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This study was aimed to explore the expression and biological function of circRNA_0005075 in gastric cancer (GC) progression and its underlying mechanism. First, the expression level of circRNA_0005075 and microRNA-431 (miR-431) in GC tissues were detected with the quantitative real-time polymerase chain reaction. In addition, after down-regulated the circRNA_0005075 expression by plasmid transfection in GC cells, the Cell Counting Kit-8 (CCK-8), EDU, transwell assay were conducted to evaluate the function of circRNA_0005075 or miR-431 on cell proliferation, metastasis in vitro. Moreover, p53 and Epithelial-mesenchymal transition (EMT) pathway related proteins were also measured with western blotting. Then, our data revealed that CircRNA_0005075 was found to be significantly up-regulated in GC tissues as well as GC cell lines, and the GC patients with higher CircRNA_0005075 expression were more likely to have poor outcomes. Down-regulation of CircRNA_0005075 could significantly suppress the GC cell proliferation and cell metastasis ability, while the addition of miR-431 inhibitors could counteract this effect. Importantly, we discovered that the silencing of circRNA_0005075 could weaken the micro-RNA sponge function for miR-431, and then upregulate the expression of p53 and forbid the EMT signalling pathway, and finally suppress the tumourigenesis of GC. To sum up, CircRNA_0005075 could inhibit cell growth and metastasis of GC through regulating the miR-431/p53/EMT axis. SIGNIFICANCE OF THE STUDY: The research clearly elucidated the potential role and relative regulatory mechanism of circRNA_0005075 in gastric cancer (GC) progression. Briefly, circRNA_0005075 could directly inhibit the expression level of miR-431, then regulate the p53/Epithelial-mesenchymal transition axis, and finally inhibit cell growth and metastasis in GC. Consequently, circRNA_0005075 might act as an oncogene in the GC procession, which provides a promising way for the treatment of GC.

BackgroundUnfolded protein response (UPR)-mediated tumor-promoting functions have been identified in multiple cancers, and this study focused on investigating the role and molecular mechanisms of UPR in modulating gastric cancer (GC) pathogenesis.MethodsThe bioinformatics analysis was performed to examine the expression status of cancer associated genes in patients with stomach adenocarcinoma (STAD) and predict the targeting sites of miR-224-5p with LncRNA MIR503HG and TUSC3. Genes expressions were quantified by Real-Time qPCR, Western Blot and immunohistochemistry (IHC). Cell proliferation, viability, apoptosis and mobility were evaluated by MTT assay, trypan blue staining assay, flow cytometer and transwell assay, respectively. The binding sites were validated by dual-luciferase reporter gene system assay.ResultsLncRNA MIR503HG and TUSC3 were downregulated, but miR-224-5p was upregulated in GC tissues and cells, in contrast with their normal counterparts. Further gain- and loss-of-function experiments validated that the malignant phenotypes in GC cells, including cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and tumorigenesis, were negatively regulated by LncRNA MIR503HG. Mechanistically, LncRNA MIR503HG upregulated TUSC3 in GC cells through sponging miR-224-5p, resulting in the repression of GC progression. Finally, we validated that knock-down of ATF6, but not other two branches of UPR (PERK1 and IRE1), partially rescued cell proliferation and EMT in the GC cells with LncRNA MIR503HG overexpression.ConclusionsTargeting the LncRNA MIR503HG/miR-224-5p/TUSC3 signaling cascade suppressed ATF6-mediated UPR, resulting in the blockage of GC development.

Introduction: We evaluated the feasibility and efficacy of chemoradiotherapy with concurrent regional arterial chemotherapy (CRT/RAC) for locally bulky unresectable rectal cancer (LBURC). Case Presentation: We retrospectively reviewed 9 patients with LBURC who received CRT/RAC between January 2012 and December 2018. The regimen consisted of chemoradiotherapy and 3 cycles of regional arterial chemotherapy. Surgery was performed 6 weeks after completion of radiotherapy. The median longest tumor diameter was 10 cm (range 8.2–13.6). Grade 3 toxicity and postoperative complications occurred in 3 and 4 patients, respectively. All patients showed partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST). One patient refused the operation after completion of the scheduled regimen but then had a bowel obstruction and had to undergo urgent surgery. Of the 8 patients who underwent scheduled surgery, all had R0 resection without multivisceral resection; 3 achieved pathological complete response and 5 exhibited good tumor regression. The median follow-up period was 35 months (range 9–63). Recurrences occurred in 3 of 9 patients (pelvic relapses in 2 and lung in 1). Conclusion: CRT/RAC appeared to be beneficial to LBURC, as it achieves remarkable rates of R0 resection, good tumor regression, and pathologic complete response. These preliminary results have to be confirmed in larger cohorts of patients.

