Effect of platelet-derived growth factor-BB on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension and its mechanism / 中国当代儿科杂志

OBJECTIVES@#To study the effect of platelet-derived growth factor-BB (PDGF-BB) on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH).@*METHODS@#A total of 128 neonatal rats were randomly divided into four groups: PDGF-BB+HPH, HPH, PDGF-BB+normal oxygen, and normal oxygen (n=32 each). The rats in the PDGF-BB+HPH and PDGF-BB+normal oxygen groups were given an injection of 13 μL 6×1010 PFU/mL adenovirus with PDGF-BB genevia the caudal vein. After 24 hours of adenovirus transfection, the rats in the HPH and PDGF-BB+HPH groups were used to establish a neonatal rat model of HPH. Right ventricular systolic pressure (RVSP) was measured on days 3, 7, 14, and 21 of hypoxia. Hematoxylin-eosin staining was used to observe pulmonary vascular morphological changes under an optical microscope, and vascular remodeling parameters (MA% and MT%) were also measured. Immunohistochemistry was used to measure the expression levels of PDGF-BB and proliferating cell nuclear antigen (PCNA) in lung tissue.@*RESULTS@#The rats in the PDGF-BB+HPH and HPH groups had a significantly higher RVSP than those of the same age in the normal oxygen group at each time point (P<0.05). The rats in the PDGF-BB+HPH group showed vascular remodeling on day 3 of hypoxia, while those in the HPH showed vascular remodeling on day 7 of hypoxia. On day 3 of hypoxia, the PDGF-BB+HPH group had significantly higher MA% and MT% than the HPH, PDGF-BB+normal oxygen, and normal oxygen groups (P<0.05). On days 7, 14, and 21 of hypoxia, the PDGF-BB+HPH and HPH groups had significantly higher MA% and MT% than the PDGF-BB+normal oxygen and normal oxygen groups (P<0.05). The PDGF-BB+HPH and HPH groups had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group at all time points (P<0.05). On days 3, 7, and 14 of hypoxia, the PDGF-BB+HPH group had significantly higher expression levels of PDGF-BB and PCNA than the HPH group (P<0.05), while the PDGF-BB+normal oxygen group had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group (P<0.05).@*CONCLUSIONS@#Exogenous administration of PDGF-BB in neonatal rats with HPH may upregulate the expression of PCNA, promote pulmonary vascular remodeling, and increase pulmonary artery pressure.

Efficacy and Safety of Jianpi Jieyu Decoction for Patients with Mild-to-Moderate Depression of Xin (Heart)-Pi (Spleen) Deficiency Syndrome: A Multi-centre Randomized Controlled Study / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome.@*METHODS@#In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded.@*RESULTS@#From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05).@*CONCLUSION@#Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).

Effect and mechanism of vascular endothelial growth factor-A on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension / 中国当代儿科杂志

OBJECTIVE@#To study the role of vascular endothelial growth factor-A (VEGF-A) in pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH) by regulating survivin (SVV).@*METHODS@#A total of 96 neonatal rats were randomly divided into three groups: HPH+VEGF-A group, HPH group, and control group. Each group was further randomly divided into 3-, 7-, 10-, and 14-day subgroups (@*RESULTS@#The HPH group had a significantly higher mean RVSP than the control and HPH+VEGF-A groups at each time point (@*CONCLUSIONS@#Prophylactic intratracheal administration of exogenous VEGF-A in neonatal rats with HPH can inhibit pulmonary vascular remodeling and reduce pulmonary arterial pressure by upregulating the expression of SVV in the early stage of hypoxia. This provides a basis for the interventional treatment of pulmonary vascular remodeling in neonatal HPH.

Change of Hepcidin in Patients with Iron Overload at the Tibet Plateau / 中国实验血液学杂志

OBJECTIVE@#To explore the possible etiological factors of iron overload through detecting plasma hepcidin level of adult males at Tibet plateau.@*METHODS@#81 Tibetan male adult patients hospitalized in our department during January 2017 - December 2018 were selected, and divided into iron overload group and non-iron overload group. The difference in serum ferritin, serum iron, total iron binding capacity, hemoglobin, HBSAg, ALT, AST, albumin, creatinine and hepcidin of patients in each group were tested. To analyze the differences between groups. The regression analysis was applied to analyze the relationship between laboratory index and hepcidin.@*RESULTS@#The plasma hepcidin of iron overload group was significantly higher than that of the non-iron overload group [93.69 (65.57-133.92) ng/ml vs 63.93 (40.01-90.65) ng/ml] (P=0.005). And there was a positive correlation between plasma hepcidin and ferritin (β=0.03 ng/ml，95%CI 0.01-0.05) (P<0.01) and BMI (β=5.71 ng/ml，95%CI 0.54-10.88) (P<0.05）.@*CONCLUSION@#Iron overload at Tibet plateau can not be attributed to hepcidin deficiency in Tibetan adult male patients. Iron metabolism disorders in Tibetan population may be associated with metabolic syndrome.

