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Wei Zheng,1 Xin-Ni Luo,1 Hai-Yan Li,1 Xiao-Yin Ke,1 Qing Dai,1 Chan-Juan Zhang,1 Xiang-Yang Zhang,1,2 Yu-Ping Ning1 1The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China; 2Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA Background: Region-specific differences in the prevalence of insomnia symptoms in outpatient clinics in China have received little systematic study. This study was conducted preliminarily to examine region-specific differences in the risk of insomnia symptoms in Chinese outpatients. Method: In total, 4,399 adult outpatients (urban vs rural residents: 1,768 vs 2,631) who completed three questions focusing on insomnia symptoms were included. Their sociodemographic and clinical information were collected with standardized questionnaires. Results: The prevalence of self-reported insomnia symptoms in urban residents (23.4%) was more frequent than the prevalence in rural residents (21.2%). The estimated prevalence of insomnia symptoms was significantly lower in rural than urban residents after adjusting for the potential confounders (P=0.015). Similarly, more urban (22.9%) than rural (13.4%) residents with insomnia symptoms had significantly higher treatment rates (χ2=14.9, P

Yi Zheng,1,* Yasong Du,2,* Lin Yan Su,3 Yanlei Zhang,4 Zheng Yuan,4 Yun Chen,4 Qing Qing Liu,4 Xiao Yan Ke5 1Beijing Anding Hospital of Capital Medical University, Beijing, China; 2Shanghai Mental Health Center, Shanghai, China; 3The Second Xiangya Hospital of Central South University, Changsha, China; 4Lilly Suzhou Pharmaceutical Co. Ltd, Shanghai, China; 5Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China *These authors contributed equally to this work Purpose: The Questionnaire – Children with Difficulties (QCD) has been developed and used to evaluate daily-life problems in children during specified periods of the day. The objective of this study was to evaluate the reliability and validity of the QCD for Chinese children or adolescents with attention-deficit/hyperactivity disorder (ADHD).Patients and methods: Outpatients with ADHD aged 6–18 years who visited psychiatry clinics were enrolled at four study centers in China. Patients with severe psychiatric disorders were excluded. Parents of all enrolled patients were given the QCD, the Swanson, Nolan and Pelham IV (SNAP-IV), and the Weiss Functional Impairment Scale-Parent (WFIRS-P) questionnaires and were asked to complete all three questionnaires. The reliability of the QCD was examined by Cronbach’s alpha, which assessed the internal consistency of the questionnaire. Concurrent criterion validity of QCD scores was examined by Spearman’s correlation of QCD with SNAP-IV and WFIRS-P scores.Results: A total of 200 Chinese patients were analyzed (average age, 10.4±2.66 years). The majority of patients were male (77.5%), and 49.0% had the combined ADHD subtype. Cronbach’s alpha for QCD was 0.88. Correlation coefficients of the QCD total score with SNAP-IV total score and WFIRS-P average score were -0.47 and -0.57, respectively. Correlations for the QCD with SNAP-IV and WFIRS-P were statistically significant (P

Xinpei Zhang,1 Jinlong Shi,2 Jilei Zhang,1 Xinrui Yang,1 Gaoqi Zhang,1 Siyuan Yang,1 Jing Wang,1 Xiaoyan Ke,1 Lin Fu1 1Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing 100191, China; 2Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing 100853, China Purpose: The incidence of DNMT3A mutations in acute myeloid leukemia (AML) is quite high and often confers a poorer prognosis. Another common gene involved in AML is IDH1/2. However, the influence of IDH1/2 mutations on outcomes in DNMT3A-mutated patients remains unknown. This study aims to determine the effect of IDH1/2mut on the prognosis in patients with DNMT3A-mutated AML. Patients and methods: We screened patients from The Cancer Genome Atlas database and selected 51 patients with AML and the DNMT3A mutation, among which 16 patients (31.4%) had both DNMT3A and IDH1/2mut. Results: Among our sample, 11 cases had the IDH1 mutation (21.7%), and 5 cases had the IDH2 mutation (9.8%). Patients in the DNMT3AmutIDH1/2wild group showed a greater number of NPM1 mutation (P=0.022), and higher event-free survival (EFS) and overall survival (OS) after hematopoietic stem cell transplantation (HSCT) (P=0.010 and P=0.007, respectively). Patients in the DNMT3AmutIDH1/2mut group showed no increase in EFS or OS after HSCT or chemotherapy. Other factors, like white blood cells, bone marrow blasts, peripheral blood blasts, and mutated recurrent gene numbers had no significant influence on EFS and OS. Conclusion: The IDH1/2 gene had little influence on the prognosis of patients with the DNMT3A mutation. For patients in the DNMT3AmutIDH1/2wild group, HSCT had a more favorable therapeutic effect. For patients with DNMT3A and IDH1/2mut, chemotherapy and HSCT appeared to have similar efficacy. Keywords: acute myeloid leukemia, molecular mutations, prognosis, next-generation sequencing

Dan Li,1 Ke Yang,1 Jie-Si Li,1 Xi-Yu Ke,1 Yu Duan,1 Ruo Du,1 Ping Song,1 Ke-Fu Yu,1 Wei Ren,1 Dan Huang,1 Xing-Huo Li,1 Xin Hu,1 Xuan Zhang,1 Qiang Zhang1,21Department of Pharmaceutics, 2State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaBackground: Considering the observations that linoleic acid conjugated with paclitaxel (CLA-PTX) possesses antitumor activity against brain tumors, is able to cross the blood–brain barrier, but has poor water solubility, the purpose of this study was to prepare a novel CLA-PTX microemulsion and evaluate its activity against brain tumors in vitro and in vivo.Methods: The in vitro cytotoxicity of a CLA-PTX microemulsion was investigated in C6 glioma cells. The in vivo antitumor activity of the CLA-PTX microemulsion was evaluated in tumor-bearing nude mice and rats. The pharmacokinetics of the CLA-PTX microemulsion were investigated in rats, and its safety was also evaluated in mice.Results: The average droplet size of the CLA-PTX microemulsion was approximately 176.3 ± 0.8 nm and the polydispersity index was 0.294 ± 0.024. In vitro cytotoxicity results showed that the IC50 of the CLA-PTX microemulsion was 1.61 ± 0.83 µM for a C6 glioma cell line, which was similar to that of free paclitaxel and CLA-PTX solution (P > 0.05). The antitumor activity of the CLA-PTX microemulsion against brain tumors was confirmed in our in vivo C6 glioma tumor-bearing nude mice as well as in a rat model. In contrast, Taxol® had almost no significant antitumor effect in C6 glioma tumor-bearing rats, but could markedly inhibit growth of C6 tumors in C6 glioma tumor-bearing nude mice. The pharmacokinetic results indicated that CLA-PTX in solution has a much longer circulation time and produces higher drug plasma concentrations compared with the CLA-PTX microemulsion. The results of the acute toxicity study showed that the LD50 of CLA-PTX solution was 103.9 mg/kg. In contrast, the CLA-PTX microemulsion was well tolerated in mice when administered at doses up to 200 mg/kg.Conclusion: CLA-PTX microemulsion is a novel formulation with significant antitumor efficacy in the treatment of brain tumors, and is safer than CLA-PTX solution.Keywords: CLA-PTX, microemulsion, pharmacokinetics, brain tumor, antitumor efficacy, safety

Background: Autism spectrum disorder (ASD) is a multifactorial, pervasive, neurodevelopmental disorder, of which intestinal symptoms collectively represent one of the most common comorbidities., Methods: In this study, 1,222 children with ASD and 1,206 typically developing (TD) children aged 2-7 years were enrolled from 13 cities in China. Physical measurement and basic information questionnaires were conducted in ASD and TD children. The Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Behavior Checklist (ABC) were used to evaluate the clinical symptoms of children with ASD. The six-item Gastrointestinal Severity Index (6-GSI) was used to evaluate the prevalence of intestinal symptoms in two groups., Results: The detection rates of constipation, stool odor, and total intestinal symptoms in ASD children were significantly higher than those in TD children (40.098% vs. 25.622%, 17.021% vs. 9.287%, and 53.601% vs. 41.294%, respectively). Autistic children presenting with intestinal comorbidity had significantly higher scores on the ABC, SRS, CARS, and multiple subscales than autistic children without intestinal symptoms, suggesting that intestinal comorbidity may exacerbates the core symptoms of ASD children., Conclusion: Intestinal dysfunction was significantly more common in autistic than in TD children. This dysfunction may aggravate the core symptoms of children with ASD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Conflicts of Interest: Chen YX, None; Deng H, None; Ke XY, None; Fu M, None.

The photochemistry of noncovalent interactions to promote organic transformations is an emerging approach to providing fresh opportunities in synthetic chemistry. Generally, the external substance is necessary to add as an interaction partner, thereby sacrificing the atom economy of the reaction. Herein, we describe a catalyst-free and noncovalent interaction-mediated strategy to access the olefination of N -tosylhydrazones using acetone as a solvent and an interaction partner. This protocol also features broad substrate scope, excellent functional group compatibility, and mild reaction conditions without transition metals. Moreover, the gram-scale synthesis of olefins and the generation of pharmaceutical intermediates highlighted its practical applicability. Lastly, mechanistic studies indicate that the reaction was initiated via noncovalent interactions between acetone and N -tosylhydrazone anion, which is also supported by density functional theory calculations.

