Objective Toevaluatethevalueofcombineddeterminationofvariousindicesintheclinicaldiagnosisofacutepancreatitis (AP)through dynamic measurements of the levels of peripheral serum C-reactive protein (CRP),lipase (LPS),interleukin-1β(IL-1β),andintercellularadhesionmolecule1(ICAM-1),aswellaschangesintheirlevels,inpatientswithAP.Methods Atotalof86 patients with AP who were treated in Fourth Affiliated Hospital of China Medical University from January 2010 to December 2012 were select-ed,among whom there were 39 patients with severe acute pancreatitis (SAP)and 47 patients with mild acute pancreatitis (MAP).Serum sam-ples were collected from these patients on days 1,3,5,and 7 of admission.Twelve healthy subjects were selected as controls.Enzyme-linked immunosorbent assay was applied to measure the levels of CRP,IL-1β,and ICAM-1 ,and the dry slides method was applied to measure the concentration of serum LPS.The t test and χ2 test were applied for comparison of continuous data and categorical data between groups, respectively.Results Onday1ofadmission,thepatientsinMAPgrouphadsignificantlyhigherlevelsofCRP,IL-1β,andLPSthan those in control group (t=-74.126,-60.135,and -364.153,respectively;all P<0.001);on day 1 of admission,the patients in SAP group had significantly higher levels of CRP,ICAM-1,IL-1β,and LPS than those in control group (t=-121.355,-25.728,-89.422,and -415.840,respectively;all P<0.001).The peak concentration of each index appeared on day 1 or 3 of admission,and decreased progressively in the course of therapy.The patients in SAP group had significantly higher levels of serum CRP,LPS,IL-1β,and ICAM-1thanthoseinMAPgroup(allP<0.05).Conclusion CombineddeterminationofserumCRP,LPS,IL-1β,andICAM-1 levels has a certain clinical value in early identification of severity of AP.

ObjectiveTo investigate the expression of survivin,COX-2 and bcl-2 in non-Hodgkin lymphoma(NHL)and the significance and correlation between them.MethodsImmunohistochemistry MaxVision systems for survivin,COX-2 and bcl-2 were conducted on 44 NHL and 20 reactive lymphoid hyperplasia (RH).ResultsThe positive expression rates of survivin,COX-2,bcl-2 in NHL were 70.45 ％(31/44),68.18 ％ (30/44),63.64 ％ (28/44),respectively,and these in RH were 40.00 ％ (8/20),40.00 ％(8/20) and 20.00 ％ (4/20),respectively.There was positive correlation between the expression of COX-2 and survivin (r =0.306,P =0.043),survivin and bcl-2 protein (r =0.339,P =0.040) in NHL.ConclusionCOX-2,survivin,bcl-2 are highly expressed in NHL.To detect the expression of them has clinical value to diagnosis NHL and to estimate the malignant degree of lymphoma.There are a positive correlations between the expression of COX-2 and survivin protein,and between the expression of survivin and bcl-2 protein,which indicates that they may play a synergistic role in the occurrence and development of NHL.

Objective To summarize the first experience with ultrasound-guided percutaneous ab lation treatment (PAT) for recurrent hepatoblastoma (HB) after liver resection in children.Methods From August 2013 to April 2015,PAT was used to treat 6 children with a total of 9 recurrent HB,including 5 patients with 8 tumors in the liver and 1 patient with 1 tumor in the lung.The mean size of ablated tumors was (1.5 ± 0.8) cm,and the tumor size range was 0.7 cm to 3.1 cm.Results Four patients were performed percutaneous radiofrequency ablation (RFA) for recurrent HB;and 2 patients were performed percutaneous ethanol injection (PEI).Ablation success was achieved in all patients (6/6,100％).The complete ablation rate after the first ablation session was 88.9％ (8/9) on a tumor-by-tumor basis.Only 1 patient developed a fever with temperature ＞ 39 ℃;it was resolved by conservative therapy.During the follow-up period of 5-30 months,3 patients died to tumor progression.The 1-and 2-year overall survival rates after ablation were 83.3％ and 41.7％,respectively.Conclusions PAT is a safe and promising therapy for children with recurrent HB after liver resection,and further investigation in large-scale randomized clinical trials is required to determine its role in the treatment of this disease.

