Vitamin D3 improves iminodipropionitrile-induced tic-like behavior in rats through regulation of GDNF/c-Ret signaling activity.

Children with chronic tic disorders (CTD), including Tourette syndrome (TS), have significantly reduced serum 25-hydroxyvitamin D [25(OH)D]. While vitamin D3 supplementation (VDS) may reduce tic symptoms in these children, its mechanism is unclear. The study aim was to investigate the effects and mechanisms of vitamin D deficiency (VDD) and VDS on TS model behavior. Forty 5-week-old male Sprague-Dawley rats were randomly divided into (n = 10 each): control, TS model, TS model with VDD (TS + VDD), or TS model with VDS (TS + VDS; two intramuscular injections of 20,000 IU/200 g) groups. The VDD model was diet-induced (0 IU vitamin D/kg); the TS model was iminodipropionitrile (IDPN)-induced. All groups were tested for behavior, serum and striatal 25(OH)D and dopamine (DA), mRNA expressions of vitamin D receptor (VDR), glial cell line-derived neurotrophic factor (GDNF), protooncogene tyrosine-protein kinase receptor Ret (c-Ret), and DA D1 (DRD1) and D2 (DRD2) receptor genes in the striatum. TS + VDD had higher behavior activity scores throughout, and higher total behavior score at day 21 compared with TS model. In contrast, day 21 TS + VDS stereotyped behavior scores and total scores were lower than TS model. The serum 25(OH)D in TS + VDD was < 20 ng/mL, and lower than control. Striatal DA of TS was lower than control. Compared with TS model, striatal DA of TS + VDD was lower, while in TS + VDS it was higher than TS model. Furthermore, mRNA expression of VDR, GDNF, and c-Ret genes decreased in TS model, and GDNF expression decreased more in TS + VDD, while TS + VDS had higher GDNF and c-Ret expressions. VDD aggravates, and VDS ameliorates tic-like behavior in an IDPN-induced model. VDS may upregulate GDNF/c-Ret signaling activity through VDR, reversing the striatal DA decrease and alleviating tic-like behavior.

Circulating retinol and 25(OH)D contents and their association with symptoms in children with chronic tic disorders.

The present study measured serum levels of vitamin A (VA) and vitamin D (VD) in children with chronic tic disorders (CTD) and investigated their potential association with CTD and comorbidity of attention deficit hyperactivity disorder (ADHD) and the association of their co-insufficiencies or deficiencies with CTD symptoms. A total of 176 children (131 boys and 45 girls, median age of 9 years) with CTD were recruited as the CTD group. During the same period, 154 healthy children were selected as the healthy control (HC) cohort. Circulating retinol and 25-hydroxyvitamin D (25[OH]D) levels were measured for all participants using high-performance liquid chromatography (HPLC) and tandem mass spectrometry. The Yale Global Tic Severity Scale (YGTSS) was employed for the assessment of tic status and CTD impairment. The Swanson, Nolan, and Pelham Rating Scale (SNAP-IV) and the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) were used to evaluate comorbidity symptoms. CTD pediatric participants exhibited markedly diminished circulating retinol and 25(OH)D levels compared to HCs. Moreover, VA and VD deficiencies and their co-insufficiencies/deficiencies were more prevalent in CTD participants than HCs. Circulating 25(OH)D levels were inversely proportional to the YGTSS motor tic scores. YGTSS scores in CTD children with only VA or VD insufficiency or deficiency or with VA and VD co-insufficiency/deficiency did not differ from those in CTD children with normal VA and VD. CTD children with comorbid ADHD displayed reduced circulating retinol and 25(OH)D concentrations and elevated prevalence of VD deficiency compared to CTD participants without comorbid ADHD. Lower serum retinol content was intricately linked to the presence of elevated CTD and comorbid ADHD. VA and VD deficiencies and their co-insufficiencies/deficiencies were markedly enhanced in CTD pediatric participants compared to HCs. Lower VA concentration was linked to the presence of enhanced CTD and comorbid ADHD. Therefore, children with CTD, especially with comorbid ADHD, may be at a higher risk of VA or VD deficiency, which may prompt the clinicians to consider whether blood tests for VA and VD in CTD children would be helpful for clinical care.

Reliability and validity of the Chinese version of the kiddie-schedule for affective disorders and schizophrenia-present and lifetime version DSM-5 (K-SADS-PL-C DSM-5).

