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Objective:To establish and validate a malignant risk prediction model of solitary pulmonary nodules (SPNs) with pulmonary fibrosis in long-term smokers based on 18F-flurodeoxyglucose (FDG) PET/CT. Methods:PET/CT images of 222 SPNs combined with pulmonary fibrosis which were shown in integrated CT scan in 169 patients (all males; age 68(63, 75) years) were analyzed retrospectively. All patients were examined in PET/CT Center of the Affiliated Hospital of Qingdao University from January 2011 to December 2019 and all had definite smoking history. The benign and malignant nodules were judged according to the pathological diagnosis or follow-up imaging data of lung lesions (follow-up≥2 years). The clinical characteristics (age, smoking index), morphological characteristics (longest diameter of lesion, density, location, distribution, relative position of fibrosis, spiculation, lobulation, calcification, vacuole, vascular convergence, pleural indentation, emphysema and severity of bilateral pulmonary fibrosis) and metabolic characteristics (maximum standardized uptake value (SUV max)) of the benign and malignant lesions were analyzed by χ2 test and Mann-Whitney U test. Then multivariate logistic regression analysis was applied to select independent risk factors of malignant nodules, and a risk prediction model was established and verified by the area under the receiver operating characteristic (ROC) curve and k-fold cross validation ( k=10) respectively. Results:Among 169 patients, 222 SPNs were detected (157 malignant nodules, 65 benign nodules). Univariate analysis showed that smoking index, speculation, lobulation, vascular convergence sign, calcification, emphysema, nodule size, relative position of nodule and fibrosis, SUV max and severity of bilateral pulmonary fibrosis were significantly different between the benign and malignant nodules ( z values: 2.514-9.858, χ2 values: 4.353-18.442, all P<0.05). Result of multivariate logistic regression analysis showed that calcification, vascular convergence and SUV max were the independent risk factors of malignant nodules combined with pulmonary fibrosis (odds ratio ( OR): 0.048-2.534, all P<0.05). The risk prediction model was as follow: P=1/(1+ e - x), x=-1.839-3.033×calcification+ 0.930×vascular convergence+ 0.754×SUV max(with calcification/vascular convergence=1, without calcification/vascular convergence=0). The area under ROC curve was 0.932(95% CI: 0.895-0.969), and the sensitivity and specificity of the model were 87.9% and 86.2%, respectively. Results of k-fold cross validation showed that the prediction accuracy of 10 test sets was 0.847±0.075, and was 0.862±0.010 in training sets. Conclusions:Calcification, vascular convergence and SUV max are independent risk factors of malignant SPNs combined with pulmonary fibrosis in long-term asymptomatic smokers. The model based on the above variables presents high diagnostic efficiency in diagnosing malignant SPNs.
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@#ObjectiveTo explore the expression of Pannexin1 in patients with acute ischemic stroke（AIS）and its association with severity and prognosis. MethodsA total of 113 patients with AIS admitted to our hospital from January 2017 to January 2020 were selected as case group，who were divided into mild impairment group（NIHSS<4 points，n=42），moderate impairment group（NIHSS 4～15 points，n=45），severe impairment group（NIHSS>15 pointe，n=26）according to the degree of neurological impairment. Also，the patients were divided into small infarction group（infarction volume<5 cm3，n=37），moderate infarction group（infarction volume 5～10cm3，n=51）and large infarction group（infarction volume>10cm3，n=25）according to the volume of cerebral infarction. 90 days after treatment，the patients were divided into good prognosis group（mRS<=2 points，n=81）and poor prognosis group（mRS 3～5 points，n=32）according to the modified Rankin Scale（mRS）. At the same time，58 healthy volunteers were randomly selected as control group. The Pannexin1 level were detected by enzyme-linked immunosorbent assay. ResultsThe level of Pannexin1 in case group was higher than that in control group（P<0.05）. With the aggravation of neurological impairment and the increase of cerebral infarction volume，the level of Pannexin1 in AIS patients increased gradually（P<0.05）. The level of Pannexin1 in good prognosis group was lower than that in bad prognosis group（P<0.05）. The Pearson’s product moment correlation analysis showed that Pannexin1 was positively associated with NIHSS score，infarct volume and mRS score（r=0.632，0.598，0.671；P<0.05）. The AUC of Pannexin1 in predicting poor prognosis was 0.865，the sensitivity and specificity were 87.50% and 86.42% respectively. ConclusionSerum Pannexin1 highly express in patients with AIS，which is closely related to the severity of the disease and prognosis. Early detection of Pannexin1 can be used as a biochemical index to judge the severity of disease and predict poor prognosis.
