Objective: To assess diagnostic performance of multi-parametric MRI including MR elastography (MRE), susceptibility-weighted imaging (SWI) and T₁ρ imaging in detecting the early stage of liver fibrosis (LF). Methods: Eighty healthy rabbits were randomly divided into LF group (n=60) and control group (n=20). The LF group (n=12) and control group (n=5) were randomly selected at the end of the 4^th, 5^th, 6^th, 15^th week after injection of 50% CCl₄ oil solution, respectively. All rabbits underwent 3.0 T MRI scans and histopathological Scheuer staging. Differences between groups were examined using one-way analysis of variance with Dunnett's T3 test. Spearman correlation was used to analyze the correlation between liver stiffness (LS), liver-to-muscle SI ratio (SIR), T₁ρ value in different LF stages. ROC curve analysis was used to assess the diagnostic performance. Results: Fifty-five rabbits were included in our study, which covered F0 (n=14), F1 (n=11), F2 (n=10), F3 (n=9) and F4 (n=11). Significant differences of all characteristic values were found among different LF stages (P<0.05).There were significant differences in LS values between F0 and F2, F3, F4, respectively; F1 and F3, F4, respectively; F2 and F4; F3 and F4 (P<0.05). There were significant differences in SIR between F0 and F2, F3, F4, respectively; F1 and F2, F3, F4, respectively; F2 and F4 (P<0.05). T₁ρ value showed significant differences between F0, F1, F2, F3 and F4, respectively (P<0.05). LS, SIR, and T₁ρ values were correlated with LF stage (r=0.910, -0.808, 0.512, respectively, P<0.01). The area under curve (AUC) for LS value were greater than those for the other two methods (0.953 for≥F1, 0.949 for≥F2, 0.986 for≥F3, 0.979 for F4). The AUCs of the combination of MRE and SWI for detecting≥F1 was 0.965, for≥F2 was 0.983, for≥F3 was 0.991, and for F4 was 0.950. Combining all three MR methods showed the highest diagnostic performance for staging LF with AUCs of 0.969, 0.985, 0.996 and 1.000. Conclusion MRE is the most prominent MRI method, and combination of MRE and SWI show higher diagnostic performance than the others for staging LF; however, combining all three MR methods exhibits the most excellent diagnostic efficacy.

Objective To assess diagnostic performance of multi?parametric MRI including MR elastography (MRE), susceptibility?weighted imaging (SWI) and T1ρ imaging in detecting the early stage of liver fibrosis (LF). Methods Eighty healthy rabbits were randomly divided into LF group (n=60) and control group (n=20). The LF group (n=12) and control group (n=5) were randomly selected at the end of the 4th, 5th, 6th, 15th week after injection of 50% CCl4 oil solution, respectively. All rabbits underwent 3.0 T MRI scans and histopathological Scheuer staging. Differences between groups were examined using one?way analysis of variance with Dunnett's T3 test. Spearman correlation was used to analyze the correlation between liver stiffness (LS), liver?to?muscle SI ratio (SIR), T1ρ value in different LF stages. ROC curve analysis was used to assess the diagnostic performance. Results Fifty?five rabbits were included in our study, which covered F0 (n=14), F1 (n=11), F2 (n=10), F3 (n=9) and F4 (n=11). Significant differences of all characteristic values were found among different LF stages (P<0.05).There were significant differences in LS values between F0 and F2, F3, F4, respectively; F1 and F3, F4, respectively; F2 and F4; F3 and F4 (P<0.05). There were significant differences in SIR between F0 and F2, F3, F4, respectively; F1 and F2, F3, F4, respectively; F2 and F4 (P<0.05). T1ρ value showed significant differences between F0, F1, F2, F3 and F4, respectively (P<0.05). LS, SIR, and T1ρ values were correlated with LF stage (r=0.910, -0.808, 0.512, respectively, P<0.01). The area under curve (AUC) for LS value were greater than those for the other two methods (0.953 for≥F1, 0.949 for≥F2, 0.986 for≥F3, 0.979 for F4). The AUCs of the combination of MRE and SWI for detecting≥F1 was 0.965, for≥F2 was 0.983, for≥F3 was 0.991, and for F4 was 0.950. Combining all three MR methods showed the highest diagnostic performance for staging LF with AUCs of 0.969, 0.985, 0.996 and 1.000.Conclusion MRE is the most prominent MRI method, and combination of MRE and SWI show higher diagnostic performance than the others for staging LF; however, combining all three MR methods exhibits the most excellent diagnostic efficacy.

