2.Changes of MAPK and Akt signaling pathways in hearts and placentas of aborted fetuses with congenital heart disease.
Jie XU ; Zhong-Zhou YANG ; Shu ZHANG ; Shao-Gen WU ; Ya-Li HU
Chinese Journal of Contemporary Pediatrics 2010;12(5):327-332
OBJECTIVETo study the changes of MAPK and Akt signaling pathways in hearts and placentas of aborted fetuses with congenital heart disease (CHD), and investigate their roles in the pathogenesis of CHD.
METHODSTen aborted fetuses with severe CHD (CHD group) and 7 gestational age-matched non-cardiac malformation aborted fetuses (control group) were enrolled. Western blot analysis was undertaken to assess the expression of p38, p38alpha, p-p38, MEF2, ERK, p-ERK, Akt, p-Akt(Ser473) and p-Akt(Thr308) in left ventricles and placentas of the fetuses, while semi-quantitative reverse transcription polymerase chain reaction analysis was used to detect the expression of p38alpha isoforms mRNA in hearts.
RESULTSCompared with the heart samples of the control group, the protein expression levels of p38 and its alpha isoform in 4 cases, p-p38 in 6 cases, MEF2 in 2 cases, p-ERK in 8 cases, Akt in 4 cases, p-Akt(Ser473) and p-Akt(Thr308) in 8 cases decreased, while the protein expression levels of p-p38 in 2 cases and p-Akt(Thr308) in 1 case increased. P-p38 protein level in 3 cases and p-ERK protein level in 2 cases decreased in placentas compared with the control group. The changes of protein expression of MAPK and Akt signaling pathway in hearts were not consistent with those in placentas in the CHD group. The expression of p38alpha isoform2 mRNA showed descent tendency in 4 heart samples with CHD, while the expression of other three p38alpha isoforms mRNA was reduced in only 1 sample compared with the control group.
CONCLUSIONSDysfunction of MAPK and Akt signaling pathways is tissue-specific in aborted fetuses with CHD. The perturbed two signaling pathways in hearts may contribute to the pathogenesis of human CHD.
Female ; Fetus ; metabolism ; Heart Defects, Congenital ; metabolism ; Humans ; MAP Kinase Signaling System ; physiology ; Myocardium ; metabolism ; Phosphatidylinositol 3-Kinases ; physiology ; Placenta ; metabolism ; Pregnancy ; Proto-Oncogene Proteins c-akt ; physiology ; Signal Transduction ; physiology ; p38 Mitogen-Activated Protein Kinases ; physiology
3.Application of titanium mesh in anterior cervical subtotal corpectomy with locking plate for cervical spondylotic myelopathy.
Jian-Li SHAO ; Zhi-Zhong LI ; Jing WANG ; Gen-Long JIAO
Journal of Southern Medical University 2009;29(6):1226-1228
OBJECTIVETo evaluate the clinical effect of titanium mesh in anterior cervical subtotal subcorpectomy with locking plate for treatment of cervical spondylotic myelopathy.
METHODSThirty-eight patients with cervical spondylotic myelopathy were treated with anterior cervical subtotal corpectomy using titanium mesh and locking plate. The JOA score of the patients were assessed before and after the operation, and the pre- and postoperative lateral cervical radiographs were taken to observe the instability of the titanium mesh, dynamic plates and changes of the cervical curvature.
RESULTSThe patients were followed up for 12-18 months. Radiographic cervical fusion was achieved in 12-16 months (36 cases) or 18 months (2 cases) postoperatively. The degree of Jordosis was improved and the height of the anterior spinal column and physical curvature were effectively maintained after the operation. The titanium mesh and locking plate showed no signs of loosening and the JOA scores was significantly improved after the operation (P<0.05).
CONCLUSIONTitanium mesh in anterior cervical subtotal corpectomy with locking plate allows effective treatment of cervical spondylotic myelopathy, but the indications of this procedure must be carefully evaluated. The long-term effect of this approach still needs verification by further follow-up data.
Aged ; Bone Plates ; Cervical Vertebrae ; surgery ; Decompression, Surgical ; Female ; Humans ; Male ; Middle Aged ; Orthopedic Procedures ; methods ; Spinal Cord Compression ; etiology ; surgery ; Spinal Fusion ; methods ; Spondylosis ; complications ; surgery ; Surgical Mesh ; Titanium
4.Comparing the effect of high frequency oscillatory ventilation and conventional mandatory ventilation on the myocardial function of rabbit with inhalation injury.
