The PK bioanalysis method study of c-Met antibody-drug conjugate (RC108) in cynomolgus monkey / 药学学报

Antibody-drug conjugate (ADC) has the characteristics of low toxicity and high efficiency, and plays an important role in cancer treatment. However, due to the complexity of its structure, it brings difficulties in pharmacokinetic (PK) bioanalysis. This study established an analytical method for the detection of ADC (RC108) in cynomolgus monkey plasma by ligand-binding assay (LBA) and liquid chromatography tandem mass spectrometry (LC-MS/MS), which was used to analyze and quantify the total antibody, bound antibody and free drug in cynomolgus monkey plasma. Based on the LBA method, rabbit anti-RC108 Fab and mouse anti-MMAE (monomethyl auristatin E) mAb were pre-coated in 96-well plates as the total antibody and antibody binding reagents, respectively. The samples to be tested were added, and then the detection reagents were added in turn. Goat anti-human IgG (H+L)-HRP, chromogenic solution tetramethylbenzidine (TMB), H2SO4 terminate the reaction, read data at 450 nm/630 nm wavelength of microplate reader; LC-MS/MS analysis method quantifies MMAE concentration, and refer to relevant regulations for methodological validation. The analytical method for quantifying total antibody, bound antibody and free drug of RC108 drug obtained good accuracy and precision, and the selectivity, dilution linearity, hook effect, parallelism and stability were verified. Meet the requirements of biological analysis. Finally, a bioanalytical method for the determination of the concentration of the test substance RC108 (total antibody, conjugated antibody, free MMAE) in cynomolgus monkey plasma with high sensitivity and high throughput was established by LBA and LC-MS/MS method. Subsequent non-clinical research on PK research in cynomolgus monkeys will provide technical support.

Prognostic Significance of LPCAT1 in Adult Acute Myeloid Leukemia Patients with FAB Subtype M2 / 中国实验血液学杂志

OBJECTIVE@#To study the prognostic value of LPCAT1 in acute myeloid leukemia (AML).@*METHODS@#TaqMan-based reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect relative expression of LPCAT1 in 214 newly diagnosed adult AML patients and 24 normal controls. Survival functions were estimated using the Kaplan-Meier method and were compared by the Log-rank test. A Cox proportional hazard regression model was used to identify prognostic factors.@*RESULTS@#The expression level of LPCAT1 in adult AML was 34.37%(1.83%-392.63%), which was significantly lower than 92.81%(2.60%-325.84%) of normal controls (P<0.001). The prognostic significance of LPCAT1 was evaluated in 171 non-acute promyelocytic leukemia patients with complete clinical information and prognostic data. Survival analysis showed that the expression level of LPCAT1 had no significant effect on the prognosis of the whole cohort. However, in AML patients with FAB subtype M2 (AML-M2), the 2-year relapse-free survival (RFS) rate of patients with low LPCAT1 expression was 35.4%(95%CI: 0.107-0.601), which was significantly lower than 79.2%(95%CI: 0.627-0.957) of patients with high LPCAT1 expression (P=0.012). Multivariate analysis showed that low expression of LPCAT1 was an independent risk factor for RFS of AML-M2 patients (HR=0.355, 95%CI: 0.126-0.966, P=0.049).@*CONCLUSION@#In adult AML patients LPCAT1 shows low expression. Low LPCAT1 expression is an independent risk factor for RFS in M2-AML patients.

