ObjectiveTo explore the optimal method of protecting bone marrow in postoperative concurrent chemoradiotherapy of stage Ⅱ - Ⅲ rectal cancer by comparing two techniques of intensitymodulated radiotherapy (IMRT). MethodsFifteen patients with stage Ⅱ - Ⅲ rectal cancer after surgery had CT simulation. Clinical target volume, small bowel, bladder and bone marrow were contoured. Two IMRT treatment plannings with and without bone marrow-sparing (BMS-IMRT and IMRT) were separately designed. The dose distribution was compared based on that 95％ of the planning target volume received the prescribed dose. ResultsBMS-IMRT had an advantage over IMRT in terms of conformity indices ( 1. 06∶1. 04, t =- 2. 61, P =0. 023 ), but inferior to I M RT for homogeneity indices ( 0. 81 : 0. 75, t =- 2. 34, P =0.037)).Compared with IMRT, BMS-IMRT reduced the V5, V10, V20, V30, V40 of bone marrow (97.09％∶98.72％, t=-2.34, P=0.037;92.38％∶96.46％, t=-2.41, P=0.033;83.36％∶91.70％, t=-3. 18, P=0.008;51.47％∶69.65％, t=-4.92, P=0.000;36.34％∶49.57％, t=-2.66, P =0. 021 ). The doses received by small bowel and bladder were similar between BMS-IMRT and IMRT, except that the V20 of bladder was lower in BMS-IMRT (77. 32％∶92. 39％, t =-3.52, P=0. 004). Conclusions BMS-IMRT reduces low dose volume of bone marrow without increasing dose to other risk organs.BMS-IMRT might reduce acute hematologic toxicity and increase the feasibility of postoperative concurrent chemoradiotherapy in stage Ⅱ -Ⅲ rectal cancer.

OBJECTIVE Oxidative sress is one of the key factor responsible for occurrence and development of hepatic fibrosis, a common consequence of chronic liver injury of multiple etiology. Nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a major regulator of a celular defense system against oxidative stress. Xiaochaihutang (XCHT), a compound of seven botanical extracts used for liver diseases traditionally in East Asia. However, few studies have investigated its anti-hepatic fibrosis effects and pathophysiological mechanism of action. The present study was designed to confirm the anti-hepatic fibrosis effects and explore its potential mechanism of action by investigating the intervention of Nrf2 pathway. METHODS Liver fibrosis was induced by repeated injection of Carbon tetrachloride (CCl4) over a period of 9 weeks. Starting from the 6th week, the animals in treatment groups were given the appropriate dose of XCHT granules and silybin. Biochemical parameters, histological changes of the liver and alpha-smooth muscle actin (α-SMA) were determined. The expressions of Nrf2, Keap1, Nqo1, HO-1, Gclc and Gclm were assessed by RT-PCR and Western blot. RESULTS CCl4 caused a significant fibrosis damage in the rat liver and the liver functions and fibrosis degree were significantly improved by XCHT (5 g·kg- 1 and 10 g·kg- 1). XCHT (5 g·kg- 1 and 10 g·kg- 1) treatment significantly decreased the number of cells labeled with α-SMA antibodies. Moreover, XCHT (5 g·kg-1 and 10 g·kg-1) significantly increase Nqo1, HO-1, Gclc and Gclm expressions in the liver. CONCLUSION These studies establish XCHT is a potentially useful therapeutic agent for treatment of hepatic fibrosis and it might be via regulation of Nrf2 pathway in rats against oxidative stress, making further efforts to inhibiting the activated HSCs. Activation or up-regulation of Nrf2 pathway may be an alternative treatment strategy for liver fibrosis.