BACKGROUND: As the Diagnostic and Statistical Manual of Mental Disorders fifth version (DSM-5) was published, the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version (K-SADS-PL) was modified to adapt the new version (K-SADS-PL DSM-5). We translated it to Chinese (K-SADS-PL-C DSM-5) and described its reliability and validity. METHODS: A total of 154 groups of 6 to 18-year-old children and their guardians were included. Trained interviewers interviewed subjects using the K-SADS-PL-C DSM-5. Interrater reliability was assessed by audio recording. Parent-reported scales, like child behavior checklist (CBCL), the Chinese version of Swan-son Nolan and Pelham, version IV scale-parent form (SNAP-IV), social responsiveness scale (SRS-1), and children-reported scales like depression self-rating scale for children (DSRSC) and the screen for child anxiety related emotional disorders (SCARED) were used to examine the validity of depressive disorder, ADHD, ASD, and ODD. RESULTS: The K-SADS-PL-C DSM-5 had fair to excellent interrater (0.537-1.000) and test-retest (0.468-0.885) reliability of affective disorder and neurodevelopment disorder. The convergent validity of affective disorder and neurodevelopment disorder was good, and their divergent validity was acceptable. LIMITATIONS: i) Clinical questionnaires were insensitive in classifying disorders and had limitations in derived diagnoses. ii) Samples only came from clinical environment, iii) covered limited disease species, and iv) were small. CONCLUSION: The K-SADS-PL-C DSM-5 can support reliable and valid diagnoses for children with affect, neurodevelopmental, and behavioral disorders in China.

[Effect of Jingfang Granules on carrageenan-induced tail thrombosis in mice based on ERK/p38 MAPK signaling pathway].

The present study explored the anti-inflammatory and anti-thrombotic mechanism of Jingfang Granules on tail thrombosis induced by carrageenan in mice. Thirty-two male ICR mice were randomly divided into a control group, a model group, a Jingfang Granules group, and a positive drug(aspirin) group, with eight mice in each group. The thrombosis model was induced by intraperitoneal injection of carrageenan(45 mg·kg~(-1)) combined with low-temperature stimulation, and the mice were treated with drugs for 7 days before modeling. Twenty-four hours after modeling, blood was detected for four blood coagulation indices in each group. The enzyme-linked immunosorbent assay(ELISA) was used to detect the activity of plasma interleukin-6(IL-6), interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), and other inflammatory factors. The tails of mice in each group were cut off to observe tail lesions and measure the length of the thrombus. The protein expression and phosphorylation level of extracellular signal-regulated kinase 1/2(ERK1/2) and p38 mitogen-activated protein kinase(p38 MAPK) in spleen tissues were detected by Western blot. The results showed that dark red thrombus appeared in the tails of mice in each group. The length of the black part accounted for about 40% of the total tail in the model group. Additionally, the model group showed prolonged prothrombin time(PT), increased fibrinogen(FIB) content, and shortened activated partial thromboplastin time(APTT). Compared with the model group, the groups with drug intervention displayed shortened black parts in the tail and improved four blood coagulation indices(P<0.05). As revealed by ELISA, the expression levels of TNF-α, IL-1ß, and IL-6 in the mouse plasma were significantly up-regulated in the model group, and those in the groups with drug intervention were reduced as compared with the model group(P<0.05). As demonstrated by Western blot, the protein expression and phosphorylation levels of ERK1/2 and p38 MAPK in the spleen tissues were significantly elevated in the model group, while those in the Jingfang Granules group were down-regulated as compared with the model group with a significant difference. Jingfang Granules can inhibit tail thrombosis of mice caused by carrageenan presumedly by inhibiting the activation of ERK1/2 and p38 MAPK signaling pathways.

Non-parental caregivers, low maternal education, gastrointestinal problems and high blood lead level: predictors related to the severity of autism spectrum disorder in Northeast China.

BACKGROUND: The prevalence of autism spectrum disorder (ASD) has increased rapidly in recent years. Environmental factors may play an important role in the pathogenesis of ASD. These factors may include socioeconomic factors, nutritional factors, heavy metal exposure, air pollution, etc. Our aim is to analyze possible environmental factors associated with the severity of ASD. METHODS: All participating children were divided into two groups (mild and moderate/severe) according to the severity of their symptoms, as determined by their Childhood Autism Rating Scale (CARS) scores. The socioeconomic, demographic factors and the nutritional factors that may affect the severity of ASD were included in the logistic regression to analyze whether they were predictors that affected the severity of ASD. RESULTS: Logistic regression showed that caregivers(P = 0.042), maternal education (P = 0.030), gastrointestinal problems (P = 0.041) and a high serum concentration of lead (P = 0.003) were statistically significantly associated with ASD severity. CONCLUSION: Many environmental factors affect the severity of ASD. We concluded that non-parental caregivers, low maternal education, gastrointestinal problems and high blood lead level maybe predictors that affected the severity of ASD in northeast China.

Screening of ADHD symptoms in primary school students and investigation of parental awareness of ADHD and its influencing factors: A cross-sectional study.

