Intervention of asprosin attenuates oxidative stress and neointima formation in vascular injury.

AIMS: Asprosin, a newly discovered hormone, is linked to insulin resistance. This study shows the roles of asprosin in vascular smooth muscle cells (VSMCs) proliferation, migration, oxidative stress and neointima formation of vascular injury. METHODS: Mouse aortic VSMCs were cultured, and platelet-derived growth factor-BB (PDGF-BB) was used to induce oxidative stress, proliferation and migration in VSMCs. Vascular injury was induced by repeatedly moving a guidewire in the lumen of carotid artery in mice. RESULTS: Asprosin overexpression promoted VSMC oxidative stress, proliferation and migration, which were attenuated by toll-like receptor 4 (TLR4) knockdown, antioxidant NAC, NOX1 inhibitor ML171 or NOX2 inhibitor GSK2795039. Asprosin overexpression increased NOX1/2 expressions, while asprosin knockdown increased heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase-1 (NQO-1) expressions. Asprosin inhibited Nrf2 nuclear translocation. Nrf2 activator sulforaphane increased HO-1 and NQO-1 expressions, and prevented asprosin-induced NOX1/2 upregulation, oxidative stress, proliferation and migration. Exogenous asprosin protein had similar roles to asprosin overexpression. PDGF-BB increased asprosin expressions. PDGF-BB-induced oxidative stress, proliferation and migration were enhanced by Nrf2 inhibitor ML385, but attenuated by asprosin knockdown. Vascular injury increased asprosin expression. Local asprosin knockdown in the injured carotid artery promoted HO-1 and NQO-1 expressions, but attenuated the NOX1 and NOX2 upregulation, oxidative stress, neointima formation and vascular remodeling in mice. INNOVATION AND CONCLUSION: Asprosin promotes oxidative stress, proliferation and migration of VSMCs via TLR4-Nrf2-mediated redox imbalance. Inhibition of asprosin expression attenuates VSMC proliferation and migration, oxidative stress and neointima formation in the injured artery. Asprosin might be a promising therapeutic target for vascular injury.

Convergent Validity Between the Motor Domain of PediaTracTM and Ages and Stages in Term and Preterm Infants at 2, 4, 6, and 9 Months of Age.

The primary aim of this study was to evaluate the convergent validity of the Motor domain (MOT) of PediaTracTM v3.0, an online developmental tracking instrument based on caregiver reports, with fine and gross motor domains (ASQ-FM and ASQ-GM) of the Ages and Stages Questionnaire (ASQ-3) in infants between 2- and 9 months of age. Participants were caregivers of 571 infants born term or preterm (gestational age <37 weeks) enrolled in a multi-site psychometric study of PediaTracTM. Findings revealed significant correlations between MOT and ASQ-3 scores at 2, 4, 6, and 9 months across time periods, term-preterm status, and biological sex. A significantly higher percentage of infants born preterm, compared with those born at term, was identified as a moderate or high risk on both the ASQ-3 and PediaTrac. Future investigations are warranted to further examine the psychometric properties of the MOT domain, including sensitivity, specificity, and positive and negative predictive value.

A comparative study on fundamental movement skills among children with autism spectrum disorder and typically developing children aged 7-10.

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition with unique differences in social interaction, communication, and a spectrum of behavioral characteristics. In the past, motor disturbance in individuals with ASD has not been considered a significant core deficit due to the predominant focus on sociability and communication issues. However, recent studies indicate that motor deficits are indeed associated with the fundamental symptoms of ASD. As there is limited research on the motor behavior of children with ASD, particularly in China, the objective of this study is to investigate the development of fundamental movement skills (FMS) in children with ASD and compare them to typically developing children. Method: The study recruited 108 children with ASD (87 boys, 21 girls) aged 7-10 years from two special education rehabilitation centers in Wuhan, China. For comparison, a control group of 108 typically developing children, matched by age and gender, was randomly selected from three local primary schools. FMS were assessed using the Movement Assessment Battery for Children - Second Edition (MABC-2), which evaluates manual dexterity, aiming and catching, as well as static and dynamic balance. Group differences on MABC-2 percentile scores were analyzed using descriptive statistics and Mann-Whitney U test. Effect sizes were also calculated for practical significance. Results: Findings from the study showed that a significant majority, around 80%, of children with ASD either displayed motor challenges or were at risk of developing such delays. When comparing to their typically developing peers, children with ASD scored notably lower in areas of manual dexterity, ball skills, and both static and dynamic balance (with all these findings being statistically significant at p < 0.001). Interestingly, gender did not show a significant influence on these results (p > 0.05). Conclusion: In addition to addressing the other skill development areas outlined in the diagnostic manual for ASD, clinicians diagnosing and treating children with ASD should also assess the presence of motor skill development. For individuals with ASD who have co-existing motor difficulties, it is essential to offer evidence-based interventions tailored to their specific needs.