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis(OSF),a premalignant disease that is largely induced by betel quid chewing.However,the lack of available models has challenged studies of angiogenesis in OSF.Here,we found that the expression of thrombospondin 1(THBS1),an endogenous angiostatic protein,was elevated in the stroma of tissues with OSF.Using a fibroblast-attached organoid(FAO)model,the overexpression of THBS1 in OSF was stably recapitulated in vitro.In the FAO model,treatment with arecoline,a major pathogenic component in areca nuts,enhanced the secretion of transforming growth factor(TGF)-β1 by epithelial cells,which then promoted the expression of THBS1 in fibroblasts.Furthermore,human umbilical vein endothelial cells(HUVECs)were incorporated into the FAO to mimic the vascularized component.Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs(vFAOs).Consistently,treatment with arecoline reduced the expression of CD31 in vFAOs,and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36,a receptor of THBS1.Finally,in an arecoline-induced rat OSF model,THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo.Overall,we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

The safety of Chinese patent medicine has become a focus of social. It is necessary to carry out work on post-marketing clinical safety evaluation for Chinese patent medicine. However, there have no criterions to guide the related research, it is urgent to set up a model and method to guide the practice for related research. According to a series of clinical research, we put forward some views, which contained clear and definite the objective and content of clinical safety evaluation, the work flow should be determined, make a list of items for safety evaluation project, and put forward the three level classification of risk control. We set up a model of post-marketing clinical safety evaluation for Chinese patent medicine. Based this model, the list of items can be used for ranking medicine risks, and then take steps for different risks, aims to lower the app:ds:risksrisk level. At last, the medicine can be managed by five steps in sequence. The five steps are, collect risk signal, risk recognition, risk assessment, risk management, and aftereffect assessment. We hope to provide new ideas for the future research.
Clinical Trials as Topic ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; etiology ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; economics ; therapeutic use ; Herbal Medicine ; economics ; legislation & jurisprudence ; Humans ; Patents as Topic ; Product Surveillance, Postmarketing ; Quality Control

No abstract available.
Humans*

This study was aimed to evaluate IKAROS6 expression in patients with chronic myelogenous leukemia (CML) and its clinical significance. cDNAs from 73 CML patients were amplified by PCR and sequenced for IKAROS expression to elucidate clinical characteristics in IKAROS6 positive patients. The results showed that there was no IKAROS6 gene expression in 8 healthy controls and 15 CML patients in chronic phase and accelerated phase, and 15 cases (35.71%) were IKAROS6 positive in lymphoblast crisis samples among 42 newly diagnosed CML; however, none was found in myeloblast crisis of 16 newly diagnosed CML. Among 42 lymphoblast crisis of CML, the complete remission (CR) rate of IKAROS6 expression positive patients reached 40% (6/15), which was obviously lower than that in IKAROS6 negative patients (85.19%, 23/27) (p < 0.01), IKAROS6 positive patients relapsed after CR for 15 (2 - 18) months with relapse rate 66.7% (4/6), which was higher than that in expressed wild type IKAROS gene patients (21.74%, 5/23) (p < 0.05). It is concluded that abnormal expression of IKAROS gene dominated by IKAROS6 isoforms can be detected in lymphoblast crisis samples of CML patients. Abnormal expression of IKAROS gene may be an important factor in lymphoblast crisis of CML. Therefore, detection of IKAROS gene expression may be important for target therapy and evaluation of clinical prognosis of CML patients.
Adolescent ; Adult ; Aged ; Child ; Female ; Gene Expression ; Humans ; Ikaros Transcription Factor ; genetics ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Male ; Middle Aged ; Prognosis ; Young Adult

