Rapid eye movement sleep behavior disorder （RBD） is a type of parasomnia closely associated with neurodegenerative diseases related to α-synucleinopathies， such as Parkinson disease， dementia with Lewy bodies， and multiple system atrophy， and early diagnosis is of great importance for disease monitoring and intervention.At present， RBD is mainly diagnosed based on video polysomnography （v-PSG） and nocturnal abnormal behaviors， but the application of v-PSG is limited by its high technical demands.Various validated RBD-related scales have become essential tools for auxiliary diagnosis， which provides methods and tools for the diagnosis of RBD and the assessment of disease progression and outcomes.

Objective To determine the epidemic characteristics of forty-two coronavirus disease 2019 （COVID-19） cluster outbreaks in Hangzhou city and provide scientific evidence for further prevention and control measures. Methods Data of the COVID-19 cluster outbreaks in Hangzhou were obtained from the National Public Health Emergency Management Information System. Epidemic characteristics were summarized by reviewing the epidemiological investigation reports. Results A total of forty-two COVID-19 cluster outbreaks were documented in Hangzhou in 2020， including 130 confirmed cases and 7 cases with asymptomatic infection. The majority occurred from January to February， 2020. Moreover， 92.86% （39/42） of the cluster outbreaks were familial transmission. The proportion of the cluster outbreaks involving 2 cases accounted for 54.7% （23/42）. In the secondary cases， family members accounted for 84.15% （69/82）. Conclusion The COVID-19 cluster outbreaks in Hangzhou mainly occur in families， and the majority of the secondary cases is family members.

Objective: To investigate the epidemiological characteristics of malaria in Hangzhou City from 2004 to 2021, so as to provide the evidence for formulating the post-elimination control strategy for malaria in Hangzhou City. Methods: The epidemic situation of malaria in Hangzhou City from 2004 to 2021 were collected from the National Information System for Disease Control and Prevention in China, and the temporal, spatial and human distributions of malaria cases and the source of malaria infections were analyzed in Hangzhou City during the pre-elimination stage (2004 to 2009), the elimination stage (2010 to 2015) and the post-elimination stage (2016 to 2021). Results: Totally 602 malaria cases were reported in Hangzhou City from 2004 to 2021,and the annual mean incidence of malaria was 0.22/105, 0.20/105 and 0.18/105 during the pre-elimination, elimination and post-elimination stages, appearing a tendency towards a decline. Men accounted for 63.96%, 85.07% and 93.75% of all malaria cases and there were 67.86%, 82.84% and 80.00% of cases at ages of 18 to 50 years during the pre-elimination, elimination and post-elimination stages, both appearing a tendency towards a decline (χ2trend=56.748, P<0.001; χ2trend=39.971, P<0.001). The predominant occupation of malaria cases shifted from farmers or migrant workers to multiple occupations, and the proportion of commercial servants increased from 4.87% during the pre-elimination stage to 24.38% during the post-elimination stage (χ2trend=73.308, P<0.001). The proportion of Plasmodium vivax malaria cases reduced from 96.43% during the pre-elimination stage to 7.50% during the post-elimination stage, and the proportion of P. falciparum malaria cases increased from 3.57% to 71.25%, while P. ovale, P. malariae and mixed infections were identified since 2010. There was a significant season-specific incidence of P. vivax malaria during the pre-elimination stage, and the period between May and October was an epidemic season; however, there was no season-specific incidence of P. vivax malaria during the elimination and post-elimination stages. The regional distribution of malaria cases presented a tendency towards a shift from suburb and rural areas to urban areas (χ2trend=74.229, P<0.001). No local cases were detected in Hangzhou City since 2010, and 94.22% of malaria cases were overseas imported cases after malaria elimination, including 90.61% from Africa. Conclusions oung and middle-aged men were high-risk populations for malaria in Hangzhou City from 2004 to 2021, and overseas commercial servants gradually became the predominant source of malaria infections, with malaria parasite species tending to be diverse. Improving the management of overseas imported cases and timely identification and treatment of cases are major interventions to consolidate malaria elimination achievements in Hangzhou City.