Guang-hua GUO ; Shao-gen WANG ; Zhong-hua FU ; Ming YANG ; Xing-heng WU ; Feng ZHU
Chinese Journal of Burns 2010;26(4):300-303
OBJECTIVETo compare the effect of high frequency oscillatory ventilation (HFOV) and conventional mandatory ventilation (CMV) on the myocardial function of rabbits with inhalation injury.
METHODSSteam inhalation injury model was reproduced in 16 New Zealand albino rabbits. They were randomly divided into CMV group (n = 8) and HFOV group (n = 8) by drawing lots, and they received ventilation in metered volume and HFOV treatment respectively. Heart blood was drawn from rabbits before they were sacrificed 4 hours after treatment to determine the plasma activity of lactate dehydrogenase 1 (LDH1) and creatine phosphorylated kinase (CPK-MB). Myocardial tissue from left ventricle was harvested and homogenized to determine the concentration of TNF-α and IL-8, the activity of caspase-1, and the activity of myosin-light-chain kinase (MLCK) and the ATPase of myosin light chain (MLC-ATPase) by enzyme-linked immunosorbent assay, spectrophotometry, and the nuclide liquid scintillation technique respectively. Part of the myocardial tissue sample was examined pathologically. Data were processed with analysis of variance.
RESULTS(1) The activities of LDH1 and CPK-MB in plasma were obviously higher in CMV group than in HFOV group [(643 ± 108), (342 ± 48) U vs. (233 ± 92), (186 ± 36) U, with F value respectively 10.326 and 9.846, P values all below 0.01]. (2) The contents of TNF-α, IL-8 and the activity of caspase-1 in myocardial tissue homogenate were obviously higher in CMV group than in HFOV group [(181 ± 35), (89 ± 19) pg/g, and (0.56 ± 0.27) g/g protein vs. (94 ± 21), (43 ± 11) pg/g, and (0.24 ± 0.12) g/g protein, with F value respectively 8.239, 7.826, 5.716, P values all below 0.01]. (3) The activities of MLC-ATPase and MLCK were lower in CMV group than in HFOV group [(0.24 ± 0.12) µmol×mg(-1)×min(-1), (3.3 ± 1.1) mmol×mg(-1)×min(-1) vs. (0.48 ± 0.16) µmol×mg(-1)×min(-1), (7.7 ± 1.7) mmol×mg(-1)×min(-1), with F value respectively 4.125, 4.766, P values all below 0.01]. (4) No obvious necrosis, degeneration or inflammatory cell infiltration was observed in myocardial tissue of rabbits in 2 groups under light microscope; but the myocardial fiber was slightly swollen, and it was less marked in the HFOV group.
CONCLUSIONSThe influence of HFOV on myocardial myosin phosphorylation system of rabbits with inhalation injury is less than that of CMV.
Animals ; Burns, Inhalation ; metabolism ; physiopathology ; therapy ; High-Frequency Ventilation ; Myocardium ; metabolism ; Myosin-Light-Chain Kinase ; metabolism ; Rabbits ; Respiration, Artificial
5.Effects of high frequency oscillatory ventilation and its combination with pulmonary surfactant treatment on inflammatory response in rabbit lung with inhalation injury.
Guang-hua GUO ; Shao-gen WANG ; Zhong-hua FU ; Ming YANG ; Xing-heng WU
Chinese Journal of Burns 2009;25(5):363-367
OBJECTIVETo investigate the effects of high frequency oscillatory ventilation (HFOV) and its combination with administration of pulmonary surfactant (PS) on inflammatory response of lung tissue in rabbits with inhalation injury.
METHODSSevere steam inhalation injury models were reproduced in 24 New Zealand albino rabbits. They were divided into control group (n = 8), HFOV group (n = 8), and HFOV + PS group (n = 8) according to the random number table, and they received ventilation in metered volume, HFOV, and HFOV + PS treatment respectively. Lung tissue samples of rabbits were collected at 3.5 h after treatment for pathological inspection and pulmonary injury score, assay of the activity of myeloperoxidase (MPO) and cysteinyl aspartate-specific protease 1 (caspase-1), and the determination of the contents of TNF-alpha, IL-18, IL-10, IL-13 and their mRNA expression.
