Research Progress on Cardiotoxicity of PD-1/PD-L1 Immune Checkpoint Inhibitors / 肿瘤防治研究

Cardiotoxicity is a serious complication of antineoplastic drugs. With the continuous development of antineoplastic drugs, immune checkpoint inhibitors have been used in the treatment of a variety of cancers. PD-1/PD-L1 immune checkpoint inhibitors have been widely concerned in recent years. This article reviews the manifestations and possible mechanisms of cardiotoxicity induced by PD-1/PD-L1 immune checkpoint inhibitors, and the detection methods and treatment of cardiotoxicity.

Inhibition of MicroRNA-15a/16 Expression Alleviates Neuropathic Pain Development through Upregulation of G Protein-Coupled Receptor Kinase 2

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-1β and tumor-necrosis factor-α in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and NF-κB in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.

Value of multi-parametric MRI in mammographically detected breast imaging reporting and data systems 3 to 4 exclusive microcalcifications / 中华放射学杂志

Objective@#To assess the value of multi-parametric MRI in mammographically detected breast imaging reporting and data systems (BI-RADS) 3 to 4 exclusive microcalcifications.@*Methods@#A retrospective analysis was performed in 152 patients with mammographically detected BI-RADS 3 to 4 exclusive microcalcifications from January 2013 to December 2017. All patients underwent bilateral breast multi-parametric MRI before surgical biopsy. Microcalcifications were classified according to BI-RADS by two radiologists with more than 10 years′ experience in breast imaging. The area under the curve (AUC), sensitivity and specificity of BI-RADS 3 to 4 exclusive microcalcifications diagnosis by mammography and mammography plus MRI were calculated and compared using pathology as the gold standard.@*Results@#A total of 152 lesions (93 benign lesionsand 59 malignant lesions) were assessed in this study. The positive predictive value (PPV) of mammography for BI-RADS 3, 4A, 4B and 4C microcalcifications diagnosis were 22.2%(16/72), 5.0%(1/20), 48.5%(17/35) and 100.0%(25/25) respectively. The PPV of MRI for BI-RADS 2, 3, 4, 5 microcalcifications diagnosis were 1.6%(1/62), 7.1%(2/28), 72.2%(13/18) and 97.7%(43/44).The area under curve, sensitivity and specificity of mammography for BI-RADS 3 to 4 microcalcifications diagnosis were 0.676,72.9% and 60.2%. The area under curve, sensitivity and specificity of mammography plus MRI for BI-RADS 3 to 4 microcalcifications diagnosis were 0.982, 94.9% and 93.6%.@*Conclusions@#Multi-parametric MRI can improve the diagnostic accuracy in mammographically detected BI-RADS 3 to 4 exclusive microcalcifications, which is helpful to differentiate benign and malignant breast lesions with microcalcifications and avoid unnecessary biopsies.

Value of multi?parametric MRI in mammographically detected breast imaging reporting and data systems 3 to 4 exclusive microcalcifications / 中华放射学杂志

Objective To assess the value of multi-parametric MRI in mammographically detected breast imaging reporting and data systems (BI-RADS) 3 to 4 exclusive microcalcifications. Methods A retrospective analysis was performed in 152 patients with mammographically detected BI-RADS 3 to 4 exclusive microcalcifications from January 2013 to December 2017. All patients underwent bilateral breast multi-parametric MRI before surgical biopsy. Microcalcifications were classified according to BI-RADS by two radiologists with more than 10 years′ experience in breast imaging. The area under the curve (AUC), sensitivity and specificity of BI-RADS 3 to 4 exclusive microcalcifications diagnosis by mammography and mammography plus MRI were calculated and compared using pathology as the gold standard. Results A total of 152 lesions (93 benign lesionsand 59 malignant lesions) were assessed in this study. The positive predictive value (PPV) of mammography for BI-RADS 3, 4A, 4B and 4C microcalcifications diagnosis were 22.2%(16/72),5.0%(1/20),48.5%(17/35) and 100.0%(25/25) respectively. The PPV of MRI for BI-RADS 2, 3, 4, 5 microcalcifications diagnosis were 1.6%(1/62),7.1%(2/28),72.2%(13/18) and 97.7%(43/44).The area under curve, sensitivity and specificity of mammography for BI-RADS 3 to 4 microcalcifications diagnosis were 0.676,72.9% and 60.2%. The area under curve, sensitivity and specificity of mammography plus MRI for BI-RADS 3 to 4 microcalcifications diagnosis were 0.982, 94.9% and 93.6%. Conclusions Multi-parametric MRI can improve the diagnostic accuracy in mammographically detected BI-RADS 3 to 4 exclusive microcalcifications, which is helpful to differentiate benign and malignant breast lesions with microcalcifications and avoid unnecessary biopsies.

