Understanding the association between adverse childhood experiences and subsequent attention deficit hyperactivity disorder: A systematic review and meta-analysis of observational studies.

OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood, which may be related to adverse childhood experiences (ACEs). Our study aims to explore the association between ACEs and subsequent ADHD, and analyze the potential moderators. METHODS: Literature search was conducted by a combined computer-assisted and manual method. Studies were included if they had reported the association between ACEs and subsequent ADHD. Overall estimates of odds ratios (ORs) were obtained using random-effects meta-analyses, meta-regressions and further stratified analyses were conducted to examine potential moderator variables. RESULTS: Totals of 70 studies involving nearly 4 million participants from among 6,452 unique articles were included. In the primary analyses, ACEs were found to be associated with subsequent ADHD (OR = 1.68, 95% CI: 1.54-1.83), and the negative effects of different forms of ACEs for ADHD were nonequivalent. Such as lived in the stepfamily, been adopted or fostered, and experienced sexual abuse were more deleterious than others. It was found that individuals who had experienced multiple ACEs or who are female were more vulnerable to ADHD. CONCLUSIONS: The findings provide critical evidence for understanding the association between ACEs and ADHD. ACEs could increase the susceptibility of ADHD, especially for individuals who ever experienced multiple ACEs and females.

Efficacy of Online Intervention for ADHD: A Meta-Analysis and Systematic Review.

Background: With the popularity of computers, the internet, and the global spread of COVID-19, more and more attention deficit hyperactivity disorder (ADHD) patients need timely interventions through the internet. At present, there are many online intervention schemes may help these patients. It is necessary to integrate data to analyze their effectiveness. Objectives: Our purpose is to integrate the ADHD online interventions trials, study its treatment effect and analyze its feasibility, and provide reference information for doctors in other institutions to formulate better treatment plans. Methods: We searched PubMed, EMBASE and Cochrane libraries. We didn't limit the start date and end date of search results. Our last search was on December 1, 2021. The keyword is ADHD online therapy. We used the Cochrane bias risk tool to assess the quality of included studies, used the standardized mean difference (SMD) as an effect scale indicator to measure data. Random effects model, subgroup analysis were used to analyze the data. Results: Six randomized controlled trials (RCTs) were identified, including 261 patients with ADHD. These studies showed that online interventions was more effective than waiting list in improving attention deficit and social function of adults and children with ADHD. The attention deficit scores of subjects were calculated in six studies. The sample size of the test group was 123, the sample size of the control group was 133, and the combined SMD was -0.73 (95% confidence interval: -1.01, -0.44). The social function scores of subjects were calculated in six studies. The sample size of the experimental group was 123 and the control group was 133. The combined SMD was -0.59 (95% confidence interval: -0.85, -0.33). Conclusions: The results show that online interventions of ADHD may be an effective intervention. In the future, we need more online intervention researches to improve the symptoms of different patients, especially for some patients who have difficulties in accepting face-to-face treatment.

Which Factor Is More Relevant to the Effectiveness of the Cognitive Intervention? A Meta-Analysis of Randomized Controlled Trials of Cognitive Training on Symptoms and Executive Function Behaviors of Children With Attention Deficit Hyperactivity Disorder.

Objective: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by developmentally inappropriate inattention, hyperactivity, and impulsivity. Multiple cognitive training appeared to be more effective than working memory training, but the evidence remains insufficient, particularly for the subgroup symptoms and executive function behaviors at home. Further analysis of the impact of factors on the effectiveness would facilitate the development of cognitive training. Methods: We searched PubMed, Cochrane Library, Psyche, Embase, Chinese Biomedical Literature Database, CNKI, and Weifang Database, and included randomized controlled trials (RCTs) of children with ADHD undergoing cognitive intervention. Metaanalysis and univariate metaregression were performed by STATE. The risk of bias was assessed with the Cochrane risk of bias tool 2.0 by the two investigators separately. This study was registered with INPLASY, number INPLASY202140065. Results: We included 17 RCTs in the systematic review, with a combined 1,075 participants. For metaanalyses of both subgroups of ADHD symptoms and the executive function behaviors, the test of published bias failed to reach the p < 0.05 level. When all of the training are considered together, cognitive training can improve the presentation of inattention symptoms [SMD = -0.390, 95%CI (-0.675, -0.104)] and executive function behaviors (SMD = -0.319, 95%CI (-0.527, -0.111)]. In the subgroup analysis, the effects of working memory training on both presentations were not statistically significant. In contrast, the multiple cognitive training had significant effects on the presentation of inattention symptoms [SMD = -0.507, 95% CI (-0.722, -0.292)], hyperactivity/impulsivity [SMD = -0.305, 95% CI (-0.518, -0.09)], and the executive function behaviors [SMD = -0.499, 95%CI (-0.707, -0.290)]. In addition, metaregression analysis showed that only training frequency did significantly impact the symptoms of ADHD and the executive function behaviors. Conclusion: This study showed that improvements in symptoms and executive function behaviors were related to the domains of cognitive intervention. The findings suggest that multiple domains of cognitive training and moderate training frequency may have wider clinical benefits. All the above results highlight further research in refining the executive functions of children with ADHD and developing individually tailored cognitive intervention on homes based for children with vulnerable executive functions. Systematic Review Registration: [http://inplasy.com/], [INPLASY202140065].

