Reconstructed Mid-Face Lifting After Tissue Expansion by Suspending the Expander Capsule.

BACKGROUND: An obvious saggy tendency was observed in the expanded flaps from mid-facial reconstruction and resulted in an unsatisfactory postoperative cosmetic outcome. At the time of this writing, the authors introduced a novel technique of mid-face lifting to correct the phenomenon by suspending the expander capsule. METHODS: From September 2018 to August 2023, 11 patients who had undergone our mid-face lifting technique were enrolled in our study. The expanded flap was divided into 2 layers during the surgical procedure. The upper layer, which consists of the skin and the subcutaneous layer, was lifted, and the lower layer, consisting of the expander capsule and SMAS system, was left at the base. Then a capsular flap was lifted from the base and folded upward to lift the reconstructed mid-face. The capsular flap was fixed in the temporal or mastoid region when the saggy tendency was corrected, and the mid-facial contour became symmetric. Finally, the upper layer was trimmed and fixed at the base. Facial movements were restricted after the surgery. RESULTS: The saggy tendency of all the expanded flaps was corrected, and the mid-facial symmetry was rebuilt immediately after the surgery. The effect were long-lasting at 3 months to 2 years of follow-ups. No serious postoperative complications occurred. The patients or their legal guardians were satisfied with the esthetic improvement. CONCLUSION: Reconstructed mid-face lifting with capsular flap was an effective and reliable way to correct the saggy tendency of a mid-facial expanded flap and rebuilt the mid-facial symmetry.

Endogenous crude Scutellaria baicalensis polysaccharide robustly enhances one-pot extraction and deglycosylation of baicalin.

With the extensive application of baicalein in the treatment of cardiovascular and cerebrovascular diseases, its clinical and market demand has gradually expanded. But the natural yield of baicalein is very low, and it is mainly prepared by the deglycosylation of baicalin. However, the insolubility of baicalin in water significantly limits the deglycosylation of it under biocatalysis. To make biocatalysis of baicalin more efficient and environmental, a strategy was designed to enhance its water solubility through the solubilization mechanism of endogenous biological macromolecules, and the effect on the activity of glucuronidase was further explored. The results showed that wrapping with Scutellaria baicalensis polysaccharide (SBP) significantly improved the solubility of baicalin in water (the water solubility of baicalin increased by 23 times, BI/SBP = 1/12, w/w). It was not only contributed to the efficient production of baicalein by one-pot method, but also effectively improved the deglycosylation rate of baicalin (increase by 47.04 % in aqueous solution). With the help of the solubilization of endogenous polysaccharide on baicalin in aqueous solution, a green, low-cost and efficient method (one-pot method) was designed to simultaneously extract and enzymatic hydrolyze baicalin to prepare baicalein. Under the same conditions, the yield of one-pot method is 87.17 %, which was much higher than that of the conventional method (29.38 %). In addition, one-pot method with the aid of endogenous polysaccharide could simply and conveniently prepare aglycone of other insoluble natural flavonoids, which has a wide range of industrial application value.

Treatment for benign skin lesion in zygomatic-infraorbital region by the expanded multi-lobe cervicofacial advancement rotation flap in pediatric patients.

PURPOSE: Benign skin lesions in zygomatic-infraorbital regions severely influence pediatric patients' appearance as well as mental health. Treatments are difficult for the high requirements of patients' guardians in both function and aesthetics. The present study aims to introduce a surgical method, Expanded Multi-Lobe Cervicofacial Flap, which combines the advantages of the classical cervicofacial advancement rotation flap and the tissue expansion technique. METHODS: A total of 21 pediatric patients were enrolled. The treatment process included 2 stages: implantation of the skin tissue expander and flap transfer. The excessive skin created by tissue expansion extended the coverage area of the multi-lobe flap. RESULTS: In this retrospective study, follow-up periods were all more than 12 months (20.8 ± 6.7). In the last follow-ups, the flaps were all in good condition, and No facial organ displacement was observed. The patients' guardians were satisfied with the outcomes. CONCLUSIONS: Using the expanded multi-lobe cervicofacial flap for the zygomatic-infraorbital benign skin lesion repair is effective, and this method is especially applicable to the pediatric population.

