OBJECTIVETo observe the effect of adrenomedullin (ADM) on the pulmonary vascular collagen metabolism in hypoxic rats in order to study the effect of ADM on chronic hypoxic pulmonary vascular structural remodeling and its possible mechanism.

METHODSNineteen male Wistar rats were randomly divided into three groups: normal control (n=6), hypoxia (n=7) and ADM-treated hypoxia (n=6). ADM was subcutaneously administered into rats of the ADM-treated hypoxia group by mini-osmotic pump (300 ng/h) for two weeks. After two weeks of hypoxic challenge, mean pulmonary arterial pressure (mPAP) was evaluated using a right cardiac catheterization procedure. The ratio of right ventricular mass to left ventricular plus septal mass[RV/ (LV+S)] was measured. The changes of pulmonary vascular microstructure were observed. Meanwhile, the expression levels of collagen I, collagen III and transforming growth factor (TGF)-β in pulmonary arteries were detected by immunohistochemical assay.

RESULTSmPAP and RV/(LV+S) increased significantly in the hypoxia group compared with normal controls (P<0.01). The muscularization of small pulmonary vessels and the relative medial thickness of pulmonary arteries increased obviously in the hypoxia group compared with those in the normal control group (P<0.01). Meanwhile, the expression levels of collagen I, collagen III and TGF-β of pulmonary arteries in the hypoxia group increased markedly compared with those in the normal control group. However, mPAP and RV/(LV+S) were significantly reduced in the ADM-treated hypoxia group compared with those in the hypoxia group (P<0.01). ADM ameliorated pulmonary vascular structural remodeling of hypoxic rats, with a decrease in the expression of collagen I, collagen III and TGF-β of pulmonary arteries.

CONCLUSIONSADM might play a regulatory role in the development of hypoxic pulmonary hypertension and hypoxic pulmonary vascular remodeling, through inhibiting the expression of TGF-β and alleviating the collagen accumulation of pulmonary arteries.

Adrenomedullin ; pharmacology ; Animals ; Collagen ; metabolism ; Hypertension, Pulmonary ; etiology ; metabolism ; Hypoxia ; complications ; Male ; Pulmonary Artery ; metabolism ; Rats ; Rats, Wistar ; Transforming Growth Factor beta ; analysis ; physiology

OBJECTIVETachycardia induced cardiomyopathy (TIC), secondary to various tachyarrhythmias, is a reversible condition which can lead to cardiac enlargement and heart failure. The impairment of both structure and function of heart can be reverted completely or partially if tachyarrhythmias are ceased without delay. This study aimed to explore the clinical characteristics, therapeutic regimen and outcome of TIC in children.

METHODSClinical data of 12 children with TIC, who came from Peking University First Hospital from Feb. 2003 to Jun. 2009, were retrospectively analyzed and followed up. The echocardiogram data on admission were compared with those from 12 homochronous cases with idiopathic dilated cardiomyopathy matched with 12 TIC cases in age and gender.

RESULTSAtrial tachycardia is the commonest arrhythmia in 12 TIC cases (75%). Four cases underwent catheterization for radiofrequency ablation and all succeeded. The cardiac rhythm of 6 out of 8 cases treated with drugs became sinus rhythm after 3 days to 2 weeks antiarrhythmic drugs treatment. The remaining 2 cases still retained atrial rhythm, but the ventricular heart rates declined to normal. The left ventricular end-diastolic dimensions of the 12 cases were decreased compared with those of pretherapy [(37.5 ± 5.3) mm vs. (43.0 ± 5.7) mm, P < 0.01], and the left ventricular ejection fractions were increased [(60.5% ± 5.6%) vs. (33.7% ± 10.3%), P < 0.01], after (3.4 ± 2.3) months. In our (4.3 ± 2.4) year-follow-up, all cases were fine, except in one case the tachyarrhythmia relapsed because of discontinuation of the drug treatment by her parents. The left ventricular end-diastolic dimensions in 12 TIC cases were smaller than those of the 12 age- and gender-matched idiopathic dilated cardiomyopathy [(43.0 ± 5.7) mm vs. (54.8 ± 7.5) mm, t = 7.9, P < 0.01], and the ejection fractions were higher [(33.7% ± 10.3%) vs. (21.8% ± 7.5%), t = 3.7, P < 0.01].

CONCLUSIONThe diagnosis of TIC should be considered for the children with tachycardia, cardiac enlargement and cardiac insufficiency. The degree of cardiac enlargement and cardiac insufficiency might be of value for the differential diagnosis between TIC and idiopathic dilated cardiomyopathy. The rhythm control and ventricular rates control could all result in a favorite therapeutic efficacy.

