1.The study of combination treatment of dexmedetomidine and ulinastatin to acute lung injury induced by is-chemia reperfusion in rats
Jingjing ZENG ; Di REN ; Junfu LU ; Yongwen FENG
The Journal of Practical Medicine 2016;32(13):2112-2115
Objective To study the protection effect of dexmedetomidine and ulinastatin on acute lung in-jury caused by hepatic ischemia reperfusion. Methods 50 rats were randomly divided into 5 groups: the blank group, saline group, the dexmedetomidine group, the ulinastatin group, the dexmedetomidine and ulinastatin group. Ischemia-reperfusion models were established and drugs were administrated through femoral vein. The levels of MDA, SOD and ICAM were detected. Results Compared with the blank group, the rest of the groups of PaO2, pH and SOD activity were significantly lower (P < 0.05), and BE, pathological grading, MDA, ICAM levels were significantly higher (P<0.05). PaO2, pH and SOD activity of ulinastatin group were significantly lower in the phys-iological saline group (P < 0.05), BE, pathological grading, MDA level, ICAM levels were significantly elevated in the physiological saline group (P<0.05). Conclusion Combination of dexmedetomidine and ulinastatin have protection effect on acute lung injury caused by hepatic ischemia reperfusion, its mechanism may be related to in-hibit neutrophil aggregation, improve their antioxidant capacity and inhibition of lipid peroxidation.
2.Clinical effect of intraoperative electron beam radiotherapy in treatment of unresectable locally advanced pancreatic cancer
Miaoli ZHENG ; Yongwen SONG ; Qinfu FENG ; Yingtai CHEN ; Yirui ZHAI ; Minghui LI ; Hui FANG ; Jianwei ZHANG ; Pan MA ; Chengfeng WANG
Chinese Journal of Radiation Oncology 2017;26(4):405-409
Objective To assess the prognostic benefits of intraoperative radiotherapy (IORT) with electron beam among patients with unresectable locally advanced pancreatic cancer.Methods Between January 2009 and December 2014,167 patients with unresectable locally advanced pancreatic cancer received IORT with electron beam (10-20 Gy) in our hospital.After surgery,12 patients were treated with external beam radiotherapy,56 patients with chemoradiotherapy (CRT),and 17 patients with chemotherapy.Overall survival (OS),local recurrence,and toxicities were retrospectively analyzed.The Kaplan-Meier method was used to calculate survival rates,the log-rank test was used for survival difference analysis and univariate prognostic analysis,and the Cox model was used for multivariate prognostic analysis.Results The follow-up rate was 100%.The median OS time was 10.3 months,and the 2-year OS rate was 22%.The median progression-fiee survival (PFS) time was 6.3 months,and the 2-year PFS rate was 9.9%.The cancer-specific survival (CSS) time was 11.2 months,and the 2-year CSS rate was 23.6%.In the patients treated with IORT alone at doses of<15 Gy,15 Gy and>15 Gy,the median OS times were 6.2 months vs.9.1 months vs.22.2 months,and the 1-year OS rates were 10.0% vs.39.6% vs.74.4% (P=0.000).Among the patients receiving postoperative adjuvant therapy,those treated with IORT+CRT had the best survival,with a median OS time of 11.6 months (P=0.033).The univariate analysis showed that IORT dose (P =0.000),tumor size (P =0.006),and IORT applicator diameter (P =0.007) were prognostic factors.The multivariate analysis showed that IORT dose (P=0.000) and IORT combined with CRT (P=0.006) were independent prognostic factors.Conclusions IORT with electron beam is an effective and safe treatment strategy for unresectable locally advanced pancreatic cancer.After protecting surrounding organs,increasing the IORT dose can improve the survival.IORT combined with CRT should be recommended because it improves survival for unresectable locally advanced pancreatic cancer without increasing toxicities.
