OBJECTIVEDuring the critical period of brain development, insufficiency of thyroid hormone results in severe mental retardation and learning deficit. This study was designed to investigate the effects of hypothyroidism on apoptosis and the expression of Bcl-2 and Bax gene in the developing rat hippocampus neurons and to explore the mechanism of brain development regulated by thyroid hormone.

METHODHypothyroidism was induced by administration of propylthiouracil (PTU, 50 mg/d) solution to the dams from gestational day 15 by gavage. Pups from both hypothyroid and control groups were harvested at postnatal day 1 (P1), P5, P10 and P15, respectively. Blood samples were collected at the time of death for the determination of thyroid hormone. Serum free tri-iodothyronine (FT(3)) and free thyroxine (FT(4)) were measured by using chemoluminescence. Hippocampus collected from the control and hypothyroid pups were examined under light and transmissional electron microscopy. Measurement of DNA fragmentation was carried out by agarose gel electrophoresis. The expression of Bcl-2 and Bax protein in the developing rat hippocampus neurons was performed by Western blotting.

RESULTSSignificantly lower circulating FT(4) and FT(3) levels confirmed the hypothyroid status of the experimental pups. The shrunken and contracted degenerations increased in hippocampus neurons of hypothyroid pups under light microscopy. Enhanced apoptotic cells were found in hippocampus neurons of hypothyroid pups under transmission electron microscopy, especially at P10 and P15. Extensive DNA fragmentation was seen throughout development in hippocampus of hypothyroid pups, but not in the euthyroid controls except for basal level at P10. The expression of Bcl-2 in the hippocampus neurons of hypothyroid pups was significantly lower than that of euthyroid controls at all stages of development (P1: 1.95 +/- 0.27 vs. 2.59 +/- 0.19, P < 0.05, P5: 1.86 +/- 0.24 vs. 2.47 +/- 0.17, P < 0.05, P10: 1.29 +/- 0.22 vs. 1.86 +/- 0.28, P < 0.05 and P15: 1.21 +/- 0.27 vs. 2.18 +/- 0.17, P < 0.01, respectively). The relative amount of expression varied significantly with age in the control pups. The level of Bcl-2 was high in hippocampus neurons of euthyroid at P1, P5, and decreased significantly at P10, and showed a trend of recovery at P15. Similar age-related variation in the expression of Bcl-2 gene was observed in the hypothyroid group at P1, P5 and P10, but the level was maintained low at P15. The expression of Bax in the hippocampus neurons of hypothyroid pups was significantly higher than that of control pups at all stages of development (P1: 1.69 +/- 0.14 vs. 1.24 +/- 0.23, P < 0.05, P5: 1.78 +/- 0.16 vs. 1.29 +/- 0.17, P < 0.05, P10: 1.92 +/- 0.18 vs. 1.45 +/- 0.14, P < 0.05 and P15: 1.86 +/- 0.14 vs. 1.51 +/- 0.12, P < 0.05, respectively). The ratio of Bcl-2/Bax in hippocampus neurons of hypothyroid pups was lower than that of age-matched controls (P1: 1.16 +/- 0.17 vs. 2.12 +/- 0.35, P < 0.05, P5: 1.05 +/- 0.16 vs. 1.94 +/- 0.36, P < 0.05, P10: 0.68 +/- 0.17 vs. 1.29 +/- 0.16, P < 0.05 and P15: 0.67 +/- 0.19 vs. 1.45 +/- 0.22, P < 0.01, respectively).

CONCLUSIONThyroid hormone significantly prevents apoptosis of hippocampus neurons. Congenital hypothyroidism increases not only the extent but also the duration of apoptosis by down-regulation of the anti-apoptotic gene Bcl-2 and maintaining a high level of the pro-apoptotic gene Bax.