Cardiomyopathies ; diagnosis ; Cardiomyopathy, Dilated ; diagnosis ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Retrospective Studies ; Tachycardia ; diagnosis

OBJECTIVETo evaluate the value of magnetic resonance dynamic contrast-enhanced (MR-DCE) and magnetic resonance diffusion-weighted imaging (MR-DWI) in the differentiation of benign and malignant musculoskeletal tumors.

METHODSSixty-three patients with pathologically confirmed musculoskeletal tumors were examined with MR-DCE and MR-DWI. Using single shot spin echo planar imaging sequence and different b values of 400, 600, 800 and 1000 s/mm(2), we obtained the apparent diffusion coefficient (ADC) of the lesions. ADC values were measured before and after MR-DCE, with a b value of 600 s/mm(2). The 3D fast acquired multiple phase enhanced fast spoiled gradient recalled echo sequence was obtained for multi-slice of the entire lesion. The time-signal intensity curve (TIC), dynamic contrast-enhanced parameters, maximum slope of increase (MSI), positive enhancement integral, signal enhancement ratio, and time to peak (T(peak)) were also recorded.

RESULTSADC showed no significant difference between benign and malignant tumors when the b value was 400, 600, 800, or 1000 s/mm(2), and it was not significantly different between benign and malignant tumors in both pre-MR-DCE and post-MR-DCE with b value of 600 s/mm(2). TIC were classified into four types type1 showed rapid progression and gradual drainage; type2 showed rapid progression but had no or slight progression; type 3 showed gradual progression; and type 4 had no or slight progression. Most lesions of type1 or type2 were malignant, whereas most lesions of type 3 or type 4 were benign. When using type1 and type 2 as the standards of malignancy, the diagnostic sensitivity and specificity was 87.23% and 50.00%, respectively. The types of TIC showed significant difference between benign and malignant musculoskeletal tumors(χ(2)=17.009,P=0.001). When using MSI 366.62 ± 174.84 as the standard of malignancy, the diagnostic sensitivity and specificity was 86.78% and 78.67%, respectively. When using T(peak)≤70s as the standard of malignancy, the diagnostic sensitivity and specificity was 82.89%and 85.78%, respectively. Positive enhancement integral and signal enhancement ratio showed no significant difference between benign and malignant musculoskeletal tumors.

CONCLUSIONSTIC, MSI and T(peak) of MR-DCE are valuable in differentiating benign from malignant musculoskeletal tumors. T(peak) has the highest diagnostic specificity, and TIC has the highest diagnostic sensitivity. The mean ADC value are no significant difference between benign and malignant tumors.

Adolescent ; Adult ; Aged ; Bone Neoplasms ; diagnosis ; Child ; Diagnosis, Differential ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Muscle Neoplasms ; diagnosis ; Young Adult

OBJECTIVETo explore therapeutic effects of bone setting manipulation for the treatment of over degree II supination-eversion fractures of ankle,and analyze manipulative reduction mechanism.

METHODSFrom 2005 to 2008, 95 patients with over degree II supination-eversion fractures of ankle were treated respectively by manipulation and operation. There were 43 cases [11 males and 32 females with an average age of (44.95 +/- 12.65) years] in manipulation group, and 2 cases were degree II, 11 cases were degree III, and 30 cases were degree IV. There were 52 cases [21 males and 31 females with an average age of (39.96 +/- 13.28) years] in operative group,and 6 cases were degree II, 18 cases were degree III, and 28 cases were degree IV. Bone setting manipulation and hard splint external fixation were applied to manipulative group. Operative reduction internal fixation was performed in operative group. X-ray was used to evaluate reduction of fracture before and after treatment, 2 months after treatment. Ankle joint function was evaluated according to Olerud-Molander scoring system after 6 months treatment.

RESULTSAll patients were followed up with good reduction. Three cases occurred wound complication in operative group, but not in manipulative group. In manipulation group, 19 cases got excellent results, 20 cases good and 4 cases fair; while in operative group, 30 cases got excellent results, 20 cases good and 2 cases poor. There were no significant differences in fracture reduction and ankle joint function recovery between two groups (P > 0.05). Efficacy of operative treatment was better than that of manipulative treatment at degree IV fracture (P < 0.05).

