1.Neural Stem Cells Transfected with Leukemia Inhibitory Factor Promote Neuroprotection in a Rat Model of Cerebral Ischemia.
Lili TIAN ; Wenli ZHU ; Yuanchu LIU ; Ye GONG ; Aowei LV ; Zhen WANG ; Xiaoli DING ; Shaowu LI ; Ying FU ; Yi LIN ; Yaping YAN
Neuroscience Bulletin 2019;35(5):901-908
Leukemia inhibitory factor (LIF) contributes to the neuroprotection by neural stem cells (NSCs) after ischemic stroke. Our aim was to explore whether LIF-transfected NSCs (LIF-NSCs) can ameliorate brain injury and promote neuroprotection in a rat model of cerebral ischemia. To accomplish this goal, we transfected NSCs with a lentivirus carrying the LIF gene to stably overexpress LIF. The LIF-NSCs reduced caspase 3 activation under conditions of oxygen-glucose deprivation in vitro. Transient cerebral ischemia was induced in rats by 2 h of middle cerebral artery occlusion (MCAo), and LIF-NSCs were intravenously injected at 6 h post-ischemia. LIF-NSC treatment reduced the infarction volume and improved neurological recovery. Moreover, LIF-NSCs improved glial cell regeneration and ameliorated white matter injury in the MCAo rats. The NSCs acted as carriers and increased the expression of LIF in the lesions to protect against cerebral infarction, suggesting that LIF-NSCs could be a potential treatment for cerebral infarction.
2.Survival analysis of preoperative involved-field irradiation with concurrent chemotherapy for patients with Siewert's type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction
Xin HUANG ; Jun WANG ; Qun ZHAO ; Yunjie CHENG ; Yuan TIAN ; Yi WANG ; Feng CAO ; Shaowu JING ; Wenpeng JIAO ; Yajing WU
Chinese Journal of Radiation Oncology 2018;27(7):649-655
Objective To analyze the clinical efficacy,toxicity and survival prognosis of patients diagnosed with Siewert type Ⅱ and Ⅲ locally advanced adenocarcinoma of esophagogastric junction (AEG) undergoing preoperative involved-field irradiation with concurrent chemotherapy. Methods A total of 45 cases were recruited in this prospective clinical trial. Prior to surgery, patients received 2 cycles of chemotherapy with XELOX and concurrent radiotherapy ( a total of 45 Gy in 25 fractions,5 times weekly). After 6-8 weeks,they underwent surgical resection. After the surgery,patients received 6 cycles of adjuvant chemotherapy. The completion of preoperative neoadjuvant chemoradiotherapy, postoperative pathological status,TNM down-staging effect and adverse reactions were observed. Kaplan-Meier method was applied to estimate survival analysis. Results All 45 patients completed preoperative neoadjuvant chemoradiotherapy. Among them, 39 patients completed 2 cycles of chemotherapy, and 6 patients completed 1 cycle of chemotherapy. The median time of surgical interval was 6 weeks. The R0resection rate was 96%.The pathological complete response (pCR) rate was 22%. The TNM down-staging rate was 69%.The incidence of acute radiation-induced esophagitis or gastritis was 44% and the incidence of radiation-induced pneumonitis was 7%. The incidence of grade 1-3 leukocytopenia,thrombocytopenia and neutropenia was 78%,47% and 44%,respectively. In terms of gastrointestinal reactions,the incidence of nausea,vomiting and loss of appetite was 62%,24% and 71%,respectively. No hematologic or nonhematologic adverse effects was observed at grade 4 or 5.The median follow-up time was 30 months. 11 patients died of cancer,1 patient was treatment-related death in the perioperative period and 1 patient died of pneumonia. The 1-,2-and 3-year progression-free survival (PFS) rates were 90%,70% and 67%,respectively. The 1-,2-and 3-year overall survival rates were 95%,80% and 75%,respectively. The 1-,2-and 3-year local control rates were 95%,84% and 84%, respectively. The 1-, 2-and 3-year distant metastasis rates were 7%, 25% and 25%, respectively. Conclusions Preoperative involved-field irradiation with concurrent chemotherapy yields relatively high clinical efficacy and is well tolerated by patients with Siewert typeⅡandⅢlocally advanced AEG.Patients are recommended to receive 4 cycles of adjuvant chemotherapy following neoadjuvant chemoradiotherapy and surgery.
