Influencing factors of clinical efficacy of roxadustat among hemodialysis patients.

OBJECTIVE: To explore independent influencing factors for clinical efficacy of roxadustat in hemodialysis patients. METHODS: Hemodialysis patients treated with roxadustat were enrolled. The plasma trough concentrations of roxadustat were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A multiple logistic regression model was established to determine the factors that affect clinical efficacy of roxadustat in patients undergoing hemodialysis. RESULTS: A total of 67 hemodialysis patients were enrolled in the study. The results showed that age, blood trough concentration of roxadustat, and baseline hemoglobin (Hb) level were independent factors of clinical efficacy of roxadustat (OR = 1.06, p = .025 for age; OR = 1.001, p = .037 for plasma concentration; and OR = 0.941, p = .003 for baseline Hb), with an AUC score of 0.859. CONCLUSIONS: Age, blood trough concentration of roxadustat, and baseline Hb level were independent influencing factors of the response to roxadustat in hemodialysis patients.

RNA splicing analysis contributes to reclassifying variants of uncertain significance and improves the diagnosis of monogenic disorders.

BACKGROUND: Numerous variants of uncertain significance (VUSs) have been identified by whole exome sequencing in clinical practice. However, VUSs are not currently considered medically actionable. OBJECTIVE: To assess the splicing patterns of 49 VUSs in 48 families identified clinically to improve genetic counselling and family planning. METHODS: Forty-nine participants with 49 VUSs were recruited from the Reproductive and Genetic Hospital of CITIC-Xiangya. Bioinformatic analysis was performed to preliminarily predict the splicing effects of these VUSs. RT-PCR and minigene analysis were used to assess the splicing patterns of the VUSs. According to the results obtained, couples opted for different methods of reproductive interventions to conceive a child, including prenatal diagnosis and preimplantation genetic testing (PGT). RESULTS: Eleven variants were found to alter pre-mRNA splicing and one variant caused nonsense-mediated mRNA decay, which resulted in the reclassification of these VUSs as likely pathogenic. One couple chose to undergo in vitro fertilisation with PGT treatment; a healthy embryo was transferred and the pregnancy is ongoing. Three couples opted for natural pregnancy with prenatal diagnosis. One couple terminated the pregnancy because the fetus was affected by short-rib thoracic dysplasia and harboured the related variant. The infants of the other two couples were born and were healthy at their last recorded follow-up. CONCLUSION: RNA splicing analysis is an important method to assess the impact of sequence variants on splicing in clinical practice and can contribute to the reclassification of a significant proportion of VUSs. RNA splicing analysis should be considered for genetic disease diagnostics.

A DMD case caused by X chromosome rearrangement.

Duchenne/Becker muscular dystrophy (DMD/BMD) is one of the most common progressive muscular dystrophy diseases with X-linked recessive inheritance. It is mainly caused by the deletion, duplication and point mutation of DMD gene. In rare cases, it is also caused by the destruction of DMD gene by chromosomal structural rearrangement. Here, we report a case of Duchenne/Becker Muscular dystrophy (DMD/BMD) with typical symptoms but unknown genetic defects after MLPA and next generation sequencing tests in other hospitals. Interestingly, we find a pericentric inversion of X chromosome (Chr.X: g. [31939463-31939465del; 31939466-131765063 inv; 131765064-131765067del]) in this patient. We then use the karyotyping, FISH, long-read sequencing and Sanger sequencing technologies to characterize the chromosome rearrangement. We find that this chromosomal aberration disrupt both the DMD gene and the HS6ST2 gene. The patient present with typical DMD symptoms such as muscle weakness, but no obvious symptoms of Paganini-Miozzo syndrome. Our results suggest that the destruction of DMD gene by structural rearrangement is also one of the important causes of DMD. Therefore, we suggest to provide further genetic testing for those DMD patients with unknown genetic defects through routine genetic testing. Cost-effective karyotyping and FISH should be considered firstly to identify chromosome rearrangements. Long-read sequencing followed by Sanger sequencing could be useful to locate the precise breakpoints. The genetic diagnosis of this case made it possible for reproductive intervention in the patient's family.

