Impact of preoperative balance training on postoperative functional recovery of patients after total knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: Previous studies' results on the impact of preoperative balance training on postoperative functional recovery after total knee arthroplasty (TKA) appeared to be ambiguous. Thus, this systematic review and meta-analysis were performed to investigate the effects of preoperative balance training on walking ability, balance-specific performance, and other functional indicators in elderly patients post-TKA. MATERIALS AND METHODS: Patient data were obtained from databases including PubMed, Physiotherapy Evidence Database (PEDro), CINAHL, SPORTDiscus, and Scopus. The inclusion criteria followed the Population-Intervention-Comparison-Outcome (PICO) principle. The assessment process involved meticulous screening, judicious data extraction, and rigorous evaluation of trial method quality, conducted by two independent researchers. Based on standardized mean differences and 95% confidence intervals, meta-analysis was performed employing a random-effects model or fixed-effects model. RESULTS: Preoperative balance training appears to be a potentially effective intervention for enhancing the knee osteoarthritis (KOA) patients' knee joint function (RR = 1.16, 95% CI: -2.58, 4.91), isometric knee flexion (RR = 2.49, 95% CI: -2.53, 7.50), knee extension (RR = -0.13, 95% CI: -0.45, 0.18), knee society score (KSS) (RR = 2.18, 95% CI: -1.51, 5.88), stair test (RR = -0.73, 95% CI: -1.84, 0.37), and timed up and go (RR = -1.18, 95% CI: -1.60, -0.76). CONCLUSIONS: Compared to interventions with less emphasis on balance training, rehabilitation programs highly emphasizing balance training significantly enhance the walking ability, balance specificity, and functional indicators of elderly patients post-TKA. This includes rehabilitation programs for senior TKA patients, with a focus on activities meant to improve the sensory system, balance in particular.

ABCC1 is a predictive biomarker for prognosis and therapy in hepatocellular carcinoma.

OBJECTIVE: Liver neoplasm is one of the most fatal malignancies worldwide, among which hepatocellular carcinoma (HCC) (MIM #114550, https://omim.org/) is the most prevalent type. ABCC1 (MIM *158343) is a membrane-bound protein that relies on ATP hydrolysis to transport substrates and is associated with tumour drug resistance and malignant potential. However, the relationship between ABCC1, HCC prognosis, and immune infiltration remains elusive. MATERIALS AND METHODS: We analysed the mRNA expression of ABCC1 using data from public databases. Immunohistochemistry staining was performed to identify ABCC1 expression in tumour samples. We further investigated the correlation between ABCC1 and clinicopathological features. We investigated the connection between ABCC1 and HCC prognosis using survival and Cox regression analyses. We investigated the underlying pathways of ABCC1 in HCC using functional enrichment analysis and GSEA. We determine the relationship between ABCC1 and immune cell infiltration via an integrated immune landscape analysis. RESULTS: Our investigation revealed the upregulation of ABCC1 expression in HCC (p < 0.01), which was verified in clinical samples (p < 0.01). In addition, ABCC1 is adversely associated with HCC clinical features and prognosis (p < 0.05). GO/KEGG analysis and GSEA identified that ABCC1 participates in multiple immune- and tumour-related pathways (p < 0.05). Immune cell infiltration analysis indicated that ABCC1 was positively correlated with various immune cells, among which, the strongest correlation was with macrophages (p < 0.001). Furthermore, we observed significant variations in immune checkpoints between the ABCC1-low and ABCC1-high groups (p < 0.01). This indicated that patients with a high expression of ABCC1 might respond poorly to immune checkpoint blockade (ICB) therapy (p = 9.2e-07). CONCLUSIONS: Our study identified ABCC1 as a predictor of HCC prognosis and response to therapy.

A novel nomogram associated with regulatory T cells infiltration by weighted gene co-expression network analysis for predicting survival in patients with colon cancer.

