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.

Risk Factors of the Occurrence and Treatment Failure of Refractory Peritoneal Dialysis-Associated Peritonitis: A Single-Center Retrospective Study From China.

BACKGROUND: This study aimed to investigate the clinical characteristics and prognosis of refractory peritoneal dialysis (PD)-associated peritonitis as well as the risk factors of its occurrence and treatment failure. METHODS: A single-center retrospective cohort study was conducted among 519 patients undergoing PD from January 2007 to October 2021. According to the International Society for Peritoneal Dialysis guidelines, all episodes occurred in our center were divided into two groups: refractory and nonrefractory. Demographic, biochemical, and pathogenic bacteria and treatment outcome data were collected. RESULTS: During the 15-year period, 282 episodes of peritonitis occurred in 166 patients undergoing PD. The refractory rate was 34.0% (96/282). Gram-positive organisms were the leading cause of peritonitis (47.9%); however, gram-negative organisms were predominant in refractory peritonitis (34.4%, p = 0.002). Multiple logistic regression revealed that gram-negative organism-based peritonitis, longer PD duration, and female sex were the significant independent predictors of refractory peritonitis. Among 96 refractory episodes, white blood cell (WBC) count, dialysate WBC on Day 3, and PD duration ≥5 years were the independent risk factors of treatment failure. CONCLUSIONS: Gram-negative organism-based peritonitis, longer PD duration, and female sex were the independent risk factors of refractory peritonitis. Refractory peritonitis with higher WBC count, higher dialysate WBC on Day 3, and PD duration ≥5 years increased treatment failure risk and required immediate PD catheter removal. The timely identification of refractory peritonitis with high risk of treatment failure as well as timely PD catheter removal is important.

Histone acetyltransferase HAM1 interacts with molecular chaperone DNAJA2 and confers immune responses through salicylic acid biosynthetic genes in cassava.

Cassava bacterial blight (CBB) is one of the most serious diseases in cassava production, so it is essential to explore the underlying mechanism of immune responses. Histone acetylation is an important epigenetic modification, however, its relationship with cassava disease resistance remains unclear. Here, we identified 10 histone acetyltransferases in cassava and found that the transcript of MeHAM1 showed the highest induction to CBB. Functional analysis showed that MeHAM1 positively regulated disease resistance to CBB through modulation of salicylic acid (SA) accumulation. Further investigation revealed that MeHAM1 directly activated SA biosynthetic genes' expression via promoting lysine 9 of histone 3 (H3K9) acetylation and lysine 5 of histone 4 (H4K5) acetylation of these genes. In addition, molecular chaperone MeDNAJA2 physically interacted with MeHAM1, and MeDNAJA2 also regulated plant immune responses and SA biosynthetic genes. In conclusion, this study illustrates that MeHAM1 and MeDNAJA2 confer immune responses through transcriptional programming of SA biosynthetic genes via histone acetylation. The MeHAM1 & MeDNAJA2-SA biosynthesis module not only constructs the direct relationship between histone acetylation and cassava disease resistance, but also provides gene network with potential value for genetic improvement of cassava disease resistance.

GSK2795039 prevents RIP1-RIP3-MLKL-mediated cardiomyocyte necroptosis in doxorubicin-induced heart failure through inhibition of NADPH oxidase-derived oxidative stress.

Doxorubicin (DOX), which is widely used for the treatment of cancer, induces cardiomyopathy associated with NADPH oxidase-derived reactive oxygen species. GSK2795039 is a novel small molecular NADPH oxidase 2 (Nox2) inhibitor. In this study, we investigated whether GSK2795039 prevents receptor-interacting protein kinase 1 (RIP1)-RIP3-mixed lineage kinase domain-like protein (MLKL)-mediated cardiomyocyte necroptosis in DOX-induced heart failure through NADPH oxidase inhibition. Eight-week old mice were randomly divided into 4 groups: control, GSK2795039, DOX and DOX plus GSK2795039. H9C2 cardiomyocytes were treated with DOX and GSK2795039. In DOX-treated mice, the survival rate was reduced, left ventricular (LV) end-systolic dimension was increased and LV fractional shortening was decreased, and these alterations were attenuated by the GSK2795039 treatment. GSK2795039 inhibited not only myocardial NADPH oxidase subunit gp91phox (Nox2) protein, but also p22phox, p47phox and p67phox proteins and prevented oxidative stress 8-hydroxy-2'-deoxyguanosine levels in DOX-treated mice. RIP3 protein and phosphorylated RIP1 (p-RIP1), p-RIP3 and p-MLKL proteins, reflective of their respective kinase activities, markers of necroptosis, were markedly increased in DOX-treated mice, and the increases were prevented by GSK2795039. GSK2795039 prevented the increases in serum lactate dehydrogenase and myocardial fibrosis in DOX-treated mice. Similarly, in DOX-treated cardiomyocytes, GSK2795039 improved cell viability, attenuated apoptosis and necrosis and prevented the increases in p-RIP1, p-RIP3 and p-MLKL expression. In conclusion, GSK2795039 prevents RIP1-RIP3-MLKL-mediated cardiomyocyte necroptosis through inhibition of NADPH oxidase-derived oxidative stress, leading to the improvement of myocardial remodeling and function in DOX-induced heart failure. These findings suggest that GSK2795039 may have implications for the treatment of DOX-induced cardiomyopathy.

