Supplementary Material for: Systematic review and meta-analysis: Association between preoperative ustekinumab and surgical complications in Crohn's disease patients

Introduction: The impact of ustekinumab (UST) therapy on surgical complications in patients with Crohn's disease (CD) remains controversial. The aim of this meta-analysis is to explore the link between these two. Methods: Databases (PubMed, Web of Science, Cochrane, and Springer Link) were searched until April 2022. Studies of CD patients who received UST and no UST prior to surgery (including no biological therapy, anti-TNF-α agent, and VDZ) were included. Primary outcomes included overall complications, infectious complications, and non-infectious complications. Results: Nine studies totaling 3,225 CD patients were enrolled; 332 patients received UST treatment. There was no evidence of difference in the overall complications (OR=0.84, p=0.37, 95%CI=[0.57-1.23], I2=40%) between CD patients who had UST treatment preoperatively and those who had no UST treatment. There was no evidence of a difference in infectious complications (OR=1.15, p=0.35, 95%CI=[0.86-1.53], I2=2%). Additionally, there was no significant no evidence of difference between these group in terms of non-infectious complications and death. Specifically, there were no evidence of difference in overall complications, infection complications (including wound complications, sepsis, abscess and anastomotic leakage), and non-infection complications (ileus, readmission, and return to operation), compared with no biological therapy and anti-TNF-α agents. At the same time, no significant evidence of difference was discovered in the comparison of preoperative UST and VDZ therapy in terms of overall complications, infectious complications (sepsis and abscess), and non infectious complications (intestinal obstruction, readmission, and recovery surgery). Conclusion: In general, compared with other biological agents, preoperative use of UST in the treatment of CD patients is usually safe and does not increase surgical complications

Supplementary Material for: Association between sleep and Alzheimer’s disease: A bibliometric analysis from 2003 to 2022

Introduction: Alzheimer’s disease (AD) often presents with sleep disorders, which are also an important risk factor for AD, affecting cognitive function to a certain extent. This study aimed to reveal the current global status, present hotspots, and discuss emerging trends of sleep and AD using a bibliometric approach. Methods: Research and review articles related to sleep and AD from 2003 to 2022 were extracted from the Web of Science Core Collection. VOSviewer 1.6.18.0, Scimago Graphica, and CiteSpace 6.2.R2 were used to map the productive and highly cited countries, institutions, journals, authors, references, and keywords in the field. Results: Overall, 4,008 publications were included in this bibliometric analysis. The number of publications and citations showed an increasing trend over the past two decades. The USA and China had the largest and second largest, respectively, number of publications and citations and cooperated with other countries more closely. Ancoli-Israel Sonia published the most papers, and Holtzman David M was co-cited most frequently. The most productive journal was Journal of Alzheimer’s Disease, and Neurology was the most frequently cited journal. The risk factors, β-amyloid, tau, neuroinflammation, astrocytes, glymphatic system, orexin, functional connectivity, and management have been the main research directions of researchers over the past few years and may be the future trend of valuable research. Conclusion: We identified hotspots and emerging trends including risk factors, Aβ, tau, neuroinflammation, the glymphatic system, orexin, and management, which may help identify new therapeutic targets and improve clinical efficacy of sleep and AD

Supplementary Material for: Activin B Promotes Initiation and Development of Hair Follicles in Mice

Activin B has been reported to promote the regeneration of hair follicles during wound healing. However, its role in the development and life cycle of hair follicles has not been elucidated.<b> </b>In our study, the effect of activin B on mouse hair follicles of cultured and neonatal mouse skin was investigated. In these models, PBS or activin B (5, 10 or 50 ng/ml) was applied, and hair follicle development was monitored. Hair follicle initiation and development was examined using hematoxylin and eosin staining, alkaline phosphatase activity staining, Oil Red O+ staining, and the detection of TdT-mediated dUTP-biotin nick end-labeling cell apoptosis. Activin B was found to efficiently induce the initiation of hair follicles in the skin of both cultured and neonatal mice and to promote the development of hair follicles in neonatal mouse skin. Moreover, activin-B-treated hair follicles were observed to enter the anagen stage from the telogen stage and to remain in the anagen stage. These results demonstrate that activin B promotes the initiation and development of hair follicles in mice

