The neuroprotective effects of Galectin-1 on Parkinson's Disease via regulation of Nrf2 expression.

OBJECTIVE: Parkinson's disease (PD) is one of the neurodegenerative diseases. Galectin-1 (Gal-1) is expressed in the central nervous system. Our study sought to explore the neuroprotective effect of Gal-1 in 1­methyl­4­phenyl pyridine ion (MPP+)-induced cytotoxicity on SH-SY5Y cells. MATERIALS AND METHODS: SH-SY5Y cells were cultured in vitro, pretreated with Gal-1, and then exposed to MPP+. Thereafter, the generation of reactive oxygen species (ROS) in SH-SY5Y cells was investigated. The effects of Gal-1 on DNA breakage, cell damage (release of lactate dehydrogenase (LDH)), viability, and apoptosis in SH-SY5Y cells were examined by comet assay, LDH assay, WST-1 assay, and flow cytometry, respectively. Additionally, the regulatory effect of Gal-1 on Nrf2 expression was examined by western blot. Zebrafish embryos were pretreated with Gal-1 and then exposed to MPP+. The locomotor ability of zebrafish larvae was then investigated. RESULTS: MPP+ induced the production of ROS in cells, which can be alleviated by pretreatment with Gal-1. Gal-1 protected cells from MPP+-induced cytotoxicity by preventing DNA breakage and cell injury. Gal-1 inhibited apoptosis in SH-SY5Y cells. The neuroprotective effect of Gal-1 could be abolished when Nrf2 expression knockdown. Moreover, exposure to MPP+ decreased the locomotor activity of zebrafish, which was attenuated by pretreatment with Gal-1. CONCLUSIONS: Our study demonstrated that the administration of Gal-1 could protect neurons from cellular stress by preventing apoptosis and eliminating ROS. Moreover, the neuroprotective effect of Gal-1 in neuronal cells could be related to the activation of Nrf2 expression. Therefore, Gal-1 could be a promising strategy for treating PD.

Effects of PPARγ agonist pioglitazone on cardiac fibrosis in diabetic mice by regulating PTEN/AKT/FAK pathway.

OBJECTIVE: The aim of this study was to explore the role of pioglitazone (PIO), a peroxisome proliferator-activated receptor-gamma (PPARγ) agonist, in cardiac fibrosis of diabetic mice. MATERIALS AND METHODS: A total of 60 adult male C57/B6 mice were divided into 3 groups using a random number table, namely, control group (Sham group, n=20), diabetic cardiomyopathy group (DCM group, n=20), DCM + PIO group (n=20). Streptozocin (STZ) was injected into mice at a dose of 125 mg/Kg to induce the model of diabetes in vivo. After successful induction, mice in DCM + PIO group were intragastrically given PIO at 10 mg/kg/d once a day for 6 weeks. Meanwhile, those in Sham group and DCM group were given the same volume of normal saline. After 6 weeks, ejection fraction % (EF%), fraction shortening % (FS%) and heart rate of mice in each group were examined via echocardiography. Picrosirius red (PSR) staining assay was conducted to detect collagen deposition in myocardial tissues of mice in each group. The protein expression level of PPARγ in mouse myocardial tissues in each group was measured through Western blotting and immunohistochemical staining assays. Hematoxylin-eosin (H&E) staining assay was carried out to evaluate the myocardial hypertrophy of mice in each group. The protein expression level of transforming growth factor-ß (TGF-ß) in mouse myocardial tissues in each group was measured through immunohistochemical staining assay. In addition, Western blotting was employed to detect the expression of proteins related to the phosphate and tension homology deleted on chromsome ten (PTEN)/protein kinase B (AKT)/focal adhesion kinase (FAK) signaling pathway in myocardial tissues of mice in each group. RESULTS: The messenger ribonucleic acid (mRNA) and protein expression levels of PPARγ in mouse myocardial tissues were significantly lower in DCM group than those in Sham group (p<0.05). PPARγ agonist PIO could significantly increase the protein expression of PPARγ in myocardial tissues of DCM mice. The results of cardiac Doppler ultrasound revealed that PIO significantly upregulated EF% and FS% in DCM mice (p<0.05). Besides, PIO remarkably reduced collagen deposition and TGF-ß protein expression in myocardial tissues in DCM mice (p<0.05). H&E staining results showed that PIO notably attenuated myocardial hypertrophy in DCM mice (p<0.05). Furthermore, it was discovered that PIO markedly elevated PTEN protein in myocardial tissues of DCM mice and inhibited the phosphorylation of AKT and FAK proteins (p<0.05). CONCLUSIONS: The protective effect of PIO against cardiac fibrosis in diabetic mice may be related to its regulation on the PTEN/AKT/FAK signaling pathway. Our findings suggest that PIO is expected to become a targeted drug for the treatment of DCM in clinical practice.