3.MRI characteristics of solid papillary carcinomas in situ of breast
Li'na ZHANG ; Weisheng ZHANG ; Qingwei SONG ; Ailian LIU ; Shaowu WANG ;
Chinese Journal of Interventional Imaging and Therapy 2017;14(9):539-542
Objective To evaluate MRI characteristics of solid papillary carcinomas (SPCs) in situ of the breast.Methods A retrospective study included 5 patients with pathologically confirmed SPC in situ was performed.MRI data before operation including conventional MRI,dynamic contrast enhanced MRI (DCE-MRI) and DWI were analyzed.Results All the lesions showed iso/hypointensity on T1 FSPGR sequence,iso/hyperintensity on FSE T2WI sequence and STIR sequence.Mass enhancements were observed for all lesions with oval or irregular shapes on DCE-MRI.The margin of lesions were circumscribed,and internal enhancements were homogeneous or heterogeneous.Time intensity curve appeared a rapid increase in initial contrast phases and platform or outflow types in delayed phases.All the lesions on DWI showed slightly hyperintensity with the ADC value range from 1.34 × 10-3 mm2/s to 1.96)× 10-3 mm2/s.Conclusion MRI manifestations of SPC are characteristics,which may provide valuable information to distinguish SPC in situ from other invasive breast carcinomas.
4.Effect of nutritional status and inflammatory markers on acute adverse reactions during concurrent chemoradiotherapy for esophageal carcinoma
Qian WANG ; Jun WANG ; Yi WANG ; Shaowu JING ; Qing LIU ; Feng CAO ; Wenpeng JIAO ; Congrong YANG ; Yunjie CHENG ; Yajing WU
Chinese Journal of Radiation Oncology 2017;26(9):1012-1018
Objective To examine the effects of different pre-treatment nutritional status and inflammatory markers on acute adverse reactions in esophageal cancer patients during concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy.Methods The acute adverse reactions of 338 eligible esophageal cancer patients who received concurrent IMRT and chemotherapy in our hospital from 2006 to 2014 were reviewed.The effects of different pre-treatment nutritional status, such as body mass index level (BMI), albumin level (ALB), total lymphocyte count (TLC), the presence or absence of anemia, and inflammatory indicators including neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR), on acute adverse reactions in the patients were examined.Data were analyzed using the chi-square test with continuity correction and logistic regression analysis.Results The incidence rate of malnutrition in the patients based on their nutritional status was 5.62%-54.14%.The incidence rate of grade≥2 acute radiation esophagitis (RE) was significantly higher in the low ALB group than in the normal ALB group (P=0.000).The incidence rate of adverse reactions in the hematologic system increased as TLC decreased (P=0.006), but the incidence rate of acute radiation pneumonitis (RP) was reduced as TLC decreased (P=0.001).In addition, the incidence rate of grade ≥2 acute RE was significantly higher in the anemia group than in the non-anemia group.Inflammatory marker analysis demonstrated that the incidence rate of acute RE was significantly higher in the high NLR group and high PLR group than in the low NLR group and low PLR group (P=0.000 and P=0.024, respectively).Logistic regression analysis of nutritional status and inflammatory markers showed that TLC was an independent risk factor for acute adverse reactions in the hematologic system (P=0.001), and ALB and PLR were independent risk factors for acute RE (P=0.017 and P=0.011,respectively).Conclusions Nutritional status and inflammatory markers are associated with concurrent chemoradiotherapy-induced acute adverse reactions in esophageal carcinoma patients, and hence may be valuable indicators of acute adverse reactions during treatment.In addition, nutritional treatment and support care should be actively provided to the patients to prevent the development of acute adverse reactions during treatment.
