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Few therapies are currently available for patients with KRAS-driven cancers, highlighting the need to identify new molecular targets that modulate central downstream effector pathways. Here we found that the microRNA (miRNA) cluster including miR181ab1 is a key modulator of KRAS-driven oncogenesis. Ablation of Mir181ab1 in genetically engineered mouse models of Kras-driven lung and pancreatic cancer was deleterious to tumor initiation and progression. Expression of both resident miRNAs in the Mir181ab1 cluster, miR181a1 and miR181b1, was necessary to rescue the Mir181ab1-loss phenotype, underscoring their nonredundant role. In human cancer cells, depletion of miR181ab1 impaired proliferation and 3D growth, whereas overexpression provided a proliferative advantage. Lastly, we unveiled miR181ab1-regulated genes responsible for this phenotype. These studies identified what we believe to be a previously unknown role for miR181ab1 as a potential therapeutic target in 2 highly aggressive and difficult to treat KRAS-mutated cancers.

Viral diseases of the central nervous system (CNS) represent a major global health concern. Difficulties in treating these diseases are caused mainly by the biological tissues and barriers, which hinder the transport of drugs into the CNS. To counter this, a nanobody-mediated virus-targeting drug delivery platform (SWCNTs-P-A-Nb) is constructed for CNS viral disease therapy. Viral encephalopathy and retinopathy (VER), caused by nervous necrosis virus (NNV), is employed as a disease model. SWCNTs-P-A-Nb is successfully constructed by employing single-walled carbon nanotubes, amantadine, and NNV-specific nanobody (NNV-Nb) as the nanocarrier, anti-NNV drug, and targeting ligand, respectively. Results showed that SWCNTs-P-A-Nb has a good NNV-targeting ability in vitro and in vivo, improving the specific distribution of amantadine in NNV-infected sites under the guidance of NNV-Nb. SWCNTs-P-F-A-Nb can pass through the muscle and gill and be excreted by the kidney. SWCNTs-P-A-Nb can transport amantadine in a fast manner and prolong the action time, improving the anti-NNV activity of amantadine. Results so far have indicated that the nanobody-mediated NNV-targeting drug delivery platform is an effective method for VER therapy, providing new ideas and technologies for control of the CNS viral diseases. IMPORTANCE CNS viral diseases have resulted in many deadly epidemics throughout history and continue to pose one of the greatest threats to public health. Drug therapy remains challenging due to the complex structure and relative impermeability of the biological tissues and barriers. Therefore, development in the intelligent drug delivery platform is highly desired for CNS viral disease therapy. In the study, a nanobody-mediated virus-targeting drug delivery platform is constructed to explore the potential application of targeted therapy in CNS viral diseases. Our findings hold great promise for the application of targeted drug delivery in CNS viral disease therapy.

MicroRNAs (miRNAs) are a type of ncRNAs with 18-25 nucleotides in length and reported to play crucial roles in human cancers. Bladder cancer is one of the most common causes of cancer-related death. The discovery of new early biomarkers for BC may improve the patients' response to the treatment thus obtaining higher outcomes. The present study identified 7 miRNAs were up-regulated in bladder serum cancer samples compared to normal samples, including hsa-miR-185-5p, hsa-miR-663a, hsa-miR-30c-5p, hsa-miR-3648, hsa-miR-1270, hsa-miR-200c-3p, and hsa-miR-29c-5p. The dysregulation of these miRNAs were correlated to advanced stage and overall survival time in bladder cancer patients. Moreover, we identified a predictive model to predict the prognosis of bladder cancer. Kaplan-Meier survival curve analyses showed that bladder cancer patients with high-risk scores had significantly worse overall survival time than bladder patients with lower risk scores. Furthermore, we constructed a miRNA-mRNA regulating network. Bioinformatics analysis showed these miRNAs were involved in regulating sarcomere organization, positive regulation of multicellular organism growth, phosphorylation, phosphatidylinositol-mediated signaling, and peroxisome proliferator activated receptor signaling pathway. We thought this study could provide novel noninvasive early biomarkers for bladder cancer.

Purpose The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and methods A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involved and divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were compared before and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR (p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longer median RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335, respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase (AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels >200 ng/mL.