Objective: The present study aimed to compare the differences in positive screening rates of attention deficit hyperactivity disorder (ADHD) symptoms between parents and teachers in the same sample of primary school students. Concurrently, parental awareness and information sources of ADHD were investigated, and possible relevant factors affecting parental awareness and their influence on positive screening rate of ADHD were analyzed. Methods: A cross-sectional study was conducted in Changchun, China, between September 2020 and January 2021. Parents of 1,118 primary school students and 24 head teachers were recruited in the survey. Data were collected through a structured self-administered questionnaire. It consisted of socio-demographic characteristics, ADHD symptom screening questionnaire, parental awareness, and information sources of ADHD. Results: Among the 1,118 primary school students, 30 (2.7%) and 60 (5.4%) students were positive for Swanson, Nolan, and Pelham Rating Scale (SNAP-IV) screening in the parent version and teacher version, respectively. Parents had lower positive screening rates for ADHD symptoms than teachers. Relationship with children (mother, OR = 1.552, 95% CI = 1.104-2.180), bachelor degree or above of parents (OR = 1.526, 95% CI = 1.054-2.210), children's sex (girl, OR = 1.442, 95% CI = 1.093-1.904), and age (OR = 1.344, 95% CI = 1.030-1.754), children's grade (grade 2, OR = 0.522, 95% CI = 0.310-0.878; grade 3, OR = 0.388, 95% CI = 0.185-0.782), information sources of ADHD (medical staff, OR = 1.494, 95% CI = 1.108-2.015; family/relative/friend, OR = 1.547, 95% CI = 1.148-2.083; TV/Internet, OR = 3.200, 95% CI = 2.270-4.510) were the factors related to the parental awareness of ADHD. Conclusion: Parents and teachers of primary school students recognize ADHD symptoms differently. The positive screening rate of ADHD among teachers was significantly higher than that of parents. Relationship with children, educational level of parents, children's sex, age, and grade, and information sources of ADHD are the relevant factors affecting parental awareness of ADHD. More efforts should be made to disseminate ADHD knowledge through mass media, and medical staff. Fathers, parents with low educational level, and parents of grade 2 and 3 pupils should be encouraged to acquire more knowledge on ADHD to improve the early recognition rate of ADHD symptoms. Clinical trial registration: [http://www.chictr.org.cn/showproj.aspx?proj=54 072], identifier [ChiCTR2000033388].

[Clinical Characteristics and Prognosis of Adult Acute Myeloid Leukemia with NUP98 Gene Rearrangement].

OBJECTIVE: To investigate the clinical characteristics, outcomes and prognosis of adult acute myeloid leukemia (AML) patients with NUP98 gene rearrangement. METHODS: The clinical data of adult AML patients with NUP98 gene rearrangement from January 2015 to December 2019 were retrospectively analyzed, including clinical characteristics, laboratory examination, genetic anomaly, treatment strategy and survival. RESULTS: A total of 15 patients with NUP98 gene rearrangement were detected in 410 adult AML patients (3.7%). The ratio of male to female among 15 patients was 1.1∶1, and the median age was 43 (17-76) years old. The main FAB types were M2 and M4/M5, and including one unclassified. According to the genetic prognosis, 11 cases were intermediate risk, while 4 cases were high risk. The main type of NUP98 gene rearrangement was NUP98-HOXA9 (13/15, 86.7%). 10 patients underwent next generation sequencing, in which 5 patients showed epigenetic gene mutations, 3 patients showed FLT3-ITD or WT1 mutations, and 2 patients showed no mutation. After induction therapy, 13 of 15 patients achieved complete remission（CR）. 7 of 8 patients with standard induction therapy achieved CR. 7 elder or intolerance patients with demethylation drug and chemotherapy all achieved CR. The median follow-up time was 28 months. The median OS of 15 the patients was 31.5 months (95% CI 10.7%-52.2%), and the median OS of the patients in non-allogeneic hematopoietic stem cell transplantation (Allo-HSCT) group was 18.5 months (95% CI 17.8%-19.1%). The median OS was not reached for the patients in the Allo-HSCT group. CONCLUSION: Allo-HSCT can significantly improve the prognosis of AML patients with NUP98 rearrangement. NUP98 rearrangement can be accompanied by epigenetic gene mutations. For the elderly or patients who do not tolerate standard induction therapy, demethylation drugs combined with chemotherapy can achieve good outcomes.

Correlation Between Screen Time and Autistic Symptoms as Well as Development Quotients in Children With Autism Spectrum Disorder.

