Supplementary Material for: Comparison between transpancreatic sphincterotomy and needle-knife precut in difficult cannulation of endoscopic retrograde cholangiopancreatography: an up-to-date meta-analysis and systematic review

Background Selective cannulation, which is essential for endoscopic retrograde cholangiopancreatography (ERCP), may be difficult. The aim of this study was to compare transpancreatic sphincterotomy (TPS) and needle-knife precut (NKP) in difficult cannulation during ERCP. Methods PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched for relevant studies from January 1990 to April 2022. A meta-analysis focusing on cannulation success and post-ERCP complications was performed by Review Manager. Results Seventeen eligible studies involving 2340 patients were included. Our results showed that the TPS group had a higher cannulation success rate (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.27–0.87, p = 0.02) and less bleeding (OR 1.94, 95% CI 1.09–3.47, p = 0.03) compared with the NKP group. There was no significant difference between NKP and TPS in the rates of post-ERCP pancreatitis (OR 0.83, 95% CI 0.59–1.18, p = 0.30), perforation (OR 2.04, 95% CI 0.69–6.03, p = 0.20), and adverse events (OR 1.29, 95% CI 0.94–1.77, p = 0.12). Conclusion TPS appears to be associated with a higher cannulation success rate and less bleeding than those with NKP, with equal post-ERCP pancreatitis, perforation, and adverse events rates between TPS and NKP. Further large-scale trials are warranted to support our findings

Supplementary Material for: Exercise Regulates Myokines on Aging-related Diseases through Muscle-brain Crosstalk

Background: The related functions of skeletal muscle and brain decrease significantly with age, and muscle-brain-related diseases are primarily associated with each other. Exercise can promote the secretion of myokines in skeletal muscle, showing a beneficial effect on the function of both, reflecting muscle-brain crosstalk. However, the key mechanism of action of exercise-regulated myokines in muscle-brain diseases remains unclear. Methods: Web of Science, PubMed, EBSCO, OVID, and China National Knowledge Infrastructure were searched from July 2022 to February 2023 using “myokine,” “myokines,” “exercise,” “training,” “physical activity,” “aging,” “brain” and “crosstalk” as keywords. Results: Twenty-four experimental studies were selected from 2,941 studies involving seven common myokines. The exercises studied included aerobic exercise, resistance exercise, combined aerobic and resistance exercise, high-intensity interval training (HIIT), and high-intensity circuit training (HICT). Eighteen of the studies mentioned brain-derived neurotrophic factor (BDNF), four mentioned insulin-like growth factor 1 (IGF-1), three mentioned cathepsin B (CATB), and four mentioned irisin. There were four with vascular endothelial growth factor (VEGF), five with interleukin 6 (IL-6), and three with fibroblast growth factor 21 (FGF-21). There are multiple studies involving multiple myokines at the same time. Conclusions: Type, duration, intensity, and frequency of exercise may affect the expression of myokines in muscle-brain crosstalk. Both low- to moderate-intensity aerobic exercise three times a week for 12 weeks or more and resistance exercise two or three times a week with low or moderate-intensity for 12 weeks have a strong effect on the expression of myokines. However, there are few studies on the effects of combined aerobic and resistance exercise, HIIT, and HICT on myokines, and more empirical studies are required in the future

Supplementary Material for: Use of Epinephrine in Patients with Drug-Induced Anaphylaxis: An Analysis of the Beijing Pharmacovigilance Database

<i>Background:</i> Few studies assessing the use of epinephrine in drug-induced anaphylaxis (DIA) in the hospital setting are available. We utilized the Beijing Pharmacovigilance Database (BPD) to evaluate the appropriateness of epinephrine for DIA management. <i>Methods:</i> DIA cases collected in the BPD from January 2004 to December 2014 were adjudicated and analyzed for demographics, causative drugs, clinical signs, outcomes, initial treatment, route, dosing, and cardiovascular adverse events (CAE) of epinephrine. <i>Results:</i> DIA was primarily caused by antibiotics (38.4%), radiocontrast agents (11.9%), traditional Chinese medicine injections (10.9%), and chemotherapeutic drugs (10.3%). Only 708 (59.5%) patients received epinephrine treatment. Patients who received epinephrine were more likely to experience wheezing (<i>p</i> < 0.001) and respiratory arrest (<i>p</i> < 0.001). Among 518 patients with a complete record of the epinephrine administration route, the percentage of patients receiving it by intramuscular (IM) injection, subcutaneous (SC) injection, intravenous (IV) bolus injection, or IV continuous infusion was 16.9, 31.5, 43.5, and 8.1%, respectively. Among the 427 patients with a record of both the administration route and the dosing, an overdose was more likely with IV bolus (94.1%) in contrast to IM injection (56.6%; <i>p</i> < 0.001) or SC injection (43.7%; <i>p</i> < 0.001). Among the patients analyzed for CAE (<i>n</i> = 349), 17 patients accounted for 19 CAE, and 13 (76.5%) of these patients were overdosed with pinephrine. <i>Conclusion:</i> Underuse, inappropriate IV bolus use, and overdosing were the 3 major problems with epinephrine use in DIA in China. Educational training for health care professionals on the appropriate use of epinephrine in managing anaphylactic reactions is suggested

