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Background: Autism spectrum disorder (ASD) is a multifactorial, pervasive, neurodevelopmental disorder, of which intestinal symptoms collectively represent one of the most common comorbidities. Methods: In this study, 1,222 children with ASD and 1,206 typically developing (TD) children aged 2-7 years were enrolled from 13 cities in China. Physical measurement and basic information questionnaires were conducted in ASD and TD children. The Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Behavior Checklist (ABC) were used to evaluate the clinical symptoms of children with ASD. The six-item Gastrointestinal Severity Index (6-GSI) was used to evaluate the prevalence of intestinal symptoms in two groups. Results: The detection rates of constipation, stool odor, and total intestinal symptoms in ASD children were significantly higher than those in TD children (40.098% vs. 25.622%, 17.021% vs. 9.287%, and 53.601% vs. 41.294%, respectively). Autistic children presenting with intestinal comorbidity had significantly higher scores on the ABC, SRS, CARS, and multiple subscales than autistic children without intestinal symptoms, suggesting that intestinal comorbidity may exacerbates the core symptoms of ASD children. Conclusion: Intestinal dysfunction was significantly more common in autistic than in TD children. This dysfunction may aggravate the core symptoms of children with ASD.

To assess safety and ocular hypotensive efficacy of VVN539 ophthalmic solution in a first-in-human study. Multicenter, double-masked, randomized, vehicle-controlled, dose-response, parallel-comparison study. Sixty-eight subjects with ocular hypertension (OHT) or open-angle glaucoma enrolled at 5 private practices. After washout of ocular hypotensive medications as required, the subjects were randomized to receive either VVN539 ophthalmic solution 0.02%, 0.04%, or vehicle once-daily (QD) in the morning (5 days), once-daily in the evening (6 days) and then twice-daily (6 days). Comparison of VVNM539 to its vehicle in mean intraocular pressure (IOP) at each diurnal time point (8:00am, 10:00am, and 4:00pm) at visit 4 (day 7), visit 5 (day 14), and visit 6 (day 21). Mean IOP decreased throughout dosing in the active groups to between 18 and 20 mmHg in both active groups, to between 22 to 23 mmHg in the vehicle group. VVN539 0.04% was statistically superior to vehicle at all 9 diurnal time points (QD AM, QD PM, and twice daily, P ≤ 0.0109). VVN539 0.02% was statistically superior to vehicle at only 6 of 9 diurnal time points (selected QD times and twice daily). The most common ocular treatment-emergent adverse event was conjunctival hyperemia (11 [47.8%], 10 [4.5%], and 1 [4.3%]), followed by ocular hyperemia (3 [13.0%], 5 [22.7%] and 0), respectively. There were no clinically significant changes of note in visual acuity, biomicroscopy, dilated ophthalmoscopy, blood chemistry, hematology, or cardiovascular measures. In conclusion, the results of this initial phase II study indicate that VVN539 ophthalmic solution showed clinically and statistically significant ocular hypertensive activity and was relatively well tolerated for the treatment of subjects with primary open-angle glaucoma or OHT. Additional studies will be required for a more complete evaluation of the utility of VVN539 ophthalmic solution. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The present research examined the perceived teachers' charismatic leadership and entrepreneurial intentions of college students. Based on the theory of emotional contagion, this study proposes a mediating model of entrepreneurial passion between college students' perception of teachers' charismatic leadership and entrepreneurial intentions. A questionnaire survey was conducted in 420 college students in Jiangsu Province, China. The results showed that college students' perceived teachers' charismatic leadership had a significant positive effect on entrepreneurial passion. Moreover, perceived teachers' charismatic leadership of college students was found to have a significant positive predictive effect on entrepreneurial intentions, and entrepreneurial passion had a significant positive effect on entrepreneurial intentions. The mediation model analysis indicated that entrepreneurial passion played a partial mediating role between college students' perception of teachers' charismatic leadership and entrepreneurial intentions. The study results deepened our understanding of the inner influence mechanism of college students' perception of teachers' charismatic leadership and entrepreneurial intentions, in addition to providing a practical basis for college educators.

Abstract Chronic postsurgical pain (CPSP), with a high prevalence and rising epidemic of opioids crisis, is typically derived from acute postoperative pain. Our knowledge on the forming of chronic pain mostly derives from mechanistic studies of pain processing in the brain and spinal cord circuits, yet most pharmacological interventions targeting CNS came to be unhelpful in preventing CPSP. Revealing the peripheral mechanisms behind the transition from acute to chronic pain after surgery could shine a light on the novel analgesic regimens. Based on two recognized animal models in simulation of acute and chronic postsurgical pain, we provide a next-generation RNA sequencing (RNA-seq) data set to evaluate the time-course transcriptomic variation in the tissue of skin, muscle and dorsal root ganglion (DRG) in these two pain models. The aim of this study is to identify the potential origin and mechanism of the persistent postoperative pain, and further to explore effective and safer analgesic regimens for surgical patients.

