1.Research progress of anti-acute marrow leukemia drugs by targeting FLT3
Hui-ya JIA ; Bo YANG ; Xiao-meng ZHANG ; Jian-hong GONG ; Ya WU ; Yan-le ZHI
Acta Pharmaceutica Sinica 2023;58(3):605-615
Acute myeloid leukemia (AML) is a genetic heterogeneous disease in which primordial and juvenile myeloid cells proliferate or accumulate abnormally in bone marrow, peripheral blood and other tissues, resulting in damage to normal hematopoietic function. Studies have shown that about 30% of AML patients have FMS-like tyrosine kinase 3 (FLT3), FLT3 abnormal regulation is closely related to the occurrence and development of AML. At present, FLT3 has become an important target for developing small molecular targeted drugs. Currently, a variety of FLT3 inhibitors and FLT3 degraders have been developed targeting FLT3, and some compounds have exhibited good anti-AML activity. This article summarizes and sorts out the current mainstream drugs for AML therapeutic targeting FLT3, in order to provide a reference for the development and design of AML drugs.
2.Analysis of risk factors of skin lesion of population exposed to arsenic via drinking water in Inner Mongolia
Zhi-wei, GUO ; Ya-juan, XIA ; Ke-gong, WU ; Yan-hong, LI
Chinese Journal of Endemiology 2011;30(6):638-641
Objective To study the risk factors of skin lesion (keratosis and abnormal skin pigmentation) of population exposed to arsenic via drinking water in Inner Mongolia.Methods A cluster sampling method was used to select 902 cases from Linhe district,Hanghou and Wuyuan county in Inner Mongolia and physical examination was done.They were interviewed for information by questionnaire.The sample of fingernails and drinking water were collected.Water arsenic (As) was analyzed by inductively coupled plasma mass spectrometry (ICPMS); fingernail As and Se content were analyzed by instrumental neutron activation analysis(INAA).Data were analyzed by univariate and multivariate non-conditional Logistic regression.Results Single factor analysis showed that risk factors of keratosis were age,pesticide,arsenic in nails,smoking,years of smoking,drinking of alcohol,arsenic content in drinking water,fluorosis and duration of drinking arsenic-containing water,while occupation,nail selenium content and vitamin were protective factors.There were 10 risk factors for pigment abnormalities,which were age,pesticide,arsenic in nails,smoking,years of smoking,numbers of cigarette smoked daily,drinking of alcohol,fluorosis,the arsenic content in drinking water and duration of drinking arseniccontaining water,while sex,occupation and nails with selenium were protective factors.The multivariate factor analysis showed that the risk factors of keratosis were age,pesticide and arsenic content in drinking water(OR =1.387,1.583,1.321,all P < 0.05),while occupation and vitamin were protective factors(OR =0.307,0.260,all P < 0.05).The risk factors of abnormal skin pigmentation were age,pesticide,arsenic in nails,fluorosis and arsenic content in drinking water(OR =1.724,2.636,2.741,3.699,1.863,all P < 0.05),while sex was protective factor(OR =0.255,P < 0.01 ).Conclusions Many factors have influence on endemic arsenism and a composite measure should be implemented to prevent it such as excluding arsenic from drinking water,health education,and a reasonably intake of nutrients.
3.Influence of arsenic exposure on menstruation
Wei-hong, YANG ; Zhi-wei, GUO ; Xiao-hong, HAN ; Ya-juan, XIA ; Ke-gong, WU ; Yan-hong, LI
Chinese Journal of Endemiology 2013;(1):27-29
Objective To study the influence of arsenic exposure on menstruation.Methods A cluster sampling method was applied to select the subjects of women aged 10 to 65 from Linhe,Hangjinhouqi and Wuyuan counties in Inner Mongolia in 2004.Drinking water samples were collected to detect arsenic levels,and menstrual related situation was surveyed.The subjects were divided into four groups according to drinking water arsenic concentration:control(≤0.01 mg/L),low(> 0.01-0.10 mg/L),moderate(> 0.10-0.20 mg/L) and high(> 0.20mag/L).Results A total of 602 women were surveyed.There were 83 subjects exposed to arsenic before menarche and their menarche age was (14.37 ± 1.54) years old.There were 90 people exposed to arsenic before menopause and the menopause age was (48.13-0.41) years old.The age of menarche and menopause were positively related to the years of arsenic exposure,and correlation coefficients were 0.268 and 0.278 (all P < 0.05).Compared to control group(14.0%,16/112),menstrual abnormality rate decreased in low(12.1%,21/173) and high dose groups(10.2%,19/186),while increased in the moderate dose group(18.2%,16/88),but the differences were not statistically significant(x2 =3.664,P > 0.05).Conclusions Long-term arsenic exposure delays the menarche and menopause age,suggesting that arsenic has certain endocrine disruption or estrogen-like effects.
