This randomized clinical study was to assess and compare the efficacy and safety of two chemoradiotherapy (cisplatin + 5-fluorouracil + radiotherapy and cisplatin + docetaxel + radiotherapy) regimens in patients with unresectable local advanced oesophageal squamous cell carcinoma. Previously untreated patients with histologically or cytologically confirmed squamous cell carcinoma were randomly assigned into two groups (each had 45 patients): cisplatin + 5-fluorouracil + radiotherapy (PF) group and cisplatin + docetaxel + radiotherapy (DP) group. All patients received radiotherapy of 50.4 Gy (28 fractions of 1.8 Gy) over 5 weeks (5 fractions a week). Chemotherapy for PF group comprises 5-fluorouracil at days 1-4 (250 mg/m(2)/day) and cisplatin (75 mg/m(2)) at day 1 of every 28-day cycle; full treatment course included 4 cycles. Chemotherapy for DP group comprises docetaxel (75 mg/m(2)) and cisplatin (75 mg/m(2)) at day 1 of every 28-day cycle; full treatment course included 4 cycles. Response, survival, progression and toxicity of both regimens were studied. Overall response rate (ORR) was 53.3 % for PF group and 73.3 % for DP group. Median overall survival (OS) time was 22.3 months for PF group and 43.2 group months for DP: Patients of DP group had a significant longer overall median survival time (P < 0.05). Toxicity was acceptable; patients of PF group and patients of DP group did not showed significant difference in serious haematological event incidence (24.4 vs. 35.6 %, P > 0.05). ORR and OS favour DP over PF in the treatment of patients with unresectable local advanced oesophageal squamous cell carcinoma.

Computed Tomography (CT) imaging technique is widely used in geological exploration, medical diagnosis and other fields. In practice, however, the resolution of CT image is usually limited by scanning devices and great expense. Super resolution (SR) methods based on deep learning have achieved surprising performance in two-dimensional (2D) images. Unfortunately, there are few effective SR algorithms for three-dimensional (3D) images. In this paper, we proposed a novel network named as three-dimensional super resolution convolutional neural network (3DSRCNN) to realize voxel super resolution for CT images. To solve the practical problems in training process such as slow convergence of network training, insufficient memory, etc., we utilized adjustable learning rate, residual-learning, gradient clipping, momentum stochastic gradient descent (SGD) strategies to optimize training procedure. In addition, we have explored the empirical guidelines to set appropriate number of layers of network and how to use residual learning strategy. Additionally, previous learning-based algorithms need to separately train for different scale factors for reconstruction, yet our single model can complete the multi-scale SR. At last, our method has better performance in terms of PSNR, SSIM and efficiency compared with conventional methods.scanning electron microscopy (SEM) image. Li proposed a voxel SR reconstruction algorithm 11 based on sparse representation, which can improve the resolution in all directions.Zhang et al. extended adjusted anchored neighborhood regression algorithm (A+) 14 , to 3D and proposed high frequency modified 3DA+ algorithm 15 , where a correlative dictionary and mapping matrix between high frequency and low frequency was established. In reconstruction stage, the matched dictionary atom and mapping matrix were searched for each input of the 3D block to complete SR.Unfortunately, the aforementioned algorithms are focused on 2D images, in view of the fact of 3D-CT images of rock, the following issues remain to be solved: First, the computational intensity and memory of 3D image data is far greater than the 2D images, so the method to handle with 2D images can't be directly transferred to 3D model; Second, CT samples are not as convenient as 2Dimages to obtain, that is to say, it's not easy to get substantial alignments of rock CT samples to training network. In addition, CT image of rock has the characteristics of low contrast, single texture, and complex pore structure, which all bring difficulty to task of SR; Third, during training network and reconstruction stage, the calculation and time complexity have to be taken account to ensure our work can be carried out on the general computing equipment. Hence, it is desirable to devise a new network to cope with SR for voxel images.In order to enhance resolution of CT images of rock from three directions (i.e., x, y ,z), we propose a novel network, termed as 3D super-resolution convolutional neural network (3DSRCNN), to promote resolution for volumetric images. Bef...

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the most common complications in COVID-19. Elastase has been recognized as an important target to prevent ALI/ARDS in the patient of COVID-19. Cyclotheonellazole A (CTL-A) is a natural macrocyclic peptide reported to be a potent elastase inhibitor. Herein, we completed the first total synthesis of CTL-A in 24 linear steps. The key reactions include three-component MAC reactions and two late-stage oxidations. We also provided seven CTL-A analogues and elucidated preliminary structure–activity relationships. The in vivo ALI mouse model further suggested that CTL-A alleviated acute lung injury with reductions in lung edema and pathological deterioration, which is better than sivelestat, one approved elastase inhibitor. The activity of CTL-A against elastase, along with its cellular safety and well-established synthetic route, warrants further investigation of CTL-A as a candidate against COVID-19 pathogeneses.