Currently, glioblastoma (GBM) is the most common malignant tumor of the central nervous system in adults. Fibroblast activation protein (FAP) is a member of the dipeptidyl peptidase family, which has catalytic activity and is engaged in protein recruitment and scaffolds. Recent studies have found that FAP expression in different types of cells within the GBM microenvironment is typically upregulated compared with that in lower grade glioma and is most pronounced in the mesenchymal subtype of GBM. As a marker of cancer-associated fibroblasts (CAFs) with tumorigenic activity, FAP has been proven to promote tumor growth and invasion via hydrolysis of molecules such as brevican in the extracellular matrix and targeting of downstream pathways and substrates, such as fibroblast growth factor 21 (FGF21). In addition, based on its ability to suppress antitumor immunity in GBM and induce temozolomide resistance, FAP may be a potential target for immunotherapy and reversing temozolomide resistance; however, current studies on therapies targeting FAP are still limited. In this review, we summarized recent progress in FAP expression profiling and the understanding of the biological function of FAP in GBM and raised the possibility of FAP as an imaging biomarker and therapeutic target.

Objective To investigate whether serum levels of fibroblast growth factor 21 (FGF21) and fatty acid-binding protein-4 (FABP4) are associated with missed abortion (MA) in humans. Design Cross-sectional study. Setting University-affiliated hospital. Patient(s) Patients with MA at 8–12 weeks of gestation. Intervention(s) None. Main Outcome Measures(s) Serum levels of FGF21 and FABP4 were tested by enzyme-linked immunosorbent assay. Placental samples were collected during dilation and curettage surgery, and the expression of FGF21 and its related genes were measured using quantitative polymerase chain reaction. Result(s) In the discovery cohort, 78 patients with MA and 79 healthy pregnant women matched for maternal age and body mass index were nested from a prospective cohort. Circulating levels of FGF21 and FABP4 were significantly and independently elevated in patients with MA relative to the levels in the healthy controls. A single measurement of FGF21 serum level effectively discriminated MA with an area under the receiver operating characteristics curve of 0.80 (95% confidence interval: 0.73–0.87). Importantly, in our external validation cohort that comprised subjects with MA (n = 34) or induced abortion (n = 27), the FGF21 serum levels achieved an area under the receiver operating characteristics curve of 0.85 (95% confidence interval: 0.75–0.96) when identifying those with MA. Nevertheless, expression of FGF21 in the placenta was not associated with its serum concentration. Placental tissues from patients with MA exhibited impaired FGF21 signaling. Conclusion(s) Our results suggested that serum levels of FGF21 and FABP4 were associated with MA. Circulating FGF21 may serve as a potential biomarker for the recognition of MA.

Objective. Systematically evaluate the efficacy of physical ablation combined with TKI in the treatment of advanced non-small cell lung cancer (NSCLC). Methods. We performed a comprehensive search of databases including OVID, PubMed, EMBASE, the Cochrane Library, and three Chinese databases (China National Knowledge Infrastructure, Wanfang Database, and Chongqing Weipu Database). The aim was to identify randomized controlled trials (RCT) investigating physical ablation as the treatment for advanced NSCLC. We also evaluated the methodological quality of the included studies and summarized the data extracted for meta-analysis with Review Manager 5.3. Results. A total of 9 studies, including 752 patients, were evaluable. The meta-analysis results show that the complete response rate (CRR) (RR: 2.23, 95% CI: 1. 46 to 3.40, P 0.01), partial response rate (PRR) (RR: −2.25, 95% CI: 1.41 to 3.59, P 0.01), and disease control rate (DCR) (RR: −2.80, 95% CI: 1.64 to 4.80, P < 0.01) of patients with advanced NSCLC who received physical ablation combined with TKI therapy were higher than those who did not receive physical ablation therapy. The control groups from seven of the studies had a total of 606 patients with targeted therapies and chemotherapy. The complete response rate was (CRR) (RR: 2.48, 2.4895% CI: 1.55 to 2.47, P 0.01), partial response rate (PRR) (RR: −1.66, 95% CI: 1.20 to 2.31, P < 0.01), and disease control rate (DCR) (RR: −2.68, 95% CI: 1.41 to 5.06, P < 0.01) for patients with advanced NSCLC who had received physical ablation combined with targeted therapies and chemotherapy, compared to patients who had not received physical ablation therapy. This difference was statistically significant. Above all, these results showed that the clinical efficacy of physical ablation combined EGFR-TKIs therapy (regardless of whether it was combined with chemotherapy) was better than that of EGFR-TKIs therapy alone. Conclusion. Physical ablation combined with TKI treatment in patients with advanced NSCLC can improve efficacy.

