Triple-negative breast cancer (TNBC) is typically associated with poor prognosis due to its only partial response to chemotherapy and lack of clinically established targeted therapies coupled with an aggressive disease course. Aerobic glycolysis is a hallmark of reprogrammed metabolic activity in cancer cells, which can be repressed by small-interfering RNA (siRNA). However, the lack of effective carriers to deliver vulnerable siRNA restricts the clinical potentials of glycolysis-based gene therapy for TNBC. Herein, we develop a tumor-targeted, biomimetic manganese dioxide (MnO2)-shrouded metal-organic framework (MOF) based nanomedicine to deliver siRNA against pyruvate kinase muscle isozyme M2 (siPKM2), wherein PKM2 is a rate-limiting enzyme in glycolysis, to inhibit the reprogrammed glycolysis of TNBC. This MOF-based genetic nanomedicine shows excellent monodispersity and stability and protects siPKM2 against degradation by nucleases. The nanomedicine not only substantially blocks the glycolytic pathway but also improves intracellular hypoxia in TNBC cells, with a resultant O-2-enhanced anticancer effect. In the mice orthotopic TNBC model, the nanomedicine shows a remarkable therapeutic effect. Meanwhile, the Mn2+ ions released from acid microenvironment-responsive MnO2 enable in vivo monitoring of the therapeutic process with magnetic resonance imaging (MRI). Our study shows great promise with this MRI-visible MOF-based nanomedicine for treating TNBC by inhibition of glycolysis via the RNA interference.

BACKGROUND:Postoperative liver failure is the most severe complication in cirrhotic patients with hepatocellular carcinoma (HCC) after major hepatectomy. Current available clinical indexes predicting postoperative residual liver function are not sufficiently accurate.AIM:To determine a radiomics model based on preoperative gadoxetic acid-enhanced magnetic resonance imaging for predicting liver failure in cirrhotic patients with HCC after major hepatectomy.METHODS:For this retrospective study, a radiomics-based model was developed based on preoperative hepatobiliary phase gadoxetic acid-enhanced magnetic resonance images in 101 patients with HCC between June 2012 and June 2018. Sixty-one radiomic features were extracted from hepatobiliary phase images and selected by the least absolute shrinkage and selection operator method to construct a radiomics signature. A clinical prediction model, and radiomics-based model incorporating significant clinical indexes and radiomics signature were built using multivariable logistic regression analysis. The integrated radiomics-based model was presented as a radiomics nomogram. The performances of clinical prediction model, radiomics signature, and radiomics-based model for predicting post-operative liver failure were determined using receiver operating characteristics curve, calibration curve, and decision curve analyses.RESULTS:Five radiomics features from hepatobiliary phase images were selected to construct the radiomics signature. The clinical prediction model, radiomics signature, and radiomics-based model incorporating indocyanine green clearance rate at 15 min and radiomics signature showed favorable performance for predicting postoperative liver failure (area under the curve: 0.809-0.894). The radiomics-based model achieved the highest performance for predicting liver failure (area under the curve: 0.894; 95%CI: 0.823-0.964). The integrated discrimination improvement analysis showed a significant improvement in the accuracy of liver failure prediction when radiomics signature was added to the clinical prediction model (integrated discrimination improvement = 0.117, P = 0.002). The calibration curve and an insignificant Hosmer-Lemeshow test statistic (P = 0.841) demonstrated good calibration of the radiomics-based model. The decision curve analysis showed that patients would benefit more from a radiomics-based prediction model than from a clinical prediction model and radiomics signature alone.CONCLUSION:A radiomics-based model of preoperative gadoxetic acid-enhanced MRI can be used to predict liver failure in cirrhotic patients with HCC after major hepatectomy.

