BACKGROUND Using regional homogeneity (ReHo) blood oxygen level-dependent functional MR (BOLD-fMRI), we investigated the structural and functional alterations of brain regions among patients with methamphetamine-associated psychosis (MAP). MATERIAL AND METHODS This retrospective study included 17 MAP patients, 16 schizophrenia (SCZ) patients, and 18 healthy controls. Informed consent was obtained from all patients before the clinical assessment, the severity of clinical symptoms was evaluated prior to the fMRI scanning, and then images were acquired and preprocessed after each participant received 6-min fRMI scanning. The participants all underwent BOLD-fMRI scanning. Voxel-based morphometry was used to measure gray matter density (GMD). Resting-state fMRI (rs-fMRI) was conducted to analyze functional MR, ReHo, and functional connectivity (FC). RESULTS GMD analysis results suggest that MAP patients, SCZ patients, and healthy volunteers show different GMDs within different brain regions. Similarly, the ReHo analysis results suggest that MAP patients, SCZ patients, and healthy volunteers have different GMDs within different brain regions. Negative correlations were found between ReHo- and the PANSS-positive scores within the left orbital interior frontal gyrus (L-orb-IFG) of MAP patients. ReHo- and PANSS-negative scores of R-SFG were negatively correlated among SCZ patients. The abnormal FC of R-MFG showed a negative correlation with the PANSS score among MAP patients. CONCLUSIONS The abnormalities in brain structure and FC were associated with the development of MAP.

BACKGROUND It is well established that inflammation and apoptosis of renal tubular epithelial cells caused by hyperglycemia contribute to the development of diabetic nephropathy (DN). Although microRNAs (miRNAs) are known to have roles in inflammation-related disorders, the exact role of miR-34b in DN has not been defined, and the regulatory mechanism has been unclear. This study aimed to clarify the role of miR-34b in DN pathogenesis. MATERIAL AND METHODS Expression of miR-34b, IL-6R, and other key factors of inflammation, apoptosis (TNF-alpha, IL-1ß, IL-6, caspase-3) in high glucose (HG)-induced HK-2 cells were measured by real-time PCR, Western blot, and flow cytometric cell apoptosis assays. We used luciferase reporter assay to detect the target of miR-34b. Moreover, the targeting gene of miR-34b and its downstream JAK2/STAT3 signaling pathway were explored. RESULTS It was demonstrated that miR-34b overexpression inhibited apoptosis and expression levels of TNF-alpha, IL-1ß, IL-6, and caspase-3 in HG-treated HK-2 cells. We also found that IL-6R is a direct target of miR-34b, which could rescue inflammation and apoptosis in HG-treated HK-2 cells transfected with miR-34b mimic. Furthermore, we showed that overexpression of miR-34b inhibited the IL-6R/JAK2/STAT3 signaling pathway in HG-treated HK-2 cells. CONCLUSIONS Our data suggest that overexpression of miR-34b improves inflammation and ameliorates apoptosis in HG-induced HK-2 cells via the IL-6R/JAK2/STAT3 pathway, indicating that miR-34b could be a promising therapeutic target in DN.

BACKGROUND Recently, long noncoding RNAs (lncRNAs) have received wide attention in the area of tumor progression. Dysregulation of lncRNAs has been shown to participated in colon cancer, a known malignant tumor. This study aimed to identify the way lncRNA PVT1 affects the progression of colon cancer. MATERIAL AND METHODS Both human colon cancer tissues and 30 paired adjacent normal tissue samples, as well as the colon cancer cells, were collected. Then quantitative real-time (qRT-PCR) was performed to detect the expression of lncRNA PVT1 and miR-26b. Furthermore, the role of PVT1 was determined by function assays such as cell proliferation assay, invasion assay, and wound healing assay. The mechanism was studied using western blot assay and luciferase assay. RESULTS We demonstrate that the expression of PVT1 was significantly higher in tumor tissue compared with the adjacent normal tissue with a lower expression of miR-26b. Moreover, PVT1 promoted tumor growth, migration, and invasion in vitro. In addition, further experiments revealed that miR-26b was a direct target of PVT1 and could inhibit cell migration, invasion, and proliferation in colon cancer. CONCLUSIONS Our results suggest that PVT1 could promote metastasis and proliferation of colon cancer via endogenous sponging and inhibiting the expression of miR-26b, which may highlight the significance of lncRNA PVT1 in colon cancer tumorigenesis.