Lesion-aware convolutional neural network for chest radiograph classification.

AIM: To investigate the performance of a deep-learning approach termed lesion-aware convolutional neural network (LACNN) to identify 14 different thoracic diseases on chest X-rays (CXRs). MATERIALS AND METHODS: In total, 10,738 CXRs of 3,526 patients were collected retrospectively. Of these, 1,937 CXRs of 598 patients were selected for training and optimising the lesion-detection network (LDN) of LACNN. The remaining 8,801 CXRs from 2,928 patients were used to train and test the classification network of LACNN. The discriminative performance of the deep-learning approach was compared with that obtained by the radiologists. In addition, its generalisation was validated on the independent public dataset, ChestX-ray14. The decision-making process of the model was visualised by occlusion testing, and the effect of the integration of CXRs and non-image data on model performance was also investigated. In a systematic evaluation, F1 score, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) metrics were calculated. RESULTS: The model generated statistically significantly higher AUC performance compared with radiologists on atelectasis, mass, and nodule, with AUC values of 0.831 (95% confidence interval [CI]: 0.807-0.855), 0.959 (95% CI: 0.944-0.974), and 0.928 (95% CI: 0.906-0.950), respectively. For the other 11 pathologies, there were no statistically significant differences. The average time to complete each CXR classification in the testing dataset was substantially longer for the radiologists (∼35 seconds) than for the LACNN (∼0.197 seconds). In the ChestX-ray14 dataset, the present model also showed competitive performance in comparison with other state-of-the-art deep-learning approaches. Model performance was slightly improved when introducing non-image data. CONCLUSION: The proposed LACNN achieved radiologist-level performance in identifying thoracic diseases on CXRs, and could potentially expand patient access to CXR diagnostics.

Clinical features and survival impact of EBV-positive diffuse large B-Cell lymphoma with different age cutoffs.

OBJECTIVE: In 2016 WHO classification, EBV +DLBCL of the elderly was replaced by EBV+ DLBCL NOS. This is due to the fact that many young patients of EBV+ DLBCL were found in recent years. PATIENTS AND METHODS: In this study, we retrospectively analyzed clinical features and survival outcomes of EBV positive DLBCL patients in different age groups. All the patients treated at a single center. RESULTS: When we use different ages (40, 50 and 60 years old) as cutoffs, the prevalence of EBV positive DLBCL was 12.0%, 12.3% and 13.0% in younger patients and 19.0%, 15.4% and 13.8% in elder patients respectively. Whatever the age cutoff was, EBV positive associated with unfavorable clinical prognosis in elder groups. When we use 40 and 50 years old as age cutoffs, poor impacts of EBV positive on overall survival and progression-free survival were observed only in elder patients, but not in younger patients. It should be noted that when we use 60 years old as age cutoff, the results were the opposite. CONCLUSIONS: EBV+ DLBCL patients with age of 40 to 60 years old showed poorer prognostic features than EBV- DLBCL patients; however, patients in other age groups did not show evident differences in prognosis between EBV+ DLBCL patients and EBV- DLBCL patients. This finding was not reported before.

An update on the status of COVID-19: a comprehensive review.

The last two decades have witnessed two large-scale pandemics caused by coronaviruses, including severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS). At the end of 2019, another novel coronavirus, designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hit Wuhan, a city in the center of China, and subsequently spread rapidly to the whole world. Latest reports revealed that more than 800 thousand people in over 200 countries are involved in the epidemic disease by SARS-CoV-2. Due to the high mortality rate and the lack of optimum therapeutics, it is crucial to understand the biological characteristics of the virus and its possible pathogenesis to respond to the SARS-CoV-2. Rapid diagnostics and effective therapeutics are also important interventions for the management of infection control. However, the rapid evolution of SARS-CoV-2 exerted tremendous challenges on its diagnostics and therapeutics. Therefore, there is an urgent need to summarize the existing research results to guide decision-making on the prioritization of resources for research and development. In this review, we focus on our current understanding of epidemiology, pathogenesis, diagnostics and therapeutics of coronavirus disease 2019 (COVID-19).

