ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 （ACSL4） signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group， sham-operation group， model group， trimetazidine group （5.4 mg·kg^-1）， low-， medium-， and high-dose group （3.51， 7.02，14.04 g·kg^-1） of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome， and continuous treatment for 7 d was conducted， while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed， and indicators such as electrocardiogram， echocardiography， and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin （HE） staining， and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid （12-HETE） and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe²⁺， lipid peroxidation （LPO）， glutathione （GSH）， and T-GSH/glutathione disulfide （GSSG） in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species （ROS）. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， ACSL4， and ly-sophosphatidylcholine acyltransferase3 （LPCAT3） in myocardial tissue. ResultsCompared with those in the normal group， the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage， bow-back elevation of the ST segments， elevated T waves， J-point elevation， and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction （LVEF） and left ventricular fraction shortening （LVFS） （P<0.01）. Blood rheology showed that the viscosity of the whole blood （low， medium， and high rate of shear） was significantly increased （P<0.01）. HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken， and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles， and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased （P<0.01）. The content of Fe²⁺， LPO， and ROS in myocardial tissue was significantly increased （P<0.01）. The content of GSH was significantly decreased （P<0.01）， and T-GSH/GSSG was decreased （P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased （P<0.05， P<0.01）， while those of ACSL4 and LPCAT3 increased significantly （P<0.01）. Compared with the model group， the general macroscopic symptoms and electrocardiogram results of rats in low-， medium- and high-dose groups of Xuefu Zhuyutang were alleviated， and the differences in LVEF/LVFS ratios were all significantly increased （P<0.05， P<0.01）. The differences in whole-blood viscosity （low， medium， and high rate of shear） were all significantly decreased （P<0.01）. The results of HE staining and transmission electron microscopy showed that the morphology， structure， and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. The content of Fe²⁺， LPO， and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and the content of GSH and T-GSH/GSSG was significantly increased （P<0.05， P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and ACSL4 and LPCAT3 were decreased to different degrees in the low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway， thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.

The diagnosis of Parkinson's disease(PD)mainly relies on clinical appearance of patients,and the routine magnetic resonance scan has difficulty in finding the abnormality of that,which is not able to meet the requirement of early and precise quantification for the PD lesion area.Diffusion magnetic resonance imaging(dMRI)technique is a noninvasive method of examining the microstructure of living tissue.Diffusion weighted imaging(DWI)and diffusion tensor imaging(DTI)were the most widely used in clinical practice.However,the principles of them have limitation,which are not able to fully outline the microstructure of brain tissue.This paper discussed several new dMRI techniques that are able to make up conventional dMRI model,which included diffusion kurtosis imaging(DKI),neurite orientation dispersion and density imaging(NODDI)and diffusion tensor imaging index of perivascular space(DTI-ALPS).Moreover,this paper summarized the applications of above imaging technique in exploring the changes of the microstructure of brain tissue of PD patients,so as to provide more imaging information for the pathological changes of PD patients.

Objective:To evaluate the effect of stroke volume variation (SVV)-guided fluid therapy on perioperative haemodynamics and tissue perfusion in the patients with end-stage renal disease (ESRD) undergoing parathyroidectomy.Methods:One hundred and twenty-one patients of either sex, aged 18-64 yr, of American Society of Anesthesiologists Physical Status classification Ⅲ, with body mass index of 18-28 kg/m 2, with ESRD undergoing elective parathyroidectomy, who received haemodialysis treatment within 24 h before surgery, were enrolled in this study. The patients were divided into standard restrictive fluid therapy group (group SRT, n=61) and goal-directed fluid therapy group (group GDT, n=60) using a random number table method. Group SRT received restrictive fluid therapy, with a continuous infusion of 0.9% normal saline at a rate of 4 ml·kg -1·h -1. Group GDT received goal-directed fluid therapy guided by SVV, and when the SVV≥10% lasted for 5 min, the 0.9% normal saline 3 ml/kg was infused within 5 min until SVV<10%. Systolic blood pressure (SBP) was maintained at ≥90 mmHg or mean arterial pressure(MAP) at ≥65 mmHg throughout the perioperative period in both groups. The intraoperative volume of fluid infused, usage rate and consumption of intraoperative vasoactive drugs were recorded, and arterial blood lactate (Lac) level, MAP, heart rate, cardiac output, and inferior vena cava collapse index (IVC-CI) after removal of endotracheal tube at the end of surgery were measured. MAP was continuously recorded within 12 h after surgery, and MAP variability (CV MAP) was calculated. The occurrence of cardiovascular and cerebrovascular events within 30 days after operation was also recorded. Results:Compared with group SRT, the intraoperative volume of fluid infused was significantly increased, the usage rate of ephedrine and norepinephrine was decreased, the consumption of ephedrine was reduced, and the percentage of postoperative IVC-CI<50% and cardiac output were increased, the percentage of Lac≥2.0 mmol/L and CV MAP were decreased ( P<0.05), and no significant change was found in the incidence of cardiovascular and cerebrovascular events within 30 days after surgery in group GDT ( P>0.05). Conclusions:Compared with restrictive fluid therapy, SVV-guided fluid therapy can optimize the perioperative hemodynamics and tissue perfusion in the patients with ESRD undergoing parathyroidectomy.

