Junbo Zhang

Serotonin inhibits apoptosis of pulmonary artery smooth muscle cell by pERK1/2 and PDK through 5-HT1B receptors and 5-HT transporters

BACKGROUND Decreased apoptosis of pulmonary artery smooth muscle cells (PASMCs) plays a key role in pulmonary vascular remodeling in pulmonary hypertension (PH). However, the cause and mechanism of this decrease in apoptosis are still unclear. Serotonin (5-HT) has been shown to be involved in PH by inducing PASMC proliferation through the activation of 5-HT1B receptors (5-HT1BR) and 5-HT transporter (5-HTT). 5-HT1BR and 5-HTT are also involved in abnormal apoptosis in many other pathological processes. Therefore, we hypothesized that 5-HT induces decreases in PASMC apoptosis through 5-HT1BR and 5-HTT. METHODS PASMCs were treated with 5-HT, and their proliferation and apoptosis were assayed. 5-HT1BR agonists, 5-HT1BR antagonist, 5-HTT antagonist, combined 5-HT1BR/5-HTT antagonists, extracellular signal-regulated kinase (ERK1/2) activation inhibitor peptide I (EPI) and pyruvate dehydrogenase kinase (PDK) inhibitor sodium dichloroacetate (DCA) were used to explore the mechanism by which 5-HT induce decrease in PASMC apoptosis. RESULTS PASMCs stimulated by 5-HT showed an increase in proliferation and a decrease in apoptosis, accompanied by increase in pERK1/2, PDK, and mitochondrial transmembrane potential. The effects of 5-HT on the proliferation and apoptosis of PASMCs were similar to those of 5-HT1BR agonists and were markedly prevented by 5-HT1BR antagonist, 5-HTT antagonist, combined 5-HT1BR/5-HTT antagonists, EPI, or DCA. CONCLUSIONS 5-HT inhibits PASMC apoptosis through 5-HT1BR or 5-HTT. pERK1/2 and PDK are involved in the process of 5-HT inhibition PASMC apoptosis through 5-HT1BR or 5-HTT.

Magnet compression technique: a novel method for rectovaginal fistula repair.

Dear Editor: Though the morbidity of rectovaginal fistula (RVF) is not high in humans, surgical repair is difficult to finish and does not work well actually. As the statistical data shows, when the RVF is repaired firstly, its success rate is 70–79 %, but when the fistula is repaired for a second or more times, its success rate is decreased to 40–85%. In clinic, there are many ways to repair the RVF, but until now, the standard therapy is still uncertain, so the fistula was almost repaired clinically according to its surrounding conditions. Magnetic compression technique (MCT) can be applied to the anastomosis between two hollow organs based on the noncontact magnetism from two magnets. As far, based on MCT, there were repor ts about vascular anas tomosis , choledochojejunostomy, and gastroenteric anastomosis continuously. It is a simple and effective method which can accomplish many kinds of anastomoses with no suture. Most of all, it can finish the one-stage anastomosis even when the tissues are inflammatory. This time, the MCT is successfully applied to repair of RVF. The details are as follows. A 38-year-old female’s chief complaint was that she received vaginal tightening surgery for 2 years with vagina defecating stool-like object. Two years ago, the patient received vaginal tightening surgery for her flabby vagina. One week after the operation, she found there was gas defecated via vagina with stool. Then she was diagnosed with rectovaginal fistula. One year ago, she was operated on to repair the rectovaginal fistula. Unfortunately, the symptom above recurred 1 week after the operation. Six months ago, the patient received the same repair operation which turned to be a failure that the rectovaginal fistula appeared again 1 week after the second repair operation. The two repair operations both failed to close the fistula. Now, the patient came to the hospital for a radical therapy. The physical examination was done. At the lithotomy position, at the direction of 7 o’clock, 2 cm far from the bottom of vagina, there was a 2-mm in diameter fistula, which is firm and solid, with tissue around the boarder red and swollen and granulation tissue hypertrophying but without apparent inflammatory exudate. The body and the neck of uterus and the adnexa of the uterus were all normal. Considering the experience of the two former operations, we decided to repair the fistula with magnet compression technique. The entire study was carried out in strict accordance with protocols approved by the Medical Ethics Committee of The First Affiliated of Xi’an Jiaotong University (Permit Number: 2014-57). We designed an embowedmagnet which is 50 mm in length, 12 mm in chord length, and 4 mm thick in accordance with the size of the fistula. The magnet is made from N45 neodymium-iron-boron permanent magnet and covered with titanium nitride coating. The magnet weighs 7.81 g. And the magnetic intensity is 3400GS. Xiao-Peng Yan and Yu-Liang Zou contributed equally to this work.