Temporal-fasciae-complex sheet suspension for correction of severe recurrent blepharoptosis.

BACKGROUND: Multiple surgical methods were performed to correct the blepharoptosis. However, the recurrence of blepharoptosis is not uncommon in clinical practice. The Temporal-Fasciae-Complex Sheet (TFC sheet) was an ideal autologous material in correcting the severe blepharoptosis. In the present retrospected study, we introduced our experience in the correction of severe recurrent blepharoptosis with the technique of TFC sheet suspension, and describe the follow-up results to illustrate its effectiveness and practicality. METHODS: A total of 16 patients (23 eyes) with severe recurrent blepharoptosis were enrolled in this study. All the patients were performed with temporal-fasciae-complex sheet suspension surgeries for revision> 12 months after the primary surgeries by the same treatment group. The margin-to-reflex distance 1 (MRD1), correction effect, and eyelid symmetry were used to evaluate clinical outcomes. RESULTS: 19 eyelids (82.6%) showed good correction results, and 5 eyelids (21.7%) showed fair correction results. The average value of preoperative-MRD1(pre-MRD1) was - 0.17 ± 0.97, and the average value of postoperative-MRD1(post-MRD1) was 4.01 ± 1.24. There was a statistically significant difference between pre-MRD1 and post-MRD1 (p < 0.0001). Good symmetry was observed in 13 patients (81.3%). All patients enrolled were satisfied with the surgical results. CONCLUSION: The Temporal-Fasciae-Complex Sheet Suspension is an effective and safe method for correcting the recurrent blepharoptosis.

Using the "Frontalis-Free Orbital Septum-Complex Flap" in the Correction of Unilateral Congenital Ptosis.

Congenital ptosis has deleterious effects on the appearance and vision-related function. Patients need timely and effective treatments. A new surgical practice was performed using the discarded fibrous and thickened orbital septum to prolong the advanced frontalis muscular flap and reduce iatrogenic injuries in the frontalis. A 5-year-old boy with severe unilateral congenital ptosis was enrolled and got satisfactory surgical effects without complication. The "frontalis-free orbital septum-complex flap" is a new and relatively ideal method. The purpose of this paper is to demonstrate this surgical practice and provide a new idea for correcting congenital ptosis with the thickened and fibrotic orbital septum.

Identification and functional analyses of a novel FOXL2 pathogenic variant causing blepharophimosis, ptosis, and epicanthus inversus syndrome.

AIM: To discover the molecular pathogenic basis of the blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES), and to predict the clinical subtype according to in vitro experiments, which is significant to the prognosis. METHODS: A 3-year-old sporadic female patient with typical clinical manifestations of BPES was enrolled. The coding region of forkhead box L2 (FOXL2) gene was sequenced, and the functional assays were performed in vitro by Western blotting, subcellular localization experiment, luciferase reporter assay, and quantitative real-time polymerase chain reaction. RESULTS: A novel FOXL2 point pathogenic variant (c.274G>T) was detected, resulting in a truncated protein (p.E92*). Functional studies demonstrated that the FOXL2 pathogenic variant induced the subcellular mislocalization and the abnormal transcriptional activity on promoters of the steroidogenic acute regulatory protein (StAR or STARD1) gene and the odd-skipped related 2 transcription factor (OSR2) gene. CONCLUSION: A novel pathogenic variant is identified to expand the spectrum of the known FOXL2 mutations. The in vitro experiments provide reference data and more insights to the molecular pathogenesis of BPES. The predicted high risk of ovarian insufficiency makes it significant for the patient enrolled to have further follow-up and therapy concerning female endocrinology.

PTB Regulates the Metabolic Pathways and Cell Function of Keloid Fibroblasts through Alternative Splicing of PKM.

