Association between serum potassium, risk and prognosis of peritonitis in peritoneal dialysis patients - results from the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study.

BACKGROUND: Hypokalemia has been associated with an increased risk of peritoneal dialysis (PD)-associated peritonitis. However, hypokalemia is commonly associated with malnutrition, inflammation, and severe coexisting comorbidities, which thus are suspected of being potential confounders. This study was aimed at testing whether hypokalemia was independently associated with the occurrence and prognosis of PD-associated peritonitis. METHODS: A national-level dataset from the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study was used to explore the independent association of serum potassium with PD-associated peritonitis. Unmatched and propensity score-adjusted multivariate competing risk models, as well as univariate competing risk models following 1:1 propensity score matching, were conducted to balance potential biases between patients with and without hypokalemia. The association between potassium levels prior to peritonitis and treatment failure due to peritonitis was also investigated. RESULTS: During a median follow-up of 25.7 months in 7220 PD patients, there was a higher incidence of peritonitis in patients with serum potassium below 4.0 mmol/L compared to those with higher serum levels (677 [0.114/patient-year] vs. 914 [0.096/patient-year], P = 0.001). After adjusting for demographics, laboratory tests, residual renal function, and medication use, baseline potassium levels below 4.0 mmol/L were not linked to an increased risk of peritonitis, with a hazard ratio of 0.983 (95% CI 0.855-1.130, P = 0.810). This result remained consistent in both the propensity score adjusted multivariate competing risk regression (HR = 0.974, 95% CI 0.829-1.145, P = 0.750) and the univariate competing risk regression after 1:1 propensity score matching (Fine-Gray test, P = 0.218). The results were similar when analyzing patients with serum potassium level above or below 3.5 mmol/L. Lastly, hypokalemia before the occurrence of peritonitis was not independently associated with treatment failure. CONCLUSION: Hypokalemia was not found to be an independent risk factor for PD-associated peritonitis or treatment failure of peritonitis in China.

Deep-learning assisted zwitterionic magnetic immunochromatographic assays for multiplex diagnosis of biomarkers.

Magnetic nanoparticle (MNP)-based immunochromatographic tests (ICTs) display long-term stability and an enhanced capability for multiplex biomarker detection, surpassing conventional gold nanoparticles (AuNPs) and fluorescence-based ICTs. In this study, we innovatively developed zwitterionic silica-coated MNPs (MNP@Si-Zwit/COOH) with outstanding antifouling capabilities and effectively utilised them for the simultaneous identification of the nucleocapsid protein (N protein) of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) and influenza A/B. The carboxyl-functionalised MNPs with 10% zwitterionic ligands (MNP@Si-Zwit 10/COOH) exhibited a wide linear dynamic detection range and the most pronounced signal-to-noise ratio when used as probes in the ICT. The relative limit of detection (LOD) values were achieved in 12 min by using a magnetic assay reader (MAR), with values of 0.0062 ng/mL for SARS-CoV-2 and 0.0051 and 0.0147 ng/mL, respectively, for the N protein of influenza A and influenza B. By integrating computer vision and deep learning to enhance the image processing of immunoassay results for multiplex detection, a classification accuracy in the range of 0.9672-0.9936 was achieved for evaluating the three proteins at concentrations of 0, 0.1, 1, and 10 ng/mL. The proposed MNP-based ICT for the multiplex diagnosis of biomarkers holds substantial promise for applications in both medical institutions and self-administered diagnostic settings.

Cut-off values of haemoglobin and clinical outcomes in incident peritoneal dialysis: the PDTAP study.

BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.

Retraction of "0D/2D Coordination Complexes: Magnetic Studies, Protection, and Mechanism against Ischemic Myocardial Damage by Reducing the Activation of the PI3K/Akt Signaling Pathway".

[This retracts the article DOI: 10.1021/acsomega.0c05601.].

Clinical characteristics and management of hemodialysis patients with pre-dialysis hypertension: a multicenter observational study.