Transfer and Retention Effects of a Motor Program in Children With Autism Spectrum Disorders.

The current study examined the acquisition, retention, and transfer effects of a motor program. Children with autism spectrum disorder participated in a 9-week program that targeted 13 fundamental motor skills based upon the Test of Gross Motor Development-3. Assessments were conducted before and after the program, as well as at 2-month follow-up. Significant improvements were found on not only the trained fundamental motor skills (acquisition) but also the untrained tasks on balance (transfer). The follow-up tests revealed continuous improvement on the trained locomotor skills (retention), as well as the untrained skills on balance (retention + transfer). These findings highlight the importance of continuous support and long-term participation on motor practices.

How does change in leisure-time physical activity influence the growth trajectory of depressive symptoms in college students?

Objectives: This longitudinal study was designed to examine the growth trajectory of depressive symptoms among early-stage college students and how the development of vigorous, moderate, and light leisure-time physical activity (LTPA) was related to the growth trajectory. Participants: Four hundred and eighty-eight first- and second-year undergraduate students completed measures of depressive symptoms and LTPA at the beginning, middle, and end of a semester. Methods: Latent growth mixture modeling (LGMM) was conducted. Results: On average, students reported mild levels of depressive symptoms with significant variability at the semester start, but the symptoms elevated over time. LGMM identified two trajectories: low/gradual (75.8%) and high/increasing (24.2%). For both groups, neither vigorous nor moderate LTPA development predicted the growth trajectory of depressive symptoms. However, the change of light LTPA was negatively and significantly associated with the growth trajectory. Even when controlling for covariances, increased light LTPA still had a unique effect on buffering depressive symptoms. Conclusion: There is great potential in targeting comprehensive LTPA strategies to improve college students' mental health and promote an active lifestyle.

Primary hepatic paraganglioma with megacolon: A case report.

Primary hepatic paraganglioma (PGL) is a rare neuroendocrine tumor characterized by clinical manifestations including paroxysmal hypertension, palpitation, abdominal pain and constipation. In the present study, the case of a 21-year-old woman with pathologically confirmed hepatic PGL with megacolon following surgery is reported. The patient initially visited Beijing Tiantan Hospital (Beijing, China) for hypoferric anemia. A triple-phase CT scan of the whole abdomen showed a large hypodense mass with a solid periphery and strong arterial enhancement of the peripheral solid portion of the liver. The sigmoid colon and rectum were obviously distended, filled with gas and intestinal contents. The patient was preoperatively diagnosed with iron deficiency anemia, liver injury and megacolon and then underwent partial hepatectomy, total colectomy and enterostomy. Microscopically, the liver cells exhibited an irregular zellballen pattern. In addition, immunohistochemical staining revealed that liver cells were positive for CD56, chromogranin A, vimentin, S-100, melan-A and neuron-specific enolase. Therefore, the diagnosis of primary PGL of the liver was confirmed. These findings suggested that primary hepatic PGL should not be excluded when megacolon occurs and comprehensive imaging evaluation is of great importance for its diagnosis.

