Investigating the epidemiological relevance of secretory otitis media and neighboring organ diseases through an Internet search.

Background: This study examined the epidemiological correlations between secretory otitis media (SOM) and diseases of neighboring organs. We measured changes in disease incidences during the 2020 COVID-19 pandemic using Internet big data spanning from 2011 to 2021. Methods: This study used the Baidu Index (BI) to determine the search volume for the terms "secretory otitis media (SOM)", "tonsillitis", "pharyngolaryngitis", "adenoid hypertrophy (AH)", "nasopharyngeal carcinoma (NPC)", "nasal septum deviation (NSD)", "rhinosinusitis", "allergic rhinitis (AR)", and "gastroesophageal reflux disease (GERD)" in Mandarin from January 2011 to December 2021. The correlations between these terms were analyzed using Spearman's correlation coefficients. The results were compared search data from 2019 and 2021 to assess the effects of isolation on SOM in 2020. Results: The seasonal variations trends of SOM and other diseases coincided well (P < 0.05), except for AR. During the 11-year timeframe, the monthly searches for rhinosinusitis, NSD, tonsillitis, pharyngolaryngitis, and NPC were statistically correlated with SOM (R = 0.825, 0.594, 0.650, 0.636, 0.664, respectively; P < 0.05). No correlation was found between SOM and AR, SOM and AH, or SOM and GERD (R =  - 0.028, R = 0.259, R = 0.014, respectively, P > 0.05). The total search volumes for SOM, rhinosinusitis, NPC, and AH decreased in 2020 compared to 2019. Discussion: SOM exhibited a discernible epidemiological connection with rhinosinusitis, nasal septal deviation (NSD), tonsillitis, pharyngolaryngitis, and nasopharyngeal carcinoma (NPC). A decrease in public gatherings was observed to effectively reduce the incidences of SOM. This underscores the pivotal role of social measures in influencing the prevalence of SOM and emphasizes the intricate interplay between SOM and various associated health factors, with implications for public health strategies.

Detecting shifts in nonlinear dynamics using Empirical Dynamic Modeling with Nested-Library Analysis.

Abrupt changes in system states and dynamical behaviors are often observed in natural systems; such phenomena, named regime shifts, are explained as transitions between alternative steady states (more generally, attractors). Various methods have been proposed to detect regime shifts from time series data, but a generic detection method with theoretical linkage to underlying dynamics is lacking. Here, we provide a novel method named Nested-Library Analysis (NLA) to retrospectively detect regime shifts using empirical dynamic modeling (EDM) rooted in theory of attractor reconstruction. Specifically, NLA determines the time of regime shift as the cutting point at which sequential reduction of the library set (i.e., the time series data used to reconstruct the attractor for forecasting) optimizes the forecast skill of EDM. We illustrate this method on a chaotic model of which changing parameters present a critical transition. Our analysis shows that NLA detects the change point in the model system and outperforms existing approaches based on statistical characteristics. In addition, NLA empirically detected a real-world regime shift event revealing an abrupt change of Pacific Decadal Oscillation index around the mid-1970s. Importantly, our method can be easily generalized to various systems because NLA is equation-free and requires only a single time series.

Analysis of lncRNAs profiles associated with ferroptosis can predict prognosis and immune landscape and drug sensitivity in patients with clear cell renal cell carcinoma.

Ferroptosis is a novel kind of iron- and reactive oxygen-induced cell death, investigation into ferroptosis-associated long noncoding RNAs (FALs) in clear cell renal cell carcinoma (ccRCC) is scarce. The goal of the research was to look at FALs' possible predictive significance, as well as their interaction with the immune microenvironment and therapeutic responsiveness of ccRCC. The Cancer Genome Atlas database was employed to retrieve RNA sequencing data from 530 individuals with ccRCC. Patients with ccRCC were randomly assigned to one of two groups: training or testing. Pearson's correlation analysis through the identified ferroptosis-related genes was implemented to screen for FALs. Finally, a FALs signature composed of eight lncRNAs was discovered for predicting survival outcomes in ccRCC patients. ccRCC patients in the training, testing, and overall cohorts were separated into low-risk and high-risk groups based on their risk score. The FALs signature was identified to be an independent factor for overall survival in the multivariate Cox analysis (hazard ratio = 1.013, 95% confidence interval = 1.008-1.018, p < 0.001). A clinically prognostic nomogram was created depending on the FALs signature and clinical characteristics. The nomogram provides greater clinical practicability and may reliably estimate patients' overall survival. The FALs signature may additionally precisely represent ccRCC's immunological environment, immunotherapy reaction, and drug sensitivity. The eight FALs and their signature provide precise and reliable methods for evaluating the clinical effects of in ccRCC patients, and they could be biological markers and targets for therapy.

