Supplementary Material for: Disease burden of colorectal cancer in China from 1990 to 2019: Age and sex-specific time trends and 10-year forecast

Introduction: Colorectal cancer (CRC) is the third most prevalent malignant tumor worldwide and the second leading cause of cancer-related death.Aimed to report the disease burden of CRC in China from 1990 to 2019 and predict the trend of mortality burden over the next 10 years. Methods: The age-period-cohort (APC) model was implemented to analyze the trends of mortality from CRC in China from 1990 to 2019, and the autoregressive integrated moving average (ARIMA) model was used to predict the trends of CRC incidence and mortality from 2020 to 2029. Results: From 1990 to 2019, the incidence of CRC in China increased from 105,911 cases (95% uncertainty interval (UI): 93,808-119,021) to 607,900 cases (95% UI: 521,805-708,420). The age-standardized incidence rate (ASIR) increased from 12.52 per 100,000 (95% UI: 11.15-14.03) to 30.55 per 100,000 (95% UI: 26.37-35.5), with an estimated annual percentage change (EAPC) of 3.66 (95% confidence interval (CI): 3.37-3.95), showing an upward trend. The age-standardized mortality rate (ASMR) increased from 10.18 per 100,000 (95% UI: 9.03-11.37) to 13.86 per 100,000 (95% UI: 11.92-16.01), with an EAPC of 1.39 (95% CI: 1.14-1.63), also showing an upward trend. The age group with the highest incidence and mortality in 2019 was 65-69 years old for both sexes, and the age group with the highest mortality was 70-74 years old. Males had higher relative risks of incidence and mortality than females. Low-calcium diet was the risk factor for both sexes and females alone in 1990, while low-milk diet was the risk factor in 2019; however, smoking remained the risk factor for males. The ARIMA model predicted an increase in both disease and mortality burden of CRC over the next 10 years. Conclusion: The disease and mortality burden of CRC in China showed an overall upward trend from 1990 to 2019, with higher burden in males than females, and the situation remains extremely severe in the next decade

Supplementary Material for: Meta-Analysis Shows Strong Positive Association of the TNF-α Gene with Tumor Stage in Bladder Cancer

There is no consensus on the association between the <i>tumor necrosis factor-</i>α<i> (TNF-</i>α<i>)</i> gene promoter –308 A/G single nucleotide polymorphisms and bladder cancer risk. To obtain a more precise estimation of this correlation, we conducted a meta-analysis. The PubMed, MEDLINE, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases were searched for relevant published studies. Seven case-control studies with a total of 1,311 cases and 1,436 controls were identified and analyzed. A notable correlation was observed between the <i>TNF-</i>α genotype and bladder cancer grade (<i>AA+GA </i>vs. <i>GG;</i> odds ratio 1.96, 95% confidence interval 1.37–2.80, p = 0.0002). In summary, this meta-analysis demonstrates that the <i>TNF-</i>α –308 <i>AA+GA</i> genotype may be a marker to the tumor-invasive stage of bladder cancer

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

Supplementary Material for: Novel LAGE3 pathogenic variants combined with TRPC6 and NUP160 variants in Galloway-Mowat syndrome: a case report

Abstract Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disorder characterized by early-onset nephrotic syndrome and microcephaly with brain anomalies in children. Researchers studying GAMOS reported the first pathogenic variant identified was the WDR73 gene, and more recently, four new pathogenic genes, OSGEP, LAGE3, TP53RK, and TPRKB, have been identified. In the present study, we report a new mutation of c.290T>G（p.L97R）LAGE3 in a 4-year-old boy with specific urological and nephrological complications. The patient presented with early-onset proteinuria, brain atrophy, delayed language and motor development, and axial hypotonia. This patient also had mutations in two other genes: TRPC6 and NUP160，make the clinical presentation of this patient more diverse.Our novel findings add to the spectrum of pathogenic variants in the LAGE3 gene. In addition, early genetic diagnosis of GAMOS is essential for genetic counseling and prenatal care

Erratum: Atorvastatin Protects Myocardium Against Ischemia-Reperfusion Injury Through Inhibiting miR-199a-5p

