Objective To evaluate the effects of renin-angiotensin system (RAS) blockades [angiotensin-converting enzyme inhibitors (ACEI) and angiotensin Ⅱ type 1 receptor blockers (ARB)]on contrast-induced nephropathy (CIN) in patients undergoing angiography.Methods Pubmed,Embase,Cochrane library,Wanfang database and CNKI were searched.The literature limited range was from their start year to July 2015.Randomized controlled trials (RCTs) and non-randomized controlled trials of renin-angiotensin system blockades in influencing CIN were assessed.Two investigators extracted data and performed quality analysis independently from all trims included.Rev man 5.3 software was used.Results 16 trials with a total of 15 897 patients were identified.There were 7490 patients who received renin-angiotensin system blockades and 8407 patients in control group.The meta analysis revealed a higher CIN incidence in ACEI/ARB group than that in control group (14.35％ vs 12.13％,P=0.04,OR=1.44,95％CI 1.01-2.04).For patients with renal insufficiency,ACEI/ARB group had a higher CIN incidence than control group (12.23％ vs 7.32％,P=0.02,OR=1.80,95％CI 1.10-2.94),and the serum creatinine changes in ACEI/ARB group were higher than those in control group.There was statistical difference in serum creatinine changes between groups (P=0.02,MD=0.08,95％CI 0.02-0.15).Conclusions Renin-angiotensin system blockades can increase theincidence of CIN in patients undergoing angiography.Renin-angiotensin system blockades can contribute to CIN for patients with renal insufficiency.

Objective To analyze the clinical features and prognostic factors of patients with malignant tumor complicated by acute kidney injury (AKI),and provide the basis for preventing AKI and improving the prognosis.Methods Malignant tumor patients complicated by AKI were screened with the electronic medical records system from January 2001 to December 2012 at the Affiliated Hospital of Qingdao University.The clinical characteristics in the 12 years were analyzed by statistical analysis and compared.The risk factors of the hospital mortality in malignancies tumor complicated by AKI were analyzed by Logistic regression analysis.Results A total of 100 patients with malignant tumor complicated by AKI were collected,accounting for 24.94％ of AKI patients and 1.66‰ of malignant tumor patients at the same period.Malignancies were consist of hematologic malignancies (11％),non-metastatic solid tumor (47％),metastatic solid tumor (42％).The most common factor leading to AKI for malignancies was post-renal obstruction (64％),followed by nephrotoxic drugs or contrast agents (24％),hypovolemia (18％).There was no significant change of the etiologies for AKI between the first six-year and the second six-year (P ＞ 0.05).The hospital mortality of patients with malignant tumor complicated by AKI was 25％,and multivariate Logistic regression analysis showed that multiple etiologies (OR=13.356),multiple organ failure (OR=222.256),and metastatic solid tumors (OR=8.497) were the independent risk factors for hospital mortality.Conclusions AKI is a common complication in patients with malignant tumors,and the most common factor leading to AKI is postrenal obstruction.The hospital mortality in malignancies with AKI is high,which should get the attention of clinicians.

Objective To explore the prevalence and risk factors of hyperuricemia(HUA) in patients with chronic kidney disease(CKD) on stages 3-5 and to investigate the effect of uric acid on renal function during the past 15 years.Methods Patients with CKD on stages 3-5 who admitted to the Nephrology Department of Affiliated Hospital of Qingdao University from January 2000 to December 2014 were recruited.The prevalence of HUA in patients with CKD on stages 3-5 were analyzed statistically,the risk factors of HUA and the effect of uric acid on the estimated glomerular filtration rate(eGFR) were analyzed by regression analysis.Results (1)The prevalence of HUA was 55.6%,and there was no significant difference between male and female in the 3 547 patients who met the inclusion criteria(χ2=0.184,P=0.683).The prevalence of HUA for CKD on stage 3,4,5 was 42.6%,59.1%,61.2%,respectively.(2)The independent risk factors of HUA in patients with CKD on stages 3-5 were hypertension(OR:1.209(95%CI:1.002-1.458)),increased BMI(OR:1.039(95%CI:1.015-1.062)),increased total cholesterol(OR:1.411(95%CI:1.274-1.564)),increased CKD stage(OR:1.891(95%CI:1.515-2.359),OR:1.898(95%CI:1.481-2.431)) and decreased HDL-C(OR:0.178(95%CI:0.134-0.238))(P<0.05).(3)In patients with CKD on stages 3-5,multiple regression analysis showed that after adjusting for confounding factors,each 100 mol/L-higher uric acid at baseline led to a change in the rate of the baseline eGFR decline of 1.49 ml.min-1.(1.73 m2)-1[95% CI:-2.20--1.05).(4)In 348 hyperuricemic patients with CKD on stage 3,Logistic regression analysis showed that persistent HUA was associated with a higher risk for eGFR decreasing more than 10 ml/min/(1.73 m2) 1 year later(hazard ratio(HR)=2.645,95%CI:1.388-5.039,P=0.003).Conclusion The prevalence of HUA in patients with CKD stages 3-5 is high.Hypertension,hyperlipidemia and overweight are risk factors of HUA.HUA is an independent risk factor for renal function deterioration.