Extent of agreement between the body fluid model of Sysmex XN-20 and the manual microscopy method.

BACKGROUND: Although the correlations concerning cellular component analysis between the Sysmex XN-20 body fluid (BF) model and manual microscopy have been investigated by several studies, the extent of agreement between these two methods has not been investigated. METHODS: A total of 90 BF samples were prospectively collected and analyzed using the Sysmex XN-20 BF model and microscopy. The extent of agreement between these two methods was evaluated using the Bland-Altman approach. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic accuracy of high-fluorescence (HF) BF cells for malignant diseases. RESULTS: The agreements of white blood cell (WBC), red blood cell (RBC), and percentages of neutrophils, lymphocytes, and monocytes between the Sysmex XN-20 BF model and manual microscopy were imperfect. The areas under the ROC curves for absolute and relative HF cells were 0.67 (95% confidence interval [CI]: 0.56-0.78) and 0.60 (95% CI: 0.48-0.72), respectively. CONCLUSION: Due to the Sysmex XN-20 BF model's imperfect agreement with manual microscopy and its weak diagnostic accuracy for malignant diseases, the current evidence does not support replacing manual microscopy with this model in clinical practice.

[Pathogen Identification for An Imported Case with African Trypanosomiasis].

Objective: To perform laboratory diagnosis for an imported case of human African trypanosomiasis and identify the pathogen. Methods: Clinical and epidemiological information was collected. Blood and cerebrospinal fluid samples were collected, stained with Wright-Giemsa, and microscopically examined. Genomic DNA from the blood samples was amplified with primers specific for Trypanosoma sp. expression site-associated gene (ESAG), Trypanosoma brucei gambiense specific glycoprotein (TgsGP) and 18S rRNA（M18S-Ⅱ-Tb） gene, and Trypanosoma brucei rhodesiense specific serum resistance associated （SRA） gene. Complete blood count, blood chemistry, and CSF examination were also conducted. Results: The patient had a 4-month history of lower extremity weakness and swelling of surface lymph nodes. Physical examination showed somnolence, and occasional emotional abnormalities, accompanied by anemia (hemoglobin 85 g/L), electrolyte disturbance (sodium 124 mmol/L; chlorine 87 mmol/L) and significantly increased nonspecific immune globulin protein （globulin 63 g/L）. Epidemiological survey showed that the patient suffered insect bites and stings for several times during his work in the Republic of Gabon in Africa. Microscopic examination revealed flagella of trypanosome in peripheral blood. PCR amplification produced bands of 286, 308, and 150 bp with primers specific for ESAG, TgsGP and M18S-Ⅱ-Tb, respectively. Conclusion: The patient was diagnosed with Trypanosoma brucei gambiense infection from the clinical information, epidemiological history, etiology and PCR results.

[Preliminary effect of VEGF promoter-driven recombinant adenovirus containing double suicide genes on apoptosis of human gastric carcinoma cells].

