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It has been controversial whether patients with hepatocellular carcinoma (HCC) should receive glucocorticoid therapy during chemotherapy. Recent studies have demonstrated that glucocorticoids increase the therapeutic sensitivity of tumors to some chemotherapeutic drugs, but the specific mechanism remains unclear. In the present study, dexamethasone (Dex) was used to treat HCC stem cells. The results demonstrated that Dex reduced stemness maintenance and self‑renewal of HCC stem cells, promoted epithelial‑to‑mesenchymal transition, inhibited migration and angiogenesis and, more importantly, increased cell sensitivity to the herpes simplex virus thymidine kinase/ganciclovir drug system in vitro and in vivo. Further mechanistic analyses demonstrated that Dex inhibited small ubiquitin‑like modifier (SUMO) modification of several proteins in HCC stem cells, including hypoxia‑inducible factor (HIF)‑1α, an important hypoxia tolerance protein, and octamer‑binding transcription factor 4 (Oct4), a crucial stemness maintenance protein. Inducing deSUMOylation of HIF‑1α and Oct4 reduced their accumulation in the nucleus, thereby inhibiting tumor angiogenesis and stemness maintenance. These findings provide a new perspective to the study of the mechanism underlying the anti‑hepatocarcinogenesis effects of Dex. Due to the few side effects of glucocorticoids at low doses and their anti‑inflammatory effects, the appropriate combination of glucocorticoids and chemotherapeutic drugs is expected to improve the survival of HCC patients and their prognosis.

Idiopathic pulmonary fibrosis (IPF) is a refractory chronic respiratory disease with progressively exacerbating symptoms and a high mortality rate. There are currently only two effective drugs for IPF; thus, there is an urgent need to develop new therapeutics. Previous experiments have shown that ginkgolic acid (GA), as a SUMO-1 inhibitor, exerted an inhibitory effect on cardiac fibrosis induced by myocardial infarction. Regarding the pathogenesis of PF, previous studies have concluded that small ubiquitin-like modifier (SUMO) polypeptides bind multiple target proteins and participate in fibrosis of multiple organs, including PF. In this study, we found altered expression of SUMO family members in lung tissues from IPF patients. GA mediated the reduced expression of SUMO1/2/3 and the overexpression of SENP1 in a PF mouse model, which improved PF phenotypes. At the same time, the protective effect of GA on PF was also confirmed in the SENP1-KO transgenic mice model. Subsequent experiments showed that SUMOylation of SMAD4 was involved in PF. It was inhibited by TGF-β1, but GA could reverse the effects of TGF-β1. SENP1 also inhibited the SUMOylation of SMAD4 and then participated in epithelial-mesenchymal transition (EMT) downstream of TGF-β1. We also found that SENP1 regulation of SMAD4 SUMOylation affected reactive oxygen species (ROS) production during TGF-β1-induced EMT and that GA prevented this oxidative stress through SENP1. Therefore, GA may inhibit the SUMOylation of SMAD4 through SENP1 and participate in TGF-β1-mediated pulmonary EMT, all of which reduce the degree of PF. This study provided potential novel targets and a new alternative for the future clinical testing in PF.

Esophageal cancer (EC) is a highly prevalent malignancy in China. According to the data released by National Cancer Registry Center of China in 2015, the prevalence of EC was 21.17/100,000 in China in 2012, ranking fifth among all malignancies; the mortality rate was 15.58/100,000, ranking fourth. It is expected that there will be 477,900 new EC cases nationwide in 2015, whereas 375,000 people will die from EC (1,2). Worldwide, EC is the 8 th most common malignancy, with 416,000 new cases in 2012 (3). At present, EC treatment is based on multidisciplinary treatment, but surgery remains the most effective therapy in optimizing long-term prognosis in patients without metastatic disease. The ideal surgical approach is a matter of debate.

A primary cardiac tumor is a rare clinical entity which was reported an incidence of 0.03% in previous autopsy series. 75% cardiac tumors are cardiac myxoma and cardiac hemangiomas constitute only 1–2% of primary cardiac tumors. With the development of modern medical imaging technology and the enhancement of people’s health awareness, more and more asymptomatic cardiac hemangiomas were found and confirmed eventually. Here, we described a case of a 71-year-old man, who was hospitalized with intermittent palpitation for 1 year and a large mass of the heart was removed successfully via sternotomy which was confirmed as atrial hemangioma by postoperative histopathology. Furthermore, a comprehensive review of atrial hemangioma was conducted to date and a few recommendations for the diagnosis and treatment of this uncommon disorder were provided for clinicians.

In order to help people better understand the culture of the Republic of China (ROC), experience the cultural connotation of ROC, and facilitate the research by researchers and the inheritance of ROC culture, this article proposes a ROC textbook retrieval system. The system is mainly divided into four modules: login and registration, book retrieval, online reading, and document downloading. We summarized and classified existing ROC textbooks, and converted them into electronic materials by scanning to build a database of ROC textbooks. According to the characteristics of textbooks, a fast retrieval algorithm is proposed to provide users with book search, online reading and other functions on the client interface, enabling users to search and read ROC textbooks online at all times and places through electronic devices, accumulating cultural literacy. Users can also download books and documents according to their own needs.

