Extremely unbalanced data here refers to datasets where the values of independent or dependent variables exhibit severe unbalance in proportions, such as extremely unbalanced case-control ratio, very low incidence rate of disease, heavily censored time-to-event data, and low-frequency or rare variants. In such scenarios, the statistic derived from hypothesis test using the classical statistical method, e.g., logistic regression model and Cox proportional hazard regression model, might deviate from theoretical asymptotic distribution, resulting in inflation or deflation of type I error. With the increased availability and exploration of resources from large-scale population cohorts in genome-wide association study (GWAS), there is a growing demand for effective and accurate statistical approaches to handle extremely unbalanced data in independent and non-independent samples. Our study introduces classical statistical methods in genetic statistics firstly, then, summarizes the failure of classical statistical methods in dealing with extremely unbalanced data through simulation experiments to draw researchers' attention to the extremely unbalanced data in GWAS.

Group A Streptococcus (GAS) are important human pathogens.In recent years, the M1 UK strain has attracted widespread attention in the United Kingdom and other countries because it has been associated with a surge in scarlet fever and an increase in invasive GAS infections.Author conducted a whole-genome sequencing study of 42 GAS strains from 2016 to 2018 in Shenzhen, and found that a GAS strain isolated from a child with scarlet fever in Shenzhen area in 2018 was homologous to M1 UK, which is the first strain of M1 UK confirmed in the mainland of China.For this reason, hereby publish it with a view to attracting the attention of our domestic counterparts and safeguarding public health safety.

Objective To investigate visual impairment students' quality of life and its influencing factors in Braille learning class at Quanzhou Special School. Methods November, 2020, 52 students (aged seven to 26) with the best corrected distance visual acuity of the better eye above 0.02 were investigated with near visual acuity, contrast sensitivity and Chinese-version Low Vision Quality of Life Questionnaire (CLVQOL). The subjects were divided into second grade blindness group, first grade low vision group and second grade low vision group according to the best corrected distance visual acuity of the better eye. Results There were significant differences in distance visual acuity (Z = 45.671, P < 0.001), near visual acuity (Z = 24.972, P < 0.001), and contrast sensitivity (CS) ( Z = 13.285, P = 0.001) among three groups. There was a correlation between near visual acuity and distance visual acuity (r = 0.74, P < 0.001), CS to distance visual acuity (r = -0.58, P < 0.001) and near visual acuity (r = -0.57, P < 0.001), score of CLVQOL and CS (r = 0.44, P < 0.001). There were significant differences in the total score (Z = 10.145, P = 0.006), distance visual acuity subscale (Z = 13.586, P = 0.001), psychological adjustment subscale (Z = 7.824, P = 0.020), reading and fine work subscale (Z = 7.923, P = 0.019) of CLVQOL among the three groups. Conclusion Quality of life is different with the visual impairment for students in special school, especially the distance visual acuity, psychological adjustment and fine reading. CS correlates to the quality of life of visually impaired students, which needs to be a part of evaluation of visual function.

Objective:To investigate the feasibility of nebulizing injectable Tobramycin for the treatment of Pseudomonas aeruginosa (Pa) in pediatric cystic fibrosis (CF) patients. Methods:The clinical data of 3 CF children with Pa infection who were treated by nebulizing injectable Tobramycin in Shenzhen Children′s Hospital from September 2017 to March 2021 were retrospectively analyzed.The efficacy and safety were explored.The nebulized injectable Tobramycin (160 mg/dose) was given twice daily after airway clearance.After one-month treatment course, oral Ciprofloxacin would be given [30 mg/(kg·d)] to patients for another 1 month if Pa was still positive in repeat sputum cultures.Results:There were 2 males and 1 female in 3 cases recruited.The youngest patient was 1-year-old when receiving Tobramycin treatment.After airway clearance and inhalation of injectable Tobramycin, all had improvements in respiratory symptoms and chest CT scan.Two cases took additional oral Ciprofloxacin as Pa was still positive after the 1-month treatment course of Tobramycin.Pa turned to negative in all 3 cases after treatment for 3 months to 1.5 years.Besides, after treatment all the 3 patients had normal liver and renal functions, and normal hearing in multiple follow ups.One patient had a normal brainstem auditory evoked potential in the reexamination.Conclusions:Nebulizing injectable Tobramycin would be a reasonable alternative to inhaled Tobramycin solution for treating pediatric CF patients with Pa in view of the present condition in mainland China.However, it is still worth further study and discussion.

