The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Objective:To explore the causal association between insulin-like growth factor-1(IGF-1)and colorectal cancer(CRC)based on two sample Mendelian randomization(MR)analysis.Methods:A bidirectional two sample MR analysis was conducted based on publicly aggregated data from the IEU OpenGWAS project.The inverse variance weighted(IVW)method was used as the main analysis model to assess the causal relationship between IGF-1 and CRC.Additional analyses were performed using weighted median(WM),MR-Egger regression,weighted mode estimator(WME),and simple mode(SM)methods.Sensitivity analysis was performed to assess the robustness of the results.Results:A total of 386 single nucleotide polymorphisms(SNPs)were selected as instrumental variables(IVs)with IGF-1 as the exposure factor.The MR analysis results revealed a positive causal association between IGF-1 and the risk of CRC[odds ratio(OR)=1.178,95％confidence interval(CI):1.092-1.272)](P＜0.001),and the association remained significant after adjusting for height[OR(95％CI)=1.214(1.111,1.327)](P＜0.001).Cochran's Q-test showed heterogeneity among the IVs(P＜0.05),while the horizontal pleiotropy of IV was not detected by the MR-Egger regression(P＞0.05).The leave-one-out analysis showed that the MR results were robust.Reverse MR analysis indicated no reverse causal relationship between IGF-1 and CRC[OR(95％CI):1.017(0.997,1.037)](P=0.103).Conclusion:There is a causal relationship between IGF-1 level and CRC,and elevated IGF-1 level could be a risk factor for CRC.

To summarise the clinical experience of treating insomnia with the method of resolving depression， regulating the middle， and tranquilising mind. It is believed that the key to the pathogenesis of insomnia lies in qi depression， disharmony of qi pivot， and disharmony of qi and blood， and the core treatment is to resolve depression， regulating the middle， and tranquilising mind. The self-prescribed Jieyu Anmian Formula （解郁安眠方） could be used as the basic treatment， then modified according to the performance of the patient and syndromes. For syndrome of liver depression restricting spleen， the treatment should soothe liver and invigorate spleen， resolve depression and regulate the middle； for syndrome of liver depression and phlegm coagulation， the treatment should resolve depression and phlegm， support the earth and free the wood； for syndrome of liver depression transforming into fire， the treatment should soothe liver and clear fire， resolve depression and dysphoria； for syndrome of qi stagnation and blood stasis， the treatment should activate blood and regulate the middle， resolve depression and tranquilise mind.

Objective In this study,a risk prediction model for Alzheimer's disease(AD)was constructed based on Alzheimer's disease neuroimaging initiative(ADNI)database to provide a theoretical basis for a better understanding of AD,as well as to provide a reference basis for the rational allocation of health resources and the development of preventive and control strategies.Methods The ADNIMERGE,UPENNBIOMK,ADNINIGHTINGALELONG and DXSUM datasets from the ADNI database were downloaded and random forest algorithm was used for the missing values imputation.Variable screening was performed by LASSO regression.Borderline-1 SMOTE resampling was used to adjusted for intergroup balance,and the variables were incorporated into base classifiers including XGBoost,random forest,bagging,AdaBoost,and support vector machine.Enhanced integrated classifiers were then constructed based on voting and Stacking strategies.Youden index,area under curve(AUC),F-score,G-mean,accuracy,Matthews correlation coefficient(MCC)and Kappa on the validation set were used to evaluate and compare the model efficacy.Results The performance of the classifiers based on balanced data were improved for both base and enhanced integrated classifiers.The performance of stacking and voting enhanced integrated classifiers constructed based on advantageous base classifiers have better performance compared to the base classifiers.After data balancing,the XGBoost performed better in the base classifiers(AUC:0.9090,accuracy:0.9091)and voting algorithm performs better in enhanced integrated classifiers(AUC:0.9178,accuracy:0.9179).Conclusion After Borderline-1 SMOTE resampling adjusted,the performance of both base classifiers and the enhanced integrated classifiers were all improved.For balanced data,XGBoost classifier and the voting enhanced integrated classifier can effectively assist in clinical prediction of Alzheimer's disease progression.