To explore the role of methotrexate (MTX) in regulating the number of regulatory T cells (Treg) and the mRNA expression of transcription factor Foxp3.
 Methods: 1) We analyzed the number of Treg and the mRNA expression of Foxp3 by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR) respectively in patients with psoriasis vulgaris, patients with psoriasis vulgaris after the 8-week treatment of MTX, and healthy people. 2) BALB/c female mice were smeared with imiquimod (IMQ) cream for 6 days. We recorded the change of the lesion in mice every day. The morphological changes of lesion in mice were evaluated by the psoriasis area and severity index (PASI) and HE staining. 3) The mouse model was randomly divided into a control group and an MTX group. The MTX group was treated with different doses of MTX (38.5 and 77.0 nmol/L) on the third day of this experiment. The morphological changes of lesion in mice were evaluated by PASI and HE staining. We tested the number of Treg and the expression level of Foxp3 mRNA in splenic lymphocytes.
 Results: 1) The number of Treg and the expression level of Foxp3 mRNA were lower in psoriasis vulgaris patients than those in the healthy control group (P<0.05). After 8-week treatment of MTX, the number of Treg was increased (P<0.05) and Foxp3 mRNA level was up-regulated (P<0.01). 2) Typical psoriasis-like skin lesions, such as red scaly skin plaque were found after topical application of IMQ. Both the number of Treg in the splenic lymphocytes of mice and the Foxp3 mRNA level of Treg were reduced by IMQ (P<0.01 and P<0.05). 3) Different doses of MTX for mice showed the ability to improve skin lesion, increase the number of Treg in the spleen of mice and Foxp3 mRNA level in psoriatic dermatitis of mice (P<0.05).
 Conclusion: MTX is able to regulate the number of Treg and Foxp3 mRNA expression in psoriasis.
Adjuvants, Immunologic ; pharmacology ; Aminoquinolines ; pharmacology ; Animals ; Case-Control Studies ; Female ; Forkhead Transcription Factors ; metabolism ; Humans ; Imiquimod ; Immunosuppressive Agents ; administration & dosage ; pharmacology ; Lymphocyte Count ; Methotrexate ; administration & dosage ; pharmacology ; Mice ; Mice, Inbred BALB C ; Psoriasis ; drug therapy ; immunology ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Random Allocation ; Spleen ; cytology ; T-Lymphocytes, Regulatory ; cytology ; drug effects ; metabolism