Venous thromboembolism (VTE) is a relatively frequent complication in hospitalized patients, especially in those with risk factors. The benefit of using direct oral anticoagulants (DOACs) for prevention is controversial. This systematic review was performed as part of the American Society of Hematology (ASH) guidelines on VTE, developed in partnership with McMaster University. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Epistemonikos were used as data sources from date of inception to November 2019. We included randomized trials in patients hospitalized for an acute medical disease, evaluating any DOACs vs other pharmacological prophylaxis, and included 3 trials with low risk of bias. We analyzed the effects of DOACs vs low-molecular-weight heparins (LMWHs) at 2 different time points: at the end of the short-term treatment phase (both drugs given for the same period of time) and at the end of the extended prophylaxis period (extended DOACs vs a shorter course of LMWHs). We observed that the use of DOACs did not reduce the risk of pulmonary embolism or symptomatic deep venous thrombosis (DVT) in comparison with LMWHs. However, the risk of major bleeding was slightly increased. Additionally, we observed that the benefit of DOACs previously reported was largely based on the reduction of asymptomatic DVT and was not apparent when only symptomatic events were considered. The use of DOACs in hospitalized medical patients slightly increases the risk of major bleeding with no appreciable benefit over LMWHs.

Thrombolytic therapy might reduce venous thromboembolism-related mortality and morbidity, but it could also increase the risk of major bleeding. We systematically reviewed the literature to evaluate the effectiveness and safety of thrombolytics in patients with pulmonary embolism (PE) and/or deep venous thrombosis (DVT). We searched Medline, Embase, and Cochrane databases for relevant randomized controlled trials up to February 2019. Multiple investigators independently screened and collected data. We included 45 studies (4740 participants). Pooled estimates of PE studies indicate probable reduction in mortality with thrombolysis (risk ratio [RR], 0.61; 95% confidence interval [CI], 0.40-0.94) (moderate certainty) and possible reduction in nonfatal PE recurrence (RR, 0.56; 95% CI, 0.35-0.89) (low certainty). Pooled estimates of DVT studies indicate the possible absence of effects on mortality (RR, 0.77; 95% CI, 0.26-2.28) (low certainty) and recurrent DVT (RR, 0.99; 95% CI, 0.56-1.76) (low certainty), but possible reduction in postthrombotic syndrome (PTS) with thrombolytics (RR, 0.70; 95% CI, 0.59-0.83) (low certainty). Pooled estimates of the complete body of evidence indicate increases in major bleeding (RR, 1.89; 95% CI, 1.46-2.46) (high certainty) and a probable increase in intracranial bleeding (RR, 3.17; 95% CI 1.19-8.41) (moderate certainty) with thrombolytics. Our findings indicate that thrombolytics probably reduce mortality in patients with submassive- or intermediate-risk PE and may reduce PTS in patients with proximal DVT at the expense of a significant increase in major bleeding. Because the balance between benefits and harms is profoundly influenced by the baseline risks of critical outcomes, stakeholders involved in decision making would need to weigh these effects to define which clinical scenarios merit the use of thrombolytics. ispartof: BLOOD ADVANCES vol:4 issue:7 pages:1539-1553 ispartof: location:United States status: published