BACKGROUND Colorectal cancer (CRC) is one of the most common malignancies worldwide, with high morbidity and mortality rates. The purpose of this study was to identify potential biomarkers in the progression of CRC. MATERIAL AND METHODS Gene and isoform expression datasets of CRC was downloaded from The Cancer Genome Atlas (TCGA). EBSeq of R was used for the normalization of gene and isoform expression, as well as the identification of differential expression genes (DEGs) and isoforms (DEIs) of CRC samples compared with normal samples. The enriched functions of DEGs and DEIs were obtained based on the Database for Annotation, Visualization and Integrated Discovery (DAVID). An independent dataset, GSE38832, was downloaded from the Gene Expression Omnibus (GEO) database for survival analysis of genes with sustained decreased/increased expression values at both gene and isoform levels with the development of CRC. RESULTS A total of 2301 genes and 4241 isoforms were found to be significantly differentially expressed in stage I-IV CRC samples. They are closely associated with muscle or cell system activity. Sixteen genes were screened out with sustained decreased/increased expression values at both gene and isoform levels with the development of CRC. Aberrant CBX8 and CD96 expressions were found to be significantly associated with CRC survival. CONCLUSIONS Through combined analysis of gene and isoform expression profiles, we identified several potential biomarkers that may play an important role in the development of CRC and could be helpful in its early diagnosis and treatment.

BACKGROUND The aim of this study was to explore the influence of mitofusin-2 (Mfn-2) on phosphatidylinositol transfer protein 3 (PITPNM3) and tumor growth and the potential mechanism behind the regulation of Mfn-2 on PITPNM3 in hepatic carcinoma cell line SMMC-7721. MATERIAL AND METHODS We obtained promoter sequence of PITPNM3 gene from University of Santa Cruz (UCSC) genomic database, and we predict transcriptional factor of PITPNM3 genes by JASPAR database. Target transcription factor was determined by comparison of binding sites number for promoter. SMMC-7721 cells were transfected with expression plasmid containing Mfn-2, transcription factor gene and PITPNM3. The cells transfected with empty vector were used as control. Real-time polymerase chain reaction was used to determine the mRNA level of target genes. Co-immunoprecipitation (Co-IP) assay was used to determine the interaction between Mfn-2 and target transcription factor. Chromatin immunoprecipitation assay (ChIP) assay was used to determine the binding of transcription factor with PITPNM3 promoter. Tumorigenicity assay was used to compare the effect of Mfn-2, SP1, and PITPNM3 on tumor development. RESULTS SP1 was selected as the target transcriptional factor. In the Co-IP assay, Mfn-2 was shown to interact with SP1. In the ChIP assay Mfn-2 transfection resulted in decreased binding number of SP1 with PITPNM3 promoter. Furthermore, PITPNM3 mRNA levels were significantly increased in SMMC-7721 cells transfected with SP1 but were decreased after transfection with Mfn-2. In nude mice, PITPNM3 and SP1 upregulation lead to larger tumor lump and conversely Mfn-2 upregulation lead to smaller tumor lump. CONCLUSIONS Mfn-2 could suppress expression of PITPNM3 through interaction with transcription factor SP1; Mfn-2 may have anti-tumor activity; SP1 and PITPNM3 may promote tumor development.