Erratum: Inflammatory Cytokine TSLP Stimulates Platelet Secretion and Potentiates Platelet Aggregation via a TSLPR-Dependent PI3K/Akt Signaling Pathway

<b><i>Aims: </i></b>Thymic stromal lymphopoietin (TSLP) plays an important role in inflammatory diseases and is over-expressed in human atherosclerotic artery specimens. The present study investigated the role of TSLP in platelet activation and thrombosis models <i>in vitro</i> and <i>in vivo</i>, as well as the underlying mechanism and signaling pathway. <b><i>Methods and Results: </i></b>Western blotting and flow cytometry demonstrated that the TSLP receptor was expressed on murine platelets. According to flow cytometry, platelet stimulation with TSLP induced platelet degranulation and integrin αIIbβ3 activation. A TSLPR deficiency caused defective platelet aggregation, defective platelet secretion and markedly blunted thrombus growth in perfusion chambers at both low and high shear rates. TSLPR KO mice exhibited defective carotid artery thrombus formation after exposure to FeCl₃. TSLP increased Akt phosphorylation, an effect that was abrogated by the PI3K inhibitors wortmannin and LY294002. The PI3K inhibitors further diminished TSLP-induced platelet activation. TSLP-mediated platelet degranulation, integrin αIIbβ3 activation and Akt phosphorylation were blunted in platelets that lacked the TSLP receptor. <b><i>Conclusion: </i></b>This study demonstrated that the functional TSLPR was surface-expressed on murine platelets. The inflammatory cytokine TSLP triggered platelet activation and thrombus formation via TSLP-dependent PI3K/Akt signaling, which suggests an important role for TSLP in linking vascular inflammation and thrombo-occlusive diseases

Supplementary Material for: rs4711751 and rs1999930 Are Not Associated with Neovascular Age-Related Macular Degeneration or Polypoidal Choroidal Vasculopathy in the Chinese Population

<b><i>Purpose:</i></b> rs1999930 and rs4711751 have recently been identified as novel variants associated with advanced age-related macular degeneration (AMD) in populations of European ancestry. We aimed to investigate whether these two single nucleotide polymorphisms (SNPs) were associated with neovascular AMD (nAMD) or with polypoidal choroidal vasculopathy (PCV), a variant of AMD in Asians, using a Chinese case-control study. <b><i>Methods:</i></b> A total of 900 subjects, including 300 controls, 300 cases with nAMD and 300 cases with PCV, were included in the present study. Genomic DNA was extracted from venous blood leukocytes. The allelic variants of rs1999930 and rs4711751 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The differences in allele distribution between cases and controls were tested by a χ² test, with additional adjustments for age and gender using logistic regression. The statistical power was also calculated. Values of p < 0.05 were considered statistically significant. <b><i>Results:</i></b> No statistically significant association was observed between the two polymorphisms of nAMD or PCV phenotype (p > 0.05 for all comparisons). The difference remained insignificant after correction for age and gender (p > 0.05 for all comparisons). The statistical powers to detect the association between these two SNPs and nAMD or PCV range from 0.05 to 0.36, assuming conventional levels of statistical significance. <b><i>Conclusions:</i></b> In the present study, we could not replicate the reported association of these two SNPs and either nAMD or PCV in a Chinese population, suggesting that they are unlikely to be a major AMD and PCV susceptibility gene locus in the Chinese population. Considering the low power value, a large sample size is required to draw more reliable conclusions

Supplementary Material for: Transgenic Overexpression of IL-37 Protects Against Atherosclerosis and Strengthens Plaque Stability

<b><i>Background/Aims:</i></b> Recently, studies have shown that interleukin-37 (IL-37) is involved in atherosclerosis-related diseases. However, the regulatory mechanisms of IL-37 in atherosclerosis remain unknown. This study aims to determine the role of IL-37 in atherosclerosis and to investigate the underlying mechanisms involved. <b><i>Methods:</i></b> IL-37 expression in human atherosclerotic plaques was detected by immunohistochemical staining and real-time reverse transcription polymerase chain reaction (RT-PCR). Oil Red O staining was used to measure the size of plaques. Cell apoptosis <i>in vitro</i> and <i>in vivo</i> was tested by flow cytometric analysis and terminal deoxynucleotidyl-transferase mediated dUTP nick-end labeling (TUNEL) staining, respectively. Protein expression levels of IL-37, IL-18Rα and p-Smad3 were measured by Weston blotting. <b><i>Results:</i></b> Immunohistochemical staining revealed that IL-37 was highly expressed in human atherosclerotic plaques. Intracellular cytokine staining revealed that infiltrated CD4⁺ T lymphocytes and vascular smooth muscle cells (VSMCs), but not macrophages, were the major sources of IL-37. Mice that overexpressed IL-37 exhibited significant improvements in their atherosclerotic burden, as demonstrated by reduced plaque size, increased collagen levels, and reduced numbers of apoptotic cells <i>in vivo</i>. Subsequently, mechanistic studies showed that IL-37 played an anti-atherosclerotic role, at least partially, through reducing inflammation by promoting the differentiation of the T helper cell anti-inflammatory phenotype, and through increasing plaque stability by decreasing matrix metalloproteinase (MMP)-2/13-mediated degradation of collagen and inhibiting VSMCs apoptosis. <b><i>Conclusion:</i></b> IL-37 may be a novel potential therapeutic target in patients with atherosclerotic heart disease