Feasibility Study of Beam Angle Optimization Based on Scripts in Automated-planning for Liver Cancer / 中国医疗器械杂志

OBJECTIVE@#To study the feasibility and potential benefits of beam angle optimization (BAO) to automated planning in liver cancer.@*METHODS@#An approach of beam angle sampling is proposed to implement BAO along with the module Auto-planning in treatment planning system (TPS) Pinnacle. An in-house developed plan quality metric (PQM) is taken as the preferred evaluating method during the sampling. The process is driven automatically by in-house made Pinnacle scripts both in sampling and scoring. In addition, dosimetry analysis and physician's opinion are also performed as the supplementary and compared with the result of PQM.@*RESULTS@#It is revealed by the numerical analysis of PQM scores that only 15% patients whose superior trials evaluated by PQM are also the initial trials. Gantry optimization can bring benefit to plan quality along with auto-planning in liver cancer. Similar results are provided by both dose comparison and physician's opinion.@*CONCLUSIONS@#It is possible to introduce a full automated approach of beam angle optimization to automated planning process. The advantages of this procedure can be observed both in numerical analysis and physician's opinion.

Correlation between body mass index and elbow vein grading in patients with metabolic syndrome based on superficial vein evaluation / 中国实用护理杂志

Objective:To analyze the correlation between body mass index (BMI) and the graded expression, subcutaneous depth, and diameter of elbow veins (cephalic vein, median vein, basilic vein) in patients with metabolic syndrome, to provide a method and theoretical basis for precise puncture of peripheral veins in obese patients.Methods:From January to October 2021, a total of 767 patients with metabolic syndrome with gastric volume reduction were selected as the study subjects by retrospective cohort study from the first Affiliated Hospital of Nanjing Medical University. According to the quartile Q1, M and Q3 of BMI level, they were divided into four groups: group A, group B, group C and group D. The subcutaneous depth and diameter of the cephalic vein, median vein and basilic vein were measured by B-ultrasound, and the three veins were evaluated and graded according to the grading criteria of superficial veins.The correlation between BMI and the subcutaneous depth and diameter of the three elbow veins was analyzed, and collected data such as puncture method and puncture times. Results:There was no significant correlation between BMI and subcutaneous depth and vessel diameter of the basilic vein ( r = 0.041 and 0.046, both P>0.05), the level of BMI was positively correlated with the subcutaneous depth and diameter of cephalic vein ( r = 0.275 and 0.117, both P<0.05) and median vein ( r = 0.236 and 0.148, both P<0.05), and a linear regression relationship was found ( OR values were 1.013-1.031, all P<0.05). 187 cases had direct puncture conditions under direct vision, and the success rate of one puncture was 86.63%(162/187).Venipuncture was completed under the guidance of B-mode ultrasound for 25 cases with failure under direct vision and 580 cases without direct puncture conditions under direct vision, the success rate of one puncture was 98.51% (596/605). Conclusions:With the increase of BMI level in patients with metabolic syndrome, the depth and diameter of both cephalic vein and median vein increase, venous exposure is difficult to express. The visual vein puncture guided by B-ultrasound is more accurate and catheterization is more reliable.

Value of international normalized ratio-to-platelet ratio in the diagnosis of liver fibrosis in patients with primary biliary cholangitis / 临床肝胆病杂志

Objective To investigate the value of international standardized ratio-to-platelet ratio (INPR) versus aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) in the diagnosis of liver fibrosis in patients with primary cholangitis (PBC). Methods A retrospective analysis was performed for the patients who underwent liver biopsy and were diagnosed with PBC in The First Affiliated Hospital of Zhengzhou University from October 2013 to March 2021. Scheuer score was used to systematically evaluate the degree of liver fibrosis (S0-S4 stage). According to the results of liver biopsy, the degree of liver fibrosis was classified as significant liver fibrosis (≥S2), progressive liver fibrosis (≥S3), and liver cirrhosis (S4). Related data including general information, liver function, routine blood test results, and blood coagulation were collected, and related formulas were used to calculate the values of the noninvasive serological models INPR, APRI, and FIB-4. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the chi-square test was used for comparison of categorical data between multiple groups. A Spearman correlation analysis was used to evaluate the correlation between noninvasive models and liver fibrosis stage. The receiver operating characteristic (ROC) curve was used to evaluate the efficacy of the noninvasive serological models in the diagnosis of liver fibrosis degree, and the DeLong method was used for comparison of the area under the ROC curve (AUC). Results A total of 143 patients with PBC were enrolled in the study, among whom 4 had stage S0 liver fibrosis, 50 had stage S1 liver fibrosis, 46 had stage S2 liver fibrosis, 26 had stage S3 liver fibrosis, and 17 had stage S4 liver fibrosis. There was a significant difference in INPR value between the PBC patients with different liver fibrosis degrees ( χ 2 =27.347, P 0.05). Conclusion INPR is a simple and accurate noninvasive model for the evaluation of liver fibrosis and has a certain value in the diagnosis of liver fibrosis in PBC.

