Child, Preschool ; Humans ; Hypercalcemia ; etiology ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; complications

Anoikis is a form of apoptosis induced upon cell detachment from extracellular matrix.It has been determined that acquisition of resistance to anoikis is a critical step for tumor cell metastasis.MiR-21,the most prominent oncomiR,plays an important role in tumor progression.In this study,we revealed that up-regulation of miR-21 in human esophageal adenocarcinoma (EA) is associated with lymph node metastasis and poor survival rate.Because of the established anti-apoptosis effect of miR-21,it is tempting to speculate that miR-21 might contribute to tumor metastasis by regulating anoikis,qRT-PCR analysis demonstrated that miR-21 expression in OE33/AR cells (subpopulation of human EA OE33 cells that acquired resistance to anoikis) was significantly increased.Also,transfection of miR-21 mimics provided OE33 cells resisting to anoikis.By luciferase assays,we verified that PDCD4 and PTEN were the functional targets of miR-21.In mouse model,via tail vein injection experiment,we showed that the metastasis formation of OE33 cells in vivo could be mediated by changing the miR-21 expression pattern.Taken together,our findings suggested that miR-21 was involved in the regulation of anoikis in human EA cells.Targeting miR-21 may provide a novel strategy to prevent metastasis.

Child, Preschool ; Coronary Aneurysm ; etiology ; pathology ; Coronary Vessels ; pathology ; Female ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; complications ; pathology

OBJECTIV: e To find the correlation between real best corrected visual acuity (BCVA) and testing results of microperimetry and visual evoked potential (VEP) and to explore a new method in recording BCVA in macular disease. METHODS: Sixty-two patients with macular disease (macular disease group, 62 eyes) and eighteen healthy volunteers (control group, 36 eyes) had BCVA, microperimetry and VEP recorded. RESULTS: (1) By microperimetry, the values of retinal mean sensitivity and fixation percentage in macular disease group were lower than that in control group. The bicurve ellipse area in macular disease group was higher than that in control group. By VEP, P100 amplitude under 0.5 cpd and 2 cpd in macular disease group were significantly higher than that in control group and the latency was prolonged (P < 0.05). (2) In macular disease group, BCVA had significant positive correlation with retinal mean sensitivity, bicurve ellipse area, macular central 2 degrees and 4 degrees fixation percentage, respectively (P < 0.05). There was a significant correlation between retinal mean sensitivity and P100 amplitude (P < 0.05). (3) Multiple linear regression equation was y = 0.053 x1+0.008 x3+3.897 (y was BCVA, while x1 was retinal mean sensitivity and x3 was P100 amplitude under 2 cpd). CONCLUSION Combined use of microperimetry and VEP is useful in the assessment of BCVA in macular disease.
Case-Control Studies ; Evoked Potentials, Visual/physiology* ; Eye ; Humans ; Macula Lutea/physiopathology* ; Retina ; Retinal Diseases/pathology* ; Tomography, Optical Coherence ; Visual Acuity/physiology* ; Visual Field Tests/methods*

OBJECTIVETo observe the effect of Kanli Granule (KG) on myocardial mechanics in pressure overload induced diastolic heart failure (DHF) rats.

METHODSTotally 60 male Wistar rats were divided into the sham-operation group, the model group, the KG group, and the Valsartan group according to random digit table, 15 in each group. The pressure overload induced DHF model was established in all groups except the sham-operation group using abdominal aortic constriction surgery. Totally 7 rats died after modeling (with the mortality of 10. 67%) , and the rest 53 finished the following test. Rats in the KG group were administered with KG extract (calculated as 6. 75 g crude drug/kg) by gastrogavage. Rats in the Valsartan group were administered with Valsartan (7.2 µg/g) by gastrogavage. Equal volume of double distilled water was administered to rats in the model group and the sham-operation group by gastrogavage. All rats were intervened for 32 weeks. The response of isolated heart papillary muscle tonus to isoprenaline (ISO) and adenylate cyclase (Forskolin) was respectively observed. The enhancement phenomenon after resting development force (DF) of isolated heart papillary muscle tonus, and changes of DF in different Ca²⁺ concentrations were observed.