BACKGROUND: Hypertension is a leading preventable risk factor for cardiovascular disease in hemodialysis patients. Pre-dialysis systolic blood pressure (SBP) more than 160 mmHg was thought to be associated with increased risk of cardiovascular events and all-cause mortality. The present study was performed to explore the clinical characteristics and management of hemodialysis patients with pre-dialysis SBP ≥ 160 mmHg. METHODS: A total of 1233 patients undergoing hemodialysis from nine hemodialysis centers were enrolled. Pre-dialysis and home BP were measured and clinical data were collected. The characteristics of patients with pre-dialysis SBP ≥ 160 mmHg were explored. Clinical parameters between hypertensive and non-hypertensive patients were compared. The partial correlation analyses performed to identify the associations between BP and clinical parameters. RESULTS: There were 24.6% of the hemodialysis patients had pre-dialysis SBP ≥ 160 mmHg and the average SBP was 173.8 ± 10.9 mmHg. Only 21.4% of the patients achieved dry weight after dialysis and up to 30.2% of patients were not given combination therapies of antihypertensive drugs. Compared to patients with pre-hemodialysis SBP < 160 mmHg, patients with pre-dialysis SBP ≥ 160 mmHg had lower target-reaching rate of Kt/v and higher incidences of intradialytic hypotension and muscle spasm. Most patients (96%) with pre-dialysis SBP ≥ 160 mmHg had home SBP≥ 135 mmHg. Patients with home SBP ≥ 160 mmHg had higher left ventricular weight index and lower hemoglobin levels when compared to their counterparts with home SBP <160 mmHg. CONCLUSIONS: Pre-dialysis SBP ≥ 160 mmHg is common in clinical practice and most of the patients could diagnosed to be hypertensive according to their home SBP. Patients with pre-dialysis SBP ≥ 160 mmHg are more likely to be subjected to dialysis insufficiency and intradialytic complications. Achieving dry weight and sufficient pharmacologic interventions should be strengthened to improve BP control in the hemodialysis population.

Telemedicine and Clinical Outcomes in Peritoneal Dialysis: A Propensity-Matched Study.

INTRODUCTION: Telemedicine (TM) has shown to provide potential benefits on clinical outcomes in patients with chronic kidney disease but limited evidences published in the peritoneal dialysis (PD) population. This study aimed to explore the long-term effects of TM on the mortality and technique failure. METHODS: The Peritoneal Dialysis Telemedicine-assisted Platform Cohort Study (PDTAP Study) was conducted prospectively in 27 hospitals in China since 2016. Patient and practice data were collected through the doctor-end of the TM app (Manburs) for all participants. TM including self-monitoring records, on-line education materials, and real-time physician-patient contact was only performed for the patient-end users of the Manburs. The primary outcome was all-cause mortality. The secondary outcomes were cause-specific mortality and all-cause and cause-specific permanent transfer to hemodialysis. RESULTS: A total of 7,539 PD patients were enrolled between June 2016 and April 2019, with follow-up till December 2020. Patients were divided into two cohorts: TM group (39.1%) and non-TM group (60.9%). A propensity score was used to create 2,160 matched pairs in which the baseline covariates were well-balanced. There were significantly lower risks of all-cause mortality (HR 0.59 [0.51, 0.67], p < 0.001), CVD mortality (HR 0.59 [0.49, 0.70], p < 0.001), all-cause transfer to hemodialysis (0.57 [0.48, 0.67], p < 0.001), transfer to hemodialysis from PD-related infection (0.67 [0.51, 0.88], p = 0.003), severe fluid overload (0.40 [0.30, 0.55], p < 0.001), inadequate solute clearance (0.49 [0.26, 0.92], p = 0.026), and catheter-related noninfectious complications (0.41 [0.17, 0.97], p = 0.041) in the TM group compared with the non-TM group. CONCLUSION: This study indicated real-world associations between TM usage and reduction in patient survival and technique survival through a multicenter prospective cohort.

The Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study: Design and methods.

