Expressions and Clinical Significance of Notch1 and Hes1 in Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expressions of Notch1 and Hes1 in diffuse large B-cell lymphoma (DLBCL), and their correlations with clinical features.@*METHODS@#Immunohistochemistry (IHC) was performed on DLBCL samples (54 cases) and lymphadenitis tissues (20 cases) to evaluate the expressions of Notch1 and Hes1, and analyze their correlations with clinical characteristics of patients. Based on Oncomine database, the expressions of Notch1 and Hes1 mRNA and DNA were also explored.@*RESULTS@#IHC result showed that the positive expression rates of Notch1 and Hes1 in DLBCL patients were significantly higher than those in the control group (P <0.05). In DLBCL patients, the expression of Notch1 was closely associated with B symptoms, Ann Arbor stage, lymphocyte count and the level of lactate dehydrogenase (P <0.05), while the expression level of Hes1 was significantly higher in patients with B symptoms (P <0.05). Notch+/Hes1+ expression was found in 21 DLBCL tissues (38.9%), and there was a correlation between Notch1 and Hes1 expression (r =0.296, P <0.05). Bioinformatics analysis (Oncomine database) showed that the mRNA expressions of Notch1 and Hes1 in the Brune dataset were significantly higher than those in the control tissues (P <0.05).@*CONCLUSION@#The expressions of Notch1 and Hes1 in DLBCL are significantly higher than those in lymphadenitis, and correlated with B symptoms and Ann Arbor stage, suggesting that Notch1 and Hes1 play important roles in the occurrence and development of DLBCL.

New eudesmane sesquiterpenoids from Atractylodis Macrocephalae Rhizoma and their inhibitory activities against SREBPs / 中国中药杂志

Three sesquiterpenoids were isolated and purified from the 95% ethanol extract of Atractylodis Macrocephalae Rhizoma by column chromatography on silica gel, Sephadex LH-20, ODS, and high-performance liquid chromatography(HPLC). Their chemical structures were identified on the basis of spectroscopic analysis and physiochemical properties as(7Z)-8β,13-diacetoxy-eudesma-4(15),7(11)-diene(1), 7-oxo-7,8-secoeudesma-4(15),11-dien-8-oic acid(2), and guai-10(14)-en-11-ol(3). Compounds 1 and 2 are new compounds and compound 3 was obtained from Compositae family for the first time. Compounds 1, 2, and 3 showed weak inhibitory activities against sterol regulatory element-binding proteins(SREBPs).

High-throughput screening of Saccharomyces cerevisiae efficiently producing tyrosine / 生物工程学报

Tyrosine is an important aromatic amino acid. Besides its nutritional value, tyrosine is also an important precursor for the synthesis of coumarins and flavonoids. Previously, our laboratory constructed a Saccharomyces cerevisiae strain LTH0 (ARO4K229L, ARO7G141S, Δaro10, Δzwf1, Δura3) where tyrosine feedback inhibition was released. In the present study, heterologous expression of betaxanthins synthesis genes DOD (from Mirabilis jalapa) and CYP76AD1 (from sugar beet B. vulgaris) in strain LTH0 enabled production of yellow fluorescence. The engineered strain LTH0-DOD-CYP76AD1 was subjected to UV combined with ARTP mutagenesis, followed by flow cytometry screening. Among the mutants screened, the fluorescence intensity of the mutant strain LTH2-5-DOD-CYP76AD1 at the excitation wavelength of 485 nm and emission wavelength of 505 nm was (5 941±435) AU/OD, which was 8.37 times higher than that of strain LTH0-DOD-CYP76AD1. Fourteen mutant strains were subjected to fermentation to evaluate their tyrosine producing ability. The highest extracellular tyrosine titer reached 26.8 mg/L, which was 3.96 times higher than that of strain LTH0-DOD-CYP76AD1. Heterologous expression of the tyrosine ammonia lyase FjTAL derived from Flavobacterium johnsoniae further increased the titer of coumaric acid to 119.8 mg/L, which was 1.02 times higher than that of the original strain LTH0-FjTAL.

