1.Monitoring stem cell transplantation in rat cerebral ischemic infarction model with 131I-FIAU/TK reporter gene system
Tao, WU ; Rui, AN ; Bin-qing, ZHANG ; Xun, SUN ; Jun-tao, LANG
Chinese Journal of Nuclear Medicine 2011;31(5):301-305
Objective To study the biodistribution of 131 I-2'-deoxy-1-β-D-arabinofuranosy1-5-iodouracil (FIAU) in the rat middle cerebral artery occlusion model and the expression of thymidine kinase (TK) gene in brain tissue after gene-modified stem cell transplantation,and thus evaluate the possibility of further noninvasive monitoring of stem cell transplantation therapy in cerebral infarction.Methods Adenovirus recombinant Ad5-TK-intemal ribosome entry site-brain derived heurotrophic factor-enhanced green florecent protein(IRES-BDNF-EGFP) carrying TK-IRES-BDNF gene was prepared.Cerebral infarction model was established in rats by intraluminal middle cerebral artery occlusion with nylon monofilament.Gene modified bone marrow mesenchymal stem cells were transplanted via intraparenchymal route,lateral ventricle,carotid artery and tail vein,respectively.The normal rats were used as controls.131 I- FAU was prepared to be the tracer for biodistribution study and the % ID/g was calculated based on measurement of the tissue radioactivity counts.The expression of TK gene was evaluated by quantitative real-time PCR (QR-PCR) and Western blot analysis.Data were analyzed with independent-samples t-test,one-way analysis of variance (ANOVA) test,and Pearson linear correlation test.Results The % ID/g of infarcted brain tissue in the intraparenchymal group was 0.124 ± 0.013,which was significantly higher than that in lateral ventricle group (0.052 ±0.004),carotid artery group (0.061 ±0.002),tail vein group (0.059 ±0.005) and control group (0.005 ±0.001) (t =2.913 - 5.652,all P<0.05),while there were no statistically significant differences among the other route transplanted groups ( t =0.694 - 1.448,all P > 0.05 ).The differences of % ID/g between the infarcted and contralateral sides of brain tissue in all transplanted groups were statistically significant (t =9.004 - 15.734,all P < 0.05 ),while there was no statistically significant difference of this parameter between both sides of brain tissue in control group (t =1.511,P =0.182).The expression of TK gene in intraparenchymal group was significantly higher than other groups (t =7.482 -12.371,all P <0.05).The expression levels ofTK gene on QR-PCR showed a positive correlation with %ID/g of the brain tissue ( r =0.971,P < 0.001 ).Similarly,the ratio of TK/β-actin by the Western blot analysis correlated with the % ID/g ( r =0.899,P =0.002 ).Conclusion Intraparenchymal route may be the way of choice for cell transplantation therapy of cerebral infarction.If suitable radionuclide tracer is available,PET or SPECT may be potentially used for noninvasive monitoring of stem cell transplantation in cerebral infarction in vivo.
2.Expression and distribution characteristics of human orthology of mammalian enabled in glioma
Xue-Tao DONG ; Xue-Jun YANG ; Hua-Min WANG ; Wei WANG ; Yu LI ; Bin ZHANG ; Sheng-Ping YU ; Hao-Lang MING
Chinese Journal of Neuromedicine 2011;10(2):132-136
Objective To observe the expression and distribution characteristics of human orthology of mammalian enabled (hMena) in human glioma, and analyze the correlation of its expression with the pathological grade of the glioma. Methods Sixty-five specimens of glioma with different pathological grades were collected; among these samples, according to the WHO classification, grade Ⅰ was noted in 9, grade Ⅱ in 16, grade Ⅲ in 19 and grade Ⅳ in 21; in 6 of these patients with grade Ⅳ glioblastoma multiforme, tissues from the lesion, the junctional zone between the glioma and the normal brain tissue, and the surrounding area (with a diameter of 1.5 cm) were separated under the assistance of neuronavigation system. Another 5 normal brain tissues from patients with cerebral hemorrhage performed decompression were chosen as controls. Immunohistochemistry and Western blotting were used to detect the expression and distribution characteristics of hMena. Results The hMena expression was negative in control brain tissue, and its positive rates of gliomas with different grades were 11.11% (1/9), 25% (4/16), 84.21% (16/19) and 90.48% (19/21) in gliomas of grade Ⅰ, grade Ⅱ, grade Ⅲ and grade Ⅳ, respectively; and these staining was mainly located in cytoplasm; the hMena expression in gliomas with different grades was significantly different (x2=34.935, P=0.000). The expression rate of hMena was positively correlated with the increasing grade of WHO classification (rs=0.682, P=0.000).Western blotting indicated that, in gliomas with different pathological grades, hMena expression levels increased gradually with the increase of pathological grade. Conclusion The hMena protein might play a role in the malignant progression of glioma.