The de novo aberration rate of prenatal karyotype was comparable between 1496 fetuses conceived via IVF/ICSI and 1396 fetuses from natural conception.

PURPOSE: To evaluate the cytogenetic risk of assisted reproductive technology (ART) by comparing the incidence of de novo chromosomal abnormalities between fetuses conceived via in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and natural conception. MATERIALS AND METHODS: Prenatal invasive diagnostic testing (amniocentesis and cytogenetic analysis) was performed on 1496 fetuses conceived via IVF/ICSI (IVF/ICSI group) and 1396 fetuses from natural conception (NC group). The incidence of de novo chromosomal abnormalities (including aneuploidy and chromosomal structure abnormalities) was used to evaluate the cytogenetic risk of ART. For statistical analysis, χ2-test was used for binary dependent variable. The significance level was P < 0.05 and confidence interval was 95%. RESULT(S): The IVF/ICSI group displayed a modest increase in the overall de novo chromosomal abnormality rate compared with that in the NC group but with no statistical significance (6.75% vs. 6.16%; χ2 = 0.42, P > 0.05). The incidence of abnormal karyotypes was also not significantly different between the IVF/ICSI and NC groups in different maternal ages, including ≥ 35 years group (7.55% vs. 9.60%, χ2 = 1.40, P > 0.05) and < 35 years group (6.20% vs. 4.54%, χ2 = 2.51, P > 0.05). Moreover, there was no difference in the proportion of aneuploid and structural abnormalities in detected karyotypes between the IVF/ICSI and NC groups. Logistic regression analysis showed no significant association between the method of pregnancy and de novo chromosomal abnormalities (odds ratio (OR) 1.03; 95% CI 0.71-1.50; P = 0.86) after adjusting for other confounding factors. CONCLUSION(S): Fetuses conceived via IVF/ICSI had a slight but not statistically significant increase in de novo abnormal karyotypes compared to those in naturally conceived fetuses. Our findings indicate no significant association between de novo fetal chromosomal abnormalities and the pregnancy method in high-risk pregnancies in the second trimester. For these pregnancies with a high risk but with a normal karyotype, further genetic testing is required for diagnosis.

C-X-C Motif Chemokine Ligand 16 Is a Potent Predictor of Outcomes in Dialysis Patients.

INTRODUCTION: C-X-C motif chemokine ligand 16 (CXCL16) is an inflammatory marker that has been found to be predictive of outcomes in patients with cardiovascular disease. Our previous work has also demonstrated its relation to cardiac injury in dialysis patients. However, it is yet unclear whether there is an association between CXCL16 and adverse outcomes in dialysis patients. We aimed to evaluate its prognostic value along with several traditional inflammatory markers in the current study. METHODS: This is a multicenter longitudinal study of prevalent dialysis patients. Circulating inflammatory markers including CXCL16, C-reactive protein (CRP), tumor necrosis factor-α, and interleukin-6 (IL-6) were measured using a multiplex assay. The primary outcomes were all-cause mortality and a composite of major adverse cardiovascular events (MACEs). The associations between biomarkers and outcomes were analyzed using Cox proportional hazards regression models. RESULTS: Of the 366 participants with available plasma samples, the average age was 52.5 (±12.1) years, and there were 160 (43.7%) female participants. For all-cause mortality, logarithmically transformed CXCL16, IL-6, and CRP were independent predictors after adjustment for covariates. When the 3 markers were included in the same model, CXCL16 was the only one remaining its significance. For MACEs, logarithmically transformed CXCL16 and IL-6 were significant predictors when analyzed separately and CXCL16 was an independent predictor even after adjustment for IL-6. When the biomarkers were analyzed as categorical variables, only CXCL16 was associated with both outcomes. Adding CXCL16 to established risk factors improved risk prediction as revealed by Net Reclassification Index (NRI). CONCLUSION: Using a multimarker approach, we determined that CXCL16 is a potent predictor of all-cause mortality and cardiovascular events in dialysis patients. Our data suggest CXCL16 may improve risk stratification and could be a potential interventional target.

