BACKGROUND: Fms-like tyrosine kinase-3 (FLT3) gene is one of the receptors for growth factors in early hematogenesis. By binding to its ligand (FL), FLT3 regulates the proliferation and differentiation of hematopoietic stem/pregenitor cells via cell signal transduction pathway. FLT3 juxtamembrane internal tandem duplication (ITD)mutation is correlated with leukemia onset, development and act as an independent factor for poor prognosis.OBJECTIVE: To explore the relationship between Flt-3/ITD mutation and acute leukemia (AL), and analyze its clinical implication.DESIGN: A repetitive measurement.SETTING: Department of Biochemistry and Molecular Biology, Shenyang Medical College.PARTICIPANTS: Totally 147 samples of leukemia patients were diagnosed by morphological bone marrow biopsy in Shenyang Central Hospitals affiliated to Shenyang Medical College from January 1999 to October 2004. They were 95 males and 52 females with the mean age of 14.5 years old (5-23 years old). According to FAB standard, there were 62 patients with acute leukemia [including 33 cases of acute myelocytic leukemia (AMLs, M1, M2), 3 cases of acute myelo-monocytic leukemia (AMMOLs, M4), 18 cases of acute monocytic leukemia (AMOLs, M5), 8 cases of acute megakaryocytic leukemia (AMKLs, M7)], 43 patients with acute lymphoblastic leukemia (ALLs), 13 patietns with juvenile chronic myelocytic leukemia (JCMLs) and 29 patients with myelodysplastic syndrome (MDSs). Informed contents were obtained from all the participants.METHOD: Flt-3/ITD was detected with polymerase chain reaction (PCR) sequence in the 147 leukemia patients.MArN OUTCOME MEASURES: The clinical manifestations and prognosis were observed in the ALL patients with Flt-3/ITD;The Flt-3 gene expression, Flt-3/ITD positive rate, duplication region and length were detected in all kinds of leukemia.to Flt-3 gene products, including 3 cases of AMLs (M1, M2), 1 case of AMMOL (M4), and 1 case of AMOL (M5). DNA sequencing and blast alignment revealed that ITDs existed in all samples with unusual products within exon 11, in various region and length (33-72 bp). Expression of Flt-3 in different levels was found in 43 cases of ALL, 29 cases of Flt-3/ITD all died short after the diagnosis, and the mean life span of was only 10.8 months.

BRCA1 is a breast cancer susceptibility gene,which related to breast cancer,ovarian cancer and other cancers.The occurrence of breast cancer is related to gene mutation.In recent years,more and more researches indicated some clinical characteristics of breast cancer relevant to BBCA1,such as the reaction to chemotherapy,radiotherapy and operation. This review will provide guidance for future application of BRCA1 in clinic by introducing the clinical progression of it.

Irritable bowel syndrome(IBS)is a commonly seen functional gastrointestinal disorder. Its main clinical manifestations were abdominal pain,abdominal distention and altered bowel habits. Currently,the pathogenesis of IBS has not been clarified. Studies showed that IBS was caused by many factors,including life style,gene polymorphism,food hypersensitivity,psychological factors,brain-gut axis abnormality and intestinal flora disorder. This article reviewed the advances in study on pathogenesis of IBS.

Allergens ; immunology ; Child ; Cross Reactions ; Humans ; Hypersensitivity ; immunology ; Latex Hypersensitivity ; immunology

Objective To explore clinical effect of arthroscopic circumpatellar denervation in anterior knee pain of patellofemoral osteoarthritis and its correlation with cartilage degeneration.Methods Totally 104 patients with anterior knee pain of patellofemoral osteoarthritis were randomly divided into two groups.Patients in control group(n =52) were treated with arthroscopic debridement,and those in combined group(n =52) were treated with arthroscopic debridement plus circumpatellar denervation.All the patients were followed-up for 6 months.The WOMAC scores,knee function recovery were compared between two groups,and the changes of WOMAC score among different degrees of cartilage degeneration were analyzed.Results The WOMAC score of pain,morning stiffness and joint function were significantly improved in combined group than those in control group at 6 months after surgery(P ＜ 0.05).At 6 months after surgery,the score of range of activity and walking distance in both groups were all increased,and combined group had more remarkable increase than that of control group(P ＜ 0.05).Compared with before surgery,the total WOMAC score in patients with grade Ⅰ-m at 6 months after surgery significantly decreased (P ＜ 0.05),while there was no significant difference in patients with grade Ⅳ level between before surgery and 6 months after surgery (P ＞ 0.05).Conclusion Arthroscopic debridement plus circumpatellar denervation for anterior knee pain of patellofemoral osteoarthritis can effectively relieve pain symptom,promote the recovery of knee joint function,especially suitable for patients with cartilage degeneration of Ⅰ ～ Ⅲ.