Altered hippocampal functional connectivity in primary Sjögren syndrome: a resting-state fMRI study.

Structural and metabolic abnormalities in the hippocampus have been associated with the pathophysiological mechanism of central nervous system involvement in primary Sjögren syndrome (pSS). Nevertheless, how hippocampal function is altered in pSS remains unknown. The purpose of our study is to investigate the alterations in hippocampal functional connectivity (FC) in pSS by using resting-state functional magnetic resonance imaging (rs-fMRI). Thirty-eight patients with pSS and 38 age- and education level-matched healthy controls (HCs) underwent magnetic resonance imaging examination. Prior to each MRI examination, neuropsychological tests were performed. Left and right hippocampal FCs were analyzed by using seed-based whole-brain correlation and compared between pSS and HCs. Spearman correlation analysis was performed between the z-value of hippocampal FC in brain regions with significant difference between the two groups and neuropsychological tests/clinical data in pSS. Compared with the controls, the patients with pSS showed decreased hippocampal FC between the left hippocampus and the right inferior occipital gray (IOG)/inferior temporal gray (ITG), as well as between the right hippocampus and right IOG/middle occipital gray (MOG), left MOG, and left middle temporal gray. In addition, increased hippocampal FCs were detected between the left hippocampus and left putamen, as well as between the right hippocampus and right cerebellum posterior lobe. Moreover, the visual reproduction score positively correlated with the FC between right hippocampus and right IOG/MOG. The white matter hyperintensity score negatively correlated with the FC between left hippocampus and right IOG/ITG. In conclusion, patients with pSS suffered decreased hippocampal FC mainly sited in the occipital and temporal cortex with right hippocampal laterality. Altered hippocampal FC might be a potential biomarker in detecting brain function changes and guiding neuroprotection in pSS.

Influences of urinary kallidinogenase on neuronal apoptosis in cerebral infarction rats through Nrf2/ARE oxidative stress pathway.

OBJECTIVE: To investigate the influences of urinary kallidinogenase on neuronal apoptosis in rats with cerebral infarction through the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) oxidative stress pathway. MATERIALS AND METHODS: A total of 30 male rats were divided into group A (model control group), group B (rat model of cerebral infarction) and group C (rat model of cerebral infarction + medical treatment with urinary kallidinogenase). The percentage of cerebral infarct volume and the apoptosis of brain cells in the three groups of rats were detected via 2,3,5-Triphenyltetrazolium chloride (TTC) staining, the pathological morphology of brain tissues in the three groups of rats was observed via hematoxylin and eosin (HE) staining, and the protein levels of Nrf2 and superoxide dismutase 1 (SOD1) in the brain tissues in the three groups of rats were measured using the Western blotting assay. RESULTS: The degree of neurological deficit in group B was remarkably higher than that in group A (p<0.05), and it was markedly decreased in group C compared to that in group B, displaying statistically significant differences (p<0.05). Compared to that in group A, the cell apoptosis was significantly aggravated in group B, while a remarkably alleviated cell apoptosis was observed in group C compared to that of group B, and the differences were statistically significant (p<0.05). The cerebral infarct volume accounted for 34.87% of the whole brain volume in group B, and a mild cerebral infarction was detected in group C, with a percentage of cerebral infarct volume of 21.14%. Group B showed a more evident increase in the cerebral infarct volume than in group C (p<0.05). Compared to those of group A, pyknotic nuclei and neuron staining of brain tissue cells were evidently increased, and the neuronal cell injury was aggravated in group B. Moreover, prominently decreased pyknotic nuclei and neuron staining (p<0.05) as well as mild neuronal cell injury (p<0.05) were detected in group C compared to those in group B. The levels of Nrf2 and SOD1 protein in the brain tissues in group B were remarkably lower than those of group C (p<0.05). CONCLUSIONS: Urinary kallidinogenase can inhibit the neuronal apoptosis in rats and protect the rats from cerebral infarction, whose mechanism is associated with the activation of the Nrf2/ARE oxidative stress pathway.

MiR-137-5p alleviates inflammation by upregulating IL-10R1 expression in rats with spinal cord injury.