The catalytic asymmetric diastereodivergent synthesis of axially chiral 2-alkenylindoles was established via chiral phosphoric acid-catalyzed addition reactions of C3-unsubstituted 2-alkenylindoles with o -hydroxybenzyl alcohols under different reaction conditions. Using this strategy, two series of 2-alkenylindoles bearing both axial and central chirality were synthesized in a diastereodivergent fashion with moderate to high yields and good stereoselectivities (up to 99% yield, 95:5 er, >95:5 dr). Moreover, theoretical calculations were performed on the key transition states leading to different stereoisomers, which provided an in-depth understanding of the origin of the observed stereoselectivity and diastereodivergence of the products under different reaction conditions. More importantly, these 2-alkenylindoles were utilized in asymmetric catalysis as chiral organocatalysts and in medicinal chemistry for evaluation of their cytotoxicity, which demonstrated their potential applications. This study has not only established the catalytic atroposelective synthesis of axially chiral 2-alkenylindoles, but also provided an efficient strategy for catalytic asymmetric diastereodivergent construction of indole-based scaffolds bearing both axial and central chirality., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Co-published by University of Science and Technology of China and American Chemical Society.)

Objective: To investigate serum vitamin A and vitamin D status in children aged 2-<7 years in 20 cities in China. Methods: A cross-sectional study was conducted. A total of 2 924 healthy children aged 2-<7 years were recruited from September 2018 to September 2019 from 20 cities in China, categorized by age groups of 2-<3 years, 3-<5 years, and 5-<7 years. The demographic and economic characteristics and health-related information of the enrolled children were investigated. Body weight and height were measured by professional staff members. The serum vitamin A and vitamin D levels were detected by high-performance liquid chromatography-tandem mass spectrometry. Chi-square test and Logistic regression were applied to analyze the association between vitamin A and vitamin D deficiency and insufficiency as well as their underlying impact factors. Results: The age of the 2 924 enrolled children was 4.33 (3.42, 5.17) years. There were 1 726 males (59.03%) and 1 198 females (40.97%). The prevalences of vitamin A and vitamin D deficiency in enrolled children were 2.19% (64/2 924) and 3.52% (103/2 924), respectively, and the insufficiency rates were 29.27% (856/2 924) and 22.20% (649/2 924), respectively. Children with both vitamin A and vitamin D deficiencies or insufficiencies were found in 10.50% (307/2 924) of cases. Both vitamin A ( χ 2 = 7.91 and 8.06, both P =0.005) and vitamin D ( χ 2 = 71.35 and 115.10, both P <0.001) insufficiency rates were higher in children aged 3-<5 and 5-<7 years than those in children aged 2-<3 years. Vitamin A and vitamin D supplementation in the last 3 months was a protective factor for vitamin A and D deficiency and insufficiency, respectively ( OR =0.68 and 0.22, 95% CI 0.49-0.95 and 0.13-0.40, both P <0.05). The rates of vitamin A and D insufficiency was higher in children with annual household incomes <60 000 RMB than in those with annual household incomes ≥60 000 RMB ( χ 2 = 34.11 and 10.43, both P <0.01). Northwest and Southwest had the highest rates of vitamin A and vitamin D insufficiency in children aged 2-<7 yeas, respectively ( χ 2 = 93.22 and 202.54, both P <0.001). Conclusions: Among 20 cities in China, children aged 2-<7 years experience high rates of vitamin A and vitamin D insufficiency, which are affected by age, family economic level, vitamin A and vitamin D supplementation, and regional economic level. The current results suggest that high level of attention should be paid to vitamin A and vitamin D nutritional status of preschool children.

Childhood trauma refers to trauma experiences encountered during childhood and adolescence. Maternal childhood trauma experiences have a lasting impact on the next generation, affecting their physical and mental well-being. The mechanisms involved include the hypothalamic-pituitary-adrenal axis, inflammatory factors, brain structure and function, gene interactions, and parenting styles. This paper systematically reviews the mechanisms of the impact of maternal childhood trauma on intergenerational transmission, providing insights for the prevention of intergenerational transmission of childhood trauma.

Objective: To analyze the diagnostic and prognostic values of flow cytometry (FC) in diffuse large B cell lymphoma (DLBCL) with bone marrow involvement (BMI). Methods: The clinical data of 412 patients with newly diagnosed DLBCL, including 243 males and 169 females, aged 64 (28-92) years old, in the Department of Hematology at Peking University Third Hospital from December 2012 to June 2022 were retrospectively analyzed. All patients underwent bone marrow biopsy (BMB) and bone marrow FC. The patients with BMI by FC were further detected by fluorescence in situ hybridization (FISH) for gene analysis. The positive rates and consistency of BMI detected by BMB and FC were evaluated. According to the results of BMB and FC examinations, all patients were divided into four groups: the BMB + FC + group (115 cases), the BMB - FC + group (50 cases), the BMB + FC - group (8 cases, the results did not include in statistical analysis because of small sample size), and the BMB - FC - group (239 cases). The clinical features, treatment response rates, 5-year survival rates, and immunophenotype characteristics by FC in different groups were analyzed. Results: Among the 412 patients with DLBCL, the positivity rates of BMB and FC for BMI detection were 29.9% (123/412) and 40.0% (165/412), respectively. Good consistency between BMB and FC was found (Kappa=0.841, P =0.001). The numbers of extranodal involvement≥2, splenomegaly, huge mass, higher Ki-67 score, higher international prognostic index (IPI) score, thrombocytopenia, and elevated lactate dehydrogenase level were more prevalent in the BMB + FC + group than those in the BMB - FC + group and the BMB - FC - group (all P <0.05). The treatment response rate in BMB + FC + group was 63.5% (73/115), which was lower than those in BMB - FC + group (88.0%, 44/50, P =0.048) and BMB - FC - group (90.0%, 215/239, P =0.032), respectively. The 5-year overall survival rates in three groups were (53.6±9.7) %, (72.5±8.6) %, and (75.2±7.6) %, respectively, with a statistically significant difference ( P =0.037). According to the FISH results of bone marrow, 102 cases were diagnosed as not otherwise specified (NOS), 48 cases were diagnosed as double hit lymphoma (DHL), and 15 cases were diagnosed as triple hit lymphoma (THL). Compared with NOS subtypes, the tumor cells in DHL or THL subtypes had higher proportion of increased side scatter (SSC), higher positive rates of CD10 expression, CD38 strong expression and CD56 expression, and lower proportion of surface immunoglobulin light chain restriction (all P <0.05). Conclusions: FC is well consistent with BMB in diagnosing DLBCL with BMI. Combined with FISH detection, FC can contribute to the auxiliary diagnosis and risk stratification for DHL and THL, and provide reference for the prognostic evaluation in DLBCL with BMI.

Importance: Multiple studies indicate a possible correlation between ADD3 rs2501577 and biliary atresia susceptibility; however, a conclusive determination has yet to be made., Objective: Investigate the role of ADD3 rs2501577 in biliary atresia susceptibility across diverse populations., Data Sources: The study protocol has been registered on PROSPERO, an international platform for systematic review registration (PROSPERO ID: CRD42023384641). The following databases will be searched until February 1, 2023: PubMed, Embase, Cochrane, CBM, Web of Science, and CNKI., Study Selection: Eight studies were selected from seven papers to assess the data. A total of 7651 participants were included, consisting of 1662 in the BA group and 5989 in the NC group., Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed while conducting the systematic reviews and meta-analyses. Two authors independently assessed the quality of the included studies using the Newcastle-Ottawa Quality Assessment Scale. The significance of the pooled odds ratio (OR) was evaluated with a Z test, and statistical heterogeneity across studies was assessed using the I2 and Q statistics. Publication bias was assessed using Egger's and Begg's tests., Main Outcome(s) and Measure(s): The primary study outcome was the development of biliary atresia. Subgroup analysis was performed based on race, region, and assessment of Hardy-Weinberg equilibrium (HWE)., Results: The studies indicate that the ADD3 rs2501577 susceptibility locus increases the risk of developing biliary atresia, regardless of allelic, homozygote, dominant, and recessive gene inheritance models. Furthermore, ADD3 has been found to be associated with apoptosis, cell cycle, and cell damage repair based on functional analysis., Conclusions and Relevance: The ADD3 rs2501577 polymorphic locus is associated with an increased risk of biliary atresia, particularly in Asian populations. This study recommends further investigation of the ADD3 rs2501577 locus in Asian populations to validate its role in the diagnosis of biliary atresia., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To analyze the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating T lymphoblastic leukemia/lymphoma (T-ALL/LBL) . Methods: This study retrospectively evaluated 119 adolescent and adult patients with T-ALL/LBL from January 2006 to January 2020 at Peking University Third Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Patients were divided into chemotherapy-only, chemotherapy followed by allo-HSCT, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) groups according to the consolidation regimen, and the 5-year overall survival (OS) and progression-free survival (PFS) rates of each group were compared. Results: Among 113 patients with effective follow-up, 96 (84.9%) patients achieved overall response (ORR), with 79 (69.9%) having complete response (CR) and 17 (15.0%) having partial response (PR), until July 2022. The analysis of the 96 ORR population revealed that patients without transplantation demonstrated poorer outcomes compared with the allo-HSCT group (5-year OS: 11.4% vs 55.6%, P =0.001; 5-year PFS: 8.9% vs 54.2%, P <0.001). No difference was found in 5-year OS and 5-year PFS between the allo-HSCT and auto-HSCT groups ( P =0.271, P =0.197). The same results were achieved in the CR population. Allo-HSCT got better 5-year OS (37.5% vs 0) for the 17 PR cases ( P =0.064). Different donor sources did not affect 5-year OS, with sibling of 61.1% vs hap-haploidentical of 63.6% vs unrelated donor of 50.0% ( P >0.05). No significant difference was found in the treatment response in the early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP) and non-ETP populations. The ETP group demonstrated lower 5-year OS compared with the non-ETP group in the chemotherapy alone group (0 vs 12.6%, P =0.045), whereas no significant difference was found between the ETP and non-ETP groups in the allo-HSCT group (75.0% vs 62.9%, P =0.852). Multivariate analysis revealed that high serum lactate dehydrogenase level, without transplantation, and no CR after chemotherapy induction were independently associated with inferior outcomes ( P <0.05) . Conclusion: Allo-HSCT could be an effective consolidation therapy for adult and adolescent patients with T-ALL/LBL. Different donor sources did not affect survival. Allo-HSCT may overcome the adverse influence of ETP-ALL/LBL on OS.

