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The aim of this paper was to study the role of phosphoinositide 3-kinase(PI3 K), protein kinase B(Akt) and mamma-lian target of rapamycin(mTOR) in the inhibition of premature ovarian failure induced by D-galactose(D-gal) in mice model by ginsenoside Rg_1(Rg_1). Fifty-four female SPF BALB/c mice were randomly divided into PBS group, D-gal group, and Rg_1 group. In the D-gal group, D-galactose(200 mg·kg~(-1)·d~(-1)) was injected subcutaneously into the neck and back for 42 days. In the PBS group, an equal amount of phosphate buffered saline(PBS) was injected into the neck and back for 42 days. In addition to the therapy of D-gal group, Rg_1 group was given Rg_1(20 mg·kg~(-1)·d~(-1)) through intraperitoneal injection since the 15 th day for 28 days, at the same time, the D-gal group and the PBS group were also given an equal amount of PBS through intraperitoneal injection since the 15 th day for 28 days. After the treatment, the estrous cycle changes of the mice were detected, and the ovarian SA-β-Gal staining was used to detect the changes of ovarian aging. Western blot was used to detect the changes in protein expressions of PI3 K, Akt, mTOR, S6 k, LC3-Ⅱ and P16~(INK4 a). Fluorescence quantitative PCR was used to detect the changes in mRNA expressions of PI3 K, Akt, mTOR, S6 k, LC3-Ⅱ and P16~(INK4 a). According to the findings, compared with the PBS group, the D-gal group began to show estrous cycle disorder in the 3 rd week,the ovarian SA-β-Gal staining positive granulosa cells increased in the D-gal group, the expression of senescence marker P16~(INK4 a) increased, while the expression of autophagy signaling molecule LC3-Ⅱ decreased. After treatment with Rg_1, the positive rate of ovarian SA-β-Gal staining in Rg_1 group decreased, the expression level of autophagy signaling molecule LC3-Ⅱ in Rg_1 group was higher than that in D-gal group, while the expression level of senescence marker P16~(INK4 a) was lower than that in D-gal group. Compared with the PBS group, the protein and mRNA expressions of PI3 K, Akt, mTOR and S6 k in the D-gal group were up-regulated, the protein expressions of Akt, mTOR and S6 k in the Rg_1 group were up-regulated, and the mRNA expressions of PI3 K and mTOR were up-regulated. After treatment with Rg_1, the protein expressions of PI3 K, Akt, mTOR and S6 k in the Rg_1 group were lower than those in the D-gal group, while the mRNA expressions of Akt, mTOR and S6 k in the Rg_1 group were lower than those in the D-gal group. The finding ssuggested that Rg_1 has the effect in delaying ovarian premature failure in D-gal-induced mouse models, and PI3 K/Akt/mTOR autophagy signaling pathways play an important role.
Subject(s)
Animals , Female , Humans , Mice , Autophagy , Ginsenosides , Mice, Inbred BALB C , Phosphatidylinositol 3-Kinases , Primary Ovarian Insufficiency , Proto-Oncogene Proteins c-akt , TOR Serine-Threonine KinasesABSTRACT
Objective: To investigate the clinical features in patients with respiratory disease and/or hypoxia related severe pulmonary hypertension. Methods: Our research included in 2 groups: Hypoxia related pulmonary hypertension group, the patients with respiratory disease and/or hypoxia combining severe pulmonary hypertension, n=31 and Severe idiopathic pulmonary hypertension group, n=41. The diagnosis was confirmed by right heart catheterization; the patients treated in our hospital from 2016-01 to 2017-01 were consecutively enrolled and studied. Clinical features and treatment were compared between 2 groups. Results: Compared with Severe idiopathic pulmonary hypertension group, the patients' mean age, BMI and blood pressure were higher in Hypoxia related pulmonary hypertension group, while the majority clinical features were similar between 2 groups. In Hypoxia related pulmonary hypertension group, more patients had obstructive sleep apnea-hypopnea syndrome (OSAHS) with the higher AHI and the lower mean blood oxygen pressure at night, increased diameters of left atria and ventricle, elevated NT-proBNP level and reduced 6 minutes walking distance; some patients tried target drug therapy, calcium channel blocker therapy or continuous positive airway pressure therapy. Conclusion: Respiratory disease especially OSAHS should be screened from the patients with severe pulmonary hypertension. In addition to basic respiratory and hypoxia medication, further investigation is needed to confirm whether the prognosis could be improved by calcium channel blocker therapy and target drug therapy.
