Objective To investigate the effect of dihydroartemisinin(DHA)for enhancing the inhibitory effect of cisplatin(DDP)on DDP-resistant nasopharyngeal carcinoma cell line HNE1/DDP and explore the mechanism.Methods CCK-8 method was used to assess the survival rate of HNE1/DDP cells treated with DHA(0,5,10,20,40,80,and 160 μmol/L)and DDP(0,4,8,16,32,64,128 μmol/L)for 24 or 48 h,and the combination index of DHA and DDP was calculated using Compusyn software.HNE1/DDP cells treated with DHA,DDP,or their combination for 24 h were examined for cell viability,proliferation and colony formation ability using CCK-8,EdU and colony-forming assays.Flow cytometry was used to detect cell apoptosis and intracellular reactive oxygen species(ROS).The expression levels of apoptosis-related proteins cleaved PARP,cleaved caspase-9 and cleaved caspase-3 were detected by Western blotting.The effects of N-acetyl-cysteine(a ROS inhibitor)on proliferation and apoptosis of HNE1/DDP cells with combined treatment with DHA and DDP were analyzed.Results Different concentrations of DHA and DDP alone both significantly inhibited the viability of HNE1/DDP cells.The combination index of DHA(5 μmol/L)combined with DDP(8,16,32,64,128 μmol/L)were all below 1.Compared with DHA or DDP alone,their combined treatment more potently decreased the cell viability,colony-forming ability and the number of EdU-positive cells,and significantly increased the apoptotic rate,intracellular ROS level,and the expression levels of cleaved PARP,cleaved caspase-9 and cleaved caspase-3 in HNE1/DDP cells.N-acetyl-cysteine pretreatment obviously attenuated the inhibitory effect on proliferation and apoptosis-inducing effect of DHA combined with DDP in HNE1/DDP cells(P<0.01).Conclusion DHA enhances the growth-inhibitory and apoptosis-inducing effect of DDP on HNE1/DDP cells possibly by promoting accumulation of intracellular ROS.

Objective To investigate the effect of dihydroartemisinin(DHA)for enhancing the inhibitory effect of cisplatin(DDP)on DDP-resistant nasopharyngeal carcinoma cell line HNE1/DDP and explore the mechanism.Methods CCK-8 method was used to assess the survival rate of HNE1/DDP cells treated with DHA(0,5,10,20,40,80,and 160 μmol/L)and DDP(0,4,8,16,32,64,128 μmol/L)for 24 or 48 h,and the combination index of DHA and DDP was calculated using Compusyn software.HNE1/DDP cells treated with DHA,DDP,or their combination for 24 h were examined for cell viability,proliferation and colony formation ability using CCK-8,EdU and colony-forming assays.Flow cytometry was used to detect cell apoptosis and intracellular reactive oxygen species(ROS).The expression levels of apoptosis-related proteins cleaved PARP,cleaved caspase-9 and cleaved caspase-3 were detected by Western blotting.The effects of N-acetyl-cysteine(a ROS inhibitor)on proliferation and apoptosis of HNE1/DDP cells with combined treatment with DHA and DDP were analyzed.Results Different concentrations of DHA and DDP alone both significantly inhibited the viability of HNE1/DDP cells.The combination index of DHA(5 μmol/L)combined with DDP(8,16,32,64,128 μmol/L)were all below 1.Compared with DHA or DDP alone,their combined treatment more potently decreased the cell viability,colony-forming ability and the number of EdU-positive cells,and significantly increased the apoptotic rate,intracellular ROS level,and the expression levels of cleaved PARP,cleaved caspase-9 and cleaved caspase-3 in HNE1/DDP cells.N-acetyl-cysteine pretreatment obviously attenuated the inhibitory effect on proliferation and apoptosis-inducing effect of DHA combined with DDP in HNE1/DDP cells(P<0.01).Conclusion DHA enhances the growth-inhibitory and apoptosis-inducing effect of DDP on HNE1/DDP cells possibly by promoting accumulation of intracellular ROS.

Purpose To investigate the expression of SMOC2 in papillary thyroid carcinomas(PTC)and its efficacy in joint diagnosis with CK19,Galectin-3,MC and BRAF V600E.Methods Bioinformatics was uesd to analyze the mR-NA expression differences of SMOC2 in PTC and benign thyroid tissues in the Gene Expression Omnibus database and The Canc-er Genome Atlas database.Detection of SMOC2 protein expres-sion in paraffin tissue of 75 cases of PTC and 45 cases of papilla-ry thyroid hyperplasia(PTH)was used by using EnVision meth-od,combined with CK19,Galectin-3,and MC and BRAF V600E for sensitivity and specificity analysis.Results The bioinformatics analysis results showed that the mRNA expression level of SMOC2 in PTC tissue was significantly lower than that in benign thyroid tissue(P<0.05),and the area under the curve(AUC)predicted by SMOC2 for PTC diagnosis was 0.910(P<0.001).The immunohistochemical results showed that the ex-pression of SMOC2 in PTC was significantly lower than that in PTH tissue(P<0.001),and the AUC of SMOC2 for PTC diag-nosis was 0.898(P<0.001).The AUC of SMOC2 combined with CK19,Galectin-3,MC and BRAF V600E in the diagnosis of PTC was 1.000(P<0.001),and the AUC values of the combination of other markers were lower than 1.000.Conclu-sion The expression of SMOC2 in PTC is significantly de-creased,which can be used as an important marker for the diag-nosis and differential diagnosis of PTC.Combined with CK19,Galectin-3,MC and BRAF V600E,the sensitivity and specifici-ty of PTC can be improved to a certain extent.

