Objective To explore the correlations of serum vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) with grading of myelofibrosis (MF) in patients with myeloproliferative neoplasms (MPN). Methods Ninety patients with Philadelphia chromosome negative (Ph-)MPN were selected as MPN group. According to the grading criteria for myelofibrosis by the World Health Organization (WHO) in 2016, MPN patients were divided into pre-fibrosis or early fibrosis group with 54 cases and significant fibrosis group with 36 cases; another 50 healthy volunteers were selected as the control group. Levels of serum VEGF, MMP-9 and TIMP-1 were detected by enzyme-linked immunosorbent assay, and the ratio of TIMP-1 to MMP-9 (TIMP-1/MMP-9) was calculated. Spearman rank correlation test was used to analyze the correlations of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 with MF grading. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of each indicator alone or their combination for diagnosing MPN or distinguishing MF grading. Results Compared with the control group, the serum levels of VEGF, MMP-9 and TIMP-1 in the MPN group increased significantly (P < 0.05). Values of area under the curve (AUC) of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 for diagnosing MPN were 0, 834, 0.745, 0.923 and 0.618 respectively; the AUC of the combined diagnosis of MPN by VEGF, MMP-9 and TIMP-1 was 0.960; when the optimal cut-off value was 0.627, the sensitivity was 85.56%, and the specificity was 92.00%. Compared with the pre-fibrosis or early fibrosis group, the serum levels of VEGF, TIMP-1 and TIMP-1/MMP-9 in the significant fibrosis group increased significantly (P < 0.05). Spearman correlation analysis showed that VEGF (r=0.378, P=0.001), TIMP-1 (r=0.512, P < 0.001) and TIMP-1/MMP-9 (r=0.353, P=0.001) were positively correlated with the MF grading of MPN patients (P < 0.05). ROC curve analysis showed that the values of AUC of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis were 0.723, 0.523, 0.802 and 0.708 respectively; the AUC of the combined detection of VEGF, TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis was 0.838; when the optimal cut-off value was 0.530, the sensitivity was 72.22%, and the specificity was 85.19%. Conclusion Serum VEGF, TIMP-1 and TIMP-1/MMP-9 can reflect the MF progression of MPN patients, and the combined detection of these indicators can predict the MF degree of MPN patients.

Objective:To identify the prevalence of multimorbidity among a Chinese population, analyze the risk of all-cause mortality with different multimorbidity patterns, and the impact of exercise on the risk of multimorbidity-related mortality and life lost.Methods:The study was based on 437 408 MJ Health Management Center participants. The classification decision tree was used to explore multimorbidity patterns composed of hypertension, diabetes, chronic kidney disease (CKD), and chronic obstructive pulmonary disease (COPD). The Cox proportional hazards model was used to calculate the all-cause mortality hazard ratio ( HR) for different multimorbidity patterns. Using Chiang's life table method, years of life lost were the difference in life expectancy for those with and without multimorbidity. Results:The prevalence rate of multimorbidity was 8.7%. Among multivariate patterns, the most common ones were "hypertension+CKD" (3.6%), "hypertension + diabetes + CKD" (1.1%) and "hypertension+diabetes+CKD+COPD" (0.1%). Compared with a healthy population, patterns with the highest mortality risk were "diabetes+CKD" ( HR=3.80, 95% CI: 3.45-4.18), "diabetes+CKD+COPD" ( HR=4.34, 95% CI: 3.43-5.49) and "hypertension+ diabetes+CKD+COPD" ( HR=4.75,95% CI:4.15-5.43). Through low-intensity and moderate to high-intensity exercise, the increased HRs were attenuatedcompared with the inactive population. People with single disease and multimorbidity shortened life by 4.6 and 13.4 years, while exercise attenuated 2.3 and 4.6 years of life lost, of which low-intensity and moderate to high-intensity exercise saved 1.5 and 3.7 years of life lost due to chronic diseases. Conclusions:Multimorbidity patterns based on "diabetes + CKD" cause the highest mortality risk, and physical activity in reducing mortality was significant for either with or without multimorbidity. Higher exercise intensity leads to a greater relative reduction of mortality risk.