Supplementary Material for: A common variant of ARRB2 promoter region Associated with the Prognosis of Heart Failure

Introduction The role of ARRB2 in cardiovascular disease has recently gained increasing attention. However, the association between ARRB2 polymorphisms and heart failure (HF) has not yet been investigated. Methods A total of 2386 hospitalized patients with chronic heart failure were enrolled as the first cohort and followed up for a mean period of 20.2 months. Meanwhile, ethnically and geographically matched 3000 individuals without evidence of HF were included as healthy controls. We genotyped the common variant in ARRB2 gene to identify the association between variant and HF. A replicated independent cohort enrolling 837 patients with chronic HF was applied to validate the observed association. A series of function analysis were conducted to illuminate the underlying mechanism. Results We identified a common variant rs75428611 associated with the prognosis of HF in two-stage population: adjusted P = 0.001, HR = 1.31 (1.11-1.54) in additive model and adjusted P = 0.001, HR = 1.39 (1.14-1.69) in dominant model in first-stage population; adjusted P = 0.04, HR = 1.41 (1.02-1.95) in additive model and adjusted P = 0.03, HR = 1.51 (1.03-2.20) in dominant model in replicated stage. However, rs75428611 did not significantly associate with the risk of HF. Functional analysis indicated that rs75428611‐G allele increased the promoter activity and the mRNA expression level of ARRB2 by facilitating transcription factor SRF binding, but not the A allele. Conclusions Our findings demonstrate that rs75428611 in promoter of ARRB2 is associated with the risk of HF mortality. It is a promising potential treatment target for HF

Supplementary Material for: Association of Initial Twice-Weekly Hemodialysis Treatment with Preservation of Residual Kidney Function in ESRD Patients

<b><i>Background:</i></b> Residual kidney function (RKF) has consistently been a predictor of greater survival in maintenance hemodialysis (MHD) patients. The relationship between hemodialysis (HD) treatment frequency and RKF preservation has not been well examined. We hypothesized that initial twice-weekly HD helps in maintaining a longer RKF. <b><i>Methods:</i></b> In a dialysis center in Shanghai, 168 ESRD patients were screened and finally 85 patients were identified for this main cohort study. We first examined these 85 MHD patients; 30 of them were initiated with twice-weekly HD for 6 months or longer and 55 patients were started and maintained on thrice-weekly HD treatment. Then a subcohort study in 48 incident MHD patients was implemented to assess the independent risk factors responsible for RKF decline during the first year of HD therapy. Multivariate logistic regression analysis was then employed to examine the odds ratio of RKF loss. <b><i>Results:</i></b> The main cohort study showed that the clinical outcomes were almost the same between the two groups in 85 patients, but the percent of patients with RKF loss was significantly lower in the twice-weekly group compared with the thrice-weekly group, especially during the first year of HD initiation. In the 48 incident MHD patients, we found no significant differences between the two groups except for variations in the HD frequency, weekly Kt/V. The multivariate analysis showed that factors such as the male gender, HD frequency, URR and intradialytic hypotension episode were associated with RKF loss, and the odds ratio of RKF loss for each additional HD treatment per week was 7.2. <b><i>Conclusion:</i></b> Twice-weekly HD during the first year of dialysis therapy appears to be associated with better RKF preservation

Supplementary Material for: Transplantation of Telocytes Attenuates Unilateral Ureter Obstruction-Induced Renal Fibrosis in Rats

