Clinical significance of expression of tumor immunogenic cell death related molecules / 国际肿瘤学杂志

Tumor immunogenic cell death is a type of regulatory cell death, which is driven by stress including chemotherapy drugs, radiotherapy, oncolytic virus, nano carrier drugs and photodynamic force. It can induce specific immune response to tumor death cell antigen. The further study can provide theoretical basis and new ideas for anti-tumor immunity and clinical immunotherapy of tumor.

The biological clock gene BMAL1 inhibits the proliferation, migration and invasion of radiation-resistant nasopharyngeal carcinoma cell line 5-8FR by regulating PI3K/Akt/MMP-2/9 signaling pathway / 中华放射肿瘤学杂志

Objective:To investigate the effect of BMAL1 gene on the proliferation, migration and invasion ability of radiation-resistant nasopharyngeal carcinoma cell line (5-8FR) and the molecular mechanism. Methods:A multi-target click model was constructed for radiation-resistant nasopharyngeal carcinoma cell line 5-8FR by low-dose fractionated irradiation, and the results of clone formation assay were used to fit the multi-target click model and calculate the sensitization ratio of radiotherapy. The expression levels of PI3K/Akt/MMP-2/9 signaling pathway-related proteins in 5-8FR and control 5-8F cell lines were detected by Western blot. The overexpression and knockdown vectors of BMAL1 gene were constructed and transfected with 5-8F and 5-8F cell lines, respectively. The BMAL1 gene overexpression (pcDNA-BMAL1) and its control (pcDNA) and interference (BMAL1-shRNA) and control (con-shRNA) cell lines were stably transfected with nasopharyngeal carcinoma cell line 5-8F and radiation-resistant cell line 5-8FR, respectively. Western blot was performed to verify the infection efficiency and detect the changes of PI3K/Akt/MMP-2/9 signaling pathway-related proteins after overexpression or interference of BMAL1 gene in both groups of cells. CCK-8 assay, cell scratch test and Transwell chamber test were conducted to investigate the proliferation, migration and invasion capabilities of 5-8FR cell line after overexpression or interference of BMAL1 gene. Results:BMAL1 gene expression was down-regulated, and those of PI3K/Akt pathway proteins and downstream related molecules of MMP-2 and MMP-9 were up-regulated, and TIMP-2 and TIMP-1 expression was down-regulated in nasopharyngeal carcinoma radiation-resistant cell lines. Overexpression of BMAL1 gene inhibited the expression of PI3K/Akt pathway proteins and downstream related molecules of MMP-2 and MMP-9, promoted the expression of TIMP-2 and TIMP-1, and inhibited the proliferation, migration and invasion capabilities of radiation-resistant nasopharyngeal carcinoma cells, while interference with BMAL1 gene yielded the opposite results. Conclusions:BMAL1 gene can reverse the expression of PI3K/Akt/MMP-2/9 signaling pathway-related proteins in radiation-resistant nasopharyngeal carcinoma cell lines and inhibit the proliferation, migration and invasion capabilities of radiation-resistant nasopharyngeal carcinoma cell lines.

IRE1α deficiency impairs autophagy in chondrocytes by upregulating calcium homeostasis endoplasmic reticulum protein / 南方医科大学学报