Objective:To investigate the clinical characteristics and risk factors of postinfectious bronchiolitis obliterans(PIBO)after severe adenovirus pneumonia(SAP).Methods:We retrospectivly analyzed 78 children who were hospitalized for SAP at Shenzhen Children′s Hospital from April 2015 to April 2020.The cases were divided into PIBO group( n=26) and non-PIBO group( n=52) based on the diagnosis results.The general conditions, clinical characteristics, and laboratory data from two groups were analyzed, and the risk factors for PIBO were explored. Results:A total of 78 children were included in this study.There were 18 (69.2%) males and eight (30.8%) females in PIBO group; the average age of onset in PIBO group was younger than that in non-PIBO group[(11.77±3.24)months vs.(15.08±6.48)months, P=0.027]. The cough duration[(11.35±7.35)days vs.(7.15±5.67)days, P=0.010], and heat duration[(13.12±6.78)days vs.(8.62±4.76)days, P=0.007] were longer in PIBO group than those in non-PIBO group.The white blood cell count[(12.46±7.23)×10 9/L vs.(9.17±3.66)×10 9/L), P<0.05], platelet count[(390.12±209.03)×10 9/L vs.(284.69±83.33)10 9/L, P<0.05], C-reactive protein[(37.04±32.16)mg/L vs.(18.14±18.33)mg/L, P<0.05], procalcitonin[(3.51±3.33)μg/L vs.(1.09±1.37)μg/L, P<0.05], lactate dehydrogenase(LDH)[(1 155.88±842.94)IU/L vs.(414.00±218.94)IU/L, P<0.01] were all higher in PIBO group than those in non-PIBO group; The roportion of patients with mycoplasma pneumoniae infection[5(19.2%) cases vs.4(7.7%) cases, P<0.05], admitted to PICU[18(69.2%) cases vs.8(15.4%) cases, P<0.01] , using invasive mechanical ventilation[10(38.5%) cases vs.5(9.6%) cases, P<0.01], using hormones[23(88.5%) cases vs.21(40.4%) cases, P<0.01], and using human immunoglobulin[20 (76.9%) cases vs.10(19.2%) cases, P<0.01] were higher in PIBO group than those in non-PIBO group.The multivariate Logistic regression using stepwise method showed that older age ( OR=0.942, 95% CI 0.890-0.997) was a protective factor for PIBO, while higher LDH levels ( OR=1.005, 95% CI 1.002-1.008), using intravenous corticosteroids ( OR=6.622, 95% CI 0.924-47.436), and using human immunoglobulin ( OR=9.681, 95% CI 1.742-53.802) were the risk factors for PIBO in SAP ( P<0.05). The receiver operating characteristic curve was constructed through the combination of age of onset, LDH level, using intravenous hormone, and using human immunoglobulin.The area under the curve reached 0.954.The overall best cut-off value of the prediction model was 0.272, the sensitivity was 92.3%, and the specificity was 86.5%.When LDH=462 IU/L, the area under the curve reached the maximum value of 0.882, the sensitivity was 100.0%, and the specificity was 61.5%. Conclusion:SAP children with characteristics such as younger age, long cough and fever duration, high inflammatory index, LDH level higher than 462 IU/L, admitted to PICU, mechanical ventilation and need hormones and human immunoglobulin, should be alert to the risk of PIBO.

