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.The study on retention of gastroscopy skills after simulator training
Yang BAI ; Fa-chao ZHI ; Qiang NG ZHA ; Ya-li ZHANG ; Qing-feng DU ; Bo JIANG
Chinese Journal of Medical Education Research 2011;10(11):1398-1400
ObjectiveTo investigate whether the eight- year program students retain the skills from the endoscopy simulator gastroscopy training.Methods4 trainees accepted virtual reality simulator gastroscopy training and performed a standardized VR gastroscopy scenario at the end of training,and after a median 12 months without practice ( retention ).The intensified training was done by trainees based on the differences between the training end and the retention for a median 12 months and the number of intensified training times was found.ResultsThe significant differences existed in the overinsufflation and opeirational force and time.The score at the training end was better than after retention.Through the average 5.5 times intensified trainings the original levels could be reached.ConclusionThrough Endoscopy Simulator the key skills could be retained well and through a litde training the original levels could also be reached.
3.Killing efficacy of a medical disinfection ultrasonic coupling agent on five kinds of multidrug-resistant organisms
Dong LI ; Man-Yu LI ; Ya-Ping GUO ; Zhi YANG
Chinese Journal of Infection Control 2018;17(4):355-358
Objective To observe the efficacy of a medical disinfectant ultrasonic coupling agent on the killing of five clinically isolated multidrug-resistant organisms(MDROs).Methods From March 2016 to May 2017,a disin-fection ultrasonic coupling agent containing active ingredient,including triclosan and propylene glycol,was used to conduct carrier quantitative germicidal test on five clinically isolated MDROs,the killing efficacy to MDROs was ob-served.Results After 1.5,3.0,and 4.5 minute disinfection time,the killing logarithms values of disinfection ultra-sonic coupling agent to five MDROs(multidrug-resistant Acinetobacter bau m annii[MDR-AB],methicillin-resistant Staphylococcus aureus[MRSA],multidrug-resistant Pseudomonas aeruginosa[MDR-PA],carbapenem-resistant Klebsiella pneumoniae[CRKP],and extended-spectrum β-lactamase Escherichia coli[ESBLs-EC])were all>3.0. Conclusion Medical disinfection ultrasonic coupling agent can effectively kill five common MDROs,and can take the place of disinfectant during ultrasonic examination.
4.Effects of chronic arsenic exposure on estrogen receptor-binding fragment-associated gene 9 and estrogen-responsive finger protein mRNA expression in female rat's myocardium
Zhi-wei, GUO ; Wei-hong, YANG ; Xiao-hong, HAN ; Ya-juan, XIA
Chinese Journal of Endemiology 2013;(1):24-26
Objective To observe the effects of chronic arsenic exposure on estrogen receptor-binding fragment-associated gene 9 (Ebag9) and estrogen-responsive finger protein (efp) mRNA expression in female rat' s myocardium.Methods Fifty female Wistar rats were randomly divided into five groups according to arsenic (As2O3) concentrations in drinking-water:0.00(control),0.05,0.10,0.20,0.40 mg/L groups and RT-PCR was used to detect Ebag9 and efp mRNA expression of myocardium at the 32 weeks of experiment.Results Ebag9 and efp mRNA expression levels in 0.00,0.05,0.10,0.20,0.40 mg/L groups were respectively as follows:0.54 ±0.14,0.52 ± 0.10,0.48 ± 0.24,0.58 ± 0.13,0.45 ± 0.19 and 0.85 ± 0.14,0.86 ± 0.12,0.87 ± 0.09,0.99 ±0.10,0.86 ± 0.19.Compared to the control group,Ebag9 mRNA level of the 0.20 mg/L group was increased,and decreased in other groups,but the difference between two groups was not significant(all P > 0.05).Compared to control group,the efp mRNA level of 0.20 mg/L group increased significantly(P < 0.05),and showed increased tendency in other arsenic groups,but the difference between two groups was not significant (all P > 0.05).Conclusions Ebag9 and efp mRNA expression have changed in myocardium of rats exposed to chronic arsenic.Arsenic may has endocrine disruptor effect to female rat's myocardium.