OBJECTIVE@#To explore the mechanism by which inositol-requiring enzyme-1α (IRE1α) regulates autophagy function of chondrocytes through calcium homeostasis endoplasmic reticulum protein (CHERP).@*METHODS@#Cultured human chondrocytes (C28/I2 cells) were treated with tunicamycin, 4μ8c, rapamycin, or both 4μ8c and rapamycin, and the expressions of endoplasmic reticulum (ER) stress- and autophagy-related proteins were detected with Western blotting. Primary chondrocytes from ERN1 knockout (ERN1 CKO) mice and wild-type mice were examined for ATG5 and ATG7 mRNA expressions, IRE1α and p-IRE1α protein expressions, and intracellular calcium ion content using qPCR, Western blotting and flow cytometry. The effect of bafilomycin A1 treatment on LC3 Ⅱ/LC3 Ⅰ ratio in the isolated chondrocytes was assessed with Western blotting. Changes in autophagic flux of the chondrocytes in response to rapamycin treatment were detected using autophagy dual fluorescent virus. The changes in autophagy level in C28/I2 cells overexpressing CHERP and IRE1α were detected using immunofluorescence assay.@*RESULTS@#Tunicamycin treatment significantly up-regulated ER stress-related proteins and LC3 Ⅱ/LC3 Ⅰ ratio and down-regulated the expression of p62 in C28/I2 cells (P < 0.05). Rapamycin obviously up-regulated LC3 Ⅱ/LC3 Ⅰ ratio (P < 0.001) in C28/I2 cells, but this effect was significantly attenuated by co-treatment with 4μ8c (P < 0.05). Compared with the cells from the wild-type mice, the primary chondrocytes from ERN1 knockout mice showed significantly down-regulated mRNA levels of ERN1 (P < 0.01), ATG5 (P < 0.001) and ATG7 (P < 0.001), lowered or even lost expressions of IRE1α and p-IRE1α proteins (PP < 0.01), and increased expression of CHERP (P < 0.05) and intracellular calcium ion content (P < 0.001). Bafilomycin A1 treatment obviously increased LC3 Ⅱ/ LC3 Ⅰ ratio in the chondrocytes from both wild-type and ERN1 knockout mice (P < 0.01 or 0.05), but the increment was more obvious in the wild-type chondrocytes (P < 0.05). Treatment with autophagy dual-fluorescence virus resulted in a significantly greater fluorescence intensity of LC3-GFP in rapamycin-treated ERN1 CKO chondrocytes than in wild-type chondrocytes (P < 0.05). In C28/I2 cells, overexpression of CHERP obviously decreased the fluorescence intensity of LC3, and overexpression of IRE1α enhanced the fluorescence intensity and partially rescued the fluorescence reduction of LC3 caused by CHERP.@*CONCLUSION@#IRE1α deficiency impairs autophagy in chondrocytes by upregulating CHERP and increasing intracellular calcium ion content.

Effect of Buyang Huanwutang on Keap1/Nrf2/HO-1 Antioxidant Signaling Pathway in Rats with Idiopathic Pulmonary Fibrosis / 中国实验方剂学杂志

ObjectiveTo study the effect of Buyang Huanwutang on Kelch-like Ech-related protein 1 （Keap1）/nuclear factor E2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） antioxidant signaling pathway in rats with idiopathic pulmonary fibrosis （IPF） and explore the mechanism of this prescription in the treatment of IPF. MethodForty SPF-grade male SD rats were assigned into a sham operation group， a model group， a Buyang Huanwutang group， and a nintedanib group according to random number table method， with 10 rats in each group. IPF rat model was established by intratracheal infusion of bleomycin （0.005 g·kg-1） in other groups except the sham operation group. Buyang Huanwutang group was administrated with Buyang Huanwutang (14.84 g·kg-1)，intragastric administration of nitedanib suspension (0.1 g·kg-1)，sham operation group and model group were given equal volume of normal saline， for 28 days. After lung function test， serum and lung tissue samples were collected. Hematoxylin-eosin （HE） staining and Masson trichrome staining were employed to observe the pathological changes of the lung tissue. The content of hydroxyproline （HYP） in lung tissue was detected. The levels of malondialdehyde （MDA） in serum and lung tissue， and the activities of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px） and catalase （CAT） were determined. The mRNA and protein levels of Keap1， Nrf2， and HO-1 was determined by Real-time fluorescent quantitative polymerase chain reaction， immunohistochemical staining， and Western blot. ResultCompared with the sham operation group， the modeling increased the resistance and elasticity and decreased the compliance of respiratory system （P<0.01）， elevated the lung index， pathological score， and HYP content in lung tissue （P<0.01）， and enriched MDA in serum and lung tissue， while it decreased the activities of SOD， GSH-Px， and CAT （P<0.01）. Furthermore， the modeling down-regulated the mRNA and protein levels of Keap1 and up-regulated those of Nrf2 and HO-1 in lung tissue （P<0.01）. Compared with the model group， Buyang Huanwutang decreased the resistance and elasticity and increased the compliance of respiratory system （P<0.01）， lowered the lung index， pathological score， and HYP content in lung tissue （P<0.01）， and reduced MDA in serum and lung tissue， while it increased the activities of SOD， GSH-Px， and CAT （P<0.01）. Additionally， Buyang Huanwutang down-regulated the expression of Keap1 and up-regulated that of Nrf2 and HO-1 in lung tissue （P<0.05， P<0.01）. ConclusionBuyang Huanwutang can activate Keap1/Nrf2/HO-1 signaling pathway to enhance the antioxidant capacity and slow down the pathological process of IPF in rats.