Objective:To investigate the effects of microRNA-451 on proliferation, invasion and migration of multiple myeloma RPMI-8226 cells and its mechanism.Methods:RPMI-8226 cells cultured in vitro were divided into blank control group (untransfected), negative control (NC) group and miR-451 mimic transfected (miR-451) group. The expression of miR-451 was detected by real-time quantitative PCR (qRT-PCR), cell proliferation was detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) array and clone formation experiment, cell invasion and migration were detected by Transwell, and the expressions of c-Myc, MMP-2 and MMP-9 proteins were detected by western blot. The targeting relationship between miR-451 and c-Myc was detected by double luciferase reporter gene assay. Results:Compared to the blank control group, the expression level of miR-451 was increased (2.85±0.27 vs 1.02±0.06), while the cell survival rate [(47.28±3.15)% vs (93.65±6.52)%], cloning formation rate [(15.03±1.34)% vs (28.48±2.12)%], invasive cell number (86.65±5.58 vs 135.47±9.85), migrating cell number (106.36±6.48 vs 165.28±11.05) and the expression level of c-Myc(0.35±0.03 vs 0.66±0.05), MMP-2 (0.20±0.02 vs 0.48±0.03) and MMP-9 (0.28±0.03 vs 0.59±0.06) protein were significantly decreased in the miR-451 group ( P<0.05). In the negative control group, the expression level of miR-451, cell viability, clone formation rate, invasive cell number, migrating cell number, c-Myc protein, MMP-2 protein and MMP-9 protein were 0.94±0.05, (95.16±5.04)%, (27.55±2.26)%, (128.96±8.32) and (158.65±8.76), 0.68±0.06, 0.51±0.03, 0.54±0.03, respectively. There were no significant differences between the blank control group and the NC group ( P>0.05). Double luciferase reporter gene experiment confirmed that c-Myc was a potential target gene of miR-451. Conclusion:miR-451 can inhibit the proliferation, invasion and migration of RPMI-8226 cells by targeting c-Myc.

Objective:To investigate the effects of microRNA-451 on proliferation, invasion and migration of multiple myeloma RPMI-8226 cells and its mechanism.Methods:RPMI-8226 cells cultured in vitro were divided into blank control group (untransfected), negative control (NC) group and miR-451 mimic transfected (miR-451) group. The expression of miR-451 was detected by real-time quantitative PCR (qRT-PCR), cell proliferation was detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) array and clone formation experiment, cell invasion and migration were detected by Transwell, and the expressions of c-Myc, MMP-2 and MMP-9 proteins were detected by western blot. The targeting relationship between miR-451 and c-Myc was detected by double luciferase reporter gene assay. Results:Compared to the blank control group, the expression level of miR-451 was increased (2.85±0.27 vs 1.02±0.06), while the cell survival rate [(47.28±3.15)% vs (93.65±6.52)%], cloning formation rate [(15.03±1.34)% vs (28.48±2.12)%], invasive cell number (86.65±5.58 vs 135.47±9.85), migrating cell number (106.36±6.48 vs 165.28±11.05) and the expression level of c-Myc(0.35±0.03 vs 0.66±0.05), MMP-2 (0.20±0.02 vs 0.48±0.03) and MMP-9 (0.28±0.03 vs 0.59±0.06) protein were significantly decreased in the miR-451 group ( P<0.05). In the negative control group, the expression level of miR-451, cell viability, clone formation rate, invasive cell number, migrating cell number, c-Myc protein, MMP-2 protein and MMP-9 protein were 0.94±0.05, (95.16±5.04)%, (27.55±2.26)%, (128.96±8.32) and (158.65±8.76), 0.68±0.06, 0.51±0.03, 0.54±0.03, respectively. There were no significant differences between the blank control group and the NC group ( P>0.05). Double luciferase reporter gene experiment confirmed that c-Myc was a potential target gene of miR-451. Conclusion:miR-451 can inhibit the proliferation, invasion and migration of RPMI-8226 cells by targeting c-Myc.