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Objective To develop a model of malignant risk prediction of solitary pulmonary nodules(SPN) with the metabolic characteristics of the lesion.Methods A total of 362 patients (291 malignant cases and 71 benign cases;194 males,168 females;median age:61 years) who underwent PET/CT imaging from January 2013 to July 2017 were analyzed.The diagnosis of malignant SPN was based on pathological results,and that of benign SPN was based on pathological or follow-up results.Differences of clinical/imaging characteristics in patients with benign and those with malignant SPN were analyzed.Risk factors were screened by multivariate non-conditional logistic regression analysis.The self-verification of the model was done by the receiver operating characteristic (ROC) curve analysis,out-of-group verification was performed by k-fold cross-validation.Results There were statistically significant differences in age,maximum standardized uptake value (SUVmax),size,lobulation,spiculation,pleural traction,vessel connection,calcification,vacuole,and emphysema between patients with benign and malignant nodules (all P＜0.05).The risk factors for malignant nodules included age,SUVmax,size,lobulation,calcification and vacuole.The odds ratio (OR) values (95％ CI) were 1.040(1.007-1.075),1.612(1.287-2.017),1.149(1.074-1.230),4.650(2.138-10.115),0.216(0.085-0.548),and 3.043(1.302-7.111),respectively.The logistic regression model was as follows:P=1/(1+e-x),x=-5.583+0.039×age+0.477×SUVmaxx+0.139×size+1.537×lobulation-1.532×calcification+ 1.1 13×vacuole.The estimated area under the curve (AUC) for the model was 0.915(95％ CI:0.883-0.947),sensitivity was 89.7％,specificity was 78.9％.K-fold cross-validation showed that the training accuracy was 0.899±0.011,the predictive accuracy was 0.873±0.053.Conclusions The risk factors for malignant nodules included age,SUVmax,size,lobulation,calcification and vacuole.After verification,the model has a satisfactory accuracy.It may help clinics make accurate decisions.
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Objective To analyze the diagnosis and treatment of pancreatic sinistral portal hypertension (PSPH).Methods A total of 28 patients with PSPH were retrospectively analyzed,and the clinical characteristics,diagnosis and treatment experience of the disease were summarized.Results There were primary pancreatic diseases in all the cases,including 16 cases of pancreatitis and 12 cases of pancreatic tumor in the tail.12 cases underwent distal pancreatectomy plus spleenectomy,2 cases did spleenectomy and pericardial devascularization,9 cases received miscellaneous surgical procedures,and 5 case were managed by non-surgical medical treatments.After 1 year of follow-up,20 of 23 postoperative patients were alive and well.Among the 5 conservatively treated patients,2 had repeated upper gastrointestinal bleeding.Conclusion PSPH,especially caused by chronic pancreatitis yields to personalized surgical procedures based on pancreatectomy.
