[Microglia differential genes and their functions in paraquat-induced Parkinson's disease-like in mice's brains based on single-cell RNA sequencing].

Objective: To analyze the differential genes and related signaling pathways of microglia subpopulations in Parkinson's disease (PD) -like mouse brains induced by paraquat (PQ) based on single-cell RNA sequencing, and provide clues to elucidate the mechanism of PQ-induced PD-like changes in the brain of animals. Methods: In September 2021, six male 6-week-old C57BL/6 mice were randomly divided into control group and experimental group (three mice in each group) . The mice were injected with saline, 10.0 mg/kg PQ intraperitoneally, once every three days, and 10 consecutive injections were used for modeling. After infection, the brains of mice were taken and 10×Genomics single-cell RNA sequencing was performed. Microglia subpopulations were screened based on gene expression characteristics, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The differential genes of microglia subpopulations between the experimental group and control group were further screened, and functional enrichment analysis was performed using bioinformatics tools. Mouse microglia (BV2 cells) were treated with 0, 60, 90 µmol/L PQ solution, respectively. And real-time fluorescence quantitative PCR experiments were conducted to validate the expressions of differential genes hexokinase 2 (Hk2) , ATPase H+ Transporting V0 Subunit B (Atp6v0b) and Neuregulin 1 (Nrg1) . Results: Cluster 7 and Cluster 20 were identified as microglia subpopulations based on the signature genes inositol polyphosphate-5-phosphatase d, Inpp5d (Inpp5d) and transforming growth factor beta receptor 1 (Tgfbr1) , and they reflected the microglia-activated M2 phenotype. The bioinformatics analysis showed that the characteristic genes of identified microglia subpopulations were enriched in endocytosis. In terms of molecular function, it mainly enriched in transmembrane receptor protein kinase activity and cytokine binding. The up-regulated genes of Cluster 7 were mainly enriched in lysosomal pathway, endocytosis pathway, and down-regulated genes were mainly enriched in neurodegenerative disease and other signaling pathways. The up-regulated genes of Cluster 20 were mainly enriched in signaling pathways related to PD, and down-regulated genes were mainly enriched in cyclic adenosine 3', 5'-monophosphate (cAMP) signaling pathways, neurological development, synaptic function and other signaling pathways. The results of real-time fluorescence quantitative PCR showed that the expressions of Hk2 mRNA and Atp6v0b mRNA increased and the expression of Nrg1 mRNA decreased in the 90 µmol/L PQ-treated BV2 cells compared with the 0 µmol/L, and the differences were statistically significant (P<0.05) . Conclusion: Microglia are activated in the PQ-induced PD-like mouse model and polarized toward the M2 phenotype. And their functions are associated with lysosomal (endocytosis) , synaptic functions and the regulation of PD-related pathways.

[The cutoff value of small airway dysfunction in children with bronchial asthma].

Objective: To explore the cutoff value for assessing small airway dysfunction in children with asthma. Methods: A total of 364 asthmatic children aged 5 to 14 years, with normal ventilatory function, followed up at the Asthma Clinic of the Children's Hospital of Capital Institute of Pediatrics from January 2017 to January 2018, were selected as the case group. Concurrently, 403 healthy children of the same age range and without any symptoms in the community were chosen as the control group, and pulmonary function tests were conducted. The values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow at 50% of FVC (FEF50), forced expiratory flow at 75% of FVC (FEF75) and maximum mid-expiratory flow (MMEF) were compared between case group and control group. Statistical tests such as t-test, χ2 test, or Mann-Whitney U test were used to analyze the differences between the groups. Receiver operating characteristic (ROC) curves were constructed, and the maximum Youden Index was utilized to determine the optimal cutoff values and thresholds for identifying small airway dysfunction in asthmatic children. Results: This study comprised 364 children in the case group (220 boys and 144 girls) and 403 children in the control group (198 boys and 205 girls). The small airway parameters (FEF50%pred, FEF75%pred, MMEF%pred) in the asthmatic group were significantly lower than in the control group (77% (69%, 91%) vs. 95% (83%, 109%), 67% (54%, 82%) vs. 84% (70%, 102%), 76% (66%, 90%) vs. 97% (86%, 113%), Z=12.03, 11.35, 13.66, all P<0.001). The ROC curve area under the curve for FEF50%pred, FEF75%pred, MMEF%pred was 0.75, 0.74, and 0.79, respectively. Using a cutoff value of 80% for FEF50%pred achieved a sensitivity of 56.9% and specificity of 81.4%. A cutoff value of 74% for FEF75%pred resulted in a sensitivity of 67.3% and specificity of 69.2%. Finally, using a cutoff value of 84% for MMEF%pred achieved a sensitivity of 67.9% and specificity of 77.2%. Conclusion: In the presence of normal ventilatory function, utilizing FEF50<80% predicted or MMEF<84% predicted can accurately serve as criteria for identifying small airway dysfunction in children with controlled asthma.