Background and objectives Irreversible electroporation (IRE) is a non-thermal focal therapy that utilizes high voltage electric pulses to permanently rupture the cellular membrane and induce cell death. In this multi-center study, we evaluated the safety and efficacy of IRE in patients with locally advanced pancreatic cancer (LAPC). Methods From 2012 to 2015, we performed laparotomic and laparoscopic IRE in a total of 70 patients with stage III LAPC. Either gemcitabine-based or TS-1 (Tegafur, Gimeracil, and Oteracil) chemotherapy was applied for at least 3 months before the IRE. Results No IRE-related deaths occurred. A median follow-up of 28.1 months showed that six patients (8.6%) experienced local recurrence and 24 (34%) experienced distant progression. The overall median survival from the time of treatment was 22.6 months, and the progression-free survival (PFS) was 15.4 months. The overall survival in the patients who used gemcitabine-based reagents was 19.1 months and that of those who used TS-1 was 28.7 months. The PFS for these two groups were 13.2 months and 26.4 months; the difference is significant. Conclusions Our study suggests that IRE is safe and effective for the control of LAPC. We surmise that the addition of IRE to a chemotherapy regimen may provide a survival advantage.

This study presents a detailed fabrication method, together with validation, discussion, and analysis, for state-of-the-art silicon carbide (SiC) etching of vertical and bevelled structures by using inductively coupled plasma reactive ion etching (ICP-RIE) for microelectronic applications. Applying different gas mixtures, a maximum bevel angle of 87° (almost vertical), large-angle bevels ranging from 40° to 80°, and small-angel bevels ranging from 7° to 17° were achieved separately using distinct gas mixtures at different ratios. We found that SF6 with additive O2 was effective for vertical etching, with a best etching rate of 3050 Å/min. As for the large-angle bevel structures, BCl3 + N2 gas mixtures show better characteristics, exhibiting a controllable and large etching angle range from 40° to 80° through the adjustment of the mixture ratio. Additionally, a Cl2 + O2 mixture at different ratios is applied to achieve a small-angel bevels ranging from 7° to 17°. A minimum bevel angel of approximately 7° was achieved under the specific volume of 2.4 sccm Cl2 and 3.6 sccm O2. These results can be used to improve performance in various microelectronic applications including MMIC via holes, PIN diodes, Schottky diodes, JFETs’ bevel mesa, and avalanche photodiode fabrication.

We read with interest the leading article by Gerbes et al 1 published in Gut. This roundtable meeting article proposed that hepatocellular carcinoma (HCC) staging linked to first-line treatment indication can help clinicians guide patients through treatment decision-making process, patients and researchers need reliable ways to stage disease and predict prognosis. Controversies always exist during multidisciplinary team (MDT) decision-making for HCC patients within the Milan criteria (MC) due to the lack of evidence-based studies of composite multiparametric evaluations among the three potential curative therapies: liver transplantation (LT), liver resection (LR) and local ablation (LA).2–4 Herein, we retrospectively evaluated the efficacy of LT, LR and LA for HCC patients within the MC and explored an individualised assessment prediction model to assist with MDT decision-making. Institutional ethics committees approved the retrospective analyses of consecutive HCC patients admitted to two medical centres of Nankai University (Tianjin, China) between November 2011 and March 2016. A total of 283 HCC patients within the MC were finally enrolled and classified into LT (n=100), LR (n=89) and LA (n=94) groups based on the first-line treatments. Under the three treatment groups, subgroups were divided according to …

Migraine is a primary neuropsychological disorder, although its etiology and pathogenesis are unknown. It has been reported that using contingent negative variation, the periodicity of migraine attacks is three days in adults. However, there is still a lack of relevant reports about the periodicity of migraine without aura in adults. Therefore, we investigated the changes of contingent negative variation in adults with migraine without aura from three to seven days after migraine attacks in order to provide the basis for exploring the circulation periodicity of migraine without aura. This prospective, observational study involved a group of 34 individuals with migraine without aura, who were screened during the three to seven days after a migraine attack without aura. A healthy group (31 individuals) was used as controls to assess the amplitudes of contingent negative variation and habituation of early contingent negative variation. Indices of the amplitudes included overall contingent negative variation, initial contingent negative variation, terminal contingent negative variation, and postoperative negative contingent variation. Differences between these indicators were analyzed. No significant difference was found between the patient and control groups for either the amplitudes of these measures of contingent negative variation or habituation of the early contingent negative variation for three to seven days after a migraine attack without aura (all P > 0.05). Thus, the study reported here found that the periodicity of migraine attacks without aura in adults is more than three days.