MicroRNAs (miRNAs) have been demonstrated to be essential regulators in the development and progression of various cancers. The role of miR-188-5p in gastric cancer (GC) has not been determined. In this study, we found that the expression of miR-188-5p was downregulated in GC tissues compared with adjacent normal tissues. The lowly expressed miR-188-5p was significantly associated with lymph node metastasis and advanced TNM stage. Moreover, overexpression of miR-188-5p significantly inhibited GC cell proliferation, migration, and invasion but promoted cellular apoptosis. Mechanistically, we identified transcription factor ZFP91 as a target gene of miR-188-5p in GC. We found that miR-188-5p overexpression significantly inhibited the expression of ZFP91 in GC cell lines. There was an inverse correlation between the expression of miR-188-5p and ZFP91 in GC tissues. We found that restoration of ZFP91 in miR-188-5p-overexpressed MGC-803 and SGC-7901 cells promoted cell proliferation, migration, and invasion. Finally, we also showed that overexpression of miR-188-5p inhibited tumor growth in vivo. Taken together, our findings indicated that miR-188-5p serves as a tumor suppressor in human GC by targeting ZFP91, suggesting that miR-188-5p might be a promising therapeutic target for GC treatment.

An earlier report showed that herpes simplex virus 1 (HSV-1) expresses two microRNAs (miRNAs), miR-H28 and miR-H29, late in the infectious cycle. The miRNAs are packed in exosomes and, in recipient cells, restrict the transmission of virus from infected cells to uninfected cells. We now report that (i) miR-H28 induced the synthesis of gamma interferon (IFN-γ) in both infected cells and cells transfected with miR-H28, (ii) IFN-γ accumulated concurrently with viral proteins in infected cells, (iii) IFN-γ was produced in HEp-2 cells derived from cancer tissue and in HEK293T cells derived from normal tissue, and (iv) HSV-1 replication was affected by exposure to IFN-γ before infection but not during or after infection. The results presented in this report support the growing body of evidence indicating that HSV-1 encodes functions designed to reduce the spread of infection from infected cells to uninfected cells, possibly in order to maximize the transmission of virus from infected individuals to uninfected individuals. IMPORTANCE In this report, we show that IFN-γ is produced by HSV-1 viral miR-H28 and viral replication is blocked in cells exposed to IFN-γ before infection but not during or after infection. The inevitable conclusion is that HSV-1 induces IFN-γ to curtail its spread from infected cells to uninfected cells. In essence, this report supports the hypothesis that HSV-1 encodes functions that restrict the transmission of virus from cell to cell.

Objectives: This study evaluates the efficacy of Chinese herbal medicines after percutaneous coronary intervention (PCI). Background: PCI is the primary treatment for coronary atherosclero...

Background. Whether traditional Chinese medicine preparation combined therapy can improve the efficacy of chemotherapy is controversial. This meta-analysis evaluates the efficacy of traditional Chinese medicine preparation combined with chemotherapy. Method. Three databases were searched from inception through August 2018. Eligible randomized controlled trials (RCTs) involving the combined treatment of chemotherapy and traditional Chinese medicine preparation compared to chemotherapy alone for treating cancer were retrieved. The methodological quality of the included RCTs was assessed with Cochrane Collaboration’s risk of bias assessment tool. Meta-analysis was adopted to make comprehensive comparisons between the experimental and control groups. Results. Four RCTs were included in this review, comprising 256 subjects. The majority of the RCTs were judged as being of poor methodological quality. Meta-analysis showed that the combination of traditional Chinese medicine preparation and chemotherapy appeared to be more effective than chemotherapy alone, for the treatment of cancer, as assessed by the disease control rate (RR: 1.41, 95% CI: 1.11 to 1.79) and the objective response rate (RR: 2.71, 95% CI: 1.28 to 5.77). There were no statistically significant differences between the groups in terms of bone marrow suppression (RR: 0.88, 95% CI: 0.57 to 1.37) or gastrointestinal reaction (RR: 1.12, 95% CI 0.75 to 1.69). Conclusions. Traditional Chinese medicine preparation combined with chemotherapy may improve objective response rates and disease control rates more than chemotherapy alone. The evidence that combined traditional Chinese medicine preparation can reduce the side effects of chemotherapy is insufficient. More rigorous randomized controlled trials are needed to confirm these conclusions.