Keloids, benign fibroproliferative cutaneous lesions, are characterized by abnormal growth and reprogramming of the metabolism of keloid fibroblasts (KFb). However, the underlying mechanisms of this kind of metabolic abnormality have not been identified. Our study aimed to investigate the molecules involved in aerobic glycolysis and its exact regulatory mechanisms in KFb. We discovered that polypyrimidine tract binding (PTB) was significantly upregulated in keloid tissues. siRNA silencing of PTB decreased the mRNA levels and protein expression levels of key glycolytic enzymes and corrected the dysregulation of glucose uptake and lactate production. In addition, mechanistic studies demonstrated that PTB promoted a change from pyruvate kinase muscle 1 (PKM1) to PKM2, and silencing PKM2 substantially reduced the PTB-induced increase in the flow of glycolysis. Moreover, PTB and PKM2 could also regulate the key enzymes in the tricarboxylic acid (TCA) cycle. Assays of cell function demonstrated that PTB promoted the proliferation and migration of KFb in vitro, and this phenomenon could be interrupted by PKM2 silencing. In conclusion, our findings indicate that PTB regulates aerobic glycolysis and the cell functions of KFb via alternative splicing of PKM.

Dynamic Design of a Quad-Stable Piezoelectric Energy Harvester via Bifurcation Theory.

The parameter tuning of a multi-stable energy harvester is crucial to enhancing harvesting efficiency. In this paper, the bifurcation theory is applied to quantitatively reveal the effects of structural parameters on the statics and dynamics of a quad-stable energy harvester (QEH). Firstly, a novel QEH system utilizing the geometric nonlinearity of springs is proposed. Static bifurcation analysis is carried out to design quad-stable working conditions. To investigate the cross-well and high-energy vibration, the complex dynamic frequency (CDF) method, suitable for both weakly and strongly nonlinear dynamic problems, is then applied to deduce the primary response solution. By using the unfolding analysis in singularity theory, four steady-state properties and dozens of primary resonance modes are demonstrated. Based on the transition set, the effective bandwidth for energy harvesting can be customized to adapt well to various vibration environments by parametric adjustment. Finally, the experimental tests verify that the output power can reach up to 1 mW. The proposed QEH and its mechanics optimization can guide energy supply for next-generation wireless systems and low-power sensors under magnetic forbidding environments.

Emission Characteristics and Health Risks of Volatile Organic Compounds (VOCs) Measured in a Typical Recycled Rubber Plant in China.

The continued development of the automotive industry has led to a rapid increase in the amount of waste rubber tires, the problem of "black pollution" has become more serious but is often ignored. In this study, the emission characteristics, health risks, and environmental effects of volatile organic compounds (VOCs) from a typical, recycled rubber plant were studied. A total of 15 samples were collected by summa canisters, and 100 VOC species were detected by the GC/MS-FID system. In this study, the total VOCs (TVOCs) concentration ranged from 1000 ± 99 to 19,700 ± 19,000 µg/m3, aromatics and alkanes were the predominant components, and m/p-xylene (14.63 ± 4.07%-48.87 ± 3.20%) could be possibly regarded as a VOCs emission marker. We also found that specific similarities and differences in VOCs emission characteristics in each process were affected by raw materials, production conditions, and process equipment. The assessment of health risks showed that devulcanizing and cooling had both non-carcinogenic and carcinogenic risks, yarding had carcinogenic risks, and open training and refining had potential carcinogenic risks. Moreover, m/p-xylene and benzene were the main non-carcinogenic species, while benzene, ethylbenzene, and carbon tetrachloride were the dominant risk compounds. In the evaluation results of LOH, m/p-xylene (25.26-67.87%) was identified as the most key individual species and should be prioritized for control. In conclusion, the research results will provide the necessary reference to standardize the measurement method of the VOCs source component spectrum and build a localized source component spectrum.

P2X7 receptor signaling promotes inflammation in renal parenchymal cells suffering from ischemia-reperfusion injury.

