Histomorphometryof the vertebra and its correlations with MRI signal intensity in rabbits with fluoride treatment / 中华骨科杂志

Objective To analyze histomorphometrical characteristics of the bone and bone marrow tissues of the lumbar vertebrae in rabbits with fluoride treatment,and its correlation with signal intensity of MRI.Methods Forty New Zealand albino rabbits aged three months old were randomly divided into fluoride exposure of 30 cases and control of 10 cases,male and female,half each.One hundred milligrams of sodium fluoride were added to the municipal water each liter (fluoride content 100 mg/L) as drinking waterto fluorine for 180 days.Twenty-four of 30 cases with fluoride exposure had complete data (male10 casesand female14 cases).The same municipal water was used as control drinking water (fluoride content ＜ 0.9 mg/L).Eight of 10 cases with control had complete data (male andfemale in half).Twenty-four cases with fluoride treatment and complete data were classified into sensitive and resistant type according to the MRI signal intensity of the lumbar vertebra.Histomorphometrics of the vertebra and its correlation with the MRI signal intensity,and sensitivity in early diagnosis of osteofluorosis and feasibility of susceptibility to osteofluorosis detected with MRI were analyzed.Results Theratios of trabecular bone volume (BV),hematopoietic cell volume (HV) and fluid volume (FV) in bone marrow tissue to total cavernous tissue volume (TT) in group with fluoride treatment were 18.3％±2.6％,45.2％±6.0％ and 10.4％±5.7％ respectively.These were 14.5％±2.8％,36.3％±7.3％ and 6.2％±2.1％ in control group respectively.These parameters in fluoride group were significantly increased compared to control group.The ratio 26.0％± 8.0％ of adipocyte volume (AV) to TV in fluoride group was significantly lower than that 43.3％±5.6％ in control group.Two of 24 cases with fluoride exposure (8.3％,2/24) were sensitive and the remaining 22 (91.7％,22/24) were in resistance.The valuesof BV/TT,HV/TV and FV/TV were considered to be sensitive,resistant and control from large to small,while AV/TV value were opposite.A comparison resuhs of signal intensity in MRI showed that vertebra T1WI contrast to noise ratio (CNR) in the sensitive was the minimum (3.0±0.8),followed by resistance (21.3±3.8) andmaximum in the control (28.3±3.1),but CNR of FsT2WIwas opposite.There were positive associations between T1WI and AV/TV,FV/TV and BV/TV,and between FsT2WI and FV/TV and BV/ TV.There were inverse associationsbetween FsT2WI and AV/TV.Theoptimal threshold value of the vertebra T1WI CNR was 23.2 or lessin early diagnosis of skeletal fluorosis,with sensitivity of 83.3％ and specificity of 100％.FsT2WI was 5.7 or more,with sensitivity of 45.8％ and specificity of 100％.Conclusion The pathogenesis of osteofluorosis is relative to changes in bone marrow microenvironment and cells number in bone marrow tissue,and is correlated to MRI signal intensity.

Effects of Early Intervention on Brain Injury in Premature Infants with Neonate Respiratory Failure / 中国康复理论与实践

Objective To explore the effects of early intervention on brain injury in premature infants with neonate respiratory failure (NRF). Methods 151 premature infants in neonatal intensive care unit (NICU) who were diagnosed as NRF within 24 hours after birth in our hospital were studied. All of them accepted endotracheal intubation and mechanical ventilation, and were complicated with brain injury. According to their admission date and their parents' desire, these premature infants were divided into routine group (n=71) and intervention group (n=80). Both 2 groups received similar routine care, and the intervention group accepted touching, passive exercise and stimulation of hearing, vision and touch in addition. Active motor training and family intervention were also given to the intervention group after dis-charge. They were assessed with Neonatal Behavioral Neurological Assessment (NBNA) at the corrected age of 40 weeks, Infant Neurologi-cal International Battery (Infanib) at the corrected age of 3 and 6 months, mental development index (MDI) and psychomotor development index (PDI) at the corrected age of 6, 12 and 18 months, Gesell Development Schedules at the corrected age of 18 months. Results There was no significant difference in NBNA score between 2 groups at 40 weeks of gestational age (P>0.05). The percentage of normal ones with Infanib was higher in the intervention group than in the routine group at the age of 3 and 6 months (P<0.05). The MDI and PDI were signifi-cantly higher in the intervention group than in the routine group at the age of 6, 12 and 18 months (P<0.001). The scores of gross motor, fine motor, adaptation, language and social skills were significantly higher in the intervention group than in the routine group at the age of 18 months (P<0.001). The incidence of sequelae was lower in the intervention group (12.5%) than in the routine group (25.4%) (P<0.05). Con-clusion Early intervention can promote the intelligence and motor development, and improve the outcome of brain injury in the premature infants with NRF.

