Objective To investigate the effect of 6-paradol on the proliferation, migration, and invasion of human intrahepatic cholangiocarcinoma cells and its mechanism. Methods Human intrahepatic cholangiocarcinoma cell lines HCCC 9810 and HUCCT1 were treated with different concentrations of 6-paradol or an equal volume of DMSO (control group), and then CCK-8 assay, plate colony formation assay, wound healing assay, and Transwell assay were used to measure cell proliferation, migration, and invasion. The bioinformatics software Swiss Target Prediction was used to predict the protein targets of 6-paradol, and Western blot was used to measure the protein expression levels of STAT3, p-STAT3, SRC, p-mTOR, p21, Bcl-2, and p53; Drug Affinity Responsive Target Stability (DARTS) assay was used to investigate the interaction between 6-paradol and STAT3. After cholangiocarcinoma HCCC 9810 and HUCCT1 cells were transfected with STAT3 overexpression plasmid or sh-p21 plasmid, quantitative real-time PCR was used to measure the mRNA expression levels of STAT3 and p21, and Western blot was used to measure the protein expression levels of STAT3 and p21; CCK-8 assay, wound healing assay, and Transwell assay were used to measure cell proliferation, migration, and invasion. The t -test was used for comparison of data between two groups; an analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the control group, the 6-paradol treatment groups had significant reductions in cell proliferation, migration, and invasion ( P < 0.05). Compared with the control group, the 6-paradol treatment groups had significant reductions in the expression levels of STAT3 and p-STAT3 (all P < 0.05) and a significant increase in the expression level of p21 (all P < 0.05), while there were no significant changes in the expression levels of Bcl-2, SRC, and p-mTOR (all P > 0.05). In the 6-paradol treatment groups, the proportion of STAT3 hydrolyzed by protease was reduced by 48.66% and 45.33%, respectively ( t =16.64 and 8.76, both P < 0.05); after transfection with STAT3 overexpression plasmid or p21-silencing plasmid in cholangiocarcinoma cells, there was a significant increase in the mRNA expression level of STAT3 ( t HCCC 9810 =2.82, t HUCCT1 =5.60, both P < 0.05) and a significant reduction in the mRNA expression level of p21 ( t HCCC 9810 =6.84, t HUCCT1 =3.91, both P < 0.05). CCK-8 assay showed that for HCCC 9810 and HUCCT1 cells treated with 6-paradol for 48 and 72 hours, the STAT3 overexpression group had a significantly higher proliferation rate than the single administration group, and the p21 silencing group also had a significantly higher proliferation rate than the single administration group ( P < 0.05). The wound healing assay showed that the HCCC 9810 and HUCCT1 cells with STAT3 overexpression or p21 silencing had a significantly higher wound healing rate than the single administration group (all P < 0.05). Transwell assay showed that the HCCC 9810 and HUCCT1 cells with STAT3 overexpression or p21 silencing had significant increases in migration rate and invasion rate compared with the single administration group (all P < 0.05). Conclusion 6-Paradol inhibits the proliferation, migration, and invasion of cholangiocarcinoma cells by targeting the STAT3-p21 pathway.