Toxic As(Ⅲ) and Cd(Ⅱ) ions in water can be transferred and enriched into human bodies through the food chain, causing serious health damage at excessive levels. In this study, fulvic acid (FA) was selected as the modifier of iron-manganese-nickel layered double hydroxide (FeMnNi-LDH), and a stable layered composite (FA@FeMnNi-LDH) was prepared using the co-precipitation method, which could adsorb As(Ⅲ) anions and Cd(Ⅱ) cations simultaneously, especially with the higher adsorption capacity of the cation Cd(Ⅱ). Its structure was characterized by XRD, TEM, FT-IR, and XPS, and the adsorption capacity and mechanisms of As(Ⅲ) and Cd(Ⅱ) in water by the composite were also investigated. The results showed that with typical characteristic peaks of layered double hydroxides, the synthesized composite possessed a stable structure, maximum FA loading capacity, and optimal adsorption performance. The adsorption kinetics of As(Ⅲ) and Cd(Ⅱ) conformed to the pseudo-second-order kinetic model, and the adsorption isotherms well-followed the Langmuir model, with the maximum adsorption capacity at 25℃ being 249.60 mg·g -1 for As(Ⅲ) and 156.50 mg·g -1 for Cd(Ⅱ), respectively. The composite exhibited a good adsorption performance on As(Ⅲ) and Cd(Ⅱ) in the range of pH 2-7 and pH 4-7, respectively. The competitive adsorption effect of co-existed anions on As(Ⅲ) showed a sequence of PO 4 3- >CO 3 2- >NO 3 - , and that of co-existed cations on Cd(Ⅱ) was Pb 2+ >Cu 2+ >K + . The adsorption capacity of As(Ⅲ) and Cd(Ⅱ) decreased with the increase in the concentration of competing ions. The main adsorption mechanism for As(Ⅲ) was ion-exchange occurring in the interlayers of LDH, and that for Cd(Ⅱ) was coordination complexation occurring with the loaded FA, respectively. In conclusion, the prepared FA@FeMnNi-LDH composite material posed a good application prospect for adsorption removal of As(Ⅲ) and Cd(Ⅱ) in water and their toxicity control.

The present study investigated the association between the presence of periodontitis and aortic calcification (AC) risk among Chinese adults. A total of 6059 individuals who underwent regular health check-ups and received a diagnosis of periodontitis between 2009 and 2016 were included. The outcome was AC, assessed by a chest low-dose spiral CT scan. Cox proportional hazards regression analysis was used to assess the association between periodontitis and AC risk after adjusting for several confounders. After a median follow-up period of 2.3 years (interquartile range: 1.03-4.97 years), 843 cases of AC were identified, with 532 (12.13%) and 311 (18.59%) patients in the non-periodontitis group and periodontitis group, respectively. Multivariate analyses demonstrated that, compared with those without periodontitis, the hazard ratio and 95% confidence interval for AC risk in participants with periodontitis was 1.18 (1.02-1.36) ( P = .025) in the fully adjusted model. Stratified analyses showed that the positive relationship between periodontitis and AC was more evident in males and participants <65 years of age (p interaction = .005 and .004, respectively). Our results show that the presence of periodontitis was positively associated with AC among Chinese adults, especially among males and younger participants.

Objective: To investigate the influece of early relapse in the era of novel drugs on the prognosis of the patients with newly diagnosed multiple myeloma（NDMM） and risk factors, and to provide the basis for the early identification of the high-risk patients and guiding the treatment., Methods: The clinical data of the patients with NDMM admitted to our hospital from November 2011 to May 2022 were retrospectively analyzed. According to whether the progression free survival（PFS） was more than 12 months, they were divided into early relapse group（≤12 months） and late relapse group（＞12 months）. The high-risk factors of the patients in two groups were analyzed, including age, anemia, renal insufficiency, hypercalcemia, increasing of lactate dehydrogenase（LDH） level, Extramedullary disease (EMD), International Staging System（ISS） stage, Revised International Staging System （R-ISS） stage, cytogenetic abnormalities(CA) detected by fluorescence in situ hybridization（FISH）, and treatment efficacy. The meaningful clinical indicators were screened, and multivariate analysis was used to explore the high-risk factors of early relapse., Results: 170 patients with NDMM were collected, including 25 cases in early relapse group and 145 cases in late relapse group. The median OS time of the patients in early death group was 20 months, and 140 months in late relapse group by the end of follow-up, there was significant difference in OS of the patients between two groups（ P <0.001）. Fifteen patients（56.0％）in early relapse group obtained ≥VGPR, and 113（77.9%） patients in late relapse group, the difference was statistically significant（ P =0.011）. Survival outcomes remained poor among early relapse patients irrespective of depth of response to initial therapy. Multivariate analysis showed that the EMD and high-risk CA predicted early relapse., Conclusion: The prognosis of patients with early relapse in NDMM is poor. EMD and high-risk CA is an independent prognostic factor of early relapse.

Objective: To investigate the clinical features and prognosis of MYC/BCL2 double-expression diffuse large B-cell lymphoma (DEL) . Methods: The clinical data, including clinical characteristics, survival, and prognostic factors, of 166 patients with DEL treated at Peking University Third Hospital from January 2016 to December 2020 were retrospectively analyzed. Results: A total of 410 patients with diffuse large B-cell lymphoma were collected, including 166 cases (40.5%) of DEL. There were 82 males and 84 females with a median age of 63.5 (21-95) years at diagnosis. A total of 110 patients (66.3%) were aged over 60 years at initial diagnosis, 106 patients (106/163, 65.0%) had elevated lactate dehydrogenase (LDH) at diagnosis, 74 patients (74/160, 46.2%) had β(2) microglobulin level over 3 mg/L at diagnosis, and 107 patients (107/163, 65.6%) had≥2 extranodal involvement. Sixty-five patients (65/166, 39.2%) had B symptoms, 131 patients (131/165, 79.4%) had stage Ⅲ and Ⅳ disease at initial diagnosis, 41 patients (41/161, 25.5%) had an International Prognostic Index (IPI) score of 0-2 at initial diagnosis, and 38 patients (38/161, 23.6%) had an IPI score of 3 at initial diagnosis. Eighty-two patients (82/161, 50.9%) had an IPI score of 4-5 at initial diagnosis. Nine (9/56, 16.1%) patients with DEL had MYD88 and CD79B mutations. Univariate analysis showed that age over 60 years ( P =0.004) , increased β(2) microglobulin level ( P =0.002) , and high IPI score ( P =0.003) were associated with poor overall survival (OS) . Increased β(2) microglobulin level ( P =0.031) , LDH level ( P =0.017) , stage Ⅲ-Ⅳ ( P =0.001) , high IPI score ( P =0.013) , immunohistochemical p53 mutation ( P =0.049) , and PIM1 mutation ( P =0.039) were associated with poor progression-free survival (PFS) . Multivariate analysis showed that IPI score of 4-5 was an independent risk factor for the prognosis of DEL ( HR =2.622, 95% CI 1.398-4.917, P =0.003) . Survival analysis showed that there was a significant difference in the PFS between patients with DEL and those without DEL (65.6% vs 75.1%, P =0.002) . However, there was no significant difference in the OS (81.8% vs 83.6%, P =0.226) . In patients with DEL, the overall response rate of R-EPOCH regimen was higher than that of RCHOP or RCHOP-like regimen (81.5% vs 63.4%, P =0.004) . Conclusion: DEL is a group of aggressive lymphomas with relatively poor PFS. The R-EPOCH regimen may improve the overall prognosis of patients.

