Objective To investigate the effect of pretreatment with dexmedetomidine alone or in combination with sufentanil on myocardial ischemia-reperfusion (I/R) injury in rats.Methods Fifty healthy male Sprague-Dawley rats,weighing 250-300 g,were anesthetized with intraperitoneal pentobarbital sodium 60 mg/kg.Myocardial I/R was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 min of reperfusion.The rats were then randomly divided into 5 groups (n =10 each):sham operation group (group S),group I/R,dexmedetomidine pretreatment group (group DP),sufentanil pretreatment group (group SP),and dexmedetomidine + sufentanil pretreatment group (group DS).In group S the anterior descending branch was only exposed but not ligated.Dexmedetomidine 0.5μg/kg and sufentanil 0.1μg/kg were injected intraperitoneally 30 min before ischemia in groups DP and SP,respectively.Dexmedetomidine 0.5 μg/kg and sufentanil 0.1 μg/kg were injected intraperitoneally 30 min bbefore ischemia in group DS.Arterial blood samples were collected at 120 min of reperfusion for determination of serum creatine kinase (CK) and lactic dehydrogenase (LDH)concentrations.The rats were sacrificed at 120 min of reperfusion and hearts were removed for microscopic examination.Myocardial infarct size was calculated.The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in myocardial tissues were measured.Results Compared with group S,the serum CK and LDH concentrations were significantly increased,the myocardial infarct size was enlarged,and SOD activity was decreased in the other groups,MDA content was significantly increased in groups I/R,DP and SP (P ＜ 0.05 or 0.01).Compared with group I/R,the serum CK and LDH concentrations,MDA content and myocardial infarct size were significantly decreased,and SOD activity was increased in groups DP,SP and DS (P ＜ 0.05).Compared with group DS,the serum CK concentration was significantly increased,the myocardial infarct size was enlarged,and MDA content was increased in groups DP and SP,and LDH concentration was significantly increased and SOD activity was decreased in group DP (P ＜ 0.05).The pathological changes were significantly attenuated in groups DP and SP compared with group DS.Conclusion Dexmedetomidine pretreatment can reduce myocardial I/ R injury in rats,dexmedetomidine combined with sufentanil pretreatment provides better efficacy than either alone,and inhibition of lipid peroxidation is involved in the mechanism.

Objective To evaluate the effect of ulinastatin on oxidative stress injury to myocardial cells in diabetic rats in vitro.Methods The H9c2 cells were cultured in DMEM culture medium and the cells at the logarithmic growth phase were seeded in 96-well plates (density 1 × 104 cells/ml,200 μl/well) or in 6-well plates (density 1× 105 cells/m1,2 ml/well).The cells were randomly divided into 4 groups (n=18 each) using a random number table:normal control group (group C),high-glucose group (group HG),high-glucose + oxidative stress group (group HG+OS),ulinastatin +high-glucose+oxidative stress group (group U+HG+OS).The cells were cultured in high-glucose DMEM culture medium (25.0 mmol/L) for 48 h in group HG.After the cells were cultured in high-glucose DMEM culture medium for 24 h,H2O2 with the final concentration of 500 μmol/L was added to the high-glucose culture medium,and the cells were continuously cultured for 24 h in HG+OS and U+HG+OS groups.In group U+HG+OS,ulinastatin 400 U/ml was added to the high-glucose culture medium.The cells were collected for determination of cell viability,H9c2 apoptosis,activity of superoxide dismutase (SOD) and contents of malonadehyde (MDA).Apoptosis rate was calculated.The cell culture supernatant was collected for detection of lactate dehydrogenase (LDH) activity.Results Compared with group C,the cell viability and SOD activity were significantly decreased,and the apoptosis rate,MDA content and LDH activity were increased in the other groups.Compared with HG group,the cell viability and SOD activity were significantly decreased,and the apoptosis rate,MDA content and LDH activity were increased in HG+OS and U+HG+OS groups.Compared with group HG+OS,the cell viability and SOD activity were significantly increased,and the apoptosis rate,MDA content and LDH activity were decreased in group U + HG+ OS.Conclusion Ulinastatin can mitigate oxidative stress injury to myocardial cells in diabetic rats,and inhibited cell apoptosis is involved in the mechanism.

