Quantifying the spatial nonstationary response of environmental factors on purse seine tuna vessel fishing.

To investigate the spatial and temporal patterns of environmental factors influencing the activity of purse seine tuna fishing vessels, data on fishing efforts of purse seine tuna fleets and environmental factors in the Western and Central Pacific Ocean (WCPO) from 2015 to 2020 were utilized to develop a geographically weighted regression (GWR) model. The results showed that fishing activity was primarily concentrated in the area between 140°E and 175°W, and between 10°S and 5°N. The GWR model showed excellent fitting performance and was suitable for correlation analysis. The environmental factors had a significant spatially heterogeneous effect on the fishing activity of purse seine tuna fishing vessels. The sea surface temperature, primary productivity at 200 m depth, and dissolved oxygen below the surface had the greatest spatially heterogeneous effect and are important environmental variables influencing the activity of purse seine tuna vessels in the WCPO. This study provides new methods for exploring the spatial distribution of fishing vessel activity to support science-based conservation and management.

Case Report of a Female Patient with Adult-onset Still's Disease and Review of The Literature.

BACKGROUND: Adult-onset Still's disease (AOSD), which presents many non-specific symptoms, such as rash leukocytosis, spiking fever, and sore throat, is a rare auto inflammatory disease. Other clinical features that are frequently observed include lymphadenopathy, arthralgia, serositis, splenomegaly, and hepatomegaly. Laboratory tests show high levels of C-reactive protein, ferritin, and erythrocyte sedimentation rate reflecting the systemic inflammatory process in AOSD patients. CASE PRESENTATION: The patient was a middle-aged woman with a high fever (39.8 C), sore throat, rashes on limbs with pruritus, mainly at the joints (elbow, knee, and ankle), muscle aches, dizziness, infirmity, weakness, and poor appetite without arthralgia. The ferritin level was above 1500 (normal value: 14-233) ng/L. Antineutrophil, antinuclear antibodies, and rheumatoid factor were negative. Combining the symptoms such as fever, rash, stress-induced acute inflammation, arthritis, and ferritin levels, the patient was eventually diagnosed with adult Still's disease. She received methylprednisolone 40mg intravenously every 12 hours for one week. On the second week, the dose was reduced to 40mg in the morning and 20mg in the evening, and finally, the dose was reduced to 40mg oral intake in the morning and 8mg in the evening. After half a month of treatment, the patient's high fever and skin rashes subsided, and the other symptoms also gradually relieved. CONCLUSIONS: A case of a middle-aged woman diagnosed with adult Still's disease is reported, and the possible pathogenesis and treatment of the disease are discussed. This case highlights the importance of early diagnosis and timely treatment of adult Still's disease to prevent potentially fatal complications.

Tripartite motif protein 11 (TRIM11), an oncogene for human lung cancer via the DUSP6-mediated ERK1/2 signaling pathway.

Evidence suggests that Tripartite Motif Containing 11 (TRIM11) has pro-tumor activity in human non-small cell lung cancer (NSCLC). However, the roles and underlying mechanisms of TRIM11 in NSCLC have not yet been fully elucidated. In this work, human lung cancer cell lines (A549, H446, and H1975) were transfected with siRNA or lentiviruses to knockdown or overexpress TRIM11 and dual-specificity phosphatase 6 (DUSP6). The cell tumor response was assessed by determining the rate of proliferation, apoptosis, the uptake of 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl) amino]-2-deoxyglucose (2-NBDG), and the secretion of lactic acid (LD). Dominant-negative (dn)-MEK1 was used to block the ERK1/2 pathway. The mechanism was investigated by assessing the protein levels of pyruvate kinase isozymes M2 (PKM2) and DUSP6, as well as the activation of ERK1/2 pathway. Our data confirmed the anti-cancer effect of siTRIM11 in human lung cancer by demonstrating inhibition of cancer cell proliferation, induction of apoptosis, prevention of 2-NBDG uptake, suppression of LD production, and prevention of lung cancer cell (A549) tumorigenicity in nude mice. The underlying mechanism involved the up-regulation of DUSP6 and the inhibition of ERK1/2 activity. Overexpression of TRIM11 induced tumorigenesis of NSCLC in vitro, and the activation of ERK1/2 was significantly reversed by DUSP6 overexpression or additional dn-MEK1 treatment. Interestingly, we confirmed TRIM11 as a deubiquitinase that regulated DUSP6 accumulation, indicating that lung cancer progression is regulated via the DUSP6-ERK1/2 pathway. In conclusion, TRIM11 is an oncogene in NSCLC, likely through the DUSP6-mediated ERK1/2 signaling pathway.