Background: Electronic screen media play an increasingly vital role in children's entertainment; however, excessive screen time may negatively influence child development. The purpose of this study was to investigate the relationship between the screen time of children with autism spectrum disorder (ASD) and their autistic symptoms and development quotients (DQs). Methods: We compared the screen time of 101 children with ASD and 57 typically developing (TD) children. Then, we performed a correlation analysis to determine the correlations between the screen time and the ASD-related scale scores and developmental quotients of the Gesell Developmental Schedules (GDS) of ASD children. We further divided the ASD group into subgroups according to the screen time and age and then separately conducted the above correlation analyses by subgroup. Result: The results showed that the screen time of the children with ASD was longer than that of the TD children (3.34 ± 2.64 h vs. 0.91 ± 0.93 h). The screen time of the children with ASD was positively correlated with the Childhood Autism Rating Scale (CARS) score (r = 0.242, P = 0.021) and "taste, smell and touch" item of CARS(r = 0.304, P = 0.005), and negatively correlated with the language DQ of the GDS (r = -0.236, P = 0.047). The subgroup analysis showed that in the longer screen time subgroup of ASD children, the screen time was positively correlated with the CARS score (r = 0.355, P = 0.026) and negatively correlated with the DQs of all domains of the GDS (P < 0.05). In addition, in the younger age group of ASD children, the screen time was positively correlated with the CARS score (r = 0.314, P = 0.021) and negatively correlated with the DQs of all domains of the GDS, except for the personal-social behavior domain (P < 0.05). Conclusion: Compared with TD children, children with ASD have a longer screen time. The screen time is related to autism-like symptoms and the DQs of children with ASD. The longer the screen time, the more severe the symptoms of ASD (especially sensory symptoms), and the more obvious the developmental delay, especially in ASD children with a longer screen time and younger age, particularly in the language domain.

Serum Levels of Vitamin A and Vitamin D and Their Association With Symptoms in Children With Attention Deficit Hyperactivity Disorder.

Objective: To measure levels of vitamin A (VA) and vitamin D (VD) and the symptomatic association of their co-deficiencies on attention deficit hyperactivity disorder (ADHD) in Chinese children (6-9 years). Methods: Eighty-two children (69 boys and 13 girls; mean age = 7.1 ± 0.9 years at the time of the diagnosis) with ADHD were recruited as ADHD group. A total of 106 healthy children were recruited as the healthy control (HC) group. Serum levels of retinol and 25-hydroxyvitamin D (25(OH)D) of all children were evaluated using high-performance liquid chromatography (HPLC) and HPLC-tandem mass spectrometry. The Swanson, Nolan, and Pelham IV Rating Scale (SNAP-IV) was employed to assess the clinical symptoms of ADHD. Results: Children suffering from ADHD had significantly reduced serum levels of retinol and 25(OH)D compared with those of HCs, and the prevalence of VA deficiency and VD deficiency were higher in children suffering from ADHD. Serum concentrations of 25(OH)D and retinol were linked closely with the presence or absence of ADHD after adjustment for age, body mass index, season of blood sampling, and sun exposure. Serum concentrations of 25(OH)D and retinol showed a negative correlation with the total scores of SNAP-IV. Children with ADHD as well as VA and VD co-deficiency had increased SNAP-IV total scores and ADHD inattention subscale scores. Conclusion: VA deficiency and VD deficiency in children with ADHD were increased in comparison with that in HCs. VA and VD co-deficiency associated with ADHD symptom severity. Attention should be paid to regular testing of VA levels and VD levels. However, the mechanism of VA and VD in ADHD needs to be further studied. Interventional studies on VA and VD supplementation are recommended to further verify the relationship between VA and VD co-deficiency and ADHD.

[Prognosis and Genetic Characteristics of Patients with Plasma Cell Leukemia].

OBJECTIVE: To evaluate the clinical characteristics, genetic abnormalities, treatment efficacy and prognostic factors in patients with plasma cell leukemia(PCL). METHODS: 30 patients diagnosed as PCL in our hospital from January 1993 to December 2019 were enrolled, and the clinical characteristics, laboratory findings, therapeutic regimes, and survival data of the patients were retrospectively analyzed. RESULTS: The median age of the 30 patients was 56.5 (28-80) years old, among them, 25 patients were primary plasma cell leukemia, and 5 patients were secondary plasma cell leukemia. Complex karyotypes and subdiploids were most common in cytogenetic abnormalities. Among the 20 cases of chromosome G banding, 11 (55%) cases were complex karyotypes and 8 (40%) cases were hypodiploid. Fluorescent in situ hybridization (FISH) test showed that among 11 cases, 6 cases showed 17p13 deletion, 8 cases showed at least two kinds of abnormalities, which including t (14; 16), t (8; 14), t (11;14), 17p13 deletion, and 13q14 deletion. The median overall survival (OS) time was 10.5 months for all patients. The median OS time of the patients in ECOG score ≤ 2 group was 21.5 months, which was significantly longer than those in the ECOG score>2 group(1.2 months) (P=0.017). The median OS time of the patients treated with novel agents (including proteasome inhibitor and/or immunomodulator) was 24.9 months, which was significantly longer than the patients treated with traditional chemotherapy group(10.5 months) (P＜0.001). For the patients treated with novel agents, the median OS time of patients accepted two novel agents combination was 30.9 months, which was longer than those of single novel agent(11.5 months) (P=0.021). The effect of genetic abnormolity to the OS of the patients showed no statistical difference. Multivariate statistical analysis showed that ECOG score>2 was the independent prognostic factor of plasma cell leukemia patients. There were two patients underwent allogeneic hematopoietic stem cell transplantation in the study,but died due to the pulmonary infection within 6 months after transplantation. CONCLUSION: In the era of novel agents, ECOG score is an independent prognostic factor of plasma cell leukemia. Multiple novel agents treatment should be underwent as soon as possible to improve the prognosis of the patients. Pulmonary infection is a common factor that cause the death of the patients after allogeneic hematopoietic stem cell transplantation.