Objective: To investigate the clinical significance of plasma amino-terminal pro-brain natriuretic peptide(NT-proBNP) in children with bacterial meningitis. Methods: From April 2013 to March 2017, 32 children with bacterial meningitis in PICU of the Second People′s Hospital of Liaocheng Affiliated to Taishan Medical College were selected.The patients were evaluated the severity of the disease by Glasgow coma scale(GCS). Thirty-five cases who admitted to the hospital in the same period were selected as the control group, excluding congenital heart disease, chronic cardiac dysfunction, cardiomyopathy, myocarditis, heart failure, chronic renal insufficiency.The blood samples were collected from the hospital in 24h, and the levels of the plasma NT-proBNP, procalcitonin(PCT), C-reactive protein(CRP) and Na ions were determined. Results: Compared with the control group, the levels of the plasma NT-proBNP was significantly increased[(7 123.97±6 901.60)ng/L vs.(39.29±19.41)ng/L, t=5.839, P<0.01], the level of PCT was significantly increased[(25.14±2.35)ng/dL vs.(0.63±0.15ng/dL, t=10.820, P<0.01], the level of CRP was significantly increased[(97.89±4.63mg/dL vs.(5.23±1.22mg/dL, t=21.130, P<0.01], and the GCS was significantly decreased(t=18.132, P<0.01) in children with bacterial meningitis group.The plasma NT-proBNP level of children with GCS<8points[(13 328.08±7 938.85)ng/L]was significantly higher than that in children with GCS 8~14points[(3 401.50±1 526.75)ng/L](t=5.816, P<0.01) and GCS≥15points[(39.74±18.64)ng/L](t=5.816, P<0.01). There was a significant positive correlation between the level of plasma NT-proBNP and PCT(r=0.969, P<0.01), also a significant positive correlation between the level of plasma NT-proBNP and CRP(r=0.961, P<0.01), while a significant negative correlation between the level of plasma NT-proBNP and sodium ions(r=0.886, P<0.01) in children with bacterial meningitis by Pearson correlation test. Conclusion Detection of the plasma NT-proBNP has significant clinical significance for early diagnosis and assessment of the severity of the illness of children with bacterial meningitis.

Objective To analyze the antimicrobial resistance, distribution of resistance genes and staphylococcal cassette chromosome mec ( SCCmec) in 99 strains of mecA gene-positive Staphylococcus epi-dermidis strains isolated from early pregnancy cervical swabs and external environment in Beijing Chaoyang District from 2015 to 2016. Methods Kirby-Bauer disk diffusion method was performed to detect the sus-ceptibility of the 99 Staphylococcus epidermidis strains to cefoxitin. Microbroth dilution method was used to test their susceptibility to vancomycin, daptomycin, penicillin, erythromycin, compound sulfamethoxazole, tetracycline, ciprofloxacin, clindamycin, gentamicin and chloramphenicol. PCR was used to detect drug re-sistance genes of ermA, ermB, ermC, msrA, norA1, norA2, sul1, sul2, sul3, aac(6')/aph(2″), ant(4', 4″), ant(6) and tetM and to analyze the SCCmec types ofⅠ, Ⅱ, Ⅲ, Ⅳa, Ⅳb, Ⅳc, Ⅳd and Ⅴ. The results were compared with those of capillary electrophoresis. SPSS was used for data analysis. Results All of the 99 mecA-positive Staphylococcus epidermidis strains were sensitive to vancomycin and 93. 94％ of them were sensitive to datomycin. The resistance rates to penicillin, erythromycin, cefoxitin, compound sulfame-thoxazole, tetracycline, ciprofloxacin, clindamycin, gentamicin and chloramphenicol were 97. 98％, 85. 86％, 79. 80％, 52. 54％, 27. 27％, 43. 43％, 36. 36％, 23. 23％ and 11. 11％. The strains that car-ried the genes of norA1, norA2, ermA, ermB, ermC, msrA, sul1, sul2, sul3, aac(6')/aph(2″), ant(4', 4″), ant(6) and tetM accounted for 100％, 93. 94％, 0. 00％, 3. 03％, 17. 17％, 57. 58％, 50. 51％, 12. 12％, 4. 04％, 30. 30％, 8. 08％, 4. 04％ and 25. 26％, respectively. Among the 99 strains, 5. 05％, 0％, 43. 43％, 10. 10％, 0. 00％, 3. 03％, 3. 03％ and 19. 19％ belonged to SCCmecⅠ, Ⅱ, Ⅲ, Ⅳa,Ⅳb,Ⅳc,Ⅳd andⅤ, respectively, and 4. 04％ (4/99) were positive to two SCCmec types. The types of 12. 12％ (12/99) of the strains were unidentified. Conclusions All of the 99 strains of mecA-positive Staphylococcus epidermidis were sensitive to vancomycin. Among them, the strains carrying multidrug resist-ance genes accounted for 89. 90％. The main mechanisms of resistance to macrolides, sulfonamides and ami-noglycosides in local strains were related to the resistance genes of msrA, sul1 and aac ( 6')/aph ( 2″) . SCCmec Ⅲ was the prevalent type. There were 88. 37％ of SCCmec Ⅲ type strains and 75％ of unknown type strains carrying multiple resistance genes. Apart from that, the isolated strains of other SCCmecⅢtypes all carried multiple resistance genes.