Clinical Features and Prognosis of Multiple Myeloma Patients with Secondary Primary Malignancies / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics and prognosis of multiple myeloma(MM) patients with secondary primary malignancies.@*METHODS@#The clinical data of newly diagnosed MM patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2019 were retrospectively analyzed. The patients with secondary primary malignancies were retrieved, and their clinical features and prognosis were evaluated.@*RESULTS@#A total of 1 935 patients with newly diagnosed MM were admitted in this period, with a median age of 62 (18-94) years old, of which 1 049 cases were hospitalized twice or more. There were eleven cases with secondary primary malignancies (the incidence rate was 1.05%), including three cases of hematological malignancies (2 cases of acute myelomonocytic leukemia and 1 case of acute promyelocytic leukemia) and eight cases of solid tumors (2 cases of lung adenocarcinoma, and 1 case each of endometrial cancer, esophageal squamous cell carcinoma, primary liver cancer, bladder cancer, cervical squamous cell carcinoma, and meningioma). The median age of onset was 57 years old. The median time between diagnosis of secondary primary malignancies and diagnosis of MM was 39.4 months. There were seven cases with primary or secondary plasma cell leukemia, the incidence rate was 0.67%, and the median age of onset was 52 years old. Compared with the randomized control group, the β2-microglobulin level in the secondary primary malignancies group was lower (P=0.028), and more patients were in stage I/II of ISS (P=0.029). Among the 11 patients with secondary primary malignancies, one survived, ten died, and the median survival time was 40 months. The median survival time of MM patients after the secondary primary malignancies was only seven months. All seven patients with primary or secondary plasma cell leukemia died, with a median survival time of 14 months. The median overall survival time of MM patients with secondary primary malignancies was longer than that of the patients with plasma cell leukemia (P=0.027).@*CONCLUSION@#The incidence rate of MM with secondary primary malignancies is 1.05%. MM patients with secondary primary malignancies have poor prognosis and short median survival time, but the median survival time is longer than that of patients with plasma cell leukemia.

Gene Mutation and Overexpression of Newly Diagnosed Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients.@*METHODS@#Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH).@*RESULTS@#Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression.@*CONCLUSION@#There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.

Effect of CDK1 Interferes with the Regulation of PLK1, Aurora B and TRF1 on the Proliferation of Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of CDK1 interference regulation of PLK1, Aurora B and TRF1 on the proliferation of leukemia cells.@*METHODS@#The human myelogenous leukemia cell line HL-60 was selected as the research object, and the effect of TRF1 expression and its changes on cell proliferation and cycle was investigated by regulating intracellular CDK1 expression. The objects were divided into 5 groups, including control group, shRNA-NC group, CDK1-shRNA group, pcDNA group and pcDNA-CDK1 group. RT-PCR was used to detect the CDK1 expression of cells in each group; colony formation was used to detect the proliferation of the cells. Western blot was used to detect the expression of CDK1, PLK1, Aurora B, TRF1, and cyclin p53, p27, cyclinA.@*RESULTS@#The phosphorylation level of PLK1, Aurora B and the expression of TRF1 in the CDK1-shRNA group were significantly down-regulated as compared with those in the control group (P<0.05). Compared with the control group, the cells in CDK1-shRNA group showed lower clone formation rate, the increasing of cycle-associated proteins p53 and p27 and the decreasing of cyclinA expression (P<0.05). It was shown that interfered CDK1 expression could inhibit the proliferation of HL-60 cells and prolong the time that they enter mitosis, thereby extending the cell cycle. Compared with the control group, the overexpressed CDK1 in the pcDNA-CDK1 group made the phosphorylation level of PLK1, Aurora B, and TRF1 expression increase significantly (P<0.05), also the colony formation rate (P<0.05). The cycle-related proteins p53 and p27 was down-regulated, while cyclinA expression was up-regulate significantly (P<0.05). The results indicted that overexpressed CDK1 could stimulate adverse reactions, thereby promoting the proliferation of HL-60 cells and shortening the cell cycle.@*CONCLUSION@#Knocking out CDK1 can inhibit the phosphorylation of PLK1 and Aurora B and negatively regulate TRF1, thereby inhibiting the proliferation of leukemia cells.