Autism spectrum disorder (ASD) is a prevalent and complex neurodevelopmental disorder which has strong genetic basis. Despite the rapidly rising incidence of autism, little is known about its aetiology, risk factors, and disease progression. There are currently neither validated biomarkers for diagnostic screening nor specific medication for autism. Over the last two decades, there have been remarkable advances in genetics, with hundreds of genes identified and validated as being associated with a high risk for autism. The convergence of neuroscience methods is becoming more widely recognized for its significance in elucidating the pathological mechanisms of autism. Efforts have been devoted to exploring the behavioural functions, key pathological mechanisms and potential treatments of autism. Here, as we highlight in this review, emerging evidence shows that signal transduction molecular events are involved in pathological processes such as transcription, translation, synaptic transmission, epigenetics and immunoinflammatory responses. This involvement has important implications for the discovery of precise molecular targets for autism. Moreover, we review recent insights into the mechanisms and clinical implications of signal transduction in autism from molecular, cellular, neural circuit, and neurobehavioural aspects. Finally, the challenges and future perspectives are discussed with regard to novel strategies predicated on the biological features of autism., (© 2022. The Author(s).)

Objectives: To quantify the burden and variation trends of cancers in children under 5 years at the global, regional, and national levels from 1990 to 2019., Methods: Epidemiological data for children under 5 years who were diagnosed with any one childhood cancer were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) from 1990 to 2019. The outcomes were the absolute numbers and rates of incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for different types of cancer., Results: In 2019, 8,774,979.1 incident cases (95% uncertainty interval [UI]: 6,243,599.2 to11,737,568.5) and 8,956,583.8 (6,446,323.9 to 12,364,520.8) prevalent cases of cancer in children under 5 years were identified worldwide; these cancers resulted in 44,451.6 (36,198.7 to 53,905.9) deaths and 3,918,014.8 (3,196,454.9 to 4,751,304.2) DALYs. From 1990 to 2019, although the numbers of incident and prevalent cases only decreased by -4.6% (-7.0 to -2.2) and -8.3% (-12.6 to -3.4), respectively, the numbers of deaths and DALYs clearly declined by -47.8% (-60.7 to -26.4) and -47.7% (-60.7 to -26.2), respectively. In 2019, the middle sociodemographic index (SDI) regions had the highest incidence and prevalence, whereas the low SDI regions had the most mortality and DALYs. Although all of the SDI regions displayed a steady drop in deaths and DALYs between 1990 and 2019, the low-middle and low SDI regions showed increasing trends of incidence and prevalence. Leukemia remained the most common cancer globally in 2019. From 1990 to 2019, the burdens of leukemia, liver cancer, and Hodgkin's lymphoma declined, whereas the incidence and prevalence of other cancers grew, particularly testicular cancer., Conclusions: The global childhood cancer burden in young children has been steadily decreasing over the past three decades. However, the burdens and other characteristics have varied across different regions and types of cancers. This highlights the need to reorient current treatment strategies and establish effective prevention methods to reduce the global burden of childhood cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ren, Liao, Tan, Cheng, Zhu, Zheng, Ma, Mu, Li, Zhang, OuYang, Li, Cui, Ke, Luo, Xiong, Liu, Li, Liang, Zeng, Su and Han.)

Objective: To investigate the expression of PD-L1 and PD-1 in pathological tissue of patients newly diagnosed with diffuse large B-cell lymphoma (DLBCL)., Methods: Data of DLBCL patients who visited the Department of Hematology, Peking University Third Hospital from May 2014 to March 2017 were collected, and a total of 21 patients with pathological tissue sections which were still available at the initial treatment were selected. The patients were divided into complete remission (CR) group and refractory relapse (RR) group according to clinical outcome. The expression and proportion of PD-1 and PD-L1 in pathological tissue sections were detected by multiplex fluorescence immunohistochemical staining, and the differences in the expression of different molecular markers in different clinical characteristics and different prognosis were compared using non-parametric test., Results: The ratio of PD-L1 + cells to PD-1 + cells (PD-L1 + : PD-1 + ) was 5.14±3.825 in increased lactate dehydrogenase (LDH) group, which was significantly higher than 0.76±0.563 in non-increased LDH group (P=0.001). The ratio of PD-L1 + : PD-1 + in increased Treg cells group was 1.41±1.454, which was lower than 6.42±4.426 in decreased Treg cells group (P=0.023)., Conclusion: The increased expression ratio of PD-L1 to PD-1 in pathological tissue sections of newly diagnosed DLBCL patients is associated with poor prognostic clinical characteristics.

Objective: To explore the influence of parents on the medication adherence of their children., Study Design: A cross-sectional online investigation., Methods: A questionnaire with 41 questions was designed based on the health belief model (HBM) distributed and collected online in 28 cities around China through multi-stage stratified sampling. The reliability of the questionnaire was assessed with Cronbach's α coefficient and split-half reliability, and its validity was evaluated with exploratory factor analysis and content validity index. The structural equation model (SEM) was constructed to explore the relationship between the parents' health beliefs and their children's medication adherence. Subgroup analysis was conducted to study the differences between parents with different demographic characteristics (male and female, rural and urban)., Results: 573 questionnaires were included for analysis, with an effective rate of 62.97%. The Cronbach'α coefficient of the questionnaire was 0.821 > 0.6, the split-half reliability was 0.651 > 0.6, the I-CVI of each dimension were >0.78, and the S-CVI/AVE (I-CVI average) was 0.95 > 0.9. The result of the questionnaire exploratory factor analysis met the standard. According to the SEM, self-efficacy (λ = 0.177), perceived susceptibility (λ = -0.244), and perceived severity (λ = 0.243) were direct influencing factors of children's medication adherence. In the subgroup analysis, the model established by each subgroup was consistent with the model established by the overall sample. The absolute values of females' perceived susceptibility, severity, and self-efficacy for their children's medication adherence path coefficients were higher than males'., Conclusion: Parents' perceived severity and self-efficacy may positively impact on their children's medication adherence, while parents' susceptibility to children's medication non-adherence may negatively impact on children's medication adherence. Objective constraints, perceived barriers, and benefits may in directly impact on children's medication adherence. Women's health beliefs appear to have a more significant impact on their children's medication adherence than men's. It may be an effective strategy to increase their children's medication adherence by improving parents' health beliefs. Medical staff should explain medication adherence knowledge to the parents of children, and inform the children of the possible consequences of non-adherence with medication, to improve the subjective perception of parents on the severity of children's non-adherence with medication, and improve parents' self-efficacy in rational medication for children. In addition, attention should be paid to the mental health of the parents, and more social and psychological support., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ge, Liu, Xu, Zhang, Lai, Fu, Ke, Zhao, Bian and Wu.)

Circular RNAs (circRNAs) are produced by head-to-tail back-splicing which is mainly facilitated by base-pairing of reverse complementary matches (RCMs) in circRNA flanking introns. Adenosine deaminases acting on RNA (ADARs) are known to bind double-stranded RNAs for adenosine to inosine (A-to-I) RNA editing. Here we characterize ADARs as potent regulators of circular transcriptome by identifying over a thousand of circRNAs regulated by ADARs in a bidirectional manner through and beyond their editing function. We find that editing can stabilize or destabilize secondary structures formed between RCMs via correcting A:C mismatches to I(G)-C pairs or creating I(G).U wobble pairs, respectively. We provide experimental evidence that editing also favors the binding of RNA-binding proteins such as PTBP1 to regulate back-splicing. These ADARs-regulated circRNAs which are ubiquitously expressed in multiple types of cancers, demonstrate high functional relevance to cancer. Our findings support a hitherto unappreciated bidirectional regulation of circular transcriptome by ADARs and highlight the complexity of cross-talk in RNA processing and its contributions to tumorigenesis., (© 2022. The Author(s).)

Novel advances in the field of brain imaging have enabled the unprecedented clinical application of various imaging modalities to facilitate disease diagnosis and treatment. Electrical impedance tomography (EIT) is a functional imaging technique that measures the transfer impedances between electrodes on the body surface to estimate the spatial distribution of electrical properties of tissues. EIT offers many advantages over other neuroimaging technologies, which has led to its potential clinical use. This qualitative review provides an overview of the basic principles, algorithms, and system composition of EIT. Recent advances in the field of EIT are discussed in the context of epilepsy, stroke, brain injuries and edema, and other brain diseases. Further, we summarize factors limiting the development of brain EIT and highlight prospects for the field. In epilepsy imaging, there have been advances in EIT imaging depth, from cortical to subcortical regions. In stroke research, a bedside EIT stroke monitoring system has been developed for clinical practice, and data support the role of EIT in multi-modal imaging for diagnosing stroke. Additionally, EIT has been applied to monitor the changes in brain water content associated with cerebral edema, enabling the early identification of brain edema and the evaluation of mannitol dehydration. However, anatomically realistic geometry, inhomogeneity, cranium completeness, anisotropy and skull type, etc., must be considered to improve the accuracy of EIT modeling. Thus, the further establishment of EIT as a mature and routine diagnostic technique will necessitate the accumulation of more supporting evidence., (© 2022. The Author(s).)