The pharmaceutical ethynylestradiol (EE) is a potent endocrine modulator. Application enlargement of ethynylestradiol in clinics and abuse in livestock farming and fishing make it important to explore ethynylestradiol toxicological action on vertebrate embryonic development and to establish an in vivo method for EE toxicity detection efficiently and conveniently. In the present study, using a model animal zebrafish and 17alpha-ethynylestradiol as a representative compound, we have investigated EE2 teratogenicity, target tissues and target genes on zebrafish embryo. The results show that median teratogenesis concentration (TC50) of EE2 is 0.8 microg x mL(-1), and median lethal dose (LD50) is 3.3 microg x mL(-1). Targets of EE2 action were implicated in brain, eyes, heart, muscle, skeleton, pigment and viscera. Embryonic cardiac arrhythmia caused by EE2 is probably resulted from heart abnormal structure. The embryonic stage sensitive to EE2 mainly started at cleavage and last up to the organogenesis with time-accumulating effect. RT-PCR results indicate that EE2 treatment disturbed gene expression pattern at the early period of zebrafish embryonic development by suppressing transcription of gene boz that promotes brain development, upregulating genes for trunk and tail, such as ntl, spt, shh, and perturbing Nodal signal expression of TGFbeta superfamily, for example, cyc, sqt and oep. Using zebrafish, an efficient in vivo method for quick evaluation of EE toxicity on embryonic development has been developed.

Objective To study the effects of different doses of UVA1 on the development of hypertrophic scar in rabbit ears induced by excision of full-thickness skin. Methods A hypertrophic scar model was established by excision of full-thickness skin (2 cm×5 cm) on the ventral surface of rabbit ears. A total of 18 New Zealand rabbits were randomly divided into 3 equal groups to receive UVA1 radiation on the left ears immediately, 1 month, and 2 months after the excision, respectively, and every group were classified into two subgroups to be irradiated with 60 and 110 J/cm2 of UVA1, respectively, for 30 sessions. The right ears served as control without irradiation. HE staining and Masson staining were used to examine the dermal thickness and collagen content in scar, respectively. Results Compared with pre-irradiation, the dermal thickness (t = 5.85, 4.94, respectively, both P＜0.05) and collagen content (t = 6.50, 8.02, respectively,both P＜0.05) significantly decreased in scar irradiated with UVA1 of 110 J/cm2 one and two months after the excision. The difference value in dermal thickness and collagen content at the beginning and at the end of the study significantly differed between irradiated and non-irradiated ears in the rabbits treated with UVA1 of 110 J/cm2 (P＜0.05). The effects of UVA1 on dermal thickness and collagen content were dose-dependent (P＜0.05). On the contrary, the dermal thickness and collagen content markedly increased in scars of rabbits irradiated with UVA1 immediately after the excision (P＜0.05 ). Conclusions To begin UVA1 exposure of hypertropic scar in rabbits after epithelialization may lead to the softening of scar, thinning of skin, and decrease of collagen content. However, immediate irradiation with UVA1 after wound could not prevent the development of hypertrophic scar in rabbits, in contrast, it exacerbated the severity of scar.