We performed a retrospective, case-control study to evaluate whether the urine flow acceleration (UFA, mL/s(2)) is superior to maximum uroflow (Qmax, mL/s) in diagnosing bladder outlet obstruction (BOO) in patients with benign prostatic hyperplasia (BPH). In this study, a total of 50 men with BPH (age: 58±12.5 years) and 50 controls (age: 59±13.0 years) were included. A pressure-flow study was used to determine the presence of BOO according to the recommendations of Incontinence Control Society (ICS). The results showed that the UFA and Qmax in BPH group were much lower than those in the control group [(2.05±0.85) vs. (4.60±1.25) mL/s(2) and (8.50±1.05) vs. (13.00±3.35) mL/s] (P<0.001). According to the criteria (UFA<2.05 mL/s(2), Qmax<10 mL/s), the sensitivity and specificity of UFA vs. Qmax in diagnosing BOO were 88%, 75% vs. 81%, 63%. UFA vs. Omax, when compared with the results of P-Q chart (the kappa values in corresponding analysis), was 0.55 vs. 0.35. The prostate volume, post void residual and detrusor pressure at Qmax between the two groups were 28.6±9.8 vs. 24.2±7.6 mL, 60.4±1.4 vs. 21.3±2.5 mL and 56.6±8.3 vs. 21.7±6.1 cmH2O, respectively (P<0.05). It was concluded that the UFA is a useful urodynamic parameter, and is superior to Qmax in diagnosing BOO in patients with BPH.
Case-Control Studies ; Humans ; Male ; Middle Aged ; Prostatic Hyperplasia ; physiopathology ; Retrospective Studies ; Urinary Bladder Neck Obstruction ; diagnosis ; physiopathology ; Urine ; physiology

This study was purpose to analyze the frequency and of isocitrate dehydrogenase 2 (IDH2) gene mutation in acute myeloid leukemia (AML) and its clinic significance. The multiplex polymerase chain reaction (PCR) and sequencing were performed to screen 192 AML patients for exon 4 of the IDH2 gene. FLT3, NPM1, CEBPA, c-kit and WT1 mutations were also included in analysis. The results showed that IDH2 mutation was found in 14 (7.29%) of 192 patients. There were 9 AML patients with R140Q mutation, 1 patient with R140W mutation, and 1 patient with R172K mutation. IDH2 aberrations significantly more were detected in French-American-British (FAB) M5 (P < 0.005) than other types. There was no statistical difference in age, sex, WBC, platelet count, bone marrow blasts count, hemoglobin as compared with IDH2 wild-type. For immunotype analysis, IDH2 mutation patients were more likely to express CD34 and CD13, less CD36. IDH2 mutation combined with FLT3/ITD mutation was found in 7 cases, with CEBPA mutation in 4 cases, with NPM1 mutation in 4 cases, with Dnmt3a mutation in 5 cases, neither with c-kit, IDH1 or WT1 mutation for no one, which revealed a significant interaction between IDH2 mutation and the FLT3/ITD positive genotype, Dnmt3a mutated, and IDH1 wild-type. IDH2 mutation was detected in 5 (8.47%) of 59 CN-AML. There was no significant difference of IDH2 mutation incidence between the normal and abnormal karyotype. The CR rate was higher in IDH2 R140 mutated patients than wild-type ones, but there was no significant in the two group. It is concluded that the rate of IDH2 mutation is 7.29% in Chinese AML patients and 7.81% in CN-AML. IDH2 mutation is significantly associated with AML-M5, FLT3/ITD, Dnmt3a, IDH1 wild-type and fusion gene wild-type, but not with age, leucocyte and platelet counts in peripheral blood, karyotype, NPM1, CEBPA, c-kit or WT1 mutation. And IDH2 R140 mutation has no impact on CR rate.
Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; DNA (Cytosine-5-)-Methyltransferases ; genetics ; Female ; Genotype ; Humans ; Isocitrate Dehydrogenase ; genetics ; Karyotyping ; Leukemia, Myeloid, Acute ; epidemiology ; genetics ; Male ; Middle Aged ; Mutation ; Nuclear Proteins ; genetics ; Prognosis ; Remission Induction ; WT1 Proteins ; genetics ; Young Adult ; fms-Like Tyrosine Kinase 3 ; genetics

OBJECTIVETo explore the effect of serum restriction on the invasiveness and expressions of insulin-like growth factor-1 (IGF-1) and matrix metalloproteinase-2 (MMP-2) in human trophoblast HTR-8/SVneo cells in vitro.