OBJECTIVE: Traditional diagnostic strategies are unable to accurately discriminate between patients with poor and satisfied prognosis in colon cancer. Therefore, it is urgently recommended to identify new biomarkers in favor of better selection of patients at higher risk of recurrence or poor outcomes, with the aim of early intervention or avoiding overtreatment. MATERIALS AND METHODS: The weighted gene correlation network analysis (WGCNA), together with the proportion of tumor infiltrating immune cells, were employed to screen the key module related to immune infiltration. Using these genes among the key module, a predictive signature was generated via LASSO and multi-Cox regression method. Moreover, a novel nomogram was further developed by combining important clinical parameters and the predictive signature. RESULTS: Genes among the green module, indicating the highest correlation with regulatory T cells (Tregs), were incorporated into the establishment of predictive model. Then, a Tregs-related risk signature (TRRS) consisting of four genes (NRG1, TEX11, OVOL3 and FCRL2) was established, which performed well in predicting the mortality risk of colon cancer in both internal and external validation groups (p=0.004 for TCGA training set, p=0.016 for TCGA testing set and p=0.03 for GSE39582 dataset). Combining TNM stage and age, we developed a nomogram for 1-, 3-, 5-year OS, presenting a more reliable predictive performance in survival based on the receiver operating characteristic (ROC) curves and calibration curves (3-year AUC: 0.83 and 0.74 in the TCGA and GEO database, respectively). CONCLUSIONS: We constructed a four-gene signature for predicting the prognosis of patients with colon cancer, and further developed the nomogram together with TNM stage and age to improve the predictive efficacy.

Intervention effect of Potentilla discolor-Euonymus alatus on intestinal flora of type 2 diabetes mellitus rats.

OBJECTIVE: With this study, we aimed at exploring the regulation mechanism of Potentilla discolor-Euonymus alatus on intestinal flora of T2DM (Type 2 Diabetes Mellitus) rats induced by high-fat diet combined with streptozotocin. MATERIALS AND METHODS: T2DM rats were induced by high-fat diet combined with streptozotocin. There were normal control group, model group, metformin group, high-dose Chinese medicine group and low-dose Chinese medicine group. Each group included 10 rats. Normal control group: normal feeding, no modeling, ordinary feed, and gavage of 0.9% normal saline. Model group: T2DM rats, high-fat diet, and gavage of 0.9% normal saline. Metformin group: T2DM rats, high-fat diet and fed with metformin solution. High-dose Chinese medicine group: T2DM rats, high-fat diet, and gavage of concentrated Chinese medicine at a dose of 6 times the clinical dose. Low-dose Chinese medicine group: T2DM rats, high-fat diet, and gavage of concentrated Chinese medicine at a dose twice the clinical dose. The general situation of T2DM rats was observed, and the changes of intestinal flora were observed with 16SrDNA sequencing. RESULTS: The T2DM rats induced by high-fat diet combined with streptozotocin were molded. After intervention, at the class level, the ratio of γ-proteobacteria was 22.30% in the model group, 11.97% in the metformin group, 3.24% in the high-dose Chinese herbs group and 1.72% in the low-dose Chinese herbs group; the ratio of Erysipelothrix insidiosa was 4.73% in the model group, 4.68% in the metformin group, 3.93% in the high-dose Chinese herbsgroup and 2.92% in the low dose group; the ratio of Lactinobacillus was 2.30% in the model group, 0.01% in the metformin group, 0.00% in the high-dose Chinese herbs group, and 0.00% low-dose Chinese herbs group; at the portal level, the Firmicutes/Bacteroides was 0.88 in the normal control group, 3.40 in the model group, 1.71 in the metformin group, 2.74 in high-dose Chinese medicine group, and 1.34 in low-dose Chinese medicine group; at the genus level, the relative abundance of Lactobacillus in the model group was 3.28%, that of Akkermansia was 1.99%, that of Shigella coli was 22.08%, and that of Vibrio phaseus was 7.67%. All of them were improved after the intervention of metformin and traditional Chinese medicine. CONCLUSIONS: Potentilla discolor-Euonymus Alatus could improve the composition and structure of intestinal flora in T2DM rats and regulate the diversity of intestinal flora. The ratio of Firmicutes/Bacteroidetes was adjusted, mainly to increase the number of Bacteroides; the flora related to intestinal barrier was adjusted, mainly to increase the number of Lactobacillus and Akkermansia bacteria.

The relationship between hepatitis B virus serum DNA, RNA and quantitative hepatitis B surface antigen, and the predictive value for mother-to-child transmission: an observational cohort study.