Extracellular adenosine triphosphate (ATP) and its receptor, P2X7 receptor (P2X7R), are playing an important role in the pathological process of renal ischemia-reperfusion injury, but their underlying mechanism remains unclear. Also, the effects of tubular epithelium-expressed P2X7 receptor on ischemia acute kidney injury is still unknown. The aim of this study is to clarify if this mechanism involves the activation of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in the renal tubular epithelial cells. In our research, we used male C57BL/6 wild type and P2X7R (-/-) mice, cultured human proximal tubular epithelial cells, and kidneys from acute kidney injury patients. Mice underwent for unilateral nephrectomy combined with the lateral renal pedicle clamping. Cultured cells were subjected to hypoxia/reoxygenation or ATP. Apyrase and A438079 were used to block the extracellular ATP/P2X7 receptor pathway. We also constructed radiation-induced bone marrow (BM) chimeras by using P2X7R (-/-) mice and P2X7R (+/+) wild-type mice. P2X7 receptor deficiency protected from renal ischemia-reperfusion injury and attenuated the formation of NLRP3 inflammasome. By using BM chimeras, we found a partial reduction of serum creatinine and less histological impairment in group wild-type BM to P2X7R (-/-) recipient, compared with group wild-type BM to wild-type recipient. In renal tubular epithelial cells, hypoxia/reoxygenation induced ATP release and extracellular ATP depletion reduced the expression of active IL-1ß. ATP activated the NLRP3 inflammasome in renal tubular epithelial cells, which were blunted by transient silence of P2X7 receptor, as well as by P2X7 receptor blocking with A438079. In human samples, we found that patients with Stage 3 AKI had higher levels of P2X7 receptor expression than patients with Stage 1 or Stage 2. Extracellular ATP/P2X7 receptor axis blocking may protect renal tubular epithelial cells from ischemia-reperfusion injury through the regulation of NLRP3 inflammasome.

Asymmetric dimethylarginine compartmental behavior during high-flux hemodialysis.

AIM: The accumulation of uremic toxins, such as asymmetric dimethylarginine (ADMA), has emerged as one of the major cardiovascular disease-related risk factors in patients with end-stage renal disease (ESRD). Based on the low molecular weight of ADMA, hemodialysis (HD) should theoretically effectively remove ADMA. In this study, we investigated the clearance behavior of ADMA during high-flux HD. METHODS: Eight HD patients without residual renal function were included. Blood samples were collected at 0, 30, 60, 120 and 240 min after dialysis started, as well as 1 h and 48 h after dialysis. ADMA level was detected by HPLC-MS/MS. Herein, the ADMA level in blood cells and the ADMA protein binding rate were measured. Accordingly, the dialyzer extraction ratio was also determined. RESULTS: The reduction ratio (RR) of ADMA (corrected for hemoconcentration) was significantly lower, at only 37.21 ± 6.44%, than that of urea and creatinine (p < .05). Interestingly, its clearance from plasma was precipitous early in dialysis and became slowly from 60 to 240 min. Additionally, a greater inlet erythrocyte than plasma concentration was found for ADMA. The dialyzer extraction ratio was comparable between ADMA and creatinine or urea (83 ± 5% for ADMA vs. 84 ± 3% and 88 ± 2% for creatinine and urea, respectively; both p>.05). Urea and creatinine had a slight rebound ratio of less than 10% at 1 h after the completion of HD. In contrast, considerable rebound of approximately 30% was detected in ADMA. CONCLUSION: This study suggests that ADMA may present a multicompartmental distribution that cannot be representatively reflected by the urea kinetics model.

Early serum cystatin C-enhanced risk prediction for acute kidney injury post cardiac surgery: a prospective, observational, cohort study.