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Objective To analyze the expression of glucose transport protein (Glut)-l,Glut-3 and hexokinase (HK)-Ⅱ in non-small-cell lung cancer (NSCLC) lesions and pulmonary inflammatory lesions and discuss the correlation of them with 18F-fluorodeoxyglucose (FDG) uptake.Methods Twenty-four patients with NSCLC and 22 patients with pulmonary inflammatory lesions (25 males,21 females;age range:37-81 years) who underwent PET/CT from November 2012 to May 2016 were retrospectively analyzed.All patients had surgery and were confirmed by pathology.The expression of Glut-1,Glut-3 and HK-Ⅱ in the lesions was detected by immunohistochemistry.Immunohistochemical staining scores and maximum standardized uptake value (SUVmax) were calculated.One-way analysis of variance,the least significant difference t test,two-sample t test and Spearman correlation analysis were used.Results The SUVmax of NSCLC lesions was 8.71 ± 7.62,higher than that of pulmonary inflammatory lesions (3.29 ± 2.16;t =3.220,P＜ 0.05).Immunohistochemical staining scores of Glut-1,Glut-3 and HK-Ⅱ were 3.75±0.99,4.04±1.00 and 4.00±0.78 for NSCLC lesions respectively,and were all higher than those of pulmonary inflammatory lesions (2.32±0.65,2.89±0.83,2.41±0.50;t values:5.340,5.160,8.130,all P＜0.01).The expression of Glut-1 and HK-Ⅱ was positively correlated with SUVmax in NSCLC lesions (rs values:0.414,0.457,both P＜0.05).The expression of Glut-1,Glut-3 and HK-Ⅱ was not correlated with SUVmax(rs values:0.392,0.070,-0.066,all P＞0.05),but the expression of Glut-3 was higher than that of Glut-1 and HK-Ⅱ (F=4.123,t values:0.970,0.150,all P＜0.05) in pulmonary inflammatory lesions.Conclusions The expression of Glut-1,Glut-3 and HK-Ⅱ is higher in NSCLC lesions than that in pulmonary inflammatory lesions.Glut-1 and HK-Ⅱ are the important factors for 18F-FDG uptake in NSCLC.Glut-3 may play an important role in 18F-FDG uptake in pulmonary inflammatory lesions.
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Objective To investigate the effect of long term low-dose manganese exposure on testicular spermatogenic cell mitochondria morphology and apoptosis of male offspring rat.Methods Thirty-two healthy female SD rats were divided into the control group,low,middle and high dose groups.2,4 and 8 mg/kg MnCl2 · 4H2 O or normal saline was intraperitoneally injected for 8 weeks(once daily,5 d/week).The manganese exposure continued during the pregnant period and lactation period.Eight 12-week-old offspring male rats were killed in each group,the structure of seminiferous tubules and mitochondria morphology in spermatogenic cells were observed.The expression of Opa1,Drp1 and Caspase9,and the apoptosis of spermatogenic cells were detected.Results With the increase of administered-MnCl2 dosage,the number of spermatogenic cell layers decreased,spermatogenic cells arranged in disorder,the number reduced,etc;the mitochondria separation and swelling of spermatogenic cells were found in the middle and high dose groups;the expression of Opa1 was gradually decreased in the middle and high dose groups(P＜0.05,P＜0.01),while the expression of Drp1 and Caspase9 was gradually increased with the manganese dose increase(P＜0.05,P＜0.01);the apoptotic index of spermatogenic cells in the manganese exposure group was significantly increased with the increase of administeredMnCl2 dosage(P＜0.05).Conclusion Long term low dose of manganese exposure could regulate the expression of Opa1/Drp1 gene and affect the function of mitochondria,leads to apoptosis of spermatogenic cells in male offspring rat.
