BACKGROUND:Vocuolar-type ATPase (V-ATPase) is highly expressed in osteoclasts and especial y plays an important role in osteoclastic bone resorption. Tumor necrosis factor-αis a potent stimulator of bone resorption. However, the effect of tumor necrosis factor-αon expression and activity of V-ATPase is stil not clear.
OBJECTIVE:To investigate the mechanism of tumor necrosis factor-αto promote osteoclastic bone resorption by observing expression and activity of V-ATPase.
METHODOsteoclasts cultured in vitro were intervened by different concentrations of tumor necrosis factor-α(5, 10, 30μg/L) in order to observe the changes in expression and enzyme activity of V-ATPase and its effects on bone resorption of osteoclasts. Under an inverted microscope, we observed the formation of resorption lacunas, and bone resorption area was analyzed using Image J software.
RESULTS AND CONCLUSION:The expression and activity of V-ATPase increased significantly after 48 hours of tumor necrosis factor-αintervention and the increase of tumor necrosis factor-αconcentration might enhance this effect. In addition, osteoclastic bone resorption was promoted after intervention with tumor necrosis factor-α. The bone-resorbing capabilities of osteoclasts increased in paral el with the concentration of tumor necrosis factor-α.The results suggested that tumor necrosis factor-α, as a significant inflammatory mediator involved in the pathological process of bone resorption, not only promotes formation of osteoclasts but also enhances bone-resorbing capabilities of osteoclasts by increasing V-ATPase expression and activity.

A high performance liquid chromatography tandem mass spectrometric ( HPLC-MS/MS ) method was developed for the determination of seven perfluorinated alkyl acidin ( C4-C10 ) and perfluorooctane sulfonate in water. After the particulate was removed by leaching, surrogate standard was added, then the sample was loading to a pre-conditioned WAX cartridge for purification, and then the eluent was concentrated and analyzed by HPLC-MS/MS. Due to the situation that the fluoride polymer was unavoidable to be used in the LC system, a delay column was employed and the perfluorooctanoic acid ( PFOA ) of interference was departed from the PFOA in sample. The method detection limit ( MDL) of PFOA was 0. 8 ng/L, and the lowest quantitative concentration (LQC) was 3. 2 ng/L. For other compounds, the MDL was ranged from 0. 2 to 1. 2 ng/L, and the LQC was 0. 8-4. 8 ng/L. This method also had good reproducibility, for six duplicated samples, the relative standard deviations ( RSD ) of all target compounds were less than 16%. And the recoveries of target compounds at six spiked matrix samples ranged from 87% to 129%, and the RSD were less than 15%. Because of the connection of delay column, the background was well controlled, and a relatively lower MDL were obtained.

Objective To explore the risk factors of hypertension in patients with IgA nephropathy in South China. Methods The clinical and renal pathological data of 280 primary IgA nephropathy patients diagnosed by biopsy were analyzed to extinguish the risk factors of hypertension. Results A total of 96 patients were suffered with hypertension (34.3%). A single-variable analysis showed that the age (≥40 years), body weight (≥60 kg), absence of macrohematuria, duration of disease (≥60 months), blood urea nitrogen≥8 mmol/L, serum creatinine (≥133 μmol/L), hyperuricaemia, degree of 24 h-proteinuria (≥1.5 g), segmental glomerular lesions (≥25% ), globe glomerular sclerosis (≥10%), tubular atrophy (≥25%), interstitial fibrosis (≥25%), interstitial inflammation (≥25% ) and arteriole hypertrophy (≥10% ) were all risk factors related to hypertension; multivariate logistic regression analysis showed that serum creatinine, age, arteriole hypertrophy, body weight and 24 h-proteinuria were the independent risk factors. Conclusion Many factors were related the hypertension in patients with IgA nephropathy, while serum creatinine, age, arteriole hypertrophy, body weight and 24 h-proteinuria were the independent risk factors of hypertension.

