Objective To investigate the changes of glucocorticoid receptor (GR) gene expression in the hippocampus of rats following scald burn stress and the role of N methyl D aspartate (NMDA) receptor in this change. Methods Adult male Wistar rats inflicted with 30% TBSA full thickness scalding were applied as severe scalding stress model. GR mRNA levels in the hippocampus were detected with RT PCR. Results A significant decrease of GR mRNA levels was observed in the hippocampus 2 h after the scalding stress. The decrease could be inhibited when MK 801, an NMDA receptor antagonist, was administered prior to stress, and be augmented with the administration of NMDA, an NMDA receptor agonist, but not be affected by normal saline. Conclusion NMDA receptors are involved in the scalding stress induced down regulation of GR gene expression in the rat hippocampus.

Objective To investigate the changes of HPA axis activity following scald stress and to elucidate if NMDA receptor is involved in this change. Methods Adult male Wistar rats were inflicted with 30% TBSA full thickness scalding burn, which was applied as severe trauma stress model. Using this model, we detected the changes of serum cortisol and ACTH concentration in scald rats pretreated with intrahippocampal microinjection of NMDA receptor antagonist MK801 or NMDA receptor 1 antisense oligodeoxynucleotide. Results Intrahippocampal microinjection of MK 801 6 ?g resulted in an significant decrease of serum cortisol and ACTH concentration at 2 h after burn, and microinjection of MK 801 12 ?g resulted in a more significant decrease of these values. In accordance with microinjection of MK 801, intrahippocampal microinjection of NMDA receptor 1 antisense oligodeoxynucleotide of 10 nmol/L and 20 nmol/L also resulted in a significant and a more significant decrease of serum cortisol and ACTH concentration after burn. Conclusion Hippocampal NMDA receptor plays an important role in over excitation of HPA axis following burn.

OBJECTIVETo observe the change of the gene expression of N-methyl-D-aspartate receptors (NMDAR) subunits in rat hippocampus after scalding.

METHODSThe backs of the rats were shaved and immersed in warm water for 10 sec. to make control group (C), and the backs shaved and immersed in hot water (90 degrees C) for 10 sec to make 30% full skin scalding model as the scalding group (S). The mRNA expression of the subunits of rat hippocampus NMDAR-NMDAR1, NMDAR2A, NMDAR2B, NMDAR2D was determined with RT-PCR technique in C group and at 0.5, 1, 2 and 4 postburn hours (PBHs) in S group.

RESULTS(1) There exhibited no obvious change of the mRNA expression of all the subunits of NMDAR at 0.5 and 1 PBH in S group when compared with that in C group. But the mRNA expression of NMDAR1 increased for 24.3% and 20.9% and that of NMDAR2A increased for 27.8% and 27.6% at 2 and 4 PBHs respectively when compared with that in C group (P < 0.05). In addition, the mRNA expression of NMDAR2B and NMDAR2D revealed no change after scalding.

CONCLUSIONThe receptor channel constructed by NMDAR1/NMDAR2A demonstrated increased mRNA expression at 2 PBH, which might lead to the further opening of NMDAR after scalding which might participate in the maladjustment of HPA axis during scalding stress and the following pathophysiological changes.

Animals ; Burns ; metabolism ; pathology ; Disease Models, Animal ; Female ; Gene Expression ; Hippocampus ; metabolism ; pathology ; Male ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate ; biosynthesis ; genetics

Objective:To explore the value of MRI high-resolution T2WI based-radiomics in predicting pathologic complete response (pCR) after neoadjuvant therapy for rectal cancer.Methods:This retrospective study included 80 patients with rectal cancer confirmed by postoperative pathology, who underwent high-resolution imaging of rectal MRI before neoadjuvant therapy from January 2018 to March 2019 in our hospital. After manually delineating the volume of interest (VOI) of the lesion in the high-resolution T2WI image, the radiomics features were extracted, and the least absolute shrinkage and selection operator (LASSO) algorithm was adopted to reduce the dimension and select the features that were valuable for tumor pCR. Using Random algorithm, the data were randomly divided into training set ( n=64) and test set ( n=16) for machine learning, and 4 kinds of machine learning models including decision tree (DT), logistic regression (LR), random forests (RF) and extreme gradient boosting (XGBoost) were established and ROC curves were drawn. The area under the curve (AUC), sensitivity, specificity and 95% CI were respectively calculated, and the difference of ROC curves was compared with DeLong test. Results:Among 80 patients with rectal cancer, there were 15 cases by pCR, accounting for 18.75%, and 65 cases were non-pCR, accounting for 81.25%. A total of 1 409 imaging features were extracted. After dimension reduction by LASSO algorithm, 8 most valuable features were selected. The AUC of DT, LR, RF and XGBoost in the test set group was 0.870, 0.801, 0.912, 0.945, the AUC of XGBoost was the largest, and the differences between XGBoost and DT, LR, RF were statistically significant ( P=0.008; P=0.006; P=0.009), and the pairwise comparisons of DT, LR, RF showed no statistically significant difference ( PLR-RF=0.083; PDT-LR=0.113; PDT-RF=0.879). The sensitivity was 78.57%, 64.29%, 78.57%, 85.71%, and the specificity was 95.38%, 84.62%, 92.31%, 98.46% respectively. The 95% CI was 0.775-0.935, 0.696-0.882, 0.827-0.964, 0.870-0.984. Conclusion:The radiomics based on high-resolution T2WI images has predictive value for pCR after neoadjuvant treatment of rectal cancer. XGBoost model has better predictive efficiency than DT, LR and RF, and can be used to guide clinical individualized treatment and related interventions.

