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Chronic obstructive pulmonary disease （COPD） is characterized by long treatment course and poor prognosis. The pathogenesis has not been fully elucidated but is mostly related to the non-specific inflammation of the airway and surrounding tissues. T helper 1 （Th1） and T helper 2 （Th2） are generated by CD4+ T cell differentiation， and are in a dynamic equilibrium when the body is in normal state. The balance between pro-inflammatory cytokines and anti-inflammatory cytokines regulated by Th1/Th2 is vital for maintaining the immune homeostasis in respiratory tract. Chronic inflammatory state changes the level of inflammatory cells in the body， and there is immune disorder in T lymphocytes in the onset stage of COPD. Th1 cells are predominantly expressed in the stable stage of COPD， while Th2 cells are predominantly expressed in the acute exacerbations of COPD （AECOPD）. Th1/Th2 immune imbalance aggravates the inflammatory reaction， and thus restoring the immune balance between them and inhibiting the inflammatory reaction are critical for the treatment of COPD. At present， there has been no satisfactory treatment plan for COPD. Chinese medicine has a long history of preventing and treating COPD， with remarkable curative effect and few adverse reactions. A large number of animal experiments and clinical studies on Chinese medicine intervention of Th1/Th2 immune balance in COPD have indicated that Th1/Th2 immune balance is an important potential target for treating COPD by Chinese medicine， which can correct chronic inflammatory state by regulating the immune disorder of the body. It has also been found that Th1/Th2 balance plays an important immunoregulatory role in inflammatory response， but little is known about its specific mechanism in the pathogenesis of COPD. On this basis， this paper summarized and analyzed the biological characteristics of Th1/Th2 and their mechanism in the pathogenesis of COPD， as well as the intervention effect of single Chinese medicine or its effective components and Chinese medicine compound on Th1/Th2 immune balance in COPD. It further explored the pathogenesis of COPD and the potential therapeutic targets of Chinese medicine in interfering with Th1/Th2 immune balance in COPD， providing reference for further study on prevention and treatment of COPD with Chinese medicine.
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OBJECTIVE@#To explore the characteristics of cytogenetics and molecular genetics in patients with multiple myeloma(MM).@*METHODS@#Fluorescence in situ hybridization(FISH) was used for molecular genetics analysis in 86 cases of newly diagnosed MM, at the same time the chromosome karyotype analysis was performed in 20 cases. Specimen were bone marrow cells.@*RESULTS@#FISH detection showed that 68 cases of MM (79.07%) had at least one type of the molecular genetic abnormalities. The positive rates of IgH rearrangement, 1q21 amplification, D13S319 deletion, RB1 deletion and.P53 deletion were 62.79%, 26.74%, 24.42% ,13.95% and 1.16%, respectively. The positive rate of IgH was significantly higher than that of any other probes(P<0.01). The positive rate of IgH was 79.41% in 68 cases. Out of which the positive rate of IgH single and combined with 1, 2, 3, 4 probes was 59.26%, 24.07%, 11.11%, 5.56% and 0 respectively. The positive rate of IgH only was very signficantly higher than that of combined with any other probes(P<0.01).The positive rate of 1q21 was 33.82% in 68 cases, Out of which the positive rates of 1q21 or combined with 1,2,3,4 probes was 21.74%, 43.48%, 21.74%,13.04% and 0 respectively, the 1q21 probe showed positive as combined with other probes(P<0.01), especially with IgH(P<0.05). The positive rates of D13S319 were 30.88% in 68 cases of patients, out of which the positive rates of D13S319 single or combined with 1, 2, 3, 4 probes was 14.29%, 28.57%, 42.86%, 14.29% and 0 respectively, the D13S319 combined with other probes appeared more significant positive(P<0.01), especially with 1 or 2 probes (P< 0.01). The positive rate of RB1 was 17.65% in 68 cases, the positive rate of RB1 singl or combined with 1, 2, 3, 4 probes were 0, 25%, 50%, 25% and 0, the RB1 appeared positive always combined with other probes, especially with D13S319 probe (P<0.01). The positive rate of P53 was 1.47%, as combined with RB1 and D13S319 probes. The chromosomal karyotyping showed that 3 cases carried abnormal chromosomal and 17 cases carried normal chromosome, Out of which 17 cases showed positive by FISH. There was a significant difference of sensitivity between FISH combined with chromosome karvotyping and single chromosome karvotype (P< 0.01).@*CONCLUSION@#The genetic abnormalies display obvious heterogenicity in MM. The sensitivity of FISH is higher than that of chromosomal karvotyping. If FISH and chromosome karvotyping are combined, the positive rate of abnormality can be raised.