Clinical information and management status of de novo stage IV breast cancer patients: a Chinese multicenter investigation (CSBrS-002) / 中华医学杂志(英文版)

BACKGROUND@#Although de novo stage IV breast cancer is so far incurable, it has entered an era of individualized treatment and chronic disease management. Based on systemic treatment, whether the surgical resection of primary or metastatic foci of de novo stage IV breast cancer can bring survival benefits is currently controversial. We aimed to explore the clinicopathological factors and current status of the management of de novo stage IV breast cancer in China to provide a reference for clinical decisions.@*METHODS@#Based on the assistance of Chinese Society of Breast Surgery, a retrospective study was conducted to analyze the clinical data of patients with de novo stage IV breast cancer in 33 centers from January 2017 to December 2018. The relationship between basic characteristic (age, menstrual status, family history, reproductive history, pathological type, estrogen receptor [ER] status, progesterone receptor [PR] status, human epidermal growth factor receptor 2 [HER2] status, Ki-67 percentage, and molecular subtype), and metastasis sites (lung metastasis, liver metastasis, and bone metastasis) was examined by Pearson Chi-square tests.@*RESULTS@#A total of 468 patients with de novo stage IV breast cancer were enrolled. The median age of the enrolled patients was 51.5 years. The most common pathological type of primary lesion was invasive carcinoma (97.1%). Luminal A, luminal B, HER2 overexpressing, and triple-negative subtypes accounted for 14.3%, 51.8%, 22.1%, and 11.8% of all cases, respectively. Age, PR status, and HER2 status were correlated with lung metastasis (χ2 = 6.576, 4.117, and 8.643 and P = 0.037, 0.043, and 0.003, respectively). Pathological type, ER status, PR status, and molecular subtype were correlated with bone metastasis (χ2 = 5.117, 37.511, 5.224, and 11.603 and P = 0.024, <0.001, 0.022, and 0.009, respectively). Age, PR status, HER2 status, Ki-67 percentage, and molecular subtype were correlated with liver metastasis (χ2 = 11.153, 13.378, 10.692, 21.206, and 17.684 and P = 0.004, <0.001, 0.001, <0.001, and 0.001, respectively). Combined treatment with paclitaxel and anthracycline was the most common first-line chemotherapy regimen for patients with de novo stage IV breast cancer (51.7%). Overall, 91.5% of patients used paclitaxel-containing regimens. Moreover, 59.3% of hormone receptor-positive patients underwent endocrine therapy.@*CONCLUSIONS@#In 2018, 1.07% of patients from all studied centers were diagnosed with de novo stage IV breast cancer. This study indicated that 95.1% of patients received systemic therapy and 54.2% of patients underwent surgical removal of the primary lesion in China.

Effect of Buyang Huanwutang on Protein Expression of MAP-2， NF-M and GAP-43 After Sciatic Nerve Transection Anastomosis in Rats / 中国实验方剂学杂志

Objective:To investigate the effects of Buyang Huanwutang on the expression of microtubule-associated protein-2（MAP-2）， neurofilament-M（NF-M）， and growth associated protein-43（GAP-43）in rat sciatic nerve after sciatic nerve transection and anastomosis. To explore the mechanism of Buyang Huanwutang promoting peripheral nerve regeneration. Method:SD rats were selected as the experimental subjects， and sciatic nerve transection model was selected as the experimental model. They were randomly divided into model group， sham operation group， Buyang Huanwutang group high， medium and low dose （29.6， 14.8， 7.4 g·kg^-1）group， and mecobalamin （0.156 mg·kg^-1）group， the model group and the sham operation group were given distilled water intragastric administration. After successful modeling， each group was treated with relevant drugs for 4 weeks. After 4 weeks， sciatic nerve function index（SFI）， degree of inclined plate test and hematoxylin-eosin（HE）of sciatic nerve in each group were tested. The expression levels of MAP-2， NF-M， and GAP-43 at the sciatic nerve anastomosis site were detected by immunohistochemistry and Western blot. Result:Compared with sham operation group， the expression levels of SFI， inclined plate test， MAP-2， NF-M and GAP-43 in model group were significantly increased （<italic>P</italic><0.01）. Compared with model group， the expression levels of SFI， inclined plate test， MAP-2， NF-M and GAP-43 in Buyang Huanwutang high， medium and low-dose groups were significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:Buyang Huanwutang has a positive effect on nerve regeneration after sciatic nerve transection and anastomosis in rats.

