Evaluating the link between immune characteristics and attention deficit hyperactivity disorder through a bi-directional Mendelian randomization study.

Context: Despite the recognition of attention deficit hyperactivity disorder (ADHD) as a multifaceted neurodevelopmental disorder, its core causes are still ambiguous. The objective of this study was to explore if the traits of circulating immune cells contribute causally to susceptibility to ADHD. Methods: By employing a unified GWAS summary data covering 731 immune traits from the GWAS Catalog (accession numbers from GCST0001391 to GCST0002121), our analysis focused on the flow cytometry of lymphocyte clusters, encompassing 3,757 Sardinians, to identify genetically expected immune cells. Furthermore, we obtained summarized GWAS statistics from the Psychiatric Genomics Consortium to evaluate the genetic forecasting of ADHD. The studies employed ADHD2019 (20,183 cases and 35,191 controls from the 2019 GWAS ADHD dataset) and ADHD2022 (38,691 cases and 275,986 controls from the 2022 GWAS ADHD dataset). Through the examination of genome-wide association signals, we identified shared genetic variances between circulating immune cells and ADHD, employing the comprehensive ADHD2022 dataset. We primarily utilized inverse variance weighted (IVW) and weighted median methods in our Mendelian randomization research and sensitivity assessments to evaluate diversity and pleiotropy. Results: After adjusting for false discovery rate (FDR), three distinct immunophenotypes were identified as associated with the risk of ADHD: CD33 in Im MDSC (OR=1.03, CI: 1.01~1.04, P=3.04×10-5, PFDR =0.015), CD8br NKT %T cell (OR=1.08, 95%CI: 1.04~1.12, P=9.33×10-5, PFDR =0.023), and CD8br NKT %lymphocyte (OR=1.08, 95%CI: 1.03~1.12, P=3.59×10-4, PFDR =0.066). Furthermore, ADHD showed no statistical effects on immunophenotypes. It's worth noting that 20 phenotypes exist where ADHD's appearance could diminish 85% of immune cells, including FSC-A in myeloid DC (ß= -0.278, 95% CI: 0.616~0.931, P=0.008), CD3 in CD45RA- CD4+ (ß= -0.233, 95% CI: 0.654~0.960, P=0.017), CD62L- monocyte AC (ß=0.227, 95% CI: 0.038~1.518, P=0.019), CD33 in CD33br HLA DR+ CD14dim (ß= -0.331, 95% CI: 0.543~0.950, P=0.020), and CD25 in CD39+ resting Treg (ß=0.226, 95% CI: 1.522, P=0.022), and FSC-A in monocytes (ß= -0.255, 95% CI: 0.621~0.967, P=0.234), among others. Conclusion: Studies indicate that the immune system's response influences the emergence of ADHD. The findings greatly improve our understanding of the interplay between immune responses and ADHD risk, aiding in the development of treatment strategies from an immunological perspective.

Effect of psoralen on rat osteoblasts injuries induced by TCP wear particles in vitro and its mechanism / 中国应用生理学杂志

To investigate the effect and mechanism of psoralen on calvarial osteoblasts injuries caused by tricalcium phosphate (TCP) wear particles in vitro. Primary osteoblasts were obtained from the calvaria of neonatal SD rat by the series of digestion and were identified with ALP staining. Calvarial osteoblasts were treated with TCP wear particles for 48 h to establish the in vitro model of osteoblasts injuries. The rat osteoblasts were randomly divided into control group, TCP wear particles (0.1 mg/ml) group, psoralen treated (at the concentrations of 10, 10, 10 mol/L) groups. WST assay and the flow cytometry were used to detect the cell viability of osteoblasts and apoptosis, respectively. Chemical colorimetry was performed to examine ALP activity of osteobalsts. When the osteoblasts were treated for 14 day, mineral nodules formation was observed with alizarin red S staining. Western blot was applied to examine protein expressions of glucose regulated protein78/94(GRP78/94), inositol dependent enzyme 1 alpha (IREα), spliced X-box binding protein 1 (XBP1s) and phosphorylated c-Jun N-terminal kinase (p-JNK) in calvarial osteoblasts. Compared with control group, the cell viability of osteoblasts, ALP activity and mineral nodules formation in TCP group were decreased significantly (P＜0.05), while the percentage of apoptosis and protein expressions of GRP78/94, IRE1α, XBP1 and p-JNK were obviously increased in calvarial osteoblasts (P＜0.05). Compared with TCP group, the injuries of calvarial osteoblasts and cell apoptosis in psoralen treated groups were obviously decreased (P＜0.05), and the expression levels of GRP78/94, IRE1α, XBP1 and p-JNK were down-regulated remarkably (P＜0.05). Psoralen prevents osteoblasts injuries caused by TCP wear particles through IRE1α-XBP1s-JNK signaling pathway activation.