<b><i>Objective: </i></b>This study aimed to evaluate the protective effects of atorvastatin against myocardial ischemia/reperfusion (I/R) injury in cardiomyocytes and its possible underlying mechanism. <b><i>Method</i></b><b><i>: </i></b>Direct cytotoxic effect of OGD/R on cardiomyocytes with and without atorvastatin pretreatment was evaluated. Effects of atorvastatin on expression of GSK-3β and miR-199a-5p were determined using RT-PCR and Western blot. In addition, GSK-3β expression with miR-199a-5p upregulation and downregulation was detected using RT-PCR, Western blot, and immunohistochemistry. <b><i>Results</i></b><b><i>: </i></b>Pretreatment with atorvastatin significantly improved the recovery of cells viability from OGD/R (p<0.05). In addition, the atorvastatin pretreatment significantly increased GSK-3β expression both in mRNA level and protein level and decreased miR-199a-5p expression in mRNA level (p<0.05). Upregulation and downregulation of miR-199a-5p respectively decreased and increased GSK-3β expression both in mRNA level and protein level. <b><i>Conclusion</i></b><b><i>: </i></b>These results suggested that atorvastatin provides the cardioprotective effects against I/R injury via increasing GSK-3β through inhibition of miR-199a-5p

Supplementary Material for: Serum Squamous Cell Carcinoma Antigen in Psoriasis: A Potential Quantitative Biomarker for Disease Severity

<b><i>Background:</i></b> An objective and quantitative method to evaluate psoriasis severity is important for practice and research in the precision care of psoriasis. <b><i>Objectives:</i></b> We aimed to explore serum biomarkers quantitatively in association with disease severity and treatment response in psoriasis patients, with serum squamous cell carcinoma antigen (SCCA) evaluated in this pilot study. <b><i>Methods:</i></b> 15 psoriasis patients were treated with adalimumab. At different visits before and after treatment, quantitative body surface area (qBSA) was obtained from standardized digital body images of the patients, and the psoriasis area severity index (PASI) was also monitored. SCCA were detected by using microparticle enzyme immunoassay. The serum biomarkers were also tested in healthy volunteers as normal controls. Receiver-operating characteristic (ROC) curve analysis was used to explore the optimal cutoff point of SCCA to differentiate mild and moderate-to-severe psoriasis. <b><i>Results:</i></b> The serum SCCA level in the psoriasis group was significantly higher (<i>p</i> < 0.05) than in the normal control group. After treatment, the serum SCCA levels were significantly decreased (<i>p</i> < 0.05). The SCCA level was well correlated with PASI and qBSA. In ROC analysis, when taking PASI = 10 or qBSA = 10% as the threshold, an optimal cutoff point of SCCA was found at 2.0 ng/mL with the highest Youden index. <b><i>Conclusion:</i></b> Serum SCCA might be a useful quantitative biomarker for psoriasis disease severity

Supplementary Material for: Individual Genetic Variations Related to Satiety and Appetite Control Increase Risk of Obesity in Preschool-Age Children in the STRONG Kids Program

<b><i>Background/Aims:</i></b> The burden of the childhood obesity epidemic is well recognized; nevertheless, the genetic markers and gene-environment interactions associated with the development of common obesity are still unknown. In this study, candidate genes associated to satiety and appetite control pathways with obesity-related traits were tested in Caucasian preschoolers from the STRONG Kids project. <b><i>Methods:</i></b> Eight genetic variants in genes related to obesity (BDNF, LEPR, FTO, PCSK1, POMC, TUB, LEP, and MC4R) were genotyped in 128 children from the STRONG Kids project (mean age 39.7 months). Data were analyzed for individual associations and to test for genetic predisposition scores (GPSs) with body mass index (BMI) and anthropometric traits (Z-scores, e.g. height-for-age Z-score, HAZ). Covariates included age, sex, and breastfeeding (BF) duration. <b><i>Results:</i></b> Obesity and overweight prevalence was 6.3 and 19.5%, respectively, according to age- and sex-specific BMI percentiles. Individual genetic associations of MC4R and LEPR markers with HAZ were strengthened when BF duration was included as a covariate. Our GPSs show that, as the number of risk alleles increased, the risk of higher BMI and HAZ also increased. Overall, the GPSs assembled were able to explain 2-3% of the variability in BMI and HAZ phenotypes. <b><i>Conclusion:</i></b> Genetic associations with common obesity-related phenotypes were found in the STRONG Kids project. GPSs assembled for specific candidate genes were associated with BMI and HAZ phenotypes

Supplementary Material for: Body mass index and all-cause mortality in elderly patients with percutaneous coronary intervention: A meta-analysis