Recently, salvia miltiorrhiza has made a great progress in research of central nervous system (CNS) injury and neurodegeneration. Salvia miltiorrhiza and its active ingredients can exert multiple effects involving reduction of cell loss, attenuation of oxidative stress, improvement of micro-circulation and promotion of neuroregeneration, and show a protective effect on CNS diseases. Regulation of oxidative stress and removing accumulated metabolite may be the important mechanisms by which salvia miltiorrhiza exerts neuroprotective effects. This study will systematically discuss the pharmacological effects and possible mechanisms of salvia miltiorrhiza based on the core pathological changes in CSN diseases, and evaluate its drug safety through combing the related toxicology researches to provide a reference for clinical transformation of Chinese medicine in threatment of CNS diseases.

Objective To investigate the effect of Chinese herbal compound"Jisuikang"on the phagocyto-sis of neuronal debris by microglial cells. Methods To prepare serum containing drugs of JSK and divide them into the low,middle and high dose groups,the blank serum group and LPS+blank serum group. BV2 was labeled by lentiviral vectors containing the green fluorescent protein gene (GFP). To establish the damage neuron model and mix injured neurons with the transfected microglia. To observe the situation of microglia which was affected by serum containing drugs devour the neuronal debris. Results The middle and high dose of JSK showed greater phagocytic percentage and phagocytic index than those of the control group(P<0.001). In comparison of LPS+blank serum group,no significant difference was found in the middle and high dose of JSK. However,to the phagocytic index, which was better than that of LPS+blank serum group(P<0.05). Conclusion JSK may enhance the engulfment of neuron debris by BV2,which could provide a better living environment for the growth of neurons.

Background and objective Eye is a rare site of lung cancer metastasis, and ocular metastasis is one of the largest challenges to cancer patients' quality of life (QOL). Here we present our experience on ocular metastasis of lung cancer and review relevant literature in an attempt to investigate the clinical features, treatment, and prognosis of these tumors. Methods The records of 9 patients with ocular metastasis of lung cancer treated at our hospital were analyzed. A literature re-view identified 42 cases reported in the last 10 years and their medical records were retrospectively estimated. Results The me-dian age of our patients was 51 years (range 41-61). Diagnosis of lung cancer included non-small cell lung carcinoma (NSCLC) in 7 patients, in which adenocarcinoma (ADC) were recorded in 6 patients, small cell lung carcinoma (SCLC) in 1 patient, and unknown in 1 patient. The site of ocular metastasis included choroid (n=8) and iris (n=1). In the literature review, SCLC con-stituted 21.4% (n=9) and ADC constituted 47.6% (n=20). Choroid presented to be the most common site for eye metastasis (66.7%, n=28). As for disease control rate, systemic chemotherapy for lung cancer patients with ocular metastasis presented to be only 28%. Meanwhile, combination of systemic treatment with ocular treatment could improve patients' eye symptoms effectively. Conclusion The most common lung cancer that metastasizes to the eye is ADC. The choroid is the most common site for ocular metastasis. Ocular treatment can improve patients' eye symptoms, while the effect of systemic chemotherapy treatment is limited.

Background and objective Epidermal growth factor receptor (EGFR) and KRAS gene are important driver genes of non-small cell lung cancer (NSCLC).The studies are mainly focused on detection ofEGFR gene for advanced NSCLC,and the mutation feature of EGFR and KRAS gene in early NSCLC tissue is unknown.This study aims to investigate the mutations of EGFR and KRAS gene in NSCLC,and the relationship between the genotype and clinicopathologic features.Methods The hotspot mutations in EGFR and KRAS gene in 754 tissue samples of stage Ⅰ-Ⅲa NSCLC from Department of Pathology,Peking Union Medical College Hospital were detected by modified amplification refractory mutation system (ARMS) real-time PCR kit,and analyzed their correlation with clinical variables.Results The hotspot mutation rates in EGFR and KRAS were 34.5％ and 13.1％ respectively,and there were EGFR-KRAS double mutations in 3 samples.The mutation rate of EGFR was higher in females than that in males (39.5％ vs 29.4％,P=0.076),significantly increased in adenocarcinomas (38.7％) compared to that in the other forms of NSCLC (P＜0.01),but still lower than that reported in some Asian studies of advanced adenocarcinoma (-50％).Meanwhile,the mutation rate of KRAS was remarkably higher in males than that in females (16.6％ vs 9％,P=0.048),increased in adenocarcinomas compared to that in the other forms of NSCLC,but the difference was not significant (P=0.268).Samples harbored EGFR mutation were younger than those harbored KRAS mutation (P=0.031,5),and had significant difference in gender between the two groups (P＜0.01).Conclusion The mutation rate of EGFR in stag Ⅰ-Ⅲa NSCLC patients was lower than that in advanced NSCLC patients.And the percentage of the NSCLC patients with EGFRKRAS double mutations is 0.9％.

