Chronic spontaneous urticaria: therapeutic mechanism of omalizumab and assessment of its clinical efficacy / 中华皮肤科杂志

Chronic spontaneous urticaria (CSU) is characterized by recurrent wheals with severe itching, and greatly affects the life quality of patients. The European guideline on chronic urticaria recommends the anti-IgE monoclonal antibody omalizumab as the only third-line therapy for patients with CSU whose condition can not be controlled by high doses of antihistamines. Although a lot of researches have shown that omalizumab is effective and safe for the treatment of CSU, its therapeutic mechanisms have not yet been fully elucidated. This review summarizes therapeutic mechanisms of omalizumab in the treatment of CSU, and indices for predicting and monitoring its clinical efficacy.

Chronic spontaneous urticaria: therapeutic mechanism of omalizumab and assessment of its clinical efficacy / 中华皮肤科杂志

Chronic spontaneous urticaria (CSU) is characterized by recurrent wheals with severe itching,and greatly affects the life quality of patients.The European guideline on chronic urticaria recommends the anti-IgE monoclonal antibody omalizumab as the only third-line therapy for patients with CSU whose condition can not be controlled by high doses of antihistamines.Although a lot of researches have shown that omalizumab is effective and safe for the treatment of CSU,its therapeutic mechanisms have not yet been fully elucidated.This review summarizes therapeutic mechanisms of omalizumab in the treatment of CSU,and indices for predicting and monitoring its clinical efficacy.

Sleep quality in preschool children in three provinces along the middle and lower reaches of the Yangtze River / 中国学校卫生

Objective@#To analyze the detection rate of sleep problems such as sleep delay and deficiency in preschool children in the middle and lower reaches of the Yangtze River in China,and to provide the reference for the standard of sleeping mode among preschool students.@*Methods@#From October to November 2017, a questionnaire survey was conducted among 27 200 preschool children in 11 cities in Hubei, Anhui and Jiangsu provinces in the middle and lower reaches of the Yangtze River in China. Epidemiology of sleep delays, deficiencies and sleep patterns in preschool children was described.@*Results@#The detection rate of sleep problems in preschool children in the middle and lower reaches of the Yangtze River was 15.3%. Taking the length of sleep and bedtime as the main analysis points, it was found that the average sleeping time point of each age group was 21:31, and the detection rate of bedtime delay was 86.5%. The average length of sleep was (10.60±1.12) hours. The detection rate of sleep deprivation in preschool children was 15.7%. Sleep delay was positively correlated with girls, age increase and parents’ higher educational level (P<0.05), and negatively correlated with living in the city, non-only child and bedroom without TV (P<0.01) .The detection rate of sleep deprivation was positively correlated with children of high age group (4yearold group：OR=1.32，95%CI=1.19-1.46；5-year-old group：OR=2.10，95%CI=1.91-2.32；6-year-old group：OR=2.47，95%CI=2.20-2.77)(P<0.01), and negatively correlated with no TV in bedroom (OR=0.91，95%CI=0.84-0.98) and no light in sleep (OR=0.87，95%CI=0.78-0.97)(P<0.05).@*Conclusion@#Preschool children sleep delay and sleep deprivation and other sleep problems are more prominent, affected by family environment and other factors.

Determination of six alkaloids in six types of Coptidis Rhizoma pieces by RP-HPLC and spectrum-effect relationships with anti-diabetes pharmacodynamics data / 中国中药杂志