Mechanism of Traditional Chinese Medicine in the Prevention and Treatment of Psoriasis： A Review / 中国实验方剂学杂志

Psoriasis is a common clinical chronic inflammatory skin disease with a complex and diverse etiology and unrevealed pathogenesis. In traditional Chinese medicine （TCM）， psoriasis is caused by internal and external factors. To be specific， external factors such as external wind， cold， dampness， heat， insects， and other pathogenic factors can result in Qi obstruction， blood stasis， and loss of nourishment in the skin， and internal and external factors such as wind， dampness， and toxic qi attacking the exterior， heat and dryness in the blood aspect， difficulty in flourishing due to blood dryness， and blood deficiency in the body， combined with external contraction of wind and dryness trigger the disease. Modern doctors have conducted research from the blood aspect， including blood heat， blood deficiency， blood stasis， and blood dryness. Modern medicine believes that it is related to genetics， immunity， infection， and other factors， and the research on its mechanism focuses on genetic susceptibility， immune system disorder， bacterial infection， and other aspects. At present， various clinical therapies are available， mainly including systematic treatment and local external application of drugs. While treating psoriasis， TCM mainly employs oral administration or external application of Chinese medicine and traditional therapies to regulate the immune system and gene targets and resist oxidation， with high safety and few adverse reactions. At present， although the research on the mechanism of TCM in the treatment of psoriasis has been gradually deepened， there are few detailed summaries on the mechanism of TCM in the prevention and treatment of psoriasis. Based on the research on TCM and western medicine in the treatment of psoriasis， this paper reviewed the mechanism of TCM in the prevention and treatment of psoriasis and proposed a comprehensive clinical and experimental research profile， aiming to provide references for further exploring the pathogenesis， treatment， and corresponding mechanism of psoriasis.

Assessment of residual risk of hepatitis C virus transmission by blood transfusion in Taiyuan / 中国输血杂志

【Objective】 To analyze the epidemic of hepatitis C virus (HCV) in voluntary blood donors , and to assess the residual risk of HCV transmission by blood transfusion in Taiyuan. 【Methods】 The HCV screening results of voluntary blood donors in Taiyuan from 2016 to 2021 were collected by blood center information system, and the epidemiologic feature of first-time and repeated donors were analyzed. The incidence-window period model was used to assess the residual risk of HCV transmission by transfusion in first-time/repeated donors as well as that in repeated donors under different blood screening modes. 【Results】 Of the 662 705 samples in Taiyuan from 2016 to 2021, the HCV positive rate of the first-time donors was 1.83‰(595/325 009) and the residual risk of HCV transmission was 14.91/100 000. The HCV positive rate of the repeated donors was 0.04‰ (13/337 696) and the residual risk was 0.31/1 000 000. The total residual risk of HCV transmission was 7.47/1 000 000. A total of 337 696 blood samples of repeated blood donors were tested, the repeated blood donors’ residual risk of transfusion-transmitted HCV was 0.31/100 000 after dual ELISA tests , and 0.06/100 000 after dual ELISA and once NAT, which reduce by 80.65% since NAT were adopted. 【Conclusion】 The residual risk of HCV transmission from repeated donors was less than that from first-time donors. The blood screening mode of HCV by dual ELISA and once NAT can effectively reduce the residual risk of transfusion-transmitted HCV and improve blood safety. The rate of repeat blood donation needs to be increased by continuously optimizing the recruitment strategy of blood donors.