Significance of anti-Jo-1 antibody's clinical stratification in idiopathic inflammatory myopathy and disease spectrum / 北京大学学报(医学版)

OBJECTIVE@#To investigate the significance of anti-histidyl tRNA synthetase (Jo-1) antibody in idiopathic inflammatory myopathies (IIM) and its diseases spectrum.@*METHODS@#We enrolled all the patients who were tested positive for anti-Jo-1 antibody by immunoblotting in Peking University People's Hospital between 2016 and 2022. And the patients diagnosed with anti-synthetase antibody syndrome (ASS) with negative serum anti-Jo-1 antibody were enrolled as controls. We analyzed the basic information, clinical characteristics, and various inflammatory and immunological indicators of the patients at the onset of illness.@*RESULTS@#A total of 165 patients with positive anti-Jo-1 antibody were enrolled in this study. Among them, 80.5% were diagnosed with connective tissue disease. And 57.6% (95/165) were diagnosed with IIM, including ASS (84/165, 50.9%), immune-mediated necrotizing myopathy (7/165, 4.2%) and dermatomyositis (4/165, 2.4%). There were 23.0% (38/165) diagnosed with other connective tissue disease, mainly including rheumatoid arthritis (11/165, 6.7%), undifferentiated connective tissue disease (5/165, 3.0%), interstitial pneumonia with autoimmune features (5/165, 3.0%), undifferentiated arthritis (4/165, 2.4%), Sjögren's syndrome (3/165, 1.8%), systemic lupus erythematosus (3/165, 1.8%), systemic vasculitis (3/165, 1.8%), and so on. Other cases included 3 (1.8%) malignant tumor patients, 4 (2.4%) infectious cases and so on. The diagnoses were not clear in 9.1% (15 /165) of the cohort. In the analysis of ASS subgroups, the group with positive serum anti-Jo-1 antibody had a younger age of onset than those with negative serum anti-Jo-1 antibody (49.9 years vs. 55.0 years, P=0.026). Clinical manifestations of arthritis (60.7% vs. 33.3%, P=0.002) and myalgia (47.1% vs. 22.2%, P=0.004) were more common in the ASS patients with positive anti-Jo-1 antibody. With the increase of anti-Jo-1 antibody titer, the incidence of the manifestations of arthritis, mechanic hands, Gottron sign and Raynaud phenomenon increased, and the proportion of abnormal creatine kinase and α-hydroxybutyric dehydrogenase index increased in the ASS patients. The incidence of myalgia and myasthenia were significantly more common in this cohort when anti-Jo-1 antibody-positive ASS patients were positive for one and more myositis specific antibodies/myositis associated autoantibodies (P < 0.05).@*CONCLUSION@#The disease spectrum in patients with positive serum anti-Jo-1 antibody includes a variety of diseases, mainly ASS. And anti-Jo-1 antibody can also be found in many connective tissue diseases, malignant tumor, infection and so on.

Epidemiological characteristics and genotypes of parechovirus A from children with acute diarrhea in Beijing in 2021 / 公共卫生与预防医学

Objective To investigate the epidemiological chatacteristics and genotypes of parechovirus A (PeV-A) from children with acute diarrhea in Beijing in 2021. Methods Fecal samples were randomly collected from outpatient children under 60 months with acute diarrhea in a sentinel hospital in Beijing from January to December of 2021. RNA was extracted and detected for PeV-A by real-time RT-PCR. Nested RT-PCR was performed to amplify the VP3/VP1 conjunction region. PeV-A genotypes were determined based on sequencing and NCBI BLAST. Group A rotavirus, norovirus, enteric adenovirus, astrovirus and sapovirus were also detected for co-infection analysis. Phylogenetic and statistical analyses were performed using bioinformatics and statistical software. Results Of the 198 stool samples, 11 were positive for PeV-A, with a detection rate of 5.56% (11/198). Among them, 2 cases were co-infected with enteric adenovirus. 81.82% (9/11) of PeV-A infected cases were under 24 months. The highest detection rate was observed in fall, which was 12.50% (7/56). 90.91%（10/11）of PeV-A infection occurred in summer and fall. Among the 11 PeV-A isolates, 9 were sequenced successfully, of which 7 belonged to PeV-A1B genotype and 2 belonged to PeV-A3 genotype. Conclusion PeV-A1B and PeV-A3 are identified in children with acute gastroenteritis in Beijing in 2021. Infants and young children under 2 years old are the high-risk population for PeV-A infection. Most infections occur in summer and fall.