Clinical study on dynamic contrast-enhanced MRI in tumor bed of breast cancer with different region of interest selections / 中国癌症杂志

Background and purpose: The technique of dynamic contrast-enhanced MRI (DCE-MRI) is widely applied in differential diagnosis between benign and malignant tumor and therapeutic estimation of neoadjuvant chemotherapy in clinic. However, there is no standard quantitative measurement method. This study aimed to assess the variability of different region of interest (ROI) selections for tumor bed of breast cancer using DCE-MRI, and to ascertain the optimal ROI delineation. Methods: We retrospectively analyzed DCE-MRI of 30 patients diagnosed with breast cancer by pathology. The ROIs were delineated by 2 different observers using iCAD software with 4 methods, including whole tumor (Whole), the slice containing the most enhancing voxels (SliceMax), 3 slices centered in SliceMax (Partial) and the 5％ most enhancing contiguous voxels within SliceMax (5Max), to generate the volume transfer constant (Ktrans), the extracellular volume fraction (Ve) and rate constant (Kep). And the reproducibilities of the measurements were assessed using the Bland-Altman method. Results: In the analysis of ROIs delineation, the Ktrans, Ve and Kep reported by different observers were 1.26±0.54 vs 1.25±0.53, 0.75±0.23 vs 0.73±0.22 and 1.93±1.46 vs 1.95±1.51 (P＞0.05) using the method of Whole, and 1.28±0.43 vs 1.26±0.43, 0.74±0.21 vs 0.80±0.27, 1.95±1.53 vs 1.93±1.43 (P＞0.05) using the method of Partial, and 1.30±0.33 vs 1.32±0.33, 0.77±0.20 vs 0.73±0.24, 1.82±1.53 vs 1.87±1.45 (P＞0.05) using the method of SliceMax, and 1.31±0.35 vs 1.35±0.33, 0.77±0.20 vs 0.98±0.25, 1.97±1.36 vs 1.73±1.55 using the method of 5Max (P＜0.05). Using the methods of ROI delineation except 5Max, there was no significant difference between Ktrans, Ve and Kep reported by different observers. The bias vs limits of agreement were 0.002 vs-0.013 to 0.012,-0.003 vs-0.023 to 0.017, 0.006 vs-0.018 to 0.029,-0.035 vs-0.054 to 0.018 measured with Whole method, SliceMax, Partial and 5Max respectively using the Bland-Altman method. Conclusion: It may be reliable to measure functional parameters of primary tumors in breast cancer using DCE-MRI according to the methods of Whole, Partial and SliceMax.

Dynamic contrast enhanced MRI and diffusion weighted imaging features of granulomatous mastitis: compared with breast cancer / 中华放射学杂志