Objective To investigated the influence of different combined treatment sequence of stereotactic body radiation therapy (SBRT) and chemotherapy (CT) on the survival of very elderly patients with locally advanced pancreatic cancer ( LAPC) .Methods The data of LAPC patients ≥60 years old treated by CyberKnife SBRT at Shanghai Changhai Hospital from January 2012 to December 2016 was retrospectively analyzed.According to treatment sequences , patients were divided into three groups:CT+SBRT group ( first chemotherapy and then SBRT ) , SBRT+CT group ( first SBRT and then chemotherapy ) and CT+SBRT+CT group ( first chemotherapy , then SBRT and finally chemotherapy ) .Patients were recommended to receive a 6-month chemotherapy .Intravenous administration of 1000 mg/m2 gemcitabine was initiated on day 1, 8, and 15 every 4 weeks or S-1 was orally given at a dose of 80 mg/m2 for 28 days followed by a 14-day rest , which repeated for 6 cycles.Radiotherapy parameters: the median total prescription dose was 36(30-45)Gy; the median per fraction dose was 7(5-9)Gy;the median number of fractions was 5(5-8) fractions;the median biological equivalent dose (BED10) were 61.92(48-85.5) Gy, respectively.The interval between SBRT and chemotherapy ranged from 2 to 3 weeks.Patients were followed every 3 months.The main outcome measures were overall survival ( OS) and median progression free survival ( PFS) .Second outcome measure was adverse events.Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0) was employed to evaluate adverse events , and RTOG/EORTC was used to assess the adverse events of radiotherapy .Overall survival (OS) and PFS were calculated by Kaplan-Meier method.Univariate and multivariate logistic regression model were used to analyze the independent risk factors .Results A total of 260 patients were enrolled in the study , including 28 patients treated with CT+SBRT, 163 patients undergoing SBRT +CT and 69 patients treated with CT+SBRT+CT.The median OS and PFS were 13.2(95％CI 12.8-13.6)months and 8.2(95％CI 7.7-8.7)months, respectively.OS in CT +SBRT, SBRT +CT and CT +SBRT +CT group was 12.2 (10.9-13.9),13.4 ( 12.9-13.9 ) and 13.1 ( 12.7-13.5 ) months, and the differences were not statistically significant(P=0.425).PFS in CT+SBRT, SBRT+CT and CT+SBRT+CT group was 6.4(5.9-6.9), 8.3(7.8-8.8) and 8.2(7.2-9.2)months, and the differences were statistically significant (P=0.008).In univariate analysis , ECOG, SIRI, the extent of decreased CA 19-9 after treatment and BED 10 were important factors of OS.In multivariate analysis, the CA19-9 response and BED10 were independent factors for OS . Multivariate analysis showed that the extent of decreased CA 19-9 after treatment and BED 10 were important factors of OS.In CT+SBRT group, patients had lower ECOG score (χ2 =115.325,P<0.001) and earlier clinical staging (χ2 =24.788, P<0.001 ).In SBRT +CT group, patients had advanced staging (χ2 =159.759,P<0.001) and lymph node metastasis(χ2 =40.925,P<0.001).Only 1 patient experienced grade 3 radiotherapy associated duodenitis .The adverse events of patients who were first treated by chemotherapy included grade 3 neutropenia in 4 patients and grade 3 gastrointestinal reaction in 5 patients.The adverse events of patients who were first treated by radiotherapy included grade 3 neutropenia or/and leucopenia in 18 patients and grade 3 abdominal pain, nausea or vomit in 16 patients.The adverse events of CT +SBRT+CT patients included grade 3 neutropenia or/and leucopenia in 4 patients and grade 3 abdominal pain or nausea in 5 patients.There was no grade ≥4 adverse events.Conclusions For very elderly patients with LAPC , the survival of patients who received pre-SBRT chemotherapy , post-SBRT chemotherapy and pre-and post-SBRT chemotherapy was comparable , but SBRT+CT group and CT +SBRT+CT group had longer PFS than CT +SBRT group.

OBJECTIVE Disturbance of K+ ion balance in inner ear is associated in age-related hearing loss. Our study is to investigate the role of NKCC1 and Na-K-ATPase in cochlea and auditory function regulated by with different expression of NKCC1 and Na-K-ATPase. METHODS Auditory threshold of young or old C57BL/6J mice was measured by auditory brainstem response(ABR). The expression of NKCC1 and Na-K-ATPase in mice cochlea were evaluated by reverse transcription polymerase chain reaction(RT-PCR) and western blotting. Furosemide and Ouabain were applied in vivo to inhibit NKCC1 and Na-K-ATPase in C57BL/6J mice. RESULTS C57BL/6J mice developed hearing loss at 12M by ABR threshold shifting to (75±10), (78±26) and (81±14)dB SPL at frequencies of 8, 16 and 32 kHz; PCR showed that the relative expression of NKCC1 and Na-K-ATPase mRNA in the aged group decreased, which were 0.52±0.06 and 0.35±0.04 times higher than those in the young control group, the difference was statistically significant(t =7.466 and 16.11, all P＜0.05). WB showed that relative expression of NKCC1 and Na-K-ATPase protein level in the aged group decreased by 0.79±0.02 and 0.68±0.05 times as much as that of the young control group, the difference was statistically significant(t =8.857 and 6.771, P all＜0.05). After applied with Furosemide and Ouabain to suppress the two ion transporters, the ABR threshold increased to (50±17), (53±21), (55±17)dB SPL and (56±6), (70±17), (73±6)dB SPL at frequencies of 8, 16 and 32 kHz. CONCLUSION In vivo experiment of C57BL/6J suggested that NKCC1 and Na-K-ATPase might be related to age related hearing loss.