[Research progress on biomarkers and detection methods for Alzheimer's disease diagnosis in vitro].

Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset, posing a serious threat to human physical and mental health. The cognitive impairments caused by AD are generally diffuse and overlap symptomatically with other neurodegenerative diseases. Moreover, the symptoms of AD are often covert, leading to missed opportunities for optimal treatment after diagnosis. Therefore, early diagnosis of AD is crucial. In vitro diagnostic biomarkers not only contribute to the early clinical diagnosis of AD but also aid in further understanding the disease's pathogenesis, predicting disease progression, and observing the effects of novel candidate therapeutic drugs in clinical trials. Currently, although there are numerous biomarkers associated with AD diagnosis, the complex nature of AD pathogenesis, limitations of individual biomarkers, and constraints of clinical detection methods have hindered the development of efficient, cost-effective, and convenient diagnostic methods and standards. This article provides an overview of the research progress on in vitro diagnostic biomarkers and detection methods related to AD in recent years.

[Clinical implications of thrombolytic therapy for patients with acute intermediate-high risk pulmonary embolism in Tibet plateau, China].

At present, clinical studies and case reports of systemic thrombolytic therapy for patients with acute pulmonary embolism in Tibet Plateau are very rare. There is little understanding of the risk factors, clinical characteristics, and thrombolytic therapy for patients with acute pulmonary embolism at intermediate-high risk in Tibet Plateau. In this paper, we reported the data of 4 patients with acute intermediate-high risk pulmonary embolism treated with thrombolytic therapy in Lhasa People's Hospital. The demographic characteristics, clinical manifestations, treatment, and outcomes were analyzed. We summarized the clinical features and raised scientific issues. We aimed to provide basic data to improve the standardized diagnosis and treatment of acute pulmonary embolism in plateau, and to point out the direction of future clinical research in this field.

[Analysis of the impact of health management measures for entry personnel on imported Dengue fever in Guangdong Province, 2020-2022].

Objective: To explore the impact of health management measures for entry personnel (entry management measures) against COVID-19 on the epidemiological characteristics of imported Dengue fever in Guangdong Province from 2020 to 2022. Methods: Data of imported Dengue fever from January 1, 2016 to August 31, 2022, mosquito density surveillance from 2016 to 2021, and international airline passengers and Dengue fever annual reported cases from 2011 to 2021 in Guangdong were collected. Comparative analysis was conducted to explore changes in the epidemic characteristics of imported Dengue fever before the implementation of entry management measures (from January 1, 2016 to March 20, 2020) and after the implementation (from March 21, 2020 to August 31, 2022). Results: From March 21, 2020, to August 31, 2022, a total of 52 cases of imported Dengue fever cases were reported, with an imported risk intensity of 0.12, which were lower than those before implementation of entry management measures (1 828, 5.29). No significant differences were found in the characteristics of imported cases before and after implementation of entry management measures, including seasonality, sex, age, career, and imported countries (all P>0.05). 59.62% (31/52) of cases were found at the centralized isolation sites and 38.46% (20/52) at the entry ports. However, before implementation of entry management measures, 95.08% (1 738/1 828) of cases were found in hospitals. Among 51 cases who had provided entry dates, 82.35% (42/51) and 98.04% (50/51) of cases were found within seven days and fourteen days after entry, slightly higher than before implementation [(72.69%(362/498) and 97.59% (486/498)]. There was significant difference between the monthly mean values of Aedes mosquito larval density (Bretto index) from 2020 to 2021 and those from 2016 to 2019 (Z=2.83, P=0.005). There is a strong positive correlation between the annual international airline passengers volume in Guangdong from 2011 to 2021 and the annual imported Dengue fever cases (r=0.94, P<0.001), and a positive correlation also existed between the international passenger volume and the annual indigenous Dengue fever cases (r=0.72, P=0.013). Conclusions: In Guangdong, the entry management measures of centralized isolation for fourteen days after entry from abroad had been implemented, and most imported Dengue fever cases were found within fourteen days after entry. The risk of local transmission caused by imported cases has reduced significantly.

