Radiomics analysis from magnetic resonance imaging in predicting the grade of nonfunctioning pancreatic neuroendocrine tumors: a multicenter study.

OBJECTIVES: To explore the potential of radiomics features to predict the histologic grade of nonfunctioning pancreatic neuroendocrine tumor (NF-PNET) patients using non-contrast sequence based on MRI. METHODS: Two hundred twenty-eight patients with NF-PNETs undergoing MRI at 5 centers were retrospectively analyzed. Data from center 1 (n = 115) constituted the training cohort, and data from centers 2-5 (n = 113) constituted the testing cohort. Radiomics features were extracted from T2-weighted images and the apparent diffusion coefficient. The least absolute shrinkage and selection operator was applied to select the most important features and to develop radiomics signatures. The area under receiver operating characteristic curve (AUC) was performed to assess models. RESULTS: Tumor boundary, enhancement homogeneity, and vascular invasion were used to construct the radiological model to stratify NF-PNET patients into grade 1 and 2/3 groups, which yielded AUC of 0.884 and 0.684 in the training and testing groups. A radiomics model including 4 features was constructed, with an AUC of 0.941 and 0.871 in the training and testing cohorts. The fusion model combining the radiomics signature and radiological characteristics showed good performance in the training set (AUC = 0.956) and in the testing set (AUC = 0.864), respectively. CONCLUSION: The developed model that integrates radiomics features with radiological characteristics could be used as a non-invasive, dependable, and accurate tool for the preoperative prediction of grade in NF-PNETs. CLINICAL RELEVANCE STATEMENT: Our study revealed that the fusion model based on a non-contrast MR sequence can be used to predict the histologic grade before operation. The radiomics model may be a new and effective biological marker in NF-PNETs. KEY POINTS: The diagnostic performance of the radiomics model and fusion model was better than that of the model based on clinical information and radiological features in predicting grade 1 and 2/3 of nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs). Good performance of the model in the four external testing cohorts indicated that the radiomics model and fusion model for predicting the grades of NF-PNETs were robust and reliable, indicating the two models could be used in the clinical setting and facilitate the surgeons' decision on risk stratification. The radiomics features were selected from non-contrast T2-weighted images (T2WI) and diffusion-weighted imaging (DWI) sequence, which means that the administration of contrast agent was not needed in grading the NF-PNETs.

Prediction of Therapeutic Effect to Treatment in Patients with Colorectal Liver Metastases Using Functional Magnetic Resonance Imaging and RECIST Criteria: A Pilot Study in Comparison between Bevacizumab-Containing Chemotherapy and Standard Chemotherapy.

BACKGROUND: Response Evaluation Criteria in Solid Tumors (RECIST) criteria are widely used for evaluating the therapeutic effect of colorectal liver metastases (CRLM) patients, but showed undesirable accuracy. OBJECTIVE: This study aimed to evaluate the value of functional MRI compared with RECIST criteria in predicting the therapeutic effect in CRLM patients receiving neoadjuvant chemotherapy with and without bevacizumab. METHODS: Overall, 137 patients with CRLM who received neoadjuvant chemotherapy followed by hepatic resection between January 2013 and November 2018 were included and were divided into the bevacizumab and non-bevacizumab groups. Apparent diffusion coefficient (ADC) values of pre- and post-treatment diffusion-weighted imaging (DWI) were generated on the whole-volume (ADCmean), periphery (ADCperi), and isocenter (ADCcentral) of the tumor at the maximum slice. Overall survival (OS) and relapse-free survival (RFS) were used as prognostic indicators. RESULTS: Post-treatment ADCmean was significantly associated with OS (p = 0.001) and RFS (p = 0.008) in the bevacizumab group, while RECIST-defined response was found to be only significantly associated with RFS in the non-bevacizumab group (p = 0.042). When categorizing the bevacizumab group by the post-treatment ADCmean cut-off value of 1.15 ×10-3 mm2/s, patients in the ADC response group showed significantly better OS than the non-response group (3-year OS: 91.5% vs. 64.5%, p = 0.001). However, no significant difference was found between RECIST-defined response and non-response in either OS (3-year OS: 60.2% vs. 44.0%, p = 0.104) or RFS (3-year RFS: 26.2% vs. 17.4%, p = 0.129) in the bevacizumab group. CONCLUSIONS: DWI-related parameters such as post-treatment ADCmean could accurately reflect the therapeutic effectiveness and predicting survival in patients treated with bevacizumab, which is superior to the RECIST criteria.

Correlation Between the Distance to Mesorectal Fascia and Prognosis of cT3 Rectal Cancer: Results of a Multicenter Study From China.