Objective To investigate the effects of restraint stress (RS) in different periods on SOD and MDA of normal rat serums and mucosal tissues. Methods 32 adult male Wistar rats were randomly divided into normal control group (NC group, n=8), and restraint stress groups of 3 days, 5 days and 7 days (RS3, RS5 and RS7 groups, n=8 at each group). The comparisons were done between all the groups in terms of the general extent of gastric mucosal injury, gastric mucosal injury ulcer index (UI), water content, the activity of super oxide dismutase (SOD), and the level of malondialdehyde (MDA) in serum and mucosal. Results Compared with NC group, gastric mucosal injuries in RS group were more severe, the UI and water content was proportionally related with the restraint periods. Meanwhile, the serum and mucosal SOD in the RS groups were all increased, and with prolonged restraints, the SOD were decreased, but the serum and mucosal MDA were increased (P<0.01) and SOD/MDA in the mucosa lowered as well (P<0.01). Conclusion Restraint stress may cause mucosal injury proportional to the stress time and related with lowered SOD/MDA in mucosal tissues.

Objective To investigate the role of TRPV1 in exacerbation of gastric mucosal injury in a rat water immersion restraint stress (WIRS) model by acute postoperative pain. Methods Thirty Wistar rats were randomly divided into normal controlled group (N group, n=10), WIRS model group (WIRS group, n=10) and surgery after WIRS group (WS group, n = 10). The general extent of gastric mucosal injury was observed and assessed for gastric mucosal ulcer index (UI), intragastric pH and serum SOD/MDA ratio were measured and the expression of TRPV1 mRNA in gastric mocusal was accessed by Real-time Quantitative PCR. Immunohistochemistry was performed to detect the mean density of TRPV1. Results Compared with NC group, WIRS group showed obvious gastric mocusal injure with higher UI , lower values of intragastric pH serum SOD/MDA ratio and TRPV1 (P<0.05). The treatment with surgery after onset of WIRS significantly aggravated the gastric mucusal erosion and hemorrhage, with UI increased (P < 0.05), the value of intragastric pH, serum SOD/MDA ratio and TRPV1 further reduced (P < 0.05). Meanwhile, TRPV1 was inversely correlated with UI, and positively associated with intragastric pH and serum SOD/MDA ratio. Conclusion TRPV1 expression in gastric mocusal of AMGL model is inhibited by acute postoperative pain. TRPV1 may involve in the exacerbation of gastric mucosal injury in WIRS model by acute postoperative pain.

Objective To observe the coexistence expression of TRPV1 and μ-opoid receptorin spinal dorsal root ganglion (DRG) projected to stomach , and to investigate the relationship between TRPV1 andμ-opoid receptorand its clinical significance in rats with acute gastric mucosal lesion induced by water immersion and restraint stress. Methods FortyWistar rats were randomly assigned to 3 groups, including normal control group(group NC, n = 10), WIRS group (group WIRS, n = 20), and sufentanil pretreatment group (group SP, n = 10). A rat model of gsatric mucosal lesion was induced by WIRS. 6 hours after WIRS treatment, gastric tissues were excised and microscopically observed; ulcer index (GI) was noted. The coexistence expression of TRPV1 and μ-opioid receptor in DRG neurons was detected by immunofluorescence assay, and the levels of CGRP was measured by ELASA. Results As compared withgroup WIRS, the degree of gastric injury was obviously relieved in group SF. Coexistence of TRPV1 and μ-opioid receptor was detected in thoracic DRG neurons projected to stomach; the CGRP level was higher in group WIRS than in group NC. ConclusionsTRPV1 isinvolved in protection of acute gastric mucosal lesion. Activation of μ-opioid receptor can induce TRPV1 to release CGRP, resulting in protection of gastric mucosa.