OBJECTIVES: The primary objective of the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study is to explore potential predictors and their effects on patient survival, technique survival, and the occurrence of infectious and noninfectious complications. DESIGN: The PDTAP study is a national-level cohort study in China. A newly developed PD telemedicine application provided a unique and convenient way to collect multicenter, structured data across units. SETTING: The PDTAP study was underway in 27 hospitals from 14 provinces located at 7 geographical regions (northwest, northeast, north, central, southwest, southeast, and south) in China. PARTICIPANTS: Our study aims to enroll at least 7000 adult patients with end-stage renal disease receiving PD. METHODS: Approval has been obtained through the ethics committees of all hospitals. All participants signed the informed consent form after the center had received ethics board approval in accordance with the Declaration of Helsinki. MAIN OUTCOME MEASURES: Patient survival, technique survival, hospitalization, and the occurrence of infectious and noninfectious complications. CONCLUSIONS: The PDTAP study aims to explore potential predictors and their effects on patient survival, technique survival, and infectious and noninfectious complications using a newly developed PD telemedicine system to collect multicenter, structured data in real-world practice. Substantial and transformable findings in relation to PD practices were expected. This study also developed a national-level infrastructure for further collaboration and ancillary investigation.

Identification of immune features of HIV-infected patients with antiretroviral therapy through bioinformatics analysis.

BACKGROUND: Acquired immunodeficiency syndrome (AIDS) is a disease arising from human immunodeficiency virus (HIV). Antiretroviral therapy (ART) is a main therapeutic regimen for inhibiting HIV proliferation and viability. Identification of differentially expressed genes (DEGs) in HIV-infected patients with and without ART could provide theoretical evidence for deep research into the efficacy of ART and corresponding mechanism. METHODS: In this study, mRNA microarray data (GSE108296) of HIV-infected patients who received and didn't receive ART were downloaded from Gene Expression Omnibus (GEO) database. DEGs were obtained through differential analysis with R package limma. Then, protein-protein interaction (PPI) analysis was performed to identify hub genes and functional modules. Besides, immune-related DEGs were screened, followed by GO annotation and KEGG pathway enrichment analysis. Moreover, various immune cells and immune functions in samples were analyzed by ESTIMATE, ssGSEA and CIBERSORT, based on which the immune function of HIV-infected patients who received and didn't receive ART was evaluated. RESULTS: A total of 109 DEGs were obtained from differential analysis. Among them, 19 immune-related DEGs were identified and subjected to GO and KEGG enrichment analyses. Furthermore, PPI network analysis was undertaken on the 109 DEGs. 10 hub genes and 3 functional modules were further screened. It was shown that these genes and functional modules were correlated with immune functions and relevant signaling pathways. ESTIMATE, ssGSEA and CIBERSORT results displayed that HIV-infected patients with ART presented a relatively high immune level. CONCLUSION: According to bioinformatics analysis, we reasonably posited that HIV-infected patients who received ART had an increased immune level relative to patients who didn't receive ART.

0D/2D Coordination Complexes: Magnetic Studies, Protection, and Mechanism against Ischemic Myocardial Damage by Reducing the Activation of the PI3K/Akt Signaling Pathway.

The synthesis of two new coordination compounds was carried out by applying 4-(3-carboxyphenyl)picolinic acid (H2cppa) as building units under the hydrothermal reaction conditions, whose chemical formulae are [Cu(Hcppa)2(H2O)2]·2H2O (1) and [Cu(µ3-cppa)(H2O)2] (2). The analysis of structures suggested that 1 featured a discrete molecular structure, which was extended into the three-dimensional supramolecular network with the topology of pcu topology, whereas complex 2 showed a two-dimensional layered network with the fes topology. The magnetic performances of the two synthesized compounds reveal antiferromagnetic coupling between consecutive metal ions. Their application values on ischemic myocardial damage were assessed, and the detailed mechanism of the synthetic complexes was also investigated. The Elabscience Annexin V detection kit was used in this research to determine the percentage of apoptotic cardiomyocytes after different complex treatments. In addition, the relative expression of PI3K/Akt in the myocardium after the application of the compound was determined using the real-time reverse transcription polymerase chain reaction assay.

The effect of BCM guided dry weight assessment on short-term survival in Chinese hemodialysis patients : Primary results of a randomized trial - BOdy COmposition MOnitor (BOCOMO) study.