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Humans , Chromosome Aberrations , Chromosomes, Human, Pair 13 , In Situ Hybridization, Fluorescence , Multiple Myeloma , Genetics , Retrospective StudiesABSTRACT
Many studies have confirmed that dysregulation of microRNAs (miRNAs) expression can cause disruption of the hematopoietic system and contribute to leukemogenesis by regulating the expression of some oncogenes and anti-oncogenes. Chronic lymphocytic leukemia (CLL) is a malignant proliferative disease of B lymphocytes with significant heterogeneity in the incidence of individuals, disease progression, treatment response and clinical prognosis. The increasing studies have shown that the mutation or abnormal expression of miRNAs is closely related to CLL occurrence, progression, prognosis and curative efficacy. Certain miRNAs are involved in the intricate interplay with B-cell receptor (BCR) signaling pathway. The review discusses the latest progress of miRNAs expression in BCR signaling pathway and CLL onset and progression.
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Aim To study the protective effect of CDPS on acute aging mouse model induced by D-galactose (D-gal) and its mechanism.Methods (1) The acute aging mouse model was induced by D-gal.After CDPS (25、50、100 mg·kg-1) treatment, the improving effect on learning and memory in mice was examined in vivo.(2) We also established the aging model on PC12 cells in vitro.After CDPS treatment (150、200 mg·L-1), the level of p-CREB in the nucleus was detected by Western blot, and the content of cAMP, PKA and brain derived neurotrophic factor (BDNF) levels were examined by the Elisa kits.Moreover, cAMP, PKA and BDNF were detected in PC12 cells under the condition that H89, the inhibitor of PKA, co-cultured with PC12 cells after CDPS treatment.(3) The UPLC/Q Exactive MS method was developed for determining the concentration of glutamic acid, dopamine and norepinephrine, which secreted in PC12 cells after CDPS treatment.Results (1) In vivo, CDPS significantly improved the memory impairment in aging mice induced by D-gal in the Morris assay.(2) In vitro, CDPS could significantly increase the expression of p-CREB (P<0.05), PKA, cAMP and BDNF (P<0.05).The H-89 abolished the increase of p-CREB (P<0.05), PKA, cAMP and BDNF (P<0.05) in PC12 aging cells induced by D-gal after CDPS treatment.(3) CDPS increased the release of dopamine, norepinephrine, and glutamate secreted in PC12 cells.Conclusion CDPS could significantly improve the learning and memory ability on aging mouse model in vivo, and reversed the damage in PC12 cells induced by D-gal by activating cAMP/PKA/CREB signal cascade, increase the expression of BDNF, and increasing modestly the release of excitatory neurotransmitter.