BACKGROUND: The cT3 substage criteria based on extramural depth of tumor invasion in rectal cancer have several limitations. OBJECTIVE: This study proposed that the distance between the deepest tumor invasion and mesorectal fascia on pretherapy MRI can distinguish the prognosis of patients with cT3 rectal cancer. DESIGN: This is a cohort study. SETTING: This study included a prospective, single-center, observational cohort and a retrospective, multicenter, independent validation cohort. PATIENT: Patients who had cT3 rectal cancer with negative mesorectal fascia undergoing neoadjuvant chemoradiotherapy followed by radical surgery were included in 4 centers in China from January 2013 to September 2014. INTERVENTION: Baseline MRI with the distance between the deepest tumor invasion and mesorectal fascia, extramural depth of tumor invasion, and mesorectum thickness were measured. MAIN OUTCOME MEASURES: The cutoff of the distance between the deepest tumor invasion and mesorectal fascia was determined by time-dependent receiver operating characteristic curves, supported by a 5-year progression rate from the prospective cohort, and was then validated in a retrospective cohort. RESULTS: There were 124 and 274 patients included in the prospective and independent validation cohorts. The distance between the deepest tumor invasion and mesorectal fascia was the only predictor for cancer-specific death (HR, 0.1; 95% CI, 0.0-0.7) and was also a significant predictor for distant recurrence (HR, 0.4; 95% CI, 0.2-0.9). No statistically significant difference was observed in prognosis between patients classified as T3a/b and T3c/d. LIMITATIONS: The sample size is relatively small, and the study focused on cT3 rectal cancers with a negative mesorectal fascia. CONCLUSIONS: A cutoff of 7 mm of the distance between the deepest tumor invasion and mesorectal fascia on baseline MRI can distinguish cT3 rectal cancer from a different prognosis. We recommend using the distance between the deepest tumor invasion and mesorectal fascia on baseline MRI for local and systemic risk assessment and providing a tailored schedule of neoadjuvant treatment. See Video Abstract at http://links.lww.com/DCR/B682.CORRELACIÓN ENTRE LA DISTANCIA DE LA FASCIA MESORRECTAL Y EL PRONÓSTICO DEL CÁNCER DE RECTO cT3: RESULTADOS DE UN ESTUDIO MULTICÉNTRICO DE CHINAANTECEDENTES:Los criterios de subestadificación cT3 basados en la profundidad extramural de invasión tumoral en el cáncer de recto tienen varias limitaciones.OBJETIVO:Este estudio propuso que la distancia entre la invasión tumoral más profunda y la fascia mesorrectal en la resonancia magnética preterapia puede distinguir el pronóstico de los pacientes con cT3.DISEÑO:Estudio de cohorte.ENTORNO CLINICO:El estudio incluyó una cohorte observacional, prospectiva, unicéntrica, y una cohorte de validación retrospectiva, multicéntrica e independiente.PACIENTE:Se incluyeron pacientes con cáncer de recto cT3 con fascia mesorrectal negativa sometidos a quimio-radioterapia neoadyuvante seguida de cirugía radical en cuatro centros de China desde enero de 2013 hasta septiembre de 2014.INTERVENCIÓN:Imágenes de resonancia magnética de referencia fueron medidas con la distancia entre la invasión tumoral más profunda y la fascia mesorrectal; la profundidad extramural de la invasión tumoral y el grosor del mesorrecto.PRINCIPALES MEDIDAS DE VALORACION:El límite de la distancia entre la invasión tumoral más profunda y la fascia mesorrectal se determinó mediante curvas características operativas del receptor dependientes del tiempo y se apoyó en la tasa de progresión a 5 años de la cohorte prospectiva, y luego se validó en una cohorte retrospectiva.RESULTADOS:Se incluyeron 124 y 274 pacientes en la cohorte de validación prospectiva e independiente, respectivamente. La distancia entre la invasión tumoral más profunda de la fascia mesorrectal fue el único predictor de muerte específica por cáncer (Hazard ratio: 0.1, 95% CI, 0,0-0,7); y también fue un predictor significativo de recurrencia distante Hazard ratio: 0,4, 95% CI, 0,2-0,9). No se observaron diferencias estadísticamente significativas en el pronóstico entre los pacientes clasificados como T3a/b y T3c/d.LIMITACIONES:El tamaño de la muestra es relativamente pequeño y el estudio se centró en los cánceres de recto cT3 con fascia mesorrectal negativa.CONCLUSIONES:Un límite de 7 mm de distancia entre la invasión tumoral más profunda y la fascia mesorrectal en la resonancia magnética de referencia puede distinguir el cáncer de recto cT3 de diferentes pronósticos. Recomendamos la distancia entre la invasión tumoral más profunda y la fascia mesorrectal en la resonancia magnética de referencia para la evaluación del riesgo local y sistémico, proporcionando un programa personalizado de tratamiento neoadyuvante. Consulte Video Resumen en http://links.lww.com/DCR/B682. (Traducción- Dr. Francisco M. Abarca-Rendon).

Metal-Organic-Framework-Derived Atomically Dispersed Mn-N-C Electrocatalysts Boosting Oxygen Reduction Modulated by Anion Exchange of Permanganate.

Mn-N-C materials have received increasing interest in recent years because of their low Fenton reactivity and ORR activity comparable to those of their Fe-N-C and Co-N-C counterparts. In this contribution, an atomically dispersed Mn-N-C electrocatalyst with a prominent oxygen reduction performance was constructed by employing a cationic Cd-MOF as a precursor that can facilely and accurately introduce MnO4- anions through anion exchange. The best-performing Mn-N-C catalyst displays a 0.96 V (vs RHE) Eonset (onset potential) and a 0.87 V (vs RHE) E1/2 (half-wave potential) in an alkaline solution, which exceed those of the benchmark Pt/C catalyst. In particular, the maximal power density of the self-made zinc-air battery reaches 200 mW·cm-2, surpassing that of most reported Mn-N-C materials.

