Circulating miR-30e-3p induces disruption of neurite development in SH-SY5Y cells by targeting ABI1, a novel biomarker for schizophrenia.

Schizophrenia (SCZ) represents a set of enduring mental illnesses whose underlying etiology remains elusive, posing a significant challenge to public health. Previous studies have shown that the neurodevelopmental process involving small molecules such as miRNA and mRNA is one of the etiological hypotheses of SCZ. We identified and verified that miR-30e-3p and ABI1 can be used as biomarkers in peripheral blood transcriptome sequencing data of patients with SCZ, and confirmed the regulatory relationship between them. To further explore their involvement, we employed retinoic acid (RA)-treated SH-SY5Y differentiated cells as a model system. Our findings indicate that in RA-induced SH-SY5Y cells, ABI1 expression is up-regulated, while miR-30e-3p expression is down-regulated. Functionally, both miR-30e-3p down-regulation and ABI1 up-regulation promote apoptosis and inhibit the proliferation of SH-SY5Y cells. Subsequently, the immunofluorescence assay detected the expression location and abundance of the neuron-specific protein ß-tubulinIII. The expression levels of neuronal marker genes MAPT, TUBB3 and SYP were detected by RT-qPCR. We observed that these changes of miR-30e-3p and ABI1 inhibit the neurite growth of SH-SY5Y cells. Rescue experiments further support that ABI1 silencing can correct miR-30e-3p down-regulation-induced SH-SY5Y neurodevelopmental defects. Collectively, our results establish that miR-30e-3p's regulation of neurite development in SH-SY5Y cells is mediated through ABI1, highlighting a potential mechanism in SCZ pathogenesis.

Safety and efficacy evaluation of personalized exercise prescription during chemotherapy for lung cancer patients.

BACKGROUND: To explore the safety and effectiveness of personalized exercise intervention during chemotherapy for lung cancer patients who were relatively weak and with compromised cardiopulmonary function. METHODS: Thirty-eight lung cancer patients treated with chemotherapy at Peking University Third Hospital were enrolled in this prospective study. The exercise group (N = 21) received individualized exercise guidance based on personal test results and exercised regularly, while the control group (N = 17) only received exercise education and planed exercise methods according to their own preferences. Both groups underwent three fitness tests and clinical indicator assessments at 0, 6, and 12 weeks after starting the exercise, and the differences in trends of various indicators between the two groups were compared. RESULTS: No exercise-related adverse events occurred during the 12-week exercise period. After 12 weeks of exercise training, in terms of fitness, the exercise group showed significant improvements in 6-min walk test (6MWT) (p < 0.001), peak oxygen consumption (VO2peak) (p = 0.005), muscle content (p < 0.001), muscle percentage (p < 0.001), and grip strength (p = 0.008) compared to the control group. In terms of clinical indicators, the exercise group showed significant improvements in vital capacity (p = 0.018), D-dimer (p = 0.031), and C-reactive protein (CRP) (p = 0.01), uric acid (p = 0.003), triglycerides (p < 0.001), functional average score (p < 0.001), and main symptom average score (p = 0.004) compared to the control group in trends over time. CONCLUSION: Rehabilitation exercises using individualized exercise prescriptions tailored by exercise prescription specialists during chemotherapy are safe for lung cancer patients. Adhering to exercise can achieve comprehensive improvements in physical fitness and quality of life at 12 weeks.

Changes in Intestinal Flora and Serum Metabolites Pre- and Post-Antitumor Drug Therapy in Patients with Non-Small Cell Lung Cancer.

OBJECTIVE: this study aimed to identify the relationships between gut microbiota, metabolism, and non-small cell lung cancer (NSCLC) treatment outcomes, which are presently unclear. METHODS: in this single-center prospective cohort study, we investigated changes in the gut microbiota and serum metabolite profile in 60 patients with NSCLC after four cycles of anticancer therapy. RESULTS: The microbial landscape of the gut exhibited a surge in Proteobacteria and Verrucomicrobiota populations, alongside a decline in Firmicutes, Actinobacteriota, and Bacteroidota. Furthermore, a significant shift in the prevalence of certain bacterial genera was noted, with an increase in Escherichia/Shigella and Klebsiella, contrasted by a reduction in Bifidobacterium. Metabolomic analysis uncovered significant changes in lipid abundances, with certain metabolic pathways markedly altered post-treatment. Correlation assessments identified strong links between certain gut microbial genera and serum metabolite concentrations. Despite these findings, a subgroup analysis delineating patient responses to therapy revealed no significant shifts in the gut microbiome's composition after four cycles of treatment. CONCLUSIONS: This study emphasizes the critical role of gut microbiota changes in NSCLC patients during anticancer treatment. These insights pave the way for managing treatment complications and inform future research to improve patient care by understanding and addressing these microbiota changes.