To establish a method for determining the contents of six alkaloids (jatrorrhizine hydrochloride, columbamine hydrochloride, epiberberine hydrochloride, coptisine hydrochloride, palmatine hydrochloride, berberine hydrochloride) in six types of Coptidis Rhizoma pieces (crude pieces, ginger juice stir-fried pieces, vinegar stir-fried pieces, wine steamed pieces, wine stir-fried pieces, evodiae juice stir-fried pieces) by RP-HPLC, and explore the relationship with the curative effect of traditional Chinese medicine (TCM) and pharmacodynamics results. The chromatographic column was Welch XtimateTM C₁₈ (4.6 mm×250 mm, 5 μm), with 0.1% triethylamine solution (adjust pH at 10 with ammonium bicarbonate and ammonia) as mobile phase A and acetonitrile as mobile phase B for gradient elution (0-15 min, 10%-25%B; 15-25 min, 25%-30%B; 25-40 min, 30%-45%B) at a rate of 1.0 mL•min⁻¹. The column temperature was set at 30 ℃, and the wavelength was set at 270 nm. The six alkaloids showed a good linear relationship within the range of 0.85-16.96 mg•L⁻¹ (r=0.999 7), 1.25-24.96 mg•L⁻¹ (r=0.999 9), 2.05-40.96 mg•L⁻¹ (r=0.999 9), 3.65-72.96 mg•L⁻¹ (r=0.999 9), 2.88-57.60 mg•L⁻¹ (r=0.999 8), and 13.25-264.96 mg•L⁻¹ (r=0.999 6) respectively. The average recoveries (n=9) of the six alkaloids were 102.4% (RSD 1.2%), 101.8% (RSD 1.3%), 100.3% (RSD 1.8%), 100.7%(RSD 1.8%), 101.2% (RSD 1.5%) and 97.90% (RSD 2.0%) respectively, and their average contents were 3.55, 4.49, 9.12, 19.17, 15.69, 62.56 mg•g⁻¹, respectively. This determination method was accurate and repeatable, which could be used for the content determination in six types of Coptidis Rhizoma pieces. Data analysis on contents determination and preliminary pharmacodynamics results was conducted by using principal component analysis (PCA) and hierarchical clustering analysis (HCA). The analysis results showed that three types of Coptidis Rhizoma pieces (wine steamed pieces, wine stir-fried pieces, and evodiae juice stir-fried pieces) had significant differences with crude pieces, and the wine steamed Coptidis Rhizoma pieces showed most difference with crude pieces especially, mainly related to triglyceride (TG) and fasting blood glucose levels (FBG) in serum. In addition, columbamine hydrochloride was most affected among the six alkaloids. Those three types of Coptidis Rhizoma pieces (wine steamed pieces, wine stir-fried pieces, and evodiae juice stir-fried pieces), had more advantages for "anti-diabetes" in TCM clinical application, especially in the treatment of diabetic hyperlipidemia.

Regulation of miR-1 and miR-133 a on L-type calcium channel Cavβ2 and α1C subunits in rat cardiomyocyte hypertrophy / 基础医学与临床

Objective To investigate the regulation of miR-1 and miR-133 a on L-type calcium channel β2 subunit ( Cavβ2 ) and α1C subunit during rat cardiomyocyte hypertrophy .Methods Cardiomyocyte hypertrophy was in-duced by isoproterenol (ISO, 10μmol/L).The targets of miR-1 and miR-133a were predicted by online database microCosm and Targetscan , respectively .The 3′untranslated region sequences of Cavβ2 andα1C were respectively cloned into reporter vector and then transiently transfected into HEK 293 cells.The luciferase activities of samples were measured for demonstrating the expression of luciferase reporter vector .The protein expression of Cavβ2 andα1C were evaluated by Western blot .The expression levels of Cavβ2 andα1C were inhibited by RNAi to determine theeffectsofCavβ2andα1Concardiomyocytehypertrophy.Results 1)Cavβ2wasoneofpotentialtargetsof miR-1,α1C was the one of potential targets of miR-133a.2) The luciferase activities of HEK293 cells with the plasmid containing widetype Cavβ2 3′UTR sequence or α1 C significantly decreased ( P <0.05 , P <0.01 ) . 3 ) Upregulation of the miR-1 and miR-133 a by miR-1 mimic and miR-133 a mimic transfection suppressed pro-tein expression of Cavβ2 and α1C, respectively(P<0.01, P<0.05).4)Downregulation of Cavβ2 andα1C by RNAi could markedly inhibit the increase of cell surface area ( P<0.01 ) , mRNA expression of ANP andβ-MHC (P<0.05).Conclusions Cavβ2 is the target gene of miR-1 and α1C is the target gene of miR-133a.miR-1 and miR-133a can negatively regulate the expression of L-type calcium channel Cavβ2 andα1C subunit, inhibi-ting cardiomyocyte hypertrophy.