Abstract Type 2 diabetes mellitus (T2DM) seriously threatens human health and the quality of life, cognitive impairment is considered as a common complication of T2DM. Neuroimaging meta-analysis found brain functional and structural abnormality in patients with T2DM. Therefore, the purpose of the meta-analysis was to identify brain regions of patients with T2DM-related cognitive impairment (T2DM-CI) where functional and structural indicators changed together or could not synchronize. A literature screening of neuroimaging studies on cognitive impairment in T2DM was conducted from 1 January 2007 to 26 May 2023 in PubMed, Web of Science, Cochrane Library, and Medline databases. The functional indicators we studied were amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and degree centrality (DC), while the structural indicator was gray matter (GM), which included gray matter volume (GMV) and cerebral cortical thickness. Studies reporting ALFF, ReHo, DC and GM abnormalities between T2DM-CI and healthy controls (HCs) were selected and their significant peak coordinates (x, y, z) and effect size (t-value) were extracted to perform a meta-analysis using anisotropic effect size sign differential mapping (AES-SDM) 5.15 software. Moreover, the brain regions with significant differences obtained from meta-analysis were saved as masks and then validated in our data. Total 19 studies and 20 datasets were involved in this study. Compared to HCs, combining ALFF, ReHo, and DC measurements, the brain activity of the left anterior cingulate/paracingulate gyri (ACC.L, BA24) in T2DM-CI patients increased significantly, while the brain activity of the left lingual gyrus (LING.L, BA18) in T2DM-CI patients decreased significantly. The GM indicator of the right superior temporal gyrus (STG.R, BA42) and left inferior occipital gyrus (IOG.L, BA19) in T2DM-CI patients decreased significantly. Meta-regression analysis showed the negative relationship between the brain activity reduction in LING.L and the percentage of female patients, as well as the negative relationship between GM reduction in IOG.L and T2DM duration. Furthermore, we validated a decrease in brain activity in the LING.L of T2DM-CI patients in our independent dataset. The decrease of brain activity in LING.L and the decrease of GM in IOG.L were closely related to visual impairment in T2DM-CI patients. These abnormal brain regions may be the main targets for future research, early intervention can delay the further development of cognitive impairment in T2DM patients and improve their quality of life, which also provided early biomarkers for clarifying the mechanism of cognitive impairment in T2DM.

Abstract Background The aim of this study was to assess the prognostic significance of serum direct bilirubin (DBIL) for patients newly diagnosed with myelodysplastic syndromes (MDS). Methods The clinical, laboratory, and follow-up data of MDS patients were collected, and the associations of DBIL levels with overall survival (OS) and leukemia-free survival (LFS) were analyzed. Result In total, 262 MDS patients were assigned to the high DBIL level group or the normal DBIL level group in the retrospective study. High DBIL was associated with older age, reduced hemoglobin, higher levels of β2-microglobin, lactate dehydrogenase, and serum ferritin, along with the number of co-mutations (> 1) and a higher frequency of ASXL1, KIT, and KRAS mutations. Multivariate analyses found that high DBIL level was an independent adverse predictor for OS (p = 0.002, hazard ratio = 2.723, 95%CI = 1.442–5.143) but not for LFS (p = 0.057, hazard ratio = 1.678, 95%CI = 0.986–2.857). A novel nomogram based on DBIL, sex, age, β2-microglobulin, lactate dehydrogenase, the Revised International Prognostic Scoring System (IPSS-R) was constructed, which demonstrated superior accuracy compared with the IPSS-R (C-index, 0.790 vs. 0.731, respectively). Conclusion An elevated DBIL level was identified as an independent adverse prognostic factor for MDS patients. An individualized prediction model was established and validated to improve prediction of OS and LFS.

Abstract Abdominal pain is a major symptom of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, and has a significant impact on patients’ quality of life. Given the evolving understanding of IBD pathology and management strategies, there is an urgent need to review the recent research findings. In this review, we have analyzed the epidemiology, pathophysiology, and management of abdominal pain in IBD over the past decade. We draw on the current literature and highlight emerging trends, challenges, and advances in this field. By synthesizing key findings, this review provides insights into the complex interplay between abdominal pain, disease progression, and therapeutic interventions for IBD.