Background: Acute kidney injury (AKI) is a common post-cardiac surgery complication. It leads to increased morbidity and mortality. The aim of our study is to identify the prevalence and risk factors of AKI and to demonstrate if early postoperative serum cystatin C (sCyC) could accurately predict the development of AKI.Methods: We prospectively studied 628 patients undergoing elective cardiac surgery. Pre-morbid and operative variables known to be or potentially associated with AKI or other adverse outcomes were examined. AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. Blood samples for biomarker measurement were collected at baseline, within 10 h of surgical completion and daily for three days. Logistic regression was used to assess predictive factors for AKI including 10 h sCyC. Model discrimination was assessed using receiver operator characteristic (ROC) curves.Results: AKI occurred in 178 (28.3%) patients, Stage 1 in 17.5%, Stage 2 in 8.6% and Stage 3 in 2.2%. Mortality rose progressively with increased AKI stage (non-AKI 0.2%, Stage 1 1.8%, Stage 2 11.1% and Stage 3 35.7%). Age > 75 years, baseline estimated glomerular filtration rate (eGFR), proteinuria, diabetes mellitus, hypertension, hyperuricaemia, NYHA classification >2, recent myocardial infarction were associated with AKI in univariate analysis. A multivariate logistic model with clinical factors (age, eGFR, hypertension, NYHA classification >2, combined surgery and operation time) demonstrated moderate discrimination for AKI (area under ROC curve [AUC] 0.75). The 10 h postoperative sCyC levels strongly associated with AKI. After multivariable adjustment, the highest quartile of sCyC was associated with 13.1 - higher odds of AKI, compared with the lowest quartile. Elevated 10 h sCyC levels associated with longer hospital stay, longer intensive care unit stay and duration of mechanical ventilation. The addition of 10 h sCyC improved model discrimination for AKI (AUC 0.81).Conclusions: AKI following cardiac surgery was identified using KDIGO criteria in around one fourth of the patients. These patients had significantly increased morbidity and mortality. When added to prediction model, 10 h sCyC may enhance the identification of patients at higher risk of AKI, providing a readily available prognostic marker.

Urine klotho is a potential early biomarker for acute kidney injury and associated with poor renal outcome after cardiac surgery.

BACKGROUND: Current paradigms of detecting acute kidney injury (AKI) are insensitive and non-specific. Klotho is a pleiotropic protein that is predominantly expressed in renal tubules. In this study, we evaluated the diagnostic and prognostic roles of urine Klotho for AKI following cardiac surgery. METHODS: We conducted a prospective study involving 91 patients undergoing cardiac surgery. AKI was defined according to the AKIN definition. The renal outcomes within 7 days after operation were evaluated. Perioperative levels of urine Klotho and urine neutrophil gelatinase-associated lipocalin (NGAL) were measured by using ELISA. RESULTS: Of 91 participants, 33 patients (36.26%) developed AKI. Of these AKI patients, 21 (63.64%), 8 (24.24%), and 4 (12.12%) were staged 1, 2, and 3, respectively. Serum creatinine in AKI patients began to slightly increase at first postoperative time and reached the AKI diagnostic value 1 day after operation. Postoperative urine Klotho peaked at the first postoperative time (0 h after admission to the intensive care unit (ICU)) in patients with AKI, and was higher than that in non-AKI patients up to day 3. The AUC of detecting AKI for urine Klotho was higher than urine NGAL at the first postoperative time and 4 h after admission to the ICU. In a multivariate model, increased first postoperative urine Klotho may be an independent predictor for AKI occurrence following cardiac surgery. The concentrations of first postoperative urine Klotho were higher in AKI stage 2 and 3 than those in stage 1 (p < 0.05), and were higher in patients with incomplete recovery of renal function than those with complete recovery (p < 0.05). CONCLUSIONS: Urine Klotho may serve as an early biomarker for AKI and subsequent poor short-term renal outcome in patients undergoing cardiac surgery.

Use of Both Serum Cystatin C and Creatinine as Diagnostic Criteria for Cardiac Surgery-Associated Acute Kidney Injury and Its Correlation with Long-Term Major Adverse Events.