Objective To investigate the value of susceptibility weighted imaging (SWI) with T1ρimaging in staging of hepatic fibrosis(HF) in rabbits. Methods Eighty selected white rabbits from New Zealand were randomly divided into the HF group (n=60) and the control group (n=20). Rabbits in the HF group were injected subcutaneously with 50％CCl4 oil solution to establish HF model,and the normal control rabbits were injected with saline solution subcutaneously.The HF group(n=15) and control group(n=5) were randomly selected at the 4th, 5th, 6th and 10th week after injection, to undergo liver MR scan. The liver signal intensity (SI liver), the muscle signal intensity (SI muscle),liver-to-muscle SI ratios (SIR) and liver T1ρvalues were measured. Scheuer was adopted to stage the rabbits in HF. One-way analysis of variance was used to compare the differences between SIR and T1ρ values in different stages of HF pathological. Spearman correlation was used to analyze the correlation between SIR and T1ρ values in the different stage of HF pathological.The ROC were used to compare the efficacy between SIR and T1ρvalues in the diagnosis of HF pathological stage. Results Among the final qualified 68 rabbits in the study, 17 in F0 phase, 11 in F1 phase, 16 in F2 phase, 11 in F3 phase, and 13 in F4 phase. The SIR were (0.977 ± 0.013), (0.960 ± 0.015), (0.802 ± 0.026), (0.786 ± 0.022), (0.541 ± 0.116); T1ρ values were (22.301 ± 1.849), (24.034 ± 0.867), (25.374 ± 1.309),(25.364±1.945),(30.948±2.925) ms.There were statistically significant in SIR between F0 and F2,F0 and F3, F0 and F4, F1 and F2, F1 and F3, F1 and F4, F2 and F4, F3 and F4 (P<0.01). There were statistically significant in T1ρvalues between F0 and F1,F0 and F2,F0 and F3,F0 and F4,F1 and F2,F1 and F4,F2 and F4, F3 and F4(P<0.05). SIR were negatively correlated with HF staging while T1ρ values were positively. ROC showed that the AUC of the T1ρvalues was slightly larger than SIR in the F4 group(0.992>0.966),and the AUC of the SIR was greater than T1ρvalues in the other groups. Conclusion SWI and T1ρvalues can provide an important objective basis in staging of HF. Both of them have great clinical application prospects but SIR diagnostic efficiency is slightly better than that of T1ρvalues.

Background and purpose: Peritoneal metastasis of gastric cancer is mainly discovered in the ad-vanced cancer. Nonetheless, the clinical applicability of each tumor biomarker in peritoneal metastasis of gastric cancer is still ambiguous. Therefore, this study investigated the diagnostic value and clinical significance of CEA, CA125 and CA72-4 in gastric carcinoma patients with peritoneal metastases. Methods: A total of 108 gastric carcinoma patients with peritoneal metastases from Jan. 2008 to Dec. 2013 were studied. All patients were diagnosed by imaging, operations and pathological examination, and also received intravenous or intraperitoneal chemotherapy. Serum tumor markers such as CEA, CA125 and CA72-4 were determined during diagnosis and before each chemotherapy. The diagnostic sensitivity of single marker and combined detection with 2 or 3 markers were analyzed. The correlations among the serum tumor markers and clinical pathological factors, chemotherapeutic effects and survival time were analyzed. Results: Positive rates of CEA, CA125 and CA72-4 were 20.4%, 46.3% and 45.4% in gastric cancer patients with peritoneal metastases, respectively. For these patients, the positive rates of CEA/CA125, CEA/CA72-4, CA125/CA72-4 and CEA/CA125/CA72-4 were 54.7%, 52.8%, 69.5% and 79.6%, respectively. The combined detection of 3 tumor markers was much better than single marker detection (P<0.05). Positive rates of CEA, CA125 and CA72-4 were correlated with the ECOG scale (P<0.05). Positive rate of CA125 was associated with ascites (P<0.001), while positive rate of CA72-4 was associated with ovarian metastasis (P<0.05). Median survival time of patients with positive rates of CEA, CA125 and CA72-4 was significantly lower than that of the patients with normal levels of these markers (P<0.05). Compared with pre-treatment, the levels of all three tumor markers significantly declined after three cycles of chemo-therapy (P<0.05). The decline in CA125 level after chemotherapy was significantly correlated with decreased amount of ascites (P<0.05). The tumor markers turned negative after 3 cycles chemotherapy in patients with positive markers upon initial diagnosis, their survival was significantly prolonged (P<0.001). Conclusion: Combined detection of serum CEA, CA125 and CA72-4 can significantly promote diagnostic rate of gastric cancer with peritoneal metastasis, and may be helpful in evaluating chemotherapeutic effects and predicting prognosis.