[Epidemiological characteristics of norovirus acute gastroenteritis outbreaks and influencing factors in China, 2007-2021].

Objective: To analyze the epidemiological characteristics of norovirus-caused acute gastroenteritis outbreaks in China, identify the factors influencing the scale of outbreaks, and provide scientific evidences for early control of norovirus infection outbreaks. Methods: The descriptive epidemiological analysis approach was applied to analyze the incidence of national norovirus infection outbreaks by using the data from the Public Health Emergency Event Surveillance System in China from January 1, 2007 to December 31, 2021. The unconditional logistic regression model was applied to analyze the risk factors that affected the outbreaks' scale. Results: A total of 1 725 norovirus infection outbreaks were recorded in China from 2007 to 2021, with an upward trend in the number of the reported outbreaks. The southern provinces had their annual outbreak peaks from October to March; the northern provinces had two outbreak peaks from October to December and from March to June annually. The outbreaks occurred mainly in southeastern coastal provinces with a trend of gradual spread to central, northeastern and western provinces. The outbreaks mainly occurred in schools and childcare setting (1 539 cases, 89.22%), followed by enterprises and institutions (67 cases, 3.88%) and community households (55 cases, 3.19%). Human to human transmission was the main infection route (73.16%), and norovirus GⅡ genotype was the predominate pathogen causing the outbreaks (899 cases, 81.58%). The time interval between the onset of the primary case and the outbreak reporting M (Q1, Q3) was 3 (2, 6) days and the case number of the outbreak M (Q1, Q3) was 38 (28, 62). The timeliness of outbreak reporting was improved in recent years and the scale of the outbreaks showed a decreasing trend over the years, the differences in reporting timeliness and outbreak scale among different settings were significant (P<0.001). The factors that affected outbreaks' scale included the outbreak setting, transmission route, outbreak reporting timeliness and type of living areas (P<0.05). Conclusions: From 2007 to 2021, the number of the norovirus-caused acute gastroenteritis outbreaks increased in China and the more areas were affected. However, the outbreak scale showed a decreasing trend and the outbreak reporting timeliness was improved. It is important to further improve the surveillance sensitivity and reporting timeliness for the effective control of the outbreak scale.

[Determination of methylmercury in urine by direct mercury analyzer].

Objective: To develop asolvent extraction-direct mercury analyzer method for determination of methylmercury in urine. Methods: After the urinehydrolyzesd by hydrobromic acid, methylmercury was extracted by tolueneand reverse-extracted from L-cysteine solution, it was then detectedbydirect mercuryanalyzer. Results: The linear range was 0.2-50.0 µg/L, and the related coefficient was 0.9999. The relative standard deviations (RSD) within the group were 5.04%-6.64%, and the RSD between the group were 5.65%-8.11 %. The average recovery efficiencies were 85.4%-95.5%. The detection limitation was 0.0482 µg/L and the quantification concentrations was 0.1607 µg/L. Conclusion: The method, which has low detection limit, high sensitivity, easy to operate, is stability for the determination of methylmercury in urine.

[Casticin inhibits the proliferation, migration and invasion of bladder cancer cells by inhibition of TM7SF4 expression].