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BACKGROUND: The complexity of the anatomic structure of proximal tibia made it difficult for treatment with intramedullary nailing and rate of complications was high. With the improved design and fixation technique of the intramedullary nails, the excellent and good rate of application of this technique is also increasing. Using intramedullary nailing to treat proximal tibial fractures is getting popular. OBJECTIVE: To summarize the latest techniques of intramedullary nailing for proximal tibial fractures. METHODS: 742 literatures were retrieved with keywords of "proximal tibial fracture" and "intramedullary nail" in English and Chinese respectively from PubMed, Web of science, WanFang and CNKI database. By analyzing their titles and summaries, based on the relevance to the subject, 57 articles were selected for this review after excluding 685 articles. RESULTS and CONCLUSION: (1) Due to the complexity of the anatomic structure of the proximal tibia and the limitations of both the fixation techniques and the structure of traditional intramedullary nails, rates of complications were high when intramedullary techniques were used to treat proximal tibial fractures. (2) With the development of intramedullary nail technique, newly designed intramedullary nails appeared, which increased proximal intramedullary nails, improved the position and direction of lock pin. Holding power was strong on the proximal fracture blocks. (3) The introduction of techniques such as combining with plates, Poller screws and improved approval increased the strength of the fixation of proximal tibial fractures. (4) Most of the biomechanical tests have proven that compared to other techniques, intramedullary nailing provides better stability. The intramedullary nailing has advantages of being minimal invasion, less blood transport damage, strong fixation, early postoperative activity and short healing time. It is especially effective for multi-level tibial fractures and proximal tibial fractures with severe soft tissue damages. (5) Deep knowledge of the anatomic structure of the proximal tibia and nailing procedure can help surgeons achieve satisfactory clinical results.
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<p><b>OBJECTIVE</b>To compare the clinical effects of three fixation methods at the level of fracture in treating thoracolumbar fractures.</p><p><b>METHODS</b>From June 2012 to June 2015, 67 patients with thoracolumbar fractures were treated with posterior short-segment pedicle fixation. There were 45 males and 22 females, aged from 13 to 63 years old with an average of 42.5 years. According to the methods of fixation at the level of fracture, the patients were divided into three groups. Group A included 26 patients treated by traditional posterior fixation alone. Group B included 19 patients treated by posterior fixation with unilateral pedicle fixation at the level of fracture. In group C, 22 patients were treated by posterior fixation with bilateral fracture-level screws. Radiological parameters and clinical outcomes were compared among the three groups.</p><p><b>RESULTS</b>All the patients were followed up for 12 to 26 months with an average of 17.6 months. No complications such as incision infection, poor wound healing, internal fixation loosening and breakage were found. Preoperative, postoperative 1 week, and final follow-up, there were no significance differences among the three groups with respect to the relative height of the fractured vertebra (>0.05). The sagittal Cobb angles among the three groups were similar preoperatively, and a week after operation (>0.05). At latest follow-up, the sagittal Cobb angles and the correction loss of Cobb angle in group A were significantly larger than that of groups B and C (<0.05), while there was no statistical difference between group B and group C (>0.05). With respect to visual analogue scale (VAS) scores for back pain, the three groups were similar at preoperatively, a week after operation and the latest follow-up(>0.05).</p><p><b>CONCLUSIONS</b>Compared to traditional posterior fixation alone, unilateral or bilateral pedicle fixation at the level of fracture can significantly decrease the loss of correction in the middle-long term, and reduce the incidence of tardive kyphosis deformity and can obtain satisfactory radiological results and clinical outcomes with safe surgical procedures.</p>