Prognostic Value of CD123 in Acute Myeloid Leukemia Patients with Intermediate Risk in Normal Karyotype / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of CD123 in patients with acute myeloid leukemia (AML) and its relationship between clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis.@*METHODS@#365 patients with newly diagnosed AML (except M3) treated in the First Affiliated Hospital of Zhengzhou University were enrolled and retrospective analysis, and multi-parameter flow cytometry was performed to detect the expression of CD123 in myeloid leukemia cell population. CD123≥20% was defined as positive. Clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis of CD123@*RESULTS@#The positive rate of CD123 in 365 newly diagnosed AML patients was 38.9%. Compared with the CD123@*CONCLUSION@#CD123 positive indicates that AML patients have higher tumor burden and are more difficult to reach remission. It is an independent risk factor for OS and EFS in patients with normal karyotype and intermediate risk, which is important to evaluate the prognosis of patients with AML without specific prognostic marker.

Gene Mutation in Acute Lymphoblastic Leukemia by DNA Sequencing / 中国实验血液学杂志

OBJECTIVE@#To analyze the characteristics of gene mutation in adult ALL and its clinical significance.@*METHODS@#Clinical data of 134 primary adult ALL patients and DNA sequencing results of 16 kinds of gene mutation were collected. The characteristic of gene mutation and clinical significances were statistically analyzed.@*RESULTS@#In 31 cases of 134 ALL cases (23.13%) the gene mutations were detected as follows: 19 cases of 114 B-ALL cases (16.67%), 11 cases of 19 T-ALL cases (57.89%) and 1 case of T/B-ALL. The incidence of T-ALL gene mutation was significantly higher than that of B-ALL (χ@*CONCLUSION@#There may be multiple gene mutations in adult ALL patients. IL7R and NOTCH1 are the most common gene mutations and NOTCH1 mutation may indicate poor prognosis. Detection of gene mutations is helpful to understand the pathogenesis of ALL and evaluate the prognosis of adult ALL patients.

Adiponectin Receptor Agonist AdipoRon Inhibits the Proliferation of Myeloma Cells via the AMPK/Autophagy Pathway / 中国实验血液学杂志

OBJECTIVE@#To investigate the inhibitory effect of adiponectin receptor agonist AdipoRon on proliferation of myeloma cell lines and its possible mechanism.@*METHODS@#The myeloma cell lines Sp2/0-Ag14 and MPC-11 were treated with different concentration of AdipoRon. The cell proliferation was detected by CCK-8. Western blot was used to determine the protein level of the signaling pathway. RT-PCR was used to quantify the mRNA copy number of adiponectin receptor AdipoR1 and AdipoR2 in the bone marrow cells from 21 patients with multiple myeloma (MM). Twenty-three normal bone marrow samples were served as control.@*RESULTS@#AdipoRon significantly inhibited the proliferation of MM cell lines Sp2/0-Ag14 and MPC-11 in a concentration-dependent and time-dependent manner. Western blot showed that AdipoRon induced an increase of the expression levels of apoptosis-related proteins cleaved caspase-3 and cleaved PARP. AdipoRon upregulated p-AMPK and its downstream p-ACC in MPC-11. In addition, AdipoRon upregulated LC3-II/LC3-I level and down-regulated the protein level of p62. The expression level of AdipoR1 in MM cells was significantly higher than that in normal controls, and the expression level of AdipoR2 in MM cells was significantly lower than that in normal controls.@*CONCLUSION@#Adiponectin receptors are expressed differentially between MM patients and normal subjects. AdipoRon, an adiponectin receptor agonist, can inhibit myeloma cell proliferation and induce apoptosis, and AMPK/autophagy pathway may be one of its mechanisms.