Effect and Mechanism of Shaofu Zhuyutang on Endothelial Injury of Rats with Cold Coagulation and Blood Stasis Syndrome Based on Nrf2/ARE Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effect of Shaofu Zhuyutang on nuclear factor erythroid-2-related factor 2 （Nrf2） /antioxidant response element （ARE） signaling pathway in blood vessels by establishing the model of rats with cold coagulation and blood stasis syndrome， and to explore the protective effect and mechanism of Shaofu Zhuyutang on vascular endothelial injury. Method:The 50 SPF rats were randomly divided into high dose group （4.8 g·kg-1）， middle dose group （2.4 g·kg-1）， low dose group （1.2 g·kg-1）， model group and normal group （ten of each group）. The rat model of cold coagulation and blood stasis syndrome was established by subcutaneous injection of epinephrine hydrochloride combined with ice bath. At the same time of modeling， the drug was administered by gavage. After 28 days of continuous administration， the hemorheology indexes were detected by automatic hemorheology instrument. Levels of nitric oxide （NO）， endothelin （ET）-1， superoxide dismutase （SOD）， glutathione （GSH-Px）， intercellular adhesion molecule-1（ICAM-1）， vascular cell adhesion molecule-1（VCAM-1）， von Willebrand factor （vWF） in serum were determined by ELISA. Hematoxylin and eosin （HE） staining was used to observe the endothelial injury of vascular tissue of thoracic aorta. The protein expression of Nrf2 and HO-1 in vascular tissue of thoracic aorta was detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）was used to observe the expression of Nrf2 and heme oxygenase-1 （HO-1） mRNA in vascular tissue of thoracic aorta. Result:Compared with the blank group， model group rats whole blood viscosity and plasma viscosity were significantly increased （P<0.05，P<0.01）， vWF， ICAM 1， VCAM 1 content increased significantly （P<0.01）， NO， SOD， gsh-px levels decreased significantly （P<0.01）， significantly increased the content of ET-1（P<0.01）， thoracic aorta vascular tissue Nrf2， HO-1 mRNA expression was significantly increased （P<0.01）， Nrf2 protein expression in the cell nucleus increased significantly （P<0.05）， The protein expression level of Nrf2 in cytoplasm was significantly decreased （P<0.05）， while the protein expression level of HO-1 was significantly increased （P<0.01）. Compared with model group， the whole blood viscosity （high and middle cut）， plasma viscosity， were significantly reduced in high and meduim-dose Shaofu Zhuyutang groups（P<0.05，P<0.01）. The levels of vWF， ICAM-1， VCAM-1 and ET-1 in serum were significantly reduced （P<0.05，P<0.01）， NO， SOD and GSH-Px increased significantly （P<0.05，P<0.01）. The pathological changes such as hyperplasia， swelling and shedding of endothelial cells of thoracic aorta， rupture of internal elastic membrane and disorder of smooth muscle arrangement were improved. The expression levels of Nrf2， HO-1 protein and gene were significantly increased in vascular tissue of thoracic aorta （P<0.01）. Conclusion:Shaofu Zhuyutang has a protective effect on vascular endothelial injury in rats with cold coagulation and blood stasis syndrome. The mechanism of action is related to the activation of Nrf2/ARE signaling pathway， which leading to the increased expression of antioxidant enzymes and decreased the expression of adhesion factors.

Clinical Significance of C-X-C Motif Chemokine Receptor 4 and Integrin αvβ6 Expression in Breast Cancer / 한국유방암학회지

Purpose@#C-X-C motif chemokine receptor 4 (CXCR4) and integrin αvβ6 play important roles in the malignant progression of multiple cancers. However, it remains unclear whether the expression of one or both proteins in breast cancer (BC) is of clinical significance. In this study, we investigated the expression of CXCR4 and integrin αvβ6 in BC tissues and their correlation with clinicopathological characteristics, including survival. @*Methods@#CXCR4 and αvβ6 expression in 111 BC tissues was examined by immunocytochemistry. Correlations between the expression of the 2 proteins and patient clinicopathological characteristic were investigated using the Kaplan–Meier method and the Cox proportional hazards model. @*Results@#CXCR4 and αvβ6 were overexpressed in BC tissue compared with normal breast tissue. Overexpression of both molecules was related to lymph node status (p = 0.013 and p = 0.022, respectively). αvβ6 overexpression was also associated with tumor size (p = 0.044). A positive correlation was detected between the expression of CXCR4 and αvβ6 (r = 0.649, p = 0.001), and co-overexpression of both molecules was associated with tumor size (p = 0.018) and lymph node metastasis (p = 0.015). Kaplan–Meier analysis revealed that overexpression of CXCR4, αvβ6, or both molecules was associated with short overall survival (OS; p < 0.001, p < 0.001, and p = 0.009, respectively) and disease-free survival (DFS; p < 0.001, p = 0.005, and p = 0.019, respectively). Multivariate analysis indicated that lymph node metastasis was an independent prognostic factor for unfavorable OS and DFS (p = 0.002 and p = 0.005, respectively), whereas co-overexpression of CXCR4 and αvβ6 was an independent prognostic factor only for OS (p = 0.043). @*Conclusion@#CXCR4 and αvβ6 may play synergistic roles in the progression of BC, and co-targeting of CXCR4 and αvβ6 could be a potential strategy for the prevention and treatment of BC.

