Lupus Recipe inhibits cGVHD-induced lupus nephritis in mice and promote renal LC3-associated autophagy.

Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE). The chronic graft versus host disease (cGVHD) mouse model is a well-established model of SLE. LC3-associated autophagy plays a critical role in extracellular particle clearance, including pathogens and apoptotic cells. Lupus Recipe (LR) is a Chinese herbal compound that has been proven to be effective in treating SLE. In the study, we investigated the protective effects of LR or LR combined with prednisone on cGVHD mouse model and LC3-associated autophagy in the kidney. The mice were subjected to six groups. The LR treatment group received LR at the dosage of 1.15 and 2.3 g/kg/day, respectively. The corticosteroid treatment group received prednisone at a dosage of 5 mg/kg/day. The combination treatment group received LR at a dosage of 2.3 g/kg/day, and prednisone at 2.5 mg/kg/day. LR treatment reduced proteinuria and serum triglyceride levels, as well as spleen weight. LR also alleviated pathologic damage and immunoglobulin G deposition in the kidney. LR combined with a low dose of prednisone significantly improved kidney function and decreased serum triglyceride, total cholesterol, and spleen weight. In addition, combination treatment relieved kidney injury more effectively than LR alone. Western blot revealed that LR treatment or LR combined with prednisone increased the LC3-associated autophagy protein of Rubicon and Nox2, as well as LC3I levels in the kidney tissues. In conclusion, LR inhibited the manifestation of cGVHD-induced LN, which may attribute to the increased levels of LC3-associated autophagy.

Horizontal Tourism Coopetition Strategy for Marketing Performance - Evidence From Theme Parks.

Unprecedentedly impacted by COVID-19, tourism enterprises are pushed to adopt new strategic management to cope with the changes in tourists' consumer perception for sustainable development, such as corporate and compete simultaneously with their competitors. Our study aims to investigate the intermediate role of coopetition, including the three dimensions of resource similarity, market commonality, and willingness to cooperate in the marketing and performance relationships. Primary data on 360 observers were collected via questionnaire distribution to theme park managers in China with 85.3% accuracy in response rate. Structural equation modeling (SEM) was used to verify the intermediate effect of coopetition on marketing performance in tourism enterprises. The results of SEM indicate (1) the intermediate role of tourism coopetition, including the three dimensions existing in the relationship between tourism marketing and performance, (2) more significant positive impact on non-financial performance than that on financial performance, and (3) the mechanism of implementing coopetition. This study gives supportive evidence for tourism enterprises to implement coopetition and highlights the implications for appropriately developing coopetition strategies and tactics to achieve the synergy effect for the individual enterprises and the spillover effect for the destination regarding policy-making, mindset, and partner selection.

Risk Factors and Clinical Outcomes of Cognitive Impairment in Diabetic Patients Undergoing Peritoneal Dialysis.

INTRODUCTION: Cognitive impairment (CI) is common in patients with CKD or diabetes mellitus (DM). However, the relevance between DM and CI in diabetic patients undergoing peritoneal dialysis (PD) has not been clearly established. This study aimed to explore the role of DM in CI, the association of glycemic control with CI, and clinical outcomes of CI in diabetic PD patients. METHODS: Continuous ambulatory PD (CAPD) patients followed up in our PD center between 2014 and 2016 were enrolled. The participants were followed until an endpoint was reached or December 2017. Demographic data and clinical characteristics were collected, and laboratory parameters were measured. The Montreal Cognitive Assessment (MoCA) was used to evaluate global cognitive function, and a score of <26 was considered to indicate CI. A propensity score matching according to age, gender, and mean arterial pressure was conducted between the DM and non-DM groups. RESULTS: A total of 913 CAPD patients were enrolled, of whom 186 (20.4%) had diabetes. After appropriate matching, 175 patients in the DM group and 270 patients in the non-DM group were included. Patients with diabetes had a higher prevalence of CI and lower scores for visuospatial/executive function, naming, language, delayed recall, and orientation. Higher HbA1c (odds ratio [OR], 1.547; 95% confidence interval [95% CI], 1.013-2.362) and cardiovascular disease (CVD; OR, 2.926; 95% CI, 1.139-7.516) significantly correlated with a risk of CI in diabetic patients. During a median of 26.0 (interquartile range 13.5-35.6) months of follow-up, diabetic patients with CI demonstrated a significantly lower survival rate than those without CI, and CI was an independent risk factor for mortality after adjustment (hazard ratio, 7.224; 95% CI, 1.694-30.806). However, they did not show worse technique survival or higher peritonitis rate than patients without CI. CONCLUSIONS: HbA1c and CVD are independent risk factors for CI in diabetic patients undergoing CAPD, and CI is independently associated with a higher risk of mortality.

