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With the research progress on the biology and pathogenesis of cancer, immune checkpoint inhibitors (ICIs) have come into being, bringing a new hope for the survival of patients with advanced cancer and opening a new era of cancer immunotherapy. However, with the wide application of immunotherapy in clinical practice, ICI-related adverse events (irAEs) have gradually emerged and are widely known by first-line clinicians. ICIs primarily activate T cells that can attack normal tissues and organs in the body and cause a variety of adverse reactions. Checkpoint inhibitor pneumonitis (CIP) is one of the rare complications with poor prognosis in irAEs. This article reviews the therapeutic mechanism of some ICIs; the incidence, risk factors, pathogenesis, and clinical and imaging manifestations of CIP; and the classification and treatment management of CIP.
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Objective To study classification of vascular sign of tiny ground glass nodules-like lung adenocarcinoma in HRCT, and explore its value to differentiate benign from malignant of the ground glass nodules(GGN).Methods 87 patients with tiny ground glass nodules-like lung adenocarcinoma examined on HRCT were retrospectively evaluated.According to the new pathological classification standard of lung adenocarcinoma,they were divided into three groups:(1)pre-invasive group(n=25),including 14 cases of atypical adenomatous hyperplasia(AAH)and 11 cases of adenocarcinoma in situ(AIS);(2)minimally invasive adenocarcinoma (MIA)group(n=35);(3)invasive adenocarcinoma(IAC)group(n=27).The lesions were divided into three types according to the grinding of glass composition proportion:Type A,pure ground glass nodules(pGGN);Type B,mixed ground glass nodules (mGGN)which contained glass composition≥50%;Type C,mGGN which contained glass composition < 50%.The vascular sign of GGN were divided into four types:Type 1,without vessels passing through the GGN,or vessels passing by GGN;Type 2,intact vessels passing through GGN,but vascular morphology is normal;Type 3,single vessels passing through GGN,and distorted,stiff vessels seen within GGN;Type 4,two or more vessels passing through GGN,and branches between vessels formed in GGN,and the diameter of vessel was irregular,partial enlargement.The relationship among the size of the GGN,content of the grinding of glass proportion and the vascular sign of GGN were analyzed both in axial images and reconstruction images.Results There were significant differences in size among the three groups(P=0.032,P=0.000,P=0.000).There were significant differences between content of the grinding of glass proportion and classification of vascular sign of GGN(P=0.000).Type 1 and type 2 vascular sign were dominant in the infiltrating former group,a total of 24 cases(96%).The incidence of type 3 and type 4 vascular sign in MIA group and IAC group was 60% and 74% respectively,and there were significant differences with the infiltrating former group(P=0.000,0.000).Further analysis indicated that type 3 was more commonly seen in MIA with comparison to type 4 which was more likely seen in IAC,the difference was statistically significant(P=0.043).Conclusion To study HRCT vascular sign of tiny ground glass nodules-like lung adenocarcinoma can improve the ability of the GGN benign and malignant diagnosis,provide reliable basis for clinical diagnosis and treatment.
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Objective To evaluate the application of abbreviated protocol (AP) of magnetic resonance imaging (MRI) in screening of breast cancer with dense breast tissue.Methods Total 478 patients with dense breast tissue,who had negative X-ray mammography (MG),underwent dynamic contrast-enhanced MRI (DCE-MRI).The AP MRI,which consisted of first postcontrast subtracted (FAST) and maximum-intensity projection (MIP),and full diagnostic protocol (FDP) MRI images were analyzed by Breast Imaging Reporting and Data System (BI-RADS).Among 478 patients the histopathological diagnosis was available in 39 cases (41 breast lesions).With pathological diagnosis as gold standard,the sensitivity,specificity,positive predictive value (PPV) and negative predictive value (NPV) of AP and FDP in breast cancer detection were evaluated.Results In 41 breast lesions there were 16 malignant lesions and 25 benign lesions.FDP detected all 16 malignant lesions,including 9 cases of ductal carcinoma in situ,6 cases of invasive ductal carcinoma and 1 case of mucinous carcinoma;AP detected 15 out of 16 cases of breast cancer.The sensitivity of FDP and AP in detection of breast malignant lesions was 16/16 and 15/16,respectively (x2 =0.725,P =0.224).The specificity of FDP and AP was 92％ (23/25) and 76％ (19/25),respectively (x2 =6.327,P =0.012).Conclusion For women with dense breast tissue AP of MRI can be used in early screening of breast cancer.