Pretention of Defensive Medicine in Rehabilitation for Stroke / 中国康复理论与实践

Objective:To investigate the defensive medicine of physicians in the process of rehabilitation. Methods:Defensive medicine were investigated from the medical records of 220 inpatients included in the clinical pathway of stroke rehabilitation from January, 2016 to January, 2018. Results:There might be some defensive medicine behaviours for diagnosis, treatment, prevention of medical tangle, etc., in stroke rehabilitation. Conclusion:It is needed to reduce defensive medicine in various ways.

Advance in Sexual Dysfunction for Patients with Breast Cancer (review) / 中国康复理论与实践

Breast cancer is one of the most common malignant tumors in women and it has a 5-year survival rate of over 80%. However, sexual dysfunction limits comprehensive rehabilitation. A correct understanding of present situation of sexual dysfunction provides the basis for its evaluation and prediction, which is of great significance to their rehabilitation. This article reported on the current situation, related factors, assessment, and prediction of sexual dysfunction in patients with breast cancer undergoing rehabilitation.

A prospective clinical study with long-term follow-up of the correlation between dynamic contrast-enhanced magnetic resonance parameters and prognosis in patients with locally advanced nasopharyngeal carcinoma / 中华放射医学与防护杂志

Objective:To explore the relationship between semi-quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and long-term prognosis of locally advanced nasopharyngeal carcinoma, and to find prognostic indicators from non-invasive images of locally advanced nasopharyngeal carcinoma.Methods:Data were collected from January 2011 to January 2012 via a prospective clinical trial with locally advanced nasopharyngeal carcinoma. Clinical information was from 71 patients who completed the treatment plan with long-term follow-ups and UICC 2010 stage Ⅲ, Ⅳ A, Ⅳ B. The patients received three cycles of Taxotere-Platinol-Fluorouracil (TPF) regimen chrono-chemotherapy, followed by two cycles of concurrent paclitaxel chemotherapy with intensity-modulated radiotherapy (IMRT). DCE-MRI examination was performed before induction chemotherapy to obtain DCE-MRI related semi-quantitative parameters. Correlation analysis was conducted between DCE-MRI related semi-quantitative parameters and short-term efficacy of nasopharyngeal lesions after concurrent radiotherapy and chemotherapy. Results:Of all 77 patients, 71 completed treatment and were followed up from 9 to 86 months, with a median follow-up of 77 months, with 80.2% and 67.6% in 3- and 5-year OS, 73.2% and 60.5% in 3- and 5-year PFS, respectively. Evaluation of short-term efficacy of nasopharyngeal lesions after concurrent chemoradiotherapy: the difference in tissue arrival time of contrast agent between complete response (CR) group and partial response (PR) group was statistically significant ( t=0.537, P<0.05). Univariate survival analysis found that OS ( χ2=3.982, P<0.05) and PFS ( χ2=4.019, P<0.05) in the group with short contrast arrival time were significantly higher than those in the group with long contrast arrival time. OS ( χ2=7.593, P<0.05) and PFS ( χ2=5.624, P<0.05) of patients aged over 45 years were significantly lower than those aged less than 45 years. Cox multivariate regression model showed that advanced clinical stage (stage Ⅳ A, Ⅳ B) ( P=0.048) and age≥45 years ( P=0.031) were independent prognostic factors of OS in patients with nasopharyngeal carcinoma. Long arrival time of contrast agent ( P=0.018), age≥45 years ( P=0.004), advanced N(2-3) stage ( P=0.032) and enhancement peak<3 000 ( P=0.005) were independent prognostic factors of PFS in patients with nasopharyngeal carcinoma. Conclusions:The arrival time of the contrast agent in DCE-MRI may be a reliable prognostic factor for locally advanced nasopharyngeal carcinoma.

Value of 3D-ASL, MRS and DTI in the diagnosis and treatment of radiation-induced temporal lobe injury of nasopharyngeal carcinoma / 国际肿瘤学杂志

Radiotherapy is the main treatment of nasopharyngeal carcinoma (NPC). With the continuous improvement of radiotherapy technology, the survival time of NPC patients is significantly improved, but the complications after radiotherapy have been paid more and more attention, in which the incidence of radiation-induced temporal lobe injury is higher, which seriously affects the quality of life of patients, and even reduces the survival rate. Therefore, it is particularly important to find a method for the examination of early radiation-induced temporal lobe injury. Three-dimensional arterial spin labeling (3D-ASL) analysis of cerebral blood flow (CBF) changes before and after radiotherapy, magnetic resonance spectroscopy (MRS) analysis to determine the changes of NAA/Cr, Cho/NAA, Cho/Cr ratio in the anterior and posterior temporal lobe before and after radiotherapy, and diffusion tensor imaging (DTI) to determine the changes of temporal lobe average diffusion coefficient (ADC) and anisotropy fraction (FA) before and after radiotherapy can help in the early diagnosis of radiation brain injury, especially through the combined use of the above three tests. It is expected to provide a feasible basis for the early diagnosis of radiation encephalopathy, and early nutritional neurotherapy is of great significance to improve the quality of life and survival rate of patients.

