1.Research on antitumor effects of small molecule inhibitors of deubiquitinases: new progress and new ideas
Xiang-ning LIU ; Jia-min DU ; Mei-jia QIAN ; Xiao-wu DONG ; Bo YANG ; Hong ZHU ; Qiao-jun HE
Acta Pharmaceutica Sinica 2022;57(3):547-556
The abnormality of ubiquitin proteasome pathway is an important factor leading to the imbalance of protein homeostasis. In this process, the deubiquitinase responsible for removing the ubiquitin chain of protein substrate is very important. Its abnormal activity or expression can cause the functional changes of key oncogenic/tumor suppressor proteins, which directly or indirectly lead to the occurrence, development and malignant evolution of tumors. Based on this, the discovery and research of small molecule inhibitors targeting deubiquitinases have become a hot field of anti-tumor candidate drugs. This review will focus on the regulatory effect and mechanism of ubiquitin proteasome pathway, especially deubiquitinase on tumor, introduce the application of deubiquitinase small molecule inhibitors in tumor treatment, and discuss the research status and latest progress of small molecule inhibitors, so as to provide ideas for the research of new anti-tumor strategies based on deubiquitinase.
2.Study on inhibitory effect of different extract fractions from longdan xiegan decoction on biofilms of Candida albicans.
Li-Hua YU ; Ke-Qiao LU ; Gao-Xiang SHI ; Yuan-Yuan YAN ; Liang HE ; Jing SHAO ; Tian-Ming WANG ; Chang-Zhong WANG
China Journal of Chinese Materia Medica 2014;39(7):1280-1284
OBJECTIVETo observe the inhibitory effect of different extract fractions from Longdan Xiegan decoction on biofilms of Candida albicans, and discuss its possible mechanism.
METHODThe micro-dilution method and the XTT reduction assay were adopted to explore the antifungal activity of different extract fractions from Longdan Xiegan decoction and detect the inhibitory effect of different extracts on biofilms of C. albicans. The expression quantity of the adhesion related gene ALS1 and hypha formation SUN41 were detected by qRT-PCR.
RESULTThe MICs of extracts from Longdan Xiegan decoction, including petroleum ether, water, butanol, methanol and ethyl acetate, against C. albicans were > 1 000, > 1 000, > 1 000, 125, 125 mg x L(-1). The SMIC50 against biofilms of C. albicanswere > 1 000, > 1000, > 1 000, 500, 500 mg x L(-1). The SMIC50 were > 1 000, > 1 000, > 1 000, > 1 000 and 1 000 mg x L(-1). 1 000 mg x L(-1) ethyl acetate extracts could considerably inhibit the expression of the adhesion related gene ALS1 and hypha formation SUN41.
CONCLUSIONThe ethyl acetate extract showed the greatest activity against Candida albicans biofilms.
Antifungal Agents ; pharmacology ; Biofilms ; drug effects ; growth & development ; Candida albicans ; drug effects ; growth & development ; Candidiasis ; drug therapy ; microbiology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Hyphae ; drug effects ; growth & development ; Microbial Sensitivity Tests
4.Epidemiological study on human echinococcosis in Hobukesar Mongolian Autonomous County of Xinjiang
Gui-zhi, WANG ; Xiao-hui, FENG ; Xiang-dong, CHU ; ERXIDING ; AMINA ; Ji-xia, ZHOU ; Qiao, WANG ; Jin-hua, HE ; Hao, WEN
Chinese Journal of Endemiology 2009;28(2):214-217
Objective To investigate the characteristics and distribution of human eehinococcosis in Hobukesar Mongolian Autonomous County (HMAC) in Xinjiang. Methods Using cluster sampling methods, the 2 counties (Tiebukenwusa and Narenhebuke) in HMAC were chosen as focusing areas for investigation. A survey of human echinococcosis including questionnaire, serological test and abdominal ultrasonic scan was carried out. Results The prevalence of human echinococcosis was 9.0% (64/712) by ultrasound and surgical history, including 8.7% (62/712) for cystic eehinococcosis(CE), 0.3%(2/712) for alveolar echinococcosis(AE) and 15.6%(111/712) for total of serological positives in HMAC. CE prevalence rate of different occupations, age, family slaughtering livestock and drinking water source had significant differences(P<0.05). Herdsmen as the highest risk group showed a CE prevalence of the 13.4% (27/201) in comparison with other occupations. The ages between 20 to<40 year-old were at the highest risk stage with 12.8% incidence. But CE prevalence rate of different gender, ethnic and education groups had not significant differences(P>0.05). Conclusions HMAC could be considered as a high endemic human CE region in Xinjiang. The current study reported the main risk factors may include occupations, age difference and drinking water source.