Objective: To explore whether RhoA plays a role in the migration and invasion of the salivary adenoid cystic carcinoma cell lines SACC-LM and SACC-83. Methods: Total RNA and total protein were extracted from 20 salivary adenoid cystic carcinoma (SACC) and normal adjacent tissues frozen in liquid nitrogen to detect RhoA expression. RhoA-siRNA was constructed to transfect two cell lines (SACC-LM and SACC-83) for cytological experiments. The research included an experimental group (RhoA-siRNA transfection), negative control group (siRNA-NC transfection) and blank group by transient transfection with liposomes. Expression of RhoA mRNA and protein as well as the protein expression of biomarkers of epithelial-mesenchymal transition (EMT) were analyzed, including E-cadherin, N-cadherin, and Vimentin. Furthermore, the changes in invasion and migration of cells in each group were analyzed by comparing the number of transmembrane cells in the Transwell assay and the results of the scratch test. Results: Compared with normal adjacent tissues, RhoA protein and mRNA levels increased in SACC tissues. Compared with the control group, the relative expression levels of RhoA mRNA and protein decreased (P < 0.01), the relative expression levels of E-cadherin protein increased, and the relative expression levels of N-cadherin and vimentin protein increased in the experimental group (P < 0.01). Additionally, the trial results revealed that RhoA knockdown restrained cell migration and invasion (P < 0.01). Conclusion RhoA expression increased in SACC tissue. Silencing RhoA in vitro could effectively restrain cell migration and invasion in SACC-LM and SACC-83 cells through the regulation of EMT signaling pathways.

Objective To screen for malignant tumors and high-risk factors in rural residents over 60 years old， so as to prevent and control the occurrence and development of tumors in the future. Methods The survey was conducted with reference to part of the questionnaire in the "Urban Cancer Early Diagnosis and Treatment Project and Evaluation of High-risk Populations". Clinical examinations included serum tumor marker detection， CT screening for lung cancer， occult blood （+） plus colonoscopy screening for colorectal cancer， and mammography screening. Individuals who were positive in the abovementioned clinical tests were defined as high-risk subjects. Results A total of 271 high-risk subjects （1.91%） were screened out of 14 161. Among the high-risk subjects， 71 cases of malignant tumors （26.19%） were found， with an incidence rate of 501.38 per 10⁵. The top five tumors （63.38% of all diagnosed） were mainly concentrated in lung， upper digestive tract， blood system， urinary system， and rectum-colon. The proportion of malignant tumors detected by positive indicators was 61.54% of blood； 46.15% of carcinoembryonic antigen and carbohydrate antigen 125； 23.08% of alpha-fetoprotein； 16.66% of lung CT； and 3.09% of prostate PSA. The positive indicators in the high-risk subjects were mainly for the tumors in the prostate， lungs， liver， and CEA/CA125. The subjects with positive test indicators had lower average annual income in the last 5 years than the normal subject group （χ²=3.380， P=0.040）. The subjects with positive test indicators had higher proportion in family history of tumors than the normal group （χ²=2.596， P=0.046）. People in thehigh-risk group had a higher proportion than the normal group in suffering from hypertension， liver disease， gastrointestinal disease， respiratory system disease， and surgical treatment. Patients with high-risk tumors were found to have higher proportion than the normal group in showing pre-tumor clinical symptoms in the last 1 year. Study of the tumor-related risk factors found that the high-risk group had a higher proportion of high-fat/high-cholesterol diet， alcohol drinking， passive smoking， and personality depression. Conclusion High tumor risk factors have been identified in this population. It is necessary to strengthen the corresponding intervention and follow-up treatment of precancerous diseases in the future. We recommend the government to conduct tumor screening among high-risk groups to improve cost-effectiveness.

Objective: To investigate the nutritional status and its relationship with the indexes of physical function and physical capacity among primary and middle school students in Xiamen, so as to provide statistical support for improving their nutritional status and physical health. Methods: A total of 2 752 primary and middle school students aged between 6 and 18 years old were selected in Xiamen. They were divided into malnutrition group, normal group and overweight and obesity group according to the national standards. Statistical analysis was carried out by chi square test, Kruskal wallis test and partial correlation analysis. Results: The prevalence of malnutrition among primary and secondary school students in Xiamen was 8.4%(231), the prevalence of overweight and obesity was 24.2%(667), and the prevalence of overweight and obesity among boys(31.4%) was higher than girls( 17.0 %).The distribution of nutritional status between different ages was statistically significant ( χ 2=40.43, P <0.05). On the lung activity index, both boys and girls were shown to be overweight and obesityConclusion The prevention and control situation of overweight between primary and secondary school students in Xiamen city, is more serious. Overweight and obesity are related to decline in physical function and physical fitness. Nutritional status should be paid more attention for physical fitness improvement among students.