The Association between Serum Uric Acid and Appendicular Skeletal Muscle Mass and the Effect of Their Interaction on Mortality in Patients on Peritoneal Dialysis.

BACKGROUND: Serum uric acid (SUA) has been revealed to be positively associated with the body composition parameters in hemodialysis patients, but few studies have investigated that in patients on peritoneal dialysis (PD). The aim of this study was to identify the relationship between SUA and appendicular skeletal muscle mass (ASM) and the effect of their interaction on mortality in PD patients. METHODS: This was a single-center retrospective cohort study. Patients who underwent multifrequency bioelectrical impedance analysis between January 1, 2013, and December 31, 2016, and had data on SUA values were enrolled. All patients were followed up until December 31, 2019. RESULTS: In total, 802 prevalent PD patients (57.9% male), with mean age of 46.2 ± 14.2 years were enrolled. The average SUA and ASM were 6.8 ± 1.3 mg/dL and 21.2 ± 4.9 kg. According to multiple linear regression models, SUA was positively associated with relative ASM in middle-aged and older PD patients (standardized coefficients [ß] 0.117; 95% confidence interval [CI] 0.027, 0.200; p = 0.010). Further sex-stratified analysis showed that the association existed only in males (ß 0.161; 95% CI 0.017, 0.227; p = 0.023). Moreover, the presence of hyperuricemia was found to predict lower risk of all-cause mortality (hazard ratio [HR] 0.514, 95% CI 0.272, 0.970; p = 0.040) only in patients with lower relative ASM. And, the adjusted HR of every 1 mg/dL elevated SUA level was 0.770 (95% CI 0.609, 0.972; p = 0.028) for all-cause mortality in the lower relative ASM subgroup. CONCLUSIONS: There exists a positive association between the SUA and ASM, and the ASM significantly affected the association between SUA and all-cause PD mortality.

Roles of peritoneal clearance and residual kidney removal in control of uric acid in patients on peritoneal dialysis.

BACKGROUND: There have been few systematic studies regarding clearance of uric acid (UA) in patients undergoing peritoneal dialysis (PD). This study investigated peritoneal UA removal and its influencing factors in patients undergoing PD. METHODS: This cross-sectional study enrolled patients who underwent peritoneal equilibration test and assessment of Kt/V from April 1, 2018 to August 31, 2019. Demographic data and clinical and laboratory parameters were collected, including UA levels in dialysate, blood, and urine. RESULTS: In total, 180 prevalent patients undergoing PD (52.8% men) were included. Compared with the normal serum UA (SUA) group, the hyperuricemia group showed significantly lower peritoneal UA clearance (39.1 ± 6.2 vs. 42.0 ± 8.0 L/week/1.73m2; P = 0.008). Furthermore, higher transporters (high or high-average) exhibited greater peritoneal UA clearance, compared with lower transporters (low or low-average) (42.0 ± 7.0 vs. 36.4 ± 5.6 L/week/1.73 m2; P < 0.001). Among widely used solute removal indicators, peritoneal creatinine clearance showed the best performance for prediction of higher peritoneal UA clearance in receiver operating characteristic curve analysis [area under curve (AUC) 0.96; 95% confidence interval [CI], 0.93-0.99]. Peritoneal UA clearance was independently associated with continuous SUA [standardized coefficient (ß), - 0.32; 95% CI, - 6.42 to - 0.75] and hyperuricemia [odds ratio (OR), 0.86; 95% CI, 0.76-0.98] status, only in patients with lower (≤2.74 mL/min/1.73 m2) measured glomerular filtration rate (mGFR). In those patients with lower mGFR, lower albumin level (ß - 0.24; 95%CI - 7.26 to - 0.99), lower body mass index (ß - 0.29; 95%CI - 0.98 to - 0.24), higher transporter status (ß 0.24; 95%CI 0.72-5.88) and greater dialysis dose (ß 0.24; 95%CI 0.26-3.12) were independently associated with continuous peritoneal UA clearance. Furthermore, each 1 kg/m2 decrease in body mass index (OR 0.79; 95% CI 0.63-0.99), each 1 g/dL decrease in albumin level (OR 0.08; 95%CI 0.01-0.47), and each 0.1% increase in average glucose concentration in dialysate (OR 1.56; 95%CI 1.11-2.19) were associated with greater peritoneal UA clearance (> 39.8 L/week/1.73m2). CONCLUSIONS: For patients undergoing PD who exhibited worse residual kidney function, peritoneal clearance dominated in SUA balance. Increasing dialysis dose or average glucose concentration may aid in controlling hyperuricemia in lower transporters.