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Objective To evaluate the image quality,diagnosis accuracy and dose reduction of split-bolus CT urography (CTU) with low voltage scan and sinogram affirmed iterative reconstruction (SAFIRE).Methods A total of 80 cases of consecutive patients with confirmed or suspected urinary system disease needed CTU examination were divided into two groups (control group and test group) by using random number table.In control group,convention scan (120 kV) with one time injection was used.But low voltage scan (80 kV) with SAFIRE algorithm and split-bolus injection (SBI) was used in experiment group.The radiation dose,image quality and diagnosis accuracy were compared.Results A total of 77 cases completed CTU examination successfully in the two groups,including 39 cases in control group and 38 cases in test group.The effective dose reduced from (26.68 ± 4.07) in control group to (3.93 ± 0.85) mSv in test group (t =-33.78,P ＜ 0.05).Subjective image quality score was (4.49 ± 0.79) in control group and (4.39 ± 1.53) in test group,with no significantly statistical difference (Z =2.71,P ＞ 0.05).Signal-to-noise ratio (SNR) of objective image quality in test group was higher than that in control group (127.3±15.9 vs.109.6 ± 13.2,t =4.49,P＜0.05).But there was no significantly statistical difference in contrast-to-noise ratio (CNR) between control group(100.8 ± 12.9)and test group (109.0 ± 14.4,P ＞ 0.05).For diagnosis accuracy,no statistical difference were found between two groups(84.62％ and 81.58％,P ＞ 0.05).Conclusions The combination of low voltage scan with SAFIRE algorithm and split-bolus injection CTU could reduce the radiation dose significantly,but the objective image quality,CNR (except SNR) of subjective image quality and diagnosis accuracy were all unaffected obviously.
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Objective To evaluate the effect of iodine contrast agent on the biological responses of CT examination. Methods A total of sixty patients with suspected urinary tract disease who underwent computed tomography urography ( CTU ) examination were randomly divided into control group and experimental group. The control group was treated with routine CTU, where only CT scan was performed on the first day. CTU was added after 3 days. The test group was treated with fractional injection CTU and injected with enhanced scanning agent on the first day. Before and after CT examination, the patients′peripheral blood was collected and the number of γ-H2AX foci in lymphocytes ( mononuclear cells) was measured by immunofluorescence, and the differences of DNA damage in these two groups were observed. Results Before and after CT examination, the number ofγ-H2AX foci was 0. 06 ± 0. 02 and 1. 06 ± 0. 27 in the lymphocytes of control group,0. 06 ± 0. 03 and 1. 42 ± 0. 50 in the test group, respectively. Hence, the number ofγ-H2AX foci in the test group was increased by 38. 14%. Moreover, the change ofγ-H2AX foci in these two groups was not influenced by gender, but correlated with ages( between≤50 years old and>50 years old) in control group (t= -4. 76, P<0. 05) and in test group(t= -8. 16, P <0. 05). Conclusions The iodine contrast agent can increase DNA damage of CT examination, and therefore the use of iodine contrast agent in CT should be reduced as much as possible in clinical work.
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Objective To investigate the effect of chronic low-dose manganese chloride exposure on cell cycle and apoptosis of spermatogenic cells in offspring rat. Methods 32 healthy female SD rats were randomly divided into control and manganese exposure groups(n=8).The manganese exposure group respectively received 2,4 and 8 mg/Kg MnCl2·4H2O,while the control group was treated with equal volume saline for 8 weeks(1 time/d,5 d/w).After mating with normal male SD rats and determining conception,female rats were continued to be ex-posed to manganese during pregnancy and lactation. There were. 8 offspring male rats in each group. In the 12th week,the offspring rates were randomly executed and their testes were used to observe the structure of seminifer-ous tubules by HE staining. The expression of FOXO3A,cell cycle associated proteins P16,P21,CDK2, CDK4,CDK6 and apoptosis related proteins BIM,Caspase-9 in the testis of offspring male rats were detected by western blotting. In addition,the apoptosis of spermatogenic cells was detected by TUNEL. Results(1)With the increase of administered-MnCl2 dosage,the seminiferous tubule showed various changes,including layers of spermatogenic cell decreased,spermatogenic cells arranged in disorder,the number of mature sperm in the lumen of seminiferous tubule significantly reduced.(2)The expression of FOXO3A,P16 and P21 increased while CDK2 and CDK4 decreased gradually with the increase manganese exposure dose. CDK6 expression was not significantly changed in all groups.(3)The expression of BIM,Caspase-9 and apoptotic index of spermatogen-ic cells increased gradually with the increase of manganese dose. Conclusion Chronic low-dose of manga-nese exposure could induce expression of FOXO3A,further cause cell cycle arrest and apoptosis of spermatogen-ic cells in offspring rat.