A Developmental Profile of Children With Autism Spectrum Disorder in China Using the Griffiths Mental Development Scales.

The purpose of this study was to profile the mental development of children aged 18 to 96 months with autism spectrum disorder (ASD) using the Chinese version of the Griffiths Mental Development Scales (GMDS), and to explore the relationships between developmental levels and ASD severity, the sex of the child and the age of ASD diagnosis. Children with ASD (n = 398; 337 boys, 61 girls) were recruited and ASD severity evaluated using the Autism Behavior Checklist and the Childhood Autism Rating Scale, while the GMDS was used to evaluate the children's mental development. Study participants were divided into groups according to GMDS general and subscale quotients, ASD severity, sex, and age. The majority of groups divided according to the GMDS quotients exhibited an unbalanced distribution in respect of the six domains of the GMDS and there were significant differences within the six subscale quotients. Autism severity, sex and age had significant effects on the overall level of development of autistic children. The quotients recorded for the children with more severe ASD were significantly lower than those for the children with less severe ASD. A markedly higher proportion of developmental delay was recorded for girls than boys in relation to the performance subscale. The locomotor quotient decreased in line with age at diagnosis, while autism severity and age had significant effects on the general and subscale quotients and sex had a significant effect on performance quotient. Children with ASD exhibit an uneven cognitive development profile, and their overall developmental levels are affected by autism severity, sex and age. Specific cognitive domains differ according to sex in children with ASD. Locomotor skills tend to decrease according to the age at diagnosis for autistic children aged 18 to 84 months. Autism severity and age are also associated with the level of functioning in different cognitive areas. These findings contribute to define the cognitive developmental profiles of children with ASD.

[Intelligence structure and clinical features of school-age children with attention deficit hyperactivity disorder and specific learning disorder].

OBJECTIVE: To study the intelligence structure and clinical features of children with attention deficit hyperactivity disorder (ADHD) and specific learning disorder (SLD). METHODS: A retrospective analysis was performed on 88 school-age children with ADHD. According to the presence or absence of SLD, they were divided into two groups: simple ADHD group with 45 children and ADHD+SLD group with 43 children. Intelligence structure and clinical features were compared between the two groups. RESULTS: Compared with the simple ADHD group, the ADHD+SLD group had significantly lower verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and full intelligence quotient (FIQ) (P<0.05), significantly lower scores of VIQ factors (including information, similarities, arithmetic, and recitation) (P<0.05), and significantly lower scores of PIQ factors (including picture completion, picture arrangement, block design, and object assembly) (P<0.05). The development of SLD was negatively correlated with FIQ, VIQ, and PIQ. It was also negatively correlated with the scores of intelligence structure factors (including information, similarities, arithmetic, recitation, picture completion, picture arrangement, block design, and object assembly) (P<0.05). CONCLUSIONS: Children with ADHD and SLD have poorer FIQ, VIQ, and PIQ than those with ADHD alone, which mainly manifests as the weak abilities of most intelligence structure factors. It is necessary to pay attention to the management and intervention of SLD in school-age children with ADHD.

Phthalate exposure linked to high blood pressure in Chinese children.