Objective: To explore the effect and mechanism of Casticin (CAS) on the proliferation, migration and invasion of bladder cancer T24 cells. Methods: T24 cells were cultured in vitro and divided into control group, 5, 10, 20 µmol/L CAS groups, si-NC group, si-TM7SF4 group, CAS+ pcDNA group and CAS+ pcDNA-TM7SF4 group. Cell counting kit-8 (CCK-8) was used to detect cell proliferation; Transwell was used to detect cell migration and invasion; western blot was used to detect the protein expressions of cyclin D1, p21, MMP-2, MMP-9 and TM7SF4, and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of TM7SF4 mRNA. Results: The inhibition rates of T24 cells in the 5, 10, 20 µmol/L CAS groups were (17.68±1.41)%, (33.54±3.16)% and (61.44±5.50)%, respectively, higher than (0.00±0.00)% of the control group (P<0.001), but the numbers of migration and invasion were 72.83±5.66, 59.13±4.27, 41.25±3.22 and 55.83±5.15, 42.19±3.06, 31.13±3.22, respectively, lower than 86.11±5.16 and 68.82±5.29 of the control group (P<0.001). The protein expression levels of cyclin D1, MMP-2, MMP-9, TM7SF4 and the expression levels of TM7SF4 mRNA in the 5, 10, and 20 µmol/L CAS groups were lower than the control group (P<0.001). However, the protein expression levels of p21 were 0.37±0.03, 0.51±0.04, and 0.66±0.06, respectively, higher than 0.25±0.03 in the control group (P<0.001). The inhibition rate of T24 cells in the si-TM7SF4 group was (50.35±4.67)%, higher than (6.31±0.58)% in the si-NC group (P<0.001), but the numbers of migration and invasion were 53.51±4.18 and 42.92±3.81, lower than 85.26±4.99 and 67.93±4.64 of the si-NC group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2, MMP-9 in the si-TM7SF4 group were lower than the si-NC group (P<0.001). However, the protein expression level of p21 in the si-TM7SF4 group was higher than the si-NC group (P<0.001). The inhibitory rate of T24 cells in the CAS+ pcDNA-TM7SF4 group was (21.45±2.46)%, lower than (64.06±4.49)% of the CAS+ pcDNA group (P<0.001), but the number of migration and invasion in the CAS+ pcDNA-TM7SF4 group were 75.66±6.57 and 59.35±5.40, higher than 40.43±3.85 and 30.25±3.32 in the CAS+ pcDNA group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2 and MMP-9 in the CAS+ pcDNA-TM7SF4 group were higher than the CAS+ pcDNA group (P<0.001), but the protein expression level of p21 was lower than the CAS+ pcDNA group (P<0.001). Conclusion: CAS may suppress the proliferation, migration and invasion of bladder cancer T24 cells by inhibiting the expression of TM7SF4.

[Review of risk evaluation scores for benign end stage liver diseases recipients].

Liver transplant is an unreplaceable method for benign end-stage liver disease. The risk evaluation for the waiting list recipients and for post-transplant survival could provide practical indication for organ allocation. In recent years, there are two major kinds of evaluation scores. The first kind of evaluation scores is based on model for end-stage liver disease(MELD) score,including SOFT/P-SOFT score,UCLA-FRS score and BAR score. The other evaluation system is based on the concept of acute-on-chronic liver failure,including CLIF-C-ACLF score,TAM score,AARC-ACLF score and COSSH-ACLF score. The scores based on ACLF have been shown superior power in predicting waiting list survival and post-transplant prognosis than MELD. This article reviews the two kinds of evaluation scores,aiming for the better allocation policy and the better prognosis of benign end-stage liver disease.

[Review of risk evaluation scores for benign end stage liver diseases recipients].

Liver transplant is an unreplaceable method for benign end-stage liver disease. The risk evaluation for the waiting list recipients and for post-transplant survival could provide practical indication for organ allocation. In recent years, there are two major kinds of evaluation scores. The first kind of evaluation scores is based on model for end-stage liver disease(MELD) score,including SOFT/P-SOFT score,UCLA-FRS score and BAR score. The other evaluation system is based on the concept of acute-on-chronic liver failure,including CLIF-C-ACLF score,TAM score,AARC-ACLF score and COSSH-ACLF score. The scores based on ACLF have been shown superior power in predicting waiting list survival and post-transplant prognosis than MELD. This article reviews the two kinds of evaluation scores,aiming for the better allocation policy and the better prognosis of benign end-stage liver disease.

[Analysis on characteristics and influencing factors of COVID-19 confirmed cases with viral nucleic acid re-positive after discharge in Guangdong Province].