Background Immunotherapy with IFNβ is a promising strategy for treating malignant glioma. However, systemic administration of IFNβ is inadequate because of low intratumoral concentration and major adverse effects. This study aimed to determine whether mesenchymal stem cells (MSCs) can be used as cellular vehicles to locally deliver IFNβ for glioma therapy by using in vivo MRI tracking. Methods A recombinant lentiviral vector encoding IFNβ and ferritin heavy chain (FTH) reporter genes was constructed to transduce MSCs. The effectiveness and safety of transduction were assessed. After the IFNβ and FTH overexpressed MSCs (IFNβ-FTH-MSCs) were transplanted into intracranial orthotopic rat F98 gliomas via peritumoral, intracerebral, intratumoral or intra-arterial injection, MRI was performed to track IFNβ-FTH-MSCs and to evaluate their therapeutic effect on glioma in vivo, as validated by histologic analysis, quantitative PCR and ELISA assays. Results MSCs were efficiently and safely transduced to upregulate their IFNβ secretion and FTH expression by the constructed lentivirus. After peritumoral injection, IFNβ-FTH-MSCs appeared as hypointense signals on MRI, which gradually diminished but remained visible until 11 days. Compared with other administration routes, only peritumoral injection of IFNβ-FTH-MSCs showed a remarkable inhibition on the glioma growth. Nearly 30% of IFNβ-FTH-MSCs survived up to 11 days after peritumoral injection, while most of IFNβ-FTH-MSCs injected via other routes died within 11 days. IFNβ-FTH-MSCs grafted peritumorally secreted IFNβ persistently, leading to pronounced Batf3 + dendritic cells and CD8 + T lymphocyte infiltration within the glioma. Conclusions MSCs can be used as cellular vehicles of IFNβ to treat malignant glioma effectively via peritumoral injection.

Embedding an enzyme within a MOF as exoskeleton (enzyme@MOF) offers new opportunities to improve the inherent fragile nature of the enzyme, but also to impart novel biofunctionality to the MOF. Despite the remarkable stability achieved for MOF-embedded enzymes, embedding patterns and conversion of the enzymatic biofunctionality after entrapment by a MOF have only received limited attention. Herein, we reveal how embedding patterns affect the bioactivity of an enzyme encapsulated in ZIF-8. The enzyme@MOF can maintain high activity when the encapsulation process is driven by rapid enzyme-triggered nucleation of ZIF-8. When the encapsulation is driven by slow coprecipitation and the enzymes are not involved in the nucleation of ZIF-8, enzyme@MOF tends to be inactive owing to unfolding and competing coordination caused by the ligand, 2-methyl imidazole. These two embedding patterns can easily be controlled by chemical modification of the amino acids of the enzymes, modulating their biofunctionality.

Portable devices featured with fast analysis and affordable methodologies for clinical diagnostics have stimulated the rapid development of point-of-care (POC) technologies, potentially lowering the mortality rate. Herein, we demonstrated a portable, robust, and user-friendly intelligent metal-organic frameworks (MOFs) paper device, called smartphone-assisted biomimetic MOFs nanoreactor colorimetric paper (SBMCP), for on-demand POC detection of endogenous biomolecules. The concept of this paper platform was analogous to the intracellular cascades signal transduction, wherein the single/multiple enzymes components trapped within a ZIF-8 exoskeleton allowed the sensitive and selective recognition of target analyte via the accessible micropores network of ZIF-8, and then transferred the recognition event to a visual color signal based on the cascade reaction. Meanwhile, the ZIF-8 exoskeleton also endowed the enzymes with significantly elevated stability. As a result, this robust and portable SBMCP sensor enabled the on-site analysis of different important disease-related biomolecules through modulating the enzyme cascades, combining with a custom-designed smartphone application for signal readout. In the SBMCP assay, no sophisticated instruments or professional skill of the user was required, only 5 μL sample volume was needed, and the whole analysis process could be achieved within a portable MOFs paper and pervasive smartphone, endowing this new assay with the merits of low-cost, time-saving and easy-to-use. We demonstrated this SBMCP sensor was capable of real-time colorimetric detection of glucose and uric acid in diabetes and gout events. It is believed that this portable biosensor platform proposed herein potentially represents promising alternatives for POC diagnosis, especially applicable in developing world and resource-limited settings.

