Objective:To investigate the effect of nuclear factor-erythroid 2-related factor 2 (Nrf2) gene on the proliferation and apoptosis of colorectal adenocarcinoma cells in vitro, and the role of Nrf2 gene in regulation of epithelial-mesenchymal transition (EMT) pathway.Methods:Three Nrf2 small interfering RNA (siRNA) sequences were designed and synthesized, namely siRNA-223, siRNA-538 and siRNA-756, and the unrelated sequences were designed and synthesized. The plasmids carrying various siRNA sequences of Nrf2 were constructed, and the plasmids carrying siRNA sequences and the plasmids carrying unrelated sequences were transfected into human colorectal adenocarcinoma Caco-2 cells, namely interference group and empty vector group, respectively. Additionally, Caco-2 cells without any treatment were used as the control group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting (WB) methods were used to detect the relative expression of Nrf2 gene in transcription and translation levels in each group of cells, in order to verify the interference effect of Nrf2; the siRNA with the best interference effect was selected for subsequent experiments. CCK-8 method was used to detect the proliferation ability of each group of cells (expressed as absorbance value); RT-qPCR was used to detect the relative expression of EMT pathway-related factors [vimentin (Vim), N-cadherin (N-cad) and E-cadherin (E-cad)] in transcription level in each group of cells; WB method was used to detect the expression of pro-apoptotic protein Bax in each group of cells.Results:The results of RT-qPCR and WB methods showed that compared with the control group and the empty group, the relative expression of Nrf2 gene in transcription and translation levels in Caco-2 cells of the siRNA-756 interference group were the lowest, and the differences were statistically significant (all P < 0.05). The CCK-8 results showed that the absorbance values of Caco-2 cells in the control group, empty group and siRNA-756 interference group after 48 hours of culture were (100±5)%, (94±4)% and (82±5)%, respectively; compared with the control group and the empty group, the siRNA-756 interference group had lower absorbance value, and the differences were statistically significant (all P < 0.05). The results of RT-qPCR method showed that the relative expression of Vim and N-cad in transcription level in the siRNA-756 interference group were higher than those in the control group and the empty vector group, and the differences were statistically significant (all P < 0.05); the relative expression of E-cad in transcription level was lower than those in the control group and the empty vector group, and the differences were statistically significant (both P < 0.05). The results of WB method showed that the relative expression of Bax protein in the siRNA-756 interference group was higher than that in the control group, and the difference was statistically significant ( P < 0.05). Conclusions:Interference with Nrf2 expression in vitro can weaken the proliferation and anti-apoptotic abilities of human colorectal adenocarcinoma Caco-2 cells. The mechanism may be that Nrf2 regulates the expression of Vim, N-cad and E-Cad in the EMT pathway to enhance the EMT ability of tumor cells.

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Tumor Microenvironment/genetics*