BACKGROUND:Biomechanical compatibility is the necessary condition to ensure the stable osseointegration with implants that then can function over a long period; therefore, it is especialy important to get knowledge about distribution of stress and strain between the maxilary central incisor and its surrounding bone tissue. OBJECTIVE: Based on five different anatomical types of natural teeth, to study the regularity of stress distribution between the maxilary central incisor root and implant.METHODS: According to the five different anatomical types of natural maxilary central incisors, UGNX and ANSYS were used to set up three-dimensional finite element models (B1, B2, M1, M2, P1) for the implant and surrounding structures, which were under 100 N static load at angles of 0o, 30o, 45o, 60o, 90o with the long axis of teeth. Then, the stress distribution between the five kinds of maxilary central incisor roots and implants was analyzed. RESULTS AND CONCLUSION:Among the five different anatomical types, the equivalent stress for both the natural central incisor and implant were increased with the increasing of angles, and the implant had a higher raising trend. The equivalent stress for the natural tooth concentrated upon B1 for the maximum value and M1 for the minimum value; while the equivalent stress for the implant focused on the maximum value at M1 and the minimum value at M2. There was a gap of 2%-31% between the equivalent stresses for the natural tooth roots and a gap of 4%-21% for the implants. The stress distribution range for the implant was just smaler than that for the natural tooth roots. It implies that the bit force of implant and natural tooth is in positive proportion to the bite angles, and the bite force that implant can burden is smaler than that the central incisor can.

OBJECTIVETo observe the impact of plant sterol esters (PSE) mixed in low fat milk powder (2.5 g of PSE/day) on plasma cholesterol levels in hypercholesterolemic subjects during a 6-week intervention period.

METHODSIn this double-blind, randomized, placebo-controlled study, 59 subjects (19 males, mean age (60.28 ± 6.98) years) with primary hypercholesterolemia (fasting LDL cholesterol between 3.4-6.0 mmol/L) were randomly divided into two groups (treatment group, 2.5 g of plant sterol esters a day, n = 30) and placebo group (n = 29). Blood samples were collected at week 0, 3 and 6. The primary outcome was change in plasma LDL-cholesterol (LDL-C). Secondary outcomes were changes in total cholesterol (TC), HDL cholesterol (HDL-C), triglycerides (TG), anthropometry and blood biochemistry.

RESULTSLDL-C significantly reduction from baseline (4.18 ± 0.54) mmol/L to (3.44 ± 0.61) mmol/L (-17.7%, P < 0.05) at week 3 and (3.35 ± 0.39) mmol/L (-19.9%, P < 0.05) at week 6 in the treatment group, whereas in placebo group from (4.11 ± 0.54) mmol/L at baseline to (3.47 ± 0.60) mmol/L (-15.57%, P < 0.05) and (3.61 ± 0.39) mmol/L (-12.17%, P < 0.05) at week 3 and week 6, respectively. TC was reduced from (6.30 ± 0.86) mmol/L at baseline to (5.92 ± 0.75) mmol/L (-6.03%, P > 0.05) at week 3 and (5.43 ± 0.77) mmol/L (-13.8%, P < 0.05) at week 6 in treatment group, from (6.20 ± 0.76) mmol/L at week 0 to (5.70 ± 0.76) mmol/L (-8.06%, P < 0.05) at week 3 and (5.84 ± 0.75) mmol/L (-5.81%, P < 0.05) at week 6 in placebo group. PSE-enriched milk did not affect plasma HDL-C level and TG level at both week 3 and week 6. After normalization to the placebo group, the treatment group showed significant reduction in LDL-C and total cholesteron after 6 weeks. The observed difference of reduction was 7.69% (-0.33 mmol/L, P < 0.05) for LDL-C and 8.00% (-0.51 mmol/L, P < 0.05) for TC between the two groups. There were no significant changes in safety parameters, including blood biochemistry tests during the study period.