3.Protective effect of penehyclidine hydrochloride on secondary lung injury after traumatic shock in rats
Zhe DENG ; Zhongjiang ZHAO ; Shi LIANG ; Xinjian YANG ; Yongwen FENG ; Xinke MENG ; Dehong LIU ; Zuhui PU ; Jiwu SUN
Chinese Journal of Trauma 2012;28(6):556-560
Objective To observe the interfering effect of different doses of penehyclidine hydrochloride (PHC) on the mRNA expressions of nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) in the lung tissue of rats with traumatic shock so as to investigate the protective role of PHC in secondary long injury following traumatic shock and the underlying mechanism.Methods The traumatic shock model was established.A total of 104 Wistar rats were randomly divided into four groups:control group,shock group,low dose PHC group ( P1 group) and high dose PHC group ( P2 group).At the beginning of resuscitation,the rats in P1 and P2 groups were given transjugular intravenous injection of 2 ml/kg isotonic saline containing 0.15 mg/kg and 0- 45 mg/kg PHC respectively,while the rats in shock and control groups were injected only isometric isotonic saline.The rats in the four groups were killed at 2 h,6 h,12 h and 24 h after resuscitation respectively to detect the mRNA expressions of NF-κB and iNOS by using RT-PCR and determine the lung wet/dry weight (W/D) ratio,lung permeability index (LPI) and lung injury score (LIS).Results The mRNA expressions of NF-κB and iNOS,lung W/D ratio,LPI and LIS at all the time intervals in the shock,P1 and P2 groups were all significantly increased as compared with those in the control group (P<0.05).Howerver,the P2 group showed significant reduction in aspects of the mRNA expressions of NF- κB and iNOS,lung W/D ratio,LPI and LIS at all time points and P1 group also had significant decrease regarding the mRNA expressions of NF-κB and iNOS,lung W/D ratio at2 h,6 h,and LPI and LIS at 2 h,6 h,12 h,as compared with the shock group.Meanwhile,P2 group showed evident decrease at 6 h concerning the mRNA expressions of NF-κB and iNOS,lung W/D ratio,LPI and LIS as compared with P1 group (P < 0.05 ).Conclusions PHC,especially at a large dosage,can significantly mitigate the long injury secondary to traumatic shock,and the mechanism may be associated with the inhibition of mRNA expressions of NF-κB and iNOS.
4.The cholinergic pathway alleviates acute oxygen and glucose deprivation induced renal tubular cell injury by reducing the secretion of inflammatory medium of macrophages
Ming WU ; Lefeng WU ; Junfu LU ; Mingli LI ; Yun LI ; Ji XU ; Wenlan LIU ; Fen LIU ; Yongwen FENG
Medical Journal of Chinese People's Liberation Army 2017;42(8):663-667
Objective To investigate the effects of cholinergic pathway on acute renal tubular cell injury induced by acute oxygen and glucose deprivation. Methods Rat kidney macrophages were isolated and cultured for constructing macrophages and renal epithelial cells co-cultivating model of oxygen-glucose deprivation (OGD), and the model cells were divided into three groups: OGD alone group, acetylcholine (ACh 100μmol/L)+OGD group and ACh + galantamine (Gal 10μmol/L)+OGD group. The cells underwent OGD treatment for 1 hour, and normally cultured for 24 hours. The expressions of TNF alpha, IL-1 beta, and IL-10 in supernatant fluid were detected by ELISA, the renal tubular cell viability was determined by MTT assay, the expression of acetylcholine esterase (AChE) mRNA and protein were determined by RT-qPCR and Western blotting. The activity of AChE was determined by colorimetric method. Results The expressions of TNF alpha (pg/ml) in OGD, Ach+OGD group, Ach+Gal+OGD groups were 140.2±44.81, 119.46±4.42 and 103.31±1.62 respectively (P<0.05), those of IL-1β (pg/ml) were 172.26±13.51,144.34±5.53 and 119.37±11.42 respectively (P<0.05), and those of IL-10 (pg/ml) were 181.47±16.01, 173.62±10.12 and 188.36±8.73 respectively (P>0.05); The values of renal tubular cell proliferation were 55.02%±6.28%, 66.65%±6.47%, and 79.75%±4.22% respectively (P<0.01); the expressions of AChE mRNA in macrophages were 4.07±0.03, 4.22±0.15 and 3.98±0.29 respectively in the three groups (P>0.05); those of AchE protein were 0.66±0.07, 0.74±0.04 and 0.67±0.06 respectively (P>0.05); The activity of AChE (kU/L) was 0.51±0.02, 0.35±0.05 and 0.32±0.04 respectively (P=0.001, 0.001 and 0.368). Conclusions ACh and Gal could inhibit the secretion of inflammatory mediators and cholinesterase activity and can reduce the acute hypoxic renal tubular cell injury. The modulation of the cholinergic pathway in macrophages may be the important treatment method for acute renal injury in the future.