SN-38, an active metabolite of irinotecan, inhibits transcription of nuclear factor erythroid 2-related factor 2 and enhances drug sensitivity of colorectal cancer cells.

Nuclear factor erythroid 2-related factor 2 (Nrf2) significantly contributes to drug resistance of cancer cells, and Nrf2 inhibitors have been vigorously pursued. Repurposing of existing drugs, especially anticancer drugs, is a straightforward and promising strategy to find clinically available Nrf2 inhibitors and effective drug combinations. Topoisomerase inhibitors SN-38 (an active metabolite of irinotecan), topotecan, mitoxantrone, and epirubicin were found to significantly suppress Nrf2 transcriptional activity in cancer cells. SN-38, the most potent one among them, significantly inhibited the transcription of Nrf2, as indicated by decreased mRNA level and binding of RNA polymerase II to NFE2L2 gene, while no impact on Nrf2 protein or mRNA degradation was observed. SN-38 synergized with Nrf2-sensitive anticancer drugs such as mitomycin C in killing colorectal cancer cells, and irinotecan and mitomycin C synergistically inhibited the growth of SW480 xenografts in nude mice. Our study identified SN-38 and three other topoisomerase inhibitors as Nrf2 inhibitors, revealed the Nrf2-inhibitory mechanism of SN-38, and indicate that clinically feasible drug combinations could be designed based on their interactions with Nrf2 signaling.

Radiofrequency ablation combined with toripalimab for recurrent hepatocellular carcinoma: A prospective controlled trial.

OBJECTIVE: The effectiveness and security of radiofrequency ablation (RFA) in combination with toripalimab (anti-PD-1) for the treatment of recurrent hepatocellular carcinoma (HCC) was studied in this article. METHODS: Total of 40 patients were enrolled in the study between September 2019 and November 2021. Data follow-up ends in April 2022. The study's main focus is on recurrence free survival (RFS), while the secondary objectives was safety. Chi-square tests, Kaplan-Meier, and Cox proportional hazards models were utilized to analyze the data. RESULTS: The median follow-up period was 21.40 months, and the median RFS was 15.40 months in the group that received combination therapy, which was statistically significantly different (HR: 0.44, p = 0.04) compared with the RFA group (8.2 months). RFS rates (RFSr) at 6, 12 and 18 months in the combination therapy groups and RFA groups were 80% vs 65%, 62.7% vs 35% and 48.7% vs 18.8%, respectively. Between the two groups, significant difference of RFSr was found at 18 months (p = 0.04). No statistical differences were observed between the two groups in terms of safeness (p > 0.05). The subgroup analysis indicated that the combination of RFA and anti-PD-1 led to better RFS than RFA alone. Moreover, patients benefited more from combination therapy in the groups younger than 60 years (HR: 0.26, p = 0.018), male (HR: 0.32, p = 0.028) and Child-Pugh grade A (HR: 0.38, p = 0.032). CONCLUSIONS: Combining RFA with anti-PD-1 showed improved RFS and was deemed safe for patients with recurrent HCC who had previously undergone RFA treatment alone.

Assessment of causal relationships between omega-3 and omega-6 polyunsaturated fatty acids in bipolar disorder: a 2-sample bidirectional mendelian randomization study.

Omega-3 fatty acids may be protective against bipolar disorder (BD), whereas omega-6 fatty acids and an increased omega-6:omega-3 ratio may increase the risk of BD. This causal relationship has not yet been established. We attempted to prove the existence of these causal relationships in this study. Datasets on omega-3, omega-6, and omega-6:omega-3 ratios were obtained from the UK Biobank. The EBI database was used to obtain the BD dataset. SNPs associated with fatty acids were identified as instrumental variables (IVs) that met the criteria of P < 5 × 10-8, LD (R2 > 0.01), and kb < 10 000. The main analytical method in this study was the inverse variance weighted (IVW) method. Furthermore, we employ a variety of methods for sensitivity analysis. According to the IVW analysis, higher omega-3 levels were associated with a lower risk of BD (OR = 0.884, 95%CI: 0.796-0.982, P < 0.05). An increase in the omega-6:omega-3 ratio was associated with an increased risk of BD (OR = 1.172, 95%CI: 1.046-1.314, P < 0.05), but no causal relationship between omega-6 levels and BD risk was unearthed. Our MR findings suggest that the ratio of omega-3, omega-6:omega-3 is associated with the risk of BD. It is important to be concerned about the risk of BD in individuals with low serum omega-3 intake and a high omega-6:omega-3 ratio.

