Venous thromboembolism after oral and maxillofacial oncologic surgery : report and analysis of 14 cases in Chinese population

Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) is a leading cause of death in cancer patients. The aim of this study was to explore the potential risk factor of VTE in oral and maxillofacial oncological surgery. The data of patients who received operation in our institution were gathered in this retrospective study. A diagnosis of VTE was screened and confirmed by computer tomography angiography (CTA) of pulmonary artery or ultrasonography examination of lower extremity. Medical history and all perioperative details were analyzed. 14 patients were diagnosed as VTE, including 6 cases of PE, 7 cases of DVT, 1case of DVT and PE. The mean age of these patients was 62.07 years. Reconstruction was performed in 12 patients of these cases, most of which were diagnosed as malignance. Mean length of surgery was 8.74 hours, and lower extremity deep venous cannula (DVC) was performed in all these patients. We analyzed several characters of oral and maxillofacial surgery and suggested pay attention to lower extremity DVC which had a high correlation with DVT according to our data

Protective effect of dehydroandrographolide on obstructive cholestasis in bile duct-ligated mice

Background: Dehydroandrographolide (DA) is the main contributor to the therapeutic properties of the medicinal plant Andrographis paniculata (AP). However, it is unknown whether DA has a hepatoprotective effect on obstructive cholestasis in mice and humans. Methods: We administered DA to mice for 5 days prior to bile duct ligation (BDL) and for the 7 days. Liver function markers, liver histology and necrosis, compensatory responses of hepatocytes, liver fibrosis and the expression of hepatic fibrogenesis markers were evaluated in BDL mice and/or human LX-2 cells. Results: Mice treated with DA demonstrated lower levels of serum alanine transarninase (ALT), milder liver damage, liver necrosis and fibrosis formation than in vehicle control with carboxymethylcellulose (CMC) mice after BDL. DA treatment also enhanced the Mrp3 expression of hepatocytes but not Mrp4 following BDL. Further, DA treatment in BDL mice significantly reduced liver mRNA and/or protein expression of Tgf-β, Col1a1, α-Sma and Mmp2. This result was also supported by hydroxyproline analysis. The molecular mechanisms of DA treatment were also assessed in human hepatic stellate cell line (LX-2 cell). DA treatment significantly inhibited Tgf-β-induced Col1a1, Mmp2 and α-Sma expression in human LX-2 cells. These data suggested that DA treatment reduced liver damage through development of a hepatic adaptive response and inhibition of the activation of HSCs, which led to a reduction in liver fibrosis formation in BDL mice. Conclusions: DA treatment protected against liver damage and fibrosis following BDL and might be an effective therapy for extrahepatic cholestasis due to bile duct obstruction

Prognostic value of log odds of positive lymph nodes, lymph node ratio, and N stage in patients with colorectal signet ring cell carcinoma: A retrospective cohort study

AimLittle attention has been paid in the prognosis of colorectal signet ring cell carcinoma (SRCC). This study aims to explore the predictive capacity of log odds of positive lymph nodes (LODDS), lymph node ratio (LNR), and pN stage in the prognosis of patients with colorectal SRCC.MethodsA retrospective cohort study was designed, and data were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Data on demographic characteristics, clinicopathological features, and treatment were extracted. Outcomes were overall survival (OS) and cancer-specific survival (CSS). Association of LODDS, LNR, and pN stage with OS and CSS were explored using Cox proportional hazard model and Cox competing risk model, respectively, with results showing as hazard ratio and 95% confidence interval (CI). Predictive performance of LODDS, LNR, and pN stage in OS and CSS was assessed by calculating C-index.ResultsA total of 2,198 patients were included in this study. LODDS, LNR, and pN stage were associated with the OS and CSS of colorectal SRCC patients (all P < 0.05). LODDS showed a good performance in the OS (C-index: 0.704, 95% CI: 0.690–0.718), which was superior to LNR (C-index: 0.657, 95% CI: 0.643–0.671) and pN stage (C-index: 0.643, 95% CI: 0.629–0.657). The C-index of LODDS, LNR, and pN stage for CSS was 0.733 (95% CI: 0.719–0.747), 0.713 (95% CI: 0.697–0.729), and 0.667 (95% CI: 0.651–0.683), respectively.ConclusionsLODDS displayed a better predictive capacity in the OS and CSS than LNR and pN stage, indicating that LODDS may be effective to predict the prognosis of colorectal SRCC in the clinic

Ultrasound hyperthermia induces apoptosis in head and neck squamous cell carcinoma : an in vitro study