Objective:To investigate the influence of effects of transarterial chemoembo-lization (TACE) before liver transplantation on the prognosis of hepatocellular carcinoma.Methods:The retrospective cohort study was conducted. The clinicopathological data of 311 hepatocellular carcinoma patients undergoing TACE before liver transplantation who were admitted to the Third Medical Center of Chinese PLA General Hospital from January 2005 to December 2012 were collec-ted. There were 276 males and 35 females, aged from 47 to 59 years, with a median age of 52 years. All the 311 patients underwent TACE before liver transplantation. Observation indicators: (1) effects of hepatocellular carcinoma patients undergoing TACE and its relationship with clinicopathological factors; (2) follow-up; (3) influencing factors for prognosis of hepatocellular carcinoma patients after liver transplantation. Follow-up was conducted using outpatient examination or telephone interview to detect recurrence and metastasis of tumor and survival and graft loss of patients up to December 2017. The patients were followed up every 2 to 4 weeks within 3 months after liver transplantation, and once every 1 to 3 months thereafter. Measurement data with normal distri-bution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the nonparametric rank sum test. The COX regression model was used for univariate and multivariate analyses. The Kaplan-Meier method was used to draw survival curves and calculate survival rates, and the Log-rank test was used for survival analysis. Results:(1) Effects of hepatocellular carcinoma patients undergoing TACE and its relationship with clinicopathological factors. Of the 311 patients undergoing TACE, 57 cases had pathologic complete response (pCR) and 254 cases had pathologic partial response (pPR), respectively. Cases with alpha fetoprotein (AFP) <20 μg/L,20?400 μg/L, >400 μg/L, cases with microvascular invasion, cases with tumor number as single nodule, cases with tumor distribution at right lobe of liver, cases with tumor caliber of feeding artery (CFA) >1 mm were 26, 26, 5, 51, 6, 43, 46 in patients with pCR, versus 87, 64, 103, 158, 59, 125, 159 in patients with pPR, showing significant differences in the above indicators ( Z=3.35, χ2=4.54, 15.71, 12.89, 6.79, P<0.05). (2) Follow-up. All the 311 patients were followed up for 47.0 to 59.0 months, with a median follow-up time of 44.6 months. There were 11 cases undergoing tumor recurrence and 11 cases undergoing tumor metastasis in the 57 patients with pCR, and there were 96 cases undergoing tumor recurrence and 66 cases under-going tumor metastasis in the 254 patients with pPR. The 1-, 3-, 5-year tumor recurrence free rates were 98.2%, 91.1%, 80.3% in the 311 patients, respectively. The 1-, 3-, 5-year tumor recurrence free rates were 100.0%, 91.1%, 80.3% in the 57 patients with pCR, versus 82.0%, 68.4%, 59.4% in the 254 patients with pPR, showing significant differences in the above indicators ( χ2=13.47, P<0.05). Cases with graft loss were 11 and 96 in the 57 patients with pCR and the 254 patients with pPR, respectively, showing a significant difference ( χ2=7.06, P<0.05). (3) Influen-cing factors for prognosis of hepatocellular carci-noma patients after liver transplantation. Results of univariate analysis showed that gender, basic diseases as viral hepatitis C, AFP (20?400 μg/L, >400 μg/L), Milan criteria, microvascular invasion, tumor number, tumor distribution, tumor CFA, times of TACE, effects of TACE were related factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation ( hazard ratio=0.49, 3.97, 1.78, 1.84, 2.41, 1.96, 3.00, 1.76, 0.19, 2.01, 3.07, 95% confidence interval as 0.30?0.81, 2.23?7.05, 1.03?3.06, 1.18?2.85, 1.63?3.56, 1.28?3.01, 2.04?4.40, 1.20?2.59, 0.13?0.28, 1.28?3.14, 1.63?5.76, P<0.05). Results of multi-variate analysis showed that AFP >400 μg/L, exceeding Milan criteria, tumor number as multiple nodule,effects of TACE as pPR were independent risk factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation ( hazard ratio=1.59, 2.06, 1.99, 2.05, 95% confidence interval as 1.22?2.07, 1.35?3.13, 1.29?3.07, 1.02?4.10, P<0.05) and tumor CFA >1 mm was an independent protective factor influencing prognosis of hepatocellular carcinoma patients after liver transplantation ( hazard ratio=0.10, 95% confidence interval as 0.05?0.19, P<0.05). Conclusions:The effects of TACE are related to AFP, microvascular invasion, tumor number, tumor distribution and tumor CFA. AFP >400 μg/L, exceeding Milan criteria, tumor number as multiple nodule,effects of TACE as pPR are independent risk factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation and tumor CFA >1 mm is an independent protective factor influencing prognosis of hepatocellular carcinoma patients after liver transplantation.

Circulating tumor cells are found in patients’ peripheral blood circulation, which are the key to tumor metastasis and recurrence. We can achieve early diagnosis and treatment of the tumor if we could detect circulating tumor cells through peripheral blood vessels. It is of great significance to improve the prognosis of hepatocellular carcinoma patients by studying the relationships between hepatocellular carcinoma and peripheral circulating tumor cells. Hence, this paper reviews the recent progress in the detection and clinical application of circulating tumor cells in hepatocellular carcinoma in order to provide references for clinical and related studies.

