Supplementary Material for: Wang's Forceps-Assisted Catheter Reposition and Fixation: An Easy and Reliable Rescue Method

<p>Catheter migration and omental wrap are the most common causes of catheter malfunction, which usually result in catheter removal or replacement. The conventional open surgery for catheter reposition has many disadvantages. A new tunnel is needed throughout the procedure of catheter replacement causing more pain and frustration to the patients. Another drawback is that the incidence of catheter migration after conventional catheter reposition surgery is still as high as it was before the procedure. Wang's forceps, an instrument commonly used in our peritoneal dialysis center, is easy and effective in catheter insertion and fixation. Recently, we have successfully used the Wang's forceps to resolve the catheter displacement for 10 patients, including 1 patient who suffered from catheter tip migration 3 times and had undergone conventional catheter rescue by both open surgery and laparoscopy. This new technique was easy and reliable, and the original tunnel was maintained, which reduced pain and risk of infection in the patients. These advantages may grant the Wang's forceps technique favorable over the conventional surgical approach.</p

Erratum: Ischemic Preconditioning Attenuates Renal Ischemia-Reperfusion Injury by Inhibiting Activation of IKKβ and Inflammatory Response

<i>Background:</i> Renal ischemia-reperfusion (I/R) injury is a major cause of acute renal failure (ARF). The transcription factor nuclear factor-κB (NF-κB) has been implicated as a key mediator of reperfusion injury. Activation of NF-κB is dependent upon the phosphorylation of its inhibitor, IκB, by the specific inhibitory κB kinase (IKK) subunit, IKKβ. We hypothesized that ischemic preconditioning (IPC) reduces acute renal damage following I/R injury by inhibiting activation of IKKβ. As neutrophil gelatinase-associated lipocalin (NGAL), an early predictive biomarker of acute kidney injury, is regulated by NF-κB, we approached the relationship between NGAL and IKKβ. <i>Method:</i> Thirty male Sprague-Dawley rats were randomly divided into 3 groups after right kidney nephrectomy. Group A rats were sham-operated controls. Group B rats were 45-min ischemic in the left renal artery while Group C rats were pre-treated with 3 cycles of 2-min ischemia and 5-min reperfusion. All the rats were sacrificed at 24 h after reperfusion. We harvested kidneys and serum to do further analysis, including histological and functional parameters, expressions of NGAL and IKKβ in renal tissues. <i>Results:</i> Compared with rats subjected to I/R injury, pre-treated rats had a significant decrease in serum creatinine level (Scr) and tubulointerstitial injury scores (Scr, 86.79 ± 12.98 vs. 205.89 ± 19.16 μmol/l, p < 0.01; tubulointerstitial injury scores, 1.3 ± 0.48 vs. 3.8 ± 0.79, p < 0.01). In addition, expressions of IKKβ (0.95 ± 0.21 vs. 1.74 ± 0.17, p < 0.05) and NGAL (1.71 ± 0.032 vs. 2.66 ± 0.078, p < 0.05) at renal tubule in pre-treated rats were attenuated significantly compared with rats subjected to ischemia-reperfusion injury. Moreover, our study showed that IKKβ and NGAL were in positive correlation (R = 0.965 > R_0.01(30) = 0.448, p < 0.01). <i>Conclusions:</i> The evidence suggests that IKKβ may play a role in renal I/R injury and give rise to the generation of NGAL. It appears that IPC may attenuate renal injury and the expression of NGAL following acute I/R injury. IKKβ may offer a clinically accessible target for preventing renal injury following I/R

Supplementary Material for: Metabonomic Profiling Reveals Difference in Altered Metabolic Pathways Between Chronic Kidney Disease and High-Fat-Induced Insulin Resistance in Rats

<b><i>Background/Aims:</i></b> Chronic kidney disease (CKD) is closely correlated with the development of insulin resistance (IR). Until now, the underlying molecular mechanisms remain to be elucidated. This study aimed to identify metabolites and molecular pathways unique to CKD-induced IR. <b><i>Methods:</i></b> Ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS) analysis coupled with orthogonal partial least square discriminant analysis (OPLS-DA) were performed to profile metabolites in the serum, liver, and muscle tissues and to analyze molecular pathways in relation to CKD- and high fat diet (HFD)-induced IR in the rats. <b><i>Results:</i></b> At 18 weeks after the 5/6 Nx operation, CKD induction was demonstrated by renal histology and biochemical tests. Furthermore, both CKD-induced IR and HFD-induced IR rats showed significantly greater levels of fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR). In the UPLC-MS in combination with OPLS-DA analysis, we identified 101, 59, and 41 differential metabolites in the serum, liver, and muscle, which were associated with the CKD-induced IR, while 58, 38, and 17 differential metabolites in the serum, liver, and muscle were revealed in the HFD-induced rats compared to controls. Moreover, compared to HFD-induced IR rats, those with CKD-induced IR exhibited abnormal pathways primarily in the tryptophan metabolism, arginine metabolism, and trimethylamine oxide metabolite. Interestingly, altered metabolites in the CKD-induced IR and HFD-induced IR displayed an opposite direction. <b><i>Conclusion:</i></b> Alterations in metabolites and relevant pathways were significantly different between the CKD- and HFD-induced IR rats. These findings may offer important information regarding the pathogenesis specific to IR caused by the decline in the renal function