Hyperthermia is considered an efficient complement in the treatment of head and neck squamous cell carcinoma (HNSCC). Hyperthermia induces cell apoptosis in a temperature- and time-dependent manner. However, the molecular mechanism of hyperthermia remains unclear. The aim of this study was to investigate the mechanism of apoptosis induced by ultrasound hyperthermia in HNSCC cell lines HN-30 and HN-13. We examined the dynamic changes of early apoptosis and secondary necrosis in HN-30 and HN-13 cells treated by hyperthermia at 42°C for 10 min. We further examined mitochondrial membrane potential in vitro by ultrasound hyperthermia for different heating temperatures (38-44°C, 10 min) and heating times (42°C, 10-50 min). After heating by ultrasound at 42°C for 10 min, the apoptosis index achieved its highest level at 8 h after treatment, decreased rapidly and remained constant at a reduced level at 12 h. The level of secondary necrosis increased with the level of early apoptosis but remained at a higher level until 14 h. The level of secondary necrosis correlated with the level of early apoptosis (HN-13: r=0.7523, P=0.0030; HN-30: r=0.6510, P=0.016). The fractions of cells with low mitochondrial membrane potential (??) in the heating-temperature grads group and heating-time grads group decreased significantly over time. Therefore, HN-30 and HN-13 cells developed apoptosis after ultrasound hyperthermia treatment with decreases in the mitochondrial transmembrane potential level. Ultrasound hyperthermia induces apoptosis in HN-30 and HN-13 cells, possibly via the mitochondrial caspase pathway

Clinical implication of PD-L2 in the prognosis assessment of HNSCC immunotherapy

Background and purpose: Programmed death-1 (PD-1) monoclonal antibody therapy plays an increasingly important role in the treatment of head and neck squamous cell carcinoma (HNSCC). However, low response rate and lack of predictive biomarkers are still the challenging problems. This study aimed to confirm that programmed death ligand-2 (PD-L2) is a predictive biomarker for the outcome of HNSCC anti-PD-1 immunotherapy. Methods: The samples and clinical data of 50 HNSCC patients undergoing PD-1 monoclonal antibody immunotherapy were collected. Immunohistochemical staining was used to analyze the level of programmed death ligand-1 (PD-L1) and PD-L2. Kaplan-Meier overall survivals were analyzed using SPSS 26.0 software, grouped by the basic clinical characteristics and the PD-L1 and PD-L2 levels. Survival curves were plotted using GraphPad Prism. Results: HNSCC had a relatively high expression rate of PD-L2 with more than 80% of cases detected as PD-L2 positive. The expression of PD-L2 significantly correlated with the clinical outcome of immunotherapy, with a mean survival of 18.8 (16.0-21.7) months for patients with high PD-L2 expression and 11.0 (9.1-12.8) months for patients with low PD-L2 expression, this difference being statistically significant. Conclusion: PD-L2 has the potential to be used as a predictive biomarker for HNSCC anti-PD-1 immunotherapy

G9a Is Essential for EMT-Mediated Metastasis and Maintenance of Cancer Stem Cell-Like Characters in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a particularly aggressive cancer with poor prognosis, largely due to lymph node metastasis and local recurrence. Emerging evidence suggests that epithelial-to-mesenchymal transition (EMT) is important for cancer metastasis, and correlated with increased cancer stem cells (CSCs) characteristics. However, the mechanisms underlying metastasis to lymph nodes in HNSCC is poorly defined. In this study, we show that E-cadherin repression correlates with cancer metastasis and poor prognosis in HNSCC. We found that G9a, a histone methyltransferase, interacts with Snail and mediates Snail-induced transcriptional repression of E-cadherin and EMT, through methylation of histone H3 lysine-9 (H3K9). Moreover, G9a is required for both lymph node-related metastasis and TGF-β-induced EMT in HNSCC cells since knockdown of G9a reversed EMT, inhibited cell migration and tumorsphere formation, and suppressed the expression of CSC markers. Our study demonstrates that the G9a protein is essential for the induction of EMT and CSC-like properties in HNSCC. Thus, targeting the G9a-Snail axis may represent a novel strategy for treatment of metastatic HNSCC

Autocrine Epiregulin Activates EGFR Pathway for Lung Metastasis Via EMT in Salivary Adenoid Cystic Carcinoma

Salivary adenoid cystic carcinoma (SACC) is characterized by invasive local growth and a high incidence of lung metastasis. Patients with lung metastasis have a poor prognosis. Treatment of metastatic SACC has been unsuccessful, largely due to a lack of specific targets for the metastatic cells. In this study, we showed that epidermal growth factor receptors (EGFR) were constitutively activated in metastatic lung subtypes of SACC cells, and that this activation was induced by autocrine expression of epiregulin (EREG), a ligand of EGFR. Autocrine EREG expression was increased in metastatic SACC-LM cells compared to that in non-metastatic parental SACC cells. Importantly, EREG-neutralizing antibody, but not normal IgG, blocked the autocrine EREG-induced EGFR phosphorylation and the migration of SACC cells, suggesting that EREG-induced EGFR activation is essential for induction of cell migration and invasion by SACC cells. Moreover, EREG-activated EGFR stabilized Snail and Slug, which promoted EMT and metastatic features in SACC cells. Of note, targeting EGFR with inhibitors significantly suppressed both the motility of SACC cells in vitro and lung metastasis in vivo. Finally, elevated EREG expression showed a strong correlation with poor prognosis in head and neck cancer. Thus, targeting the EREG-EGFR-Snail/Slug axis represents a novel strategy for the treatment of metastatic SACC even no genetic EGFR mutation