Clinical comparison of intravenous thrombolysis and bridging artery thrombectomy in hyperacute ischemic stroke with unknown time of onset.

INTRODUCTION: The aim of the study was to explore the clinical efficacy and safety of intravenous thrombolysis and bridging artery thrombectomy for hyperacute ischemic stroke with unknown onset time. METHODS: One hundred and twenty-eight patients with hyperacute cerebral infarction and without a clear time of onset were randomly divided into intravenous thrombolysis (n = 66) and bridging artery thrombectomy groups (n = 62). RESULTS: In the intravenous thrombolysis group, 37 patients' vessels had recanalization, 32 patients' 24-hour National Institute of Health Stroke Scale (NIHSS) score improved, and 42 patients' 90-day modified Rankin Scale (mRS) score was good. In the bridging artery thrombectomy group, 62 patients' vessels had recanalization, 28 patients' 24-hour NIHSS score improved, and 38 patients' 90-day mRS score was good. CONCLUSIONS: The benefits and adverse events between intravenous thrombolysis and bridging artery thrombectomy for ischemic stroke with unknown time of onset are similar.

FXa cleaves the SARS-CoV-2 spike protein and blocks cell entry to protect against infection with inferior effects in B.1.1.7 variant

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human natural defense mechanisms against SARS-CoV-2 are largely unknown. Serine proteases (SPs) including furin and TMPRSS2 cleave SARS-CoV-2 spike protein, facilitating viral entry. Here, we show that FXa, a SP for blood coagulation, is upregulated in COVID-19 patients compared to non-COVID-19 donors and exerts anti-viral activity. Mechanistically, FXa cleaves the SARS-CoV-2 spike protein, which prevents its binding to ACE2, and thus blocks viral entry. Furthermore, the variant B.1.1.7 with several mutations is dramatically resistant to the anti-viral effect of FXa compared to wild-type SARA-CoV-2 in vivo and in vitro. The anti-coagulant rivaroxaban directly inhibits FXa and facilitates viral entry, whereas the indirect inhibitor fondaparinux does not. In a lethal humanized hACE2 mouse model of SARS-CoV-2, FXa prolonged survival while combination with rivaroxaban but not fondaparinux abrogated this protection. These preclinical results identify a previously unknown SP function and associated anti-viral host defense mechanism and suggest caution in considering direct inhibitors for prevention or treatment of thrombotic complications in COVID-19 patients.

Dual roles of a novel oncolytic viral vector-based SARS-CoV-2 vaccine: preventing COVID-19 and treating tumor progression

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer patients are usually immunocompromised and thus are particularly susceptible to SARS-CoV-2 infection resulting in COVID-19. Although many vaccines against COVID-19 are being preclinically or clinically tested or approved, none have yet been specifically developed for cancer patients or reported as having potential dual functions to prevent COVID-19 and treat cancer. Here, we confirmed that COVID-19 patients with cancer have low levels of antibodies against the spike (S) protein, a viral surface protein mediating the entry of SARS-CoV-2 into host cells, compared with COVID-19 patients without cancer. We developed an oncolytic herpes simplex virus-1 vector-based vaccine named oncolytic virus (OV)-spike. OV-spike induced abundant anti-S protein neutralization antibodies in both tumor-free and tumor-bearing mice, which inhibit infection of VSV-SARS-CoV-2 and wild-type (WT) live SARS-CoV-2 as well as the B.1.1.7 variant in vitro. In the tumor-bearing mice, OV-spike also inhibited tumor growth, leading to better survival in multiple preclinical tumor models than the untreated control. Furthermore, OV-spike induced anti-tumor immune response and SARS-CoV-2-specific T cell response without causing serious adverse events. Thus, OV-spike is a promising vaccine candidate for both preventing COVID-19 and enhancing the anti-tumor response. One Sentence SummaryA herpes oncolytic viral vector-based vaccine is a promising vaccine with dual roles in preventing COVID-19 and treating tumor progression

The K18-hACE2 Transgenic Mouse Model Recapitulates Non-Severe and Severe COVID-19 in Response to Infectious Dose of SARS-CoV-2 Virus

