BACKGROUND Emerging studies have shown the effectiveness of mobile health (mHealth) interventions in reducing depressive symptoms among people living with HIV. Most of these studies included only short-term follow-up, with limited data on long-term effects. OBJECTIVE The purpose of this study is to assess the long-term effects of a randomized controlled trial called Run4Love on depressive symptoms among people living with HIV at 1-year and 3-year follow-ups. METHODS A total of 300 people living with HIV with depressive symptoms were recruited and randomized to an intervention or a control group in Guangzhou, China, from September 2017 to January 2018. The intervention group received a 3-month Run4Love program, including adapted evidence-based cognitive behavioral stress management courses and exercise promotion via WeChat (Tencent), a popular social media app. The control group received usual care and a brochure on nutrition. The primary outcome was reduction in depressive symptoms, measured using the Center for Epidemiological Studies–Depression (CES-D) scale. Data used in this study were collected at baseline and at the 1-year and 3-year follow-ups. Generalized estimating equations were used to examine the group differences at 1-year and 3-year follow-ups. RESULTS Approximately half of the participants completed the assessment at 1-year (149/300, 49.7%) and 3-year (177/300, 59%) follow-ups. At 1-year follow-up, participants in the intervention group reported significant reduction in depressive symptoms compared with the control group (CES-D: from 23.9 to 18.1 in the intervention group vs from 24.3 to 23.3 in the control group; mean −4.79, SD 13.56; 95% CI −7.78 to −1.81; <i>P</i>=.002). At 3-year follow-up, between-group difference in CES-D remained statistically significant (from 23.9 to 20.5 in the intervention group vs from 24.3 to 24.4 in the control group; mean −3.63, SD 13.35; 95% CI −6.71 to −0.54; <i>P</i>=.02). No adverse events were reported during the 3-year follow-up period. CONCLUSIONS The mHealth intervention, Run4Love, significantly reduced depressive symptoms among people living with HIV, and the intervention effects were sustained at 1-year and 3-year follow-ups. Further research is needed to explore the mechanisms of the long-term effects of mHealth interventions such as Run4Love and to implement these effective interventions among people living with HIV. CLINICALTRIAL Chinese Clinical Trial Registry ChiCTR-IPR-17012606; https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR-IPR-17012606 INTERNATIONAL REGISTERED REPORT RR2-10.2196/10274
Background: Ticagrelor belongs to a new class of P2Y12 receptor inhibitor that has been widely used for antiplatelet therapy. This study aimed to explore the effect of single nucleotide polymorphisms (SNPs) in metabolic enzymes, transporters, and other relevant variants on the pharmacokinetics (PK) of ticagrelor and its active metabolite, AR-C124910XX. Methods: The study population comprised 68 healthy Chinese volunteers who were enrolled in a ticagrelor bioequivalence clinical trial. The PK profile of ticagrelor was evaluated after orally administering a single 90-mg dose of ticagrelor in tablet form. The plasma concentrations of ticagrelor and AR-C124910XX were determined through liquid chromatography-tandem mass spectrometry. Plasma DNA samples were used to explore the effect of gene polymorphisms on the PK of ticagrelor and AR-C124910XX with whole-exome sequencing. Results: Female participants had a higher maximum plasma concentration/weight ratio (Cmax/W; p < 0.001) and a shorter half-life (T1/2; p < 0.05) for ticagrelor than their male counterparts. In addition, a higher area under the curve/weight ratio (AUC/W; p < 0.001), and longer T1/2 (p < 0.001) and time to reach the maximum plasma concentration (Tmax; p < 0.001), as well as a lower apparent drug clearance (CL/F; p < 0.001), were observed among healthy volunteers in the fed trial compared to those enrolled in the fasting trial. For AR-C124910XX, higher Cmax/W (p < 0.001) and AUC/W (p < 0.001) but lower CL/F (p < 0.001) and apparent volume of distribution (Vd/F; p < 0.001) were observed among female participants. Healthy volunteers enrolled in the fasting trial exhibited higher Cmax/W (p < 0.001) and AUC/W (p < 0.01), shorter Tmax (p < 0.001), and lower CL/F (p < 0.001) and Vd/F (p < 0.001) than those enrolled in the fed trial. Upon confirmation through multivariate analysis, the CYP4F2 rs2074900 A/A carriers were associated with higher Cmax/W and AUC/W and lower CL/F and Vd/F than the CYP4F2 rs2074900 A/G and G/G carriers. Conclusion: This study is the first to show that the CYP4F2 rs2074900 SNP had a remarkable effect on ticagrelor PK, which is significant since it adds to the limited pharmacogenetic information on ticagrelor.