Currently, China’s State Key Laboratories (SKLs) play a vital role in the trend of scientific innovation in this amazing country. Specifically, SKLs as essential bases for national high-level research and talent training, are crucial in improving the country’s independent innovation capacity, core competitiveness, scientific and technical breakthrough, thereby leading China from a manufacturing to an innovating power. In this setting, analysis of the scientific input-output efficiency (IOE) may offer suggestion for decision-making in terms of funds optimization and management. An objective and reasonable approach of such analysis so far remains challenging, in light of so many factors associated with the scientific input-output issues. This can be shown in a recent attempt to look at the IOE of 20 independent research teams in State Key Laboratory of Respiratory Disease (SKLRD).

Purpose To assess whether urea-based cream (UBC) has prophylactic benefits on sorafenib-induced hand-foot skin reaction (HFSR) in patients with advanced hepatocellular carcinoma (HCC). Patients and Methods In this randomized, open-label trial, 871 patients with advanced HCC throughout China were treated with 10% UBC three times per day plus best supportive care (BSC; n = 439) or BSC alone excluding all creams (n = 432), starting on day 1 of sorafenib treatment, for up to 12 weeks. HFSR was assessed every 2 weeks and at 14 weeks for patients completing the study. Once HFSR occurred, patients were allowed any cream, including a UBC. Results The 12-week incidence of any grade HFSR was significantly lower in the UBC group versus the BSC-alone group (56.0% v 73.6%, respectively; odds ratio [OR], 0.457; 95% CI, 0.344 to 0.608; P < .001), as was the incidence of grade ≥ 2 HFSR (20.7% v 29.2%, respectively; OR, 0.635; 95% CI, 0.466 to 0.866; P = .004). Median time to first occurrence of HFSR was significantly longer in the UBC group than the BSC-alone group (84 v 34 days, respectively; hazard ratio, 0.658; 95% CI, 0.541 to 0.799; P < .001). Elevated AST was associated with increased risk of HFSR but did not alter the treatment effect of UBC. UBC plus BSC, compared with BSC alone, did not affect the sorafenib dose reduction or interruption rate (9.1% v 11.8%, respectively; P = .1937), response rate (11.1% v 10.1%, respectively; P = .6674), or disease control rate (98.8% v 98.2%, respectively; P = .5350) at week 12. Conclusion UBC prophylaxis in patients with advanced HCC starting sorafenib reduced HFSR rates, extended the time to first occurrence of HFSR, and improved patient quality of life compared with BSC. Blinded, randomized, placebo-controlled trials to determine the role of UBC on the incidence and severity of HFSR are warranted.

Background The prognosis of hepatocellular carcinoma with portal vein tumor thrombus remains extremely poor. This pilot study aimed to evaluate the technical feasibility, effectiveness and safety of transcatheter chemoembolization for tumors in the liver parenchyma plus intra-arterial ethanol embolization for portal vein tumor thrombus. Methods A pilot study was carried out on 31 patients in the treatment group (transcatheter chemoembolization plus intra-arterial ethanol embolization) and 57 patients in the control group (transcatheter chemoembolization alone). Enhanced computed tomography/magnetic resonance images were repeated 4 weeks after the procedure to assess the response. Overall survival and complications were assessed until the patient died or was lost to follow-up. Results Median survival was 10.5 months in the treatment group (2.4 ± 1.7 courses) and 3.9 months in the control group (1.9 ± 1 courses) (P = 0.001). Patients in the treatment group had better overall survival (at 3, 6 and 12 months, respectively), compared to patients in the control group (90.3% vs. 59.6%, 64.5% vs. 29.8%, and 41.9% vs. 10.6%; p = 0.001). Furthermore, the rate of portal vein tumor thrombus regression was higher in the treatment group (93.1%) than in the control group (32.1%) (P

A concept for characterizing a radiofrequency (RF) patch biosensor combined with volume-fixed structures is presented for timely monitoring of an individual's glucose levels based on frequency variation. Two types of patch biosensors-separately integrated with a backside slot (0.53μL) and a front-side tank (0.70μL) structure-were developed to achieve precise and efficient detection while excluding the effects of interference due to the liquidity, shape, and thickness of the tested glucose sample. A glucose test analyte at different concentrations (50-600mg/dL) was dropped into the volume-fixed structures. It fully interacted with the RF patch electromagnetic field, effectively and sensitively changing the resonance frequency and magnitude of the reflection coefficient. Measurement results based on the resonance frequency showed high sensitivity up to 1.13MHz and 1.97MHz per mg/dL, and low detection limits of 26.54mg/dL and 15.22mg/dL, for the two types of patch biosensors, respectively, as well as a short response time of less than 1s. Excellent reusability of the proposed biosensors was verified through three sets of measurements for each individual glucose sample. Regression analysis revealed a good linear correlation between glucose concentrations and the resonance frequency shift. Moreover, to facilitate a multi-parameter-sensitive detection of glucose, the magnitude of the reflection coefficient was also tested, and it showed a good linear correlation with the glucose concentration. Thus, the proposed approach can be adopted for distinguishing glucose solution levels, and it is a potential candidate for early-stage detection of glucose levels in diabetes patients.