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Objective To explore the multi-modal MRI characteristics of breast cancers in dense breasts.Methods 120 patients with breast cancer shown on mammography underwent breast MRI,which were solitary and confirmed by pathological examination. According to the BI-RADS classification of breast,the 120 cases were divided into two groups including dense type breast and non-dense type one.The differences in morphological features,ADC values (b=1 000 s/mm2 )and time-signal intensity curve (TIC)of the lesions between two groups were analyzed and compared.Statistical analysis was performed using SPSS1 6.0.Results The breast cancers in dense breast were vulnerable to have a spiculated margin (44/68 in the dense breast group vs.1 6/52 in the non-dense breast group,P =0.000).The size of the lesion in dense breast (1.83 ±0.98)cm was bigger than that in non-dense breast (1.40±0.46)cm (P =0.005).The non-mass-like enhancement of the lesion in dense breast was much more than that in non-dense breast (P =0.000).In addition,the average ADC values of the lesion in dense breast (0.89±0.12)×10 -3 mm2/s were lower than in non-dense breast (0.95±0.10)×10 -3 mm2/s(P =0.01 6).Conclusion The breast cancer in the dense breast has different MRI findings in comparison with non-dense breast.
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Objective To evaluate the value of proton magnetic resonance spectrum (1H-MRS) in the differential diagnosis of Alzheimer's disease (AD) and vascular dementia (VD) patients with white matter lesions (WMLs).Methods Multi voxel 1H-MRS were performed to 30 patients with AD,30 patients with VD,and 30 normal control volunteers.The levels of the N-acetylaspartate (NAA),myo-inositol (mI),glutamate (Glu),and creatine (Cr) were measured in the white matter adjacent to the lateral ventricles.The ratios of NAA/Cr,mI/Cr and Glu/Cr were calculated and compared among the group.Comparisons of the 1H-MRS indexes among AD,VD and NC group were conducted by one-way ANOVA.Results NAA/Cr ratios of the region of interesting in AD (1.59±0.15)and VD(1.53±0.12) group were significantly decreased compared with NC (1.79±0.22)group (P＜0.05),and Glu/Cr ratios of the region of interesting in AD(0.41±0.03) and VD(0.49±0.04) group were significantly decreased compared with NC(0.57±0.05) group (P＜0.05).However,there were not significant differences for NAA/Cr ratios of the paraventricular white matter region between AD and VD group (P＞0.05),and Glu/Cr ratios in AD and VD groups were significantly different (P＜0.05).A significantly increased mI/Cr was found in AD (0.68±0.05) group than in VD(0.57±0.04) and NC(0.55±0.03) groups (P＜0.05),and there were no significant changes in mI/Cr ratios between VD and NC groups (P＞0.05).Conciusion Multi-voxel 1H-MRS is an effective method in the differential diagnosis of dementia,and changes of the mI/Cr and Glu/Cr ratios of the white matter adjacent to the lateral ventricles may help to identify the AD and VD patients.
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Objective To investigate the clinical value of multi-slice spiral CT (MSCT)in diagnosis of internal abdominal hernia (IAH).Methods The MSCT findings in 1 5 patients with IAH confirmed by surgery were retrospectively analyzed.Results MSCT showed intestinal obstruction in 14 patients with strangulating intestinal obstruction in 8.The typical features of MSCT were as follows:translocated position of intestines (occupying effect),closed loop intestinal obstruction (gathered intestinal loops with different forms),assembled,expanded and translocated blood vessels of mesenteries,and thickened intestinal walls with ischemic edema and abnormal density.Surgical results showed paraduodenal hernia in 2,transomental hernia in 2,transmesenteric hernia in 5,ankylenteron strap hernias in 4,pericecal hernia in 1 and hernia through the Douglas fossa in 1,Intestinal obstruction in 14 and strangulating intestinal obstruction in 8 were also confirmed by surgery.The CT findings of IAH were correlated with the surgical results,and the accurate rate of grading of intestinal obstruction with CT was also consistent with the surgical results (Kappa=0.758,t=3.462,P=0.001).Conclusion IAH can be diagnosed accurately by MSCT in most patients,MSCT is helpful for guiding the surgical programs.