5.Knockdown of miR-296-5p alleviates nerve function damage after cere-bral infarction by activating ACE2 signaling pathway
Jibo LI ; Duanou XIAO ; Bin HE ; Feng XU ; Yongwen FENG
Chinese Journal of Pathophysiology 2024;40(8):1455-1462
AIM:To explore the effect of microRNA-296-5p(miR-296-5p)on neurological damage after cere-bral infarction(CI)and its regulatory relationship with angiotensin-converting enzyme 2(ACE2)signaling pathway medi-ated proliferation of endothelial progenitor cell(EPC).METHODS:Serum samples from 70 patients diagnosed with CI and accompanied by neurological damage in our hospital(CI group)and 70 healthy volunteers(healthy group)were se-lected.The mRNA expression of miR-296-5p,ACE2,and Mas in the serum of both groups were detected by RT-qPCR.The rat model of CI was constructed and SD rats were randomly divided into healthy control group,model control group,sh-miR-296-5p group,and ACE2 overexpression group(OE-ACE2 group).Neurological severity scores(NSS)score was evaluated.The CI status of rats in each group was observed by TTC staining.The mRNA expression of miR-296-5p,ACE2,and Mas in serum of rat was detected by RT-qPCR.EPC were isolated and cultured routinely,and were randomly divided into control group,sh-miR-296-5p group,OE-ACE2 group,OE-miR-296-5p+OE-ACE2 group,and sh-miR-296-5p+sh-ACE2 group.The viability of EPC was detected by CCK-8.Apoptosis of EPC was detected by flow cytometry.The mRNA expression of miR-296-5p,ACE2,and Mas in EPC was detected by RT-qPCR.The relationship between miR-296-5p and ACE2 was verified by dual luciferase reporter gene assay.RESULTS:(1)Clinical trial:compared with the healthy group,the level of miR-296-5p in serum of CI patients was obviously increased(P<0.05),while the mRNA ex-pression levels of ACE2 and Mas were obviously reduced(P<0.05).(2)Animal experiments:compared with the healthy control group,the NSS score,CI area,the level of miR-296-5p in serum,and the mRNA expression level of Mas in the model control group were obviously increased(P<0.05),while the mRNA expression level of ACE2 was obviously de-creased(P<0.05).Compared with the model control group,the NSS score,CI area,the level of miR-296-5p in serum,and the mRNA expression level of Mas in the sh-miR-296-5p group and OE-ACE2 group were obviously reduced(P<0.05),while the mRNA expression level of the ACE2 was obviously increased(P<0.05).(3)Cell experiment:Com-pared with the control group,the A450 and the level of miR-296-5p of EPC cells in the sh-miR-296-5p group and OE-ACE2 group were obviously reduced(P<0.05),the apoptosis rate,the mRNA expression level of ACE2,and Mas were obvious-ly increased(P<0.05).Compared with the sh-miR-296-5p group,the A450 and the level of miR-296-5p in the sh-miR-296-5p+sh-ACE2 group were obviously increased(P<0.05),the apoptosis rate,the mRNA expression level of ACE2,and Mas were obviously reduced(P<0.05).Compared with the OE-ACE2 group,the level of A450 and miR-296-5p in OE-miR-296-5p+OE-ACE2 group were obviously increased(P<0.05),the apoptosis rate,the mRNA expression level of ACE2,and Mas were obviously reduced(P<0.05).CONCLUSION:Knockdown of miR-296-5p may inhibit EPC proliferation by mediating the ACE2 signaling pathway,and alleviate neurological damage after CI.