Reproductive risks and preimplantation genetic testing intervention for X-autosome translocation carriers.

RESEARCH QUESTION: What is the genetic cause of multiple congenital disabilities in a girl with a maternal balanced X-autosome translocation [t(X-A)]? Is preimplantation genetic testing (PGT), to distinguish non-carrier from euploid/balanced embryos and prioritize transfer, an effective and applicable strategy for couples with t(X-A)? DESIGN: Karyotype analysis, whole-exome sequencing and X inactivation analysis were performed for a girl with congenital cardiac anomalies, language impairment and mild neurodevelopmental delay. PGT based on next-generation sequencing after microdissecting junction region (MicroSeq) to distinguish non-carrier and carrier embryos was used in three couples with a female t(X-A) carrier (cases 1-3). RESULTS: The girl carried a maternal balanced translocation 46,X,t(X;1)(q28;p31.1). Whole-exome sequencing revealed no monogenic mutation related to her phenotype, but she carried a rare skewed inactivation of the translocated X chromosome that spread to the adjacent interstitial 1p segment, contrary to her mother. All translocation breakpoints in cases 1-3 were successfully identified and each couple underwent one PGT cycle. Thirty oocytes were retrieved, and 13 blastocysts were eligible for biopsy, of which six embryos had a balanced translocation and only four were non-carriers. Three cryopreserved embryo transfers with non-carrier status embryos resulted in the birth of two healthy children (one girl and one boy), who were subsequently confirmed to have normal karyotypes. CONCLUSIONS: This study reported a girl with multiple congenital disabilities associated with a maternal balanced t(X-A) and verified that the distinction between non-carrier and carrier embryos is an effective and applicable strategy to avoid transferring genetic and reproductive risks to the offspring of t(X-A) carriers.

[Analysis and prenatal diagnosis of FMR1 gene mutations among patients with unexplained mental retardation].

OBJECTIVE: To analyze the (CGG)n repeats of FMR1 gene among patients with unexplained mental retardation. METHODS: For 201 patients with unexplained mental retardation, the (CGG)n repeats of the FMR1 gene were analyzed by PCR and FragilEaseTM PCR. Prenatal diagnosis was provided to carriers of pre- and full-mutations. The pattern of X chromosome inactivation (XCI) was determined for women with mental retardation and full mutations. RESULTS: For the 201 patients with unexplained mental retardation, 15 were identified with full mutations of the FMR1 gene. The prevalence of fragile X syndrome (FXS) in patients with unexplained mental retardation was determined as 7.5% (15/201). Prenatal diagnosis was provided for 6 pregnant women with pre- or full mutations. Analysis revealed that women with mental retardation and full FMR1 mutations exhibited a skewed XCI pattern with primary expression of the X chromosome carrying the mutant allele. CONCLUSION: FXS has a high incidence among patients with unexplained mental retardation. Analysis of FMR1 gene (CGG)n repeats in patients with unexplained mental retardation can facilitate genetic counseling and prenatal diagnosis for their families. FMR1 gene (CGG)n repeats screening should be recommended for patients with unexplained mental retardation.