Curcuma wenyujin Y. H. Chen et C. Ling n-Butyl Alcohol Extract Inhibits AGS Cell Helicobacter pylori Promoted Invasiveness by Down-Regulating Caudal Type Homeobox Transcription Factor and Claudin-2 Expression / 中国结合医学杂志

OBJECTIVE@#To investigate the effects and possible mechanisms of action of Curcuma wenyujin Y. H. Chen et C. Ling n-Butyl alcohol extract (CWNAE) on repression of human gastric cancer (GC) AGS cell invasion induced by co-culturing with Helicobacter pylori (HP).@*METHODS@#AGS cells were cultured with HP of positive or negative cytotoxin-associated gene A (CagA) and vacuolating cytotoxin gene A (VacA) expression (CagA+/- or VacA+/-) and divided into 5 group. Group A was cultured without HP as a control, Group B with HP, Group C with HP, Group D with HP and CWNAE, and Group E with HP and CWNAE. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and tumor invasion assays, examinations of morphology and ultramicroscopic structures, quantitative real-time polymerase chain reaction and Western blots were performed to measure the effects and uncover the mechanisms behind these effects of HP and CWNAE on the epithelial-mesenchymal transition (EMT) of AGS cells.@*RESULTS@#The 10% inhibitory concentration of CWNAE against AGS cells after a 48 h incubation was 19.73±1.30 μg/mL. More AGS cells were elongated after co-culturing with HP than after culturing with HP. In tumor invasion assays, HP significantly enhanced the invasiveness of AGS cells compared to the other experimental groups (all P value <0.05), and this effect was inhibited by CWNAE. Treatment with CWNAE normalized tight junctions and reduced the number of pseudopodia of AGS cells co-cultured with HP. HP up-regulated zincfinger ebox binding homeobox 1 (ZEB1) in AGS cells after co-culturing for 24 h. Expression of caudal type homeobox transcription factor (CDX-2) and claudin-2 was significantly increased by HP (P<0.05), but not by HP.@*CONCLUSION@#HP promoted the invasiveness of AGS cells through up-regulation of ZEB1 transcription and claudin-2 and CDX-2 expression. CWNAE inhibited these effects of HP on AGS cells by down-regulating ZEB1 transcription, and CDX-2 and claudin-2 expression.

Analysis of follow-up results of chrono-chemotherapy or conventional chemotherapy combined with intensity modulated radiotherapy in locally advanced nasopharyngeal carcinoma / 中华肿瘤杂志

Objective@#To evaluate the long-term effect and safety of chrono-chemotherapy combined with intensity modulated radiotherapy (IMRT) in locally advanced nasopharyngeal carcinoma (NPC).@*Methods@#160 patients with locally advanced NPC were randomly divided into a chrono group and conventional group according to random number table. In the first stage, all patients underwent two cycles of induced chemotherapy, consisting of docetaxel, cisplatin and 5-Fu every 21 days. Notably, patients received chrono-moduated chemotherapy according to circadian rhythm in the chrono group, and conventional chemotherapy in the conventional group. Then, 21 days after the completion of first stage, three cycles of concurrent cisplatin chemotherapy every 21 days were given to all patients during IMRT. The median follow-up after the completion of radiotherapy was 31 months. Long-term side effects and the survival of patients were observed.@*Results@#Patients in the chrono group had significantly lower rates of hearing loss (22.72%), dysphagia (0) and neck fibrosis (4.54%) compared with those in the conventional group (39.13%、8.69%, 15.94%, respectively, all P<0.05). Meanwhile, the 1- year overall survival rates (97.0% vs 92.8%), 3-year overall survival rates (80.3% vs 81.2%), 1-year progression free survival rates (95.5% vs 87.0%), 3-year progression free survival rates (71.2% vs 73.9%), 1-year locoregional relapse-free survival rates (97.0% vs 95.7%), 1-year locoregional relapse-free survival rates (92.4% vs 92.8%), 1-year distant metastasis-free survival rates (97.0% vs 98.6%) and 3-year distant metastasis-free survival rates (90.9% vs 91.3%) between the chrono group and the conventional group were not statistically significant (all P>0.05).@*Conclusions@#Compared with conventional chemotherapy, chrono-chemotherapy combined with IMRT didn′t affect long-term survival, but reducing the incidence of adverse events in patients with locally advanced NPC.