Background: Cancer has become a major disease endangering human health around the world. Conventional chemotherapy suffers from many side effects including pain, cardiotoxicity, hepatotoxicity, and renal toxicity. This review aims to describe a natural product of resveratrol as a chemoprotective and synergistic agent in the modulation of cancer chemotherapy. Methods: The publications were identified by comprehensive searching of SciFinder, PubMed, Web of Science, and our own reference library. Search terms included combinations of "resveratrol," "cancer," "natural products," "chemotherapy," and "side effects." Selection of material focused on resveratrol reducing the side effects on cancer chemotherapy. Results: Thirty one references were referred in this review to outline resveratrol as a potent chemoprotective and synergistic agent in cancer chemotherapy, including 22 papers for describing the chemoprotective effects, and 9 papers for illustrating the synergistic effects. Conclusion: This study provides a systematic summary of resveratrol serving as a potent chemoprotective and synergistic agent to reduce the associated-side effects and enhance the therapeutic outcomes in cancer chemotherapy. Further studies in terms of resveratrol on a large amount of preclinical tests and clinical trials are highly demanded.

Excessive and persistent inflammation after injury lead to chronic wounds, increased tissue damage or even aggressive carcinogenic transformation. Effective wound repair could be achieved by inhibiting overactive immune cells to the injured site. In this study, we obtained high concentration of PD-L1 in exosomes from either genetically engineered cells overexpressing PD-L1 or IFN-γ stimulated cells. We found that exosomal PD-L1 is specially bound to PD-1 on T cell surface, and suppressed T cell activation. Interestingly, exosomal PD-L1 promoted the migration of epidermal cells and dermal fibroblasts when pre-incubated with T cells. We further embedded exosomes into thermoresponsive PF-127 hydrogel, which was gelatinized at body temperature to release exosomes to the surroundings in a sustained manner. Of importance, in a mouse skin excisional wound model, exosomal PD-L1 significantly fastened wound contraction and reepithelialization when embedded in hydrogel during inflammation phase. Finally, exosomal PD-L1 inhibited cytokine production of CD8+ T cells and suppressed CD8+ T cell numbers in spleen and peripheral lymph nodes. Taken together, these data provide evidence on exosomal PD-L1 exerting immune inhibitory effects and promoting tissue repair.

