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.

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.

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.

OBJECTIVETo investigate whether Resolvin E1 (RvE1) could protect against ox-LDL-induced injury on human vein vascular endothelial cells and reveal related molecular mechanisms.

METHODSHuman 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-α 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.

RESULTCompared 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 + RvE1 group compared to ox-LDL group (P < 0.01), these beneficial effects of RvE1 could be blocked by PI3K inhibitor wortmanin (P < 0.05).

CONCLUSIONThe present data showed that RvE1 could effectively protect against ox-LDL-induced endothelial cell injury, which might be mediated by PI3K-AKT signaling pathway.

Apoptosis ; drug effects ; Cells, Cultured ; Eicosapentaenoic Acid ; analogs & derivatives ; pharmacology ; Endothelial Cells ; drug effects ; metabolism ; Humans ; Lipoproteins, LDL ; adverse effects ; Signal Transduction ; Umbilical Veins ; cytology

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

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.

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

OBJECTIVETo construct a recombinant plasmid containing the coding region of tight junction protein claudin-1 gene to understand the functional role of claudin-1 in human colorectal carcinoma.

METHODSThe total RNA was extracted using Trizol from human colorectal carcinoma cell line SW620, and the DNA for claudin-1 was obtained by means of RT-PCR. The PCR product was inserted into the plasmid pEGFP-C1 after restriction endonuclease digestion and ligation. The recombinant plasmid was then transfected into human colorectal carcinoma cell line SW480.

RESULTSThe sequence of the recombinant plasmid was verified by restriction endonuclease and DNA sequence analysis, and the target protein expression was detected mostly on the cell membrane.

CONCLUSIONThe expression vector claudin-1/pEGFP-C1 has been constructed successfully and the target protein can be expressed in human colorectal carcinoma cell line.

Cell Line, Tumor ; Claudin-1 ; Cloning, Molecular ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; Genetic Vectors ; genetics ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Membrane Proteins ; genetics ; metabolism ; Microscopy, Confocal ; RNA, Messenger ; biosynthesis ; genetics ; Recombinant Fusion Proteins ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tight Junctions ; metabolism ; Transfection

To construct plasmid of recombinant protein candidate vaccine of respiratory syncytial virus, express it in E. coli, and to investigate its immunogenicity and protective efficacy. A CD8+ T cell epitope from respiratory syncytial virus (RSV) M2 protein F/M2:81 - 95 and the G:125-225 (G1) gene fragments from RSV-G protein containing B cell epitopes were amplified by PCR method and then inserted into the prokaryotic expression vector pET-DsbA after bonding to a linker. The fusion protein DsbA-G1-Linker-F/M2:81-95 (D-G1LF/M2) was expressed successfully in E. coli BL21 (DE3). The product was proved to be RSV-specific by Western-blot. After purified by affinity chromatography on Ni+ Sepharose and renatured by gradient dialysis. D-G1LF/M2 was used to immune BALB/c mice. D-G1LF/M2 induced high anti-D-G1LF/M2 IgG, anti-RSV IgG and neutralizing antibody titers in serum and lung of BALB/c mice, and elicied RSV-specific CTL responses. The IgG subclass distribution revealed that IgG1/IgG2a ratio was 2.66. Viral titration indicated that D-G1LF/M2 could protect BALB/c mice against RSV challenge in lung.
Animals ; Antibodies, Viral ; blood ; immunology ; Escherichia coli ; genetics ; metabolism ; Humans ; Immunoglobulin G ; blood ; immunology ; Mice ; Mice, Inbred BALB C ; Plasmids ; genetics ; immunology ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; immunology ; Respiratory Syncytial Virus Infections ; prevention & control ; Respiratory Syncytial Virus Vaccines ; biosynthesis ; genetics ; immunology ; Respiratory Syncytial Virus, Human ; genetics ; immunology ; Viral Envelope Proteins ; genetics ; Viral Fusion Proteins ; genetics ; Viral Proteins ; genetics

OBJECTIVETo investigate the optimal time and method of the early repair of the full layer eyelid defect caused by chemical burn.

METHODSFree nasal septum mucosal cartilage flap with muscle flap, skin grafting, or skin flap were performed in 18 cases (19 eyelids) with chemical burn within 4 postburn weeks. Eyelid reconstruction and corneal transplantation were performed at the same time in 4 patients.

RESULTSAll the reconstructed eyelids and transplanted cornea survived. The incidence of severe complications, such as exposure keratitis, corneal ulcer and eyeball perforation decreased.

CONCLUSIONFull layer eyelid defect caused by chemical burn should receive early reconstruction and repair, including timely reconstruction of eyelid for the sake of protecting the eyesight and of alleviating the inflammatory reactions, and the corneal transplantation should be done at the same time to avoid corneal perforation. Nasal septum mucosal cartilage flap could be ideal for the eyelid reconstruction.

Adult ; Burns, Chemical ; surgery ; Corneal Transplantation ; Eyelids ; injuries ; surgery ; Female ; Humans ; Male ; Middle Aged