ULK1 phosphorylates Exo70 to suppress breast cancer metastasis

乳腺癌是威胁女性生命健康的“头号杀手”，而远处转移是乳腺癌患者死亡的主要原因。因此，了解乳腺癌如何发动侵袭和转移，对于有效治疗乳腺癌、延长病人生存期具有重要意义。本研究中，该团队发现ULK1通过结合并磷酸化胞泌蛋白复合体关键亚基Exo70来抑制乳腺癌转移。ULK1对Exo70上Ser47，Ser59和Ser89位点的磷酸化，严重地削弱了Exo70的自身寡聚化和与其它胞外分泌复合体亚基的结合，进而减少了细胞运动伪足形成以及基质金属蛋白酶的分泌，从而抑制乳腺癌细胞的迁移和侵袭。该论文首次揭示了胞外分泌复合体重要成员Exo70在乳腺癌中受到ULK1和ERK1/2的双重磷酸化调控，从而使得乳腺癌细胞可以根据外环境来决定潜伏还是发动侵袭转移，为乳腺癌的治疗提供了新的理论基础。 本论文的通讯作者为占艳艳副教授、郭巍教授和胡天惠教授。医学院博士生毛丽媛、占艳艳副教授、吴斌博士和医学院博士生于强为共同第一作者。【Abstract】Increased expression of protein kinase ULK1 was reported to negatively correlate with breast cancer metastasis. Here we report that ULK1 suppresses the migration and invasion of human breast cancer cells. The suppressive effect is mediated through direct phosphorylation of Exo70, a key component of the exocyst complex. ULK1 phosphorylation inhibits Exo70 homo-oligomerization as well as its assembly to the exocyst complex, which are needed for cell protrusion formation and matrix metalloproteinases secretion during cell invasion. Reversely, upon growth factor stimulation, Exo70 is phosphorylated by ERK1/2, which in turn suppresses its phosphorylation by ULK1. Together, our study identifies Exo70 as a substrate of ULK1 that inhibits cancer metastasis, and demonstrates that two counteractive regulatory mechanisms are well orchestrated during tumor cell invasion.This work was supported by the grants from the National Natural Science Foundation of China (81572589, U1405228, 81472568, and 31770860), the Natural Science Foundation of Fujian grant (2017J06020, 2018J01400, 2017R1036-4, 2017R1036-6, 2016R1034-1, and 2016R1034-4), and the Xiamen Science and Technology grant (3502Z20159013) to Y.-y.Z. and T.H., and National Institute of Health R01 GM111128 to W.G.该论文的研究成果是在国家自然科学基金和福建省基金的资助下，与美国宾夕法尼亚大学和清华大学共同协作完成的

Global lung function initiative 2012 reference values for spirometry in Asian Americans

Background Spirometry reference values specifically designed for Asian Americans are currently unavailable. The performance of Global Lung Function Initiative 2012 (GLI-2012) equations on assessing spirometry in Asian Americans has not been evaluated. This study aimed to assess the fitness of relevant GLI-2012 equations for spirometry in Asian Americans. Methods Asian subjects who never smoked and had qualified spirometry data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2011–2012. Z-scores of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC were separately constructed with GLI-2012 equations for North East (NE) Asians, South East (SE) Asians, and individuals of mixed ethnic origin (Mixed). In addition, Proportions of subjects with observed spirometry data below the lower limit of normal (LLN) were also evaluated on each GLI-2012 equation of interest. Results This study included 567 subjects (250 men and 317 women) aged 6–79 years. Spirometry z-scores (z-FEV1, z-FVC, and z-FEV1/FVC) based on GLI-2012 Mixed equations had mean values close to zero (− 0.278 to − 0.057) and standard deviations close to one (1.001 to 1.128); additionally, 6.0% (95% confidence interval (CI) 3.1–8.9%) and 6.4% (95% CI 3.7–9.1%) of subjects were with observed data below LLN for FEV1/FVC in men and women, respectively. In contrast, for NE Asian equations, all mean values of z-FEV1 and z-FVC were smaller than − 0.5; for SE Asian equations, mean values of z-FEV1/FVC were significantly smaller than zero in men (− 0.333) and women (− 0.440). Conclusions GLI-2012 equations for individuals of mixed ethnic origin adequately fitted spirometry data in this sample of Asian Americans. Future studies with larger sample sizes are needed to confirm these findings

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis