DNA methylation clocks for estimating biological age in Chinese cohorts.

Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation at specific CpG sites. However, available DNA methylation (DNAm) age predictors are based on datasets with limited ethnic representation. Moreover, a systematic comparison between DNAm data and other omics datasets has not yet been performed. To address these knowledge gaps, we generated and analyzed DNA methylation datasets from two independent Chinese cohorts, revealing age-related DNAm changes. Additionally, a DNA methylation (DNAm) aging clock (iCAS-DNAmAge) and a group of DNAm-based multi-modal clocks for Chinese individuals were developed, with most of them demonstrating strong predictive capabilities for chronological age. The clocks were further employed to predict factors influencing aging rates. The DNAm aging clock, derived from multi-modal aging features (compositeAge-DNAmAge), exhibited a close association with multi-omics changes, lifestyles, and disease status, underscoring its robust potential for precise biological age assessment. Our findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace, providing basis for evaluating aging intervention strategies.

Comprehensive nutritional index for predicting overall survival in hepatocellular carcinoma patients after multiple transarterial chemoembolization.

BACKGROUND AND OBJECTIVES: Little is known about nutritional status in patients with hepatocellular carcinoma (HCC) after multiple rounds of transarterial chemoembolization (TACE). We established a comprehensive nutritional index (CNI) and evaluated its prognostic value for overall survival (OS) and time to progression (TTP). METHODS AND STUDY DESIGN: HCC patients (N=282) who underwent multiple TACE treatments were enrolled. CNI was established by principal component analysis based on body mass index, usual body weight percentage, hemoglobin, total lymphocyte count, and albumin; the cutoff value was determined by receiver operating characteristic curve and Youden index analysis. The correlation between CNI and treatment-related complications was analyzed with Spearman's method. The Kaplan-Meier method with log-rank test and Cox proportional hazards model were used to compare the prognostic values of CNI, prognostic nutritional index (PNI), and nutrition risk index (NRI) for OS and TTP. RESULTS: Nutritional status declined after repeated TACE (p<0.001). CNI (cutoff= 0.251) varied according to albumin-bilirubin grade, tumor size, and number of TACE treatments (p<0.001 or 0.025) and was negatively correlated with rate of serious complications (r=-0.185, p=0.002). Patients with low CNI had shorter OS (p=0.014) and TTP (p=0.007); high CNI predicted longer OS (hazard ratio [HR], 0.72; 95% confidence interval [CI]: 0.52-1.00, p=0.048) and TTP (HR, 0.69; 95% CI: 0.50-0.94, p=0.019). Post-treatment PNI and NRI were unrelated to prognosis (p>0.05). CONCLUSIONS: HCC patients have poor nutritional status after multiple TACE treatments, which predicts shorter OS and TTP. The prognostic performance of CNI is superior to those of PNI and NRI.

Relationship between T-cell receptor α gene polymorphisms and symptomatic differences in patients with narcolepsy type 1.

BACKGROUND: Recent genome-wide association studies have identified an important role of T-cell receptor α (TRA) gene in the development of narcolepsy type 1. However, the role of TRA haplotype polymorphisms in the symptomatic diversity of narcolepsy remains unclear. This study aimed to investigate whether TRA polymorphisms can influence the symptomatic diversity of narcolepsy. METHODS: Totally, 903 patients with narcolepsy type 1 were included in the study. Patients were divided into different groups according to their symptoms. First, 13 genotyped single nucleotide polymorphisms in the TRA were assessed for their association with symptoms of narcolepsy. We used the Chi-square test to determine differences in genotype frequencies in patients with narcolepsy. Further, we identified the haplotypes and variations of the TRA and tested their association with the symptoms of narcolepsy using a logistic regression model. RESULTS: According to the results of the logistic regression, TRA haplotypes TG and CT were significantly associated with auditory hallucination, with odds ratios of 1.235 (95% confidence interval [CI], 1.012-1.507) and 1.236 (95% CI, 1.012-1.511), respectively (P < 0.05). CONCLUSIONS: The patterns of haplotype in TRA (haplotypes TG and CT) are associated with hypnagogic auditory hallucination in patients with narcolepsy type 1. However, further studies are needed to confirm our results and explore the underlying mechanisms.