Cardiac valve calcification in patients with end stage renal disease and its correlation with left ventricular function / 医学研究生学报

ObjectiveCardiovascular calcification is a highly common complication in patients with end stage renal disease. The aim of this study was to explore the effect of cardiac valve calcification (VC) on left ventricular function and morphology in patients with end stage renal disease by echocardiography. Methods Echocardiography results of 137 patients with end stage renal disease who underwent hemodialysis in the general hospital of the eastern theater of war from June 2013 to August 2013 were retrospectively analyzed. The morphological structure and function parameters of the left ventricle were measured by echocardiography and tissue doppler imaging to assess cardiovascular calcification. Logistic regression analysis was used to investigate the independent risk factors of cardiac valve calcification.Results VC was found in 55 patients (40.1%) in this study. The age [(52.7±11.1) vs (42.6±12.3)], low density lipoprotein [(2.7±0.8)mg/dL vs (2.2±0.6)mg/dL], cholesterol [(5.2±1.1)mg/dL vs (4.5±0.9)mg/dL] levels were higher, while serum creatinine [(10.7±2.7)mg/dL vs (13.2±8.5)mg/dL] was lower in patients with VC than patients without VC (P<0.05). Logistic regression analysis showed that the older age, longer dialysis time and higher mean value of mitral annular systolic values were the independent risk factors for VC. The morphological and structural parameters of the left ventricle of the group with VC were higher than those of the group without VC (P<0.05), while the parameters of left ventricular diastolic function of the group with VC were lower than those of the group without VC (P<0.05).ConclusionVC diagnosed by echocardiography in patients with end stage renal disease may indicate significantly higher incidence of left ventricular hypertrophy and reduction of left ventricular diastolic function in comparison to those without VC.

Analysis of HFE and Non-HFE Mutations in a Tibet Cohort with Iron Overload / 中国实验血液学杂志

OBJECTIVE@#The explore the molecular basis of iron-overload in Tibet nationality population of Tibet.@*METHODS@#The inpatients with iron-overload in our department from Dec. 1st 2014 to Jul.31st 2016 were enrolled in this study. Abdominal MRI and the mutation sites C282Y and H63D in HFE exon were examined. For HFE mutation-negative patients, the non-HFE mutation was detected, including 5 HJV mutations of G320V, p.Q312X, p.D249H, p.I281T, p.C321X and 2 TFR2 mutations: (Y250X, I238M), and 2 SLC40A1 mutations: (V162del, N144H).@*RESULTS@#Among 113 iron overload patients, only one showed homozygous p.H63D mutation, and one showed heterozygosis p.H63D mutation. In 73 patients accepted non-HFE gene detection, only one was heterozygosis p.D249N mutation in HJV, and one was heterozygosis p.I238M mutation in TFR2.@*CONCLUSION@#Currently, the pathogenic gene for Tibetan iron-overload has not yet been found.

Influence of comprehensive rehabilitation intervention on serum NT-proBNP level ,anxiety and depres-sion in AMI patients / 心血管康复医学杂志

Objective :To explore influence of comprehensive rehabilitation intervention on serum NT-proBNP level , anxiety and depression in AMI patients .Methods : A total of 90 AMI patients treated in our hospital were selected , randomly and equally divided into routine rehabilitation (RR) group and comprehensive rehabilitation (CR) group , both groups were intervened for six months .Serum NT-proBNP level within 6h after onset ,2d ,6d ,12d and one month after intervention ,scores of Hamilton rating scale for anxiety (HAMA) ,Hamilton rating scale for depres-sion (HAMD) and general quality of life inventory (GQOLI )-74 before ,and one ,three , six months after inter-vention were measured and compared between two groups .Results : Compared with RR group ,there was significant reduction in serum NT-proBNP level [6d : (3126-33 ± 91-32 ) ng／L vs.(1799-16 ± 76-83 ) ng／L , one month :(1358-91 ± 53-01) ng／L vs.(505-13 ± 38-93) ng／L] on 2d ,6d ,12d and one month after intervention , P＝0-001 all ;significant reductions in scores of HAMA and HAMD [six months :HAMA ,(19-8 ± 1-6) scores vs.(10-3 ± 1-9) scores ;HAMD ,(20-2 ± 1-9) scores vs .(11-6 ± 1-5) scores] on three and six months after intervention , P＝0-001 all ;significant rise in scores of physical function [ (48-4 ± 1-8) scores vs .(49-7 ± 1-2) scores] and material life [ (51-5 ± 1-1) scores vs .(54-4 ± 1-9) scores] on three months after intervention ,and all dimension scores of GQOLI-74 on six months after intervention in RR group , P＝0-001 all.Conclusion : Comprehensive rehabilitation intervention can significantly reduce serum NT-proBNP level , improve anxiety and depression in AMI patients , which contributes to improving quality of life in these patients .It′s worth extending .