Adjuvant interferon (IFN) therapy following curative treatment for hepatocellular carcinoma (HCC) has been extensively investigated; however, the clinical benefits with different hepatitis backgrounds remain unclear. Medline, Embase, PubMed and the Cochrane Library databases were searched to identify randomized trials and cohort studies that enrolled HCC patients who received curative surgery or ablation therapy followed by IFN and control subjects; the studies were required to include data on early or late recurrence and mortality rates of HCC. Hepatitis B virus (HBV) associated with HCC (HBV-HCC) and hepatitis C virus (HCV) associated with HCC (HCV-HCC) were separately analyzed and recurrence, mortality and clinicopathological factors were compared. A total of 14 studies (9 randomized trials and 5 cohort studies, including 1,385 patients in total) were eligible for meta-analysis. IFN was found to decrease mortality and early recurrence rates, but exerted no effect on late recurrence rate. The effect of IFN differed between HBV-HCC and HCV-HCC cases. In HCV-HCC, IFN significantly reduced mortality as well as recurrence rates. However, in HBV-HCC patients, IFN reduced mortality rather than recurrence rates, although it also reduced the recurrence rate in certain subgroups. In conclusion, the effect of adjuvant IFN on postoperative recurrence differed between HBV-HCC and HCV-HCC cases; therefore, different strategies with adjuvant IFN should be used to treat HCC with different hepatitis backgrounds.

Lung cancer is the leading cause of cancer mortality worldwide, and the cause of death is metastasis. The epithelial-to-mesenchymal transition (EMT) plays a key role in the process of metastasis. Macrophages within the lung cancer microenvironment release cytokines, such as interleukin-6 (IL-6), and promote lung cancer cell invasion and metastasis. However, the interaction between macrophages and lung cancer cells and the effect of this interaction on the expression of IL-6, EMT, and the invasiveness of lung cancer cells remain unclear. Therefore, we established an in vitro co-culture model of human lung adenocarcinoma A549 or H1299 cells with THP-1-derived macrophages to illuminate the important role of macrophages in the invasion of lung cancer. In this study, we demonstrated that the concentrations of IL-6 in the co-culture supernatants were significantly increased compared with controls. Thus, a complex chemical cross-talk is induced by the indirect cell-to-cell contact between lung cancer cells and THP-1-derived macrophages. THP-1-derived macrophages appeared to play an important initiator role in the process. The analysis of the mRNA expression profiles of the sorted cells from the co-culture system revealed that the co-cultured lung cancer cells are the main source of the observed increase in IL-6 secretion. In addition, the interactions between lung cancer cells and THP-1-derived macrophages are bidirectional. The THP-1-derived macrophages underwent differentiation towards the M2-macrophage phenotype during the co-culture process. The expression of IL-6 was correlated with the induction of EMT, which contributed to a significant increase in the invasiveness of the A549 and H1299 cells in vitro. In addition, the addition of an anti-IL-6 antibody reversed these changes. In summary, we demonstrated that the in vitro co-culture of A549 or H1299 cells with THP-1-derived macrophages upregulates IL-6 expression, which increases the invasion ability of the A549 and H1299 cells through the EMT pathway. The THP-1-derived macrophages that interacted with the lung cancer cells differentiated towards the M2-macrophage phenotype. Thus, the inhibition of IL-6 or of the interactions between lung cancer cells and macrophages may be an effective target for anti-cancer therapy in patients with non-small cell lung cancer.