Etiological diagnostic value of metagenomic next-generation sequencing in peritoneal dialysis-related peritonitis / 中华肾脏病杂志

Objective:To explore the etiological diagnostic value of metagenomic next-generation sequencing (mNGS) in peritoneal dialysis (PD)-related peritonitis.Methods:The study was a retrospective cohort study. The clinical data of patients with PD-related peritonitis who were treated and underwent microbial cultivation and mNGS test at the same time from June 2020 to July 2021 in the Affiliated Drum Tower Hospital, Medical School of Nanjing University were analyzed. The positive rate, detection time and consistency between mNGS test and traditional microbial culture were compared.Results:A total of 18 patients with age of (50.4±15.4) years old and median dialysis time of 34.0 (12.4, 62.0) months were enrolled in the study, including 11 males and 7 females. Pathogenic microorganisms were isolated in 17 patients by mNGS test, with a positive rate of 17/18, which was higher than 13/18 of microbial culture, but the difference was not statistically significant ( P=0.219). Both mNGS test and microbial culture isolated positive pathogenic bacteria in 12 patients, and mNGS test isolated the same types of pathogenic bacteria as microbial cultivation did in 11 patients. In five patients with negative microbial culture, mNGS test also isolated pathogenic microorganisms, including 3 cases of Staphylococcus epidermidis, 1 case of Mycobacterium tuberculosis and 1 case of Ureaplasma urealyticum. In 1 patient, microbial culture isolated pathogenic bacteria ( Escherichia coli) whereas mNGS test did not. The detection time of mNGS was 25.0 (24.0, 27.0) h, which was significantly shorter than 89.0 (72.8, 122.0) h of microbial culture ( Z=3.726, P<0.001). Conclusions:mNGS test can improve the detection rate of pathogenic microorganisms in PD-related peritonitis and greatly shorten the detection time, and has good consistency with microbial culture. mNGS may provide a new approach for pathogen identification of PD-related peritonitis, especially refractory peritonitis.

Effects of tumor necrosis factor-alpha/extracellular signal-regulated kinase pathway on migration ability of HaCaT cells and full-thickness skin defects in mice / 中华烧伤杂志