Objective To investigate the predictive value of diffusion-weighted (DW) magnetic resonance imaging (MRI) for invasiveness of hilar cholangiocarcinoma (HC).Methods The retrospective casecontrol study was conducted.The clinicopathological data of 65 HC patients who were admitted to the Sun Yat-sen Memorial Hospital from January 2012 to November 2017 were collected.Patients received DW MRI before treatment,and 2 senior imaging doctors analyzed imaging data and measured the apparent diffusion coefficient (ADC) for the primary lesions of HC.Observation indicators:(1) MRI situations of HC;(2) relationship between ADC and clinicopathological factors;(3) receiver operator characteristic (ROC) curve analysis;(4) treatment and follow-up situations.According to patients' conditions,treatment plans were done within 2 weeks after MRI and patients underwent radical resection of HC.Follow-up using telephone interview was performed to detect tumor recurrence up to December 2017.Measurement data with normal distribution were represented as (x)±s,and comparisons between group and among group were respectively analyzed using the t test and one-way ANOVA.Spearman's rank correlation was performed to analyze the relationship between ADC and clinicopathological factors.ROC curves assessed the diagnostic efficiency of ADC.Results (1) MRI situations of HC:MRI and magnetic resonanced cholangio-pancreatography (MRCP) in 65 patients showed varying degrees of soft rattan-like dilations of intrahepatic bile ducts and truncation signs of bile tracts in hepatic port.Of 65 patients,tumors in 23,7 and 35 patients were respectively pedunculated type,polypoid type and infiltrating type.The pedunculated-type lesions of 23 patients presented as low signal on T1WI and slightly high signal on T2WI;after enhanced scans of MRI,pedunculated-type lesions of 7 patients demonstrated moderate homogenous enhancement in 3 patients,ring-like enhancement with internal liquefaction necrosis in 10 patients and moderate heterogeneous enhancement in 10 patients,respectively.The polypoid-type lesions presented as low signal on T1WI and high signal on T2WI,and moderate homogenous enhancement by enhanced scans of MRI.There were varying degrees of bile duct wall thickness and irregular nodules in the infiltrating-type lesions of 35 patients,showing moderate enhancement by enhanced scans of MRI.All the lesions of 65 patients using DW MRI demonstrated restricted diffusion,showing a clear boundary between lesions and normal surrounding bile ducts or liver tissues;heterogeneous enhancement lesions by MRI scans presented as heterogeneously high signal on DWI and heterogeneously low signal on ADC map,and necrotic area of lesions showed low signal on DWI;homogenous enhancement by MRI scans presented as homogenously high signal on DWI and homogenously low signal on ADC map.(2) Relationship between ADC and clinicopathological factors:ADC was respectively (1.382±0.165)× 10-3 mm2/s,(1.343±0.138)× 10-3 mm2/s,(1.291-±0.226)×10-3 mm2/s,(1.111±0.243)×10-3 mm2/s in stage Ⅰ,Ⅱ,Ⅲ and Ⅳ (TNM staging) and (1.441± 0.355) × 10-3 mm2/s,(1.226 ± 0.177) × 10-3 mm2/s,(1.061 ± 0.228) × 10-3 mm2/s in highdifferentiated,moderate-differentiated and low-differentiated tumors (pathological grading) and (1.403±0.176)× 10-3 mm2/s,(1.121±0.238)× 10-3 mm2/s in Ki-67 score ≤ 10％ and ＞ 10％ and (1.115±0.241)× 10-3 mm2/s,(1.347±0.174)× 10-3 mm2/s in HC patients with and without lymph node metastasis,with statistically significant differences in the above indicators (F =4.158,9.866,t =11.607,13.464,P＜0.05).Results of Spearman's rank correlation analysis showed that ADC had a negative correlation with TNM staging,pathological grading and Ki-67 score (r=-0.532,-0.522,-0.409,P＜0.05).(3) ROC curve analysis:using 1.225×10-3 mm2/s as a critical value of ADC,the sensitivity and specificity of ADC in the diagnosis of stage Ⅰ-Ⅱ HC and stage Ⅲ-Ⅳ HC were 70.5％ and 81.0％,and area under ROC curve was 0.705 (95％CI:0.62-0.84,P＜0.05).Using 1.100×10-3 mm2/s as a critical value of ADC,the sensitivity and specificity of ADC in the diagnosis of lowdifferentiated HC and moderate-and high-differentiated HC were 88.2％ and 64.3％,and area under ROC curve was 0.814 [95％ confidence interval (CI):0.69-0.90,P＜0.05].Using 1.243×10-3 mm2/s as a critical value of ADC,the sensitivity and specificity of ADC in the diagnosis of Ki-67 score ≤ 10％ and ＞ 10％ were 66.7％ and 75.0％,and area under ROC curve was 0.783 (95％CI:0.62-0.90,P＜0.05).Using 1.222×10-3 mm2/s as a critical value of ADC,the sensitivity and specificity of ADC in the diagnosis of lymph node metastasis were 91.3％ and 71.4％,and area under ROC curve was 0.873 (95％CI:0.76-0.94,P＜0.05).(4) Treatment and followup situations:65 patients underwent successful radical resection of HC.Thirty-three patients were followed up for 1-24 months.Of 33 patients,5 had tumor recurrence within 6 months postoperatively,including 4 with ADC ＜ 1.100× 10-3 mm2/s,13 had tumor recurrence after 6 months postoperatively,and 15 didn't have tumor recurrence or metastasis,including 1 with ADC ＜ 1.100× 10-3 mm2/s.Conclusions There are different ADC in differentTNM staging,pathological grading,Ki-67 score and with or without lymph node metastasis of HC.ADC of DWMRI can be used as a preoperative imaging predictor for invasiveness of HC.