Downregulation of PTCD1 in Bladder Urothelial Carcinoma Predicts Poor Prognosis and Levels of Immune Infiltration.

Pentatricopeptide repeat domain 1 (PTCD1) was reported to regulate mitochondrial metabolism and oxidative phosphorylation. However, the effect and mechanism of PTCD1 in the development of bladder urothelial carcinoma (BLCA) remain unclear. The databases from The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) were used to analyze the expression changes, clinical features, and prognostic values of PTCD1. A nomogram was built to predict the prognostic outcomes of BLCA cases. The potential genes interacting with PTCD1 were explored by Weighted Gene Coexpression Network Analysis (WGCNA). The estimation of associations between PTCD1 and tumor mutations, tumor immunities, and m6A methylations was performed. The study found that the gradual decrease of PTCD1 expression was observed with the increase of stage and grade. Low PTCD1 expression was greatly correlated with higher pathological stage, N stage, and poor prognosis in TCGA cohorts; interestingly, low-grade BLCA cases all exhibited high expression of PTCD1. HPA database analysis implied that the expression of PTCD1 protein in BLCA was lower than that in normal bladder tissue, and the protein expression of PTCD1 in high-grade BLCA was lower than that in low-grade BLCA. Multivariate Cox regression analysis indicated that PTCD1 may serve as an independent factor influencing prognosis of BLCA. Mechanistically, PTCD1 played a regulatory role in BLCA progression through multiple tumor-related pathways containing PI3K-Akt signaling, ECM-receptor interaction, oxidative phosphorylation, and extracellular matrix organization. WGCNA reported that PTCD1 had a strong positive correlation with POLR2J, ZNHT1, ATP5MF, PDAP1, BUD31, and COPS6. Besides, the mRNA expression of PTCD1 was negatively associated with immune cells' infiltrations, immune functions, and checkpoints, especially with some m6A methylation regulators in BLCA. In sum, downregulation of PTCD1 expression may be involved in the development of BLCA and remarkably correlated with poor prognosis. Meantime, it showed an influence in immune cell infiltration and may serve as an agreeable prognostic indicator in BLCA.

The Efficacy of Mirabegron in Medical Expulsive Therapy for Ureteral Stones: A Systematic Review and Meta-Analysis.

Background: This study aimed to assess the efficacy of mirabegron (50 mg daily) as a medical expulsive therapy for ureteral stones in adults. Materials and Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science from inception to July 2021 to collect the clinical trials. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies by using the Cochrane risk of bias tool. Review Manager 5.3 software was used for the meta-analysis. Results: A total of four studies were included, involving 398 patients: 197 patients in mirabegron group and 201 patients in control group. The meta-analysis showed that the stone expulsion rate was higher in the mirabegron group than in the control group (OR: 2.12; 95% CI: 1.33 to 3.40; p=0.002). Subgroup analysis identified that the stone expulsion rate of patients with stone size <5/6 mm was significantly higher than that of patients with stone size ≥5/6 mm (OR: 0.31; 95% CI: 0.13 to 0.72; p=0.006). But no significant difference was identified between the mirabegron group and the control group for the stone expulsion interval (MD: -1.16, 95% CI: -3.56 to 1.24; p=0.35). In terms of pain episodes, the mirabegron group was significantly lower than that of the control group (MD: -0.34, 95% CI: -0.50 to 0.19; p < 0.0001). Conclusions: The medical expulsive therapy with mirabegron had a significant effect in improving the stone expulsion rate for patients with ureteral stones, especially in those whose stone size <5/6 mm. Mirabegron had no effect on the stone expulsion interval but did decrease the pain episodes.