Histone deacetylase 9 regulates disease resistance through fine-tuning histone deacetylation of melatonin biosynthetic genes and melatonin accumulation in cassava.

Melatonin participates in plant growth and development and biotic and abiotic stress responses. Histone acetylation regulates many plant biological processes via transcriptional reprogramming. However, the direct relationship between melatonin and histone acetylation in plant disease resistance remains unclear. In this study, we identified cassava bacterial blight (CBB) responsive histone deacetylase 9 (HDA9), which negatively regulated disease resistance to CBB by reducing melatonin content. In addition, exogenous melatonin alleviated disease sensitivity of MeHDA9 overexpressed plants to CBB. Importantly, MeHDA9 inhibited the expression of melatonin biosynthetic genes through decreasing lysine 5 of histone 4 (H4K5) acetylation at the promoter regions of melatonin biosynthetic genes, thereby modulating melatonin accumulation in cassava. Furthermore, protein phosphatase 2C 12 (MePP2C12) interacted with MeHDA9 in vivo and in vitro, and it was involved in MeHDA9-mediated disease resistance via melatonin biosynthetic pathway. In summary, this study highlights the direct interaction between histone deacetylation and melatonin biosynthetic genes in cassava disease resistance via histone deacetylation, providing new insights into the genetic improvement of disease resistance via epigenetic regulation of melatonin level in tropical crops.

Effect of different dialysis duration on the prognosis of peritoneal dialysis-associated peritonitis: a single-center, retrospective study.

BACKGROUND: Peritoneal dialysis (PD)-associated peritonitis is a serious complication observed in peritoneal dialysis patients. Herein, we investigated the clinical characteristics and treatment outcomes of PD peritonitis in patients with different PD durations. METHODS: All peritonitis episodes from January 2007 to December 2020 at Peking University People's hospital PD center were retrospectively analyzed and divided into the long-dialysis duration (≥60 months, LDD) and short-dialysis duration (<60 months, SDD) groups. Clinical characteristics and outcomes were compared between these groups. The risk factors for treatment failure were analyzed using a logistic regression model. RESULTS: During 14 years, 156 patients had 267 peritonitis episodes. There were 83 (31.1%) peritonitis episodes in the LDD group and 184 (68.9%) in the SDD group. No statistical difference was noted in peritonitis causes and the composition of causative pathogens between the two groups. The hospitalization, treatment failure, and transfer-to-hemodialysis rates, and peritonitis-related mortality were significantly higher in the LDD group than in the SDD group (all p < .05). Logistic regression analysis revealed that PD duration was an independent risk factor for PD-associated hospitalization, treatment failure and peritonitis-related death (p < .05). The receiver operating characteristic curve analysis results showed that when the cutoff value of PD duration was 5.5 years, the sensitivity of predicting PD peritonitis treatment failure was 51.1%, specificity was 78.8%, and the area under the curve was 0.679 (95% confidence interval: 0.594-0.765, p < .001). CONCLUSIONS: PD duration is an independent risk factor for poor prognosis in PD peritonitis. Careful and active attention should be paid to the prevention of peritonitis in PD patients with long PD duration.

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 Association between Baseline Serum Lipids and Mortality in Peritoneal Dialysis Patients.