Objective:To investigate the clinicopathological characteristics of early-onset colorectal cancer.Methods:The retrospective and descriptive study was conducted. The clincopatholo-gical data of 59 206 patients with colorectal cancer in the Surveillance, Epidemiology, and End Results Program of the United States of America From January 1,2010 to December 31,2019 were collected. There were 33 213 males, 25 993 males, aged (50±7)years. Observation indicators: (1) demographic and oncological characteristics of colorectal cancer patients; (2) comparison of clinico-pathological characteristics between early-onset and late-onset colorectal cancer. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison among groups was conducted using the Kruskal-Wallis H test. Count data were described as absolute numbers, and comparison among groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the non-parameter H test. Patients with early-onset colorectal cancer were segmented by age, and missing data for categorical variables is set as unknown. Results:(1) Demographic and oncological characteristics of colorectal cancer patients. Of 59 206 patients, there were 23 104 cases with early-onset colorectal cancer and 36 102 cases with late-onset colorectal cancer, and cases aged 13-29 years, cases aged 30-34 years, cases aged 35-39 years, cases aged 40-44 years, cases aged 45-49 years, cases aged 55-59 years were 1 041, 1 740, 3 288, 6 050, 10 985, 15 303,20 799, respectively. (2) Comparison of clinicopathological charac-teristics between early-onset and late-onset colorectal cancer. ① There were significant differences in gender, tumor location, degree of tumor differentiation, tumor histological type, tumor TNM staging, tumor T staging, tumor N staging, tumor M staging, preoperative carcinoembryonic antigen (CEA), perineural invasion, cancer nodule, tumor diameter between patients with early-onset and late-onset colorectal cancer ( P<0.01). Results of further analysis showed that cases with tumor located in ileocecal region, ascending colon, colon liver region, transverse colon were 2 329, 2 139, 579, 1 303 in the 6 350 patients with early-onset right colon cancer. The above indicators were 4 563, 3 945, 902, 1 951 in the 11 361 patients with late-onset right colon cancer. There was a significant difference in the above indicators between the two groups of patients ( χ2=114.27, P<0.01). Cases with tumor located in splenic region of the colon, descending colon, sigmoid colon, rectum sigmoid junction were 553, 1 354, 6 404, 2 431 in the 10 742 patients with early-onset left colon cancer. The above indicators were 865, 1 798, 9 668, 3 610 in the 15 941 patients with late-onset left colon cancer. There was a significant difference in the above indicators between the two groups of patients ( χ2=35.60, P<0.01). ②Of 23 104 patients with early-onset colorectal cancer, cases aged 13-29 years, cases aged 30-34 years, cases aged 35-39 years, cases aged 40-44 years, cases aged 45-49 years were 1 041, 1 740, 3 288, 6 050, 10 985, respectively. There were significant differences in gender, degree of tumor differentiation, tumor histological type, tumor TNM staging, tumor T staging, tumor N staging, pre-operative CEA, perineural invasion, cancer nodule, tumor diameter among patients of different age groups ( P<0.01). Results of further analysis showed that cases with tumor located in ileocecal region, ascending colon, colon liver region, and transverse colon were 91, 117, 45, 69 in the 6 350 early-onset right colorectal cancer patients aged 13-29 years. The above indicators were 165, 136, 47, 115, 304, 313, 93,201, 614, 535, 151, 330, 1 155, 1 038, 243, 588 in early-onset right colorectal cancer patients aged 30-34, 35-39, 40-44, 45-49 years, respectively. There was a significant difference in the above indicators among the five groups of patients ( H=36.63, P<0.01). Cases with tumor located in splenic region of the colon, descending colon, sigmoid colon, rectum sigmoid junction were 32, 83, 260, 95 in the 10 742 early-onset left colorectal cancer patients aged 13-29 years. The above indica-tors were 53, 112, 452, 171, 95, 230, 867, 342, 149, 337, 1 702, 665, 224, 592, 3 123, 1 158 in the 10 742 early-onset left colorectal cancer patients aged 30-34, 35-39, 40-44, 45-49 years, respectively. There was a significant difference in the above indicators among the five groups of patients ( H=47.84, P<0.01). Conclusions:Compared with late-onset colorectal cancer, early-onset colorectal cancer are more likely to occur in the left colon and rectum, with poorly differentiated and undifferentiated tumors, histological type of mucinous adenocarcinoma, TNM staging of stage Ⅲ and Ⅳ, higher proportion of nerve infiltration and cancer nodules, and larger tumor diameter. There are significant differences in clinicopathological characteristics of tumors among patients with early-onset colorectal cancer of different age groups.

Objective:To observe the effect of intravenous anesthesia with target-controlled infusion (TCI) of remifentanil combined with propofol on hemodynamics in middle-aged and elderly patients with intracranial aneurysm clipping. Methods:Totally 40 cases of middle-aged and elderly patients undergoing intracranial aneurysm clipping were divided into combined anesthesia group and propofol group according to the random number table. The combined anesthesia group was treated with remifentanil combined with propofol target intravenous anesthesia, and propofol group was treated with propofol intravenous hypotension. The changes of mean arterial pressure(MAP),heart rate(HR),cardiac output(CO) and heart index(CI) before the induction of anesthesia (T1), tracheal intubation (T2), before aneurysm clipping(T3), after aneurysm clipping(T4) and extubation (T5) were observed. The anesthesia maintenance time, extubation time, postoperative wake-up time and adverse reactions were compared. Results:There were no significant differences in MAP and HR between the groups(P > 0.05), the levels of MAP,HR,CO and CI at T2,T3and T4were significantly lower than those at T1,and CO and CI were significantly lower in combined group than those in propofol group(P < 0.05). Conclusion:TCI remifentanil combined with propofol can maintain hemodynamic stability, shorten extubation time and wake-up time, and reduce the incidence of adverse reactions in the patients with intracranial aneurysm clipping.