Objective: To investigate the clinical characteristics and treatment outcome of patients with Burkitt lymphoma., Methods: The clinical data of 27 patients with Burkitt Lymphoma were collected and retrospectively analyzed, the clinical characteristics, laboratory data, survival and the factors affecting the prognosis were also analyzed., Results: Among the 27 patients (mainly for adults), the median age was 30 (15-83) years old, the ratio of male and female was 3.5∶1. There was no EB virus infection in all the patients, 92.6% of the patients showed extranodal organs involvement, 40.7% of them were leukemic stage, 85.2% patients belonged to Ⅲ and Ⅳ stage, 74.1% patients belonged to high/high-middle risk according to IPI index. In the terms of molecular biology, five patients were treated with next-generation sequencing test, and the MYC gene mutations were detected out in alt the patients, and the most common mutations were CCND3, ID3 and TP53. The overall response rate (ORR) for all the patients was 85.2%, the complete response (CR) rate was 63.0%, and the partial response rate was 22.2%, the 5-year progression-free survival rate and overall survival rate of the patients was 76.6% and 76.6%, respectively, which showed that the efficacy of the patients in high-dose methotrexate treatment group was higher than that in the non-high high-dose methotrexate treatment group. For the patients treated with LMB89 chemotherapy, the CR was 78.6%, ORR was 100%, the 5-year survival rate was 92.9%, which was superior to the patients treated with other regimens. Auto-hematopoietic stem cell transplantation as consolidation treatment could improve the prognosis for those patients who could not tolerate high-dose chemotherapy. Univariate analysis showed that ECOG score, the level of LDH>500 U/L, WBC level, CNS involvement, short-term effect and LMB89 regimen were the risk factors affecting the prognosis of the patients., Conclusion: The adult Burkitt lymphoma are highly aggressive. For the patients in high-dose methotrexate treatment group, especially LMB89 regimen can improve the survival of the patients, and to choose HSCT as a consolidation treatment can be a choice for those patients who could not tolerate high-dose chemotherapy.

Glutamate excitotoxicity in cerebral ischemia/reperfusion is an important cause of neurological damage. The aim of this study was to investigate the mechanism of Na+, K+-ATPase (NKA) involved in l ow concentration of ouabain (Oua, activating NKA)-induced protection of rat cerebral ischemia-reperfusion injury. The 2,3,5-triphenyltetrazolium chloride (TTC) staining and neurological deficit scores (NDS) were performed to evaluate rat cerebral injury degree respectively at 2 h, 6 h, 1 d and 3 d after reperfusion of middle cerebral artery occlusion (MCAO) 2 h in rats. NKA α1/α2 subunits and glutamate transporter-1 (GLT-1) protein expression were investigated by Western blotting. The cerebral infarct volume ratio were evidently decreased in Oua group vs MCAO/R group at 1 d and 3 d after reperfusion of 2 h MCAO in rats (*p ＜ 0.05 ). Moreover, NDS were not significantly different (p ＞ 0.05 ). NKA α1 was decreased at 6 h and 1 d after reperfusion of 2 h MCAO in rats, and was improved in Oua group. However, NKA α1 and α2 were increased at 3 d after reperfusion of 2 h MCAO in rats, and was decreased in Oua group. GLT-1 was decreased at 6 h, 1 d and 3 d after reperfusion of 2 h MCAO in rats, and was improved in Oua group. These data indicated that l ow concentration of Oua could improve MCAO/R injury through probably changing NKA α1/α2 and GLT-1 protein expression, then increasing GLT-1 function and promoting Glu transport and absorption, which could be useful to determine potential therapeutic strategies for patients with stroke. Low concentration of Oua improved rat MCAO/R injury via NKA α1/α2 and GLT-1., (© 2021 Société Française de Pharmacologie et de Thérapeutique.)

Objective: To study the characteristics and risk factors of psychological and behavioral problems of children and adolescents of different ages and genders in long-term home-schooling during the coronavirus disease-2019 pandemic. Further, to provide scientific basis for more targeted psychological intervention and coping strategies in the future. Methods: A cross-sectional survey using an online questionnaire was conducted on students aged 6-16 years old in five representative cities of North (Beijing), East (Shanghai), West (Chongqing), South (Guangzhou) and Middle (Wuhan) in China. In this study, the social behavior and psychological abnormalities which was defined as the positive of any dimension were investigated in multiple dimensions during long-term home-schooling. The influencing factors of psycho-behavioral problems were analyzed by Logistic regression, and the confounding factors were corrected with graded multivariable adjustment. Results: A total of 6 906 valid questionnaires were collected including 3 592 boys and 3 314 girls, of whom 3 626 were children (6-11 years old) and 3 280 were adolescents (12-16 years old). The positive detection rate of psychosocial-behavioral problems were 13.0% (900/6 906) totally, 9.6% (344/3 592) in boys and 16.8% (556/3 314) in girls respectively, and 7.3%(142/1 946) in boys aged 6-11, 14.0%(235/1 680) in girls aged 6-11, 12.3%(202/1 646) in boys aged 12-16, 19.6%(321/1 634) in girls aged 12-16 respectively. There were significant differences between the psychological problems group and the non-psychological problems group in gender, parent-offspring conflict, number of close friends, family income change, sedentary time, homework time, screen exposure time, physical activity, dietary problems (χ²=78.851, 285.264, 52.839, 26.284, 22.778, 11.024, 10.688, 36.814, 70.982, all P <0.01). The most common symptoms in boys aged 6-11 years were compulsive activity, schizoid and depression, in girls aged 6-11 years were schizoid/compulsive activity, hyperactivity and social withdrawal, in boys aged 12-16 years were hyperactivity, compulsive activity and aggressive behavior, and in girls aged 12-16 years were schizoid, anxiety/compulsive activity and depression/withdrawal, respectively. After graded multivariable adjustment, besides the common risk factors, homework time and online study time were the risk factors of 6-11 years old groups [boys OR (95% CI ): 1.750 (1.32-2.32), 1.214(1.00-1.47), girls: 1.579(1.25-1.99), 1.222(1.05-1.42), all P <0.05], videogames time were the risk factors of 12-16 years old groups [ boys: 2.237 (1.60-3.13), girls: 1.272 (1.00-1.61), all P <0.05]. Conclusions: Some children and adolescents may have psychological and behavioral problems during long-term home-schooling. The psychological and behavioral manifestations differed in age and gender subgroups, which deserve special attention in each subgroups. Schools, families and specialists should actively provide precise psychological support and comprehensive intervention strategies according to special features and risk factors.

BACKGROUND The digestive tract is the most common site of extranodal involvement in diffuse large B cell lymphoma (DLBCL) and its prognostic evaluation is different from that of ordinary DLBCL. Currently, for gastrointestinal lymphoma, in addition to the Ann Arbor staging system, the Lugano and the TNM staging systems are commonly used. However, there is no effective prognostic model to identify poor prognosis in patients with localized gastrointestinal diffuse large B cell lymphoma (GI-DLBCL). MATERIAL AND METHODS This study included 82 patients with GI-DLBCL that had a median follow-up of 75 months, and developed a model (HLAMA) with 5 variables: hemoglobin, age, lactate dehydrogenase (LDH), serum albumin, and the maximum intra-abdominal lesion diameter (MIALD). The specific indicators are: HGB <105 g/L (2 points); LDH ≥300 U/L; age ≥75 years, ALB <38 g/L, MIALD ≥4 cm (each scoring 1 point). We also developed a simplified model, which includes only 3 variables (HGB, LDH, and age). RESULTS HLAMA model and the simplified model both demonstrated good ability to predict prognosis of patients with GI-DLBCL (P<0.001), performing better than the IPI score as it could distinguish low-risk groups in relatively elderly patients (60-75 years old). CONCLUSIONS This study established a prognostic model for diffuse large B cell lymphoma of the gastrointestinal tract. Both the HLAMA model and its simplified version are similar to the IPI score, but could be considered better as they can provide a simpler and more accurate prognostic assessment in patients with GI-DLBCL. For patients with localized GI-DLBCL, our model could distinguish high-risk patients.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Folate has been demonstrated to be associated with ASD. However, current studies on the correlation between folate and symptoms of children with ASD have inconsistent conclusions, use mainly small samples, and lack age-stratified analysis. This study aimed to explore the association between serum folate and symptoms of autistic children at different age groups from a multi-center perspective. Methods: We enrolled 1,300 children with ASD and 1,246 typically developing (TD) children under 7 years old from 13 cities in China. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood autism rating scale (CARS) were used to evaluate the symptoms of children with ASD. China neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) scale was used to evaluate the neurodevelopment of children with ASD. Serum folate was measured by chemiluminescence assay in the two groups. Results: The serum folate levels of children with ASD were lower than that of TD children. In terms of core symptoms of ASD, we found that the serum folate levels were not associated with ABC, SRS, and CARS scores in ASD children of all ages but negatively associated with communication warning behavior scores of CNBS-R2016 in ASD children aged three and under. Concerning development quotients, it was at the age of three and under that serum folate levels were positively associated with gross motor, fine motor, language, and general quotient of ASD children. These ASD children aged three and under were further divided into two groups according to the median of serum folate (14.33 ng/mL); we found that compared to ASD children with folate ≤ 14.33 ng/mL, those with folate >14.33 ng/mL had lower communication warning behavior score and higher gross motor, fine motor, adaptive behavior, language, person-social, and general development quotients. Conclusion: We found that serum folate status was primarily associated with the neurodevelopment of children with ASD aged three and under. Furthermore, relatively higher serum folate levels may be more beneficial for children with ASD. Our results suggest that folate level should be paid more attention in ASD children, especially in early life, to better promote the intervention of ASD children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Yang, Chen, Dai, Wu, Jia, Hao, Li, Zhang, Ke, Yi, Hong, Chen, Fang, Wang, Wang, Jin, Dong, Chen and Li.)