BACKGROUND: Lack of accurate and effective assessment tools of fluid status is one of the major challenges to reach proper dry weight (DW) in chronic hemodialysis (HD) population. The aim of this randomized study was to evaluate the effect of bioimpedance guided DW assessment on long-term outcomes in Chinese HD patients. Eligible patients were randomly assigned (1:1) to two groups in each center, the control group and body composition monitor (BCM) group. In the BCM group, DW has been evaluated by bioimpedance technic every 2 months during follow-up. The primary composite endpoint consisted of death, acute myocardial infarction, cerebral infarction, cerebral hemorrhage, and peripheral vascular disease. METHODS: A total of 445 patients were recruited from 11 hemodialysis centers from Beijing, Tianjin and Shijiazhuang cities from Jan 1, 2013 to Dec 31, 2014. They were randomized into either BCM group or control group. All patients have been followed up for 1 year or until Dec 31, 2014 or censoring. RESULTS: At baseline, there were no significant differences between two groups in terms of demographic parameters, dialysis vintage, percentage of vascular access, and comorbid conditions. At the end of the study, 18 (4.04%) patients had died (11 in control group and 7 in BCM group). Kaplan-Meier survival analysis showed no significant difference in survival rates between two groups (log-rank test P = 0.07). However, there was an increasing trend of survival rates in BCM group compared to the control group. In the multivariable Cox analysis, there was a nonsignificant trend toward less primary composite end points in the BCM group in the adjusted analysis, the hazard ratio was impressive (0.487, 95% CI 0.217-1.091, P = 0.08). CONCLUSION: Bioimpedance technic has been applied to assess fluid status for decades and has been proved to be a promising tool for clinical practice. Although short-term outcomes were not improved in the randomized, controlled trial, the ascending trend in survival has been observed. Further studies are needed to investigate the survival benefit of bioimpedance method in DW assessment in a larger sample with longer follow-up period. TRIAL REGISTRATION: ClinicalTrials.org, NCT01509937. Registered 13 January 2012.

Large-scale immuno-magnetic cell sorting of T cells based on a self-designed high-throughput system for potential clinical application.

In this contribution, we designed four types of immuno-magnetic nanoparticles for separation of different T cells (CD3+, CD4+, CD8+ and CD14+ T cells), and we established a new large-scale immuno-magnetic cell sorting procedure to achieve an enrichment of particular T cells using our designed auto-IMACS device. This device could achieve recyclable large-scale cell sorting, for which the throughput of the system reached ∼4000 mL and the maximum cell capacity was 4 × 1010. The collected cells were analyzed by flow cytometry and visual cytology data, and the effective selection rates of CD3+, CD4+, CD8+ and CD14+ T cells were 79.3%, 74.1%, 57.1% and 67.9%, respectively. The sorted CD8+ T cells still retained good cytotoxic activity against specific cells. In addition, the sorted T cells can also be further incubated in vitro and proliferated, and even could be infused back into patients for immunotherapy in the near future.

Superparamagnetic Fe3O4-PEG2K-FA@Ce6 Nanoprobes for in Vivo Dual-mode Imaging and Targeted Photodynamic Therapy.

The development of targeted nanoprobes is a promising approach to cancer diagnostics and therapy. In the present work, a novel multifunctional photo/magnet-diagnostic nanoprobe (MNPs-PEG2K-FA@Ce6) has been developed. This nanoprobe is built using folic acid (FA), bifunctional polyethylene glycol (PEG2K) and photosensitizer chlorin e6 (Ce6). The MNPs-PEG2K-FA@Ce6 nanoprobes are superparamagnetic, can be synthesized on a large scale by a one-pot hydrothermal process without further surface modification and are stable in an aqueous environment for eight months. Compared with free Ce6 nanoprobes in vitro studies, the MNPs-PEG2K-FA@Ce6 nanoprobes significantly enhance cellular uptake efficiency and promote the effectiveness of photodynamic therapy (PDT) with the assistance of 633 nm laser irradiation. The unique nanoprobes show superior penetration and a retention time of more than six days with less accumulation in the liver allowing highly effective tumor recognition and monitoring. Additionally, there was little damage to healthy organs or tissues. These exciting new nanoprobes could be potential building blocks to develop new clinical therapies and translational medicine.

The application of CT voiding urethrography in the evaluation of urethral stricture associated with fistula: a preliminary report.

