Objective To investigate the protective effect of PF-562271,a FAK inhibitor,against aging platelet-induced injury in human umbilical vein endothelial cells(HUVECs).Methods Cultured HUVECs were treated with vehicle,lipopolysaccharide(LPS),LPS+aging platelets,or LPS+aging platelets+PF-562271.The changes in protein expressions of FAK,pFAK and PECAM-1 in the treated cells were detected using Western blotting and immunofluorescence assay,and the level of reactive oxygen species(ROS)was detected with flow cytometry.The changes of barrier function of the cells were assessed with cell permeability test and transendothelial cell resistance test.RT-qPCR was used to analyze mRNA expressions of inflammatory factors,and pro-inflammatory cytokine levels in the culture supernatants was determined with enzyme-linked immunosorbent assay.Immunofluorescence assay was used to examine the effect of the ROS inhibitor vitamin C on PECAM-1 expression in the cells with different treatments.Results Treatment of HUVECs with LPS and aging platelets significantly increased cellular protein expressions of FAK,pFAK and PECAM-1,which were effectively lowered by addition of PF-562271(P<0.05).LPS and aged platelets obviously enhanced ROS production in the cells,which was inhibited by the addition of PF-562271(P<0.001).PF-562271 significantly alleviated the damage of endothelial cell barrier function of the cells caused by LPS and aging platelets(P<0.01).The expressions of TNF-α,IL-6 and IL-8 in HUVECs increased significantly after exposure to LPS and aging platelets,and were obviously lowered after treatment with PF-562271(P<0.05).Treatment with vitamin C significantly decreased the expression of PECAM-1 protein in the cells(P<0.01).Conclusion The FAK inhibitor PF-562271 alleviates endothelial cell damage induced by LPS and aging platelets by lowering cellular oxidative stress levels and reducing inflammatory responses.

Objective To investigate the protective effect of PF-562271,a FAK inhibitor,against aging platelet-induced injury in human umbilical vein endothelial cells(HUVECs).Methods Cultured HUVECs were treated with vehicle,lipopolysaccharide(LPS),LPS+aging platelets,or LPS+aging platelets+PF-562271.The changes in protein expressions of FAK,pFAK and PECAM-1 in the treated cells were detected using Western blotting and immunofluorescence assay,and the level of reactive oxygen species(ROS)was detected with flow cytometry.The changes of barrier function of the cells were assessed with cell permeability test and transendothelial cell resistance test.RT-qPCR was used to analyze mRNA expressions of inflammatory factors,and pro-inflammatory cytokine levels in the culture supernatants was determined with enzyme-linked immunosorbent assay.Immunofluorescence assay was used to examine the effect of the ROS inhibitor vitamin C on PECAM-1 expression in the cells with different treatments.Results Treatment of HUVECs with LPS and aging platelets significantly increased cellular protein expressions of FAK,pFAK and PECAM-1,which were effectively lowered by addition of PF-562271(P<0.05).LPS and aged platelets obviously enhanced ROS production in the cells,which was inhibited by the addition of PF-562271(P<0.001).PF-562271 significantly alleviated the damage of endothelial cell barrier function of the cells caused by LPS and aging platelets(P<0.01).The expressions of TNF-α,IL-6 and IL-8 in HUVECs increased significantly after exposure to LPS and aging platelets,and were obviously lowered after treatment with PF-562271(P<0.05).Treatment with vitamin C significantly decreased the expression of PECAM-1 protein in the cells(P<0.01).Conclusion The FAK inhibitor PF-562271 alleviates endothelial cell damage induced by LPS and aging platelets by lowering cellular oxidative stress levels and reducing inflammatory responses.

Objective    To analyze the clinical efficacy of right minithoracotomy approach in the treatment of patients with regurgitation after left-sided valve surgery (LSVS). Methods    The clinical data of 77 patients who suffered tricuspid regurgitation (TR) after LSVS and received surgical treatment in the Heart Center of Henan Provincial People's Hospital from 2012 to 2019 were selected. According to the operation method, the patients were divided into a right minithoracotomy group (n=32), including 13 (40.6%) males, aged 57.3±5.3 years and a median sternotomy group (n=45), including 17 (37.8%) males, aged 55.7±6.6 years. Preoperative and postoperative clinical data of the two groups were compared and analyzed. Results    There was no significant difference in preoperative data between the two groups. There were 24 patients of tricuspid valvuloplasty (TVP) and 8 patients of tricuspid valve replacement (TVR) in the right minithoracotomy group. There were 29 patients of TVP and 16 patients of TVR in the median sternotomy group. The operation time, postoperative hospitalization time, intubation time and ICU stay time of the right minithoracotomy group were shorter than those of the median sternotomy group (P<0.001). The operative bleeding, postoperative drainage in 24 hours, postoperative blood transfusion rate and incision poor healing of the right minithoracotomy group were significantly decreased compared with those of the median sternotomy group (P<0.05). The extracorporeal circulation time between the two groups was not significantly different (P=0.382). The postoperative complications and mortality of the righ minithoracotomy group were significantly lower than those of the median sternotomy group (P<0.05). Conclusion    The procedure of right minithoracotomy access can reduce perioperative morbidity and mortality compared with the median sternotomy, and results in satisfied clinical efficacy.