Current status and prospect of treatments for recurrent hepatocellular carcinoma.

Owing to its heterogeneous and highly aggressive nature, hepatocellular carcinoma (HCC) has a high recurrence rate, which is a non-negligible problem despite the increasing number of available treatment options. Recent clinical trials have attempted to reduce the recurrence and develop innovative treatment options for patients with recurrent HCC. In the event of liver remnant recurrence, the currently available treatment options include repeat hepatectomy, salvage liver transplantation, tumor ablation, transcatheter arterial chemoembolization, stereotactic body radiotherapy, systemic therapies, and combination therapy. In this review, we summarize the strategies to reduce the recurrence of high-risk tumors and aggressive therapies for recurrent HCC. Additionally, we discuss methods to prevent HCC recurrence and prognostic models constructed based on predictors of recurrence to develop an appropriate surveillance program.

Establishment of a schizophrenia classifier based on peripheral blood signatures and investigation of pathogenic miRNA-mRNA regulation.

To date, the diagnosis of schizophrenia (SCZ) mainly relies on patients' or guardians' self-reports and clinical observation, and the pathogenesis of SCZ remains elusive. In this study, we sought to develop a reliable classifier for diagnosing SCZ patients and provide clues to the etiology and pathogenesis of SCZ. Based on the high throughput sequencing analysis of peripheral blood miRNA expression profile and weighted gene co-expression network analysis (WGCNA) in our previous study, we selected eleven hub miRNAs for validation by qRT-PCR in 51 SCZ patients and 51 controls. miR-939-5p, miR-4732-3p let-7d-3p, and miR-142-3p were confirmed to be significantly up-regulated, and miR-30e-3p and miR-23a-3p were down-regulated in SCZ patients. miR-30e-3p with the most considerable fold change and statistically significance was selected for targeting validation. We first performed bioinformatics prediction followed by qRT-PCR and verified the up-regulation of potential target mRNAs (ABI1, NMT1, HMGB1) expression. Next, we found that the expression level of ABI1 was significantly up-regulated in SH-SY5Y cells transfected with miR-30e-3p mimics. Lastly, we conducted a luciferase assay in 293T cells confirming that miR-30e-3p could directly bind with the 3'untranslated region (3'-UTR) of ABI1, revealing that miR-30e-3p might play a role in the polymerization of neuronal actin and the reconstruction of the cytoskeleton via the downstream regulation of ABI1. In addition, we constructed a classifier by a series of bioinformatics algorithms and evaluated its diagnostic performance. It appears that the classifier consists of miRNAs and mRNAs possess a better discrimination performance than individual miRNA or mRNA in SCZ.

Effect of Chemotherapy in Stage II-IV Large-Cell Lung Carcinoma and Construction of Its Predictive Nomograms: A SEER Analysis.

OBJECTIVES: Large-cell lung carcinoma (LCLC) is generally poorly differentiated with a poor prognosis. This study aimed to explore the impact of chemotherapy on the prognosis of patients with stage II-IV LCLC and to construct nomograms to predict overall survival (OS) and cancer-specific survival (CSS). METHODS: Propensity score matching analysis was used to balance the effects of baseline characteristics. The Kaplan-Meier method was used to analyze the prognostic impact of chemotherapy on LCLC patients. Cox regression analysis was used to identify prognostic risk factors, and then nomograms were constructed and validated. RESULTS: Overall, we identified 2,532 patients with LCLC from the Surveillance, Epidemiology, and End Results (SEER) database. The chemotherapy group showed better OS and CSS compared to the non-/unknown chemotherapy group for stage II-IV LCLC patients (p < 0.05). Two nomograms were plotted based on the results of Cox regression analysis. The areas under the curves (AUCs) of 1-, 3-, and 5-year OS were 0.786, 0.824, and 0.837, and the AUCs of CSS were 0.785, 0.821, and 0.836, respectively. The calibration curves showed excellent agreement between the prediction and the actual observation, and the decision curve analysis demonstrated good clinical utility. CONCLUSIONS: Chemotherapy could improve the prognosis among stage II-IV LCLC patients. In addition, the nomograms showed good predictive ability, which could be useful in making clinical decisions.