Background: The ‘obesity paradox’ in elderly patients suffering from percutaneous coronary intervention (PCI) remains a source of controversy. The present meta-analysis focused on exploring the real existence of ‘obesity paradox’ in these patients. Methods: As of November 2022, PubMed, Cochrane and Embase databases were comprehensively searched to identify articles reporting all-cause mortality according to diverse body mass index (BMI) categories after PCI among the old cases developing coronary artery disease (CAD). Summary estimates of risk ratios (RRs) were assigned four BMI groups, including underweight, normal weight, overweight, and obesity groups. Results: There were altogether nine articles involving 25,798 cases selected for further analysis. Relative to normal weight group, overweight and obesity groups had decreased all-cause mortality (RR 0.86, 95%CI 0.77-0.95 for overweight group; RR 0.57,95%CI 0.40-0.80 for obesity group), while underweight group had elevated all-cause mortality (RR 1.52, 95%CI 1.01-2.29). Conclusions: Our study revealed an ‘obesity paradox’ relation of BMI with all-cause mortality in elderly cases receiving PCI. In comparison with normal weight group, overweight and obesity groups had decreased all-cause mortality, while underweight group had increased all-cause mortality

Supplementary Material for: Association of Leptin Gene -2548 G/A Polymorphism with Obesity: A Meta-Analysis

<b><i>Background:</i></b> A common single-nucleotide polymorphism identified in the 5′-untranslated region of the leptin gene (LEP -2548 G/A polymorphism) may be associated with obesity, but the existing research findings are inconsistent, so we conducted this meta-analysis. <b><i>Methods:</i></b> Medline, Embase and ISI Web of Science databases were searched to identify relevant studies. Meta-analysis of the total and subgroup populations was conducted using allelic, additive, dominant and recessive models, and odds ratios and their 95% confidence intervals were calculated in a fixed-effect model if no heterogeneity (evaluated as I² statistic) existed. Otherwise, a random-effects model was adopted. Subgroup analysis was performed by ethnicity. Meta-regression and the HETRED analysis were used to explore the potential sources of between-study heterogeneity. Egger's test and influence analysis were conducted to evaluate the publication bias and study power, respectively. <b><i>Results:</i></b> The final selection enrolled 9 studies, including 2,988 subjects (1,372 obese subjects and 1,616 controls). No significant association was identified between the LEP -2548 G/A polymorphism and obesity for all genetic models in the overall population and Caucasians. We found a significant association with allelic, additive and dominant models for subjects of mixed race from South America. Notwithstanding, this significance should be treated cautiously for it is based on a rather small sample (788 involved subjects). <b><i>Conclusions:</i></b> In total, the combined analysis of data from current and published studies suggested that the LEP -2548 G/A polymorphism does not contribute to the development of obesity, despite the fact that a significant association exists in a small subgroup from South America. Further studies are needed to elucidate the relationship

Supplementary Material for: Effects of Hyperferritinemia on Functional Outcome in Acute Ischemic Stroke Patients with Admission Hyperglycemia

Introduction: Hyperferritinemia, presented as elevated serum ferritin level, is an indicator of high iron status which plays roles in secondary brain injury after acute ischemic stroke (AIS). However, the effects of hyperferritinemia and poor outcomes remain uncertain. Additionally, admission hyperglycemia quite frequently accompanies AIS patients, which is associated with unfavorable outcome. Thus, we aimed to investigate the effects of hyperferritinemia on 3-month and 1-year functional outcomes in AIS patients and especially those with admission hyperglycemia. Methods: AIS patients within 24 h of onset were enrolled at West China Hospital from October 2016 to December 2019. Serum ferritin and blood glucose levels were tested on admission. Poor functional outcome at 3 months and 1 year was defined as modified Rankin Scale score ≥3. Multivariable analysis was used to investigate the associations between hyperferritinemia and 3-month and 1-year outcomes. Subgroup analysis was performed in patients with and without hyperglycemia. Results: Of 723 patients (mean age 68.11 years, 60.6% males) finally included, 347 (48.0%) had hyperferritinemia. The incidence of poor outcome was 45.2% at 3 months and 41.2% at 1 year. Patients with hyperferritinemia had a higher frequency of poor 3-month outcome (51.8% vs. 39.2%, p = 0.001) and poor 1-year outcome (46.8% vs. 36.1%, p = 0.004). In all AIS patients, hyperferritinemia was not independently associated with poor functional outcome at 3 months or 1 year after adjusting for confounders (all p > 0.05). In AIS patients with hyperglycemia, hyperferritinemia was an independent factor correlated with poor 3-month outcome (OR = 1.711, 95% CI 1.093–2.681, p = 0.019) but not with poor 1-year outcome (p > 0.05). Conclusions: High iron status, presented as hyperferritinemia, is associated with poor 3-month functional outcome in AIS patients with hyperglycemia. Evaluating serum ferritin level may be conducive to assess the risk of short-term poor outcome in AIS patients with hyperglycemia. Further studies will be required to confirm our findings