OBJECTIVETo observe the effect of 11R-VIVIT on lipopolysaccharide (LPS)-induced expression of urokinase-type plasminogen activator receptor (uPAR) in podocytes.

METHODSA LPS-induced proteinuria mouse model and in vitro cultured podocytes treated with LPS were both divided into control group, LPS group and LPS+11 R-VIVIT group. The mRNA and protein expressions of uPAR in mouse kidney tissues and the podocytes were measured by real-time qPCR, laser scanning confocal microscopy and Western blotting.

RESULTSCompared with LPS group, LPS+11 R-VIVIT group showed a significantly lowered urine albumin/creatinine ratio (P<0.001) and markedly reduced mRNA and protein expressions of uPAR (PuPAR mRNA<0.001; PuPAR=0.001).

CONCLUSION11R-VIVIT can ameliorate proteinuria probably by decreasing the expression of uPAR in podocytes.

Animals ; Disease Models, Animal ; Lipopolysaccharides ; adverse effects ; Male ; Mice ; Mice, Inbred C57BL ; Oligopeptides ; pharmacology ; Podocytes ; drug effects ; metabolism ; Proteinuria ; drug therapy ; metabolism ; Receptors, Urokinase Plasminogen Activator ; metabolism

A case of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) with ocular masses as the main manifestation was reported. The patient was a middle-aged female, the initial symptom was eye swelling, pulmonary nodules were found before eye surgery, and further examination revealed proteinuria, hematuria and renal insufficiency. Renal pathology showed ANCA-associated glomerulonephritis. The final diagnosis was eye, kidney and lung lesions caused by AAV. Treatment with glucocorticoids and cyclophosphamide resulted in improvement in eye, kidney, and pulmonary lesions. Atypical clinical manifestations of AAV may lead to delayed diagnosis, and attention should be paid to the exclusion of AAV for ocular masses of unknown cause.

Objective:To construct a porcine model of ischemia with non-obstructive coronary artery (INOCA) and explore the diagnostic value of a one-stop noninvasive method including CT myocardial perfusion imaging (CT-MPI) and coronary CT angiography (CCTA).Methods:Twelve swines were divided into the experimental group (9) and the normal group (3). Coronary microvascular dysfunction (CMD) porcine model was constructed in the experimental group by inducing diabetes mellitus, chronic kidney disease, and hypercholesterolemia. Invasive coronary angiography (ICA) and functional examination were performed on all 7+3 trial swines to clarify the INOCA diagnosis after completion of the modeling. Then, CT-MPI and CCTA were performed on all individuals to explore the CT-MPI and CCTA characteristics of INOCA porcine models. CT-MPI parameters, including myocardial blood flow (MBF), and myocardial blood volume (MBV) in rest and stress conditions, and CCTA parameters, including severity of stenosis and CAD-RADS, were analyzed.Results:ICA and functional tests showed that all swines in the experimental group met the diagnostic criteria for INOCA, which meant that INOCA porcine model was constructed successfully. CCTA results confirmed that there was no obstructive coronary stenosis in all 10 swines which were examined, which was consistent with ICA findings. CT-MPI results demonstrated that the mean MBF values, as well as the mean MBV values, in the rest and stress condition of each swines in the experimental group were lower than those of the control group. In contrast to the control group, the mean MBF and MBV values of swines in the experimental group in stress condition were generally lower than those in resting condition.Conclusions:In this study, a porcine model of CMD is successfully constructed by inducing hypercholesterolemia+diabetes mellitus+chronic kidney disease. ICA and invasive functional tests show that this CMD model meet the diagnostic criteria for INOCA. It has been confirmed that one-stop CT multimodality examination including CT-MPI and CCTA can be used for the diagnosis of INOCA as a noninvasive diagnostic method.