Seroprevalence of IgM and IgG Antibodies against SARS-CoV-2 in Asymptomatic People in Wuhan: Data from a General Hospital Near South China Seafood Wholesale Market during March to April in 2020 / 生物医学与环境科学（英文）

The aim of this study was to estimate the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 in asymptomatic people in Wuhan. This was a cross-sectional study, which enrolled 18,712 asymptomatic participants from 154 work units in Wuhan. Pearson Chi-square test,

Antagonism of resveratrol on oxidative stress injury of follicular granulosa cells / 解剖学报

Objctive To investigate the protective effect of resveratrol on oxidative stress damage of follicular granulosa cells induced by hydrogen peroxide. Methods Granulosa cells were collected from the follicular fluid of in vitro fertilization(IVF) patients after oocyte retrieval and cultured. The cultured granulosa cells were divided into four groups: control group, injury model group, 10 μmol / L resveratrol group and 50 μmol / L resveratrol group. Cell viability was determined by CCK-8 assay, malondialdehyde(MDA) content by thiobarbituric(TBA) assay, superoxide dismutase(SOD) level by water soluble tetrazdium-1(WST-1) assay, apoptosis by AnnexinV-FITC / PI double-staining flow cytometry, Bcl-2 and Caspase-3 protein expression by Western blotting, and progesterone secretion by competitive ELISA. Resutls Compared with the control group, the cell viability, SOD level, Bcl-2 protein expression and progesterone secretion were significantly decreased in the injury model group, while MDA content, apoptosis rate and Caspase-3 apoptotic protein expression were significantly increased (P<0. 05) . Compared with the injury model group, the 10 μmol / L resveratrol group showed no statistically significant differences in various parameters; however, the cell viability, SOD level, progesterone secretion, and Bcl-2 and silent information regulator factor 2 related enzyme 1(SIRT1) protein expression were significantly increased, and the MDA content, apoptosis rate, and Caspase-3 apoptotic protein expression were significantly decreased in the 50 μmol / L resveratrol group (P < 0. 05) . Conclusion 50 μmol / L resveratrol can increase the activity of SIRT1, enhance the anti-oxidation and anti-apoptosis ability of granulosa cells and improve the function of granulosa cells.

Practice and exploration of fine and rational drug use management in hospital / 中华医院管理杂志

Under the background of deepening the medical and health system reform, it is necessary to explore the measures of fine and rational drug use management and strengthen the rational drug use. Through giving full play to the management functions of pharmacy administration and pharmacotherapeutics committee, formulating the performance evaluation index system of pharmacy affairs in the hospital, adhering to the prescription doctor′s advice review and prescription pre audit, continuing to carry out drug dynamic monitoring, implementing standardized-path antimicrobial drug management, the hospital implemented refined and rational drug use management. Before and after the management, the average drug cost, prescription unqualified rate, auxiliary drug amount and antibacterial drugs related indicators were significantly improved, suggesting that fine pharmacy management could promote the rational use of drugs in the whole hospital, promote the transformation of pharmacists′ work, and control the unreasonable growth of drug costs.

Predictive value of laboratory tests on severity of newly hospitalized patients with COVID-19 / 中华检验医学杂志