Protective role of antioxidant supplementation for depression and anxiety: A meta-analysis of randomized clinical trials.

BACKGROUND: New research supports an integrated approach to treating depression, and lifestyle modifications should be a regular component of both preventative and treatment programs. Therefore, in order to investigate the relationship between various antioxidant supplements and depressive status, we carried out a meta-analysis of randomized controlled trials (RCT). METHODS: We thoroughly searched PubMed, Medline, Scopus, and Web of Science databases to screen publications focusing on the effects of antioxidant supplements on depression status. The meta-analysis mainly compared depression scores between groups that received antioxidant supplements and controls. We also pooled studies reporting changes in anxiety status as a secondary outcome. RESULTS: 52 studies with 4049 participants were eventually identified. The meta-analysis found that the positive effect of antioxidant supplementation, such as magnesium (SMD = 0.16, p = 0.03), zinc (SMD = 0.59, p = 0.01), selenium (SMD = 0.33, p = 0.009), CoQ10 (SMD = 0.97, p = 0.05), tea and coffee (SMD = 1.15, p = 0.001) and crocin (MD = 6.04, p < 0.00001), on depressive status were all significant. And antioxidant supplementation also showed significant improvement in anxiety (SMD = 0.40, p < 0.00001). Subgroup analysis by scale types and countries were performed, and antioxidant supplementation's positive effects on depressive and anxiety states remained significant. LIMITATIONS: This study did not limit the characteristics of the included population, and the diversity of scales also contributed to the heterogeneity. CONCLUSION: Intake of antioxidant supplements is associated with improved depression and anxiety states, further affirms the therapeutic potential of antioxidant supplements as adjunctive therapy to conventional antidepressants.

Long-term effects of antipsychotics on mortality in patients with schizophrenia: a systematic review and meta-analysis

Objective: To gather current evidence on the impact of antipsychotics on long-term mortality in patients with schizophrenia. Methods: We systematically searched for articles in Embase, PubMed, and PsycINFO reporting the long-term mortality (follow-up > 1 year) of patients with schizophrenia who were using any antipsychotics. We then conducted multiple meta-analyses to determine differences in long-term mortality between different types of antipsychotics. Results: We identified 45 articles that provided unadjusted long-term mortality rates, including 46,171 deaths during 2,394,911 person-years. The pooled mortality rate was 9.9 (95%CI = 7.4-12.7) per 1,000 person-years. The unadjusted crude mortality rate of antipsychotic drug users was lower than that of non-users (risk ratio [RR] = 0.546, 95%CI = 0.480-0.621), first-generation antipsychotics caused higher all-cause mortality than second-generation antipsychotics (RR = 1.485, 95%CI = 1.361-1.620), and polypharmacy had better effects than monotherapy on long-term mortality (RR = 0.796, 95%CI = 0.689-0.921). As for the causes of death, heart disease and cardiovascular disease ranked highest among cause-specific mortality (5.6 per 1,000 person-years). Conclusion: Since antipsychotics had a beneficial effect on long-term mortality in schizophrenia, greater precaution should be taken with patients who do not take them. However, since disease severity, comorbidities, and other confounding factors cannot be fully controlled, further research and verification are needed.

Identification of potential biomarkers and their correlation with immune infiltration cells in schizophrenia using combinative bioinformatics strategy.