OBJECTIVE: To explore the relationships between hepatitis B virus (HBV) DNA, HBV RNA and hepatitis B surface antigen (HBsAg) and to evaluate their predictive value for mother-to-child transmission of HBV. DESIGN: An observational cohort study. SETTING: First Hospital of Jilin University. POPULATION: HBsAg-positive and hepatitis B e antigen (HBeAg) -positive pregnant women were recruited. METHODS: Blood samples were collected from mothers before delivery, and HBV infection of infants was evaluated at 7 months of age. RESULTS: Overall, 268 mothers and 271 infants were enrolled. HBV DNA and HBsAg levels were correlated (rs = 0.699; P < 0.001), and HBV DNA (rs = 0.500; P < 0.001) and HBsAg (rs = 0.372; P < 0.001) were both correlated with HBV RNA. The areas under the curve for HBV DNA, HBsAg and HBV RNA for prediction of infection were 0.69 (95% CI 0.57-0.82), 0.63 (95% CI 0.51-0.76) and 0.65 (95% CI 0.52-0.78), respectively. Higher HBV DNA (odds ratio [OR] 4.77, 95% CI 1.44-15.86), higher HBsAg (OR 4.13, 95% CI 1.12-15.25) and higher HBV RNA (OR 3.19, 95% CI 1.09-9.32) were risk factors for HBV infection. Analysis of the HBV DNA-RNA-HBsAg Score revealed that it was an independent predictive factor for mother-to-child transmission (the OR of Score 3 was 8.81, 95% CI 2.79-27.82). CONCLUSION: HBV DNA, HBV RNA and HBsAg were correlated in HBeAg-positive pregnant women. HBsAg could be considered as a substitute marker of HBV DNA for HBeAg-positive pregnant women in low-income regions. We should pay special attention to pregnant women with high levels of all three markers. TWEETABLE ABSTRACT: HBsAg could be considered as a substitute marker of HBV DNA for HBeAg-positive pregnant women in low-income regions. Special attention should be given to pregnant women with high levels of all three markers (HBV DNA, HBV RNA and HBsAg).

MiR-150 inhibits proliferation of mantle-cell lymphoma cells via regulation of MET.

OBJECTIVE: The aim of this study was to explore the influences of micro ribonucleic acid (miR)-150 on the proliferation and apoptosis of mantle-cell lymphoma (MCL) cells and to investigate the potential underlying mechanism. PATIENTS AND METHODS: Differentially expressed miRNAs in MCL tissues were excavated via microarray analysis of miRNA expression profiles. Subsequently, the expression of miRNAs were verified by quantitative Reverse Transcription-Polymerase Chain Reaction (RT-qPCR). The influence of miRNA expression on the survival of patients was detected based on clinical data. Besides, the potential targets of miRNAs were determined using Luciferase reporter gene assay combined with qRT-PCR and Western blotting. Primary tumor cells were extracted, and the influences of miR-150 expression on cell proliferation were detected via Cell Counting Kit (CCK)-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) staining assay. Finally, Western blotting and flow cytometry were performed to explore the impact of miR-150 on the apoptosis of primary tumor cells. RESULTS: Microarray analysis of miRNA expression profiles and RT-qPCR verified that the expression levels of hsa-miR-486, hsa-miR-4746, and hsa-miR-3158 rose considerably in MCL tissues, while those of hsa-miR-29b-3p, hsa-miR-150, and hsa-miR-142-5p remarkably declined. According to the results of survival analysis, the survival time was notably prolonged in patients with higher expression levels of miR-150 and miR-486, especially in those with higher expression level of miR-150. Luciferase reporter gene assay and RT-qPCR and Western blotting results demonstrated that miR-150 negatively regulated the expression level of MET. Subsequent CCK-8 assay and EdU staining results revealed that up-regulation of miR-150 significantly suppressed the proliferation of primary MCL cells. Finally, Western blotting and flow cytometry found that increased expression of MET remarkably facilitated the apoptosis of primary MCL cells. CONCLUSIONS: MiR-150 inhibits the proliferation and promotes the apoptosis of MCL cells by negatively regulating MET expression.

MiR-16 inhibits pituitary adenoma cell proliferation via the suppression of ERK/MAPK signal pathway.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-16 inhibits pituitary adenoma cell proliferation via the suppression of ERK/MAPK signal pathway, by D.-W. Wang, Y.-Q. Wang, H.-S. Shu, published in Eur Rev Med Pharmacol Sci 2018; 22 (5): 1241-1248-DOI: 10.26355/eurrev_201803_14464-PMID: 29565480" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14464.

Long noncoding RNA LUCAT1 promotes migration and invasion of prostate cancer cells by inhibiting KISS1 expression.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA LUCAT1 promotes migration and invasion of prostate cancer cells by inhibiting KISS1 expression, by C. Liu, L. Wang, Y.-W. Li, Y.-S. Cui, Y.-Q. Wang, S. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23 (8): 3277-3283-DOI: 10.26355/eurrev_201904_17689-PMID: 31081080" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17689.

