Objective:To investigate the prognostic significance of D-dimer level in patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 70 newly diagnosed DLBCL patients who were admitted to Tianjin People's Hospital from January 2015 to June 2019 were retrospectively analyzed. The optimal cut-off value of D-dimer for survival was determined according to the receiver operating characteristic (ROC) curve, and the patients were grouped. The differences of coagulation related indexes and clinicopathological features between patients with different D-dimer levels were compared. Kaplan-Meier method was used for univariate analysis of overall survival (OS), and Cox regression model was used for multivariate analysis of OS.Results:According to ROC curve, the best cut-off value of D-dimer for survival was 0.75 mg/L. The proportion of patients with different clinical staging, international prognostic index score, lactate dehydrogenase level had statistically significant differences between the D-dimer ≥0.75 mg/L group (36 cases) and <0.75 mg/L group (34 cases) (all P < 0.05). The prothrombin time of D-dimer ≥ 0.75 mg/L group and < 0.75 mg/L group were (13.5±0.9) s and (13.0±0.8) s, respectively, and the activated partial thromboplastin time were (37±5) s and (34±6) s, respectively,and the differences were statistically significant (all P < 0.05). Univariate analysis showed that the 5-year OS rates of DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ, international prognostic index score > 2, lactate dehydrogenase level > 240 U/L, B symptoms, D-dimer level ≥0.75 mg/L were decreased (all P < 0.05). Multivariate Cox regression analysis showed that D-dimer ≥0.75 mg/L was an independent risk factor for OS of DLBCL patients ( HR=0.368, 95% CI 0.144-0.944, P= 0.038). Conclusion:The level of D-dimer can be used as a clinical indicator to judge the prognosis of DLBCL patients, and the prognosis of patients with high D-dimer level is poor.

Objective:To explore the key genes and its biological functions of aldosterone producing adenoma (APA) using bioinformatics analysis.Methods:Differentially expressed genes of APA were identified from two training datasets GSE60042 and GSE64957 in GEO database. Function and pathway enrichment analyses for differentially expressed genes were performed and transcriptional regulation network among these genes were determined. Hub genes were extracted by node analysis from the protein-protein interaction (PPI) network. The expression of key genes was verified by a testing dataset GSE8514. Receiver operating characteristic(ROC) curve analysis was applied to assess the diagnostic efficiency of key genes in APA. The biofunction of each key gene were determined by gene set enrichment analysis (GSEA).Results:A total of 68 differentially expressed genes, including 33 up-regulated genes and 35 down-regulated genes, were detected from the training datasets. These genes were mainly enriched in aldosterone biosynthetic process, calcium signaling pathway, serotonin receptor signaling pathway, transcriptional activator activity, and regulation of transcription. JUN and VDR were at the center of the transcriptional factor-gene network. Furthermore, we identified nine Hub genes from the PPI network. In testing dataset, CYP11B2 and VDR showed the higher expression, while JUN, NFKBIZ, EGR3, and KLF6 showed lower expression in APA (all P<0.05), and the value of area under ROC curve analysis was 0.936, 0.833, 0.953, 0.854, 0.868, and 0.929, respectively. GSEA indicated the alter of key genes in APA led to up-regulation of the steroid biosynthesis, cell adhesion molecules, immune cells signaling pathway, and complement and coagulation cascades [all normalized enrichment score (NES)>1.5, P<0.05], but down-regulation of the DNA replication, ribosome, and autophagy (all NES<-1.5, P<0.05). Conclusion:Results of bioinformatics indicate that JUN and VDR are key transcriptional factors, and CYP11B2, NFKBIZ, EGR3, and KLF6 are the key genes for APA, which are involved in the steroid biosynthesis, cell adhesion molecules, immune cells signaling pathway in APA.

Objective:To construct an out-of-hospital health management content system for children with type 1 diabetes (T1DM) to provide a basis for clinical nursing staff to carry out targeted health education and evaluation.Methods:A research group was established in April 2019. Guided by mobile health, the first draft of out-of-hospital health management system for children with T1DM was constructed through literature review, semi-structured interviews and expert meetings. A total of 20 experts were selected from pediatric wards of 11 Class Ⅲ Grade A children's specialties or general hospitals in Beijing, Shanghai, Henan Province, Zhejiang Province and other provinces, and the Delphi method was applied for 2 rounds of consultation. The out-of-hospital health management content system for T1DM children based on mobile health was constructed and revised to form the final draft.Results:After 2 rounds of expert consultation, the opinions of 20 experts reached consensus. The recovery rates of the 2 rounds of expert consultation questionnaire were both 100.0%, the expert familiarity was 0.96, the expert judgment basis was 0.98 and the authority coefficient was 0.97. Finally, out-of-hospital health management content system for T1DM children consisted of 6 first-level indicators, 14 second-level indicators and 69 third-level indicators.Conclusions:The out-of-hospital health management content system for T1DM children in this study is scientific and comprehensive, which can provide theoretical references and unified standards for clinical nurses to conduct out-of-hospital health management and evaluation effect based on mobile health.

