1.Research progress in antisense drug mechanism and chemical modification strategies
Lei LI ; Yi-xuan ZHENG ; Chun-ying MA ; Wen-hua FENG
Acta Pharmaceutica Sinica 2022;57(9):2709-2719
Over the past three decades, more and more antisense drugs have been approved for marketing or clinical trails. Antisense technology has become the focus of pharmaceutical research due to its unique advantages in treating diseases and strong clinical development potential. There is a big difference from traditional small molecule chemical drugs, and macromolecular protein biological drugs. Antisense drugs are a very independent drug form. Antisense drugs were initially used to treat diseases with single gene mutations, but recently they have gradually begun to be used for the treatment of common diseases. Rational antisense drug design is crucial for disease treatment based on genetics. This paper reviews the latest progress in the field of action mechanism, chemical modification and delivery strategy of antisense drugs, and analyzes the current intractable problems. It is believed that with the resolution of these problems, the research of antisense drugs can reach a new level.
2.Comparative Study of the Effects of Application at Different Acupoints on the Quality of Life in Allergic Rhinitis Patients Based on Treating
yang Zheng ZHU ; ming Kai QI ; hua Li XUAN
Shanghai Journal of Acupuncture and Moxibustion 2017;36(12):1396-1400
Objective To observe the effects of application at different acupoints in improving the quality of life in allergic rhinitis patients. Method Seventy-seven patients with allergic rhinitis were randomized into a 12-point application group (39 cases) and a 6-point application group (38 cases), to receive Dong Bing Xia Zhi (treating cold-induced diseases in summer) application during each of the three periods of canicular days at corresponding points, 2 h each time. Rhinitis Quality of Life Questionnaire (RQLQ) was evaluated before and after the treatment, and half a year later. Result After the treatment, the total effective rate was 92.3% in the 12-point application group versus 71.1% in the 6-point application group, and the 12-point application group was significantly better (P<0.05); half a year later, the total effective rate was 87.2% in the 12-point application group versus 63.2% in the 6-point application group, and the 12-point group was significantly better (P<0.05); regarding the RQLQ, the 6-point application group didn't gain marked improvement in sleep quality after the treatment and half a year later (P>0.05), but the 12-point application group showed marked improvement (P<0.05); the rest component scores in RQLQ were significantly improved after the treatment and half a year later compared to those before the treatment in both groups (P<0.05); after the treatment, the 12-point application group was superior to the 6-point application group in comparing the reductionof all component scores and general score except the non-nose/eye symptoms score (P<0.05); half a year later, except the non-nose/eye symptoms and behavior scores, the 12-point application group was superior to the 6-point application group in comparing the reduction of all component scores and general score (P<0.05). Conclusion Dong Bing Xia Zhi acupoint application can effectively improve the quality of life in allergic rhinitis patients, especially with acupoints selected based on holism.
3.Analysis on pathogenic bacteria and drug sensitivity of canalicular inflammation
Xiao-Zhao, YANG ; Hua, YANG ; Xian-Ning, LIU ; Xuan, ZHENG ; Yi, ZHANG
International Eye Science 2016;16(10):1976-1977
AIM: To analyze the pathogenic bacteria and drug sensitivity in cases of canalicular inflammation.
●METHODS: Lacrimal sac secretion from 57 cases ( 57 eyes) with canalicular inflammation. used to do bacterial cultures and drug sensitivity tests. Grind open the sulfur particles from canaliculus for bacterial smear.
●RESULTS:After squeeze canalicular, there are 56 sulfur granules from 57 patients. All of the Sulfur particles smears were found in actinomycetes. A total of 55 from 57 cases of lacrimal secretions for bacterial culture were positive, and 63 strains were cultured. The main pathogen are Staphylococcus epidermidis, Streptococcus viridans and pneumococcus. Drug susceptibility test results showed that:rifampicin, cefoxitin, chloramphenicol, and mezlocillin are sensitivity.
●CONCLUSION:Actinomycetes were the main pathogens to canalicular inflammation, and most of the presence of co- infection with other bacteria. Rifampin, cefoxitin, chloramphenicol, and mezlocillin are sensitivity canalicular inflammation.
4.Study on HPLC fingerprint of Callicarpa nudiflora and determination of ten components.