<b><i>Background/Aims:</i></b> Previous studies imply that telocytes may have a protective effect on fibrosis in various organs, including the liver, colon, and heart. The effect of telocytes on renal fibrosis remains unknown. Herein, this study was designed to investigate the effect of telocytes on renal fibrosis and the potential mechanisms involved. <b><i>Methods:</i></b> In a unilateral ureteral obstruction (UUO)-induced renal fibrosis model, telocytes were injected via the tail vein every other day for 10 days. The degree of renal damage and fibrosis was determined using histological assessment. The expression of collagen I, fibronectin, epithelial-mesenchymal transition markers, and Smad2/3 phosphorylation was examined by western blot analyses. Real-time PCR and enzyme-linked immunosorbent assay were performed <i>in vivo</i> to detect the levels of transforming growth factor (TGF)-β1 and various growth factors. <b><i>Results:</i></b> Telocytes attenuated renal fibrosis, as evidenced by reduced interstitial collagen accumulation, decreased expression of fibronectin and collagen I, upregulation of E-cadherin, and downregulation of α-smooth muscle actin. Furthermore, telocytes decreased serum TGF-β1 levels, suppressed Smad2/3 phosphorylation, and increased the expression of hepatocyte growth factor (HGF) in rat kidney tissue following UUO. Blockage of HGF counteracted the protective effect of telocytes on UUO-treated kidneys. Through the detection of HGF mRNA levels <i>in vitro</i>, we found that telocytes had no effect on HGF expression compared with renal fibroblasts. <b><i>Conclusion:</i></b> Telocytes attenuated UUO-induced renal fibrosis in rats, likely through enhancing the expression of HGF in an indirect manner

Supplementary Material for: General Anesthesia may have Similar Outcomes with Conscious Sedation in Thrombectomy Patients with Acute Ischemic Stroke: A Real-World Registry in China

<b><i>Background and Purpose:</i></b> Clinical trials showed that anesthesia may not influence the functional outcome in stroke patients with endovascular therapy; however, data are lacking in China. Using real-world registry data, our study aims to compare the effects of general anesthesia or conscious sedation on functional outcomes in stroke patients treated with thrombectomy in China. <b><i>Methods:</i></b> Consecutive patients with acute anterior circulation stroke receiving thrombectomy in 21 stroke centers between January 2014 and June 2016 were included in this study. The propensity score analysis with 1: 1 ratio was used to match the baseline variables between patients with general anesthesia and the conscious sedation. The 90-day modified Rankin Scale (mRS), symptomatic intracranial hemorrhage (sICH), and death were compared between groups. <b><i>Results:</i></b> Of the 698 patients undergoing endovascular treatment, 138 were treated with general anesthesia and 560 with conscious sedation. After propensity score matching, 114 general anesthesia and 114 conscious sedation patients were matched. The proportions of patients with 90-day mRS 0–2 were not significantly different between general anesthesia and conscious sedation groups (41.2% [47/114] vs. 46.5% [53/114], <i>p</i> = 0.470), nor were the rates of sICH (21.9% [25/114] vs. 12.3% [14/114], <i>p</i> = 0.072) and 90-day mortality (31.6% [36/114] vs. 21.9% [25/114], <i>p</i> = 0.145). <b><i>Conclusion:</i></b> Anesthesia patterns may have no significant impacts on clinical outcomes in patients with acute anterior circulation occlusion stroke undergoing endovascular treatment in the real-world practice in China

Supplementary Material for: Association between Triglyceride-Glucose Index and 1-year Recurrent Stroke after Acute Ischemic Stroke: Results from the Xi’an Stroke Registry Study of China

Introduction: The triglyceride-glucose (TyG) index is reported to be related to poor functional outcomes and all-cause mortality post-stroke. However, the association between TyG index and recurrent stroke after acute ischemic stroke (AIS) has not been well described. We aimed to identify whether the TyG index was associated with 1-year recurrent stroke after AIS. Methods: Baseline patient information was collected at admission, and the TyG index was calculated. Recurrent stroke events were followed up at 1, 3, 6, and 12 months after diagnosis. We then examined the association between the TyG index and risk of 1-year recurrent stroke using multivariable Cox regression models and restricted cubic spline analyses. Results: Among 2,288 participants, the mean TyG index was 8.8 0.7. Those in the fourth quartile (Q4) demonstrated higher recurrent stroke risk than those in Q1 (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI], 0.98–2.72; p = 0.059). Subgroup analysis revealed a sex-specific association between TyG index and recurrent stroke (p for interaction = 0.022). Additionally, restricted cubic splines analyses showed a non-linear association between the TyG index and 1-year recurrent stroke. In females, patients in the Q4 had a 2.95-fold increased recurrent stroke risk than did patients in the Q1 (adjusted HR =2.95; 95% CI, 1.09–7.94; p = 0.032); the risk increased when the TyG index was > 8.73. However, no significant correlation was observed in males. Conclusion: A non-linear association was found between the TyG index and 1-year recurrent stroke risk. Subsequently, a high TyG index could predict an increased 1-year recurrent stroke risk in female AIS patients