Objective To study the possible mechanisms of influence of different doses of UVA1 on the development of hypertrophic scar in rabbit ears induced by excision of full-thickness skin. Methods A hypertrophic scar model was established by excision of full-thickness skin on the ventral surface of rabbit ears.A total of 24 New Zealand white rabbits were randomly and equally divided into 4 groups to receive UVA1 radiation on the left ear immediately (U0 group), 1 month (U1 group), 2 months (U2 group) and 3 months (U3 group) after the excision, respectively, and each group were classified into two subgroups to be irradiated with UVA1 of 60 (middle) and 110 (high) J/cm2, respectively, for 30 sessions. The right ears served as the control without irradiation. Skin samples were obtained from the ears of rabbits before the first and after the last irradiation, transmission electron microscopy (TEM) was used to observe the ultra-structure and morphology of collagen fiber and fibroblasts, and immunohistochemical staining was performed to measure the expressions of matrix metalloproteinases (MMP)-1, tissue inhibitor of metalloproteinase (TIMP)-1, transforming growth factor (TGF)-β1, proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) in skin samples. Results Compared with the unirradiated skin, irradiated skin showed higher expression levels of MMP-1 (P ＜ 0.05), which were 10.43 ± 1.61 and 11.16 ± 1.57 in middle- and high-U1 group, 8.63 ± 2.61 and 7.33 ± 1.58 in middle- and high-U2 gorup, 5.74 ± 1.43 and 3.11 ± 0.27 in middle- and high-U3 group respectively. The expression level of TGF-β1 in irradiated skin was 12.51 ± 4.13 and 12.02 ± 5.02 in middle- and high-U1 group, respectively, 18.74 ± 6.42 and 19.69 ± 4.52 in middle- and high-U2 group, respectively, 20.51 ± 1.78 and 29.45 ± 6.55 in middle- and high-U3 group, respectively. A significant decrease was observed in the expression of PCNA in irradiated skin in middle- and high-U1 group (2.67 ± 0.44 and 2.04 ± 0.65), middle- and high-U2 group (4.50 ± 0.97 and 5.82 ± 0.68), middle- and high-U3 group (7.45 ± 1.47 and 8.16 ±1.07) in comparison with unirradiated skin (all P＜ 0.05). There was a lower expression of TIMP-1 in irradiated skin of high-U1, -U2, and -U3 group (12.74 ± 4.58, 15.17 ± 3.26, 20.72 ± 3.31, all P＜ 0.05) as well as α-SMA in that of high-U1, middle-U1 and high-U2 group (1.33 ± 0.34, 2.04 ± 0.20, 3.60 ± 1.75, all P＜ 0.05) compared with the unirradiated skin. Further more, a significant increment was observed in the expressions of TGF-β1 (23.90 ± 2.92, P ＜ 0.05) in irradiated skin of high-U0 group, PCNA(7.42 ± 0.65 and 7.59 ± 0.31 ),TIMP-1 (29.82 t 1.94 and 33.51 ± 1.19) and α-SMA (6.31 ± 0.61 and 2.97 ± 0.56) in irradiated skin of middle- and high-U0 group, but a decline in the expression of MMP-1 (.25 ± 0.38, P＜ 0.05) in irradiated skin of high-U0 group in comparison with the unirradiated skin. TEM showed that the collagen fiber diameter turned small, and fibroblasts, most of which were quiescent, showed a reduction in cytoplasm volume with the presence of immature organelles, after high-dose UVA1 irradiation. Conclusions The therapeutical effect of UVA1 on scar may be realized by accelerating the degradation of matrix proteins and decelerating the proliferation of fibroblasts and myofibroblasts via downregulating the expressions of TGF-β1, TIMP-1 and α-SMA and upregulating the expression of MMP-1. However, the results would be opposite if the interference with UVA1 irradiation is given at the early stage of wound healing.