3.Individualized diagnosis and treatment of neurofibromatosis type Ⅱ guided by molecular genetic analysis
Wei WANG ; Xue-Jun YANG ; Hua-Min WANG ; Xue-Tao DONG ; Yu LI ; Hao-Lang MING ; Bin ZHANG ; Sheng-Ping YU ; Bing-Cheng REN ; Chong CHEN ; Bin LIU ; Zhi-Feng LIU
Chinese Journal of Neuromedicine 2011;10(6):564-569
Objective To establish a molecular genetic analysis method applicable clinically for genetic diagnosis of patients with neurofibromatosis type Ⅱ (NF2) and their offsprings, and further guide the genetic counseling of NF2 family, condition monitoring, follow-up as well as clinical intervention of the patients. Methods Ten patients with NF2, admitted to our hospital from January 2009 to January 2010, were chosen;tumorigenic Schwann cells in Schwannoma were isolated and purified for primary culture. Genomic DNA was extracted from tumorigenic Schwann cells and from the blood of 2 patients and their offsprings who agreed to accept gene sequencing;the NF2 gene was sequenced (El-15 and El7 exons and adjacent introns). According to the implication of NF2 gene sequencing, genetic counseling was given to the NF2 family, and the potential NF2 patients in offsprings were followed up in a long-term. Results Schwannoma tissue and genomic DNA bank were established initially. Totallysame NF2 gene mutations were detected in genomic DNA extracted both from tumorigenic Schwann cells and blood cells in the same patient. By comparing the genotypes between the patients and the offsprings,consistent NF2 gene mutations were found between a female patient and her daughter aged 3, but not completely consistent gene mutations between another female patient and her son aged 15. All of the mutations in NF2 gene were located in the control region near the exons. Based on the patient's clinical manifestations and symptoms, reasonable plans for clinical interventions and follow-up were developed.Conclusion Schwannoma tissue and genomic DNA bank could supply the bio-resource for genetic molecular testing and treatment studies. Molecular genetic analysis would apply in clinical practice guidance, NF2 risk prediction, and follow-up plan for high-risk NF2 individuals. Early diagnosis and treatment, condition monitoring and long term follow-up and personalized clinical intervention are needed to improve the quality of life and prolong the survival.
4.Obstetric outcomes in Chinese women with endometriosis: a retrospective cohort study.
Hong LIN ; Jin-Hua LENG ; Jun-Tao LIU ; Jing-He LANG
Chinese Medical Journal 2015;128(4):455-458
BACKGROUNDThe effect of endometriosis on obstetric outcomes is still ambiguous. The aim of our study was to determine the association between endometriosis and adverse obstetric outcomes in a cohort of Chinese women.
METHODSA retrospective cohort study was undertaken to compare obstetric outcomes between 249 women with endometriosis and 249 women without endometriosis. All women were nulliparous and achieved singleton pregnancies naturally. Women with endometriosis were diagnosed during surgery and confirmed histologically. Odds ratios (ORs) and 95% confidence intervals (CIs) of measures of obstetric outcomes were calculated.
RESULTSWomen with endometriosis showed significantly increased risks of preterm labor (adjusted OR, 2.42; 95% CI, 1.05-5.57), placenta previa (adjusted OR, 4.51; 95% CI, 1.23-16.50), and cesarean section (adjusted OR, 1.93; 95% CI, 1.31-2.84). No significant differences were observed in the incidence of pregnancy-induced hypertension, fetal growth restriction, small for gestational age, placental abruption, or luteal support in the first trimester between the two groups.
CONCLUSIONSWomen with endometriosis are at a higher risk of preterm labor, placenta previa, and cesarean section during pregnancy and need additional care.