Dong-kun ZHENG ; Wei-kang CHEN ; Shuang-cheng MA ; Jie WANG ; Chen-xuan LUO ; Yue-hua LUO
China Journal of Chinese Materia Medica 2015;40(9):1776-1782
This study is to establish the HPLC fingerprint and determine eight components of Callicarpa nudiflora, and provide a scientific basis for the identification and quality control. The Waters sunfire C18 column (4.6 mm x 250 mm, 5 µm) was used and the detection wavelength was 330 nm . The column temperature was 30 °C. The mobile phases were acetonitrile (A) and 0.1% formic acid (B) eluting in a gradient program at a flow rate of 1.0 mL · min(-1). The chromatographic fingerprint similarity evaluation system for tradition Chinese medicine(2012) was used for analysis. C. nudiflora from different samples were of high similarity in fingerprint and the separation of ten components was good. There was an obvious difference between other samples and C. nudiflora leaves. In quantitative analysis, the ten components showed good regression(R2 > 0 999 0) with linear ranges, and their recoveries were in the range of 96.0%-105.0%. The established qualitative and quantitative methods are highly specific, simple and accurate, which can be used for the identification and quality control of C. nudiflora.
Callicarpa
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chemistry
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Chromatography, High Pressure Liquid
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methods
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Drugs, Chinese Herbal
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analysis
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isolation & purification
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Plants, Medicinal
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chemistry
5.Determinants of Detection of Stones and Calcifications in the Hepatobiliary System on Virtual Nonenhanced Dual-energy CT.
Da-Ming ZHANG ; Xuan WANG ; Hua-Dan XUE ; Zheng-Yu JIN ; Hao SUN ; Yu CHEN ; Yong-Lan HE
Chinese Medical Sciences Journal 2016;31(2):76-82
Objective To retrospectively determine the features of stones and calcifications in hepatobiliary system on virtual nonenhanced (VNE) dual-energy computed tomography (CT), and to evaluate the possibility of VNE images in diagnosis for those lesions.Methods A total of 128 gall stones and calcifications of the liver found in 110 patients were examined with triple phase abdominal CT scan from July 2007 to December 2011, in which true nonenhanced (TNE) phase and arterial phase were performed with single-energy CT (120 kVp) and portal venous phase was performed with dual-energy CT (100 kVp and 140 kVp). VNE images were generated from the portal venous phase dual-energy CT data sets by using commercially VNC software. The mean CT values for the stone, liver, bile and paraspinal muscle, mean lesion density and size in area dimension, contrast-to-noise ratio (CNR) of lesion to the liver or bile, and image noise were assessed and compared between VNE and TNE images. The effective dose and size-specific dose estimate (SSDE) were also calculated.Results The mean CT values of the lesions measured on VNE images declined significantly compared with those measured on TNE images (164.51±102.13 vs. 290.72±197.80 HU, P<0.001), so did the lesion-to-liver CNR (10.80±11.82 vs.18.81±17.06, P<0.001) and the lesion-to-bile CNR (17.24±14.41 vs. 21.32±17.31, P<0.001). There was no significant difference in size of lesions area between VNE and TNE images (0.69±0.88 vs. 0.72±0.85 cm, P=0.062). Compared to the 128 lesions found in TNE images, VNE images showed the same density in 30 (23.4%) lesions, lighter density in 88 (68.8%) lesions, while failed to show 10 (7.8%) lesions, and showed the same size in 61 (47.7%) lesions and smaller size in 57 (44.5%) lesions. The CT cutoff values of lesion and size were 229.21 HU and 0.15 cm, respectively. The total effective dose for triple phase scan protocol with TNE images was 19.51±7.03 mSv, and the SSDE was 39.84±11.10 mGy. The effective dose for dual phase scan protocol with VNE images instead of TNE images was 13.29±4.89 mSv, and the SSDE was 27.83±9.99 mGy. Compared with TNE images, the effective dose and SSDE of VNE images were down by 32.05%±3.69 % and 30.63%±2.34 %, respectively.Conclusions Although the CT values and CNR of the lesions decreased in VNE images, the lesions of which attenuation greater than 229.21 HU and size larger than 0.15 cmcould be detected with good reliability and obvious dose reduction. There was good consistency in the size of stones and calcifications in hepatobiliary system between VNE images and TNE images, which ensured the possibility of the clinical application of VNE images.