Objective:To analyze the laboratory tests in newly hospitalized patients with COVID-19　and their predictive values for the severity of the disease.Methods:83 patients, including 54 males and 29 females, with median interquartile range of 63(53-70)years diagnosed with covid-19　who were managed by Fujian medical team from January 27, 2020 to February 20, 2020 in Wuhan JinYinTan Hospital were studied retrospectively. According to the severity of the disease, they were divided into common, severe and critical groups. White blood cell (WBC), lymphocyte (LYM), loctate dehydrogenase (LDH), interleukin-6 (IL-6), procalcitonin (PCT), serum ferritin (SF), erythrocyte sedimentation rate (ESR), hypersensitive C-reactive protein (hs-CRP) and D-Dimer (D-D) on admission were analyzed retrospectively. And the predictive value of each indicator for critical group was analyzed by Logistic regression.Results:On admission, in common, severe and critical groups, WBC (×10 9/L) values were 7.10±3.88, 7.73±3.77 and 9.07±5.61, respectively ( F = 1.315, P=0.274); IL-6　(μg/L) values were 11.76(9.42-15.18), 11.93(10.15-15.63) and 11.24(8.06-13.75), respectively( Z=0.591, P=0.744);D-D (mg/L) values were 0.70(0.48-1.12), 1.67(1.07-7.14) and 1.96(0.71-8.18), respectively( Z=3.363, P=0.186).There were no significant differences among three groups. On admission, in common, severe and critical groups, LYM(×10 9/L) values were 1.10±0.33, 0.80±0.35 and 0.66±0.32, respectively( F=11.415, P<0.001); SF(μg/L) values were 470.83±283.43, 835.66±819.43, and 1341.15±949.54, respectively ( F=7.98, P=0.001); ESR(mm/h) values were 30.76±15.70, 42.55±22.51 and 51.04±25.09, respectively( F=5.181, P=0.008); LDH(U/L) values were 314.71±105.46, 325.69±109.85 and 444.03±181.07, respectively( F=7.17, P=0.001); hs-CRP(μg/L)values were 16(7.20-19.90), 31.00(20.00-87.60) and 80.50(33.70-113.00), respectively( Z=12.185, P=0.002);PCT(μg/L) values were 0.025(0.02-0.05), 0.05(0.02-0.13) and 0.09(0.05-0.39), respectively( Z=9.694, P=0.008). There were significant differences among three groups. Pairwise comparison showed that the LYM value in common group was higher than those in severe and critical groups, and the hs-CRP values in severe and critical groups were higher than that in common group,while SF, ESR, LDH and PCT values in critical group were all higher than those in severe and common groups( P<0.05). Conclusions:On admission, WBC, LYM, ESR and LDH are helpful to predict the severity of COVID-19. Although the level of IL-6 is increased, it may not be meaningful to judge the severity of COVID-19.

Construction of a highly efficient synthetic lycopene engineered Saccharomyces cerevisiae / 生物工程学报

Lycopene, as a high value-added terpene compound, has been widely concerned by researchers at home and abroad. Firstly, the ability of lycopene synthesis of Saccharomyces cerevisiae model strains S288c and YPH499 was analyzed and compared. The results showed that YPH499 was more suitable for lycopene synthesis as yeast chassis. Subsequently, the effects of constitutive promoters GPDpr, TEF1pr and inducible promoters GAL1pr, GAL10pr on Lycopene synthesis were compared. The results showed that when GPDpr and TEF1pr were used as promoters of crtE, crtB and crtI in lycopene synthesis pathway, the production of lycopene was 15.31 mg/L after 60 h fermentation in shaking flask. When GAL1pr and GAL10pr were used as promoters, the production was 123.89 mg/L, which was 8.09 times higher. In addition, the methylvaleric acid (MVA) pathway was further modified to overexpress the key enzyme gene of N-terminal truncation, tHMG1 (3-hydroxy-3-methylglutaryl coenzyme A reductase). The lycopene production was 265.68 mg/L, and the yield per cell was 72.79 mg/g. The Saccharomyces cerevisiae strain designed and constructed in this study can express lycopene in high yield per cell, thus could be used in the industrial production of lycopene after further construction and optimization.

The protective effect of water-soluble proteins from selenium-enriched Bifidobacterium longum on lipopolysaccharide-induced injury in rat IEC6 cells / 中国药理学通报

To investigate the protective effect of selenium-enriched Bifidobacterium longum preparation on rat IEC6 cells via the application of lipopolysaccharide (LPS)-induced IEC6 cell injury model. Methods The experiment was divided into five groups; negative control group treated with phosphoric acid equilibrium salt solution, model group treated with LPS, and low, medium, high concentration group in which IEC6 cells were treated with LPS plus 10, 30, 100 mg • L"1 water-soluble proteins from selenium-enriched Bifidobacterium longum respectively. After treatment with LPS for 24 hours, IEC6 cell viability, apoptosis, mitochondria membrane potential, and the expression of zonula occludens 1 (ZO-1) and Occludin were detected. Results LPS induced rat intestinal epithelial cell damage, such as the decrease of cell viability, the increase of cell apoptosis, the collapse of mitochondria membrane potential, and the decrease of cell tight junction protein expression. Water-soluble proteins from selenium-enriched Bifidobacterium longum inhibited LPS-induced IEC6 cell damage, decreased cell apoptosis and increased cell tight junction between cells. Conclusion Water-soluble proteins from selenium-enriched Bifidobacterium longum have protective effect on LPS-induced rat intestinal epithelial cell injury.