INTRODUCTION: Lipid disturbances are common in ESRD patients. In peritoneal dialysis (PD) patients, dyslipidemia is even more common. This study aimed to examine whether serum lipids were associated with prognosis of PD patients. METHODS: Patients from a multicenter retrospective cohort were used for the present study. The primary endpoint was all-cause mortality. Cox regression was used to analyze the association between serum lipids including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, and triglycerides and the prognosis. RESULTS: The results showed that lower total cholesterol and LDL levels at the initiation of PD predicted higher all-cause mortality in PD patients. Multivariate analysis reveal that the association disappeared after adjusting for age, gender, albumin, prealbumin, protein catabolic rate normalized to body weight, C-reactive protein, and residual renal function. Further analysis showed that patients with lower total cholesterol/LDL had a higher mortality only during the first 24 months of follow-up. In the patients who survived >2 years after PD, lower total cholesterol/LDL was not associated with higher long-term all-cause mortality any more. CONCLUSION: Lower total cholesterol/LDL levels at the initiation of PD were associated with overall mortality in PD patients. The association could be potentially modified by malnutrition, inflammation, and residual renal function or disappeared after 24 months.

Dual-Energy CT-Based Nomogram for Decoding HER2 Status in Patients With Gastric Cancer.

OBJECTIVE. The purpose of this study was to develop and evaluate a dual-energy CT (DECT)-based nomogram for noninvasive identification of the status of human epidermal growth factor receptor 2 (HER2; also known as ERBB2) expression in gastric cancer (GC). MATERIALS AND METHODS. A total of 206 patients with histologically proven GC who underwent pretreatment DECT were retrospectively recruited and randomly allocated to a training cohort (n = 144) or a test cohort (n = 62). Information on clinical characteristics, qualitative imaging features, and quantitative DECT parameters was collected. Univariate analysis and multivariate logistic regression were implemented to screen independent predictors of HER2 status. An individualized nomogram was built, and its discrimination, calibration, and clinical usefulness were assessed. RESULTS. Tumor location, the iodine concentration of the tumor in the venous phase, and the normalized iodine concentration of the tumor in the venous phase were significant factors predictive of HER2 status (all p < .05). After these three indicators were integrated, the proposed nomogram showed a favorable diagnostic performance, with AUCs of 0.807 (95% CI, 0.718-0.897) in the training cohort and 0.815 (95% CI, 0.661-0.968) in the test cohort. The nomogram showed a preferable fitting (all p > .05 by the Hosmer-Lemeshow test) and would offer more net benefits than simple default strategies within a wide range of threshold probabilities in both cohorts. CONCLUSION. The DECT-based nomogram has great application potential in terms of detecting HER2 status in GC, and can serve as a novel substitute for invasive testing.

TCGA-TCIA-Based CT Radiomics Study for Noninvasively Predicting Epstein-Barr Virus Status in Gastric Cancer.

OBJECTIVE. The purpose of this study was to investigate the value of TCGA-TCIA (The Cancer Genome Atlas and The Cancer Imaging Archive)-based CT radiomics for noninvasive prediction of Epstein-Barr virus (EBV) status in gastric cancer (GC). MATERIALS AND METHODS. A total of 133 patients with pathologically confirmed GC (94 in the training cohort and 39 in the validation cohort) who were identified from the TCGA-TCIA public data repository and two hospitals were retrospectively enrolled in the study. Two-dimensional and 3D radiomics features were extracted to construct corresponding radiomics signatures. Then, 2D and 3D nomograms were built by combining radiomics signatures and clinical information on the basis of multivariable analysis. Their performance and clinical practicability were determined, validated, and compared with respect to discrimination, calibration, reclassification, and time spent on tumor segmentation. RESULTS. Both 2D and 3D nomograms were robust and showed good calibration. The AUCs of the 2D and 3D nomograms showed no significant difference in the training cohort (0.919 vs 0.945, respectively; p = .41) or validation cohort (0.939 vs 0.955, respectively; p = .71). The net reclassification index showed that the 3D nomogram revealed no significant improvement in risk reclassification when compared with the 2D nomogram in the training cohort (net reclassification index, 0.68%; p = .14) and the validation cohort (net reclassification index, 6.06%; p = .08). Of note, the time spent on 3D segmentation (median, 907 seconds) was higher than that spent on 2D segmentation (median, 129 seconds). CONCLUSION. The 2D and 3D radiomics nomograms might have the potential to be used as effective tools for prediction of EBV in GC. When time spent on segmentation is considered, the 2D nomogram is more highly recommended for clinical application.