Objective To investigate the radiological features of granulomatous mastitis (GM) in dynamic contrast enhanced MRI (DCE-MRI) and DWI and to differentiate it from the breast cancer in diagnose.Methods Forty five cases of GM and 64 cases of breast cancer confirmed by surgical histopathology or biopsy were retrospectively analyzed in the study.All of the patients were examined preoperatively by DCE-MRI and DWI.Including lesion type,location,enhancement pattern,nipple retraction,supplying arteries,skin thickening and axillary adenopathy in the two groups were evaluated and analyzed by using x2 test.One-way ANOVA was employed to compare the ADC values between the abscess area of GM and non-abscess area,and the difference among the breast cancer lesion area.Dynamic enhancement MR pharmacokinetic parameters were used to measure including early-phase enhancement rate (EER),peak enhancement ratio(Emax),and time to peak ehhancement(Tmax).The statistical differences of EER,Emax and Tmax between the two groups were calculated by using Wilcoxon test.Results In 45 cases of GM,DCE MR images showed nonmass-like lesions (43 patients) and mass-like lesions (2 patients); the nipple involved(16 patients) and segment involved (29 patients);rim-like with heterogeneous enhancement (40 patients) and heterogeneous enhancement (5 patients); nipple retraction (24 patients) supplying arteries dilatation (42 patients),skin thickening (29 patients),and axillary adenopathy (17 patients).Corresponding to the radiological features above,in the 64 breast cancer cases,it showed 54,10,5,59,30,34,16,51,12 and 20,respectively.There were statistical significance between GM and breast cancer in lesion type,location,enhancement pattern,and nipple retraction (x2=67.574,13.075,20.297,20.398 and 23.510,respectively,all P＜0.01).But no differences were existed between 2 groups in supplying arteries and axillary adenopathy(x2=3.928 and 0.502,P＞0.05).EER,Emax and Tmaxin GM were 146.58％,191.13％,195.00 s in GM and 118.13％,159.43％,183.33 s in breast cancer,respectively.Significant statistic differences between GM and breast cancer were found in EER and Emax(Z values were-2.271 and-2.948,P＜0.01).But it did not show significant difference in Tmax (Z =-0.548,P＞0.05).The ADC values of GM on abscess area,non-abscess area,and breast cancer lesion area were (8.0±2.6) × 10-3,(11.3± 1.7) × 10-3 and (8.2± 1.1) × 10-3mm2/s,respectively.There were significant differences in the groups (F=52.167,P＜0.01).Conclusions The characteristic of radiological findings can be found in GM by using advanced MR imaging techniques.DCE-MRI combined with DWI is useful in the differential diagnosis between GM and breast cancer.

Risk factors for retained common bile duct stones of laparoscopic cholecystectomy / 国际外科学杂志

Objective To investigate the related risk factors caused the retained common bile duct (CBD)stones after laparoscopic cholecystectomy,to provide the evidence for preventing from retained common bile duct stones of laparoscopic cholecystectomy.Methods Selected 654 cases of laparoscopic cholecystectomy patients as the objects whom hospitalized in Beijing Chuiyongliu Hospital from January 2002 to June 2013.All cases were divided into the group of retained CBD stones (27cases) and the group of non-retained CBD stones (627 cases).Collected the potentially relevant factors of two groups with the retained CBD stones,including medical history of jaundice and pancreatitis,common bile duct internal diameter (B Ultrasound) ≥ 8 mm,acute cholecystitis,emergency surgery,gallbladder removal order,calot triangle adhesion,sludge calculus,stones neck incarcerated,fulltype stones,cystic duct thickening,cystic duct reserved≥ 1 cm,the minimum diameter stones ≤5 mm,the number of gallbladder stones ≥ 5,partial cholecystectomy,purulent bile.Statistics analyses was proceeded using the IBM SPSS 20.0.Result Through dichotomy logistic regression analysis to the univariate analysis results with statistical significance,sorted the results according to the influence degree,found the independent risk factors:common bile duct internal diameter (B Ultrasound) ≥8 mm,gallbladder removal order (retrograde removal),medical history of jaundice pancreatitis,cystic duct reserved ≥ 1 cm,sludge calculus,in total of 5 indexes,which caused the retained CBD stones after laparoscopic cholecystectomy.Conclusion There are several independent risk factors for retained CBD stoes after LC such as medical history of jaundice and pancreatitis,common bile duct internal diameter (B Ultrasound) ≥ 8 mm,the order of cholecystectomy (retrograde remoral),shudeg calculus and the remaining length of bile duct ≥ 1 cm.The surgeons should pay close attention to them and take appropriate measures in the preoperation and intraoperation of LC,which contribute to preventing the acurence of postoperative retaimed CBD stone.

