2.Smad4-dependent TGF-β directly up-regulates Notch4 in cerebrovascular endothelial cells
Guimei YANG ; Fangfei LI ; Youliang WANG ; Jun WANG ; Yu LAN
Military Medical Sciences 2017;41(6):415-418
Objective To find out whether NOTCH receptors can serve as direct downstream targets of transforming growth factor β(TGF-β)/Smad4 signaling in endothelial cells.Methods Real-time PCR and Western blotting were performed to verify whether the expression of notch1 and notch4 was regulated by TGF-β pathway.Luciferase reporter assay was employed to investigate how the promoter of notch1 and notch4 was regulated by TGF-β.Then, ChIP assay was used confirm whether the promoter of notch1 and notch4 physically interacted with SMAD protein.Results TGF-β1 and bone morphogenetic protein 4 (BMP4) treatment increased the expression of both notch1 and notch4 at the transcriptional level.In addition, SMAD4 was physically associated with the SMAD binding sites on the notch4 promoter, which was largely enhanced under the treatment of TGF-β1 and BMP4.Importantly, TGF-β1 and BMP4 failed to transactivate notch4 in the absence of endogenous SMAD4 or the SMAD binding regions on the notch4 promoter.Conclusion The expression of NOTCH receptor can be directly up-regulated by SMAD4-mediated TGF-β/BMP signaling in cerebrovascular endothelial cells.
3.Clinical value of fetal system ultrasound union real-time three-dimensional ultrasound to diagnose the abnormalities of fetal palms and feet
Lan MU ; Suzhen RAN ; Jun WEI ; Zhengchun YANG ; Yun LIN
Chongqing Medicine 2015;(25):3520-3522
Objective To explore the clinical value of fetal syetem ultrasound union real-time three-dimensional ultrasound to diagnose the abnormalities of fetal palms and feet in medium-term pregnancy.Methods The results of fetal syetem ultrasound u-nion real-time three-dimensional ultrasound in 23 675 cases during dmedium-term pregnancy in our department from January 2009 to November 2013 were retrospectively analyzed,including 47 350 palms and feet.Results If using the fetal syetem ultrasound u-nion real-time three-dimensional ultrasound to examine fetal palms and feet more than three times,the display rate of palms and feet was 100.0%,while the first-time display rate of finger and toes was 81.2%,second-time display rate was 97.2% and the third-time and more display rate more thatn 99.8%.136 cases hand-foot deformity were diagnosed,including 37 cases of hand gesture abnor-malities,6 cases of finger abnormalities,93 cases of food abnormalities,and the main abnormality was strephexopodia.Of all the 136 cases,there were 2 cases also with Trisomy 18,4 cases with Trisomy 21.Conclusion Malformations of fetal palms and feet can be detected by fetal system ultrasound combined with real-time three-dimensional ultrasonography during the second trimester,which is important indicators of prenatal screening for chromosomal abnormalities.
4.Variation of CREB and NMDAR1 Proteins Induced by Auditory Deprivation and Intracochlear Electrical Stimulation in Infant Rats
Biyun FAN ; Zhendong LU ; Lan CHENG ; Jun YANG
Journal of Audiology and Speech Pathology 2016;24(3):245-250
Objective To observe the expression of cAMP -response element binding protein (CREB) and N-methyl-D-aspartic acid receptor (NMDA ) after intracochlear electrical stimulation in the auditory cortex and inferior colliculus in infant rats with auditory deprivation .Methods Sixty six SD infant rats were randomly divided into 6 groups (11 rats each group):4 weeks ,and 6 weeks after injection of ototoxic drug ,the control group ,and 3 weeks and 5 weeks after injection of ototoxic drug with intra -cochlear electrical stimulation for one week .Gentami-cin sulphate (350 mg/kg body weight) and frusemide (200 mg/kg body weight) were injected subcutaneously in the skin folds on the lateral abdominal side and the dorsal neck area ,respectively .The expression of CREB and NMDAR1protein were detected by immunohistological staining .Results The results of immunohisto -chemistry revealed that protein expression of CREB and NMDAR1 in 4 week group of injection increased as compared to the control group ,while decreasing as compared to intracochlear electrical stimulation group ,significantly .However ,protein expression of CREB and NMDAR1 in 6 week group of injection decreased as compared to the control group and in-tracochlear electrical stimulation group ,significantly .Conclusion Auditory deprivation could result in the expres-sion of protein of CREB and NMDAR1 in auditory cortex and inferior colliculus increasing in an early stage and then de-creasing in infant rats .Intracochlear electrical stimulation could result in the expression of proteins of CREB and NMDAR 1 in auditory cortex and inferior colliculus increasing in infant rats .The dynamic variation of CREB and NMDAR1 expression in rat auditory cortex and inferior colliculus reflects synaptic plasticity in neurons of auditory pathway .