Objective: To investigate the effects of tumor necrosis factor-alpha (TNF-α)/extracellular signal-regulated kinase (ERK) pathway on the migration ability of HaCaT cells and full-thickness skin defects in mice. Methods: The experimental research method was adopted. According to the random number table (the same below), HaCaT cells were divided into the normal oxygen group and the hypoxia group cultured under hypoxia (with oxygen volume fraction of 1%, the same below) condition. After 24 hours of culture, the significantly differentially expressed genes between the 2 groups were screened using the microarray confidence analysis software SAM4.01. The significance of the number of each gene in the signaling pathway was analyzed through the Kyoto encyclopedia of genes and genomes to screen the significantly differentially signaling pathways (n=3). HaCaT cells were cultured for 0 (immediately), 3, 6, 12, and 24 h under hypoxia condition. The secretion level of TNF-α was detected by enzyme-linked immunosorbent assay (ELISA), and the number of samples was 5. HaCaT cells were divided into normal oxygen group, hypoxia alone group, and hypoxia+inhibitor group cultured with FR180204 (an ERK inhibitor) and under hypoxia condition. The cells were cultured for 3, 6, 12, and 24 h. The migration ability of the cells was detected by scratch test (n=12). The expressions of phosphorylated nuclear factor kappa B (p-NF-κB), phosphorylated p38 (p-p38), phosphorylated ERK1/2 (p-ERK1/2), N-cadherin, and E-cadherin in HaCaT cells were detected by Western blotting under hypoxic condition for 0, 3, 6, 12, and 24 h (n=3). Sixty-four BALB/c male mice aged 6 to 8 weeks were used to make a full-thickness skin defect wound model on the dorsum of the mice. The mice were divided into the blank control group and the inhibitor group treated with FR180204, with 32 mice in each group being treated accordingly. On post injury day (PID) 0, 3, 6, 9, 12, and 15, the wound conditions of mice were observed and the healing rate was calculated (n=8). On PID 1, 3, 6, and 15, hematoxylin-eosin staining was used to observe neovascularization, inflammatory cell infiltration, and epidermal regeneration on wound, Masson staining was used to observe collagen deposition on wound, the expressions of p-NF-κB, p-p38, p-ERK12, N-cadherin, and E-cadherin in wound tissue were detected by Western blotting (n=6), the number of Ki67 positive cells and the absorbance value of vascular endothelial growth factor (VEGF) were detected by immunohistochemistry (n=5), the protein expressions of interleukin 6 (IL-6), IL-10, IL-1β, and CCL20 in wound tissue were detected by ELISA (n=6). Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, factorial design analysis of variance, Tukey test, least significant difference test, and independent sample t test. Results: After 24 hours of culture, compared with normal oxygen group, 7 667 genes were up-regulated and 7 174 genes were down-regulated in cells in hypoxic group. Among the above differentially expressed genes, the TNF-α signaling pathway had significant change (P<0.05) with large number of genes. Under hypoxia condition, the expression of TNF-α at 24 h of cell culture was (11.1±2.1) pg/mL, which was significantly higher than (1.9±0.3) pg/mL at 0 h (P<0.05). Compared with normal oxygen group, the migration ability of cells in hypoxia alone group was significantly enhanced at 6, 12, and 24 h of cell culture (with t values of 2.27, 4.65, and 4.67, respectively, P<0.05). Compared with hypoxia alone group, the migration ability of cells in hypoxia+inhibitor group was significantly decreased at 3, 6, 12, and 24 h of cell culture (with t values of 2.43, 3.06, 4.62, and 8.14, respectively, P<0.05). Under hypoxia condition, the expressions of p-NF-κB, p-ERK1/2, and N-cadherin were increased significantly at 12 and 24 h of cell culture compared with 0 h of culture (P<0.05), the expression of p-p38 was significantly increased at 3, 6, 12, and 24 h of cell culture (P<0.05), the expression of E-cadherin was significantly decreased at 6, 12, and 24 h of cell culture (P<0.05), the expression of p-ERK1/2, p-NF-κB, and E-cadherin was time-dependent. Compared with blank control group, on PID 3, 6, 9, 12, and 15, the wound healing rate of mice in inhibitor group was significantly decreased (P<0.05); there were more inflammatory cell infiltration around the wound edge of mice in inhibitor group on PID 3, 6, and 15, especially on PID 15, a large number of tissue necrosis and discontinuous new epidermal layer were observed on the wound surface, and collagen synthesis and new blood vessels were reduced; the expression of p-NF-κB in the wound of mice in inhibitor group was significantly decreased on PID 3 and 6 (with t values of 3.26 and 4.26, respectively, P<0.05) but significantly increased on PID 15 (t=3.25, P<0.05), the expressions of p-p38 and N-cadherin were significantly decreased on PID 1, 3, and 6 (with t values of 4.89, 2.98, 3.98, 9.51, 11.69, and 4.10, respectively, P<0.05), the expression of p-ERK1/2 was significantly decreased on PID 1, 3, 6, and 15 (with t values of 26.69, 3.63, 5.12, and 5.14, respectively, P<0.05), the expression of E-cadherin was significantly decreased on PID 1 (t=20.67, P<0.05) but significantly increased on PID 6 (t=2.90, P<0.05); the number of Ki67 positive cells and absorbance value of VEGF of wound in inhibitor group were significantly decreased on PID 3, 6, and 15 (with t values of 4.20, 7.35, 3.34, 4.14, 3.20, and 3.73, respectively, P<0.05); the expression of IL-10 in the wound tissue of the inhibitor group was significantly decreased on PID 6 (t=2.92, P<0.05), the expression of IL-6 was significantly increased on PID 6 (t=2.73, P<0.05), the expression of IL-1β was significantly increased on PID 15 (t=3.46, P<0.05), and CCL20 expression levels were significantly decreased on PID 1 and 6 (with t values of 3.96 and 2.63, respectively, P<0.05) but significantly increased on PID 15 (t=3.68, P<0.05). Conclusions: The TNF-α/ERK pathway can promote the migration of HaCaT cells, and regulate the healing of full-thickness skin defect wounds in mice by affecting the expression of inflammatory cytokines and chemokines.