Exercise may effectively reduce side effects caused by chemotherapy. However, no meta-analyses of exercise during or postchemotherapy for cancer patients have been definitely performed to guide clinical practice.To evaluate and summarize available scientific evidence to provide recommendations of an exercise intervention for cancer patients undergo chemotherapy.A systematic review and meta-analysis were performed with databases searching of MEDLINE, Cochrane Library, and Embase from their inception to October 15, 2017. Literature was selected to identify randomized controlled trials of exercise during or postchemotherapy for cancer patients. Risk-of-bias assessment was performed by two reviewers independently. Data were analyzed using the Cochrane Collaboration's RevMan 5.3 (Review Man, Copenhagen, Denmark).A total of 10 trials with 838 participants were included in our study. Exercise could have a beneficial effect in cancer patients undergo chemotherapy in the outcome of physical fitness (MD: 0.16, 95% CI: 0.08-0.25, p .01 and MD: 2.46, 95% CI: 1.44-3.47, p .01) and depression (MD: -1.36, 95% CI: -2.68 to -0.04, p = .04), but not in FACT-G, FACT-B, anxiety, weight, and BMI (all p .05). Exercise sequence (during or postchemotherapy) did not influence the effect of exercise for cancer patients undergo chemotherapy. In total, six studies were assessed as an overall low risk of bias. Subgroup analyses and sensitivity analyses reached results similar to those of the meta-analyses, which reflected our results were reliable and robust.Exercise seems to have a beneficial effect on physical fitness and depression, but not on quality of life, anxiety, weight, and BMI. More specific and detailed description of the implementation of exercise programs should be proposed in the future.

Background: Heart failure with reduced ejection fraction (HFrEF) has contributed to an increasing number of deaths and readmissions over the past few decades. Despite the appearance of standard treatments, including diuretics, β-receptor blockers and angiotensin-converting enzyme inhibitor (ACEI), there are still a large number of patients who have progressive deterioration of heart function and, inevitably, end-stage heart failure. In recent years, new medications for treating chronic heart failure have been clinically applied, but there is controversy surrounding drug selection and whether patients with HFrEF benefit from these medications. Therefore, we aimed to compare and rank different new pharmacological treatments in patients with HFrEF. Methods: We performed a network meta-analysis to identify both direct and indirect evidence from relevant studies. We searched MEDLINE, EMBASE, and PsycINFO through the OVID database and CENTRAL through the Cochrane Library for clinical randomized controlled trials investigating new pharmacological treatments in patients with HFrEF published up to September 30, 2018. We included trials of ivabradine, levosimendan, omega-3, tolvaptan, recombinant human B-type natriuretic peptide (rhBNP), isosorbide dinitrate and hydralazine (ISDN/HYD) and angiotensin-neprilysin inhibition (LCZ696). We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool. Based on these items, more than half of the entries were judged as having an overall low to moderate risk of bias; the remaining studies had a high or unclear risk of bias. The outcomes investigated were left ventricle ejection fraction (LVEF %), heart rate (HR) and serum level of B-type natriuretic peptide (BNP). We performed a random-effects network meta-analysis within a Bayesian framework. Results: We deemed 32 trials to be eligible that included 3810 patients and 32 treatments. Overall, 32 (94.1%) trials had a low to moderate risk of bias, while 2 (5.9%) trials had a high risk of bias. The quality of the included studies was rated as low in regard to allocation concealment and blinding and high in regard to other domains according to the Cochrane tools. As for increasing LVEF%, levosimendan was better than placebo (–3.77 (–4.96, –2.43)) and was the best intervention for improving ventricle contraction. As for controlling HR, n3-PUFA was better than placebo (4.01 (–0.44, 8.48)) and was the best choice for regulating HR. As for decreasing BNP, omega-3 was better than placebo (941.99 (–47.48, 1952.89) and was the best therapy for improving ventricle wall tension. Conclusions: Our study confirmed the effectiveness of the included new pharmacological treatments for optimizing the structural performance and improving the cardiac function in the management of patients with HFrEF and recommended several interventions for clinical practice.