Novel mutations of PKD genes in Chinese patients suffering from autosomal dominant polycystic kidney disease and seeking assisted reproduction.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD), the commonest inherited kidney disease, is generally caused by heterozygous mutations in PKD1, PKD2, or GANAB (PKD3). METHODS: We performed mutational analyses of PKD genes to identify causative mutations. A set of 90 unrelated families with ADPKD were subjected to mutational analyses of PKD genes. Genes were analysed using long-range PCR (LR-PCR), direct PCR sequencing, followed by multiplex ligation-dependent probe amplification (MLPA) or screening of GANAB for some patients. Semen quality was assessed for 46 male patients, and the correlation between mutations and male infertility was analysed. RESULTS: A total of 76 mutations, including 38 novel mutations, were identified in 77 families, comprising 72 mutations in PKD1 and 4 in PKD2, with a positive detection rate of 85.6%. No pathogenic mutations of GANAB were detected. Thirty-seven patients had low semen quality and were likely to be infertile. No association was detected between PKD1 mutation type and semen quality. However, male patients carrying a pathogenic mutation in the Ig-like repeat domain of PKD1 had a high risk of infertility. CONCLUSION: Our study identified a group of novel mutations in PKD genes, which enrich the PKD mutation spectrum and might help clinicians to make precise diagnoses, thereby allowing better family planning and genetic counselling. Men with ADPKD accompanied by infertility should consider intracytoplasmic sperm injection combined with preimplantation genetic diagnosis to achieve paternity and obtain healthy progeny.

Night-time blood pressure and pulse wave velocity in dialysis patients.

BACKGROUND: Ambulatory blood pressure (ABP) monitoring and carotid-femoral pulse wave velocity (cfPWV) provide important cardiovascular risk information for dialysis patients. This study aims to evaluate the risk factors of cfPWV and the associations between ambulatory blood pressure, especially night-time blood pressure and cfPWV. METHODS: We conducted a cross-sectional study in patients on maintenance hemodialysis. ABP and cfPWV were measured on a midweek interdialytic day. Associations were determined using Pearson's correlation analysis and multiple stepwise regression model. RESULTS: Systolic BPs and pulse pressures, but not diastolic BPs, were significantly and positively associated with cfPWV. In a stepwise regression model, age, diabetes mellitus and all-period systolic BP were independently associated with cfPWV. When day-time and night-time BPs were included in the analysis, respectively, only night-time systolic BP and age remained as independently associated with cfPWV. CONCLUSION: Ambulatory BPs are potent associates of cfPWV and night-time systolic BP, rather than day-time BPs, is an independently predictor of cfPWV. Our results support the view that controlling of nocturnal hypertension provides a unique cardiovascular protection effect.

[Discussion on the standard of clinical genetic testing report and the consensus of gene testing industry].

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

Interaction of Soluble CXC Ligand 16 and Cardiac Injury Markers in Hemodialysis Patients.

BACKGROUND: Recent data suggest that there is a pathogenic role for CXC ligand 16 (CXCL16) in cardiovascular diseases. Little is known about circulating CXCL16 in patients with kidney dysfunction. We explored the relationships of plasma CXCL16 with cardiac injury markers in a group of dialysis patients. METHODS: Plasma CXCL16 and C-reactive protein (CRP) were measured in 366 patients who were on maintenance hemodialysis. Cardiac injury was evaluated via measurements of the circulating B-type natriuretic peptide (BNP), N-terminal prohormone of brain natriuretic peptide (NT proBNP), Troponin I (TnI), and Troponin T (TnT). Sixty healthy subjects who were frequency matched with the patients on the basis of age and gender were recruited as healthy controls. RESULTS: The mean age of the patients was 52.5 ± 12.1 years and 56.3% were male. Circulating CXCL16 was significantly higher in the patients than in the controls (patients vs. CONTROLS: 477.3 (367.0-647.1) pg/mL vs. 229.5 (203.8-254.5) pg/mL; p < 0.001). The log-transformed (log-) CXCL16 level was correlated with all 4 cardiac markers (log-BNP, log-NTproBNP, log-TnI, and log-TnT) with high levels of significance (all p < 0.001), even after extensive controls for the covariates. In contrast, CRP was correlated only with BNP (marginally) and NT proBNP and was not correlated with troponins. CONCLUSION: We showed, for the first time, highly significant relationships of circulating CXCL16 level with cardiac injury markers in dialysis patients. Our data suggest that circulating CXCL16 is possibly involved in the pathological process of cardiovascular damage in dialysis patients and may serve as a therapeutic target for cardiac protection in these patients.

[Karyotyping and analysis of 5α -reductase-2 gene mutation in 25 patients with hypospadias].