Expression level of miRNA-210-3p in cervical cancer and its prognostic potential.

OBJECTIVE: The purpose of this study was to detect the expression level of microRNA-210-3p (miRNA-210-3p) in cervical cancer (CC) tissues and its clinical significance. PATIENTS AND METHODS: Expression levels of miRNA-210-3p in collected CC tissues, normal cervical tissues and cervical intraepithelial neoplasia (CIN) tissues (CIN I, CIN II, and CIN III) were tested by reverse transcriptase-polymerase chain reaction (RT-PCR). The relationship between miRNA-210-3p level and clinical data of CC patients was analyzed. Moreover, the receiver operating characteristic (ROC) was introduced for assessing the diagnostic potential of miRNA-210-3p in CC. RESULTS: Results revealed that miRNA-210-3p level was higher in CC tissues relative to normal cervical tissues and CIN tissues. Its expression was not correlated with age, pathological subtype, and tumor size of CC patients. However, miRNA-210-3p level was closely linked to FIGO stage, tumor differentiation, and lymphatic metastasis in CC. Based on depicted ROC, miRNA-210-3p was able to distinguish CC from normal cervical tissues and CIN tissues. CONCLUSIONS: MiRNA-210-3p is upregulated in CC, and its level is closely correlated with FIGO stage, tumor differentiation, and lymphatic metastasis in CC patients. Besides, miRNA-210-3p produces a pronounced diagnostic efficacy, so it can be utilized as a novel hallmark for diagnosing CC and predicting the disease progression.

MiR-942-5p alleviates septic acute kidney injury by targeting FOXO3.

OBJECTIVE: Sepsis refers to the systemic inflammatory response caused by infection. Acute kidney injury (AKI) in sepsis is very common, and there are many complicated mechanisms for the occurrence of septic AKI. This article aimed to study the role of miR-942-5p in inflammation and apoptosis of septic AKI and its potential mechanism. MATERIALS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to detect the expression of RNAs. The protein expression was detected using Western blot. The contents of inflammatory factors in the cell supernatant were detected using commercial enzyme-linked immunosorbent assay (ELISA) kits. Cell Counting Kit-8 (CCK-8) assay was utilized to compare the cell viability of each group. Terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining and flow cytometry were used to observe cell apoptosis. RESULTS: MiR-942-5p expression was reduced in lipopolysaccharide (LPS)-treated HK-2 cells. MiR-942-5p mimic could observably increase miR-942-5p expression. The overexpression of miR-942-5p dramatically inhibits the expression of inflammatory factors and Bax, but increase Bcl-2 expression. MiR-942-5p overexpression greatly reversed the LPS-induced decrease in viability of HK-2 cells. In addition, we observed that LPS can markedly increase the number of apoptosis, while miR-942-5p mimic can reduce it. CONCLUSIONS: Taken together, our results demonstrated that miR-942-5p expression was reduced in the LPS-treated HK-2 cells, and miR-942-5p overexpression can inhibit LPS-induced inflammation and apoptosis of HK-2 cells via targeting FOXO3.

LncRNA FOXC2-AS1 regulated proliferation and apoptosis of vascular smooth muscle cell through targeting miR-1253/FOXF1 axis in atherosclerosis.