Background The prognosis for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is extremely poor..Objectives This study aimed to evaluate the safety and effectiveness of transarterial ethanol ablation (TEA) for the treatment of HCC with PVTT..Methods Patients were treated with TEA for PVTT under cone-beam computed tomography and traditional transarterial chemoembolization (TACE) with epirubicin for intrahepatic lesions..Results Seventeen men were successfully treated with TACE plus TEA. The mean overall survival was 18.3 ± 9.0 months (95% CI: 13.7 - 3.0 months). The quality of life (QoL) score increased from 56.9 ± 15.7 before the procedure to 88.5 ± 11.7 at 4 weeks after the procedure. Lipiodol accumulation grades of 3, 2, 1, and 0 were obtained in 3 (17.6%), 8 (47.1%), 6 (35.3%), and 0 (0%) patients, respectively..Conclusions TEA is a safe and effective method for treating patients with PVTT, offering advantages for QoL, response rate after TEA, and OS..

As pigs are susceptible to infection with both avian and human influenza A viruses, they have been proposed to be an intermediate host for the adaptation of avian influenza viruses to humans. In April 2006, a disease caused by highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) occurred in several pig farms and subsequently overwhelmed almost half of China with more than 2,000,000 cases of pig infection. Here we report a case in which four swine H9N2 influenza viruses were isolated from pigs infected by highly pathogenic PRRSVs in Guangxi province in China. All the eight gene segments of the four swine H9N2 viruses are highly homologous to A/Pigeon/Nanchang/2-0461/00 (H9N2) or A/Wild Duck/Nanchang/2-0480/00 (H9N2). Phylogenetic analyses of eight genes show that the swine H9N2 influenza viruses are of avian origin and may be the descendants of A/Duck/Hong Kong/Y280/97-like viruses. Molecular analysis of the HA gene indicates that our H9N2 isolates might have high-affinity binding to the alpha2,6-NeuAcGal receptor found in human cells. In conclusion, our finding provides further evidence about the interspecies transmission of avian influenza viruses to pigs and emphasizes the importance of reinforcing swine influenza virus (SIV) surveillance, especially after the emergence of highly pathogenic PRRSVs in pigs in China.

Pigs are susceptible to both human and avian influenza viruses and have been proposed to be intermediate hosts, or mixing vessels, for the generation of pandemic influenza viruses through reassortment or adaptation to the mammalian host. In this study, we summarize and report for the first time the coexistence of wholly human-like H3N2 viruses, double-reassortant H3N2 viruses, and triple-reassortant H3N2 viruses in pigs in China by analyzing the eight genes of swine influenza A (H3N2) viruses found in China from 1970 to 2006. In 1970, the first wholly human-like H3N2 (Hong Kong/68-like) viruses were isolated from pigs in Taiwan, and then in the next years Victoria/75-like, Sydney/97-like, New York/99-like, and Moscow/99-like swine H3N2 viruses were regularly isolated in China. In the 1980s, two triple-reassortant viruses were isolated from pigs. Recently, the double-reassortant viruses containing genes from the human (HA and NA) and avian (PB2, PB1, PA, NP, M, and NS) lineages and the triple-reassortant viruses containing genes from the human (HA and NA), classical swine (NP), and avian (PB2, PB1, PA, M, and NS) lineages emerged in pigs in China. The coexistence of wholly human-like and reassortant viruses provides further evidence that pigs serve as intermediate hosts, or mixing vessels, and emphasizes the importance of reinforcing swine influenza virus surveillance in China.

Influenza A viruses of subtypes H1N1 and H3N2 have been reported widely in pigs, associated with clinical disease. These mainly include classical swine H1N1, avian-like H1N1, and human-like or avian-like H3N2 viruses. From 2005 to 2006, we carried out swine influenza virus surveillance in eight provinces of China. Here we report, for the first time, the isolation and genetic analysis of a human-like influenza H1N1 virus from a pig in a farm of Guangdong province of southern China, a host suspected to generate new pandemic strains through genetic reassortment. Each of the eight gene segments is of human origin. Phylogenetic analysis indicates that these genes form a human lineage, suggesting that this virus is the descendant of recent human H1N1 influenza viruses. In addition, four swine H3N2 viruses were also isolated. The three H3N2 viruses from Guangdong province are descendants of recent human viruses, while an H3N2 virus from Heilongjiang province derives from early human viruses. Isolation and genetic analysis of human H1N1 and H3N2 influenza viruses from pigs in China provides further evidence about the interspecies transmission of human influenza viruses to pigs and emphasizes the importance of reinforcing swine influenza virus surveillance.

