miR-744-5p promotes T-cell differentiation via inhibiting STK11.

T cells utilized in adoptive T cell immunotherapy are typically activated in vitro. Although these cells demonstrate proliferation and anti-tumor activity following activation, they often face difficulties in sustaining long-term survival post-reinfusion. This issue is attributed to the induction of T cells into a terminal differentiation state upon activation, whereas early-stage differentiated T cells exhibit enhanced proliferation potential and survival capabilities. In previous study, we delineated four T cell subsets at varying stages of differentiation: TN, TSCM, TCM, and TEM, and acquired their miRNA expression profiles via high-throughput sequencing. In the current study, we performed a differential analysis of miRNA across these subsets, identifying a distinct miRNA, hsa-miR-744-5p, characterized by progressively increasing expression levels upon T cell activation. This miRNA is not expressed in TSCM but is notably present in TEM. Target genes of miR-744-5p were predicted, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, revealing that these genes predominantly associate with pathways related to the 'Wnt signaling pathway'. We established that miR-744-5p directly targets STK11, influencing its expression. Further, we investigated the implications of miR-744-5p on T cell differentiation and functionality. Overexpression of miR-744-5p in T cells resulted in heightened apoptosis, reduced proliferation, an increased proportion of late-stage differentiated T cells, and elevated secretion of the cytokine TNF-α. Moreover, post-overexpression of miR-744-5p led to a marked decline in the expression of early-stage differentiation-associated genes in T cells (CCR7, CD62L, LEF1, BCL2) and a significant rise in late-stage differentiation-associated genes (KLRG1, PDCD1, GZMB). In conclusion, our findings affirm that miR-744-5p contributes to the progressive differentiation of T cells by downregulating the STK11 gene expression.

The genetic diversity of Oncomelania hupensis robertsoni, intermediate hosts of Schistosoma japonicum in hilly regions of China, using microsatellite markers.

BACKGROUND: The elimination of schistosomiasis remains a challenging task, with current measures primarily focused on the monitoring and control of Oncomelania hupensis (O. hupensis) snail, the sole intermediate host of Schistosome japonicum. Given the emerging, re-emerging, and persistent habitats of snails, understanding their genetic diversity might be essential for their successful monitoring and control. The aims of this study were to analyze the genetic diversity of Oncomelania hupensis robertsoni (O. h. robertsoni) using microsatellite DNA markers; and validate the applicability of previously identified microsatellite loci for O. hupensis in hilly regions. METHODS: A total of 17 populations of O. h. robertsoni from Yunnan Province in China were selected for analysis of genetic diversity using six microsatellite DNA polymorphic loci (P82, P84, T4-22, T5-11, T5-13, and T6-27). RESULTS: The number of alleles among populations ranged from 0 to 19, with an average of 5. The average ranges of expected (He) and observed (Ho) heterozygosity within populations were 0.506 to 0.761 and 0.443 to 0.792, respectively. The average fixation index within the population ranged from - 0.801 to 0.211. The average polymorphic information content (PIC) within the population ranged from 0.411 to 0.757, appearing to be polymorphic for all loci (all PIC > 0.5), except for P28 and P48. A total of 68 loci showed significant deviations from Hardy-Weinberg equilibrium (P < 0.05), and pairwise Fst values ranged from 0.051 to 0.379. The analysis of molecular variance indicated that 88% of the variation occurred within snail populations, whereas 12% occurred among snail populations. Phylogenetic trees and principal coordinate analysis revealed two distinct clusters within the snail population, corresponding to "Yunnan North" and "Yunnan South". CONCLUSIONS: O. h. robertsoni exhibited a relatively high level of genetic differentiation, with variation chiefly existing within snail populations. All snail in this region could be separated into two clusters. The microsatellite loci P82 and P84 might not be suitable for classification studies of O. hupensis in hilly regions. These findings provided important information for the monitoring and control of snail, and for further genetic diversity studies on snail populations.

Impact of painful physical symptoms on first-episode major depressive disorder in adults with subthreshold depressive symptoms: A prospective cohort study.