In Korea and China, ilaprazole is a widely used proton pump inhibitor in the treatment of gastric ulcers. In this study, a specific and sensitive LC-MS/MS method has been developed and validated for the quantification of ilaprazole enantiomers in the rat plasma, using R-lansoprazole as the internal standard. The enantioseparation was achieved on a CHIRALPAK AS-RH column (4.6 mm × 150 mm, i.d. 5μm), with a mobile phase composed of 10 mM ammonium acetate aqueous solution and acetonitrile (60:40, V/V), at a flow-rate of 0.5 mL/min. The method was validated over the concentration range of 0.5-300 ng/mL for both, R- and S -ilaprazole. The lower limit of quantification was 0.5 ng/mL for both enantiomers. The relative standard deviation (RSD) of intra- and inter-day precision of R-ilaprazole and S-ilaprazole was less than 10.9％, and the relative error accuracy (RE) ranged from -0.5％-2.0％. Finally, the method was successfully evaluated in rats in a stereoselective pharmacokinetic study of the ilaprazole racemate.

Objective: To understand the mechanism of chemotherapy resistance in nasopharyngeal carcinoma under hypoxic conditions through the perspective of protein SUMOylation modification. Methods: Cobalt chloride (CoCl₂) was used to establish the hypoxic model of human nasopharyngeal carcinoma CNE1 cells. Then, the cell cycle was detected by flow cytometry, and the expression level of small ubiquitin-related modifier(SUMO) and cyclin-dependent kinase 6 (CDK6) proteins were detected by western blotting. MTT assay was used to determine the median lethal dose (IC₅₀) of cancer cells against cisplatin, and enzyme-linked immunosorbent assay (ELISA) was used to determine lactate dehydrogenase (LDH) level. Results: The cell cycle of CNE1 induced by hypoxia was arrested in G0/G1 phase.The results of Western blot showed that the protein expression level of CDK6 in CNE1 cells was lower than that in the control group (0.83±0.25 vs. 0.43±0.21, t=14.67, P=0.003). The protein level of conjugated SUMO1 was significantly lower than that in the control group (2.69±0.48 vs. 1.38±0.31, t=17.22, P=0.001), while the level of free SUMO1 protein was significantly higher than that in the control group (2.01±0.43 vs. 2.60±0.59, t=15.45, P=0.002).The LC50 of CNE1 cells in the control group was significantly lower than that in the hypoxic group (29.44 μg/ml vs. 97.72 μg/ml, t=12.79, P=0.001). After CNE1 cells received 50 μg/ml cisplatin for 48 h, the LDH content in the supernatant of the control group was significantly higher than that in the hypoxic group ((541.49±64.59) ng/ml vs. (234.67±41.03) ng/ml, t=11.94, P=0.007)). The apoptosis rate of CNE1 cells in the control group was significantly higher than that in the hypoxic group ((76.64±5.37)% vs. (32.84±4.77) ng/ml, t=8.49, P=0.003)). Conclusion Hypoxia can dissociate the covalent modification of CDK6 and SUMO1, inhibit cell cycle and increase the chemotherapy resistance of nasopharyngeal carcinoma.

Objective: To investigate the prognostic value of prognostic nutritional index (PNI) in patients with diffuse large B-cell lym-phoma (DLBCL). Methods: We retrospectively reviewed the medical records of 82 patients with DLBCL treated at Tianjin Union Medi-cal Center between June 2010 and June 2016. The optimal cutoff value of PNI was determined using a receiver operating characteristic (ROC) curve and the Youden index. The relationship of high and low PNI with the clinical characteristics of the patients, therapeutic ef-ficacy, and prognosis were analyzed. Results: Overall, mean PNI of the patients was 46.17±8.8. When the PNI was 44.15, the Youden in-dex was found to be maximal, with a sensitivity of 74.6% and specificity of 67.2%. There were 38 patients (46.3%) in the low PNI group (<44.15) and 44 patients (53.7%) in the high PNI group (≥44.15). Data analysis showed that PNI was correlated with Eastern Coopera-tive Oncology Group performance status (ECOG PS), Ann Arbor stage, international prognostic index (IPI) score, and lactic acid dehydro-genase (LDH) level (P<0.05). The total effective rate of the low PNI group was significantly lower than that of the high PNI group (65.8% vs. 86.4%; χ2=4.848; P=0.028). The 3-year overall survival (OS) rate of the entire group of patients was 69.1%. The 1-, 2-, and 3-year OS rates of the low PNI group (86.8%, 67.8%, and 56.9%, respectively) were significantly lower than that of the high PNI group (96.7%, 89.5%, and 80.2%, respectively; χ2=9.421, P=0.002). Univariate analysis showed that PNI<44.15, ECOG PS≥2, IPI>2, stageⅢ/Ⅳ, and lymphocyte count<1.0×109/L had a significant impact on predicting OS (P<0.05). Multivariate analysis showed that PNI<44.15 (P=0.006) and stageⅢ/Ⅳ(P=0.011) were independent factors for predicting OS. Conclusions: PNI might be used as a simple and feasible clinical prognostic indicator in patients with DLBCL.