Many studies have identified changes in gene expression in brains of schizophrenia patients and their altered molecular processes, but the findings in different datasets were inconsistent and diverse. Here we performed the most comprehensive analysis of gene expression patterns to explore the underlying mechanisms and the potential biomarkers for early diagnosis in schizophrenia. We focused on 10 gene expression datasets in post-mortem human brain samples of schizophrenia downloaded from gene expression omnibus (GEO) database using the integrated bioinformatics analyses including robust rank aggregation (RRA) algorithm, Weighted gene co-expression network analysis (WGCNA) and CIBERSORT. Machine learning algorithm was used to construct the risk prediction model for early diagnosis of schizophrenia. We identified 15 key genes (SLC1A3, AQP4, GJA1, ALDH1L1, SOX9, SLC4A4, EGR1, NOTCH2, PVALB, ID4, ABCG2, METTL7A, ARC, F3 and EMX2) in schizophrenia by performing multiple bioinformatics analysis algorithms. Moreover, the interesting part of the study is that there is a correlation between the expression of hub genes and the immune infiltrating cells estimated by CIBERSORT. Besides, the risk prediction model was constructed by using both these genes and the immune cells with a high accuracy of 0.83 in the training set, and achieved a high AUC of 0.77 for the test set. Our study identified several potential biomarkers for diagnosis of SCZ based on multiple bioinformatics algorithms, and the constructed risk prediction model using these biomarkers achieved high accuracy. The results provide evidence for an improved understanding of the molecular mechanism of schizophrenia.

Identification of Peripheral Blood miRNA Biomarkers in First-Episode Drug-Free Schizophrenia Patients Using Bioinformatics Strategy.

Schizophrenia (SCZ) is a polygenic, complex mental disorder of which a diagnosis is often made based on psychiatric history and clinical observation with few available objectives and detectable biomarkers. To identify co-expressed miRNA modules in schizophrenia patients and verify the possibility of using peripheral blood miRNAs as novel biomarkers, high-throughput sequencing was performed on 15 first-episode schizophrenia patients (FES) and 15 healthy controls (CTL). We found 79 differential expressed miRNAs (DEMs) in FES patients and three FES-related co-expression miRNA modules by miRNA-seq data standardized difference analysis and weighted gene co-expression network analysis (WGCNA). Then, 41 hub miRNAs were screened from the intersection of key modules and DEMs, among which miR-9-5p, miR-144-3p, miR-328-3p, and miR-4467 were selected for qRT-PCR verification in a larger sample (FES = 35, CTL = 60). The level of miR-9-5p in FES patients was downregulated, and miR-4467 was upregulated with better diagnostic performance (AUC = 0.719). The target genes of miR-9-5p engage in the biological processes (BP) such as body behaviour, neuronal differentiation regulation, nervous system development, and neurotrophin signaling pathways. Their hub target genes were also located, including NEDD4, EIF4G1, FBXL16, and FBXL3. Summarily, miR-9-5p and miR-4467 hold promise in blood diagnosis for SCZ, and miR-9-5p might affect the onset and development of SCZ through target regulation of neurodevelopment-related mRNAs. Our findings revealed the complex relationship between the miRNA co-expression network and FES, providing more verifiable biomarkers for SCZ early diagnosis and clues for the etiology of schizophrenia.

Pan-cancer analysis on the role of PIK3R1 and PIK3R2 in human tumors.

Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1) is believed to function as a tumor suppressor, while Phosphoinositide-3-Kinase Regulatory Subunit 2 (PIK3R2) as a tumor driver. However, there is no systematic pan-cancer analysis of them. The pan-cancer study comprehensively investigated the gene expression, genetic alteration, DNA methylation, and prognostic significance of PIK3R1 and PIK3R2 in 33 different tumors based on the TIMER, GEPIA, UALCAN, HPA, cBioPortal, and Kaplan-Meier Plotter database. The results indicated that PIK3R1 is lowly expressed in most tumors while PIK3R2 is highly expressed in most tumors, and abnormal gene expression may be related to promoter methylation. Moreover, not only mutations, downregulation of PIK3R1 and upregulation of PIK3R2 were found to be detrimental to the survival of most cancer patients as well. Furthermore, the expression of both PIK3R1 and PIK3R2 was associated with the level of immune infiltration in multiple tumors, such as breast invasive carcinoma. Our study conducted a comparatively comprehensive analysis of the role of PIK3R1 and PIK3R2 in a variety of cancers, contributing to further study of their potential mechanisms in cancer occurrence and progression. Our findings suggested that PIK3R1 and PIK3R2 could serve as prognostic markers for several cancers.

Characteristics and Clinical Implication of UGT1A1 Heterozygous Mutation in Tumor.

BACKGROUND: The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear. METHODS: A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization. RESULTS: There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not. CONCLUSIONS: In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.

[Clinical Characteristics and Prognosis of 76 Lung Adenocarcinoma Patients 
Harboring EGFR Mutations with Pleural Effusion at Initial Diagnosis: 
A Single-center Retrospective Study].