OBJECTIVE: To explore the genotype-phenotype correlation of Cardio-facio-cutaneous syndrome (CFCS) caused by MAP2K1 gene variants. METHODS: Genomic DNA was extracted from peripheral blood sample from a child patient and his parents. Whole exome sequencing (WES) was carried out for the patient. Suspected variant was verified by Sanger sequencing. RESULTS: The patient was a 1-year-8-month old Chinese male who manifested short stature, psychomotor retardation, relative macrocephaly, distinctive facial features, and congenital heart disease. WES test revealed a heterozygous missense c.389A>G (p.Tyr130Cys) variant in the MAP2K1 gene. Sanger sequencing has confirmed the variant as de novo. According to ACMG/AMP guidelines, the variant was classified as pathogenic. CONCLUSION Compared with previously reported CFCS cases due to MAP2K1 variants. The patient showed obvious behavioral problems, good appetite and tricuspid regurgitation, which may to be novel features for CFCS.
China ; Ectodermal Dysplasia ; genetics ; Facies ; Failure to Thrive ; genetics ; Genetic Association Studies ; Genetic Variation ; Heart Defects, Congenital ; genetics ; Heterozygote ; Humans ; Infant ; MAP Kinase Kinase 1 ; genetics ; Male ; Mutation ; Whole Exome Sequencing

Objective To investigate the relationship between the phenotypes and the patterns of genetic mutations in the corresponding resistance genes (rpoB, katG, inhA, ahpC, rrs, rpsL, embB and gyrA) in resistant Mycobacterium tuberculosis (MTB) isolates. Methods Rifampicin-resistant gene (rpoB), isoniazid-resistant genes (katG, inhA, ahpC), streptomycin-resistant genes (rrs, rpsL), ethambutol-resistant gene (embB) and quinolinone-resistant gene (gyrA) were amplified by PCR with sequence-specific primers, then mutants screened by single-stranded conformation polymorphism (SSCP) were sequenced. Results rpoB mutation with predominant Ser450Trp pattern was 94. 9% (56/59) in 59 rifampicin-resistant isolates;katG mutation rate was 38. 9% (35/90) and the main pattern was Ser315Thr, but only 3 inhA mutants and no ahpC mutation were determined in 90 isoniazid-resistant isolates;gyrA mutation with main Asp94Gly then Ala90Val pattern was 82.4% (28/34) in 34 quinolinone-resistant isolates;the total mutation rate was 77.4% in 31 streptomycin-resistant isolates, of which 15 isolates mutated in rrs with main pattern A514C or A1041G, 10 isolates mutated in rpsL Lys88Arg;and embB mutation with main Met306Val accounted for 19.4% (6/31) in 31 ethambutol-resistant isolates. Conclusions The results showed that resistance of resistant MTB may be complicated, and DNA sequencing-based mutation analysis could efficiently detect the molecular makers such as rpoB, katG, gyrA, rrs, rpsL and embB in resistant MTB isolates. Meanwhile, it is notable that the rpoB mutation pattern in our isolates is different from previous report, further effort are needed to confirm the characteristics. The spectrum of potential resistance-related mutations in MTB clinical isolates may lay substantial foundation for the rapid molecular diagnosis and rational use of drug to MTB patients.