Correlation and clinical significance of expressions of HIF-1α and Sema4D in colorectal carcinoma tissues / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the expressions of hypoxia-inducible factor 1 alpha(HIF-1α) and Semaphorin 4D(Sema4D) in colorectal carcinoma and normal colorectal tissues, and to investigate their correlation and clinical significance.</p><p><b>METHODS</b>The expressions of HIF-1α and Sema4D were examined in 86 cases of colorectal carcinoma and 52 normal colorectal tissues by SP immunohistochemical staining. Correlation between these two expressions and association of the expressions with clinicopathological characters and prognosis were analyzed.</p><p><b>RESULTS</b>The positive rates of HIF-1α and Sema4D protein in colorectal carcinoma tissues were significantly higher than those in normal colorectal tissues(58.1% vs. 7.7%, χ(2)=34.624, P<0.01; 60.5% vs. 11.5%, χ(2)=31.839, P<0.01). HIF-1α and Sema4D protein expressions were closely associated with colorectal carcinoma histological types(P=0.003, P=0.010), TNM staging (P=0.003, P=0.017) and lymphatic metastasis (P=0.003, P=0.020), and a significant correlation was observed between the expressions of HIF-1α and Sema4D protein (r=0.567, P<0.01). The 5-year overall survival rate was 37%. Univariate analysis showed that 5-year survival rates of patients with positive and negative HIF-1α protein expression were 24% and 56%(P=0.003), and those with positive and negative Sema4D protein expression were 23% and 59%(P=0.001). Multivariate Cox analysis showed that expression of Sema4D was an independent prognostic factor of colorectal cancer patients(P=0.026), while expression of HIF-1α was not(P=0.501).</p><p><b>CONCLUSION</b>Combined detection of HIF-1α and Sema4D has the potential to predict the development trend of colorectal carcinoma and prognosis of patients.</p>

Hypoxia-inducible factor-1α and semaphorin4D genes involved with tumor-associated macrophage-induced metastatic behavior and clinical significance in colon cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypoxia promotes tumor angiogenesis and hypoxia-inducible factor-1 alpha (HIF-1α) plays a pivotal role in this process. Recently identified pro-angiogenic factor, semaphorin4D (Sema4D) also promotes angiogenesis and enhances invasive proliferation in some tumors. Furthermore, tumor-associated macrophages (TAMs) can increase the expression of HIF-1α and Sema4D in cancer cells and thus influence tumor growth and progression. The purpose of this study was to evaluate the effect of TAMs on the expression of Sema4D and HIF-1α and the impact of biologic behavior in colon cancer cells.</p><p><b>METHODS</b>Immunohistochemistry was used to analyze HIF-1α and Sema4D expression in 86 curatively resected colon cancer samples and 52 normal colon tissues samples. The relationship between their expression and clinicopathological factors was analyzed. Furthermore, macrophage-tumor cell interactions, such as metastasis, angiogenesis, were also studied using in vitro co-culture systems. Statistical analysis was performed using SPSS 17.0 software (SPSS Inc., USA). Differences between two groups were analyzed with Student's t test.</p><p><b>RESULTS</b>HIF-1α (58%) and Sema4D (60%) were expressed at a significantly higher level in tumors than in normal tissues (P < 0.01, for both). Furthermore, HIF-1α and Sema4D expression was significantly correlated with lymphatic metastasis, specific histological types and TNM stages (P < 0.05), but not with age and tumor size (P > 0.05). Sema4D expression was correlated with that of HIF-1α (r = 0.567, P < 0.01). TAMs markedly induced HIF-1α and Sema4D expression in colon cancer cells and subsequently increased their migration and invasion.</p><p><b>CONCLUSIONS</b>HIF-1α and Sema4D expression are closely related to lymphatic metastasis, specific histological types and TNM stages in colon cancer. Furthermore, TAMs promote migration and invasion of colon cancer cells and endothelial tube formation, possibly through up-regulation of HIF-1α and Sema4D.</p>

