Stemness related lncRNAs signature for the prognosis and tumor immune microenvironment of ccRCC patients.

Long non-coding RNAs (lncRNAs) and cancer stem cells (CSCs) are crucial for the growth, migration, recurrence, and medication resistance of tumors. However, the impact of lncRNAs related to stemness on the outcome and tumor immune microenvironment (TIME) in clear cell renal cell carcinoma (ccRCC) is still unclear. In this study, we aimed to predict the outcome and TIME of ccRCC by constructing a stem related lncRNAs (SRlncRNAs) signature. We firstly downloaded ccRCC patients' clinical data and RNA sequencing data from UCSC and TCGA databases, and abtained the differentially expressed lncRNAs highly correlated with stem index in ccRCC through gene expression differential analysis and Pearson correlation analysis. Then, we selected suitable SRlncRNAs for constructing a prognostic signature of ccRCC patients by LASSO Cox regression. Further, we used nomogram and Kaplan Meier curves to evaluate the SRlncRNA signature for the prognose in ccRCC. At last, we used ssGSEA and GSVA to evaluate the correlation between the SRlncRNAs signature and TIME in ccRCC. Finally, We obtained a signtaure based on six SRlncRNAs, which are correlated with TIME and can effectively predict the ccRCC patients' prognosis. The SRlncRNAs signature may be a noval prognostic indicator in ccRCC.

Comparison of macular changes and visual outcomes between femtosecond laser-assisted cataract surgery and conventional phacoemulsification surgery for high myopic cataract patients.

BACKGROUND: To evaluate differences in log MAR best-corrected visual acuity (BCVA) improvement and postoperative central foveal thickness (CFT) and choroidal thickness (CT) changes between conventional phacoemulsification surgery (CPS) and femtosecond laser-assisted cataract surgery (FLACS) for high-myopia cataracts. METHODS: This was a retrospective and observational study. One hundred and two eyes of 102 patients with high-myopia cataracts were examined. CPS was performed in 54 eyes, and FLACS was performed in 48 eyes. All eyes underwent logMAR BCVA, CFT and CT of three different sectors preoperatively and one week and six months postoperatively. RESULTS: The logMAR BCVA improved significantly after surgery in both groups (both P < 0.001), but no difference was observed in BCVA improvement between the groups (P = 0.554). Moreover, no significant differences were reflected in the changes in CFT, nasal 1 mm CT or temporal 1 mm CT between the two groups, and only subfoveal choroidal thickness (SFCT) in the CPS group decreased significantly compared with that in the FLACS group at any postoperative time (P = 0.003 and 0.026). AL, preoperative logMAR BCVA, and CT of the three regions exhibited a notable correlation with postoperative BCVA (all P < 0.05) according to univariate logistic regression analysis. However, only the AL, preoperative logMAR BCVA and SFCT remained significant in the multivariate model. Postoperative logMAR BCVA revealed a positive correlation with AL and preoperative logMAR BCVA but a negative correlation with SFCT. CONCLUSIONS: FLACS was not superior to CPS in improving BCVA but had less impact on SFCT in the treatment of high-myopia cataracts. Eyes with a longer AL, worse preoperative logMAR BCVA and thinner SFCT had a high risk of worse postoperative BCVA.

Mechanism of electroconvulsive therapy in schizophrenia: a bioinformatics analysis study of RNA-seq data.

OBJECTIVE: The molecular mechanism of electroconvulsive therapy (ECT) for schizophrenia remains unclear. The aim of this study was to uncover the underlying biological mechanisms of ECT in the treatment of schizophrenia using a transcriptional dataset. METHODS: The peripheral blood mRNA sequencing data of eight patients (before and after ECT) and eight healthy controls were analyzed by integrated co-expression network analysis and the differentially expressed genes were analyzed by cluster analysis. Gene set overlap analysis was performed using the hypergeometric distribution of phypfunction in R. Associations of these gene sets with psychiatric disorders were explored. Tissue-specific enrichment analysis, gene ontology enrichment analysis, and protein-protein interaction enrichment analysis were used for gene set organization localization and pathway analysis. RESULTS: We found the genes of the green-yellow module were significantly associated with the effect of ECT treatment and the common gene variants of schizophrenia ( P  = 0.0061; family-wise error correction). The genes of the green-yellow module are mainly enriched in brain tissue and mainly involved in the pathways of neurotrophin, mitogen-activated protein kinase and long-term potentiation. CONCLUSION: Genes associated with the efficacy of ECT were predominantly enriched in neurotrophin, mitogen-activated protein kinase and long-term potentiation signaling pathways.