4.Perioperative airway management for patients with morbid obesity.
Ya-hong GONG ; Xue-rong YU ; Yu-guang HUANG
Acta Academiae Medicinae Sinicae 2011;33(3):224-227
The excess fatty tissues on the head, neck, thorax, and abdomen of morbid obese patients can impede the patency of the upper airway and impair lung functions. Meanwhile, these patients often have comorbidities such as obstructive sleep apnea, hypoventilation syndrome, chronic obstructive pulmonary disease, and asthma, which may result in difficult airway, intraoperative hypoventilation, and postoperative respiratory depression. Therefore, perioperative airway management for morbid obese patients may pose a big challenge to anesthesiologists. Anesthesiologists should know well about the pathophysiological features of respiratory system and grasp rational management principles, so as to improve the safety and effectiveness of perioperative airway management and optimize the clinical prognosis.
Airway Management
;
Anesthesia
;
methods
;
Humans
;
Obesity
;
surgery
;
Perioperative Care
5.Resolvin E1 protects against ox-LDL-induced injury on vascular endothelial cells
Ya-Feng CHEN ; Hong JIANG ; Xia GONG ; Jing-Yuan WAN
Chinese Journal of Cardiology 2011;39(11):1039-1043
Objective To investigate whether Resolvin E1 ( RvE1 ) could protect against ox-LDL-induced injury on human vein vascular endothelial cells and reveal related molecular mechanisms.Methods Human vein vascular endothelial cells were randomly assigned to six groups,which were treated with saline,RvE1,wortmanin,ox-LDL,ox-LDL and RvE1,ox-LDL and RvE1 and wortmanin,respectively.After 48 h,survival rates were determined by MTT,apoptosis rate of cells were determined by flow cytometry,TNF-αt contents were assayed by ELISA,caspase 3 and 9 activities were measured by microplate reader,and the expression of p-AKT and LOX-1 were determined by Western blot.Result Compared with normal saline group,survival rate was markedly decreased and apoptosis rate,TNF-α content,caspase 3 and 9 activities,and the expression of LOX-1 were significantly increased in ox-LDL group ( P < 0.01 ).Survival rate was significantly increased and apoptosis rate,TNF-α content,caspase 3 and 9 activities,and the expression of LOX-1 were significantly decreased in ox-LDL + RyE1 group compared to ox-LDL group (P < 0.01 ),these beneficial effects of RvE1 could be blocked by PI3K inhibitor wortmanin ( P < O.05 ).Conclusion The present data showed that RvE1 could effectively protect against ox-LDL-induced endothelial cell injury,which might be mediated by PI3K-AKT signaling pathway.
6.Treatment of the Glucose Fluctuation of Type-2 Diabetes from the Perspective of Spleen and Kidney Deficiency
Ya LIU ; Guang-Ming GONG ; Hong GAO
Journal of Nanjing University of Traditional Chinese Medicine 2015;(6):505-507
To reduce glucose fluctuation of Type-2 diabetes,though difficult,is of great significance in clinical practice. Spleen in TCM refers to the systematic function,including that of the pancreas in modern medicine.This paper holds that the treating of the glucose fluctuation can be under the guideline of spleen(pancreas) and kidney deficiency theory,which is very important and can provide effective ways.