tients with chronic heart failure / 心血管康复医学杂志

Objective :To study influence of exercise rehabilitation on serum levels of N terminal pro brain natriuretic peptide (NT‐proBNP) and high sensitive cardiac troponin T (hscTnT) and cardiac function indexes in patients with chronic heart failure (CHF).Methods :A total of 140 CHF patients treated in our hospital were randomly and equal‐ly divided into routine group (received routine treatment ) and exercise rehabilitation group (received exercise reha‐bilitation based on routine group ) ,both groups were treated for three weeks .Serum levels of NT‐proBNP ,hscTnT and cardiac function indexes were measured and compared between two groups before and after rehabilitative inter‐vention .Results :Compared with routine group after three‐week treatment ,there were significant reductions in ser‐um levels of NT‐proBNP [ (2. 60 ± 0. 53) μg／L vs.(2. 11 ± 0.52) μg／L] ,hscTnT [ (0.38 ± 0. 12) μg／L vs.(0. 30 ± 0.09) μg／L] ,left ventricular end‐diastolic dimension (LVEDd) [ (56.78 ± 6.21) mm vs.(50. 10 ± 4.21) mm] , left ventricular end‐systolic dimension (LVESd) [ (48. 11 ± 5. 88) mm vs.(35.00 ± 6.20) mm] ,left atrial diameter (LAD) [ (44. 01 ± 5.69) mm vs.(34.26 ± 6.09) mm] and left ventricular mass index (LVMI) [ (185.01 ± 31. 34) g／m2 vs.(125.89 ± 43. 52) g／m2 ] ,and significant rise in LVEF [ (43.10 ± 6.21)% vs.(52.13 ± 5.10)%] and left ventricular early／late diastolic peak flow velocity (E／A) [ (0. 94 ± 0. 44) vs.(1.40 ± 0.56)] in exercise rehabilita‐tion group , P＝0.001 all .Conclusion :Exercise rehabilitation can significantly reduce serum NT‐proBNP and hscTnT levels ,improve cardiac function in CHF patients .

Protective effects of heat shock protein 70 against hypoxic pulmonary hypertension in neonatal rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of heat shock protein 70 (HSP70) against hypoxic pulmonary hypertension (HPH) in neonatal rats.</p><p><b>METHODS</b>A total of 128 neonatal rats were randomly divided into blank control group, HPH model group, empty virus group, and HSP70 group, with 32 rats in each group. Before the establishment of an HPH model, the rats in the blank control group and HPH model group were given caudal vein injection of 5 μL sterile saline, those in the empty virus group were given caudal vein injection of 5 μL Ad-GFP (1 010 PFU/mL), and those in the HSP70 group were given caudal vein injection of 5 μL Ad-HSP70 (1 010 PFU/mL). HPH model was prepared in the HPH model, empty virus, and HSP70 groups after transfection. At 3, 7, 10, and 14 days after model establishment, a multi-channel physiological recorder was used to record mean pulmonary arterial pressure (mPAP), optical and electron microscopes were used to observe the structure and remodeling parameters of pulmonary vessels, and Western blot was used to measure the protein expression of HSP70, hypoxia-inducible factor-1α (HIF-1α), endothelin-1 (ET-1), and inducible nitric oxide synthase (iNOS) in lung tissues.</p><p><b>RESULTS</b>At 3, 7, 10, and 14 days after model establishment, the HPH model group and the empty virus group had a significantly higher mPAP than the blank control group (P<0.05). On days 7 and 10 of hypoxia, the blank control group and the HSP70 group had significantly lower MA% and MT% than the HPH model group and the empty virus group (P<0.01); on day 14 of hypoxia, the HPH model group, empty virus group, and HSP70 group had similar MA% and MT% (P>0.05), but had significantly higher MA% and MT% than the blank control group (P<0.01). On days 3, 7 and 10 of hypoxia, the HSP70 group had significantly higher protein expression of HSP70 than the HPH model group, empty virus group, and blank control group (P<0.01); the HSP70 group had significantly lower expression of HIF-1α, ET-1, and iNOS than the HPH model group and the empty virus group (P<0.05) and similar expression of HIF-1α, ET-1, and iNOS as the blank control group (P>0.05).</p><p><b>CONCLUSIONS</b>In neonatal rats with HPH, HSP70 transfection can increase the expression of HSP70 in lung tissues, downregulate the expression of HIF-1α, ET-1, and iNOS, alleviate pulmonary vascular remodeling, and reduce pulmonary artery pressure; therefore, it may become a new strategy for the treatment of HPH in neonates.</p>

