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.

The global morbidity of invasive fungal diseases (IFD) tends to increase, especially in immunocompromised people.Due to the atypical symptoms, unclear etiological mechanism, and emerging antifungal resistance, IFD challenge current clinical diagnosis and treatment.The World Health Organization (WHO) developed the first WHO fungal priority pathogens list in 2022.The most concerning fungal pathogens were listed and summarized to promote further understanding of the epidemiology of IFD and antifungal drug resistance.It is hoped to provide a basis for the prevention and interventions of IFD.

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 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 find the differentially expressed long non-coding RNA (lncRNA) between db/db mice that with nephropathy (DN) or not (DM).Methods In this study,3 DM db/db mice and 2 DN db/db mice proven by renal biopsy were randomly selected,and 3 healthy db/m mice as normal control group.Then,differentially expressed lncRNAs,mRNAs and their fragments per kilobase million (FPKM) in kidney samples were detected by high-throughput next generation sequencing technology.Sequencing data were analyzed to filter out the differentially expressed lncRNA,and theirfunction was preliminarily investigated by bioinformatics analysis and functional enrichment analysis to predict their target genes.Total RNAs of kidneys from these 8 mice were extracted to run real time PCR (RT-qPCR) for verifying the outcomes of the high-throughput sequencing.Results The urinary microalbumin/creatinine ratio (UACR),serum creatinine,and glomerular basement membrane thickness of DN db/db mice were higher than those of DM db/db mice (all P ＜ 0.05),while there was not significant difference in glucose between DM and DN mice.Totally 160 lncRNAs were up-regulated and 99 lncRNAs were down-regulated in kidneys of DN mice compared with those of DM mice,in which the differentially expressed lncRNAs with FPKM value≥2 and differential expression≥ 1 fold between groups were screened and verified by RT-qPCR.Finally three lncRNAs whose variation trend were consistent with the outcomes of the high-throughput sequencing were obtained.Conclusion There was a significantly different expression pattern of lncRNA between the kidneys of DN and DM mice,which may be involved in the progress of DN.

To explore differential expression of long non-coding RNA (lncRNA) in patients with coronary artery disease plus clopidogrel resistance.
 Methods: Patients underwent percutaneous coronary intervention (PCI) and treated with clopidogrel were recruited, and their clinical data and blood samples were collected. Patients were divided into a clopidogrel sensitive group and a clopidogrel resistance group according to platelet aggregation rate. lncRNA microarray and real-time RT-PCR were performed in 5 and 34 patients in each group, respectively.
 Results: lncRNA microarray showed that 11 lncRNAs in peripheral leukocytes were up-regulated and 8 lncRNAs were down-regulated in clopidogrel resistant group. Real-time PCR indicated that two lncRNAs (NONHSAT083775.2 and NONHSAT107804.2) in leukocytes were up-regulated and one lncRNA (NONHSAT133455.2) was down-regulated in the clopidogrel resistant group compared with the clopidogrel sensitive group, consistent with the results of lncRNA microarray.
 Conclusion: Clopidogrel resistance is associated with the up-regulation of lncRNA NONHSAT083775.2 and NONHSAT107804.2 and the down-regulation of NONHSAT133455.2.
Clopidogrel ; Coronary Artery Disease ; genetics ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; RNA, Long Noncoding

Objective To evaluate the effect of over-expression of phosphatase and tensin homolog does on chromosome ten (PTEN) in podocytes on kidney under high fat diet (HFD) in vivo and clarify the mechanism how PTEN regulates scavenger receptor A (SR-A) expression exposed to oxidized low density lipoprotein (ox-LDL) in podocytes in vitro.Methods The podocyte-specific PTEN knockin (PPKI) mice were fed with HFD to establish mouse model of lipid-induced renal injury.Mice were divided into four groups:ND+Ctrl group,ND+PPKI group,HFD+Ctrl group and HFD+PPKI group.After 24 weeks of dietary intervention,all mice were tested for clinical and biochemical parameters,including serum creatinine (Scr) as well as urine albumin excretion rate (UAER);renal lipid content was measured by oil red O staining and cholesterol quantitative analysis;the pathological changes of glomeruli were observed by PAS staining and electron microscope.Podocyte injury was induced by ox-LDL in vitro.Western blotting was used to detect the changes of SR-A expression induced by ox-LDL after YAP-siRNA interfering (si-YAP),as well as YAP phosphorylation induced by ox-LDL after interfering by PTEN-siRNA (si-PTEN) and PTEN phosphatase inhibitor (Bpv-PTEN),and overexpressing by recombinant adenovirus (ad-PTEN).Results Compared with ND+Ctrl group,HFD+ Ctrl group significantly aggravated the levels of Scr and UAER,the expression of SR-A in podocytes,renal lipid content,mesangial matrix expansion,effacement of podocyte foot processes,and incrassation of glomerular basement membrane (all P ＜ 0.05).Conversely,compared with HFD+Ctrl group,HFD+ PPKI group obviously alleviated the above lipid-induced renal damage (all P ＜ 0.05).In vitro,the expression of SR-A in podocytes was up-regulated when stimulated with ox-LDL (P ＜ 0.05),and the knockout of YAP significantly down-regulated the expression of SR-A induced by ox-LDL (P ＜ 0.05).Exposed to ox-LDL,the expression of p-YAP increased in podocytes (P ＜ 0.05);over-expression of PTEN inhibited p-YAP up-regulation induced by ox-LDL (P ＜ 0.05),while either knockdown of PTEN or inhibition of PTEN phosphatase activity displayed opposite effect (all P ＜ 0.05).Conclusions Over-expression of PTEN in podocytes protected the kidney against damage from HFD in vivo and PTEN might suppress SR-A mediated lipid uptake via dephosphorylating p-YAP to prevent podocyte injury from ox-LDL.