BACKGROUND Percutaneous endoscopic lumbar discectomy (PELD) has gained popularity as a minimally invasive surgery for treating lumbar disc herniation. However, there is limited research focusing on the reoperation rate and its associated factors. This study aims to investigate the rate of reoperation and identify the causes and risk factors for reoperation after PELD. MATERIAL AND METHODS We conducted a retrospective analysis of patients who underwent PELD (interlaminar and transforaminal approaches) at our hospital from November 2016 to May 2020. A matched case-control design was employed to identify relevant risk factors for reoperation, with a matching ratio of 1:3. Clinical characteristics and radiological parameters were compared, and univariate analysis was performed using independent samples t-test and chi-squared test. RESULTS Among the 435 patients included in the study, the reoperation rate for those with a minimum 2-year follow-up was 6.2% (27/435). The causes of reoperation and their respective rates were as follows: recurrence of lumbar disc herniation (3.2%, 14/435), incomplete decompression (1.8%, 8/435), persistent low back pain (0.7%, 3/435), and postoperative infection (0.5%, 2/435). Univariate analysis revealed that age (P=0.015), Pfirrmann grade IV-V (P=0.017), and lack of active straight leg raise exercises (P=0.026) were significantly associated with reoperation. Multiple logistic regression analysis indicated that age (P=0.001), Pfirrmann grade IV-V (P=0.033), and lack of active straight leg raise exercises postoperatively (P=0.003) were independent risk factors for reoperation after PELD. CONCLUSIONS The primary cause of reoperation in lumbar disc herniation patients after PELD was recurrence of the herniation. Additionally, severe disc degeneration, older age, and lack of active straight leg raise exercises were identified as significant risk factors associated with an increased reoperation rate.

BACKGROUND We aimed to investigate the prevalence trends and explore the influencing factors of post-stroke depression based on the National Health and Nutrition Examination Survey (NHANES) database, including data from 2005 to 2018. MATERIAL AND METHODS A total of 1298 patients with stroke were included in this study. Multivariate logistic regression analysis was performed to select influencing factors. Subgroup analysis was conducted based on different populations. The odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS The prevalence of post-stroke depression was 16.35% in 2005 and 23.29% in 2018, and presented a linear upward trend by year (F=195.00, P<0.001) from 2005 to 2018. Age (≥60 years vs <60 years; OR=0.40; 95% CI, 0.30-0.54), sex (female vs male; OR=1.37; 95% CI, 1.02-1.84), education level (junior middle school or below vs college or above; OR=0.64; 95% CI, 0.46-0.90), annual household income (≥$20,000 vs <$20,000; OR=0.60; 95% CI, 0.45-0.80), and sleep disorders (sleep disorders vs no sleep disorders; OR=4.07; 95% CI, 3.01-5.49) were associated with the risk of post-stroke depression. The age-based subgroup analysis showed that sex and education level were not influencing factors of post-stroke depression in patients ≥60 years, and education level was not related to the risk of post-stroke depression among men in the sex-based analysis. CONCLUSIONS Stroke patients with sleep disorders, age <60 years, and female sex may have an increased risk of post-stroke depression.

BACKGROUND Mitophagy, a selective autophagy process, plays various roles in tumors. Prohibitin 2 (PHB2) is an inner-mitochondrial membrane protein that participates in parkin-induced mitophagy. However, the role of PHB2 in non-small cell lung carcinoma (NSCLC) has not been previously reported. MATERIAL AND METHODS PHB2 protein or PHB2-mRNA in NSCLC and paired normal tissues was determined by Western blot, qRT-PCR, and immunohistochemical staining. Cell proliferation was detected by CCK-8 assay. Cell migration was evaluated by wound healing and transwell migration assays. A 3D live-cell confocal system was used to monitor autophagic flux. Mitochondrial autolysosomes were observed by transmission electron microscopy (TEM). Finally, we performed JC-1 assay to measure mitochondrial membrane potential (MMP). RESULTS The level of PHB2 was significantly increased in human NSCLC specimens compared to paired adjacent specimens. Inhibition of PHB2 expression attenuated mitophagy in A549 and H1299 cells, as indicated by decreased levels of LC3 II/I and parkin markers and increased level of p62 protein. Furthermore, the inhibition caused reduction in mitochondrial autolysosomes and autophagic flux, as shown by TEM and live-cell imaging, respectively. In addition, PHB2 inhibition caused a remarkable increase in MMP and suppressed the proliferation and migration of A549 and H1299 cells. CONCLUSIONS Our results suggest that downregulation of PHB2 reduced parkin-mediated mitophagy, which suppressed proliferation and migration of A549 and H1299 cells.