Accurate evaluation of lymph node metastasis in bladder cancer (BCa) is important for disease staging, treatment selection, and prognosis prediction. In this study, we aimed to evaluate the diagnostic accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) for metastatic lymph nodes in BCa and establish criteria of imaging diagnosis.

目的 探讨自身免疫性胰腺炎CT和MRI的影像学特点,提高对自身免疫性胰腺炎的认识和影像学诊断水平.方法 回顾性分析45例经激素治疗或手术病理证实的自身免疫性胰腺炎患者的CT和MRI影像学资料,观察胰腺及周围组织、胰管和胆管的影像学表现,总结自身免疫性胰腺炎CT和MRI的影像学特点.结果 45例自身免疫性胰腺炎患者中,男性32例,女性13例,其中37例患者表现为胰腺的弥漫性肿大,8例患者表现为胰腺局限性肿大,CT检查中有27例患者的胰腺病灶平扫密度减低;MRI检查中有16例患者胰腺病灶出现信号的改变,表现为T1WI上低信号,T2WI上稍高信号;45例患者胰腺病灶均表现为延迟强化方式改变.10例患者的CT和7例患者的MRI表现为胰管狭窄,2例患者的CT和1例的患者MRI表现为胆总管狭窄.14例患者的CT及MRI表现胰腺周围的"假包膜"征象.结论 自身免疫性胰腺炎在CT和MRI上具有一定的影像学特点,结合实验室相关检查有助于该疾病的诊断.

膀胱癌是泌尿系统最常见的恶性肿瘤,易发生复发、转移.相对于淋巴结转移阴性的患者,淋巴结转移阳性的患者复发、转移概率更高,而且往往是致死性的.准确预测淋巴结转移与否对于患者治疗策略的选择具有重要指导意义.目前诊断淋巴结转移的金标准为术后病理,术前主要依靠影像学,但是准确性不太理想.本文就膀胱癌盆腔淋巴结转移的影像学诊断方法,包括CT、MRI及PET/CT、SPECT/CT及前哨淋巴结显像等作一综述.

Objective: To investigate the clinical significance of Gd-EOB-DTPA to predict and evaluate the liver function. Materials and Methods: Gd-EOB-DTPA-enhanced MR images of 98 patients were conducted on a 3.0 Tesla MRI. The values of relative enhancement ratio (rER) and Child-Pugh scores were calculated. Serologic testing was obtained within 7 days before and after MRI. The comparison between different Child-Pugh groups was accomplished by One-Way ANOVA. Spearman rank correlation was applied to analyze the relationship between the rER values and serologic results. Results:The results showed statistical differences among rER values of different Child-Pugh groups and normal group (P<0.05). The mean values are respectively 2.281±0.275, 2.092±0.474,1.824±0.246, 1.711±0.433. Comparative analysis between every two groups was applied and the results showed that normal and Child-Pugh B, normal and Child-Pugh C, Child-Pugh A and Child-Pugh B indicated statistical significance. The linear regression analysis showed that P value between rERs and values of TBIL, ALT, AST, PT, PTA, PA, ChE were less than 0.05, which was significant statistically. Conclusions: The rER values of EOBMRI could be used to evaluate liver function and to identify mild, moderate liver damage significantly. It got the most intimate relation with prothrombin activity and prealbumin.