Objective: To investigate the key points and effect of damage control neurosurgery (DCNS) and nursing strategy of patients with neurosurgery in bilateral frontal contusion. Methods: According to the principle of damage control nursing strategy of neurosurgery, 33 cases of bilateral frontal contusion from September 2017 to January 2019 were treated by adjusting the internal environment disorder after trauma, increasing plasma osmotic pressure and maintaining blood oxygen saturation, craniotomy and decompression operations when patients grew worse. Patients were followed up for 6 months with the corresponding nursing practice given to the patients out of hospital. Results: Among the 33 cases, 25 of them received successful conservative treatment, 8 were converted to surgery. The operation rate was 24.2%. Six months after treatment, there were 27 cases with GOS ≥ 4, including 22 cases GOS ≥ 4 in the conservative treatment group and 5 cases GOS ≥ 4 in the surgery transfer group. Conclusion: The application of DCNS in the treatment of bilateral frontal contusion and take appropriate nursing strategy intervention can reduce the operation rate, prevent complications and promote patient’s recovery.

Background/Aims An updated systematic review and meta-analysis was conducted to assess the effect of prophylactic dexamethasone for tracheal intubation of general anesthesia on postoperative sore throat (POST). Methods Comprehensive literature search of databases for randomized controlled trials (RCTs), including Embase, PubMed, and Cochrane Library, which evaluate the effect of prophylactic dexamethasone on POST was conducted. RevMan 5.0 and STATA 12.0 software were used to perform meta-analyses. Results Fourteen RCTs totaling 1,837 patients were included for analysis. Compared with placebo, a significant reduction in the incidence of POST (OR 0.44, 95% CI 0.33-0.58, P

Introduction: Essential thrombocythemia/thrombocytosis (ET) is characterized by increased bleeding and thrombosis risk during the perioperative period. We report the case of a woman with ET and sigmoid colon cancer, in whom the postoperative course was complicated by anastomotic bleeding. A systematic review was conducted to seek guidance for the management of such patient in the perioperative period. Methods: A systematic literature review was conducted using EMBASE, Medline, and PubMed databases to detect relevant English language articles. Published studies with full-text articles were included. Two authors independently searched and extracted the data. Any differences were resolved by consensus. Studies on abdominal surgery were manually retrieved. Results: Four case reports (including our case report) that described abdominal surgery in patients with ET were included. All patients were females, with a mean age of 47 years. Laparoscopic surgery was performed in 2 patients, and open surgery was performed in the other 2 patients. Two patients had postoperative bleeding that occurred on the first postoperative day. There was one case of pseudohyperkalemia after surgery and one case of Budd-Chiari syndrome caused by hepatic vein thrombosis. No guidelines for patients with ET undergoing abdominal surgery were found. Conclusion: In conclusion, there are currently no definitive guidelines for the perioperative management of patients with ET. Furthermore, there are few reports of ET in patients with malignancy undergoing surgery. Further studies in this unique group of patients are required.

Background Electrical impedance tomography is a continuous imaging method capable of measuring lung volume changes. The purpose of this study was to examine whether EIT was capable of evaluating the degree of obstructive ventilatory defect (OVD) on the global and regional level. Methods 41 healthy subjects with no lung diseases and 67 subjects suffering from obstructive lung diseases were examined using EIT and spirometry during forced vital capacity (FVC) maneuver. The subjects were divided into control group (n = 41), early airway obstruction group (n = 26), mild group (n = 17), moderate group (n = 16) and severe group (n = 8) according to the degree of obstruction. Forced expiratory volume in 1 second (FEV1) and FEV1/FVC were determined by EIT. The mode index (MI) was proposed to evaluate the degree of global and regional obstruction; the effectiveness of MI was validated by evaluating posture related change of lung emptying capacity in sitting and supine postures; the degree of regional obstruction was determined according to the cut-off values of MI obtained from receiver operating characteristic (ROC) analysis; regional obstruction was located in the four-quadrant region of interest (ROI) and the contour-map ROI with contour lines at the cut-off values of MI. Results Significant differences were found between different groups (P