Adult ; Cesarean Section ; statistics & numerical data ; Endometriosis ; epidemiology ; physiopathology ; Female ; Humans ; Obstetric Labor, Premature ; epidemiology ; Placenta Previa ; epidemiology ; Pregnancy ; Pregnancy Outcome ; Retrospective Studies
5.Different fractionation schedules of radiotherapy in preoperative concurrent chemoradiotherapy for thoracic esophageal cancer:a clinical study
Jiahua LYU ; Tao LIU ; Tao LI ; Fang LI ; Junchao WANG ; Chuan YANG ; Jun ZHANG ; Jie WANG ; Jinyi LANG
Chinese Journal of Radiation Oncology 2018;27(6):576-580
Objective To investigate the clinical efficacy and safety of preoperative hypofractionated and conventionally-fractionated chemoradiotherapy for thoracic esophageal cancer. Methods A total of 86 patients with thoracic esophageal cancer receiving chemoradiotherpy in Sichuan Cancer Hospital between 2002 and 2011 were enrolled and randomized into the preoperative hypofractionated chemoradiotherapy group ( group A, n=41, 30 Gy in 10 fractions for 2 weeks ) and conventionally-fractionated chemoradiotherapy group ( group B, n=45, 40 Gy in 20 fractions for 4 weeks ) . Surgery was performed at 2-6 weeks after chemoradiotherapy. The probability of patients' survival was estimated by Kaplan-Meier method and analyzed by log-rank test. Results In groups A and B, the pathological downstaging rates were 68% and 56%( P=0. 270) , the R0 resection rates were 95% and 89%( P=0. 437) and the pCR rates of 32% and 24%( P=0. 480).The 1-,3-and 5-year overall survival (OS) rates were 78% and 69%,44% and 44%,29% and 33%(P=0. 114,0. 223,0. 289), and the progression-free survival (PFS) rates were 71% and 62%,39% and 38%,24% and 29%(P=0. 211,0. 689,0. 331), respectively. The incidence rate of chemoradiothery-and surgery-related adverse events did not differ between two groups (P=0. 089-0. 872).The average length of hospital stay, radiotherapy cost and preoperative treatment costs in group A were significantly less compared with those in group B (P=0. 000,0. 000,0. 000). Conclusions Both preoperative hypofractionated and conventionally-fractionated chemoradiotherapy can be used as the regimen of preoperative chemoradiotherapy in patients with resectable thoracic esophageal carcinoma. Compared with conventionally-fractionated chemoradiotherapy, preoperative hypofractionated chemoradiotherapy has shorter treatment cycle, shorter length of hospital stay and lower radiotherapy cost, which is more easily accepted by patients.
6.Resveratrol pretreatment alleviates NLRP3 inflammasomemediated cardiomyocyte pyroptosis by targeting TLR4/MyD88/ NF-κB signaling cascade in coronary microembolization-induced myocardial damage
Chang-Jun LUO ; Tao LI ; Hao-Liang LI ; You ZHOU ; Lang LI
The Korean Journal of Physiology and Pharmacology 2023;27(2):143-155
Percutaneous coronary intervention and acute coronary syndrome are both closely tied to the frequently occurring complication of coronary microembolization (CME). Resveratrol (RES) has been shown to have a substantial cardioprotective influence in a variety of cardiac diseases, though its function and potential mechanistic involvement in CME are still unclear. The forty Sprague–Dawley rats were divided into four groups randomly: CME, CME + RES (25 mg/kg), CME + RES (50 mg/kg), and sham (10 rats per group). The CME model was developed. Echocardiography, levels of myocardial injury markers in the serum, and histopathology of the myocardium were used to assess the function of the cardiac muscle. For the detection of the signaling of TLR4/MyD88/NF-κB along with the expression of pyroptosisrelated molecules, ELISA, qRT-PCR, immunofluorescence, and Western blotting were used, among other techniques. The findings revealed that myocardial injury and pyroptosis occurred in the myocardium following CME, with a decreased function of cardiac, increased levels of serum myocardial injury markers, increased area of microinfarct, as well as a rise in the expression levels of pyroptosis-related molecules. In addition to this, pretreatment with resveratrol reduced the severity of myocardial injury after CME by improving cardiac dysfunction, decreasing serum myocardial injury markers, decreasing microinfarct area, and decreasing cardiomyocyte pyroptosis, primarily by blocking the signaling of TLR4/MyD88/NF-κB and also reducing the NLRP3 inflammasome activation. Resveratrol may be able to alleviate CME-induced myocardial pyroptosis and cardiac dysfunction by impeding the activation of NLRP3 inflammasome and the signaling pathway of TLR4/MyD88/NF-κB.