RESULTS(1) In the ISO response test: Compared with the sham-operation group, the amplifications of DF, ±df/dt, -df/dt were obviously elevated in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously lowered in the KG group (P < 0.01), and the amplification of ±df/dt was also reduced in the Valsartan group (P < 0.01). (2) In the Forskolin response test: Compared with the sham-operation group, the amplifications of DF and ±df/dt obviously increased in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously reduced in the KG group (P < 0.01), and the amplification of DF was also reduced in the Valsartan group (P < 0.05). (3) In post-resting DF enhancement test: Compared with the sham-operation group, the amplification of DF showed gradually decreasing tendency along with prolonged resting time in the model group, and they were obviously lowered at all time points (P < 0.05). Compared with the model group, the amplification of DF was gradually increasing along with prolonged resting time in the KG group. The amplification of DF at post-resting 240 s was obviously larger in the KG group than in the model group (P < 0.05). The amplification of post-resting DF still showed gradually decreasing tendency along with prolonged resting time in the Valsartan group, with increased amplifications of DF at post-resting 60 s and 120 s (P < 0. 05) (4) The amplifications of DF in different Ca²⁺ concentrations: Compared with the sham-operation group, the amplifications of DF were significantly elevated in different Ca²⁺ concentrations (1.75, 3.5, 7.0 mmol/L ) (P < 0.05, P < 0.01). Compared with the model group, there was no statistical difference in amplification of DF in different Ca²⁺ concentrations in the KG group (P > 0.05). The amplifications of DF in different Ca²⁺ concentrations were significantly reduced in the Valsartan group (P < 0.05).

CONCLUSIONSThe ISO response and the Forskolin response were enhanced in isolated heart papillary muscle tonus of pressure overload induced DHF rats; enhanced post-resting DF was reduced; DF in different supra-physiologic levels of Ca²⁺ was still enhanced. KG could significantly improve excessive enhancement of pressure overload induced DHF rats in ISO response and Forskolin response, and improve enhancement of post-resting myocardium.

Animals ; Colforsin ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Heart ; drug effects ; physiopathology ; Heart Failure, Diastolic ; drug therapy ; Isoproterenol ; pharmacology ; Male ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVETo investigate the origin of childhood B-cell acute lymphoblastic leukemia (B-ALL) and its epitopes recognized by cytotoxic T lymphocytes (CTL) in immunoglobulin heavy chain variable region (IgHV).

METHODSSeven IgHV gene families were respectively amplified by PCR and directly sequenced in 108 childhood ALL. The amino acid sequences were deducted from sequenced nucleotides. Bioinformatics was applied to analyses of recombination patterns, somatic mutations and germline gene segments usage, and to prediction of epitopes recognized by CTL.

RESULTSIgHV gene rearrangements were identified in 66% of the cases, including 37 (52.1%) monoallelic rearrangements, 26 (36.6%) biallelic rearrangements and 8 (11.3%) oligoclonal rearrangements. Among the obtained 40 B-ALL IgHV gene sequences, 8 (20.0%) were in frame rearrangements without stop codons. V(H3) (11/40), V(H4) (11/40) and V(H1) (8/40) amounted to 75% rearranged V(H) families. V(H)(4-59) and V(H)(4-34) were the most frequently rearranged V(H)(4) family gene segments. Usage of D2 and D3 families was most prominent (35.9% and 28.2%, respectively). Increased frequency of D7-27 (15.4%) was found as compared to that of normal peripheral B lymphocytes (P = 0.02). J(H)(6) was found in 47.5% rearrangements followed by J(H)(4) (27.5%). 8/40 (20.0%) DJ(H) junctions lacked N nucleotides, which was higher than that reported for normal peripheral B lymphocytes (P = 0.02). 17.5% B-ALL IgHV contained scattered replacement mutations with replacement (R) to silent (S) substitution ratio (R/S ratio)

CONCLUSIONB-ALL originated from progenitor or precursor B lymphocytes. B-ALL IgHV genes are of germline characteristics. Potential T cell epitopes were derived from framework regions 1 and 3 of immunoglobulin heavy chain in B-ALL.