OBJECTIVE: To study the effect of the adenovirus containing CD/TK fusion gene controlled by the human vascular endothelial growth factor (VEGF) promoter on apoptosis of human gastric carcinoma cells SGC-7901. METHODS: VEGF-expressing SGC-7901 cells were infected by the recombinant adenovirus Ad-VEGFP-CD/TK, and the infection efficiencies were observed with fluorescence microscopy. The toxic effect and intracellular calcium concentration induced by 5-fluorocytosine (5-FC) and ganciclovic (GCV) were determined by light microscopy, electron microscopy and flow cytometry. RESULTS: The transfection efficiency of the recombinant adenovirus in SGC-7901 cells increased with the viral titer. At the multiplicity of infection (MOI) of 100, 5-FC and GCV could induce apoptosis of SGC-7901 cells within a given dose range in a dose- and time-dependent manner, and apoptotic changes of the cells were observed with electron microscopy. Apoptotic peak was also detected by flow cytometry. Cell cycle analysis revealed increased cell percentage in G(0)-G(1) phase and decreased percentage of cells in G(2)-M and S phases in response to treatment with the pro-drugs, which also induced marked elevation of intracellular calcium concentration in the infected cells. CONCLUSIONS: CD/TK fusion gene system driven by VECF promoter selectively induces apoptosis of VEGF-expressing SGC-7901 cells, the action of which is probably mediated by intracellular calcium variation.

Kinase domain insert containing receptor promoter controlled suicide gene system selectively kills human umbilical vein endothelial cells.

AIM: To study the selective killing of human umbilical vein endothelial cells (HUVECs) by a double suicide gene under the regulation of a kinase domain insert containing receptor (KDR) promoter and mediated by an adenoviral gene vector. METHODS: Human KDR promoter was cloned by polymerase chain reaction (PCR), and two recombinant adenoviral plasmids pAdKDR-CdglyTK, pAdCMV-CDglyTK were constructed according to a two-step transformation protocol. These two newly constructed plasmids were then transfected into 293 packaging cells to grow adenovirus, which were further multiplied and purified. HUVECs and LoVo cells were infected with either of the two resultant recombinant adenoviruses (AdKDR-CDglyTK and AdCMV-CDglyTK) respectively, and the infection rates were estimated by detection of green fluorescent protein (GFP) expression. Infected cells were cultured in culture media containing different concentrations of 5-fluorocytosine (5-FC) and ganciclovir (GCV), and the killing effects were measured. RESULTS: The two recombinant adenoviral plasmids pAdKDR-CdglyTK, pAdCMV-CDglyTK were successfully constructed and transfected into 293 cells. The resultant recombinant adenoviruses infected cells caused similar infection rates; and the infected cells exhibited different sensitivity to the prodrugs: HUVECs infected with AdCMV-CDglyTK and LoVo cells infected with AdCMV-CDglyTK were highly sensitive to the prodrugs, and HUVECs infected with AdKDR-CDglyTK were similarly sensitive but significantly more sensitive than the LoVo cells infected with AdKDR-CdglyTK (P < 0.001). CONCLUSION: Selective killing of HUVECs may be achieved by gene transfer of double suicide gene under the regulation of the KDR promoter. This finding may provide an optional way to target gene therapy of malignant tumors by abrogation of tumor blood vessels.

Kinase domain insert containing receptor promotor controlled suicide gene system kills human umbilical vein endothelial cells.

AIM: To evaluate the killing effect of double suicide gene mediated by adenovirus and regulated under kinase domain insert containing receptor (KDR) promoter on human umbilical vein endothelial cells. METHODS: By PCR technology, human KDR promoter gene, Escherichia coli (E. coli) cytosine deaminase (CD) gene and the herpes simple virus-thymidine kinase (TK) gene were cloned. Plasmid pKDR-CDglyTK was constructed with them. Then, a recombinant adenoviral plasmid pAdKDR-CDglyTK was constructed in a "two-step transformation protocol". The newly constructed plasmids were transfected to 293 packaging cells to grow adenoviruses, which were further propagated and purified. Human umbilical vein endothelial cells (HUVEC) were infected with a different multiplicity of infection (MOI) of resultant recombinant adenovirus, the infection rate was measured with the aid of (GFP) expression. Infected cells were cultured in culture media containing different concentrations of (GCV) and/or 5-(FC), and the killing effects were measured. RESULTS: Recombinant adenoviruses AdKDR-CDglyTK were successfully constructed, and they infected HUVEC cells efficiently. Our data indicated that the infection rate was relevant to MOI of recombinant adenoviruses. HUVEC cells infected with AdKDR-CDglyTK were highly sensitive to the prodrugs, their survival rate correlated to both the concentration of the prodrugs and the MOI of recombinant adenoviruses. Our data also indicated that the two prodrugs used in combination were much more effective on killing transgeneic cells than GCV or 5-FC used alone. CONCLUSION: Prodrug/KDR-CDglyTK system is effective on killing HUVEC cells, its killing effect correlates to the concentration of prodrugs and recombinant adenovirus' MOI. Combined use of the two prodrugs confers better killing effects on transgeneic cells.