Correlation between axial lengths and anterior segment parameters evaluated by swept-source optical coherence tomography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the correlation between axial lengths and anterior segment parameters using swept-source optical coherence tomography(SS-OCT).METHODS:For the cross-sectional clinical study, a total of 109 adult volunteers with different degrees of myopia recruited from January 1, 2022, to March 31, 2022, at the ophthalmology clinic of the First Affiliated Hospital of Zhengzhou University were included. Participants were divided into 4 groups based on axial length(AL): group A(AL≤24.0mm), group B(24.0mm&#x003C;AL≤25.0mm), group C(25.0mm&#x003C;AL≤26.0mm)and group D(AL&#x003E;26.0mm). Anterior segment examinations were performed using SS-OCT, including: central corneal thickness(CCT), lens thickness(LT), anterior chamber depth(ACD), anterior chamber width(ACW), angle opening distance(AOD500), angle recess area(ARA500), trabecular iris space area(TISA500), trabecular iris angle(TIA500), crystalline lens rise(CLR). The relationships between these data and AL, spherical equivalent(SE)were analyzed.RESULTS:There was no difference in the comparison of CCT among the four groups(P&#x003E;0.05). There were differences in SE, LT, ACD, ACW, AOD500, ARA500, TISA500, TIA500 and CLR among the four groups(all P&#x003C;0.01). SE and LT were negatively correlated with AL(r=-0.75, -0.41, all P&#x003C;0.01); ACD, ACW and CLR were positively correlated with AL(r=0.58, 0.45, 0.54, all P&#x003C;0.01); AOD500, ARA500, TISA500 and TIA500(temporal and nasal side)were positively correlated with AL(all P&#x003C;0.01). ACD and CLR were negatively correlated with SE(r=-0.21,-0.25, all P&#x003C;0.01), and LT was positively correlated with SE(r=0.21, P&#x003C;0.05).CONCLUSION:As AL increases, CCT remains unchanged while the ACD and ACW increase. The position of the crystalline lens moves backward and LT decreases.

Spatiotemporally resolved metabolomics and isotope tracing reveal CNS drug targets

Deconvolution of potential drug targets of the central nervous system (CNS) is particularly challenging because of the complicated structure and function of the brain. Here, a spatiotemporally resolved metabolomics and isotope tracing strategy was proposed and demonstrated to be powerful for deconvoluting and localizing potential targets of CNS drugs by using ambient mass spectrometry imaging. This strategy can map various substances including exogenous drugs, isotopically labeled metabolites, and various types of endogenous metabolites in the brain tissue sections to illustrate their microregional distribution pattern in the brain and locate drug action-related metabolic nodes and pathways. The strategy revealed that the sedative-hypnotic drug candidate YZG-331 was prominently distributed in the pineal gland and entered the thalamus and hypothalamus in relatively small amounts, and can increase glutamate decarboxylase activity to elevate γ-aminobutyric acid (GABA) levels in the hypothalamus, agonize organic cation transporter 3 to release extracellular histamine into peripheral circulation. These findings emphasize the promising capability of spatiotemporally resolved metabolomics and isotope tracing to help elucidate the multiple targets and the mechanisms of action of CNS drugs.

Etiological diagnostic value of metagenomic next-generation sequencing in peritoneal dialysis-related peritonitis / 中华肝脏病杂志

Objective: To explore the etiological diagnostic value of metagenomic next-generation sequencing (mNGS) in peritoneal dialysis (PD)-related peritonitis. Methods: The study was a retrospective cohort study. The clinical data of patients with PD-related peritonitis who were treated and underwent microbial cultivation and mNGS test at the same time from June 2020 to July 2021 in the Affiliated Drum Tower Hospital, Medical School of Nanjing University were analyzed. The positive rate, detection time and consistency between mNGS test and traditional microbial culture were compared. Results: A total of 18 patients with age of (50.4±15.4) years old and median dialysis time of 34.0 (12.4, 62.0) months were enrolled in the study, including 11 males and 7 females. Pathogenic microorganisms were isolated in 17 patients by mNGS test, with a positive rate of 17/18, which was higher than 13/18 of microbial culture, but the difference was not statistically significant (P=0.219). Both mNGS test and microbial culture isolated positive pathogenic bacteria in 12 patients, and mNGS test isolated the same types of pathogenic bacteria as microbial cultivation did in 11 patients. In five patients with negative microbial culture, mNGS test also isolated pathogenic microorganisms, including 3 cases of Staphylococcus epidermidis, 1 case of Mycobacterium tuberculosis and 1 case of Ureaplasma urealyticum. In 1 patient, microbial culture isolated pathogenic bacteria (Escherichia coli) whereas mNGS test did not. The detection time of mNGS was 25.0 (24.0, 27.0) h, which was significantly shorter than 89.0 (72.8, 122.0) h of microbial culture (Z=3.726, P<0.001). Conclusions: mNGS test can improve the detection rate of pathogenic microorganisms in PD-related peritonitis and greatly shorten the detection time, and has good consistency with microbial culture. mNGS may provide a new approach for pathogen identification of PD-related peritonitis, especially refractory peritonitis.