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<p><b>OBJECTIVE</b>To explore the role of peak oxygen consumption in assessment of heart function of patients with pulmonary hypertension.</p><p><b>METHODS</b>From September 2010 to April 2012, 101 patients [29 male, mean age: (32.6 ± 11.4 )years] with pulmonary hypertension diagnosis by right heart catheterization were enrolled. Correlations among peak oxygen consumption, New York Heart Association (NYHA) class, NT-proBNP, 6 minute walking distance (6MWD) and cardiac index are analyzed.</p><p><b>RESULTS</b>There were 44 cases with NYHA class II (43.6%), 49 cases with NYHA class III (48.5%), mean 6MWD was (421 ± 91 )m, NT-proBNP was (1262 ± 816) ng/L, pulmonary vascular resistance was (1031 ± 582) dyn·s(-1)·cm(-5), CI was (3.5 ± 2.3) L·min(-1)·m(-2), peak oxygen consumption was( 13.8 ± 4.1)ml·min(-1)·kg(-1). 6MWD, pulmonary vascular resistance and peak oxygen consumption were related to CI (r = 0.299, -0.541, 0.341, respectively, all P < 0.05), but NYHA class and NT-proBNP were not correlated to CI. Multiple regression analysis demonstrated that peak oxygen consumption (B = 0.135, P = 0.004) but not 6MWD was correlated with CI after adjusting age, sex and pulmonary vascular resistance. ROC analysis found that the sensitivity and specificity using peak oxygen consumption <15.2 ml·min(-1)·kg(-1) as a cut-off value was 92.6% and 57.5%, respectively, for diagnosing severe heart dysfunction.</p><p><b>CONCLUSIONS</b>The correlation between peak oxygen consumption and CI is better than that of NYHA class, 6MWD, and NT-proBNP with CI. Peak oxygen consumption less than 15.2 ml·min(-1)·kg(-1) could be used to detect reduced CI in patients with pulmonary hypertension.</p>
Subject(s)
Adult , Female , Humans , Male , Young Adult , Exercise Test , Heart , Hypertension, Pulmonary , Diagnosis , Metabolism , Natriuretic Peptide, Brain , Blood , Oxygen Consumption , Peptide Fragments , BloodABSTRACT
<p><b>OBJECTIVE</b>To explore the demographic characteristics and clinical features of patients with idiopathic pulmonary arterial hypertension (IPAH) in China.</p><p><b>METHODS</b>Between March 2007 and September 2010, IPAH diagnosis was confirmed by right heart catheterization in 150 adult patients from 31 clinical centers in China. Clinical and hemodynamic data were analyzed and patients were divided into WHO functional class I/II and WHO functional class III/IV group.</p><p><b>RESULTS</b>The mean age of 150 patients were 36 ± 13 years with female patient/male patient ratio of 2:1, and mean BMI was (21.3 ± 3.5) kg/m(2). Fatigue (n = 123, 82.0%) and dyspnea (n = 112, 74.7%) are the most common symptoms. Accentuated pulmonic second sound (P(2)) was detected in 92.0% (n = 138) of patients during physical examination, which was also the most common sign. About 49.0% (n = 73) patients were WHO functional class I/II patients and 46.0% (n = 68) patients were WHO functional class III/IV patients. Six minutes walking distance (6MWD) and Borg dyspnea score was (337 ± 101) m and 2.0 (2.0, 4.0), respectively. Right ventricular hypertrophy was suggested by ECG in 93.1% (n = 140) patients. Right atrial pressure was (10 ± 6) mm Hg, mean pulmonary artery pressure was (61 ± 16) mm Hg, cardiac index was (2.3 ± 0.8) L×min(-1)×m(-2) and pulmonary vascular resistance (1484 ± 699) dyn×s(-1)×cm(-5) in this cohort. 