BACKGROUND: Malignant pleural effusion is one of the common clinical manifestations of patients with lung adenocarcinoma. Patients with pleural effusion at the initial diagnosis of lung adenocarcinoma usually indicate poor prognosis. Epidermal growth factor receptor (EGFR) mutations mainly occur in patients with lung adenocarcinoma. Patients with different mutant subtypes have different prognosis. The clinical characteristics and prognostic factors of patients with EGFR mutated lung adenocarcinoma of different molecular subtypes combined with pleural effusion at initial diagnosis are still unclear. This study was designed to explore the clinical characteristics and prognostic factors of these patients in order to provide management recommendations for them. METHODS: A retrospective analysis of the clinical characteristics, treatment, outcomes and progression-free survival (PFS) of first-line treatment in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis admitted to Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital from January 2012 to June 2021 was performed. Pearson's chi-square test or Fisher's exact test were performed for comparison between groups. Kaplan-Meier method was performed for survival analysis and Cox proportional risk regression model was performed for multivariate analysis. RESULTS: 76 patients met the inclusion criteria in this study. The incidences of EGFR classical mutations 19del, 21L858R and non-classical mutations were 46.0%, 38.2% and 15.8%, respectively among these patients. There was no significant difference between the three mutations in terms of gender, age, presence of dyspnea at presentation, whether other distant metastases were combined, site of pleural effusion, volume of pleural effusion, presence of other combined effusions, tumor-node-metastasis (TNM) stage, presence of other gene mutations, and treatment of pleural effusion (P>0.05). In patients with EGFR classical mutations 19del or 21L858R or non-classical mutations subtype, the proportion of chemotherapy in first-line regimens were 17.1%, 20.7% and 58.3%, respectively (P=0.001); and first-line disease control rates were 94.3%, 75.9% and 50%, respectively (P=0.003); pleural effusion control rates were 94.3%, 79.3% and 66.7%, respectively (P=0.04); PFS were 287 d, 327 d and 55 d, respectively (P=0.001). Univariate analysis showed that EGFR mutation subtype, control of pleural effusion, first-line treatment agents, and first-line treatment efficacy were significantly associated with PFS (P<0.05). Cox multifactorial analysis showed that only EGFR mutation subtype and first-line treatment efficacy were independent prognostic factors for PFS (P<0.05). CONCLUSIONS: PFS was significantly better for classical mutations than for non-classical mutations in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis. Improving the efficacy of first-line therapy is the key to improve the prognosis of these patients.

Identification of potential blood biomarkers for early diagnosis of schizophrenia through RNA sequencing analysis.

Schizophrenia (SCZ) is a highly heritable, polygenic complex mental disorder with imprecise diagnostic boundaries. Finding sensitive and specific novel biomarkers to improve the biological homogeneity of SCZ diagnosis is still one of the research hotspots. To identify the blood specific diagnostic biomarkers of SCZ, we performed RNA sequencing (RNA-seq) on 30 peripheral blood samples from 15 first-episode drug-naïve SCZ patients and 15 healthy controls (CTL). By performing multiple bioinformatics analysis algorithms based on RNA-seq data and microarray datasets, including differential expression genes (DEGs) analysis, WGCNA and CIBERSORT, we first identified 6 specific key genes (TOMM7, SNRPG, KRT1, AQP10, TMEM14B and CLEC12A) in SCZ. Moreover, we found that the proportions of lymphocyte, monocyte and neutrophils were significantly distinct in SCZ patients with CTL samples. Therefore, combining various features including age, sex and the novel blood biomarkers, we constructed the risk prediction model with three classifiers (RF: Random Forest; SVM: support vector machine; DT: decision tree) through repeated k-fold cross validation ensuring better generalizability. Finest result of Area under Receiver Operating Characteristic (AUROC) score of 0.91 was achieved by RF classifier and with a comparable good performance of AUROC 0.77 in external validation dataset. A lower AUROC of 0.63 was demonstrated when it was further applied to a Bipolar disorder (BPD) cohort. In conclusion, the study identified three peripheral core immunocytes and six key genes associated with the occurrence of SCZ, and further studies are required to test and validate these novel biomarkers for early diagnosis and treatment of SCZ.

Dilemma and solutions of treatment delay in cancer patients during the COVID-19 pandemic: A single-center, prospective survey.