PURPOSE: This study was designed to evaluate the clinical utility of CT voiding urethrography (2D/3D reformatted CT images and virtual cystourethroscopy) in terms of its ability to detect urethral stricture associated with fistula. METHODS: In the study period, 80 patients were found to have signs or symptoms of urine leakage, as detected by voiding CT scanning. 2D/3D reformatted CT images and the virtual cystourethroscopic view were generated by the software. Conventional urethrography and traditional cystourethroscopy were also used prior to operation. The accuracy of these techniques was compared to the actual findings during the operation. RESULTS: For 58 male patients suffering from urethral strictures associated with fistulas, the detection rate of the fistulas by 2D/3D reformatted CT images was superior to conventional urethrography for characterizing the site of the fistula and the length of the urethral stricture (P < 0.05). The detection rate of the fistula by 3D virtual cystourethroscopy was similar to that by traditional cystourethroscopy (P > 0.05). The duration of the examination was shorter for 3D virtual cystourethroscopy than for traditional cystourethroscopy (P < 0.05). The same results were observed in 22 cases that featured a urethrovaginal fistula. CONCLUSION: CT voiding urethrography is a useful technique for the diagnosis of urethral disease, especially in male patients suffering from urethral stricture associated with fistula.

Analysis of 589,306 genomes identifies individuals resilient to severe Mendelian childhood diseases.

Genetic studies of human disease have traditionally focused on the detection of disease-causing mutations in afflicted individuals. Here we describe a complementary approach that seeks to identify healthy individuals resilient to highly penetrant forms of genetic childhood disorders. A comprehensive screen of 874 genes in 589,306 genomes led to the identification of 13 adults harboring mutations for 8 severe Mendelian conditions, with no reported clinical manifestation of the indicated disease. Our findings demonstrate the promise of broadening genetic studies to systematically search for well individuals who are buffering the effects of rare, highly penetrant, deleterious mutations. They also indicate that incomplete penetrance for Mendelian diseases is likely more common than previously believed. The identification of resilient individuals may provide a first step toward uncovering protective genetic variants that could help elucidate the mechanisms of Mendelian diseases and new therapeutic strategies.

Acute kidney injury in China: a cross-sectional survey.

BACKGROUND: Acute kidney injury (AKI) has become a worldwide public health problem, but little information is available about the disease burden in China. We aimed to evaluate the burden of AKI and assess the availability of diagnosis and treatment in China. METHODS: We launched a nationwide, cross-sectional survey of adult patients who were admitted to hospital in 2013 in academic or local hospitals from 22 provinces in mainland China. Patients with suspected AKI were screened out on the basis of changes in serum creatinine by the Laboratory Information System, and we reviewed medical records for 2 months (January and July) to confirm diagnoses. We assessed rates of AKI according to two identification criteria: the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition and an increase or decrease in serum creatinine by 50% during hospital stay (expanded criteria). We estimated national rates with data from the 2013 report by the Chinese National Health and Family Planning Commission and National Bureau of Statistics. FINDINGS: Of 2,223,230 patients admitted to the 44 hospitals screened in 2013, 154,950 (7·0%) were suspected of having AKI by electronic screening, of whom 26,086 patients (from 374,286 total admissions) were reviewed with medical records to confirm the diagnosis of AKI. The detection rate of AKI was 0·99% (3687 of 374,286) by KDIGO criteria and 2·03% (7604 of 374,286) by expanded criteria, from which we estimate that 1·4-2·9 million people with AKI were admitted to hospital in China in 2013. The non-recognition rate of AKI was 74·2% (5608 of 7555 with available data). Renal referral was done in 21·4% (1625 of 7604) of the AKI cases, and renal replacement therapy was done in 59·3% (531 of 896) of those who had the indications. Delayed AKI recognition was an independent risk factor for in-hospital mortality, and renal referral was an independent protective factor for AKI under-recognition and mortality INTERPRETATION: AKI has become a huge medical burden in China, with substantial underdiagnosis and undertreatment. Nephrologists should take the responsibility for leading the battle against AKI. FUNDING: National 985 Project of China, National Natural Science Foundation of China, Beijing Training Program for Talents, International Society of Nephrology Research Committee, and Bethune Fund Management Committee.