7.Puerarin pretreatment attenuates cardiomyocyte apoptosis induced by coronary microembolization in rats by activating the PI3K/Akt/GSK-3β signaling pathway
Zhi-Qing CHEN ; You ZHOU ; Jun-Wen HUANG ; Feng CHEN ; Jing ZHENG ; Hao-Liang LI ; Tao LI ; Lang LI
The Korean Journal of Physiology and Pharmacology 2021;25(2):147-157
Coronary microembolization (CME) is associated with cardiomyocyte apoptosis and cardiac dysfunction. Puerarin confers protection against multiple cardiovascular diseases, but its effects and specific mechanisms on CME are not fully known. Hence, our study investigated whether puerarin pretreatment could alleviate cardiomyocyte apoptosis and improve cardiac function following CME. The molecular mechanism associated was also explored. A total of 48 Sprague-Dawley rats were randomly divided into CME, CME + Puerarin (CME + Pue), sham, and sham + Puerarin (sham + Pue) groups (with 12 rats per group). A CME model was established in CME and CME + Pue groups by injecting 42 μm microspheres into the left ventricle of rats. Rats in the CME + Pue and sham + Pue groups were intraperitoneally injected with puerarin at 120 mg/kg daily for 7 days before operation. Cardiac function, myocardial histopathology, and cardiomyocyte apoptosis index were determined via cardiac ultrasound, hematoxylin-eosin (H&E) and hematoxylin-basic fuchsin-picric acid (HBFP) stainings, and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Western blotting was used to measure protein expression related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway. We found that, puerarin significantly ameliorated cardiac dysfunction after CME, attenuated myocardial infarct size, and reduced myocardial apoptotic index. Besides, puerarin inhibited cardiomyocyte apoptosis, as revealed by decreased Bax and cleaved caspase-3, and up-regulated Bcl-2 and PI3K/Akt/GSK-3β pathway related proteins. Collectively, puerarin can inhibit cardiomyocyte apoptosis and thus attenuate myocardial injury caused by CME. Mechanistically, these effects may be achieved through activation of the PI3K/Akt/GSK-3β pathway.
8.Puerarin pretreatment attenuates cardiomyocyte apoptosis induced by coronary microembolization in rats by activating the PI3K/Akt/GSK-3β signaling pathway
Zhi-Qing CHEN ; You ZHOU ; Jun-Wen HUANG ; Feng CHEN ; Jing ZHENG ; Hao-Liang LI ; Tao LI ; Lang LI
The Korean Journal of Physiology and Pharmacology 2021;25(2):147-157
Coronary microembolization (CME) is associated with cardiomyocyte apoptosis and cardiac dysfunction. Puerarin confers protection against multiple cardiovascular diseases, but its effects and specific mechanisms on CME are not fully known. Hence, our study investigated whether puerarin pretreatment could alleviate cardiomyocyte apoptosis and improve cardiac function following CME. The molecular mechanism associated was also explored. A total of 48 Sprague-Dawley rats were randomly divided into CME, CME + Puerarin (CME + Pue), sham, and sham + Puerarin (sham + Pue) groups (with 12 rats per group). A CME model was established in CME and CME + Pue groups by injecting 42 μm microspheres into the left ventricle of rats. Rats in the CME + Pue and sham + Pue groups were intraperitoneally injected with puerarin at 120 mg/kg daily for 7 days before operation. Cardiac function, myocardial histopathology, and cardiomyocyte apoptosis index were determined via cardiac ultrasound, hematoxylin-eosin (H&E) and hematoxylin-basic fuchsin-picric acid (HBFP) stainings, and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Western blotting was used to measure protein expression related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway. We found that, puerarin significantly ameliorated cardiac dysfunction after CME, attenuated myocardial infarct size, and reduced myocardial apoptotic index. Besides, puerarin inhibited cardiomyocyte apoptosis, as revealed by decreased Bax and cleaved caspase-3, and up-regulated Bcl-2 and PI3K/Akt/GSK-3β pathway related proteins. Collectively, puerarin can inhibit cardiomyocyte apoptosis and thus attenuate myocardial injury caused by CME. Mechanistically, these effects may be achieved through activation of the PI3K/Akt/GSK-3β pathway.