Animals ; Animals, Newborn ; Apoptosis ; physiology ; Down-Regulation ; Hippocampus ; metabolism ; Hypothyroidism ; physiopathology ; Neurons ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; bcl-2-Associated X Protein ; metabolism

Objective To investigate the prevalence for endemic fluorosis of drinking water type and to discuss the relationship between endemic fluorosis and urinary fluorine in Linyi county, Shanxi province. Methods In 2006, three counties were selected as heavy, medium and control areas according to the distributing feature of the disease. The dental fluorosis in each spots was examined by Dean method. The levels of urinary fluorine were determined by fluorine selective ion electrode. The skeletal fluorosis of adults were examined by X-ray. Results There was evident differences of dental fluorosis and skeletal fluoresis among the heavy and the medium endemic fluorosis and control areas(X~2 = 410.945, P < 0.01 ), the prevalence of dental fluoresis in the medium area and the heavy area were 92.34% (253/274), 90.09% ( 291/323), significantly higher than in the control area[23.27% (64/275), X~2 = 274.927,268.287, all P < 0.01]. The heavy area had the highest rate of the skeletal fluorosis rate [59.75% (141/236) ], the medium area had the middle-level of the skeletal fluorosis rate[24.76%(52/210), X~2 = 183.578, P< 0.01]. Urine fluorine contents in both beavy[ (4.69 ± 0.17)mg/L] and medium areal (4.86 ± 0.13)mg/L] were higher than that in the control areas[ (1.75 ± 0.04)mg/L, H = 411.197, P< 0.01], and there was linear relevance between the different degree of skeletal fluorosis and urine fluorine contents (r = 0.508, P < 0.01). Conclusions The local fluoresis condition of Linyi county in Shanxi province was serious. The degree of skeletal fluorosis is associated with the fluoride content in urine.

This study evaluated the clinical effect of impaction bone graft and distal press-fit fixation for the reconstruction of severe femoral bone defect in revision total hip arthroplasty. A total of 234 patients (involving 236 hips) with Paprosky III and IV femoral bone defects were treated with the revision total hip arthroplasty from June 1998 to Aug. 2006. Impaction bone graft technique was used for 112 hips, with allogeneic freeze-dried bone as bone graft and SPII as prosthesis. With 124 hips, modular distal press-fit fixation and tapered femoral stem (MP stem) were employed. After the operation, the subjects were followed up on regular basis and results were assessed by using the Harris Hip Score (HHS) and 12-item Short Form Health Survey (SF-12). Radiolucence, subsidence and loosening were observed and complications, including infection, fracture, dislocation etc. were recorded. A 6-14-year follow-up showed that prostheses failed, due to infection, in 4 patients of impaction bone graft group and that 6 patients in the press-fit fixation group experienced prosthesis failure, with the survival rates for the two techniques being 96.43% and 95.16%, respectively. One-way ANOVA showed that prosthesis survival was significantly associated with surgery-related complications (P<0.05) and was not related to the type of the bone defects (P>0.05). The rate of complications bore significant association with the type of bone defects in the two groups (P<0.05). Our study showed that the two revision methods could achieve satisfactory mid-term and long-term results for the reconstruction of severe bone defects. It is of great significance for attaining high prosthesis survival rate to select suitable operation on the basis of the type of bone defect. Careful operative manipulation and post-operative rehabilitation aimed at reducing complications are also important.

OBJECTIVETo compare the difference of anterior knee pain after total knee arthroplasty (TKA) between the ways using periosteal dissector and electric scalpel to release medial collateral ligament and pes anserinus.

METHODSFrom September 2009 to September 2012, 220 patients with unilateral osteoarthritis were treated with primary TKA in hospital 301. All the patients were randomly divided into periosteal dissector group (110 cases) or electric scalpel group (110 cases). In the periosteal dissector group, there were 47 males and 63 females,with an average age of (58.8 +/- 17.2) years old; the degree of genuavarus was (14.0 +/- 3.5) degrees; the weight was (65.6 +/- 12.8) kg; the body mass index (BMI) was (26.6 +/- 3.6) kg/m2. In the electric scalpel group,there were 49 males and 61 females,with an average age of (59.6 +/- 16.7) years old;the degree of genuavarus was (15.0 +/- 4.7) degrees; the weight was (66.4 +/- 13.4) kg; the BMI was (27.4 +/- 4.1) kg/m2. The mean follow-up period was 24.6 months. The AKS, VAS and HSS were used to evaluate clinical results.