Abstract Background At present, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment, as the first-line treatment of lung adenocarcinoma (LUAD) with EGFR mutation, has achieved good clinical efficacy, but most patients will eventually develop acquired resistance. Therefore, there is an urgent need to develop a strong standard to identify drug-resistant patients with EGFR mutation who can benefit from other treatments. Methods Based on the differentially expressed genes between osimertinib (OSI)-resistant cells (PC9OR, H1975OR) and non OSI-resistant LUAD cells (PC9, H1975), the EGFR mutant LUAD prognosis related genes from TCGA database, and the immune genes from ImmPort and InnateDB websites, we constructed an immune prognosis model of OSI resistance to predict the outcome of EGFR mutant LUAD patients. Then, according to the risk score, EGFR mutant LUAD patients were divided into high- and low-risk groups, and the molecular, immune characteristics and responsiveness to chemotherapy and targeted drugs were analyzed. Next, PSMD11 was knocked down using siRNA to evaluate the effects of PSMD11 on PC9OR and H1975OR cells. Finally, the correlation between PSMD11 and OSI resistance was determined in vitro via CCK-8, colony formation assays and flow cytometry, and in vivo via western blot and immunohistochemistry. Results We constructed an immune prognostic prediction model consisting of four OSI-resistant genes (C3, PSMD11, G3BP1, TRIB2), and clarified its accuracy in predicting the prognosis of EGFR mutant LUAD patients. According to the risk score classification, high-risk EGFR mutant patients were more sensitive to traditional chemotherapy and targeted drugs, with higher expression of immune checkpoints PD-1, LAG3, IDO1, and more infiltration of CD8 + T cells, M0/M1 macrophages and NK cells. In addition, knockdown of PSMD11 could inhibit cell proliferation, promote cell apoptosis, and increase the sensitivity of drug-resistant cells to OSI. And compared with individual treatment, the combination treatment of PSMD11-siRNA and OSI in PC9OR and H1975OR cells could significantly inhibit cell proliferation and promote tumor growth. In addition, PSMD11 could promote the progression of OSI-resistant LUAD by activating the NF-κB/IL-6/STAT3 signaling pathway. Conclusions our work provide a powerful prediction tool for further screening OSI-resistant LUAD patients suitable for chemotherapy, targeted therapy and immunotherapy.
Circadian rhythm disorder is a significant risk factor for mental diseases, and the recovery of circadian rhythm function has gradually become a signal of effective antidepressant therapy. Sini powder (SNP) is a classical, traditional Chinese formula for depression treatment. However, few clinical reports have been recorded. This randomized, double-blinded, controlled trial (ChiCTR1900022700) aimed to explore the efficacy of SNP on depression via regulating circadian rhythm. In total, 36 patients with major depressive disorder (MDD) were enrolled for 4-weeks medication and 6-weeks follow-up. HAMD-24 score and circadian rhythm index, including dim light melatonin onset (DLMO) and phase angle difference (PAD), were included in the assessment. DLMO and PAD were statistically significant in the SNP group after 4 weeks of treatment (p < .05) and with greater improvement in DLMO (p = .03). In addition, DLMO and the HAMD-24 score showed a positive correlation (p < .05); the HAMD-24 score degree decreased significantly over time (p < .001). Similarly, interaction effects were shown significantly between group and time (p = .049). The duration of SNP supplementation was relatively short, and the sample size was relatively small. SNP granules combined with paroxetine tablets have definite efficacy in improving the circadian rhythms of MDD patients, reflecting the therapeutic advantages of traditional Chinese medicine as antidepressants.