Raddeanin A suppresses lung cancer cell proliferation via induction of apoptosis and increased production of ROS.

At present, in vitro cell experiments have confirmed that RaddeaninA can effectively inhibit the proliferation of some tumor cells, but the effect of RaddeaninA on lung cancer cells has not been observed. Therefore, this study explored its effect on lung cancer cells and its mechanism of action. Human lung cancer cell lines were treated with serum-free medium and varied concentrations of Raddeanin A. Cell proliferation and apoptosis were determined using MTT, and flow cytometric assays, respectively. The intracellular level of ROS was determined using DCFH-DA assay. Protein and mRNA expressions of bax, bcl-2 and cyt c were measured using Western blotting and qRT-PCR. RaddeaninA treatment can promote PC-9 cell apoptosis in a time and dose-dependent manner (p<0.05). Treatment of PC-9 cells with Raddeanin significantly and dose-dependently increased the activities of caspase-9 and caspase-3 (p<0.05), and led to significant and dose-dependent increases in ROS levels (p<0.05). Treatment of PC-9 cells with Raddeanin A led to significant and dose-dependent decreases in mitochondrial membrane potential (p<0.05). It significantly and dose-dependently upregulated bax mRNA and protein expressions, but down-regulated bcl-2 mRNA and protein expressions significantly and dose-dependently (p<0.05). On the other hand, Raddeanin significantly and dose-dependently down-regulated cytoplasmic bax protein expression, while upregulating cyt c expression (p<0.05). Similarly, bax protein expression was significantly and dose-dependently upregulated in mitochondria, but the corresponding cyt c expression was significantly and dose-dependently down-regulated (p<0.05). Raddeanin A is a potential and effective lung cancer chemotherapy drug, which can induce lung cancer cell apoptosis and inhibit proliferation.

Patterns and risk factors of peripherally inserted central venous catheter-related symptomatic thrombosis events in patients with malignant tumors receiving chemotherapy.

OBJECTIVE: Peripherally inserted central venous catheter (PICC)-related thrombosis (PRT) is a serious complication that can lead to interruptions in chemotherapy and other supportive care, as well as increased hospital stay and costs. We conducted a retrospective study to evaluate the patterns of symptomatic PRT in patients with cancer undergoing chemotherapy and their risk factors. METHODS: A retrospective study of 938 PICC patients from our institution between November 2014 and July 2017 was performed. Symptomatic PRT events were confirmed by color Doppler ultrasonography or computed tomography pulmonary angiography in the presence of clinical symptoms. The variables of interest were extracted from the electronic medical record system. Logistic regression analysis was used to determine the risk factors for PRT. RESULTS: Of the 938 patients who were followed up for more than 120,000 patient-days, 63 patients (6.7%; 0.51 per 1000 catheter-days) had symptomatic PRT. Sixty-one patients were diagnosed with upper extremity venous thrombosis (UEVT), of which 18 were isolated superficial vein thrombosis (SVT), 19 were isolated deep vein thrombosis (DVT), and 24 were extensive venous thrombosis (EVT). Two patients were diagnosed with pulmonary embolism, and two patients were diagnosed with UEVT with pulmonary embolism. The symptomatic SVT occurred in 42 of 938 patients with cancer (4.5%), which accounted for 68.9% of all UEVT events. The median time to PRT was 21 days, and the median time to catheter removal in the PRT group was 66 days as compared with 117 days in the no PRT group. Predictors associated with increased risk of PRT were age >60 years (odds ratio [OR], 2.142; 95% confidence interval [CI], 1.118-4.103) and a chemotherapy regimen containing fluorouracil (OR, 2.429; 95% CI, 1.013-5.825). Hypertension with medication was a protective factor for PRT (OR, 0.306; 95% CI, 0.113-0.828). Among the 28 patients who did not remove their PICCs immediately after PRT was diagnosed, patients with SVT, DVT, and EVT had similar success rates of retaining catheters in situ after anticoagulant therapy (SVT, 83.3%; DVT, 62.5%; EVT, 75.0%; P = .667). CONCLUSIONS: Age >60 years and chemotherapy regimens containing fluorouracil were independent risk factors for PRT and hypertension with medication was associated with a lower risk of PRT in patients with cancer with PICCs receiving chemotherapy. PICCs-related SVT was a frequent type of PRT, which might need a better understanding and anticoagulant therapy in patients with cancer with PICCs.