5, 7, 2', 4', 5'-Pentamethoxyflavanone regulates M1/M2 macrophage phenotype and protects the septic mice / 中国天然药物

Flavonoids have been reported to exert protective effect against many inflammatory diseases, while the underlying cellular mechanisms are still not completely known. In the present study, we explored the anti-inflammation activity of 5, 7, 2', 4', 5'-pentamethoxyflavanone (abbreviated as Pen.), a kind of polymethoxylated flavonoid, both in vitro and in vivo experiments. Pen. was showed no obvious toxicity in macrophages even at high dosage treatment. Our results indicated that Pen. significantly inhibited both mRNA and protein level of proinflammatory cytokines, IL-1β, IL-6, TNF-α and iNOS, which was characteristic expressed on M1 polarized macrophages. These effects of Pen. were further confirmed by diminished expression of CD11c, the M1 macrophage surface marker. Further researches showed that the mechanism was due to that Pen. downregulated the activity of p65, key transcription factor for M1 polarization. On the other hand, Pen. also enhanced M2 polarization with upregulation of anti-inflammatory factors and increase of M2 macrophage surface markers, which lead to the balance of M1 and M2 macrophages. Moreover, in vivo research verified that Pen. treatment alleviated LPS-induced sepsis in mice by increasing survival rate, decreasing inflammatory cytokines and improving lung tissue damage. In summary, our results suggested that Pen. modulated macrophage phenotype via suppressing p65 signal pathway to exert the anti-inflammation activity.

Quantitative effect of the expression level of key genes in naringenin synthesis on the accumulation level of target products / 生物工程学报

Naringenin is a natural flavonoid compound with anti-inflammatory, anti-oxidation, anti-viral, anti-atherosclerosis and other pharmacological activities. It is also an important precursor of other flavonoid synthesis and with great value of application. At present, the production of flavonoids such as naringenin by microbial methods has a low yield due to imbalance of metabolic pathways, which greatly limits its industrial application. In this study, a naringenin-producing strain of Saccharomyces cerevisiae Y-01 was used in the research object. The expression levels of 4-coumaric acid: CoA ligase (4CL), chalcone synthase (CHS) and chalcone isomerase (CHI) were controlled by promoter and copy numbers to investigate the quantitative effect of key enzyme expression level on the accumulation level of target products. The results showed that the correlation between naringenin production and 4CL or CHI expression was not significant while there was a positive correlation with the expression level of CHS. Strain Y-04 with high yield of naringenin was obtained by regulating the expression level of chs gene, and the yield was increased by 4.1-folds compared with the original strain Y-01. This study indicated that CHS is a key regulatory target of naringenin synthesis. Rational regulation of CHS expression can significantly promote the accumulation of naringenin. The related results provide an important theoretical reference for the use of metabolic engineering to strengthen microbial synthesis of important flavonoids such as naringenin.

Development and verification of an FLP/FRT system for gene editing in Bacillus licheniformis / 生物工程学报

Few tools of gene editing have been developed in Bacillus licheniformis at present. In order to enrich the tools, an FLP/FRT gene editing system that can repeatedly use a single selectable marker was constructed in Bacillus licheniformis, and the system was verified by knocking out an alpha amylase gene (amyL), an protease gene (aprE) and knocking in an exogenous Vitreoscilla hemoglobin gene (vgb). First, knock-out plasmids pNZTT-AFKF of amyL and pNZTT-EFKF of aprE were constructed using thermosensitive plasmid pNZT1 as a carrier. The two knock-out plasmids contained respective homology arms, resistance genes and FRT sites. Then the knock-out plasmids were transformed into Bacillus licheniformis and the target genes were replaced by respective deletion cassette via twice homologous exchange. Finally, an expression plasmid containing FLP recombinase reading frane was introduced and mediated the excision of resistance marker. In order to expand the practicability of the system, knock-in plasmid pNZTK-PFTF-vgb was constructed, with which knock-in of vgb at pflB site was carried out successfully. The results showed that amyL and aprE were successfully knocked out and the marker kanamycin cassette exactly excised. The activities of amylase and protease of deletion mutants were reduced by 95.3% and 80.4% respectively. vgb was successfully knocked in at pflB site and the marker tetracycline cassette excised. The expression of integrated vgb was verified via real-time PCR. It is the first time to construct an FLP/FRT system for gene editing in Bacillus licheniformis, which could provide an effective technical means for genetic modification.

