed that the presence of cardiovascular disease (CVD, odds ratio [OR] 2.177, 95% confidence interval [95%CI] 1.214-3.903, P=0.009), age≤ 55 (OR 2.282, 95%CI 1.062-4.906, P=0.035), non-independent operator (OR 0.440, 95%CI 0.206-0.938, P=0.034), lower values of potassium (OR=0.671,95%CI 0.472-0.954, P=0.026) and higher values of calcium-phosphate product (OR 1.410, 95%CI 1.065-1.868, P=0.017) were associated with peritonitis. Besides CVD (risk ratio [RR] 2.591, 95%CI 1.893-3.543, P< 0.001) and non-independent operator (RR 0.583, 95%CI 0.439-0.776, P< 0.001), a lower level of education (RR 0.641, 95%CI 0.487-0.842, P=0.001) was associated with higher peritonitis rates in log-linear analysis. Spearman analyses indicated that the time to the 1st episode was negatively related to the peritonitis rate (r=-0.291, P=0.001). Time-dependent Cox regression showed no association between the time to the 1st episode and patient survival (P=0.151). Patients with a high peritonitis rate (HPR) demonstrated worse technique survival (P< 0.001). CONCLUSION: The present study has revealed several center-based features and modifiable risk factors for peritonitis. The presence of CVD and the need for assistance with PD operation not only increased the odds of peritonitis but were also associated with more peritonitis episodes. Time to first peritonitis was related to the peritonitis rate but not associated with patient survival. Patients with HPR had worse technique survival.

Fabrication of a Nanoscale Magnesium/Copper Metal-Organic Framework on Zn-Based Guided Bone Generation Membranes for Enhancing Osteogenesis, Angiogenesis, and Bacteriostasis Properties.

Recently, zinc (Zn) and its alloys have demonstrated great potential as guided bone regeneration (GBR) membranes to treat the problems of insufficient alveolar bone volume and long-term osseointegration instability during dental implantology. However, bone regeneration is a complex process consisting of osteogenesis, angiogenesis, and antibacterial function. For now, the in vivo osteogenic performance and antibacterial activity of pure Zn are inadequate, and thus fabricating a platform to endow Zn membranes with multifunctions may be essential to address these issues. In this study, various bimetallic magnesium/copper metal-organic framework (Mg/Cu-MOF) coatings were fabricated and immobilized on pure Zn. The results indicated that the degradation rate and water stability of Mg/Cu-MOF coatings could be regulated by controlling the feeding ratio of Cu2+. As the coating and Zn substrate degraded, an alkaline microenvironment enriched with Zn2+, Mg2+, and Cu2+ was generated. It significantly improved calcium phosphate deposition, differentiation of osteoblasts, and vascularization of endothelial cells in the extracts. Among them, Mg/Cu1 showed the best comprehensive performance. The superior antibacterial activity of Mg/Cu1 was demonstrated in vitro and in vivo, which indicated significantly enhanced bacteriostatic activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli as compared to that of the bare sample. Bimetallic Mg/Cu-MOF coating could properly coordinate the multifunction on a Zn membrane and could be a promising platform for promoting its bone regeneration, which could pave the way for Zn-based materials to be used as barrier membranes in oral clinical trials.

The road to evolution of ProTx2: how to be a subtype-specific inhibition of human Nav1.7.

The human voltage-gated sodium channel Nav1.7 is a widely proven target for analgesic drug studies. ProTx2, a 30-residue polypeptide from Peruvian green tarantula venom, shows high specificity to activity against human Nav1.7, suggesting its potential to become a non-addictive analgesic. However, its high sensitivity to human Nav1.4 raises concerns about muscle side effects. Here, we engineered three mutants (R13A, R13D, and K27Y) of ProTx2 to evaluate their pharmacological activities toward Nav1.7 and Nav1.4. It is demonstrated that the mutant R13D maintained the analgesic effect in mice while dramatically reducing its muscle toxicity compared with ProTx2. The main reason is the formation of a strong electrostatic interaction between R13D and the negatively charged amino acid residues in DII/S3-S4 of Nav1.7, which is absent in Nav1.4. This study advances our understanding and insights on peptide toxins, paving the way for safer, effective non-addictive analgesic development.

Chinese botanical drugs targeting mitophagy to alleviate diabetic kidney disease, a comprehensive review.

Diabetic kidney disease (DKD) is one of the chronic microvascular complications caused by diabetes, which is characterized by persistent albuminuria and/or progressive decline of estimated glomerular filtration rate (eGFR), and has been the major cause of dialysis around the world. At present, although the treatments for DKD including lifestyle modification, glycemic control and even using of Sodium-glucose cotransporter 2 (SGLT2) inhibitors can relieve kidney damage caused to a certain extent, there is still a lack of effective treatment schemes that can prevent DKD progressing to ESRD. It is urgent to find new complementary and effective therapeutic agents. Growing animal researches have shown that mitophagy makes a great difference to the pathogenesis of DKD, therefore, exploration of new drugs that target the restoration of mitophagy maybe a potential perspective treatment for DKD. The use of Chinese botanical drugs (CBD) has been identified to be an effective treatment option for DKD. There is growing concern on the molecular mechanism of CBD for treatment of DKD by regulating mitophagy. In this review, we highlight the current findings regarding the function of mitophagy in the pathological damages and progression of DKD and summarize the contributions of CBD that ameliorate renal injuries in DKD by interfering with mitophagy, which will help us further explain the mechanism of CBD in treatment for DKD and explore potential therapeutic strategies for DKD.