5.Clinical observation on common peroneal nerve palsy treated with comprehensive therapy.
Li-Juan YANG ; Ya-Li LIU ; Shu-Bin WANG ; Zhi-Gao JIN
Chinese Acupuncture & Moxibustion 2014;34(4):334-336
OBJECTIVETo compare the difference of the clinical efficacy on common peroneal palsy between the comprehensive therapy of electroacupuncture, moxibustion and moving cupping method and western medication.
METHODSNinety cases of common peroneal nerve palsy were randomized into a comprehensive therapy group and a western medication group, 45 cases in each one. In the comprehensive therapy group, electroacupuncture was applied to Yanglingquan (GB 34), Zusanli (ST 36), Xuanzhong (GB 39), Jiexi (ST 41), Taichong (LR 3), Zulinqi (GB 41) and the others, combined with warm moxibustion and moving cupping on the lateral side of the affected leg. The comprehensive therapy was used once a day. In the western medication group, vitamin B1 , 10 mg each time, 3 times a day; and mecobalamine, 0. 5 mg each time, three times a day were prescribed for oral administration. In the two groups, 15 days made one session, and the efficacy was observed after 2 sessions treatment.
RESULTSThe total effective rate of the improvement of sensory function and motor nerve function was 97. 8% (44/45) in the comprehensive therapy group and was 82. 2% (37/ 45) in the western medication. The efficacy in the comprehensive therapy group was better than that of the western medication (P<0. 01). The electrophysiological examination showed that the amplitude of motor conduction of deep peroneal nerve and that of sensory conduction of surficial peroneal nerve after treatment were improved remarkably as compared with those before treatment in the comprehensive therapy group (both P<0. 05). The amplitude of motor conduction of deep peroneal nerve was improved significantly in the comprehensive therapy group as compared with that in the western medication group (P<0. 05).
CONCLUSIONThe comprehensive therapy of electroacupuncture, moxibustion and moving cupping method achieves the significant efficacy on common peroneal nerve palsy as compared with western medication.
Adolescent ; Adult ; Aged ; Combined Modality Therapy ; Electroacupuncture ; Female ; Humans ; Male ; Middle Aged ; Moxibustion ; Paralysis ; physiopathology ; therapy ; Peroneal Nerve ; physiopathology ; Young Adult
6.Expression of heat shock protein 70 in lung tissues of acute paraquat poisoned rats and intervention of ulinastatin
Zhi-Jian ZHANG ; Cong-Yang ZHOU ; Ya-Juan LUO ; Hua-Wei XIONG
World Journal of Emergency Medicine 2010;1(3):229-233
BACKGROUND: Paraquat (PQ) is an effective herbicide and is widely used in agricultural production, but PQ poisoning is frequently seen in humans with the lung as the target organ. Clinically pulmonary pathological changes are often used to predict the severity and prognosis of the patients. In this study, we observed the expression of heat shock protein 70 (HSP70) in rat lung after PQ poisoning and to investigate the therapeutic effects of ulinastatin. METHODS: Seventy-two adult healthy SD rats were randomly divided into a control group (group A, n=24), a poisoning group (group B, n=24), and an ulinastatin group (group C, n=24). The rat models of acute PQ poisoning were established by intra-gastric administration of 80 mg/kg PQ to rats of groups B and C, and the rats of group C were intra-peritoneally injected with 100000 IU/kg ulinastatin 30 minutes after poisoning. The expression of HSP70 in lung tissue was observed, and W/D and histopathological changes in the lung tissue were compared 12, 24, 48 and 72 hours after poisoning. The expression of HSP70 in the lung tissue was assayed by using RT-PCR. All quantitative data were processed with one-way analysis of variance to compare multiple sample means. RESULTS: Compared to group A, the expression of HSP70 in the lung of rats in groups B and C increased significantly at all intervals (P<0.05). The pathological changes in lung tissue of rats with PQ poisoning included congestion, leukocytes infiltration and local hemorrhage, whereas those of group C were significantly lessened. CONCLUSION: Ulinastatin may ameliorate acute lung injury to some extent after PQ poisoning in rats by enhancing the expression of HSP70.