6 MWD (305 m ± 89 m vs. 377 m ± 88 m) was significantly shorter while Borg dyspnea score [3.0 (3.0, 5.0) vs. 2.0 (2.0, 3.0)] was significantly higher in WHO functional class III/IV patients than in WHO functional class I/II patients. Similarly hemodynamic parameters were also worse in WHO functional class III/IV patients than in WHO functional class I/II patients (all P < 0.05).</p><p><b>CONCLUSION</b>Idiopathic pulmonary arterial hypertension patients in this cohort affect mostly young adults, dominated by female gender and lower body mass index. Fatigue and dyspnea are the most common symptoms and accentuated pulmonic second sound (P(2)) is the most common sign. IPAH patients are often displaying severe functional and hemodynamic disturbance at first visit to hospitals. Dyspnea and hemodynamic impairment are related to 6MWD and WHO functional class.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Familial Primary Pulmonary Hypertension , Hemodynamics , Hypertension, Pulmonary , Diagnosis , Ventricular FunctionABSTRACT
<p><b>BACKGROUND</b>Iloprost has been used to test acute pulmonary vasoreactivity in idiopathic pulmonary arterial hypertension (PAH). We aimed to investigate the acute hemodynamic and oxygenation responses and tolerability to 20 µg aerosolized Iloprost in Chinese patients with pulmonary hypertension.</p><p><b>METHODS</b>Between March 2005 and May 2010, 212 pulmonary hypertension patients inhaled a single dose of 20 µg Iloprost over 10 - 15 minutes for vasoreactivity testing. The acute hemodynamic and oxygenation responses and adverse events were recorded.</p><p><b>RESULTS</b>Iloprost decreased total pulmonary resistance ((1747 ± 918) dyn×s×cm(-5) vs. (1581 ± 937) dyn×s×cm(-5), P < 0.001), increased stroke volume ((45.0 ± 22.1) ml vs. (47.0 ± 24.2) ml, P = 0.002), and cardiac output ((3.7 ± 1.7) L/ml vs. (3.9 ± 1.9) L/min, P = 0.009). Heart rate and systemic vascular resistance remained stable during inhalation. However, systemic arterial blood oxygen saturation fell slightly ((91.0 ± 6.8)% vs. (90.3 ± 6.7)%, P = 0.002). Pulmonary and systemic arterial blood pressures declined within 1 - 3 minutes after inhalation initiation and reached their lowest levels within 10 - 15 minutes. Idiopathic PAH responded more favorably than pulmonary hypertension due to other causes (P £0.001) and patients with less severe pulmonary hypertension have better responses to Iloprost. No adverse events requiring medical care or leading to termination of inhalation occurred.</p><p><b>CONCLUSIONS</b>Inhalation of 20 µg Iloprost showed potent and selective pulmonary hemodynamic effects and was well tolerated in the Chinese pulmonary hypertension patients. Patients with idiopathic PAH and less severe pulmonary hypertension responded more favorably to inhalation of Iloprost.</p>
Subject(s)
Humans , Administration, Inhalation , China , Hemodynamics , Hypertension, Pulmonary , Drug Therapy , Iloprost , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To express and purify HBoV VP2 protein, and the monoclonal antibody against HBoV VP2 protein was prepared with hybridoma technique.</p><p><b>METHODS</b>The HBoV VP2 cloned into vector pET-30a was expressed in E. coil. After purified by immobilized metal affinity chromatography, the BALB/c mouse was immunized with purified protein as antigen. The positive hybridoma cells were screened with hybridoma technique and ELISA assay. Isotype and titer of the monoclonal antibody were detected.</p><p><b>RESULTS</b>The recombinant HBoV VP2 protein was expressed and purified, and then the monoclonal antibody was obtained with hybridoma technique. The titer of the IgG monoclonal antibody was up to 1:4 x 10(5).</p><p><b>CONCLUSION</b>Monoclonal antibody against recombinant HBoV VP2 protein was prepared and the antibody titer was high. This work may provide a new method in rapid diagnosis and study of HBoV.</p>
Subject(s)