Exoelectrogenic microorganisms are the research basis of microbial electrochemical technologies such as microbial fuel cells, electrolytic cells and electrosynthesis. However, their applications are restricted in organic degradation, power generation, seawater desalination, bioremediation, and biosensors due to the weak ability of biofilm formation and the low extracellular electron transfer (EET) efficiency between exoelectrogenic microorganisms and electrode. Therefore, engineering optimization of interaction between exoelectrogenic microorganisms and electrode interface recently has been the research focus. In this article, we review the updated progress in strategies for enhancing microbe-electrode interactions based on microbial engineering modifications, with a focus on the applicability and limitations of these strategies. In addition, we also address research prospects of enhancing the interaction between electroactive cells and electrodes.
Bioelectric Energy Sources ; Biofilms ; Electrodes ; Electron Transport ; Electrons

Objective To study the impact of RAS status on prognosis of patients after liver resection for colorectal cancer liver metastases (CRLM).Methods The data of 545 consecutive CRLM patients who underwent liver resection at the Hepatopancreatobiliary Surgery Department I,Peking University Cancer Hospital between January 1st,2008 and December 31st,2016,were retrospectively reviewed.According to the inclusion and exclusion criteria,356 patients were eventually included into this study.There were 232 males and 124 females,with ages ranging from 21 to 83 years.The clinical and follow-up data of patients with wild-type and mutant RAS were compared.Survival was estimated by the Kaplan-Meier method,and the difference was compared by the log-rank test.Factors influencing survival of these patients were assessed by univariate and multivariate Cox regression analyses.Results There were 247 patients with wild-type RAS and 109 patients with mutant RAS,respectively.The median overall survival of patients with wild-type and mutant RAS were 74 and 30 months respectively.Compared with mutant RAS patients,wild-type RAS patients had significantly better cumulative survival and disease free survival rates (both P ＜ 0.05).Multivariate Cox regression analyses revealed disease free interval from primary to metastases ≤ 12 months (HR =1.673,95％ CI:1.016-2.637),largest hepatic tumor diameter ＞ 5 cm (HR =1.717,95 ％ CI:1.102-2.637),and mutant RAS (HR =1.836,95％ CI:1.322-2.550) were independent risk factors for patients with colorectal cancer liver metastases after hepatic resection.Conclusion Mutant RAS was a poor prognostic factor of survival after liver resection in CRLM patients

Objective:To compare the prognosis of patients with a single compared to multiple colorectal cancer liver metastases (CRLM) after hepatectomy.Methods:The clinical data of 490 patients with colorectal cancer liver metastases who underwent hepatectomy at Department of Hepatopancreatobiliary Surgery Ⅰ, Peking University Cancer Hospital & Institute from January 2006 to December 2016 were retrospectively studied. There were 314 males and 176 females. The median age was 58 years (range 21 to 83 years). There were 200 patients in the single liver metastasis group and 290 patients in the multiple liver metastases group. The tumor recurrence and survival outcomes on follow-up were analyzed. Survival curves were plotted using the Kaplan-Meier method. Both overall survival and disease-free survival between two groups were compared by the log-rank test. Univariate and multivariate Cox regression analyses were used to analyze independent risk factors of overall survival.Results:The 1-, 3-, 5-, 10-year overall survival rates for the single versus the multiple liver metastases groups were 92.5%, 58.6%, 51.0%, 38.8% versus 90.7%, 53.2%, 41.1%, 29.9%. The differences were significant ( P<0.05). The disease-free survival was also significantly better in the single than the multiple groups ( P<0.05). Cox multivariate analysis showed that right-sided primary colonic tumor, preoperative carbohydrate antigen 19-9 level ≥50 U/ml, and RAS mutant were independent factors influencing survival in patients with single liver metastasis; while primary colonic tumor N 1-2, liver metastases diameter ≥5 cm, and RAS mutant were independent factors influencing survival in patients with multiple tumors. If the three independent factors affecting overall survival of patients with multiple liver metastases were assigned 1 point for each factor, the number of patients with scores of 0, 1, 2, and 3 were 50, 145, 84, and 11, respectively. The long-term survival of patients with a low score (0, 1) was similar to those with a single liver metastasis (both P>0.05). However, patients with a high score (2, 3) showed significantly worse long-term survival when compared with patients with a single liver metastasis (both P<0.05). Conclusions:The prognosis of patients with single colorectal liver metastasis was better than those with multiple liver metastases after hepatectomy. For patients with multiple liver metastases with fewer associated risk factors, surgical resection could still result in long-term survival outcomes which were comparable to those patients with a single liver metastasis.