Inhibitory effect of apatinib on HCT-116 cells and its mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the inhibitory effects of apatinib on colorectal carcinoma HCT-116 cells in vitro and the signaling pathways involved.</p><p><b>METHODS</b>The cytotoxicity of different concentrations (0, 0.5, 1, 1.5, and 2 µmol/L) of apatinib in HCT-116 cells was assessed by MTT assay, using capecitabine as the positive control. The apoptosis rate of apatinib-treated HCT-116 cells was detected using flow cytometry, and the expressions of Bcl-2, Bax, and caspase-3 were determined with quantitative real-time PCR and Western blotting. The effect of apatinib on the expressions of Akt, pAkt, Erk1/2 and pErk1/2 in HCT-116 cells was evaluated using Western blotting.</p><p><b>RESULTS</b>Apatinib significantly inhibited the proliferation of HCT-116 cells in a concentration-dependent manner with an ICvalue of 1.335 µmol/L. Flow cytometric analysis showed that apatinib significantly increased the apoptotic rate of HCT-116 cells dose-dependently. Apatinib induced the expression of the pro-apoptotic genes Bax and caspase-3 at both the mRNA and protein levels while inhibited the expression of the anti- apoptotic gene Bcl-2. The expressions of p-Akt and p-Erk1/2 were decreased in HCT-116 cells after apatinib treatment, but the total protein levels did not undergo obvious changes.</p><p><b>CONCLUSION</b>Apatinib inhibits the proliferation and induces apoptosis of HCT-116 cells by suppressing the phosphorylation of Erk1/2 and Akt in the MAPK/Erk and PI3K/Akt signaling pathways.</p>

Demographic and clinical differences between early- and late-onset major depressions in thirteen psychiatric institutions in China.

BACKGROUND: Little is known about the demographic and clinical differences between early- and late-onset depressions (EOD and LOD, respectively) in Chinese patients. This study examined the demographic and clinical profile of EOD (<=25 years) compared to LOD (>25 years) in China. METHODS: A consecutively recruited sample of 1178 patients with MDD was assessed in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The cross-sectional data of patients' demographic and clinical characteristics and prescriptions of psychotropic drugs including antidepressants, mood stabilizers, antipsychotics and benzodiazepines were recorded using a standardized protocol and data collection procedure. RESULTS: Two hundred and seventy five (23.3%) of the 1178 patients fulfilled criteria for EOD. In multiple logistic regression analyses, compared to LOD patients their EOD counterparts were more likely to be unmarried and unemployed, had more atypical and psychotic depressive episodes, had bipolar features, while they had more lifetime depressive episodes. CONCLUSIONS: The demographic and more severe clinical features of EOD in Chinese patients were basically consistent with those found in Western populations. The association between socio-cultural factors and development of EOD warrants further studies.

Suicide risk in major affective disorder: results from a national survey in China.

BACKGROUND: This study investigated suicide risk and its correlates among major affective disorder patients in China and examined possible risk factors for future suicide among individuals with major affective disorder to inform appropriate interventions and management approaches to minimize and prevent suicide. METHODS: A total of 1478 major affective disorder patients were consecutively examined in 13 mental health centers in China. The patients' socio-demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. DSM-IV diagnoses were established using the Mini International Neuropsychiatric Interview (MINI), and suicide risk was assessed by the suicide risk module of the MINI. RESULTS: Of the patients, 963 (65.2%) were in the nonsuicidal risk group and 515 (34.8%) were in the suicidal risk group. Compared to major depressive disorder patients, bipolar disorder patients had higher suicide risk levels (χ2=10.0, df=1, P=0.002); however, there were no statistically significant differences (χ2=2.6, df=1, P=0.1) between bipolar disorder-I and bipolar disorder-II patients. Suicide risk factors were associated with 6 variables in major affective disorder patients, as follows: male gender, unemployed, more frequent depressive episodes (>4 in the past year), depressive episodes with suicidal ideation and attempts, depressive episodes with psychotic symptoms, and no current antidepressant use. LIMITATIONS: Most of the data were retrospectively collected and, therefore, subject to recall bias. CONCLUSIONS: This study suggested that bipolar disorder patients have a higher suicide risk than major depressive disorder patients. The factors that were significantly associated with suicide risk may aid in identifying major affective disorder patients who are at risk for future suicidal behavior.

Gender differences in demographic and clinical features and prescribing patterns of psychotropic medications in patients with major depressive disorder in China.

PURPOSE: Little is known about gender differences associated with major depressive disorder (MDD) in China. This study examined gender differences associated with other demographic and clinical characteristics and psychotropic drug treatment in Chinese patients with MDD. METHODS: A total of 1178 patients with MDD from 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide were enrolled. Cross-sectional data including patients' demographic and clinical characteristics and prescriptions of psychotropic medications were recorded using a standardized protocol and data collection procedure. RESULTS: The sample consisted of 793 female and 385 male patients. Univariate analyses revealed that male patients were younger than female patients, had a younger age of onset of depression, had less lifetime depressive episodes and had more bipolar features (i.e. patients who screened positive for hypomanic symptoms on the 32-item Hypomania Checklist, but did not meet the diagnostic criteria for DSM-IV bipolar disorders as measured by the Mini International Neuropsychiatric Interview). Also, men were more likely to be employed than women and less likely to have depressive episodes following stressful life events. In multivariate analyses, being employed, having bipolar features and not having depressive episodes following stressful life events were independently associated with being a male patient with major depressive disorder. There was no difference in use of psychotropic medications by gender. CONCLUSIONS: Most gender differences in MDD patients in this study are not consistent with findings of Western studies suggesting that gender differences in MDD may be determined by both biological and sociocultural differences among ethnically different patient populations.

Association between thrombelastography system and thromboembolic and bleeding events in Chinese aged people.