Anti-tumor effect of Sendai virus Tianjin strain defective interfering particles on tumor-bearing mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the anti-tumor effect and its mechanism of Sendai virus Tianjin strain defective interfering particles (DIP) on mouse models of colon carcinoma.</p><p><b>METHODS</b>CT26 cells (5×10(6)/0.1 ml) were subcutaneously injected into the back of Bal B/c mice to establish murine colon carcinoma model. After the tumors reached 5 mm in diameter, the mice were randomly divided into Tianjin strain DIP group and saline control group. The former was intratumorally injected with Tianjin strain DIP (0.1 ml) once a day on day 4, 7, 10 and 13 after CT26 cell inoculation. The latter was intratumorally injected with the same volume of saline. Tumor volume and survival rate of the mice were calculated to confirm the anti-tumor effect of DIP. Flow cytometry and ELISA were used to examine the maturation and release of cytokines IL-6, IFN-α and TNF-α from murine myeloid dendritic cells (DCs) induced by Tianjin strain DIP. Moreover, real-time RT-PCR and immunohistochemistry were performed to identify whether the Tianjin strain DIP could induce infiltration of CD11c(+) DCs, CD4(+) and CD8(+) T cells in the tumors.</p><p><b>RESULTS</b>On day 22 after CT26 cell inoculation, the average tumor volume of the Tianjin strain DIP group was (33.2 ± 2.0) mm(3), significantly smaller than that of the control group [(2 376.0 ± 130.8)mm(3), P < 0.01]. On day 50 after CT26 cell inoculation, the survival rate of mice was 90.0% in the Tianjin strain DIP group, much higher than that of the control group (30.0%, P < 0.01). Flow cytometry analysis showed that the expression of markers of DCs maturation, including CD40, CD80 and CD86, was dose-dependently increased by DIP or intact virus. No statistically significant difference was found betweent the DIP and intact virus groups. ELISA results showed that DIP could stimulate the secretion of IL-6, IFN-α and TNF-α from mouse DCs. The secretion of all of the cytokines was dose-dependently increased by DIP or intact virus. Real-time RT-PCR revealed that the expression of CD4, CD8 and CD11c mRNAs was increased in tumors treated with DIP compared with that of the saline group at all time points. Moreover, the expression level of all of them remained maximal at 120 h after the last treatment. Immunohistochemical staining revealed that the ratios of CD4(+), CD8(+) T cells or CD11c(+) DCs to total cells were (21.60 ± 1.49)%, (22.12 ± 2.84)% and (23.05 ± 2.91)%, respectively, in the DIP-treated tumors. In the tumors treated by saline, the ratios were (2.62 ± 0.60)%, (4.05 ± 0.12)% and (3.10 ± 0.09)%, respectively. The difference between experimental group and control group had statistical significance.</p><p><b>CONCLUSIONS</b>Tianjin strain DIP may exert anti-tumor effect on tumor-bearing mice. The mechanism is related with the antitumor immunity induced by DCs and T cells.</p>

Clinical observation on the treatment of locally advanced cervical cancer by recombinant human adenovirus-p53 combined with neoadjuvant chemotherapy / 肿瘤研究与临床

