BACKGROUND:Clinical fol ow-up studies have shown that alendronate is effective to prevent femoral head col apse fol owing traumatic osteonecrosis of the femoral head, but its mechanism remains poorly understood. OBJECTIVE:To analyze the effects and mechanisms of alendronate on prevention of col apse in traumatic osteonecrosis of the femoral head. METHODS:Total y 45 Sprague-Dawley rats were randomly divided into three groups, with 15 rats in each group. Placebo group received physiological saline after establishing models of avascular necrosis of the femoral head. Alendronate group received treatment of alendronate after model induction. Sham surgery group received an equal volume of physiological saline. At 5 weeks after model establishment, the rats were sacrificed. Femoral samples at the modeling side were col ected for general observation, X-ray irradiation, Micro-CT and histological detection. RESULTS AND CONCLUSION:General observation revealed that the femoral head was obviously deformed in the placebo group, but mild deformity was visible in the alendronate group. The ratio of height to width of the femoral head ranked as fol ows:sham surgery group>alendronate group>placebo group, showing significant differences. Micro-CT scanning results demonstrated that the mean number of bone trabecula was more in the alendronate group than in the placebo group, but less than sham surgery group, showing significant differences. The mean thickness of bone trabecula was less in the alendronate group than in the placebo group, but no significant difference was detectable as compared with the sham surgery group. The mean spacing of bone trabecula was less in the alendronate group than in the placebo group, but larger than in the sham surgery group, showing significant differences. Bone volume, bone surface area and bone mineral density were larger in the alendronate group than in the placebo group, but less than sham surgery group, showing significant differences. Histological detection results demonstrated that apparent sequestrum existed and osteoclasts were obviously inhibited in the alendronate group. The number of osteoclasts was noticeably less in the alendronate group than in the placebo group. Osteoblasts and new vessels were suppressed to some degrees. Results suggested that alendronate can inhibit curing reaction through inhibiting osteoclast and osteoblast activity and vessel formation, which can final y slow down the absorption of necrotic bone and preserve femoral head mass and shape. Thus, alendronate can be used as a preventive against femoral head col apse in rats with traumatic osteonecrosis of the femoral head.

BACKGROUND:Many patients underwent aspirin anticoagulation in preventing cardiovascular disease before hip and knee replacement. No report addressed the effect of aspirin on blood loss during perioperative stage in patients receiving hip and knee replacement. OBJECTIVE:To observe the effect of perioperative continuous low-dose aspirin anticoagulation application on total hip arthroplasty or total knee arthroplasty. METHODS: A total of 40 patients with primary total hip arthroplasty or total knee arthroplasty were enroled in the Department of Orthopedics, Tianjin First Center Hospital from December 2012 to August 2013. According to anticoagulation scheme, they were divided into two groups (n=20). In the observation group, 100 mg/d aspirin anticoagulation was continuously used before replacement for a long period, and the medicine was not withdrawn except the day of replacement. In the control group, aspirin anticoagulation was not used, and their ages were similar to the observation group. The operation was conducted by the same physician in the observation and control groups. 10 patients received total hip arthroplasty and 10 patients received total knee arthroplasty in both groups. Bleeding was stopped actively during replacement. After replacement, pressurized ice compress was used to reduce bleeding. At 48 hours after replacement, wound drainage, perioperative hemoglobin and the incidence of complications were recorded. Joint function recovery was observed at 3 months of folow-up. RESULTS AND CONCLUSION:Hemoglobin levels before and after operation, postoperative blood drainage at 48 hours, perioperative hemoglobin changes, the incidence of complication, and joint function score at 3-month folow-up did not show significant difference between both groups. These findings indicate that it is safe to use some measures for reducing blood loss and continue low-dose aspirin in the perioperative period. The use of aspirin did not impact blood loss.

Objective To explore the reasonable nursing interventions of advanced schistosomiasis patients. Methods The medical records of 52 advanced schistosomiasis patients hospitalized from 2008 to 2013 were collected,and the nursing interven-tions were summarized. Results The 52 cases of advanced schistosomiasis included 38 men and 14 women,with a mean age of 65.8 years(57-75 years). Totally 53.8%of the subjects were schistosome positive by IHA test,67.3%positive by ELISA,and 21.2%positive of HBsAg. There were 13 cases of ascites type,34 cases of megalosplenia type,and 5 cases of dwarfism type of ad-vanced schistosomiasis. Following the therapy together with nursing interventions,73.1%achieved clinical cure,23.1%achieved stable,and 3.8%achieved improvement. The major nursing interventions involved basic nursing,diet nursing,treatment nursing, physiological nursing and surgical nursing. Conclusion The scientific and reasonable nursing interventions can improve the ther-apeutic efficacy and prognosis in advanced schistosomiasis patients,as well as improve their quality of life.