Through introducing mutations into ribosomes by obtaining spontaneous drug resistance of microorganisms, ribosome engineering technology is an effective approach to develop mutant strains that overproduce secondary metabolites. In this study, ribosome engineering was used to improve the yield of butenyl-spinosyns produced by Saccharopolyspora pogona by screening streptomycin resistant mutants. The yields of butenyl-spinosyns were then analyzed and compared with the parent strain. Among the mutants, S13 displayed the greatest increase in the yield of butenyl-spinosyns, which was 1.79 fold higher than that in the parent strain. Further analysis of the metabolite profile of S13 by mass spectrometry lead to the discovery of Spinosyn α1, which was absent from the parent strain. DNA sequencing showed that there existed two point mutations in the conserved regions of rpsL gene which encodes ribosomal protein S12 in S13. The mutations occurred a C to A and a C to T transversion mutations occurred at nucleotide pair 314 and 320 respectively, which resulted in the mutations of Proline (105) to Gultamine and Alanine (107) to Valine. It also demonstrated that S13 exhibited genetic stability even after five passages.
Genetic Engineering ; Macrolides ; metabolism ; Point Mutation ; Ribosomal Proteins ; genetics ; Ribosomes ; metabolism ; Saccharopolyspora ; metabolism

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 explore the application value of quantitative analysis of tissue diffusion by ultrasound elastography in evaluating the evolution of achilles tendinopathy and indirectly reflecting the feature of tendon biomechanics.Methods Rabbits underwent 0.1 ml (group M) or 0.3 ml (group S)collagenase or 0.2 ml saline (group C) injection.The percentage of area displaying blue (％AREA) in the area of interest was measured by the diffusion quantitative technique of ultrasound elastography at baseline and 1,3,7 and 14 days after model.The achilles tendon was obtained for pathological examination to observe the changes of collagen fibers and tested to measure the maximum tensile load by the universal testing machine.Results (1) The ％AREAs in group M and S at 1,3,7 and 14 days after model were smaller than those in group C (P ＜0.05),and reached its lowest value at 3 days after model.％ AREA in groupSwas significant lower than that in group M at 3 or 7 days after model (P ＜0.05).(2) The maximum tensile loads in group M at 1,3 and 7 days after model were smaller than those in group C (P ＜0.05),but there was no significant difference between group M and C at 14 days after model (P ＞0.05).The maximum tensile load in group S was significant lower than those in group M and C after model (P ＜0.05),and arrived its lowest point at 3 days after model.(3) The ％AREA was positively associated with the maximum tensile load of achilles tendon (r =0.87,P ＜0.001).Conclusions Ultrasound elastography can dynamically monitor the evolution of achilles tendinopathy and reflect the biomechanical state of achilles tendon.

BACKGROUND:The knee joint acts as the body’s largest and most complex joint, which is a commonly seen perplex in patients because of synovium and cartilage diseases. Moreover, clinical physicians are often confused on the ultrasonic diagnosis of synovium and cartilage diseases.
OBJECTIVE: To review the ultrasound misdiagnosed cases of knee cartilage and synovial lesions and to summarize the common misconceptions and discrimination methods.
METHODS: A retrospective analysis was performed in the ultrasound misdiagnosed cases of knee cartilage and synovial lesions reported from 2002 to 2014, and then the common misconceptions and corresponding identification methods were summarized.
RESULTS AND CONCLUSION: High-frequency ultrasound is most likely to have six “mistaken ideas” addressing knee cartilage and synovial lesions: (1) cartilage degeneration; (2) synovial calcification; (3) echo intensity from synovial lesions; (4) blood flow in the synovium; (5) synovial effusion; (6) lesions involving intraarticular structures. High-frequency ultrasound runs through dynamical observation and contrast observation of bilateral knee joint lesions, which is a valuable imaging method for diagnosis of cartilage and synovial diseases based on vigilance at the “mistaken ideas” and mastery of the distinguishing ideas and methods.

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.