Adolescent ; Child ; Child, Preschool ; Female ; Gene Rearrangement ; Genes, Immunoglobulin ; HLA-A Antigens ; genetics ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Immunoglobulin Variable Region ; genetics ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; immunology

OBJECTIVETo induce anti-B-cell acute lymphoblastic leukemia (B-ALL) cytotoxic T lymphocyte response against immunoglobulin heavy chain frame-derived nonapeptide.

METHODSThe peptide, QLVQSGAEV, containing IgHV1 frame region 3rd-11th amino acids (IgHV1(3-11)), was synthesized. IgHV1(3-11)-T2 binding tests were performed. HLA-A * 0201-positive normal peripheral blood mononuclear cells (PBMNC) were stimulated by IgHV1(3-11)-loaded antigen presenting cells three times at weekly intervals. HLA-A * 0201/IgHV1(3-11) tetramers were used to detect the proliferation of IgHV1(3-11)-specific CD8(+) T cells in the culture. Seven IgHV gene families of B-ALL patients were respectively amplified by PCR and the PCR products were sequenced to select IgHV1 and IgHV3 family monoallelic functional rearrangements. Among them, HLA-A * 0201 positive individuals were subsequently identified. Cytotoxicity of IgHV1(3-11)-specific CD8(+) T cells against HLA-A * 0201-positive IgHV1/IgHV3 family B-ALL cells was measured by MTT assay.

RESULTSThe synthesized IgHV1(3-11) up-regulated HLA-A * 0201 expression on T2 cell surface by 1.63-folds. The percentage of IgHV1(3-11)-specific CD8(+) T cells in HLA-A * 0201-positive normal PBMNC was increased from 1.64% after second stimulation to 82.57% after third stimulation. At effector: target ratio of 20:1, the killing rate of IgHV1(3-11)-specific CD8(+) T cells against IgHV1 family B-ALL cells was 18.24%, being 1.8-folds as that against IgHV3 family B-ALL cells (P = 0.01).

CONCLUSIONCytolytic T lymphocytes generated in vitro against immunoglobulin heavy chain frame-derived nonapeptides can kill B-ALL cells expressing these peptides.

Cells, Cultured ; Humans ; Immunoglobulin Heavy Chains ; immunology ; pharmacology ; Leukemia, B-Cell ; immunology ; pathology ; T-Lymphocytes, Cytotoxic ; drug effects ; immunology

Objective To investigate the distribution of surfactant protein-C( SP-C) gene single nu-cleotide polymorphisms and to study the association between the SP-C gene polymorphisms and neonatal respiratory distress syndrome( NRDS) in infants. Methods Fifty-one infants with NRDS( NRDS group) and 51 infants without RDS( control group) were selected. PCR gene analysis and polymerase chain reaction were used to establish the genotype and allele frequencies of SP-C exon 4(T138N) and exon 5(S186N),SP-C exon 4 and 5 for the mutation,and then the association between the polymorphisms and NRDS was analyzed. Results SP-C gene mutations were not found in exon 4 and 5. In the Mongol nationality of the Inner Mon-golia region,SP-C exon 4(T138N) genotypes could check out three genotypes:namely AA,AC and CC. The frequencies of allele A and allele C of SP-C exon 4(T138N) were not statistically different between NRDS group and control group(χ2 =0. 454,P=0. 797). In the Mongol nationality,SP-C exon 5(S186N) genotypes could check out three genotypes:namely AA,AG and GG. The frequencies of allele A and allele G of SP-C exon 5(S186N) were not statistically different between NRDS group and control group(χ2 =0. 493,P =0. 782). Conclusion SP-C exon 4(T138N) and exon 5(S186N) gene polymorphism in Inner Mongolia newborns displays no significant correlation with sex,birth weight or gestational age. SP-C gene mutations are not found in exon 4 and 5. SP-C gene exon 4(T138N) and exon 5(S186N) polymorphisms are not found to be associated with NRDS in Mongol nationality of the Inner Mongolia.