Objective To determine the effect of NEL-like type 1 gene (NELL-1) transfection in vivo in the repair of traumatic femoral head necrosis.Methods Twenty-four SD rats were randomly divided into three groups (8 rats per group) according to the lottery method,ie,sham group (served as normal control),NELL-1 treatment group (injected NELL-1 gene by recombinant adenovirus vectors around the hip one week after osteonecrosis model induced surgically) and placebo group (given an equal volume of saline solution at the same time after the induction of osteonecrosis).Femurs were taken from the animals 5 weeks after surgery.Gross observation was performed for morphology changes,X-ray assessment for femoral head height and length ratio (H/L),Micro-CT measure for bone parameters of femoral head including total volume (TV),bone volume (BV),total mineralized content (TMC),trabecular thickness (Tb.Th) and trabecular space (Tb.SP),and histological study for osteocytes,osteoblasts and osteoclasts.Results Preserved femoral head shape was noted in NELL-1 treatment group compared to the obvious flattening of the femoral head in placebo group.No heterotopic osteogenesis was observed in any group.Femoral head H/L ratio for 0.753 2 ± 0.040 2 in NELL-1 treatment group was higher than 0.598 4 ± 0.037 0 in placebo group (P ＜ 0.05),but lower than 0.920 2 ± 0.037 0 in sham group (P＜0.05).TV,BV,TMC and BMD between NELL-1 treatment and sham groups did not differ significantly (P ＞ 0.05),but all were increased compared to placebo group (P ＜ 0.05).There was no significant differences in Tb.Th and Tb.SP among three groups (P ＞ 0.05).Most osteocytes were alive in NELL-1 treatment group.More active osteoblasts and osteoclasts were noted in NELL-1 treatment group than those in placebo group.Conclusion NELL-1 gene transfection can preserve femoral head shape and bone content,promote osteoblast activity and neovascularization and hence is an effective treatment for rat traumatic osteonecrosis.However,the activity of osteoclasts is stimulated simultaneously.

On the basis of the theory of formal concept analysis (FCA), a new method for generation of an attribute hierarchical graph is proposed in this paper. This method can solve the problems of how to mine and express classification knowledge and rules in compatibility of prescription. In this paper, we view prescriptions as objects that possess certain attributes of the named drugs. First, the formal context is established based on theory. Then optimization of the original formal context and extracts the connotation and extension of the concept are followed, constructing attribute hierarchical graph. Finally, useful knowledge from the hierarchical diagram of attributes based on the way of knowledge representation is mined. The result showed that the method for discovering Traditional Chinese Prescription (TCP) diagnostic knowledge is feasible and effectual for small samples. The research of large samples is 13th open question of FCA. It is an international subject to be studied urgently.
Concept Formation ; Drug Combinations ; Drug Prescriptions ; standards ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; standards

AIM:To investigate the impact and regulatory mechanisms of zinc finger protein 36-like protein 1(ZFP36L1)on pancreatic carcinoma cell growth.METHODS:The ZFP36L1 expression in pancreatic carcinoma and its correlation with patient prognosis were analyzed using online databases UALCAN and GEPIA.Western blot was utilized to detect ZFP36L1 protein expression in pancreatic ductal cells(HPNE)and three different pancreatic carcinoma cell lines.CCK-8 and cell colony formation assays were performed to evaluate the effects of ZFP36L1 on pancreatic cancer cell prolif-eration.Wound healing and Transwell assays were used to assess the impact of ZFP36L1 expression changes on pancreatic carcinoma cell migration and invasion.Flow cytometry experiments were used to analyze the effect of ZFP36L1 on the pan-creatic carcinoma cell cycle process.Bioinformatics analysis was conducted to predict potential ZFP36L1 interacting pro-teins.Co-immunoprecipitation experiments were carried out to confirm the interaction between ZFP36L1 and mitogen-acti-vated protein kinase 14(MAPK14).Rescue experiments were performed to assess the function of MAPK14 in ZFP36L1-regulated pancreatic carcinoma cell growth.RESULTS:(1)ZFP36L1 is highly expressed in pancreatic carcinoma and is positively correlated with poor prognosis in pancreatic carcinoma patients.Compared to HPNE,ZFP36L1 is highly ex-pressed in MIA PaCa-2 and ASPC-1 cells,but relatively low in PANC-1 cells.(2)ZFP36L1 overexpression significantly increased the cell viability,colony formation,migration,and invasion abilities of PANC-1 and MIA PaCa-2 cells,while siRNA interference of ZFP36L1 led to opposite results.(3)ZFP36L1 promotes the entry of pancreatic carcinoma cells into the S phase of the cell cycle.(4)ZFP36L1 interacts with MAPK14 to regulate pancreatic cancer cell growth.MAPK14 overexpression reversed the cell viability and migration abilities of pancreatic carcinoma cells overexpressing ZFP36L1.Furthermore,it also decreased the cell viability and migration abilities of pancreatic carcinoma cells with ZFP36L1 inter-ference.CONCLUSION:ZFP36L1 is a potential oncogene in pancreatic carcinoma growth and may regulate pancreatic carcinoma cell growth through cell cycle modulation and interaction with MAPK14.