OBJECTIVE: To analyze the karyotypes and SRD5A2 gene mutations in 25 patients with sporadic or familial hypospadias. METHODS: The patients included 10 adults and 15 children, whose chromosomes were analyzed by G-banded karyotyping, and the SRD5A2 genes were sequenced. RESULTS: Two patients were found to have an abnormal karyotype, while eight have carried compound heterozygous mutations of the SRD5A2 gene, which included 5 genotypes formed by 6 types of mutations, i.e., p.G203S/p.R227Q, p.R227Q/p.R246Q, p.Q6X/p.Q71X, p.L20P/p.G203S, and p.Q71X/p.R227Q. Mutations of the SRD5A2 gene were present in 32% (8/25) of all patients, 35% (8/23) in those with a normal karyotype, and 44.4% (8/18) in those with proximal type hypospadia. Bioinformatic analysis, literature review and pedigree analysis confirmed that all such mutations are pathogenic. CONCLUSION: Chromosomal anomalies and mutations of the SRD5A2 gene are the main cause of hypospadias. Sequencing of the SRD5A2 gene may explain the etiology of nearly half of the patients with proximal type of hypospadas but a normal karyotype, which can facilitate genetic consulting.

[Paramyotonia congenita caused by a novel mutation of SCN4A gene in a Chinese family].

OBJECTIVE: To detect SCN4A gene mutation in a pedigree with paramyotonia congenita in order to facilitate genetic counseling and assisted reproduction. METHODS: Clinical data of the family was collected. DNA was extracted from peripheral blood samples. Potential mutation of the SCN4A gene was screened using PCR-Sanger sequencing. Potential mutation was detected in 3 affected relatives, 4 unaffected relatives and 100 unrelated healthy controls. Bioinformatics software was used to predict the effect of mutation on the protein function and conservation of the sequence at the mutation site across various species. RESULTS: A novel missense mutation c.4427T>C (p.Met1476Thr) was detected in the exon 24 of the SCN4A gene in the proband and other 3 affected relatives, but not in 4 unaffected relatives and 100 unrelated controls. Bioinformatic analysis indicated that the codon is highly conserved across various species, and that the mutation has caused damage to the structure and function of SCN4A protein. CONCLUSION: The c.4427 T>C (p.Met1476Thr) mutation of the SCN4A gene may contribute to the paramyotonia congenita. Detection of SCN4A gene mutation is an effective method for the diagnosis of paramyotonic congenita.

[Gene mutation analysis and prenatal diagnosis of a family with Bartter syndrome].

OBJECTIVE: To investigate the mutation of related genes and prenatal diagnosis of a family with Bartter syndrome (BS). METHODS: The high-throughput capture sequencing technique and PCR-Sanger sequencing were used to detect pathogenic genes in the proband of this family and analyze the whole family at the genomic level. After the genetic cause was clarified, the amniotic fluid was collected from the proband's mother who was pregnant for 5 months for prenatal diagnosis. RESULTS: The proband carried compound heterozygous mutations of c.88C>T(p.Arg30*) and c.968+2T>A in the CLCNKB gene; c.88C>T(p.Arg30*) had been reported as a pathogenic mutation, and c.968+2T>A was a new mutation. Pedigree analysis showed that the two mutations were inherited from the mother and father, respectively. Prenatal diagnosis showed that the fetus did not inherit the mutations from parents and had no mutations at the two loci. The follow-up visit confirmed that the infant was in a healthy state, which proved the accuracy of genetic diagnosis and prenatal diagnosis. CONCLUSIONS: The compound heterozygous mutations c.88C>T(p.Arg30*) and c.968+2T>A in the CLCNKB gene are the cause of BS in the proband, and prenatal diagnosis can prevent the risk of recurrence of BS in this family.

Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice.

BACKGROUND: Uncoupling protein 2 (UCP2) is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. METHODS: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC), and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip) or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. RESULTS: TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls). ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. CONCLUSIONS: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

Autophagy inhibition induces podocyte apoptosis by activating the pro-apoptotic pathway of endoplasmic reticulum stress.

