2.Recent progress of targeted small molecular CDK9 degraders based on PROTAC technology
Jin-xiu LI ; He-wei DONG ; Wei HOU
Acta Pharmaceutica Sinica 2022;57(9):2696-2708
CDKs proteins are a kind of cell cycle protein-dependent kinases, which serve as important roles in controlling cell division and transcriptional stages. Among them, CDK9, as a key regulator responsible for the transcriptional elongation of cells, drives the development of various malignant cells and is considered as an important target in the field of anti-tumor drug development. However, the CDK family proteins feature high conservativeness and similarity in structure, leading to the poor selectivity and severe side effects for traditional small-molecular CDK9 inhibitors, which has limited their clinical applications. In view of this, there is an urgent need to investigate CDK9 targets through a novel strategy. The PROTAC is an emerging drug discovery strategy that the degrader could specifically recognize the target protein through indirect linkage with ubiquitin ligases and ultimately eliminate the target protein through the ubiquitination degradation system. This paper provides a brief overview of the structure and function of CDK9 protein, its relationship with the poor prognosis of clinical diseases, as well as the currently reported small molecular inhibitors. The latest research progress on the targeted degradation of CDK9 protein based on PROTAC technology is highlighted. Finally, the development prospects of this target protein in this novel technology field are summarized and prospected, aiming to provide a reference for the development of antitumor drugs in this direction.
3.Effect of denopamine on alveolar fluid clearance in hypoxic rat lungs
Naijing LI ; Xiu GU ; Wei LI ; Shengqi LI
Chinese Journal of Pathophysiology 1986;0(04):-
AIM:To study the effect of ?1-adrenergic agonist on alveolar fluid clearance in hypoxic rat lungs. METHODS: Rats were exposed to 10% oxygen. Alveolar fluid clearance (AFC) and lung water content (TLW) were calculated in rats exposed to hypoxia for 24 h and 48 h. Isotonic 5% albumin in solutions with different pharmacological agents were instilled into the distal airways in the hypoxia exposed and room air-exposed rat lungs, and the AFC was examined. RESULTS: As compared with the room air-exposed rats (17.50%?2.66%), AFC in the rats exposed to 10% oxygen was not decreased (18.70%?3.19%), AFC in the rats exposed to 10% oxygen for 48 h was decreased (8.59%?2.60%). Denopamine, a ?1-adrenergic agonist, increased AFC significantly in the rats exposed to room air and hypoxia. The potency of 10-5 mol/L denopamine was similar to that of 10-5mol/L terbutaline. The denopamine effect was partly blocked by inhibitors of sodium transport amiloride and ouabain (AFC were 11.80%?2.79% and 8.53%?2.17%). CONCLUSION: Denopamine, a selective ?1-adrenergic agonist, stimulates alveolar fluid clearance in rats exposed to hypoxia through the active sodium transport, and may have therapeutical effect on pulmonary edema after acute lung injury.
4.Childhood eosinophilic gastroenteritis in a case.
Zai-ling LI ; Xiu-li LIU ; Xiu-jing KOU ; Ling WEI
Chinese Journal of Pediatrics 2005;43(8):633-635
Child
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Colitis
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diagnosis
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Colon, Sigmoid
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pathology
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Diagnosis, Differential
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Diarrhea
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etiology
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Eosinophilia
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complications
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diagnosis
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Female
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Gastroenteritis
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complications
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diagnosis
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pathology
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Humans
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Sigmoid Diseases
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complications
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diagnosis
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pathology
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Sigmoidoscopy
5.Celomic and retroperitoneal lipoleiomyosarcoma: report of a case.