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OBJECTIVE:To study the improvement effect of lanthanum hydroxide on chronic renal failure (CRF) hyperphos-phatemia in rats. METHODS:CRF hyperphosphatemia rat model were induced and then randomly divided into model group,lan-thanum carbonate group [0.3 g/(kg·d)],calcium carbonate group [4.2 g/(kg·d)] and lanthanum hydroxide high-dose,medium-dose and low-dose groups [1.5,1,0.5 g/(kg·d)] with 10 rats in each group. They were given adenine 0.2 g/(kg·d)intragastrically in the morning,and then given relevant medicine intragastrically in the afternoon;a week later,they stopped taking adenine but con-tinued to take relevant medicine for 22 d. 10 normal rats were selected as normal control group. General examination was conduct-ed,and renal coefficient,serum contents of calcium,phosphorus,PTH,creatinine(Scr)and usea nitrogen(BUN)were detected after last medication as well as renal pathological change. RESULTS:Compared with normal control group,model group showed CRF sign,renal coefficient,the contents of phosphorus,PTH,Scr and BUN were increased,while the content of calcium was de-creased(P<0.01);renal section showed obvious pathological characteristics. Compared with model group,CRF sign of rats were improved in lanthanum carbonate group,calcium carbonate group and lanthanum hydroxide groups. The renal coefficient (except for lanthanum hydroxide high-dose group),serum contents of phosphorus(except for calcium carbonate group),PTH(except for lanthanum hydroxide low-dose group and calcium carbonate group),Scr(except for lanthanum hydroxide low-dose group and calci-um carbonate group)and BUN were all decreased,while serum content of calcium and calcium-phosphorucs product(only in calci-um carbonate group)was increased(P<0.05 or P<0.01). There was no statistical significance in other difference. The renal sec-tion pathological characteristics were improved. CONCLUSIONS:Lanthanum hydroxide can improve renal function and reduce the level of serum phosphorus in CRF hyperphosphatemia model rats.
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Objective To study the possibility of direct identification of pathogens from positive blood cul-tures by methods of separation gel tube -centrifugation.Methods 216 cases of positive blood culture were collected from 2015.7 to 2015.12.The bacterias were purified from blood culture bottle by separation gel tube.After washing 2 times,identified by MALDI -TOF MS.At the same time,traditional culture,smears and identification were done. Compared the results of identification by two methods.Results 216 cases of positive blood culture were single bacte-rial infection.By Gram stain,89 strains were Gram positive,119 strains were Gram negative and 8 strains were fungal spores.190 cases of positive blood culture were identified by MALDI -TOF MS,it concluded 67 Gram positive strains,111 Gram negative strains,4 anaerobe strains and 8 fungus.Compared with traditional culture,the coincidence rate reached up to 87.9%,Gram positive strains 78.8%,Gram negative strains 93.2%,anaerobe strains 100.0%and fungus 100.0%.Conclusion It takes less than 30 minutes purified from blood culture bottle by separation gel tube.And the time of identification is shorter than traditional culture.This method is good for clinical diagnosis and treatment.
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Aim To investigate whether the effect of Aβ25-35 on Bcl-2 and Bax gene transcription through DNA methylation in SH-SY5Y cell.Methods Differ-ent concentrations of Aβ25-35 (0, 25, 50 μmol? L-1 ) were treated with SH-SY5Y cells for 48 h or 72 h in vitro.The optimal concentration and time of Aβ25-35 in-duced SH-SY5 Y apoptosis were determined by MTT method.Protein expression levels of Bcl-2 and Bax of Aβ25-35-treated groups were determined by Western blot.Real time PCR was used to detect the mRNA lev-els of DNA methyltransferase including DNMT 1 , DN-MT3a, DMT3b, MeCP2. Methylation specific PCR ( MSP) was used to analyze the effect of Aβ25-35 media-ted Bcl-2 and Bax gene promoter methylation .Results 25 μmol? L-1 Aβ25-35 was exposed to SH-SY5Y cells for 72 h, MTT assay showed that cell viability was (68.49 ±9.83 )%, which was significantly reduced compared with the control group ( P 0.05 ); MSP results showed that Bcl-2 and Bax unmethylated ampli-fication was positive , methylated amplification was neg-ative in control group , Bcl-2 and Bax unmethylated amplification was positive and methylated amplification was negative in Aβ25-35-treated group.Conclusion DNA methylation of Bcl-2 and Bax gene promoter are not affected during Aβ25-35 induced SH-SY5Y cell ap-optosis .
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With increasing use of carbapenem antibiotics , carbapenems-resistant gram-negative bacteria are spreading, and carbapenemase-producing is the main mechanism of carbapenems resistance . Rapid and accurate identification of carbapenemase and its type is of great importance to timely and effective treatment and control of infections .Chromogenic /Fluorogenic culture media, modified Hodge test and double disk synergy test are traditional methods for carbapenemase detection , but all are time-consuming. Biochemical method is more time efficient and with high sensitivity and specificity , but cannot be used to identify subtypes.Now matrix-assisted laser desorption ionization -time-of-flight mass spectrometry (MALDI-TOF MS) has been successfully applied in the identification of species , subtypes and detection of drug -resistant genes.And among various carbapenemase gene detection techniques , next generation sequencing (NGS) can also be used for the detection of integrons , transposons and plasmids, which is important in both epidemiology and resistant mechanism studies .This article reviews the advantages and disadvantages of various methods for phenotype and gene detection of carbapenemase .