Vibrio parahaemolyticus, the main pathogen causing seafood related food poisoning worldwide, has strong biofilm formation ability. ToxR is a membrane binding regulatory protein, which has regulatory effect on biofilm formation of V. parahaemolyticus, but the specific mechanism has not been reported. c-di-GMP is an important second messenger in bacteria and is involved in regulating a variety of bacterial behaviors including biofilm formation. In this study, we investigated the regulation of ToxR on c-di-GMP metabolism in V. parahaemolyticus. Intracellular c-di-GMP in the wild type (WT) and toxR mutant (ΔtoxR) strains were extracted by ultrasonication, and the concentrations of c-di-GMP were then determined by enzyme linked immunosorbent assay (ELISA). Three c-di-GMP metabolism-related genes scrA, scrG and vpa0198 were selected as the target genes. Quantitative real-time PCR (q-PCR) was employed to calculate the transcriptional variation of each target gene between WT and ΔtoxR strains. The regulatory DNA region of each target gene was cloned into the pHR309 plasmid harboring a promoterless lacZ gene. The recombinant plasmid was subsequently transferred into WT and ΔtoxR strains to detect the β-galactosidase activity in the cellular extracts. The recombinant lacZ plasmid containing each of the target gene was also transferred into E. coli 100λpir strain harboring the pBAD33 plasmid or the recombinant pBAD33-toxR to test whether ToxR could regulate the expression of the target gene in a heterologous host. The regulatory DNA region of each target gene was amplified by PCR, and the over-expressed His-ToxR was purified. The electrophoretic mobility shift assay (EMSA) was applied to verify whether His-ToxR directly bound to the target promoter region. ELISA results showed that the intracellular c-di-GMP level significantly enhanced in ΔtoxR strain relative to that in WT strain, suggesting that ToxR inhibited the production of c-di-GMP in V. parahaemolyticus. qPCR results showed that the mRNA levels of scrA, scrG and vpa0198 significantly increased in ΔtoxR strain relative to those in WT strain, suggesting that ToxR repressed the transcription of scrA, scrG and vpa0198. lacZ fusion assay showed that ToxR was able to repress the promoter activities of scrA, scrG and vpa0198 in both V. parahaemolyticus and E. coli 100λpir. EMSA results showed that His-ToxR was able to bind to the regulatory DNA regions of scrA and scrG, but not to the regulatory DNA region of vpa0198. In conclusion, ToxR inhibited the production of c-di-GMP in V. parahaemolyticus via directly regulating the transcription of enzyme genes associated with c-di-GMP metabolism, which would be beneficial for V. parahaemolyticus to precisely control bacterial behaviors including biofilm formation.
Vibrio parahaemolyticus/metabolism* ; Escherichia coli/metabolism* ; Bacterial Proteins/metabolism* ; Transcription Factors/genetics* ; Gene Expression Regulation, Bacterial

OBJECTIVE: To detect fusion gene with pathological significance in a patient with refractory and relapsed acute B cell lymphoblastic leukemia (B-ALL) and to explore its laboratory and clinical characteristics. METHODS: Transcriptome sequencing was used to detect potential fusion transcripts. Other laboratory results and clinical data of the patient were also analyzed. RESULTS: The patient was found to harbor TCF3 exon 17-ZNF384 exon 7 in-frame fusion transcript. The minimal residual disease (MRD) has remained positive after multiple chemotherapy protocols including CD19-, CD22- targeted chimeric antigen receptor T cells immunotherapy. The patient eventually achieved complete remission and sustained MRD negativity after allogeneic hemopoietic stem cell transplantation (allo-HSCT). CONCLUSION Transcriptome sequencing can effectively detect potential fusion genes with clinical significance in leukemia. TCF3-ZNF384 positive B-ALL has unique laboratory and clinical characteristics, may not well respond to chemotherapy and immunotherapy, and is more likely to relapse. Timely allo-HSCT treatment may help such patients to achieve long-term disease-free survival. TCF3-ZNF384 positive B-ALL is not uncommon in pediatric patients but has not been effectively identified.
B-Lymphocytes ; Basic Helix-Loop-Helix Transcription Factors/genetics* ; Child ; Hematopoietic Stem Cell Transplantation ; Humans ; Laboratories ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Trans-Activators/genetics* ; Transcriptome