CONCLUSIONBone setting manipulation is a good method for treating supination-eversion ankle joint fractures, which has advantages of simple and safe operation, reliable efficacy. For ankle join fracture at degree IV, manipulative reduction should be adopted earlier, and operative treatment also necessary

Adult ; Ankle Injuries ; physiopathology ; therapy ; Ankle Joint ; physiology ; Case-Control Studies ; Female ; Fractures, Bone ; physiopathology ; therapy ; Humans ; Male ; Manipulation, Orthopedic ; methods ; Supination

To establish a fingerprint for Cimicifugae Rhizoma from different producing areas. Column kromasil (4.6 mm x 250 mm, 5 microm) was employed with acetonitrile-0.1% formic acid solution as the mobile phase for gradient elution. The flow rate was 1.0 mL x min(-1), the detection wavelength was 254 nm. Twenty chromatographic peaks were extracted as the common peaks of fingerprint, and 21 batches of samples were compared and classified with such methods as similarity evaluation, cluster analysis and principle component analysis. The results showed 12 common peaks and three categories of samples. The method was so highly reproducible, simple and reliable that it could provide basis for quality control and evaluation of Cimicifugae Rhizoma from different producing areas.
Chromatography, High Pressure Liquid ; methods ; Cimicifuga ; chemistry ; Drug Stability ; Quality Control

OBJECTIVECytokines such as VEGF and IGF play an important role in maintaining the function of blood vascular endothelium. And Akt1 is an important molecule in the intra-cellular signaling transduction. This study aims to investigate the molecular mechanism of Shugan Yiyang (SGYY) capsule in the treatment of arteriogenic erectile dysfunction (AED) by detecting the expressions and phosphorylation of VEGF, IGF and Akt1 in AED rats.

METHODSWe established AED models in 60 three-month-old adult male SD rats by bilateral ligation of the internal iliac artery, and assigned them to a sham operation group, a model control group, a sildenafil group, a low-dose SGYY group (0.5 g/[kg x d]) and a high-dose SGYY group (1 g/[kg x d]). After 30 days of gavage, we assayed the plasma concentrations of VEGF and IGF in the carotid artery of the rats by ELISA, detected the expressions of VEGF and IGF mRNA by real-time PCR and determined the expression and phosphorylation of Aktl protein in the corpus cavernosum penis by Western blot.

RESULTSIn the model control group, the expressions of VEGF and IGF mRNA were 0.41 +/- 0.06 and 0.42 +/- 0.06, the plasma concentrations of VEGF and IGF were (28.59 +/- 24.97) pg/ml and (15.82 +/- 4.37) ng/ml, and the expression of p-Aktl/Akt1 was 0.93 +/- 0.14. While in the high-dose SGYY group, the expressions of VEGF and IGF mRNA were 0.77 +/- 0.04 and 0.78 +/- 0.05, the plasma concentrations of VEGF and IGF were (95.83 +/- 37.34) pg/ml and (20.45 +/- 3.83) ng/ml, and the expression of p-Aktl/Aktl was 1.43 +/- 0.50. All the parameters above were significantly higher in the high-dose SGYY than in the model control group (P < 0.05), and so were they in the low-dose SGYY group except the plasma concentration of IGF (P < 0.05).

CONCLUSIONSGYY can significantly upregulate the expressions of VEGF, IGF and Akt1 in the corpus cavernosum penis of AED rats, and improve the function of blood vascular endothelium, which is probably an important mechanism of SGYY capsule acting on AED.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Erectile Dysfunction ; drug therapy ; etiology ; metabolism ; Insulin-Like Growth Factor I ; metabolism ; Male ; Phytotherapy ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Sprague-Dawley ; Somatomedins ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

To improve the recognition of angioimmunoblastic T-cell lymphoma (AITL) and to reduce misdiagnosis, a case diagnosed as AITL with large granular lymphocytosis was reported and the related articles were reviewed. A series of clinical tests, pathologic examination and immunohistochemical test, TCR gene rearrangement detection by multiple PCR and assay of lymphocyte immunophenotypes were carried out. The results indicated that the patient was characterized by fever, skin rash, generalized lymphadenopathy, splenomegaly, pleural effusion, ascites, anemia and thrombocytopenia, increase of circulating large granular lymphocytes with CD3(-) and CD16(+), CD56(+) were detected, T-cell receptor γ-chain gene was rearranged. More large granular lymphocytes with abnormal mitosis were found in ascites. The histological and immunohistochemical changes observed by the lymph node biopsy were compatible with AITL, some cells of which were CD56-positive. In conclusion, AITL is characterized by aggressive progress and generally occurs in elderly patients, its clinical prognosis is poor, the large granular lymphocytosis may be an autoimmune response to the tumor cells or originate from tumor stem/progenitor cells.
Humans ; Immunoblastic Lymphadenopathy ; complications ; immunology ; pathology ; Immunophenotyping ; Leukemia, Large Granular Lymphocytic ; complications ; immunology ; pathology ; Male ; Middle Aged

BACKGROUNDAlveolar echinococcosis (AE) is a disease in human and animals, and the cure rate is unsatisfactory. This study aimed to investigate the curative efficacy of different doses of locally applied radiotherapy on alveolar echinococcosis in rats.