Objectives:To investigate the effect of non-optimal temperature exposure during pregnancy on the risk for preterm birth and identify the susceptible exposure window. At the same time, the interaction between non-optimal temperature and pollutants exposure during pregnancy on preterm birth was analyzed, in order to provide strong clues for the influence of non-optimal temperature exposure during pregnancy on the risk for preterm birth.Methods:A total of 1 852 pregnant women were recruited from September 2021 to June 2023 in Fujian Provincial Maternal and Child Health Care Center. Questionnaire survey was conducted, and their health records were analyzed. The permanent address of each pregnant woman was matched with Fifth Generation European Centre for Medium-Range Weather Forecasts Atmospheric Reanalysis of the Global Climate and a geo-statistical combination model based on satellite remote sensing data collection, then follow-up for pregnancy outcome was conducted. Distributed lag nonlinear model was used to assess the association between exposure to non-optimal temperature during pregnancy and the risk for preterm birth and a multiplicative interaction model was used to assess the interaction between exposure to pollutants and non-optimal temperatures during pregnancy on the risk for preterm birth.Results:After adjusting for potential confounders such as maternal age, occupation, Gross Domestic Product of the region, pre-pregnancy preconception BMI, newborn sex, the weekly susceptibility windows of extreme low temperature ( P1, P3, P5) were week 1-22 , and the weekly susceptibility windows of extreme high temperature ( P95, P97, P99) were week 27 and week 32-36. Extreme low temperature [ P1 ( OR=1.147, 95% CI: 1.041-1.265), P5 ( OR=1.284, 95% CI: 1.035-1.501)] and extreme high temperature [ P97 ( OR=1.146, 95% CI: 1.039-1.263), P99 ( OR=1.216, 95% CI: 1.099-1.345)] exhibited multiplicative interaction with PM 2.5. Conclusions:Exposure to non-optimal temperature during pregnancy was associated with an increased risk for preterm birth. The susceptible exposure windows of extreme low temperature were mainly in early and mid-pregnancy, and the susceptible exposure windows of extreme high temperature were mainly in late-pregnancy. Exposure to non-optimal temperatures and pollutants during pregnancy was associated with an increased risk for preterm birth.

Objective:To compare the clinical characteristics of neovascular age-related macular degeneration (nAMD) patients with or without secondary subretinal fibrosis (SF).Methods:A retrospective case-control study. A total of 88 patients (92 eyes) diagnosed with nAMD at Department of Ophthalmology, Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2020 to January 2024 were enrolled in this study. All eyes underwent best-corrected visual acuity (BCVA), color fundus photography, and optical coherence tomography (OCT) examinations. BCVA was measured using the international standard visual acuity chart and converted to logarithm of the minimum angle of resolution for statistical analysis. SF area was measured on color fundus images. OCT was used to assess the presence of shallow irregular retinal pigment epithelial (RPE) elevation, RPE detachment, ellipsoid zone/external limiting membrane disruption, subretinal fluid and/or intraretinal fluid, thinning of the inner nuclear layer or inner plexiform layer, complete RPE and outer retinal atrophy (cRORA), epiretinal membrane, and suprachoroidal fluid. Device-integrated software measured central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), and the height and width of subfoveal fibrosis in SF eyes. Based on the presence of SF, patients were divided into the SF group (47 eyes) and the non-SF (NSF) group (45 eyes). Baseline characteristics, OCT, and color fundus photography imaging features were compared between groups. Independent samples t tests were used for intergroup comparisons, and multiple linear regression was performed to analyze potential factors influencing SF height. Results:Compared with the NSF group, the SF group had a longer disease duration, longer symptom onset to initial treatment interval to receiving anti-vascular endothelial growth factor (VEGF) drug treatment, a lower proportion of patients receiving 3 anti-VEGF drug injections within 6 months, worse BCVA, thicker SFCT, higher rates of pigment epithelial detachment and inner nuclear layer or inner plexiform layer thinning, and a lower rate of subretinal fluid ( P<0.05). No significant differences were observed in CRT or the proportions of irregular retinal pigment epithelia, ellipsoid zone/external limiting membrane disruption, cRORA, suprachoroidal fluid, or epiretinal membrane between the two groups ( P>0.05). Conclusion:nAMD eyes with secondary SF exhibit distinct OCT imaging features compared to NSF eyes.