The correlation between orexin-A and early postoperative cognitive function in elderly patients undergoing lumbar surgery under general anesthesia / 解放军医学杂志

Objective To analyze the correlation between serum orexin-A (OXA) and early postoperative cognitive function in elderly patients undergoing lumbar spinal surgery under general anesthesia. Methods A total of 76 elderly patients (age ≥65 years) underwent lumbar spine surgery under general anesthesia from December 2018 to December 2019 in the Affiliated Hospital of Inner Mongolia Medical University were collected. All the enrolled patients were evaluated by the same doctor with the Montreal cognitive assessment scale (MoCA) on one day before the surgery and one to three days after the surgery, and venous blood was extracted from the patient on the operation day and one day after the operation, and the serum levels of OXA and S100β were measured by ELISA. According to the results of cognitive function assessment, the patients were divided into postoperative cognitive dysfunction (POCD) group and non-postoperative cognitive dysfunction (NPOCD) group. The differences in serum OXA and S100β protein levels between the two groups and their correlation with MoCA scores were statistically analyzed. Results There was no statistically significant difference in the MoCA score, serum OXA level, and S100β protein level before surgery, and heart rate (HR), mean artery pressure (MAP), bispectral index (BIS) and pulse oxygen saturation (SpO2) levels before anesthesia induction (T0), at the start of surgery (T1), at 1h after the start of surgery (T2), at the withdrawal time (T3), and at 15 minutes after extubation (T4) between the two groups (P>0.05). At the first, second, and third day after operation, the MoCA scores of the POCD group were lower than those before the operation, and they were both lower than those of the NPOCD group, the difference was statistically significant (P<0.001). There was a statistically significant difference in serum OXA levels between the two groups after the operation (P<0.05). The postoperative S100β protein level was higher than that before the operation in the two groups, and the POCD group increased more significantly, the difference between the two groups after the operation was statistically significant (P<0.05). The postoperative OXA level was positively correlated with the MoCA score (r=0.545, 0.531, 0.779) and negatively correlated with the S100β protein level (r=-0.591, -0.362, -0.743) in the two groups, and the difference was statistically significant (P<0.05). Conclusions The level of serum OXA is positively correlated with early postoperative cognitive function in elderly patients undergoing lumbal spine surgery under general anesthesia, suggesting that OXA may be a potential target for reducing the risk of postoperative cognitive dysfunction in such patients, so as to provide new ideas for preventing and improving the postoperative cognitive dysfunction in elderly patients in the future.

NPM1 High Mutant Allele Burden is an Adverse Prognostic Factor for AML Patients with Mutated NPM1 / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features, accompanying gene mutation characteristics and prognostic factors of adult patients with acute myeloid leukemia with mutated NPM1 (NPM1AML).@*METHODS@#Seventy-three patients with newly diagnosed adult NPM1AML were selected. The mutations of 22 genes were detected by second generation sequencing and 43 fusion genes of AML were detected by real-time fluorescent quantitative PCR. The Kaplan-Meier survival curve and Cox multivariate regression analysis were used to study the prognostic factors.@*RESULTS@#A total of 74 NPM1 site mutations were detected in 73 patients with NPM1AML. The incidence rates were 92.0% L287fs, 2.7% Q289fs and W288fs, 1.4% L258fs and Q289H, among which 1 patient had 2 NPM1 mutations; the different mutation sites had no effect on the prognosis of NPM1AML. The median value of NPM1 variant allele frequency (VAF) was 35.4% (1.8%-56.6%). Based on the uppermost quartile of 38.4%, the patients were classified as NPM1 VAF>38.4% (NPM1AML) and NPM1 VAF≤38.4% (NPM1AML). Compared with NPM1AML, the early mortality rate was statistically significantly higher (33.3% vs 7.3%, P38.4% was an independent prognostic factor for EFS (HR=3.1, 95% CI 1.6-6.4, P<0.01) and OS (HR=3.0, 95% CI 1.4-6.2, P<0.01).@*CONCLUSION@#The NPM1 gene mutation in AML patients often is accompanied by other gene mutations, while the coexistence of fusion genes is rare; high NPM1 mutant allele burden is an independent prognostic factor for adult AML patients with mutated NPM1.