Background: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment., Methods: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR., Results: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities., Conclusion: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients., Clinical Trial Registration: ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Objective: To study the association of serum levels of trace elements with core symptoms in children with autism spectrum disorder (ASD)., Methods: From September 2018 to September 2019, an investigation was performed for 1 020 children with ASD and 1 038 healthy children matched for age and sex in the outpatient service of grade A tertiary hospitals and special education institutions in 13 cities of China. Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood Autism Rating Scale (CARS) were used to assess the core symptoms of the children with ASD. The inductively coupled plasma mass spectrometry was used to measure serum levels of trace elements magnesium, iron, copper, and zinc., Results: The children with ASD had significantly lower serum levels of magnesium, copper, and zinc than the healthy children ( P < 0.05). The children with severe ASD had significantly lower serum levels of magnesium and zinc than those with mild-to-moderate ASD ( P < 0.05). The results of partial correlation analysis showed that serum magnesium level was negatively correlated with the total score of ABC and the score of communication ( r =-0.318 and -0.282 respectively; P 0.001), and serum zinc level was negatively correlated with the total score of ABC and the scores of communication and somatic movement ( r =-0.221, -0.270, and -0.207 respectively; P < 0.001)., Conclusions: The serum levels of magnesium and zinc may be associated with core symptoms in children with ASD, which requires further studies. The nutritional status of trace elements should be monitored for children with ASD in clinical practice.

Homocysteine (Hcy) is a sulfur-containing amino acid that originated in methionine metabolism and the elevated level of Hcy in plasma is considered to be an independent risk factor for cardiovascular diseases (CVD). Endothelial dysfunction plays a major role in the development of CVD, while the potential mechanism of Hcy-induced endothelial dysfunction is still unclear. Here, in Hcy-treated endothelial cells, we observed the destruction of mitochondrial morphology and the decline of mitochondrial membrane potential. Meanwhile, the level of ATP was reduced and the reactive oxygen species was increased. The expressions of dynamin-related protein 1 (Drp1) and phosphate-Drp1 (Ser616) were upregulated, whereas the expression of mitofusin 2 was inhibited by Hcy treatment. These findings suggested that Hcy not only triggered mitochondrial dysfunction but also incurred an imbalance of mitochondrial dynamics in endothelial cells. The expression of mitochondrial calcium uniporter (MCU) was activated by Hcy, contributing to calcium transferring into mitochondria. Interestingly, the formation of mitochondria-associated membranes (MAMs) was increased in endothelial cells after Hcy administration. The inositol 1,4,5-triphosphate receptor (IP3R)-glucose-regulated protein 75 (Grp75)-voltage-dependent anion channel (VDAC) complex, which was enriched in MAMs, was also increased. The accumulation of mitochondrial calcium could be blocked by inhibiting with the IP3R inhibitor Xestospongin C (XeC) in Hcy-treated cells. Then, we confirmed that the mitochondrial dysfunction and the increased mitochondrial fission induced by Hcy could be attenuated after Hcy and XeC co-treatment. In conclusion, Hcy-induced mitochondrial dysfunction and dynamics disorder in endothelial cells were mainly related to the increase of calcium as a result of the upregulated expressions of the MCU and the IP3R-Grp75-VDAC complex in MAMs., (© 2021 Wiley Periodicals LLC.)

Molecular profiling of the most aggressive brain tumor glioblastoma (GBM) on the basis of gene expression, DNA methylation, and genomic variations advances both cancer research and clinical diagnosis. The enhancer architectures and regulatory circuitries governing tumor-intrinsic transcriptional diversity and subtype identity are still elusive. Here, by mapping H3K27ac deposition, we analyze the active regulatory landscapes across 95 GBM biopsies, 12 normal brain tissues, and 38 cell line counterparts. Analyses of differentially regulated enhancers and super-enhancers uncovered previously unrecognized layers of intertumor heterogeneity. Integrative analysis of variant enhancer loci and transcriptome identified topographies of transcriptional enhancers and core regulatory circuitries in four molecular subtypes of primary tumors: AC1-mesenchymal, AC1-classical, AC2-proneural, and AC3-proneural. Moreover, this study reveals core oncogenic dependency on super-enhancer-driven transcriptional factors, long noncoding RNAs, and druggable targets in GBM. Through profiling of transcriptional enhancers, we provide clinically relevant insights into molecular classification, pathogenesis, and therapeutic intervention of GBM., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

This study aimed to determine the levels of health-related behaviours (physical activity, screen exposure and sleep status) among Chinese students from primary, secondary and high schools during the pandemic of COVID-19, as well as their changes compared with their status before the pandemic. A cross-sectional online survey of 10,933 students was conducted among 10 schools in Guangzhou, China, between 8th and 15th March, 2020. After getting the informed consent from student's caregivers, an online questionnaire was designed and used to obtain time spending on health-related behaviours during the pandemic of COVID-19, as well as the changes compared with 3 months before the pandemic, which was completed by students themselves or their caregivers. Students were stratified by regions (urban, suburban, exurban), gender (boys and girls), and grades (lower grades of primary school, higher grades of primary schools, secondary schools and high schools). Data were expressed as number and percentages and Chi-square test was used to analyse difference between groups. Overall, the response rate of questionnaire was 95.3% (10,416/10,933). The median age of included students was 13.0 (10.0, 16.0) years and 50.1% (n = 5,219) were boys. 41.4%, 53.6% and 53.7% of total students reported less than 15 min per day in light, moderate and vigorous activities and 58.7% (n = 6,113) reported decreased participation in physical activity compared with the time before pandemic. Over 5 h of screen time spending on online study was reported by 44.6% (n = 4,649) of respondents, particular among high school students (81.0%). 76.9% of students reported increased screen time compared with the time before pandemic. Inadequate sleep was identified among 38.5% of students and the proportion was highest in high school students (56.9%). Our study indicated that, during the COVID-19 pandemic, the school closure exerted tremendous negative effects on school-aged children's health habits, including less physical activity, longer screen exposure and irregular sleeping pattern.

Autism spectrum disorder (ASD), a representative disease of children's neurodevelopmental disorders, brings huge pressure and financial burden to families and society. It is of great significance to explore its etiology and pathogenesis. Therefore, we established an ASD Cohort based on the existing China National Birth Cohort (CNBC), which applied parallel design to recruit and follow up families who achieved pregnancy after receiving assisted reproductive technologies (ART) and families with spontaneous conception. The main aims of this study are to compare the incidence of ASD among children born after ART with those born under spontaneous pregnancy, and to evaluate the impact of ART on the neurobehavioral development of offspring. Additionally, with a variety of clinical and behavioral related information collected during pregnancy and at early life of offspring, we are able to investigate the risk factors associated with ASD comprehensively. This article briefly introduces the objectives, contents, preliminary progress, strength and limitations, as well as further prospects of the ASD cohort study, mainly focusing on the overall design and current progress.

Soft tissue sarcoma (STS) is a heterogeneous disease that arises from connective tissues. Clinical outcome of patients with advanced tumors especially de-differentiated liposarcoma and uterine leiomyosarcoma remains unsatisfactory, despite intensive treatment regimens including maximal surgical resection, radiation, and chemotherapy. MAP kinase-interacting serine/threonine-protein kinase 1 and 2 (MNK1/2) have been shown to contribute to oncogenic translation via phosphorylation of eukaryotic translation initiation factor 4E (eIF4E). However, little is known about the role of MNK1/2 and their downstream targets in STS. In this study, we show that depletion of either MNK1 or MNK2 suppresses cell viability, anchorage-independent growth, and tumorigenicity of STS cells. We also identify a compelling antiproliferative efficacy of a novel, selective MNK inhibitor ETC-168. Cellular responsiveness of STS cells to ETC-168 correlates positively with that of phosphorylated ribosomal protein S6 (RPS6). Mirroring MNK1/2 silencing, ETC-168 treatment strongly blocks eIF4E phosphorylation and represses expression of sarcoma-driving onco-proteins including E2F1, FOXM1, and WEE1. Moreover, combination of ETC-168 and MCL1 inhibitor S63845 exerts a synergistic antiproliferative activity against STS cells. In summary, our study reveals crucial roles of MNK1/2 and their downstream targets in STS tumorigenesis. Our data encourage further clinical translation of MNK inhibitors for STS treatment.