Three-dimensional structure and morphology of the mandible in type 1 diabetes mellitus mice / 中国组织工程研究

BACKGROUND: Diabetes mel itus is one of the most common systemic diseases, which often leads to the changes of the jaw and other bone structure, as wel as the abnormal changes of mineral metabolism. OBJECTIVE: To observe the three-dimensional structure and histopathological changes of the mandible in type 1 diabetes mel itus mice. METHODS: The mice were randomly divided into control group and diabetes mel itus group. The diabetes mel itus group received intraperitoneal injection of 50 mg/kg streptozotocin for 5 days to establish a type 1 diabetes mel itus model, and the control group received intraperitoneal injection of citrate buffer. RESULTS AND CONCLUSION: At 3 weeks after modeling, the micro-CT technique was used to observe the three-dimensional structure of the mandibles in the two groups. The quantitative analysis on the microstructure of cancel ous bone and cortical bone showed that the bone mineral density, bone volume fraction, trabecular number and trabecular thickness of cancel ous bone in the interest region in the mandible of type 1 diabetes mel itus mice were significantly decreased when compared with that in the control group (P < 0.01, P < 0.05), while the structure model index was increased significantly (P < 0.05); the mineral density and area of cortical bone were decreased in the diabetes mel itus group (P < 0.05). Hematoxylin-eosin staining showed that the number and volume of mandibular trabeculae of type 1 diabetes mel itus mice were decreased. The results suggest that the three-dimensional structure of the cancel ous bone and cortical bone in the streptozotocin-induced type 1 diabetes mel itus mice are changed significantly, and the microstructure change of the cancel ous bone is more obvious.

Comparison of the efficacy of XELOX and FOLFOX4 in the treatment of locally advanced unresectable gastric cancer / 中华消化外科杂志

Objective To compare the efficacy of XELOX and FOLFOX4 in the treatment of locally advanced unresectable gastric cancer. Methods The clinical data of 72 patients with gastric cancer who were admitted to the Shandong Provincial Hospital from July 2006 to October 2009 were prospectively analyzed. Of all the patients, 3 lost follow-up, and 69 patients with locally advanced unresectable gastric cancer were randomly divided into XELOX group ( n = 36 ) and FOLFOX4 group ( n = 33 ) according to the random number table.All patients received chemotherapy for six weeks. The efficacy of the two regimens were evaluated by the multidiscipline team six weeks later. The cell cycle of patients with complete or partial remission and received surgical treatment was detected by flow cytometry. All data were analyzed using the Pearson chi-square test, Levene test or t test. Results The curative rates of XELOX and FOLFOX4 were 53% (19/36) and 52% (17/33), respectively,with no significant difference between the two groups ( x2= 0. 01 , P ＞ 0. 05 ). The incidences of nausea and vomiting, phlebitis and hand-foot syndrome were 25% (9/36), 6% (2/36) and 19% (7/36) in the xELOX group, and 55% ( 18/33), 39% (13/33) and 3% (1/33) in the FOLFOX4 group, respectively, with significant difference between the two groups ( x2 = 6.31, 11.59, 4.53, P ＜ 0.05 ). Nineteen patients in the XELOX group and 17 patients in the FOLFOX4 group received surgical resection of the gastric cancer, and no complications such as anastomotic leakage and hemorrhage occurred postoperatively. In the XELOX group, the s-phase fraction (SPF),proliferation index (PI) and G2/M of the gastric cancer cells were 5.89% ± 0.79%, 9.22% ± 1.99% and 5.19% ± 1. 66% after neoadjuvant chemotherapy, which were significantly lower than 6.76% ± 1.21%, 10.44% ±2.12% and 6. 04% ± 0. 57% before neoadjuvant chemotherapy, while the ratio of gastric cancer cells in the G0/G1 phase after neoadjuvant chemotherapy was 90.39% ±4.78%, which was significantly higher than 87.54%±6.34% before neoadjuvant chemotherapy (x2 =3.61, 2.52, 2. 15, 2.91, P ＜0.05). In the FOLFOX4group, the SPF, PI and G2/M of the gastric cancer cells were 6.09% ± 0.96%, 10.65 % ± 2.47% and 4.88% ±0.87% after neoadjuvant chemotherapy, which were significantly lower than 7.15% ± 1.45%, 11.87% ± 2.33%and 5.67% ± 1.03% before neoadjuvant chemotherapy, while the ratio of gastric cancer cells in the G0/G1 phase after neoadjuvant chemotherapy was 91.45% ± 5.22%, which was significantly higher than 88.01% ± 4.23%before neoadjuvant chemotherapy ( x2 = 3.50, 2.06, 3.37, 2.94, P ＜ 0.05 ). There was a significant difference in PI between XELOX group and FOLFOX4 group after neoadjuvant chemotherapy ( x2 = 2.66, P ＜ 0.05 ).Conclusions XELOX and FOLFOX4 are safe and effective in the treatment of locally advanced unresectable gastric cancer, and they can significantly restrain the proliferation of gastric cancer cells. XELOX regimen is more effective than FOLFOX4 regimen.