This paper expounded the problems and dilemma existing in the ethical practice education of ima-ging medical students, which was the separation between professional education and ethical education, and the sep-aration between medical ethics and medical education, and formed "two layers of skin". This paper analyzed the reason was that the education department and education manager neglected management;the quality of teachers was not high and the ability was weak;students had no enthusiasm and interest in ethical education and lack of medical ethics practice education platform. This paper put forward the strategy of integration of professional and ethical edu-cation, the objective of integration, integration content and the six paths and methods of integration. Namely: the scientific design and organization implementation of education manager;improving teachers' quality ability;paying attention to teachers ' words and deeds to influence students; reforming traditional teaching mode and innovating teaching methods;constructing ethical clinical practice education platform using medical imaging, and constructing education platform of consultation and case discussion.

Objective To investigate the gamma (γ) passing rates for volumetric-modulated arc therapy (VMAT) dosimetric verification with different techniques.Methods A total of 12 VMAT plans for the treatment of different anatomical sites in cancer patients were chosen.The Octavius 4D system was used to measure the dose distributions in two different settings:the gantry was rotating (three-dimensional (3D) and 2D γ-analysis) and the gantry was fixed at 0°(2D γ-analysis).The γ passing rates were analyzed with 3%/3 mm and 2%/2 mm criteria, using the paired t test or Wilcoxon signed-rank test.The 2D γ passing rates for different irradiation methods were calculated.Results For the 3D and 2D dose distributions obtained at a rotating gantry angle as well as the 2D dose distribution obtained at zero gantry angle, the average γ passing rates were 96.03%, 96.98%, and 98.90% for 3%/3 mm (P=0.227, P=0.000, P=0.003);82.08%, 84.04%, and 90.90% for 2%/2 mm (P=0.379, P=0.000, P=0.000).For the 2D dose distributions obtained with different irradiation methods, the average γ passing rate was 98.99% for 3%/3 mm and 93.68% for 2%/2 mm.Conclusions The VMAT dosimetric verification based on a 3D volumetric dosimeter at a rotating gantry position can be clinically useful for delivery quality assurance (QA), and can achieve the most reliable dose calculation for VMAT, which has more referential values.

Objective To investigate the feasibility of detector array in Monaco modeling for MLC parameters adjustment.Methods One parameter was fixed, and then the other parameter was changed.The γ pass rates of the test beams, namely 3ABUT, 7SegA, and FOUR L, were assessed to determine the values of leaf transmission and leaf offset.A total of 12 tumor cases from different anatomical sites were randomly selected.Two-dimensional dose verification (rack angle zero) of Step& Shot and dMLC plans as well as three-dimensional dose validation of VMAT plan were performed using Octavius 4D system.The γ pass rates were analyzed at a standard of 3%/3 mm.Meanwhile, the point dose verification for these three plans was analyzed to obtain the dose deviations.Results The values of leaf transmission and leaf offset were 0.0105 and-0.08 mm, respectively.The average γ pass rates (%) of Step& Shot, dMLC, and VMAT plans were 88.59±2.94, 87.81±3.28, and 87.45±2.24 before adjustment and 98.45±1.23, 98.9±1.01, and 96.03±1.66 after adjustment.In addition, the average dose deviations (%) according to the point dose verification were 0.85±0.75, 0.95±0.39, and 0.98±0.40 before adjustment and 0.97±0.57, 1.08±0.76, and 0.86±0.45 after adjustment.Conclusions Octavius detector 729 ionization chamber array is a feasible and reliable device in Monaco modeling for MLC parameters adjustment.

OBJECTIVETo study the cell morphology change in dormancy and proliferation stage of colorectal cancer stem cells in order to provide reference to the treatment of colorectal cancer.