Animals , Mice , Antibodies, Monoclonal , Allergy and Immunology , Capsid Proteins , Genetics , Allergy and Immunology , Human bocavirus , Allergy and Immunology , Hybridomas , Mice, Inbred BALB C , Plasmids , Recombinant Proteins , Allergy and ImmunologyABSTRACT
ObjectiveTo investigate the value of 18F-FDG SPECT myocardial imaging in evaluating haemodynamic change,treatment outcome and prognosis for idiopathic pulmonary arterial hypertension (IPAH).MethodsAll 24 patients with IPAH underwent 18 F-FDG SPECT myocardial imaging.Right ventricle/left ventricle (RV/LV)-FDG uptake was calculated by ROI method drawing over the central areas of left and right ventricular free walls.All patients underwent right heart catheterization within 3 days after imaging studies.Mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) were recorded.After six month pharmaceutical treatment,15 IPAH patients were re-examined with 18F-FDG SPECT myocardial imaging followed by repeated right heart catheterization within 3 days.Plasma N-terminal pro-brain naturetic peptide (NT-proBNP) and endothelin-1 ( ET-1 ) were measured in 17 patients using electrochemiluminescent immunoassay and enzyme immunoassay respectively.All patients were followed up for 12 months at least.Correlations between RV/LV-FDG uptake and mPAP and PVR were determined by simple linear regression analysis.Change of RV/LV-FDG before and after treatment was calculated using Student's t-test.Survival in groups with RV/LV FDG uptake ≥ 1.15 and RV/LV-FDG uptake ＜ 1.15 were compared using Log-rank test.ResultsSignificant correlations were found between RV/LV-FDG uptake and mPAP (r =0.562,P ＜ 0.01 ),and between RV/LV-FDG uptake and PVR ( r =0.574,P ＜ 0.01 ).There were no significant correlation between RV/LV-FDG uptake and NT-proBNP( r =0.18 1,P ＞ 0.05 ),but a significant correlation between RV/LV-FDG and ET-1 was observed (r =0.669,P ＜ 0.01 ).The RV/LV-FDG uptake in patients with positive treatment outcome ( n =6) decreased from 1.38 ± 0.52 to 0.92 ±0.26 (t =4.018,P ＜ 0.05) after 6 months treatment.In contrast,no significant change of RV/LV-FDG uptake was seen in those patients (n =9) with negative treatment outcome ( t =1.861,P ＞ 0.05 ).The mean follow-up time was (21 ±8) months.Mean survival time for the patients with RV/LV- FDG uptake ≥ 1.15was 28 months (95％ confidence interval:24-32 months),which was significantly lower than 34 months survival (95％ confidence interval:33-35 months) for the patients with RV/LV-FDG ＜ 1.15 (x2 =3.956,P ＜0.05 ).Conclusions Detection of right ventricle myocardial glucose metabolism level with 18F-FDG SPECT may be a practical method for evaluating haemodynamic change,treatment outcome and prognosis of IPAH.
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Objective To investigate the value of the Wells score and D-dimer assay in assisting pulmonary perfusion imaging (PPI) for the diagnosis of acute pulmonary embolism (APE). Methods One hundred twenty-one patients with suspected APE were studied from January, 2006 to December, 2008. All patients underwent the Wells score, the quantitative D-dimer assay, chest X-ray photography, and PPI. The diagnostic sensitivity, specificity, positive predictive value and negative predictive value of PPI with the assistance of Wells score and D-dimer assay were calculated. Results Fifty (41.3%) patients were diagnosed with APE. PPI combined with chest X-ray photography (Q/X scan) showed positive results in 49 patients. The sensitivity, specificity, positive predictive value and negative predictive value of the Q/X scan were 86.0% (43/50), 91.5% (65/71), 87.8% (43/49) and 90.3% (65/72), respectively. With assistance of Wells score >4 and D-dimer≥0. 5 mg/L, Q/X scan had a positive predictive value of 100.0% (29/29), for patients with Wells score ≤4 and D-dimer<0.5 mg/L, the negative predictive value for Q/X scan was 100.0% (41/41). Conclusion Combined with Wells score and D-dimer assay, PPI can make accurate diagnosis of APE.