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Objective To investigate the eftect of radiation dose of dual-source computed tomography (CT) dual energy single-phase enhanced scan in patients with esophageal cancer.Methods The prospective study was conducted.The clinicopathological data of 56 patients with esophageal cancer who were admitted to the Lishui Hospital of Zhejiang University between January 2015 and December 2016 were collected.All the patients were divided into the experimental group (undergoing dual-source CT dual energy single-phase enhanced scan) and control group (undergoing dual-phase CT enhanced scan) bv randomised block method.TNM classification of esophageal cancer (Seventh Edition) published by American Joint Committee on Cancer (AJCC) was used as a standard TNM staging.Two observers independently read films.All the patients underwent radical resection of esophageal cancer or palliative surgery,and then received adjuvant radiochemotherapy.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival of patients up to March 2017.Observation indicators:(1) consistencies of T staging,N staging and M staging;(2) accuracies of T staging,N staging and M staging (pathological results as a gold standard);(3) radiation dose of CT scan;(4) treatment and follow-up situations.The Kappa test was used for evaluating the consistency,κ≥0.75 as a good consistency,0.40≤κ＜0.75 as a normal consistency and κ＜0.40 as a poor consistency.Comparisons of count data and ratio were done by the chi-square test.Comparisons of measurement data were analyzed by the t test.Results A total of 50 patients were enrolled in the study,including 25 in the experimental group and 25 in the control group.(1) Consistencies of T staging,N staging and M staging:all the 50 patients finished successfully CT scans.Two observers considered that consistencies of T staging,N staging and M staging in the 2 groups were normal (κ =0.452,0.618,0.729,P＜0.05).Consistencies of N staging and M staging were superior to T staging.(2) The pathological results were used as a gold standard.Accuracies of T staging,N staging and M staging in the experimental and control groups were 72％,76％ and 88％,84％ and 92％,88％,respectively,with no statistically significant difference between the 2 groups (x2 =0.10,0.37,0.50,P＞0.05).(3) Radiation dose of CT scan:volume CT dose index (CTDIvol),dose length production (DLP) and effective radiation dose (E) were (10.35±2.01) mGy,(400.63± 34.13) mGy · cm,(5.61 ± 0.47) mSv in the experimental group and (3.55 ± 0.60)mGy,(140.66± 10.89) mGy · cm,(1.98±0.17) mSv in the control group,respectively.There were statistically significant differences in CTDIvol and E between the 2 groups (t =16.23,36.30,P＜0.05).(4) Treatment and follow-up situations:of 50 patients,43 patients received treatments,including 32 undergoing radical resection (11 receiving postoperative adjuvant chemotherapy),6 undergoing palliative surgery,3 receiving single radiotherapy and 2 receiving single chemotherapy.Thirty-six of 43 patients were followed up for 3-18 months,with a median time of 6 months.During follow-up,1-year survival rate was 61.1％.Conclusion Dual-source CT dual energy single-phase enhanced scan in patients with esophageal cancer cannot reduce accuracy of TNM staging,but decreased effectively radiation dose.