BACKGROUND/AIMS: Cardiac surgery-associated acute kidney injury (CSA-AKI) was traditionally defined as an increase in serum creatinine (sCr) after cardiac surgery. Recently, serum cystatin C (sCyC) has been proposed to be a better biomarker in the prediction of AKI. The clinical utility and performance of combining sCyC and sCr in patients with AKI, particularly for the prediction of long-term outcomes, remain unknown. METHODS: We measured sCyC together with sCr in 628 patients undergoing cardiac surgery. sCyC and sCr were assessed at baseline and 24 and 48 h after surgery. CSA-AKI determined by sCr (CSA-AKIsCr) was defined as an sCr increase greater than 0.3 mg/dL or 50% from baseline. Major adverse events (MAEs; including death of any cause and dialysis) at 3 years were assessed. RESULTS: CSA-AKIsCr developed in 178 patients (28.3%). Three-year follow-up was available for 621 patients; MAEs occurred in 42 patients (6.8%). An increase in sCyC concentration ≥30% within 48 h after surgery was detected in 228 patients (36.3%). This was the best sCyC cutoff for CSA-AKIsCr detection (negative predictive value = 88.8%, positive predictive value = 58.3%). To evaluate the use of both sCyC and sCr as CSA-AKI diagnostic criteria, we stratified patients into 3 groups: non-CSA-AKI, CSA-AKI detected by a single marker, and CSA-AKI detected by both markers. By multivariable logistic regression analysis, the independent predictors of MAEs at 3 years were group 2 (non-CSA-AKI group as the reference, CSA-AKI detected by a single marker: odds ratio [OR] = 3.48, 95% confidence interval [CI]: 1.27-9.58, p = 0.016), group 3 (CSA-AKI detected by both markers: OR = 5.12, 95% CI: 2.01-13.09; p = 0.001), and baseline glomerular filtration rate (OR = 2.24; 95% CI: 1.27-3.95; p = 0.005). CONCLUSION: Combining sCyC and sCr to diagnose CSA-AKI would be beneficial for risk stratification and prognosis in patients after cardiac surgery.

A Clinical Score to Predict Severe Acute Kidney Injury in Chinese Patients after Cardiac Surgery.

BACKGROUND/AIMS: Cardiac surgery-associated severe acute kidney injury (SAKI) is associated with high mortality and poor quality of life. A prognostic score for SAKI may enable prevention of complications. METHODS: This observational study of 2,552 patients undergoing cardiac surgery from January 2006 to December 2011 in our institution established associations between predictor variables and postoperative SAKI from a cohort of 1,692 patients and developed a clinical score that was assessed in a validation cohort of 860 patients. RESULTS: Postoperative SAKI occurred in 262 -patients (10.3%). We identified 7 independent and significant risk factors in the derivation model (adjusted OR 95% CI): age ≥81 years (vs. age < 40 years, 4.30, 1.52-12.21), age 61-80 years (vs. age < 40 years, 2.84, 1.24-6.52), age 41-60 years (vs. age < 40 years, 1.62, 0.68-3.87), hypertension (1.65, 1.13-2.39), previous cardiac surgery (3.62, 1.27-10.32), -hyperuricemia (2.02, 1.40-2.92), prolonged operation time (1.32, 1.17-1.48), postoperative central venous pressure < 6 mm H2O (3.53, 2.38-5.23), and low postoperative cardiac output (4.78, 2.97-7.69). The 7-variable risk prediction model had acceptable performance characteristics in the validation cohort (C statistic 0.80, 95% CI 0.74-0.85). The difference in the C statistic was 0.21 (95% CI 0.12-0.29, p < 0.001) compared with the Cleveland Clinic score. CONCLUSION: We developed and validated a practical risk prediction model for SAKI after cardiac surgery based on routinely available perioperative clinical and laboratory data. The prediction model can be easily applied at the bedside and provides a simple and interpretable estimation of risk.

Serum miR-192 Is Related to Tubulointerstitial Lesion and Short-Term Disease Progression in IgA Nephropathy.

BACKGROUND/AIMS: Clinical manifestation and renal histology serve as the current "gold standard" for evaluation of renal lesions in IgA nephropathy. MiR-192 is regarded as a potential noninvasive biomarker for kidney disease. We sought to elucidate a relationship between intrarenal, serum, and urinary exosomal miR-192 with renal lesions and disease progression in IgA nephropathy. METHODS: Serum and urinary exosomal miR-192 were detected and correlated with clinical and pathological parameters from consecutive IgA nephropathy patients (n = 50) and healthy control patients (n = 25). Patients then received a follow-up of 24 months after biopsy. Disease progression was defined as a 40% reduction in estimated glomerular filtration rate. Expression of miR-192 was quantified by Taqman RT-PCR. Intrarenal -miR-192 was detected in 8 IgA nephropathy patients and 4 matched patients receiving kidney nephrectomy as controls via in situ hybridization. TGF-ß1 and E-cadherin expression in renal tissue was evaluated using immunohistochemistry. RESULTS: Intrarenal miR-192 was correlated with serum miR-192 (r = 0.690, p = 0.013). Both intrarenal and serum miR-192 decreased in IgA nephropathy patients and were correlated with estimated glomerular filtration ratio. Patients with lower intrarenal and serum miR-192 levels had a higher interstitial fibrosis and tubular atrophy score, more severe lesions in tubular atrophy, and interstitial inflammation. Renal E-cadherin expression was correlated (r = 0.484, p = 0.004) and TGF-ß1 was inversely correlated (r = -0.527, p < 0.001) with serum miR-192 in IgA. Patients with higher serum miR-192 had a lower disease progression rate over the course of 2 years (0 vs. 16%, p = 0.028). No correlation was found in urinary exosomal miR-192 with the clinical and pathological parameters mentioned earlier. CONCLUSIONS: Lower serum miR-192 in IgA nephropathy patients indicates lower intrarenal miR-192 expression, more severe tubular atrophy, interstitial inflammation, and fibrotic tendency (with higher TGF-ß and E-cadherin in renal miR-192). IgA nephropathy patients with higher serum miR-192 are less likely to have renal function decline over the course of 2 years.