Objective:To investigate the potential correlation between miR-223 level in leukocytes and platelet responses to clopidogrel in patients with coronary artery disease.Methods:A cohort of 188 outpatients,who conducted percutaneous coronary intervention (PCI) and received dual antiplatelet therapy,were recruited.The patient's electronic health data were collected,and their blood samples were obtained for measurement of adenosine diphosphate (ADP)-induced whole-blood platelet aggregation.Extreme cases ofplatelet responses to clopidogrel (ultra-vs.non-responder) were measured with miR-223-3p levels in leukocytes.Results:Both groups had similar miR-223-3p levels in leukocytes.There were no significant differences in other demographic and clinical data except for metrics of ADP-induced whole-blood platelet aggregation between the 2 group.Conclusion:MiR-223-3p in peripheral leukocytes is not associated with the altered platelet responses to clopidogrel in PCI outpatients.

Objective To observe the clinical efficiency and safety of docetaxel(TXT) or irinotecan(CPT-11) combined with oxaliplatin(L-OHP) and S-1 in the treatment of advanced gastric cancer.Methods Totally 62 cases of patients with stage Ⅲ B-Ⅳ advanced gastric cancer in the Department of Gastrointestinal Surgery of our hospital were collected from 1st January 2010 to 1st March 2016,and were divided into two groups:TXT combined with L-OHP and S-1 group (modified DCF group,33 patients) and CPT-11 combined with L-OHP and S-1 group (modified ICF group,29 patients).All patients in the two groups were completed at least 1 cycle of chemotherapy until disease progression or intolerable toxicity.At the end of chemotherapy,the curative effects,untoward reactions and effects of surgery after neoadjuvant chemotherapy treatment were compared and analyzed.Results The objective response rate (ORR) in the modified DCF group(60.6％) was higher than that in the modified ICF group (51.7％),while no statistically significant difference was found in short-term effects between the two groups (Z=-0.837,P=0.403).There was no statistically significant difference in the incidences of main untoward reactions,including gastrointestinal reaction,myelosuppression,neurotoxicity,alopecia and liver function abnormal,between the two groups (P＞0.05).The radical resection rate of the modified DCF group and the modified ICF group after neoadjuvant chemotherapy was 66.7 ％ and 62.1 ％ respectively,the difference between the two groups was not statistically significant (x2=0.143,P=0.706).After neoadjuvant chemotherapy,the main postoperative complications were anastomotic leakage,anastomotic obstruction,abdominal infection,pulmonary infection,incision infection and gastric motility disorder,and no statistically significant difference was found in the incidence of postoperative complications between the two groups (P＞0.05).The was no statistically significant difference in quality of life after chemotherapy between the two groups (P＞0.05).Conclusion TXT or CPT-11 combined with L-OHP and S-1 has similar efficacy in the treatment of advanced gastric cancer,which could reduce tumour size,improve radical resection rate.Furthermore,untoward reactions of the two neoadjuvant chemotherapy protocols are almost the same,and can be tolerated.It is worthy of further research and application.

Objective To compare the diuretic efficacy of torasemide as a 2-hour continuous infusion and as a bolus injection of equal dose in patients with nephrotic syndrome,and to investigate a preferable administration mode of torasemide for these patients.Methods Twenty-three hospitalized patients were randomized to receive torasemide 20 mg or 40 mg per day by either 2-hour intravenous infusion or bolus injection,and interchanged after 48 hours of washout.Results Patients received torasemide by 2-hour intravenous infusion exhibited significantly higher daily urinary volume,chloride excretion,sodium excretion and fractional excretion of sodium (FENa) within 24 hours than those by bolus injection (P ＜ 0.05).Significantly lower bound-state torasemide excretion,higher ratio of urinary volume to torasemide excretion and a markedly larger area under the curve in the plasma concentrationtime profiles were also observed in the infusion group (P ＜ 0.05).Conclusion 2-hour continuous infusion delivers a better diuretic effect compared with a bolus injection of equal dose of torasemide in patients with nephrotic syndrome.