Background Bronchiolar adenoma(BA) is a recently recognized, rare tumor of the bronchioles. It can be divided into proximal and distal types according to the proportion of mucinous and ciliated cells on the luminal surface. BA is often misdiagnosed because it has similar ultrasonographic, gross and histological presentations as other diseases. Here, we report a rare case of BA characterized by many fused nodules. Case presentation A 68-year-old woman attended the Tianjin Taida Hospital surgical Clinic mainly because of “intermittent cough for >1 month”. Chest computed tomography (CT) showed multiple solid nodules in the upper and lower left lung. The nodules had irregular outlines, with a maximum diameter of 65 mm. A double needle lung biopsy specimen was removed guided by ultrasound under local anesthesia. Histologically, the biopsy specimen was finally diagnosed as the distal type of BA. Conclusion BA with diffuse pulmonary nodules is rare. Diagnosis of BA needs comprehensive analysis of imaging, gross specimen analysis, histopathology, and immunohistochemical staining to make a correct diagnosis and avoid misdiagnosis. There are few studies on prognosis, which needs close follow-up and more data accumulation.

With the development of three dimensional printing, the personalization products are more and more welcomed by all kinds of industry fields. In daily life, creative application products are also wildly required. So the special design is very important for 3D application. This paper tells us an evolution solution on a coin classifier which used in the bank, home or on the bus to classify money for passengers. In this paper, two different structures of modeling are compared to get the optimization design for utility value. This study attempts to show the novel way on material and structure to help optimize ways to 3D application.

Content-based histopathological image retrieval (CBHIR) has become popular in recent years in histopathological image analysis. CBHIR systems provide auxiliary diagnosis information for pathologists by searching for and returning regions that are contently similar to the region of interest (ROI) from a pre-established database. It is challenging and yet significant in clinical applications to retrieve diagnostically relevant regions from a database consisting of histopathological whole slide images (WSIs). In this paper, we propose a novel framework for regions retrieval from WSI database based on location-aware graphs and deep hash techniques. Compared to the present CBHIR framework, both structural information and global location information of ROIs in the WSI are preserved by graph convolution and self-attention operations, which makes the retrieval framework more sensitive to regions that are similar in tissue distribution. Moreover, benefited from the graph structure, the proposed framework has good scalability for both the size and shape variation of ROIs. It allows the pathologist to define query regions using free curves according to the appearance of tissue. Thirdly, the retrieval is achieved based on the hash technique, which ensures the framework is efficient and adequate for practical large-scale WSI database. The proposed method was evaluated on an in-house endometrium dataset with 2650 WSIs and the public ACDC-LungHP dataset. The experimental results have demonstrated that the proposed method achieved a mean average precision above 0.667 on the endometrium dataset and above 0.869 on the ACDC-LungHP dataset in the task of irregular region retrieval, which are superior to the state-of-the-art methods. The average retrieval time from a database containing 1855 WSIs is 0.752 ms. The source code is available at https://github.com/zhengyushan/lagenet.

In 1883, Leyden successfully performed percutaneous transthoracic needle biopsy (PTNB) of the lung in three patients with pneumonia according the records (1); three years later, Menetrier was the first recorded to employ this technique for the diagnosis of lung cancer (2).

Hypothermia therapy has a positive effect on patients with severe brain injury. Recent studies have shown that mild hypothermia increases the survival of bone marrow-derived mesenchymal stem cells (BMSCs) in a hypoxic environment; however, the underlying mechanisms are not yet fully understood. Small ubiquitin-like modifiers (SUMOs) are sensitive to temperature stress reactions and are considered to exert a protective effect. In this study, we examined the protective effects of hypothermia on BMSCs in terms of SUMO protein modification. First, we found that mild hypothermia inhibited the proliferation and differentiation of BMSCs and increased cell tolerance to a hypoxic environment. Second, hypothermia significantly increased the levels of SUMO modification of multiple proteins in BMSCs. The knockdown of SUMO1/2/3 induced the rapid aging of the BMSCs, while the inhibition of the SUMO-conjugating enzyme, Ubc9, reduced cell proliferation and increased the proportion of BMSCs differentiating into nerve cells. Moreover, the tolerance of BMSCs to the hypoxic environment was significantly decreased. Lastly, we investigated 4 reported SUMO target proteins, anti-proliferating cell nuclear antigen, octamer-binding transcription factor 4, p53 and hypoxia-inducible factor-1α, to confirm that SUMO modification was indeed involved in maintaining the proliferation, inhibiting differentiation and enhancing the resistance of BMSCs against adverse conditions. Taken together, our results indicate that the SUMO pathway is involved in the response to hypothermic stress, and that SUMOylation may be an important protective mechanism against hypothermia for the survival of BMSCs under unfavorable conditions.

The present study aimed to investigate the effect of glutathione S-transferase A1 (GSTA1) on lung cancer cell viability, invasion and adhesion in the presence of nicotine in vitro. Furthermore, the effect of GSTA1 on the epithelial-mesenchymal transition (EMT), a process strongly associated with lung cancer metastasis, was examined. Human lung carcinoma A549 cells were treated with various concentrations of nicotine (0.01, 0.1, 1 and 10 µM) and levels of GSTA1 mRNA and protein were measured by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. To knock down GSTA1 expression, GSTA1-small interfering RNA was transfected into A549 cells. Cell viability, invasion and adhesion abilities were determined by MTT, Transwell-Matrigel invasion and cell adhesion assays, respectively. The expression of the epithelial cell markers E-cadherin and keratin, and the mesenchymal cell markers vimentin and N-cadherin in A549 cells were examined by western blot analysis. The current study indicated that the expression of GSTA1 was increased in A549 cells following nicotine treatment. GSTA1 suppression inhibited the viability, invasion and adhesion of lung cancer cells. In addition, the increase in lung cancer cell viability, invasion and adhesion by nicotine was suppressed following GSTA1 knockdown. Furthermore, GSTA1 affected the expression of EMT markers in nicotine-treated or untreated lung cancer cells. Thus the present study demonstrates that GSTA1 promotes lung cancer cell invasion and adhesion and mediates the effect of nicotine on lung cancer cell metastasis in vitro. Furthermore, the results demonstrated that GSTA1 exerts its effect on lung cancer cell metastasis by promoting the EMT.