METHODSThe subpopulation of EpCAM(high)/CD44(+)/CD133(+) was isolated from fresh colorectal cancer tissues. These cells were tested by xenograft assay in NOD/SCID nude mice. Colorectal cancer stem cells underwent three-dimensional culture, and the growth curve of stem cells was drawn by WST-1. The expression of P27 and Ki-67 was examined by flow cytometry to understand the phase of dormancy and proliferation of colorectal cancer stem cells. Then the morphological differences of colorectal cancer stem cells between dormant and proliferation stages were recognized by immunofluorescence staining of actin.

RESULTSThe percentage of EpCAM(high)/CD44(+)/CD133(+) was 1.6%, and the subpopulation was confirmed to be colorectal cancer stem cells by means of the experiment of tumorigenicity in vivo. The growth curve of colorectal cancer stem cells was "S" type. Colorectal cancer stem cells grew slowly in the first three days. The expression of P27 was gradually up-regulated, and the level of Ki-67 was very low. These cells remained quiescence, which was the so-called dormancy. The expression of Ki-67 of colorectal cancer stem cells was at high level since the fourth day, and the P27 level was very low. According to the growth curve, this period belonged to the proliferative stage of colorectal cancer stem cells. On immunofluorescence staining, colorectal cancer stem cells with high level of P27 were round, large, and few pseudopodium, but no obvious death was found. These cells showed characteristics of dormancy. In contrast, the stem cells with high level of Ki-67 had much pseudopodium, showing proliferation and invasion.

CONCLUSIONSCancer recurrence and metastasis may be associated with the change of growth state of cancer stem cells. Colorectal cancer stem cells in the proliferation stage show greater proliferative and invasive ability as compared to the dormancy stage, which provides a new perspective for the treatment of colorectal cancer, and recurrence and metastasis of other tumors.

Animals ; Antigens, CD ; Antigens, Neoplasm ; Cell Adhesion Molecules ; Cell Cycle Checkpoints ; Cell Proliferation ; Cell Shape ; Colorectal Neoplasms ; Epithelial Cell Adhesion Molecule ; Glycoproteins ; Mice ; Mice, Inbred NOD ; Mice, Nude ; Mice, SCID ; Neoplasm Recurrence, Local ; Neoplastic Stem Cells ; cytology

Objective To investigate the association of nitrotyrosine with coronary heart disease (CHD) in type 2 diabetes mellitus.Methods The nitrotyrosine levels were determined in 109 patients of type 2 diabetes mellitus without CHD (T2DM).One hundred and fifty-two patients of type 2 diabetes mellitus with CHD (T2DM-CHD) and 103 healthy control subjects by ELISA.Results T2DM-CHD patients had significantly increased nitrotyrosine compared with T2DM group and the control group [ ( 78.17±10.68 )nmol/L,(70.50 ± 9.13) nmol/L vs ( 63.23 ± 11.55 ) nmol/L,Ps ＜ 0.01 ].Nitrotyrosine was correlated with total cholesterol,triglyceride,fasting glucose and Gensini Score (r=0.361,P=0.009;r =0.206,P=0.001 ;r=0.347,P=0.026; r=0.466,P ＜ 0.001 ).Multivariable logistic regression showed nitrotyrosine was independently associated with CHD combined with type 2 diabetes mellitus ( OR=1.094,95％ CI:1.053-1.137 ; P ＜ 0.01 ).Conclusion Nitrotyrosine plays an important role in the formation and development of cardiovascular disease in tvoe 2 diabetes.

Objective To evaluate the effects of respiratory on dose distributions in threedimensional conformal radiotherapy (3 DCRT) and intensity-modulated radiotherapy (IMRT).Methods The dose distributions were measured with a PTW 2D-ARRAY seven29 placed on a home-made moving platform to simulate the respirator.Dosimetric comparisions for 3DCRT and IMRT plans were performed by means of Gamma analysis with 3％ and 3 mm,respectively.Dose distribution measured for static treatment plans.Results The respiratory could reduce the target does and conformal index.The r pass rate (3％3 mm in 3 DCRT was greater than it in IMRT ((53.58 ± 0.74) ％,(30.71 ± 1.00) ％,t =57.91,P ＜ 0.01).The failed points were mainly near the field edge,but located in the whole target volumes for IMRT plans.Conclusions It is undesirable to use IMRT techniques for tumors with large motion amplitude.3DCRT can give a reliable dose distribution by reasonably selecting the PTV margin.