Evaluation of Regional Wall Motion in Patients with Suspected Coronary Artery Disease by Real-Time Three-Dimensional Echocardiography and Two-Dimensional Speckle Tracking Imaging / 天津医药

Objective To evaluate the clinical value of the regional wall motion in patients with suspected coronary artery disease by real-time three-dimensional echocardiography (RT-3DE) and two-dimensional speckle tracking imaging (2D-STI). Methods A total of 143 hospitaized patients with suspected coronary artery disease and normal wall motion de?tected by two-dimensional echocardiography (2DE) were enrolled and devided into group A (coronary stenosis ≥75%) 73 cases and group B (coronary stenosis<75%) that include 70 cases according to coronary angiography results. Left ventricu?lar segmental ejection fraction (sEF) was measured by RT-3DE and peak systolic longitudial strain (SL) was measured by 2D-STI. ROC curves of the two measurements were generated and compared. Differences in sEF and SL between group A and group B were respectively analyzed. Results (1)Both sEF of RT-3DE and SL of 2D-STI in group A were significantly low?er than those in group B (P<0.05);(2)sEF was positively correlated with SL(r=0.689,P<0.05);(3)Compared with SL, sEF had larger area under ROC curve in some segments of left ventricle where both parameters are abnormal for the diagnosis of the coronary stenosis ≥75% (0.922 vs 0.874). Conclusion Regional wall motion of left ventricular can be measured by both RT-3DE and 2D-STI which can be both used to estimate the extend of stenosis of coronary artery. And RT-3DE is su?perior over 2D-STI.

Thrombosis in deep veins of lower extremities of cardiovascular disease patients after fracture / 中华老年心脑血管病杂志

Objective To study the deep vein thrombosis (DVT ) in lower extremities of patients with or without cardiovascular disease after fracture .Methods Five hundred and eighty-four frac-ture patients were divided into cardiovascular disease (CVD) group (n=235) and non-cardiovas-cular disease (NCVD) group (n=349) .Patients in CVD group were further divided into subgroup A (with essential hypertension) ,subgroup B (with CHD) ,and subgroup C(accompanying essen-tial hypertension and CHD) .Incidence of DVT in CVD group ,NCVD group ,subgroups A-C at different ages after fracture was compared .Results The incidence of DVT was significantly high-er in CVD group than in NCVD group (P14 after fracture ,and in patients with their age ≥60 years than in those with their age <60 years .Conclusion DVT is easier to occur in CVD patients with their age ≥ 60 years than in those with their age <60 years after fracture .DVT usually occurs within 1 week af-ter fracture .Importance attached to high risk population and measures taken as soon as possible against it can reduce DVT after fracture .

Analysis on risk factors of aortic valve calcification and its correlation with coronary heart disease / 中华老年医学杂志

Objective To analyze the risk factors of aortic valve calcification,and discuss its correlation with coronary artery disease.Methods A total of 188 patients who underwent coronary angiography (CAG) and transthoracic echocardiography (TTE) were divided into two groups:101cases with aortic valve calcification (AVC) and 87 cases without AVC (NAVC).General data such as sex,age,height,weight and hypertension history,results of blood test such as glucose,lipid and homocysteine(HCY)level were recorded.Results In AVC versus NAVC group,age were (67.0±9.0) years vs.(59.4 ± 6.9) years (t =6.74,P =0.000),men were 36 cases (35.6％) vs.44 cases (50.6％) (t=4.26,P=0.039),hypertension patients were 72 cases (71.3％) vs.50 cases (57.5％)(x2=3.92,P=0.048),total cholesterol were (5.4 ± 1.0) mmol/L vs.(4.5 ± 1.0)mmol/L (t =5.70,P=0.000),triglyceride were (2.2 ± 1.1 ) mmol/L vs.( 1.6 ± 0.8) mmol/L (t =4.04,P =0.000),HCY were (17.6±8.8) μmol/L vs.(14.9±6.6) μmol/L (t=2.86,P=0.028),respectively.One-way analysis showed that age,sex,hypertension,total cholesterol,triglyceride had relationship with aortic valve calcification.When we divided the cases into two groups (with and without coronary disease),there is no significant difference in HCY(t=0.88,P=0.382) between the two groups.Logistic regression indicated that age,total cholesterol,triglycerides,HCY were independent risk factors of aortic valve calcification,the incidence of aortic valve calcification was related with the severity of coronary artery lesion (x2 =9.48,P =0.024 ).Conclusions The independent risk factors of aortic valve calcification are age,cholesterol,triglyceride,HCY.Higher incidence of aortic valve calcification may result in greater severity coronary artery lesion.