Semantic image segmentation of brain MRI with deep learning. / åŸºäºŽæ·±åº¦å­¦ä¹ çš„è„‘éƒ¨MRI解剖结构的语义分割.

OBJECTIVES: Previous studies on brain MRI image segmentation, such as threshold method, boundary detection method, and region method did not achieve good performance in complex scenes. Based on the deep learning segmentation technology, this study constructed a neural network model by using the algorithm of atrous convolution combined with conditional random field (CRF) to segment the thalamus, caudate nucleus, and lenticular nucleus in brain MRI, which laid a good foundation for MRI diagnosis of brain diseases. METHODS: A total of 1 200 MRI-Flair images of the brain were randomly selected, and 3 anatomical structures of thalamus, caudate nucleus, and lenticular nucleus were manually labeled, of which 1 000 were used as training data sets and 200 were used as test data sets. The neural network model was established by using deep convolutional neural networks (DCNN) combined with CRF algorithm. The training data set was input into the model, and the parameterized neural network model was obtained after iteration for 30 000 times. The test data set was used to evaluate, test, and output the predicted image. RESULTS: The model optimization results showed that the new brain MRI segmentation model DeepXAG had the highest accuracy. Therefore, DeepXAG was selected as the segmentation algorithm. The mean intersection over union (mIOU) of the DeepXAG model was 72.3%, which was significantly higher than other classical segmentation algorithms (CRF-RNN1, FCN-8s2, DPN3, RefineNet4, and PSPNet5). CONCLUSIONS: The DeepXAG algorithm has good accuracy and robustness in segmenting the anatomical structure of brain MRI images.

Different type and dosage of heparin were not associated with the progression of coronary artery calcification in haemodialysis patients.

AIM: Several studies have verified that unfractionated heparin (UFH) and low molecular heparin (LWMH) can induce bone loss, and bone mineral density has been inversely associated with vascular calcification in some clinical researches. But few have focused on the relationship between types and dosages of heparin and the progression of vascular calcification. We observed the progression of coronary artery calcification (CAC) in maintenance haemodialysis (MHD) patients who were treated with UFH and LMWH. METHODS: This was a prospective prevalent cohort study of MHD patients. Computed tomography was performed at enrolment and 2 years after enrolment, and CAC score was obtained. Demographic and clinical data, baseline and time-average laboratory indices were collected. Multiple linear regression and logistic regression were used to estimate the influencing factors of progression of CAC. RESULTS: In this study, (i) we initially enrolled 69 HD patients, and then 56 patients finished the follow-up. (ii) Among the total 56 patients, 27 patients (48.2%) were treated with UFH, 14 (25.0%) with LMWH and 15 (26.8%) with both. The median baseline CAC scores of three groups (UFH, LMWH and both users) were 91.0 (1.0, 1052.0), 134.0 (0, 1292.0) and 250.5 (27.0, 1139.0), respectively, with no significant difference (P = 0.663); the median CAC progression scores were 42.0 (0, 364.0), 172.0 (7.0, 653.0) and 118.5 (0, 434.0), respectively, with no significant difference (P = 0.660). (iii) Pearson and spearman correlation analysis shown that the progression of CAC was not associated with cumulative dosage of heparin used. (iv) After adjusted for diabetes mellitus, time-averaged intact parathyroid hormone, phosphate and alkaline phosphatase, logistic regression analysis showed using different types of heparin was not an independent risk factor for CAC progression; and multiple linear regression analysis showed that the type of heparin used was not associated with CAC progression. CONCLUSION: There were no significant differences in the effects of the types and dosages of heparin on CAC progression in patients on haemodialysis.

The effects of dialysis modalities on the progression of coronary artery calcification in dialysis patients.