7.The effects of dexamethasone and hyperbaric oxygen on the survival of subdermal vascular networks
Tao ZHANG ; Shu-Ya GUO ; Tang-Hong JIA ; Wei-Ming GONG ; Bing-Wei SUN ; Shu-Heng LIU ; Hong-Liang SONG ; Zhen-Hua LI ;
Chinese Journal of Physical Medicine and Rehabilitation 2003;0(05):-
Objective To study the effects of dexamethasone (DEX) and/or hyperbaric oxygen (HBO) on the subdermal vascular network (SVN).Methods SVNs were selected on dorsal skin flaps of 40 Wistar rats.The animals were divided randomly into a control group,a DEX group,a HBO group and a HBO+DEX group.Cranially based,2.5 cm?10 cm dorsal SVN skin flaps were sharply incised and elevated between the dartos and SVN,then sutured to their beds.On the 7th postoperative day,the surviving flap area was measured along with the number of new capillary,the thickness of meat tissue and the number of infiltrated neutrophilie granulocytes in the SVN skin flap.Results The mean surviving flap area for the control group was 7.90 cm~2,for the DEX group it was 10.48 cm~2,for the HBO group 15.53 cm~2,and for the DEX+HBO group it was 15.58 cm~2.The improvement in surviving flap area was highly statistically signifieant compared with the control.The improvement was also statistical- ly significant when the HBO group or HBO+DEX group was compared with the DEX group.However,no statistically significant difference was found between the HBO group and HBO+DEX group.Conclusion In a rat dorsal skin flap model,DEX or HBO improved skin flap viability,but DEX alone is not as efficacious as HBO or as DEX+ HBO.DEX plus HBO showed no additive beneficial effect over HBO alone.
8.Involvement of p38-p53 signal pathway in resveratrol-induced apoptosis in MCF-7 cells.
Ya-hong ZHANG ; Jing-gong GUO ; Zi-hua GUO ; Song-qiang XIE
Acta Pharmaceutica Sinica 2011;46(11):1332-1337
This paper is to report the study of resveratrol-induced apoptosis and its mechanisms in MCF-7 cells. MTT assay was performed to assess the cytotoxicity of resveratrol on MCF-7 cells. Hoechst 33258 staining was used to observe cellular morphologic changes in apoptosis. Apoptosis was measured by flow cytometric analysis and the protein expression was examined by Western blotting analysis. The results indicated that resveratrol could inhibit MCF-7 cell growth in a time- and concentration-dependent manner. Remarkable morphologic changes in the cells after 60 micromol L(-1) resveratrol treatment, including cell nuclear shrinkage, DNA condensation and apoptotic bodies, were observed by Hoechst 33258 staining. Resveratrol could induce apoptosis and activate p38 and p53 in a time dependent manner in MCF-7 cells. In addition, the cell growth inhibitory ratio and the apoptotic ratio of resveratrol-treated group decreased markedly by the p38 MAPK inhibitor SB203580 or p53 inhibitor pifithrin-alpha. Further experiments confirmed that resveratrol-induced p53 activation was reduced by SB203580 whereas the activation of p38 was not affected by pifithrin-alpha. In conclusion, resveratrol induced apoptosis in MCF-7 cells could be through activating p38-p53 signal pathway.