Objective:To explore the effects of BCR-ABL downstream pathway inhibitors, such as RAF inhibitor SB590885, JAK inhibitor AZD1480, PI3K-mTOR double target inhibitor BEZ235 on chronic myelogenous leukemia (CML) cells, and the effect of BEZ235 on the proliferation, apoptosis of CML cells and the sensitivity of imatinib in vitro.Methods:K562 cells were treated with different concentrations of the drugs. MTS method was applied to detect the proliferation inhibition rate of K562 cells, and 50% inhibitory concentration (IC 50) of all drugs for 48 h was calculated. The cell apoptosis rate was tested by using flow cytometry with Annexin V-FITC/PI double staining. The cell cycle was tested by using flow cytometry with PI staining. K562 cells, imatinib-resistant and T315I-mutant human CML KBM7R cells and imatinib-resistant CML primary cells of patients were treated with different concentrations of the drugs. MTS method was used to test the proliferation inhibition of cells, and IC 50 of all drugs for 48 h was evaluated. KBM7R cells or primary cells of CML patients were treated with 1.0 μmol/L BEZ235, 1.0 μmol/L imatinib or the combination of both, respectively. Flow cytometry with PI staining was used to detect the cell cycle of KBM7R cells. Flow cytometry with Annexin V-FITC/PI double staining was used to detect the cell apoptosis rate in CML primary cells. The expressions of p-AKT, cleaved Caspase-3 and Cyclin D1 proteins were detected by using Western blot. Results:SB590885, AZD1480 and BEZ235 could inhibit the proliferation of K562 cells, and the IC 50 after the treatment of K562 cells for 48 h was (11.49±3.14), (4.83±1.26) and (0.37±0.21) μmol/L, respectively. SB590885, AZD1480 and BEZ235 could promote the apoptosis of K562 cells. The cell apoptosis rates were increased compared with the control group without drug treatment (all P < 0.01). SB590885 and BEZ235 induced G 0/G 1 block (both P < 0.05). AZD1480 induced G 2/M block ( P < 0.05). BEZ235 could inhibit the proliferation of K562 cells, KBM7R cells and CML primary cells, and their IC 50 for 48 h was (0.37±0.21), (0.43±0.27) and (0.49±0.24) μmol/L, respectively. Compared with imatinib alone, the different concentrations of imatinib combined with 0.2 μmol/L BEZ235 could increase the proliferation inhibition of K562 cells, KBM7R cells and CML primary cells, and could reduce the IC 50 of imatinib. After the treatment of imatinib alone and combination with BEZ235 for 48 h, the imatinib IC 50 of K562 cells was (0.14±0.05) and (0.09± 0.04) μmol/L ( t = 1.531, P = 0.249), the imatinib IC 50 of KBM7R cells was (3.93±2.29) and (0.44±0.22) μmol/L ( t = 2.837, P = 0.047), the imatinib IC 50 of the primary cells was (3.12±1.53) and (0.39±0.23) μmol/L ( t = 3.925, P = 0.042). The cell apoptotic rate of the primary cells was (4.9±1.4)%, (13.1±3.2)%, (8.8±2.0)% and (40.6±6.0)%, respectively in the control group without drug treatment, 1.0 μmol/L BEZ235, 1.0 μmol/L imatinib and the combination of 1.0 μmol/L BEZ235 and 1.0 μmol/L imatinib after the treatment of 24 h ( F = 71.031, P < 0.01). Compared with imatinib alone, the expressions of p-AKT and Cyclin D1 proteins were decreased, and the expression of cleaved Caspase-3 protein was increased after the treatment of KBM7R cells for 12 h in the combination group of both BEZ235 and imatinib. Conclusions:BCR-ABL downstream pathway inhibitors can effectively inhibit the proliferation and promote the apoptosis of K562 cells. BEZ235 can inhibit the proliferation and promote the apoptosis of K562 cells, imatinib-resistant and T315I-mutant human KBM7R cells and imatinib-resistant CML primary cells of patients, which has a synergistic effect to imatinib.

Objective:To analyze variant patterns and characteristics of focal physiological uptake (FPU) in the tongue on 18F-fluorodeoxyglucose (FDG) PET/CT imaging in patients without a history of oral tumor surgery and radiotherapy. Methods:A total of 6 233 consecutive patients who underwent routine whole-body PET/CT scan between January 2013 and December 2017 in the First Hospital of Shanxi Medical University were investigated retrospectively, and 324 patients with a history of oral surgery and radiotherapy were excluded, the remaining 5 909 patients (3 418 males, 2 491 females, age range: 2-95 (average: 58) years) were enrolled. A part of the patients underwent local PET/CT scan and CT scan with diagnostic dose, covering the oral cavity on mouth-opening position. The morphological characteristics of FPU patterns were analyzed, and the maximum standardized uptake value (SUV max) was measured. Results:Seventy-six FPUs in 76 patients (49 males, 27 females, age range: 40-83 (average 64) years) identified by routine whole-body PET/CT scan were confirmed by clinical examination from a specialist in stomatology or follow-up for more than 6 months. Forty-one of the 76 patients subsequently underwent local PET/CT scan and diagnostic CT scan on mouth-opening position. The incidence of FPU in the tongue was 1.29%(76/5 909). The FPU patterns could be classified into three types: type Ⅰ with FDG uptake involved only anterior part of the tongue body in the midline (near the tip of the tongue), which showed as a " dotted" shape( n=68; 1.15%, 68/5 909); type Ⅱ with FDG uptake involved mainly middle part of the genioglossus muscle, which showed as a " bar-shorted" shape ( n=5; 0.08%, 5/5 909); type Ⅲ with FDG uptake involved large part of the tongue body and the genioglossus, which showed as a " T" shape( n=3; 0.05%, 3/5 909). The SUV max in patients with type Ⅰ and type Ⅱ were 5.53(4.53, 7.30), 19.50(17.10, 22.74) respectively. The SUV max in 3 patients with type Ⅲ were 23.34, 27.50 and 35.14, respectively. Conclusion:In patients without a history of oral tumor surgery and radiotherapy, the FPU in the tongue has its specific pattern, and PET/CT scan on mouth-opening position helps to reveal the detailed features.