OBJECTIVE: This study aims to explore the potential functions of miR-137-5p and interleukin-10R1 (IL-10R1) in mediating the immune inflammation after spinal cord injury (SCI). MATERIALS AND METHODS: Firstly, primary microglia were isolated from the spinal cord of newborn rats. Expression levels of miR-137-5p and IL-10R1 in LPS-induced microglia were determined by quantitative Real-time polymerase chain reaction (qRT-PCR). In addition, mRNA expressions of Janus kinase (Jak1) and signal transducer and activator of transcription 3 (STAT3) were also examined by qRT-PCR. SCI model in rats was established and randomly assigned to three different groups: Sham group, SCI group and miR-137-5p mimic group. Within one week of spinal injury, relative levels of miR-137-5p and IL-10R1 in rats of different groups were detected by qRT-PCR. The mRNA levels of JAK1, tyrosine kinase (Tyk2) and STAT3 in rats were also measured. Moreover, protein expression of IL-1ß, TNF-α and IL-6 in rats was measured by Western blotting. Finally, the improvement of locomotor function in three groups of rats within 4 weeks via BBB rating scale. RESULTS: Transfection of miR-137-5p mimics upregulated relative levels of IL-10R1, JAK1 and STAT3 in in vitro cultured microglia. Similarly, IL-10R1/JAK1/STAT3 pathway was activated in rats administrated with miR-137-5p mimics. Nevertheless, relative levels of classical inflammatory stimulators IL-1ß, TNF-α and IL-6 were downregulated accordingly by miR-137-5p overexpression. Moreover, miR-137-5p effectively improved the locomotor function of rats after SCI. CONCLUSIONS: MiR-137-5p exerts an anti-inflammatory response by upregulating IL-10R1, thus improving locomotor function and alleviating spinal cord injury.

Effects of MiR-146a on repair and inflammation in rats with spinal cord injury through the TLR/NF-κB signaling pathway.

OBJECTIVE: This study aims to investigate the effects of micro ribonucleic acid-34a (miR-34a) on repair and inflammation of rats with spinal cord injury (SCI) through the toll-like receptor (TLR)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. MATERIALS AND METHODS: In this study, 12 healthy rats (control group (CG)) and 24 SCI rats (experimental group (EG-1)) were selected as subjects. A total of 12 experimental rats randomly selected from EG-1 were injected with 5 µL agomiR-146 as EG-2 group. Serum levels of miR-146a, TLR, NF-κB, interleukin-8 (IL-8) and IL-6 of rats in CG and EG-1 were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Furthermore, the protein levels of miR-146a, TLR, NF-κB, IL-8 and IL-6 in rats of CG and EG were detected via Western blotting. Spinal cord tissue sections of SCI rats after treatment with agomiR-146 were observed by hematoxylin and eosin staining (H&E) staining. RESULTS: The mRNA level of miR-146a in SCI rats was significantly lower than that in healthy rats, and the difference was statistically significant (p < 0.05). The mRNA levels of TLR, NF-κB, IL-8 and IL-6 in SCI rats were markedly higher than those in healthy rats, showing significant differences (p < 0.05). However, the relative mRNA level of miR-146a in EG-2 group was significantly higher than that in EG-1 group, with a significant difference (p < 0.05). Relative level of miR-146a was not significantly different between EG-2 group and CG group (p > 0.05). Meanwhile, the mRNA levels of TLR, NF-κB, IL-8 and IL-6 in EG-2 group were evidently lower than those in EG-1 group, displaying significant differences (p < 0.05). CONCLUSIONS: MiR-146a can promote the repair of SCI and reduce inflammatory responses in rats through the TLR/NF-κB signaling pathway.

Meta-analysis of Early Versus Late Ureteric Stent Removal After Kidney Transplantation.