5.Spermatic cord seal-up injection for acute epididymitis: clinical observation of 56 cases.
Liang QIAO ; Zhi-Quan LIU ; Jun XIANG ; Chen LIN ; Xiang-E LIU ; Ying HE ; Cheng-Hao YAN
National Journal of Andrology 2013;19(7):622-625
OBJECTIVETo investigate the clinical effect of spermatic cord seal-up injection on acute epididymitis and its mechanisms.
METHODSA total of 120 cases of acute epididymitis were allocated to a trial group (n = 56), aged 18 - 78 (38.4 +/- 9.6) years, and a control group (n = 64), aged 14 -82 (41.3 +/- 7.2) years. The patients in the trial group were given seal-up injections of a mixture of lidocaine, gentamicin (or Amikacin) and dexamethasone into the spermatic cord, qd or bid, for 2 courses of 5 days each, with an interval of 3 to 5 days. Those in the control group were treated by intravenous drip of penicillin, qd, intramuscular injection of Streptomycin, bid, and oral medication of SMZCo (SMZ-TMP), bid, with the initial dose doubled. After less than 2 weeks of treatment, we compared the therapeutic effects between the two groups of patients.
RESULTSIn the trial group, 53.6% of the patients were basically cured, 37.5% obviously improved and 91.1% improved (total rate of effectiveness). The average treatment time for the improved cases was (9.2 +/- 0.5) d. In the control group, 40.6% of the patients were basically cured, 31.2% obviously improved and 71.8% improved (total rate of effectiveness). The average treatment time for the improved cases was (12.8 +/- 0.7) d. There were significant differences between the two groups in the total rate of effectiveness and the average treatment time for the improved cases (P < 0.05).
CONCLUSIONSpermatic cord seal-up injection for acute epididymitis deserves wide clinical application for its simple operation, good tolerance, short therapeutic course and high safety and efficacy.
Acute Disease ; Administration, Topical ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Epididymitis ; therapy ; Humans ; Male ; Middle Aged ; Spermatic Cord ; Young Adult
6.Myocardial perfusion evaluation post percutaneous transluminal septal myocardial ablation in patients with hypertrophic obstructive cardiomyopathy by ⁹⁹Tc(m) MIBI SPECT MPI.
Xiao-Xin SUN ; Yue-Qin TIAN ; Shu-Bin QIAO ; Jian-Song YUAN ; Fu-Jian DUAN ; Dao-Yu WANG ; Feng GUO ; Zuo-Xiang HE
Chinese Journal of Cardiology 2011;39(6):497-502
OBJECTIVETo evaluate the myocardial perfusion and function in patients with hypertrophic obstructive cardiomyopathy (HOCM) before and after percutaneous transluminal septal myocardial ablation (PTSMA).
METHODSSixty-eight patients with hypertrophic obstructive cardiomyopathy were included and (99)Tc(m)-MIBI SPECT MPI was applied before and at 1 week after PTSMA, six-month follow-up was finished in 11 patients. Semi quantity and QGS quantity perfusion and function assessment was performed in 17 LV segments.
RESULTSMyocardial perfusion post-PTSMA was significantly reduced in 98% patients, especially in basal anterosepta, basal interseptal, mid-anteroseptal, mid-interseptal and apical septal segments compared with pre-PTSMA (all P < 0.05). Perfusion was significantly increased at 6 months follow-up than at 1 week post-PTSMA but still lower than pre-PTSMA (all P < 0.05). LVEF (evaluated by gated SPECT) was similar before and after the procedure (P > 0.05). Regional wall motion after PTSMA was lower than pre-PTSMA in basal anterior, basal anteroseptal, basal interseptal and basal inferior (P < 0.05). Regional wall thinkening was lower than pre-PTSMA in basal interseptal, mid-anteroseptal, mid-interseptal (P < 0.05).
CONCLUSIONS(99)Tc(m) MIBI SPECT can be used to monitor myocardial perfusion post PTSMA in patients with HOCM.