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Objective To label neural stem cells (NSCs) with superparamagnetic iron oxides (SPIO) and to explore the tropism of NSCs after transplantation into the hippocampus of APP/PS1 AD mice by MRI.Methods NSCs from C57BL/6 mouse were cultured and identified.Feridex and Poly-L-Lysine were added into the medium to be co-cultured to make magnetic labeled NSCs and transmission electron microscopy was used to identify the iron particles in NSCs.Transgenic (tg) and wild-type (wt) mice at 12 months of age were divided into three groups: SPIOs labeled NSCs group (A and C),unlabeled NSCs group(B).Feridex-labeled NSCs were migrated into the hippocampus of APP/PS1 AD mice to monitor in vivo by MRI.After 1,2,4 and 6 weeks,the mice were sacrificed and their brain tissues were sectioned to investigate the migration of SPIO labeled NSCs and compared with MRI.Results NSCs of C57BL/6 mice were cultured successfully.Transmission electron microscope showed visible iron granules in cytoplasm.MRI detection of labeled cells: T2WI and T2* WI showed remarkable low signal intensity at the hippocampus injection points 1 week after transplantation,particularly on T2* WI.Area of low signal intensity enlarged increasingly along the injection points after 2 weeks.At 4 weeks,area of low signal intensity spread throughout the hippocampus,but intensity shadowed Six weeks later,low signal intensity almost disappeared.There was no obvious low signal change in unlabeled cell transplantation group.For wt mice,size and location of low signal did not appear obvious change at all designated time points.Prussian blue positive cells were observed in the hippocampus,indicating that NSCs labeled with SPIO could survive,migrate and differentiate in the brain of the APP/PS1 AD mice.Changes of pathology were well correlated with the area where a signal intensity loss was observed in MRI 1,2,4 and 6 weeks after transplantation Conclusions Diffuse migration of transplanted NSCs labeled with SPIO is observed in the hippocampus in APP/PS1 tg mice,and MRI technique is an ideal method for tracking labeled stem cells after grafting in vivo.
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Objective To explore the effect of neural stem cell(NSCs) transplantation on proton magnetic resonance spectroscopy (1H-MRS) and the behavior in APP/PS1 double transgenic AD mice.Methods NSCs from C57BL/6 mice were cultured and amplified.APP/PS1 double transgenic AD mice (n=30) aged 12 months were used as the study group,and mild-type mice (n=15) were used as the control group(group C).Animals in the study group were randomly divided into two subgroups:one receiving NSCs (group A) and the other receiving PBS transplantation (group B) in bilateral hippocampal CA1 of the AD model mice.Animals in the group C were not treated.1 H-MRS and Morris water maze (MWM) were performed before transplantation and 4 weeks after transplantation,and compared with the histopathological results.Results 1H-MRS showed that there was no significant change in NAA/Cr(1.01±0.08 and 1.03±0.05) and mI/Cr (0.69±0.05 and 0.71±0.06) ratios between group A and group B before transplantation (P＞ 0.05),but the changes were significant compared with the group C (NAA/ Cr:1.21±0.05; mI/Cr:0.58±0.06) (P＜0.05).Four weeks after transplantation,NAA/ Cr ratio(1.18± 0.09) was increased and mI/Cr ratio (0.53±0.04) was decreased in group A.The difference was significant compared with the group B at the same time points (P＜0.05).MWM showed the escape latency in group A was significantly shorter than that in group B after transplantation (P＜0.05).In addition,group A also showed an exclusive preference for the target quadrant,and spent more time ((35.21±5.44) s) in the 3rd quadrant compared with group B (P＜0.05).For number of platform crossings,similar results were also shown (5.75± 3.23).Nissl's staining showed that the number of neurons in the hippocampal area increased more significantly in group A than those in group B(P＜0.05).Conclusion NSCs transplantation can improve spatial learning and memory via neurons regeneration in APP/PS1 double transgenic AD mice,and 1H-MRS is able to display intracranial metabolite changes after NSCs transplantation.
