Extremely unbalanced data refers to datasets with independent or dependent variables showing severe imbalances in proportions, which might lead to deviation of classical test statistics from theoretical distribution and difficulties in controlling type Ⅰ error. The increased availability of genome-wide resources from large population cohorts has highlighted the growing demand for efficient and accurate statistical methods for the process of extremely unbalanced data to improve the development of genetic statistical methods. This paper introduces two widely used correction methods in current genome-wide association study for extremely unbalanced data, i.e. Firth correction and saddle point approximation, describes their effectiveness in controlling type Ⅰ errors confirmed by simulation experiments, finally, and summarizes the commonly used software for extremely unbalanced genomic data to provide theoretical reference and suggestion for its application for the statistical analysis on extremely unbalanced data in future.

Extremely unbalanced data refers to datasets with independent or dependent variables showing severe imbalances in proportions, which might lead to deviation of classical test statistics from theoretical distribution and difficulties in controlling type Ⅰ error. The increased availability of genome-wide resources from large population cohorts has highlighted the growing demand for efficient and accurate statistical methods for the process of extremely unbalanced data to improve the development of genetic statistical methods. This paper introduces two widely used correction methods in current genome-wide association study for extremely unbalanced data, i.e. Firth correction and saddle point approximation, describes their effectiveness in controlling type Ⅰ errors confirmed by simulation experiments, finally, and summarizes the commonly used software for extremely unbalanced genomic data to provide theoretical reference and suggestion for its application for the statistical analysis on extremely unbalanced data in future.

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.

Objective:To investigate the effect of robot-assisted intelligent graded pain management in managing acute postoperative pain for patients undergoing hip and knee joint replacement.Methods:Totally patients who underwent hip and knee joint replacement surgery between February and December 2022 at the First Affiliated Hospital of Zhengzhou University were selected by convenience sampling. Patients were randomly assigned into two groups: a control group ( n=78), receiving standard pain management, and an observation group ( n=78), receiving robot-assisted intelligent graded pain management. Postoperative data collected and compared between groups included use of patient-controlled analgesia (PCA), analgesic consumption, time to first ambulation, length of hospital stay, and pain management quality. Results:The observation group showed statistically significant reductions in PCA duration, fentanyl dosage, and lappaconitine hydrobromide dosage compared to the control group ( P<0.05). In addition, the time to first ambulation was earlier, and the postoperative hospital stay was shorter in the observation group ( P<0.05). In terms of pain management quality, the observation group reported lower pain scores and higher satisfaction scores than the control group ( P<0.05) . Conclusions:Robot-assisted intelligent graded pain management effectively reduces the time of PCA and the use of analgesics for patients undergoing hip and knee joint replacement surgery. It facilitates earlier ambulation, shortens hospital stays, and improves the quality of acute postoperative pain control.

Objective:To investigate the effect of robot-assisted intelligent graded pain management in managing acute postoperative pain for patients undergoing hip and knee joint replacement.Methods:Totally patients who underwent hip and knee joint replacement surgery between February and December 2022 at the First Affiliated Hospital of Zhengzhou University were selected by convenience sampling. Patients were randomly assigned into two groups: a control group ( n=78), receiving standard pain management, and an observation group ( n=78), receiving robot-assisted intelligent graded pain management. Postoperative data collected and compared between groups included use of patient-controlled analgesia (PCA), analgesic consumption, time to first ambulation, length of hospital stay, and pain management quality. Results:The observation group showed statistically significant reductions in PCA duration, fentanyl dosage, and lappaconitine hydrobromide dosage compared to the control group ( P<0.05). In addition, the time to first ambulation was earlier, and the postoperative hospital stay was shorter in the observation group ( P<0.05). In terms of pain management quality, the observation group reported lower pain scores and higher satisfaction scores than the control group ( P<0.05) . Conclusions:Robot-assisted intelligent graded pain management effectively reduces the time of PCA and the use of analgesics for patients undergoing hip and knee joint replacement surgery. It facilitates earlier ambulation, shortens hospital stays, and improves the quality of acute postoperative pain control.

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.

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 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.