METHODSHTR-8/SVneo cells were cultured in the presence of 1%, 5%, or 10% fetal bovine serum (FBS) for 48 h. Fluorescence quantitative PCR and immunofluorescence staining were employed to examine the changes in IGF-1 and MMP-2 expressions at both the mRNA and protein levels in HTR-8/SVneo cells; MTT assay and Transwell invasion assay were used to assess the changes of the cell proliferation and the cell invasion ability, respectively. MMP-2 expression, cell proliferation and invasiveness were also assessed in the cells treated with recombinant human IGF-1.

RESULTSHTR-8/SVneo cells exhibited significantly lowered cell proliferation in cultures containing low concentrations of FBS (P<0.05). The expressions of IGF-1 and MMP-2 at both mRNA and protein levels were significantly down-regulated and the invasiveness was significantly lowered in cells cultured in the medium containing 1% FBS as compared with those of cells cultured in the presence of 5% and 10% FBS (P<0.05). Treatment of the cells with recombinant human IGF-1 significantly up-regulated MMP-2 expression (P<0.05) and increased the cell invasiveness (P<0.05).

CONCLUSIONSFBS restriction down-regulates IGF-1 expression in human trophoblast HTR-8/SVneo cells and suppress the cell invasiveness possibly by suppressing MMP-2 expression. Treatment with recombinant human IGF-1 can up-regulate MMP-2 expression and promote the invasiveness of HTR-8/SVneo cells.

OBJECTIVETo explore the association between early menarche with anthropometry measurements among adolescent girls in China.

METHODSResearch material was selected from the data of 2010 Chinese National Surveys on Students Constitution and Health. Probability unit regression method was used to calculate the age of 10th percentile (P 10) at menarche and menarche age before the P 10 was defined as early menarche(9.0-11.6 years old). A total of 1072 girls with early menarche were screened. Each girl with early menarche was frequency matched with two girls who hadn't achieved menarche and with the age difference less than 0.1 yr and from the same urban or rural locations. A total of 2144 girls without menarche were screened. Participants' data of height, weight, sitting height, chest circumference, body mass index(BMI) and height and sitting height index were analyzed. t test and wilcoxon test were used to analyze the anthropometry measurements differences between the two groups, Chi square test was used to analyze the differences of overweight and obesity between the two groups. Multilevel model was used to explore the association between early menarche with anthropometry measurements and overweight and obesity.

RESULTSA total of 1072 girls with early menarche and 2144 girls without menarche. Early menarche girls' height, sitting height, chest circumference, weight and BMI were (151.42 ± 7.46) cm, (80.86 ± 4.21) cm, (73.88 ± 7.72) cm, (44.32 ± 9.35) kg, and (19.18 ± 3.03) kg/m(2), while they were (144.86 ± 7.55) cm, (76.96 ± 4.05) cm, (67.25 ± 6.94) cm, (36.07 ± 7.88) kg and (16.64 ± 2.48) kg/m(2) in girls without menarche. The difference between two groups were significant(Z values were -22.20, -23.69, -24.38, -23.12, -20.17, -6.33 respectively with all P values < 0.01). Multilevel analysis results showed that in 9.0-11.6 years old girls early menarche was associated with anthropometry measurements(all P values < 0.05). Compared with girls without menarche, girls with early menarche had a relative higher height, sitting height, weight, chest circumference, with increments of 5.28 cm, 3.37 cm, 5.53 cm, 6.37 kg, 1.79 kg/m(2). Within subgroup analysis, there were parabolic trends with age in the height, weight and sitting height differences and "U" trend in chest circumference difference between girls with early menarche and girls without menarche.In 9.0-10.8 years old, 10.9-11.0 years old and 11.1-11.2 years old groups, the risk of overweight and obesity among girls with early menarche were 2.98 (95%CI:1.92-4.63) times, 6.76 (95%CI:2.79-16.39) times, 2.99 (95%CI:1.40-6.40) times of girls without menarche.

CONCLUSIONThe early onset of menarche is related with height, sitting height, weight and chest circumference, and it is closely associated with overweight and obesity among adolescent girls in China.

Body Mass Index ; Child ; Child Development ; China ; epidemiology ; Female ; Humans ; Menarche ; Overweight ; epidemiology ; Pediatric Obesity ; epidemiology