Objective·To identify different comorbidity types resulting from the spontaneous association of psychopathological symptoms among male drug addicts,explore the relationship between latent types and drug addiction,and examine the mediating role of psychological distress.Methods·Four hundred and fifty male drug addicts,recruited by Yunnan First Compulsory Isolation Drug Rehabilitation Center according to the 2017 revised Drug Addiction Identification Method by the Ministry of Public Security,were enrolled as participants.The Symptom Checklist-90(SCL-90),Craving Automated Scale for Substances(CAS-S),and Psychache Scale(PAS)were used to assess the severity of psychopathological symptoms,drug addiction,and psychological distress,respectively.Latent class analysis was employed to identify different types of psychopathological comorbidity that may exist in the participants,and the types were named based on the analysis results.Variance analysis was used to test differences in the severity of drug addiction and psychological distress among different latent types,and a mediation model was established to explore the mediating role of psychological distress between different latent types and drug addiction.Results·Latent class analysis identified three types of psychopathology:high,medium,and low levels,with decreasing positive rates and numbers of comorbidity in each type based on the ten psychopathological symptoms included in the SCL-90.There were significant differences in the severity of psychological distress and drug addiction among the three types of participants.Psychopathological symptoms positively predicted the severity of psychological distress and drug addiction.Psychological distress completely mediated the relationship between medium levels of psychopathology and drug addiction,while partially mediating the relationship between high levels of psychopathology and drug addiction.Conclusion·There are three types of psychopathological comorbidity among male drug addicts:high,medium,and low.Psychological distress plays a complete mediating role between medium levels of psychopathology and drug addiction,and a partial mediating role between high levels of psychopathology and drug addiction.

Objectives:To investigate the effect of non-optimal temperature exposure during pregnancy on the risk for preterm birth and identify the susceptible exposure window. At the same time, the interaction between non-optimal temperature and pollutants exposure during pregnancy on preterm birth was analyzed, in order to provide strong clues for the influence of non-optimal temperature exposure during pregnancy on the risk for preterm birth.Methods:A total of 1 852 pregnant women were recruited from September 2021 to June 2023 in Fujian Provincial Maternal and Child Health Care Center. Questionnaire survey was conducted, and their health records were analyzed. The permanent address of each pregnant woman was matched with Fifth Generation European Centre for Medium-Range Weather Forecasts Atmospheric Reanalysis of the Global Climate and a geo-statistical combination model based on satellite remote sensing data collection, then follow-up for pregnancy outcome was conducted. Distributed lag nonlinear model was used to assess the association between exposure to non-optimal temperature during pregnancy and the risk for preterm birth and a multiplicative interaction model was used to assess the interaction between exposure to pollutants and non-optimal temperatures during pregnancy on the risk for preterm birth.Results:After adjusting for potential confounders such as maternal age, occupation, Gross Domestic Product of the region, pre-pregnancy preconception BMI, newborn sex, the weekly susceptibility windows of extreme low temperature ( P1, P3, P5) were week 1-22 , and the weekly susceptibility windows of extreme high temperature ( P95, P97, P99) were week 27 and week 32-36. Extreme low temperature [ P1 ( OR=1.147, 95% CI: 1.041-1.265), P5 ( OR=1.284, 95% CI: 1.035-1.501)] and extreme high temperature [ P97 ( OR=1.146, 95% CI: 1.039-1.263), P99 ( OR=1.216, 95% CI: 1.099-1.345)] exhibited multiplicative interaction with PM 2.5. Conclusions:Exposure to non-optimal temperature during pregnancy was associated with an increased risk for preterm birth. The susceptible exposure windows of extreme low temperature were mainly in early and mid-pregnancy, and the susceptible exposure windows of extreme high temperature were mainly in late-pregnancy. Exposure to non-optimal temperatures and pollutants during pregnancy was associated with an increased risk for preterm birth.