Background Emerging studies have shown the effectiveness of mobile health (mHealth) interventions in reducing depressive symptoms among people living with HIV. Most of these studies included only short-term follow-up, with limited data on long-term effects. Objective The purpose of this study is to assess the long-term effects of a randomized controlled trial called Run4Love on depressive symptoms among people living with HIV at 1-year and 3-year follow-ups. Methods A total of 300 people living with HIV with depressive symptoms were recruited and randomized to an intervention or a control group in Guangzhou, China, from September 2017 to January 2018. The intervention group received a 3-month Run4Love program, including adapted evidence-based cognitive behavioral stress management courses and exercise promotion via WeChat (Tencent), a popular social media app. The control group received usual care and a brochure on nutrition. The primary outcome was reduction in depressive symptoms, measured using the Center for Epidemiological Studies–Depression (CES-D) scale. Data used in this study were collected at baseline and at the 1-year and 3-year follow-ups. Generalized estimating equations were used to examine the group differences at 1-year and 3-year follow-ups. Results Approximately half of the participants completed the assessment at 1-year (149/300, 49.7%) and 3-year (177/300, 59%) follow-ups. At 1-year follow-up, participants in the intervention group reported significant reduction in depressive symptoms compared with the control group (CES-D: from 23.9 to 18.1 in the intervention group vs from 24.3 to 23.3 in the control group; mean −4.79, SD 13.56; 95% CI −7.78 to −1.81; P=.002). At 3-year follow-up, between-group difference in CES-D remained statistically significant (from 23.9 to 20.5 in the intervention group vs from 24.3 to 24.4 in the control group; mean −3.63, SD 13.35; 95% CI −6.71 to −0.54; P=.02). No adverse events were reported during the 3-year follow-up period. Conclusions The mHealth intervention, Run4Love, significantly reduced depressive symptoms among people living with HIV, and the intervention effects were sustained at 1-year and 3-year follow-ups. Further research is needed to explore the mechanisms of the long-term effects of mHealth interventions such as Run4Love and to implement these effective interventions among people living with HIV. Trial Registration Chinese Clinical Trial Registry ChiCTR-IPR-17012606; https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR-IPR-17012606 International Registered Report Identifier (IRRID) RR2-10.2196/10274
Chromobox (CBX) proteins are important Polycomb family proteins in the development of gastric cancer. Nonetheless, the relationship between CBXs and gastric cancer microenvironment remains unclear.Multiple databases were used for the analysis of CBXs expression and clinical value in gastric cancer patients. A Cox regression analysis was used to evaluate the prognostic importance of CBXs. Thereafter, regression analysis of LASSO Cox was used to construct the prognostic model. Spearman's correlation between risk score and immune infiltration was analyzed using the McP-counter algorithm. A predicted nomogram was developed to predict the overall survival of gastric cancer patients after 1, 2, and 3 years.In contrast with normal tissues, mRNA and protein expression levels of CBX2/3 were significantly high in gastric cancer tissues, whereas those of CBX6/7 were low. CBXs significantly correlated with immune subtypes and molecular subtypes. A prognostic gene model based on five CBX genes (CBX1, CBX2, CBX3, CBX7, and CBX8) predicted the overall survival of gastric cancer patients. A significant correlation was noted between the risk score of the CBXs-related prognostic gene model and immune-cell infiltration. Low risk patients could achieve a better response to immune checkpoint inhibitors. A predictive nomogram constructed using the above five CBX genes revealed that overall survival rates over 1, 2, and 3 years could be reasonably predicted. Therefore, the roles of CBXs were associated with chromatin modifications and histone methylation, etc. Conclusion: In summary, we identified a prognostic CBXs model comprising five genes (CBX1, CBX2, CBX3, CBX7, and CBX8) for gastric cancer patients through bioinformatics analysis.