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Objective To explore the value of 1H-MRS on the evaluation of Alzheimer's disease (AD) with neural stem cells (NSCs) transplantation in an APP-PS1 double transgenic (tg) AD mouse model.Methods NSCs from C57BL/6 mice were cultured and amplified.APP-PS1 tg mice (n =30) aged 12 months were used as the study group,and mild-type mice (n =15) were used as the control group.Animals in the study group were randomized into two subgroups,the AD mice in one subgroup received NSCs transplantation (NSCs group) and in another subgroup received phosphate buffer saline (PBS,PBS group)in bilateral hippocampal CA1.Animals in the control group were not treated.Using a 7.0 T high-fieldstrength MR imager,1H-MRS was performed before and 6 weeks after transplantation to measure the area under the peak of n-acetyl aspartate (NAA),glutamate (Glu),myo-inositol ( mI),choline (Cho) and creatine (Cr) in the hippocampal area,NAA/Cr,Glu/Cr,mI/Cr and Cho/Cr ratio were calculated and compared with histopathological results (including Nissl's staining and electron microscope examination).Comparisons among NSCs,PBS and control groups were conducted by one-way ANOVA.Results NSCs from C57BL/6 mice were cultured successfully. Before transplantation,the mean NAA/Cr,Glu/Cr and mI/Cr in NSCs,PBS and control groups were 0.89 ± 0.05,0.88 ± 0.04 and 1.15 ± 0.05,0.40 ± 0.03,0.39 ± 0.03 and 0.45 ± 0.05,0.67 ± 0.05,0.67 ± 0.05 and 0.52 ± 0.04,respectively,and differences were statistically significant (F =148.918,7.529,59.468,P ＜ 0.01 ). There were no significant differences in NAA/Cr,mI/Cr and Glu/Cr ratios between NSCs and PBS groups before transplantation (t =0.147,0.096,0.207,P ＞ 0.05 ),but the differences were significant compared with the control group (t =0.255,0.467,0.171 and t =0.269,0.527,0.151,P ＜0.05).Six weeks after transplantation,the mean NAA/Cr,Glu/Cr and mI/Cr in three groups were 1.13 ±0.07,0.86 ±0.05 and 1.14 ±0.05,0.45 ± 0.04,0.38 ± 0.02 and 0.44 ± 0.03,0.58 ± 0.04,0.67 ± 0.04 and 0.53 ± 0.04,respectively,and differences were statistically significant ( F =112.092,23.076,44.367,P ＜ 0.01 ).NAA/Cr and Glu/Cr ratios were increased and mI/Cr was decreased in NSCs group,and the difference was significant compared with PBS group at the same time point ( t =0.271,0.071,0.089,P ＜ 0.05 ).There were no significant differences in NAA/Cr and Glu/Cr ( t =0.013,0.012,P ＞ 0.05 ),but there was a significant difference in mI/Cr between NSCs and control groups ( t =0.046,P ＜ 0.05).There were no significant differences in Cho before and after transplantation among the three groups (P ＞ 0.05 ). Nissl's staining showed that the number of neurons in the hippocampal area increased more significantly in tg mice receiving NSCs than that without receiving NSCs.Electron microscopy showed that most hippocampal NSCs in NSCs group were morphologically normal with abundant organelles,while hippocampal NSCs in PBS group were swollen with sparse synapses.Conclusion 1H-MRS is able to display intracranial metabolite changes before and after NSCs in APP-PS1 double transgenic AD mice and has an applicable value in evaluating the therapeutic effect of NSCs on AD.
