Adult ; Androstadienes ; therapeutic use ; Aromatase Inhibitors ; therapeutic use ; Breast Neoplasms ; drug therapy ; Female ; Humans ; Middle Aged ; Nitriles ; therapeutic use ; Triazoles ; therapeutic use

Objective To investigate the significance of anti-mutated citrullinated vimentin(MCV)an- tibody in rheumatoid arthritis(RA)and study the correlation among anti-CCP,other antoantibodies and clinical manifestations of RA.Methods Anti-MCV antibody was detected by enzyme-linked immunosorbent assay (ELISA)in 166 serum samples including 74 from RA(18 cases with early RA and 56 cases with late RA),50 from non-RA rheumatic diseases and 42 cases of healthy blood donors.At the same time,other antuoantibod- ies were detected by different techniques,and their clinical meaning was investigated with the corresponding clinical data.Results Anti-MCV was found in 78%(58/74)of RA.The sensitivity and specificity of Anti- MCV in RA were 78% and 95%.The positive and negative predictive value was 97% and 71%.The average cut off concentration of Anti-MCV was(552?380)U/ml in RA,(162?63)U/ml in non-RA and(63?46)U/ml in healthy control.Anti-MCV was strongly correlated to anti-CCP(r=0.502,P=0.000),then AKA(r=0.408)anti APF(r=0.369).No differences was found between Anti-MCV and other clinical/laboratory parameters(P＞0.05). Conclusion Anti-MCV antibody may be a valuable diagnostic parameter for RA.Anti-MCV is more strongly correlated to anti-CCP than APE and AKA.It may not relate to disease activity and/or severity.

Objective:To study the clinical application of laparoscopic combined with multi-video debridement in treatment of complicated infectious pancreatic necrosis (CIPN).Methods:The clinical data of 34 patients with CIPN who were treated at the Department of General Surgery, Xuanwu Hospital, Capital Medical University from August 2017 to December 2019 were retrospectively studied. Based on the different video methods used, these patients were divided into 3 groups: the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group. The number of operations, operation time, blood loss, postoperative complication rates, mortality rates and total length of hospital stay were compared.Results:There were 13 patients in the laparoscopic combined with intraoperative ultrasound group, with age of (56.4±13.4) years. There were 7 patients in the laparoscopic combined with choledochoscopy group, with age of (48.0±8.4) years. There were 14 patients in the laparoscopic group with age of (51.4±15.6) years. The number of operations of the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group were (2.2±1.1), (1.6±0.8), (2.9±1.4), respectively. The number of operations of the laparoscopic combined with choledochoscopy group were significantly less than that of the laparoscopic group ( P<0.05), but there were no significant differences among the other groups ( P>0.05). The operation time of the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group were (70.5±22.9) min, (65.7±19.9) min, (51.5±15.4) min, respectively. The operation time of the laparoscopic combined with intraoperative ultrasound group was significantly longer than that of the laparoscopic group ( P<0.05), but there were no significant differences among the other groups ( P>0.05). There were no differences in blood loss, postoperative complication rate, mortality rates and total lengths of hospital stay among the three groups ( P>0.05). Conclusion:Laparoscopic combined with multi-video debridement after making full use of the advantages of each of the video methods, can be used to improve treatment outcomes of patients with CIPN.

OBJECTIVE Neuroinflammation plays a critical role in neurodegenerative disorders, although the inflammation may not the initiating factor. Parkinson disease (PD) is characterized patho?logically by the accumulation of alpha synuclein (α-syn) and the loss of the dopamine (DA) neurons in the substantia nigra (SN), which has been reported to be induced by the stereotaxic injection of lipopolysaccharide (LPS) to the SN region in rodents. This study is to investigate the therapeutic benefit of the inhibition of miR-873 in PD. METHODS Rats received the right-unilaterally injection with concentrated LV-sponge or LV-EGFP 3 d before LPS treatment, 7 or 14 d after LPS treatment. The animals were tested for rotational behavior with the dopaminergic agonist apomorphine dissolved in sterile saline at 21 d after LPS injection. The regulation of miR-873 on the genes related with cholesterol transport and inflammation was assayed in SH-SY5Y cells and U251 cells. RESULTS TLR4-MyD88 signaling pathway was involved the regulation of miR-873 by LPS. The luciferase assay showed that HMGCR, ABCA1 and A20 were down- stream genes of miR- 873. The transfection of miR- 873 decreased the cholesterol levels in cell membrane, but increased in lysosome in SH-SY5Y cells. Compared with the control SH-SY5Y cells, cholesterol levels were higher in lysosome with α-synuclein overexpression or LPS treatment. The transfection of miR-873 increased the α-syn levels in lysosome in cells with α-synuclein overexpression. The loss of dopaminergic neuorns induced by LPS was significantly respectively decreased by 22.8%, 35.6% and 57% after the inhibition of miR-873 at 3 d before LPS treatment, 7 or 14 d after LPS treatment. Compared with LPS-treated group, the number of the rotation of rats was decreased by 60.4%, 33.5% and 13.2% after the inhibition of miR-873 at 3 d before LPS treatment, 7 or 14 d after LPS treatment. The inhibition of miR-873 significantly decreased accumulation of α-syn. The mRNA levels of HMGCR, ABCA1 and A20 in SN were decreased by LPS treatment, which was attenuated by the injection of LV- sponge. CONCLUSION The selective regulation of miR- 873 can protect the dopaminergic neurons from the LPS-induced damage. The inhibition of miR-873 can attenuate the relocation of cholesterol in lysosome and the accumulation of α-syn in neurons induced by LPS via the regulation of HMGCR, ABCA1 and A20.