Background Iron is an essential nutrient element, and iron metabolism is related to many diseases. Ferroptosis is an iron-dependent form of regulated cell death associated with ischemic stroke (IS). Hence, this study intended to discover and validate the possible ferroptosis-related genes involved in IS. Materials and methods GSE16561, GSE37587, and GSE58294 were retrieved from the GEO database. Using R software, we identified ferroptosis-related differentially expressed genes (DEGs) in IS. Protein-protein interactions (PPIs) and enrichment analyses were conducted. The ROC curve was plotted to explore the diagnostic significance of those identified genes. The consistent clustering method was used to classify the IS samples. The level of immune cell infiltration of different subtypes was evaluated by ssGSEA and CIBERSORT algorithm. Validation was conducted in the test sets GSE37587 and GSE58294. Results Twenty-one ferroptosis-related DEGs were detected in IS vs. the normal controls. Enrichment analysis shows that the 21 DEGs are involved in monocarboxylic acid metabolism, iron ion response, and ferroptosis. Moreover, their expression levels were pertinent to the age and gender of IS patients. The ROC analysis demonstrated remarkable diagnostic values of LAMP2, TSC22D3, SLC38A1, and RPL8 for IS. Transcription factors and targeting miRNAs of the 21 DEGs were determined. Vandetanib, FERRIC CITRATE, etc., were confirmed as potential therapeutic drugs for IS. Using 11 hub genes, IS patients were categorized into C1 and C2 subtypes. The two subtypes significantly differed between immune cell infiltration, checkpoints, and HLA genes. The 272 DEGs were identified from two subtypes and their biological functions were explored. Verification was performed in the GSE37587 and GSE58294 datasets. Conclusion Our findings indicate that ferroptosis plays a critical role in the diversity and complexity of the IS immune microenvironment.
Murine double minute 2 (MDM2) plays an important role in the carcinogenesis of many cancers including osteosarcoma. We performed a systemic review and meta-analysis to assess the effects of MDM2 polymorphisms on osteosarcoma risk and survival of patients with osteosarcoma. PubMed, Web of Science, and Wanfang databases were searched for eligible studies on the associations of MDM2 polymorphisms with osteosarcoma risk and survival of patients with osteosarcoma. Pooled odds ratio (OR) or hazard ratio (HR) with 95 % confidence intervals (95 % CIs) was used to assess the effects of MDM2 polymorphisms on osteosarcoma risk and survival of patients with osteosarcoma. Overall, MDM2 rs2279744 polymorphism was associated with a risk of osteosarcoma (allele model, OR = 1.60, 95 % CI 1.23–2.07, P < 0.001; codominant model, OR = 2.47, 95 % CI 1.46–4.19, P = 0.001; recessive model, OR = 2.13, 95 % CI 1.32–3.46, P = 0.002; dominant model, OR = 1.61, 95 % CI 1.12–2.33, P = 0.01). MDM2 rs1690916 polymorphism was also associated with a risk of osteosarcoma (OR = 0.60, 95 % CI 0.46–0.77, P < 0.001). However, MDM2 rs2279744 polymorphism was not associated with the overall survival of patients with osteosarcoma (codominant model, HR = 1.01, 95 % CI 0.53–1.91, P = 0.98; recessive model, HR = 1.07, 95 % CI 0.54–2.11, P = 0.85; dominant model, HR = 1.04, 95 % CI 0.65–1.66, P = 0.87). The meta-analysis suggests that MDM2 polymorphisms have some effects on the risk of osteosarcoma but have no effect on the survival of patients with osteosarcoma. Future studies are needed to further assess the effects of MDM2 polymorphisms on the risk and survival of osteosarcoma.
To explore the effect of sleep deprivation on blood corpuscle and immunity. Methods:The blood corpuscle and immunity of 20 healthy male adults was tested during and after 56 hours of sleep deprivation. Results: After 56 hours of sleep deprivation,increase in counts of WBC granulocytes and RBC ( P 0.005) were found. The counts of immunity globing IgG and alexin CH50 reduced, The counts of T lymphocyte CD 3、CD 16+56 showed some reduction. Conclusion:Sleep deprivation had some effection on human immunity.
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