Objective:To explore the effects and mechanisms of bortezomib on the proliferation and apoptosis of acute T lymphocyte leukemia cell line Jurkat.Methods:MTT assay was used to test the influence of bortezomib on the proliferation of Jurkat cells.Flow cytometry was used to detect the influence of bortezomib on apoptosis of Jurkat cells.Real-time quantitative polymerase reaction(RT-PCR) was used to detect the effects of bortezomib on the expression of Bax, Bcl-2 and Cox-2 genes in Jurkat cells.Results:The inhibition rates of 5ng/mL, 10ng/mL, 20ng/mL and 40ng/mL bortezomib on Jurkat cells at 24h were (13.23±0.71)%, (39.53±0.95)%, (53.07±1.12)%, (60.43±0.75)%, respectively, and the inhibition rates at 48h were (25.20±0.96)%, (52.80±1.30)%, (60.67±0.64)%, (75.10±1.35)%, respectively.The inhibitory rates of proliferation of Jurkat cells at 72h were (38.37±0.93)%, (60.94±0.85)%, (73.83±5.08)%, (88.37±1.55)%, respectively.The inhibitory rates of proliferation of Jurkat cells increased with the increase of drug concentration and the prolongation of action time, and the differences were statistically significant( F=1 602.202, 1 085.089, 181.034, all P<0.05). Bortezomib (5ng/mL, 10ng/mL, 20ng/mL and 40ng/mL) treatment for 24h, 48h and 72h, the apoptosis rate of Jurkat cells increased with the increase of drug concentration and the prolongation of action time, the differences were statistically significant( F=1 288.571, 223.378, 251.175, all P<0.05). The expression of Bax mRNA in Jurkat cells increased with the increase of drug concentration and time( F=258.446, 518.929, 276.764, all P<0.05). The Bcl-2 mRNA and Cox-2 mRNA expression levels decreased with the increase of drug concentration and the prolongation of action time( FBcl-2 mRNA=236.848, 264.849, 343.968, FCox-2 mRNA=679.404, 1288.681, 1541.850, all P<0.05). Conclusion:Bortezomib can inhibit the proliferation and induce apoptosis of Jurkat cells.Bortezomib can increase the expression of Bax mRNA and decrease the expression of Bcl-2 and Cox-2 mRNA, which may be the molecular mechanism of bortezomib to promote apoptosis.

Objective To observe the long?term survival and adverse reactions in patients with stage T4 N (+) Ⅲ middle and lower thoracic esophageal carcinoma undergoing intensity?modulated radiotherapy ( IMRT) . Methods From 2004 to 2010, 300 patients with stage T4 N (+) Ⅲ middle and lower thoracic esophageal carcinoma, consisting of 202 treated with three?dimensional conformal radiotherapy ( 3DCRT ) and 98 treated with IMRT, were enrolled as subjects. All patients received conventionally fractionated radiotherapy with a prescribed dose of 60 Gy. The long?term survival and adverse reactions were compared between patients treated with the two different radiotherapy regimens. The survival rates were calculated by the Kaplan?Meier method and analyzed by the log?rank test. Results The 5?and 7?year sample sizes were 239 and 120, respectively. The 3DCRT group had significantly lower 1?, 3?, 5?, and 7?year local control (LC) and overall survival (OS) rates than the IMRT group (64. 4% vs. 68. 3%, 40. 6% vs. 55. 3%, 38. 3% vs. 51. 9%, 34. 2% vs. 51. 9%, P=0. 048;54. 5% vs. 63. 3%, 19. 8% vs. 34. 7%, 14. 7% vs. 24. 4%, 10. 9% vs. 20. 3%, P=0. 013) . The stratified analysis showed that for patients older than 65 years, with the length of esophageal lesion>8. 0 cm before radiotherapy, the largest diameter of esophageal lesion in computed tomography image>4. 6 cm, gross tumor volume ( GTV)>60 cm3 , metastases to adjacent tissues or organs, stage N2 , and without chemotherapy, the IMRT group had a significantly higher OS rate than the 3DCRT group (P=0. 022,0. 003,0. 022,0. 034,0. 016,0. 044,0. 047). The GTV Dmin and GTVD100 were significantly higher in the IMRT group than in the 3DCRT group ( P=0. 000,0. 000) , while the Dmax of the spinal cord was significantly lower in the IMRT group than in the 3DCRT group ( P=0. 000) . Compared with the 3DCRT group, the IMRT group had a significantly higher incidence of acute radiation?induced esophagitis, particularly grade 1?2 esophagitis (P=0. 000). The mortality rate caused by local tumor was significantly higher in the 3DCRT group than in the IMRT group ( P= 0. 039 ) . Conclusions In the treatment of locally advanced middle and lower thoracic esophageal carcinoma, IMRT is safe and effective;it significantly improves the LC rate and long?term survival without severe toxicity to normal tissues. The results of this retrospective study need to be confirmed by prospective randomized controlled studies.