BACKGROUND: Exposure to phthalate esters may be linked to the risk of high blood pressure (HBP), but limited evidence is available in Chinese children. OBJECTIVE: To investigate the associations between nine phthalate metabolites (mPAEs) and systolic/diastolic BP, pulse pressure (PP), mean arterial pressure (MAP), and the risk of HBP. METHODS: In this cross-sectional study, a total of 1044 primary school children (6-8 years old) were enrolled from Shenzhen, China, between 2016 and 2017. Nine mPAEs were analyzed from urine using ultra-performance liquid chromatography and tandem mass spectrometry. A multivariable linear regression model was used to explore the associations between phthalate exposure and systolic/diastolic BP, PP, and MAP. A binary logistic regression model was used to examine the associations between phthalate exposure and the risk of HBP. RESULTS: Monomethyl phthalate (MMP) concentrations were significantly higher in HBP children than normal BP children. MMP, monoisobutyl phthalate (MiBP), monobutyl phthalate (MnBP), mono(5-carboxy-2-ethylpentyl) phthalate, mono-[(2-carboxy methyl)hexyl] phthalate (MCMHP), the sum of four short-chain mPAEs (∑LMW), and the sum of all nine mPAEs (∑9mPAEs) were significantly positively associated with increases in systolic BP z-score, while only MMP was significantly positively associated with diastolic BP z-score. MMP, MiBP, MnBP, MCMHP, ∑LMW, and ∑9mPAEs were significantly associated with increases in PP, while MMP and MnBP were significantly associated with increases in MAP. MMP was significantly associated with the risk of HBP, with an odds ratio of 1.87 (95% CI: 1.23, 2.85). CONCLUSIONS: The present study suggests that dimethyl phthalate exposure increases the risk of HBP. And some types of phthalates are associated with elevations in systolic/diastolic BP z scores, PP, and MAP in Chinese children.

Risk factors and associations with clinical outcomes of cytomegalovirus reactivation after haploidentical versus matched-sibling unmanipulated PBSCT in patients with hematologic malignancies.

In allogeneic hematopoietic stem cell transplantation recipients, cytomegalovirus (CMV) infection can cause overt CMV-associated disease, which is a main cause of transplantation-associated mortality. CMV infection correlates closely with donor's type. We therefore examined whether risk factors of CMV reactivation and clinical endpoints in patients with hematologic malignancies after allogeneic peripheral blood stem cell transplantation (PBSCT) differed between using matched-sibling donors (MSD-SCT) and haploidentical donors (HID-SCT). In this retrospective cohort study, we enrolled in 200 consecutive patients received an unmanipulated G-CSF-mobilized allogeneic PBSCT. Ninety (45%) patients received MSD-SCT and 110 (55%) received HID-SCT. Quantitative PCR was used for monitoring of CMV reactivation after transplantation. One-year cumulative incidence of CMV DNAemia was 55.0%, ranging from 23.5% in MSD-SCT group to 81.0% in HID-SCT group (p < 0.001). Although univariate analyses showed that non-myeloid malignancies, disease in complete remission status at transplantation, pretreatment with antithymocyte globulin, HLA-haploidentical donors, male donors, previous Epstein-Barr virus DNAemia, and absolute lymphocyte count on day 30 < 0.6 × 109/L were respectively associated with CMV reactivation after transplantation in total cohort of recipients (all p < 0.05), haploidentical donors were found to be the only independent predictor in multivariate analyses (Hazard ratio = 6.4, p < 0.001). Furthermore, univariate analyses revealed that non-myeloid malignancies and previous Epstein-Barr virus DNAemia were respectively associated with CMV reactivation in MSD-SCT recipients, and female was associated with CMV reactivation in HID-SCT recipients (all p < 0.05). In HID-SCT recipients, but not MSD-SCT recipients, previous CMV DNAemia was associated with a lower cumulative incidence of acute graft-versus-host disease (49.2% vs. 72.6%, p < 0.001). CMV DNAemia did not play a role in the relapse rate, but it was strongly associated with an increased risk of non-relapse mortality either in total cohort of recipients (30.5% vs. 13.7%; p = 0.003) or in the HID-SCT subgroup (36.0% vs. 16.7%; p = 0.030). Relapse-free survival and overall survival in total cohort of recipients with CMV DNAemia were both inferior to those without CMV DNAemia (45.3% vs. 57.6% and 54.8% vs. 65.8%, respectively; both p < 0.05). However, in subgroup analysis according to donor's type, neither relapse-free survival nor overall survival was impacted by CMV status (both p > 0.05). This study addressed differences in incidence, risk factors, and associations with clinical outcomes of CMV reactivation after haploidentical versus matched-sibling PBSCT.

Effects of Dietary Fat Profile on Gut Microbiota in Valproate Animal Model of Autism.

Autism spectrum disorder (ASD) is a developmental disability which may cause significant social, communication, and behavioral challenges. Besides certain essential symptoms, a lot of ASD individuals also suffer the comorbidity of gut microbiota dysbiosis, which possibly causes a variety of gastrointestinal (GI) difficulties. Interestingly, evidence has indicated that behavioral output may be modulated through the communication between the central nervous system and gut microbiota via the gut-brain axis. Polyunsaturated fatty acids (PUFAs) and n-3 fatty acids (n-3 PUFA) are structurally and functionally crucial components for the brain, and the state of n-3 PUFAs also affects the gut microbiota. However, how varying intake ratios of n-3/n6 PUFAs affect the gut microbiota composition in ASDs is not well-understood. Pregnant female Wistar rats with intraperitoneal administration of valproate acid (VPA) at embryonic day (E) 12.5 and their male offspring were grouped and fed three diets: a control chow (VPA group), omega-3 deficient (A group), and n-3/n6 (1:5) diet (B group). The diet of pregnant female Wistar rats with intraperitoneal administration of saline and their male offspring was a control chow (normal group). Microbial composition and species abundance were investigated accordingly by the 16S rRNA gene-based metagenomics analysis on the fecal samples. Results showed that fecal microbial abundance was decreased because of VPA administration in the period of pregnancy, and the changing pattern of gut microbiota was similar to that reported in ASD patients. Furthermore, the n-3/n6 (1:5) diet increased the fecal microbial abundance and decreased the elevated Firmicutes. In conclusion, n-3/n6 PUFAs (1:5) diet supplementation may alter gut microbiota composition in VPA-exposed rats. This study put forward a new strategy for the intervention and treatment of autism by n-3/n-6 PUFAs ratio supplementation intakes.