Acute cerebral infarction can progress rapidly, and there are limited specific and effective treatments. Small ubiquitin‑like modifiers (SUMOs) provide an important post‑translational modification of proteins. Following cerebral infarction, multiple proteins can combine with SUMOs to protect nerve cells. Furthermore, moderate hypothermia (core body temperature, 33‑34˚C) can increase the level of SUMOylation on multiple proteins. In the present study, it was examined whether moderate hypothermia increases the survival rate of bone marrow stromal stem cells (BMSCs) implanted in the cerebral ischemic penumbra via SUMOylation of multiple proteins. Firstly, BMSCs were exposed to oxygen‑glucose deprivation (OGD) under moderate hypothermic (33˚C) conditions. Subsequently, adult rats with middle cerebral artery occlusion were treated with a combination of BMSCs and moderate hypothermia (32‑34˚C). The results demonstrated that hypothermia promoted the combination of multiple proteins with SUMOs in BMSCs, and induced transport of SUMOs from the cytoplasm to the nucleus. Moderate hypothermia additionally reduced damage to BMSCs following OGD and improved BMSC survival following transplantation into the penumbra. These data suggest that moderate hypothermia may protect against BMSC injury via rapid SUMOylation of intracellular proteins. Thus, BMSC transplantation combined with moderate hypothermia may be a potential therapeutic strategy to treat cerebral infarction.

The Polycomb group genes are a general class of regulators that are responsible for maintaining homeotic gene expression throughout cell division. Polycomb group expression plays an important role in oncogenesis of several types of human cancer. Melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 are key Polycomb group proteins. Studies have shown that melanoma nuclear protein 18 is a potential tumor suppression, and B-cell-specific Moloney leukemia virus insert site 1 is overexpressed in several human malignancies. However, the roles of melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 in esophageal squamous cell carcinoma are still unclear. In this study, we analyzed the expression levels of melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 in 89 esophageal cancer tissues and paired normal mucosal tissues using immunohistochemistry, Western blotting, and quantitative real-time polymerase chain reaction analyses. We found that the expression of melanoma nuclear protein 18 in the carcinoma tissues was significantly lower than that in the noncancerous mucosal tissues (P < .05), and B-cell-specific Moloney leukemia virus insert site 1 expression in the carcinoma tissues was significantly higher than that in the noncancerous mucosal tissues (P < .05). In addition, the expression of melanoma nuclear protein 18 was correlated with clinical stage, depth of invasion, and lymph node metastasis (P < .05) but was not correlated with gender, age, degree of differentiation, or disease-free survival (P > .05). B-cell-specific Moloney leukemia virus insert site 1 expression was strongly correlated with the degree of differentiation, clinical stage, and lymph node metastasis (P .05). Moreover, there was a negative correlation between melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 expressions in esophageal squamous cell carcinoma (P < .05). Our study suggests that melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 may play a crucial role in esophageal squamous cell carcinoma. Melanoma nuclear protein 18 or B-cell-specific Moloney leukemia virus insert site 1 may be a potential biomarker for diagnosis and prognosis of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) accounts for almost 90% of esophageal cancer cases and is the sixth most common cause of cancer-associated mortality worldwide. Cisplatin is the standard therapeutic reagent for ESCC; however, chemoresistance frequently occurs after a few weeks, which leads to ESCC recurrence. Aberrant expression of B lymphoma Mo-MLV insertion region 1 homolog (BMI1) has been reported to activate multiple growth-regulatory pathways, induce antiapoptotic abilities in numerous types of cancer cells and promote chemoresistance. However, to the best of our knowledge, the role of BMI1 in cisplatin-resistant ESCC, and the interaction between BMI1 and its homologue melanoma nuclear protein 18 (Mel18) remain unknown. The present study identified that knockdown of BMI1 promoted cytotoxic effects of cisplatin, and co-inhibition of Mel18 and BMI1 enhanced cisplatin-induced apoptosis and cytotoxicity. Inhibition of BMI1 and Mel18 also suppressed the expression of c-Myc. Furthermore, this combined inhibition sensitized esophageal xenograft tumors to cisplatin to a greater extent compared with BMI1 inhibition alone. In summary, the current study demonstrated that inhibition of BMI1 and Mel18 could increase the sensitivity of esophageal cancer cells to cisplatin via inhibition of c-Myc. Therefore, combined targeting of BMI1 and Mel18 may serve as a promising therapeutic strategy for sensitizing ESCC to chemotherapy.

Safety and feasibility of the self-made thoracic needled suspending device with a snare in the uniportal video-assisted thoracic lobectomy and segmentectomy for the treatment of non-small cell lung cancer were explored. In total, 80 pulmonary lung major resections (including lobectomy and segmental resections) with systematic mediastinal lymphadenectomy were retrospectively analyzed. Patients were randomly divided into an observation group and a control group. In the observation group, the device was used to hang affected lungs, left and right vagus nerve at the level of tracheal bifurcation, the arch of azygos vein, left phrenic nerve and left and right bronchus on the chest wall to offer a better exposure of the operation field. In the control group, the conventional uniportal video-assisted thoracic surgery was performed without using the self-made device. Systematic mediastinal lymphadenectomy was performed in both groups. Operation time, intraoperative blood loss, postoperative extubation time, hospital stay and perioperative complications in the early stage of patients in both groups were compared. The operation time 120.2±40.32 min, intraoperative blood loss 100.51±50.23 ml, and postoperative suction drainage volume 208±97.56 ml/day in the observation group were significantly different from those in the control group (P0.05). The self-made thoracic needled suspending device with a snare is an excellent helper for uniportal video-assisted thoracic surgery, because it helps to expose surgical field and has no postoperative cicatrisation at puncture point on the wall of the chest. The device and its use are worthy of promotion.