Delayed diagnosis of congenital myasthenia due to associated mitochondrial enzyme defect.

Clinical phenotypes of congenital myasthenic syndromes and primary mitochondrial disorders share significant overlap in their clinical presentations, leading to challenges in making the correct diagnosis. Next generation sequencing is transforming molecular diagnosis of inherited neuromuscular disorders by identifying novel disease genes and by identifying previously known genes in undiagnosed patients. This is evident in two patients who were initially suspected to have a mitochondrial myopathy, but in whom a clear diagnosis of congenital myasthenic syndromes was made through whole exome sequencing. In patient 1, whole exome sequencing revealed compound heterozygous mutations c.1228C > T (p.Arg410Trp) and c.679C > T (p.Arg227*) in collagen-like tail subunit (single strand of homotrimer) of asymmetric acetylcholinesterase (COLQ). In patient 2, in whom a deletion of exon 52 in Dystrophin gene was previously detected by multiplex ligation-dependent probe amplification, Sanger sequencing revealed an additional homozygous mutation c.1511_1513delCTT (p.Pro504Argfs*183) in docking protein7 (DOK7). These case reports highlight the need for careful diagnosis of clinically heterogeneous syndromes like congenital myasthenic syndromes, which are treatable, and for which delayed diagnosis is likely to have implications for patient health. The report also demonstrates that whole exome sequencing is an effective diagnostic tool in providing molecular diagnosis in patients with complex phenotypes.

Molecular genetic testing in clinical diagnostic assessments that demonstrate correlations in patients with autosomal recessive inherited retinal dystrophy.

IMPORTANCE: Inherited retinal dystrophies (IRDs) are a group of retinal degenerative diseases presenting genetic and clinical heterogeneities, which have challenged the genetic and clinical diagnoses of IRDs. Genetic evaluations of patients with IRD might result in better clinical assessments and better management of patients. OBJECTIVE: To determine the genetic lesions with phenotypic correlations in patients with diverse autosomal recessive IRD using next-generation sequencing. DESIGN, SETTING, AND PARTICIPANTS: A cohort of 20 Chinese families affected with autosomal recessive IRD were recruited (with data on their detailed family history and on their clinical condition). To identify disease-causing mutations in the patients, the targeted sequence capture of IRD-relevant genes using 2 in-house-designed microarrays, followed by next-generation sequencing, was performed. Bioinformatics annotation, intrafamilial cosegregation analyses, in silico analyses, and functional analyses were subsequently conducted for the variants identified by next-generation sequencing. MAIN OUTCOMES AND MEASURES: The results of detailed clinical evaluations, the identification of disease-causing mutations, and the clinical diagnosis. RESULTS: Homozygous and biallelic variants were identified in 11 of the 20 families (55%) as very likely disease-causing mutations, including a total of 17 alleles, of which 12 are novel. The 17 alleles identified here include 3 missense, 6 nonsense, 4 frameshift, and 4 splice site mutations. In addition, we found biallelic RP1 mutations in a patient with cone-rod dystrophy, which was not previously correlated with RP1 mutations. Moreover, the identification of pathogenic mutations in 3 families helped to refine their clinical diagnoses. CONCLUSIONS AND RELEVANCE: In this study, to our knowledge, many mutations identified in those known loci for autosomal recessive IRD are novel. Specific RP1 mutations may correlate with cone-rod dystrophy. Genetic evaluations with targeted next-generation sequencing might result in a better clinical diagnosis and a better clinical assessment and, therefore, should be recommended for such patients.

Crystal cell oriented-rotation triggered phase transition of porous upconversion nanocrystals synthesis in hydrothermal system.

The phase transition of upconversion nanocrystals (UNs) from cubic to hexagonal structure is of fundamental importance in improving the luminescence intensity by about one or two orders of magnitudes, but the mechanism is still not well understood and efforts to completely transfer the phase from cubic to hexagonal structure remains a difficult and challenging task. Here, we describe a hydrothermal system in which an anion induces the phase transition process to give simultaneous control over the size, morphology, phase and emission properties. We first confirm that the crystal cell oriented-rotation driven by an anion in a hydrothermal system promoted the phase transition, and the energy zones figure of the phase transition from cubic to hexagonal structure has been figured out. We have successfully applied the structural mechanics finite element calculations to validate the reaction process. We have also demonstrated that porous UNs can be rationally tuned in size (down to fifteen nanometers), phase (cubic or hexagonal) and emission properties at precisely defined conditions, and were effective for in vitro and in vivo CT imaging.