6.Value of 3D-OCT in the diagnosis of macular disease before cataract surgery
Lin, LIU ; Hua, ZHENG ; Ni, LI ; Ping, TONG ; Yong-Gang, SHUI ; Lan, YU ; Shan, LIU ; Fei, SU ; Xuan-Chu, DUAN
International Eye Science 2017;17(9):1765-1767
AIM:To investigate the value of 3D-optical coherence tomography (OCT) in the diagnosis of macular disease before phacoemulsification.METHODS:Clinical records of 423 cataract patients (512 eyes) who underwent phacoemulsification combined with intraocular lens implantation in our hospital from June to December in 2015 were retrospectively analyzed.In addition to preoperative routine examination of fundus, Topcon 3D-OCT 2000 was used to examine the macula, the detection rate of macular disease was compared, risk factors of cataract combined with macular disease were analyzed.RESULTS:The OCT image results of 305 cases (384 eyes, 72.1%) were successfully obtained, 133 cases showed macular disease (146 eyes), the detection rate was 28.5% (95%CI:27.64%-29.40%);the macular disease of 35 cases (37 eyes) were detected by routine examination of fundus before operation, the detection rate was 7.2% (95%CI:6.72%-7.74%);the detection rate of 3D-OCT was significantly higher than routine examination of fundus for macular disease (χ2=79.05, P<0.01).Female, over 65 years old, surgical history of diseased eye, and high myopia were risk factors of cataract combined with macular disease, the relative risk was 1.705 (95%CI:1.091,2.664), 1.893 (95%CI:1.219,2.939), 6.593 (95%CI:2.027,21.447) and 95%CI:5.130 (2.841,9.263) respectively, the risk of cataract combined with macular disease showed an increasing trend with rising age.CONCLUSION:In preoperative examination of cataract patients, 3D-OCT has higher sensitivity in the detection of macular disease, especially for women, over 65 years old, high myopia and surgical history of diseased eye, 3D-OCT can be used as a routine preoperative examination.
7.Transfection of CTGF siRNA inhibits transdifferentiation in human lens epithelium cell line B3 in vitro
Hua, ZHUANG ; Ning-Xuan, ZHENG ; Jing, WU ; Wei, XU ; Jian-Zhang, HU ; Mao-Song, XIE ; Jian, GUO ; Guo-Xing, XU
International Eye Science 2017;17(8):1387-1393
AIM: To investigate the expression of connective tissue growth factor (CTGF) and α-SMA in human lens epithelium cell (HLEC) line B3 after transfection by liposome-coated siRNA targeting CTGF.METHODS: HLECs were transfected with small interfering RNA (siRNA) targeting CTGF,labeled with 5`-fluorescein isothiocyanate (5`-FITC) and coated with lipofectamine.The transfection ratio was evaluated via fluorescence intensity.Cell counting kit-8 (CCK-8) assay was performed to assess cytoviability of both non-transfected and transfected HLECs.Quantitative RT-PCR,cell immunochemistry and Western blot analysis were conducted to detect the expression changes of CTGF and α-SMA after transfection.RESULTS: A highly effective transfection ratio was observed in siRNA co-transfected with lipofectamine.The transfection ratio reached 95% at 24h.The proliferation of HLECs was inhibited by siRNA after 72h transfection.The expression of CTGF and α-SMA significantly decreased in HLECs after transfected by CTGF siRNA for 24h.This effect was not found in negative control siRNA.CONCLUSIONS: SiRNA targeting CTGF decreased CTGF and α-SMA expression in HLECs,which is a potential therapeutic strategy for posterior capsular opacification.
8.Association of Ureaplasma urealyticum colonization with development of bronchopulmonary dysplasia: a systemic review and meta-analysis.
Xiao-dan, ZHENG ; Dan, LI ; De-hua, YANG ; Xuan, XIANG ; Hong, MEI ; Jia-rui, PU ; Qiang-song, TONG ; Li-duan, ZHENG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2014;34(2):265-9
There is controversy regarding the roles of Ureaplasma urealyticum (U. urealyticum) colonization in the development of bronchopulmonary dysplasia (BPD). This study explored the association between U. urealyticum and bronchopulmonary dysplasia at 36 weeks post-menstrual age (BPD36). Studies published before December 31, 2013 were searched from Medline, Embase, Ovid, Web of Science, and Cochrane databases, with the terms "Ureaplasma urealyticum", "chronic lung disease", or "BPD36" used, and English language as a limit. The association between U. urealyticum colonization and BPD36 was analyzed with RevMan 4.2.10 software, using the odds ratio (OR) and relative risk (RR) for dichotomous variables. Out of the enrolled 81 studies, 11 investigated the BPD36 in total 1193 infants. Pooled studies showed no association between U. urealyticum colonization and subsequent development of BPD36, with the OR and RR being 1.03 (95% CI=0.78-1.37; P=0.84) and 1.01 (95% CI= 0.88-1.16, P=0.84), respectively. These findings indicated no association between U. urealyticum colonization and the development of BPD36.