In order to effectively eliminate the random noise in the noise image, based on the principle of Canny operator, an adaptive median filter is used to optimize, and an improved wavelet domain image denoising algorithm is proposed. The algorithm divides the noise image by wavelet decomposition into an approximate component for adaptive Wiener filtering, the detail component is extracted by the Canny operator based on the adaptive median filter, and the processed components are reconstructed to obtain the denoised image. The simulation results show that the proposed algorithm performs well in the random noise, and the PSNR value is greater than 24 dB. In this paper, the PSNR of the noise of the random noise is higher than that of other algorithms, and the maximum is about 12 dB, which verifies the effectiveness of the algorithm. The improved wavelet domain image denoising algorithm can remove the random noise of the image, which is a kind of excellent denoising algorithm.

Intraoperative bleeding is the most crucial safety concern of video-assisted thoracic surgery (VATS) for a major pulmonary resection. Despite the advances in surgical techniques and devices, intraoperative bleeding is still not rare and remains the most common and potentially fatal cause of conversion from VATS to open thoracotomy. Therefore, to guide the clinical practice of VATS lung surgery, we proposed the International Interest Group on Bleeding during VATS Lung Surgery with 65 experts from 10 countries in the field to develop this consensus document. The consensus was developed based on the literature reports and expert experience from different countries. The causes and incidence of intraoperative bleeding were summarised first. Seven situations of intraoperative bleeding were collected based on clinical practice, including the bleeding from massive vessel injuries, bronchial arteries, vessel stumps, and bronchial stumps, lung parenchyma, lymph nodes, incisions, and the chest wall. The technical consensus for the management of intraoperative bleeding was achieved on these seven surgical situations by six rounds of repeated revision. Following expert consensus statements were achieved: (I) Bleeding from major vascular injuries: direct compression with suction, retracted lung, or rolled gauze is useful for bleeding control. The size and location of the vascular laceration are evaluated to decide whether the bleeding can be stopped by direct compression or by ligation. If suturing is needed, the suction-compressing angiorrhaphy technique (SCAT) is recommended. Timely conversion to thoracotomy with direct compression is required if the operator lacks experience in thoracoscopic angiorrhaphy. (II) Bronchial artery bleeding: pre-emptive clipping of bronchial artery before bronchial dissection or lymph node dissection can reduce the incidence of bleeding. Bronchial artery bleeding can be stopped by compression with the suction tip, followed by the handling of the vascular stump with energy devices or clips. (III) Bleeding from large vessel stumps and bronchial stumps: bronchial stump bleeding mostly comes from accompanying bronchial artery, which can be clipped for hemostasis. Compression for hemostasis is usually effective for bleeding at the vascular stump. Otherwise, additional use of hemostatic materials, re-staple or a suture may be necessary. (IV) Bleeding from the lung parenchyma: coagulation hemostasis is the first choice. For wounds with visible air leakage or an insufficient hemostatic effect of coagulation, suturing may be necessary. (V) Bleeding during lymph node dissection: non-grasping en-bloc lymph node dissection is recommended for the nourishing vessels of the lymph node are addressed first with this technique. If bleeding occurs at the site of lymph node dissection, energy devices can be used for hemostasis, sometimes in combination with hemostatic materials. (VI) Bleeding from chest wall incisions: the chest wall incision(s) should always be made along the upper edge of the rib(s), with good hemostasis layer by layer. Recheck the incision for hemostasis before closing the chest is recommended. (VII) Internal chest wall bleeding: it can usually be managed with electrocoagulation. For diffuse capillary bleeding with the undefined bleeding site, compression of the wound with gauze may be helpful.

The majority of cancer stem cells exist in the G0, or quiescent phase of the cell cycle. However, the cells can escape quiescence following routine radiotherapy and chemotherapy, resulting in tumor recurrence. Presently, achieving the accurate regulation of cancer stem cell growth in order to study a specific state, including the quiescent (mostly G0 or G1 phase), proliferative (mostly S phase) or differential (mostly G2/M phase) states, can be challenging. This makes the determination of cell cycle state-specific characteristics and analysis of potential intervention treatments difficult, particularly for quiescent cells. Breast cancer stem cells were cultured on a soft or hard agar matrix surface in the presence or absence of stem cell growth factors. Cells could be successfully limited in either the quiescent, proliferative or differentiated states. These findings provide a foundation for further study of the cell cycle in breast cancer stem cells.