A comprehensive analysis and characterization of a SARS-CoV-2 infection model that mimics non-severe and severe COVID-19 in humans is warranted for understating the virus and developing preventive and therapeutic agents. Here, we characterized the K18-hACE2 mouse model expressing human (h)ACE2 in mice, controlled by the human keratin 18 (K18) promoter, in epithelia, including airway epithelial cells where SARS-CoV-2 infections typically start. We found that intranasal inoculation with higher viral doses (2x103 and 2x104 PFU) of SARS-CoV-2 caused lethality of all mice and severe damage of various organs, including lungs, liver, and kidney, while lower doses (2x101 and 2x102 PFU) led to less severe tissue damage and some mice recovered from the infection. In this humanized hACE2 mouse model, SARS-CoV-2 infection damaged multiple tissues, with a dose-dependent effect in most tissues. Similar damage was observed in biopsy samples from COVID-19 patients. Finally, the mice that recovered after infection with a low dose of virus also survived rechallenge with a high dose of virus. Compared to other existing models, the K18-hACE2 model seems to be the most sensitive COVID-19 model reported to date. Our work expands the information available about this model to include analysis of multiple infectious doses and various tissues with comparison to human biopsy samples from COVID-19 patients. In conclusion, the K18-hACE2 mouse model recapitulates both severe and non-severe COVID-19 in humans and can provide insight into disease progression and the efficacy of therapeutics for preventing or treating COVID-19. ImportanceThe pandemic of COVID-19 has reached 112,589,814 cases and caused 2,493,795 deaths worldwide as of February 23, 2021, has raised an urgent need for development of novel drugs and therapeutics to prevent the spread and pathogenesis of SARS-CoV-2. To achieve this goal, an animal model that recapitulates the features of human COVID-19 disease progress and pathogenesis is greatly needed. In this study, we have comprehensively characterized a mouse model of SARS-CoV-2 infection using K18-hACE2 transgenic mice. We infected the mice with low and high doses of SARS-CoV-2 virus to study the pathogenesis and survival in response to different infection patterns. Moreover, we compared the pathogenesis of the K18-hACE2 transgenic mice with that of the COVID-19 patients to show that this model could be a useful tool for the development of anti-viral drugs and therapeutics.

Effects of tumor treating fields (TTF) arrays on the radiation doses to glioblastoma / 中华放射医学与防护杂志

Objective:To preliminarily explore the effects of tumor treating fields (TTF) arrays on the dose distribution in the treatment of Glioblastoma (GBM) using combined radiotherapy and concurrent TTF.Methods:EDR2 and MatriXX plate ionization chamber were employed to measure the absorbed doses of tissues at different depths (< 1 mm, 3 mm, 5 mm, 1 cm, 1.5 cm, 3 cm, 5 cm, 10 cm, and 15 cm) in the case that TTF arrays and latex-free foam were attached and not attached on the surface. Then the absorbed doses were calculated, compared, and analyzed. For the volumetric arc therapy (VMAT) of 10 GBM patients, deep dose verification was performed using the Sun Nuclear ArcCheck 3D dose verification system and the D99%, Dmean, and D1% of tumors and OARs were assessed. Results:The surface dose increased by 173% in the case that TTF arrays and latex-free foam were attached to the surface compared with the case of the surface with nothing attached. The surface dose increased by 61.7% due to the attachment of low-density latex-free foam. The dose deviation gradually decreased with an increase in the depth and stabilized (about 4%) at a depth of greater than 1.5 cm. As indicated by the VMAT verification result, the D99%, Dmean, and D1% of PTV and CTV decreased by 1.1%-1.2% and the Dmean and D1% of OARs (i.e., brainstem, pituitary gland, optic chiasma, optic nerve, eyeball, and eye crystal) decreased by 0.7%-1.5% in the case that TTF array and latex-free foam were attached on the surface compared with the case the surface with nothing attached. Conclusions:The combined radiotherapy and concurrent TTF in the GBM treatment will lead to a slight reduction of the absorbed doses of targets and OARs but a significant increase in the absorbed doses of the scalp. Therefore, it is recommended that the scalp doses should be reduced as far as possible in the design of the radiation treatment plan to reduce the adverse reactions on the scalp of GBM patients.