Objective:To assess the value of coronary CT angiography(CCTA) based vessel characteristics and plaque features in diagnosing ischemic stenosis.Methods:From April 2014 to June 2021, 129 patients (including a total of 158 coronary arteries) who underwent CCTA, then completed invasive coronary angiography (ICA) as well as fractional flow reserve(FFR) within 30 days were retrospectively enrolled. All coronary arteries were divided into ischemic group (FFR≤0.80, n=77) and non-ischemic group (FFR>0.80, n=81). Vascular characteristics, high-risk plaque features, quantitative parameters and the morphology of plaque were obtained from CCTA images. Independent samples t-test, Wilcoxon rank sum test and χ 2 test were used to compare afore-mentioned variables between the ischemic group and the non-ischemic group. The logistic regression model was used to analyze the risk predictors for ischemic stenosis. Results:Compared with non-ischemic group, the stenosis degree of coronary arteries in ischemic group was more serious(72.09%±8.55% vs. 63.52%±13.49%; t=4.765, P<0.001). The proportion of left anterior descending artery(LAD) lesions in ischemic group was higher than that of non-ischemic group [88.31%(68/77)vs. 55.56%(45/81); χ 2=20.793, P<0.001]. In terms of CCTA plaque characteristics, the ischemic group demonstrated longer plaque length, smaller minimum lumen area, larger plaque burden, increased percent plaque diffuseness, and diffuse lesions were more common. As for morphological characteristics of plaque, the proportions of plaques with rectangle shape, proximal longitudinal eccentric shape and distal longitudinal eccentric shape were higher than those of non-ischemic group, whereas cosine eccentric plaques were more common in the non-ischemic group( P<0.001). Multivariate logistic regression analysis showed that the stenosis severity(OR =1.09, 95 %CI 1.04-1.14, P<0.001), LAD involvement(OR =4.23,95 %CI 1.01-17.72, P=0.049), diffuse lesion(OR =6.71,95 %CI 1.43-31.52, P=0.016), proximal longitudinal eccentric shape (OR =3.77,95 %CI 1.27-11.16, P=0.017), and distal longitudinal eccentric shape (OR =3.91,95 %CI 1.19-12.85, P=0.025) were the independent influence factors for ischemic stenosis. Conclusion:The CCTA-based stenosis degree of coronary artery, LAD involvement, diffuse lesion, proximal longitudinal eccentric shape, distal longitudinal eccentric shape were important influence factors for ischemic stenosis.

Purpose To investigate the feasibility of CT-based feature tracking technology to quantify left ventricular myocardial strain(MS)and its significance in hypertrophic obstructive cardiomyopathy(HOCM).Materials and Methods A total of 35 HOCM patients who underwent cardiac coronary angiography from March 2019 to December 2021 in the First Affiliated Hospital of the Air Force Military Medical University were retrospectively included,and a total of 60 cases who were negative for cardiac coronary angiography among those who visited the hospital with suspected coronary artery disease were randomly enrolled.Conventional cardiac functional parameters and MS parameters were quantified via post-processing software,and differences of parameters between the groups were analyzed.The diagnostic efficacy of MS parameters for HOCM was further evaluated.Results Compared to the control group,the HOCM group exhibited significant increases in various conventional left ventricular functional parameters,including left ventricular wall thickness,mass,mass index,end-diastolic volume and stroke volume(t=2.119 to 24.861,all P<0.05).However,there were no statistically significant differences in end-systolic volume and cardiac output between the two groups(P>0.05).The global longitudinal and radial strain values of HOCM group were significantly lower than those of control group(t=12.857,-6.427,P<0.01),while the endocardial global circumferential strain of HOCM group was significantly higher than that of control group(t=-2.369,P<0.05).Among MS parameters,global longitudinal strain exhibited the best diagnostic efficacy for HOCM,with an area under the curve of 0.997.A cutoff value of≤20.78%for global longitudinal strain showed that the sensitivity and specificity was 100%and 95%,respectively.Conclusion The MS parameters quantified by the CT-based feature tracking technique are superior to left ventricular ejection fraction in quantifying left ventricular function,with the highest sensitivity and specificity for early myocardial function impairment of longitudinal strain.In addition,the technique has good repeatability and is expected to become a new indicator for the assessment of myocardial function in HOCM.

