Objective To investigate the expression of exosomal α-synuclein(α-syn),serum lipocalcitin-2(LCN-2)levels and the relationship with disease severity in Parkinson's disease(PD)patients.Methods 106 PD patients admitted to Yulin Hospital,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2020 to June 2023 were selected.The PD patients were divided into the early group(n=31),the middle group(n=45)and the late group(n=30)according to their conditions,and 92 healthy volunteers who had outpatient medical checkups during the same period were selected as the control group.The exosome α-syn and serum LCN-2 levels were detected,and the differences in exosome α-syn and serum LCN-2 levels were compared in PD patients with different disease severity levels.Factors affecting the prevalence of PD and the value of exosomal α-syn and serum LCN-2 in diagnosing PD were analyzed.Results The levels of exosomal α-syn(3 086.23±359.46 pg/ml)and serum LCN-2(4.92±1.32ng/ml)in the PD group were higher than those in the control group(1 993.24±244.35 pg/ml,1.96±0.34 ng/ml),and the differences were statistically significant(t=24.636,20.909,all P<0.05).The levels of exosomal α-syn(3 312.72±53.46pg/ml)and serum LCN-2(5.76±0.28ng/ml)in the late-stage group were higher than those in the early-stage(2 843.65±65.29pg/ml,4.02±0.32ng/ml)and the middle-stage group(3 102.35±105.48pg/ml,4.98±0.41ng/ml),and the differences were statistically significant(t=9.092～30.644,all P<0.05).Family history of PD,high level of exosomal α-syn and high level of LCN-2 were the risk factors for the development of PD(Wald χ2=8.121,7.002,4.805,all P<0.05).The AUC(95%CI)of diagnosing PD with serum LCN-2 in combination with exosome α-syn was higher than that of exosome α-syn,while serum LCN-2 alone was used for diagnosis(Z=4.869,5.103,all P<0.05).Conclusion Serum exosomal α-syn and serum LCN-2 levels are significantly higher in PD patients,which can be associated with the exacerbation of PD,and combined exosomal α-syn and serum LCN-2 can assess the risk of developing PD.

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.

Objective To investigate the expression of exosomal α-synuclein(α-syn),serum lipocalcitin-2(LCN-2)levels and the relationship with disease severity in Parkinson's disease(PD)patients.Methods 106 PD patients admitted to Yulin Hospital,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2020 to June 2023 were selected.The PD patients were divided into the early group(n=31),the middle group(n=45)and the late group(n=30)according to their conditions,and 92 healthy volunteers who had outpatient medical checkups during the same period were selected as the control group.The exosome α-syn and serum LCN-2 levels were detected,and the differences in exosome α-syn and serum LCN-2 levels were compared in PD patients with different disease severity levels.Factors affecting the prevalence of PD and the value of exosomal α-syn and serum LCN-2 in diagnosing PD were analyzed.Results The levels of exosomal α-syn(3 086.23±359.46 pg/ml)and serum LCN-2(4.92±1.32ng/ml)in the PD group were higher than those in the control group(1 993.24±244.35 pg/ml,1.96±0.34 ng/ml),and the differences were statistically significant(t=24.636,20.909,all P<0.05).The levels of exosomal α-syn(3 312.72±53.46pg/ml)and serum LCN-2(5.76±0.28ng/ml)in the late-stage group were higher than those in the early-stage(2 843.65±65.29pg/ml,4.02±0.32ng/ml)and the middle-stage group(3 102.35±105.48pg/ml,4.98±0.41ng/ml),and the differences were statistically significant(t=9.092～30.644,all P<0.05).Family history of PD,high level of exosomal α-syn and high level of LCN-2 were the risk factors for the development of PD(Wald χ2=8.121,7.002,4.805,all P<0.05).The AUC(95%CI)of diagnosing PD with serum LCN-2 in combination with exosome α-syn was higher than that of exosome α-syn,while serum LCN-2 alone was used for diagnosis(Z=4.869,5.103,all P<0.05).Conclusion Serum exosomal α-syn and serum LCN-2 levels are significantly higher in PD patients,which can be associated with the exacerbation of PD,and combined exosomal α-syn and serum LCN-2 can assess the risk of developing PD.

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.

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.

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 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.