Effect of radiation therapy and prognostic factors in hepatocellular cancer patients with cardiophrenic angle or superior diaphragmatic lymph nodes metastasis / 中华放射医学与防护杂志

Objective:To study the effects of radiotherapy and the prognostic factors in hepatocellular cancer (HCC) patients with cardiophrenic angle or superior diaphragmatic lymph nodes metastasis (LNM).Methods:We retrospectively analyzed 56 HCC patients with cardiophrenic angle or superior diaphragmatic LNM who were treated with or without external beam radiation therapy (EBRT) in Zhongshan Hospital of Fudan University from Jan 2010 to Aug 2020. Patients were divided into two groups according to whether they received radiotherapy, EBRT group and non-EBRT group, and each group had 28 patients. Radiation fields included or excluded primary tumor in EBRT group, and the cardiophrenic angle or superior diaphragmatic LNM did not receive any local treatment in non-EBRT group. The response rate, survival rate, local control rate, prognostic risk factors of the two groups were studied.Results:After EBRT, the partial response rate and complete response rate were 32.1%(9/28) and 32.1%(9/28). The median survival rate of EBRT group was 16.1 months (95% CI 9.00-23.21, RR=3.63) vs. 6.9 months (95% CI 4.63-8.77, RR=1.06) for the non-EBRT group, with statistically significant difference ( χ2=15.53, P<0.05). Cardiophrenic angle or superior diaphragmatic lymph nodes 1-year local control rate for EBRT group and non-EBRT group were 37.0% vs. 10.7%, with statistically significant difference ( χ2=5.28, P<0.05). Since diagnosis of cardiophrenic angle or superior diaphragmatic LNM, 4 patients (14.3%) in the EBRT group vs. 13 patients (46.4%) in the non-EBRT group had higher alpha-fetoprotein (AFP) level after 3 months compared with the AFP before EBRT ( χ2=6.84, P<0.05). Multivariate analysis showed that multiple intrahepatic tumors, maximal diameter of intrahepatic tumors >5 cm, AFP≥400 μg/L, no EBRT were poor prognostic factors. Conclusions:EBRT can prolong overall survival and improve the control rate of lymph node of HCC patients with cardiophrenic angle or superior diaphragmatic LNM. Patients with multiple intrahepatic tumors, maximal diameter of intrahepatic tumors >5 cm, AFP≥400 μg/L and no EBRT have poor prognosis.

Comparison of dose distributions among five radiotherapy apparatuses in stereotactic body radiation therapy for pancreatic cancer / 中华放射肿瘤学杂志

Objective:To compare the dose distribution among CyberKnife, Tomotherapy, Edge, Triology and γ-knife in stereotactic body radiation therapy (SBRT) for pancreatic cancer.Methods:Clinical data of 10 panreatic cancer patients receiving CyberKinife treatment were retrospectively analyzed. The treatment plans were designed by five apparatuses from five centers according to the uniform requirement. All plans were transferred to MIM system for the extraction of parameters, which mainly included D min, D mean and D max of PTV, conformity index (CI), new conformity index (nCI), homogeneity index (HI), gradient index (GI), coverage, D max and dose-volume of the stomach and bowel. Results:The best CI and nCI were obtained in Triology ( P<0.001), and the worst HI was found in γ-knife ( P<0.001). The best GI was found in CyberKnife, followed by γ-knife and Tomotherapy, and Edge showed the worst GI ( P<0.001). The highest D min of PTV was found in both Edge and Triology, while lower D min of PTV was found in CyberKnife and Tomotherapy ( P<0.001). Additionally, γ-knife provided the highest D mean and D max of PTV ( P<0.001). Regarding the organs at risk, the lowest D max and D 5cm 3 of the bowel ( P<0.001), D max of the stomach ( P=0.003), D max( P=0.001), D 5cm 3 ( P<0.001) and D 10cm 3 ( P=0.005) of the duodenum, D max( P<0.001) and D 0.35cm 3 ( P<0.001) of the spinal cord were found in CyberKnife. The highest D max of the bowel was found in γ-knife. Furthermore, the highest D 5cm 3 of the duodenum was demonstrated in Edge ( P<0.001) and Tomotherapy provided the highest D max( P<0.001) and D 0.35cm 3 of the spinal cord ( P<0.001). Conclusions:All five radiotherapy apparatuses can meet the requirement of SBRT for pancreatic cancer. More rapid dose fall-off could be obtained via CyberKnife and γ-knife. Triology and Edge provide better target conformity. CyberKnife can better protect the gastrointestinal tract.