5.Early Mitotic Inhibitor 1 Regulates DNA Re-replication Mediated by Human Papillomavirus Subtype 16 E7 in Response to DNA Damage.
Ya-Fei LIU ; Yan-Jun SHEN ; Yang YANG ; Lan CHAO ; Fang YANG
Acta Academiae Medicinae Sinicae 2020;42(4):485-490
To explore the molecular mechanism of human papillomavirus subtype 16(HPV-16)E7 oncogene-induced DNA re-replication in response to DNA damage. Flow cytometry was performed to examine the cell cycle changes in RPE1 E7 cells stably expressing HPV-16 E7 and its control cell RPE1 Vector after DNA damage.Immunoblotting assay was used to evaluate the early mitotic inhibitor 1(Emi1)expression in RPE1 E7 and RPE1 Vector cells with or without DNA damage.The changes of the proportion of polyploidy was detected by flow cytometry in DNA-damaged RPE1 E7 cells interfered by Emi1 small interfering RNA. Compared with the control cells,the proportion of polyploids in RPE1 E7 cells was significantly increased in response to DNA damage(=6.397,=0.0031).Emi1 protein expression was significantly increased in DNA damaged RPE1 E7 cells(=8.241,=0.0012).The polyploid ratio of RPE1 E7 cells was significantly reduced after Emi1 was interfered by two independent small interfering RNAs(=2.916,=0.0434;=3.452,=0.0260). In response to DNA damage,Emi1 promoted DNA re-replication caused by HPV-16 E7.
DNA Damage
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DNA Replication
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Human papillomavirus 16
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Mitosis
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Oncogene Proteins, Viral
6.Effect of peroxisome proliferator-activated receptor-gamma excitomotor on the expression of nuclear factor-kappa B and apoptosis of retinal ganglion cells in rat retina with diabetes mellitus
Wen-jun, GOU ; Ke, OU-YANG ; Hong-bin, LV ; Qing-lan, LI ; Qi, ZHOU ; Jun, ZHANG
Chinese Journal of Experimental Ophthalmology 2012;30(8):709-714
Background As one of the most common microvascular complication of diabetes in eyes,diabetic retinopathy (DR) is one of the most important cause of blindness.Nuclear factor-kappa B (NF-κB) is involved in the occurrence and development of the disease through the activation of a series of inflammatory cytokines.Objective The present study was to investigate the effects of peroxisome proliferator-activated receptor-gamma (PPAR-γ) excitomotor,rosiglitazone,on NF-κB expression and apoptosis of the retinal ganglion cells (RGCs) in the retina with diabetes mellitus. Methods Ninety SPF male Wistar rats were randomized into normal control group,diabetic control group and rosiglitazone group.Diabetes mellitus was induced by intraperitoneal injection of 50 mg/kg streptozotocin(STZ).Then 3 mg/kg rosiglitazone was intragastricly administered once per day in the rosiglitazonegroup,and the same volume of saline solution was used at the same way in the normal control group and diabetic control group from 3 days after modeling.The rats were sacrificed and the eye cups specimen was made at 4,8 and 12 weeks after usage of drugs.Retinal histopathological examination was performed by hematine-eosin staining,and expression of NF-κB p65 protein in retina and apoptotic index(AI) of RGCs were detected by immunohistochemistry and TUNEL assay,respectively in different time points mentioned above.The use of the animals complied with the Regulations for the Administration of Affairs Concerning Experimental Animals by State and Technology Commission.Results The blood glucose level was significantly elevated at various time points in the diabetic control group and rosiglitazone group compared with normal control group (P<0.01 ),and that of the rosiglitazone group was significantly declined in comparison to the diabetic control group (q =0.81,0.82,1.23,P> 0.05 ).Normal retinal structure was seen in the normal control group,and edema retinal cell and disorder of retinal layers were exhibited in the diabetic control group.Retinal structure was almost normal in the rosiglitazone group.The NF-κB p65 was expressed weakly in the retina of normal control group,but the expression of NF-κB p65 was significantly elevated in the diabetic control group and rosiglitazone group compared with the normal control group(P<0.01 ).However,the expression of NF-κB p65(A value)was significantly decreased in the rosiglitazone group compared with diabetic control group at 8 weeks and 12 weeks( q=17.77,15.30,P<0.01 ).There were a few apoptotic cells in rat retina of the normal control group.Compared with the normal control group,the AI of the diabetic control group and rosiglitazone group was significantly reduced(P<0.01 ).However,the AI of RGCs in the rosiglitazone group was significantly lower than that of diabetic control group in various time points (q =19.28,27.39,49.92,P<0.01 ). Conclusions As one of the PPAR-γexcitomotors,rosiglitazone can inhibit apoptosis of RGCs through downregulating the expression of NF-κB in rat retina with diabetes mellitus,indicating a protective effect of rosiglitazone on retina in diabetic rat.