Xiu-zhen LI ; Hong-quan WEI ; Bai-zhou LI
Chinese Journal of Pathology 2011;40(5):343-344
Abdominal Neoplasms
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metabolism
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pathology
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surgery
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Actins
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metabolism
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Angiomyolipoma
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metabolism
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pathology
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Desmin
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metabolism
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Diagnosis, Differential
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Humans
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Leiomyosarcoma
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metabolism
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pathology
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surgery
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Liposarcoma
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metabolism
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pathology
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surgery
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Male
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Middle Aged
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Neoplasms, Multiple Primary
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metabolism
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pathology
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surgery
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Retroperitoneal Neoplasms
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metabolism
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pathology
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surgery
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S100 Proteins
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metabolism
6.Contrast enhanced ultrasonographic features of benign focal liver lesions
Jiu-wei, ZHANG ; Xiu-yun, WANG ; Qi, WANG ; Tian-tian, LI ; Xiu-hua, YANG
Chinese Journal of Medical Ultrasound (Electronic Edition) 2013;(9):52-55
Objective To summarize the contrast enhanced ultrasonographic (CEUS) features of benign focal liver lesions, on and to investigate the value of contrast enhanced ultrasound techniques in the diagnosis of benign focal liver lesion. Methods The contrast enhanced ultrasonographic performance of 68 benign focal liver lesions cases which were dififcult for routine ultrasound diagnosis and conifrmed by pathology or follow-up were retrospectively analyzed. Chi-square test of four-fold table were used to compare the diagnostic coincidence rate of conventional ultrasound and contrast-enhanced ultrasound. Results The 68 cases of benign focal liver lesions included complex cysts (n=7), liver hydatids (n=2), liver abscess (n=15), focal nodular hyperplasia (n=8), angiomyolipoma (n=2), hepatocellular adenoma (n=4), focal fat accumulation (n=16), inlfammatory pseudotumor (n=12), solitary necrotic nodule (n=1), intrahepatic biliary cystadenoma (n=1). There were no enhancement among 7 complex cysts, 2 liver hydatids and 1 solitary necrotic nodule. Isoenhancement was detected in focal fat accumulation (n=16);hypoenhancement during the arterial phase and sustained enhancement during the portal or late phase was found in focal nodular hyperplasia (n=8) and angiomyolipoma (n=2). Grid-like enhancements during the arterial phase and isoenhancement or hypoenhancement during the portal phase, and hypoenhancement during the late phase was presented in liver abscess (n=15). Hyperenhancement during the arterial phase were detected in 4 cases of hepatocellular adenoma, 3 of which showed isoenhancement or hyperenhancement during the portal and delayed phase, one case showed hypoenhancement during the portal phase. Eight cases of all the inlfammatory pseudotumor showed no enhancement during all phases;3 cases showing grid enhancement during the arterial phase and the enhancement washed out rapidly;1 case showed mild edge enhancement during the arterial phase and hypoenhancement during the delayed phase. The solid part of the intrahepatic biliary cystadenoma showed hyperenhancement during the arterial phase and hypoenhancement during the portal and late phase.The central area showed no enhancement during all phase. The coincidence rate between pathology and conventional ultrasound diagnosis was 61.8%(42/68). The coincidence rate between pathology and contrast- enhanced ultrasound diagnosis was 92.6%(63/68). The coincidence rate of contrast-enhanced ultrasound diagnostic was higher than that of conventional ultrasound, with a statistically signiifcant difference (χ2=8.17, P < 0.01). Conclusion Real-time gray-scale contrast-enhanced sonography can improve the accuracy of the diagnosis and differential diagnosis for benign focal liver lesions.
8.Clinical Features and Risk Factors of Elderly Patients with Post-stroke Hypertension
Xiu-li YANG ; Xiao-wei MA ; Xiao LIU
Chinese Journal of Rehabilitation Theory and Practice 2006;12(8):665-666
ObjectiveTo investigate the clinical features and risk factors of elderly hospitalized patients with post-stroke hypertension (PSH).MethodsThe data including sex, age and blood pressure of 300 elderly PSH patients were analyzed retrospectively to find out the influence factors related to PSH.ResultsCompared with younger patients, the elderly patients had lower incidence of limb paralysis, disturbance of consciousness, while high frequency of headache and emesis on admission; hypertension, diabetes, smoking and alcohol abuse were significantly less frequent, while coronary heart disease and pneumonia were more common in elderly patients. Blood pressure especially systolic pressure of elderly PSH patients raised obviously .ConclusionElderly stroke patients have distinctive risk factors and clinical features, which are different from younger patients.