RESULTSPathological change in different degree of rabbit lung tissue in each group were observed, and they were most obvious in the control group, and least in the HFOV + PS group. The lung tissue injury scores of control group, HFOV group, and HFOV + PS group was 3.71 +/- 0.43, 2.87 +/- 0.26, and 2.08 +/- 0.28 respectively. The difference between either two of them were statistically significant (P < 0.01). The MPO content and caspase-1 activity of rabbits in HFOV and HFOV + PS groups were obviously lower than those in control group (P < 0.01), and MPO content and caspase-1 activity of rabbits in HFOV + PS group were obviously lower than those in HFOV group (P < 0.05). In HFOV group and HFOV + PS group, the contents of TNF-alpha, IL-18 and their mRNA expression in lung tissue homogenates were obviously lower than those in control group (P < 0.01); while the contents of IL-10, IL-13 and their mRNA expression were obviously higher than those in control group (P < 0.01). Changes in these contents and expression in HFOV + PS group were more obvious than those in HFOV group (P < 0.05).
CONCLUSIONSHFOV can alleviate inflammatory response in rabbit lung tissue and pulmonary injury induced by inhalation injury, and the effect is more obvious when combined with PS.
Animals ; Burns, Inhalation ; complications ; therapy ; Disease Models, Animal ; High-Frequency Ventilation ; Inflammation ; Lung Injury ; etiology ; therapy ; Pulmonary Surfactants ; therapeutic use ; Rabbits
6.Significance of detecting platelet associated antibody and platelet membrane glycoprotein for diagnosis of immune thrombocytopenia.
Jian-Feng SHAO ; Qian-Gang ZHAN ; Zhong-Min LIU ; Yong-Gen ZHONG ; Yun-Li GUAN ; Jia-Ping FU ; Wei-Ying FENG ; Da-Jun LOU
Journal of Experimental Hematology 2004;12(2):224-227
The aim of this study was to explore application value of detecting platelet associated antibody and platelet membrane glycoprotein in the diagnosis and prognosis for immune thrombocytopenia. The platelet associated immunoglobulin (PAIg) and platelet membrane glycoprotein (CD41, CD61, GPIIb/IIIa) in 76 cases of immune thrombocytopenia and 30 healthy subjects were determined by FCM. The results showed that PAIg level in ITP patients included PAIgG (31.25 +/- 18.06)%, PAIgM (32.41 +/- 15.51)%, PAIgA (23.39 +/- 16.67)% which were remarkedly higher than in health control (10.48 +/- 5.05)%, (9.40 +/- 4.42)% and (7.23 +/- 3.61)% (P < 0.001). In patients with secondary immune thrombocytopenia (chronic aplastic anemia, SLE, Evans syndrome, liver cirrhosis hypersplenism, etc), PAIg level was higher than that in control group, while the platelet membrane glycoprotein in the blood of these patients was lower than that in control group. The level of PAIg decreased (P < 0.05) after treatment, but platelet membrane glycoprotein increased (P < 0.01). The result suggested that measurements for platelet membrane glycoprotein and platelet associated antibody by FCM were practical with high sensitivity, rapidity and simplicity used as a routine method in diagnosis and evaluation of the therapeutic effects in immune thrombocytopenia patients.
Adolescent
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Adult
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Aged
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Blood Platelets
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immunology
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Child
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Female
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Flow Cytometry
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Humans
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Immunoglobulins
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blood
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Integrin beta3
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analysis
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Male
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Middle Aged
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Platelet Glycoprotein GPIIb-IIIa Complex
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analysis
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Platelet Membrane Glycoprotein IIb
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analysis
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Platelet Membrane Glycoproteins
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analysis
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Purpura, Thrombocytopenic, Idiopathic
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blood
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diagnosis
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Thrombocytopenia
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blood
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diagnosis
7.Correlation between serum uric acid levels and obstructive sleep apnea/hypopnea syndrome in children.
Zhen-yun HUANG ; Da-bo LIU ; Gen-ping WAN ; Jian-wen ZHONG ; Zong-yu TAN ; Wei WEI ; Jia-jian XU ; Jian-bo SHAO ; Shu-yao QIU
Chinese Journal of Pediatrics 2011;49(3):218-221
OBJECTIVETo explore the level of serum uric acid (UA) in children with obstructive sleep apnea/hypopnea syndrome (OSAHS).