Supplementary Material for: Association between Triglyceride-Glucose Index and 1-year Recurrent Stroke after Acute Ischemic Stroke: Results from the Xi’an Stroke Registry Study of China

Introduction: The triglyceride-glucose (TyG) index is reported to be related to poor functional outcomes and all-cause mortality post-stroke. However, the association between TyG index and recurrent stroke after acute ischemic stroke (AIS) has not been well described. We aimed to identify whether the TyG index was associated with 1-year recurrent stroke after AIS. Methods: Baseline patient information was collected at admission, and the TyG index was calculated. Recurrent stroke events were followed up at 1, 3, 6, and 12 months after diagnosis. We then examined the association between the TyG index and risk of 1-year recurrent stroke using multivariable Cox regression models and restricted cubic spline analyses. Results: Among 2,288 participants, the mean TyG index was 8.8 0.7. Those in the fourth quartile (Q4) demonstrated higher recurrent stroke risk than those in Q1 (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI], 0.98–2.72; p = 0.059). Subgroup analysis revealed a sex-specific association between TyG index and recurrent stroke (p for interaction = 0.022). Additionally, restricted cubic splines analyses showed a non-linear association between the TyG index and 1-year recurrent stroke. In females, patients in the Q4 had a 2.95-fold increased recurrent stroke risk than did patients in the Q1 (adjusted HR =2.95; 95% CI, 1.09–7.94; p = 0.032); the risk increased when the TyG index was > 8.73. However, no significant correlation was observed in males. Conclusion: A non-linear association was found between the TyG index and 1-year recurrent stroke risk. Subsequently, a high TyG index could predict an increased 1-year recurrent stroke risk in female AIS patients

Supplementary Material for: Association between Triglyceride-Glucose Index and 1-year Recurrent Stroke after Acute Ischemic Stroke: Results from the Xi’an Stroke Registry Study of China

Introduction: The triglyceride-glucose (TyG) index is reported to be related to poor functional outcomes and all-cause mortality post-stroke. However, the association between TyG index and recurrent stroke after acute ischemic stroke (AIS) has not been well described. We aimed to identify whether the TyG index was associated with 1-year recurrent stroke after AIS. Methods: Baseline patient information was collected at admission, and the TyG index was calculated. Recurrent stroke events were followed up at 1, 3, 6, and 12 months after diagnosis. We then examined the association between the TyG index and risk of 1-year recurrent stroke using multivariable Cox regression models and restricted cubic spline analyses. Results: Among 2,288 participants, the mean TyG index was 8.8 0.7. Those in the fourth quartile (Q4) demonstrated higher recurrent stroke risk than those in Q1 (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI], 0.98–2.72; p = 0.059). Subgroup analysis revealed a sex-specific association between TyG index and recurrent stroke (p for interaction = 0.022). Additionally, restricted cubic splines analyses showed a non-linear association between the TyG index and 1-year recurrent stroke. In females, patients in the Q4 had a 2.95-fold increased recurrent stroke risk than did patients in the Q1 (adjusted HR =2.95; 95% CI, 1.09–7.94; p = 0.032); the risk increased when the TyG index was > 8.73. However, no significant correlation was observed in males. Conclusion: A non-linear association was found between the TyG index and 1-year recurrent stroke risk. Subsequently, a high TyG index could predict an increased 1-year recurrent stroke risk in female AIS patients