Perioperative second-line chemotherapy is beneficial for resectable liver metastases that occur during or early after adjuvant chemotherapy for colorectal cancer.

BACKGROUND: The prognosis of patients with liver metastases during or early after adjuvant chemotherapy for colorectal cancer (CRC) is significantly worse. This study aimed to explore the efficacy of perioperative second-line chemotherapy in prolonging survival in those patients. METHODS: Patients who underwent liver resection, with resectable liver metastases that occurred within 12 months after the last cycle of adjuvant chemotherapy for CRC, from January 2006 to December 2019, were included. The long-term outcome of overall survival (OS) and progression-free survival (PFS) between different groups was analyzed. RESULTS: A total of 200 patients were included, of whom 112 underwent direct hepatectomy and 88 received upfront second-line chemotherapy. OS and PFS were significantly better in patients receiving upfront second-line chemotherapy than direct surgery (PFS, P = 0.016; OS, P = 0.013). Further analysis showed that perioperative second-line chemotherapy could provide a greater survival benefit, which was also confirmed by propensity score matching (OS: P = 0.03; PFS: P = 0.04). Multivariate analysis determined that perioperative second-line chemotherapy was an independent factor influencing OS (OR [95% CI]: 0.468 [0.294-0.744], P = 0.001) and PFS (OR [95% CI]: 0.517 [0.353-0.758], P = 0.001). DISCUSSION: Perioperative second-line chemotherapy could improve the survival of patients who underwent hepatectomy, with resectable liver metastases that occurred during or early after adjuvant chemotherapy for CRC.

MRI measurements predict major low anterior resection syndrome in rectal cancer patients.

PURPOSE: Current low anterior resection syndrome (LARS) score is lagging behind and only based on clinical symptoms patient described. Preoperative imaging indicators which can be used to predict LARS is unknown. We proposed preoperative MRI parameters for identifying major LARS. METHODS: Patients receiving curative restorative anterior resection from Sept. 2007 to Sept. 2015 were collected to complete LARS score (median 75.7 months since surgery). MRI measurements associated with LARS were tested, and a multivariate logistic model was conducted for predicting LARS. Receiver operating characteristic curve was used to evaluate the model. RESULTS: Two hundred fifty-five patients undergoing neoadjuvant chemoradiotherapy and 72 patients undergoing direct surgery were enrolled. The incidence of major LARS in NCRT group was significantly higher (53.3% vs.34.7%, P = 0.005). In patients with neoadjuvant chemoradiotherapy, the thickness of ARJ (TARJ), the distance between the tumor's lower edge and anal rectal joint (DTA), and sex were independent factors for predicting major LARS; ORs were 0.382 (95% CI, 0.198-0.740), 0.653 (95% CI, 0.565-0.756), and 0.935 (95% CI, 0.915-0.955). The AUC of the multivariable model was 0.842 (95% CI, 0.794-0.890). In patients with direct surgery, only DTA was the independent factor for predicting major LARS; OR was 0.958 (95% CI, 0.930-0.988). The AUC was 0.777 (95% CI: 0.630-0.925). CONCLUSIONS: Baseline MRI measurements have the potential to predict major LARS in rectal cancer, which will benefit the decision-making and improve patients' life quality.

Deep learning-assisted magnetic resonance imaging prediction of tumor response to chemotherapy in patients with colorectal liver metastases.

Accurate evaluation of tumor response to preoperative chemotherapy is crucial for assigning appropriate patients with colorectal liver metastases (CRLM) to surgery or conservative therapy. However, there is no well-recognized method for predicting pathological response before surgery. Our study constructed and validated a deep learning algorithm using prechemotherapy and postchemotherapy magnetic resonance imaging (MRI) to predict pathological response in CRLM. CRLM patients from center one who had ≤5 lesions and were scheduled to receive preoperative chemotherapy followed by liver resection between January 2013 and November 2016, were included prospectively and chronologically divided into a training cohort (80% of patients) and a testing cohort (20% of patients). Patients from center two were included January 2017 and December 2018 as an external validation cohort. MRI-based models were constructed to discriminate according to pathology tumor regression grade (TRG) between the response (TRG1/2) and nonresponse (TRG3/4/5) groups at the lesion level. From center one, 155 patients (328 lesions) were included; chronologically, 101 (264 lesions) in the training cohort and 54 (64 lesions) in the testing cohort. The model achieved better accuracy (0.875 vs 0.578) and AUC (0.849 vs 0.615) than RECIST for discriminating response; it also distinguished the survival outcomes after hepatectomy better than the RECIST criteria. Evaluations of the external validation cohort (25 patients, 61 lesions) also showed good ability with an AUC of 0.833. In conclusion, the MRI-based deep learning model provided accurate prediction of pathological tumor response to preoperative chemotherapy in patients with CRLM and may inform individualized treatment.

The different response of cardiomyocytes and cardiac fibroblasts to mitochondria inhibition and the underlying role of STAT3.