Integrin α5 promotes migration and cisplatin resistance in esophageal squamous cell carcinoma cells.

Cisplatin, as one of the front-line chemotherapeutic drugs, is employed for the treatment of esophageal squamous cell carcinoma (ESCC). However, the occurrence of cisplatin resistance and metastasis remain as challenges in clinical therapy. To investigate the mechanism involved in cisplatin resistance, in this study, we established cisplatin resistant cell lines (Res) from Eca109 and TE-1 parental cells (Par), and we observed that fibronectin (FN)-mediated cell migration and spreading abilities are significantly increased in Res cells when compared to Par cells. Furthermore, we found that the integrin α5 expression is remarkably upregulated in Res cells, and inhibition of α5 results in more apoptosis and endows the Res cells resensitize to cisplatin in vitro and in vivo. In a mechanistic manner, we identified the expression of BARD1 is significantly increased in Res cells, and silencing of BARD1 reverse the effects of α5 on cisplatin resistance. Moreover, we found that the α5/FAK/PI3K/AKT signal axis is activated in Res cells, which mediates the increased expression of BARD1, as well as the cisplatin resistance and cell survival. Thus, our results demonstrate that α5 is required for cisplatin resistance through the promotion of FAK/PI3K/AKT/BARD1 signaling to prevent cells from apoptosis and enhance the DNA damage repair ability. Taken together, our study provides plausible mechanisms of α5-mediated cisplatin resistance in ESCC cells, highlighting that inhibition of α5 may be a potential target for improving efficacy in cisplatin-based chemotherapy.

Oligomeric proanthocyanidins protects A549 cells against H2O2-induced oxidative stress via the Nrf2-ARE pathway.

Oxidative signaling and oxidative stress contribute to aging, cancer and diseases resulting from lung fibrosis. In this study, we explored the anti-oxidative potential of oligomeric proanthocyanidins (OPCs), natural flavonoid compounds. We examined the protective effects of OPCs against hydrogen peroxide (H2O2)-induced oxidative stress in non-small cell lung cancer cells (A549). We demonstrated that OPC markedly attenuated H2O2-induced A549 cell viability, as shown by by 3-[4,5-dimethylthiazol-2-yl)]-2,5-diphenyl-tetrazolium bromide (MTT) assay. At the same time, OPC inhibited H2O2-induced oxidative stress by significantly increasing the activities of superoxide dismutase, catalase and glutathione, and reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Treatment of the A549 cells with OPC significantly promoted the nuclear translocation of NF-E2-related factor 2 (Nrf2) and significantly enhanced the expression of its target genes [heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1) and thioredoxin reductase 1 (TXNRD1)] with different fold change values at both the mRNA and protein level. The knockout of Nrf2 using CRISPR/Cas9 technology attenuated OPC-mediated ARE gene transcription, and almost abolished the OPC-mediated protective effects against H2O2-induced oxidative stress. On the whole, our study suggests that OPC plays an important role in controlling the antioxidant response of A549 cells via the Nrf2-ARE pathway.

Knockdown of TRIM65 inhibits lung cancer cell proliferation, migration and invasion: A therapeutic target in human lung cancer.