Supplementary Material for: Ara h 2 and Ara h 6 Have Similar Allergenic Activity and Are Substantially Redundant

<b><i>Background:</i></b> The moderately homologous (approx. 60%) proteins Ara h 2 and Ara h 6 are the most potent peanut allergens. This study was designed to define the relative individual contributions of Ara h 2 and Ara h 6 to the overall allergenic activity of a crude peanut extract (CPE). <b><i>Methods:</i></b> Ara h 2 and Ara h 6 were removed from CPE by gel filtration chromatography. Ara h 2.01, Ara h 2.02 and Ara h 6 were further purified (>99%). The potency of each allergen and the ability of these allergens to reconstitute the allergenic activity of CPE depleted of Ara h 2 and Ara h 6 was measured with RBL SX-38 cells sensitized with IgE from sensitized peanut allergic patients. <b><i>Results:</i></b> The potency of the native proteins were significantly different (p < 0.0001) although not dramatically so, with a rank order of Ara h 2.01 > Ara h 2.02 > Ara h 6. The addition of either purified Ara h 2 or Ara h 6 independently at their original concentration to CPE depleted of both Ara h 2 and Ara h 6 restored 80–100% of the original CPE allergenic activity. Addition of both Ara h 2 and Ara h 6 consistently completely restored the allergenic activity of CPE. <b><i>Conclusions:</i></b> These studies indicate that either Ara h 2 or Ara h 6 independently can account for most of the allergenic activity in a CPE and demonstrate important redundancy in the allergenic activity of these related molecules

Supplementary Material for: Meta-Analysis of Human Leukocyte Antigen-G 3′UTR Polymorphisms Confer Susceptibility to Recurrent Miscarriage

Objectives: The current systematic review and meta-analysis have shown that specific HLA-G 3′ UTR variants are associated with recurrent miscarriage (RM). Our aim was to investigate the relevance of HLA-G 3′ UTR polymorphisms with the risk of RM. Design: A combined meta-analysis was implemented in this study. Participants/Materials, Setting, Methods: Common electronic databases including PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Cochrane Library, and Google Scholar were used to seek eligible articles up to August 2021. Results: Forty-four eligible articles with 4,467 cases and 3,955 controls were finally enrolled. Our meta-results suggested that 14 bp insertion allele was associated with elevated risk of RM (allelic model: OR = 1.18, 95% CI = 1.07–1.31, p = 0.001). Besides, a significant heterogeneity was observed between studies. Further subgroup analyses based on ethnicity revealed similar positive results in both the Caucasian and Asian subgroups but not in the Middle East subgroup. Moreover, rs1063320 G allele conferred elevated susceptibility to RM in Asian group (allelic model: OR = 1.54, 95% CI = 1.17–2.03, p = 0.002). Additionally, pooled results showed a decreased risk of RM in mothers carrying rs1710 G allele (allelic model: OR = 0.68, 95% CI = 0.55–0.85, p p = 0.002). Further stratified analyses by race showed that these positive results were mainly from the associations observed in Asian populations. Limitations: The main limitation is that the enrolled number of individuals was relatively small. Thus, the results should be cautiously considered. Conclusions: Although the current systematic review and meta-analysis have shown that specific HLA-G 3′ UTR variants are associated with RM, a high degree of bias is present and further studies are needed to validate this causative effect

Supplementary Material for: PLA1A Participates in the Antiviral Innate Immune Response by Facilitating the Recruitment of TANK-Binding Kinase 1 to Mitochondria

As a key molecule in the antiviral innate immune response, the activation of TANK-binding kinase 1 (TBK1) is under tight regulation. In this report, we identified phosphatidylserine-specific phospholipase PLA1A as a host factor that modulates the TBK1 activation. Knockdown of PLA1A expression suppressed the innate immune signaling induced by RNA viruses, while PLA1A overexpression enhanced the signaling. PLA1A functioned at the TBK1 level of the signaling pathway, as PLA1A silencing blocked TBK1, but not interferon regulatory factor 3 (IRF3) induced interferon-β (IFN-β) promoter activity. The phosphorylation and kinase activity of TBK1 was reduced in PLA1A knockdown cells. Mechanistically, PLA1A was required in TBK1-mitochondrial antiviral signaling protein (MAVS) interactions but not the interactions of TBK1 with other adaptor proteins. Furthermore, PLA1A knockdown reduced the recruitment of TBK1 and IRF3 to mitochondria, concomitant with altered mitochondria morphology

Supplementary Material for: Prevalence and Determinants of Parathyroid Dysfunction in Elderly Patients on Hemodialysis

