1.Time-course changes of intraosseous environment and shear resistance mechanical properties of jawbone in SD rats with fluorosis
Lingyan LAI ; Ying JIA ; Xue DING ; Jia HU ; Bo CHEN
Journal of Environmental and Occupational Medicine 2023;40(1):95-100
Background At present, a large number of reports focus on the bones of limbs and trunk, while there are few studies on the effect of fluorosis on jawbone which is the inevitable structural basis for the development and treatment of oral diseases. Objective To preliminarily investigate the effect of fluoride exposure on the mechanical properties of jawbone by observing the changes in the intraosseous environment and the maximum load against shearing force (LSFmax) of the jawbone in rats with chronic fluoride treatment. Methods Screening experiment: 48 SD male rats were randomly divided into a control group and three fluoride exposure groups (50, 150, and 250 mg·L−1 fluoride concentration), 12 rats in each group. The fluoride exposure groups were molded by feeding different concentrations of sodium fluoride solution, and the control group drank tap water from Guizhou area. Each group was further divided into 4 subgroups with 3 animals each according to observation time points after 0, 2, 4, and 6 months. The LSFmax of the jawbone was measured with an electronic universal ergometer, the expression of type I collagen (Col1) was shown by Sirius red staining, and the expression of runt-related transcription factor 2 (Runx2) was determined semi-quantitatively by immunohistochemistry at selected time points. Formal experiment: 12 male SD rats were randomly divided into a fluoride exposure group and a control group. The fluoride exposure group were fed with 150 mg·L−1 sodium fluoride solution, and the control group drank tap water from Guizhou. After feeding with fluoride for 5 months, the ergometer was used to measure the LSFmax of the jawbone. Osteoclasts were counted after tartrate resistant acid phosphatase (TRAP) staining. Col1, Runx2, bone morphogenetic protein 2 (BMP-2), alkaline phosphatase (ALP), and cathepsin K (Cath K) were detected semi-quantitatively by immunohistochemistry expression and Sirius red staining. Micro computed tomography (Micro CT) was used to observe the trabecular bone microstructure. Results Screening experiment: The LSFmax of the control group and the 50 mg·L−1 fluoride exposure group reached the peak value at the 2nd month, and the LSFmax of the 50 mg·L−1 fluoride exposure group reached the valley value at the 4th month. The LSFmax of the 150 mg·L−1 fluoride exposure group at the 4th month was higher than that at the 6th month (P<0.05). There was no significant difference in the LSFmax at each time point in the 250 mg·L−1 fluoride exposure group. At the same time point, there was no statistically significant difference in LSFmax among the groups. The Col1 levels of the 50 mg·L−1, 150 mg·L−1, and 250 mg·L−1 fluoride exposure groups were higher than the time point 0 from the 2nd month (P<0.05). The Runx2 showed no statistically significant difference by concentration or time. Formal experiment: After feeding with 150 mg·L−1 fluoride for 5 months, the LSFmax of the fluoride exposure group was greater than that of the control group (P<0.05). The expressions of Col1, Runx2, BMP2, ALP, and Cath K in the fluorosis exposure group were higher than those in the control group (P<0.05). There were no statistically significant differences in osteoclast count or indicators of bone trabecular microstructure. Conclusion Chronic fluoride exposure may increase the shear strength of jaw bone.
2.Expression and prognostic value of COX- 2, p16(INK4A) and p53 in patients with classical Hodgkin lymphoma.
Yunfei SHI ; Zifen GAO ; Cuiling LIU ; Xin HUANG ; Yuqin SONG ; Lingyan PING ; Lixin ZHOU ; Min ZHAO ; Xiaozheng HUANG ; Yumei LAI ; Tingting DU ; Min LI
Chinese Journal of Hematology 2015;36(11):926-932
OBJECTIVETo investigate the expression level of COX-2, p16(INK4A) and p53 in patients with classic Hodgkin's lymphoma (cHL), and to evaluate their correlation with prognosis.
METHODSThe clinical data and samples of 52 cHL cases were collected. Immunohistochemical staining was performed to analyze the proteins level mentioned above and in situ hybridization of EBV encoded RNA (EBER) to clarify the tumor EBV infection state. Correlation between the protein expression and prognosis of patients was analyzed.
RESULTSOf 52 cases, the male and female ratio was 1.6∶1, the age was from 22 to 68 years old. All lesions located primarily in lymph nodes. All samples from 52 cases were stained with COX-2, p16(INK4A) and p53, and the positive expression of COX-2 was found in 28 cases (53.8%), that of p16(INK4A) in 25 cases (48.1%)and p53 in 42 cases (80.8%). All patients were divided into two groups according to differences in age (<40 years/ ≥ 40 years), gender (male/female), EBV infection (yes/no), B symptoms (yes/no), and the Ann Arbor staging (Ⅰ-Ⅱ/Ⅲ-Ⅳ), the correlation with COX-2, p16(INK4A) and p53 expression were analyzed, and only p53 expression was correlated with Ann Arbor staging (P=0.027). The statistical analysis of correlations between COX- 2, p16(INK4A) and p53 showed that the expression of COX-2 was strongly correlated with p53 (P=0.008), and p16 (INK4A) was not related to either COX-2 or p53 (P=0.246 and 0.958). Kaplan- Meier univariate OS analysis using SPSS17.0 software showed that only COX-2 expression was an adverse prognostic factor for patients'event free survival (EFS) (P=0.003). Meanwhile COX-2 expression was a unique independent prognostic factor analyzed by COX proportional hazards regression model (HR=0.091, 95% CI 0.017-0.505, P=0.006).
CONCLUSIONThe expression rate of COX-2, p16 (INK4A) and p53 in the cHL were relatively high; and they were not statistically correlated with tumor EBV infection status; the COX-2 positive group had poor prognosis, but only event free survival time becomes statistically significant shorter. COX proportional hazard regression model was used to analyze the COX-2 expression as a independent adverse prognostic factors for EFS.
Adult ; Aged ; Cyclin-Dependent Kinase Inhibitor p16 ; genetics ; metabolism ; Cyclooxygenase 2 ; genetics ; metabolism ; Disease-Free Survival ; Epstein-Barr Virus Infections ; Female ; Hodgkin Disease ; diagnosis ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Young Adult