Identification and Validation of a Ferroptosis-Related Long Non-Coding RNA (FRlncRNA) Signature to Predict Survival Outcomes and the Immune Microenvironment in Patients With Clear Cell Renal Cell Carcinoma.

Background: The incidence of clear cell renal cell carcinoma (ccRCC) is increasing worldwide, contributing to 70-85% of kidney cancer cases. Ferroptosis is a novel type of programmed cell death and could predict prognoses in cancers. Here, we developed a ferroptosis-related long non-coding RNA (FRlncRNA) signature to improve the prognostic prediction of ccRCC. Methods: The transcriptome profiles of FRlncRNAs and clinical data of ccRCC were obtained from The Cancer Genome Atlas and ICGC databases. Patients were randomly assigned to training cohorts, testing cohorts, and overall cohorts. The FRlncRNA signature was constructed by Lasso regression and Cox regression analysis, and Kaplan-Meier (K-M) analysis was used to access the prognosis of each group. The accuracy of this signature was evaluated by the receiver operating characteristic (ROC) curve. The visualization of functional enrichment was carried out by the gene set enrichment analysis (GSEA). Internal and external datasets were performed to verify the FRlncRNA signature. Results: A FRlncRNA signature comprising eight lncRNAs (AL590094.1, LINC00460, LINC00944, AC024060.1, HOXB-AS4, LINC01615, EPB41L4A-DT, and LINC01550) was identified. Patients were divided into low- and high-risk groups according to the median risk score, in which the high-risk group owned a dramatical shorter survival time than that of the low-risk group. Through ROC analysis, it was found that this signature had a greater predictive capability than traditional evaluation methods. The risk score was an independent risk factor for overall survival suggested by multivariate Cox analysis (HR = 1.065, 95%CI = 1.036-1.095, and p < 0.001). We constructed a clinically predictive nomogram based on this signature and its clinical features, which is of accurate prediction about the survival rate of patients. The GSEA showed that primary pathways were the P53 signaling pathway and tumor necrosis factor-mediated signaling pathway. The major FRlncRNAs (LINC00460, LINC00944, LINC01550, and EPB41L4A-DT) were verified with the prognosis of ccRCC in the GEPIA and K-M Plotter databases. Their major target genes (BNIP3, RRM2, and GOT1) were closely related to the stage, grade, and survival outcomes of ccRCC by the validation of multiple databases. Additionally, we found two groups had a significant distinct pattern of immune function, immune checkpoint, and immune infiltration, which may lead to different survival benefits. Conclusions: The FRlncRNA signature was accurate and act as reliable tools for predicting clinical outcomes and the immune microenvironment of patients with ccRCC, which may be molecular biomarkers and therapeutic targets.

Intraoperative and postoperative outcomes of thulium laser enucleation versus bipolar resection in the transurethral treatment of benign prostatic hyperplasia: a meta-analysis.

To compare the intraoperative and postoperative outcomes of thulium laser enucleation of the prostate (ThuLEP) vs bipolar transurethral resection of the prostate (B-TURP) in treating patients with benign prostatic hyperplasia (BPH). Clinical trials of ThuLEP and B-TURP in treating BPH were searched systematically by using PubMed, Cochrane Library databases, and EMBASE (until May 2021). The Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist was followed. The datum was calculated by Review Manager version 5.3.0. Four articles including 782 patients were studied in this analysis. The analysis discovered that there was no significant difference in operative time and percentage of tissue removed between ThuLEP and B-TURP. But the intraoperative irrigated volume and postoperative hemoglobin (Hb) decrease in the ThuLEP group was significantly less compared with the B-TURP group. The catheterization time and hospitalization duration in the B-TURP group was significantly longer than that in the ThuLEP group. Compared with those before treatment, the micturition indexes of the two groups improved significantly. But no significant difference was identified between ThuLEP and B-TURP for the variation of international prostate symptom score, quality of life, maximum flow rate, and post-void residual. By analyzing the postoperative complications, there were no significant discrepancies between ThuLEP and B-TURP in the incidence of blood transfusion, recatheterization, transient incontinence, bladder neck contracture, and urethral stricture. The micturition indexes and clinical symptoms were significantly improved after ThuLEP and B-TURP for patients with BPH. However, ThuLEP was more effective than B-TURP in terms of intraoperative irrigated volume, postoperative Hb decrease, catheterization time, and hospitalization duration.