OBJECTIVES: This study was designed to obtain the knowledge about TEG indexes distribution in Chinese aged people, as well as to test the hypothesis that previous TEG indexes are associated with the subsequent thromboembolic and bleeding events in the aged population. METHODS: We conducted a two-year follow-up study in Chinese PLA General Hospital, Beijing, China. 403 aged people were enrolled in our study. They received TEG measurements at least once when they entered this study. We collected their demographical characteristics, clinical examination information and their outcome during their observational period. Structural equation modeling (SEM) was used to analyze the relationship between the four indexes from TEG and the outcome via a pathway of indicator. RESULTS: We found that in the "model of bleeding" (adjusted by confounding of Anticoagulants), the model fit indices with chi-square/df = 9.555/7, CFI was 0.997, TLI was 0.994 and standardized root mean square residual (SRMR) was 0.034; while in the "model of thromboembolic events" (adjusted by confounding of Anticoagulants), the model fit indices with chi-square/df = 6.070/7, CFI was1.000, TLI was 1.002 and standardized root mean square residual (SRMR) was 0.000. The "model of thromboembolic events" showed that the four indexes (R, K, MA and ANGLE) were all significantly associated with thromboembolic events, while this significance was not found in the "model of bleeding". CONCLUSIONS: Previous TEG indexes are significantly associated with the subsequent thromboembolic events in the aged population. Future study can test this association and provide more information for the clinical use.

Prescribing patterns of antidepressants, antipsychotics and mood stabilizers in bipolar patients misdiagnosed with major depressive disorder in China.

OBJECTIVE: Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD), which may lead to inappropriate treatment and poor outcomes. This study aimed to examine prescribing patterns of antidepressants, antipsychotics and mood stabilizers in BD patients misdiagnosed with MDD in China. METHODS: A total of 1487 patients originally diagnosed with MDD were consecutively screened for diagnostic revision in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The Mini International Neuropsychiatric Interview (MINI) was used to establish DSM-IV diagnoses. Data on psychotropic prescriptions were collected by a review of medical records. RESULTS: Three hundred and nine of the 1487 patients (20.8%) fulfilled DSM-IV criteria for BD; 118 (7.9%) for BD-I and 191 (12.8%) for BD-II on the MINI. Of the BD patients (n = 309), 227 (73.5%) received any use of antidepressants, 73 (23.6%) antipsychotics and 33 (10.7%) mood stabilizers. In multiple logistic regression analyses, compared with those with MDD, patients with BD-I were more likely to receive antidepressants (OR 1.7, 95% CI 1.1-2.8, p = 0.02), antipsychotics (OR 1.6, 95% CI 1.04-2.5, p = 0.04) and mood stabilizers (OR 3.9, 95% CI 2.1-7.2, p < 0.001), whereas patients with BD-II were more likely to receive mood stabilizers (OR 2.4, 95% CI 1.3-4.4, p = 0.003). There was no difference in the use of antidepressants (OR 1.1, 95% CI 0.8-1.5, p = 0.7) and antipsychotics (OR 1.3, 95% CI 0.9-1.9, p = 0.2) between BD-II and MDD. In addition, there was no difference between BD-I and BD-II in any use of antidepressants, antipsychotics and mood stabilizers. CONCLUSIONS: The prescription of antidepressants for BD patients misdiagnosed with MDD is very common, and only a very small proportion of patients received guideline-concordant treatment. Considering the potentially hazardous effects of inappropriate pharmacotherapy in this population, continuing education and training addressing the correct diagnosis of BD and rational use of psychotropic medications are needed in China.

Demographic and clinical features and prescribing patterns of psychotropic medications in patients with the melancholic subtype of major depressive disorder in China.

BACKGROUND: Little has been known about the demographic and clinical features of the melancholic subtype of major depressive disorder (MDD) in Chinese patients. This study examined the frequency of melancholia in Chinese MDD patients and explored its demographic and clinical correlates and prescribing patterns of psychotropic drugs. METHODS: A consecutively collected sample of 1,178 patients with MDD were examined in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The cross-sectional data of patients' demographic and clinical characteristics and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. The diagnosis of the melancholic subtype was established using the Mini International Neuropsychiatric Interview (MINI). Medications ascertained included antidepressants, mood stabilizers, antipsychotics and benzodiazepines. RESULTS: Six hundred and twenty nine (53.4%) of the 1,178 patients fulfilled criteria for melancholia. In multiple logistic regression analyses, compared to non-melancholic counterparts, melancholic MDD patients were more likely to be male and receive benzodiazepines, had more frequent suicide ideations and attempts and seasonal depressive episodes, while they were less likely to be employed and receive antidepressants and had less family history of psychiatric disorders and lifetime depressive episodes. CONCLUSIONS: The demographic and clinical features of melancholic MDD in Chinese patients were not entirely consistent with those found in Western populations. Compared to non-melancholic MDD patients, melancholic patients presented with different demographic and clinical features, which have implications for treatment decisions.