Cardiomyocyte loss and cardiac fibrosis are the main characteristics of cardiac ischemia and heart failure, and mitochondrial function of cardiomyocytes is impaired in cardiac ischemia and heart failure, so the aim of this study is to identify fate variability of cardiomyocytes and cardiac fibroblasts with mitochondria inhibition and explore the underlying mechanism. The mitochondrial respiratory function was measured by using Oxygraph-2k high-resolution respirometry. The STAT3 expression and activity were evaluated by western blot. Cardiomyocytes and cardiac fibroblasts displayed different morphology. The mitochondrial respiratory function and the expressions of mitochondrial complex I, II, III, IV, and V of cardiac fibroblasts were lower than that of cardiomyocytes. Mitochondrial respiratory complex I inhibitor rotenone and H2O2 (100 µM, 4 h) treatment induced cell death of cardiomyocyte but not cardiac fibroblasts. The function of complex I/II was impaired in cardiomycytes but not cardiac fibroblasts stimulated with H2O2 (100 µM, 4 h) and in ischemic heart of mice. Rotenone and H2O2 (100 µM, 4 h) treatment reduced STAT3 expression and activity in cardiomyocytes but not cardiac fibroblasts. Inhibition of STAT3 impaired mitochondrial respiratory capacity and exacerbated H2O2-induced cell injury in cardiomycytes but not significantly in cardiac fibroblasts. In conclusion, the different susceptibility of cardiomyocytes and cardiac fibroblasts to mitochondria inhibition determines the cell fate under the same pathological stimuli and in which STAT3 plays a critical role.

Assessment of pathological complete response to preoperative chemoradiotherapy by means of multiple mathematical models of diffusion-weighted MRI in locally advanced rectal cancer: A prospective single-center study.

PURPOSE: To assess stretched-exponential, mono-exponential and intravoxel incoherent motion (IVIM) models of diffusion-weighted MRI(DWI) in predicting pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in rectal cancer patients. MATERIALS AND METHODS: This prospective study recruited 98 consecutive patients with locally advanced rectal cancer who underwent 3 Tesla MR examination before, during and after CRT. The apparent diffusion coefficient (ADC), IVIM-derived parameters (D, f, and D*), and stretched-exponential model-derived parameters (DDC and α) were measured. The parameters and their corresponding changes during and after CRT were compared between pCR and non-pCR. Receiver-operating characteristic curve analysis was performed to evaluate the diagnostic performance. Coefficient of variations and intraclass correlation coefficient were calculated to assess reliability and agreement. RESULTS: Nineteen patients achieved pCR while 79 did not. The pCR group had higher ADC and α (ADC2 and α2 ), and their changes (ΔADC2 , and Δα2 ) at the endpoint than non-pCR group. α2 and ADC2 yielded similar AUCs (P = 0.339), Δα2 and ΔADC2 yielded similar AUCs (P = 0.263) ADC and α presented substantial agreement, and α presented the minimum CV (5.0-7.0%). CONCLUSION: ADC and α were useful for assessing pCR after CRT. α might be more useful because it demonstrated better diagnostic performance than IVIM-derived parameters and better reliability than ADC. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:175-183.

Anodic Oxidation of Methanol to Formaldehyde Synergizing with a Br-/Br2 Redox-Mediated Chemical Route to Produce Methyl Formate.

Methyl formate (MF) is one of the most important chemical commodities, which has a wide range of applications. Due to environmental friendliness, mild reaction conditions, and easy operations, electrosynthesis of MF has garnered increasing attention in recent years. In this work, we reported an electrosynthesis route toward MF in a halide-containing methanol solution. The thorough mechanistic investigations point out that electrosynthesis of MF is accomplished by instant reaction between aldehyde from anodic methanol oxidation, and methoxy bromide (CH3OBr) that is in-situ generated by reaction of Br2 from anodic oxidation of Br- with methoxide (CH3O-) from cathodic reduction of methanol. This method features high atomic economy only producing valuable MF and hydrogen gas, and shows distinct advantages compared to the reported MF electrosynthesis methods. Even at 200 mA/cm2, the faradaic efficiency (FE) of MF remains consistently around 60 % at the anode while a 100 % FE hydrogen gas is produced at the cathode.

Synergistic effects of CuS/TiO2 heterointerfaces: Enhanced cathodic CO2 reduction and anodic CH3OH oxidation for paired electrosynthesis of formate.

The electrochemical reduction of carbon dioxide into energy-carrying compounds or value-added chemicals is of great significance for diminishing the greenhouse effect. However, it is still imperative to replace the less-value anodic oxygen evolution reaction (OER) to improve the technical economy. Herein, we firstly reported a bifunctional CuS/TiO2 catalyst for both anodic methanol oxidation reaction (MOR) and cathodic carbon dioxide reduction (CO2R). The in-built abundant CuS/TiO2 heterointerfaces are found to boost the CO2R and MOR to produce formate. Based on the unique bifunctionality of CuS/TiO2, a paired electrosynthesis of formate was performed with a total Faradaic efficiency (FE) of about 170 %, in which the cathodic CO2R achieved a formate FE of about 70 %, and the anodic MOR exhibited an almost 100 % formate FE.