INTRODUCTION: During the COVID-19 pandemic, the protective and medical resources were limited, while a limited number of studies have concentrated on the influences of COVID-19 on the treatment of cancer patients. This survey aimed to explore the protective awareness about COVID-19, the incidence and factors influencing treatment delay, and expected treatment modality of cancer patients, so as to assist cancer patients. METHODS: A current prospective, online survey was conducted through the WeChat platform on cancer outpatients at the Department of Peking University Third Hospital in China from March 4 to April 4, 2020. RESULTS: A total of 141 patients completed the survey after excluding 35 patients with an incomplete questionnaire. Note that 100% of the patients wore masks and paid attention to hand hygiene during the hospital visits, 73.0% of the patients had a strong desire to treat cancer, and 41.8% experienced treatment delay. The rate of treatment delay among the patients treated in other departments was markedly higher than that in our department (64.7% vs. 38.7%, p = .042). The results of logistic regression analysis showed that the previous treatment department was independently correlated with treatment delay. Moreover, 51.8% of the patients preferred to receive chemotherapy in the day ward, 54.6% hoped to receive a strong contact with doctors, and 83.7% would like to receive online therapeutic consultation. CONCLUSION: The rate of treatment delay was remarkable, which may be related to previous treatment departments. Promotion of "active management of attending physician" and "telemedicine" may be highly advantageous for cancer patients during the COVID-19 pandemic.

Long-term effects of antipsychotics on mortality in patients with schizophrenia: a systematic review and meta-analysis.

OBJECTIVE: To gather current evidence on the impact of antipsychotics on long-term mortality in patients with schizophrenia. METHODS: We systematically searched for articles in Embase, PubMed, and PsycINFO reporting the long-term mortality (follow-up > 1 year) of patients with schizophrenia who were using any antipsychotics. We then conducted multiple meta-analyses to determine differences in long-term mortality between different types of antipsychotics. RESULTS: We identified 45 articles that provided unadjusted long-term mortality rates, including 46,171 deaths during 2,394,911 person-years. The pooled mortality rate was 9.9 (95%CI = 7.4-12.7) per 1,000 person-years. The unadjusted crude mortality rate of antipsychotic drug users was lower than that of non-users (risk ratio [RR] = 0.546, 95%CI = 0.480-0.621), first-generation antipsychotics caused higher all-cause mortality than second-generation antipsychotics (RR = 1.485, 95%CI = 1.361-1.620), and polypharmacy had better effects than monotherapy on long-term mortality (RR = 0.796, 95%CI = 0.689-0.921). As for the causes of death, heart disease and cardiovascular disease ranked highest among cause-specific mortality (5.6 per 1,000 person-years). CONCLUSION: Since antipsychotics had a beneficial effect on long-term mortality in schizophrenia, greater precaution should be taken with patients who do not take them. However, since disease severity, comorbidities, and other confounding factors cannot be fully controlled, further research and verification are needed.

A Novel Circular RNA circPTCD3 Promotes Breast Cancer Progression Through Sponging miR-198.

INTRODUCTION: Circular RNAs (circRNAs), a new type of non-coding RNA, have been demonstrated to play critical roles in the progression of various of malignant cancers. However, the function of circRNAs in breast cancer is not clearly understood. METHODS: qPCR was used to evaluate the gene expression. Function studies including MTT, transwell, wound healing and colony formation assay were performed to evaluate the function of circPTCD3 in breast cancer. Luciferase and RNA pull-down assays were used to verify the interaction between circPTCD3 and miR-198. The xenograft model was established to evaluate the function of circPTCD3 in vivo. RESULTS: In the present study, we identified a novel circRNA termed as circPTCD3 which was indicated to be significantly up-regulated in breast cancer tissues and cell lines. The results revealed that ectopic expression of circPTCD3 promoted the cell proliferation, migration and colony formation ability of breast cancer cells. Constantly, silencing of circPTCD3 inhibited those of breast cancer cells. Furthermore, we identified that circPTCD3 was able to target miR-198 in breast cancer cell. miR-198 has the function of inhibiting proliferation and migration of breast cancer cells which can be reversed by circPTCD3. CONCLUSION: Taken together, our findings for the first time identified a novel circRNA (circPTCD3) and revealed its oncogenic role in breast cancer. Mechanically, we reported that circPTCD3 served as a competing endogenous RNA (ceRNA) to sponge miR-198. These findings provide insights into breast cancer progression and also potential new targets for diagnosis or treatment of breast cancer.