BACKGROUND: Hemodialysis (HD) tend to have more hemodynamic changes than peritoneal dialysis (PD), which aggravates inflammation and oxidative stress. Whether HD and PD have different effects on the progression of vascular calcification? Therefore, we produced a study to explore the relationship of dialysis modalities and coronary artery calcification (CAC) progression. METHODS: This was a prospective cohort study. CT scans were performed at enrollment and 2 years later for each patient. Demographic and clinical data were collected. Tobit regression was used to compare delta CAC score between HD and PD patients. RESULTS: (1) 155 patients were enrolled, including 69 HD and 86 PD patients. (2) The baseline CAC scores were 97 (1, 744) in HD and 95 (0, 324) in PD; the follow-up CAC scores were 343 (6, 1379) in HD and 293 (18, 997) in PD. There were no significant differences in baseline, follow-up and delta CAC scores between 2 groups (P > 0.05). (3) In Tobit regression, after adjusted for variables, there was no significant difference of CAC progression in HD and PD groups (P > 0.05). (4) Logistic regression showed that older age, diabetes and higher time-averaged serum phosphate (P) were associated with faster progression of CAC (P < 0.05), but there was no evidence that HD was associated with faster CAC progression compared with PD (P = 0.879). CONCLUSIONS: There was no evidence that different dialysis modalities have different effect on CAC progression. Old age, DM and higher time-averaged P were associated with fast CAC progression.

Can virtual monochromatic images from dual-energy CT replace low-kVp images for abdominal contrast-enhanced CT in small- and medium-sized patients?

OBJECTIVE: To investigate the image quality and radiation dose of dual-energy computed tomography (DECT) with automatic spectral imaging protocol selection (ASIS) compared with those of low-kVp CT in abdominal multiphase CT. METHODS: Four groups of 60 patients each underwent abdominal scans with low-kVp CT (A, 80 kVp/300 mg I/kg, body mass index [BMI] ≤ 23.9 kg/m2; C, 100 kVp/400 mg I/kg, BMI ranging from 24 to 28.9 kg/m2) or DECT with ASIS, and the 40- to 60-keV virtual monochromatic images (VMIs) generated (B and D) were matched by age, gender, BMI, cross-sectional area, and contrast agent dose; 9 patients were excluded due to technical failures. The CT number, image noise, contrast-to-noise ratio, and subjective image quality were compared between the matched protocols (A and B or C and D) on 1.25-mm reconstructed images. RESULTS: VMIs at approximately 55 keV and 62 keV had CT numbers and contrast similar to those of 80-kVp and 100-kVp CT images, respectively. Compared to matched low-kVp images, VMIs at 50 keV provided a higher CT number and image noise and a similar or higher contrast and overall image quality. The radiation dose for DECT was higher than that of 80-kVp CT (increased by 10%), but was similar to that of 100-kVp CT. CONCLUSION: Compared to matched low-kVp CT, VMIs at 50 keV in DECT with ASIS provided similar or higher overall image quality, with no or minimal dose penalty in small- and medium-sized patients. KEY POINTS: • Virtual monochromatic images at approximately 55 keV and 62 keV have CT numbers and contrast similar to those of 80-kVp and 100-kVp CT images, respectively, with a given noise index. • The radiation dose in dual-energy CT with automatic spectral imaging protocol selection was slightly higher than that of 80-kVp CT (increased by 10%) but was similar to that of 100-kVp CT. • Dual-energy CT may be able to replace l00-kVp CT for routine clinical abdominal contrast-enhanced CT scans.

Study on the Prevalence of Vascular Calcification in Different Types of Arteries and Influencing Factors in Maintenance Peritoneal Dialysis Patients.

OBJECTIVE: To investigate the occurrence of vascular calcification (VC) in different types of arteries in patients with maintenance peritoneal dialysis (PD) patients and its influencing factors. METHODS: This study enrolled PD patients with stable status who has received PD treatment for more than 6 months in Peking University People's Hospital. We used plain X-ray films of abdomen, pelvis, and hands to quantitatively evaluate VC of large artery (abdominal aorta, iliac artery), medium artery (femoral artery, radial artery), and small artery (finger arteries). Two radiologists read and scored radiographs blindly. Demographic data, clinical characteristics, Charlson comorbidity index (CCI), baseline and time-average laboratory indices including parameters of calcium phosphorus metabolism, serum albumin, PD adequacy were collected. A logistic regression model was used to estimate the influencing factors of different sites of VC. RESULTS: (1) 154 PD patients were enrolled in this study: seventy-eight males, mean age was 60.4 ± 13.9 years, and median PD duration was 24 (16.39) months. The major primary disease was diabetic nephropathy (39%). (2) Among the 154 PD patients, the proportion of calcification of large artery was the highest (found in 100 patients, accounting for 64.9%); then the medium artery (66, 42.9%); and 15 of small artery, accounting for 9.7%. (3) Logistic regression showed that older age, longer dialysis duration, lower baseline serum intact parathyroid hormone (iPTH), and higher CCI scores were independent risk factors of large artery calcification (p < 0.05), and higher CCI scores, higher baseline serum triglycerides (TG), lower baseline serum iPTH, and time-average iPTH were independent risk factors of medium and small arteries. CONCLUSIONS: In PD patients, the occurrence of large artery calcification was higher than others. Among different sites of VC, the abdominal aortic calcification was most likely to occur, and the proportion of small artery calcification was low. Calcification of medium and small arteries can exist alone without calcification of large artery. Large artery calcification was more likely to occur in patients with older age, longer dialysis duration, lower baseline serum iPTH levels and higher CCI scores. Patients with higher CCI scores, higher baseline TG and lower baseline iPTH, and time-average iPTH were more likely to develop small and medium artery calcification.