Value of multiple models of diffusion-weighted imaging to predict hepatic lymph node metastases in colorectal liver metastases patients.

BACKGROUND: About 10%-31% of colorectal liver metastases (CRLM) patients would concomitantly show hepatic lymph node metastases (LNM), which was considered as sign of poor biological behavior and a relative contraindication for liver resection. Up to now, there's still lack of reliable preoperative methods to assess the status of hepatic lymph nodes in patients with CRLM, except for pathology examination of lymph node after resection. AIM: To compare the ability of mono-exponential, bi-exponential, and stretched-exponential diffusion-weighted imaging (DWI) models in distinguishing between benign and malignant hepatic lymph nodes in patients with CRLM who received neoadjuvant chemotherapy prior to surgery. METHODS: In this retrospective study, 97 CRLM patients with pathologically confirmed hepatic lymph node status underwent magnetic resonance imaging, including DWI with ten b values before and after chemotherapy. Various parameters, such as the apparent diffusion coefficient from the mono-exponential model, and the true diffusion coefficient, the pseudo-diffusion coefficient, and the perfusion fraction derived from the intravoxel incoherent motion model, along with distributed diffusion coefficient (DDC) and α from the stretched-exponential model (SEM), were measured. The parameters before and after chemotherapy were compared between positive and negative hepatic lymph node groups. A nomogram was constructed to predict the hepatic lymph node status. The reliability and agreement of the measurements were assessed using the coefficient of variation and intraclass correlation coefficient. RESULTS: Multivariate analysis revealed that the pre-treatment DDC value and the short diameter of the largest lymph node after treatment were independent predictors of metastatic hepatic lymph nodes. A nomogram combining these two factors demonstrated excellent performance in distinguishing between benign and malignant lymph nodes in CRLM patients, with an area under the curve of 0.873. Furthermore, parameters from SEM showed substantial repeatability. CONCLUSION: The developed nomogram, incorporating the pre-treatment DDC and the short axis of the largest lymph node, can be used to predict the presence of hepatic LNM in CRLM patients undergoing chemotherapy before surgery. This nomogram was proven to be more valuable, exhibiting superior diagnostic performance compared to quantitative parameters derived from multiple b values of DWI. The nomogram can serve as a preoperative assessment tool for determining the status of hepatic lymph nodes and aiding in the decision-making process for surgical treatment in CRLM patients.

The differential diagnosis of lung precursor glandular lesions, micro-invasive adenocarcinoma, and invasive adenocarcinoma using low dose spectral computed tomography perfusion imaging.

Background: Few studies about the association between computed tomography (CT) perfusion imaging parameters and invasiveness in lung adenocarcinoma (LUAD) have been conducted using low dose spectral CT perfusion imaging. The purpose of this study was to investigate application of spectral revolution CT low-dose perfusion imaging in the differential diagnosis of different pathological subtypes of LUAD. Methods: This was a cross-sectional study based on historical data from January 2018 to May 2019 in Peking University Cancer Hospital & Institute. A total of 62 cases were enrolled, including 2 cases of atypical adenomatous hyperplasia (AAH), 3 cases of adenocarcinoma in situ (AIS), 4 cases of minimally invasive adenocarcinoma (MIA), and 53 cases of invasive adenocarcinoma (IAC), all confirmed with pathology. The inclusion and exclusion criteria were regulated. Using Revolution low-dose CT perfusion imaging (GE, USA), the CT perfusion parameters of hemodynamics were obtained: blood flow (BF), blood volume (BV), impulse residue function time of arrival (IRF TO), maximum slope of increase (MSI), mean transit time (MTT), permeability surface area product (PS), positive enhancement integral (PEI), and maximum enhancement time (Tmax). Univariate analysis of variance (ANOVA) or Kruskal-Wallis test was used to compare the differences of CT perfusion quantitative parameters among AAH, AIS, MIA, and IAC. Mann-Whitney test was used to compare the difference of CT perfusion imaging parameters between preinvasive lesions (AAH and AIS) and invasive lung cancer (MIA and IAC). Results: Statistically significant differences in IRF TO were observed in LUAD with different invasiveness, namely, among AIS, MIA, and IAC groups (0.56±0.74 vs. 0.54±1.08 vs. 4.39±2.19, P=0.004). Statistically significant differences in IRF TO were also observed between pre-invasive lesions group (AAH and AIS) and invasive lung cancer group (MIA and IAC) (1.12±1.27 vs. 3.75±2.79, P=0.031), and between AAH + AIS + MIA groups and IAC group (0.83±1.13 vs. 4.12±2.69, P<0.001). There were no statistically significant differences in other CT perfusion parameters of hemodynamics among different pathological subtypes of LUAD (P>0.05). Conclusions: The low-dose perfusion parameter IRF TO of revolution CT has the potential to be employed in the differential diagnosis of different pathological subtypes of LUAD.

Responsive regularity of neurons in the hindlimb region of primary somatosensory cortex to different temperature thermal needle stimulation of "Zusanli"(ST36) in mice. / å°é¼ åˆçº§ä½“æ„Ÿçš®å±‚åŽè‚¢åŒºç¥žç»å ƒå¯¹"足三里"不同温度热刺激的响应规律.