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<p><b>BACKGROUND</b>Pulmonary angiography is widely performed in pulmonary hypertension patients, but its immediate effects on right heart hemodynamics and safety are not well known. The objective of this study was to investigate the right heart hemodynamic effects and safety of pulmonary angiography in Chinese patients with pulmonary hypertension.</p><p><b>METHODS</b>Between January 2008 and June 2009, pulmonary hypertension patients undergoing pulmonary angiography were consecutively enrolled. Pulmonary angiography was performed during breath-holding after deep breathing. The baseline clinical data, hemodynamic measurements before and after pulmonary angiography and complications occurring within 48 hours after angiography were recorded.</p><p><b>RESULTS</b>Ninety-five patients were included. All received non-ionic contrast medium with a volume of (75.7 ± 29.8) ml. Angiography reduced heart rate in patients with baseline mean pulmonary arterial pressure ≥ 60 mmHg (change of heart rate: (-3.1 ± 7.0) beats/min, P = 0.005), increased mean right atrial pressure, diastolic and end-diastolic right ventricular pressure in patients with baseline mean pulmonary arterial pressure < 60 mmHg (all P < 0.05). Patients with decreased mean pulmonary arterial pressure (change of mean pulmonary arterial pressure ≤ -10 mmHg) had the highest total pulmonary resistance (P = 0.009 vs. no change in mean pulmonary arterial pressure (change of mean pulmonary arterial pressure, -10 mmHg to 10 mmHg); P = 0.03 vs. increased mean pulmonary arterial pressure (change of mean pulmonary arterial pressure ≥ 10 mmHg)) and the lowest cardiac output (P = 0.018 vs. no change in mean pulmonary arterial pressure; P = 0.013 vs. increased mean pulmonary arterial pressure). There were 7 complications (7%), with 6 related to catheter and only 1 directly related to angiography. All complications were mild and no death occurred.</p><p><b>CONCLUSION</b>Pulmonary angiography has minimal effect on right heart hemodynamics and is safe in pulmonary hypertension patients.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Angiography , Contrast Media , Hemodynamics , Physiology , Hypertension, Pulmonary , Diagnostic ImagingABSTRACT
<p><b>OBJECTIVE</b>To study the effect of Hongjingtian (Gadol) injection on cardiac hemodynamics and myocardial oxygen consumption for analyzing its underlying mechanism in the treatment of coronary heart disease.</p><p><b>METHOD</b>A total of 20 dogs anesthetized with pentobarbital sodium (30 mg x kg(-1), i.v.) were evenly randomized into control group, low-dose Gadol (LDG) group, high-dose Gadol (HDG) group and Herbesser Injection group. The blood flow volume (BFV) of the left coronary artery and cardiac output (CO), left ventricular pressure (LVP), maximum ascending rate (dp/dtmax) of LVP, mean arterial pressure (MAP) of the femoral artery, oxygen contents of the coronary artery and coronary vein (venous sinus), oxygen consumption index (OCI), cardiac index (CI), coronary artery resistance (CAR) and total peripheral resistance (TPR) as well as oxygen utilization rate (OUR) were detected respectively.</p><p><b>RESULT</b>After venous injection of Gadol, CAR, MAP, TPR, OCI, myocardial oxygen consumption and heart rate lowered significantly (P < 0.05-0.01), while BFV and blood oxygen content of the venous sinus increased considerably (P < 0.05-0.01) in comparison with pre-injection. No significant differences were found in LVP and myocardial contractivity between control group and LDG, and between control and HDG groups respectively.</p><p><b>CONCLUSION</b>It showed dilation of the coronary artery and reduction of the cardiac afterload after injection of Gadol. Besides, CO and stroke volume increased considerably and the cardiac effective work was raised without any significant simultaneous increase of both myocardial contractility and LVP. A decrease in the myocardial oxygen consumption and reduction of OCI indicates an improvement of the oxygen supply of the myocardium, and a favorable regulation of the compliance of the cardiac vessels. As a result, the cardiovascular performance was ameliorated. The abovementioned improvement of these indexes may contribute to the therapeutic effect of Gadol in the treatment of coronary heart disease in clinic.</p>