Bone Metabolic Markers in Patients with Obstructive Sleep Apnea Syndrome / 中华医学杂志(英文版)

Background@#Obstructive sleep apnea syndrome (OSAS) is prevalent in obesity and is associated with many metabolic abnormalities. The relationship between OSAS and bone metabolism is still unclear. The aim of this study was to investigate the relationship between the severity of OSAS and bone metabolic markers.@*Methods@#A total of 119 obese males were enrolled in this study in spring months from 2015 to 2017. All candidates underwent polysomnography, and their bone mineral density (BMD) and the serum levels of total procollagen type 1 N-terminal propeptide (t-P1NP), N-terminal midfragment of osteocalcin (N-MID), β-C-terminal telopeptide of type 1 collagen (β-CTX), vitamin D (VD), and parathyroid hormone (PTH) were measured. The analysis of variance and Pearson correlation analysis were performed for data analyses.@*Results@#No significant differences in the mean values of BMD were observed among the obesity, mild-to-moderate OSAS, and severe OSAS groups; and the serum levels of t-P1NP and β-CTX in the severe OSAS group were significantly higher than those in the obesity group (48.42 ± 23.78 ng/ml vs. 31.98 ± 9.85 ng/ml, P < 0.001; 0.53 ± 0.24 ng/ml vs. 0.41 ± 0.13 ng/ml, P = 0.011, respectively). The serum level of VD in the obesity group was significantly higher than those in the mild-to-moderate and severe OSAS groups (both P < 0.001), and decreased as the severity of OSAS increased (P < 0.001). The serum level of PTH in the severe OSAS group was significantly higher than those in the obesity and mild-to-moderate OSAS groups (both P < 0.001). The results of correlation analysis indicated that the level of apnea-hypopnea index (AHI) was correlated with the levels of t-P1NP (r = 0.396, P < 0.001), VD (r = -0.404, P < 0.001), and PTH (r = 0.400, P < 0.001), whereas the level of minimum Osaturation (SaOmin) was correlated with the levels of VD (r = 0.258, P = 0.016) and PTH (r = -0.376, P < 0.001).@*Conclusions@#The levels of bone resorption and formation markers in patients with severe OSAS were significantly increased compared to obese men, and the severity of OSAS was correlated with the serum levels of t-P1NP, VD, and PTH.

Effect of Wenyang Decoction on the Differentiation of CD34+ Progenitor Cells in Occupational Asthma Model Rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Wenyang Decoction (WD) on the differentiation of CD34+ progenitor cells of occupational asthma (OA) model rats.</p><p><b>METHODS</b>Fifty healthy male SD rats were randomly divided into five groups, i.e., the model group, the blank control group,the WD group,the Western medicine group,the combined group, 10 in each group. Prednisone suspension (10 mg/kg) was administered to rats in the Western medicine group by gastrogavage. WD (20 g/kg) was administered to rats in the WD group by gastrogavage. Prednisone suspension plus WD was administered to rats in the combined group by gastrogavage. Normal saline was administered to rats in the model group and the blank control group by gastrogavage. The general condition of rats was observed. Expression levels of peripheral blood IL-5 and eotaxin, eosinophils (EOS), CD34+, CC chemokine receptor 3 (CCR3+) in bone marrow suspension were detected by ELISA, Wirght-Giemsa, and flow cytometry, respectively.</p><p><b>RESULTS</b>Compared with the blank control group,expression levels of IL-5 and eotaxin in peripheral blood were significantly higher (P < 0.01), and the count of EOS and CD34+ cells, as well as CD34+ /CCR3+ significantly increased (P < 0.01) in the model group. Compared with the model group, expression levels of IL-5 and eotaxin, the count of EOS, CD34+ cells, CD34+ / CCR3+ were lowered in three treated groups (P < 0.01). Compared with the Western medicine group, the count of EOS and CD34+ / CCR3+ decreased in the combined group (P < 0.01). The count of EOS was significantly lower in the combined group than in the WD group (P < 0.01).</p><p><b>CONCLUSION</b>WD could reduce levels of in vivo inflammatory factors, and restrain the differentiation and recruitment of EOS,thereby alleviating the differentiation of CD34 progenitor cells to EOS.</p>