Background: The etiology of autism spectrum disorder (ASD) has not yet been fully identified, but it seems to be triggered by complex genetic and environmental risk factors. Moreover, the tremendous etiological and clinical differences among individuals with ASD has had a major negative impact on early diagnosis and individualized treatment. Earlier diagnosis of precise clinical subtypes of ASD could lead to individualized treatment and a better prognosis. However, few large-scale epidemiological studies have explored precise clinical subtypes and clinically meaningful biomarkers, especially in China. Methods and Design: The China Multi-center Preschool Autism Project (CMPAP) includes nearly 3,000 children-1,469 individuals with ASD and 1,499 typically-developing (TD) controls-from 13 cities in China. Using a case-control design, each participant was comprehensively characterized in terms of feeding and disease history, maternal history, family history, clinical core symptoms, comorbidities, biochemical markers, genomics, urine/fecal metabonomics, and intestinal flora. In addition, data on environmental risk factors were obtained using interviews and electronic medical records. Conclusion: The study was designed to: (1) investigate age at diagnosis and treatment and family and social support for preschool children with ASD in China, (2) develop a more accurate clinical subtype and intervention system for the ICD-11, and (3) find the specific genes and environmental markers of different subtypes, which will help in the development of early diagnosis and individual intervention programs for preschool children with ASD. This study will provide the basis for improving national health policies for ASD in China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Zhu, Li, Chen, Wu, Jia, Hao, Ke, Yi, Jin, Chen and Li.)

Objective: To explore the relationship between Treg cells level in peripheral blood and prognosis of patients with diffuse large B-cell lymphoma (DLBCL)., Methods: The percentage and absolute value of Treg cells in peripheral blood of DLBCL patients were detected by flow lytometry, and their correlation to prognosis was analyzed by survival analysis. The absolute count of Treg cells was detected by using maximally selected Log-rank statistic, and it was used as cutoff point to distinguish difference survival. The new group of Treg based on cutoff point was combined with age, sex, pathological subtype, risk stratification, treatment plan, and other indicators to include in the single factor survival analysis of Kaplan-Meier. Finally, the COX proportional risk model was used to verify the effect of the above indicators on progression-free survival., Results: The absolute count of Treg cells in DLBCL patients was significantly lower in the disease progressed group than those in the remission group. The cutoff point of absolute value of the Treg cell was 19 cells /μl. The absolute count of Treg cells was an independent prognostic factor of the risk stratification., Conclusion: At the beginning of diagnosis, the reduction of the absolute count of Treg cells in peripheral blood of DLBCL patients show a poor prognosis.

Objective: To investigate the clinical features and prognostic factors of patients with extranodal NK/T cell lymphoma (ENKTL)., Methods: The clinical data of patients with ENKTL from November 2009 to November 2019 was collected and retrospectively analyzed to clarify the clinical features of ENKTL, and evaluate the factors that affected survival and prognosis., Results: Forty-seven patients with ENKTL were collected, median age was 40 (12-82) years old, and more common in males than females, at the ratio of 1.47∶ 1. The median follow-up was 28 (1-112) months, and 5-year overall survival (OS) rate was 49.3%. The 5-year OS rates of the subjects with ECOG performance stage 0-1 and ≥2 were 51.6% and 0 (P=0.001), respectively. The 5-year OS rates of International Prognostic Index (IPI) score 0-1 and ≥2 were 60.0% and 40.6% (P=0.027), respectively. The 5-year OS rates of Ann Arbor staging Ⅰ/Ⅱ and stage Ⅲ/Ⅳ were 61.3% and 31.7% (P=0.005), respectively. The 5-year OS rates of the patients with presentation of B symptoms and without presentation of B symptoms were 79.0% and 30.1% (P=0.013), respectively. The 5-year OS rates of plasma EBV-DNA level < 5×10 2 /ml and ≥ 5×10 2 /ml were 60.4% and 33.3% (P=0.003), respectively. The 5-year OS rates of the patients receiving chemotherapy alone, combined chemotherapy and radiotherapy, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) were 12.9%, 86.5%, and 62.5% (P=0.001), respectively. Univariate analysis showed that ECOG score, IPI score, Ann Arbor staging, B symptoms, the copy number of EBV-DNA, and treatment regimens were statistically significant for OS. Multivariate analysis showed that ECOG score, B symptoms, the copy number of EBV-DNA, and treatment regimens were independent factors of ENKTL OS., Conclusion: ECOG score, B symptoms, the copy number of EBV-DNA, and treatment regimens are independent prognostic factors for OS of patients with ENKTL.

T lymphoid malignancy is a group of highly heterogeneous hematological tumors. Disease recurrence and resistance to therapy are the common causes of failed treatment. Traditional therapy is radiotherapy and chemotherapy, although it has achieved great success. However, many patients still failed to survive following the treatment. With the introduction of monoclonal antibodies, immunotherapy and cellular therapy into clinical practice, the outcome of hematologic malignancies has been significantly improved. In particular, chimeric antigen receptor T cells (CAR-T) showed high efficacy in treating B-cell lymphoma and acute B lymphocytic leukemia and surpassed any previous therapeutic strategies. However, this treatment seldom succeeded in treating T cell malignancies. In this review, the history of CAR-T cells treating T cell malignancies, and the clinical trials, adverse events of previously reported were summarized briefly.

Objective: To understand the differences in lymphocyte subsets in patients with different clinical classifications of corona virus disease 19 (COVID-19)., Methods: Eighty-one patients with COVID-19 who were admitted to the isolation ward under the responsibility of three medical aid teams in the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from February 8, 2020 to March 28, 2020, were selected to collect clinical data. According to the relevant diagnostic criteria, the disease status of the patients was classified into moderate cases ( n =35), severe cases ( n =39) and critical cases ( n =7) when lymphocyte subset testing was performed. Their blood routine tests, lymphocyte subsets and other indicators were tested to compare whether there were differences in each indicator between the patients of different clinical classification groups., Results: The differences in the absolute count of total lymphocytes, T-lymphocytes, CD4 + T-lymphocytes, CD8 + T-lymphocytes and natural killer (NK) cells among the three groups of patients were all statistically significant ( P < 0.05), and the critical cases were significantly lower than the moderate and severe cases in the above indicators, and the indicators showed a decreasing trend with the severity of the disease. In 22 patients, the six indicators of the absolute count of T-lymphocytes, B-lymphocytes, CD4 + T-lymphocytes, CD8 + T-lymphocytes and NK cells, CD4 + /CD8 + ratio were all within the normal reference range in the first test, and 59 patients had abnormalities of the above indicators, with the absolute count of NK cells and CD8 + T lymphocytes decreasing most frequently (61%, 56%). The patients with the absolute count of NK cells and CD8 + T lymphocytes below the normal reference range were one group, and the remaining abnormal patients were the other group. There were more critical cases in the former group (moderate : severe : critical cases were 4 : 8 : 7 vs . 19 : 21 : 0, respectively, P =0.001), and all the deaths were in this group (6 cases vs . 0 case, P =0.001). The absolute B lymphocyte count was below the normal reference range in 15 patients, and the remaining 64 cases were within the normal range. The ratio of moderate, severe and critical cases in the reduced group was 4 : 7 : 4, and the ratio of critical cases was more in normal group which was 30 : 31 : 3, and the difference between the two groups was statistically significant ( P =0.043)., Conclusion: The more critical the clinical subtype of patients with COVID-19, the lower the absolute count of each subset of lymphocytes.

Objective: To summarize and analyze the clinical characteristics, treatment and prognosis of acute lung injury in patients with diffuse large B-cell lymphoma (DLBCL) after chemotherapy with rituximab chemotherapy, so as to improve the understanding of the disease and guide the clinical treatment., Methods: Twenty-Six patients with DLBCL were treated with rituximab chemotherapy and developed to acute lung injury in Third Hospital of Peking University from January 2013 to September 2018 were selected. The clinical features, imaging findings, chemotherapy course, therapeutic effect and prognosis were analyzed., Results: The main clinical symptoms of patients were fever, cough and chest tightness, among which 12 patients showed hypoxia and 3 patients showed respiratory failure type I. The mainly manifested chest CT was diffusive glass grinding in both lungs, and some patients were complicated with a small amount of pleural effusion. The onset chemotherapy time was mainly distributed in 2 to 4 courses, the time between the onset of symptoms and the infusion of rituximab was 8 to 49 days. 25 patients shows no obvious limitation in daily life after effective treatment, and 1 patient died of ineffective treatment., Conclusion: There are no typical clinical symptoms in the early stage of acute lung injury after rituximab chemotherapy in DLBCL. Early detection and early hormone therapy are very important to achieve good therapeutic effect.