The Incidence Prognosis and Risk Factors of Cognitive Impairment in Maintenance Haemodialysis Patients.

OBJECTIVE: To investigate the incidence and the prognosis of cognitive impairment (CI) and to find out the risk factors associated with the outcome in maintenance haemodialysis (MHD) patients. METHODS: Enrolled the patients who met the criteria as below: MHD (≥3 months) patients before July 2014, ≥18 years old and could carry on the cognitive function test (Montreal Cognitive Assessment [MoCA]). All enrolled patients were divided into 2 groups: CI group (MoCA < 26) and non-CI group (MoCA ≥26). All patients were followed up for 36 months. The incidence, demography data, medical history, haemodialysis data, laboratory examination and prognosis of CI in haemodialysis patients were prospectively compared and analyzed. Multivariate logistic regression analysis was used to investigate the risk factors of CI. Kaplan-Meier survival curve was used for survival analysis. RESULTS: In the present study, 219 patients were enrolled. The ratio of male to female was 1.46: 1. Age was 60.07 ± 12.44 and dialysis vintage was 100.79 ± 70.23 months. One hundred thirteen patients' MoCA scores were lower than 26 were divided into CI group. Education status (OR 3.428), post-dialysis diastolic pressure (OR 2.234) and spKt/V (OR 1.982) were independent risk factors for CI in MHD patients. During the follow-up period, 15 patients died (13.2%) in the CI group and 5 died (4.72%) in the non-CI group (p < 0.05). The Kaplan-Meier survival curve analysis showed that the survival rate of patients with CI was lower than that of non-CI group in MHD patients during 3 years follow-up (p = 0.046). CONCLUSION: CI is one of the most common complications in MHD patients. The mortality is high in patients who had CI. Education status, post-dialysis diastolic pressure and spKt/V are independent risk factors for CI in MHD patients.

Twice-Weekly Hemodialysis and Clinical Outcomes in the China Dialysis Outcomes and Practice Patterns Study.

INTRODUCTION: In China, a quarter of patients are undergoing 2-times weekly hemodialysis. Using data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS), we tested the hypothesis that whereas survival and hospitalizations would be similar in the presence of residual kidney function (RKF), patients without RKF would fare worse on 2-times weekly hemodialysis. METHODS: In our cohort derived from 15 units randomly selected from each of 3 major cities (total N = 45), we generated a propensity score for the probability of dialysis frequency assignment, estimated a survival function by propensity score quintiles, and averaged stratum-specific survival functions to generate mean survival time. We used the proportional rates model to assess hospitalizations. We stratified all analyses by RKF, as reported by patients (urine output <1 vs. ≥1 cup/day). RESULTS: Among 1265 patients, 123 and 133 were undergoing 2-times weekly hemodialysis with and without evidence of RKF. Over 2.5 years, adjusted mean survival times were similar for 2- versus 3-times weekly dialysis groups: 2.20 versus 2.23 and 2.20 versus 2.15 for patients with and without RKF (P = 0.65). Hazard ratios for hospitalization rates were similar for 2- versus 3-times weekly groups, with (1.15, 95% confidence interval = 0.66-2.00) and without (1.10, 95% confidence interval 0.68-1.79]) RKF. The normalized protein catabolic rate was lower and intradialytic weight gain was not substantially higher in the 2- versus 3-times weekly dialysis group, suggesting greater restriction of dietary sodium and protein. CONCLUSION: In our study of patients in China's major cities, we could not detect differences in survival and hospitalization for those undergoing 2- versus 3-times weekly dialysis, regardless of RKF. Our findings indicate the need for pragmatic studies regarding less frequent dialysis with associated nutritional management.