Objective To investigate the influence of hydroxyethyl starch solution on exogenous coagulation and active protein C (APC) in the patients with septic shock.Methods A single-center prospective study was conducted.Eighty-four consecutive patients with septic shock admitted to intensive care unit (ICU) of Peking University People's Hospital from November 2009 to October 2014 were enrolled.The patients were randomized into two study groups by random digits table:Ringer lactate solution group (RL group,n =40) and hydroxyethyl starch group (HES group,n =44),and Ringer lactate solution or hydroxyethl starch 130/0.4 was used for resuscitation respectively.Peripheral blood was collected at four time points:before resuscitation,6,12,and 24 hours after resuscitation.The prothrombin time (PT),tissue factor (TF),tissue factor pathway inhibitor (TFPI) and APC were determined,and the length of ICU stay and the mortality were recorded.Results There were no significant differences in PT,TF,TFPI,and APC before and after resuscitation in RL group.No change in PT was found after resuscitation in HES group,and no significant difference was found as compared with RL group.TF after resuscitation in HES group was decreased gradually,and the level at the 24 hours after resuscitation was significantly lower than that before resuscitation (U/L:15.80±7.32 vs.31.40±2.75,P ＜ 0.05); but there was no significant difference at all time points when compared with that of RL group (all P ＞ 0.05).TFPI at 12 hours and 24 hours after resuscitation in HES group was increased when compared with before resuscitation (μg/L:1.32±0.22,1.14±0.09 vs.0.63±0.54).TFPI in HES group was significantly higher than that in RL group (μg/L:0.84 ± 0.69,0.95 ± 0.30),but there was no significant differences between two groups (both P ＞ 0.05).APC after resuscitation in HES group was decreased gradually,which was significantly lower than that in RL group at 6,12,24 hours after resuscitation (mg/L:3.38±3.00 vs.5.98±4.12,3.31 ± 1.94 vs.5.33 ± 3.71,3.42 ± 2.64 vs.7.53 ± 4.67,P ＜ 0.05 or P ＜ 0.01).The length of ICU stay in HES group was significantly shorter than that in RL group (days:12.50 ± 8.83 vs.17.10± 16.60,t =9.037,P ＜ 0.001),but there was no significant difference in mortality between HES group and RL group [40.9％ (18/44) vs.60.0％ (24/40),x 2=2.339,P =0.126].Conclusions Both RL and hydroxyethyl starch fluid resuscitation did not affect the PT of the patients.The use of hydroxyethyl starch probably inhibits excessive activation of the exogenous coagulation and hyper-coagulation in the early stage of sepsis,and inhibits activation of protein C as well.

Objective To investigate the influences of Xuebijing injection on organs' ultra-microstructure in septic shock rats. Methods Fifteen male Sprague-Dawley (SD) rats of clean grade were selected. According to the method of random digits table, all of them were divided into three groups: sham operation group, model group and Xuebijing treated group, 5 rats being in each group. Cecal ligation and puncture (CLP) was adopted to reproduce abdominal cavity infection leading to sepsis model formation. While the rats in sham operation group just underwent abdominal median incision, abdominal exploration and closure of abdominal wall after flipping retrocecal region. In the Xuebijing treated group, within 1 hour after the operation, Xuebijing injection (4 mL/kg) was transfused through the catheter inserted in the femoral vein, and then normal saline (2 mL·kg-1·h-1) was continuously transfused until the rat being sacrificed. In the sham operation group and model group, equal volume of normal saline was given after operation. The blood pressure of all the rats was monitored continuously by a pressure device connected with a catheter inserted in the right carotid artery. The rats were observed for 12 hours, afterwards they were sacrificed, the samples of heart, lung, kidney and liver were taken, and their ultrastructural changes were observed under an electron microscope. Results The blood pressure of sham operation group was decreased a little with time extension, but within normal limits. The mean arterial pressure (MAP) of model group and Xuebijing treated group developed into a state of sepsis shock at 9 hours and 10 hours after operation respectively, and MAP were lower than 70 mmHg (1 mmHg=0.133 kPa). The MAP levels of model and Xuebijing groups at 11 hours after operation were lower significantly than those of sham operation group (mmHg:58.7±7.0, 58.7±8.3 vs. 91.0±8.2, both P<0.01), and they were persistently decreased at 12 hours after operation;the MAP in Xuebijing group was a little higher than that of model group at the same period (mmHg:55.4±4.0 vs. 48.8±12.9, P>0.05). The results of the observation with electron microscope:the structures of heart, lung, liver and kidney in sham operation group were basically normal;all the organs of model group appeared different degrees of structural damage. Compared with model group, the injury of heart and lung in Xuebijing treated group was milder, especially, the changes of cellular mitochondria were obvious;however, there was no significant difference in injury of kidney and liver between the model and Xuebijing treated groups. Conclusion Xuebijing injection can play a certain role in stabilizing the circulatory system in rats with septic shock, and can possibly ameliorate the heart and lung damage caused by infection and shock.