The protection of language function is one of the major challenges of brain surgery. Over the past century, neurosurgeons have attempted to seek the optimal strategy for the preoperative and intraoperative identification of language-related brain regions. Neurosurgeons have investigated the neural mechanism of language, developed neurolinguistics theory, and provided unique evidence to further understand the neural basis of language functions by using intraoperative cortical and subcortical electrical stimulation. With the emergence of modern neuroscience techniques and dramatic advances in language models over the last 25 years, novel language mapping methods have been applied in the neurosurgical practice to help neurosurgeons protect the brain and reduce morbidity. The rapid advancements in brain-computer interface have provided the perfect platform for the combination of neurosurgery and neurolinguistics. In this review, the history of neurolinguistics models, advancements in modern technology, role of neurosurgery in language mapping, and modern language mapping methods (including noninvasive neuroimaging techniques and invasive cortical electroencephalogram) are presented.
Brain Mapping ; Brain Neoplasms ; Humans ; Language ; Neurosurgery ; Neurosurgical Procedures

Objective:To evaluate the rationality of diving procedures and medical support through monitoring the stress, nutrition, and sleep quality of divers.Methods:The vital signs of divers were recorded by the monitor designed for high pressure condition. The bubble escape during decompression was evaluated by Doppler bubble monitor. The stress levels of divers were evaluated by the Stanford acute stress reaction questionnaire (SASRQ), and the sleep qualities of divers were evaluated by Pittsburgh sleep quality index (PSQI). The post-diving effects were evaluated by the tests of blood routine and blood biochemistry, and MRI examination of large joints (bilateral shoulders, hips, and knees).Results:The vital signs of the four divers were stable throughout the training, and there was no significant difference in the mean values of vital signs in each stage ( P>0.05). During the decompression, all Doppler bubble monitoring results were below level 2. The total scores of SASRQ before and after diving were both lower than 57 points, indicating a moderate and low stress level; the stress levels of divers decreased slightly after surfacing, but the differences were not statistically significant ( t=1.464, P=0.239). Before and after diving, the divers’ sleep quality was good, but it decreased after surfacing, and the differences were statistically significant ( t=-4.899, P=0.016). The results of blood routine test, biochemical test, and MRI of bilateral shoulders and hips of the four divers after diving were normal; the results of knee MRI showed that only one diver had a small amount of joint effusion. Conclusion:The physical and mental health of the divers in this training maintained good, indicating the procedures of and the medical support for the diving were safe and effective.

Objective:To investigate the sleep and stress state of support personnel during deep saturation diving training so as to provide reference for psychological support for such personnel on diving mission.Methods:The Pittsburgh sleep quality index (PSQI) and Stanford acute stress response questionnaire (SASRQ) were used to evaluate 61 sailors from a warship in their annual task of supporting deep saturation diving training.Results:The total score of PSQI was 12.82±3.55, with 57 people higher than 7 points, accounting for 93.44%. There were significant differences in PSQI scores among different age groups, and that of the group aged 20-29 was the highest ( F=3.573, P=0.035). The scores of daytime functional and PSQI of support personnel at different posts were significantly different, and the scores in the posts directly supporting divers are significantly lower than those in the other two kinds of posts ( F=4.945, P=0.010; F=3.806, P=0.029). The average stress level of the crew was 36.87±14.84, among them, 5 sailors were under severe stress, and 16 sailors had more than 3 positive items. Among all the investigated crew members, there was a positive correlation between the stress test score and sleep quality except for the item of "using sleeping aids" . Conclusion:Attention should be paid to the psychological state of support personnel during the whole process of saturation deep diving in order to keep the training safe and smooth.