Objective To compare the therapeutic effects between three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in patients with stage Ⅱ/Ⅲ esophageal cancer and investigate the prognostic factors.Methods Medical record of 2 132 patients with stage Ⅱ/Ⅲ esophageal cancer who underwent definitive radiotherapy with/without chemotherapy in 10 hospitals from January 2002 to December 2016 from were retrospectively analyzed.Among these patients,37.9％ of them were aged ≥ 70 years,33.9％ with neck and upper esophageal tumors and 66.1％ with middle and lower esophageal and borderline tumors.The median gross tumor volume (GTV) and lymph node gross tumor volume (GTVnd) was 41.6 cm3.Among them,32％ were stage Ⅱ] and 68％ were stage Ⅲ.A total of 723 patients received 3DCRT and 1 409 cases received IMRT.Patients received an equivalent dose in 2 Gy (EQD2) ≥ 60 Gy accounted for 86.1％,and 41.1％ of them received concurrent chemoradiotherapy.Results The median follow-up time was 60.8 months.The 1-,3-and 5-year overall survival (OS) of all patients was 73.9％,41.7％ and 32.6％,and the 1-,3-and 5-year progression-free survival (PFS) was 62.2％,37.3％ and 32％,respectively.Multivariate analysis demonstrated that age,primary tumor location,clinical stage,tumor target volume,EQD2 and concurrent chemoradiotherapy were the independent prognostic factors for OS.Age,primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS.The OS and PFS did not significantly differ among the low-risk,low-/moderate-risk,moderate-/high-risk and high-risk groups according to age≥70 years,tumor diameter＞5 cm,tumor volume ≥41.6 cm3 and stage Ⅲ (P＜0.001).After the propensity score matching (PSM) method,neither 3DCRT nor IMRT yielded significant advantages in OS or PFS (P=0.971;P=0.658).However,IMRT tended to yield survival benefits in low-risk patients (P=0.125).Conclusions Both 3DCRT and IMRT yield relatively high OS rate in patients with stage Ⅱ/Ⅲ esophageal cancer.The prognosis model established in this investigation can properly predict the survival of patients.Low-risk patients tend to obtain survival benefits from IMRT.

Objective To retrospectively analyze the effect of tumor length on the prognosis in stage Ⅱ/Ⅲ esophageal squamous cell carcinoma (ESCC) patients treated with definitive radiotherapy and to evaluate the role of tumor length in clinical stage for non-operative ESCC patients.Methods The data of 2 086 ESCC patients who were treated with definitive radiotherapy from 2002 to 2016 in 10 hospitals (3JECROG) were analyzed.The effect of tumor length on overall survival (OS) was analyzed and stratified analysis of tumor length was done in different stages of ESCC.Results The median OS and median progression-free survival (PFS) time of the whole group were 25.6 months and 18.2 months respectively.The Cox multivariate analysis showed that treatment moda,aga,alinical stage and tumor length were independent prognostic factors.The median,1-,3-,and 5-year OS were 28.9 months,77.3％,45.0％,and 36.3％ versus 21.9 months,69.9％,37.9％,and 28.1％ for patients with ≤ 5 cm and patients ＞ 5 cm respectively (P＜0.05).For stage Ⅱ patienta,abe median OS were 42.1 and 38.9 months respectively in ≤ 5 cm group and＞5 cm group (P=0.303).And for stage Ⅲ patienta,abe median OS were 23.9 and 19.3 months respectively in ≤5 cm group and＞5 cm group (P＜0.001).The median OS with N1was 24.1 and 18.4 montha,aespectively in ≤5 cm group and＞5 cm group (P＜0.001).Conclusions The tumor length was an independent prognostic factor for stage Ⅱ/Ⅲ patients treated definitive radiotherapy.The tumor length may be helpful in clinical staging of ESCa,aspecially for stage Ⅲ and N1.

Objective:To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients.Methods:The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed.Results:The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively ( P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively ( P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm 3, the median survival time of SIB and No-SIB group was 34.7 and 30.3 months ( P=0.155), respectively. In the patients whose GTV volume>50 cm 3, the median survival time of SIB and No-SIB group was 16.1 and 20.1 months ( P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group ( P<0.001). Conclusions:The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

Objective:To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation.Methods:The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed.Results:The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups ( P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy ( P<0.05). Multivariate analysis demonstrated that PGTV dose ( OR=0.693, P=0.004), radiation esophagitis ( OR=0.867, P=0.038), and radiation pneumonia ( OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions:For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.

Objective:To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation.Methods:The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed.Results:The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups ( P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy ( P<0.05). Multivariate analysis demonstrated that PGTV dose ( OR=0.693, P=0.004), radiation esophagitis ( OR=0.867, P=0.038), and radiation pneumonia ( OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions:For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.