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<p><b>OBJECTIVE</b>To investigate the role of the Notch signaling pathway, and the underlying mechanism, in development of acute liver failure (ALF) in a mouse model.</p><p><b>METHODS</b>For in vivo analysis of the role of Notch signaling in ALF, a mouse model of ALF was generated by intraperitoneal injection of 3.0 g/kg D-galactosamine. Histological specimens were stained by hematoxylin-eosin, and then studied microscopically.Expression level of Jaggedl, Notchl, NICD, and Hes5 was measured by western blotting (for protein) and real time-PCR (for mRNA). The level of CD68 protein was detected by immunohistochemical staining. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL-10, high mobility group box 1 (HMGB1) chromatin protein, and lipopolysaccharide (LPS) were measured by standard methods. For in vitro analysis of the molecular mechanism, the RAW264.7 macrophage cell line was cultured with LPS in the absence or presence of the Notch inhibitor DAPT, and the intracellular levels of Notch1, NICD, and Hes5 were measured by western blotting and real time-PCR and the extracellular levels of IL-10 and HMGB1 were detected in the supematant.</p><p><b>RESULTS</b>Compared with unmodeled (normal control) mice, the ALF modeled mice showed higher levels of serum ALT (848.40+/-94.83 U/L vs. 38.99+/-9.63 U/L), AST (911.49+/-67.65 U/L vs. 55.28+/-7.50 U/L), HMGB1 (101.91+/-12.43 µg/L vs. 20.73+/-5.37 µg/L), 1L-10 (4 627.88+/-842.45 pg/mL vs. 1 064.92+/-238.46 pg/mL) and LPS (11.80+/-0.89 EU/mL vs. 0.58+/-0.12 EU/mL), as well as higher expression of Jagged1 (mRNA: 7.63+/-1.41 vs. 1.00+/-0.00; protein: 0.71+/-0.07 vs. 0.34+/-0.07), Notch1 (mRNA: 7.10+/-0.66 vs. 1.00+/-0.00; protein: 0.66+/-0.11 vs. 0.27+/-0.08), NICD (protein: 0.76+/-0.08 vs. 0.27+/-0.08), Hes5 (mRNA: 7.95+/-0.71 vs. 1.00+/-0.00; protein: 1.20+/-0.07 vs. 0.76+/-0.07), and CD68 (protein: 7 685.05+/-417.34 vs. 2 294.01+/-392.93) (all P<0.01). In vitro, LPS increased the extracellular levels of HMGB1 (7.44+/-0.63 vs. 0.21+/-0.05), IL-10 (315.19+/-79.13 vs. 59.19+/-23.30) and the intracellular expression of Notch1 (mRNA: 6.49+/-0.73 vs. 1.00+/-0.00), NICD (protein: 0.65+/-0.10 vs. 0.23+/-0.07), and Hes5 (mRNA: 7.30+/-0.85 vs. 1.00+/-0.00; protein: 0.96+/-0.10 vs. 0.54+/-0.07) (all P<0.01). DAPT treatment led to a decrease above the index serum levels of HMGB1 (6.22+/-0.71) and IL-10 (252.06+/-57.63), and of expression of Notch 1 (mRNA: 3.20+/-0.68), NICD (protein: 0.42+/-0.05), and Hes5 (mRNA: 4.72+/-0.67; protein: 0.84+/-0.09) (P<0.01 or <0.05).</p><p><b>CONCLUSION</b>The Notch signaling pathway may plan an important role in the development of ALF upon activation of the pathway in macrophages by LPS and leading to promoted secretion of HMGB 1 and IL-10, with a greater effect on the former.</p>
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Animals , Mice , Alanine Transaminase , Aspartate Aminotransferases , Disease Models, Animal , Galactosamine , HMGB1 Protein , Lipopolysaccharides , Liver Failure, Acute , RNA, Messenger , Receptors, Notch , Metabolism , Signal TransductionABSTRACT