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Objective To compare the 18F-FDG PET metabolic characteristics and VHRCT morphological characteristics between invasive and non-invasive adenocarcinoma presenting as pure ground-glass nodules(pGGN).Methods Fifty-one patients with pGGN from October 2010 to June 2016 were retrospectively enrolled in this study.There were totally 52 lesions with sizes of no more than 30 mm and were grouped depending on pathological and follow-up diagnosis (31 lesions in the invasive adenocarcinoma group and 21 lesions in the non-invasive group).Clinical and imaging features were analyzed including age,gender,lesion location,size,density,SUVmax T/N,spiculation,lobulation,pleural indentation,vascular connection signs,vacuole sign and the air bronchogram.T test or x2-test was used in the comparison of different manifestations between the two groups.Logistic regression analysis on clinical parameters was applied.The ROC curve was used to find the cutoff of T/N.Results In the invasive adenocarcinoma group,T/N,SUV density and size were 1.97±0.71,1.16±0.54,-(431±104)HU,(18.48±5.65)mm,respectively.In the non-invasive group,T/N,SUVmax density,size were 1.20±0.28,0.64±0.20,-(533± 109)HU,(12.05±5.04)mm,respectively.The differences of T/N,SUVmax density and size had statistical significance between the two groups (t=-5.40,-4.87,-3.39,-4.21,P＜0.05).Lobulation and vascular connection signs in the invasive adenocarcinoma group were found in 21 and 13 cases respectively,while in the non-invasive group,they were present in 2 and 1 case,respectively,which showed significant differences between the two groups(x2=17.85,7.01,P＜0.05).T/N,lobulation,and vascular connection signs were the independent factors for the differentiation of benign and malignant lesions.The ORs were 52.547,8.375,72.206,respectively.When T/N=l.62,the area under the ROC curve was 0.885.The sensitivity,specificity and accuracy were 77.42％,90.48％,82.69％,respectively.Conclusions Pulmonary pGGNwith T/N no less than 1.62,lobulation and vascular connection sign indicates an invasive adenocarcinoma.
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Objective To compare the characteristics of lymph nodes on 18F-FDG imaging in patients with NHL and widespread lymph node metastases carcinoma (WLNMC) for helping the differential diagnosis.Methods A total of 40 NHL patients(22 males,18 females,average age 51 years) and 42 WLNMC patients (19 males,23 females,average age 61 years) confirmed by histopathology from November 2010 to May 2015 were included in this retrospective study.The regions and the metabolism features of the lesions on PET/CT images were observed and recorded with routine visual method.Two-sample t test and x2 test were used for statistical analysis.Results Lymph nodes of NHL were kidney-shaped (47.2％,142/301),which was significantly different from that of WLNMC with circular form (47.6％,140/294;x2 =36.261,P＜0.05).Lymph nodes of NHL mostly showed homogeneous density with no necrosis (51.8％,156/301);however,that of WLNMC showed uneven density (20.4％,60/294) or with necrosis (32.3％,95/294;x2 =26.266,P＜0.05).Both of the two kinds of lymph nodes showed the characteristic of fusion (30.6％ (92/301) vs 36.1％ (106/294);x2 =2.019,P＞0.05).The ratios of lymph nodes with clear boundary in NHL and WLNMC were significantly different:28.2％(85/301) vs 19.4％(57/294);x2 =6.413,P＜0.05.Lymph nodes with symmetric distribution were more in NHL patients (52.5％,158/301)than that in WLNMC patients (42.2％,124/294;X2=6.347,P＜0.05).Sizes of lymph nodes in NHL patients and WLNMC patients were not significantly different:(2.08±0.65) cm vs (1.97±0.81) cm;t=0.316,P＞0.05.SUVmax of lymph nodes in NHL patients (9.02±3.97) was much higher than that in WLNMC patients (6.92± 1.34;t=0.370,P＜0.05).Conclusions Some characteristics of lymph nodes on 18F-FDG PET/CT imaging,such as the distribution,morphology,density and glucose metabolism features,are different in patients with NHL and WLNMC.Those differences may be helpful for the differential diagnosis.