BACKGROUND: Ureteral stents have been widely used in kidney transplantation to prevent postoperative ureter-related complications such as ureteral stricture, ureteral obstruction, and ureteral leakage; however, a longer indwelling ureteral stent time corresponds to a greater risk of complications such as urinary tract infections. Currently, transplantation centers have not yet reached an agreement on the time to remove ureteral stents. Several randomized controlled trials (RCTs) have evaluated the optimal removal time for ureteral stents. OBJECTIVE: This meta-analysis was designed to evaluate and discuss the optimal removal time for ureteral stents after kidney transplantation. METHOD: We used key words to search PubMed, Embase, and Cochrane Library and retrieve published articles. A total of 568 kidney transplantation patients from 5 RCTs were included in this meta-analysis. We collected information regarding postoperative complications related to indwelling stents, such as ureteral stricture, ureteral obstruction, ureteral leakage, and urinary tract infection, and evaluated whether early removal of ureteral stents (≤7 days) was superior to late removal (≥14 days). RESULTS: A significant difference was observed in the incidence of urinary tract infection between the early removal group and the late removal group (risk ratio [RR] = 0.43, 95% confidence interval [CI] [0.32, 0.59], P < .01). No significant between-group difference was observed in the incidence of major urological complications (MUCs) (RR = 1.87, 95% CI [0.45, 7.70], P > .05). CONCLUSION: Early removal of ureteral stents of transplanted kidneys after kidney transplantation (≤7 days) did not significantly increase the incidence of postoperative MUCs (ureteral stricture, ureteral obstruction, and ureteral leakage) relative to late removal (≥14 days). Early removal may significantly reduce the incidence of postoperative urinary tract infection relative to late removal.

Chloroquine aggravates the arsenic trioxide (As2O3)-induced apoptosis of acute promyelocytic leukemia NB4 cells via inhibiting lysosomal degradation in vitro.

OBJECTIVE: Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML), as standing out for its distinguished sensitivity to all-trans retinoic acid and arsenic trioxide (ATO, As2O3). The As2O3-mediated degradation of PML-RARA (promyelocytic leukemia-retinoic acid receptor-α) oncoprotein via the proteasome pathway appears to be critical for such distinguished sensitivity. MATERIALS AND METHODS: The present study was to evaluate the influence by chloroquine (CQ), an inhibitor to the release of lysosomal enzymes, on the sensitivity of APL cells to As2O3. APL-derived NB4 cell line was treated with As2O3 or/and CQ in vitro. Then, the cell viability, the induction of apoptosis, and autophagy were examined with MTT assay, with TUNEL staining or with enhanced green fluorescence protein (EGFP)-light Chain 3 (LC3) reporter. The apoptosis- or autophagy-associated proteins were quantified with Western blotting assay. RESULTS: Our results demonstrated that the As2O3 treatment promoted either apoptosis or autophagy in APL NB4 cells and upregulated both apoptosis- and autophagy-associated proteins. However, additional CQ treatment deteriorated the As2O3-induced NB4 cell apoptosis, whereas aggravated the As2O3-induced accumulation of acidic vesicular organelles (AVOs) and blocked the lysosomal degradation in NB4 cells. CONCLUSIONS: Chloroquine aggravates the arsenic trioxide-induced apoptosis of APL NB4 cells via inhibiting lysosomal degradation in vitro. It implies that chloroquine might be adjuvant to sensitize APL cells to arsenic trioxide.

MiR-7 alleviates secondary inflammatory response of microglia caused by cerebral hemorrhage through inhibiting TLR4 expression.

OBJECTIVE: This study was conducted to analyze the effect of miR-7 on the inflammatory response of microglia in vitro and in vivo by constructing an intracerebral hemorrhage model. PATIENTS AND METHODS: In this study, we first established a model of cerebral hemorrhage in rat for in vivo experiments, and used lipoprotein (LPS) to induce an inflammatory response development in microglial cells, and constructed microglial inflammation models for in vitro experiments. Quantitative Real-time-polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-7 in the rat model of cerebral hemorrhage and microglia with inflammation. The effect of miR-7 on the inflammation caused by intracerebral hemorrhage was evaluated through measuring the expression of IL-1ß, IL-8 and TNF-α by enzyme-linked immunosorbent assay (ELISA). Dual luciferase reporter assay was used to detect the binding site of miR-7 to TLR4. Western blot was used to evaluate the level of TLR4 after overexpression and knockdown of miR-7 and to evaluate whether miR-7 alleviated the secondary inflammatory response of microglia after cerebral hemorrhage by inhibiting the expression of TLR4. RESULTS: The expression of miR-7 in the rat cerebral hemorrhage model and microglial inflammation model tissue was significantly lower than that in the normal control group. Expression of inflammatory cytokines including IL-1ß, IL-8 and TNF-α was significantly increased in rats with intracerebral hemorrhage and microglial inflammation in rats, and the expression of these inflammatory cytokines was partially reversed after overexpression of miR-7. Double luciferase reporter gene and ELISA results showed that miR-7 could inhibit the expression of TLR4 and relieve the secondary inflammatory response of microglia after cerebral hemorrhage. CONCLUSIONS: We demonstrated that, in in vivo and in vitro experiments, miR-7 could reduce the LPS-induced inflammatory response produced by microglial cells, and alleviate the inflammation in the brain of rats with cerebral hemorrhage.