7.Prospective experimental studies on the renal protective effect of ulinastatin after paraquat poisoning
Zhi-Jian ZHANG ; Li-Bo PENG ; Ya-Juan LUO ; Cong-Yang ZHOU
World Journal of Emergency Medicine 2012;3(4):299-304
BACKGROUND: Paraquat (PQ) is an effective herbicide and is widely used in agricultural production, but PQ poisoning is frequently seen in humans with the lung as the target organ. Currently, there are many studies on lung injury after PQ poisoning. But the kidney as the main excretory organ after PQ poisoning is rarely studied and the mechanisms of this poisoning is not very clear. In this study, we observed the expression of caspase-3 and livin protein in rat renal tissue after PQ poisoning as well as the therapeutic effects of ulinastatin. METHODS: Fifty-four Sprague-Dawley (SD) rats were randomly divided into three experimental groups: control group (group A), paraquat poisoning group (group B) and ulinastatin group (group C), with 18 rats in each group. Rats in group B and group C were administered intragastrically with 80 mg/kg PQ, rats in group C were injected peritoneally with 100000 U/kg ulinastatin once a day, while rats in group A were administered intragastrically with the same volume of saline as PQ. At 24, 48, 72 hours after poisoning, the expression of livin in renal tissue was detected by Westen blotting, the expression of caspase-3 was detected by immunohistochemistry, and the rate of renal cell apoptosis was tested by TUNEL detection. The histopathological changes were observed at the same time. RESULTS: Compared to group A, the expression of caspase-3 in the renal tissue of rats in groups B and C increased significantly at any time point. Compared with group B, the expression of caspase-3 in renal tissue of rats in group C decreased. Compared with group A, the expression of livin in renal tissue in rats of groups B and C increased significantly at any time point (P<0.01), especially in group C (P<0.01). TUNEL method showed that the rate of renal cell apoptosis index was higher in group B at corresponding time points than in group A (P<0.01), and was lower in group C at corresponding time points than in group B (P<0.01). CONCLUSION: UTI has a protective effect on the renal tissue of rats after paraquat poisoning through up-regulating the expression of livin and down-regulating the expression of caspase-3, but the regulation path still needs a further research.
8.Screening for potential biomarkers of traditional Chinese medicinechest impediment syndromesbased on plasma metabonomics
Li-Yun XU ; Xiao-Ya LUO ; Xiao-Ling SHEN ; Yu-Yang YOU ; Zhi-Hong YANG
Chinese Journal of Pharmacology and Toxicology 2018;32(4):319-319
OBJECTIVE To have a systematic pathomechanism view of three chest impediment-syndromes of Qi Deficiency and Blood Stasis syndrome(QDBS),Qi Stagnation and Blood Stasis syn-drome (QSBS), Cold Obstruction and Qi Stagnation syndrome(COQS) and further investigate the changed metabolome and related pathways for screening potential biomarkers in rat plasma. METHODS According to clinical pathogeny, three kinds of syndrome models were established to simulate the disease of chest impediment. Plasma metabonomics based on UPLC-Q-TOF/MS was applied in this research to detected small molecule metabolites for identifyingthe special potential biomarkers of three chest impediment syndromes, respectively. RESULTS Significant metabolic differences were observed between thecontrol group and three syndrome groups. Furthermore, three syndrome groups were distinguished clearly by pattern recognition method.The particular metabolites contributing most to the classification of three chest impediment syndromes were identified. In the QSBS group, the potential biomarkers could include 2-keto-glutaramic acid, L-methionine, L-homocysteic acid, octadecanamide, stearoylglycine,behenic acid,linoleylcarnitine,lysoPC(14:1(9Z)),indoxyl sulfate and cholic acid.In the COQS group, they could be aminoadipic acid, palmitic amide, oleamide, lysoPC(P-16:0), lysoPC(P-18:0), lysoPC(20:2(11Z,14Z)), 9-HETE and tauroursodeoxycholic acid. Moreover, 4-pyridoxic acid, L-palmi-toylcarnitine, lysoPC(20:0), lysoPC (22:5 (4Z,7Z,10Z,13Z,16Z)), 3- hydroxyhexadecanoic acid and arachidonic acid could be the potential biomarkers for the QDBS group. CONCLUSION Three chest impediment syndromes have their own potential biomarkers.Each special metabolite has its owndifferent metabolic pathway.Both metabolismof cysteine and methionine,and metabolism of alanine,aspartate and glutamate are the main pathways in regulation of metabolic disorders in QSBS syndrome. Lysine biosynthesis and degradation,fatty acid metabolism,and glycerophospholipid metabolism are the main pathways in regulation of metabolic disorders in COQS syndrome.Arachidonic acid metabolism, fatty acid metabolism,fatty acid elongation in mitochondria,and vitamin B6 metabolism are the main pathways in regulation of metabolic disorders in QDBS syndrome.These endogenous substances were indicated as the special potential biomarkers for three chest impediment syndromes and worth studying in depth.