Intermuscular bones are found in the myosepta in teleosts. However, there is very little information on the development and ossification of these intermuscular bones. In this study, we performed an in-depth investigation of the ossification process during development in zebrafish (Danio rerio) and Japanese eel (Anguilla japonica). In Japanese eel, a typical anguilliform swimmer, the intermuscular bones ossified predominantly from the anterior to the posterior. By contrast, in the zebrafish, a sub-carangiform or carangiform swimmer, the intermuscular bones ossified predominantly from the posterior to the anterior regions of the fish. Furthermore, tail amputation affected the ossification of the intermuscular bones. The length of the intermuscular bones in the posterior area became significantly shorter in tail-amputated zebrafish and Japanese eels, and both had less active and lower swimming speeds; this indicates that swimming might induce the ossification of the intermuscular bones. Moreover, when a greater length of tail was amputated in the zebrafish, the intermuscular bones became even shorter. Tail amputation affected the length and ossification of intermuscular bones in the anterior part of the fish, close to the head, differently between the two fish: they became significantly shorter in the zebrafish, but did not in the Japanese eel. This might be because tail amputation did not significantly affect the undulations in the anterior of the Japanese eel, especially near the head. This study shows that the ossification of intermuscular bones might be induced through mechanical force loadings that are produced by swimming., Summary: The ossification of intermuscular bones in teleost fish appears to be induced by mechanical force loadings produced by swimming.

Angiogenesis is crucial for tumor metastasis, with many compounds that inhibit tumor metastasis acting through suppression of angiogenesis. We investigated anti-angiogenic properties of Ligustrazine in a series of in vitro and in vivo models. Ligustrazine inhibited VEGF-induced HUVECs migration and tube formation in a dose-dependent manner in vitro, and had limited cytotoxicity to HUVECs and normal fibroblasts even at a dose up to 100 microg/ml. Ligustrazine also suppressed VEGF-induced rat aortic ring sprouting dose-dependently. Invivo, Ligustrazine reduced the Hb content in a Matrigel plug implanted in mice and inhibited new vessel formation in CAM. In addition, in a B16F10 spontaneous metastasis model, Ligustrazine decreased the expression of CD34 and VEGF in primary tumor tissue and reduced the number of metastasis nodi on the lung surface. Our data suggests that Ligustrazine may inhibit tumor metastasis, at least in part, through its anti-angiogenic activity.

To explore the mechanisms of MDSC trafficking and accumulation during tumor progression. In this study, we report significant CD40 upregulation in tumor-infiltrating MDSC when compared with splenic MDSC. Microarray analyses comparing CD40(high) and CD40l(ow) MDSC revealed 1872 differentially expressed genes, including CD83, CXCR5, BTLA, CXCL9, TLR1, FLT3, NOD2 and CXCL10. In vivo experiments comparing wild-type (WT) and CD40 knockout (KO) mice demonstrated that CD40 critically regulates CXCR5 expression. Consistently, the transwell analysis confirmed the essential role of CXCR5-CXCL13 crosstalk in the migration of CD40+ MDSC toward gastric cancer. Furthermore, more MDSC accumulated in the gastric cancers of WT mice when compared with KO mice, and the WT tumors mostly contained CD40+ cells. Functionally, tumors grew faster in WT than KO mice. In conclusion, we demonstrate that CD40 expression upregulates the chemokine receptor CXCR5 and promotes MDSC migration toward and accumulation within cancer. Therefore, this study provides preliminary evidence that CD40 may stimulate tumor growth by enabling immune evasion via MDSC recruitment and inhibition of T cell expansion.

This meta-analysis aimed to evaluate the short-term and pathological outcomes of laparoscopic surgery (LS) versus open surgery (OS) following neoadjuvant chemoradiotherapy (NCRT) for rectal cancer. PubMed, Embase, Web of Science, Cochrane Library, and Chinese Biomedicine Literature databases were searched for eligible studies published up to July 2013. The rates of postoperative complication, positive circumferential resection margin (CRM), and the number of lymph nodes harvested were evaluated. Three randomized controlled trials (RCTs) and five non-RCTs enrolling 953 patients were included. Compared to OS, LS had similar rate of postoperative complication [odds ratio (OR) 0.86; 95 % confidence interval (CI), 0.60 to 1.22], comparable rate of positive CRM (OR 0.41; 95 % CI, 0.16 to 1.02), and smaller number of lymph nodes (weighted mean difference −0.8; 95 % CI, −1.1 to −0.5). LS also had significantly less blood loss, faster bowel movement recovery, and shorter postoperative hospitalization than those of OS. LS is associated with favorable short-term benefits, similar postoperative complication rate, and comparable pathological outcomes for rectal cancer after NCRT compared to OS despite a slight difference in the number of lymph nodes. Additional high-quality studies are needed to validate long-term outcomes of LS following NCRT.