Lower Phase Angle Measured by Bioelectrical Impedance Analysis Is a Marker for Increased Mortality in Incident Continuous Ambulatory Peritoneal Dialysis Patients.

OBJECTIVE: Phase angle (PA) determined by bioelectrical impedance analysis has been suggested to be a predictor of death in a variety of disease conditions, but its associations with outcomes have not yet been assessed in a large continuous ambulatory peritoneal dialysis (CAPD) patient cohort. The aim of the present study was to examine the association of PA with risks for all-cause and cardiovascular death in patients treated with CAPD. METHODS: Incident CAPD patients were enrolled from January 1, 2010 to December 31, 2015 and were followed until December 31, 2017. Multifrequency bioelectrical impedance analysis was conducted in the morning with patients in a fasting state. Multivariable linear regression analyses were performed to study the relationships between PA and other variables. Cox proportional hazard models were used to evaluate the association between PA and mortality. RESULTS: A total of 760 incident CAPD patients were enrolled in this study. Patients have a median PA value of 4.59° ranging from 2.30° to 7.22°. Aging, presence of diabetes mellitus, and fluid overload were independently associated with lower PA, whereas male sex, higher body mass index, higher serum levels of albumin and creatinine, and better residual renal function were independently associated with higher PA in a multivariable linear regression model. A total of 125 (16.4%) patients died during a median follow-up of 42 months. In the Cox model with adjustment for confounders, PA was significantly associated with all-cause and cardiovascular mortality in incident CAPD patients (hazard ratio, 0.584; 95% confidence interval, 0.403 to 0.844, P = .004; hazard ratio, 0.597; 95% confidence interval, 0.359 to 0.993, P = .047, respectively). CONCLUSIONS: PA reflected a combined dimension of the illness including deranged hydration status and nutritional status. Lower PA was associated with both all-cause and cardiovascular death in patients with CAPD.

Changes in Outcomes over Time Among Incident Peritoneal Dialysis Patients in Southern China.