Objective: To analyze the epidemiological characteristics and influencing factors of COVID-19 confirmed cases with viral nucleic acid re-positive in anal and/or throat swabs after discharge during the domestic imported epidemic stage in Guangdong Province in early 2020. Methods: The COVID-19 confirmed cases with the onset time before March 1, 2020 in Guangdong Province were collected to analyze the demographic data, epidemiological characteristics, and specimen collection and testing data after discharge. Logistic regression model was used for influencing factors analysis of re-positive cases. Results: A total of 1 286 COVID-19 confirmed cases were included, the M(Q1,Q3) of age was 44(32,58)years, 617 cases were male, 224 cases were re-positive in anal and/or throat swabs with the re-positive rate 17.42%. The M(Q1,Q3) of age of re-positive cases was 35(23, 50) years, which was younger than that of re-negative cases age was those 46(33, 59) years (P<0.001). With the increase of age, re-positive rate decreased (χ2trend=52.73, P<0.001). 85.27% (191/224) of re-positive cases were found in 14 d after discharge, the duration time of re-positive status was 13(7, 24) d, and 81.69% (183/224) of re-positive cases were re-tested negative in 28 d after re-positive date. No fever and other symptoms had been observed among re-positive cases during the whole follow-up. No secondary infectious cases had been found among close contacts after 14 d of centralized isolation and sampling screening. Univariate logistic regression model analysis revealed that the influencing factors of the re-positive cases included age, occupation, clusters, clinical types, and admission time. Multivariate logistic regression model analysis revealed that age was an independent risk factor. Conclusions: SARS-CoV-2 viral nucleic acid re-positive is found in COVID-19 confirmed cases after discharge in Guangdong Province. Most re-positive cases are confirmed among 14 d after discharge and re-test to negative among 28 d after re-positive date. Age is an risk factor for re-positive cases after discharge.

[Evaluation of safety of two inactivated COVID-19 vaccines in a large-scale emergency use].

Objective: To evaluate the safety of two inactivated COVID-19 vaccines in a large-scale emergency use. Methods: Based on the "Vaccination Information Collection System", the incidence data of adverse reactions in the population vaccinated with the inactivated COVID-19 vaccines developed by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd, respectively, in emergency use were collected, and the relevant information were analyzed with descriptive epidemiological and statistical methods. Results: By December 1, 2020, the vaccination information of 519 543 individuals had been collected. The overall incidence rate of adverse reactions was 1.06%, the incidence rate of systemic adverse reactions was 0.69% and the incidence rate of local adverse reactions was 0.37%. The main systemic adverse reactions included fatigue, headache, fever, cough and loss of appetite with the incidence rates of 0.21%, 0.14%, 0.06%, 0.05% and 0.05%, respectively; the main local adverse reactions were injection site pain and injection site swelling with the incidence rates of 0.24% and 0.05%, respectively. Conclusion: The two inactivated COVID-19 vaccines by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd showed that in the large-scale emergency use, the incidence rate of general reactions was low and no serious adverse reactions were observed after the vaccinations, demonstrating that the vaccines have good safety.

[Correlation analysis between serum ferritin level and liver damage in acute stage of dengue fever].

Objective: To investigate the correlation between serum ferritin (SF) level and liver damage in the acute stage of dengue fever. Methods: A retrospective study was conducted to analyze 171 cases diagnosed with dengue fever as dengue fever group and 130 healthy patients as control group in Hangzhou 3A grade hospital from July to December 2017. Clinical data, SF and liver function related indicators were collected from both groups: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) to analyze the correlation between liver damage and SF in patients with dengue fever. Results: ALT, AST, and SF levels were significantly higher in the dengue fever group than those in the healthy control group (Z = 11.553, 15.054 and 15.163, P < 0.001). SF levels were higher in the dengue fever combined with liver damage group than those without the liver damage group (z = 6.930, P < 0.001). However, there was no statistically significant differences in age, gender, peak body temperature, and history of liver disease (P > 0.05). In addition, Spearman's correlation analysis showed that SF was positively correlated with ALT, AST, and TBIL (r = 0.464, 0.531 and 0.315, P < 0.001). Among dengue patients with different SF levels, there were significant difference in ALT, AST levels and incidence of liver damage (H = 14.240 and 17.584, χ(2) = 49.547, P < 0.001). Patients with higher SF levels had higher ALT, AST levels and incidence of liver damage. Binary logistic regression analysis showed that hyperferritinemia (SF≥500 ng/ml) was the risk factor for dengue fever combined with liver damage (OR = 8.120, P < 0.001). Furthermore, ROC curve analysis showed that the AUC for SF to judge dengue fever combined liver damage was 0.846 (95% CI: 0.785-0.908), and the sensitivity and specificity when the SF cut-off value was 1 506 ng/ml were 74.8% and 83.3%. Conclusion: There is a certain correlation between the SF level and the degree of liver damage in acute stage of dengue fever patients, and hyperferritinemia is a risk factor for dengue fever combined with liver damage.