OBJECTIVE: To investigate the impact of baseline painful physical symptoms (PPS) on subsequent first-episode major depressive disorder (MDD) in adults with subthreshold depressive symptoms, including subgroup analyses to assess whether the associations differ in individuals with and without physical diseases. METHODS: A total of 2343 adults with subthreshold depressive symptoms were recruited at 34 primary health care centers. PPS were measured at baseline. First-episode MDD during follow-up was diagnosed by professional psychiatrists using the Mini-International Neuropsychiatric Interview. RESULTS: Baseline PPS showed independent impacts on first-episode MDD in adults with subthreshold depressive symptoms without physical diseases, but not in those with physical diseases. A non-linear association (P < 0.001) was observed between PPS burden and the risk of first-episode MDD. The HRs for first-episode MDD exhibited a rapidly increasing trend between PPS burden scores of 10-16, and maintained consistently high when scores exceeded 16. The analyses for specific PPS revealed that headache, neck pain, and heart or chest pain were independently associated with first-episode MDD in participants without physical diseases, the HRs were 1.57 (1.15-2.36), 1.53 (1.02-2.30), and 1.69 (1.14-2.50), respectively. Further network analysis demonstrated that heart or chest pain serves as a bridge symptom among the seven specific PPS and first-episode MDD in those without physical diseases. CONCLUSION: PPS burden and heart or chest pain may be significant indicators for first-episode MDD in adults with subthreshold depressive symptoms without physical diseases. Future studies should investigate whether interventions targeting PPS can prevent episode MDD in this subthreshold population.

Evaluation of a novel instrument for detecting bipolar disorders in China: The Rapid Mood Screener (RMS).

OBJECTIVE: Bipolar disorder is easily misdiagnosed with major depressive disorder (MDD). The Rapid Mood Screener (RMS) was developed to address this unmet clinical need. This study aims to translate and evaluated the reliability and validity of the RMS in Chinese adults with bipolar I/II disorder (BD-I/II). METHODS: Brislin's translation and Delphi method were conducted to formulate the RMS-Chinses version (RMS-C). Patients with MDD (N = 99), BD-I (N = 77) and BD-II (N = 78) were included to assess the validity and reliability of RMS-C. The area under the curve (AUC) was computed to ascertain the ability of the Mood Disorder Questionnaire (MDQ) and RMS-C to distinguish BD-I and BD-II from MDD. The optimal cut-off scores for classification were also calculated by the maximum sensitivity and specificity. RESULTS: The intraclass correlation coefficient of the RMS-C was 0.82 (95%CI, 0.71-0.89). The content validity index by six items were 0.71, 0.86, 1.00, 0.86, 1.00, and 1.00 in turn, and by scales was 0.90. The AUCs of the RMS-C in both BD-I/II, BD-I alone and BD-II alone were 0.83 (95 % CI, 0.78-0.89), 0.82 (95 % CI, 0.75-0.89) and 0.85 (95 % CI, 0.79-0.91), respectively, and were comparably to the MDQ. The optimal RMS-C values of the presence of BD-I and BD-II were >4 and 3, respectively. CONCLUSION: The RMS-C is a valid, simple self-administer screening tool to help identify BD-I or BD-II in persons experiencing a depressive episode. Validating the impact of screening with the RMS-C on health outcomes and health economics is warranted.

The Effect of Internet-Based Cognitive Behavioral Therapy on Major Depressive Disorder: Randomized Controlled Trial.

BACKGROUND: Many people living with major depressive disorder (MDD) in China do not receive treatment owing to a lack of mental health services, along with significant stigma toward mental illness. Internet-based cognitive behavioral therapy (ICBT) has been proposed to increase access to mental health care for people with MDD. OBJECTIVE: The aims of this study were to (1) evaluate the efficacy of ICBT for depressive symptoms in patients with MDD; (2) evaluate the effect of ICBT on anxiety symptoms, nonspecific psychological distress, general self-efficacy, depression stigma, social function, and health-related quality of life (HRQoL); and (3) explore the acceptability of and satisfaction with the ICBT program among participants. METHODS: Patients with MDD were enrolled and randomized to the ICBT group or the waiting-list control (WLC) group. The ICBT group received ICBT delivered through a WeChat mini-program with general support by nonspecialists. Participants in the 2 groups were self-evaluated online at baseline and posttreatment for changes in the primary outcome (ie, depressive symptoms) and secondary outcomes (ie, anxiety symptoms, nonspecific psychological distress, general self-efficacy, depression stigma, social functional impairment, and HRQoL). Changes in outcomes were measured by changes in overall scores on respective scales, and response and remission rates were calculated based on depressive symptoms. The acceptability of and satisfaction with the ICBT program were measured by treatment adherence and participants' feelings (ie, modules seriously completed, perceived benefit, and satisfaction). RESULTS: We included 40 patients who were randomly assigned to the ICBT group and 44 who were assigned to the WLC group. Compared with the WLC group, the ICBT group had fewer depressive symptoms, fewer anxiety symptoms, less nonspecific psychological distress, and greater general self-efficacy. Moreover, the ICBT group had higher response (18/31, 58%) and remission rates (17/31, 55%). The adherence rate in the ICBT group was 78% (31/40), and the majority of participants who completed all ICBT modules were satisfied with the ICBT program. CONCLUSIONS: ICBT demonstrated greater improvements in depressive symptoms, anxiety symptoms, nonspecific psychological distress, and general self-efficacy among selected patients with MDD in comparison with the findings in waiting-list controls. The ICBT program in this study had good acceptability and satisfaction among participants. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100046425); https://tinyurl.com/bdcrj4zv.