Objective:To evaluate the rationality of diving procedures and medical support through monitoring the stress, nutrition, and sleep quality of divers.Methods:The vital signs of divers were recorded by the monitor designed for high pressure condition. The bubble escape during decompression was evaluated by Doppler bubble monitor. The stress levels of divers were evaluated by the Stanford acute stress reaction questionnaire (SASRQ), and the sleep qualities of divers were evaluated by Pittsburgh sleep quality index (PSQI). The post-diving effects were evaluated by the tests of blood routine and blood biochemistry, and MRI examination of large joints (bilateral shoulders, hips, and knees).Results:The vital signs of the four divers were stable throughout the training, and there was no significant difference in the mean values of vital signs in each stage ( P>0.05). During the decompression, all Doppler bubble monitoring results were below level 2. The total scores of SASRQ before and after diving were both lower than 57 points, indicating a moderate and low stress level; the stress levels of divers decreased slightly after surfacing, but the differences were not statistically significant ( t=1.464, P=0.239). Before and after diving, the divers’ sleep quality was good, but it decreased after surfacing, and the differences were statistically significant ( t=-4.899, P=0.016). The results of blood routine test, biochemical test, and MRI of bilateral shoulders and hips of the four divers after diving were normal; the results of knee MRI showed that only one diver had a small amount of joint effusion. Conclusion:The physical and mental health of the divers in this training maintained good, indicating the procedures of and the medical support for the diving were safe and effective.

Objective:To investigate the sleep and stress state of support personnel during deep saturation diving training so as to provide reference for psychological support for such personnel on diving mission.Methods:The Pittsburgh sleep quality index (PSQI) and Stanford acute stress response questionnaire (SASRQ) were used to evaluate 61 sailors from a warship in their annual task of supporting deep saturation diving training.Results:The total score of PSQI was 12.82±3.55, with 57 people higher than 7 points, accounting for 93.44%. There were significant differences in PSQI scores among different age groups, and that of the group aged 20-29 was the highest ( F=3.573, P=0.035). The scores of daytime functional and PSQI of support personnel at different posts were significantly different, and the scores in the posts directly supporting divers are significantly lower than those in the other two kinds of posts ( F=4.945, P=0.010; F=3.806, P=0.029). The average stress level of the crew was 36.87±14.84, among them, 5 sailors were under severe stress, and 16 sailors had more than 3 positive items. Among all the investigated crew members, there was a positive correlation between the stress test score and sleep quality except for the item of "using sleeping aids" . Conclusion:Attention should be paid to the psychological state of support personnel during the whole process of saturation deep diving in order to keep the training safe and smooth.

Objective To explore the anti-infection mechanism of carboxyamidotriazole (CAI) through studying the effects of CAI on the proliferation, apoptosis and degranulation of RBL-2H3 mass cells.Methods Compound 48/80 (C48/80) was used to induce the model of activation and degranulation in RBL-2H3 cells.The morphological change of cell degranulation was observed by neutral red staining.The release levels of histamine and β-hexosaminidase were measured by ELISA method and chromogenic assay, respectively.The cell activity was determined by CCK-8 method.And cell apoptosis was detected by Hoechst 33342 fluorescent staining.Results Compared with the control group, 10, 20, 40 μmol/L CAI inhibited C48/80-induced degranulation of RBL-2H3 cells in different degrees.CAI (20, 40 μmol/L) reduced the histamine release (P<0.01), and CAI (40 μmol/L) decreased the β-hexosaminidase release (P<0.01).In addition, the viability and apoptosis of RBL-2H3 cells were not affected at the concentrations of CAI used.Conclusions CAI can effectively inhibit the activation and degranulation of RBL-2H3 mast cells, and this effect is not through cytotoxicity.The anti-infection effect of CAI may partially due to the down-regulation of mast cell activity.

Objective To study the clinical significance of EGFR mutation in patients with advanced non -small cell lung cancer combined with malignant pleural effusion,and to provide reliable theoretical basis for clinical treatment .Methods 3 0 patients of advanced non -small -cell lung cancer complicated with malignant pleural effusion in Zhoushan island area were selected.DNA was extracted in the pleural effusion and EGFR 19,21 two loci of gene mutation was detected by sequencing PCR.EGFR and clinical characteristics of the patients (gender,age,smoking history,disease types of cases and in the level of CEA level)was compared.Results Among the 30 cases,4 cases of gene mutation,1 case of male patient,3 cases of female patients,4 cases of adenocarcinoma,4 cases of non smokers, 2 cases of EGFR19 deletion,2 cases of EGFR21 mutation.Among them,3 patients were treated by biological target therapy,the survival time was more than 1 year,and there were no obvious adverse reactions,and the effective rate was 75.00%.Conclusion The gene mutations of EGFR were detected in the patients with advanced non -small cell lung cancer combined with malignant pleural effusion,and the mutation rate 13.30%,which was high in female,non smoker and adenocarcinoma,and it could be used to treat the tumor.