Objective: To determine the relationship between mental sub-health and dietary behavior among Chinese adolescents, and to provide a scientific basis for improving adolescent mental sub-health through healthy dietary behavior. Methods: A total of 16 545 adolescents aged 13 to 22 years were sampled by random cluster sampling method in six administrative regions of China. A questionnaire survey was conducted to investigate adolescents’ dietary behaviors and mental sub-health status. Results: The proportion of boys consuming breakfast, snacks, carbonated drinks, vegetables, fish and dairy products was 76.2%, 20.2%, 19.0%, 78.4%, 52.4% and 59.2%, respectively, while the proportion of girls was 79.2%, 28.6%, 12.6%, 78.3%, 43.2% and 54.9%, respectively. Except for the "vegetable" option, dietary behaviors showed significant sex differences(χ2=20.79,320.10,229.06,150.27,32.21,P<0.01). In terms of mental sub-health, the detection rates of male adolescents’ mental sub-health status, behavioral sub-health and social sub-health were 20.7%, 26.0% and 17.2%, respectively, while those of female adolescents were 18.6%, 24.1% and 14.8%, respectively. The differences between boys and girls were statistically significant (χ2=17.32,7.66,17.46,P<0.01). Controlling for age and gender, breakfast "normally eating" and "occasionally eat", vegetables "normally eating" and "occasionally eat", fish "normally eating" and "occasionally eat", milk, dairy products "normally drink" and "occasional drink",was negatively associated with teenagers’ psychological sub-health (OR=0.60,0.73;0.50,0.65;0.74,0.77;0.73,0.69,P<0.05). Conclusion Healthy dietary behavior could be protective to avoid adolescent mental sub-health.Nutritional lectures and guideline books are needed among students and their parents.Nutritionists are encouraged to provide healthy nutritional advice to school canteen.

Objective:To analyze the characteristics of eyes with congenital optic disc pits (ODPs) through multimodal imaging.Methods:A cross-sectional study was conducted.Thirty-eight patients (38 eyes) diagnosed with congenital ODPs in the Second Hospital of Hebei Medical University from January 2009 to January 2020 were enrolled.A comprehensive summary analysis of the imaging results including fundus photography, spectral domain-optical coherence tomography (SD-OCT), infrared imaging, fundus autofluorescence (FAF), fluorescein fundus angiography (FFA) and indocyanine green angiography (ICGA) was performed.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of The Second Hospital of Hebei Medical University (No.2021-P011). Written informed consent was obtained from each subject prior to any medical examination.Results:Among the 38 eyes, there were 32 eyes with ODPs located in or below the temporal side of optic disc, 4 eyes with ODPs located above the temporal side of optic disc, and 2 eyes with ODPs located at the center of optic disc, which were round or quasi-circular pale depression, and dark red eminences with clear or unclear boundaries between milk spots were found in 29 eyes with optical-disc macular degeneration (ODP-M) by fundus photography.SD-OCT examination showed that the structure of lamina cribrosa in the lesion area in all ODPs patients was incomplete, which presented a dark area with no tissue reflection, and the fissure led to the deep optic nerve.Fluid was found in the outer nuclear layer in all ODP-M patients, and there were 27 eyes with fluid in the inner nuclear layer, 13 eyes in the ganglion cell layer, and 4 eyes under the inner limiting membrane.Among the 29 eyes with ODP-M, there were 21 eyes with retinoschisis in outer layer, 27 eyes with neuroepithelial detachment.In the 27 eyes with neuroepithelial detachment, spot-like high reflection and reduced or disappeared ellipsoid band reflectance were seen above the neuroepithelium in 18 eyes.In infrared images, there were circular or quasi-circular low-reflection areas in the temporal side of the optic disc, and the lesion of ODP-M eyes presented low-reflection areas.FAF examination showed that in 27 eyes with ODP-M, there was a hypofluorescent region at the posterior pole consistent with the lesion range, among which, there was a granular or sheet-like hyperfluorescence at the center of the hypofluorescent region in 18 eyes.FFA showed that the optic disc depression in the arterial phase of patients was in a localized hypofluorescence state.During the venous phase, fluorescein dye extravasation along the temporal side of the optic disc could be found.A strong fluorescent arc with unclear boundaries at the temporal edge of the optic disc was formed in the late stage of angiography.Among the 29 eyes with ODP-M, the area of the macular lesion showed hyperfluorescence during the late stage of angiography in 27 eyes with neuroepithelial detachment, and no extension of dye toward the macula was found.ICGA showed that the optic disc depression of ODPs patients presented a localized hypofluorescence, and the lesion showed hyperfluorescence in 27 of the 29 ODP-M eyes with neuroepithelial detachment.Conclusions:Multimodal imaging can be helpful to realize the early diagnosis, etiology analysis of ODPs and make treatment plan.