Lung cancer is the most commonly diagnosed type of cancer worldwide. Although TRIM65 is an important protein involved in white matter lesion, the role of TRIM65 in human cancer remains less understood. Here, we reported that TRIM65 was significantly overexpressed in lung cancer tissues compared with adjacent normal lung tissues. Furthermore, TRIM65 expression was closely related to overall survival of patients with lung cancer. Knock down of TRIM65 in two lung cancer cell lines, SPC-A-1 and NCI-H358, resulted in a significant reduction in cell proliferation, migration, invasion and adhesion and a dramatic increase in G0-G1 phase arrest and apoptosis. In vivo tumorigenesis experiment also revealed that depletion of TRIM65 expression inhibited NCI-H358 cell growth. Moreover, based on gene set enrichment analysis (GSEA) with The Cancer Genome Atlas (TCGA) dataset, we found that TRIM65 was positive related to cell cycle, metastasis up and RHOA-REG pathways, which was further validated by RT-PCR and Western blot in TRIM65 knockdown lung cancer cells and indicated a possible mechanism underlying its effects on lung cancer. In summary, our study suggests that TRIM65 may work as an oncogene and a new effective therapeutic target for lung cancer treatment.

Methylation status and protein expression of RASSF1A in endometriosis.

Ras association domain family 1A (RASSF1A) gene inactivation by promoter hypermethylation is a common event in the development of a variety of types of human cancer. Accumulated evidence has demonstrated that DNA methylation serve a critical role in the pathogenesis of endometriosis. The aim of the present study was to analyze the methylation status and protein expression of RASSF1A in endometriosis (EMS). The ectopic and corresponding eutopic endometrium tissues were collected from 45 women with EMS (EMS group) and normal endometrium tissues from 20 women without EMS (control group). The methylation status of RASSF1A was examined by methylation specific polymerase chain reaction (MSP). Immunohistochemistry was performed to measure RASSF1A protein level in endometrium tissues. In normal endometrium samples, RASSF1A protein expression was significantly higher at the secretory phase than the proliferative phase. RASSF1A protein expression in the ectopic endometrium tissues and eutopic endometrium tissues were significantly reduced than in normal endometrium (P<0.05). The frequency of aberrant methylation of RASSF1A was 55.56% in ectopic endometrium and 33.33% in paired eutopic endometrium, whereas such methylation was not detected in normal endometrium. Moreover, RASSF1A promoter hypermethylation was frequently associated with reduced expression of RASSF1A, and was common in advanced stage in ectopic endometrium of EMS. Epigenetic inactivation of RASSF1A through aberrant promoter methylation may be important in the formation and progression of EMS, and assessment of RASSF1A methylation status in eutopic endometrium may be a potentially useful biomarker to enhance the early detection of EMS.

TRIM11 overexpression promotes proliferation, migration and invasion of lung cancer cells.

BACKGROUND: Tripartite Motif Containing 11 (TRIM11), a member of TRIM proteins, is overexpressed in high-grade gliomas and plays an oncogenic function in glioma biology. However, little is known about the role of TRIM11 in lung cancer. METHODS: We analyzed TRIM11 mRNA expression in lung cancer tissues and adjacent non-neoplastic tissues by real-time PCR. We then explored the function of TRIM11 in lung cancer cells by small interfering RNA-mediated downregulation of this protein followed by analyses of cell proliferation, migration and invasion. RESULTS: TRIM11 was highly expressed in lung cancer tissues and lung cancer cell lines. The higher expression of TRIM11 was correlated with the poorer prognosis of patients. Suppressing of TRIM11 expression in lung cancer cells with higher expression of TRIM11 (A549 and NCI-H446 cells) significantly reduced cell growth, motility and invasiveness. We further demonstrated that knockdown of TRIM11 affected the expression of cell proliferation-related proteins (Cyclin D1 and PCNA), and epithelial-mesenchymal transformation-related proteins (VEGF, MMP-2, MMP-9, Twist1, Snail and E-cadherin). The activity of ERK and PI3K/AKT was also suppressed in TRIM11 knocked down cells. Further experiments in lung cells with lower expression of TRIM11 (NCI-H460 and NCI-H1975 cells) with AKT inhibitor suggested that TRIM11 may promote cell motility and invasiveness through AKT pathway. CONCLUSIONS: Our results indicate that TRIM11 acts as an oncogene in lung cancer through promoting cell growth, migration and invasion. Our findings may have important implication for the detection and treatment of lung cancer.