9.Long-term results of extensive aortoiliac occlusive disease (EAIOD) treated by endovascular therapy and risk factors for loss of primary patency.
Xiao-Lang JIANG ; Yun SHI ; Bin CHEN ; Jun-Hao JIANG ; Tao MA ; Chang-Po LIN ; Da-Qiao GUO ; Xin XU ; Zhi-Hui DONG ; Wei-Guo FU
Chinese Medical Journal 2020;134(8):913-919
BACKGROUND:
Although endovascular therapy has been widely used for focal aortoiliac occlusive disease (AIOD), its performance for extensive AIOD (EAIOD) is not fully evaluated. We aimed to demonstrate the long-term results of EAIOD treated by endovascular therapy and to identify the potential risk factors for the loss of primary patency.
METHODS:
Between January 2008 and June 2018, patients with a clinical diagnosis of the 2007 TransAtlantic Inter-Society Consensus II (TASC II) C and D AIOD lesions who underwent endovascular treatment in our institution were enrolled. Demographic, diagnosis, procedure characteristics, and follow-up information were reviewed. Univariate analysis was used to identify the correlation between the variables and the primary patency. A multivariate logistic regression model was used to identify the independent risk factors associated with primary patency. Five- and 10-year primary and secondary patency, as well as survival rates, were calculated by Kaplan-Meier analysis.
RESULTS:
A total of 148 patients underwent endovascular treatment in our center. Of these, 39.2% were classified as having TASC II C lesions and 60.8% as having TASC II D lesions. The technical success rate was 88.5%. The mean follow-up time was 79.2 ± 29.2 months. Primary and secondary patency was 82.1% and 89.4% at 5 years, and 74.8% and 83.1% at 10 years, respectively. The 5-year survival rate was 84.2%. Compared with patients without loss of primary patency, patients with this condition showed significant differences in age, TASC II classification, infrainguinal lesions, critical limb ischemia (CLI), and smoking. Multivariate logistic regression analysis showed age <61 years (adjusted odds ratio [aOR]: 6.47; 95% CI: 1.47-28.36; P = 0.01), CLI (aOR: 7.81; 95% CI: 1.92-31.89; P = 0.04), and smoking (aOR: 10.15; 95% CI: 2.79-36.90; P < 0.01) were independent risk factors for the loss of primary patency.
CONCLUSION
Endovascular therapy was an effective treatment for EAIOD with encouraging patency and survival rate. Age <61 years, CLI, and smoking were independent risk factors for the loss of primary patency.
Arterial Occlusive Diseases/surgery*
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Endovascular Procedures/methods*
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Female
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Humans
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Iliac Artery/surgery*
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Kaplan-Meier Estimate
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Male
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Middle Aged
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Retrospective Studies
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Risk Factors
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Stents
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Survival Rate
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Treatment Outcome
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Vascular Patency
10. Retrospective study of low-to-moderate dose glucocorticoids on viral clearance in patients with novel coronavirus pneumonia
Qin NI ; Cheng DING ; Yongtao LI ; Hong ZHAO ; Jun LIU ; Xuan ZHANG ; Yanfei CHEN ; Yongzheng GUO ; Liang YU ; Hongzhen JU ; Jingjing TAO ; Ping YI ; Guanjing LANG ; Junwei SU ; Ding SHI ; Wenrui WU ; Xiaoxin WU ; Ling YU ; Jifang SHENG ; Kaijin XU
Chinese Journal of Clinical Infectious Diseases 2020;13(0):E009-E009
Objective:
To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance time in patients with COVID-19.
Methods:
A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, School of Medicine, Zhejiang University were recruited. All patients received oral abidol and/or combined lopinavir/ritonavir, darunavir antiviral, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg-1·d-1) (glucocorticoid treatment group), and 21 patients who did not use glucocorticoid were the control group. The time of stable virologic conversion insputumand the time of radiologic recovery in lungsince onset were compared between the two groups and among the normal patients.The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups.
Results:
The median ages of the glucocorticoid group and the control group were 52 [interquartile range (IQR):45, 62] years and 46 (IQR: 32, 56)years, and the differences were significant (