Objective To explore the clinical characteristics of IgG4-related disease (IgG4-RD) in Chinese by detailed clinicopathological and laboratory assessments.Methods The baseline features of 36 patients with biopsy-proven disease were reviewed.The diagnosis was confirmed by pathology review according to consensus diagnostic criteria and clinicopathologic correlation.Disease activity and damage were assessed by the IgG4-RD responder index (RI).Results Thirty (83.3％) of the patients were male,while six were female,and the average age of onset was 65.1 years.All of the 36 patients had active disease,in which submandibular gland,lymph nodes,retroperitoneal tissue were the most common affected organs in this group of patients.Among 36 patients,77.7％ had elevated serum IgG4 concentrations and 44.4％ had hypocomplementemia.Patients with elevated serum IgG4 had a higher RI,a greater number of organs involved (P ＜ 0.01 for all comparisons).The correlation between serum IgG4 level and RI (r=0.737,P ＜ 0.01) was stronger than IgG,ESR,CRP and serum complement levels.The incidence of hypocomplementemia in IgG4-RD patients with renal involvement was higher than that in IgG4-RD patients with other organs involvement (P ＜ 0.01).Twenty-eight patients received glucocorticoids therapy,and had lower RI and serum IgG4 concentration after therapy (P ＜ 0.05).Conclusions Both IgG4-RD RI and IgG4 concentration may be regarded as assessment markers of disease activity and therapeutic effect of IgG4-RD.The diagnosis of IgG4-RD should be supported by histopathology and clinical features.

Objective To study the effect of zoledronate (ZOL) on Ca2+/calmodulin-dependent kinase Ⅱ δ (CaMK Ⅱ δ) and down-stream gene expressions during osteoclast differentiation.Methods Mouse osteoclast precursors RAW264.7 cells were divided into the control group and ZOL group.The cells in both groups were induced with 50μg/L receptor activator of nuclear factor kappa B ligand (RANKL) and were harvested on 5 d,while the cells in ZOL group were also simultaneously treated with 1 × 10-6 mol/L ZOL for 2 d.Five days later,the cells were harvested and examined osteoclastogenesis,as well as gene expressions of CaMK Ⅱ δ,nuclear factor of activated T-cells cytoplasmic 1 (NFATc1),tartrate-resistant acid phosphatase (TRAP) and cell-sarcoma receptor coactivator (c-Src).Results The number of TRAP positive multinuclear osteoclasts,number and size of dentin absorption lacunae and area in the ZOL group were (20.0±3.2),(18.0±4.2) and (6 335.3± 1 043.2)μm2 respectively,which were significantly lower than (36.0 ± 8.4),(37.2 ± 5.0) and (11 636.2 ± 3 661.1) μm2 in the control group and decreased by 44.4 ％,51.6 ％ and 45.6 ％ respectively (P＜0.01).ZOL also significantly inhibited the gene expressions of CaMK Ⅱ δ,NFATc1,TRAP and c-Src,and the mRNA levels of these genes were decreased by 44.1％,49.0％,53.8％ and 49.6％ respectively,the protein level were decreased by 43.5 ％,32.2 ％,45.5 ％ and 48.0 ％ respectively.The immunofluorescent cytochemistry detection results showed the fluorescence intensity of CaMK Ⅱ δ,NFATc1,TRAP and c-Srcin in the ZOL group was significantly weakened when compared with the control group.Conclusion ZOL could significantly inhibit the osteoclast formation and bone absorption function,and down-regulates gene expressions of CaMK Ⅱ δ,NFATc1,TRAP and c-Src in osteoclast differentiation.