Objective: To evaluate the correlation between obstructive sleep apnea syndrome (OSAS) and the development of thoracic deformity in Children., Methods: A retrospective analysis was performed with the medical records of 39 pediatric OSAS patients with thoracic deformity and matching 39 without thoracic deformity as control group between January 2015 and June 2019. The contrast was performed with age, gender, height, weight, body mass index (BMI), apnea/hypopnea index (AHI), the lowest oxyhemoglobin saturation (loSpO2)at night, tonsil and adenoid size, Alkaline phosphatase (ALP)and trace elements and metals between two groups., Results: BMI, AHI, the lowest SpO2, Phosphorus and Zinc were the risk factors of thoracic deformity. Age, gender, disease history, the size of tonsil and adenoid, ALP and other trace elements were no significant difference occurred between two groups., Conclusion: OSAS characterized by apnea and hypoxia which are caused by narrow upper airway may be one cause of thoracic deformity in children. Pediatricians, thoracic and otolaryngologic surgeons should be alert to OSAS when thoracic deformities are diagnosed in children., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To analyze the significance of various abnormal signal patterns appreared in CML and B-ALL patients by using BCR/ABL/ASS1 tricolor dual-fusion probe, and to explore its application value in detecting BCR/ABL fusion gene and ASS1 gene deletion., Methods: 50 newly diagnosed CML patients and 50 newly diagnosed B-ALL patients were detected by fluorescence in situ hybridization (FISH) with BCR/ABL/ASS1 tricolor dual-fusion probe. Meanwhile, karyotype analysis was performed on all the patients using the 24 hours short-term culture and R-banding., Results: Among the 50 CML patients, Ph + was found in 49 cases, 5 normal interphase karyotype was observed in 1 case. FISH detection showed that BCR/ABL fusion gene existed in all patients (100%), while the positive signal pathway showed that 1R1G2B2F was observed in 39 cases (78%), 2R1G2B1F in 2 cases (4%) and 1R1G2B1F in 6 cases (12%), simultaneous existence of 1R1G1B1F and 1R1G2B3F in 1 case (2%), 2R1G1B1F in 1 case (2%) 1R1G3B3F in 1 case (2%). FISH detection also showed that the karyotype of 6 case at ASS1 gene deletion (1R1G1B1F) all were simple t (9; 22) translocation, and other abnormalities not were observed. Among 50 cases of B-ALL, Ph + was found in 13 cases, the numerical aberration and structural aberration of non t (9; 22) in 16 cases, normal karyotype in 20 cases, absence of mitotic phase in 1 case. FISH detection showed that 16 cases (32%) had BCR/ABL fusion gene including 13 cases (26%) of 1R1G2B2F, 1 case (2%) of stimultaneous exitance of 1R1G2B2F and 1R1G3B3F 1 case (2%) of 2R1G1B1F, 1 case (2%) of 1R1G3B2F. FISH detection also showed that 3 cases had BCR/ABL fusion gene, including 1 case with ASS1 gene deletion (2R1G1B1F), 1 case with classical t (9; 22) translocation (1R1G2B2F) and 1 case with BCR/ABL fusion gene and increase of ASS1 gene copy (1R1G3B3F)., Conclusion: Tricolor dual-fusion FISH probe for detecting BCR/ABL fusion gene and ASS1 gene deletion is simple, rapid, sensitive and stable. It can detect various forms of molecular fusion and avoid the false positive results due to coincidental overlap of signals generated by D-FISH probe and ES-FISH probe. In addition, this detection method not only can directly observe the presence or absence of ASS1 gene deletion, but also improve the reliability of the positive results of newly diagnosed BCR/ABL fusion gene and accuracy of monitoring results of minimal residual disease for the subsequent visit.

Objective: To detect the expression levels of FAM19A5 in patients with mantle cell lymphoma (MCL), and to determine the relationship between FAM19A5 and the prognosis of MCL patients., Methods: Twenty-five MCL patients were choosen in the study, cytometric bead assay was used to detected the concentration of FAM19A5 in serum and immunohistochemical analysis were used to detect the expression levels of FAM19A5 in lymph nodes. The relationship of the FAM19A5 expression in serum and tissue were analyzed, the relationship of FAM19A5 and clinical characteristics of MCL patients, treatment and prognosis of MCL patients was analyzed., Results: The average serum concentration of FAM19A5 in MCL patients was 90.55±38.24 (ng/ml), which was significantly higher than that in control (P=0.0461). The proportion of high, medium, and low expression of FAM19A5 in lymph nodes was 32%, 36% and 32%, respectively, which showed significant difference from that in control group (P=0.001). The expression of FAM19A5 in serum and lymph nodes showed significant correlation (r=0.8683，P=0.001). The serum concentration of FAM19A5 showed positive correlation with the proportion of Ki67 (P=0.0222, r=0.4554). The mean survival time without relapse/death of MCL patients with high, middle and low expression of FAM19A5 was 17, 27 and 37.5 months, respectively，which showed significant statistical difference (P=0.0360). ROC curve analysis showed that serum concentration of FAM19A5 could predict the therapeutic effect in MCL patients, the cut-off value was 91.49 ng/ml. The proportion of recurrent/death in AML patients with FAM19A5 ＞91.49 ng/ml was significantly higher than that in patients with FAM19A5＜91.49 ng/ml (P=0.0156)., Conclusion: The expression level of FAM19A5 is increased in MCL patient, and patients with high expression of FAM19A5 are more likely to relapse or die. FAM19A5 may be a new prognostic marker and potential therapeutic target for MCL.

Objective: To study the characteristics of vocalization during the still-face paradigm (SFP) before the age of 2 years and their correlation with the severity of autism spectrum disorder (ASD) symptoms at diagnosis in children with ASD., Methods: A total of 43 children aged 7-23 months, who were suspected of ASD, were enrolled as the suspected ASD group, and 37 typical development (TD) children, aged 7-23 months, were enrolled as the TD group. The frequency and durations of vocalization in the SFP were measured. The children in the suspected ASD group were followed up to the age of 2 years, and 34 children were diagnosed with ASD. Autism Diagnostic Observation Schedule (ADOS) was used to assess the severity of symptoms. The correlation of the characteristics of vocalization before the age of 2 years with the severity of ASD symptoms was analyzed., Results: Compared with the TD group, the ASD group had significant reductions in the frequency and durations of meaningful vocalization and vocalization towards people and a significant increase in the duration of vocalization toward objects (P<0.05). The Spearman correlation analysis showed that in the ASD group, the frequency and durations of total vocalization, non-speech vocalization, babbling, vocalization towards people, and vocalization towards objects were negatively correlated with the score of communication in ADOS (P<0.05). The frequency and durations of total vocalization, babbling, and vocalization towards people and the duration of vocalization towards objects were negatively correlated with the score of reciprocal social interaction in ADOS (P<0.05). The frequency of total vocalization, the duration of babbling, and the frequency and duration of vocalization towards people were negatively correlated with the score of play in ADOS (P<0.05). The frequency of total vocalization and non-speech vocalization and the frequency and durations of vocalization towards people were negatively correlated with the score of stereotyped behaviors and restricted interests in ADOS (P<0.05). The multiple linear regression analysis showed that the frequency of total vocalization was a negative predictive factor for the score of communication in ADOS (P<0.001), and the duration of vocalization towards people was a negative predictive factor for the score of reciprocal social interaction in ADOS (P<0.05)., Conclusions: SFP can better highlight the abnormal vocalization of ASD children before the age of 2 years, and such abnormalities can predict the severity of ASD symptoms early.

Objective: To compare and evaluate the sensitivity, specificity, and prognostic value of various assays for bone marrow involvement in patients with non-Hodgkin's lymphoma (NHL)., Methods: A total of 351 patients with NHL who underwent concurrent bone marrow biopsy in Third Hospital of Peking University from January 2013 to November 2017 were selected. Bone marrow biopsy (BMB), flow cytometry (FCM), gene rearrangement detection, and bone marrow morphology examination were performed for evaluation of bone marrow involvement. Bone marrow biopsy was used as the gold standard, the sensitivity and specificity of FCM, gene rearrangement and bone marrow morphology of bone marrow aspirate were analyzed, and their ROC curves were drawn. In the survival analysis of 77 patients with NHL, the overall survival (OS) time, progression-free survival (PFS) time, and complete remission rate (CRR) were counted. The survival of patients in the FCM positive group, the gene rearrangement positive group, the positive control group (BMB positive group) and the negative control group were compared., Results: The detection rate of flow cytometry and gene rearrangement of bone marrow aspirate both were higher than that of bone marrow biopsy and bone marrow morphological examination, showing better diagnostic efficacy. The sensitivity of the combined method of flow cytometry and gene rearrangement was 82.5%, while the specificity was 90% and the AUC was 0.863. The gene rearrangement detection of bone marrow aspirate possessed the role suggesting the poor prognosis for NHL patients. The 3-year survival rate of patients in the gene rearrangement-positive group (RG group) was lower than that of patients in the no-bone involvement group (All negative group) (P＜0.05). Although the survival curve of patient in RG group was not significantly different from that of patients in All negative group (P＜0.1), it still showed a poor prognosis for NHL patients. And the significance of predicting death risk was reflected in Cox regression model (P＜0.05). There was no statistical difference in the prognosis of patients in the FCM-positive group (FCM group)., Conclusion: In the bone marrow aspirate tests, flow cytometry and gene rearrangement detection have good diagnostic efficiency, and gene rearrangement can suggest the prognosis of patients. The combined detection efficacy of two methods is better.