Predictive potential of somatic symptoms for the identification of subthreshold depression and major depressive disorder in primary care settings.

Background: The presence of heterogenous somatic symptoms frequently obscures the recognition of depression in primary care. We aimed to explore the association between somatic symptoms and subthreshold depression (SD) and Major Depressive Disorder (MDD), as well as to determine the predictive potential of somatic symptoms in identifying SD and MDD in primary care. Methods: Data were derived from the Depression Cohort in China study (ChiCTR registry number: 1900022145). The Patient Health Questionnaire-9 (PHQ-9) was used to assess SD by trained general practitioners (GPs), and the Mini International Neuropsychiatric Interview depression module was used to diagnose MDD by professional psychiatrists. Somatic symptoms were assessed using the 28-item Somatic Symptoms Inventory (SSI). Results: In total of 4,139 participants aged 18-64 years recruited from 34 primary health care settings were included. The prevalence of all 28 somatic symptoms increased in a dose-dependent manner from non-depressed controls to SD, and to MDD (P for trend <0.001). Hierarchical clustering analysis grouped the 28 heterogeneous somatic symptoms into three clusters (Cluster 1: energy-related symptoms, Cluster 2: vegetative symptoms, and Cluster 3: muscle, joint, and central nervous symptoms). Following adjustment for potential confounders and the other two clusters of symptoms, per 1 increase of energy-related symptoms exhibited significant association with SD (OR = 1.24, 95% CI, 1.18-1.31) and MDD (OR = 1.50, 95% CI, 1.41-1.60) The predictive performance of energy-related symptoms in identifying individuals with SD (AUC = 0.715, 95% CI, 0.697-0.732) and MDD (AUC = 0.941, 95% CI, 0.926-0.963) was superior to the performance of total SSI and the other two clusters (P < 0.05). Conclusions: Somatic symptoms were associated with the presence of SD and MDD. In addition, somatic symptoms, notably those related to energy, showed good predictive potential in identifying SD and MDD in primary care. The clinical implication of the present study is that GPs should consider the closely related somatic symptoms for early recognition for depression in practice.

Longitudinal associations between problematic Internet use, self-esteem, and depressive symptoms among Chinese adolescents.

Problematic Internet use (PIU) has a negative impact on self-esteem among adolescents, thereby making them be vulnerable to developing depressive symptoms. However, there is a lack of longitudinal studies focusing on the process. This study aimed to explore the longitudinal associations between PIU, self-esteem, and depressive symptoms. A total of 1,736 adolescents completed this longitudinal study. The baseline survey was conducted in 2019, and the follow-up surveys were performed at 1-year and 2-year later. PIU, self-esteem, and depressive symptoms were measured. A cascade model was used to examine the longitudinal associations between PIU, self-esteem, and depressive symptoms. The mean age of participants was 13.6 (1.5) years at baseline. The final results observed significant within-time associations between PIU, self-esteem, and depressive symptoms at each time point. PIU and low level of self-esteem could predict subsequent depressive symptoms among adolescents, and depressive symptoms were also associated with subsequent PIU and self-esteem. Both PIU and self-esteem show bidirectional predictions with depressive symptoms among Chinese adolescents. Schools and parents should give more attention to adolescents prone to developing depressive symptoms and more social support to reduce their negative emotions. Health-related professionals should incorporate practical knowledge and skills into the education of adolescents to help them better control Internet use, attenuating the risk of future depressive symptoms.