Combined with the treatment of the case of chronic atrophic gastritis with tongue abnormalities, this article introduced Professor WANG Yan-gang's experience in treating tongue abnormalities from stomach. To be specific, the pathogenesis of chronic atrophic gastritis from dampness, phlegm, stagnation, blood stasis and deficiency were analyzed, and the main therapeutic principle was Clearing Heat and Expelling Dampness, Resolving Turbidity and Removing Toxin, supplemented by eliminating phlegm, dissipating stasis, freeing stagnation and nourishing yin, to treat chronic atrophic gastritis with tongue abnormalities.

Objective To examine the prediction value of diffusion-weighted magnetic resonance imaging (DWI) on radiotherapy response in esophageal cancer.Methods A total of 24 subcutaneous esophageal cancer xenograft models were randomly divided into experimental group (n =14,received a single dose of 15 Gy radiotherapy) and control group (n =10,without any treatment).MRI were required before and after radiotherapy at different check time points (1,6,13 days) of T1WI,T2WI,and DWI measurements.Apparent diffusion coefficient (ADCX) and volume (VX) of each xenograft were measured,and both △ADCX and △VX were calculated.Results The ADC values of both group were decreased at the first day,however,the decrease in experimental group were more obviously with an increase at 6 and 13 d gradually.However,the ADC values of the control group showed a persistent decline.There was no significant difference in the ADC values between the two different groups before radiotherapy (P ＞ 0.05),while significant difference was found in the ADC values (F =6.178,16.181,58.733,P ＜ 0.05) and △ADC after radiotherapy (F =9.038,12.360,35.140,P ＜ 0.05).The xenografts volume in the experimental group showed a significant growth delay.There was no significant difference in volume between the two groups (P ＞ 0.05) before radiotherapy.Significant difference in V between the two groups only began to exist at 5 d after radiotherapy (F =28.587,P ＜ 0.05).The ADC0,ADC1 of transplanted tumor in control group had linear correlation relationships with its volume of later period.After radiotherapy,the trend of r values gradually increased from-0.118 to 0.896.Conclusions ADC values may change significantly at the early stage after radiotherapy,and initial and early ADC value may have close relationship with xenograft volumes of later period,which indicates that DWI has huge potential in the prediction of radiotherapy response.

Objective To analyze the medication regularity of the prescriptions in the work of Li Dong Yuan; To provide references for inheritance of his academic ideas.Methods The prescriptions in the work of Li Dong Yuan were inputted into the TCM Inheritance Supporting System (V2.5). By using revised mutual information, complex system entropy cluster and unsupervised hierarchical clustering, the composing medication regularity was analyzed.Results Based on the analysis of 470 entries of prescriptions, the frequency of 44 entries was more than 30 times; 19 combinations contained 2 to 3 entries, including 11 entries in total; 14 medicine association rules and their confidence coefficient were obtained, which leaded to 54 new core combinations and 27 new prescriptions. Conclusion The results of this study show Li Dong Yuan’s academic idea of “internal injuries of spleen and stomach, all diseases will born”, which guides the medication regularity of using medicine with the functions of strengthening the middle jiao, invigorating yang, tonifying qi and reinforcing the stomach. The results also provide data support for further study.