Application quantitative proteomics approach to identify differentially expressed proteins associated with cardiac protection mediated by cycloastragenol in acute myocardial infarction rats.

Acute myocardial infarction (AMI) is an acute heart disease. Cycloastragenol, as a natural product, inhibits inflammation and protects cardiomyocytes. Cycloastragenol (Y006) modulates inflammation in AMI is not known. To explore the function of Cycloastragenol in AMI, this study investigated the effect of Y006 and its mechanisms both in vitro and in vivo. Y006 influences the concentration of 11 proteins, as shown by a proteomics analysis, immunohistochemistry and western blotting. Among these 11 proteins, Erk1/2, PLCG1, IKBKG, and ZEB1 are related to inflammatory regulation. BAX, COX2, and GSK3ß are involved in modulating cardiomyocyte apoptosis, and RhoA and DSC2 are directly associated with myocardial function. However, the functions of ARHGAP17 and Rit2 in heart are less well established. Additionally, Y006 suppressed TNF-α, IFN-γ and IL-17 production in PBMCs (peripheral blood monocytes) from patients with acute myocardial infarction and enhanced IL-10 and IL-4 expression. Similar results were obtained in a rat model of AMI by flow cytometry detection and ELISA. Our findings indicate that Y006 protects rats from AMI through direct or indirect inhibition of inflammation and cardiomyocyte apoptosis. However, the specific mechanism of Y006's protective function requires further study. Nonetheless, this research revealed a novel aspect for the treatment of myocardial infarction. SIGNIFICANCE: In the present study, we undertook the first proteomic evaluation of Cycloastragenol (Y006) function in acute myocardial infarction (AMI). Y006 significantly improved myocardial function in vivo by regulating multiple molecular expressions. Hypoxia is a direct reason for AMI. And our data support a role of Y006 in gene expression, cell apoptosis under hypoxia. The conclusions of this research assist to explain the potential molecular mechanism in Cycloastragenol treating AMI and supply a new method for ameliorating AMI.

[Effect of parental training based on Early Start Denver Model combined with intensive training on children with autism spectrum disorder and its impact on parenting stress].

OBJECTIVE: To explore the effect of parental training based on the Early Start Denver Model (ESDM) combined with intensive training on the treatment outcome of children with autism spectrum disorder (ASD) and its impact on parenting stress. METHODS: Seventy children aged 2-5 years who were diagnosed with ASD were enrolled in the study. They were divided into an ESDM group and a parental training group by the random number table method (n=35 each). The ESDM group received intensive training based on ESDM. In addition to intensive ESDM-based training, parents of the children in the parental training group received ESDM skills training. Both groups were assessed by Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Autism Treatment Evaluation Checklist (ATEC) and Parenting Stress Index-Short Form (PSI-SF) before and after the intervention of 3 months. RESULTS: After 3 months of intervention, the total scores of ABC, CARS and ATEC were both significantly decreased in the two groups (P<0.05). There was no significant difference in the total scores of ABC, CARS and ATEC between the two groups before and after intervention (P>0.05). The change between ABC, CARS and ATEC total scores in the two groups had no significant difference (P>0.05). After 3 months of intervention, the total scores of PSI-SF were both significantly decreased in the two groups (P<0.05). The difficult child sub-scale scores in PSI-SF were significantly decreased in the ESDM group (P<0.05). While three sub-scale scores of parent distress, parent-child dysfunctional interaction and difficult child in PSI-SF were significantly decreased in the parental training group (P<0.05). Before and after intervention of 3 months, no significant difference was found in PSI-SF total scores between the two groups. Compared with the ESDM group, the change between PSI-SF total scores and two sub-scales of PSI-SF (parent distress and difficult child) were significantly bigger in the parental training group (P<0.05). CONCLUSIONS: Both the combination of intensive training and parent training based on ESDM and ESDM intensive training alone can improve the core symptoms of children with ASD aged 2-5 years and relieve the parenting stress, however, the former is more effective in relieving parenting stress.