Prognostic and Immune Infiltration Signatures of GIMAP Family Genes in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urinary system characterized by abundant immunocytes infiltration. The impact of guanosine triphosphatases (GTPases) of immunity-associated proteins (GIMAPs) on the tumor immune microenvironment (TIME) and prognosis of ccRCC is unclear. METHODS: The expression of GIMAPs in ccRCC was determined through multiple datasets (ONCOMINE, TCGA and UALCAN). The relationship between GIMAP family members was analyzed through Spearman correlation analysis. The interaction among the GIMAPs protein was analyzed using STRING. Prognostic values of GIMAPs were evaluated by Survival analysis, Lasso and Cox regression analysis; Prognostic risk model and nomogram were constructed. The correlation between GIMAPs and TIME was explored using TIMER, Cibersort and Pearson correlation analysis. Gene set enrichment analysis (GSEA) was performed to discuss their function and mechanism in ccRCC. RESULTS: GIMAPs were over-expressed in ccRCC and significantly related to overall survival (OS) of the patients. GIMAPs were positively correlated with each other, the risk model based on GIMAPs had good prognostic value in ccRCC. GIMAPs mainly expressed in TIME and were associated with abundant immunocytic infiltration in ccRCC, the risk model also had close correlation with TIME. Our results showed GIMAPs may affect the development of ccRCC by regulating the amount and antitumor activity of immunocytes in TIME. CONCLUSIONS: GIMAPs were over-expressed in ccRCC, and their expression levels were significantly related to the OS of patients and immunocytic infiltration in TIME. GIMAPs are potential therapeutic targets and prognostic biomarkers for ccRCC.

Catalpol Alleviates Depression by Inhibiting NLRP3 Inflammasome via TLR4/MAPK/NF-Kb Pathway.

Background: We aimed to explore catalpol and NF-k. The role of antidepressant and anti-inflammatory effects of b inhibitor in depression induced by chronic unpredictable mild stress (CUMS). Methods: Under the guidance of Qiqihar Medical University, from January 2020 to January 2021, the weight, sucrose consumption and rest time of mice during swimming were monitored, the neurobehavioral changes of rats under CUMS were used to determine the experimental model; ELISA detection of iNOS, ROS, caspase-1, IL-1 ß And IL-18 expression level; Western blotting detection of TLR4, MAPK and NF-κB expression level; LPS-induced cell model. INOS, NLRP3, caspase-1, IL-1 in RT-qPCR and ELISA detection models ß And IL-18 expression level; the TLR4, MAPK and NF-κB level were detected by Western blotting. Results: CUMS can make rats lose weight, reduce sucrose consumption rate and prolong rest time. Catapol can enhance this effect; In the depression model, ROS, NLRP3, NF-κ B and iNOS were up-regulated Catalpol group MAPK, NF-κ Reduced expression of B and TLR4; ROS, caspase-1, IL-1ß, IL-18 and iNOS protein increased. Cell model group TLR4, MAPK and NF-κ. The high protein content of B decreased in catalpol group. Conclusion: Catalpol acts as anti-depressant and anti-inflammatory molecule indepression induced by CUMS. Combination of catalpol with NF-κB inhibitor might play a role in the treatment of depression through regulating the neuroinflammation.

Electroconvulsive Therapy Reduces Protein Expression Level of EP300 and Improves Psychiatric Symptoms and Disturbance of Thought in Patients with Schizophrenia.