Objective:To study the clinical efficacy of chimeric antigen receptor T-cell (CART) treatment followed by a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with B-cell acute lymphoblastic leukemia (ALL) who relapsed following the first HSCT.Methods:Retrospective analysis of the clinical characteristics and prognosis of 41 patients with B-cell ALL who received a second allo-HSCT from October 2015 to June 2020 in Hebei Yanda Lu Daopei Hospital. After the first HSCT, all patients received CD19-CART, or CD22-CART treatment following a relapse of bone marrow morphology or extramedullary leukemia.Results:A total of 41 patients (male, 21; female, 20) were included in this study. The median age at the second HSCT was 16 (3-46) years. There were 31 cases of bone marrow recurrence (75.6%) , 5 cases of extramedullary recurrence (12.2%) , and 5 cases of bone marrow and extramedullary recurrences (12.2%) . After relapse, 35 patients (85.4%) received CD19-CART treatment, 2 patients received CD22-CART treatment (4.9%) , and 4 patients received CD19-CART and CD22-CART treatments (9.8%) . The expected 3-year overall survival (OS) , leukemia-free survival, cumulative relapse incidence, and non-relapse mortality (NRM) of patients after the second HSCT were 48.9% (95% CI 23.0%-70.6%) , 41.8% (95% CI 17.3%-64.9%) , 8.8% (95% CI 2.9%-26.4%) , and 51.1% (95% CI 31.2%-83.6%) , respectively. The 1-year OS of patients who relapsed ≤6 months and >6 months after the first HSCT were 45.0% (95% CI 12.7%-73.5%) and 75.0% (95% CI 51.4% -88.8%) ( P=0.017) , respectively. Conclusion:CART bridging in the second HSCT enables some B-cell ALL patients who relapsed after the first HSCT to achieve long-term survival. However, because of the high NRM, further modifications could help improve the outcome.

Objective:To investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the risk of depression symptoms among older adults aged 65 and above in 9 longevity areas of China.Methods:Data was collected in 9 longevity areas of China from Healthy Aging and Biomarkers Cohort Study (HABCS) conducted between 2017 and 2018. Finally,2018 elderly aged 65 years and above with complete information on neutrophil count, lymphocyte count and depressive symptoms were included in this study. Information on demographic characteristics, lifestyle, and health status was collected through questionnaire and physical examination. Complete blood counts which included lymphocytes and neutrophils were obtained by testing venous blood samples. Participants were divided into four groups by the quartile of NLR level, i.e. Q1, Q2, Q3, Q4. Logistic regression model was applied to analyze the association of NLR with depression symptoms. Results:Among 2 018 older adults, the mean(±SD) age was 82.6(±10.73), 1 032(51.14%) were male, 390(19.33%) were detected with depressive symptoms. Compared with participants of NLR in the 1 st quartile, the OR(95% CI) of risk for depressive symptoms was 1.47 (0.99, 2.19), 1.67 (1.13, 2.47) and 1.95 (1.32, 2.89), respectively. Conclusion:Increased NLR level is significantly related to depressive symptoms among elderly aged 65 years and above in 9 longevity areas in China.

Objective:To investigate the association of blood arsenic level with hyperuricemia among elderly aged 65 years and older.Methods:Data was collected in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study between 2017 and 2018. 2 438 participants aged 65 years and older with complete information on blood arsenic and uric acid were included in this study. Information including demographics characteristic, life style and health status was collected by questionnaire and physical examination. Meanwhile, venous blood was collected to detect the levels of blood arsenic and uric acid. Subjects were stratified into three groups (low, middle and high) by tertiles of blood arsenic level. Logistic regression models were used to analyze the association of blood arsenic level with hyperuricemia.Results:The age of participants was (84.57±11.41) years, of which 1 172 (48.07%) were male and 1 525 (62.55%) were over 80 years old. The detection rate of hyperuricemia was 17.23% (420), and the detection rates of hyperuricemia were 11.77%, 19.25% and 20.62% among participants with low, middle and high blood arsenic, respectively ( P<0.001). After controlling confounding factors, compared with participants who had low blood arsenic, the ORs (95% CI) of hyperuricemia for the participants with middle and high blood arsenic were 1.57 (1.12-2.23) and 2.08 (1.46-2.99), respectively. Subgroups analysis showed that compared with female, the association between blood arsenic level and hyperuricemia was more obvious in males ( Pinteraction<0.05). Conclusion:Blood arsenic level is associated with the risk for hyperuricemia among the elderly aged 65 years and older in 9 longevity areas in China.