Objective To evaluate the efficacy and safety of recombinant adenovirus-p53 (rhAd-p53) combined with neoadjuvant chemotherapy in treatment of locally advanced cervical cancer.Methods Forty patients with stage Ⅰ R2-Ⅲ A locally advanced cervical cancer were randomly divided into 2 groups,gene therapy + neoadjuvant chemotherapy group (rhAd-p53+PVB group,n =20.They received one course of chemotherapy consisting of PVB.rhAd-p53 solution 1 ×1012 VP was injected intratumorally every three days for three circles since the 3rd day of PVB chemotherapy) and chemotherapy group (PVB group,n=20,the above course of chemotherapy was conducted).The volums of tumors was observed.Patients were monitored for adverse event.The expression of VEGF,p53 pertein and MVD in tumor tissue was detected by immunohistochemistry.Results The evaluation was performed three weeks after the completion of chemotherapy.The PVB group response rate (CR+PR) was 75 ％,while the effective rate was 95 ％ of the PVB combined with gene group.After using of the PVB chemotherapy,the tumor was shrunk by (11.42±2.78) cm2.However,the volums of tumor were significantly shrunk by (15.25±4.00) cm2 using the PVB combined with gene therapy,and P ＜ 0.05.The positive expression rate of VEGF,p53 protein and MVD were reduced respectively in PVB group and rhAd-p53 + PVB group with statistic significance.There were no additional adverse events by recombinant adenovirus-p53 combined with neoadjuvant chemotherapy.Conclusion A potentially gene therapeutic agent for cervical cancer treatment,intratumoral injection of rhAd-p53 is effective.

Effects of microRNA-1 on negatively regulating L-type calcium channel beta2 subunit gene expression during cardiac hypertrophy / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the negative regulation of microRNA-1 (miR-1) on L-type calcium channel beta2 subunit (Cavbeta 2) during cardiomyocyte hypertrophy and its mechanism.</p><p><b>METHODS</b>Cardiomyocyte hypertrophy was induced by isoproterenol (ISO). The cell surface area was measured by image analysis system (HJ2000). The targets of miR-1 were predicted by online database microCosm. The 3' untranslated region sequence of Cavbeta 2 was cloned into luciferase reporter vector and then transiently transfected into HEK293 cells. The luciferase activities of samples were measured to verify the expression of luciferase reporter vector. The expression of atrial natriuretic peptide (ANP), beta-myosin heavy chain (beta-MHC), miR-1 and the Cavbeta 2 mRNA were detected by qRT-PCR. The protein expression of Cavbeta 2 was detected by Western blot. The level of miR-1 was up-regulated by miR-1 mimic transfection and the expression level of Cavbeta 2 was down-regulated by RNAi, then effects of which on cardiomyocyte hypertrophy were investigated.</p><p><b>RESULTS</b>(1) The expression of miR-1 was significantly reduced in cardiomyocyte hypertrophy. Upregulating the miR-1 level could suppress the increase of cell surface area, the expression of ANP and beta-MHC mRNA (P < 0.05). (2) Cavbeta 2 was the one of potential targets of miR-1 by prediction using online database microCosm. The luciferase activities of HEK293 cells with the plasmid containing miR-1 and wide type Cavbeta 3' UTR sequence was significantly decreased when compared with that of control group (P < 0.01). Up-regulation of the miR-1 level could suppress the protein expression of Cavbeta 2. (3) The expression of Cavbeta 2 was significantly increased in cardiomyocyte hypertrophy induced by ISO. Downregulation of Cavbeta by RNAi could markedly inhibit the increase of cell surface area, the expression of ANP and beta-MHC mRNA.</p><p><b>CONCLUSION</b>Cavbeta2 is one of potential targets of miR-1 by bioinformatics prediction. The experiment data confirms that Cavbeta2 is truly the target of miR-1. MiR-1 can negatively regulate the expression of Cavbeta 2, resulting in the decrease of intracellular Ca2+ content and the attenuation of cardiomyocyte hypertrophy.</p>