9.Inhibitory effect of ginseng saponin IH901 on proliferation and metastasis of ECV304 cell line and its molecular mechanism.
Yan-Lin MING ; Zhong-Yan CHEN ; Liang-Hua CHEN ; Qing-Xuan TONG ; Zhi-Zhong ZHENG ; Guo-Hua ZHENG ; Xiao-Hui QI
Acta Pharmaceutica Sinica 2009;44(9):967-972
This study aims to investigate the inhibitory effect on proliferation and metastasis of 20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol (IH901) on ECV304 cell line. MTT assay was used to examine the effect of cell proliferation inhibition and the adhesive ability of ECV304 cells to artificial basement membrane. Morphology of cell apoptosis was observed with phase contrast microscope. Apoptosis rate and cell cycle were detected by flow cytometry (FCM). Cell migration was measured by wound healing assay. ELISA kit was used to detect VEGF and bFGF. Caspases were detected by Western blotting. Results indicated that ginseng saponin IH901 can downregulate the expression of growth promoting protein VEGF and bFGF, and upregulate pro apoptosis protein cleaved caspase-9 and cleaved caspase-3. The increase in the apoptotic sub-G1 fraction is in a dose-dependent manner, and cell cycle arrests in the G0/G1 phase was detected by FCM. Morphological examination of IH901-treated samples showed cells with chromatin condensation, cell shrinkage, and all typical characteristics of apoptotic cells. Therefore, IH901 dramatically suppresses cell proliferation and adhesion and migration of ECV304 cell line.
Cell Adhesion
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drug effects
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Cell Line
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Cell Movement
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drug effects
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Cell Proliferation
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drug effects
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Human Umbilical Vein Endothelial Cells
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cytology
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Humans
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Panax
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Sapogenins
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pharmacology
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Saponins
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pharmacology
10.A cohort study on the relationship between body mass index and blood pressure, blood lipid, blood glucose, left ventricular structure and function in adolescents during transition period.
Qi HUA ; Zhao-hui LIU ; Rong-kun LIU ; Zheng YANG
Chinese Journal of Epidemiology 2006;27(8):655-658
OBJECTIVETo investigate the relationship between body mass index(BMI) and blood pressure, blood lipid level, blood glucose, left ventricular structure and function in adolescents during transition period.
METHODSA vertical sectional survey on 193 pupils aged 7-11 years in primary school in 1996 was performed. 9 years later, the same research subjects aged 16-20 years were studied again in 2005. The subjects were divided into obesity,overweight and normal weight groups according to their BMI in 1996. Height, body weight, blood pressure, total cholesterol, triglyceride and blood glucose were collected and analyzed, and left ventricular structure and function were examined by echocardiography.
RESULTSBody mass index (24.71 kg/m(2)+/-4.57 kg/m(2), 20.54 kg/m(2)+/-2.84 kg/m(2) ), systolic blood pressure (117.22 mm Hg+/-17.44 mm Hg vs. 102.20 mm Hg+/-11.68 mm Hg), thickness of inter-ventricular septum and posterior wall (0.87 cm+/-0.12 cm vs. 0.77 cm+/-0.12 cm, and 0.91 cm+/-0.13 cm vs. 0.79 cm+/-0.31 cm), left ventricular mass and mass index (167.84 g+/-16.29 g vs. 128.95 g+/-63.00 g, and 88.12 g/m(2) +/-17.19 g/m(2) vs. 79.35 g/m(2)+/-39.01 g/m(2)) were found significantly higher in obesity group than in normal weight group 9 years later (P<0.05, P< 0.01 or P< 0.001). End diastolic volume and cardiac output were increased(P <0.05) and ejection fraction and fractional shortening decreased( P< 0.05). There were no differences found in cardiac diastolic function between the studied groups.
CONCLUSIONThe results suggested that simple obesity in childhood was an important cardiovascular risk factor when they grew into adolescents and adults. ;
Adolescent ; physiology ; Adult ; Blood Glucose ; Blood Pressure ; Body Mass Index ; Child ; China ; Cohort Studies ; Female ; Heart Ventricles ; anatomy & histology ; Humans ; Lipids ; blood ; Longitudinal Studies ; Male ; Ventricular Function, Left ; Young Adult