METHODSRats infected with Echinococcus multilocularis were randomly divided into 4 groups of 15 rats each: low-, middle-, and high-irradiation groups and a control group. Rats in the control group underwent no treatment, while rats in the irradiation groups received 6-MeV radiotherapy at 20 Gy/8 f, 40 Gy/8 f, and 60 Gy/8 f respectively, once every 3 days for a total of 8 times. One month after radiotherapy, wet weight and AE vesicle inhibitory rate were detected in rats of each group. Histopathologic and ultrastructural observations of tissues with AE lesions were performed.

RESULTSIn the treatment groups, an obvious inhibitory effect was found in AE rats; the inhibitory rates were 50%, 72%, and 82%, respectively. There were also statistical differences in pathological changes and average wet weight of the lesions compared with the control group (P < 0.05). In the treatment groups, injuries of various degrees were found in the ultrastructure of the laminated and germinal layers in the capsular wall of AE, and injury was most severe in the high-dose group.

CONCLUSIONRadiotherapy has a dose-dependent inhibitory effect on the growth of AE.

Animals ; Dose-Response Relationship, Radiation ; Echinococcosis, Hepatic ; pathology ; radiotherapy ; Female ; Rats

In the present study, the differences in systemic vascular resistance (SVR) and the correlated risk factors between Han and Korean residents were investigated. 1 647 Hans and 876 Koreans from Mudanjiang and Hailin areas of Heilongjiang Province were examined with BIOZ Cardio Dynamics Monitor. A series of factors were determined, including SVR, systemic vascular resistance index (SVRI), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), cardiac output (CO), cardiac output index (CI) and heart rate (HR). The data were analyzed with SPSS 15.0 statistic software. When SVR/SVRI were compared between Han and Korean populations by t-test, it was shown that statistic difference existed in the following age and gender groups: (1) For SVR: male 41-50, 51-60, and 61-70 (P<0.001), 31-40 (P<0.01), 19-30 (P<0.05) age groups; female 15-18, 31-40, 51-60 (P<0.001), 41-50 (P<0.01), and 61-70 (P<0.05) age groups; (2) For SVRI, male 41-50, 51-60 (P<0.05) age groups; female 10-14, 51-60 (P<0.001), 15-18, 31-40 (P<0.01), and 41-50 (P<0.05) age groups. Covariance analysis suggests that, excluding the contributions of gender, age and body mass index (BMI), the differences in SVR/SVRI between the two populations are still significant (P<0.001). Multiple linear regression analysis reveals that SVR difference between Han and Korean populations is attributed to MAP, DBP, CI, SBP, HR; While SVRI difference between two populations is attributed to MAP, DBP, SBP, CI, HR, strongly to weakly, respectively. These results suggest the higher SVR and SVRI are possibly correlated with the relatively higher blood pressure of Korean, compared with that of Han population.
Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; Blood Pressure ; Cardiac Output ; Child ; China ; Female ; Heart Rate ; Humans ; Male ; Middle Aged ; Vascular Resistance