The purpose of this study was to investigate the expression of microRNA-106b (miR-106b) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in pituitary tumor and to confirm whether miR-106b promotes proliferation and invasion of pituitary tumor cells through the PI3K/AKT signaling pathway by targeted regulation of PTEN expression, and thereby to find new targets for the treatment of pituitary tumor. Fifty-five cases of pituitary tumor tissue samples were collected, including 29 cases of invasive pituitary tumor, non-invasive 26 cases, and 8 normal pituitaries. The expression level of miR-106b in pituitary tumor tissue was detected by quantitative real-time PCR, and the expression of PTEN protein was detected by immunohistochemistry. PTEN 3'-untranslated region (UTR) luciferase vector was constructed, and dual-luciferase reporter gene assay was employed to examine the effect of miR-106b on PTEN 3'-UTR luciferase activity. AtT-20 cells were transfected with miR-106b mimics, miR-106b inhibitor, PTEN expression plasmid, and miR-106b mimics + PTEN expression plasmid respectively, and the changes in cellular proliferation and invasion were observed via MTT method and transwell assay respectively. PTEN messenger RNA (mRNA) expression was determined by quantitative real-time PCR, and western blotting was performed to detect the expression of PTEN, PI3K, AKT, and pAKT. miR-106b showed up-regulation in invasive pituitary tumor tissue: the expression level was significantly up-regulated compared with normal tissues and the non-invasive pituitary tumor tissue (P < 0.05). The positive rate of PTEN protein expression in invasive pituitary tumor tissues was significantly lower than in normal and non-invasive tissues (P < 0.01). Dual-luciferase reporter gene assay showed that miR-106b could bind to the 3'-UTR of PTEN specifically and significantly inhibited the luciferase activity, cutting the 46 % (P < 0.01). Down-regulation of miR-106b or up-regulation of PTEN could suppress cell proliferation and invasion of AtT-20 cells, and PTEN expression plasmid could partially simulate the function of miR-106b. Expression of PTEN mRNA and protein decreased significantly in AtT-20 cells overexpressing miR-106b. The expression levels of PI3K and p-AKT were significantly inhibited by miR-106b inhibitor and increased by miR-106b mimics. The expression of miR-106b showed up-regulation in pituitary tumor tissues, while the protein expression of PTEN presented opposite results. The findings of this study further demonstrated that miR-106b as an oncogene regulated the pituitary tumor cell proliferation and invasion in vitro by directly targeting PTEN through the PI3K/AKT signaling pathway. Our study suggests that miR-106b and PTEN are likely to serve as potential diagnostic biomarkers or therapeutic targets for pituitary tumor treatment in the future.

Background Long noncoding RNAs (lncRNAs) are vital mediators in human cancers including pituitary neuroendocrine tumor (PitNET) and could function as competing endogenous RNAs (ceRNAs) of microRNAs (miRNAs). The main objective of this study is to identify effect of lncRNA X-inactive specific transcript (XIST) and microRNA-424-5p (miR-424-5p) on PitNET. Methods Microarray analysis was employed to identify the PitNET-related differentially expressed lncRNAs. PitNET tissues, including both invasive and non-invasive subtypes in parallel with normal pituitary tissues were collected for the determination of the expression of XIST, miR-424-5p and basic fibroblast growth factor (bFGF) and the interaction among them. Subsequently, the expression of XIST, miR-424-5p and bFGF in PitNET cells was altered to elucidate their biological significance in the aspects of proliferation, migration, invasion, and the apoptosis. Results Both XIST and bFGF exhibited high expression, but miR-424-5p had a low expression in invasive PitNET tissues as compared to non-invasive PitNET normal pituitary tissues. Additionally, XIST competitively bound to miR-424-5p to elevate the expression of bFGF. Furthermore, depleted XIST or bFGF, or elevated miR-424-5p was revealed to suppress the proliferation, migration, invasion, and promote cell cycle arrest and apoptosis of invasive PitNET cells. miR-424-5p repressed the proliferation, migration, invasion of invasive PitNET cells by targeting bFGF. Conclusion In conclusion, the fundamental findings of the present study suggested that the functional suppression of XIST downregulated bFGF to inhibit the development of PitNET by increasing miR-424-5p expression, proposing XIST as a novel therapeutic target for PitNET.