Effect of heat shock protein 70 on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of heat shock protein 70 (HSP70) on pulmonary arterial pressure and pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH).</p><p><b>METHODS</b>A total of 128 Wistar neonatal rats were randomly divided into HPH model and blank control groups. According to the transfection solution, the HPH model group was further divided into normal saline group, empty virus group (viral vectors marked with a green fluorescent signal and not carrying the target gene), and virus+HSP70 group (viral vectors marked with a green fluorescent signal and carrying the target gene). The HPH model was established by inhalation of nitrogen-oxygen mixture (1.5 L/minutes and 8% oxygen). Pulmonary arterial pressure (mPAP) and the indicators of pulmonary vascular remodeling (MT% and MA%) were measured on days 3, 7, 10, and 14 of hypoxia.</p><p><b>RESULTS</b>On days 3, 7, and 10 of hypoxia, the normal saline and empty virus groups had significantly enhanced expression of HSP70 compared with the blank control group (P<0.01), and the virus+HSP70 group had significantly higher expression of HSP70 than the blank control, normal saline, and empty virus groups (P<0.01). On day 14 of hypoxia, the expression of HSP70 showed no significant difference between these groups (P>0.05). On days 3, 7, and 10 of hypoxia, the normal saline and empty virus groups showed continuous increases in mPAP compared with the blank control group (P<0.05). There was no significant difference in mPAP between the virus+HSP70 and blank control groups (P>0.05). On day 14 of hypoxia, there was no significant difference in mPAP among three subgroups of the HPH model group (P>0.05), but the mPAP in the three subgroups was significantly higher than in the blank control group (P<0.05). After 7 days of hypoxia, the normal saline and empty virus groups showed significantly higher MT% and MA% than the blank control group (P<0.05), but the two indicators showed no significant differences between the virus+HSP70 and the blank control groups (P>0.05). On day 14 of hypoxia, there were no significant differences in MT% and MA% among three subgroups of the HPH model group (P>0.05), but the MT% and MA% in the three subgroups were higher than in the blank control group (P<0.05).</p><p><b>CONCLUSIONS</b>HSP70 may reduce pulmonary arterial pressure and pulmonary vascular remodeling in neonatal rats with HPH.</p>

The Number of Positive Pelvic Lymph Nodes and Multiple Groups of Pelvic Lymph Node Metastasis Influence Prognosis in Stage IA-IIB Cervical Squamous Cell Carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pelvic lymph node metastasis (LNM) is an important prognostic factor in cervical cancer. Cervical squamous cell carcinoma accounts for approximately 75-80% of all cervical cancers. Analyses of the effects of the number of positive lymph nodes (LNs), unilateral versus bilateral pelvic LNM and a single group versus multiple groups of pelvic LNM on survival and recurrence of cervical squamous cell carcinoma are still lacking. The study aimed to analyze the effects of the number of positive pelvic LNs and a single group versus multiple groups of pelvic LNM on survival and recurrence.</p><p><b>METHODS</b>We performed a retrospective review of 296 patients diagnosed with Stage IA-IIB cervical squamous cell carcinoma who received extensive/sub-extensive hysterectomy with pelvic lymphadenectomy/pelvic LN sampling at Peking University People's Hospital from November 2004 to July 2013. Ten clinicopathological variables were evaluated as risk factors for pelvic LNM: Age at diagnosis, gravidity, clinical stage, histological grade, tumor diameter, lymph-vascular space involvement (LVSI), depth of cervical stromal invasion, uterine invasion, parametrial invasion, and neoadjuvant chemotherapy.</p><p><b>RESULTS</b>The incidence of pelvic LNM was 20.27% (60/296 cases). Pelvic LNM (P = 0.00) was significantly correlated with recurrence. Pelvic LNM (P = 0.00), the number of positive pelvic LNs (P = 0.04) and a single group versus multiple groups of pelvic LNM (P = 0.03) had a significant influence on survival. Multivariate analysis revealed that LVSI (P = 0.00), depth of cervical stromal invasion (P = 0.00) and parametrial invasion (P = 0.03) were independently associated with pelvic LNM.</p><p><b>CONCLUSIONS</b>Patients with pelvic LNM had a higher recurrence rate and poor survival outcomes. Furthermore, more than 2 positive pelvic LNs and multiple groups of pelvic LNM appeared to identify patients with worse survival outcomes in node-positive IA-IIB cervical squamous cell carcinoma. LVSI, parametrial invasion, and depth of cervical stromal invasion were identified as independent clinicopathological risk factors for pelvic LNM.</p>