CONCLUSIONPlant sterol ester enriched milk powder is effective in reducing LDL-C among Chinese hypercholesterolemic subjects at a dosage recommended by EFSA.

Animals ; Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Double-Blind Method ; Female ; History, 18th Century ; Humans ; Hypercholesterolemia ; diet therapy ; Lipids ; Male ; Middle Aged ; Milk ; Phytosterols ; pharmacology ; therapeutic use ; Triglycerides

Osteoporosis is a kind of systemic metabolic bone diseases ,characterized by bone loss , bone subtle structural dam-age.Leptin is a peptide hormone which secreted by fat cells , that has both positive and negative effects to the bone , and plays a role of regulating on bone metabolism .In vitro, Leptin can regulate proliferation of osteoblast and inhibit reabsorption of osteoblasts depend on osteoclast.In vivo, Leptin can inhibit the synthesis of serotonin in the brain stem and increase the sympathetic nerve signals output by the hypothalamus to the bone , it mainly has a negative effect .But clinical trials about the correlation between Leptin and senile oste-oporosis, the role of Leptin in the central nervous system and peripheral tissue problems are still unclear .In this paper, we will make a comprehensive overview about the latest research progress in the correlation between leptin and senile osteoporosis .

Objective To observe the impact of plant sterol esters ( PSE ) mixed in low fat milk powder (2.5 g of PSE/day) on plasma cholesterol levels in hypercholesterolemic subjects during a 6-week intervention period.Methods In this double-blind, randomized, placebo-controlled study, 59 subjects (19 males, mean age ( 60.28 ±6.98 ) years ) with primary hypercholesterolemia ( fasting LDL cholesterol between 3.4-6.0 mmol/L) were randomly divided into two groups ( treatment group , 2.5 g of plant sterol esters a day, n=30) and placebo group (n=29).Blood samples were collected at week 0, 3 and 6.The primary outcome was change in plasma LDL-cholesterol ( LDL-C).Secondary outcomes were changes in total cholesterol ( TC) , HDL cholesterol ( HDL-C) , triglycerides ( TG) , anthropometry and blood biochemistry.Results LDL-C significantly reduction from baseline ( 4.18 ±0.54 ) mmol/L to ( 3.44 ±0.61 ) mmol/L (-17.7%, P<0.05) at week 3 and (3.35 ±0.39) mmol/L ( -19.9%, P<0.05) at week 6 in the treatment group , whereas in placebo group from ( 4.11 ±0.54 ) mmol/L at baseline to ( 3.47 ±0.60 )mmol/L (-15.57%, P<0.05) and (3.61 ±0.39)mmol/L (-12.17%, P<0.05) at week 3 and week 6, respectively.TC was reduced from ( 6.30 ±0.86 ) mmol/L at baseline to ( 5.92 ±0.75 ) mmol/L (-6.03%, P>0.05 ) at week 3 and ( 5.43 ±0.77 ) mmol/L ( -13.8%, P <0.05 ) at week 6 in treatment group, from (6.20 ±0.76)mmol/L at week 0 to (5.70 ±0.76) mmol/L (-8.06%, P<0.05) at week 3 and (5.84 ±0.75) mmol/L ( -5.81%, P<0.05) at week 6 in placebo group.PSE-enriched milk did not affect plasma HDL-C level and TG level at both week 3 and week 6.After normalization to the placebo group , the treatment group showed significant reduction in LDL-C and total cholesteron after 6 weeks.The observed difference of reduction was 7.69% ( -0.33 mmol/L, P <0.05 ) for LDL-C and 8.00%(-0.51 mmol/L, P<0.05) for TC between the two groups.There were no significant changes in safety parameters , including blood biochemistry tests during the study period.Conclusion Plant sterol ester enriched milk powder is effective in reducing LDL-C among Chinese hypercholesterolemic subjects at a dosage recommended by EFSA.