METHODBetween Sep. 2008 and Mar. 2010, 138 children with OSAHS were enrolled in study group. Sixty-five children with accessory auricle or ptosis of upper lid were enrolled into the control group. Furthermore, according to apnea/hypopnea index (AHI) or obstructive apnea index (OAI) the study group was further divided into three subgroups (mild, moderate and severe group). At last, the study group and control group were divided into two groups according to the body mass index (BMI), separately. The fasting serum UA level was compared among the different groups. Then the correlation between the serum UA level and AHI, BMI, oxygen desaturation index, least arterial oxygen saturation (LSaO(2)) and the percentage of total sleep time with arterial oxygen saturation < 0.92 was also analyzed in OSAHS children with or without overweight and obesity respectively.
RESULTThe difference of serum UA level between the study group and control group (z = -0.443), and the difference among the three groups (χ(2) = 1.241) was not significant(P > 0.05). The serum UA level in overweight and obese children [study group, 273.0 (238.3 - 357.3); control group, 298.0 (253.0 - 336.0)] was significantly higher than that in children with normal BMI [study group, 246.5(215.8 - 300.0); control group, 266.0 (224.0 - 303.3)] (z = -2.084, -2.214, P < 0.05). That serum UA level did not correlate with the above index of OSAHS was observed in children with or without overweight and obesity in study group (P > 0.05).
CONCLUSIONFindings of higher serum UA level were not observed in children with OSAHS. There was no correlation between serum UA level and the above indices of OSAHS. The serum UA level in overweight and obese children was significantly higher than that in children with normal BMI.
Case-Control Studies ; Child ; Child, Preschool ; Humans ; Sleep Apnea, Obstructive ; blood ; Uric Acid ; blood
8.microRNA-181b promotes migration and invasion of osteosarcoma cells by targeting N-myc downstream regulated gene 2.
Jian-Li SHAO ; Zhi-Zhong LI ; Liang WANG ; Gen-Long JIAO ; Zhi-Gang ZHOU ; Guo-Dong SUN
Journal of Southern Medical University 2016;36(3):321-326
OBJECTIVETo investigate the effects of miR-181b on the migration and invasion of osteosarcoma cells.
METHODSThree cultured osteosarcoma cell lines and MG-63 cells transfected with miR-181b inhibitor were examined for miR-181b expression using qRT-PCR analysis. The cell migration and invasion of the transfected cells were assessed with Transwell assay. The targets of miR-181b were predicted using a miRNA target prediction software and the results were verified with luciferase reporter assay. The target protein expression in osteosarcoma cells lines was determined by Western blotting, and the cell migration and invasion changes following inhibition of miR-181b or its target protein were assessed using Transwell assay.
RESULTSAll the 3 osteosarcoma cells lines showed significantly up-regulated miR-181b expression. Inhibition of miR-181b expression obviously suppressed the migration and invasion of MG-63 cells. Based on luciferase reporter assay, N-myc downstream regulated gene 2 (NDRG2) was identified as the direct target gene of miR-181b, and inhibition of NDRG2 expression significantly reversed the effect of miR-181b on cell migration and invasion in MG-63 cells.
CONCLUSIONmiR-181b is over-expressed in osteosarcoma cells, and inhibition of miR-181b, which directly targets NDRG2, can suppress the migration and invasion of osteosarcoma cells.
Bone Neoplasms ; genetics ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs ; genetics ; metabolism ; Neoplasm Invasiveness ; Osteosarcoma ; genetics ; pathology ; Tumor Suppressor Proteins ; genetics ; metabolism
9.Efficacy of intramedullary and extramedullary decompression and lavage therapy under microscope for treatment of chronic cervical spinal cord injury.
Gen-Long JIAO ; Yong-Bao FAN ; De-Jun DENG ; Jian-Li SHAO ; Guo-Dong SUN ; Zhi-Zhong LI
Journal of Southern Medical University 2018;38(2):174-180
OBJECTIVETo analyze the clinical effect of spinal cord decompression and lavage therapy on chronic cervical spinal cord injury and explore the possible mechanism.