10.Effect of moxibustion on T lymphocyte subsets in peripheral blood of rats with gastric cancer
Jing TAN ; Ren-Da YANG ; Huan ZHAO ; Zhuo-Jun PENG ; Li-Zhi OUYANG ; Ya-Ping LIN ; Yan-Ping YANG
Journal of Acupuncture and Tuina Science 2019;17(3):161-167
Objective:To observe the effect of moxibustion on T lymphocyte subsets in peripheral blood of rats with gastric cancer. Methods:Sixty healthy Sprague-Dawley (SD) rats were adaptively fed for one week. By the random number table method, 10 rats were randomly selected as a blank group, and 12 rats were randomly selected to simulate the tumor transplantation process; after transplantation, 10 rats were randomly selected as a sham operation group. The remaining 38 rats were used to prepare gastric cancer models by gastric transplantation of the Walker-256 tumor tissue; 8 rats were randomly selected to verify the successful modeling after 7 d; the remaining 30 rats were randomly divided into a model group, a moxibustion group and an infrared group by the random number table method, with 10 rats in each group. From the first day of enrollment, the rats in the moxibustion group received mild moxibustion at Zhongwan (CV 12), Guanyuan (CV 4) and bilateral Zusanli (ST 36) (the first group) and bilateral Pishu (BL 20) and Weishu (BL 21) (the second group), and the two groups of acupoints were alternated every other day. The rats in the infrared group received infrared radiation on the stomach area and the area on the back between the T12-T13 spinous processes, the two areas were alternated every other day. Rats in the moxibustion group and the infrared group were treated for 20 min each time, once a day for 21 d. Rats in the blank group, the sham operation group, and the model group were simultaneously grasped and fixed, and no other treatment was performed. After 21 d of intervention, the rats in each group were fasted for 12 h, and blood was collected from the orbits. The numbers of CD3+, CD3+CD4+, CD3+CD8+ T lymphocytes in peripheral blood were determined by flow cytometry, and the ratio of CD3+CD4+/CD3+CD8+ was calculated. The rats were sacrificed and the thymus was dissected under sterile conditions to calculate the thymus index. Results:Compared with the blank group, the thymus index, peripheral blood CD3+, CD3+CD4+, CD3+CD8+ and CD3+CD4+/CD3+CD8+ ratio in the sham operation group did not change significantly (allP>0.05). Compared with the blank group, the thymus index of the model group was increased (P<0.05), the CD3+ and CD3+CD8+ T lymphocytes were increased (bothP<0.01), and the CD3+CD4+/CD3+CD8+ ratio was decreased (P<0.05). Compared with the model group, the thymus index of the moxibustion group was increased (P<0.01), and CD3+, CD3+CD4+ and CD3+CD8+ T lymphocytes and the ratio of CD3+CD4+/CD3+CD8+ in peripheral blood were increased (allP<0.05). Compared with the infrared group, the thymus index of the moxibustion group was significantly increased (P<0.05), the CD3+ and CD3+CD4+ T lymphocytes in the peripheral blood were significantly increased (bothP<0.01), and the CD3+CD8+ was increased (P<0.05). Conclusion:Moxibustion can significantly increase the thymus index of gastric cancer-bearing rats and activate CD3+CD4+ and CD3+CD8+ T lymphocytes in peripheral blood.