Quantitative Tissue Velocity Imaging in Evaluation of Left Atrial Systolic Function in Patients with Acute Myocardial Infarction / 天津医药

Objective:To evaluate the changes of the left atrial systolic function in patients with acute myocardial infarction(AMI)using quantitative tissue velocity imaging(QTVI).Methods:The systolic velocities of the middle of left atrial lateral wall,anterior wall,inferior wall and atrial septum were measured with QTV1 in 45 patients with AMI.The left atrial volume and active atrial emptying fraction(AA-EF)were measured using single-plane Simpson method.Results:(1)Compared with the control group(30 normal subjects),the diameter and volume of the left atrium,as well as AA-EF,increased obviously in patients with AMI(P ＜ 0.01).(2)Compared with the control group,the systolic velocities of the middle of left atrial lateral wall,anterior wall,inferior wall and atrial septum,as well as the average value,increased significantly in patients with AMI (P ＜ 0.05 or P ＜ 0.01).In addition,the average value of left atrial systolic velocity was closely correlated with AA-EF(r=-0.906,tr=14.001,P ＜ 0.01).Conclusion:QTVI could be used to evaluate the left atrial systolic function accurately in patients with AMI.

Relationship of vascular endothelial function and atherosclerosis in elderly patients with coronary artery disease / 中华老年医学杂志

Objective To investigate the endothelial function and atherosclerosis in patients with coronary artery disease (CAD).Methods Two-dimensional echocardiography (2-DE) was used tomeasure changes in brachial artery inner diameter as parameter of endothelium-dependant and endothelium-nondependant vascular diastolic function and pathologic characters of carotid atherosclerosis in 90 elderly CAD patients and 30 controls.Results Endothelium-dependant vascular diastolic function and endothelium-non dependant diastolic function were significantly decreased in CAD group as compared with control group [(9.08±2.28)% and (6.14±2.21)% vs.(15.58±2.20)%, P<0.01].The carotid intima-media thickness and plaque score were significantly increased in CAD group as compared with control group.Conclusions There are correlations of endothelium dysfunction and carotid atherosclerosis are relatied to with coronary atherosclerosis.

The prognostic value of tissue Doppler imaging in acute myocardial infarction patients / 中华超声影像学杂志

Objective To assess the prognostic value of tissue Doppler imaging(TDI) parameters in aeute myocardial infarction(AMI) patients. Methods After one week of AMI,102 patients underwent twodimensional/Doppler echocardiography and TDI examination.Early and late transmitral flow velocity E,A,deceleration time(DT)were measured. The average velocity of mitral valve at septal and lateral weremeasured including the systolic velocity(Sm),early diastolic velocity(Em)and late diastolic velocity(Am),Em/Am,E/Em were calculated.After 1 year follow up,the patients were divided into two groups according to whether hospitalizated due to heart failure(HF)or not. Stepwise multivariate COX regression analysis was used to identify the predictors of the cardiac event. Results In patients with H F,Sm,Em were lower than those of no HF group(P＜0.05),E,E/Em were higher than those of no HF group(P＜0.05 and0.01 respectively). Stepwise multivariate COX analysis identified that the E/Em was the only independent predictors of HF.E/Em≥12 was a useful HF predictors with a sensitivity of 84.2%,specificity of 77.1%.Conclusions E/Em ratio may assist in the risk stratification in AMI,and is a powerful predictor of HF.