[Analysis of Clinical Characteristics of Acute B Lymphoblastic Leukemia with EP300-ZNF384 Fusion Gene Positive].

OBJECTIVE: To investigate the clinical manifestations and laboratory features of B-ALL patients with EP300-ZNF384 fusion gene positive, so as to improve the understanding of this subtype disease. METHODS: The clinical data of 3 B-ALL patients with EP300-ZNF384 fusion gene positive admitted in Department of Hematology, the first medical center of Chinese PLA general hospital from February 2017 to February 2018 were collected and analyzed retrospectively. The clinical and laboratory characteristics as well as the therapentic outcome in B-ALL patients with EP300-ZNF384 fusion gene positive were analyzed. RESULTS: The fusion gene of EP300-ZNF384 was detected in 8.1%(3/37) of B-ALL patients. All cases showed the normal karyotype and aberrant CD13 and/or CD33 expression for immunophenotype. 3 patients were sensitive to traditional chemotherapy. CONCLUSION: The B-ALL with EEP300-ZNF384 fusion gene positive may be a subgroup of B-ALL with a uniqe clinical characteristis and laboatorial features. EP300-ZNF384 positive patients show a good response to conventional chemotherapy, suggesting a favorable prognosis.

Successive clinical application of vitamin D and bumetanide in children with autism spectrum disorder: A case report.

RATIONALE: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by complex interactions between genetic and environmental factors. Recent studies suggest that Vitamin D3 or bumetanide therapy may improve the core symptoms of ASD in some individuals. However, there are no guidelines that provide clinicians with evidence-based treatment regimens for the use of these therapies in ASD. PATIENT CONCERNS: A 30-month-old female was referred to our department because she did not respond when her name was called. DIAGNOSIS: The patient was diagnosed with ASD by a team of autism experts according to American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. INTERVENTIONS: The patient was administered Vitamin D3 150,000 IU intramuscularly once a month and Vitamin D3 800 IU orally each day. After 6 months, Vitamin D3 supplementation was discontinued because of lack of effectiveness. Subsequently, oral bumetanide 0.5 mg twice daily was initiated. OUTCOMES: The patient's symptoms remained unchanged after 6 months of Vitamin D3 supplementation, and her serum 25 (OH) D levels had reached 52.4 ng/mL. At the parent's request, Vitamin D3 supplementation was discontinued because of lack of effectiveness. Thereafter, bumetanide was initiated. After 1 month of bumetanide, the patient's Childhood Autism Rating Scale score was 26, which is below the cutoff score for ASD. This case report suggests that Vitamin D3 and bumetanide target different mechanisms in the pathogenesis of ASD. LESSONS: Based on these observations, we discuss three possible scenarios for Vitamin D3 supplementation and propose that bumetanide should be initiated if Vitamin D3 supplementation is ineffective (identifier ChiCTR-CCC-13004498).

Comparison Of The Children Neuropsychological And Behavior Scale And The Griffiths Mental Development Scales When Assessing The Development Of Children With Autism.

BACKGROUND: The newly revised Children Neuropsychological and Behavior Scale (CNBS-R2016) is a diagnostic assessment tool widely used in China to assess the developmental level of children aged 0 to 6 years. The purpose of this study was to determine whether the effectiveness of developmental assessment in children with autism spectrum disorder (ASD) by the CNBS-R2016 was consistent with that of the Griffiths Mental Development Scales for China (GDS-C). METHODS: In total, 139 children with ASD were recruited in this study. The Autism Behavior Checklist (ABC) and the Childhood Autism Rating Scale (CARS) were used to measure ASD severity. All subjects were evaluated with both the CNBS-R2016 and GDS-C. To determine the consistency between the CNBS-R2016 and GDS-C, Pearson correlation coefficients and Bland-Altman plots were computed. The GDS-C was used as a reference assessment, and the performance of the CNBS-R2016 was analyzed with receiver operating curves. RESULTS: No significant difference was found between the proportions of developmental delays detected by the CNBS-R2016 subscales and the corresponding GDS-C subscales. The CNBS-R2016 Communication Warning Behavior subscale quotients and the total ABC and CARS scores were significantly and positively correlated. The general and subscale quotients of the CNBS-R2016 and the corresponding quotient of the GDS-C were also significantly and positively correlated. The area under all the curves of the CNBS-R2016 was above 0.8 according to the results of the GDS-C (general or subscale quotient <70 indicates a developmental delay), and Bland-Altman plots showed no systemic bias between the two scales. CONCLUSION: The CNBS-R2016 and GDS-C tests showed good consistency in the developmental assessment of children with ASD. In addition, the CNBS-R2016 allows the simultaneous assessment of autism symptoms and the developmental level. Therefore, the CNBS-R2016 is worthy of clinical application in children aged 0-6 years.