6.Effect of MRI-guided intensity-modulated radiotherapy with bone marrow protection on hematologic toxicity in patients with rectal cancer undergoing concurrent chemoradiotherapy
Jianyang WANG ; Yuan TIAN ; Yuan TANG ; Xin WANG ; Ning LI ; Hua REN ; Hui FANG ; Yanru FENG ; Shulian WANG ; Yongwen SONG ; Yueping LIU ; Weihu WANG ; Yexiong LI ; Jing JIN
Chinese Journal of Radiation Oncology 2016;(3):244-248
Objective To reduce the radiation dose to the hematopoietic bone marrow (hBM) and acute hematologic toxicity (HT) in patients with rectal cancer undergoing intensity-modulated radiotherapy (IMRT).Methods The previously untreated patients with rectal cancer were enrolled in a prospective study.Pelvic magnetic resonance imaging ( MRI) was used to determine and delineate the distribution of hBM,and dose limitations were set (V5<95%,V10<90%,V20<80%,V30<65%).The neoadjuvant therapeutic regimen included concurrent IMRT (95% PTV 50 Gy/25 fractions,2 Gy/fractions),oxaliplatin 50 mg/m2 , qw,and capecitabine 1650 mg/m2 ,1 fractions/d (twice a day during radiotherapy).Results A total of 35 patients were enrolled and completed the therapeutic regimen.The incidence of grade 2-4 HT was 31.4%;among these patients, 9 ( 26%) experienced leucopenia, 6 ( 17%) experienced neutropenia, 1 ( 3%) experienced erythropenia,and 1(3%) experienced thrombocytopenia.No patients experienced grade ≥3 anemia.The multivariate logistic linear regression analysis showed that hBM-V5 was significantly correlated with the lowest counts of leukocytes ( P=0.005),neutrophils ( P=0.002),and platelets ( P=0.017).Conclusions The radiation dose to the hBM in the pelvis on MRI is significantly correlated with the incidence and severity of acute HT in patients with rectal cancer undergoing neoadjuvant concurrent chemoradiotherapy.Clinical Trial Registry ClinicalTrials.gov,registration number:NCT01863420.
7.Efficacy of S-1 and concurrent intensity-modulated radiotherapy for locally advanced gastric cancer:an interim study of phase Ⅱ clinical trial
Xin WANG ; Yuan TANG ; Jing JIN ; Hua REN ; Ning LI ; Tao ZHANG ; Hui FANG ; Xuesong CHEN ; Wenyang LIU ; Yanru FENG ; Jiajia ZHANG ; Yongwen SONG ; Weihu WANG ; Yueping LIU ; Shulian WANG ; Yexiong LI
Chinese Journal of Radiation Oncology 2016;25(4):351-355
Objective To observe the incidence of adverse reactions and short-term efficacy of S-1 and concurrent intensity-modulated radiotherapy ( IMRT) for locally advanced gastric cancer in a phase Ⅱclinical trial based on the phase I clinical trial.Methods Patients pathologically diagnosed with stage TN (+) gastric adenocarcinoma with local or distal metastasis after R0 resection were enrolled as subjects.IMRT was delivered 5 times per week with a total dose of 45 Gy in 25 fractions.S-1 was orally administered on the day of radiotherapy at a dose of 80 mg/m2 .Results A total of 40 patients, consisting of 6 patients from the phase I trial and 34 patients from the phaseⅡtrial, were enrolled in this study.In those patients, the age ranged between 27 and 73 years ( median age 50 years) and the male-to-female ratio was 3:1.Thirty-nine ( 98%) out of the forty patients completed radiotherapy and thirty-five ( 88%) completed concurrent chemotherapy.The most common grade 3-4 adverse reactions were nausea/anorexia ( 13%) , leukopenia ( 10%) , vomiting ( 8%) , radiation esophagitis ( 5%) , and neutropenia ( 5%) .There was no perioperative death.The 2-year overall survival and disease-free survival rates were 74% and 77%, respectively. Conclusions Postoperative S-1 and concurrent IMRT achieve satisfactory outcomes and tolerable toxicity in patients with locally advanced gastric cancer.