OBJECTIVES: To study the regularity of central response to thermal needle stimulation of "Zusanli" (ST36) at different temperature, and to analyze the temperature difference of central responses. METHODS: Six male C57BL/6j adult mice were used in the present study. For observing activities of neurons in the hindlimb region of left primary somatosensory cortex (S1HL, A/P=0.46 mm, M/L=1.32 mm, D/V=-0.14 mm) by using a fast high-resolution miniature two-photon microscopy (FHIRM-TPM), the mice were anesthetized with 3% isoflurane (inhalation), with its head fixed in a stereotaxic apparatus, then, adeno-associated virus (AAV-hSyn-GCaMP6f-WPRE-hGHpA, for showing intracellular calcium transients in neurons transfected) was injected into the left S1HL region using a micro-syringe after scalp surgical operation. The mice's right ST36 were stimulated using internal thermal needles with the temperature being 43 ℃, or 45 ℃, or 47 ℃, separately. Image J software and MATLAB 2020b software were used to process the image data of neuronal calcium activity (Ca2+ signaling) in the left S1HL region, including the instant maximum calcium peak value (ΔF/F) in 2 s, instant calcium spike frequency in 2 s, short-term calcium peak value (ΔF/F) in 3.5 min, short-term calcium spike frequency in 3.5 min, calcium peak duration in 3.5 min, maximum calcium peak value (ΔF/F) at the 1st , 2nd and 3rd min, and calcium spike frequency at the 1st, 2nd and 3rd min after thermal needle stimulation. RESULTS: In comparison with the normal temperature needle stimulation, the instant intracellular maximum calcium peak value, instant calcium spike frequency, short-term maximum calcium peak value, short-term calcium spike frequency, and calcium peak duration of S1HL neurons in response to 43 ℃, 45 ℃ and 47 ℃ internal thermal needle stimulation of ST36 were significantly increased (P<0.001, P<0.01). Comparison among the 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation showed that the 45 ℃ thermal needle stimulation was obviously superior to 43 ℃ and 47 ℃ thermal needle stimulation in increasing instant calcium spike frequency, short-term calcium spike frequency and calcium peak duration of S1HL neurons (P<0.001, P<0.01). The 47 ℃ thermal needle stimulation was stronger than 43 ℃ and 45 ℃ thermal needle stimulation in increasing the instant maximum calcium peak value (P<0.001). The maximum calcium peak value was apparently higher (P<0.001) at the 2nd min than that at the 1st and 3rd min after 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation. No significant differences were found in the short-term maximum calcium peak value among the 3 thermal needle stimulation and in the calcium spike frequency among the 3 time points after 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation. CONCLUSIONS: S1HL neurons respond to all 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation of ST36 in mice, while more actively to 45 ℃ thermal needle stimulation.

Silencing of mutant p53 by siRNA induces cell cycle arrest and apoptosis in human bladder cancer cells.

BACKGROUND: p53 is the most frequently mutated tumor-suppressor gene in human cancers. It has been reported that mutations in p53 result not only in the loss of its ability as a tumor suppressor, but also in the gain of novel cancer-related functions that contribute to oncogenesis. The present study evaluated the potential of silencing of mutant p53 by small interfering RNA in the treatment of bladder cancer cells in vitro. METHODS: We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess cell viability and flow cytometry to detect cell cycle alterations and apoptosis. The related molecular mechanisms were assessed by western blotting. We also used the MTT assay and flow cytometry to investigate if silencing of mutant p53 by knockdown with small interfering (si)RNA would change the sensitivity to cisplatin treatment. RESULTS: Using 5637 and T24 human bladder cancer cell lines characterized by mutations in p53, we found that silencing of the mutant p53 by RNA interference induced evident inhibition of cell proliferation and viability, which was related to the induction of G2 phase cell cycle arrest and apoptosis. Moreover, our study also showed that the p53-targeting siRNA cooperated with cisplatin in the inhibition of bladder cancer cells. CONCLUSIONS: These findings suggest that RNA interference targeting mutant p53 may be a promising therapeutic strategy for the treatment of bladder cancer.

Zn(II)-MOF derived N-doped carbons achieve marked ORR activity in alkaline and acidic media.

A highly efficient metal-free N-doped carbon electrocatalyst toward oxygen reduction was obtained by one-pot pyrolysis of a single Zn(II)-MOF with mixed azolate and terephthalate ligands, demonstrating E1/2 of 0.88 V (vs. RHE) in 0.1 M KOH, and 0.79 V (vs. RHE) in 0.5 M H2SO4. It represents one of the best metal-free N-doped carbon electrocatalysts for the acidic ORR.

Comparison of the diagnostic performance and clinical role of different ultrasound-based thyroid malignancy risk stratification systems for medullary thyroid carcinoma.