Effects of Biejia Ruangan Tablet-containing serum on matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in cultured renal interstitial fibroblasts / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Biejia Ruangan Tablet ([symbol in text], BRT)-containing serum on the expression of matrix metalloproteinase (MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) in cultured renal interstitial fibroblasts.</p><p><b>METHODS</b>Different BRT-containing sera were prepared by gastric gavages to rats with the high-dose (7 g/kg), mid-dose (3.5 g/kg), and low-dose (1.75 g/kg) BRT respectively. The expression of extracellular matrix in NRK-49F cells was induced by treatment with human transforming growth factor-β1 (recombined human TGF-β1), and BRT-containing serum. Western blotting and Northern blotting were used to measure type I and III procollagen, MMP-9, and TIMP-1.</p><p><b>RESULTS</b>The high dose BRT-containing serum could decrease the type I and III procollagen gene expression which boosted by TGF-β1, at the same time cut down TIMP-1 protein and gene expression which increased by TGF-β1 (P <0.05). Treatment of cells with recombined human TGF-β1 had no significant effect on MMP-9 expression and BRT-containing serum also had no effect on MMP-9 expression.</p><p><b>CONCLUSIONS</b>High dose BRT has anti-fibrosis effects in NRK-49F cells, as indicated by its inhibition of type I and III procollagen and TIMP-1 expression.</p>

High Expression of co-stimulatory molecule CD40 in silicosis patients and intervention effect of yiqi huoxue decoction / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study whether co-stimulatory molecule CD40 of alveolar macrophage (AM) participated in the occurrence and development of silicosis, and to explore the intervention of Yiqi Huoxue Decoction (YHD) in the fibrosis of silicosis patients.</p><p><b>METHODS</b>Totally 46 silicosis inpatients and outpatients were recruited and randomly assigned to the Western treatment group (A) and the Chinese medicine (CM) treatment group (B), 23 in each group. Patients in Group A received routine symptomatic treatment such as anti-inflammation, phlegm resolving, anti-spasm, and asthma relief, and so on. Patients in Group B additionally took YHD, one dose daily for 14 successive days. Besides, another 18 patients with chronic cough and sense of laryngeal foreign bodies were recruited as the normal control group, who had no obvious lesion confirmed by bronchofi6roscope and clinical diagnosis of the lung. They were treated by symptomatic supporting treatment. The alveolar lavage fluid was collected from all patients and isolated, and AM cells were cultured. The level of CD40 mRNA was detected by RT-PCR. The expression of CD40 protein was detected by Western blot.</p><p><b>RESULTS</b>Compared with the normal control group, expression levels of CD40 mRNA and CD40 protein significantly increased in Group A (P < 0.01). Compared with Group A, expression levels of CD40 mRNA and CD40 protein significantly decreased in Group B (P < 0.01).</p><p><b>CONCLUSIONS</b>Highly expressed co-stimulatory molecule CD40 of AM might participate in pulmonary fibrosis. YHD could hinder its roles, inhibit the progression of fibrosis, thereby playing an interventional role of treatment.</p>

The relationship between high-sensitive C-reactive protein and pulmonary arterial pressure among patients with pneumoconiosis combined with infection / 预防医学

Objective To explore the relationship between high -sensitive C -reactive protein (hs -CRP)and pulmonary arterial systolic pressure (PASP)among patients with pneumoconiosis combined with infection in different degrees of pulmonary dysfunction status.Methods By retrospective study,93 pneumoconiosis patients combined with infection were divided into four groups according to their degree of pulmonary dysfunction.The relationship between PASP and hs -CRP was then analyzed.Results Pulmonary arterial systolic pressures and the serum levels of hs -CRP were significantly different among four groups (P <0.05).Moreover pulmonary arterial systolic pressures and the serum levels of hs -CRP in severe group were higher than those of the other groups (all P <0.05 ).The serum levels of hs -CRP were positively correlated with pulmonary artery systolic pressure (rs =0.71 ,P <0.01 ).Conclusion The serum levels of hs -CRP are highly correlated with pulmonary arterial systolic pressures in patients with pneumoconiosis combined with infection.The serum levels of hs -CRP can reflect changes in pulmonary artery systolic pressure in some extent.