Adolescent ; Adult ; Aged ; Angioplasty, Balloon ; Cardiomyopathy, Hypertrophic ; diagnostic imaging ; surgery ; Catheter Ablation ; methods ; Female ; Humans ; Male ; Middle Aged ; Tomography, Emission-Computed, Single-Photon ; Young Adult
7.Mandibular morphology change due to mandibular angle osteotomy: a cone beam computed tomography-based three-dimensional cephalometry analysis
Shu WANG ; Wensong SHANGGUAN ; Wenwen ZHANG ; Yang ZHAO ; Jiri XI ; Xiang QIAO ; He CHEN ; Guoping WU
Chinese Journal of Medical Aesthetics and Cosmetology 2021;27(6):499-504
Objective:To investigate the effect of mandibular angle osteotomy on the morphological changes of mandible by using cone beam computed tomography (CBCT) scanning data and three-dimensional cephalometry.Methods:According to included and excluded criteria, the complete CBCT data of 20 female patients (aged 20-35 years with an average age of 25.5 years) from January 2016 to June 2018 who underwent curved mandibular angle osteotomy combined with splitting cortiectomy were selected. Seven items reflecting mandibular morphology before and after surgery were measured respectively. All the data were analyzed by the means of SPSS 12.0; linear correlation analysis and paired t test were used to evaluate the change of andibular morphology.Results:The measurement results of the mandible pre- and post-operative 10 days showed as follows: Go-Go decreased, both sides of Cd-Go, Go-Ri and MR-MA decreased, both sides of Go-Me became longer, both sides of Ar-Go-Me and MP-FH increased. The paired t-test results showed that there was significant difference before and after operation ( P<0.05), but there was no significant difference between the left and right measurement items ( P>0.05). Compared with that in 10 days after operation, the measurement items also changed 6 months after operation. There was no statistical difference between the above measurement items 6 months after surgery and 10 days after surgery ( P>0.05), and no statistical difference between the left and right sides ( P>0.05). Conclusions:The mandibular three-dimensional model which is reconstructed based on CBCT data, not only displays the three-dimensional anatomical structure that cannot be presented on X-ray film visually and comprehensively by means zoom, rotation and other operations, but also precisely and accurately shows the change of the shape of the mandible from the sagittal, coronal and horizontal plane with arbitrary cutting and rotation. The measurement of mandible is more accurate and reliable, and the surgical plan of mandibular angle osteotomy can be accurately planned preoperatively, and the operative effect can be quantitatively evaluated postoperatively.
8.Efficacy and safety of Firebird sirolimus-eluting stent in treatment of complex coronary lesions in Chinese patients: one-year clinical and eight-month angiographic outcomes from the FIREMAN registry.
Yan LI ; Cheng-xiang LI ; Hai-chang WANG ; Bo XU ; Wei-yi FANG ; Jun-bo GE ; Wei-min WANG ; Shu-bin QIAO ; Jack-P CHEN ; Wen-kuang SHEN ; Hong JIANG ; Hong-liang CONG ; Xiao-qun PU ; Yong-wen QIN ; Hui-gen JIN ; Yu CAO ; He HUANG
Chinese Medical Journal 2011;124(6):817-824
BACKGROUNDOff-label application of drug-eluting stents (DES) during percutaneous coronary intervention (PCI) was not uncommon in daily practice, however DES in treating Chinese patients with complex lesion subset was under-investigated. The primary objective of the FIREMAN registry was to evaluate the long term efficacy and safety of the Firebird sirolimus-eluting stent (SES) in treating patients with complex coronary lesions. Here we report the mid-term of one-year clinical outcomes and eight-month angiographic follow-up results of FIREMAN registry.
METHODSThe FIREMAN registry was a prospective multi-center registry, which included 1029 consecutive patients undergoing PCI with Firebird SES implantation between September 2006 and July 2007 in 45 centers in China. The clinical follow-up was designed to be performed at 1, 6, 12, 18, 24, 30 and 36 months post index procedure, and non-mandatory angiographic follow-up at 8 months was planned. One hundred percent site monitoring was conducted.
RESULTSLong lesions (59.2%), multi-vessel disease (50.4%), and small vessel disease (31.6%) were mostly found in angiography. Major adverse cardiac events (MACE) occurred in 51 (5.1%) patients at 1 year clinical follow-up, including cardiac mortality in 6 (0.6%), non-fatal myocardial infarction in 11 (1.1%), and target lesion revascularization in 36 (3.5%) of the patients. Definite and probable stent thrombosis (ST) by Academic Research Consortium (ARC) definition occurred in 12 (1.36%) patients at one-year clinical follow-up. The 8-month binary restenosis rate was 5.7% in-segment and 4.3% in-stent, respectively. Late lumen loss was (0.21 ± 0.40) mm in-segment and (0.23 ± 0.36) mm in-stent, respectively. Furthermore, Cox regression analysis revealed that diabetes, small vessel diameter, and chronic total occlusion were independent predictors of ST.