BACKGROUND: There is normally no indication for surgery in the case of non-specific low back pain. Most patients tend to seek for conservative treatment. There are different conservative treatments based on the diversity and complexity of the causes of non-specific low back pain. Current researches are not able to achieve the most sufficient and safe conservative treatment of non-specific low back pain. Manipulation, acupuncture, physiotherapy and exercise therapy are in common use of the conservative treatments to the non-specific low back pain, in which manipulation is believed to be the most effective. OBJECTIVE: To explore the effectiveness of two types of Tuina therapy in the treatment of non-specific low back pain. METHODS: The 70 patients who met the inclusion criteria of non-specific low back pain were randomly divided into spinal manipulation group and meridian massage groups. Treatment: (1)Spinal manipulation group: receive a targeted joint adjustment manipulation according to the symptoms and signs of the patients; (2) Meridian massage group: Pressing the following acupoints jinmen, shenmai, kunlun, fuyang, fuliu, gongsun, chengshan and chengjin. Palm rubbing Bladder meridian finally. Twice a week, a total of 6 times for 3 weeks. RESULT AND CONCLUSION: Tuina therapy have significant short and long term effects for chronic non-specific low back pain. Comparison of the two methods, spinal manipulation have the advantage of immediate and long-term efficacy.

The aim of this study was to investigate the prognostic significance of blood NLR in patients with intermediate-advanced hepatocellular carcinoma (HCC) who received transcatheter arterial embolization (TAE) combined with Sorafenib. A total of 40 patients with intermediate-advanced HCC from January 1, 2010, through May 31, 2013, treated with concurrent TAE in combination with Sorafenib were admitted to this study in our hospital. Potential prognostic factors, including serum NLR, were analyzed. The pretreatment mean NLR was 3.0; 21 (52.5 %) patients with elevated high NLR (>3.0). The median survival of patients with a high NLR was 14 months (95 % CI 10.1-17.9 months) compared with 26 months (95 % CI 17.4-34.6 months) for patients with a low NLR; a significant difference was found in overall survival (P = 0 0.001). Barcelona Clinical Liver Cancer staging classification and NLR >3.0 were all predictors of poorer over survival. Multivariate analysis showed that high NLR was independent factors associated with worse survival. A high periprocedural NLR independently predicts poor survival in patients with unresectable HCC undergoing TAE combined with Sorafenib.

Intermittent claudication is a form of exercise intolerance characterized by muscle pain during walking in patients with peripheral artery disease (PAD). Endothelial cell and muscle dysfunction are thought to be important contributors to the etiology of this disease, but a lack of preclinical models that incorporate these elements and measure exercise performance as a primary end point has slowed progress in finding new treatment options for these patients. We sought to develop an animal model of peripheral vascular insufficiency in which microvascular dysfunction and exercise intolerance were defining features. We further set out to determine if pharmacological activation of 5′-AMP-activated protein kinase (AMPK) might counteract any of these functional deficits. Mice aged on a high-fat diet demonstrate many functional and molecular characteristics of PAD, including the sequential development of peripheral vascular insufficiency, increased muscle fatigability, and progressive exercise intolerance. These changes occur gradually and are associated with alterations in nitric oxide bioavailability. Treatment of animals with an AMPK activator, R118, increased voluntary wheel running activity, decreased muscle fatigability, and prevented the progressive decrease in treadmill exercise capacity. These functional performance benefits were accompanied by improved mitochondrial function, the normalization of perfusion in exercising muscle, increased nitric oxide bioavailability, and decreased circulating levels of the endogenous endothelial nitric oxide synthase inhibitor asymmetric dimethylarginine. These data suggest that aged, obese mice represent a novel model for studying exercise intolerance associated with peripheral vascular insufficiency, and pharmacological activation of AMPK may be a suitable treatment for intermittent claudication associated with PAD.

Background Fibromyalgia syndrome (FMS) is characterized by widespread pain and lowered pain threshold. FMS affects an estimated 2% of the population, but optimal management of FM is still unknown. Objective To compare the treatment effect between Tuina therapy plus Baduanjin exercise with Tuina therapy only for the management of patient with fibromyalgia syndrome. Methods Patients with fibromyalgia syndrome were randomly divided into 2 groups. Patients in the experimental group received the Tuina therapy and Baduanjin exercise. Patients in the control group received Tuina therapy only. The VAS, pain threshold and FIQ scores were assessed. Result and Conclusion Tuina therapy is efficacious in relieving pain in patients with FMS. In addition, when combined with baduanjin exercise we can resolve the other core symptoms of the syndrome including fatigue and sleep disturbance. Furthermore the treatment program was effective in improving quality of life for patients with FMS.