Abdominal aortic calcification is superior to other arteries calcification in predicting the mortality in peritoneal dialysis patients - a 8 years cohort study.

BACKGROUND: In recent years, there has been a growing concern that abdominal aortic calcification (AAC) has a predictive effect on the prognosis of patients with end-stage renal disease (ESRD). However, whether other vascular calcification (VC) can predict the occurrence of adverse events in patients, and whether it is necessary to assess the calcification of other blood vessels remains controversial. This study aimed to assess VC in different sites using X-ray films, and to investigate the predictive effects of VC at different sites on all-cause mortality and cardiovascular (CV) mortality in peritoneal dialysis (PD) patients. METHODS: The data of Radiographs (lateral abdominal plain film, frontal pelvic radiograph and both hands radiograph) were collected to evaluate the calcification of abdominal aorta, iliac artery, femoral artery, radial artery, and finger arteries. Patients' demographic data, clinical characteristics, laboratory data were recorded. The total follow-up period was 8 years, and the time and cause of death were recorded. Survival curves were estimated using Kaplan-Meier analysis. COX regression analysis was used to examine independent predictors of all-cause mortality and CV mortality. RESULTS: One hundred fifty PD patients were included, a total of 79 patients (52.7%) died at the end of follow-up. After adjusting variables in the multivariate COX regression analysis, AAC was an independent predictor of all-cause mortality in PD patients (HR = 2.089, 95% CI: 1.089-4.042, P = 0.029), and was also an independent predictor of CV mortality (HR = 4.660, 95% CI: 1.852-11.725, P = 0.001). We also found that femoral artery calcification had a predictive effect on all-cause and CV mortality. But the calcification in iliac artery, radial artery, and finger arteries were not independent predictors of patients' all-cause and CV mortality in PD patients. CONCLUSION: AAC was more common in PD patients and was an independent predictor of all-cause mortality and CV mortality. The femoral artery calcification also can predict the mortality, but the calcification of iliac artery, radial artery, and finger arteries cannot predict the mortality of PD patients.

Serum Magnesium Abnormality and Influencing Factors of Serum Magnesium Level in Peritoneal Dialysis Patients: A Single-Center Study in Northern China.

BACKGROUND/AIMS: Both hypomagnesemia and hypermagnesemia have been associated with cardiovascular diseases, bone diseases, and mortality in dialysis patients. We aimed to investigate the prevalence of and influencing factors for abnormal serum Mg levels in patients on peritoneal dialysis (PD). METHODS: A cross-sectional study in Peking University People's Hospital recorded the demographic information, clinical characteristics, and laboratory data. Data were assessed and compared with the results from 2 other studies in China. RESULTS: Of 180 enrolled PD patients, the primary diseases were glomerulonephritis (38.3%) and diabetic nephropathy (38.3%). Mean serum Mg concentration was 1.02 ± 0.16 mmol/L; 67% had normal serum Mg concentrations, and 33% had hypermagnesemia. CONCLUSIONS: Hypermagnesemia is likely to occur in patients with higher serum phosphate, lower intact parathyroid hormone, and lower high-sensitivity C-reactive protein levels. Serum Mg level distributions in PD patients vary throughout China, may have different potential causes (such as geographical location and dietary habits) and should be further studied.

[Clinical efficacy of stereotactic radiation therapy combined with temozolomide on recurrent brain glioma].