Objective To observe the effect of hypoxia on the expression of epithelial growth factor receptor (EGFR) and cell apoptosis of breast and cervical cancer xenografts in nude mouse models.Methods The nude mouse models with MCF-7 and HeLa xenografts were established.The degree of hypoxia and EGFR expression were observed by confocal microscopy.The influence of EGFR expression on cell apoptosis under hypoxia was observed by TUNEL assay.Results EGFR expression was either up-regulated or down-regulated in the MCF-7 and HeLa cells with high degree of hypoxia.Furthermore,the degree of apoptosis was reduced in tumor tissues with high EGFR expression compared with that in those with low expression of EGFR.Conclusion The hypoxia in MCF-7 and HeLa cells exerts heterogeneous effect on EGFR expression.Under hypoxic conditions,EGFR exoression is negatively correlated with cell apoptosis.

Uncovering the functionally essential variations related to tumorigenesis and tumor pro-gression from cancer genomics data is still challenging due to the genetic diversity among patients, and extensive inter-and intra-tumoral heterogeneity at different levels of gene expression regulation, including but not limited to the genomic, epigenomic, and transcriptional levels. To minimize the impact of germline genetic heterogeneities, in this study, we establish multiple primary cultures from the primary and recurrent tumors of a single patient with hepatocellular carcinoma (HCC). Multi-omics sequencing was performed for these cultures that encompass the diversity of tumor cells from the same patient. Variations in the genome sequence, epigenetic modification, and gene expression are used to infer the phylogenetic relationships of these cell cultures. We find the discrepancy among the relationships revealed by single nucleotide variations (SNVs) and transcriptional/epigenomic pro-files from the cell cultures. We fail to find overlap between sample-specific mutated genes and differ-entially expressed genes (DEGs), suggesting that most of the heterogeneous SNVs among tumor stages or lineages of the patient are functionally insignificant. Moreover, copy number alterations (CNAs) and DNA methylation variation within gene bodies, rather than promoters, are significantly correlated with gene expression variability among these cell cultures. Pathway analysis of CNA/DNA methylation-related genes indicates that a single cell clone from the recurrent tumor exhibits distinct cellular characteristics and tumorigenicity, and such an observation is further confirmed by cellular experiments both in vitro and in vivo. Our systematic analysis reveals that CNAs and epigenomic changes, rather than SNVs, are more likely to contribute to the phenotypic diversity among subpop-ulations in the tumor. These findings suggest that new therapeutic strategies targeting gene dosage and epigenetic modification should be considered in personalized cancer medicine. This culture model may be applied to the further identification of plausible determinants of cancer metastasis and relapse.

Nuclear epithelial growth factor receptor (EGFR) plays an important role in the development, metastasis, treatment, and prognosis of cancer. Radiotherapy, one of the main therapies for malignant tumor, causes EGFR transfer into the nucleus along with tumor therapy, thereby reducing radiosensitivity. Insight into the biological characteristics and functions of nuclear EGFR has an important reference value for improving radiosensitivity. Therefore, this article elaborates on EGFR transport into the nucleus,the features of nuclear EGFR,and its relationship with radiosensitivity and clinical targeted therapy.

Objective To analyze the effect of tumor number on the survival of patients with colorectal liver metastases (CRLM) undergoing hepatic resection and the definition of oligometastases.Methods Clinicopathological data of patients with colorectal liver-only metastases undergoing liver resection from our database were retrospectively analyzed.Results Of all 377 patients,the median number of hepatic tumor was 2.The 5-year disease free survival rate was 24.1％.The 5-year overall survival rate was 39.8％.Survival of oligometastatic patients was not significantly different from non-oligometastatic patients (x2 =3.037,P =0.081).Survival of patients with 6-10 hepatic tumors was similar to patients with 1-5 tumors.However,survival of patients with more than 10 tumors was significantly worse than patients with liver tumor less than 10(x2 =5.386,P =0.020).In multivariate analysis,number of liver tumor,primary node status,largest hepatic tumor and gender are independent predictors of overall survival.Conclusions The number of liver tumor was an independent predictor of overall survival.The cut-off number of oligometastatic disease should be 10.