Differential expression of the anti-oncogene ARHI between patients with and without endometriosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of the anti-oncogene ARHI in the endometriotic tissue and explore its clinical significance.</p><p><b>METHODS</b>A semiquantitative analysis of the expression of ARHI mRNA and protein in the ectopic and eutopic endometrium of women with endometriosis was conducted using RT-PCR and Western blotting in comparison with that in the endometrium of women without endometriosis. Immunohistochemistry and in situ hybridization were performed for semi qualitative analysis and localization of ARHI expression.</p><p><b>RESULTS</b>The expression levels of ARHI mRNA and protein differed significantly between the groups. ARHI was expressed at significantly higher levels in ectopic endometrium than in eutopic and normal endometrium (P<0.005), but showed no significant difference between the latter two tissues (Pgt;0.05). The positivity rate ARHI DNA was 97.3% in the endometrium of women without endometriosis, 100% in the ectopic endometrium and 93.8% in the eutopic endometrium of women with endometriosis. immunohistochemistry showed an ARHI positivity of 93.2% in the endometrium of women without endometriosis, 100% in the ectopic endometrium and 92.3% in the eutopic endometrium of women with endometriosis. The expression patterns of ARHI DNA and protein were consistent. Immunohistochemistry in 5 cases of malignant endometriosis showed negative ARHI expression in 4 cases and weak positivity in 1 case.</p><p><b>CONCLUSION</b>ARHI expressions are present in the endometrium and up-regulated in ectopic endometrium, whereas in the ectopic endometrium of patients with malignant endometriosis its expression is often negative, suggesting a role of ARHI in infertility and tumorigenesis of endometriosis.</p>

Clinical value of noninvasive intermittent positive-pressure ventilation in pneumoconiosis combined with respiratory failure / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the value of noninvasive intermittent positive-pressure ventilation (NIPPV) in treatment of patients with pneumoconiosis combined with respiratory failure.</p><p><b>METHOD</b>Three were 46 inpatients with pneumoconiosis combined with respiratory failure. Twenty-six inpatients treated with conventional therapy and NIPPV were categorized as treatment group; Twenty inpatients just treated by conventional therapy served as control group. Compared with the changes of HR, RR and arterial blood gas index (PH, PaCO2, PaO2) in two groups after treatment.</p><p><b>RESULTS</b>The effective ratio of treatment group was 88.5%, control group was 60%, which had significant difference (P < 0.05); The HR in treatment group after treatment was (95.38 +/- 10.75) beats per minute, control group was [(103.00 +/- 12.56) beats per minute; The RR in treatment group was (21.69 +/- 1.37) breaths per minute, control group was [(22.60 +/- 1.57) breaths per minute]; The PaCO2 in treatment group was (52.88 +/- 10.75)mm Hg, control group was [(59.66 +/- 11.49)mm Hg]; All of those were significantly decreased than those in control group (P < 0.05). The PaO2 in treatment group was (100.77 +/- 25.3) mm Hg, control group was [(71.82 +/- 17.94) mmHg]; Compared with the control group, PaO2 in the treatment group increased significantly (P < 0.05).</p><p><b>CONCLUSION</b>NIPPV is beneficial to pneumoconiosis combined with respiratory failure in different degrees.</p>