METHODSFifty-seven patients with chronic cervical spinal cord injury treated in our hospital from January, 2008 to January, 2015 were enrolled, including 17 with multilevel cervical disc herniation, 25 with long segmental ossification of the posterior longitudinal ligament, 13 with hypertrophy or calcification of neck ligamentum flavum, and 2 with old cervical fractures. Open-door spinal canal laminoplasty via a posterior approach and decompression in simple extramedullary decompression was performed in 31 cases (group A), and open-door spinal cord incision decompression via a posterior approach, saline irrigation, and spinal canal laminoplasty in intramedullary decompression was performed in 26 cases (group B). The pre-operative cerebrospinal fluid in group B patients was collected to examine the inflammatory factors. All the patients were followed up and evaluated for pre- and postoperative JOA scores to calculate the improvement rate with regular examinations by X-ray, CT or MRI.
RESULTSImaging examinations 2 weeks after the operation showed obvious relief of the primary lesion in both groups, and the improvement of high signals was better in group B than in group A. The mean improvement rate at 12 months after the operation was 52.33% in group A and 61.52% in group B (P<0.05), and the mean JOA score was significantly higher in group B than in group A (14.80∓1.51 vs 13.58∓0.56; P<0.05). Cerebrospinal fluid leakage occurred in 3 cases, epidural hematoma in 2 cases, internal fixation loosening in 1 case in group A; portal shaft fracture and internal fixation loosening occurred in 1 case in group B. Postoperative recovery time was shorter in group B and entered the platform phase in 3 months. The inflammatory factors IFN-γ, IL-17F, IL-6 and sCD40L were all significantly higher than the normal levels after spinal cord injury, and the increment of IL-6 was the most conspicuous (P<0.05).
CONCLUSIONIntramedullary and extramedullary decompression can achieve better outcomes than extramedullary decompression in patients with chronic cervical cord injury. This may be related not only to relieving adhesions and secondary compression by cutting the dura under the microscope, but also to removal of local inflammatory factors.
10.Retrospective analysis of trastuzumab treatment in 141 patients with Her-2 positive breast cancer.
Yan WANG ; Jun-jie LI ; Gen-hong DI ; Jing-song LU ; Jiong WU ; Guang-yu LIU ; Xi-chun HU ; Zhong-hua WANG ; Wen-tao YANG ; Zhi-min SHAO
Chinese Journal of Oncology 2010;32(11):864-867
OBJECTIVETo summarize the clinical experience of trastuzumab treatment in neoadjuvant, adjuvant, metastatic setting of Chinese patients with Her-2 positive breast cancer and evaluate the efficacy of trastuzumab in combination with chemotherapy.
METHODSFrom January 2004 to December 2008, 141 outpatients with breast cancer treated with trastuzumab were investigated retrospectively. The follow-up time ranged from 3 to 319 months. The disease free survival time (DFS) of metastatic setting was calculated. The overall survival time (OS), time to treatment failure (TTF) and clinical response rate (CRR, including complete response, partial response and stable disease) of adjuvant, first-line, second-line therapy were analyzed statistically.
RESULTSIn the neoadjuvant regimen, paclitaxel plus carboplatin in combination with trastuzumab accounted for 66.7%, which achieved pathological complete response in 10 of 16 patients. In the adjuvant regimen, anthracycline or anthracycline followed by taxane accounted for 53.9%. The median DFS of 57 cases with metastatic diseases was 17 months. The CRR of first-line trastuzumab use in metastatic setting was 84.5%, compared with 44.4% of second-line use. The median TTF of first-line treatment was 24 months compared with 5 months of second-line treatment. Statistically significant differences were observed.
CONCLUSIONThe regimen of paclitaxel plus carboplatin in combination with trastuzumab deserves wide clinical use. In metastatic setting, first-line treatment of trastuzumab plus chemotherapy can achieve a higher response rate than second-line treatment. Continued trastuzumab therapy combined with different chemotherapy treatment after disease progression may obtain additive clinical advantage.
Adult ; Anthracyclines ; administration & dosage ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Bridged-Ring Compounds ; administration & dosage ; Carboplatin ; administration & dosage ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Paclitaxel ; administration & dosage ; Receptor, ErbB-2 ; metabolism ; Retrospective Studies ; Survival Rate ; Taxoids ; administration & dosage ; Trastuzumab ; Treatment Failure