OBJECTIVE: Atherosclerosis (AS) is the most dangerous factor for human death, which is responsible for coronary heart disease. Growing evidence has showed that long non-coding RNAs (lncRNAs) are involved in the development of AS. In this study, we mainly aimed at investigating the roles of FOXC2-AS1 in AS patients. PATIENTS AND METHODS: RT-PCR was performed to detect the expressions of FOXC2-AS1 and miR-1253 in serum samples of AS patients (n=35) and healthy volunteer (n=35). The correlation between FOXC2-AS1 and miR-1253 was further analyzed. Human vascular smooth muscle cells (VSMCs) were respectively treated with ox-LDL, IL-6, CRP, TNF-α and IL-8 to explore the affecting factors. P-FOXC2-AS1 was constructed and transfected into VSMCs. Cell proliferation abilities were measured by CCK-8 assay. Cell apoptotic rates were measured by flow cytometry (FACS) analysis. Western blot (WB) was performed to detect protein levels of FOXF1, Bcl-2, Bax and Cleaved Caspase3. Finally, luciferase gene reporter assay was performed to prove the relationships between FOXC2-AS1 and miR-1253, miR-1253 and FOXF1. RESULTS: We found that FOXC2-AS1 was significantly upregulated in AS patients, which could be induced by ox-LDL and IL-6 in VSMCs. MiR-1253 was decreased in AS patients, which was negatively correlated with FOXC2-AS1. Furthermore, FOXC2-AS1 overexpression promoted proliferation and inhibited apoptosis in VSMCs. Luciferase gene reporter assay showed that FOXC2-AS1 could bind to miR-1253 in VSMCs and 293 cells. Moreover, miR-1253 overexpression inhibited proliferation and promoted apoptosis of VSMCs. Luciferase reporter assay proved that miR-1253 could target at FOXF1 in VSMCs and 293 cells, which was reported to be associated with cell proliferation and apoptosis in some cancers. Additionally, miR-1253 mimic or GSK343, a FOXF1 inhibitor, was respectively transfected into VSMCs with p-FOXC2-AS1. Results showed that the promoted cell proliferation and inhibited cell apoptosis were reversed as well, confirming that FOXC2-AS1 promoted cell proliferation and inhibited apoptosis via miR-1253/FOXF1 signaling axis in AS patients. CONCLUSIONS: According to the results, we found that FOXC2-AS1 was upregulated in AS patients; furthermore, FOXC2-AS1 overexpression promoted cell proliferation and inhibited cell apoptosis via targeting miR-1253/FOXF1 signaling axis. Our results elucidated a potential mechanism underlying the role of FOXC2-AS1, which might be used as a promising marker and a potential target for AS patients.

Hexarelin protects cardiac H9C2 cells from angiotensin II-induced hypertrophy via the regulation of autophagy.

Hexarelin is a synthetic growth hormone-releasing peptide that exerts cardioprotective effects. Regulation of autophagy is known to be cardioprotective so this study examined the role of autophagy and potential regulatory mechanisms in hexarelin-elicited anti-cardiac hypertrophic action in cardiomyocytes subjected to hypertrophy. H9C2 cardiomyocytes were subjected to hypertrophy by angiotensin-II (Ang-II). Autophagic light chain-3 (LC3) and cytoskeletal proteins were determined by immunofluorescence assay. Autophagy was also detected using monodansylcadaverine (MDC) for autophagic vacuole visualization and Cyto-ID staining for autophagic flux measurement. Molecular changes were analysed by Western blotting and qRT-PCR. Apoptosis was evaluated using flow cytometry and TUNEL assay. ATP content and CCK-8 assay were used in assessing enhanced cell survival whilst oxidative stress was analysed by measuring malondialdehyde(MDA) and superoxide dismutase(SOD) levels. Ang-II induced cardiomyocyte hypertrophy, oxidative stress, apoptosis and decreased cell survival, all of which were significantly suppressed by hexarelin treatment which also enhanced autophagy in hypertrophic H9C2 cells. Furthermore, inhibition of hexarelin induced autophagy by 3-methyladenine (3MA) abolished the anti-hypertrophic function of hexarelin and also abrogated the protection of hexarelin against cell survival inhibition and apoptosis. Conversely, the application of autophagy stimulator rapamycin in H9C2 hypertrophic cells inhibited apoptosis, cell survival and reduced cell size as well. Additionally, hexarelin regulated the upstream signalling of autophagy by inhibiting the phosphorylation of mammalian target of rapamycin(mTOR). We propose that hexarelin plays a novel role of attenuating cardiomyocyte hypertrophy and apoptosis via an autophagy-dependent mechanism associated with the suppression of the mTOR signalling pathway.

Liraglutide protects from renal damage via Akt-mTOR pathway in rats with diabetic kidney disease.