Background: This study sought to investigate the applicability of different ultrasound (US) thyroid risk stratification systems in diagnosing medullary thyroid carcinoma (MTC) and determining the need for biopsy. Methods: In total, 34 MTC nodules, 54 papillary thyroid carcinoma (PTC) nodules, and 62 benign thyroid nodules were examined in this study. All the diagnoses were histopathologically confirmed postoperatively. All the thyroid nodule sonographic features were recorded and categorized by 2 independent reviewers according to the Thyroid Imaging Reporting and Data System (TIRADS) of the American College of Radiology (ACR), the American Thyroid Association (ATA) guidelines, the European Thyroid Association (EU) TIRADS, the Kwak-TIRADS, and the Chinese TIRADS (C-TIRADS). The sonographic differences and risk stratifications of the MTCs, PTCs, and benign thyroid nodules were analyzed. The diagnostic performance and recommended biopsy rates for each classification system were evaluated. Results: The risk stratifications of MTCs were all higher than the benign thyroid nodules (P<0.01) and lower than PTCs (P<0.01) with each classification system. Hypoechogenicity and malignant marginal features were independent risk factors for identifying malignant thyroid nodules, and the area under the receiver operating characteristic curve (AUC) for identifying MTCs was lower than that for identifying PTCs (0.873 vs. 0.954, respectively). The AUCs, sensitivity, specificity, positive predictive values, negative predictive values, and accuracy values of the 5 systems for MTC were all lower than those for PTC. The best cut-off values for diagnosing MTC were TIRADS (TR) 4 in the ACR-TIRADS, intermediate suspicion in the ATA guidelines, TR 4 in EU-TIRADS, and TR 4b in both the Kwak-TIRADS and the C-TIRADS. The Kwak-TIRADS had the highest recommended biopsy rate for MTCs (97.1%), followed by the ATA guidelines, the EU-TIRADS (88.2%), the C-TIRADS (85.3%), and the ACR-TIRADS (79.4%). Conclusions: The US-based thyroid malignancy risk stratification systems analyzed in this study were able to satisfactorily identify MTC and recommend biopsy, but the diagnostic performance of these systems for MTC was not as good as that for PTC.

[Moxibustion of 45 ℃ at "Zusanli" (ST36) improves vascular endothelial oxidative stress in hyperlipidemia rats].

OBJECTIVE: To explore the antioxidant effect of moxibustion on vascular endothelial function and the under-lying mechanism. METHODS: Forty male SD rats were randomly divided into blank, model, moxibustion and endothelial nitric oxide synthase (eNOS) inhibitor groups, with 10 rats in each group. Hyperlipidemia rat model was established by high fat diet for 8 weeks. Rats in the moxibustion group received 45 ℃ moxibustion at "Zusanli" (ST36) for 10 min once daily for consecutive 4 weeks. Rats in the eNOS inhibitor group received intraperitoneal injection of eNOS inhibitor L-NAME (1 mg/100 g) at the same time of moxibustion intervention. The morphology of abdominal aorta endothelium was observed by HE staining. Lipid deposition in abdominal aorta was observed by oil red O staining. The contents of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) in serum and reactive oxygen species (ROS), nitric oxide (NO), superoxide dismutase (SOD), oxidized LDL lipoprotein (ox-LDL), endothelin-1 (ET-1), eNOS, malondialdehyde (MDA) in serum and abdominal aorta were determined by ELISA. The expression of eNOS in abdominal aorta was detected by immunofluorescence. RESULTS: HE staining of the abdominal aorta showed no significant pathological abnormality in the blank group; the endovascular cortex was rough, and the inner, media and outer membrane were rough in the model group; the nucleus and surrounding tissue structure were clear and the vascular wall was smooth in the moxibustion group; abdominal aorta texture was rough in the eNOS inhibitor group. Compared with the blank group, the area of oil red O staining in abdominal aorta increased (P<0.05); the contents of serum TC, TG and LDL-C increased (P<0.01, P<0.05) while HDL-C decreased (P<0.05); the contents of ET-1 in serum and abdominal aorta were increased (P<0.01, P<0.05) while the contents of NO and eNOS were decreased (P<0.05, P<0.001); the contents of ROS, ox-LDL and MDA in serum and abdominal aorta were increased (P<0.001, P<0.01, P<0.000 1) while the content of SOD in abdominal aorta was decreased (P<0.000 1); the expression level of eNOS in abdominal aorta was decreased (P<0.05) in the model group. Compared with the model group, the area of oil red O staining in abdominal aorta decreased (P<0.05); the contents of TC, TG and LDL-C in serum decreased (P<0.05) while HDL-C increased (P<0.05); the contents of ET-1 in serum and abdominal aorta were decreased (P<0.01, P<0.05) while the contents of NO and eNOS in abdominal aorta were increased (P<0.001, P<0.01); the contents of ROS and MDA in serum and abdominal aorta were decreased (P<0.001, P<0.01, P<0.05), the content of ox-LDL was decreased (P<0.01) and the content of SOD was increased (P<0.000 1) in abdominal aorta; the expression level of eNOS in abdominal aorta was increased (P<0.05) in the moxibustion group. Compared with the moxibustion group, the contents of serum TC, LDL-C and MDA in the eNOS inhibitor group were increased (P<0.05); the contents of ET-1, ROS, ox-LDL and MDA in abdominal aorta were increased (P<0.05), the contents of NO, eNOS and SOD were decreased (P<0.05); the expression level of eNOS in abdominal aorta was decreased (P<0.05). CONCLUSION: 45 ℃ moxibustion at ST36 can protect and repair vascular endothelial injury in abdominal aorta of hyperlipidemia rats and improve the oxidative stress of vascular endothelium.