// Xianqi Zhang 1, * , Chunhong Wang 2, * , Shan Shan 2 , Xiyu Liu 3 , Zhongmin Jiang 1 , Tao Ren 2 1 Department of Thoracic Surgery, Qianfoshan Hospital, Shandong University, Shandong 250014, China 2 Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China 3 Department of Thoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, China * These authors contributed equally to this work Correspondence to: Tao Ren, email: rentaosh@126.com Zhongmin Jiang, email: qyjzm@sina.com Keywords: lung cancer, LPS, TLR4, miR-21, ROS Received: March 21, 2016 Accepted: May 16, 2016 Published: June 07, 2016 ABSTRACT Activation of Toll-like receptor 4 (TLR4) signaling in human lung cancer with lipopolysaccharide (LPS) enhances tumor progression. However, whether primary human lung cancer outgrowth could respond to LPS and underlying mechanisms are unclear. Here we determined that TLR4 activation with LPS promoted outgrowth of primary human lung cancer cells in vitro and in vivo . Mechanistically, LPS stimulation increased expression levels of microRNA-21 (miR-21) in primary human lung cancer cells. Inhibition of miR-21 blocked the enhanced lung cancer growth induced by LPS in vitro and in vivo . Up-regulation of miR-21 promoted outgrowth of primary human lung cancer. Down-regulation of miR-21 limited primary human lung cancer outgrowth. Further, TLR4 activation in primary human lung cancer cells increased their ROS levels. Scavenge of ROS abrogated the up-regulation of miR-21 in primary human lung cancer cells and attenuated LPS-induced outgrowth. For in vivo relevance, expression of TLR4 was correlated with miR-21 expression and ROS production in freshly isolated, untreated primary human lung cancer cells. These findings demonstrate an essential role of TLR4/ROS/miR-21 pathway in LPS-induced outgrowth of primary human lung cancer. Our study connected a framework of innate signaling, oxidative stress and microRNA in tumor immunity and provided clues for developing new therapeutics for lung cancer.

Esophageal squamous cell carcinoma (ESCC) accounts for almost 90% of esophageal cancer cases and is the sixth most common cause of cancer-associated mortality worldwide. Cisplatin is the standard therapeutic reagent for ESCC; however, chemoresistance frequently occurs after a few weeks, which leads to ESCC recurrence. Aberrant expression of B lymphoma Mo-MLV insertion region 1 homolog (BMI1) has been reported to activate multiple growth-regulatory pathways, induce antiapoptotic abilities in numerous types of cancer cells and promote chemoresistance. However, to the best of our knowledge, the role of BMI1 in cisplatin-resistant ESCC, and the interaction between BMI1 and its homologue melanoma nuclear protein 18 (Mel18) remain unknown. The present study identified that knockdown of BMI1 promoted cytotoxic effects of cisplatin, and co-inhibition of Mel18 and BMI1 enhanced cisplatin-induced apoptosis and cytotoxicity. Inhibition of BMI1 and Mel18 also suppressed the expression of c-Myc. Furthermore, this combined inhibition sensitized esophageal xenograft tumors to cisplatin to a greater extent compared with BMI1 inhibition alone. In summary, the current study demonstrated that inhibition of BMI1 and Mel18 could increase the sensitivity of esophageal cancer cells to cisplatin via inhibition of c-Myc. Therefore, combined targeting of BMI1 and Mel18 may serve as a promising therapeutic strategy for sensitizing ESCC to chemotherapy.

Esophageal cancer is ranked as the malignant tumor with the 6th highest morbidity and mortality rate worldwide. Chinese people are prone to develop esophageal cancer, and the number of new cases that occur every year account for more than half of the esophageal cancer patients worldwide (1,2). Although reports have confirmed the effectiveness of chemoradiotherapy for esophageal cancer, esophageal resection remains the primary means of treatment. Anastomotic leaks and pulmonary complications are the most common postoperative complications of esophageal cancer and carcinoma of the gastric cardia. Pulmonary complications have become more noticeable (3) as the incidence of postoperative anastomotic fistula (8–15%) has decreased due to the improvement of surgical techniques, the use of disposable staplers, and the continuous improvement of postoperative nutritional support Cervical and upper thoracic esophageal cancer are associated with a higher risk for postoperative pulmonary infection.

BACKGROUND Src and Fn14 are implicated in the aggressiveness of non-small cell lung cancer (NSCLC) cells, yet the molecular mechanism is not fully understood. MATERIAL AND METHODS The proliferation, migration, and invasion of HCC827 cells with Src knockdown were examined in vitro. The expression of Fn14 and the activation of NF-κB signaling pathway in Src-silenced HCC827 cells were detected by western blot. The role of Fn14 in Src-regulated cell migration/invasion and activation of NF-κB signaling was investigated by overexpressing Fn14 in Src knockdown NSCLC cells. Furthermore, the pro-metastatic role of Src was validated in a NSCLC metastasis mouse model. RESULTS Knockdown of Src inhibited the proliferation, migration, and invasion of HCC827 cells, which was associated with reduced levels of Fn14, p-IκBα, p-IKKβ, and nuclear NF-κB p65. Overexpression of Fn14 restored the potential of migration and invasion as well as the activation of NF-κB signaling in Src-silenced NSCLC cells. In addition, silencing of Src suppressed lung metastasis of HCC827 cells in mice, and inhibited the expression of Fn14 and nuclear translocation of NF-κB p65 in vivo. CONCLUSIONS The data demonstrated that the Src/Fn14/NF-κB axis plays a critical role in NSCLC metastasis.

Connexin 43 (Cx43) can be modified and regulated by small ubiquitin-like modifier (SUMO)1; however, its role in liver cancer stem cells is poorly understood. In this study, we found a significant difference in the expression of Cx43 and SUMO1 between cancer stem cells and non-cancer stem cells in liver cancer. In liver cancer stem cells, Cx43 was almost absent, although the level of SUMO1 was significantly higher than that in non-cancer stem cells. Further experiments confirmed that the conjugated site of Cx43 by SUMO1 was located in Lys-144 and Lys-237, both of which are highly conserved among species. By the co-expression of Cx43 and SUMO1 in cancer stem cells, the gap junction intercellular communication (GJIC) of liver cancer stem cells was obviously improved. Using this feature, we verified whether it could effectively increase the sensitivity of cancer stem cells to the herpes simplex virus 1 thymidine kinase (HSVtk) gene in combination with ganciclovir (GCV), a conventional chemotherapeutic drug, in vitro and in vivo. As expected, increasing the expression of Cx43 SUMOylation in liver cancer stem cells effectively enhanced their sensitivity to HSVtk/GCV. On the whole, this study revealed a novel method which may be used to effectively restore GJIC in cancer stem cells in liver cancer, which enhances their sensitivity to conventional chemotherapeutic drugs.