BACKGROUND Long non-coding RNA of myocardial infarction associated transcript (lncRNA-MIAT) has a reported role in microvascular dysfunction. This study aimed to investigate the role of lncRNA-MIAT and its effects on transforming growth factor-β1 (TGF-β1) signaling in patients with diabetic retinopathy and in ARPE-19 adult retinal pigment epithelial cells in vitro. MATERIAL AND METHODS Study participants provided plasma samples and included patients with non-proliferative diabetic retinopathy (n=52), patients with diabetes without diabetic retinopathy (n=63), and healthy controls (n=56). Plasma levels of lncRNA-MIAT and TGF-β1 were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Pearson correlation analysis was performed on the plasma data, and the diagnostic relevance of plasma levels of lncRNA-MIAT for diabetic retinopathy was evaluated by receiver operating characteristic (ROC) curve analysis. Cells of the human retinal pigment epithelial cell line, ARPE-19, were cultured in high glucose with construction and transfection of a MIAT expression plasmid vector. Viability of ARPE-19 cells was detected by the MTT assay and Western blot measured the expression levels of TGF-β1. RESULTS Plasma levels of lncRNA-MIAT were significantly increased in patients with diabetic retinopathy compared with patients with diabetes without diabetic retinopathy and with healthy controls. ARPE-19 cells cultured in a high glucose environment showed reduced cell viability and upregulation of lncRNA-MIAT expression. CONCLUSIONS Increased plasma levels of lncRNA-MIAT were significantly associated with the presence of diabetic retinopathy, and increased expression of lncRNA-MIAT reduced the viability of ARPE-19 cells in vitro by upregulating TGF-β1 signaling.

BACKGROUND Lung adenocarcinoma (LUAD) is the most common subtype of lung malignancy and is the leading cause of cancer-related mortalities worldwide. N6-methyladenosine (m6A), the most prevalent internal modification of mRNAs, plays crucial roles in regulating mRNA splicing, exportation, localization, translation, and stability. This study assessed the expression patterns and prognostic value of m6A-related genes in LUAD. MATERIAL AND METHODS The expression data of 509 LUAD samples and 20 normal samples were obtained from the Cancer Genome Atlas (TCGA) to determine the mRNA expression levels of m6A-related genomic targets. mRNA expression of 6 LUAD datasets was obtained from the Gene Expression Omnibus (GEO) repository. Subsequently, the Human Protein Atlas (HPA) and tissue microarray (TMA) cohort were used to verify the expression pattern of m6A-related genes at mRNA and protein level. The t test was used to analyze correlations between m6A-related genes and clinical features. Finally, survival analysis was performed to assess the prognostic value of m6A-related genes in LUAD patients. RESULTS We found that KIAA1429, RBM15, METTL3, HNRNPC, HNRNPA2B1, YTHDF1, and YTHDF2 were upregulated in TCGA-LUAD databases. The analysis of 7 GEO databases was consistent with the TCGA. YTHDF1 was overexpressed in LUAD patients and YTHDF2 was overexpressed in the great majority of cases. METTL3, YTHDF1, and YTHDF2 were associated with better OS and RFS. CONCLUSIONS m6A-related genes were differentially expressed in LUAD compared to matched normal patients. The m6A-related genes METTL3, YTHDF1, and YTHDF2 could serve as novel biomarkers for the prognosis of LUAD.