Dexmedetomidine Attenuates Lipopolysaccharide-Induced Sympathetic Activation and Sepsis via Suppressing Superoxide Signaling in Paraventricular Nucleus.

Sympathetic overactivity contributes to the pathogenesis of sepsis. The selective α2-adrenergic receptor agonist dexmedetomidine (DEX) is widely used for perioperative sedation and analgesia. We aimed to determine the central roles and mechanisms of DEX in attenuating sympathetic activity and inflammation in sepsis. Sepsis was induced by a single intraperitoneal injection of lipopolysaccharide (LPS) in rats. Effects of DEX were investigated 24 h after injection of LPS. Bilateral microinjection of DEX in the paraventricular nucleus (PVN) attenuated LPS-induced sympathetic overactivity, which was attenuated by the superoxide dismutase inhibitor DETC, cAMP analog db-cAMP or GABAA receptor antagonist gabazine. Superoxide scavenger tempol, NADPH oxidase inhibitor apocynin, adenylate cyclase inhibitor SQ22536 or PKA inhibitor Rp-cAMP caused similar effects to DEX in attenuating LPS-induced sympathetic activation. DEX inhibited LPS-induced superoxide and cAMP production, as well as NADPH oxidase, adenylate cyclase and PKA activation. The roles of DEX in reducing superoxide production and NADPH oxidase activation were attenuated by db-cAMP or gabazine. Intravenous infusion of DEX inhibited LPS-induced sympathetic overactivity, NOX activation, superoxide production, TNF-α and IL-1ß upregulation in the PVN and plasma, as well as lung and renal injury, which were attenuated by the PVN microinjection of yohimbine and DETC. We conclude that activation of α2-adrenergic receptors with DEX in the PVN attenuated LPS-induced sympathetic overactivity by reducing NADPH oxidase-dependent superoxide production via both inhibiting adenylate cyclase-cAMP-PKA signaling and activating GABAA receptors. The inhibition of NADPH oxidase-dependent superoxide production in the PVN partially contributes to the roles of intravenous infusion of DEX in attenuating LPS-induced sympathetic activation, oxidative stress and inflammation.

Motor networks in children with autism spectrum disorder: a systematic review on EEG studies.

Motor disturbance and altered motor networks are commonly reported in individuals with autism spectrum disorder (ASD). It has been suggested that electroencephalogram (EEG) can be used to provide exquisite temporal resolution for understanding motor control processes in ASD. However, the variability of study design and EEG approaches can impact our interpretation. Here, we conducted a systematic review on recent 11 EEG studies that involve motor observation and/or execution tasks and evaluated how these findings help us understand motor difficulties in ASD. Three behavior paradigms with different EEG analytic methods were demonstrated. The main findings were quite mixed: children with ASD did not always show disrupted neuronal activity during motor observation. Additionally, they might have intact ability for movement execution but have more difficulties in neuronal modulation during movement preparation. We would like to promote discussions on how methodological selections of behavioral tasks and data analytic approaches impact our interpretation of motor deficits in ASD. Future EEG research addressing the inconsistency across methodological approaches is necessary to help us understand neurophysiological mechanism of motor abnormalities in ASD.

Response Time Modulates the Relationship Between Implicit Learning and Motor Ability in Children With and Without Autism Spectrum Disorders: A Preliminary Study.