Background: This study aimed to analyze the dynamic changes of the scientific research innovation efficiency of Guangzhou Institute of Respiratory Diseases (GIRD) during the year 2009–2013 to explore the reason for these changes and give some suggestions on how to improve the overall efficiency of the Institute. Methods: The panel data used in this study were taken from 19 research teams of GIRD during 2009 to 2013. Data envelopment analysis (DEA) based on Malmquist index (MI) was used to analyze the performance of each research team in terms of productivity changes over time. Data were analyzed using DEAP 2.1 software. Results: The annual average increase rate of total factor productivity (TFP), technological progress, technical efficiency, pure technical efficiency, and scale efficiency was 30.4%, 22.5% , 6.4%, 0.9%, and 5.4%, respectively from 2009 to 2013. The scientific research innovation efficiency of the GIRD was generally high and kept on growing. The increase of TFP was mainly caused by the progress of tech, the descending of TFP in some teams should be mainly attributable to the declining pure technical efficiency, and scale efficiency on the whole, maintaining a stable growth at a low speed. Conclusions: To achieve higher scientific research innovation, GIRD not only needs to further improve the management level and introduce advanced management mode, but also needs to focus on optimization of resource allocation, as well as to strengthen the talent introduction, and continue to maintain the absorption of new technologies and innovation.

Background & Aims Antiangiogenic agents can sometimes promote tumor invasiveness and metastasis, but little is known about the effects of the antiangiogenic drug sorafenib on progression of hepatocellular carcinoma (HCC). Methods Sorafenib was administered orally (30 mg · kg −1 · day −1 ) to mice with orthotopic tumors grown from HCC-LM3, SMMC7721, or HepG2 cells. We analyzed survival times of mice, along with tumor growth, metastasis within liver and to lung, and induction of the epithelial-mesenchymal transition. Polymerase chain reaction arrays were used to determine the effects of sorafenib on gene expression patterns in HCC cells. We analyzed regulation of HIV-1 Tat interactive protein 2 ( HTATIP2 ) by sorafenib and compared levels of this protein in tumor samples from 75 patients with HCC (21 who received sorafenib after resection and 54 who did not). Results Sorafenib promoted invasiveness and the metastatic potential of orthotopic tumors grown from SMMC7721 and HCC-LM3 cells but not from HepG2 cells. In gene expression analysis, HTATIP2 was down-regulated by sorafenib. HCC-LM3 cells that expressed small hairpin RNAs against HTATIP2 (knockdown) formed less invasive tumors in mice following administration of sorafenib than HCC-LM3 without HTATIP2 knockdown. Alternatively, HepG2 cells that expressed transgenic HTATIP2 formed more invasive tumors in mice following administration of sorafenib. Sorafenib induced the epithelial-mesenchymal transition in HCC cell lines, which was associated with expression of HTATIP2. Sorafenib regulated expression of HTATIP2 via Jun-activated kinase (JAK) and signal transducer and activator of transcription (STAT)3 signaling. Sorafenib therapy prolonged recurrence-free survival in patients who expressed lower levels of HTATIP2 compared with higher levels. Conclusions Sorafenib promotes invasiveness and the metastatic potential of orthotopic tumors from HCC cells in mice, down-regulating expression of HTATIP2 via JAK-STAT3 signaling.

NS1 protein of Japanese encephalitis virus (JEV) is an important non-structural protein, which is able to induce protective immune response in target animals and can be used as specific serological diagnosis tool, but the epitopes on NS1 of JEV have not been identified. For epitope mapping, in this study, a series of 51 partially overlapping fragments covering entire NS1 protein were expressed with a GST-tag and then screened by a monoclonal antibody (mAb). Through enzyme-linked immunosorbent assay (ELISA), linear epitope-containing fragment, the overlapping region of NS1-18 and NS1-19 (residues 145-152), was located. Then a set of peptides derived from that overlapping region with deletions were expressed and subjected to ELISA and Western blot for further mapping purpose. Results indicated that the motif of (146)EHARW(150) is the minimal unit of the linear epitope recognized by that monoclonal antibody (mAb). Western blot showed that this epitope could be recognized by JEV-positive serum from pigs. Furthermore, it was found that the epitope is highly conserved among JEV strains through sequence alignments analysis. Notably, none of the homologous regions on NS1 proteins of other flavivirus could react with the mAb when they were tested for cross-reactivity, suggesting the potential clinical application of this epitope in differential diagnosis.