CT virtual cystourethroscopy for complex urethral strictures: an investigative, descriptive study.

PURPOSE: To compare the values of CT virtual cystourethroscopy and of conventional cystourethroscopy in diagnosing complex urethral strictures. METHODS: From January 2012 to December 2012, 33 patients, suspected of having complex urethral strictures before operation, were enrolled in this study. After CT scanning, a virtual cystourethroscopic view was software-generated. Conventional cystourethroscopy was also used before operation. The time durations of virtual cystourethroscopy and conventional cystourethroscopy were recorded. The accuracies of both techniques were compared using the actual findings from the operation. RESULTS: For 16 patients suffering from urethral strictures associated with various fistulas, the duration of examination with virtual cystourethroscopy was statistically significantly shorter than with conventional cystourethroscopy (P < 0.001). The detection rate of fistula by virtual cystourethroscopy was similar to than by conventional cystourethroscopy (P = 0.057). The same results were obtained in eight patients suffering from urethral strictures associated with false passages. Only virtual cystourethroscopy could reveal the details of the urethral lumen in nine patients suffering from long anterior urethral strictures caused by lichen sclerosus. By contrast, conventional cystourethroscopy failed in those same patients. CONCLUSION: CT virtual cystourethroscopy is a useful technique for the diagnosis of urethral disease, especially in male patients suffering from complex urethral strictures.

A randomized controlled trial of long term effect of BCM guided fluid management in MHD patients (BOCOMO study): rationales and study design.

BACKGROUND: Bioimpedance analysis (BIA) has been reported as helpful in identifying hypervolemia. Observation data showed that hypervolemic maintenance hemodialysis (MHD) patients identified using BIA methods have higher mortality risk. However, it is not known if BIA-guided fluid management can improve MHD patients' survival. The objectives of the BOCOMO study are to evaluate the outcome of BIA guided fluid management compared with standard care. METHODS: This is a multicenter, prospective, randomized, controlled trial. More than 1300 participants from 16 clinical sites will be included in the study. The enrolment period will last 6 months, and minimum length of follow-up will be 36 months. MHD patients aged between 18 years and 80 years who have been on MHD for at least 3 months and meet eligibility criteria will be invited to participate in the study. Participants will be randomized to BIA arm or control arm in a 1:1 ratio. A portable whole body bioimpedance spectroscopy device (BCM-Fresenius Medical Care D GmbH) will be used for BIA measurement at baseline for both arms of the study. In the BIA arm, additional BCM measurements will be performed every 2 months. The primary intent-to-treat analysis will compare outcomes for a composite endpoint of death, acute myocardial infarction, stroke or incident peripheral arterial occlusive disease between groups. Secondary endpoints will include left ventricular wall thickness, blood pressure, medications, and incidence and length of hospitalization. DISCUSSIONS: Previous results regarding the benefit of strict fluid control are conflicting due to small sample sizes and unstable dry weight estimating methods. To our knowledge this is the first large-scale, multicentre, prospective, randomized controlled trial to assess whether BIS-guided volume management improves outcomes of MHD patients. The endpoints of the BOCOMO study are of utmost importance to health care providers. In order to obtain that aim, the study was designed with very careful important considerations related to the endpoints, sample size, inclusion criteria, exclusion criteria and so on. For example, annual mortality of Beijing MHD patients was around 10%. To reach statistical significance, the sample size will be very large. By using composite endpoint, the sample size becomes reasonable and feasible. Limiting inclusion to patients with urine volume less than 800 ml/day the day before dialysis session will limit confounding due to residual renal function effects on the measured parameters. Patients who had received BIS measurement within 3 months prior to enrolment are excluded as data from such measurements might lead to protocol violation. Although not all patients enrolled will be incident patients, we will record the vintage of dialysis in the multivariable analysis.