Podocyte apoptosis is a major factor inducing podocyte depletion that predicts the progressive course of glomerulosclerosis. However, the molecular mechanisms underlying podocyte apoptosis are still not well understood. Autophagy is a lysosomal degradation system involving the degradation and recycling of obsolete, damaged, or harmful cytoplasmic materials and organelles. Recent advances in the understanding of the molecular processes contributing to autophagy have provided insight into the relationship between autophagy and apoptosis. However, their cross-talk remains largely obscure until now. Here, we found that podocytes both in vivo and in vitro always exhibited high basal levels of autophagy, whereas autophagy inhibition could induce podocyte apoptosis, suggesting the pro-survival role of autophagy in podocytes. Besides, we found that autophagy inhibition by 3-methyladenine (3-MA) could induce the activation of endoplasmic reticulum stress even without any external stimulations, whereas knockdown of CHOP could effectively improve podocyte apoptosis and down-regulated expression of slit-diaphragm proteins induced by autophagy inhibition. Collectively, this study demonstrated that autophagy might act as a crucial regulatory mechanism of apoptotic cell death by modulating the balance between the pro-survival pathway and the pro-apoptotic pathway of endoplasmic reticulum stress, which might provide a novel mechanistic insight into the interface between autophagy and apoptosis in the progression of podocyte injury.

Ets-1 targeted by microrna-221 regulates angiotensin II-induced renal fibroblast activation and fibrosis.

BACKGROUND: Fibroblast activation is one of the most important mechanisms for Angiotensin II (Ang II) in promoting renal fibrosis. Transcription factor Ets-1 is recognized to play a key role in kidney diseases. However, the role and mechanisms of Ets-1 in Ang-II induced fibroblast activation and kidney fibrosis are not fully understood. METHODS: Mice were treated with Ang II via osmotic mini-pumps or Ang II expression plasmid (pAng II). Cultured normal rat kidney interstitial fibroblast (NRK-49F) cells were incubated with Ang II. Role of Ets-1 in renal fibrosis and fibroblast activation were assessed by Western blot, Immunohistochemical staining'MTT, Boyden chamber and Immunofluorescence staining. Effects of miR-221 on Ets-1 and fibroblast activation were investigated by MTT, Boyden chamber, Western blot and Q-PCR. RESULTS: We found that Ets-1 was up-regulated in fibrotic kidneys. Similarly, Ang II could activate NRK-49F cells as demonstrated by up-regulated α-SMA and fibronectin(FN) expression and enhanced cell proliferation and migration. Ang II also induced Ets-1 expression in NRK-49F cells in a dose and time dependent manner. Knock-down of Ets-1 by RNA interference attenuated Ang II-induced activation of NRK-49F cells. Ets-1 was previously reported as a target of microRNA-221 (miR-221). In Ang II-induced fibrotic kidney, miR-221 was down-regulated. Similar results were observed in Ang II treated NRK-49F cells. Ectopic expression of miR-221 mimic attenuated the up-regulation of Ets-1 by Ang II in NRK-49F cells, which further prevented the activation of NRK-49F cells. However, the inhibitor of miR-221 aggravated Ang II induced Ets-1 expression and NRK-49F cells activation. CONCLUSIONS: Our study suggests that miR-221/Ets-1 axis takes an important role in mediating AngII induced interstitial fibroblast activation and renal fibrosis.

Dietary inflammatory index is associated with Vitamin D in CKD patients.