Inhibiting autophagy enhances sulforaphane-induced apoptosis

Sulforaphane (SFN), a natural anti-tumor compound from cruciferous vegetables, has been reported to induce protective autophagy to cancer cells, which might impair the anti-tumor efficiency of SFN. However, the accurate function and mechanism of SFN inducing autophagy in cancers are still obscure, especially in esophageal squamous cell carcinoma (ESCC), one of malignancies with high incidence in North China. Here, we mainly explored the potential function of autophagy upon SFN treatment in ESCC and molecular mechanism. We demonstrated that SFN could inhibit cell proliferation and induce apoptosis by activating caspase pathway. Moreover, we found activation of NRF2 pathway by SFN was responsible for the induction of autophagy and also a disadvantage element to the anti-tumor effects of SFN on ESCC, indicating that SFN might induce protective autophagy in ESCC. We, therefore, investigated effects of autophagy inhibition on sensitivity of ESCC cells to SFN and found that chloroquine (CQ) could neutralize the activation of SFN on NRF2 and enhance the activation of SFN on caspase pathway, thus improved the anti-tumor efficiency of SFN on ESCC

Anti-colonic Inflammation by Black Raspberries through Regulating Toll-like Receptor-4 Signaling in Interlukin-10 Knockout Mice

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, with a steadily rising prevalence in Western and newly industrialized countries. UC patients have a cancer incidence as high as 10% after 20 years of the disease. Although the importance of fruits and vegetables in defense against UC is beginning to be appreciated, the mechanisms remain largely unclear. In the current study, we reported that dietary black raspberries (BRBs) decreased colonic inflammation in the mucosa and submucosa of interleukin (IL)-10 knockout (KO) mice. We then used colon, spleen, and plasma from those mice to investigate whether BRBs exert their anti-inflammatory effects by correcting dysregulated toll-like receptor (TLR)-4 signaling to downregulate prostaglandin E2 (PGE2). Other studies reported that spleen is the reservoir of macrophages and depletion of macrophages in IL-10 KO mice prevents the development of colitis. Our results showed that BRBs decreased the percentages of macrophages in spleens of IL-10 KO mice. Moreover, mechanistically, the BRB diet corrected dysregulated TLR-4 signaling in cells from the colon and spleen, decreased PGE2 and prostaglandin I2, and increased 15-lipoxygenase and its product, 13-S-hydroxyoctadecadienoic acid, in plasma of IL- 10 KO mice. Therefore, we have elucidated one of the anti-inflammatory mechanisms of BRBs, and have identified biomarkers that could be indicators of response in UC patients treated with them. Our findings with BRBs could well apply to many other commonly consumed fruits and vegetables.

RICTOR/mTORC2 affects tumorigenesis and therapeutic efficacy of mTOR inhibitors in esophageal squamous cell carcinoma

Dysregulation of mTORC1/mTORC2 pathway is observed in many cancers and mTORC1 inhibitors have been used clinically in many tumor types; however, the mechanism of mTORC2 in tumorigenesis is still obscure. Here, we mainly explored the potential role of mTORC2 in esophageal squamous cell carcinoma (ESCC) and its effects on the sensitivity of cells to mTOR inhibitors. We demonstrated that RICTOR, the key factor of mTORC2, and p-AKT (Ser473) were excessively activated in ESCC and their overexpression is related to lymph node metastasis and the tumor-node-metastasis (TNM) phase of ESCC patients. Furthermore, we found that mTORC1/ mTORC2 inhibitor PP242 exhibited more efficacious anti-proliferative effect on ESCC cells than mTORC1 inhibitor RAD001 due to RAD001-triggered feedback activation of AKT signal. Another, we demonstrated that down-regulating expression of RICTOR in ECa109 and EC9706 cells inhibited proliferation and migration as well as induced cell cycle arrest and apoptosis. Noteworthy, knocking-down stably RICTOR significantly suppresses RAD001-induced feedback activation of AKT/PRAS40 signaling, and enhances inhibition efficacy of PP242 on the phosphorylation of AKT and PRAS40, thus potentiates the antitumor effect of RAD001 and PP242 both and . Our findings highlight that selective targeting mTORC2 could be a promising therapeutic strategy for future treatment of ESCC.