Significant alterations of 6-keto prostaglandin F1a and NO levels in spermatic vein plexus patients with varicocele.

To investigate the level variation of correlative factors between the spermatic vein plexus and peripheral blood in patients with varicocele, a total of 22 patients diagnosed with varicocele were enrolled in the study. All patients were performed a testicular artery-sparing microsurgical varicocelectomy. During the operation, a blood sample from the left spermatic vein plexus and a peripheral blood sample were collected. A radioimmunoassay was used to determine the 6-keto prostaglandin F1a (6-keto-PGF1a ). A colorimetric method was performed to determine the NO. The enzyme immunoassay method was used to determine the creatinine, urea nitrogen, adrenaline, noradrenaline, dopamine and 5-HT. The mean age of all patients was 29.3 ± 7.8 years. Compared with the level of 6-keto-PGF1a and NO in the peripheral blood, 6-keto-PGF1a and NO were significantly increased in left spermatic vein plexus (347.3 (230.8-415.1) versus 99.7 (80.4-119.9) pg/ml and 192.3 ± 178.5 versus 107.1 ± 73.6 µmol/L, p < .05). There were no differences in the level of creatinine, urea nitrogen, adrenaline, noradrenaline, dopamine and 5-HT between the peripheral blood and left spermatic vein plexus (p > .05). The 6-keto-PGF1a and NO concentrations in left spermatic vein plexus were significantly higher than that in peripheral blood patients with varicocele.

Biological function of microRNA-30c/SOX9 in pediatric osteosarcoma cell growth and metastasis.

OBJECTIVE: Osteosarcoma is one of the commonest malignant bone tumors, which frequently occurs in children all over the world. To find out methods to improve the therapeutic effect of osteosarcoma, it is necessary to detect the functioning mechanism of miR-30c to regulate the proliferation and metastasis of osteosarcoma cell. PATIENTS AND METHODS: In order to reveal the expression level of miR-30c, quantitative Real-time PCR (qRT-PCR) method was chosen. To evaluate cell viability and proliferation rates, colony formation and cell counting kit-8 (CCK8) assay were introduced. Based on cell migration and invasion assay, metastasis capacity of breast cancer cells was studied. Protein levels were measured by Western blotting assay and cell cycle distribution was identified by flow cytometry. Bioinformatics analysis and Luciferase assay were used to predict and verify the target gene. RESULTS: Compared with pericarcinomatous tissues (n=38), miR-30c in osteosarcoma tissues was significantly suppressed. Overexpressed miR-30c could weaken osteosarcoma cell's abilities of viability, proliferation, migration and invasion. Moreover, it could also encourage osteosarcoma cell apoptosis and block cell cycle at G0/G1 phase. According to bioinformatics analysis and Luciferase reporter assay, SOX9 was recognized as the target gene of miR-30c. Restoration of SOX9 could make miR-30c regain the ability of suppression on tumorigenesis of osteosarcoma cells. CONCLUSIONS: MiR-30c could play an important role in tumor suppression for pediatric osteosarcoma development and metastasis by targeting SOX9 in vitro. Thus, a creative and potential target was provided for diagnosis and treatment of osteosarcoma.

Hypoxia promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells via inducing Twist1 expression.

OBJECTIVE: To investigate whether hypoxia microenvironment induced hepatocellular carcinoma cells SMMC-7721 epithelial-mesenchymal transition (EMT) and to explore the underlying molecular mechanism. MATERIALS AND METHODS: In this study, SMMC-7721 cells were cultured under normoxia and hypoxia conditions, respectively. RT-PCR and Western blot were used to monitor the expression level of EMT-related markers, E-cadherin, and vimentin, as well as hypoxia inducible factor-1α (HIF-1α) and Twist1. Then we performed the transwell invasion assays to detect the ability of cell invasion. RESULTS: The results demonstrated that hypoxia micro-environment could induce hepatocellular carcinoma cells SMMC-7721 EMT and enhance the cell invasion ability. Furthermore, knockdown of Twist1 by using specific siRNA could reverse hypoxia-induced EMT process. CONCLUSIONS: Hypoxia promotes hepatocellular carcinoma cells SMMC-7721 EMT by upregulating the expression of Twist1.