5.Effects of Naotai formula on expression of Nrf2, HO-1 andhephaestin in hippocampus of cerebral ischemia/reperfusion rats
Juan HUANG ; Jun LIAO ; Xiwei PENG ; Yang LIU ; Shaowu CHENG ; Lihua QIN ; Yihui DENG ; Guozuo WANG ; Xu HE ; Jinwen GE
Chinese Pharmacological Bulletin 2017;33(10):1467-1472
Aim To investigate the effects of Naotai formula extract(NTE)on the expression of heme oxygenase-1(HO-1) and hephaestin(Heph) in hippocampus of rats after cerebral ischemia/reperfusion by Keap1-Nrf2/ARE signaling pathway.Methods Eighty rats were randomly divided into five groups as follows: sham operation group(Sham), cerebral ischemia/reperfusion group(I/R), low dose group of NTE(4.5 g·kg-1), middle dose group of NTE (9 g·kg-1) and high dose group of NTE(18 g·kg-1).Rats were pretreated by intragastric administration for three consecutive days, and then subjected to middle cerebral artery occlusion (MCAO) 2 hours before reperfusion.The rats were administered with intragastric administration for two days.After cerebral ischemia reperfusion 72 hours, the behavioral activity of rats was recorded by Zea Longa neurological score, and the infarct volume was measured by TTC staining.The expressions of Nrf2, HO-1 and Heph in hippocampus of cerebral ischemia reperfusion rats were observed by real-time quantitative PCR and Western blot, respectively.Results Compared with model group, the neurobehavioral scores significantly decreased in NTE high-dose and middle-dose groups (P<0.01);the infarct volume of NTE groups markedly decreased (P<0.01);the expression of HO-1 mRNA apparently increased (P<0.05) in NTE groups;the expression of Heph mRNA significantly increased in NTE middle-dose and high-dose groups (P<0.05);the expression of Nrf2 and Heph protein evidently increased in the NTE middle and high dose groups (P<0.05, P<0.01);and the expression of HO-1 protein also increased in NTE groups(P<0.01).Conclusions Naotai formula can relieve cerebral ischemia-reperfusion injury.The mechanism might be associated with activating Keap1-Nrf2/ARE signaling pathways, promoting HO-1 generation, advancing the expression of Heph, and then reducing brain iron deposition, to achieve the protection of neurons after cerebral ischemia-reperfusion.
6.Feasibility of intensity-modulated radiation therapy with concurrent chemotherapy in patients with Siewert type Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction before surgery
Jun WANG ; Qun ZHAO ; Xin HUANG ; Yuan TIAN ; Yong LI ; Yi WANG ; Feng CAO ; Yunjie CHENG ; Shaowu JING
Chinese Journal of Radiation Oncology 2017;26(11):1269-1275
postoperative pathological examination results and radiotherapy toxicities. Results All the 45 patients completed preoperative concurrent chemoradiotherapy and surgery, with two cycles of chemotherapy in 39 patients and one cycle in 6 patients. The rates of R0resection and pathological complete response(pCR) were 95.6%(43/45)and 22.2%(10/45), respectively. There were 10(22.2%), 17(37.8%), 15 (33.3%),and 3(6.7%)patients with tumor regression grades 0,1,2,3,respectively. The rate of lymph node metastasis was 37.8%(17/45),and the lymph node ratio was 4.33%(46/1 062). The postoperative pathological examination showed that T and N downstaging after surgery was observed in 24 and 26 patients, respectively;the proportions of patients with T3-T4tumors and positive lymph nodes after surgery declined by 51.1%(P=0.000)and 42.2%(P=0.000), respectively. The overall incidence of radiation esophagitis/gastritis was 44.4%(20/45), and the incidence rates of grade 1, 2, and 3 radiation esophagitis/gastritis were 18%,22%,and 4%,respectively. The incidence of acute radiation pneumonitis was 6.7%(3/45), all in grades 1 and 2. There was one perioperative treatment-related death. Conclusions Two cycles of XELOX chemotherapy combined with concurrent 45 Gy radiotherapy before surgery in patients with locally advanced Siewert type Ⅱ and Ⅲ AEG can achieve a relatively high pCR rate,effectively reduce the lymph node metastasis rate, achieve downstaging, and increase R0resection rate. This regimen has many good advantages,including low incidence of acute toxicities,good tolerability,and acceptable rate of perioperative treatment-related deaths. The target volume delineation involving metastatic lymph nodes is feasible.