8.Preliminary clinical application of transcatheter closure of ventricular septal defect via radial approach
Wendong TANG ; Xudong XU ; Yuan BAI ; Jian SHEN ; Feng CHEN ; Ni ZHU ; Yongwen QIN ; Xianxian ZHAO
Journal of Interventional Radiology 2018;27(2):114-117
Objective To explore the feasibility and efficacy of transcatheter closure of ventricular septal defect (VSD) through radial artery combined femoral vein approach. Methods A total of 11 patients with congenital VSD, who were admitted to authors' hospital during the period from June 2017 to November2017, were enrolled in this study. The patterns of lesion included intracristal type (n=3) and perimembranous type (n=8), and in 3 patients the VSD was associated with concant ventricular septal aneurysm. Transcatheter closure of VSD via radial approach was carried out in all patients. The mean age of the patients was (37.82±12.44) years old, and the average body weight was (62.79±14.95) kg. The transthoracic echocardiography (TTE) showed that the mean diameter of VSD was (5.87±1.91)mm. The effect of transcatheter closure therapy was assessed by intraoperative TTE and left ventriculography. All patients were followed up with electrocardiogram and TTE at 24 hours and one, 3, 6 months after transcatheter closure therapy. Results Successful closure was achieved in 10 patients, and one patient had to be transferred to surgery because the catheter could not pass through the defect. The mean diameter of the implanted occluders was (7.50±3.60)mm, the average procedural time and fluoroscopy time were (47.20±5.45) min and (13.00±3.65) min respectively. The postoperative average in-bed time was (99.00±11.97) min. Two patients developed radial artery spasm during the operation. During the follow-up period lasting for a mean of (3.50±1.90) months, no serious complications, such as dropping of occluder, residual shunt, atrioventricular block, aortic regurgitation, radial artery occlusion, etc. occurred in the 10 patients. Conclusion For the treatment of VSD, transcatheter closure through radial artery combined with femoral vein approach is safe and effective. Therefore, this technique is worthy of clinical application.