OBJECTIVE CYP2D is one of the most abundant subfamily of CYPs in the brain, especially in the cerebellum. Brain CYP2D is responsible for the metabolism of endogenous neurotransmitters such as tyramine and serotonin. Our previous studies have shown brain CYP2D can be regulated by exogenous and endogenous substances with tissue- specificity. The purpose of this study is to examine the effects of cerebral CYP2D on the mice behavior and the regulatory mechanism of brain CYP2D by growth hormone. METHODS Mice received the stereotaxic injection with CYP2D inhibitor quinine in deep cerebellar nuclei of cerebellum. The animals were tested with rotarod apparatus, balance beam, water maze, elevated plus maze and open field. The changes in CYP2D22, PPARαand PPARγ in brain regions and liver were assayed in male growth hormone receptor knockout mice, SH-SY5Y cells and HepG2 cells. RESULTS The inhibition of cerebellum CYP2D significantly affected the spatial learning and exploring ability of mice. Compared with WT mice, CYP2D expression was lower in brain regions from GHR(-/- ) male mice; however, hepatic CYP2D level was similar. Pulsatile GH decreased PPARα mRNA level, and increased mRNA levels of CYP2D6 and PPARα in SH- SY5Y cells. In HepG2 cells, pulsatile GH resulted in decreases in PPARα and PPARγ mRNA levels, but not CYP2D6. PPARα inhibitor induced CYP2D6 mRNA and protein by 1.32-fold and 1.43-fold in SH-SY5Y cells. PPARγ inhibitor decreased CYP2D6 mRNA and protein by 74.76% and 40.93%. PPARα agonist decreased the level of CYP2D22 mRNA in liver and cerebellum, while PPARγ agonist rosiglitazone resulted in diametrically increases. The luciferase assay showed that PPARγ actived the CYP2D6 gene promoter while PPARα inhibited its function. Pulsatile GH declined the binding of PPARα with CYP2D6 promoter by 40%, promoted the binding of PPARγ with CYP2D6 promoter by approximate 60%. The levels of brain and liver PPARα expression in male GHR(-/- ) mice is obviously higher than those in WT mice. The level of PPARγ in male GHR(-/- ) mice was decreased in the frontal cortex and hippocampus, while remained stable in the cerebellum and striatum; meanwhile, PPARγ was increased in the liver. CONCLUSION Brain CYP2D may be involved in learning and memory functions of central system. Masculine GH secretion altered the PPARs expression and the binding of PPARs to CYP2D promoter, leading to the elevated brain CYP2D in a tissue- specific manner. Growth hormone may specifically alter the metabolic and synthetic of important endogenous substances in the central nervous system (such as serotonin) through the specific regulation of brain CYP2D expression.

OBJECTIVETo investigate the clinical value of spiral CT with multi-planar reconstruction (MPR) and three diamensions reconstruction (3D) in the diagnosis and treatment of pelvic ring fractures.

METHODSFifty-seven patients with pelvic ring fractures were examined with digital radiography and spiral CT in our hospital from April 2004 to April 2009. According to Tile classification, there were thirty-eight cases in type A, twelve in type B and seven in type C. Expectant treatment was used in type A, while surgery, open reduction internal fixation or percutaneous lag screw internal fixation technique for sacroiliac joint due to the displacement of fractures, for type B and C. Three days to twenty-seven months after operation, spiral CT examinations were used to evaluate the location of internal fixation. Cross-check analysis of images of digital radiography and spiral CT was performed before and after operation.

RESULTSFive posterior and three anterior pelvic ring fractures were diagnosed as suspected fractures. Nine posterior and three anterior pelvic ring fractures were missdiagnosed according to plain radiographs, which were corrected by spiral CT examination. According to the postoperative imageology evaluation, the results were excellent in 15, good in 3 and bad in 1. According to clinical evaluation, 16 cases were excellent, 3 good.

CONCLUSIONSpiral CT with multi-planar reconstruction (MPR) and three diamensions reconstruction (3D) has clinical values for precise diagnosis and treatment for the complex pelvic ring fractures.