OBJECTIVE: To explore the protective effect of liraglutide on renal damage in rats with diabetic kidney disease (DKD) through the protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. MATERIALS AND METHODS: A total of 45 specific pathogen-free male Sprague-Dawley rats were divided into healthy group (no diabetes, n=15), diabetes group (diabetes, n=15), and liraglutide group (diabetes + liraglutide intervention, n=15). The differences in the biochemical indexes, lesion degree, glomerular Nephrin expression level, and mRNA and protein expressions of Akt-mTOR in renal tissues were detected in three groups via hematoxylin-eosin (HE) staining, immunohistochemistry, Western blotting, and quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), respectively. RESULTS: The albumin-to-creatinine ratio (ACR) and levels of serum creatinine (Scr), urine microalbumin (UmAlb), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) in renal tissues were the lowest in healthy group and the highest in diabetes group, while they significantly declined in liraglutide group compared with those in diabetes group. Also, there were statistically significant differences (p<0.05). The level of high-density lipoprotein cholesterol (HDL-C) in renal tissues was the highest in healthy group and the lowest in diabetes group, while it was significantly increased in liraglutide group compared with that in diabetes group. Also, there were statistically significant differences (p<0.05). In healthy group, the mesangial structure and renal tubules were normal, the tubular basement membrane was smooth and intact, and there were no interstitial widening and inflammatory cell infiltration. Compared with diabetes group, the mesangial cell proliferation and vacuolar degeneration were alleviated, while the tubular dilatation or atrophy, fibrous tissues, and inflammatory cells were reduced in liraglutide group. Moreover, the results of immunohistochemical staining revealed that the glomerular Nephrin protein was arranged uniformly and showed the blue-black particles in healthy group. The glomerular Nephrin protein expressed was significantly decreased and arranged disorderly in diabetes group compared with that in healthy group, while it was increased in liraglutide group compared with that in diabetes group (p<0.05). The protein expression of Akt-mTOR in renal tissues was the lowest in healthy group and the highest in diabetes group, while it markedly declined in liraglutide group compared with that in diabetes group, displaying statistically significant differences (p<0.05). Similarly, the mRNA expression of Akt-mTOR in renal tissues was the lowest in healthy group and the highest in diabetes group, while it markedly declined in liraglutide group compared with that in diabetes group, displaying also statistically significant differences (p<0.05). CONCLUSIONS: Liraglutide can significantly reduce the blood glucose and improve the renal function in rats by suppressing the protein expression of AKT-mTOR, thereby exerting a protective effect on renal damage in rats with DKD.

Long noncoding RNA LUCAT1 promotes migration and invasion of prostate cancer cells by inhibiting KISS1 expression.

OBJECTIVE: Recent researches have revealed the role of long noncoding RNAs (lncRNAs) in tumor development. In this study, the potential function of lncRNA LUCAT1 in the progression of prostate cancer was identified. PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was used to detect LUCAT1 expression in both prostate cancer cells and tissue samples. Moreover, the association between LUCAT1 expression level and overall survival of prostate cancer patients was analyzed. In addition, wound healing assay and transwell assay were conducted to evaluate the regulatory effect of LUCAT1 on prostate cancer cells. Furthermore, the underlying mechanism of LUCAT1 in regulating the development of prostate cancer was explored via qRT-PCR and Western blot. RESULTS: LUCAT1 expression was much higher in prostate cancer samples than controls. Besides, LUCAT1 expression was correlated with the overall survival of prostate cancer patients. Moreover, LUCAT1 overexpression promoted in vitro migration and invasion of prostate cancer cells. In addition, the mRNA and protein expression of KISS1 were downregulated after LUCAT1 overexpression. Furthermore, it was found that the expression level of KISS1 was negatively related to the expression level of LUCAT1 in prostate cancer tissues. CONCLUSIONS: LUCAT1 could enhance migration and invasion of prostate cancer cells by regulating KISS1, which might offer a potential therapeutic target for prostate cancer.

MicroRNA-494-3p alleviates inflammatory response in sepsis by targeting TLR6.

OBJECTIVE: To clarify whether microRNA-494-3p could exert an anti-inflammation effect by suppressing the expression of toll-like receptor 6 (TLR6), thus inhibiting the development of sepsis. PATIENTS AND METHODS: Plasma levels of microRNA-494-3p and TLR6 in sepsis patients and healthy controls were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Diagnostic potential of microRNA-494-3p in sepsis was evaluated by receiver operating characteristic (ROC) curve. In vitro macrophage inflammation model was established by lipopolysaccharides (LPS) induction in RAW264.7 cells. Expression levels of microRNA-494-3p, TLR6 and tumor necrosis factor-α (TNF-α) in LPS-induced RAW264.7 cells were observed. After transfection of microRNA-494-3p mimics in LPS-induced RAW264.7 cells, mRNA and protein levels of TNF-α were determined by qRT-PCR and Western blot, respectively. Meanwhile, cytoplasmic and nuclear fractions of nuclear factor-kappa B (NF-κB) p65 were respectively extracted for evaluating nuclear translocation of NF-κB p65 by Western blot analysis. Dual-luciferase reporter gene assay was performed to verify the binding between microRNA-494-3p and TLR6. Finally, rescue experiments were carried out to elucidate whether microRNA-494-3p attenuated sepsis-induced inflammation through degrading TLR6. RESULTS: Plasma level of microRNA-494-3p in sepsis patients was markedly lower than healthy controls, while plasma level of TLR6 was conversely higher in sepsis patients. With the prolongation of LPS induction in RAW264.7 cells, expression levels of TLR6 and TNF-α gradually increased, whereas microRNA-494-3p expression decreased. Transfection of microRNA-494-3p mimics in RAW264.7 cells reduced TNF-α level, and inhibited nuclear translocation of NF-κB p65. TLR6 was found to be a target gene of microRNA-494-3p, and its expression was markedly downregulated by microRNA-494-3p overexpression. Finally, we proved that the inhibitory effects of microRNA-494-3p on TNF-α level and nuclear translocation of NF-κB p65 were reversed by TLR6. CONCLUSIONS: High expression of microRNA-494-3p attenuated sepsis-induced inflammatory response by degrading TLR6.