The effect of Crocin against hypoxia damage of myocardial cell and its mechanism / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of Crocin against hypoxia damage of cardiac myocytes of neonatal rats and the regulation of HIF-1 and prolyhydroxylase (PHDs).</p><p><b>METHODS</b>A model of CoCl2 simulated hypoxia damage was established in primary cultural myocardial cell. Expression levels of HIF-1alpha, VEGF, iNOS, as well as PHD1, 2, 3 protein in myocardial cells were detected by Western blot.</p><p><b>RESULTS</b>Compared with CoCl2 group, the viability of myocardial cell was significantly increased after treated 24 h at 10(-5)mol/L Crocin (P < 0.01), HIF-1alpha, VEGF and iNOS were expressed higher than those in Crocin + CoCl2 group (P < 0.01), the expression of PHD2 was significantly increased (P < 0.01), while the expression of PHD3 was remarkably reduced in Crocin + CoCl2 Group (P < 0.01).</p><p><b>CONCLUSION</b>Crocin has better protective effect on hypoxic damage of myocardial cell. The mechanisms of protective effect of Crocin may be related to the activation of HIF-1-mediated pathway of the hypoxia response. PHDs may be involved in the pathophysiology regulated process of myocardial cells.</p>

A novel strain ZG0656 producing alpha-amylase inhibitor and fermentation, separation, properties, and application of its products / 生物工程学报

A strain ZG0656 producing a-amylase inhibitor was isolated from soil in this study. Polyphasic taxonomic studies were performed, including appearance characteristics, culture characteristics, phenotypic characteristics, cell walls chemical composition, nearly complete 16S rDNA sequence alignment with those of representative Streptomyces species. These results revealed that strain ZG0656 represents a novel variation of Streptomyces coelicoflavus, for which we propose the name S. coelicoflavus var. nankaiensis. After fermentation in a 10 L fermentor, alpha-amylase inhibitors were accumulated in the harvested broth of strain ZG0656. The alpha-amylase inhibitors we obtained were identified as aminooligosaccharides after concentration, resin-adsorption, gel-filtration, and desiccation. They could intensively inhibit alpha-amylase, depress postprandial blood glucose elevation obviously. Thus, the a-amylase inhibitors are expected to act as drugs or functional food against diabetes.

Determination of 1-deoxynojirimycin from mulberry resources and analysis of their bioactivities / 中草药

Objective To determine 1-deoxynojirimycin(DNJ) from mulberry resources and analyse their bioactivities.Methods Determination of DNJ by derivatization with 9-fluorenylmethyl chloroformate(FMOC-Cl) and followed by reversed-phase high-performance liquid chromatography(RP-HPLC) and a fluorescence detector;the inhibitory curves on ?glucosidase at the enzymatic level and the activities to(?-)glucosidase in vitro were observed in the everted sac experiment.Results A reliable quantitative method suitable for assays of DNJ from mulberry resources has been developed.The inhibitory curves of the extracts on ?-glucosidase were parallel to those of DNJ.The extracts can inhibit hydrolyzation of starch and absorption of glucose.Conclusion The medicinal parts from mulberry resources can be used for diabetic therapy as ?-glucosidase inhibitor.

Preliminary Study on Molluscicidal Effect of Active Components from Centipeda minima / 中国寄生虫学与寄生虫病杂志

The active components from Centipeda minima were extracted by water or ethanol, and identified by FTIR spectroscopy and UV-visible spectrophotometer. The molluscicidal effect of aqueous extract and ethanol extract from Centipeda minima against Oncomelania hupensis was determined as referring to the WHO guidelines for laboratory molluscicidal test. Treated with over 2.0 g/L aqueous extract and ethanol extract for five days, the mortality of O. hupensis was up to 100%, and their LC50 for snails was 0.50 g/L and 0.62 g/L, respectively. The molluscicidal activity of aqueous extract was higher than that of ethanol extract. The main components of aqueous extract and ethanol extract were sesquiterpens lactones and sterols.