9.Safty and acute toxicities of intraoperative electron radiotherapy for patients with abdominal tumors
Yirui ZHAI ; Qinfu FENG ; Minghui LI ; Xinyuan CHEN ; Chengfeng WANG ; Shulian WANG ; Yongwen SONG ; Shengji YU ; Xiang WANG ; Lixue XUAN ; Xiaoguang LI ; Ping BAI ; Jidong GAO ; Jing JIN ; Weihu WANG ; Yueping LIU ; Tiecheng WU ; Yexiong LI
Chinese Journal of Radiation Oncology 2010;19(5):448-451
Objective To investigate the safety and acute toxicities of intraoperative electron radiotherapy for patients with abdominal tumors.Methods From May 2008 to August 2009, 52 patients with abdominal tumors were treated with intraoperative electron radiotherapy,including 14 patients with breast cancer,19 with pancreatic cancer,3 with cervical cancer, 4 with ovarian cancer, 6 with sarcoma, and 6 with other tumors.Fifteen patients were with recurrent tumors.The intraoperative radiotherapy was performed using Mobetron mobile electron accelerator, with total dose of 9 - 18 Gy.In all, 29, 4 and 19 patients received complete resection, palliative resection and surgical exploration, respectively.The complications during the operations and within 6 months after operations were graded according to Common Terminology Criteria for Adverse Events v3.0 (CTC 3.0).Results The median duration of surgery was 190 minutes.Intraoperative complications were observed in 5 patients, including 3 with hemorrhage, 1 with hypotension,and 1 with hypoxemia, all of which were treated conservatively.The median hospitalization time and time to take out stitches was 12 and 13 days, respectively.And the in-hospital mortality was 4% (2/52).Twentyfour patients suffered post-operative adverse events, including 3 postoperative infections.With a median follow-up time of 183 days, 20% of patients sufferred from grade 3 to 5 adverse events, with hematological toxicities being the most common complication, followed by bellyache.Grade 1 and 2 toxicities which were definitely associated with intraoperative radiotherapy was 28% and 4%, respectively.None of grade 3 to 5 complications were proved to be caused by intraoperative radiotherapy.Conclusions Intraoperative electron radiotherapy is well tolerable and could be widely used for patients with abdominal tumors, with a little longer time to take out stitches but without more morbidities and toxicities compared surgery alone.
10.Effect of atractylenolide Ⅲ on stroke in spontaneously hypertensive rats and its mechanism
Jibo LI ; Yongwen FENG ; Wenfeng WU ; Xuezheng FAN ; Haixia LI
Journal of Clinical Medicine in Practice 2023;27(22):71-76
Objective To investigate the effect of atractylenolide Ⅲ(A Ⅲ)on stroke in spon-taneously hypertensive rats by regulating microRNA-296-5p(miR-296-5p)expression.Methods The spontaneously hypertensive rats(SHR)were given 0.9%sodium chloride solution freely for 2 months,and then fed with 1%sodium chloride solution to establish the stroke model of SHR.The rat models were randomly grouped into Model group,A Ⅲ low-dose group(A Ⅲ-L group),A Ⅲ high-dose group(A Ⅲ-H group),positive drug nimodipine group(Nim group),miR-296-5p agonist group(miR-296-5p agomir group),agomir NC group,A Ⅲ-H+miR-296-5p agomir group,and A Ⅲ-H+agomir NC group,with 12 in each group.The changes in neurological symptom scores,av-erage arterial pressure,survival time,and platelet adhesion rate were detected and recorded;hema-toxylin and eosin(HE)staining was applied to detect pathological changes in the CA1 region of the rat hippocampus;quantitative reverse transcription polymerase chain reaction(qRT-PCR)was ap-plied to detect the expression of miR-296-5p in the hippocampal CA1 region.Results Compared with the NC group,the Model group showed increases in neurological symptom score,mean arterial pressure,platelet adhesion rate,miR-296-5p expression,shortened survival time,and severe pathological damage to the hippocampal CA1 area(P<0.05);compared with the Model group,the neurological symptom scores,mean arterial pressure,platelet adhesion rate,and miR-296-5p expression in the A Ⅲ-L,A Ⅲ-H,and Nim groups decreased,the survival time was prolonged,and the pathological damage in the CA1 area of the hippocampus was alleviated(P<0.05);compared with Model group and agomir NC group,neurological symptom score,mean arterial pressure,platelet adhesion rate and miR-296-5p expression of rats in the miR-296-5p agomir group were increased,survival time was shortened,and pathological damage in hippocampal CA1 region was aggravated(P<0.05).compared with the A Ⅲ-H group and the AⅢ-H+agomir NC group,the neurological symptom score,average arterial pressure,platelet adhesion rate and miR-296-5p expression of rats were in-creased,the survival time was shortened,and the pathological damage in hippocampal CA1 region was serious in the AⅢ-H+miR-296-5p agomir group(P<0.05).Conclusion A Ⅲ may treat SHR stroke by inhibiting the expression of miR-296-5p.