Association between childhood trauma and medication adherence among patients with major depressive disorder: the moderating role of resilience.

BACKGROUND: Suboptimal medication adherence is a major reason for failure in the management of major depressive disorder (MDD), childhood trauma might be an essential risk factor of suboptimal medication adherence. This study aimed to comprehensively explore the associations between different types of childhood trauma and medication adherence among patients with MDD, and to test whether resilience has moderating effects on the foregoing associations. METHODS: Participants were from the Depression Cohort in China (ChiCTR registry number 1900022145), 282 MDD patients with completed both baseline and 12-weeks follow-up investigations were included in this study. The diagnosis of MDD was assessed by trained psychiatrists using the Mini-International Neuropsychiatric Interview (M.I.N.I.). Childhood trauma was evaluated using the Childhood Trauma Questionnaire-28 item Short Form (CTQ-SF), and resilience was evaluated using the Connor-Davidson Resilience Scale (CD-RISC). Demographic characteristics, depression symptoms, anxiety symptoms, suicidal ideation, suicidal attempt, insomnia symptoms, and painful somatic symptoms were also investigated. Participants were divided into groups of optimal and suboptimal adherence based on their Medication Adherence Rating Scale scores. Logistic regression and stratified analyses were performed. RESULTS: A total of 234 participants (83%) reported suboptimal medication adherence. After adjusting for covariates, CTQ total scores (AOR = 1.03, 95%CI = 1.01-1.06), CTQ measures of sexual abuse (AOR = 1.17, 95%CI = 1.01-1.37), and CTQ measures of physical neglect (AOR = 1.12, 95%CI = 1.02-1.23) were all associated with an increased likelihood of suboptimal adherence. There were significant moderating effects of resilience on the associations of childhood trauma (P = 0.039) and physical neglect (P = 0.034) with medication adherence. The stratification analyses showed that CTQ total scores and CTQ measures of physical neglect were independently associated with an increased risk of suboptimal adherence among patients with MDD with low-resilience or moderate-resilience, while not significantly associated with suboptimal adherence in those with high-resilience. CONCLUSION: Childhood trauma was a significant risk factor of suboptimal adherence among patients with MDD, and resilience moderated the foregoing association. Obtaining a history of childhood trauma and assessing resilience may help identify patients with suboptimal adherence when providing MDD pharmacotherapy. Psychiatrists may consider enhancing resilience to cope with the adverse effects of childhood trauma on medication adherence.

Gender differences in the association of sexual orientation with depressive symptoms: A national cross-sectional study among Chinese college students.

BACKGROUND: Depressive symptoms among the lesbian, gay, bisexual (LGB) in college students have generated worldwide concern in recent decades. This study aimed to estimate the associations between sexual orientation and depressive symptoms among Chinese college students, with a focus on gender differences. METHODS: A total of 30,733 college students were recruited from 10 Chinese province-level regions with a multistage, stratified cluster, random sampling method between March and June 2019. The 20-item Center for Epidemiologic Studies Depression Scale (CESD-20) was used to measure the depressive symptoms. Sexual orientation was assessed by asking the question, "Which of the following options best describes you?" The responses were categorized as heterosexual, gay/lesbian, bisexual, and unsure. RESULTS: In our sample (N = 30,733), the prevalence of depressive symptoms was 6.1%. Among the surveyed Chinese college students, 3.7% self-reported as LGB, and 7.2% were unsure. LGB (gay/lesbian: 14.9% for males and 6.8% for females; bisexual: 9.3% for males and 16.4% for females) had a higher risk of depressive symptoms than heterosexuals. After adjusting for control variables, LGB and unsure college students were more likely to have depressive symptoms than their heterosexual peers. For males, unsure college students reported the highest risk of depressive symptoms; for females, lesbian and bisexual college students reported the highest risk of depressive symptoms. LIMITATIONS: The cross-sectional study design and self-reported depressive symptoms and sexual orientation. CONCLUSION: LGB was associated with increased depressive symptoms among Chinese college students. Furthermore, the associations of LGB sexual orientation with depressive symptoms were more robust for females than males.