Objective To cstimnate the diagnostic performance of computer tomography (CT) and magnetic resonance imaging (MRI) for detecting metastasis in pelvic lymph nodes with normal size in patients with bladder cancer.Methods hnaging of CT and MRI and clinical data of 118 patients who underwent radical cystectomy and pelvic lymphadenectomy were reviewed.The diagnostic efficacy of CT and MRI were analyzed when taking lymph nodes short axis diameter ≥0.3 cm and ≥ 1.0 cm respectively as diagnostic criterion of metastasis with corTelation of pathological results.Results 22.7％ (27/118) of patients were confirmed lymph nodes malignancies among 118 patients based on pathology.Totally 1 705 lymph nodes were detected in surgery and 119 of them were observed malignancy according to pathological presentation.The malignant nodes were mainly distributed in the perivesical (35.4％,41/119),internal iliac (12.6％,15/119),external iliac (30.3％,36/119),obturator region (21.0％,25/119) and presarcal region (1.7％,2/119).Imaging of CT and MRI showed that when taking nodes with ≥0.3 cm in maximum short-axis diameter (MSAD) as positive,the sensitivity (Se),specificity (Sp),and positive predictive values (PPV) were 16.0％,99.2％,54.2％ and 56.5％,99.2％,86.7％ respectively.While taking MSAD≥1.0 cm as malignant,the Se,Sp and PPV of CT and MRI were 6.2％,99.9％,83.3％ and 13％,100％,100％ respectively.When taking MSAD ≥0.3 cm as positive,the Se and PPV between CT and MR were statistically different(P ＜ 0.001 and P =0.036,respectively).When taking MSAD ≥ 1.0 cm as positive,there was no statistically difference (P =0.275 and 1.000,respectively).Conclusions The incidence of normal-sized lymph node metastasis was higher in patients with bladder cancer.At this phase the MRI evaluation was superior to that of CT.When the MSAD ≥ 1.0 cm,there was no significant difference between CT and MRI.

例1男，65岁。剑突下钝痛5个月，外院CT检查提示肝S8段占位性病变。实验室检查：乙肝表面抗原、e抗原和核心抗体阳性（大三阳），癌胚抗原（CEA）值为10.9 ng/ml （正常参考值为0～5 ng/ml）。MRI检查：肝S8段2.5 cm×1.8 cm结节，边界清楚。T2WI呈稍高信号（图1）；T1WI呈低信号（图2）；DWI可见扩散受限（图3）；动态增强扫描动脉早期强化较明显，静脉期强化程度稍减低，但始终高于周围肝实质，病灶中央可见小索条状、斑点状低强化区（图4）。手术所见：肿物位于S8段，边界清楚，行肝S8段肿物切除术。术后病理：组织中可见大量淋巴细胞、浆细胞浸润，异型大细胞条呈索状或片巢状生长，核空泡状，核分裂象易见（图5）。免疫组织化学：Ki6740%阳性（+），白细胞共同抗原（LCA）、CD3、CD20、CA153、CD110灶性、CD34血管、CK19部分阳性（+），肝细胞特异性抗原（Hepatocyte）、甲胎蛋白（AFP）、EB病毒原位杂交（EBers）阴性。病理诊断：淋巴上皮瘤样癌（lymphoepithelioma-like carcinoma，LELC），周围肝组织汇管区少许淋巴细胞浸润。

目的 利用肝特异性对比剂探讨肝功能的解剖分布规律.方法 分析2012年7月～2014年6月期间行肝脏EOB-CE-MRI的47例患者影像学及临床资料,按照Child-Pugh分级(CPS)分为:正常组19例,CPS A级组15例,CPS B级组13例.采用肝脏相对强化率(LLRE)的方法进行测量,比较三组肝中央区与周围区、左叶与右叶、右前段与右后段、S2段与S3段EOB-CE-MRI平扫、肝细胞期肝实质信号以及肝细胞期肝实质相对强化率的差异.结果 运用LLRE方法三组患者肝中央区与周围区间差异有统计学意义(P＜0.001),左叶与右叶间、右前段与右后段、S2段与S3段不存在统计学差异(P＞0.05).全肝平均信号均值平扫各组间无差异,增强之后各组间存在显著性差异,P值均小于0.05.结论 肝中央区肝功能储备高于周围区,左右叶及S2、S3段之间肝功能差异不明显,全肝平均相对强化率各组之间显著不同.