7.Endothelial dysfunction in young pre-hypertension and its influencing factors
Lan WANG ; Jianjun MU ; Ruihai YANG ; Jun YANG ; Man WANG ; Chao CHU ; Bingqing XIE ; Zhenzhen DONG
Journal of Xi'an Jiaotong University(Medical Sciences) 2017;38(4):574-578,625
Objective To investigate the endothelial dysfunction in pre-hypertension and its influencing factors.Methods A total of 373 youth were divided as the subjects into hypertension group (HBP group),prehypertension group (PHT group) and normal blood pressure group (NBP group).Endothelial function was assessed based on carotid intima-media thickness (IMT),brachial artery flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV).Results IMT and baPWV in PHT group were higher than those in NBP group (P<0.05),but did not reach the significant difference when compared with HBP group (P>0.05).Compared with HBP,the levels of FMD in PHT group significantly increased (P< 0.05);however,no difference was observed in comparison with NBP group (P>0.05).In the early stage of hypertension,diastolic BP (β=-0.120,P<0.05) and body mass index (β=-0.115,P<0.05) were negatively correlated with FMD;diastolic BP (β=0.146,P<0.05),2-hour glucose (β=0.147,P<0.05),high-density lipoprotein cholestrol (β=0.150,P<0.05),and waist-hip ratio (β=0.126,P<0.05) showed a positive correlation with IMT.baPWV was correlated with systolicBP (β=0.358,P<0.01),waist circumference (β=0.254,P<0.05),fasting glucose (β=0.155,P<0.05),postprandial 2 h blood glucose (β =0.152,P <0.05),uric acid (β =0.206,P < 0.05),and C-reactive protein (β=0.099,P<0.05).Corclusion Our study shows that endothelial dysfunction may exist in the prehypertensive young,and several cardiovascular risks contribute to its development in the early stage of hypertension.
8.Diagnosis and treatment of infantile congenital subglottic hemangioma
Lan CHENG ; Qi HUANG ; Hao WU ; Jun YANG ; Li CHEN ; Zhihua ZHANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2009;(15):693-696
Objective: To discuss the diagnosis and treatment of infantile congenital subglottic hemangioma. Method:Nine patients with recurrent stridor,feeding difficulties and laryngeal obstruction were diagnosed as con-genital subglottic hemangioma with bronchia endoscopy. The lesions were unilateral in 7 cases and bilateral in 2 ca-ses. Eight cases were treated by intralesional Pingyangmycin injection after tracheotomy. Patients were discharged with metal trachea and were followed up endoscopically 2 weeks thereafter. A second treatment would be required if the tumor reduced in size but not disappeared completely. Plugging tubes and extubation would be done when the tumor disappeared completely. One case with unilateral lesion underwent power-assisted tumor resection with-out tracheotomy. Result: Hemangioma vanished completely in 6 patients with unilateral subglottic hemangioma who were treated with single stage procedure. Tumor size was found reduced significantly after one procedure and van-ished completely after a second procedure in 2 cases with bilateral subglottic hemangioma. All of the 8 cases were extubated successfully. The patient recovered thoroughly in two weeks after power-assisted tumor resection. Con-clusion: Intralesional Pingyangmycin injection after tracheotomy can relief the airway obstruction quickly, shorten the nature course of hemangioma, shorten the period of wearing trachea, has no complication such as subglottic stenosis and is thought to be a safe and effective therapy for large size hemangioma. Power-assisted tumor resec-tion under good total anesthesia without tracheotomy combined with well hemostasis is effective, less injure, and suitable for small size hemangioma.