Difficulty with implicit learning plays an important role in the symptomology of autism spectrum disorder (ASD). However, findings in motor learning are inconsistent. This study evaluated implicit sequence learning and its relationship with motor ability in children with and without ASD. We adopted a classic serial reaction time task with a retention task and three awareness tests. The Movement Assessment Battery for Children was administered to assess children's motor ability. Significant learning differences between children with and without ASD were only found in retention but not immediately after the serial reaction time task. These findings suggest that the impaired implicit learning in ASD is characterized as impaired consolidation where the relatively permanent changes are missing. Exploratory moderation analyses revealed a significant relationship between implicit learning and motor ability for individuals with faster response time. We argue the importance of response speed for optimal learning and should be weighted more for future intervention in children with ASD.

Does Symptom Severity Moderate the Relationship Between Body Mass Index and Motor Competence in Children With Autism Spectrum Disorders? An Exploratory Study.

To date, there has been little research considering both autism spectrum disorder (ASD) symptom severity and motor impairment simultaneously when investigating their associations with obesity. This study was designed to identify the moderating role of symptom severity in the relationship between motor competence and overweight/obesity for children with ASD. Seventy-eight children with a clinical diagnosis were recruited from a large autism rehabilitation center in Wuhan, China. Chi-square, partial correlation, and moderation regression analyses revealed that the prevalence of overweight and obesity was similar regardless of symptom severity. Balance was the only motor skill that correlated with body mass index. Furthermore, symptom severity significantly moderated the correlation. Children with low autism severity might be more likely to demonstrate the relationship between balance and body mass index than those with high autism severity. Combating obesity by enhancing motor competence should cautiously consider personal and environment factors such as individual severity of ASD.

Immunotherapy of Cancer by Targeting Regulatory T cells.

Regulatory T (Treg) cells maintain immune homeostasis by inhibiting abnormal/overactive immune responses to both autogenic and nonautogenic antigens. Treg cells play an important role in immune tolerance, autoimmune diseases, infectious diseases, organ transplantation, and tumor diseases. Treg cells have two functional characteristics: T cell anergy and immunosuppression. Treg cells remain immune unresponsive to high concentrations of interleukin-2 and anti-CD3 monoclonal antibodies. In addition, the activation of Treg cells after TCR-mediated signal stimulation inhibits the activation and proliferation of effector T cells. In the process of tumor development, Treg cells accumulate locally in the tumor and lead to tumor escape by inducing anergy and immunosuppression. It is believed that targeted elimination of Treg cells can activate tumor-specific effector T cells and improve the efficiency of cancer immunotherapy. Therefore, inhibition/clearance of Treg cells is a promising strategy for enhancing antitumor immunity. Here, we review studies of cancer immunotherapies targeting Treg cells.

Profiles of Health-Related Quality of Life and Their Relationships With Happiness, Physical Activity, and Fitness.

Purpose: Health-related quality of life (HRQOL) reflects a perceived sense of physical and mental well-being over time, encompassing both physical health and psychosocial health. Although these two health concepts have been often examined as a whole, few studies have explored the possibility of mixed profiles. We designed this study to identify Chinese adolescents' HRQOL profiles and their associations with happiness, physical activity, and fitness. Method: 544 high-school students completed validated Chinese-version questionnaires assessing HRQOL, happiness, and physical activity behavior while their fitness level was evaluated based on China National Fitness Test Program. A two-step cluster analysis and MANOVAs were conducted. Results: We identified four distinct clusters: low HRQOL, psychosocial health-oriented, physical health-oriented, and high HRQOL. There were significant differences among clusters in happiness, physical activity, and fitness, with "high HRQOL" group being the most adaptive cluster while "low HRQOL" group the least. Both psychosocial health-oriented and physical health-oriented clusters demonstrated dimension-related features. Conclusion: Health-related quality of life in Chinese adolescents is a multidimensional construct. Although its physical and psychosocial functioning are often interacted, different dimensions have unique but specified roles. Particularly, physical functioning might not only be associated with physical and health condition but also with positive emotion, especially when psychosocial satisfaction is lacking. It is important to pay specific attention to the interactions among the dimensions and how the interactions combine and function together to influence adolescents' behavior.