OBJECTIVETo explore the genetic cause of a female patient with severe mental retardation and a history of adverse pregnancy.

METHODSThe patient was subjected to G-banded chromosome analysis and single nucleotide polymorphism array (SNP-array) assaying. The correlation between genomic variations and the phenotype was explored.

RESULTSThe patient was found to have a complex chromosome rearrangement involving 5 chromosomes. The karyotypes of her parents were both normal. SNP-array assay has identified a 1.6 Mb microdeletion at chromosome 15q21.3 which involved 15 RefSeq genes and a 0.5 Mb microdeletion at 5q21.1 which involved one RefSeq gene.

CONCLUSIONThe microdeletions, which involved TCF12, ADMA10 and AQP9 genes, probably underlie the mental retardation shown by the patient.

Adult ; Chromosome Banding ; methods ; Chromosome Deletion ; Chromosomes ; genetics ; Female ; Genetic Testing ; methods ; Humans ; Intellectual Disability ; genetics ; Karyotype

OBJECTIVETo explore the genetic cause for a child with developmental delay.

METHODSThe karotypes of the child and her parents were analyzed with G-banding analysis. Their genome DNA was analyzed with low-coverage massively parallel copy number variation sequencing (CNV-seq) and verified by single nucleotide polymorphism array (SNP-array).

RESULTSThe karyotype of the child was ascertained as 46,XX,r(15)(p13q26.3), while both parents showed a normal karyotype. CNV-seq and SNP-array have identified a de novo 15q26.2-q26.3 deletion in the child with a size of approximately 3.60 Mb.

CONCLUSIONThe abnormal phenotype of the patient carrying the ring chromosome 15 may be attributed to the presence of the 15q26.2-q26.3 microdeletion. The deletion and haploinsufficiency of the IGF1R gene probably underlie the main clinical features of the patient.

Child, Preschool ; Chromosome Banding ; Chromosomes, Human, Pair 15 ; genetics ; DNA Copy Number Variations ; Female ; Humans ; Karyotyping ; Mosaicism ; Ring Chromosomes ; Sequence Deletion

Background:Recent studies have shown that long non-coding RNAs(lncRNAs)play important roles in carcinogenesis and cancer biology and the related context has attracted more and more attentions. PVT1,which encodes a lncRNA,is reported to be up-regulated and exhibit pro-oncogenic activity in a wide variety of human cancers. Aims:To investigate the expression of PVT1 in human pancreatic cancer cells and its effect on proliferation and apoptosis of HPAF-Ⅱ cells. Methods:One target siRNA against PVT1 was synthesized and transfected into HPAF-Ⅱ cells by using lipofactamine technique. PVT1 mRNA expression was detected by real-time PCR;capability of cell proliferation was examined by MTS and colony formation assays;cell cycle progression and apoptosis were measured by flow cytometry;and Western blotting was performed to determine the expressions of apoptosis-related proteins and proto-oncogene protein c-Myc. Results:The mRNA expression of PVT1 in several human pancreatic cancer cell lines,especially HPAF-Ⅱ cells was significantly higher than that in H6c7,a human immortalization normal pancreatic ductal epithelial cell line. Compared with HPAF-Ⅱ cells transfected with negative control siRNA or without transfection,silencing of PVT1 by siRNA-PVT1 resulted in remarkable reduction in cell proliferation,cell cycle G1 phase arrest,and notable apoptosis;meanwhile,the expressions of apoptosis-related proteins(cleaved-caspase-3 and cleaved-PARP)were up-regulated,the ratio for Bcl-2 / Bax was decreased,and the expression of c-Myc protein was down-regulated. Conclusions:LncRNA-PVT1 is highly expressed in human pancreatic cancer cell line HPAF-Ⅱ. It may affect the proliferation and apoptosis of HPAF-Ⅱ cells partially through regulating c-Myc expression.

Objective To evaluate the effect of HIV infection and highly active antiretroviral therapy (HAART) on mitochondrial function and mass in peripheral monocytes.Methods There were 14 ART-naive HIV-infected patients,14 NRTI treated HIV-infected patients and 12 healthy controls from Beijing Ditan Hospital.The mitochondrial membrane potential and mitochondrial mass in monocytes were analyzed by flow cytometry.Mitochondrial disturbances related to HIV infection and HAART in monocytes were analyzed.Results In ART-naive patients and NRTI-exposed patients,the levels of mitochondrial membrane potential in monocytes (77.74 ± 14.77,73.94 ± 12.87) were significantly lower than these in healthy controls (89.43 ±4.06) (P =0.032 8,P =0.002 6).The amount of mitochondrial mass in NRTI-exposed patients (3 329.0 ± 836.7) was significantly higher than that in healthy controls (2 075.0 ± 932.2) and that in ART-naive patients (2 592.0 ± 781.5) (P ＜ 0.05).Conclusions The abnormal of mitochondrial membrane potential and mitochondrial mass in monocytes from HIV-infected patients were related to HIV infection and the introduction of HAART.