7.Clinical value of induction chemotherapy plus concurrent radiochemotherapy for locally advanced non-small cell lung cancer:a Meta analysis
Shaowu JING ; Jun WANG ; Yunjie CHENG ; Qing LIU ; Fengpeng WU ; Congrong YANG ; Yi WANG ; Feng CAO ; Wenpeng JIAO
Chinese Journal of Radiation Oncology 2016;(3):239-243
Objective To investigate the clinical effect of induction chemotherapy plus concurrent radiochemotherapy in the treatment of locally advanced non-small cell lung cancer (NSCLC) through a meta-analysis.Methods CBM, CNKI, Cochrane Library, PubMed, and EMbase were searched for the articles on comparison between induction chemotherapy plus concurrent radiochemotherapy and concurrent radiochemotherapy for patients with locally advanced NSCLC.According to the inclusion and exclusion criteria, the data on short-term outcome and survival were collected.A Meta-analysis was performed to evaluate the clinical effect of induction chemotherapy followed by concurrent radiochemotherapy.Results A total of 5 articles were included, which involved 845 patients.The results showed that the short-term outcome and the 2-and 3-year survival rates were similar between patients receiving induction chemotherapy plus concurrent radiochemotherapy and those receiving concurrent radiochemotherapy ( OR=0.875, 95% CI 0.507-1.510, P=0.631;HR=0.770, 95% CI 0.515-1.151, P=0.203;HR=0.809, 95% CI 0.559-1.172, P=0.262), but the patients receiving induction chemotherapy plus concurrent radiochemotherapy showed a significantly higher incidence rate of grade ≥ 3 leukopenia than those receiving concurrent radiochemotherapy alone ( OR=0.637, 95% CI 0.435-0.931, P=0.020).Conclusions Induction chemotherapy plus concurrent radiochemotherapy shows no significant advantages over concurrent radiochemotherapy alone in the short-term outcome and 2-and 3-year survival rates, but it significantly increases myelosuppression.Since there are few studies involving a limited number of cases included in this analysis, more multicenter randomized trials are needed to provide more detailed data and further clarify the clinical value of induction chemotherapy plus concurrent radiochemotherapy.
8.Expression of Adult and Neonatal Nav1.5 Isoforms in the Dorsal Root Ganglia Neurons of Rats with Spared Nerve Injury
Jiatao ZHENG ; Jun WANG ; Shaowu OU ; Yunjie WANG
Journal of Shenyang Medical College 2016;18(4):229-233,236
Objective:To study the expression of adult and neonatal Nav1.5 isoforms in the dorsal root ganglia (DRG) neurons of rats with spared nerve injury (SNI) . Methods:The expression of adult and neonatal Nav1.5 isoforms in the DRG neurons of rats with SNI was detected by RT-PCR, DNA sequencing, restriction enzyme digestion, immunohistochemistry and immunofluo-rescence methods. The expression of PKC-γwas detected by Western blot. Results:Both adult and neonatal Nav1.5 isoforms were expressed in the DRG neurons, but their expression ratio was approximately 2.5∶1. In SNI rat models, the expression of both adult and neonatal Nav1.5 isoforms decreased by approximately a half in both mRNA and protein levels. In contrast, the expression of PKC-γincreased by approximately one-fold. Conclusions:Both adult and neonatal Nav1.5 isoforms expressed in the DRG neurons of rat,but their expression levels decrease in pain models. The up-regulation of PKC-γmay directly or indirectly down-regulate the expression of Nav1.5 isoforms in SNI rat models,which may further involve in the pathological process of neuropathic pain.
9.Lymph node metastasis patterns and influencing factors in patients with limited esophageal small cell carcinoma.
Wenpeng JIAO ; Jun WANG ; Email: WANGJUNZR@163.COM. ; Qing LIU ; Shaowu JING ; Congrong YANG ; Yi WANG ; Feng CAO ; Yunjie CHENG
Chinese Journal of Oncology 2015;37(12):899-903
OBJECTIVETo explore the patterns and influencing factors of lymph node metastasis in limited esophageal small cell carcinoma (PESCC).
METHODSA total of 98 limited stage PESCC patients who underwent surgery were selected for this study. The lymph node metastasis ratio at different sites, depth of invasion, tumor length and other factors were analyzed to assess their influence on lymph node metastasis.