[Effect of mild moxibustion at 45 ℃ with different durations at "Zusanli" （ST36） on the inflammatory factors in the abdominal aorta of hyperlipidemia rats].

OBJECTIVE: To investigate the effects of mild moxibustion at 45°C on the chronic inflammatory response of the abdominal aorta in rats with hyperlipidemia and the effects of different moxibustion durations. METHODS: Thirty-six SD rats were randomly divided into the following groups： blank control group (2 weeks), model group (2 weeks), moxibustion group (2 weeks), blank group (4 weeks), model group (4 weeks), and moxibustion group (4 weeks). A model of hyperlipidemia with chronic inflammation was established through high-fat diet feeding for 8 weeks. Rats in the moxibustion groups received mild moxibustion treatment at bilateral "Zusanli"(ST36) at 45 °C, 10 min every time, once a day, for consecutive 2 or 4 weeks. The morphology of the abdominal aorta in each group was observed by using HE staining. Contents of serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), oxidized low-density lipoprotein (ox-LDL), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), endothelin-1 (ET-1) and the contents of nitric oxide (NO), ox-LDL, and ET-1 in the abdominal aorta were measured by using ELISA. Protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta of rats in each group were detected by using Western blot and real-time fluorescence quantitative PCR respectively. The positive expression of IL-6 in the abdominal aorta of rats was detected by Immunofluorescence. RESULTS: Compared to the blank control group, rats in the model group had increased contents of LDL, TC, TG, ox-LDL, VCAM-1, ICAM-1, IL-6, TNF-α, and ET-1 in the serum, increased contents of ox-LDL and ET-1 in the abdominal aorta, increased protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta(P<0.01, P<0.05, P<0.001), with decreased HDL content in the serum, decreased NO content in the abdominal aorta (P<0.01, P<0.05), as well as dark pink abdominal aorta, rough textures in the adventitia, media, and intima, and rough endothelial layer. Compared to the model group(2 weeks), LDL, ICAM-1, ET-1 contents in the serum, ox-LDL content in the abdominal aorta were decreased(P<0.05), while serum IL-6 and TNF-α contents, and NO content in the abdominal aorta were significantly increased(P<0.01, P<0.05), with smoother vascular walls, and relatively clear nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(2 weeks). Compared to the model group(4 weeks), contents of LDL, TC, TG, VCAM-1, ICAM-1, IL-6, TNF-α, ox-LDL, and ET-1 in the serum, ox-LDL and ET-1 contents in abdominal aorta, protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta were significantly decreased(P<0.05, P<0.01), while HDL content in the serum and NO content in the abdominal aorta were significantly increased(P<0.05, P<0.01), with smoother vascular walls, and relatively clear nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(4 weeks). In addition, content of HDL in the serum were significantly increased(P<0.05), while TNF-α content in the serum, protein expression of IL-6 in the abdominal aorta were significantly decreased (P<0.001, P<0.05), with smoother vascular walls, and clearer nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(4 weeks), in comparison with the moxibustion group(2 weeks). CONCLUSION: Mild moxibustion of 45 °C at ST36 can improve vascular endothelial damage and inflammatory response induced by high-fat diet by regulating serum lipids, vascular tone, adhesion molecules, and inflammatory factors, of which the effect of moxibustion intervention for 4 weeks is more significant.

Prediction of hepatic lymph node metastases based on magnetic resonance imaging before and after preoperative chemotherapy in patients with colorectal liver metastases underwent surgical resection.

BACKGROUND: Patients with colorectal liver metastases (CRLM) combined with hepatic lymph node (HLN) metastases have a poor prognosis. In this study, we developed and validated a model using clinical and magnetic resonance imaging (MRI) parameters to predict HLN status before surgery. METHODS: A total of 104 CRLM patients undergoing hepatic lymphonodectomy with pathologically confirmed HLN status after preoperative chemotherapy were enrolled in this study. The patients were further divided into a training group (n = 52) and a validation group (n = 52). The apparent diffusion coefficient (ADC) values, including ADCmean and ADCmin of the largest HLN before and after treatment, were measured. rADC was calculated referring to the target liver metastases, spleen, and psoas major muscle (rADC-LM, rADC-SP, rADC-m). In addition, ADC change rate (Δ% ADC) was quantitatively calculated. A multivariate logistic regression model for predicting HLN status in CRLM patients was constructed using the training group and further tested in the validation group. RESULTS: In the training cohort, post-ADCmean (P = 0.018) and the short diameter of the largest lymph node after treatment (P = 0.001) were independent predictors for metastatic HLN in CRLM patients. The model's AUC was 0.859 (95% CI, 0.757-0.961) and 0.767 (95% CI 0.634-0.900) in the training and validation cohorts, respectively. Patients with metastatic HLN showed significantly worse overall survival (p = 0.035) and recurrence-free survival (p = 0.015) than patients with negative HLN. CONCLUSIONS: The developed model using MRI parameters could accurately predict HLN metastases in CRLM patients and could be used to preoperatively assess the HLN status and facilitate surgical treatment decisions in patients with CRLM.