Association between pulmonary vascular remodeling and expression of hypoxia-inducible factor-1α, endothelin-1 and inducible nitric oxide synthase in pulmonary vessels in neonatal rats with hypoxic pulmonary hypertension / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the association between pulmonary vascular remodeling and expression of hypoxia-inducible factor-1α (HIF-1α), endothelin-1 (ET-1) and inducible nitric oxide synthase (iNOS) in pulmonary vessels in neonatal rats with hypoxic pulmonary hypertension (HPH).</p><p><b>METHODS</b>A neonatal rat model of HPH was established as an HPH group, and normal neonatal rats were enrolled as a control group. The mean pulmonary arterial pressure (mPAP) was measured. The percentage of medial thickness to outer diameter of the small pulmonary arteries (MT%) and the percentage of medial cross-section area to total cross-section area of the pulmonary small arteries (MA%) were measured as the indicators for pulmonary vascular remodeling. The immunohistochemical reaction intensities for HIF-1α, ET-1 and iNOS and their mRNA expression in lung tissues of neonatal rats were measured. Correlation analysis was performed to determine the relationship between pulmonary vascular remodeling and mRNA expression of HIF-1α, ET-1 and iNOS.</p><p><b>RESULTS</b>The mPAP of the HPH group kept increasing on days 3, 5, 7, 10, 14, and 21 of hypoxia, with a significant difference compared with the control group (P<0.05). The HPH group had significantly higher MT% and MA% than the control group from day 7 of hypoxia (P<0.05). HIF-1α protein expression increased significantly on days 3, 5, 7 and 10 days of hypoxia, and HIF-1α mRNA expression increased significantly on days 3, 5 and 7 days of hypoxia in the HPH group compared with the control group (P<0.05). ET-1 protein expression increased significantly on days 3, 5 and 7 days of hypoxia and ET-1 mRNA expression increased significantly on day 3 of hypoxia in the HPH group compared with the control group (P<0.05). Both iNOS protein and mRNA expression were significantly higher on days 3, 5 and 7 days of hypoxia than the control group (P<0.05). Both MT% and MA% were positively correlated with HIF-1α mRNA expression (r=0.835 and 0.850 respectively; P<0.05).</p><p><b>CONCLUSIONS</b>Pulmonary vascular remodeling is developed on day 7 of hypoxia in neonatal rats. HIF-1α, ET-1 and iNOS are all involved in the occurrence and development of HPH in neonatal rats.</p>

Changes and significance of endothelin-1 in lung tissue of hypoxic pulmonary hypertension development in neonatal rats / 中华实用儿科临床杂志

Objective To know about the effect and significance of endothelin-1 (ET-1) in pathogenesis of hypoxic pulmonary hypertension(HPH) in neonatal rats.Methods The 120 newborn Wistar rats were randomly divided into hypoxic group and control group,and the rats of hypoxic group were made into HPH model.Mean pulmonary arterial pressure(mPAP) was measured on day 3,5,7,10,14 and 21 after hypoxia.The morphological change of pulmonary vessels were observed,and pulmonary vascular remodeling indexes were also obtained,including the ratio of middle wall thickness to external diameter of small pulmonary arteries (MT％) and the ratio of media cross-section area to total cross-sectional area of small pulmonary arteries(MA％).Immunohistochemistry and Western blot tests were done to determine the expression of ET-1 in lung tissue.Results 1.After hypoxia for 3,5,7,10,14,21 days,the levels of mPAP in hypoxia group[(8.492 ± 1.548) mm Hg,(10.022 ± 1.182) mm Hg,(11.470 ± 2.868) mm Hg,(16.842 ±2.154) mm Hg,(12.824 ± 2.859) mm Hg,(21.036 ± 2.590) mm Hg; 1 mm Hg =0.133 kPa] were significantly higher than those in control group[(5.141 ± 1.022) mm Hg,(8.137 ± 1.057) mm Hg,(8.730 ±0.868) mm Hg,(12.125 ±2.541) mm Hg,(8.920 ±0.744) mm Hg,(11.156 ±1.644) mm Hg] (all P ＜0.05).2.Seven days after hypoxia exposure,small pulmonary arterials remodeling was observed.MT％ [(53 ± 11) ％] and MA％ [(60 ± 9) ％]in hypoxia group were also significantly higher than those in control group [(49 ± 11) ％,(54 ± 8) ％] (all P ＜ 0.05).3.The results of immunohistochemistry:the expression intensities of ET-1 were significantly higher in hypoxia group (0.614,0.613,0.651) after hypoxia for 3,5,7 days than those in control group (0.433,0.386,0.369) (all P ＜ 0.05).4.The results of Western blot:the levels of ET-1 were significantly higher in hypoxia group(4.885 ± 1.391,4.434 ± 1.726,6.309 ± 0.330,2.353 ± 0.961) after hypoxia for 3,5,7 and 10 days than those in control group (1.698 ± 0.794,1.454 ± 0.776,2.045 ± 0.668,0.766 ± 0.515) (all P ＜ 0.05).5.The results of correlation analysis:the total expression of ET-1 protein was positively correlated with the total level of mPAP on 3-7 days after hypoxia (r =0.459,P ＜ 0.05).However,the expression of ET-1 had no significant correlation with MT％ and MA％ (rMT =-0.041,rMA =0.322,all P ＞ 0.05).Conclusions The level of ET-1 in lung tissue of HPH newborn rats increased in the early stage after hypoxia exposure and no longer increased during the late stage,which indicated that hypoxia tolerance prevailed.ET-1 acted as an early reactive marker in the process of HPH development in neonatal rats and may be mainly associated with elevated mPAP,which further prompted that through valid means to inhibit the expression of ET-1 in the early stage of hypoxia,in which the prevention and treatment of this disease may be more effective.