Clinical analysis of occupational acute toxic nephropathy by dimethyl oxalate / 中国职业医学

OBJECTIVE: To investigate the clinical features and treatment methods of occupational acute dimethyl oxalate(DMO) toxic nephropathy. METHODS: Occupational history,clinical manifestation,laboratory examination and therapy of one occupational DMO poisoning case were retrospectively analyzed. RESULTS: The patient was exposed to a large amount of DMO in a short time,with the main symptoms of dizziness,fatigue,nausea,vomiting,bloating,and oliguria.Glomerular filtration reduced after 48 hours of disease onset,serum urea nitrogen was 21. 9 mmol/L and serum creatinine was 788 μmol/L. Renal biopsy showed glomerular mesangial proliferative lesions,tubulointerstitial lesions,small arterial intima thickening and hyaline degeneration. Early treatment,including hemodialysis,hemoperfusion,hormone shock therapy,protection of myocardium,renal function,and improvement of circulation achieved a good clinical prognosis.CONCLUSION: The main clinical manifestation of acute DMO poisoning is acute kidney injury. Blood purification treatment and hormone shock therapy should be used early.

Effect of Zuotai and HgS on gene expression of drug-metabolizing enzymes in livers of mice / 中国中药杂志

Zuotai and cinnabar(96%HgS) are contained in many traditional medicines. To examine their potential effects on drug metabolism genes, mice were orally given Zuotai or HgS at doses of 10, 30, 100, 300 mg•kg⁻¹ for 7 days. HgCl2(33.6 mg•kg⁻¹) was gavaged for control. Twenty-four hour later after the last administration, livers were collected, and expressions of genes related to metabolic enzymes and transporters were examined. Zuotai and HgS had no effects on major phase-1, phase-2 and transporter genes; HgCl2 increased the expressions of CYP2B10, CYP4A10, OATP1A4, UGT1A1, UGT2A3, SULT1A1, SULT2A1, MRP1, MRP3 and MRP4; expression of OATP1A1 was decreased by HgCl2, but not by Zuotai and HgS. Therefore, Zuotai and HgS have different adverse effects on drug-metabolizing genes from HgCl2.

Ethical Analysis of Medical Purpose and Non-medical Purpose Gene Enhancement / 中国医学伦理学

As a kind of new technology, ethical issues are inevitable in medical and non-medical gene en-hancement application. It is unrealistic to unilaterally support or object to the research and application of medical and non -medical gene enhancement. Based on standardizing the ethical principle of gene enhancement tech-niques, we should build management measures of the research, development and application that adapted to ethi-cal, social and legal standards, so that we can draw on the advantages and avoid the disadvantages, and use gene enhancement reasonably and bring benefits to mankind and society.

MicroRNAs and signal transducers and activators of transcription / 第二军医大学学报

MicroRNAs (miRNAs) are important gene expression regulators and are involved in a variety of pathogeneses such as cancers and autoimmune diseases. Signal transducers and activators of transcription (STAT), the principle signaling proteins of many cytokines and growth factors, play significant roles in regulating immune cell homeostasis, cell differentiation and cell functions. In this review we discussed the recent advances in interactions between STATs and miRs, with focus on their interaction during the promotion and inhibition of immue cells and tumor cells. MiR-STAT interaction is still a new area of study, and more effort is needed to elucidate miR-STAT mechanisms.