Objective To investigate the effects of dosimetric differences in gross tumor volume ( GTV ) on local control and survival rates in patients with esophageal carcinoma undergoing three?dimensional ( 3D) radiotherapy,and to provide a basis for clinical treatment. Methods From January 2004 to December 2010, 548 patients with esophageal carcinoma received conventional fractionated 3D radiotherapy with a prescribed dose of 60 Gy. All patients were divided into low?dose group and high?dose group according to the dosimetric differences in GTV. The survival and local control rates were compared between the two groups. The survival rates were calculated using the Kaplan?Meier method and analyzed using the logrank test. The Cox regression model was used for the multivariate prognostic analysis. Results The number of sample were 456 and 216 patients at 5 and 7 years followed time. The 1?,3?,5?,and 7?year local control rates were significantly higher in the high?dose group than in the low?dose group ( 83?5% vs. 71?3%, 62?6% vs. 44?8%,57?5% vs. 41?7%,52?9% vs. 38?8%,P=0?000).The 1?,3?,5?,and 7?year survival rates were also significantly higher in the high?dose group than in the low?dose group ( 79?6% vs. 66?3%, 44?3% vs. 29?7%, 34?0% vs. 21?8%, 26?1% vs. 17?0%, P=0?000 ) . The univariate prognostic analysis using the Cox regression model showed that Dmin , Dmean , and D100 for GTV were prognostic factors ( P=0?000,0?001,0?000).In all the 548 patients,201 were assigned to the high?dose group and the others to the low?dose group. Compared with the high?dose group, the low?dose group showed significantly larger GTV (38?2 vs. 48?1 cm3,P=0?002) and more advanced T stages (P=0?035).The stratified analysis showed that the 1?,3?,5?,and 7?year local control and survival rates were significantly higher in the high?dose group than in the low?dose group,regardless of tumor location,GTV,TNM stage,or chemotherapy. The multivariate analysis using the Cox regression model indicated that tumor location and grouping based on the radiation dose to GTV were independent prognostic factors. Conclusions In 3D radiotherapy for treating esophageal carcinoma,a high?quality treatment plan and GTV dose assurance improve the survival rates in patients. The patients with lower Dmin ,Dmean ,and D100 for GTV than the prescribed dose have a poor prognosis.

Objective To investigate the parameters of diffusion?weighted magnetic resonance imaging ( DWMRI) for prediction of the efficacy of chemoradiotherapy ( CRT) for esophageal squamous cell carcinoma ( ESCC) , to determine the optimal time point and threshold for prediction, and to provide a basis for clinical practice. Methods From 2010 to 2011, 38 patients with ESCC were consecutively enrolled as subjects. All patients received three?dimensional conformal radiotherapy with 60 Gy in 30 fractions for 6 weeks. They also received concurrent or consolidation chemotherapy ( FP or TP scheme ) as adjuvant treatment. Patients received DWMRI scans before radiotherapy and at weeks 1?6 during radiotherapy. The apparent diffusion coefficient ( ADC ) values and tumor lengths obtained from serial DWMRI scans were recorded and analyzed. Comparison was made by paired t test. Repeated measurements were analyzed by analysis of variance ( ANOVA) and multivariate ANOVA. The prognosis was predicted by the Logistic model. The effectiveness analysis and threshold screening were performed using the receiver operating characteristic (ROC) curve. Results In all patients, 20(52?6%) had complete response (CR) and 18(47?4%) had partial response ( PR) . There were no significant differences in the ADC values before radiotherapy and at weeks 1?6 during radiotherapy between patients with CR and PR ( 1?82 vs. 1?42;1?92 vs. 1?49;2?06 vs. 1?67;2?35 vs. 1?79;2?62 vs. 2?11;2?71 vs. 2?18;2?96 vs. 2?28×10-3 mm2/s;P=0?006,0?003,0?012, 0?001,0?003,0?008,0?002) . The ADC value at third week during radiotherapy was the only independent prognostic factor for short?term treatment outcomes in patients with ESCC ( OR=0?134, P=0?007) . These results were also supported by the multivariate ANOVA analyses. The analysis of the ROC curve showed that at the third week during radiotherapy, the area under the ADC curve was the largest ( A z=0?857) and the diagnostic effectiveness was the best;the threshold value, sensitivity, and specificity were 2?02×10-3 mm2/s, 80?0%, and 92?9%, respectively. Eight patients who had tumor out of control or recurrence within 1 year after treatment had the ADC curve fall down at the end of the fifth week and the reduction of tumor length substantially slow down from the fifth week. Conclusions DWMRI is an effective imaging approach for monitoring tumor response to CRT in patients with ESCC. The ADC value at the end of the third week during radiotherapy may be the optimal time point for prediction of treatment outcomes. The reduction in the ADC value or non?reduction in tumor length at the end of the treatment indicates a high risk of recurrence.