Changes of hypoxia-inducible factor-1α, endothelin-1 and adrenomedullin in newborn rats with hypoxia-induced pulmonary hypertension / 中华实用儿科临床杂志

Objective To provide the foundation of theory on prevention of hypoxia-induced pulmonary hypertension (HPH) by investigating the concentrations in the serum and expression levels in the lung tissue,and by studying the roles of hypoxia-inducible factor-1 α (HIF-1 α),endothelin-1 (ET-1) and adrenomedullin (ADM) in newborn rats with HPH.Methods Seventy-two newborn rats were randomly divided into hypoxic group(hypoxia exposure) and normoxic group.The mean pulmonary arteria pressure (mPAP),concentrations in the serum and expression levels in the lung tissue of the above-mentioned factors were measured in these neonatal rats after 3,5,7,10,14 and 21 days,including hypoxic group and normoxic group,respectively.The morphology of pulmonary arterioles was observed and the vascular remodeling indexes were measured.Results 1.Compared with the normoxic group,the mPAP increased with the prolonged hypoxic time in the hypoxic group(P ＜ 0.05).2.Concentrations in the serum and expression levels in the lung tissue of HIF-1 α were higher than those of the normoxic group on 3,5,7,10,14 days (all P ＜ 0.05).The serum concentration of ET-1 elevated significantly in the hypoxic group at each time point,and ET-1 mRNA increased only on 3 and 5 days of the hypoxia group.The serum concentration of ADM level in the hypoxic group was higher than that of the normoxic group on 3 and 5 days,but lower than the normoxic group after 14 and 21 days of hypoxia,and the expression of ADM mRNA in the lung tissue was higher on 3 and 5 days in the hypoxic group.3.Morphology and ultrastructure of the pulmonary arteries change were found after 7 days of hypoxia exposure.Conclusions HIF-1α may regulate ET-1 and ADM in the pathogenesis of HPH.ET-1 plays a powerful role by pulmonary vasoconstriction and vascular remodeling,whereas ADM displays the protective effects on blood vessels in the early stages of HPH.Pulmonary vascular remodeling occurs in the hypoxic group after 7 days of hypoxia.

Effect of hypoxia-inducible factor-1α, endothelin-1 and inducible nitric oxide synthase in the pathogenesis of hypoxia-induced pulmonary hypertension of the neonatal rats / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the effect of hypoxia-inducible factor-1α (HIF-1α) in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH) of the neonatal rats through the study on the expression level of HIF-1α and its regulation factors: endothelin-1 (ET-1) and inducible nitric oxide synthase (iNOS) in blood serum and lung tissue.</p><p><b>METHODS</b>To make an HPH model of neonatal rats, 120 newborn Wistar rats were divided at random into two groups: HPH group and the regular oxygen controlled group with the same birthday. The rats of the two groups were put in the condition of hypoxia for 3, 5, 7, 10, 14, 21 days and then 10 rats of HPH group and control group were picked up, their mean pulmonary arterial pressure (mPAP), serum HIF-1α, and iNOS, and ET-1 content were tested, and finally their lung tissue was taken after they were sacrificed and the expression level of the gene mRNA of HIF-1α, iNOS and ET-1.</p><p><b>RESULTS</b>(1) The rats experienced hypoxia for 3, 5, 7, 10, 14 or 21 days had an increasing mPAP: [8.47 ± 1.45, 10.04 ± 1.69, 10.89 ± 2.97, 16.96 ± 1.97, 13.01 ± 1.93, 21.04 ± 2.13 (mm Hg)], which had a significant differences compared with control groups [5.11 ± 1.06, 8.12 ± 1.11, 8.77 ± 0.92, 12.23 ± 1.78, 8.89 ± 0.89, 11.09 ± 1.64 (mm Hg)] (P < 0.05). (2) The rats in hypoxia group had a higher serum HIF-1α [0.83 ± 0.07, 0.84 ± 0.17, 0.97 ± 0.13, 1.10 ± 0.30, 0.92 ± 0.19 (pg/nmol)] than the control group [0.26 ± 0.20, 0.37 ± 0.16, 0.44 ± 0.18, 0.41 ± 0.23, 0.66 ± 0.18 (pg/nmol)] as they experienced hypoxia for 3, 5, 7, 10, and 14 days (P < 0.05); HIF-1α mRNA expression in lung tissue (1.301 ± 0.47, 1.032 ± 0.47, 1.453 ± 0.76) was also significantly higher than that of the control group (0.231 ± 0.26, 0.425 ± 0.59, 0.692 ± 0.13) (P < 0.05); serum ET-1 levels [51.50 ± 3.19, 44.1 ± 10.81, 56.85 ± 9.10, 52.91 ± 9.59, 51.16 ± 8.87, 50.21 ± 10.41 (pg/nmol)] were clearly higher than that of the control group [9.04 ± 2.85, 21.70 ± 8.78, 19.63 ± 9.66, 18.30 ± 7.32, 19.69 ± 5.92, 16.88 ± 6.14 (pg/nmol)] (P < 0.01); ET-1 mRNA expression in lung tissue (0.037 ± 0.018) was significantly increased after 3-day hypoxia as compared with control group (0.006 ± 0.004) (P < 0.05). Serum content of iNOS (5.62 ± 0.79) µmol/L was significantly higher than the control group (1.63 ± 0.67) µmol/L (P < 0.05) after a 3-day hypoxia, but there was no significant difference after a hypoxia for 5, 7 or 10 days, compared with the control group (P > 0.05), and the content of serum iNOS after hypoxia for 14 or 21 days (4.56 ± 0.96, 5.86 ± 1.76) µmol/L was lower than that of the control group (10.35 ± 1.99, 8.44 ± 2.76) µmol/L (P < 0.05). iNOS mRNA expression in lung tissue (0.035 ± 0.024, 0.332 ± 0.198, 0.527 ± 0.098) significantly increased after hypoxia for 3, 5 or 7 days as compared with the control group (0.005 ± 0.0001, 0.008 ± 0.002, 0.040 ± 0.012) (P < 0.05).</p><p><b>CONCLUSION</b>As an initial factor, low oxygen made HIF-1α, ET-1 and iNOS expression raised in the pathogenesis of HPH of the neonatal rats and causedn a imbalance of ET-1 and NO. HIF-1α, ET-1 and iNOS altogether contributed to the occurrence and development of HPH in neonatal rats.</p>