[ ABSTRACT] AIM:To study the expression profiles and the role of Ca 2+/calmodulin-dependent kinase II delta ( CaMKIIδ) during osteoclast differentiation .METHODS:Mouse RAW264.7 cells were induced by receptor activator of nuclear factor κB ligand ( RANKL) at 50μg/L for osteoclastogenesis .Tartrate-resistant acid phosphatase ( TRAP) staining and bone resorption lacunae examination were performed to verify osteoclast formation .The expression of CaMKIIδat mR-NA and protein levels was also determined by immunofluorescent cytochemistry , RT-qPCR and Western blot at days 0, 1, 3 and 5.RESULTS:TRAP positive multinuclear cells with bone resorption function were formed after 5 d of induction. The mRNA levels of CaMKIIδdetected by RT-qPCR were 1.028 ±0.041, 2.478 ±0.087, 10.524 ±1.284 and 42.914 ± 2.667 at days 0, 1, 3 and 5, respectively, while the protein levels of CaMKIIδ detected by Western blot were 0.762, 0.963, 1.802 and 3.136, respectively.The changes of protein level were also verified by immunofluorescence cytochemis -try, in which the fluorescence intensity increased in a time-dependent manner (P<0.05).CONCLUSION:The expres-sion of CaMKIIδincreases with the differentiation of osteoclasts .CaMKIIδmay play a key role in the osteoclastogenesis .

Objective:To compare the therapeutic outcomes between use of antibiotic cement versus non-use of antibiotic cement in the treatment of tibial osteomyelitis after radical debridement.Methods:A retrospective analysis was made of the 68 patients with local tibial osteomyelitis of Cierny-Mader Type Ⅳ who had been treated at Department of Orthopaedic Trauma, The Second People’s Hospital of Shenzhen from January 2010 to June 2015. The dead space was filled with antibiotic-impregnated bone cement beans after radical debridement of the infected bone in 32 of them (cement group) but was not in 36 of them (no-cement group). The operations for both groups were performed by the same surgical team who filled the bone defects after excision of infected bone using Ilizarov bone transport. The 2 groups were compared in terms of Paley functional scores of bone and limb, external fixation index (EFI), infection recurrence rate, total hospital costs and other complications.Results:The 2 groups were comparable because there was no significant difference between them in the preoperative general data ( P>0.05). The cement group was followed up for (71.2±8.9) months and the no-cement group for (71.6±9.7) months, showing no significant difference ( P>0.05). By the Paley functional scores, the good to excellent rate for bone was 100% for both groups (32/32 versus 36/36) while the good to excellent rate for limb was 93.8% (30/32) for the cement group and 94.4% (34/36) for the no-cement group, showing no significant differences between them ( P>0.05). The EFI was (49.0±10.5) d/cm for the cement group and (49.5±11.4) d/cm for the no-cement group, showing no significant differences between them ( P>0.05). The infection recurrence rate at the final follow-up was 3.12% (1/32) for the cement group and 2.78% (1/36) for the no-cement group, showing no significant differences between them ( P>0.05). The total hospital cost was (70,944.1 ± 1,135.5) Yuan RMB for the cement group and (55,205.2 ± 897.3) Yuan RMB for the no-cement group, showing a significant difference ( P<0.05). No serious complications with sequelae were found in either of the 2 groups. Conclusion:In the treatment of local tibial osteomyelitis of Cierny-Mader Type Ⅳ, it is not necessary to fill the dead space with antibiotic cement when radical debridement is achieved.