H1N1 and H3N2 are the dominant subtypes causing swine influenza in China and other countries. It is important to develop effective vaccines against both H1N1 and H3N2 subtypes of swine influenza virus (SIV). We examined the effects of a DNA vaccine expressing an influenza HA fused to three copies of murine complement C3d in mice. Plasmids encoding soluble HA (sHA), complete HA (tmHA), or a soluble fused form of HA (sHA-mC3d3) were constructed from the H3N2 subtype of SIV. The immune response was monitored by an enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition (HI) assays, and virus neutralization tests. Analysis of antibody titers indicated that immunization with HA-mC3d3 resulted in higher titers of anti-HA antibodies and higher antibody affinities, compared with serum from mice immunized with sHA or tmHA. Furthermore, the C3d fusion increased the Th2-biased immune response, by inducing IL-4 production. Splenocytes from mice immunized with sHA-mC3d3 produced about three-fold more IL-4 than did splenocytes from mice immunized with sHA or tmHA. Seven days post-challenge with homologous virus (H3N2), no virus was isolated from the mice immunized with HA-expressing plasmids. However, 10 days post-challenge with heterologous virus (H1N1), only mice immunized with sHA-mC3d3 had no virus or microscopic lesions in the kidneys and cerebrum. In conclusion, C3d enhanced antibody responses to hemagglutinin and protective immunity against SIV of different subtypes.

Background: Drosophila oocyte determination involves a complex process by which a single cell within an interconnected cyst of 16 germline cells differentiates into an oocyte. This process requires the asymmetric accumulation of both specific messenger RNAs and proteins within the future oocyte as well as the proper organization of the microtubule cytoskeleton, which together with the fusome provides polarity within the developing germline cyst. Results: In addition to its previously described late oogenic role in the establishment of anterior-posterior polarity and subsequent embryonic axis formation, the Drosophila par-1 gene is required very early in the germline for establishing cyst polarity and for oocyte specification. Germline clonal analyses, for which we used a protein null mutation, reveal that Drosophila par-1 ( par-1 ) is required for the asymmetric accumulation of oocyte-specific factors as well as the proper organization of the microtubule cytoskeleton. Similarly, somatic clonal analyses indicate that par-1 is required for microtubule stabilization in follicle cells. The PAR-1 protein is localized to the fusome and ring canals within the developing germline cyst in direct contact with microtubules. Likewise, in the follicular epithelium, PAR-1 colocalizes with microtubules along the basolateral membrane. However, in either case PAR-1 localization is independent of microtubules. Conclusions: The Drosophila par-1 gene plays at least two essential roles during oogenesis; it is required early in the germline for organization of the microtubule cytoskeleton and subsequent oocyte determination, and it has a second, previously described role late in oogenesis in axis formation. In both cases, par-1 appears to exert its effects through the regulation of microtubule dynamics and/or stability, and this finding is consistent with the defined role of the mammalian PAR-1 homologs.

Background The novel small molecule R118 and the biguanide metformin, a first-line therapy for type 2 diabetes (T2D), both activate the critical cellular energy sensor 5′-AMP-activated protein kinase (AMPK) via modulation of mitochondrial complex I activity. Activation of AMPK results in both acute responses and chronic adaptations, which serve to restore energy homeostasis. Metformin is thought to elicit its beneficial effects on maintenance of glucose homeostasis primarily though impacting glucose and fat metabolism in the liver. Given the commonalities in their mechanisms of action and that R118 also improves glucose homeostasis in a murine model of T2D, the effects of both R118 and metformin on metabolic pathways in vivo were compared in order to determine whether R118 elicits its beneficial effects through similar mechanisms. Results Global metabolite profiling of tissues and plasma from mice with diet-induced obesity chronically treated with either R118 or metformin revealed tissue-selective effects of each compound. Whereas metformin treatment resulted in stronger reductions in glucose and lipid metabolites in the liver compared to R118, upregulation of skeletal muscle glycolysis and lipolysis was apparent only in skeletal muscle from R118-treated animals. Both compounds increased β-hydroxybutyrate levels, but this effect was lost after compound washout. Metformin, but not R118, increased plasma levels of metabolites involved in purine metabolism. Conclusions R118 treatment but not metformin resulted in increased glycolysis and lipolysis in skeletal muscle. In contrast, metformin had a greater impact than R118 on glucose and fat metabolism in liver tissue. Electronic supplementary material The online version of this article (doi:10.1186/1756-0500-7-674) contains supplementary material, which is available to authorized users.