Objective To investigate the mechanism of live combined Bifidobacterium and Lactobacillus tablets in acute liver failure (ALF) treatment.Methods Ten mice were injected intraperitoneally with 3.0 g/kg D-galactosamine to establish the model of ALF and treated with live combined Bifidobacterium and Lactobacillus tablets.Protein levels of Jagged1,Notch1,Notch intracellular domain (NICD),Hes5 and the mRNA expressions of Jagged1,Notch1,Hes5 were measured via Western blot and real time-polymerase chain reaction (PCR),respectively.The protein level of CD68 was detected by immunohistochemical staining method.Meanwhile,serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),interleukin (IL)-10,high mobility group protein B1 (HMGB1) and plasma lipopolysaccharide (LPS) were measured.Moreover,model group and control group were also established with 10 mice each.In vitro,RAW264.7 cells were cultured with normal mice plasma,plasma of ALF mice and plasma of treated mice,respectively.Real time-PCR and Western blot were used to determine the mRNA expressions of Jagged1,Notch1,Hes5 and proteins levels of Jagged1,Notch1,NICD,Hes5.The levels of IL-10,HMGB1 and LPS in the supernatant of RAW264.7 cells were detected as well.The total significant differences among groups were compared by one way ANOVA,and q test was used to evaluate the significance of subgroup differences.Results The levels of serum ALT,AST,HMGB1,IL10,plasma LPS,and the expressions of Jagged1,Notch1,NICD,Hes5,CD68 were higher in ALF model group than control group (all P＜0.01).Compared with the ALF model group,all of these indexes could be improved in mice with live combined Bifidobacterium and Lactobacillus tablets (HMGB1:[82.6±9.7] μg/L vs [101.9±12.4] μg/L,q=6.36,P＜0.01; IL-10.:[3 183±769] pg/mL vs [4 628±842] pg/mL,q=6.79,P＜0.01; plasma LPS:[7.40±0.92] EU/mL vs [11.80±0.89] EU/mL,q=18.81,P＜0.01; Jagged1 mRNA:5.55±0.71 vs 7.63±1.41,q=7.22,P＜0.01;Jagged1 protein:0.56±0.07 vs 0.71±0.07,q=7.20,P＜0.01; Notch1 mRNA:3.66±0.67 vs 7.10±0.66,q=20.06,P＜0.01; Notch1 protein:0.38±0.08 vs 0.66±0.11,q=9.57,P＜0.01;NICD protein:0.47±0.05 vs 0.76±0.07,q=12.68,P＜0.01; Hes5 mRNA:3.94±0.68 vs 7.95± 0.71,q=22.40,P＜0.01; Hes5 protein:1.04±0.12 vs 1.20±0.07,q=5.61,P＜0.01; CD68 protein:5 180±610 vs 7 685 ±417,q=16.38,P＜0.01).And the differences were statistically significant.After RAW264.7 cells cultured with the plasma of ALF model mice,the levels of HMGB1,IL-10 and LPS in the supernatant and the expressions of Jagged1,Notch1,NICD and Hes5 in cells were increased,whereas if RAW264.7 cells were cultured with the plasma of treated mice,indexes mentioned above were significantly decreased (all P＜0.01).Conclusions Live combined Bifidobacterium and Lactobacillus tablet could prevent the occurrence and development of ALF by decreasing the plasma level of LPS,inhibiting the activation of Notch signaling pathway in macrophages and reducing the secretion of HMGB1 and IL-10.
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microRNA (miRNA) refers to small (19-25 nt) single-stranded noncoding RNA molecules that work as post-transcriptional regulator for gene expression by binding to 3' untranslated regions of target mRNA,thus inducing its digestion,degradation and translational repression.Many studies have confirmed that dysregulation of miRNA expression can cause disruption of the hematopoietic system and contribute to leukemogenesis by regulating the expression of some oncogenes and anti-oncogenes.The unique miRNA expression profiles associated with cytogenetic aberrations and mutational status of protein-coding genes may reveal insight into the biology of these leukemia types.This review discussed the latest studies on miRNA expression in different cytogenetic and molecular subtypes of acute myelocytic leukemia and acute lymphoblastic leukemia.