Objective: Investigate the effects of inducible ppp2r1a knockout on main physiological function in adult mice and study the mechanism. Methods: Ppp2r1a^flox/flox mice and CAGG-CreER mice were hybridized to obtain 20 CAGG-CreER ppp2r1a^flox/flox and 20 mice in homozygous group. Two groups of mice were divided into 4 groups respectively, finally we got 8 groups with 5 mice in each group. Tamoxifen was injected intraperitoneally to acquire inducible ppp2r1a knockout mice. The knockout efficiency of PP2A Aα in vital organs was measured by Western blot. At 0, 2, 4 and 6 days after injection, we measured body weight, histopathological change, peripheral blood cell counts and blood biochemical. Real-time PCR was performed to measure expression of liver glucolipid metabolism genes. Results: After tamoxifen injection for 6 days, the knockout efficiency of PP2A Aα in vital organs was 35%, 12%, 15%, 60%, 69% and 72%, respectively in heart, liver, spleen, lung, kidney and brain. After tamoxifen injection for 6 days, the weight of homozygous mice was lower than that of wild type mice, with values of (17.42±1.76) g and (21.69±1.82) g, respectively (P<0.05). Moreover, the activity level, abdominal and renal fat were significantly decreased in homozygous mice. Homozygous mice survived no more than 7 days. Compared with wild type mice, the organ coefficient of spleen of homozygous mice was decreased at the 6th day, with values of (0.59±0.10)% and (0.36±0.05)% respectively (P<0.05). Obvious spleen atrophy and marked decrease of nucleated cells were showed by performing HE staining. Tunel staining revealed increased apoptosis ratio of splenic lymphocytes in homozygous mice. The levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) of homozygous mice were higher than wild type mice (P<0.05). The values of ALT and AST in homozygous mice were (153.68±62.80) U/L and (193.2±44.28) U/L. The corresponding values in wild type mice were (41.02±12.91) U/L and (69.40±9.55) U/L. The above results indicated that ppp2r1a knockout caused liver damage. Blood sugar level of homozygous mice was lower than in wild type mice (P<0.05), with values of (4.20±1.99) mmol/L and (8.88±0.65) mmol/L respectively. Plasma total cholesterol (TC), high density lipoprotein (HDL) and β-hydroxybutyric acid (β-HB) level of homozygous mice were higher than those of wild type mice (P<0.05). The values of TC, HDL and β-HB in homozygous mice were (3.12±0.39), (1.53±0.38) and (2.49±0.89) mmol/L. The corresponding values in wild type mice were (1.69±0.92), (0.78±0.50) and (0.45±0.30) mmol/L respectively. The above results indicated that ppp2r1a loss interfered glucose and cholesterol metabolism. In addition, we also found that the white blood cell count (WBC) and lymphocyte count (LYM) of homozygous mice were lower than in wild type mice (P<0.05). The values of WBC and LYM in homozygous mice were (1.88±0.89)×10⁹/L and (0.92±0.37)×10⁹/L respectively. The corresponding values in wild type mice were (3.91±0.80)×10⁹/L and (2.74±0.52)×10⁹/L respectively. The mRNA levels of glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PEPCK) of homozygous were lower than wild type mice (P<0.05). The fold change of G6P and PEPCK in homozygous mice was 0.46±0.11 and 0.72±0.07 respectively. The corresponding fold change in wild type mice was 1.02±0.07 and 1.02±0.06 respectively. Conclusion Whole body ppp2r1a is essential for the survival of adult mice, due to the important role in maintaining the metabolism of glucose and cholesterol of liver.