Objective: Although electroconvulsive therapy (ECT) has been employed as an effective treatment strategy and to improve mental symptoms in schizophrenia (SCZ), its action mechanisms remain unclear. Our previous study found that some genes and biological pathways were closely related to ECT through genetic technology analysis, such as LTP pathway and EP300. This study combined with healthy controls and symptomatology analysis to further explore the changes of expression of EP300 protein in treatment and related symptoms of SCZ. Methods: One hundred and one patients with SCZ and 45 healthy controls (HCs) were enrolled in this study. Patients with SCZ received acute courses of 6 times bilateral ECT. The peripheral blood of patients with SCZ (BECT: before ECT; AECT: after ECT) and the HCs was collected to calculate the changes of expression level of EP300 protein by enzyme-linked immunosorbent assay. The Positive and Negative Symptoms Scale (PANSS) was used to evaluate the severity of symptoms of SCZ patients and the efficiency of the ECT. Results: There was a statistical difference of EP300 protein expression in patients with SCZ (BECT and AECT) (F = 114.5, p < 0.05). ECT reduced plasma expression level of EP300 protein in patients with SCZ, which was not statistically different from that in HCs (t = 4.47, p = 0.20). The change of the expression level of EP300 protein in patients with SCZ (BECT and AECT) has a positive correlation with reduction rate of positive symptoms (r = 0.228, p < 0.05) and disturbance of thought (r = 0.219, p < 0.05). Conclusion: Our study suggests that the expression level of EP300 protein has a significant change in patients with SCZ treating with ECT, and EP300 may have some connections with positive symptoms and disturbance thought of patients with SCZ.

Comparison of two different intravitreal treatment regimens combined with systemic antiviral therapy for cytomegalovirus retinitis in patients with AIDS.

PURPOSE: To compare the efficacy and injection frequency of intravitreal low-dose vs. intermediate-dose ganciclovir therapy in acquired immune deficiency syndrome (AIDS) patients exhibiting cytomegalovirus retinitis (CMVR). METHODS: A prospective, single-centre, double-blinded, randomized controlled interventional study was conducted. Fifty patients with a total of 67 included eyes were randomly divided into low-dose (0.4 mg ganciclovir per week) and intermediate-dose (1.0 mg ganciclovir per week) groups. The primary clinical outcomes were the changes in best corrected visual acuity (BCVA) from baseline to the end of treatment and the 12-month follow-up visit as well as the number of intravitreal injections. RESULTS: In both groups, the median BCVA, expressed as the logarithm of the minimum angle of resolution (logMAR), improved significantly from baseline to the end of treatment (both p < 0.001), while vision loss from CMVR continued to occur at the 12-month visit. The mean number of injections was 5.8 in the low-dose group and 5.4 in the intermediate-dose group. No significant differences were detected between the two groups (p > 0.05). Regarding the location of CMVR, we found that Zone I lesions led to a worse visual outcome, more injections and a higher occurrence rate of complications than lesions in other zones (p < 0.05). CONCLUSIONS: The efficacy and frequency of injections to treat CMVR in AIDS patients were not significantly different between low and intermediate doses. Zone I lesions were associated with a worse visual outcome, more injections and a higher occurrence rate of CMVR-related complications than lesions in other zones.

RBM4 dictates ESCC cell fate switch from cellular senescence to glutamine-addiction survival through inhibiting LKB1-AMPK-axis.

Cellular senescence provides a protective barrier against tumorigenesis in precancerous or normal tissues upon distinct stressors. However, the detailed mechanisms by which tumor cells evade premature senescence to malignant progression remain largely elusive. Here we reported that RBM4 adversely impacted cellular senescence to favor glutamine-dependent survival of esophageal squamous cell carcinoma (ESCC) cells by dictating the activity of LKB1, a critical governor of cancer metabolism. The level of RBM4 was specifically elevated in ESCC compared to normal tissues, and RBM4 overexpression promoted the malignant phenotype. RBM4 contributed to overcome H-RAS- or doxorubicin-induced senescence, while its depletion caused P27-dependent senescence and proliferation arrest by activating LKB1-AMPK-mTOR cascade. Mechanistically, RBM4 competitively bound LKB1 to disrupt the LKB1/STRAD/MO25 heterotrimeric complex, subsequently recruiting the E3 ligase TRIM26 to LKB1, promoting LKB1 ubiquitination and degradation in nucleus. Therefore, such molecular process leads to bypassing senescence and sustaining cell proliferation through the activation of glutamine metabolism. Clinically, the ESCC patients with high RBM4 and low LKB1 have significantly worse overall survival than those with low RBM4 and high LKB1. The RBM4 high/LKB1 low expression confers increased sensitivity of ESCC cells to glutaminase inhibitor CB-839, providing a novel insight into mechanisms underlying the glutamine-dependency to improve the efficacy of glutamine inhibitors in ESCC therapeutics.