The effects of the 5-HT2A receptor antagonist sarpogrelate hydrochloride on chronic hypoxic pulmonary hypertension in rats

ABSTRACT Purpose of the Study: This study investigated whether sarpogrelate hydrochloride (SPG), a 5-HT2A receptor antagonist, alleviates chronic hypoxic pulmonary hypertension (CH-PH) in rats by stimulating apoptosis and inhibiting proliferation in pulmonary artery smooth muscle cells (PASMCs). Materials and Methods: Forty male Sprague-Dawley rats were pretreated with SPG (50 mg/kg/day by oral gavage) or saline vehicle and then subjected to chronic hypoxia (CH) (hypobaric chamber set to 380 mmHg, 10% oxygen) or normoxia for 14 days. Mean pulmonary artery pressure (PAP) and right ventricular hypertrophy (RVH) were measured. Hypertensive pulmonary vascular remodeling was assayed by light microscopy. Terminal deoxynucletidyl transferase dUTP nick end ligase (TUNEL) assays, western blotting, and real-time polymerase chain reaction were used to assess apoptosis, proliferation and underlying signaling pathways in PASMCs from lung tissue and isolated pulmonary artery rings. Results: CH increased mean PAP and RVH. CH increased the percentage of muscularized arteries in the peripheral pulmonary vasculature and medial wall thickness in small muscular arteries. CH increased pulmonary protein and mRNA levels of the B-cell lymphoma protein 2 (Bcl-2), pyruvate dehydrogenase kinase (PDK), phosphorylation of extracellular signal-regulated kinases 1 and 2 (pERK1/2), cyclin D1, proliferating cell nuclear antigen (PCNA) and decreased protein and mRNA levels of Bcl-2-associated X protein (BAX), cleaved caspase-3. Pretreatment with SPG, which has been shown previously to inhibit ERK1/2 phosphorylation and PDK, countered all of these effects. Isolated pulmonary artery rings incubated with 5-HT increased pERK1/2, PDK, and Bcl-2 expression, and decreased Bax expression. Conclusion: Administration of SPG ameliorated the development of CH-PH by stimulating apoptosis in and inhibiting proliferation of PASMCs.

Effects of Maternal Cortisol during Pregnancy on Children's Blood Pressure Responses

Background: It is well established that birth weight has an effect on subsequent blood pressure. Predominantly experimental studies have also reported effects of altered corticosteroid levels on subsequent cardiovascular responses. In the current study, we have examined the effects of both birth weight and maternal cortisol levels in a cohort of mothers and their pre-adolescent children. Procedure: A total of 216 women and their 7- to 9-year-old children comprised the cohort. The women had been assessed for plasma cortisol during the first (n = 71), second (n = 72) and third (n = 73) trimester. Maternal cortisol had been measured on a fasting sample taken between 9 and 11 a.m. The childrens blood pressure and heart rate were recorded in the resting state, in response to a 10-min video game stress challenge and during recovery. Resting values, incremental responses to stress and recovery were evaluated. Observation: Maternal cortisol levels increased with duration of pregnancy. There were inverse correlations between birth weight and all haemodynamic measures. The positive associations between maternal cortisol and childrens haemodynamic measures were most evident in the first and second trimesters. Birth weight was inversely related to maternal cortisol. In multiple regression analyses, the effects of maternal cortisol were more consistent than those of birth weight. Conclusion: Both birth weight and maternal cortisol are predictive of childrens resting and stress-modulated haemodynamic measures. The effects of birth weight may partly mediate the effects of maternal cortisol.

The relationship between maternal anxiety and cortisol during pregnancy and birth weight of chinese neonates

BackgroundTo determine the relationship between maternal anxiety and cortisol values and birth weight at various stages of pregnancy.MethodsTwo hundred sixteen pregnant Chinese women were assessed for anxiety and depression and had measurement of morning fasting serum cortisol. Women were assessed either in the first (71), second (72) or third (73) trimester. Birth weights of all children were recorded.ResultsThere were significant negative correlations between anxiety level and birth weight of − 0.507 (p < 0.01) and − 0.275 (p < 0.05) in trimesters 1and 2. In trimester 3 the negative relation between anxiety and birth weight of −.209 failed to reach significance (p = 0.070). There was no relation between depression and birth weight in any trimester (p > 0.5 for all). Maternal cortisol was significantly inversely related to birth weight in trimester 1 (r = − 0.322) and with borderline significance in trimester 2 (r = − 0.229). Anxiety score and maternal cortisol were significantly correlated in each trimester (r = 0.551, 0.650, 0.537). When both anxiety score and maternal cortisol were simultaneously included in multiple regression analyses only anxiety score remained significant.ConclusionWhilst both maternal anxiety score and maternal cortisol are inversely related to birth weight the associations with anxiety score were more robust perhaps indicating the importance of mechanisms other than, or in addition to, maternal cortisol in mediating the effects of anxiety. The findings indicate the importance of measures to reduce maternal anxiety, particularly of a severe degree, at all stages of pregnancy.Trial registrationThe study was approved by the Ethics Committee of the 1st Affiliated Hospital of Xi’an Jiaotong University.