Objective To evaluate the change of cardiac structure and function in patients with hypertrophic obstructive cardiomyopathy(HOCM)after ultrasound-guided percutaneous intramyocardial septal radiofrequency ablation(PIMSRA)via cardiac magnetic resonance(CMR).Methods Patients with HOCM who underwent PIMSRA,echocardiography and CMR preoperative scanning and one year after surgery were analyzed retrospectively.Myocardial structural and functional parameters were measured by Circle cardiovascular imaging post-processing software.The changes of myocardial parameters before and after surgery were compared by using paired sample t-test and Chi-square test.Results Compared with the preoperative assessment,patients'clinical symptoms and the cardiac function were significantly improved one year after surgery.The left ventricular outflow tract pressure gradient(LVOT-PG)was significantly decreased and length of mitral regurgitation was shortened one year after surgery compared with before surgery via ultrasound(P<0.05).Compared with the preoperative assessment,CMR showed that patients with end-systolic volume of left atrium,minimum volume of left atrium,transverse diameter of left atrium,thickness of ventricular septum and free wall of left ventricular at end-systolic section were significantly reduced,and left ventricular mass(LVM)was significantly decreased one year after surgery,with statistical significance between before and after surgery(P<0.001).One year after surgery,the left atrium ejection fraction(LAEF)was significantly increased(P<0.05),the maximum slope and the maximum signal intensity of the ventricular septum and the left ventricular free wall of the papillary muscle were significantly increased(P<0.001),and the peak time was significantly decreased(P<0.001)compared with before surgery.Conclusion After PIMSRA treatment,the systolic function of left atrium in HOCM patients is improved,and the microcirculation perfusion of left ventricular is significantly improved.

Objective:To explore the difference of the vessel and plaque characteristics, myocardial perfusion and cardiac function between patients with ischemia with non-obstructive coronary artery disease (INOCA) and obstructive coronary artery disease (CAD).Methods:From July 2021 to June 2022, 101 patients with angina were referred to dynamic computed tomography myocardial perfusion (CTP) and coronary computed tomography angiography (CCTA) and retrospectively included in our hospital. Based on the results of CTP and CCTA, patients were divided into INOCA (27 cases), moderate obstructive CAD (26 cases) and severe obstructive CAD (48 cases). The anatomical coronary artery stenosis, plaque characteristics and myocardial perfusion features of all patients were analyzed. Furthermore, left ventricular global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were obtained on full-phase reconstruction CCTA image by using Medis Suite 3.2 postprocessing software. Multigroup analysis used one way ANOVA or Kruskal Wallis H test. Results:Patients with INOCA were younger than patients with moderate and severe obstructive CAD ( P<0.001). INOCA patients (7.4%, 2/27) had lower rate of positive remodeling than both moderate (57.7%, 15/26, P<0.001) and severe obstructive CAD patients (33.3%, 16/48, P=0.017). The percentage of ischemic myocardium volume in patients with INOCA were similar with those in patients with severe CAD (all P>0.05), but significantly higher than those in patients with moderate CAD (all P<0.05). No significant difference in terms of GLS was detected between patients with INOCA [-17.4% (-21.6%, -11.6%)] and severe CAD [-17.6% (-21.9%, -14.8%), P=0.536], however, patients both with INOCA and severe CAD also had higher GLS than patients with moderate obstructive CAD [-22.3% (-29.8%, -19.0%), all P<0.05]. Conclusions:Based on"one-stop-shop"CTP combined with CCTA imaging, early cardiac functional changes including abnormal myocardial perfusion and myocardial strain in INOCA patients were similar to those in patients with severe obstructive CAD and more severe than those in patients with moderate obstructive CAD.