Association of fibrinogen B beta-chain gene polymorphism with factors affecting obesity / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the association of fibrinogen(Fg) B beta -854G/A, -455G/A, -249C/T, -148C/T, 448G/A and Bcl-1G/A gene polymorphisms with factors affecting obesity, and the fibrinogen function such as plasma fibrinogen concentration and molecular reactivity.</p><p><b>METHODS</b>One thousand and three hundred ninety-one subjects from Kailuan corporation were enrolled by medical examination and questionnaire survey, and were divided into normal weight, overweight and obese groups based on body mass index (BMI). Blood biochemistry, fibrinogen concentration, fibrin monomer polymerized velocity (FMPV), and FMPV/A(max) were measured. The gene polymorphisms of the six loci were detected by polymerase chain reaction-restriction fragment length polymorphism.</p><p><b>RESULTS</b>The frequencies of Bcl-1A and its mutated genotype in the overweight group were significantly higher than that in the normal weight group (P< 0.01). In all the three groups, Fg concentration, FMPV, FMPV/A(max) in individuals with B beta -854 mutated genotype were significantly higher than those with wild type genotype (P< 0.01), and in the overweight group, FMPV/A(max) in those with B beta -455 mutated genotype, FMPV in those with B beta -249 mutated genotype, were higher than those with wild type genotype (P< 0.05).</p><p><b>CONCLUSION</b>Individuals with Bcl-1A and its mutated genotype are susceptible to overweight. The B beta -455 and -249 mutated genotypes are accumulative genes for overweight by regulating the Fg function.</p>

Relationship between multi-locus fibrinogen polymorphisms and fibrinogen concentration, molecular reactivity and cerebral infarction / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the distribution characteristics of Beta-fibrinogen (Fg)B gene-854G/A, -455G/A, -249C/T, -148C/T, 448G/A and Bcl-1 G/A polymorphism in North China Han population, and the influence on plasma Fg concentration and molecular reactivity. Further more, to explore the role of Fg gene polymorphisms combining with multi-physiological and environmental factors in the development of cerebral infarction.</p><p><b>METHODS</b>Cluster sampling, health examination and questionnaires surveys of 1652 subjects from Tangshan Kailuan Group Corporation were conducted. Blood biochemistry, Fg concentration, fibrin monomer polymerized velocity (FMPV), absorbance maximum (Amax) and FMPV/Amax were measured. The six polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism.</p><p><b>RESULTS</b>In the population, the proportion of the FgB beta-249 T variation allele was 65.49%, while the proportion of the rest loci was predominantly wild type. The significant differences in Fg concentration and FMPV/Amax were found in -854 genotype groups. The Fg concentration in -854GA group was higher than those in GG and AA group. Only the distribution frequencies of FgB beta Bcl-1 A variation allele, GA and AA genotype in the cerebral infarction group were higher than those in non-infarction group, and the prevalence of cerebral infarction in AA genotype group was higher than other groups (the probability value of above-mentioned results were all P<0.01).</p><p><b>CONCLUSIONS</b>FgB beta Bcl-1A allele and variation genotype were susceptible to cerebral infarction. FgB beta-455GA/448G linkage genotype may contribute to the increased plasma Fg concentration. FgB beta-854 was one of the main controlling gene loci for plasma Fg concentration and molecular reactivity.</p>

Correlation between fibrinogen polymorphisms and the type of cerebral infarction / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the association of beta-fibrinogen(Fg) gene -148 C/T and 448 G/A polymorphisms, plasma Fg concentration, molecular reactivity and the type of cerebral infarction.</p><p><b>METHODS</b>Gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The plasma Fg concentration and the molecular reactivity were also determined.</p><p><b>RESULTS</b>The Fg concentration in MCI patients with T -148 allele was higher than that in PCI patients and controls. The MCI patients with A448 allele had higher Fg concentration, FMPV and FMPV/Amax when compared with controls, and had higher FMPV/Amax when compared with PCI patients.</p><p><b>CONCLUSION</b>FgB beta -148 and 448 mutational genotypes have impact on Fg concentrationì and therefore increase the risk of MCI.</p>