Correlation between duration of untreated psychosis and long-term prognosis in chronic schizophrenia.

Objective: To explore the relationship between the Duration of Untreated Psychosis (DUP) and long-term clinical outcome, cognitive and social function in patients with chronic schizophrenia (SCZ). Methods: A total of 248 subjects with chronic SCZ were enrolled in this study, including 156 in the short DUP group and 92 in the long DUP group. The Positive and Negative Symptoms Scale (PANSS), the Brief Negative Symptoms Scale (BNSS), the Global Assessment of Functioning (GAF) scale and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to assess all of the subjects. Results: The negative symptom scores (the PANSS and BNSS) of subjects with long DUP were significantly higher than that in subjects with short DUP. The scores of visual span and speech function in the short DUP group were significantly higher, indicative of decreasing cognitive function with time. In terms of social function, the short DUP group scored higher, with a statistically significant difference. Meanwhile, we found that the length of DUP was positively correlated with the negative symptom score of the PANSS, negatively correlated with visual span scores, and GAF scores. Conclusion: This study demonstrated that the DUP remained a significant association with negative symptom and cognition in long period of chronic SCZ.

Fungal Biomarkers in Traditional Starter Determine the Chemical Characteristics of Turbid Rice Wine from the Rim of the Sichuan Basin, China.

The fungal community in Qu plays a key role in the formation of turbid rice wine (TRW) style. The Sichuan Basin and its surrounding areas have become one of the main TRW production regions in China; however, the fungal community in Qu and how they affect the characteristics of TRW remain unknown. Therefore, this study provided insight into the fungal biomarkers in Qu from Guang'an (GQ), Dazhou (DQ), Aba (AQ), and Liangshan (LQ), as well as their relationships with compounds in TRW. The main biomarkers in GQ were Rhizopus arrhizus, Candida glabrata, Rhizomucor pusillus, Thermomyces lanuginosus and Wallemia sebi. However, they changed to Saccharomycopsis fibuligera and Mucor indicus in DQ, Lichtheimia ramose in AQ, and Rhizopus microsporus and Saccharomyces cerevisiae in LQ. As a response to fungal biomarkers, the reducing sugar, ethanol, organic acids, and volatile compounds were also changed markedly in TRWs. Among important volatile compounds (VIP > 1.00), phenethyl alcohol (14.1-29.4%) was dominant in TRWs. Meanwhile, 3-methyl-1-butanol (20.6-56.5%) was dominant in all TRWs except that fermented by GQ (GW). Acetic acid (29.4%) and ethyl palmitate (10.1%) were dominant in GW and LW, respectively. Moreover, GQ biomarkers were positively correlated with acetic acid and all unique important volatile compounds in GW. DQ biomarkers had positive correlations with unique compounds of acetoin and ethyl 5-chloro-1,3,4-thiadiazole-2-carboxylate in DW. Meanwhile, the AQ biomarkers were positively correlated with all AW unique, important, and volatile compounds. Although there were not any unique volatile compounds in LW, 16 important volatile compounds in LW were positively related to LQ biomarkers. Obviously, biomarkers in different geographic Qu played vital roles in the formation of important volatile compounds, which could contribute specific flavor to TRWs. This study provided a scientific understanding for future efforts to promote the excellent characteristics of TRW by regulating beneficial fungal communities.