Influences of up-regulation of miR-126 on septic inflammation and prognosis through AKT/Rac1 signaling pathway.

OBJECTIVE: To explore the influences of the up-regulation of micro ribonucleic acid (miR)-126 on septic inflammation and prognosis through the AKT/Rac1 signaling pathway. MATERIALS AND METHODS: Human pulmonary microvascular endothelial cells (HMVECs) were cultured and transfected with miR-126 mimics. The HMVECs in the logarithmic growth phase in different groups were incubated with thrombin. The transmembrane resistivity of HMVECs was detected as the permeability via Electric Cell-substrate Impedance Sensing (ECIS) system. The endothelial cell space was observed via immunofluorescence. The mouse model of sepsis was then established and the serum was extracted to detect interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The survival curve was plotted based on the death time. The Statistical Product and Service Solutions (SPSS) 22.0 was used for statistical analysis, and p<0.05 suggested that the difference was statistically significant. RESULTS: Thrombin could significantly increase the permeability of HMVECs, while the overexpression of miR-126 markedly inhibited the increased permeability. The overexpression of miR-126 also reduced the endothelial cell space induced by thrombin. In addition, the serum IL-6 and TNF-α levels of sepsis mice in miR-126 overexpression group were significantly decreased compared to those in the control group. Moreover, the death rate of mice exogenously expressing miR-126 was lower than that in the control group. CONCLUSIONS: The up-regulation of miR-126 inhibited the septic inflammation and improved the prognosis of sepsis mice through the AKT/Rac1 signaling pathway.

Identification and validation of novel microenvironment-based immune molecular subgroups of head and neck squamous cell carcinoma: implications for immunotherapy.

Background: Targeting the immune checkpoint pathway has demonstrated antitumor cytotoxicity in treatment-refractory head and neck squamous cell carcinoma (HNSC). To understand the molecular mechanisms underpinning its antitumor response, we characterized the immune landscape of HNSC by their tumor and stromal compartments to identify novel immune molecular subgroups. Patients and methods: A training cohort of 522 HNSC samples from the Cancer Genome Atlas profiled by RNA sequencing was analyzed. We separated gene expression patterns from tumor, stromal, and immune cell gene using a non-negative matrix factorization algorithm. We correlated the expression patterns with a set of immune-related gene signatures, potential immune biomarkers, and clinicopathological features. Six independent datasets containing 838 HNSC samples were used for validation. Results: Approximately 40% of HNSCs in the cohort (211/522) were identified to show enriched inflammatory response, enhanced cytolytic activity, and active interferon-γ signaling (all, P < 0.001). We named this new molecular class of tumors the Immune Class. Then we found it contained two distinct microenvironment-based subtypes, characterized by markers of active or exhausted immune response. The Exhausted Immune Class was characterized by enrichment of activated stroma and anti-inflammatory M2 macrophage signatures, WNT/transforming growth factor-ß signaling pathway activation and poor survival (all, P < 0.05). An enriched proinflammatory M1 macrophage signature, enhanced cytolytic activity, abundant tumor-infiltrating lymphocytes, high human papillomavirus (HPV) infection, and favorable prognosis were associated with Active Immune Class (all, P < 0.05). The robustness of these immune molecular subgroups was verified in the validation cohorts, and Active Immune Class showed potential response to programmed cell death-1 blockade (P = 0.01). Conclusions: This study revealed a novel Immune Class in HNSC; two subclasses characterized by active or exhausted immune responses were also identified. These findings provide new insights into tailoring immunotherapeutic strategies for different HNSC subgroups.