Imaging and clinical characteristics of Marchiafava-Bignami disease: six cases / 中华神经科杂志

Objective To investigate the presentation and radiologic findings of MarchiafavaBignami disease (MBD).Methods Six cases of MBD who were diagnosed and treated in our hospital were retrospectively analyzed,including the imaging examination(such as cranial CT,magnetic resonance imaging (MRI)),laboratory tests,clinical symptoms and prognosis.Results Six cases of MBD disease were presented with swelled,thickened corpus callosum,iso-or hypo-intensity on T1WI,hyper-intensity on T2WI and fluid attenuated inversion recovery and restricted diffusion on diffusion weighted imaging.Coma of acute onset was the major clinical finding in case 1,case 4 and case 6,which showed the lesions in the entire corpus callosum and extended to the white matter,and the prognosis of these cases were worse.Slow reaction and memory decrease were the clinical findings in case 2 and case 3,which showed the genu and splenium of corpus callosum involvement on MRI and CT,and returned to normal with aggressive treatment.Numbness and weakness of the lower lambs were the major clinical finding in case 5,which showed that the lesion was limited in the splenium and body of corpus callosum on MRI.The patient recovered after treatment.Conclusions MBD may present with various clinical forms,but have characteristic imaging findings.Outset form and neuroimaging characteristics of MBD are critical for improvement of the clinical outcome.

Expression of extracellular matrix metalloproteinase inducer in the unstable plaque of patients with acute coronary syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the unstable plaque of patients with acute coronary syndrome (ACS), and the impact of leukotriene B4 (LTB4) on the EMMPRIN expression in macrophages.</p><p><b>METHODS</b>The EMMPRIN expression was detected by immunohistochemistry in 11 unstable plaques from patients with ACS. Protein expression of EMMPRIN was evaluated by Western blot on macrophages differentiated from THP-1 which were stimulated with LTB4 in the absence or presence of LTB4 antagonist U75302. There are 8 study groups: 1-THP-1, 2-8-the macrophages derived from THP-1, 2-6-macrophages were stimulated by LTB4 (0, 10(-10), 10(-9), 10(-8) and 10(-7) mol/L) for 24 h, 7-8-the macrophages were pretreated by 10(-6) mol/L or 10(-7) mol/L U75302 2 h before the LTB4 (10(-7) mol/L) stimulation.</p><p><b>RESULTS</b>Abundant EMMPRIN expression was detected in macrophages and smooth muscle cells of unstable plaques from ACS patients. As to the THP-1 derived macrophages, EMMPRIN expression was significantly upregulated in a concentration-dependent manner in LTB4 stimulated groups, which was significantly higher in group 3-6 than in the THP-1 group (group 1) and macrophages group (group 2) (all P < 0.05) and pretreatment with U75302 significantly reduced the LTB4 induced upregulation of EMMPRIN in a dose-dependent manner (P < 0.05).</p><p><b>CONCLUSION</b>EMMPRIN expression is enhanced in macrophages and smooth muscle cells on unstable coronary artery plaques from ACS patients. LTB4 could stimulate EMMPRIN expression on THP-1 derived macrophages suggesting that LTB4 and EMMPRIN might be both involved in the formation and progression of unstable plaques, future studies are warranted to explore if LTB4 and EMMPRIN antagonists are effective or not for treating patients with ACS.</p>

Analysis of the hypertension dangerous factor in Wuhan male taxi drivers / 中华健康管理学杂志

Objective Discbuss the hypertension prevalence rate in the Wuhan male taxi drivers and the dangerous factor to provide the basis for its professional publie health work. Methods The Wuhan male taxi drivers were carried on the healthy physical examination who in the Hubei province medicine medical examination center during 2005-2007 and were carried on the epidemiology statistical analysis. Results The Wuhan male taxi drivers hypertension prevalence rate is 28.28%. That is higher than the common crowd. Hypertension leaves outside the heredity factor and be closely correlated with the age of harnesses, the body weight index, and so on. Conclusions The Wuhan male taxi drivers'hypertension prevalence rate is unoptimistic. We should take the synthesis preventing and controlling measure to reduce this crowd hypertension prevalence rate.

The Effect of Health Education on the Blood Glucose Controlling Target in Patients with Type 2 Diabetes Mellitus / 中国慢性病预防与控制

Objective To explore the effect of health education on the blood glucose controlling target in patients with type 2 diabetes. Methods 598 cases of patients with type 2 diabetes were randomly divided into the control group (given conventional treat- ment and medication guide) and the intervention group (besides the above-mentioned treatment, also given diabetes health management program including the systemic health education and promotion, and with stress on behavioral, psychological, dietary intervention) and observed for 7 months. Results After 7 months intervention, there were differences in the levels of glycosylated hemoglobin, fasting plasma glucose and 2h postprandial blood glucose between two groups (P