Paradoxical embolism: A report of 2 cases

Rationale: Paradoxical embolism (PDE) refers to direct passage of venous thrombi into the arterial circulation through an arteriovenous shunt. Patient concerns: Case 1 presented with initial symptoms of shock and cerebral infarction. Case 2 developed middle cerebral artery occlusion during angiography. Diagnoses: 2 cases were diagnosed as PDE. Interventions: They received thrombolytic therapy and anticoagulant therapy. Outcomes: The patients had recovery. Lessons: This report highlights the myriad clinical manifestations of PDE and underlines the importance of meticulous history taking and physical examination for early diagnosis.

The Clinical Management of Complex Pseudoaneurysms of the Femoral Artery

Objective: To evaluate the clinical course of patients treated for multiple perforations, complex femoral artery pseudoaneurysms. Methods: Seven patients with multiple perforations, complex pseudoaneurysms after femoral artery access for interventional procedures were treated. Ultrasound-guided thrombin injection (UGTI) was first used for treatment. Patients failing repeated UGTIs were treated with fibrin sealant injections. Results: Five of the seven patients treated with UGTIs had rapid thrombus formation within the pseudoaneurysm. Two patients refractory to UGTI had successful treatment using fibrin sealant injection. There were no complications and the overall cure rate was 100%. Conclusions: Treatment of complex femoral artery pseudoaneurysms is safe and effective. UGTI and fibrin sealant are useful in the treatment of complex pseudoaneurysms.

Construction of a HERG mutant L539fs/47-*558W pEGFP vector and the expression of the fusion protein in HEK293 cells

Abstract Objective To construct a human ether-a-go-go-related gene (HERG) nonsense mutant L539fs/47-*558W into the autonomously fluorescent, eukaryotic expression vector pEGFP-C2, and to verify expression of the reconstruct in human embryonic kidney-293 (HEK293) cells. Methods The mutational fragment was subcloned into pEGFP-C2-HERG by double digestion of Sbf I, Eco91 I and rejoining of T4 ligase. After verification, the recombinant pEGFP-C2-L539fs/47-*558W and pEGFP-C2-HERG were respectively transfected into HEK293 cells for 48 h by the Lipofect method to observe the expression location of the fusion protein by laser confocal imaging scanning in vivo. pcDNA3 -L539fs/47-*558W and pcDNA3-HERG were transfected to observe the expression location of the HERG protein by immunofluoresceoce. The mutant protein size was determined by Western blotting. Results The about 1 kb-sized mutation region cDNA fragment from pcDNA3-L539fs/47-*558W and the about 7.2 kb-sized target vector fragment from pcDNA3-HERG were ligated after purification and gel recovery. pEGFP-C2-L539fs/47*-558W, approximately 8.2 kb, was demonstrated successfully been constructed under agarose gel electrophoresis and further sequencing. Laser confocal imaging showed that pEGFP-C2-HERG was mainly expressed in the membrane, whereas truncated mutant-type HERG in the pEGFP-C2 vector was partially located in the cytoplasm, the others were transported to the cell membrane in living HEK293 cells. The same as the immunofluoresceoce results after transfection of pcDNA3-HERG and pcDNA3-L539fs/47-558W. Wild-type HERG-GFP fusion protein expressed 160 and 180 kDa bands. The mutant and mutant-GFP fusion proteins were 70 and 100 kDa, respectively. Conclusion pEGFP-C2-L539fs/47-*558W was successfully constructed by double digestion method GFP had no effect on its protein expression and trafficking in HEK293 cells, which laid a foundation for the further study on L539fs/47-*558W.

Non-selective pulmonary angiography for venous thromboembolism diagnosis, a better choice?

Abstract Objective To evaluate the efficiency of non-selective pulmonary angiography for pulmonary embolism diagnosis. Methods 105 consecutive subjects diagnosed with limb deep venous thrombosis (DVT) by lower limb phlebography underwent non-selective pulmonary angiography. Results 52.38% patients were diagnosed with pulmonary embolism, 21.9% with inferior vena cava thromboembolism, and 9.52% with pulmonary embolism combined with inferior vena cava thrombosis. Images obtained by non-selective pulmonary angiography had a good correlation with selective pulmonary angiography. Conclusion The non-selective pulmonary angiography was a simplified, efficient and safe method for pulmonary embolism diagnosis. Large clinical trials are still needed to further evaluate the accuracy and safety of the non-selective method.