Salvianolic acid B decreases interleukin-1β-induced colitis recurrence in mice / 中华医学杂志(英文版)

BACKGROUND@#Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease (IBD). Increasing evidences has proved that tight junction (TJ) barrier dysfunction is one of the pathological mechanisms of IBD. The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence.@*METHODS@#Eighty C57BL/6 mice were randomly divided into four groups including normal group, colitis group, sulfasalazine (SASP) treated group, and traditional Chinese drug salvianolic acid B (Sal B) treated group. Colitis was established in mice by free drinking water containing dextran sulfate sodium, after treatments by SASP and Sal B, recombinant human interleukin-1β (IL-1β) was injected intraperitoneally to induce colitis recurrence.@*RESULTS@#Compared with sham control, cell apoptosis in colitis group was increased from 100.85 ± 3.46% to 162.89 ± 11.45% (P = 0.0038), and TJ dysfunction marker myosin light chain kinase (MLCK) was also significantly increased from 99.70 ± 9.29% to 296.23 ± 30.78% (P = 0.0025). The increased cell apoptosis was reversed by both SASP (125.99 ± 8.45% vs. 162.89 ± 11.45%, P = 0.0059) and Sal B (104.27 ± 6.09% vs. 162.89 ± 11.45%, P = 0.0044). High MLCK expression in colitis group was reversed by Sal B (182.44 ± 89.42% vs. 296.23 ± 30.78%, P = 0.0028) but not influenced by SASP (285.23 ± 41.04% vs. 296.23 ± 30.78%, P > 0.05). The recurrence rate induced by recombinant human IL-1β in Sal B-treated group was significantly lower than that in SASP-treated group.@*CONCLUSIONS@#These results suggested a link between intestinal mucosal barrier dysfunction, especially TJ barrier dysfunction, and colitis recurrence. The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence. This study might provide potential treatment strategies for IBD recurrence.

Values of different fungal infection risk scoring methods for the early diagnosis of invasive Candida infection / 中国感染控制杂志

Objective To compare diagnostic value of four fungal scoring methods in invasive Candida infection,provide evidence for early diagnosis and treatment of invasive Candida infection.Methods High-risk patients with invasive Candida infection in the intensive care unit(ICU) in a hospital from 2011 to 2016 were analyzed retrospectively.According to diagnostic criteria,patients were divided into four groups:non-infection group,suspected infection group,clinically diagnosed group,and confirmed group,patients were conducted multi-diseases risk assessment (MDRA) score,invasive fungal infections risk scoring system (IFIRSS) score,Sevilla score,and Candida score,diagnostic value of four scoring methods for invasive Candida infection were evaluated.Results There were 275 high-risk patients,138 in non-infection group,63 in suspected infection group,and 74 in infection group(clinically diagnosed group:n =64;confirmed group:n =10).The age and length of hospital stay in the infection group were all higher than non-infection group (both P＜0.05).74 strains of Candida were isolated from 74 infected patients,mainly Candida albicans (n =60,81.1％).Positive rates for MDRA score,Candida score,Sevilla score,and IFIRSSscore were 41.5％(n =114),30.2％(n =83),15.3％(n =42),and 8.4％ (n =23) respectively.Of four MDRA scoring methods,MDRA had the higher sensitivity(Se,59％) but lowest specificity(Sp,66％);IFIRSS had higher Sp(91％) but very low Se (9％);Sevilla score had the highest Sp (96％)and higher Se(45％);Candida score had the highest Se(68％) and higher Sp (90％).Conclusion Sevilla score has higher Se and Sp,which can be used in early diagnosis of invasive Candida infection;Candida score has the highest coincidence with clinical diagnostic criteria for invasive Candida infection,both Se and Sp are high,which is of great value for early diagnosis of invasive Candida infection.

A systematic review of stem cells in treatment of spinal cord injury and a network Meta-analysis of the therapeutic effects via different transplantation ways / 中国组织工程研究

BACKGROUND:Stem cell transplantation has been used in the clinical treatment of spinal cord injury.However,the efficacy and safety are still controversial.Although there are many approaches for stem cell transplantation,which one is better is unclear as yet.OBJECTIVE:To systematically evaluate the efficacy and safety of stem cell transplantation for spinal cord injury,and to compare the therapeutic difference in stem cell transplantation via different approaches.METHODS:A computer-based online search was conducted in PubMed,The Cochrane Library (Issue 4,2016),Embase,CNKI,VIP,CBM,and Wan-Fang databases up to May 13,2016 to screen the relevant randomized clinical controlled trials of stem cells in the treatment of spinal cord injury.Two reviewers independently selected the studies,extracted information,and assessed the quality of included trials.Data extracted from eligible studies was pooled and meta-analyzed using Stata13.1 and Gemtc0.14.3 software.RESULTS AND CONCLUSION:A total of 10 randomized controlled trials involving 546 patients (294 in stem cells group and 252 in rehabilitation treatment group) were included.The results of meta-analysis showed that stem cell transplantation had an advantage over rehabilitation treatment in increasing American Spinal Cord Injury Association (ASIA) motor score,ASIA sensory score,Barthel Index,and decreasing the bladder residual urine volume.The incidence of low fever,abdominal distension,headache,lower limb numbness,and meningeal irritation was 14％,7％,7％,8％,and 7％,respectively.Taking the rehabilitation treatment as a common reference,the results of the network meta-analysis showed that there were no significant differences in ASIA motor score,ASIA sensory score,Barthel Index,and incidence of complications among subarachnoid injection,intravenous injection,and intralesional injection.Compared with the rehabilitation treatment,only stem cell transplantation via subarachnoid injection had significant differences in ASIA motor score [MD=9.77,95％CI (0.26,21.46)],and ASIA sensory score [MD=25.79,95％CI (10.07,45.27)].To conclude,the stem cells transplantation via subarachnoid injection is considered the most effective transplantation method.Due to the limitations of the included studies,more high-quality randomized controlled trials are required to verify the above conclusion.In addition,future studies should focus on the long-term efficacy and safety of stem cell transplantation in the treatment of spinal cord injury,and should investigate the clinical effects on spinal cord injury with different ASIA grades,types of stem cells,and transplantation time.