WOS: 000448440500021, PubMed: 30505474, …

Project name: methods for the preoperative assessment of cardiovascular functions and criteria for the assessment of risk factors in patients with lung cancer.

Patients undergoing lobectomy are at significantly increased risk of lung injury. One-lung ventilation is the most commonly used technique to maintain ventilation and oxygenation during the operation. It is a challenge to choose an appropriate mechanical ventilation strategy to minimize the lung injury and other adverse clinical outcomes. In order to understand the available evidence, a systematic review was conducted including the following topics: (I) protective ventilation (PV); (II) mode of mechanical ventilation [e.g., volume controlled (VCV) versus pressure controlled (PCV)]; (III) use of therapeutic hypercapnia; (IV) use of alveolar recruitment (open-lung) strategy; (V) pre-and post-operative application of positive end expiratory pressure (PEEP); (VI) Inspired Oxygen concentration; (VII) Non-intubated thoracoscopic lobectomy; and (VIII) adjuvant pharmacologic options. The recommendations of class II are non-intubated thoracoscopic lobectomy may be an alternative to conventional one-lung ventilation in selected patients. The recommendations of class IIa are: (I) Therapeutic hypercapnia to maintain a partial pressure of carbon dioxide at 50–70 mmHg is reasonable for patients undergoing pulmonary lobectomy with one-lung ventilation; (II) PV with a tidal volume of 6 mL/kg and PEEP of 5 cmH 2 O are reasonable methods, based on current evidence; (III) alveolar recruitment [open lung ventilation (OLV)] may be beneficial in patients undergoing lobectomy with one-lung ventilation; (IV) PCV is recommended over VCV for patients undergoing lung resection; (V) pre- and post-operative CPAP can improve short-term oxygenation in patients undergoing lobectomy with one-lung ventilation; (VI) controlled mechanical ventilation with I:E ratio of 1:1 is reasonable in patients undergoing one-lung ventilation; (VII) use of lowest inspired oxygen concentration to maintain satisfactory arterial oxygen saturation is reasonable based on physiologic principles; (VIII) Adjuvant drugs such as nebulized budesonide, intravenous sivelestat and ulinastatin are reasonable and can be used to attenuate inflammatory response.

BRLO-Tree (Block-R-Tree-Loose-Octree) is presented in this paper based on the R-Tree and Loose-Octree. The aim of the structure is to visualize the large scale and complex dynamic scenes in a 3D (three-dimensional) GIS (Geographic Information System). A new method of clustering rectangles to construct R-tree based on an improved K-means algorithm is put forward. Landform in 3D GIS is organized by R-Tree. The block is used as the basic rendering unit. The 3D objects of each block are respectively organized by a Loose-Octree. A series of techniques, based on this data structure, such as LOD (Level of Detail), relief impostors are integrated. The results of the tests show that BRLO-Tree cannot only support the large scale 3D GIS scene exhibition with wandering and fighting, but it can also efficiently manage the models in a dynamic scene. At the same time, a set of integrated techniques based on BRLO-Tree can make the rendering pictures more fluence and the rendering time vastly improved.

The Society for Translational Medicine and The Chinese Society for Thoracic and Cardiovascular Surgery conducted a systematic review of the literature in an attempt to improve our understanding in the postoperative management of chest tubes of patients undergoing pulmonary lobectomy. Recommendations were produced and classified based on an internationally accepted GRADE system. The following recommendations were extracted in the present review: (I) chest tubes can be removed safely with daily pleural fluid of up to 450 mL (non-chylous and non-sanguinous), which may reduce chest tube duration and hospital length of stay (2B); (II) in rare instances, e.g., persistent abundant fluid production, the use of PrRP/B

With the development of printed electronic, the material cost needs change from film or glass to paper which is very convenient and lower cost for users. The papers suitable for printed electronics was studied based on one layer circuit. An exploratory experiment was designed to evaluate the relationship between designed line width and visual lines. According to the surface uniform and luminescent data, the rules should be gotten with different type papers. Coated paper, paperboard and offset paper have different characters in printed electronics. Coated paper is more variable than paperboard. The luminance and surface uniform data show the result that art paper and paperboard are more suitable than the other two kinds of paper in printed electronics with substrate.

Aim The aim of this study was to observe the effect of attenuated Salmonella typhi as a tumor-targeting delivery vector for multidrug-resistance gene (MDR1) small interfering RNA (siRNA). Material and Methods The cisplatin (DDP)-resistant ovarian cancer cell line SKOV-3/DDP was established by treatment with gradually increasing concentrations of cisplatin. MDR1 siRNA expression plasmid containing short hairpin RNA (shRNA) of MDR1 gene was constructed and transformed into attenuated Salmonella typhi strain SL7207. SKOV-3/DDP cells were incubated with recombinant Salmonella and then subjected to analysis of MDR1 expression by real-time polymerase chain reaction and Western blot. SKOV-3/DDP tumor-bearing mice were established by subcutaneously injecting BALB/c nude mice with SKOV-3/DDP cells, and were orally inoculated with Salmonella carrying MDR1 siRNA plasmid and simultaneously injected intraperitoneally with cisplatin. Tumor growth and mouse survival were observed. Results Compared with parental cell line, the DDP-resistant SKOV-3/DDP cells expressed a much higher level of MDR1. The expression of MDR1 in SKOV-3/DDP cells infected with the Salmonella strain bearing MDR1 siRNA plasmid in vitro was detected to be downregulated and DDP tolerance of these cells was reversed. Tumor-bearing nude mice that were orally receiving recombinant Salmonella experienced a slow tumor growth and became more sensitive to DDP. Conclusion Attenuated Salmonella typhi may represent a promising vector for in vivo administration of RNA interference therapy against malignant tumors.