Clinical analysis of modified pancreatoduodenectomy with preservation of ascending portion of duodenum / 中华消化外科杂志

Objective To investigate the value of modified pancreatoduodenectomy in the treatment of ampullary carcinoma by comparing the efficacy of pancreatoduodenectomy with preservation of ascending portion of duodenum and that of Whipple procedure. Methods The clinical data of 133 patients with ampullary carcinoma who had been admitted to the Qilu Hospital from 1990 to 2006 were retrospectively analyzed. Of the 133 patients, 88 received Whipple procedure (group A) and 45 received pancreatoduedenectomy with preservation of ascending portion of duodenum (group B). The preoperative condition of the patients and short- and long-term efficacy of the 2 procedures were compared by Fisher exact probability, t test, chi-square test, Kaplan-Meier survival curve and Log-rank test, and the differences between the efficacy of the 2 procedures were compared. Results The operation time, time of gastrointestinal function recovery, hospital stay and ratio of patients with blood transfusion were (366±111) minutes, (7.4±1.4) days, (24±9) days and 76% (67/88) in group A, and (325±32)minutes, (4.3±1.4)days, (31±14)days, 42% (19/45) in group B, with significant difference between the 2 groups (t = 2.34, 2.08, 1.98 ; χ2 = 14.99, P < 0.05). The medium survival time of patients in groups A and B were (19.0±1.5)months and (16.9±1.7) months, with no significant difference between the 2 groups (χ2 = 0.46, P > 0.05). There was no significant difference in the occurrence of postoperative complications between the 2 groups (P > 0.05). Conclusions Pancreateduodenectomy with preservation of ascending portion of duodenum can be applied for patients with ampullary carcinoma.

Role of hypoxia inducible factor-1α and VHL in murine endochondral ossification / 上海交通大学学报（医学版）

Objective To investigate the role of hypoxia inducible factor-1α (HIF-1α) and von Hippel-Lindau (VHL) in murine endochondral ossification. Methods The knockout of HIF-1α or VHL gene in murine osteoblasts was accomplished by conditional knockout technique at 4th, 8th and 12th week, and the differences between wild-type group and knock-out group in endochondral ossification were detected by HE staining, micro-CT scanning, trabecular bone area measurement, calcium content measurement, tetracycline fluorescence labeling, Real-time PCR and Western blotting. Results After knockout of HIF-1α gene in osteoblasts, the expression of vascular endothelial growth factor ( VEGF) reduced, the rate of new bone formation stepped down, the content of calcium became less, and the trabecular bone volume decreased (P <0.05) . After knockout of VHL gene in osteoblasts, the expression of VEGF increased, the rate of new bone formation stepped up, the content of calcium became more, and the trabecular bone volume was promoted (P < 0.001). Conclusion During murine endochondral ossification, VHL/HIF-1α signal pathway promotes angiogenesis through the stimulation of VEGF expression, which subsequently accelerates osteogenesis.

Establishing and evaluating of mouse closed femur fracture / 中国矫形外科杂志

[Objective]To develop a standard closed experimental fracture model in mouse femur.[Method]A 0.45 mm stainless-steel rod was introduced into the medullary cavity and the pre-nailed femur shaft was fractured by an impact device,which resulted in a reproducible transverse fracture pattern.The fractures were examined using X-ray Micro-CT,and histological method.[Result]Transverse fractures were created in 91.67% of the experimental mice,and the fracture healing was typical secondary fracture healing.[Conclusion]The standard closed fracture model in this experiment,whose healing was typically secondary fracture healing,can be obtained easily and used in study of fracture.