[The application of Voriconazole in 76 patients with cirrhosis at Child-Pugh C stage complicated by invasive fungal infection].

Objective: To investigate the safety and efficacy of voriconazole in the patients with cirrhosis at Child-Pugh C stage complicated by invasive fungal infection(IFI). Methods: A retrospective collection of medical records of 76 patients with cirrhosis at Child-Pugh C stage complicated by IFI who were admitted to our hospital, from August 2014 to August 2017 was carried out. All the 76 patients who used voriconazole to treat IFI were divided into recommended dose group for hepatic insufficiency(56 cases) and routine dose group(20cases). The two groups were observed and compared in terms of the voriconazole's plasma concentrations, the outcomes of IFI and the rate of untoward reactions. The liver functional indicators were also compared between before and after treatment each group. We used Student's t test, Z test, chi-square test, or Fisher's exact test, as appropriate, for statistical analysis. Results: Both groups had good performance and low frequencies of side effects in the treatment of IFI, but there were also significant differences in the plasma concentrations of voriconazole and the incidence of untoward reactions between the two groups(P = 0.008 and P = 0.022). There commended dose group for hepatic insufficiency had lower adverse effect rate. The levels of direct bilirubin, alanine aminotransferase and aspartate aminotransferase were significantly lower after treatment of IFI in the recommended dose group for hepatic insufficiency(P < 0.05). Conclusion: In our research, it is relatively safe and effective to use voriconazole to treat IFI in the patients with cirrhosis at Child-Pugh C stage if according to the recommended dose regimen for cirrhosis at Child-Pugh A,B stage.

[Association between child care environment and childhood early development].

Objective: To investigate the factors related to child care environment and the association between child care environment and children's early development. Methods: Using stratified cluster random sampling, a total of 22 509 children newly enrolled to kindergarten from 187 kindergartens of 16 districts in Shanghai in 2017 were enrolled. A survey was conducted by parent-reported questionnaire. The index of child care environment (ICCE) and the early human capacity index were used to evaluate family child care environment and children's early development respectively. The sample was divided into four groups based on the ICCE score: the lowest family childcare environment (ICCE≤10 scores), lower middle (ICCE=11 scores), upper middle (ICCE=12 scores), and the highest (ICCE=13 scores). The linear regression model and Logistic regression model were used to analyze the factors related to child care environment and the association between child care environment and children's early development respectively. Results: A total of 22 067 children aged (44±7) months, including 11 425 boys (51.8%) and 10 642 girls (48.2%), participated in this study. The multnomial linear regression revealed girls, higher maternal education, higher household annual income, single-child, non-divorced parents, and early breastfeeding experience were protective factors of child care environment for children newly enrolled to kindergarten (ß=0.064, 0.238, 0.119, 0.096, 0.113, and 0.032; 95% confidence interval (CI): 0.020-0.108, 0.175-0.302, 0.058-0.180, 0.046-0.146, -0.012-0.242, and -0.051-0.116; all P<0.01). The multinomial Logistic regression revealed compared with the highest child care environment group, the odds ratio of children's early development risks in upper midclle, lower middle, and the lowest child care environment groups were 1.543 (95%CI: 1.373-1.735, P<0.01), 2.537 (95%CI: 2.254-2.856, P<0.01), and 4.198 (95%CI: 3.757-4.690, P<0.01), respectively. Conclusions: The child care environment is not only significantly related to family structure and socioeconomic status, but also to early breastfeeding experience. The child care environment plays an important role in promoting childhood early development.

[Acute lymphoblastic leukemia complicated with cerebral venous thrombosis in 14 children].