Identification of Key Biomarkers and Candidate Molecules in Non-Small-Cell Lung Cancer by Integrated Bioinformatics Analysis.

Background: Non-small cell lung cancer (NSCLC) is the most prevalent malignant tumor of the lung cancer, for which the molecular mechanisms remain unknown. In this study, we identified novel biomarkers associated with the pathogenesis of NSCLC aiming to provide new diagnostic and therapeutic approaches for NSCLC by bioinformatics analysis. Methods: From the Gene Expression Omnibus database, GSE118370 and GSE10072 microarray datasets were obtained. Identifying the differentially expressed genes (DEGs) between lung adenocarcinoma and normal samples was done. By using bioinformatics tools, a protein-protein interaction (PPI) network was constructed, modules were analyzed, and enrichment analyses were performed. The expression and prognostic values of 14 hub genes were validated by the GEPIA database, and the correlation between hub genes and survival in lung adenocarcinoma was assessed by UALCAN, cBioPortal, String and Cytoscape, and Timer tools. Results: We found three genes (PIK3R1, SPP1, and PECAM1) that have a clear correlation with OS in the lung adenocarcinoma patient. It has been found that lung adenocarcinoma exhibits high expression of SPP1 and that this has been associated with poor prognosis, while low expression of PECAM1 and PIK3R1 is associated with poor prognosis (P < 0.05). We also found that the expression of SPP1 was associated with miR-146a-5p, while the high expression of miR-146a-5p was related to good prognosis (P < 0.05). On the contrary, the lower miR-21-5p on upstream of PIK3R1 is associated with a higher surviving rate in cancer patients (P < 0.05). Finally, we found that the immune checkpoint genes CD274(PD-L1) and PDCD1LG2(PD-1) were also related to SPP1 in lung adenocarcinoma. Conclusions: The results indicated that SPP1 is a cancer promoter (oncogene), while PECAM1 and PIK3R1 are cancer suppressor genes. These genes take part in the regulation of biological activities in lung adenocarcinoma, which provides a basis for improving detection and immunotherapeutic targets for lung adenocarcinoma.

Comparison of intravitreal ranibizumab monotherapy vs. ranibizumab combined with dexamethasone implant for macular edema secondary to retinal vein occlusion.

Purpose: To compare the efficacy and the injection number of intravitreal ranibizumab (IVR) monotherapy vs. intravitreal ranibizumab plus dexamethasone (IVR + DEX) implants for macular edema (ME) secondary to retinal vein occlusion (RVO). Methods: This prospective, control trial comprised 96 eyes of 96 patients with ME due to non-ischemic RVO divided into two groups. The IVR monotherapy group consisted of 61 patients (29 with CRVO and 32 with BRVO) treated with ranibizumab with three consecutive loading doses at a monthly + pro re nata (three + PRN) regimen. The IVR + DEX implant group consisted of 35 patients (19 with CRVO and 16 with BRVO) treated with intravitreal ranibizumab plus DEX implant. All eyes underwent best-corrected visual acuity (BCVA, log MAR), central foveal thickness (CFT), and intraocular pressure (IOP). In case of recurrence, each group received initial medication. Results: At the 12-month visit, the mean log MAR BCVA that was improved from baseline was 0.23 with the IVR group and 0.30 with the IVR + DEX group. CFT decreased on average by 420 ± 292 µm with the IVR group and 393 ± 259 µm with the IVR + DEX implant group. No significant differences were detected in BCVA improvement and CFT reduction between the two groups (p > 0.05). The mean number of injections was 5.4 in the IVR group and 3.9 in the IVR + DEX implant group (p < 0.001). The mean reinjection interval for patients with the IVR + DEX implant was 131.2 ± 8.9 days (range: 98-150). The incidence of high IOP and cataract progression were significantly higher in the IVR + DEX implant group than in the IVR group (both p < 0.001). Conclusion: In RVO-ME, the IVR + DEX implant did not have synergistic efficacy, providing further improvement in BCVA and a reduction in CFT. However, the IVR + DEX implant still had an advantage in reducing the number of injections and prolonging the time between injections.