9.Chemical constituents from lipophilic parts in roots of Angelica dahurica var. formosana cv. Chuanbaizhi.
Gai-Gai DENG ; Xiu-Wei YANG ; You-Bo ZHANG ; Wei XU ; Wei WEI ; Tian-Li CHEN
China Journal of Chinese Materia Medica 2015;40(11):2148-2156
The chemical constituents from lipophilic parts in the roots of Angelica dahurica var. formosana cv. Chuanbaizhi were studied in this paper. The compounds were separated and purified by repeated column chromatographic methods on silica gel and HPLC, and the chemical structures of compounds were determined by spectral data analyses. Twenty-nine compounds were obtained and identified as isoimperatorin (1), β-sitosterol (2), imperatorin (3), bergapten (4), osthenol (5), xanthotoxin (6), isoimpinellin (7), dehydrogeijerin (8), phellopterin (9), isodemethylfuropinarine (10), 7-demethylsuberosin (11), alloimperatorin (12), xanthotoxol (13), isooxypeucedanin (14), alloisoimperatorin (15), demethylfuropinarine (16), 5-hydroxy-8-methoxypsoralen (17), oxypeucedanin methanolate (18), pabulenol (19), byakangelicin (20), marmesin (21), (+) -decursinol (22), heraclenol (23), oxypeucedanin hydrate (24), marmesinin (25), ulopterol (26), erythro-guaiacylglycerol-β-ferulic acid ether (27), threo-guaiacylglycerol-β-ferulic acid ether (28), and uracil (29). Compounds 5, 8, 11, 18, 21-23, and 26-28 were obtained from the roots of title plant for the first time.
Angelica
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chemistry
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Coumarins
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chemistry
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isolation & purification
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Furocoumarins
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chemistry
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isolation & purification
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Methoxsalen
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chemistry
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isolation & purification
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Phytochemicals
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analysis
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chemistry
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Plant Roots
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chemistry
10.Effects of sample digestion conditions on urinary iodine measurement results
Wei, MA ; Xiu-wei, LI ; Shi-chuan, LIU ; Shu-hua, LI ; Lie-jun, LIU
Chinese Journal of Endemiology 2013;32(6):694-696
Objective To study the effects of sample digestion conditions on measurement results of urinary iodine determined by As(Ⅲ)-Ce4+ catalytic spectrophotometry with ammonium persulfate digestion,and to promote the application of newly revised (the 2012 edition) national standard method for determination of urinary iodine.Methods According to the newly revised national standard method,various digestion conditions,such as ammonium persulfate concentration (0.8-1.3 mol/L,group interval 0.1),digestion instruments (heating block and drying oven) and standing time after digestion(0.5,1.0,2.0,4.0 and 22.0 h),were studied.The samples included 3 standard materials,which were GWB09108k,GWB09109f and GWB09110m containing iodine of (68.2 ± 9.0),(138.0 ± 10.0) and (221.0 ± 10.0) μg/L,and 5 urine samples with iodine concentration of 100-300 μg/L.Results Measurement results among the three groups of 0.9,1.0 and 1.1 mol/L ammonium persulfate digestion fluid showed no significant difference(P > 0.05).The digestive effect showed no significant difference between heating block and drying oven (P > 0.05) except one standard material in low concentration (GBW09108k).After digestion,samples were placed 0.5-22.0 h,the measurement results between groups showed no significant difference (P > 0.05).Conclusions Appropriate concentrations of ammonium persulfate are from 0.9 mol/L to 1.1 mol/L.Heating block is recommended for the digestion,however,when absent,drying oven can be used alternatively.The standing times from 0.5 h to 22 h after digestion have not affected the measurement results.