Effect of short hairpin RNA-induced CXCR4 silence on ovarian cancer cell.

This study was aimed to investigate the effect of down-regulating the CXC chemokine receptor-4 (CXCR4) expression on cell proliferation, invasion and migration of human ovarian cancer cell line SW626. The CXCR4 specific short hairpin RNA (shRNA) plasmid vector was constructed and then transfected into the SW626 cells. The expression of CXCR4 mRNA and protein was detected by real-time RT-PCR and western blot respectively. Cell proliferation was detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Cell invasion and migration was assayed in Biocoat Matrigel invasion chambers. The expression level of CXCR4 in SW626 cell transfected with CXCR4-siRNA was inhibited, leading to significant decrease in SW626 cell proliferation, invasion and migration. We conclude that CXCR4 is essential for tumor cell proliferation and invasion. The CXCR4 molecule is a potential therapeutic target to control ovarian cancer cell growth or metastasis.

[Clinical application of MC + PEEK cage in traumatic cervical disc herniation].

OBJECTIVE: To explore the clinical outcomes of surgical treatment for traumatic cervical disc herniation with MC + PEEK cage. METHODS: A total of 51 patients with traumatic cervical disc herniation in mono-segment were surgically treated. The patients in group A (n = 20) were treated by MC + PEEK cage while those in group B (n = 31) by anterior cervical plate with PEEK cage or titanium mesh. Various parameters of operative duration, blood loss volume, operative complications, bone union, height of intervertebral space and Japanese Orthopedic Association (JOA) score were recorded and compared. RESULTS: Fifty-one patients were followed up for an average time of 26 months (range: 6 - 40). Operative duration, blood loss volume and operative complications of group A were better than group B with statistical significance (P < 0.05). Bone union, height of intervertebral space and recovery of spinal cord function were satisfactory with no statistical difference (P > 0.05). CONCLUSION: With this new cage, traumatic cervical disc herniation may be safely and micro-invasively treated without the need of anterior cervical plate.

Short-term safety and curative effect of recombinant adenovirus carrying hepatocyte growth factor gene on ischemic cardiac disease.

BACKGROUND: Adenovirus-mediated angiogenic growth factor gene transfer provides a new therapeutic strategy for treatment of coronary heart disease. Preclinical studies showed that direct intramyocardial injection of recombinant adenovirus with hepatocyte growth factor gene (Ad-HGF) was able to promote neovascularization, improve heart function and abate the area of ischemic myocardia in animal models. However, the safety and therapeutic effect of Ad-HGF were not evaluated in clinical trials. PATIENTS AND METHODS: A open-label, safety and tolerance trial of Ad-HGF in 18 patients suffering from coronary heart disease was performed. Three groups, each with 6 patients, received 5x10(8) (low dosage), 1.5 x 10(9) (medium dosage) and 5x10(9) (high dosage) pfu of Ad-HGF/person respectively, by direct multipoint injection into the myocardium while accepting coronary artery bypass surgery. The changes of vital symptoms, blood and urea routine analyses, as well as myocardial perfusion before and after treatment were analyzed. RESULTS: There was no evidence of systemic or cardiac-related adverse events after intramyocardial administration of the Ad-HGF. Myocardial perfusion of the Ad-HGF-injected area was improved in 3 cases of the low-dose group, 5 cases of the medium-dose group, and all of the high-dose group. CONCLUSION: These preliminary clinical data indicate that direct intramyocardial administration of Ad-HGF was well tolerated and could improve myocardial perfusion with a dose-effect relationship, encouraging larger and randomized efficacy trials.