Objective To identify the risk factors for positive resection residues after endoscopic submucosal dissection ( ESD ) of early esophageal squamous carcinomas and precancerous lesions. Methods A retrospective analysis was performed in 315 patients with early esophageal squamous cancer and precancerous lesion who underwent ESD. The pathological features of all resection margins in the specimen and the follow?up outcome of the patients with positive resection margin were evaluated. Univariate and multi?variate analysis were used to determine the risk factors for resection margin residues after ESD. Results In 315 lesions,there were 290 lesions with negative resection margins and 25 with positive resection margins.The number of lesions with positive lateral, basal, or both resection margins was 13, 8, and 4, respectively. Multivariate analysis showed that the depth of invasion( submucosal layer invasion, P=0?048) was the only independent risk factor for positive basal resection margin. The proportion of circumferential extension (≥3/4,P=0?014) and the depth of invasion( exceeding muscularis mucosa, P=0?007) were independent risk factors for positive lateral resection margin. Conclusion The diameter of the lesions and the depth of tumor invasion are independent risk factors for esophageal ESD positive resection margins. Accurate evaluation of lesion extension and invasive depth is critical to avoid residual or recurrent tumor after esophageal ESD.

Objective To explore the effect and mechanism of intrathecal injecting κ-opioid receptor agonist U50, 488H on the rats with myocardial ischemia/reperfusion injury.Methods 50 Sprague–Dawley rats were randomly divided into five groups (n=10): sham group (Sham), ischemia/reperfusion group (IR), high-dose intravenous injection group (IV1), low-dose intravenous injection group (IV2), and intrathecal injection group (IT).In sham group the rats were followed by the modeling step without ligation of the left coronary and no drug injection by intravenous or intrathecal; in IR group the rats were underwent 30 minutes of myocardial ischemia followed by 120 minutes of reperfusion, and were not treated with any drug.All the rats in IV1, IV2 and IT groups were intravenous injected with U50, 488H at 1 hour before they were underwent myocardial ischemia/reperfusion as in IR group.IV1 and IV2 groups were intravenous injected with U50, 488H respectively at the dose of 0.1 mg/kg and 0.01 mg/kg, while the IT group was intrathecal injected with U50, 488H at the dose of 0.01mg/kg.All the rats from 5 groups were observed with cardiac ultrasound, myocardial sirius staining, serum CGRP and ET level.Results Compared to IR group(EF%=35.4 ±1.1,FS% =21.1 ±1.1), the rats in IT group (EF%=49.1 ±1.2,FS%=27.1 ±1.0) and IV1 group (EF%=46.3 ±2.2,FS%=26.6 ±0.6) showed better myocardial contraction (P<0.05) and reduced myocardial fibrosis (P<0.05).IT group and IV1 group also showed reduced ET but increased CGRP in the serum (P<0.05).There were no difference between IV2 group and IR group in both observation.Conclusion Pretreatment with intrathecal injection of opium κ-receptor stimulant U50, 488H not only protected the myocardial function from myocardial ischemia/reperfusion injury, but also repressed myocardial fibrosis.The protection may result from modulation of CGRP and ET.

Objective The aim of this study was to identify the clinical features and prognostic factors of leptomeningeal metastasis ( LM ) in non?small cell lung cancer ( NSCLC ) patients undergoing treatment with epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors ( TKIs ) . Methods Twenty?five cases of NSCLC with LM, treated in our hospital during January 1, 2003 to October 31, 2013, were enrolled in this study. Medical records were reviewed for clinical features and treatments, and the survival and prognostic factors were analyzed. Results NSCLC?LM were more common in female patients (64.0%), and most were adenocarcinomas (72.0%). Twenty (80.0%) patients underwent anti?cancer treatment, among them 17 patients underwent EGFR?TKIs treatment. The median overall survival ( mOS ) after the diagnosis of LM was 4.9 months for the whole group (25 cases). Patients receiving EGFR?TKIs treatment had a longer median survival than patients not receiving EGFR?TKIs (5.3 months vs. 1.2 months, P=0.022) . Eleven patients who developed LM before the targeted therapy had a prolonged median survival of 8.1 months after EGFR?TKIs treatment. The univariate analysis showed that female gender and EGFR?TKIs treatment were favorable prognostic factors influencing the survival ( P<0.05) , while age, LM at the time of initial diagnosis, LM developed during the EGFR?TKIs treatment, whole?brain radiotherapy ( WBRT), intrathecal chemotherapy, or systemic cytotoxic chemotherapy were not associated with mOS (P>0.05 for all). The multivariate analysis showed that female gender ( P=0. 012 ) and EGFR?TKIs treatment ( P=0.008 ) were significant predictors of a good prognosis. Conclusions EGFR?TKIs treatment may confer benefit for NSCLC?LM patients. Female patients and EGFR?TKIs treatment are favorable prognostic factors for survival.