OBJECTIVES: Multiple observational studies have shown that low serum level of 25-hydroxyvitamin D (25(OH)D) in patients with chronic kidney disease (CKD) have been associated with a faster progression of kidney disease and a higher risk of all-cause mortality. We aim to assess the association between dietary inflammatory index (DII) with Vitamin D in adults with CKD. METHOD: The National Health and Nutrition Examination Survey appropriated participants from 2009 to 2018 were enrolled. The patients who were under the age of 18, pregnant, and having incomplete data were excluded. DII score were calculated based on a single 24-h dietary recall interview for each participant. Mutivariable regression analysis and subgroup analysis were utilized to determine the independent associations between vitamin D with DII in CKD patients. RESULTS: In total, 4283 individuals were finally included. The results showed a negative association between DII scores and 25(OH)D with statistical significance (ß = - 1.83, 95% CI - 2.31, - 1.34, P < 0.001). In subgroup analysis stratified by gender, low eGFR, age and diabetes, the negative association between DII scores and 25(OH)D was still significant (all P for trend < 0.05). The results from interacion test indicated that the magnitude of the association was the same for the population with and without low eGFR (P for interacion = 0.464). CONCLUSION: Higher consumption of pro-inflammatory diet correlates negatively with the 25(OH)D level in CKD patients with and without low eGFR. Anti-inflammatory diet management may reduce the reduction of vitamin D in CKD patients.

The relationship between dietary inflammatory index and bone mineral density in CKD patients.

INTRODUCTION: Chronic systemic inflammation was proposed as a critical factor in the development of osteoporosis. We aim to investigate the effect of the DII on bone mineral density (BMD) in CKD patients. METHODS: 2276 participants from NHANES were enrolled. The DII score was calculated based on a single 24-h dietary recall. Total BMD was measured using Dual-energy x-ray absorptiometry. A multiple-stepwise linear regression model was used to determine associations between BMD and DII in CKD patients. RESULTS: When DII >0.35, a negative correlation was obtained between DII and BMD (all ß = -0.008 and p < 0.05). In subgroup analysis, BMD levels decreased across increasing tertiles of the DII for patients with non-osteoporosis, postmenopause, and low eGFR (p for trend ≤0.01). CONCLUSION: Higher consumption of pro-inflammatory diet correlates negatively with the BMD levels in CKD patients.

Treatment of multiple ceramic alloys before recasting.

STATEMENT OF PROBLEM: Dental laboratories often reuse dental casting alloys by recasting them, but the processing methods before recasting require further research. PURPOSE: The purpose of the study was to determine the treatment methods to remove the surface contamination of the previously melted alloys before recasting. MATERIAL AND METHODS: Cobalt-chromium (Co-Cr), commercially pure titanium (CP Ti), palladium-copper-gallium (Pd-Cu-Ga), and gold-platinum (Au-Pt) ceramic alloys were investigated in the present study. Field emission scanning electron microscopy, energy-dispersive x-ray spectroscopy (EDAX), and x-ray photoelectron spectroscopy (XPS) were used to evaluate the changes in the surface structures and compositions of Co-Cr, CP Ti, Pd-Cu-Ga, and Au-Pt ceramic alloys after airborne-particle abrasion and immersion in various chemical solutions for different time periods. The data obtained by EDAX and XPS were statistically analyzed by Kruskal-Wallis and Nemenyi tests (α=.05). RESULTS: By using appropriate mechanical and chemical treatment procedures, the contamination content of previously cast ceramic alloys was found to be below the detection limits of EDAX and XPS. The statistical results showed that, compared to the control group (new alloys after polishing), the impurity element was not detected after being treated with these methods, which was not statistically different to control group. CONCLUSIONS: The surface contamination of ceramic alloys was effectively removed by using certain mechanical and/or chemical treatment methods. Within the limitations of the present study, the most appropriate ways to treat ceramic alloys before recasting were as follows: (1) for Co-Cr ceramic alloys: Al2O3 airborne-particle abrasion and immersion in aqua regia for 15 min; (2) for CP Ti ceramic alloys: Al2O3 airborne-particle abrasion and immersion in 65% HNO3 and 40% HF 1:7 (V/V) for 60 min; (3) for Pd-Cu-Ga ceramic alloys: glass bead airborne-particle abrasion and immersion in 40% HF solution for 30 min; and (4) for Au-Pt ceramic alloys: glass bead airborne-particle abrasion.