Ethnopharmacological relevance Curcuma zedoaria (Berg.) Rosc., a traditional Chinese herb, was used widely but absolutely prohibited for the pregnant in clinic. Based on that there is abundant angiogenesis in endometrium and placenta during gestation period, we hypothesized that some components from it could inhibit angiogenesis and then damaged the supply of oxygen and nutrition to the embryo, which finally led to gestation failure. Aim of the study This study was set to demonstrate whether essential oil, major components of Curcuma zedoaria had anti-angiogenic effect. Materials and methods Essential oil of Curcuma zedoaria (EO-CZ) was abstracted by steam distillation extraction. Cell proliferation assay and two angiogenic models, rat aortic ring assay and chick embryo chorioallantoic membrane assay were presented. Furthermore, melanoma growth and experimental lung metastasis assay in mice were performed to evaluate its anti-angiogenesis effect in vivo. Immunohistochemical analysis and enzyme-linked immunosorbent assay (ELISA) were used to respectively detect the expression of CD34 and matrix metalloproteinases (MMPs). Results EO-CZ exhibited anti-proliferative effect on B16BL6 and SMMC-7721 cells, the IC50, respectively was 41.8 μg/ml and 30.7 μg/ml, and on HUVEC (Human Umbilical Vein Endothelial Cells) cells with IC50 of far more than 120 μg/ml. Both 20 μg/ml and 40 μg/ml EO-CZ indicated significant suppression on sprouting vessels of aortic ring and formation of microvessels in chick embryo chorioallantoic membrane in vitro. Moreover, solid melanoma grown in left oxter of mice was obviously inhibited after oral intake of 100 and 200 mg/kg of EO-CZ a day for 28 days, and CD34 expression indicating angiogenesis in melanoma reduced significantly compared with control; melanoma metastatic nodules in lung were detected to be inhibited, as well as MMP-2 and MMP-9 expression in serum. Conclusions Essential oil, a fat-soluble fraction of Curcuma zedoaria, presented anti-angiogenic activity in vitro and in vivo, resulting in suppressing melanoma growth and lung metastasis. And this was associated with down-regulating MMPs.

Danshensu, the major water-soluble component of Radix Salviae Miltiorrhizae (Danshen), is the basic chemical structure of various salvianolic acids. This study was to evaluate the anti-tumor activity of danshensu in a series of in vitro and in vivo models. The effect of danshensu on B16F10 melanoma cell and HUVEC proliferation were assessed by MTS assay, and cell invasion and migration were investigated by transwell chamber assay. The effect of danshensu on angiogenesis was evaluated by HUVEC migration assay, tube formation assay and chick chorioallantoic membrane assay. The expression of MMP-2, -9 and VEGF in B16F10 melanoma cell were detected by western blotting after danshensu treatment. The role of danshensu in tumor metastasis in vivo was evaluated by spontaneous and experimental B16F10 melanoma metastasis model. Although danshensu had no inhibitory effect on B16F10 melanoma cell and HUVEC proliferation, it significantly inhibited B16F10 melanoma cell invasion (at 0.05, 0.5, 5 microM) and migration (at 0.5, 5 microM). It also dramatically suppressed VEGF-induced endothelial migration (at 0.5, 5 microM), tube formation in vitro (at 4, 20 microM) and new vessel formation in CAM in vivo (100 microg/egg). Danshensu (at 5, 50 microM) significantly down-regulates protein expression of MMP-2, -9 and VEGF in B16F10 melanoma cell. In animal model, danshensu (20, 40 mg/kg) also possessed inhibitory effect on lung metastasis in spontaneous (46-day treatment) and experimental (23-day treatment) B16F10 melanoma metastasis model. All these results suggest that danshensu has anti-tumor activity by affecting on tumor angiogenesis and tumor invasion.