Clinical efficacy of gamma knife and surgery treatment of mesial temporal lobe epilepsy and their effects on EF-Tumt and EF-Tsmt expression.

OBJECTIVE: To study the clinical efficacy of gamma knife and surgery treatment of mesial temporal lobe epilepsy (MTLE) and their effects on EF-Tumt and EF-Tsmt expression. PATIENTS AND METHODS: The data of 78 cases of MTLE patients treated in our hospital from April 2011 to March 2013 were retrospectively analyzed. The patients were divided into two groups according to the treatment methods: the surgery group (including 41 cases) and the gamma knife group (including 37 cases). The clinical efficacy, the occurrence and recurrence of complications were evaluated, respectively; meanwhile, the expression of the EF-Tumt protein and EF-Tsmt protein in brain tissue were analyzed. RESULTS: The difference between the efficacy rate of the two groups showed no statistical significance (χ2=0.960, p>0.05). The complication rate of the gamma knife group was significantly lower than that of the control group (χ2=6.430, p<0.05). The recurrence rate of the patients in the gamma knife group was significantly lower than that of the patients in the surgery group (p>0.05). Within the two groups, the positive expression granum of EF-Tsmt protein and EF-Tumt protein of the two groups after treatment were significantly lower than that before treatment (p<0.05). After treatment, the positive expression granum of EF-Tsmt protein of the patients in the gamma knife group was obviously more than that of the patients in the surgery group (p<0.05). The difference between the positive expression granum of EF-Tumt protein of the two groups showed no statistical significance (p>0.05). Before and after treatment within the group, the positive cell of EF-Tsmt protein and EF-Tumt protein of the two groups of patients after treatment were significantly lower than that before treatment (p<0.05). After treatment, the difference between the EF-Tsmt protein positive cell and the EF-Tumt protein positive cell of the two groups of patients showed no statistical significance (p>0.05). CONCLUSIONS: Both surgery and gamma knife could treat MTLE effectively, and the efficacy may be related to the ability to reduce the expression of EF-Tsmt protein and EF-Tumt protein in brain tissue.

A minicircuitry comprised of microRNA-9 and SIRT1 contributes to leukemogenesis in t(8;21) acute myeloid leukemia.

OBJECTIVE: The AML1-ETO fusion protein (AE) resulting from the t(8;21) translocation is highly related to the pathogenesis and development of leukemia. microRNA-9 (miR-9) acts as a tumor suppressor gene in AE-positive acute myeloid leukemia (AML). Silent mating type information regulation 2 homolog-1 (SIRT1) is overexpressed in most cancer cells by increasing proliferation as a tumorigenic gene. The present study was performed to investigate the underlying interaction between miR-9 and SIRT1 in AE-positive AML. PATIENTS AND METHODS: Expression of miR-9 and SIRT1 in AE-positive AML patients, healthy donors and AML cell lines were detected by qPCR. Relevance between miR-9 and SIRT1 was assessed by plasmid transfection, Western blot and correlation analysis. Luciferase assay was used to confirm the target gene of miR-9. Knockdown of SIRT1 in different cell lines was achieved by shRNA transfection and CCK-8 assay was used to investigate the effects on cell proliferation. RESULTS: The miR-9 expression was lower in AE-positive cell lines compared to that in other AE-negative AML cell lines, while expression of SIRT1 was higher in AE-positive cell lines. Expression of miR-9 was also downregulated in adult primary t(8;21) AML patients compared to healthy donors. The over-expression of miR-9 decreased luciferase activity of wild-type SIRT1, which was recovered after transfection with mutant SIRT1. The miR-9 directly targets SIRT1 by binding to its 3'-untranslated region and reducing its protein levels. Importantly, miR-9 and SIRT1 mRNA levels were inversely correlated in AE-positive AML cell lines and t(8;21) AML primary leukemia cells. Knockdown of SIRT1 levels using shSIRT1 inhibited cell proliferation in AE-positive AML cell lines. CONCLUSIONS: SIRT1 is the target gene of miR-9 and the signaling pathway connecting miR-9 and SIRT1 is a therapeutic target for t(8;21) AML.