OBJECTIVE: To investigate the clinical efficacy of stereotactic radiation therapy combined with temozolomide on recurrent glioma.
 Methods: A total of 36 patients with recurrent glioma were retrospectively analyzed and divided into a control group (n=12), who received stereotactic radiation therapy, and an experimental group (n=24), who received stereotactic radiation therapy plus temozolomide. The clinical efficacy and adverse reactions for the 2 groups were compared.
 Results: Total effective rate and local control rate for clinical treatment were 66.67% and 93.94%, respectively. Late adverse reaction was not observed. The effective rate and local control rate in the experimental group were 77.27% and 95.45%, which were slight higher than those in the control group, with no statistical significance (P>0.05). The 0.5-, 1-, 2-, 3-year follow-up total survival rates were 90.91%, 63.64%, 42.42%, and 15.15%, respectively. The 0.5-, 1-, 2-, 3-year follow-up survival rates in the experimental group were 95.45%, 72.72%, 54.54% and 22.73%, respectively, while those in the control group were 81.82%, 45.45%, 18.18%, and 0%, respectively. Survival analysis showed the survival time for the experimental group was significantly longer than that of the control group (30.00 months vs 14.00 months, P=0.010).
 Conclusion: Stereotactic radiation therapy combined with temozolomide for recurrent glioma is effective, and it has positive effect on improving the clinical efficacy and survival rate for the patients.

Development of Phenyl Cyclohexylcarboxamides as a Novel Class of Hsp90 C-terminal Inhibitors.

Inhibition of the heat shock protein 90 (Hsp90) C-terminus represents a promising therapeutic strategy for the treatment of cancer. Novobiocin, a coumarin antibiotic, was the first Hsp90 C-terminal inhibitor identified, however, it manifested poor anti-proliferative activity (SKBr3, IC50 ≈700 µm). Subsequent structure-activity relationship (SAR) studies on novobiocin led to development of several analogues that exhibited improved anti-proliferative activity against several cancer cell lines. Recent studies demonstrate that the biphenyl core could be used in lieu of the coumarin ring system, which resulted in more efficacious analogues. In continuation of previous efforts, the work described herein has identified the phenyl cyclohexyl core as a novel scaffold for Hsp90 C-terminal inhibition. Structure-activity relationship (SAR) studies on this scaffold led to the development of compounds that manifest mid-nanomolar activity against SKBr3 and MCF-7 breast cancer cell lines through Hsp90 inhibition.

Protein kinase C α enhances migration of breast cancer cells through FOXC2-mediated repression of p120-catenin.

BACKGROUND: Despite recent advances in the diagnosis and treatment of breast cancer, metastasis remains the main cause of death. Since migration of tumor cells is considered a prerequisite for tumor cell invasion and metastasis, a pressing goal in tumor biology has been to elucidate factors regulating their migratory activity. Protein kinase C alpha (PKCα) is a serine-threonine protein kinase implicated in cancer metastasis and associated with poor prognosis in breast cancer patients. In this study, we set out to define the signaling axis mediated by PKCα to promote breast cancer cell migration. METHODS: Oncomine™ overexpression analysis was used to probe for PRKCA (PKCα) and FOXC2 expression in mRNA datasets. The heat map of PRKCA, FOXC2, and CTNND1 were obtained from the UC Santa Cruz platform. Survival data were obtained by PROGgene and available at http://www.compbio.iupui.edu/proggene . Markers for EMT and adherens junction were assessed by Western blotting and quantitative polymerase chain reaction. Effects of PKCα and FOXC2 on migration and invasion were assessed in vitro by transwell migration and invasion assays respectively. Cellular localization of E-cadherin and p120-catenin was determined by immunofluorescent staining. Promoter activity of p120-catenin was determined by dual luciferase assay using a previously validated p120-catenin reporter construct. Interaction between FOXC2 and p120-catenin promoter was verified by chromatin immunoprecipitation assay. RESULTS: We determined that PKCα expression is necessary to maintain the migratory and invasive phenotype of both endocrine resistant and triple negative breast cancer cell lines. FOXC2 acts as a transcriptional repressor downstream of PKCα, and represses p120-catenin expression. Consequently, loss of p120-catenin leads to destabilization of E-cadherin at the adherens junction. Inhibition of either PKCα or FOXC2 is sufficient to rescue p120-catenin expression and trigger relocalization of p120-catenin and E-cadherin to the cell membrane, resulting in reduced tumor cell migration and invasion. CONCLUSIONS: Taken together, these results suggest that breast cancer metastasis may partially be controlled through PKCα/FOXC2-dependent repression of p120-catenin and highlight the potential for PKCα signal transduction networks to be targeted for the treatment of endocrine resistant and triple negative breast cancer.