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Objective To investigate the association of SLC34A1 ( rs6420094 ) and RGS14 (rs4074995) polymorphisms with serum level of phosphorus in chronic hepatitis B virus (HBV) infection patients following long-term adefovir dipivoxil ( ADV ) treatment.Methods Ninety one patients with chronic HBV infections admitted in Third Hospital of Hebei Medical University during October 2012 and August 2013 were enrolled in the study.All patients received ADV treatment ( monotherapy or combination therapy) for at least two years, among whom 31 had hypophosphatemia and 60 had normal serum phosphorus levels.rs6420094 and rs4074995 were genotyped by polymerase chain reaction-restrictive fragment length polymorphism ( PCR-RFLP ) analysis.The relationship between allele frequency and serum phosphorus concentration was analyzed by Chi-Square test.Results In hypophosphatemia group, there were 13, 13, and 5 patients with genotype A/A, A/G and G/G at rs6420094, respectively;while in patients with normal serum phosphorus levels, there were 35, 24 and 1 patients with genotype A/A, A/G and G/G at rs6420094.The frequency of allele A at rs6420094 in patients with normal serum level of phosphorus was higher than that in hypophosphatemia group ( 78.3% vs.62.9%, χ2 =4.947, P 0.05).Conclusion The polymorphism of rs6420094 gene may be associated with the serum level of phosphorus in patients with chronic HBV infections following long-term treatment of ADV.
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Objective To investigate the impact of tumor necrosis factor-α (TNF-α) on intestinal mucosa permeability and the protective effect of probiotics in mice with acute liver failure (ALF).Methods Thirty male BALB/c mice aged 6-8 weeks were randomly divided into normal control,ALF and intervention groups (10 for each group).Mice in intervention group were fed with live combined bifidobacterium and lactobacillus (900 mg · kg-1 · d-1) by gavage,while those in normal control and ALF groups were fed with normal saline (9 mL · kg-1 · d-1).After two weeks,mice in ALF and intervention groups were given an intraperitoneal injection of D-galactosamine (3.0 g/kg) to induce liver failure,and all mice were sacrificed 9 h after the injection.Biochemical markers were tested,expressions of TNF-α mRNA in liver tissues and zonula occluden-1 (ZO-1) mRNA in ileum tissues were detected by real-time PCR,and the expression of ZO-1 protein in ileum tissues was detected by Western blotting.One-way analysis of variance or Kraskal-Wallis test was performed to explore the differences in biochemical markers,TNF-α mRNA,ZO-1 mRNA and ZO-1 protein expressions among groups,and Pearson test was used to analyze the correlations between the expression of ZO-1 protein in ileum tissues and serum level of TNF-α or plasma levels of endotoxins.Results Serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),TNF-α and plasma level of endotoxins in ALF group were significantly higher than those in normal control group (P ＜0.01) ; while compared with ALF group,the above biomarkers were significantly decreased in the intervention group (P ＜ 0.01).The expression of TNF-α mRNA in liver tissues in ALF group was higher than that in the normal control group (Z =4.038,P ＜ 0.01) ; while compared with ALF group,it was decreased in intervention group (Z =3.780,P ＜ 0.01).The expressions of ZO-1 mRNA and ZO-1 protein in ileum tissues in ALF group were lower than those in normal control group (P ＜ 0.01) ; while compared with ALF group,those in intervention group were increased (P ＜ 0.01).Pearson analysis showed that the expression of ZO-1 protein in ileum tissues was negatively correlated with serum level of TNF-α level and plasma level of endotoxin (r =-0.946 and-0.919,both P ＜ 0.01).Conclusions TNF-α may be involved in the increased permeability of intestinal mucosa in mice with ALF.Live combined bifidobacterium and lactobacillus may relieve liver damages through inhibiting endotoxin synthesis and release,and ameliorate the permeability of intestinal mucosa through up-regulating ZO-1 protein expression.