<b><i>Background:</i></b> The goal of this study was to investigate underlying factors of parathyroid dysfunction in elderly patients undergoing maintenance hemodialysis. <b><i>Methods:</i></b> A total of 286 patients on maintenance hemodialysis were included. Hemoglobin, serum creatinine (Scr), blood urea nitrogen (BUN), serum calcium, serum phosphorus (P), intact parathyroid hormone (iPTH), and serum albumin (Alb) were measured and analyzed both before and after dialysis. <b><i>Results:</i></b> A higher incidence of low iPTH level (<150 pg/l) was observed in the elderly group than that in the non-elderly group (55.8 vs. 36.7%, p < 0.05). Elderly patients had a shorter dialysis duration, lighter dry weight, lower concentrations of BUN, Scr, P, iPTH, Alb and standard protein nitrogen present rate (nPNA) compared to that of non-elderly group patients (p < 0.05). <b><i>Conclusions:</i></b> Low iPTH level occurs more frequently in elderly hemodialysis patients. Furthermore, age, serum P, serum Alb and nPNA were independently associated with a low iPTH level

Supplementary Material for: Changes in Dental Plaque Microbial Richness and Oral Behavioral Habits during Caries Development in Young Chinese Children

<b><i>Objective:</i></b> To detect changes in the microbial richness of dental plaque and oral behaviors during caries development in young Chinese children. <b><i>Methods:</i></b> Supragingival plaque samples and a survey of oral behaviors of 130 children aged 3 at baseline were analyzed at 6 months and 12 months. Total DNA was isolated from all samples and PCR-denaturing gradient gel electrophoresis analysis was conducted. <b><i>Results:</i></b> In the follow-up, 44 children had caries or cavity fillings at 6 months, a further 28 children had caries or cavity fillings at 12 months. The other 58 children remained caries-free at 12 months. According to the changes in caries status at the 12-month follow-up, all participants were divided into three groups: caries-free, caries at 6 months and caries at 12 months. The changes in oral behaviors during the 12-month follow-up were not significantly different in the three groups. The frequency of eating sweets and eating sweets before sleeping was significantly different among the three groups at baseline. At baseline, the average detectable bands of caries in the 12-month caries group were similar to those of the caries-free group; both of them were higher than that of the 6-month caries group. At 6 months, the average detectable bands of the 12-month caries group were significantly lower than that of the caries-free group although the children of the 12-month caries group were caries-free at that time. <b><i>Conclusions:</i></b> For young Chinese children, the high frequency of eating sweets and eating sweets before sleeping are risk factors of caries onset, and the decrease in microbial richness could occur 6 months before the onset of caries

Supplementary Material for: Prevention of Recurrent Bladder Tumors after Nephroureterectomy for Primary Upper Urinary Tract Urothelial Carcinoma: An Individualized Selection Strategy Based on Patient Risk Stratification Is Needed

<i>Objective:</i> To evaluate the efficacies of different chemotherapy regimens in different risk sub-groups for the prevention of bladder recurrence after radical nephroureterectomy (RNU). <i>Materials and Methods:</i> Between 2004 and 2012, we recruited 685 patients who underwent RNU for upper tract urothelial carcinoma at 4 Chinese institutions. We assessed whether the type of intravesical chemotherapy regimen affected the bladder recurrence rate in patients with different risk levels after RNU. <i>Results:</i> For all patients, the bladder recurrence rate was lower with intravesical chemotherapy than without, but no significant differences were found between the 2 intravesical chemotherapy regimens (single dose or relatively long-term therapy). We used multivariate analysis to define the risk factors for bladder recurrence and stratified patients into low-, intermediate-, and high-risk sub-groups accordingly. The bladder recurrence rate in the low-risk patients was not significantly different between patients with or without intravesical chemotherapy. However, in the intermediate-risk and high-risk patients, the rate was greater in patients without intravesical chemotherapy than in patients with. Furthermore, the rate was not significantly different between the 2 intravesical chemotherapy regimens in the intermediate-risk patients, while the efficacy of the relatively long-term regimen in high-risk patients remains unclear. <i>Conclusions:</i> Our study showed that an individualized strategy based on patient risk stratification is needed

Supplementary Material for: A Generalized Sequential Bonferroni Procedure for GWAS in Admixed Populations Incorporating Admixture Mapping Information into Association Tests

<b><i>Objective:</i></b> To develop effective methods for GWAS in admixed populations such as African Americans. <b><i>Methods:</i></b> We show that, when testing the null hypothesis that the test SNP is not in background linkage disequilibrium with the causal variants, several existing methods cannot control well the family-wise error rate (FWER) in the strong sense in GWAS. These existing methods include association tests adjusting for global ancestry and joint association tests that combine statistics from admixture mapping tests and association tests that correct for local ancestry. Furthermore, we describe a generalized sequential Bonferroni (smooth-GSB) procedure for GWAS that incorporates smoothed weights calculated from admixture mapping tests into association tests that correct for local ancestry. We have applied the smooth-GSB procedure to analyses of GWAS data on American Africans from the Atherosclerosis Risk in Communities (ARIC) Study. <b><i>Results:</i></b> Our simulation studies indicate that the smooth-GSB procedure not only control the FWER, but also improves statistical power compared with association tests correcting for local ancestry. <b><i>Conclusion:</i></b> The smooth-GSB procedure can result in a better performance than several existing methods for GWAS in admixed populations