Klotho Reduces Necroptosis by Targeting Oxidative Stress Involved in Renal Ischemic-Reperfusion Injury.

BACKGROUND/AIMS: Klotho is a multifunctional protein expressed predominantly in kidney tubular epithelium. Here, we investigated the protective effects of Klotho on necroptosis in renal ischemic-reperfusion injury (IRI) and the role of oxidative stress in this process. METHODS: Mice were subjected to bilateral renal pedicle clamping. Mouse renal tubular epithelial (TCMK-1) cells were exposed to hypoxia/reoxygenation (H/R) or H2O2. Kidney samples from acute kidney injury (AKI) patients and controls were examined by immunofluorescence. Klotho protein and N-acetyl-L-cysteine (NAC) were used to define their roles in mediating necroptosis. Necroptosis was assessed by TUNEL staining, immunoblotting, and real-time PCR. Oxidative stress was studied via ELISA, immunoblotting, colorimetric, and thiobarbituric acid reactive substances assays. RESULTS: Renal IRI induced Klotho deficiency in the serum and kidney, but an increase in the urine. The levels of the necroptotic markers receptor-interacting protein kinase (RIP) 1, RIP3, IL-1ß, and TUNEL-positive cells increased after IRI; all increases were ameliorated by Klotho. In TCMK-1 cells, Klotho and NAC attenuated the elevation in RIP1, RIP3, and LDH release induced by H/R or H2O2. Moreover, Klotho decreased the levels of oxidative stress biomarkers and elevated superoxide dismutase 2 expression in both in vivo and in vitro experiments. Studies in human samples further confirmed the Klotho deficiency and increased formation of RIP3 puncta in AKI kidneys. CONCLUSION: Klotho protects tubular epithelial cells from IRI and its anti-necroptotic role may be associated with oxidative stress inhibition.

Klotho ameliorates hydrogen peroxide-induced oxidative injury in TCMK-1 cells.

PURPOSE: Defects in Klotho gene expression in mice result in a vulnerability to oxidative injuries. We aimed to identify the expression of Klotho in a mouse tubular epithelial (TCMK-1) cell line, and also to investigate changes in Klotho expression induced by oxidative stress and the potential role of intra- and extracellular Klotho protein. METHODS: During exposure to hydrogen peroxide (H2O2), an overexpression of the Klotho gene was induced and exogenous Klotho protein was added in TCMK-1 cells. The generation of reactive oxidative species (ROS) was examined by flow cytometry, and cell viability was assessed by Cell Counting Kit-8. Cellular apoptosis was determined by flow cytometry and Hoechst 33258 staining followed by Western blotting to evaluate the expression of Klotho, antioxidant enzymes, and apoptosis-associated proteins. RESULTS: While H2O2 significantly suppressed Klotho expression, cell viability, and the expression of antioxidant enzymes in a concentration-dependent manner, cellular apoptosis was increased and p38/MAPK and JNK/MAPK were activated. Intra- and extracellular Klotho remarkably ameliorated viability inhibition, ROS generation, and cellular apoptosis induced by H2O2. Intra- and extracellular Klotho also reversed the loss of antioxidant enzymes, the elevation of cleaved Caspase-3 and Bax/Bcl-2, and the phosphorylation of JNK/MAPK and p38/MAPK. CONCLUSIONS: Klotho has posed antioxidant and anti-apoptotic effects on oxidative injuries in TCMK-1 cells, which might be partially related to its inhibition of JNK/MAPK and p38/MAPK phosphorylation and subsequent elevation of antioxidant enzymes. Increasing Klotho expression has played a protective role against oxidative stress in tubular epithelial cells.