RESULTSAll incisions healed at the first stage;no deep vein thrombosis of lower limbs or pulmonary embolism occurred. Knee infection occurred in 3 cases (1 in the periosteal dissector group and 2 in the electric scalpel group), and the 3 patients received stage 2 total knee revision using antibiotic bone cement and TC3 prosthesis. No recurrence of infection occurred during follow-up. Among the 20 patients who had anterior knee pain, 16 patients were in the periosteal dissector group and 4 patients were in the electric scalpel group. The occurrence rate of anterior knee pain in the electric scalpel group was lower than that in the periosteal dissector group. The AKS knee score and HSS score after total knee arthroplasty in the electric scalpel group were all higher than those in the periosteal dissector group, and the VAS in electric scalpel group was lower than that of periosteal dossector group.

CONCLUSIONCompared with using electric scalpel,using periosteal dissector used to release medial collateral ligament and pes anserinus may cause more anterior knee pain after total knee arthroplasty.

Adult ; Aged ; Arthroplasty, Replacement, Knee ; adverse effects ; Case-Control Studies ; Female ; Humans ; Knee Joint ; surgery ; Male ; Middle Aged ; Pain, Postoperative ; etiology ; Tibia ; pathology ; Treatment Outcome ; Young Adult

OBJECTIVETo study the efficiency of decreasing instability of large femoral head components in revision total hip arthroplasty (THA).

METHODSFrom August 2005 to December 2010, 107 patients (112 hips) with 28 mm femoral head components (28 mm group) and 46 patients (46 hips) with 36 mm femoral head components (36 mm group) in revision THA were analyzed retrospectively in order to find if the dislocation rate and Harris hip score were different between the two groups at the time of last follow-up. All the operations were performed by the first author. There were 81 male patients (85 hips) and 26 female patients (27 hips) in 28 mm group with mean age of (62±17) years (26-79 years) and 33 male patients (33 hips) and 13 female patients (13 hips) in 36 mm group with mean age of (60±16) years (31-77 years).

RESULTSThe mean follow-up period was 43.3 months (33-71 months) for 28 mm group and 26.7 months (12-37 months) for 36 mm group. There were 7 patients dislocated after revision in 28 mm group, including 2 revised with reinforcement rings (with dislocation rate 9.5%), 3 revised with impaction bone grafting technique (with dislocation rate 8.3%) and 2 revised with cementless cups (with a dislocation rate 3.6%). The dislocation rate of this group was 6.2%. While the dislocation rate of 36 mm group was 2.2%, the only dislocated patient was because of loss of gluteus medius muscle function in the index operation. If this case was excluded, the dislocation rate of 36 mm group would be 0. There was significant difference between the two groups (χ2=103.0095, P<0.01). The Harris hip score was 88±11 for 28 mm group and 89±9 for 36 mm group, there was no significant difference between the two groups (P>0.05).

CONCLUSIONThe large femoral head components can significantly decrease the instability after revision THA, which should be used in revision THA.

Adult ; Aged ; Arthroplasty, Replacement, Hip ; instrumentation ; Female ; Follow-Up Studies ; Hip Prosthesis ; Humans ; Male ; Middle Aged ; Prosthesis Failure ; Retrospective Studies