An efficient cell culture system for the studies of heterogeneous astrocytes: Time gradient digestion.

BACKGROUND: Astrocytes are the most abundant glial cell type in mammal brain, but there exists a lot of unknown in cell development and cell function. We aim to establish an astrocytes culture system for obtaining highly enriched primary astrocytes from the neonatal mouse brain and separating Aldh1l1+Gfap- and Aldh1l1+Gfap+ cells. NEW METHOD: C57BL/J6 mouse pups at postnatal 1-4 days were used for cell preparation. Brain cortex was collected and digested with 0.25% trypsin followed by 0.5 mg/ml DNase. Cells were plated on PDL-coated flasks. After 8-10 days culture, cells were shaken at 260 rpm for 4 h at 37 â„ƒ to remove oligodendrocytes and microglia cells. Time gradient digestion was performed to obtain astrocyte subtypes. The digestion time was 0-2 min and 2-4 min, and 4-6 min. Flow cytometry, Immunostaining, CCK-8 assay and EdU staining was carried out to investigate the purity of the astrocytes, the ability of cell proliferation and to identify different subtypes. RESULTS: After shaking, percentage of oligodendrocytes significantly decreased from 22.6 ± 3.6% to 7.4 ± 1.4% (CNPase+ cells) and from 4.36 ± 0.6% to 0.75 ± 0.2% (Pdgfrα+ cells) while percentage of microglia cells reduced from 4.4 ± 0.2% to 0.6 ± 0.2%. Aldh1l1+Gfap- astrocytes were the dominant cell types in 0-2 min group while Aldh1l1+Gfap+ astrocytes were the dominant cell types in 2-4 min group. Moreover, compared with Aldh1l1+Gfap+ astrocytes, Aldh1l1+Gfap- astrocytes had a higher proliferative ability. COMPARISON WITH EXISTING METHODS: Aldh1l1+Gfap- and Aldh1l1+Gfap+ cells were separated. The percentage of residual Tmem119 + and Gfap+ cells showed no significant difference. However, the percentage of Pdgfrα+ cells were significant decreased, and the time consuming of the new system was lower. The astrocytes acquired possess higher viability. CONCLUSIONS: A new astrocytes culture system with time gradient digestion was established. Highly enriched primary astrocytes from the neonatal mouse brain were obtained with short shaking time. Aldh1l1+Gfap- and Aldh1l1+Gfap+ cells were separated by different digestion condition. This system has advantages of high efficiency and low cost, which deserves promising application in management of astrocytes research in central nerve system.

A Meta-Analysis of the Efficacy of L-Carnitine/L-Acetyl-Carnitine or N-Acetyl-Cysteine in Men With Idiopathic Asthenozoospermia.

The meta-analysis was performed to access efficacy of L-carnitine/L-acetyl-carnitine (LC/LAC) and N-acetyl-cysteine (NAC) in men with idiopathic asthenozoospermia. We researched PubMed, EMBASE, and Cochrane Library databases and references to related articles. Finally, seven articles including 621 patients were analyzed. The results indicated that LC/LAC and NAC had a considerable improvement in sperm motility (p = .03 and p < .0001, respectively) and normal morphology (p = .006, p = .0002, respectively) compared with the placebo group. Besides, NAC had a significantly greater increase in sperm concentration (p < .00001) and ejaculate volume (p = .002) compared with the placebo group, and there was no significant difference in LC/LAC. For the analysis of serum hormones, NAC had no obvious differences in improving the serum testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin compared with non-treatment group. Conclusively, LC/LAC and NAC showed a greater improvement in sperm motility and normal morphology. Moreover, NAC has a positive effect on sperm concentration and ejaculate volume, whereas no obvious effect was observed in serum hormones.