Loss of membranous carcinoembryonic antigen-related cell adhesion molecule 1 expression is related to decreased relapse-free survival of hepatocellular carcinoma following liver transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Loss of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expression is an adverse prognostic factor in hepatocellular carcinoma (HCC). The purpose of this study was to investigate the expression of CEACAM1 and its effect on relapse-free survival (RFS) following liver transplantation (LT) for HCC.</p><p><b>METHODS</b>Expression of CEACAM1 was immunohistochemically detected in HCC specimens from 48 patients. The relationship between CEACAM1 expression and clinicopathologic variables, as well as tumor recurrence, was further analyzed.</p><p><b>RESULTS</b>Of the 48 HCC specimens, membranous CEACAM1 expression was detected in 25 specimens and cytoplasmic CEACAM1 expression was detected in 19 specimens. Four specimens had loss of CEACAM1 expression. Loss of membranous CEACAM1 expression was significantly associated with tumor size, tumor number, and serum α-fetoprotein levels (all P < 0.05). Patients with loss of membranous CEACAM1 had significantly poorer RFS than patients with membranous expression, determined via Kaplan-Meier analysis (P = 0.027). Multivariate analysis revealed that loss of membranous CEACAM1 expression might be an independent prognostic factor of RFS for HCC patients after liver transplantation (P = 0.037).</p><p><b>CONCLUSION</b>Loss of membranous CEACAM1 expression in HCC was closely associated with aggressive tumor biology and might be a relapsing biomarker of HCC treated with LT.</p>

Pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the changes of pulmonary vascular remodeling in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH) in neonatal rats.</p><p><b>METHODS</b>Ninety-six newborn Wistar rats were randomly divided into an HPH group (hypoxia exposure) and a control group (room air exposure). The mean pulmonary arteria pressure (mPAP), right ventricle hypertrophy index (RVHI), and vascular remodeling indexes MT% and MA% were measured 3, 5, 7, 10, 14 and 21 days after exposure (n=8 each time point). The ultrastructure of pulmonary vascular was observed under a transmission electron microscope.</p><p><b>RESULTS</b>mPAP in the HPH group 3, 5, 7, 10, 14 and 21 days after hypoxia exposure increased compared with the control group (P<0.05). With the prolonged hypoxia time, mPAP in the HPH group increased more significantly. MT%, MA% and RVHI increased significantly in the HPH group after 7 days of hypoxia exposure in a time-dependent manner compared with the control group (P<0.05). The transmission electron microscopy demonstrated that small pulmonary arterials became thickened, endothelial cell hyperplasia and degeneration, and organelles increased in the HPH group after 7 days of hypoxia exposure. Besides, collagen deposition in the extracellular matrix and the changes of pulmonary vascular remodeling were observed.</p><p><b>CONCLUSIONS</b>mPAP increases between 3 and 5 days of hypoxia exposure, resulting from pulmonary vascular spasm caused by hypoxia. After hypoxia of 7 days, the mPAP increases more significantly, pulmonary vascular remodeling occurs, and right ventricle becomes irreversibly hypertrophic. These changes may be intensified as the prolonged hypoxia time.</p>