Objective In this study,a risk prediction model for Alzheimer's disease(AD)was constructed based on Alzheimer's disease neuroimaging initiative(ADNI)database to provide a theoretical basis for a better understanding of AD,as well as to provide a reference basis for the rational allocation of health resources and the development of preventive and control strategies.Methods The ADNIMERGE,UPENNBIOMK,ADNINIGHTINGALELONG and DXSUM datasets from the ADNI database were downloaded and random forest algorithm was used for the missing values imputation.Variable screening was performed by LASSO regression.Borderline-1 SMOTE resampling was used to adjusted for intergroup balance,and the variables were incorporated into base classifiers including XGBoost,random forest,bagging,AdaBoost,and support vector machine.Enhanced integrated classifiers were then constructed based on voting and Stacking strategies.Youden index,area under curve(AUC),F-score,G-mean,accuracy,Matthews correlation coefficient(MCC)and Kappa on the validation set were used to evaluate and compare the model efficacy.Results The performance of the classifiers based on balanced data were improved for both base and enhanced integrated classifiers.The performance of stacking and voting enhanced integrated classifiers constructed based on advantageous base classifiers have better performance compared to the base classifiers.After data balancing,the XGBoost performed better in the base classifiers(AUC:0.9090,accuracy:0.9091)and voting algorithm performs better in enhanced integrated classifiers(AUC:0.9178,accuracy:0.9179).Conclusion After Borderline-1 SMOTE resampling adjusted,the performance of both base classifiers and the enhanced integrated classifiers were all improved.For balanced data,XGBoost classifier and the voting enhanced integrated classifier can effectively assist in clinical prediction of Alzheimer's disease progression.

Objective·To identify different comorbidity types resulting from the spontaneous association of psychopathological symptoms among male drug addicts,explore the relationship between latent types and drug addiction,and examine the mediating role of psychological distress.Methods·Four hundred and fifty male drug addicts,recruited by Yunnan First Compulsory Isolation Drug Rehabilitation Center according to the 2017 revised Drug Addiction Identification Method by the Ministry of Public Security,were enrolled as participants.The Symptom Checklist-90(SCL-90),Craving Automated Scale for Substances(CAS-S),and Psychache Scale(PAS)were used to assess the severity of psychopathological symptoms,drug addiction,and psychological distress,respectively.Latent class analysis was employed to identify different types of psychopathological comorbidity that may exist in the participants,and the types were named based on the analysis results.Variance analysis was used to test differences in the severity of drug addiction and psychological distress among different latent types,and a mediation model was established to explore the mediating role of psychological distress between different latent types and drug addiction.Results·Latent class analysis identified three types of psychopathology:high,medium,and low levels,with decreasing positive rates and numbers of comorbidity in each type based on the ten psychopathological symptoms included in the SCL-90.There were significant differences in the severity of psychological distress and drug addiction among the three types of participants.Psychopathological symptoms positively predicted the severity of psychological distress and drug addiction.Psychological distress completely mediated the relationship between medium levels of psychopathology and drug addiction,while partially mediating the relationship between high levels of psychopathology and drug addiction.Conclusion·There are three types of psychopathological comorbidity among male drug addicts:high,medium,and low.Psychological distress plays a complete mediating role between medium levels of psychopathology and drug addiction,and a partial mediating role between high levels of psychopathology and drug addiction.