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Objective The aim of this study was to investigate the prevalence of erectile dysfunction (ED) and to assess the risk factors of ED in male post‐stroke patients .Methods One hundred and twenty six male post‐stroke patients were invited to par‐ticipate in this study .Patients were divided into ED group and non‐ED group according to the erectile function evaluated by Interna‐tional Index of Erectile Function‐5 (IIEF‐5) .The neurological impairment was measured using the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) .Depressive symptoms was measured using the Hamilton Depression Scales (HAMD) .The global cognitive function was measured using the Mini mental Status Examination (MMSE) .The clinical and psychosocial factors were compared between the ED and non‐ED groups .Univariate and multivariate Logistic regression analyses were employed to assess the risk factors with ED .Results There were 38 patients (30 .2% ) with ED in all the 126 male post‐stroke patients .Univariate Logistic regression analyses revealed that hypertension ,diabetes ,ACEI ,and depression were significantly related to ED in male post‐stroke patients (P<0 .05) .Multivariate Logistic regression analyses revealed that ACEI and depression were independently associated with ED in male post‐stroke patients (P<0 .05) .Conclusion ED is common in Chinese male post‐stroke patients .ACEI and depression are the major determinants of ED .
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Objective:To illuminate the influence of InsB15-23 H-2Kd dtSCT to the morbidity of type 1 diabetes mellitus in NOD mice.Methods:An eukaryotic plasmid encoded membrane-expressed InsB15-23 H-2Kd dtSCT was inoculated into 3 weeks old female NOD mice subcutaneously and the blood sugar and morbidity of type 1 diabetes mellitus were monitored once a week.To illuminate the cellular mechanism of immunologic intervention of membrane-expressed InsB15-23 H-2Kd dtSCT to the course of type 1 diabetes mellitus in NOD mice,the mononuclear cell infiltration of islets was detected by tissue slice and the frequency of IGRP206 2-14 specific CTLs in PBMC was analyzed by FACs.Results: As compared with pcDNA3.1 (-) control ( 60%) and untreated NOD mice ( 80%) , mice immunized with InsB15-23 H-2Kd dtSCT exhibited low level of islet infiltration and low morbidity in 30 weeks old ( 9%) .But the frequency of IGRP206-214 specific CTLs in PBMC of 16 and 40 weeks old mice showed no difference.Conclusion:Membrane-expressed InsB15-23 H-2Kd dtSCT can protect NOD mice from type 1 diabetes mellitus in IGRP206-214 independent pattern.
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This study is to establish physiologically based pharmacokinetic (PBPK) models of famitinib in rat and monkey, and then to predict the pharmacokinetics and tissue distribution of famitinib in human based on the PBPK models. According to published paper, previous studies and the chemical properties of famitinib predicted by ACD/ADME suite and SimCYP, the PBPK models of rat and monkey were established and optimized using GastroPlus. And then, the PBPK models were applied to predict the pharmacokinetic and tissue distribution of famitinib in human. The results showed that the PBPK models of rat and monkey can fit the observed data well, and the AUC0-∞, ratios of observed and calculated data in rat and monkey were 1.00 and 0.97, respectively. The AUC0-∞, ratios of observed and predicted data in human were 1.63 (rat to human) and 1.57 (monkey to human), respectively. The rat and monkey PBPK models of famitinib were well established, and the PBPK models were applied in predicting pharmacokinetic of famitinib in human successfully. Hence, the PBPK model of famitinib in human could be applied in future drug-drug interaction study.
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Objective To evaluate the effect of physical exercise on health-related quality of life (HRQol),fatigue,depression,anxiety and body-image in breast cancer patients.Methods The Cochrane Library,Pubmed,EMBASE,CINAHL,Psycinfo,SportDiscus,CNKI and CBMdisc were searched to collect randomized controlled trials (RCTs) from 2002 to 2011 which mentioned the physical exercise to breast cancer patients.The quality of the RCTs was appraised and the data were extracted.Results In total,16 RCTs were included.Statistically significant results were found for the effect of physical exercise on HRQol,fatigue,depression,anxiety and body-image.The presence of publication bias was explored and no publication bias was detected.Sensitivity analysis were also performed and there were no significant differences with the former results.Conclusions The results indicated that physical exercise improve HRQol and psychological outcomes in breast cancer patients.Breast cancer patients should be taught to do some moderate exercises as part of their lives to promote rehabilitation.