Objective: To explore the clinical characteristics and management of childhood acute lymphoblastic leukemia (ALL) complicated with cerebral venous thrombosis (CVT). Methods: The clinical data of 14 ALL children complicated with CVT who were admitted to Department of Pediatrics of Sun Yat-sen Memorial Hospital and underwent chemotherapy from January 2011 to October 2019 were collected retrospectively. The clinical manifestations, coagulation function, imaging findings, treatment plan and prognosis of patients were analyzed. Results: CVT was diagnosed in 14 (2.8%, 14/505) cases, with a median age of 10 (3-14) years at onset, 11 cases occurred in the stage of induction remission, and the acute onsets were mainly characterized by convulsions (9 cases), consciousness disorders (6 cases) and headache (4 cases). Coagulation function test showed that, before the CVT, antithrombin Ⅲ activity was lower than 60% in 8 cases, D-dimer elevated on the day of onset in 8 cases. Arteriovenous angiography showed filling defects in single (9 cases) or multiple (5 cases) venous sinuses. The most common site of venous sinus enlargement was superior sagittal sinus (10 cases). Secondary cerebral hemorrhage was found in 5 cases. Anticoagulation therapy included combination of low-molecular-weight heparin (LMWH) and warfarin in 9 cases, sequential application of LMWH and warfarin in 2 cases, and LMWH alone in 3 cases. Patients accepted further asparaginase and no CVT recurrence or progression was found. Conclusions: The secondary coagulation dysfunction during induction remission chemotherapy is the major risk factor for CVT in ALL, which needs active monitoring and early prevention. Arteriovenous angiography can diagnose accurately, and the prognosis of anticoagulant therapy with LMWH and warfarin is optimistic.

[Analysis on the cluster epidemic of coronavirus disease 2019 in Guangdong Province].

Objective: Analysis of clustering characteristics of coronavirus disease 2019 (COVID-19) in Guangdong Province. Methods: The COVID-19 cases in Guangdong Province onset from January 1 to February 29, 2020 were collected from Chinese information system for disease control and prevention and Emergency Public Reporting System. Obtain the epidemiological survey data of the cluster epidemic situation, and clarify the scale of cluster epidemic situation, the characteristics of the index cases, family and non-family subsequent cases. Calculate serial interval according to the onset time of the index cases and subsequent cases, secondary attack rate based on the close contacts tracking results, the characteristics of different cases in the clustered epidemic were compared. Results: A total of 283 cluster were collected, including 633 index cases, 239 subsequent cases. Families are mainly clustered, the total number involved in each cluster is in the range of 2-27, M (P25, P75) are 2.0 (2.0, 4.0). During January 15 to February 29, the secondary attack rate is 2.86% (239/8 363) in Guangdong Province, the family secondary attack rate was 4.84% (276/3 697), and the non-family secondary attack rate was 1.32% (61/4 632). According to the reporting trend of the number of cases in Guangdong Province, it can be divided into four stages, the rising stage, the high platform stage, the descending stage and the low level fluctuation period. The secondary attack rate of the four stages were 3.5% (140/3 987), 2.3% (55/2 399), 2.6% (37/1 435), 1.3% (7/542), respectively. The difference was statistically significant (P=0.003). Conclusion: COVID-19 cluster mainly occurs in families in Guangdong Province. The scale of the clustered epidemic was small; the serial interval was short; and the overall secondary attack rate was low.

[Study on the pharmacokinetics of bromadiolone in oral poisoning rabbits].

Objective: To investigate the variations of bromadiolone concentration in blood and its metabolism in rabbits after oral administration of bromadiolone, and to provide reference for the study of bromadiolone metabolism. Methods: Designed absolute alcohol (1 g/kg) reagent control group, high dose (0.3 mg/kg) and low dose group (0.05 mg/kg) , there were 6 rabbits in each group. Blood samples were collected from the rabbit central auricular artery at regular intervals as 1 h, 2 h, 4 h, 8 h, 12 h, 16 h, 24 h, 36 h, 48 h, 72 h, 168 h, 336 h, 504 h after oral administration. The samples were centrifuged within 1 h. Prothrombin time (PT) , activated partial thromboplastin time (APTT) and concentrations of bromadiolone in plasma were tested. Metabolic kinetics data was analyzed by DAS 3.0.2 software. Results: Bromadiolone had no significant effect on the body weight of the experimental rabbits during the experimental period (P>0.05) . PT and APTT were significantly abnormal in different dose groups, but for occurrence of exception, PT was earlier than APTT. The concentration of bromadiolone in plasma reached the peak value 12 h after gavage in both high-dose and low-dose groups. The absorption time of t(1/2Ka) in high-dose group was 4.34 h, the clearance time of t(1/2) was 81.52 h, the absorption time of t(1/2Ka) in low-dose group was 6.90 h, and the elimination time of t(1/2) was 56.38 h. The atrioventricular model of bromadidone was three compartment model in rabbits. Conclusion: Bromadiolone can be absorbed rapidly by oral administration, but its metabolism is slow. The change of bromadiolone in vivo accords with the three compartment model.