Adolescent ; Adult ; Aged ; Female ; Fracture Fixation, Internal ; Fractures, Bone ; diagnosis ; diagnostic imaging ; surgery ; Humans ; Imaging, Three-Dimensional ; Male ; Middle Aged ; Pelvic Bones ; diagnostic imaging ; injuries ; surgery ; Reconstructive Surgical Procedures ; Tomography, Spiral Computed ; methods ; Young Adult

Pancreatic exocrine insufficiency (PEI) refers to insufficient or non-synchronous secretion of trypsin caused by various reasons, resulting in dyspepsia and other symptoms. Intestinal microbiota is a large number of microbiota on the surface of intestinal mucosa. Its main functions include intestinal immune function, forming intestinal biological barrier and participating in the regulation of nutrition and metabolism. Due to aging, some elderly people often have unexplained chronic pancreatic insufficiency, which is often characterized by unexplained weight loss and malnutrition. Several studies have shown that the composition of intestinal microbiota changes significantly with age. This article focuses on aging and its related PEI and then reviews its possible effects on intestinal microbiota, in order to provide a reference basis for individualized prevention and treatment strategies according to the changes of pancreatic exocrine function and microbiota in the elderly.

Objective To investigate the effects of metformin on the proliferation and apoptosis of human oral cancer cell line KB in vitro. Methods Human oral cancer cell line KB was exposed to different doses of metformin (0, 1.25, 2.5, 5, 10, and 20 mmol/L), and the changes in cell viability were detected using MTT assay. Colony formation of the cells was observed following an 8-day metformin exposure. The changes in mitochondrial membrane potential were measured by JC-1 assay, and PI staining was used to observe the cell apoptosis. Western blotting was employed to detect the changes in the protein expressions of GRP78 and activated caspase-3. Results Metformin exposure caused time-and dose-dependent suppression of KB cell proliferation, and exposure to 5 mmol/L metformin for 24, 48 and 72 h resulted in cell survival rates of 68.0%, 36.9%, and 14.5%, respectively. Metformin significantly inhibited KB cell colony formation. Exposure of the cells to increased concentrations of metformin gradually increased the apoptotic rate and decreased mitochondrial membrane potential. Metformin caused an initial up-regulation followed by a down-regulation of GRP78 expression in KB cells and increased the expression of activated caspase-3. Conclusion Metformin can inhibit the proliferation and induce apoptosis of KB cells, the mechanism of which may involve the activation of the mitochondrial apoptotic pathway and endoplasmic reticulum stress.

Objective To investigate the effects of metformin on the proliferation and apoptosis of human oral cancer cell line KB in vitro. Methods Human oral cancer cell line KB was exposed to different doses of metformin (0, 1.25, 2.5, 5, 10, and 20 mmol/L), and the changes in cell viability were detected using MTT assay. Colony formation of the cells was observed following an 8-day metformin exposure. The changes in mitochondrial membrane potential were measured by JC-1 assay, and PI staining was used to observe the cell apoptosis. Western blotting was employed to detect the changes in the protein expressions of GRP78 and activated caspase-3. Results Metformin exposure caused time-and dose-dependent suppression of KB cell proliferation, and exposure to 5 mmol/L metformin for 24, 48 and 72 h resulted in cell survival rates of 68.0%, 36.9%, and 14.5%, respectively. Metformin significantly inhibited KB cell colony formation. Exposure of the cells to increased concentrations of metformin gradually increased the apoptotic rate and decreased mitochondrial membrane potential. Metformin caused an initial up-regulation followed by a down-regulation of GRP78 expression in KB cells and increased the expression of activated caspase-3. Conclusion Metformin can inhibit the proliferation and induce apoptosis of KB cells, the mechanism of which may involve the activation of the mitochondrial apoptotic pathway and endoplasmic reticulum stress.

OBJECTIVETo study the effect of glycolysis inhibitor 3-bromopyruvate (3-BrPA) in inducing apoptosis of human breast carcinoma cells SK-BR-3 and the possible mechanism.

METHODSMTT assay was used to detect the growth inhibition induced by 3-BrPA in breast cancer cells SK-BR-3. The apoptotic cells were detected by flow cytometry with propidium iodide (PI). ATP levels in the cells were detected by ATP assay kit, and DHE fluorescent probe technique was used to determine superoxide anion levels; the mitochondrial membrane potential was assessed using JC-1 staining assay.

RESULTSMTT assay showed that the proliferation of SK-BR-3 cells was inhibited by 3-BrPA in a time- and concentration-dependent manner. Exposure to 80, 160, and 320 µmol·L(-1) 3-BrPA for 24 h resulted in cell apoptosis rates of 6.7%, 22.3%, and 79.6%, respectively, and the intracellular ATP levels of SK-BR-3 cells treated with 80, 160, 320 µmol·L(-1) 3-BrPA for 5 h were 87.7%, 60.6%, and 23.7% of the control levels. 3-BrPA at 160 µmol·L(-1) increased reactive oxygen levels and lowered mitochondrial membrane potential of SK-BR-3 cells.

CONCLUSION3-BrPA can inhibit cell proliferation, reduce the mitochondrial membrane potential and induce apoptosis in SK-BR-3 cells, the mechanism of which may involve a reduced ATP level by inhibiting glycolysis and increasing the reactive oxygen level in the cells.

Apoptosis ; drug effects ; Cell Line, Tumor ; Female ; Glycolysis ; Humans ; Membrane Potential, Mitochondrial ; drug effects ; Pyruvates ; pharmacology ; Reactive Oxygen Species ; metabolism