RESULTSAmong the 98 PESCC cases, 46 cases had lymph node metastasis (46.9%). 100 out of 833 lymph nodes had metastasis, with a metastasis ratio of 12.0%. For upper thoracic esophageal small cell carcinomas, lymph node metastasis ratios were 42.9%, 12.5%, 0 and 0 in the superior mediastinum, middle mediastinum, inferior mediastinum and abdominal cavity, respectively. In the middle thoracic PESCCs, the lymph node metastasis ratios were 18.8%, 7.7%, 15.7%, and 15.3%, respectively. In the lower thoracic PESCCs, the lymph node metastasis ratios were 0, 0, 27.3% and 23.5%, respectively. Lymph node metastasis rates in PESCCs at stages T1, T2, T3, T4 were 15.4%, 42.3%, 63.9%, and 80.0%, respectively. The lymph node metastasis ratios in PESCCs at stages T1, T2, T3, T4 were 2.0%, 8.3%, 17.8% and 25.0%, respectively. Lymph node metastasis rate and lymph node metastasis ratio at different T stages were of significant difference (P<0.05 for all). Lymph node metastasis rates in patients with tumor <3 cm, 3-5 cm, and >5 cm were 30.6%, 46.9% and 66.7%, respectively, and lymph node metastasis ratios were 5.4%, 11.0% and 21.1%, respectively. Lymph node metastasis rate and lymph node metastasis ratio in patients with different tumor length had significant differences (P<0.05 for all). Lymph node metastasis ratio was 11.6% in the Chr-A negative and weak positive group, much higher than 4.3% in the Chr-A positive group (P=0.013). There was a tendency that lymph node metastasis ratio of NSE-positive group was higher than that of NSE-negative and weak positive group (P=0.069). The logistic univariate analysis did not find high risk factors of distant lymph node metastasis (all P>0.05). Logistic multivariate analysis found that only depth of invasion was a risk factor of lymph node metastasis in limited PESCC (P=0.002).
CONCLUSIONSEsophagus small cell carcinomas sometimes have early lymph node metastases in many sites and distant range. The middle thoracic PESCCs tend to have extensive metastasis quite common in the upper mediastinal lymph nodes. Lower mediastinal and abdominal lymph node metastases are often seen in lower thoracic PESCCs. The depth of invasion and tumor length are main factors influencing mediastinal lymph node metastasis. The depth of invasion is an independent risk factor for lymph node metastasis.
Abdominal Cavity ; Carcinoma, Small Cell ; pathology ; secondary ; Esophageal Neoplasms ; pathology ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Mediastinum ; Multivariate Analysis ; Neoplasm Invasiveness ; Risk Factors
10.The patterns of lymph node metastasis in adenocarcinoma of esophagogastric junction:a reference for target volume delineation in radical radiotherapy
Jun WANG ; Yanjun ZHANG ; Qing LIU ; Yin GUO ; Na LI ; Yajing WU ; Yi WANG ; Feng CAO ; Shaowu JING ; Congrong YANG
Chinese Journal of Radiation Oncology 2015;(4):367-371
Objective To analyze the patterns and distribution of lymph node metastasis in patients with adenocarcinoma of the esophagogastric junction ( AEG). Methods The pathological data of 393 patients with AEG from 2006 to 2009 were analyzed. The patterns and distribution of lymph node metastasis were analyzed in patients with different Siewert subtypes, depths of tumor invasion, and maximum diameters of the tumor, and the high?risk lymphatic drainage areas were investigated. Between?group comparison was performed by χ2 test. Results The metastatic rate and ratio of abdominal lymph nodes in AEG were 69?? 2%and 31?? 31%, respectively. The incidence rates of lymph node metastasis in the cardia, lesser curvature, left gastric artery, splenic artery, splenic hilum, mesenteric root, and abdominal aorta were the highest. The metastatic rate and ratio of mediastinal lymph nodes were 16?? 4% and 8?? 3%, respectively. The incidence rates of lymph node metastasis in the lower paraesophageal, esophageal hiatus, and superior diaphragmatic areas were the highest. Compared with Siewert type II and type III AEG, Siewert type I AEG had a significantly higher mediastinal lymph node metastatic rate (P= 0?? 003) and a significantly lower abdominal lymph node metastatic ratio (P= 0?? 002).The metastatic ratios of lymph nodes in multiple abdominal regions were higher in patients with stage T3+T4 AEG and a maximum tumor diameter of ≥6 cm than in the control group, while the metastatic ratios of mediastinal lymph nodes in groups with different maximum tumor diameters were similar. The metastatic ratios of lymph nodes in the greater curvature, hepatoduodenal ligament, and inferior diaphragmatic areas were lower than 10% in all groups. Conclusions In radiotherapy for AEG, the abdominal high?risk lymphatic drainage areas involve the cardia, lesser curvature, left gastric artery, splenic artery, splenic hilum, mesenteric root, and abdominal aorta, while the mediastinal high?risk lymphatic drainage areas involve the lower paraesophageal, esophageal hiatus, and superior diaphragmatic areas. In addition, the personalized target volume design should be based on the patterns of lymph node metastasis with different Siewert subtypes and clinical pathological characteristics.

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