Meta-analysis on the Safety and Efficacy of the Reperfusion Use of a Single High Dose of Anti-T-Lymphocyte Globulin Fresenius in Kidney Transplantation.

BACKGROUND: The aim of this study was to evaluate the effects of a single high dose of the anti-T-lymphocyte globulin Fresenius (ATG-F), given before kidney transplantation, on the prevention of acute rejection response and infections and on the survival rate of the renal graft and patient. METHODS: Databases including PubMed, Embase, and the Cochrane Library were searched to identify randomized controlled trials relevant to studying the presurgical use of a single high dose of ATG-F. RESULTS: Five RCTs that included 346 patients were selected. The meta-analysis suggested that the application of ATG-F reduced the postsurgical acute rejection reaction incidence compared to that of the control group (relative risk = 0.50, 95% confidence interval = 0.35-0.71, P = .0001). However, the application of ATG-F exhibited no significant effect on the incidence of urinary tract infection, cytomegalovirus infection, and delayed graft function. Furthermore, the one-year patient survival rate and kidney graft survival rate were not affected. CONCLUSIONS: The meta-analysis suggested that the reperfusion use of a single high dose (9 mg/kg) of ATG-F could effectively reduce the incidence of postsurgical acute rejection response without affecting the occurrence of infections, the survival rates of kidney grafts and patients, or the incidence of delayed graft function.

A multi-center, controlled, randomized, open-label clinical study of levofloxacin for preventing infection during the perioperative period of ultrasound-guided transrectal prostate biopsy.

By comparing the safety and efficacy of 500 mg of oral levofloxacin for 3 days with those of intravenous antibiotics for 3 days in the prevention of infectious complications of ultrasound-guided transrectal prostate biopsy (TPB), we provided a safe and cost-effective infection preventive protocol for TPB in China. A total of 801 patients with indications for TPB in 12 centers were randomized into two groups from October 2011 to December 2015. Patients in the test group (n = 392) took 500 mg of oral levofloxacin for 3 days. Patients in the control group (n = 409) underwent intravenous antibiotics according to the traditional habits of the center for 3 days. All patients underwent ultrasound-guided TPB. Infectious complications were compared between the two groups. Different kinds of antibiotic were used in the control group. Comparing the two groups, the mean patient age was 70.6 ± 14.0 and 70.5 ± 14.0 years. The incidence of total infectious complications was 4.6 % (18/392) and 4.4 % (18/409) respectively, the incidence of asymptomatic bacteriuria was 3.1 % (12/392) and 2.7 % (11/409), the incidence of symptomatic urinary tract infection was 0.0 % and 0.2 % (1/409), the incidence of fever was 0.8 % (3/392) and 0.5 % (2/409), the incidence of bacteremia was 0.5 % (2/392) and 0.0 %, and the incidence of urosepsis was 0.3 % (1/392) and 1.0 % (4/409) respectively (all P > 0.05). The selection of antibacterial agents for TPB is in ca haotic condition in China. Oral levofloxacin at 500 mg once daily for 3 days is a safe, convenient, and cost-effective infection preventive protocol for TPB in China.

Significant alterations of serum hormone levels in the spermatic vein plexus of patients with varicoceles.

The objective of this study was to evaluate the level of hormone variation between the peripheral blood and spermatic vein plexus in patients with varicoceles. A total of 23 patients diagnosed with varicoceles were enrolled in the study. All patients underwent a testicular artery-sparing microsurgical varicocelectomy. During the operation, a blood sample from the ipsilateral spermatic vein plexus and a peripheral blood sample were collected. A radioimmunoassay was performed to determine the total testosterone, free testosterone, dihydrotestosterone and oestradiol levels. An enzyme-linked immunosorbent assay was performed to determine the albumin level. The mean age of the patients was 32.3 ± 9.3 years. Compared with the hormone level in the peripheral blood, the total testosterone, free testosterone, dihydrotestosterone, and oestrogen levels were significantly increased in the left or right spermatic vein plexus (P < 0.05). There were no differences in the albumin levels in the peripheral blood and spermatic vein plexus (P > 0.05). The mean total testosterone, free testosterone, dihydrotestosterone, and oestradiol levels in the left spermatic vein plexus were 10.8-fold, 29.0-fold, 2.0-fold, and 26.6-fold those of the peripheral blood. The hormone concentration in the spermatic vein plexus was significantly higher than that in the peripheral blood in patients with varicoceles.