The function of hyperpolarization-activated cyclic nucleotide-gated channel in diabetic cystopathy.

OBJECTIVE: We aimed at investigating changes in the expression and physiological function of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in interstitial cells of Cajal (ICC) in diabetic state. MATERIALS AND METHODS: Twenty adult female Sprague-Dawley (SD) rats were randomly assigned to control and Zucker diabetic fatty (ZDF) group. The protein and mRNA expression of HCN isoforms and C-kit in the rat bladders were detected using Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). The bladder contraction was evaluated using a bladder smooth muscle strip test. Whole cell patch-clamp techniques were used to detect the activity of HCN channels. Immunofluorescent staining was used to the positive expression of HCN and C-kit in ICC. RESULTS: cAMP, as HCN channel-specific stimulant, could increase the frequency and amplitude of spontaneous contractions in both group, while cAMP inducing contraction of ZDF rats, was still significantly lower compared with the control group. Acute bladder ICCs were isolated by collagenase digestion. Classic Ih current pattern was recorded on ICCs while Ih current amplitude of ICCs from ZDF diabetic rats was significantly lower than the control group. The expression and mRNA of HCN1-4 isoforms in ZDF diabetic rats were both significantly lower compared with the control group. Meanwhile, the number of c-kit positive cells in ZDF diabetic rats showed no significant differences compared with controls. The morphological structure of ICC in the bladder of ZDF rats was relatively loose and the number of their cell process was apparently decreased. CONCLUSIONS: The structure of ICCs in ZDF rats was relatively loose, their connection to each other was also diminished. The expression of HCN was down-regulated and its response to cAMP was also decreased. HCN channels in bladder ICCs might regulate detrusor contraction. Changes in HCN expression and activity in bladder ICCs might be one of the most important mechanisms of diabetic cystopathy.

Human papillomavirus infection and colorectal cancer in the Chinese population: a meta-analysis.

AIM: Human papillomavirus (HPV) infection has been reported in colorectal cancer in many studies. We conducted a meta-analysis to assess the association between HPV infection and colorectal cancer/adenomas in the Chinese population. METHOD: Relevant studies up to January 2018 were searched in PubMed, EMBASE, China National Knowledge Infrastructure and the Wanfang database. We used a random effects model to determine the prevalence of HPV and odds ratios (ORs) with 95% confidence intervals (CIs). The I2 statistic and P-value from the Cochrane Q-test were used to describe the heterogeneity. RESULTS: Ten case-control studies involving 766 colorectal cancer patients and 470 controls were included in the meta-analysis. Among the colorectal cancer patients, the pooled prevalence was 0.45 (95% CI 0.36-0.53). The pooled estimate for OR was 10.78 (95% CI 4.22, 27.53). Among the 193 patients with colorectal adenoma, the pooled prevalence and OR were 0.31 (95% CI 0.24-0.37) and 2.03 (95% CI 0.79, 5.26), respectively. The prevalence of HPV 16 and HPV 18 among HPV-positive cancers ranged from 57.9% to 100% and 0% to 39.7%, respectively. CONCLUSION: The results indicated that HPV infection, especially HPV 16 and HPV 18, is associated with colorectal cancer in the Chinese population.

Expressions and effects of G250, Bax and Bcl-2 in rats with renal clear cell carcinoma.

OBJECTIVE: To investigate the expressions and effects of G250, B-cell lymphoma-2 associated X protein (Bax) and Bcl-2 in rats with renal clear cell carcinoma (RCCC). MATERIALS AND METHODS: A total of 66 male Sprague-Dawley (SD) rats were selected, among which 56 were selected to establish RCCC rat model and the remaining 10 were selected as control group. Three weeks after modeling, 4 rats failed in the modeling. Expressions of G250 in RCCC rat model group and healthy rat model control group were detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR); expressions of Bcl-2 and Bax in each group were detected by Western blot and their effects were analyzed. RESULTS: The positive expression rates of G250 in 52 RCCC rats in model group and 10 healthy rats in control group were 83.3% and 0%, respectively. The results showed that expression of G250 had a certain correlation with the pathological changes of RCCC (p < 0.01). Expressions of Bax and Bcl-2 were up-regulated in the RCCC group, while expressions were down-regulated in the healthy control group (p < 0.05). CONCLUSIONS: G250, as a new specific marker of renal cell carcinoma, is involved in the pathological changes of renal cell carcinoma. Joint detection of Bax and Bcl-2 can be used as an important index for the diagnosis of RCCC.