To inhibit the proliferation and metastasis of colon cancer cells by increasing the expression level of B-cell translocation gene-2 (BTG2).Western blot assay was used to detect the expression level of BTG2 protein in the normal intestinal epithelial HIEC cells and three colon cancer cell lines SW620, HT-29 and LS174T. The expression of BTG2 protein in normal colonic epithelial tissue, colon adenoma and colon cancer tissue was detected by immunohistochemistry. The plasmid with BTG2 gene full-length sequence was transfected into colon cancer SW620 cells, and the expression of BTG2 protein was detected by Western blot. The cell growth curve was drawn by MTT test. The Ki-67-positive rate was calculated using immunofluorescence staining. The cell migration of colon cancer cells was detected by scratch test and Transwell double chamber culture system, and the pseudopodia growth of tumor cells was detected by Matrigel 3D culture system.Western blot results showed that BTG2 relative expression levels were 0.83 ± 0.12, 0.18 ± 0.04, 0.20 ± 0.05 and 0.36 ± 0.07 in normal human intestinal epithelial cells HIEC, and human colon cancer cell line SW620, HT-29 and LS174T, respectively. The results of immunohistochemistry showed that the positive expression of BTG2 protein in normal colorectal tissue, colorectal adenoma and colorectal carcinoma tissues were 82.5% (33/40), 77.5%(31/40) and 17.5% (7/40), respectively, with a significant difference between two groups (P0.05). Immunofluorescence results showed that the positive rate of Ki-67 in the control group, empty vector group and BTG2 transfection group was (76.2 ± 8.0)%, (81.4 ± 9.7)% and (50.1 ± 7.1)%, respectively, showing a significant difference between two groups (P0.05). The scratch test results showed that in the control group, empty vector group and BTG2 transfection group, the distance of SW620 cells between two sides was (79.27 ± 11.24) µm, (80.65 ± 12.17) µm and (124.77 ± 19.63) µm, respectively, with a significant difference between two groups (P0.05). Transwell results showed that in the control group, empty plasmid group and BTG2 transfection group, the SW620 cell migration rate was (78.5 ± 13.1)%, (73.2 ± 12.9)% and (47.4 ± 9.1)%, respectively, showing a significant difference between two groups (P0.05). The number of neurospheres of BTG2 transfection group was decreased SW620, which had poor ductility.BTG2 gene is involved in colon cancer cell proliferation and metastasis, and effectively restores the function of BTG2 protein. Therefore, it may be expected to become a new option in gene therapy for colon cancer.

To explore the clinical application of recombinant human endostatin (Endostar) in the treatment of patients with non-small cell lung cancer (NSCLC) in Chinese mainland.A total of 75 patients diagnosed as NSCLC were randomly divided into control group (37 cases) and treatment group (38 cases). Control group was treated with postoperative complementary chemotherapy containing two-agent platinum protocol on postoperative d21, 3 weeks as a cycle, for totally 4~6 cycles. On this basis, treatment group was added with Endostar 7.5 mg/m2 on postoperative d8~9, 3~4 h/time, qd, 14 weeks as a cycle, for totally 4 cycles. The interval between every two cycles was 7 d. The 5-year progression-free survival (PFS), 5-year survival time and complications in both groups were observed.Compared with control group, the average PFS increased evidently in treatment group by 9.8 months (41.6 months vs. 31.8 months), and there was significant difference (P0.05). And the median PFS was 42.5 months in treatment group, obviously longer than that in control group (33.7 months) by 8.8 months (P0.05). Additionally, the 5-year overall survival rate (OS), average survival time and median survival time (MST) were 47.4%, 50.1 months and 59.3 months in treatment group, significantly higher than the 29.7%, 42.1 months and 43.5 months in control group (P0.05). Only 1 patient showed poor healing of surgical wound in treatment group, but no surgery-associated complication was found in control group. Moreover, the postoperative complementary therapy-connected complication rates were 63.2% (24/38) and 59.5% (22/37) in treatment group and control group respectively, but there was no significant difference (P0.05).The application of Endostar combined with sensitive platinum-contained chemotherapeutic agents in the postoperative complementary chemotherapy can be widely used in clinic because it can significantly prolong the long-term survival time of patients with NSCLC.