Predictors of 90 d death after endovascular mechanical thrombectomy in patients with anterior circulation stroke / 国际脑血管病杂志

Objective:To investigate the risk factors for 90 d death after endovascular mechanical thrombectomy (MT) in patients with acute anterior circulation large-artery occlusive stroke.Methods:From October 2015 to March 2018, patients with acute anterior circulation large-artery occlusive stroke treated with MT in People's Hospital of Shanghai Pudong New Area and the Second Affiliated Hospital of Soochow University were enrolled retrospectively. The primary outcome events were defined as death within 90 d after operation. Univariate and multivariate logistic regression models were used to identify the independent risk factors for death within 90 d after operation. Results:A total of 116 patients were enrolled, 23 (19.8%) of them died within 90 d after operation. Univariate analysis showed that there were significant differences in age, baseline National Institutes of Health Stroke Scale (NIHSS) score, the Alberta Stroke Program Early CT Score (ASPECTS), and the proportion of the baseline NIHSS score classification (≤8, 9-15, ≥16), ASPECTS ≤7, the number of attempts to pass >3 times, modified Thrombolysis in Cerebral Infarction (mTICI) blood flow grade 2b/3, hemorrhagic transformation (HT), and symptomatic HT in the death group compared with the survival group (all P<0.05). Multivariate analysis showed that after adjusting for age, fasting blood glucose, baseline NIHSS score, number of attempts to pass >3, and mTICI grade 2b/3, lower ASPECTS (odds ratio [ OR] 0.647, 95% confidence interval [ CI] 0.456-0.917; P=0.014), longer time from onset to vascular recanalization ( OR 1.004, 95% CI 1.000-1.007; P=0.046) and symptomatic HT ( OR 13.522, 95% CI 2.719-67.258; P=0.001) were the independent predictors of death within 90 d. Conclusion:The ASPECTS, time from onset to recanalization, and symptomatic HT were the independent risk factors for death within 90 d after MT in patients with acute anterior circulation large-artery occlusive stroke.

p53-induced long non-coding RNA PGM5-AS1 inhibits the progression of esophageal squamous cell carcinoma through regulating miR-466/PTEN axis.

A growing body of evidence suggests that long non-coding RNA (lncRNA) is aberrantly expressed in human cancer and linked to cancer initiation and development. We previously identified Homo sapiens PGM5 antisense RNA 1 (PGM5-AS1) as a novel esophageal squamous cell carcinoma (ESCC)-related lncRNA by performing high-throughput RNA sequencing. However, its clinical implication and biological function in ESCC are still uncharacterized. In the present study, we found that PGM5-AS1 was frequently downregulated in ESCC tissues, plasma, and cell lines, and low PGM5-AS1 expression was positively correlated with poor differentiation, advanced tumor node metastasis (TNM) stage, and lymph node metastasis. Importantly, PGM5-AS1 was identified to be an effective diagnostic and prognostic biomarker for ESCC patients. Functional experiments revealed that exogenous expression of PGM5-AS1 significantly suppressed the proliferation, migration, and invasion of ESCC cells in vitro as well as tumor growth in vivo. Mechanistically, PGM5-AS1 was transcriptionally activated by p53 and it could directly interact with and sequester miR-466 to elevate PTEN expression, thereby inhibiting ESCC progression. Overall, our data indicate that PGM5-AS1 is a novel tumor suppressor in ESCC and restoration of PGM5-AS1 may be a promising avenue for treatment of ESCC patient.

Study on Chemical Constituents of Ethanol Extract from Euonymus amygdalifolius / 中国药房

OBJECTIVE:To study the chemical constituents of Euonymus amygdalifolius.METHODS:Silica gel column chromatogram,gel column chromatogram,TLC and semi-preparative HPLC were adopted to isolate and purify ethanol extract from E.amygdalifolius.The structure of compounds was analyzed and identified according to physical and chemical properties,spectral data (mass spectrurn,hydrogen spectrum and carbon spectrum).RESULTS:Ten compounds were isolated from ethanol extract of aerial part of E.amygdalifolius,i.e.taraxerol (1),sophoradiol (2),taraxerone (3),sorghumol (4),heptaecanoic acid (5),octadecenoic acid (6),β-Sitosterol (7),daucosterol (8),epifriedelinol (9) and friedelin (10).CONCLUSIONS:Above compounds are all isolated from E.amygdalifolius for the first time;compounds 1,2,4,5,6 are isolated and obtained from Euonymus A.for the first time.The study lay a foundation for quality evaluation of E.amygdalifolius.