Endothelial cell injury is a major contributor to cardiovascular diseases.The 2,3,5,4’-Tetrahydroxystilbene-2-O-β-D-Glucoside (TSG) contributes to alleviate human umbilical vein endothelial cells (HUVECs) injury through mechanisms still know a little. This study aims to clarify the TSG effects on gene expression (mRNA and microRNA) related to oxidative stress and endoplasmic reticulum stress induced by H2O2 in HUVECs. We found that TSG significantly reduced the death rate of cells and increased intracellular superoxide dismutase activity. At qRT-PCR, experimental data showed that TSG significantly counteracted the expressions of miR-9-5p, miR-16, miR-21, miR-29b, miR-145-5p, and miR-204-5p. Besides, TSG prevented the expression of ATF6 and CHOP increasing. In contrast, TSG promoted the expression of E2F1. In conclusion, our results point to the obvious protective effect of TSG on HUVECs injury induced by H2O2, and the mechanism may through miR16/ATF6/ E2F1 signaling pathway.

Endothelial cell injury is a major contributor to cardiovascular diseases.The 2,3,5,4’-Tetrahydroxystilbene-2-O-β-D-Glucoside (TSG) contributes to alleviate human umbilical vein endothelial cells (HUVECs) injury through mechanisms still know a little. This study aims to clarify the TSG effects on gene expression (mRNA and microRNA) related to oxidative stress and endoplasmic reticulum stress induced by H2O2 in HUVECs. We found that TSG significantly reduced the death rate of cells and increased intracellular superoxide dismutase activity. At qRT-PCR, experimental data showed that TSG significantly counteracted the expressions of miR-9-5p, miR-16, miR-21, miR-29b, miR-145-5p, and miR-204-5p. Besides, TSG prevented the expression of ATF6 and CHOP increasing. In contrast, TSG promoted the expression of E2F1. In conclusion, our results point to the obvious protective effect of TSG on HUVECs injury induced by H2O2, and the mechanism may through miR16/ATF6/ E2F1 signaling pathway.

Background Lipid metabolism in liver shows circadian-dependent profiles. The hepatotoxicity of environmental chemicals is dependent on circadian time. Objective To observe the effects of bisphenol A (BPA) exposure at different zeitgeber time (ZT) on hepatic and blood lipid metabolism and decipher the underlying mechanisms related to circadian rhythm in mice. Methods Thirty-five female C57BL/6J mice were sacrificed every 4 h in a light-dark cycle (12 h/12 h). The liver tissues were collected to describe the circadian profiles of hepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels within 24 h. Thirty female mice were divided into 6 groups by the timing (ZT3 represents the 3 h after light on, ZT15 represents the 3 h after light off) and dose (50 or 500 μg·kg⁻¹·d⁻¹) of BPA exposure to observe hepatotoxicity. Mice were gavaged with designed doses of BPA once per day for 4 weeks. Mice were maintained with ad libitum access to food and water and measured body weight weekly. After the experiment, mice were euthanatized and liver tissues were separated to determine the biochemical indicators of lipid metabolism and lipid metabolism- and circadian-related gene mRNA expressions. Results Hepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels were rhythmic during a 24 h period in mice. At ZT3 and ZT15, BPA did not alter body weight, plasma glucose, plasma total cholesterol, plasma low density lipoprotein cholesterol, and plasma triglycerides (P>0.05). The plasma high density lipoprotein cholesterol decreased in the 50 μg·kg⁻¹·d⁻¹ BPA group at ZT3 by 14.56% compared with the control group (P<0.05). The liver triglycerides increased in the 50 μg·kg⁻¹·d⁻¹ BPA group at ZT15 by 115.20% compared with the control group (P<0.05). BPA decreased Srebp1c mRNA expression level when dosing at ZT3 and increased Chrebp, Srebp1c, and Acc1 mRNA expression levels when dosing at ZT15 compared with the control group (P<0.05). BPA increased Bmal1 mRNA expression level and decreased Rev-erbα mRNA expression level at ZT3 exposure and decreased Bmal1 and increased Rev-erbα mRNA expression level at ZT15 exposure (P<0.05). Conclusion BPA exposure at light or dark period has different effects on hepatic lipid metabolism in mice. Hepatic lipid deposit appears when BPA is dosed at dark period. Rev-erbα-Bmal1 regulation circuits and the subsequent upregulation of Srebp1c and Chrebp and the target gene Acc1 may be involved.