Effect of N-acety-L-cysteine on iopromide-induced injury in renal tubular epithelial HK-2 cells and its underlying mechanisms / 医学研究生学报

Objective N-acety-L-cysteine (NAC) can attenuate the injury of podocytes and renal tubular epithelial HK-2 cells induced by contrast agents, but its specific action mechanisms needs to be further clarified. In this study, we investigated the effects of NAC on iopromide (IPM)-induced injury and the NF-κB/NLRP3 signaling pathway in HK-2 cells. Methods Renal tubular epithelial HK-2 cells were divided into seven groups, control, IPM, and IPM + NAC at 2, 4, 8, 16 and 32 mmol/L. After a 24-hour treatment of the HK-2 cells with NAC, CCK-8, DAPI staining, DCFH-DA and Western blot were employed for determination of the viability, apoptosis and morphology of the cells as well as the level of reactive oxygen species (ROS) and the expressions of Bax, Bcl-2, NLRP3, ASC, Caspase-1, IL-1β and NF-κB in the cells. Results Compared with the control, the cells of the IPM group showed a significantly reduced viability ([100 ± 4.749]% vs [48.819 ± 2.045]%, P < 0.05), increased apoptosis, elevated ROS level, and up-regulated expressions of Bax, Bcl-2, NLRP3, ASC, Caspase-1, IL-1β and NF-κB. In comparison with the IPM group, the HK-2 cells treated with NAC at 2, 4, 8, 16 and 32 mmol/L exhibited a remarkably increased viability ([55.398 ± 3.609]%, [58.953 ± 2.859]%, [61.531 ± 5.179]%, [59.845 ± 6.365]% and [59.094 ± 6.285]%) and decreased ROS level and expressions of Bax, Bcl-2, NLRP3, ASC, Caspase-1, IL-1β and NF-κB. The mean fluorescence intensity was significantly higher in the HK-2 cells of the IPM group than in the control cells (5050.85 ± 606.76 vs 1502.17 ± 55.91, P < 0.05), but remarkably decreased in those treated with NAC at 2, 4, 8, 16 and 32 mmol/L (4065.39 ± 106.59, 4162.05 ± 28.93, 3675.71 ± 50.38, 3133.79 ± 66.07 and 2675.80 ± 92.39) (P < 0.05). Conclusion NAC can effectively improve IPM-induced injury of renal tubular epithelial cells, which may be associated with its abilities of inhibiting ROS production and activating the NF-κB/NLRP3 signaling pathway.

Association between cardiopulmonary bypass time and 90-day postoperative mortality in patients undergoing arch replacement with the frozen elephant trunk: a retrospective cohort study / 中华医学杂志(英文版)

Background@#The aortic arch replacement and cardiopulmonary bypass (CPB) are both associated with the early mortality after cardiothoracic surgery. This study aimed to investigate the relationship between CPB time and 90-day post-operative mortality in patients undergoing aortic arch surgery using the frozen elephant trunk (FET) technique with selective ante-grade cerebral perfusion (SACP).@*Methods@#We retrospectively reviewed data of 377 adult patients undergoing aortic arch surgery via FET with SACP from July 1, 2017 to December 31, 2018 at Beijing Anzhen Hospital. The baseline characteristics, intra-operative data, and post-operative data were collected. Univariate and multivariate Cox regression analyses were used to determine independent predictors of 90-day postoperative mortality.@*Results@#The 90-day post-operative mortality was 13.53%. The 78.51% of patients were men. There were 318 (84.35%) type A aortic dissections and 28 (7.43%) aortic aneurysms. Among those, 264 (70.03%) were emergency operations. Median CPB time was 202.0 (176.0, 227.0) min. Multivariate Cox regression analysis revealed that CPB time was independently associated with 90-day post-operative mortality after adjusting confounding factors (hazard ratio: 1.21/10 min increase in CPB time, 95% confidence interval: 1.15–1.27, P < 0.001). Kaplan-Meier analysis based on CPB time tertiles revealed that the top tertile (median 236.0 min) was associated with reduced survival rate compared with middle and bottom tertiles (P < 0.001). Each sub-group analysis based on the complexity of the underlying disease process showed similar associations between CPB time and 90-day post-operative mortality.@*Conclusions@#CPB time remains a significant factor in determining 90-day post-operative mortality in patients undergoing aortic arch surgery using FET with SACP. Surgeons should be aware of the relationship between CPB time and 90-day post-operative mortality during operative procedures and avoid extended CPB time as far as possible.