This study was aimed to explore the clinical features and prognosis outcome of childhood T-cell acute lymphoblastic leukemia (T-ALL). The clinical data of 38 cases of newly diagnosed T-ALL from Jan 2005 to Aug 2010 were analyzed retrospectively, and 78 cases of B-ALL with intermediate and high risk were collected as control group, then the sensitive rate of patients to prednisone pretreatment, complete remission (CR) rate at day 33 after induction chemotherapy, relapse rate and 3-year event-free survival (EFS) were compared between T-ALL and B-ALL children. The results showed that no significant statistic difference were found in distribution of age, infiltration of liver, spleen and lymph nodes as well as central nervous system disease, chromosome abnormality, expression level of fusion gene and so on between T-ALL and B-ALL groups (p > 0.05), but there were significant differences in sex and number of cases with WBC count ≥ 50 × 10(9)/L between them (p < 0.05). The sensitive rate of T-ALL and B-ALL patients to prednisone pretreatment was 51.9% and 89.3% respectively (p < 0.05). The ratio failed to achieve CR at day 33 after induction chemotherapy was 15.4% and 8.1% in the two groups (p > 0.05). The relapse rate of T-ALL and B-ALL cases was 30.8% (8/26) and 14.9% (11/74) respectively (p > 0.05). The time from CR to relapse was (9.78 ± 3.48) month and (21.28 ± 14.32) month (p < 0.05). The 3 year EFS of T-ALL cases with intermediate and high risk was (37.5 ± 17.1)% and (22.2 ± 9.8)%, while 3 year EFS of B-ALL cases was (66.7 ± 7)% and (51.7 ± 9.3)% respectively (p < 0.05) according to Kaplan-Meier survival curve. It is concluded that as compared with B-ALL cases, the male ratio and initial WBC count are higher, moreover the early response to prednisone pretreatment and 3 year EFS are poor in T-ALL cases, the prognosis outcome is poor also.
Adolescent ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Humans ; Immunophenotyping ; Infant ; Male ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; immunology ; mortality ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; immunology ; mortality ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; immunology ; mortality ; Prognosis ; Retrospective Studies ; Survival Rate

Objective To screen potential active anti-cancer components of Brucea javanica.Methods This research has em-ployed comprehensive two dimensional chromatographic technology and cell membrane chromatographic technology simultaneously with mass spectrometry as detector .Results Adenosine and Bruceine B were found to be potentially anti-cancer active .Conclusion This study has combined the advantages of online , high speed and high throughput for the screen of potential active components of traditional Chinese medicine .

AIMThe clinical manifestation of chronic mountain sickness (CMS) is polycythemia, pulmonary hypertension and mionectic blood. However, the pathogenesis of it is not identified now. So it is necessary to investigate the effects of the angiogenic growth factors on the pathophysiologic development of CMS.

METHODSThe serum levels of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) in 13 healthy Tibetan natives (Native), 17 healthy people in Xining (control group) and 35 CMS patients were determined by quantitative sandwich enzyme immunoassay. Meanwhile, the levels of Hb, Hct and SaO2 were determined.

RESULTSThe serum levels of bFGF (107.26 +/- 7.86) ng/L, PDGF (630.18 +/- 9.89) ng/L and VEGF (543.74 +/- 6.76) ng/L in CMS were significantly higher than those in Natives (37.01 +/- 9.16; 292.16 +/- 6.88; 125.51 +/- 7.26) ng/L, and in control group (40.58 +/- 5.34; 287.68 +/- 8.33; 76.26 +/- 4.60) ng/L, respectively (P < 0.01). There was no difference between the natives and the control group in bFGF and PDGF (P > 0.05), while there was predominant difference between the Natives and the control group in VEGF (P < 0.01). There was a predominant positive correlation between the serum levels of bFGF, PDGF or VEGF and hemoglobin concentrations in CMS respectively (P < 0.01). And there were positive relations between angiogenic growth factors each other.

CONCLUSIONThe serum levels of bFGF, PDGF and VEGF in patients with CMS significantly increase, these angiogenic growth factors may play important role on the pathophysiologic development of CMS; the VEGF level likely contributes to the adaptation to plateau hypoxia in healthy Tibetan natives; the elevated bFGF, PDGF and VEGF levels are likely associated with excessive erythropoiesis in CMS.

Adult ; Altitude Sickness ; blood ; Case-Control Studies ; Chronic Disease ; Fibroblast Growth Factor 2 ; blood ; Humans ; Male ; Middle Aged ; Platelet-Derived Growth Factor ; metabolism ; Vascular Endothelial Growth Factor A ; blood

OBJECTIVETo investigate the mechanism for the apoptosis of hippocampus neuron induced by hypothyroidism in perinatal rats.