The prognostic value of white blood cell and hemoglobin in patients with acute aortic dissection / 中国综合临床

Objective To evaluate the prognostic value of white blood cell and hemoglobin in patients with acute aortic dissection(AAD).Methods White blood cell.hemoglobin and fibrinogen were measured in 42 AAD patients.The mortality during hospitalization was observed and the short-term prognosis in AAD patients was as-seased.Results There was 13 death during hospitalization.with the mortality of 30.95%.The value of white blood cell was higher in death group than in survival group[(13.73±6.91)×109>/L vs.(9.43±4.97)×109>/L.P< 0.05).The value of hemoglobin was lower in death group of than in survival group[(118.54±22.38)g/L vs. (131.72±18.17) g/L,P<0.05].There were no differences in the value of fibrinogen between the groups [(3.15±1.15)g/L vs.(3.48±1.24)g/L,P>0.05).The mortality in the group of elevated white blood cell(≥10.0×109>/L)was higher than that in the group of normal white blood cell(10.0×109/L)(41.18%vs.24%.P<0.05).The mortality in the group of decreased hemoglobin(≤110g/L)was higher than that in the group of nor-mal hemoglobin(>110 g/L)(50.00%vs.27.78%,P<0.05).Conclusion The value of white blood cell and he-moglobin could help to assess the short-term prognosis of patients with AAD.

Changes of left atrium and pulmonary veins in patients with atrial fibrillation by transthoracic two-dimensional and three-dimensional echocardiography / 中华超声影像学杂志

Objective To observation the changes of left atrium and pulmonary veins(PV)in patients with atrial fibrillation(AF) by transthoracic two-and three-dimensional echocardiography. Methods Transthoracic echocardiography were applied in 126 patients,which were divided into sinus rhythm(SR) group(64 cases)and AF group(62 cases),AF group were further divided into two subgroups:the paroxysmal AF and non-paroxysmal AF group.Left atrial area(LAA),left atrial volume(LAV),left atrial diameter(LAD)were measured by 2-dimensional echocardiography imaging.PV diameters were measured by three-dimensional echocardiography. Results Compared with SR group,PV diameters were significantly increased in AF group(P＜0.05).In patients with AF,PV diameters in non-paroxysmal AF group were larger than paroxysmal AF group.The four PV diameters in SR,paroxysmal AF and non-paroxysmal AF group did not show statisticant difference(P＞0.05).Compared with SR group,LAD,LAA,LAV were increased in AF group.LAD,LAA,LAV were larger in non-paroxysmal AF group than SR group and paroxysmal AF group(P＜0.05).Conclusions Left atrium and PV dilate significantly in patients with AF,transthoracic echocardiography could be a non-invasive method to observe left atrium and PV.

Dynamic contrast-enhanced MRI of breast disease: correlation of MR findings with vascular endothelial growth factor and microvessel density / 医学研究生学报

Objective: To determine the relation dynamic contrast-enhanced magnetic resonance imaging (MRI) and histologic features and angiogenesis of breast disease. Methods: Forty patients with breast disease, diagnosed by histopathology were reviewed, including imaging and pathological data. Dynamic MRI was performed by a fat-suppressed 3D-FSPGR sequence ,Time-Signal curve was acquired by Functool 2 software, then early-phase enhancement rate and E max , T max were acquired. The mean MVD and VEGF expression of the lesions were measured with immunohistology. Evaluation of inflammatory changes was assessed by histology. Results: The MVD , VEGF expression and inflammatory scores of malignant tumor were significantly higher than that of benign tumor(P0.05), The Time-SI curve between malignant and benign was significant different(P

Application of magnetic resonance imaging in breast diseases / 医学研究生学报

Recent research has revealed important potentiality for MRI in the diagnosis of breast disorders. The review describes the imaging technique, the characterization and value of breast MRI for diseases detection ,and the differentiation of benign from malignant breast diseases. Applied breast MRI correctly enhances the diagnosis of diseases, especially, breast cancer, furthermore, it brings more information to the optimal treatment.