Short-term efficacy and adverse events of intensity-modulated radiotherapy combined with chronomodulated chemotherapy for locally advanced nasopharyngeal carcinoma / 中华放射医学与防护杂志

Objective@#To compare the adverse events, immune status, and short-term efficacy between chronomodulated chemotherapy (CCR) and routine chemotherapy (RCR) combined with intensity modulated radiotherapy (IMRT)in the treatment of patients with locally advanced nasopharyngeal carcinoma.@*Methods@#A total of 159 patients with newly diagnosed locally advanced nasopharyngeal carcinoma were randomized into the CCR group and the RCR group to evaluate the short-term efficacy and adverse events.@*Results@#No significant difference was found in CR, PR, SD, and PD between the CCR group and the RCR group (P>0.05), and no significant difference was observed in the response rate (CR+ PR) between the two groups (P>0.05). The incidence of leukopenia(Z=-2.222, P<0.05), neutropenia(Z=-1.999, P<0.05), vomiting(Z=-2.298, P<0.05), and oral mucositis(Z=-3.571, P<0.05)of the CCR group was lower than those of the RCR group with statistical significance. The CD16+ 56+ lymphocyte cell count was higher in the CCR group than that in the RCR group(Z=-2.332, P<0.05).@*Conclusions@#As a novel invention, CCR combined with IMRT can reduce the incidence and severity of treatment-related adverse events and improve immune status without diminishing clinical efficacy, therefore deserving clinical application.

Application of serratus anterior muscle flap transfer in lateral part deformity of expander to implant breast reconstruction / 中华医学美学美容杂志

Objective To explore the application and clinical significance of serratus anterior muscle flap transfer in correction of lateral part deformity of expander to implant breast reconstruction.Methods Six patients who received expander-to-implant breast reconstruction were enrolled.After silicone implant replacing the tissue expander,all 6 cases represented lateral part deformity of the reconstructed breast.The turn-over serratus anterior muscle flap was used as lateral coverage of the deformed breast.Results Of all patients (6 cases),breast aesthetics were improved with incisions well-healed.There were no complications such as capsular contracture,hematoma,infection or insicional dehiscence.Conclusions Serratus anterior muscle flap can provide sufficient lateral coverage for expander-to-implant breast reconstruction.It is safe,simple and cheap to apply in improving the aesthetics of breast reconstruction.

Research progress and new ideas in circadian gene Bmal1 and oncotherapy / 中国肿瘤临床

Circadian rhythm plays a role in regulating life activities and contributes to periodicity, orderliness, and synergy in organ-isms . The Bmal1 gene is one of the core components of the circadian rhythm system; the level of Bmal1 expression differs between tu-mor and normal tissues. Studies have shown that Bmal1 plays different roles in different tumors. Therefore, understanding the role of Bmal1 in different tumorigenesis could provide a new theoretical basis for early detection or effective treatment of tumors. In recent years, with the in-depth studies on time-based approaches, chrono-chemotherapy, which combines pharmacokinetics and biotic rhythm, has become one of the important methods of tumor treatment. Radiotherapy at different times can lead to differences in ra-diosensitivity, which makes chrono-radiotherapy increasingly prominent in tumor treatment. In-depth studies on circadian rhythm in cancer biology could provide new perspectives for tumor treatment.

Clinicopathological characteristics and risk factors of female breast hyperplasia in different age groups / 中华普通外科杂志

Objective To analyze clinicopathological characteristics and the potential risk-related factors of female breast hyperplasia in different age groups.Method From Jan 2015 to Dec 2016,patients diagnosed with breast hyperplasia in 12 hospitals were evaluated.All patients completed the self-designed questionnaires on women'health,including basic demographic information,clinic examination information,radiologic information and pathologic results.The patients were divided into a young group (＜ 45 years old) and an elderly group (from 45 to 75 years old).Results There were 3 684 cases of breast hyperplasia,including 2 291 cases in young group and 1 393 cases in elder group,respectively Clinically breast pain type were most commonly observed in both young and older groups (50.3％ vs.42.7％,P ＜ 0.001).While pathological research based on biopsy showed that breast adenopathy were the most common changes in both groups (67.9％ vs.61.7％,P ＜0.001).More breast cancer cases were identified in elder group than that in young group,especially in clinically lump type patients (9.4％ vs.4.2％,P ＜ 0.001).Compared with elder group,patients in young group have different distribution characteristics regarding to fertility factors,lifestyle factors and psychology scale including anxiety and depression.Conclusion Distributions of clinicopathological characteristics and risk factors of female breast hyperplasia differ across different age groups.