Background:The present study was to investigate the changes in outcomes of incident patients who started peritoneal dialysis (PD) between 2006 - 2010 and 2011 - 2015 in Southern China.Methods:In this single-center cohort study, incident PD patients from January 1, 2006, to December 31, 2015, were enrolled. Collected data included baseline demographic, clinical, biochemical characteristics, and outcomes. Patients who initiated PD during 2006 - 2010 and 2011 - 2015 were followed up until December 31, 2011, and December 31, 2016, respectively. Peritonitis rate, patient survival, and technique survival were compared between the 2 incident cohorts.Results:A total of 2,021 incident PD patients were enrolled, with a mean age of 47.2 ± 15.2 years, 40.6% female. Compared with the 2006 - 2010 cohort (n = 1,073), patients initiating PD during 2011 - 2015 (n = 948) were younger (46.2 ± 14.8 vs 48.1 ± 15.5 years, p = 0.006), had similar baseline estimate glomerular filtration rate (eGFR) (5.81 ± 2.41 vs 5.81 ± 2.89 mL/min/1.73 m2, p = 0.109) and comparable percentage of diabetes mellitus (24.9% vs 25.7%, p = 0.682). The overall peritonitis rate in the 2011 - 2015 cohort was lower than in the 2006 - 2010 cohort (0.158 vs 0.161 episodes per year, p = 0.001). At the end of 1, 3, and 5 years, the 2006 - 2010 and 2011 - 2015 cohorts had patient survival rates of 94%, 82%, 64%, and 97%, 87%, 74%, respectively (p < 0.001). After multivariable adjustment, patients starting PD in 2011 - 2015 were associated with lower risk of all-cause mortality (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.60 - 0.98). In gender and age-stratified models, male patients had a significantly lower risk of all-cause mortality (HR 0.58, 95% CI 0.41 - 0.83), and patients with age < 65 years showed a significantly lower risk of cardiovascular (CV) mortality (HR 0.63, 95% CI 0.40 - 0.99) in 2011 - 2015 compared with 2006 - 2010. The death-censored technique survival rates were not significantly different between the 2 cohorts (p = 0.234).Conclusion:Peritonitis rates and patient survival on PD continue to improve. Patients initiating PD between 2011 and 2015 were associated with better outcomes.

Associations between serum mineral metabolism parameters and mortality in patients on peritoneal dialysis.

AIM: Disturbances in mineral metabolism markers are common in patients with chronic kidney disease but there is no consensus on the association between these markers and clinical outcomes. This study investigated associations between mineral metabolism parameters and mortality in Chinese peritoneal dialysis (PD) patients. METHODS: This was a single-centre retrospective cohort study. Incident PD patients between 1 January 2006 and 31 December 2013 with baseline phosphate, albumin-corrected calcium, and calcium-phosphate product data were enrolled. Associations between these parameters and all-cause and cardiovascular mortality were assessed using multivariable-adjusted Cox models. RESULTS: Of 1662 patients (mean age: 47.4 ± 15.3 years), 59.3% were male and 23.8% had diabetes. Over a median 38.1 month (interquartile range: 21.3-59.7 months) follow-up period, 382 (23.0%) patients died. After adjusting for confounders, the higher serum phosphate level (>1.78 mmol/L) and calcium-phosphate product level (≥4.4 mmol2 /L2 ) were significantly associated with an increased risk for all-cause mortality (hazards ratio (HR) = 1.818, 95% CI = 1.379-2.396 and HR = 1.735, 95% CI = 1.261-2.386) and cardiovascular mortality (HR = 2.069, 95% CI = 1.428-2.998 and HR = 2.175, 95% CI = 1.450-3.262), respectively. While each 1 mmol/L higher baseline albumin-corrected calcium level was associated with an 14.3% (95% CI = 0.749-0.981) lower risk for all-cause mortality after adjusting for potential confounders. CONCLUSION: Abnormalities in mineral metabolism markers, particularly higher serum phosphate and calcium-phosphate product levels, at the commencement of PD were independently associated with increased all-cause and cardiovascular mortality in this cohort of PD patients.

Reciprocal allosteric regulation of p38γ and PTPN3 involves a PDZ domain-modulated complex formation.

The mitogen-activated protein kinase p38γ (also known as MAPK12) and its specific phosphatase PTPN3 (also known as PTPH1) cooperate to promote Ras-induced oncogenesis. We determined the architecture of the PTPN3-p38γ complex by a hybrid method combining x-ray crystallography, small-angle x-ray scattering, and chemical cross-linking coupled to mass spectrometry. A unique feature of the glutamic acid-containing loop (E-loop) of the phosphatase domain defined the substrate specificity of PTPN3 toward fully activated p38γ. The solution structure revealed the formation of an active-state complex between p38γ and the phosphatase domain of PTPN3. The PDZ domain of PTPN3 stabilized the active-state complex through an interaction with the PDZ-binding motif of p38γ. This interaction alleviated autoinhibition of PTPN3, enabling efficient tyrosine dephosphorylation of p38γ. Our findings may enable structure-based drug design targeting the PTPN3-p38γ interaction as an anticancer therapeutic.