PurposeThis study was designed to explore how miR-145 regulates the mTOR signaling pathway in invasive pituitary adenoma (IPA) by targeting AKT3.MethodsA total of 71 cases of IPA tissues and 66 cases of non-IPA tissues were obtained in this study. In vitro, the IPA cells were assigned into blank control, empty plasmid, miR-145 mimic, miR-145 inhibitor, miR-145 mimic + rapamycin, miR-145 inhibitor + rapamycin and rapamycin groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to detect the protein expressions of PI3K, AKT3, mTOR mRNA and the mRNA expression of miR-145 both in vivo and in vitro. Additionally, the S6K and RPS6 mRNA and protein expressions as well as the relative phosphorylation levels were determined in vitro. MTT assay, flow cytometry and transwell assay were used to testify the cell proliferation, apoptosis and invasion ability, respectively.ResultsThe IPA tissues exhibited significantly lower expression of miR-145 but higher PI3K, AKT3 and mTOR mRNA and protein expressions when compared with the non-IPA tissues. Compared with the blank control and empty plasmid groups, the miR-145 mimic group showed significantly decreased PI3K, AKT3, mTOR, S6K and RPS6 mRNA and protein expressions as well as phosphorylation levels; besides, the IPA cell proliferation, migration and invasion ability were strongly inhibited, accompanied with the increased number of apoptotic cells. In the miR-145 inhibitor group, the PI3K, AKT3, mTOR, S6K and RPS6 mRNA and protein expressions as well as the phosphorylation levels were significantly increased; cell proliferation, migration and invasion ability were remarkably elevated, accompanied with reduced apoptotic cell number.ConclusionThe study demonstrates that miR-145 inhibits the mTOR signaling pathway to suppress the IPA cell proliferation and invasion and promotes its apoptosis by targeting AKT3.

Objective: To analyse the epidemiological characteristics, clinical symptoms, radiological aspects, treatments, and outcomes of primary central nervous system (CNS) hydatidosis and compare our results with those observed for secondary intracranial hydatidosis. Patients and Methods: We retrospectively reviewed 21 cases of primary CNS hydatid cysts operated on at the First Affiliated Hospital of Xinjiang Medical University between 1996 and 2010. Results: Of the 21 primary cases, the vast majority were intracranial hydatidosis patients (20 cases, 95.24%). Only one patient had spinal hydatidosis. Unlike previously published reports, we found that intracranial hydatid cysts were more common in adults (80.96%) than in children (19.04%), with a slight male predominance (M/F 5 1.1). All symptoms, including vomiting, nausea, and focal neurological signs, resulted from the increased intracranial pressure, which was closely associated with the cyst location. For the spinal hydatidosis patient, the primary symptom of back pain was indicative of spinal cord compression syndrome. All cysts in the 21 primary cases were pathologically similar. The recurrence percentage was 28% over 12 years. Two patients with multiple intracranial hydatid cysts died due to foramen magnum herniation. Conclusion: Despite imaging and therapeutic advances, CNS hydatidosis remains difficult to treat, and severe complications and the high incidence of recurrence result in unsatisfactory outcomes.

To explore the effects and mechanism of CTEN (COOH-terminus tensin-like molecule) on EMT, cell migration and invasion of Human lung adenocarcinoma cells. The pCMV-vector, pCMV-CTEN, Control-shRNA, and CTEN-shRNA were transfected into A549 and NCI-H1299 cells by Lipofectamine 2000. Transforming growth factor-β1(TGF-β1)and epithelial-mesenchymal transition (EMT) -related biomarkers were detected by eliseand western blot. The migration and invasion ability of A549 cells and NCI-H1299 were examined by scratch-wound assay and transwell assay respectively. We found compare with control group, the expression of TGF-β and mesenchymal markers in CTEN overexpression group were increased, and the epithelial marker was decreased, which induced the EMT process. Meanwhile, scratch-woundassay showed that the migration efficiency of A549 and NCI-H1299 cells in CTEN overexpression group were higher than that in control group.Transwell assay demonstrated that the number of cells that migrated and invaded through the membrane were obviously more than those in control group.Furthermore, Knockdown of CTEN partially reversed transforming growth factor-β1(TGF-β1)-induced changes in EMT markers. In conclusion, CTEN activated the expression of TGF-β1, thereby prompting EMT in lung adenocareinma cancer cells.