9.Clinical observation of oxycodone hydrochloride injection successive subtraction method background infusion for postoperative analgesia in patients of lobectomy under thoracoscope
Junfeng LIAO ; Wenlong TU ; Na YANG ; Zhijian LAN ; Wenyong PENG ; Jun XU
China Journal of Endoscopy 2017;23(3):14-19
Objective To observe the analgesia effect of oxycodone hydrochloride injection successive subtraction method background infusion on postoperative analgesia in patients of lobectomy under thoracoscope.Methods Ninety lobectomy under thoracoscope patients, using the random number table method patients were randomly divided into three groups:sufentanil group (group S), the constant speed oxycodone infusion group (Q1) and the decreasing background infusion oxycodone group (Q2), 30 cases in each group. On the time of 10 minutes before the end of surgery, S group was given sufentanil 0.10 μg/kg, Q1 and Q2 group was given oxycodone 0.10 mg/kg, each patient was given intravenous patient-controlled analgesia (PCIA), the group of S set electronic pump sufentanil 2.00 μg/kg (100 ml), background infusion was 0.03 μg/(kg·h), PCA dose was 0.015 μg/kg; The group of Q1 was oxycodone 1.00 mg/kg (100 ml), background dose of 15.00 μg/(kg·h), PCA dose of 15.0 μg/kg; The group of Q2 also was oxycodone 1.00 mg/kg (100 ml), on the first 12 h after operation, the background infusion was 15.00 μg/(kg·h), every 12 h later, the background infusion decreased by 20%, PCA dose was 15.00 μg/kg, all of the pump locking time was 10 minutes, lock 4 times per hour. Recorded the number of hemodynamic on the end of operation, immediate extubation and extubation after 5 minutes. On the time of postoperative 2 h, 8 h, 12 h, 24 h, 48 h, recorded the scores of NRS?, NRS (M), Ramsay. Recorded the times of PCA compression,times of medicaments remedies,the amount of drug use, adverse reactions such as respiratory depression, nausea, vomiting, itching and satisfaction of patients to postoperative analgesia.Results The MAP and HR of three groups of patients were increased in the time of tube drawing (P < 0.05), there was no significantly difference in MAP and HR among the three groups at the end of operation, immediate extubation and after 5 minutes of extubation (P > 0.05). The score of NRS ? in the groups of Q1 and Q2 was lower than group S at the time of (T3~5) (P < 0.05), the score of NRS (M) in the groups of Q1 and Q2 was lower than group S at the time of (T3~6) also. The Ramsay score of Q1 and Q2 group was higher than the group S in the point (T3~7). Which the times of PCA and remedial drug use, sleep disturbed times in the first day and second day of group Q1 and Q2 was lower than the group S (P < 0.05). The volume of drug use at 48 h in the group of Q2 was lower than the group Q1 and S (P < 0.05). Postoperative nausea and vomiting of group Q2 was lowered than group S (P < 0.05). The satisfaction of Patients to postoperative analgesia in the group Q2 and Q1 was higher than group S (P < 0.05).Conclusion Lobectomy under thoracoscope patients with postoperative application of successive subtraction method background infusion oxycodone can obtain satisfactory analgesia effect with a smooth anesthesia recovery period, satisfied analgesic effect, reduce the dosage of drugs and reduce the adverse reaction.
10.The expression of miR-221 and miR-222 in non-small cell lung cancer and their significances
Li LIAO ; Jun WANG ; Shuidong FENG ; Zhihua LAN ; Xueying LYU ; Mengyi WU ; Xin YANG
Cancer Research and Clinic 2016;28(9):590-594
Objective To explore the expression of miR-221/222 in non-small cell lung cancer (NSCLC) and its correlation with clinical pathological parameters. Methods The clinical pathological data and formalin fixed-paraffin embedded (FFPE) tissues of 55 NSCLC patients and 10 benign lesion patients who underwent surgery in the First Affiliated Hospital of Nanhua University from February 2012 to May 2014 were collected and followed. The relationship between miR-221/222 expression detected by real-time PCR and clinical pathological parameters and progression-free survival (PFS) were analyzed. The differential survival between the high expression group and the low expression group of miR-221/222 were compared. A Cox proportional hazard regression model was utilized to examine the prognostic factors of NSCLC. Results The expression level of miR-221/222 was significantly higher in tumor tissues than that in corresponding benign lesion tissues (Fold change=3.52, P=0.000;Fold change=2.01, P=0.000). There was a negative correlation between miR-221/222 expression and pathological grades (r=-0.732, P=0.000;r=-0.451, P=0.001). The relative expression of miR-221 showed a positive correlation with miR-222 (r=0.376, P=0.000). Patients with higher levels of miR-221/222 were closely associated with a shorter PFS (miR-221: 55.43 weeks vs. 81.29 weeks, P=0.028; miR-222: 45.00 weeks vs. 87.04 weeks, P=0.008). Finally, multivariate analysis demonstrated that miR-222 expression was independently associated with poor PFS (RR=2.808, P=0.033). Conclusions miR-221/222 is highly expressed in NSCLC tumor tissues with a positive correlation. A negative correlation is observed between the expression of miR-221/222 and tumor differentiation. The potential high expression of miR-221/222 is considered as tumor biomarkers for the prognosis of NSCLC patients.