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Objective To explore changes of metabolites in APP/ PS1 double transgenie mice of Alzbeimer disease (AD) by 1H-MR spectroscopy (1H-MRS) and the application value of in early diagnosis of AD.Methods 1H-MRS was performed in 35 APP/PS1 transgenie mice of AD ( study group) and 20 wild type mice ( control group) at age of 3, 6 and 9 months using a 7.0 T MR system.Sub-peak areas of N-acetyl aspartate (NAA), myo-inositol (mI) and creatine (Cr) in the cerebral cortex and hippocampus were measured, and the NAA/Cr and mI/Cr ratios were calculated.The changes in pathology between the two groups were compared.Using the lower limit of 95% confidence interval (CI) of the ml/Cr ratio and the upper limit of 95% CI of the NAA/Cr ratio of AD mice as the threshold, their influences on sensitivity,specificity and accuracy of various age groups of AD animals were compared.Comparison of the 1H-MRS indexes between study mice and wild type mice at each time point were conducted by a two-sample t test.Results The mean mI/Cr ratios of AD mice were 0.68± 0.03, 0.72± 0.04, and 0.77 ± 0.04 respectively at 3, 6 and 9 months of age; while they were 0.63 ± 0.04, 0.64 ± 0.03, and 0.64 ± 0.04 respoetively in control group, the difference was significant ( t = 2.814, 5.146, 14.437, P < 0.01 ).Compared with the control group, the mI/Cr ratio of the 3-month-old AD mice of the study group was significantly increased,and histological examination showed proliferation and activation of neuroglial cells in the cerebral cortex and hippoeampus.The mean NAA/Cr ratio were 1.17 ±0.08, 1.04 ±0.05, and 0.90 ±0.05 respectively at 3,6 and 9 months of age in study group, while they were 1.18 ±0.07, 1.16 ±0.07, and 1.18 ±0.08respectively in control group.There were no significant difference ( t = 0.752, P > 0.05 ) between the study group and control group at 3 months of age, and the NAA/Cr ratio decreased significantly only at 6 and 9 months of age ( t = - 8.514, - 5.646, P < 0.01 ).The immunohistochemical exam demonstrated the appearance of Aβ plaque.According to threshold of mI/Cr, the sensitivity of AD mice of 3, 6 and 9 months of age was 80% (28/35), 84% ( 26/31 ) and 85% ( 23/27 ), and the specificity was 85% ( 17/20 ),94% (17/18) and 100% ( 16/16), and the accuracy was 82% (45/55), 88% (43/49) and 91% (39/43),respectively.For NAA/Cr, the sensitivity of AD mice of 6 and 9 months of age was 84% (26/31) and 89% (24/27), and the specificity was 89% (16/18) and 100% (16/16), and the accuracy was 86% (42/49) and 93% (40/43), respectively.Conclusions NAA and mI are the most sensitive and specific markers for early assessment of AD, and change of mI is earlier than that of NAA.Quantitative analysis of mI may provide important clues for early diagnosis of AD.
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Objective To label rat bone marrow mesenchymal stem cells with superparamagnetic iron oxide (SPIO) and to explore the tropism of BMSCs for hepatocellular carcinoma cells after transplantation in vivo. Methods BMSCs from bone marrow of Sprague-Dawly (SD) rats were cultured isolated and purified, Labeled BMSCs was achieved using Feridex. Twenty-four hepatocellular carcinoma models of SD rats were induced two weeks before tmnsplantation. The models were divided into three groups in random: the labeled BMSCs and unlabeled BMSCs were transplanted respectively into the rat's livers of experimental group (n = 12) and control group A(n =6) via spleens, and no transplant was done for control group B (n =6). MR imaging was performed to monitor the transplanted cells after 1,3,7,14 d using 1.5 T MR system. Signal intensity ratio (SI/SI*) between tumor and hepatic tissue on T_2 * WI were measured and compared by one-factor analysis of variance. After MR imaging, Prussian blue staining was performed. MR imaging findings were compared with histological sections. Results Prussian blue staining confirmed the labeling efficiency of BMSCs was above 90%. SI/SI* of experimental group before and 1, 3, 7, 14 d after transplantation were 3.18±0.21,1.98±0.20,2.38±0.28,2.70±0.25 and 3.16±0.24 respectively. Following transplantation of BMSCs, signal intensity decrease was found in hepatocellular carcinoma of experimental group(F =56.65,P <0.05) and low signal change decreased gradually and disappeared at two weeks after transplantation, while no remarkable low signal change was seen in the control group by T_2 * WI (P > 0.05). A large number of Prussian blue staining positive cells were found in hepatocellular carcinoma in experimental group. Histological section with Prussian blue staining had a good correlation with the signal intensity changes on MR images at different time. Conclusion BMSCs display significant tropism to hepatocellular carcinoma and may be an ideal gene therapy vehicle against hepatocellular carcinoma.