A high-fat diet reverses improvement in glucose tolerance induced by duodenal-jejunal bypass in type 2 diabetic rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bariatric surgery offers successful resolution of type 2 diabetes mellitus (T2DM). However, recurrence of T2DM has been observed in a number of patients with initial resolution after bariatric surgery. This study aimed to induce reversal of the improvement of diabetes in T2DM rats after duodenal-jejunal bypass (DJB), and identify the effects of weight changes and gut hormones that might be involved.</p><p><b>METHODS</b>DJB surgery was performed in two T2DM rat models (n=20 for each group): non-obese Goto-Kakizaki (GK) rats, and moderately-obese T2DM rats induced by a combination of a high-fat diet (HFD) and low-dose streptozotocin (HS rats). The controls were sham-operated and non-treated rats. All rats were then randomly divided into HFD- and low-fat diet (LFD)-fed groups. Glucose tolerance, insulin tolerance, glucose-stimulated insulin, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretion, food intake and body weight were measured and compared with controls.</p><p><b>RESULTS</b>DJB surgery resulted in a significant improvement in glucose tolerance in both GK and HS rats fed with either HFD or LFD. In contrast to LFD-fed rats, improved glucose tolerance was impaired in GK and HS rats fed with an HFD, accompanied by re-impairment of insulin tolerance and failure in enhancement of insulin secretion. There was no significant difference in food intake and body weight between DJB-operated and control rats, and between HFD- and LFD-fed rats. Glucose-stimulated GLP-1 and PYY levels were significantly increased after DJB surgery; however, they were not significantly different between HFD- and LFD-fed rats.</p><p><b>CONCLUSION</b>An HFD reverses the improvement in glucose tolerance induced by DJB surgery in T2DM rats, primarily ascribing to the re-impairment of insulin sensitivity, but does not change body weight, GLP-1 and PYY levels.</p>

Role of hypoxia-inducible factor-1α endothelin-1 and inducible nitric oxide synthase in the pathogenesis of hypoxia-induced pulmonary hypertension of the newborn / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the roles of hypoxia-inducible factor-1α (HIF-1α), endothelin-1 (ET-1) and inducible nitric oxide synthase (iNOS) in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH) of the newborn.</p><p><b>METHODS</b>Seventy-five term hospitalized neonates with HPH (mild 29 cases, moderate 25 cases, severe 21 cases) and 22 term hospitalized neonates without HPH (control group) were enrolled between June 2006 and November 2009. Serum levels of HIF-1α, iNOS and ET-1 were measured using ELASA 1, 3 and 7 days after birth.</p><p><b>RESULTS</b>Serum concentrations of HIF-1α and ET-1 in the mild, moderate and severe HPH groups were significantly higher than those in the control group (P<0.01) 1 day after birth, and were related to the severity of HPH. The serum iNOS concentrations in the moderate and severe HPH groups were also significantly higher than those in the control group (P<0.01). By 3 days after birth, serum ET-1 concentration in the moderate HPH group and serum concentrations of HIF-1α, ET-1 and iNOS in the severe HPH group reminded significantly higher than those in the control group (P<0.05). At 7 days after birth, serum ET-1 concentration in the severe HPH group still remained higher than that in the control group (P<0.05).</p><p><b>CONCLUSIONS</b>Serum levels of HIF-1α, ET-1 and iNOS increase in neonates with HPH, resulting in an imbalance of ET-1 and NO. This may be of importance in the pathogenesis of neonatal HPH.</p>

Evaluation of left ventricular dysfunction by Tei index in neonates with hypoxemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the role of Tei index in the evaluation of left ventricular dysfunction in neonates with hypoxemia.</p><p><b>METHODS</b>Fifty-two neonates with hypoxemia (20 mild, 16 moderate, 16 severe) and 40 normal neonates (control group) were enrolled. On postnatal days 1, 3 and 7, Doppler echocardiography was used to measure the indexes reflecting systolic and diastolic cardiac functions: ejection fraction of left ventricular (LVEF), E/A ratio of mitral value and Tei index of left ventricular (LV-Tei).</p><p><b>RESULTS</b>LVEF and E/A ratio of left ventricular in the moderate hypoxemia group were significantly lower than those in the control group on postnatal days 1 and 3 (P<0.01). LVEF and E/A ratio of left ventricular in the severe hypoxemia group were significantly lower than those in the control group on postnatal days 1, 3 and 7 (P<0.01 or 0.05). Compared with the control group, LV-Tei increased significantly in the mild hypoxemia group on postnatal day 1 and increased significantly in the moderate and severe hypoxemia groups on postnatal days 1 and 3 (P<0.01). There was a negative correlation between PaO2 and LV-Tei in the hypoxemia group on postnatal days 1 and 3 (r=-0.50, P<0.05; r=-0.71, P<0.01 respectively).</p><p><b>CONCLUSIONS</b>LV-Tei can be used as a sensitive indicator for the evaluation of left ventricular dysfunction in neonates with hypoxemia.</p>