The present study examined 66 cases of gastrointestinal stromal tumors (GISTs), 20 cases of smooth muscle tumors, 20 cases of schwannomas and 20 cases of normal gastric tissues in order to analyze the expression of L1, cluster of differentiation (CD)24 and integrin β1 by immunohistochemical staining. Patients were subjected to follow-up, and survival data were evaluated. L1 expression was detected in 57.6% of GIST cases; this was a significantly higher percentage compared with that found in the smooth muscle tumor cases or the normal control group. CD24 and integrin β1 were also expressed at significantly higher levels in the GIST cases than in the normal control group, although no significant difference was found in the expression levels of these proteins in smooth muscle tumor or schwannoma cases. These higher levels of L1 and integrin β1 expression were associated with an increased risk of invasive GIST, and were significantly positively correlated with Ki-67 expression. CD24 expression was not associated with the risk of GIST invasion or Ki-67 expression. There were positive correlations between L1, CD24 and integrin β1 expression; however, these had no significant association with patient survival. Therefore, L1 alone or in conjunction with CD24 (L1 + CD24), or integrin β1 (L1 + integrin β1) can be considered a valuable indicator for the differential diagnosis of GIST. Furthermore, L1 and integrin β1 can be used alone or in combination to evaluate the biological behavior of GISTs. Future studies are required to evaluate the prognostic value of these markers.

The aim of this study was to observe the effect of attenuated Salmonella typhi as a tumor-targeting delivery vector for multidrug-resistance gene (MDR1) small interfering RNA (siRNA).The cisplatin (DDP)-resistant ovarian cancer cell line SKOV-3/DDP was established by treatment with gradually increasing concentrations of cisplatin. MDR1 siRNA expression plasmid containing short hairpin RNA (shRNA) of MDR1 gene was constructed and transformed into attenuated Salmonella typhi strain SL7207. SKOV-3/DDP cells were incubated with recombinant Salmonella and then subjected to analysis of MDR1 expression by real-time polymerase chain reaction and Western blot. SKOV-3/DDP tumor-bearing mice were established by subcutaneously injecting BALB/c nude mice with SKOV-3/DDP cells, and were orally inoculated with Salmonella carrying MDR1 siRNA plasmid and simultaneously injected intraperitoneally with cisplatin. Tumor growth and mouse survival were observed.Compared with parental cell line, the DDP-resistant SKOV-3/DDP cells expressed a much higher level of MDR1. The expression of MDR1 in SKOV-3/DDP cells infected with the Salmonella strain bearing MDR1 siRNA plasmid in vitro was detected to be downregulated and DDP tolerance of these cells was reversed. Tumor-bearing nude mice that were orally receiving recombinant Salmonella experienced a slow tumor growth and became more sensitive to DDP.Attenuated Salmonella typhi may represent a promising vector for in vivo administration of RNA interference therapy against malignant tumors.

The aim of this retrospective study is to evaluate the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) or sequential chemoradiotherapy (SCRT) with capecitabine and cisplatin for elderly patients with locally advanced esophageal squamous cell carcinoma (ESCC). A total of 75 patients elder than 65 years with histologically proven stage II–III ESCC were enrolled, in whom 40 patients were treated with CCRT consisted of two cycles of intravenous cisplatin and oral capecitabine during and after radiotherapy and 35 patients were treated with SCRT as two cycles of capecitabine plus cisplatin before and after radiotherapy. Response rate, overall survival, progression-free survival and toxicity were compared. The overall response rate (CR + PR) in the CCRT group (91.6 %) was significantly higher than that in the SCRT group (67.7 %), P = 0.023. The median PFS and median OS were significantly higher in CCRT group (19.7 and 33.6 months) than those in SCRT group (11.6 and 15.7 months), P

Epidermal growth factor receptor (EGFR) signaling regulates glioblastoma cell proliferation, survival, migration and invasion and plays a key role in tumor progression. We show that microRNA-7 (miR-7) is a common regulator of the phosphoinositide-3-kinase (PI3K)/ATK and Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways, both of which are launched by EGFR through its two direct targets, the transcription factors PI3K and Raf-1, respectively. Enforced expression of miR-7 markedly decreased expression of PI3K, phosphorylated Akt, Raf-1, phosphorylated MEK 1/2, and cyclin D1, as well as slightly reduced expression of EGFR. Forced expression of PI3K or Raf-1 transcripts lacking the 3'-untranslated region (3'-UTR) partially reversed the effects of miR-7 on cell growth inhibition and cell cycle arrest in glioma cells. Additionally, transient expression of miR-7 in glioblastoma cells strongly inhibited in vivo glioblastoma xenograft growth. We conclude that miR-7 is a potential tumor suppressor in glioblastoma that acts by targeting multiple oncogenes related to the downstream pathway of EGFR and may serve as a novel therapeutic target for malignant gliomas.

Intrinsic resistance of glioma cells to radiation and chemotherapy is currently hypothesized to be partially attributed to the existence of cancer stem cells. Emerging studies suggest that mesenchymal stem cells may serve as a potential carrier for delivery of therapeutic genes to disseminated glioma cells. However, the tropism character of mesenchymal stem cells for cancer stem cell-like glioma cells has rarely been described. In this study, we obtained homologous bone marrow-derived (BM-) and adipose tissue-derived (AT-) mesenchymal stem cells (MSCs), fibroblast, and cancer stem cell-like glioma cells (CSGCs) from tumor-bearing mice, and compared the tropism character of BM- and AT-MSCs for CSGCs with various form of existence. To characterize the cell proliferation and differentiation, the spheroids of CSGCs were cultured on the surface of the substrate with different stiffness, combined with or withdrew basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in medium. Our results showed that the CSGCs during the process of cell proliferation, but not in resting and differentiated status, display strong tropism characteristics on both BM- and AT-MSCs, as well as the expression of their cell chemokine factors which mediate cell migration. If the conclusion is further confirmed, it may expose a fatal flaw of MSCs as tumor-targeted delivery of therapeutic agents in the treatment of the CSGCs, even other cancer stem cells, because there always exist a part of cancer stem cells that are in resting status. Overall, our findings provide novel insight into the complex issue of the MSCs as drug delivery in the treatment of brain tumors, especially in tumor stem cells.