Antineoplastic Agents, Phytogenic
;
administration & dosage
;
pharmacology
;
Apoptosis
;
drug effects
;
Benzothiazoles
;
pharmacology
;
Cell Proliferation
;
drug effects
;
Dose-Response Relationship, Drug
;
Enzyme Inhibitors
;
pharmacology
;
Humans
;
Imidazoles
;
pharmacology
;
MCF-7 Cells
;
Pyridines
;
pharmacology
;
Signal Transduction
;
Stilbenes
;
administration & dosage
;
pharmacology
;
Toluene
;
analogs & derivatives
;
pharmacology
;
Tumor Suppressor Protein p53
;
antagonists & inhibitors
;
metabolism
;
p38 Mitogen-Activated Protein Kinases
;
antagonists & inhibitors
;
metabolism
9.Effect of acupuncture on hippocampal mitochondrial proteome expression in SAMP8 mouse model with Alzheimer disease
Mei-Ting LIANG ; Guang-Cheng LI ; Hong ZHU ; Qiong GONG ; Ke-Li DONG ; Cong LONG ; Ya-Yue LI ; Jiengisnur SAYRASH ; Yan-Ping YANG
Journal of Acupuncture and Tuina Science 2018;16(2):67-79
Objective:To observe the effect of acupuncture on the expression of mitochondrial proteome in hippocampus of senescence-accelerated mouse prone g (SAMPg) mice models with Alzheimer disease (AD),and to explore the possible protective mechanism of acupuncture on mitochondria.Methods:Sixty 6-month-old male SAMP8 mice were randomly divided into an acupuncture at acupoint group,an acupuncture at non-acupoint group and a model group,20 mice in each group.The 20 male senescence-accelerated mouse/resistance 1 (SAMR1) mice of the same age were used as a normal control group.Shenshu (BL 23),Baihui (GV 20),Xuehai (SP 10) and Geshu (BL 17) were selected for acupuncture intervention in acupuncture at acupoint group.After an 8-week intervention,mitochondrial tissues were extracted from the hippocampus.Differentially expressed proteins were identified by subcellular organelle proteomics.Western blot was used to verify the expressions of some related proteins in hippocampal mitochondria.Results:Compared with the model group,there were 13 differentially expressed protein spots in the acupuncture at acupoint group,of which,9 were up-regulated,including neurofilament light polypeptide (NFL),actin (cytoplasmic 1,database ID:ACTB),tubulin beta-2A chain (TBB2A),tropomodulin-2 (TMOD2),pyruvate dehydrogenase E1 component subunit beta (PDHE1-β),NADH-ubiquinone oxidoreductase 75 kDa subunit (database ID:NDUS1),heat shock cognate 71 kDa protein (HSC71),pyruvate dehydrogenase E1 component subunit alpha (PDHE1-α) and ATP synthase beta subunit (ATP-β);4 were down-regulated,including glial fibrillary acidic protein (GFAP),pyruvate dehydrogenase phosphatase 1 (PDP1),mitochondrial-processing peptidase subunit alpha (MMP-α) and adenosine kinase (ADK).According to the information provided in the protein database,most of the differentially expressed proteins involve the regulation of mitochondrial function and structure.The expression levels of NFL and TBB2A in the normal control group and the acupuncture at acupoint group were significantly higher than those in the acupuncture at non-acupoint group (P<0.05).ATP-β and NDUS1 expression levels were significantly higher in the acupuncture at acupoint group than those in the acupuncture at non-acupoint group (P<0.05);there was no significant difference between the acupuncture at non-acupoint group and the model group (P>0.05).Conclusion:Acupuncture may achieve the potential therapeutic effect on AD by regulating the structure and functional proteins of hippocampal mitochondria.
10.Predictors of long-term remission induced by short-term intensive insulin treatment in type 2 diabetic patients
Bo ZHANG ; Ya-Li AN ; Qiu-Hong GONG ; Ying SHUAI ; Shi BU ; YAN-YAN ; Jin-Ping ZHANG ; Wen-ying YANG ; Xue-li LIU ; Guang-wei LI
Chinese Journal of Endocrinology and Metabolism 1985;0(02):-
Objective To investigate the predictors of long-term remission of type 2 diabetes induced by short-term intensive insulin treatment.Methods Fifty-four cases of diabetes mellitus with the duration of illness less than 5 years received an intensive insulin treatment for 2 weeks.The standard meal test and intravenous glucose tolerance test were performed at the baseline and 24 h after treatment completion respectively.Long-term remission meant that the diabetic patients should maintain the target glyeaemic control without any hypoglyeaemie agent within one year.Results The remission rate was 57.4% (31/54) overall,and even reached to 80.6% (29/36) in patients with the duration of illness less than 6 months,whereas,the remission rate was only 11.1% (2/18) in those with the duration of illness more than 12 months.In another view,the remission rate was significantly higher in the patients with fasting plasma glucose (FPG) level of less than 7 mmol/L (78.8%,26/ 33) 24 h after intensive treatment than those with FPG level of more than 7 mmol/L (23.8%,5/21,P