Early diagnosis and treatment of pulmonary embolism in Department of Traumatic Orthopedics / 中国基层医药

Objective To analyze the early diagnosis ,treatment methods and effect of pulmonary embolism in Department of Traumatic Orthopedics .Methods From October 2014 to October 2016, 100 patients with pulmonary embolism in trauma department of orthopedics of Datong Coal Group Co three hospital were selected as the research subjects.Combined with the basic data of patients and clinical manifestations ,the early diagnosis and clinical features were summarized.The chronic respiratory questionnaire(CRQ) and quality of life assessment table(QOL) were used to evaluate the respiratory status and living quality of the patients before and after treatment .At the same time, according to the different treatment methods , the effect of simple anticoagulant or combined with thrombolytic was compared.Results Before treatment,the CRQ total score,QOL total score were (5.9 ±1.3) points,(65.78 ± 23.91)points,respectively,which after treatment were (3.1 ±0.7) points,(30.92 ±13.45) points,respectively,the differences were statistically significant ( t =11.931, 20.104, all P <0.05 ).In 100 patients, after treated by anticoagulation alone or combined with anticoagulation and thrombolytic therapy ,there were significantly effective in 54 cases,effective in 33 cases,invalid in 9 cases,and 4 cases died,the total effective rate was 87.00％.The total effective rate of anticoagulant therapy was 81.58％,which of anticoagulation combined with thrombolytic therapy was 90.32％,the difference was not statistically significant (χ2 =1.593,P>0.05).Conclusion In the perioperative period of Department of Traumatic Orthopedics , pulmonary embolism should be timely diagnosed , and reasonable treatment can improve the respiratory function and life quality of patients ,anticoagulation combined with thrombolytic therapy can improve the efficacy.

Expression and prognostic significance of esophageal squamous cell carcinoma associated long non-coding RNA-1 in esophageal squamous cell carcinoma / 中华消化杂志

Objective@#To analyze the expression and prognostic significance of esophageal squamous cell carcinoma associated long non-coding RNA-1 (ESCCAL-1) in esophageal squamous cell carcinoma (ESCC) tissues. @*Methods@#From August 2011 to May 2013, 73 patients with ESCC, who received radical resection in The First Affiliated Hospital of Zhengzhou University and Henan Cancer Hospital, were enrolled. The expressions of ESCCAL-1 in esophageal tumor tissues and corresponding adjacent non-tumor tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). T test, chi square test and multivariate analysis were performed for statistical analysis. @*Results@#The expression of ESCCAL-1 was 28.03±9.37 in esophageal tumor tissues of patients with ESCC, which was higher than that in corresponding adjacent normal tissues (11.39±4.15), and the difference was statistically significant (t=2.964, P<0.01). However there were no statistically significant differences in the expressions of ESCCAL-1 among the patients with different age, gender, histological grade, classification of Union for International Cancer Control (UICC), T stage or lymph nodes metastasis (all P>0.05). The median disease-free survival (DFS) time and overall survival (OS) time of patients with low ESCCAL-1 expression were 39 months and 42 months, respectively, which were longer than those of patients with high ESCCAL-1 expression (30 months and 37 months), and the differences were statistically significant (χ2=9.049, P=0.003; χ2=10.165, P=0.001). The results of multivariate analysis showed that ESCCAL-1 expression was the independent risk factor of DFS and OS (high risk (HR)=2.45, 95% confidence interval (CI) 1.22 to 4.93, P=0.012; HR=2.29, 95%CI 1.14 to 4.59, P=0.019). @*Conclusions@#ESCCAL-1 may be involved the genesis and development of ESCC. The expression of ESCCAL-1 in esophageal tumor tissues may be a prognostic parameter for patients with ESCC receiving radical resection.