Objective:To deepen our understanding of Methylmalonic aciduria (MMA) associated pulmonary hypertension (PH) by analyzing the characteristics of clinical presentation,pulmonary high resolusion CT(HRCT),treatment response and gene mutation.Methods:This study includes 15 cases of pediatric patients with MMA associated PH diagnosed and treated in Peking University First Hospital pediatric department between May 2012 and May 2016 with symptoms of PH as their leading presentation.Clinical symptoms and signs were recorded,Routine blood laboratory examinations was done including arterial blood gas analysis.Plasma total homocysteine (Hcy) and brain natriuretic peptide (BNP) level were measured.MMA gene mutation was analyzed.Chest HRCT was done in most of the patients.Standard treatment strategy to MMA and PH was given and follow up study was done,and the related literature was reviewed.Statistical analysis was done.The diagnosis of MMA was made by methylmalonic acid level ＞ 100 times the normal value in the urine.The diagnosis of PH was made by pulmonary arterial systolic pressure (PASP) ＞ 40 mmHg,which was estimated by the measurement of tricuspid regurgitation velocity through Doppler Echocardiography.Results:(1) Patient characteristics:There were 10 male and 5 female patients diagnosed as MMA associated PH,aged 0.5 to 13.8 years,with an average of (5.0 ± 4.3) years.The age of onset of PH was (3.7 ± 3.5) years,with an early onset type MMA in 5 cases and late-onset type in 10 cases.(2) Clinical presentation:Among the 15 cases of MMA,the first symptoms were associated with PH in 10 cases,so PH and MMA were diagnosed at the same time,and PH was diagnosed 3 to 72 months post MMA presentation in the other 5 cases.The main presentations of PH were techypnea/dyspnea and cyanosis in 11 cases each,weakness and fatigue on exertion in 6 cases,and edema in 4 cases.PH WHO functional classification (WHO FC) was Class Ⅱ in 4,Class Ⅲ in 5 and Class Ⅵ in 6 cases,with an average of Class 3.1 ± 0.8.Multi-system involvements were common with the highest frequency in the kidney (14 cases).Macrocytic anemia was present in 8 cases and subclinical hypothyroidism in 5 cases,and mild to moderate mental retardation in 4 cases.(3) Laboratory examination:PASP of the 15 patients was from 49 to 135 mmHg,with an average of (90.3 ±23.9) mm Hg.Total blood Hcy level was severely elevated to (121.2 ± 48.2) μmol/L (range:35.0-221.0 μmol/L),and Hcy ＞ 100 μmoL/L within 11 cases.Plasma BNP level was also elevated,median 794 ng/ L (range:21.0-4 995.0 ng/L) with 12 cases ＞ 300 ng/L.Blood gas analysis showed low arterial blood oxygen saturation between 70％ and 94％,with an average of 81.4％ ±8.4％.(4) Chest HRCT:chest HRCT showed a diffuse ground-glass centrilobular nodular opacities with septal line thickening in the lungs in 9 cases,and with associated mediastinal lymph node enlargement in 1 case,which indicated pulmonary veno-occlusive disease (PVOD),a rare type of pulmonary arterial hypertension (PAH).There was lung infection or edema in 3 cases,and interstitial infiltration and mesh-like feature in other 3 cases,which was inferred to interstitial lung disease.(5) Gene mutation:Genetic testing was done in 10 cases,totally 5 reported disease-causing mutations were found.There were 100％ presence of MMACHC c.80A ＞ G mutation in all the 10 patients tested,with the allelic genes of c.609G ＞ A mutation in 6 patients,including a sister and a brother from the same parents.(6).Treatment and follow up:Intramus cular hydroxocobalamin or vitamin B12 was given to all of the patients,together with betaine,levocarnidtine,folinic acid and vitamin B6.According to the severity of PH,single or combined PAH targeted drugs was given to 11 cases.By an average of (20.0 ± 13.5) days of in-hospital treatment in 13 patients (excepting 1 case treated as outpatient),symptoms remarkably resolved,WHO FC reduced to an average of Class 2.4 ±0.9,PASP dropped to (69.4 ±21.3) mmHg,and plasma Hcy and BNP level were decreased to (74.9 ± 25.9) μmol/L and (341.6 ± 180.2) ng/L,respectively.The above values all reached statistical significance (P ＜ 0.05) compared with each related value before treatment.Therewere 2 patients who expired during hospitalization despite of treatment.At the end of 3 months' follow up,all of the 13 patients disposed oxygen,and PASP significantly dropped to 38.7 ± 7.9 mmHg,and plasma BNP returned to normal,but plasma Hcy level showed no further decline.At the last follow up of 27.5 ± 19.0 (range:11-64) months,all the patients' PASP remained normal except for the 13.8-year-old boy with 6 years-long history of MMA and almost 3.6 years' history of PH still having PASP 58 mmHg.Conclusion:PH is a severe complication of MMA combined type,especially cblC type,it is more often happens in late-onset type of male patients and can be the first and leading manifestations of MMA.Its clinical symptoms are urgent and severe,characterized by tachypnea/dyspnea and cyanosis,and sometimes right heart failure,hypoxemia is usually present,chest HRCT is often indicative of PVOD,lung edema and interstitial lung disease may occur.Rapid diagnosis and targeted treatment of MMA with appropriate anti-PAH mcdication can reverse PH and save life.MMACHC gene c.80A ＞ G mutation may be the hot point of MMA cblC type associated PH.