METHODSHypothyroidism was induced by administration of propylthiouracil (PTU, 50 mg/d) solution to the dams from gestational day 15 by gavage. Pups from both hypothyroid and control groups were harvested at 1, 5, 10 and 15d, respectively. Blood samples were collected at the time of death for the determination of thyroid hormone. Serum free triiodothyronine (FT(3)) and free thyroxine (FT(4)) were measured by chemoluminescence. Hippocampus specimens were collected from the control and hypothyroid pups.Mitochondia was examined under transmission electron microscopy. Translocation of apoptogenic molecules (Bax, cytochrome C and AIF) and activation of caspase-3 were analyzed by Western Blotting.

RESULTSignificantly low circulating FT(3) and FT(4) levels confirmed the hypothyroid status of the experimental pups. Electron microscopy showed that altered morphology of mitochondria significantly increased under hypothyroid conditions. The expression of Bax in the cytosol of hypothyroid pups was higher than that of control pups at all stages of development (P<0.05),and significantly higher in mitochondria (P<0.001). The expression of cytochrome c in the cytosol of hypothyroid pups was significantly higher than that of control pups at all stages of development (1,10 and 15 d:P<0.05, 5d: P<0.001), and lower in mitochondria (P<0.05). The expression of AIF in the cytosol of hypothyroid pups was higher than that of control pups at all stages of development (P<0.001), and significantly lower in mitochondria (1, 5d: P<0.001, 10, 15 d: P<0.01). he expression of caspase-3 P20 in the cytosol of hypothyroid pups was significantly higher as compared with that of the age-matched controls (1, 15d: P<0.01, 5,1 0 d: P<0.001).

CONCLUSIONThe intrinsic death pathway in mitochondria may be one of the mechanisms with which hypothyroid induces apoptosis of hippocampus neuron in developing rats.

Animals ; Animals, Newborn ; Apoptosis ; physiology ; Female ; Hippocampus ; pathology ; Hypothyroidism ; chemically induced ; pathology ; Neurons ; pathology ; Pregnancy ; Pregnancy Complications ; pathology ; Propylthiouracil ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effects of perinatal thyroid hormone deficiency on the expression of androgen receptor (AR) mRNA in cerebral cortex and hippocampus of rats.

METHODSPerinatal hypothyroidism was induced by the administration of propylthiouracil (PTU) solution to the dams by gavage (50 mg/d) beginning at embryonic d15 throughout the lactational period. In the T(4) injected group hypothyroid rats were injected intraperitoneally with levothroxine (L-T(4)) 2 microg/100 g BW daily, starting from the day of birth. Cerebral cortex and hippocampus specimen were collected from controls,hypothyroid and T(4)-injected hypothyroid rats on postnatal d1, 5, 10, 15 and 20. Quantification of ARmRNA in cerebral cortex and hippocampus was performed with competitive RT-PCR using internal and external standardization.

RESULTAge-related increasing ARmRNA levels were observed in neonatal rats, and those in male animals were significantly higher. AR expression was higher in the hippocampus than in the cerebral cortex. ARmRNA levels in the hypothyroid pups were lower than those in age-matched controls. The mRNA levels in the T(4)-injected hypothyroid pups were significantly higher compared with the age-matched hypothyroid pups, but in hippocampus ARmRNA expression did not reach normal levels in male rats at d10 and d20, in female at d15 and d20.

CONCLUSIONThe expression of ARmRNA decreases in brain of rats with perinatal hypothyroidism. Treatment with thyroid hormone can recover ARmRNA expression in cerebral cortex, but not in hippocampus.

Animals ; Animals, Newborn ; Cerebral Cortex ; metabolism ; Female ; Hippocampus ; metabolism ; Hypothyroidism ; metabolism ; Pregnancy ; Pregnancy Complications ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Receptors, Androgen ; biosynthesis ; genetics