Downregulation of miR-29c-3p is associated with a poor prognosis in patients with laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is considered to be a common malignancy of the head and neck with poor prognosis for its late diagnosis, metastasis and recurrence. Growing evidence demonstrates that the dysregulation of miR-29c-3p (microRNA-29c-3p) plays an important role in various tumor processes. Our study investigates the expression of miR-29c-3p in LSCC and analyzes the correlation of its dysregulation with clinicopathologic parameters and prognosis. METHODS: The expression of hsa-miR-29c-3p in LSCC tissues and the adjacent normal laryngeal tissues was detected in 96 LSCC formalin-fixed paraffin-embedded tissues by quantitative real-time PCR (qRT-PCR). The SPSS statistical software package (17.0) was used to analyze the associations between miR-29c-3p expressions and various clinicopathological characteristics. The overall survival (OS) was analyzed by the Kaplan-Meier method and log-rank test, and we analyzed the independent factor of prognosis by Cox proportional hazard analysis. RESULTS: A downregulation of miR-29c-3p expression in LSCC was significantly correlated with smoking index, tumor size, tumor site, differentiation, T classification, TNM stage, and lymph node metastasis (P < 0.05), but there was no correlation with age and alcohol consumption (P > 0.05). In the multivariate survival analysis, low miR-29c-3p expression was associated with shorter overall survival (P < 0.05). Furthermore, miR-29c expression was an independent prognostic factor for laryngeal cancer patients. CONCLUSIONS: MiR-29c-3p has different expression levels at different stages of tumor progression, suggesting that miR-29c-3p may be a promising biomarker for evaluating the progression of LSCC and the prognosis of patients with LSCC. MiR-29c-3p can also be a novel molecular target for anti-laryngeal cancer therapy.

A comparison of the clinical characteristics of Chinese patients with recurrent major depressive disorder with and without dysthymia.

BACKGROUND: The relationship between major depressive disorder (MDD) and dysthymia, a form of chronic depression, is complex. The two conditions are highly comorbid and it is unclear whether they are two separate disease entities. We investigated the extent to which patients with dysthymia superimposed on major depression can be distinguished from those with recurrent MDD. METHODS: We examined the clinical features in 1970 Han Chinese women with MDD (DSM-IV) between 30 and 60 years of age across China. Logistic regression was used to determine the association between clinical features of MDD and dysthymia and between dysthymia and disorders comorbid with major depression. RESULTS: The 354 cases with dysthymia had more severe MDD than those without, with more episodes of MDD and greater co-morbidity for anxiety disorders. Patients with dysthymia had higher neuroticism scores and were more likely to have a family history of MDD. They were also more likely to have suffered serious life events. LIMITATIONS: Results were obtained in a clinically ascertained sample of Chinese women and may not generalize to community-acquired samples or to other populations. It is not possible to determine whether the associations represent causal relationships. CONCLUSIONS: The additional diagnosis of dysthymia in Chinese women with recurrent MDD defines a meaningful and potentially important subtype. We conclude that in some circumstances it is possible to distinguish double depression from recurrent MDD.

EPC-K1 Prevents ONOO(-)-induced Apoptosis in Cerebellar Granule Neurons.

The cytotoxic effect of peroxynitrite on cerebellar granule neurons was studied. Exposure of cerebellar granule neurons to 10 &mgr;mol/L peroxynitrite triggered apoptosis in vitro, which was confirmed by both morphological (nuclear morphology observed by fluorescence microscopy) and biochemical evidence (DNA fragmentation detected by ELISA). Using ESR spin labeling technique, the alteration of biophysical characteristics of neuronal cell membrane during the apoptotic process was studied. The results indicate that after treatment with peroxynitrite, the fluidity of both the surface layer and the deep layer of the neuronal cell membrane decreased markedly, and the S/W ratio of the membrane protein thiol groups increased significantly. Pre-treating cerebellar granule neurons with antioxidant EPC-K1, a novel water-soluble derivative of vitamin C and vitamin E, alleviated the oxidative injury and prevented cells from apoptosis.