Technological improvement for microorgnism isolation is important since isolation provides substantial materials for the exploitation of new microbial resources. In this study, a new approach, dispersion and differential cetrifugation (DDC), was applied in the isolation of acidophilic and acidoduric streptomycetes from 12 acid soil samples. Contrast with traditional method, the new approach yielded satisfying results with 2 - 20 times isolation efficiency and good selectivity. 45 representatives out of 249 streptomycetes isolates, which belonged to 12 color groups, showed morphology and cell wall type consistent with streptomycetes. The optimum pH range for their growth were between pH 4.5 - 5.5. It is proved that we succeeded in the rare-streptomycetes isolation using DDC approach.

Abstract: Objective　To understand the distribution and drug resistance of common pathogens of fungal bloodstream infection in Sichuan, and to provide reference for clinicians to empirically treat fungal bloodstream infection. Methods　From November 1, 2019 to December 31, 2020, fungal strains isolated from blood culture of patients diagnosed with bloodstream infection in 19 tertiary first-class general hospitals in Sichuan Province were collected for mass spectrometry identification and drug susceptibility, and the results were statistically analyzed, along with a retrospective analysis of clinical data. Results　A total of 255 fungal strains were received and identified by mass spectrometry, 215 strains of Candida spp (84.3%), 28 strains of Cryptococcus neoformans (11.0%), 4 strains of Talaromyces marneffei (1.6%) and 8 strains of others (3.1%). Among the Candida spp 90 strains of Candida albicans, 39 strains of Candida parapsilosis complex, 36 strains of Candida glabrata, 33 strains of Candida tropicalis, 8 strains of Candida guilliermondii, and 9 strains of other Candida. In the department, the ICU was predominant, accounting for 35.7%. The top four Candida (Candida albicans, Candida parapsilosis complex, Candida glabrata, Candida tropicalis) were analyzed for drug sensitivity, Candida albicans and Candida parapsilosis complex group were more sensitive to antifungal drugs, the sensitivity rates of Candida albicans to fluconazole, voriconazole, anidulafungin, caspofungin, micarafungin were 89.2%, 92.8%, 97.6%, 97.6%, 96.4%, respectively. The sensitivity rates of Candida parapsilosis to fluconazole and voriconazole were 89.7% and 94.9%, and to anidulafungin, caspofungin and micafungin were all 100%. Echinocandins had stronger antibacterial activity against Candida spp., Candida parapsilosis complex and Candida tropicalis had 100% sensitivity to echinocandins, Candida albicans had more than 95% sensitivity to echinocandins, and Candida glabrata had about 90% sensitivity to echinocandins. Candida tropicalis was less sensitive to fluconazole and voriconazole with 66.7% and 54.5%, and the sensitivity of Candida glabrata to fluconazole was mainly concentrated in susceptible dose dependent (SDD), accounting for 91.4%. The four Candida species did not show resistance to amphotericin B, all of them showed wild-type strains, Candida tropicalis showed the highest non-wild-type rate to posaconazole and itraconazole with 21.2% and 36.4%, and the drug sensitivity results of Cryptococcus neoformans showed that 4 out of 23 strains showed resistance to amphotericin B (non-wild-type) and 3 strains showed resistance to fluconazole (non-wild-type). Conclusions　The fungus of bloodstream infection is mainly Candida spp.. Among of them, Candida albicans accounts for the highest percentage, echinocandins have good antibacterial effect on Candida, Candida is sensitive to amphotericin B as wild type, but Candida tropicalis has slightly higher resistance rate to fluconazole and voriconazole, and the non-wild type rate of Cryptococcus neoformans to amphotericin B is increasing, and clinicians should pay high attention to the rational use of antifungal drugs.