This experiment was designed to construct mouse Smad6 recombinant RNA interference vectors and determine their interference effects on bone marrow mesenchymal stem cells (BMSCs). Three recombinant Smad6 RNA interference vectors were constructed by molecular clone techniques with a lenti-virus vector expressing green fluorescent protein (GFP), and the correctness of recombinant vectors was verified by DNA sequencing. Mouse BMSCs were used for transfection experiments and BMP-2 was in use for osteogenic induction of MSCs. The transfection efficiency of recombinant vectors was examined by Laser confocal scanning microscope and the interference effect of recombinant vectors on Smad6 gene expression was determined by real-time RT-PCR and Western blot, respectively. Three Smad6 recombinant RNA interference vectors were successfully constructed and their correctness was proved by DNA sequencing. After transfection, GFPs were effectively expressed in MSCs and all of three recombinant vectors gained high transfection efficiency (> 95%). Both real-time PCR and Western blot examination indicated that among three recombinant vectors, No. 2 Svector had the best interference effect and the interference effect was nearly 91% at protein level. In conclusion, Mouse recombinant Smad6 RNA interference (RNAi) vector was successfully constructed and it provided an effective tool for further studies on BMP signal pathways.
Animals ; Bone Morphogenetic Proteins ; genetics ; metabolism ; Genetic Vectors ; genetics ; Green Fluorescent Proteins ; biosynthesis ; genetics ; Lentivirus ; genetics ; metabolism ; Mesenchymal Stromal Cells ; metabolism ; Mice ; RNA Interference ; Recombinant Proteins ; biosynthesis ; genetics ; Smad6 Protein ; biosynthesis ; genetics ; Transfection

Objective To verify the criteria proposed by National Academy of Clinical Biochemistry(NACB)guidelines in investigating the factors that affect serum TSH determination, and to determine the reference range of serum TSH in iodine-sufficient areas of China. Methods In 2007, 5 348 inhabitants were enrolled from 3 iodine-sufficient areas of Liaoning Province, and were asked to fulfill the questionnaire. Serum TSH, thyroid peroxidase antibody(TPOAb), and thyroglobulin antibody(TgAb)were determined, and thyroid ultrasonography was carried out. Results The distribution of TSH levels was skewed in healthy people and closely fit the curve of Gaussian distribution after logarithmic transformation. The levels of TSH in subjects of 12-19 years of age were significantly higher than those of other age groups(P＜0.01), and no significant difference was found among the latter groups. TSH level in females [(1.68±1.90)mIU/L] was higher than in males[(1.45±1.92)mIU/L, P＜0.01]. The reference range of TSH was 0.43-4.74 mIU/L in males, and 0.48-5.39 mIU/L in females. Family history of thyroid disease, abnormal thyroid ultrasonography, and positive thyroid antibodies were the factors that influenced TSH level. Conclusion The reference range of serum TSH in iodine-sufficient areas of China is established.

OBJECTIVETo investigate the effect of thalidomide on the development of bisphosphonate-related osteonecrosis of the jaws (BRONJ).

METHODSThirty-six rats were randomly divided into groups A, B and C, and treated with saline, zoledronate and zoledronate plus thalidomide, respectively. Three weeks later, the left maxillary first molars of the rats were extracted. Four and eight weeks after tooth extraction, samples were harvested for evaluation of osteonecrosis of the jaws, microvessel density, and cell apoptosis.

RESULTSAt both of the time points, no exposed dead bone was observed at the extraction socket areas in the rats except for some small fistulas in groups B and C. Histological examination confirmed the absence of dead bone in group A, whereas small areas of dead bone were observed around the extraction socket in groups B and C. Compared with those in group A, the percentage of empty lacunae and the area of dead bone were significantly increased (P<0.01), whereas bone lacunae density was significantly decreased (P<0.01) in groups B and C at both time points. Microvessel density in groups B and C were also significantly decreased (P<0.01) by 25.87% and 55.27% at week 4, and by 45.62% and 72.84% at week 8, respectively; the apoptotic cells in groups B and C increased by 54.80% and 87.89% at week 4 (P<0.01), and by 208.08% and 250.58% at week 8 (P<0.01), respectively.

CONCLUSIONThalidomide can aggravate zoledronate-induced early-stage BRONJ, and their osteonecrosis-inducing effect of the jaw may be attributed, at least partly, to the inhibition of angiogenesis.

Animals ; Apoptosis ; Bisphosphonate-Associated Osteonecrosis of the Jaw ; pathology ; Bone Density ; Diphosphonates ; Disease Models, Animal ; Imidazoles ; Molar ; Neovascularization, Physiologic ; Rats ; Thalidomide ; adverse effects ; Tooth Extraction