Objective:To summarize the clinical characteristics of adenovirus (HAdVs) pneumonia in children.Methods:The clinical manifestations, laboratory results, imaging features and treatment courses of 541 children with HAdVs pneumonia treated in Shenzhen Children′s Hospital from January 2017 to August 2019 were retrospectively studied.Results:The number of children diagnosed with HAdVs pneumonia increased year by year.A total of 541 patients were included in this study (214 females and 327 males, median age 31 months). The majority of patients (89.3%, 483/541 cases) were less than 6 years of age.Cough (98.3%, 532/541 cases) was the most common symptom, followed by fever (93.7%, 507/541 cases), tachypnea (36.6%, 198/541 cases) and wheeting (32.5%, 176/541 cases). Thirteen point three percent patients (72/541 cases) had existing primary diseases.Severe HAdVs pneumonia was observed in 33.8% of patients (183/541 cases), the most common intrapulmonary complication were pleural effusion(18.6%, 101/541 cases) and respiratory failure (7.0%, 38/541 cases). In co-infection cases, 46.9% of the patients (254/541 cases) suffered from co-infection with mycoplasma pneumoniae, 21.6% of the patients (117/541 cases) suffered from bacterial co-infection.Ninety-eight point five percent of the patients (533/541 cases) were cured, and 1.5% of the patients (8/541 cases) died or discharged voluntarily.Convulsions [ P=0.026, OR=7.312 (95% CI: 1.267-42.191)] and bacterial co-infections [ P=0.030, OR=2.724 (95% CI: 1.101-6.741)] were independently correlated with the occurrence of severe HAdVs pneumonia. Conclusions:Pre-school aged children are at higher risks of developing HAdVs pneumonia.The majority of patients presents with fever and cough as primary manifestations.Tachypnea and wheezing are also common clinical features of HAdVs pneumonia patients.Approximately a third of children with HAdVs pneumonia may develop into severe pneumonia.The presentation of convulsion and the exis-tence of bacterial co-infections may help to predict the development of severe HAdVs pneumonia in pediatric patients.

To investigate the inhibitory effect of sildenafil on Caco-2 cell proliferation and its anti-inflammatory effect on menadione-induced NCM460 cell inflammation model, MTT assay was used to determine cell proliferation. Intracellular reactive oxygen species(ROS)and nitric oxide(NO)levels were detected by fluorescent probe. Western blot was used to detect the expression of eNOS/ERK/JNK pathway related proteins in Caco-2 cells and correlated inflammatory cytokines in NCM460 cells. The effect of sildenafil on the growth of two probiotics was determined by spectrophotometry. Results showed that sildenafil signi-ficantly inhibited the proliferation of Caco-2 cells and enhanced the expression levels of eNOS, p-eNOS, p-JNK1/2 and p-ERK1/2 proteins in Caco-2 cells; while after adding NG-nitro-L-arginine methyl ester(L-NAME), the expression levels of eNOS, p-eNOS, p-JNK1/2 and p-ERK1/2 proteins were significantly lower than those of the sildenafil group. Compared with the menadione group, sildenafil significantly reduced ROS levels in NCM460 cells and inhibited the expression levels of IL-6, IL-1β, p62, and TNF-α. Moreover, high concentrations of sildenafil had no obvious toxic effects on Lactobacillus casei and Lactobacillus rhamnosus. Thus, the results indicated that sildenafil could effectively inhibit the intestinal inflammatory response without affecting the balance of the intestinal flora, and prevent colorectal cancer by reducing the oxidative stress responses in the intestinal cells.