CONCLUSIONSThe results showed that the Firebird SES was effective and safe in treating Chinese patients with complex coronary lesions and occurrence of ST rate at one-year clinical follow-up was acceptable, however further long-term follow-up was still necessary. (NCT00552656)
Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; methods ; Asian Continental Ancestry Group ; Coronary Angiography ; Coronary Disease ; diagnostic imaging ; therapy ; Drug-Eluting Stents ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Sirolimus ; therapeutic use ; Treatment Outcome
9.Role of Fas/FasL pathway-mediated alveolar macrophages releasing inflammatory cytokines in human silicosis.
San Qiao YAO ; Qin Cheng HE ; Ju Xiang YUAN ; Jie CHEN ; Gang CHEN ; Yao LU ; Yu Ping BAI ; Chun Min ZHANG ; Yang YUAN ; Ying Jun XU
Biomedical and Environmental Sciences 2013;26(11):930-933
Adult
;
Antibodies, Monoclonal
;
pharmacology
;
Bronchoalveolar Lavage Fluid
;
cytology
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Cells, Cultured
;
Cytokines
;
biosynthesis
;
blood
;
secretion
;
Fas Ligand Protein
;
antagonists & inhibitors
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metabolism
;
Humans
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Macrophages, Alveolar
;
immunology
;
metabolism
;
Middle Aged
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Occupational Exposure
;
analysis
;
Signal Transduction
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Silicon Dioxide
;
adverse effects
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Silicosis
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blood
;
immunology
;
fas Receptor
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antagonists & inhibitors
;
metabolism
10.The effect of atorvastatin on the expression of CD55, CD59 in patients with hyperlipidemia.
Yong-ming LIU ; Jin-chun HE ; Jing-gang YANG ; Yan-ying LIU ; Xiang YAN ; Li ZHAO ; Xi-wen MA ; Dong-ya SHANG ; Cheng-dong QIAO ; Wei-xin LI ; Jin-yang WANG
Chinese Journal of Cardiology 2005;33(12):1075-1079
OBJECTIVETo study the expressions of CD55 and CD59 in patients with hyperlipidemia and the effects of atorvastatin on it, and to identify the possible influential factors.
METHODSWe selected 67 patients with hyperlipidemia, and 24 healthy people matched in terms of age, sex and body weight as control. The expressions of CD55 and CD59 on white blood cells were detected by flow cytometry, and their relationships to blood lipids, complement activation indexes (C(5a), sC(5b-9)), inflammatory factors (high sensitivity C-reactive protein (hsCRP), TNF-alpha, IL-6 were analyzed. 24 patients with hyperlipidemia were treated with atorvastatin for 8-12 weeks and the expressions of CD55 and CD59 were measured before and after atorvastatin therapy.
RESULTSThe mean fluorescence intensity (MFI) of CD55 lymphocytes and monocytes were decreased in patients with hyperlipidemia compared with control (2.07 +/- 0.28 vs 2.29 +/- 0.44 and 3.45 +/- 1.02 vs 4.33 +/- 2.32, P < 0.01 and P < 0.05, respectively). CD55 positive lymphocyte MFI was negatively correlated with waist circumference, waist-hip ratio, hsCRP and C(5a). C(5a) was negatively correlated with the MFIs of CD55 positive lymphocytes, monocytes, granulocytes, and positively with TG and diastolic blood pressure. After atorvastatin therapy, the MFIs of CD59 positive lymphocytes, monocytes and granulocytes increased (4.34 +/- 1.16 vs 3.69 +/- 0.76, 4.52 +/- 1.36 vs 3.91 +/- 0.89, 5.67 +/- 1.72 vs 4.56 +/- 1.03, P < 0.05, < 0.05 and < 0.01 respectively), which were not correlated with changes of blood lipids.
CONCLUSIONSThe expression of CD55 is down-regulated in hyperlipidemia, which might be influenced by obesity, abdominal distribution of adipose tissue and inflammatory status of hyperlipidemia, but not by blood lipids. The expression of CD55 is related with complement activation; The expression of CD59 is up-regulated after atorvastatin treatment independently of blood lipids.
Aged ; Atorvastatin Calcium ; CD55 Antigens ; metabolism ; CD59 Antigens ; metabolism ; Case-Control Studies ; Complement Activation ; Gene Expression Regulation ; Heptanoic Acids ; therapeutic use ; Humans ; Hyperlipidemias ; drug therapy ; immunology ; metabolism ; Hypolipidemic Agents ; therapeutic use ; Male ; Middle Aged ; Pyrroles ; therapeutic use