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Gut microbiota is closely related to the Parkinson's disease (PD) pathogenesis. Additionally, aggregation of α-synuclein (α-syn) is central to PD pathogenesis. Here we identified the further mechanisms of gut microbiota in PD. A mouse model with PD was established via injection of MPTP. Normal or MPTP-induced PD like animals were treated with FMT from healthy normal mice. Pole test and traction test were performed to examine the effects of FMT on motor function of PD mice. Fecal SCFAs were assessed by gas chromatography-mass spectrometry. The α-syn level in the substantia nigra pars compacta (SN) of mice was measured using western blot. Dopaminergic neurons and microglial activation in the SN were analyzed by immunohistochemistry (IHC) and immunofluorescence (IF) staining. FMT alleviated physical impairment, decreased fecal SCFAs in a mouse model of PD. Additionally, FMT decreased the expression of α-syn, as well as inhibited the activation of microglia in the SN, and blocked the TLR4/PI3K/AKT/NF-κB signaling in the SN and striatum. FMT could protect mice against PD via suppressing α-syn expression and inactivating the TLR4/PI3K/AKT/NF-κB signaling.

Background Accurate assessment of tumor response in rectal cancer could help individualize treatment. Purpose To evaluate the role of diffusion-weighted imaging (DWI) based on readout-segmented echo-planar imaging (rs-EPI) in assessing tumor response after neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Material and Methods Sixty-three patients with LARC who received neoadjuvant CRT and surgery were enrolled retrospectively. They all underwent pre- and post-CRT magnetic resonance examinations, including DWI using rs-EPI. According to pathological results, patients were grouped as pathological complete responder (pCR, n = 16) and non-pCR (n = 47). Visual assessment of residual tumor and whole-tumor histogram analysis of pre- and post-CRT apparent diffusion coefficient (ADC) map was performed by two radiologists; tumor volume on ADC map was also recorded. Results Overall inter-observer agreement was good for histogram analysis (ICC = 0.543–0.999). Tumor volume reduction rate on ADC map showed no significant difference between the two groups ( P = 0.468). Post-CRT mean, quantile values, and their percentage changes were higher in the pCR group (all P −3 mm2/s, yielding a sensitivity of 83%, specificity of 81.3%. Post-CRT 95% quantile value had the highest AUC (AUC = 0.868) among quantile values, and a higher specificity (87.5% vs. 81.3%) than mean value with comparable overall diagnostic performance ( P = 0.563). Visual assessment showed a sensitivity of 85.1%, specificity of 68.8% in selecting pCR. Conclusion Quantitative ADC value of rs-EPI DWI could reliably evaluate tumor response in patients with LARC. Post-CRT 95% quantile ADC value could help mean value to more accurately identify pCR.

To explore if there is a correlation between T2WI histogram features of the primary tumor and the existence of regional lymph node (LN) metastasis in rectal cancer. Eighty-eight patients with pathologically proven rectal adenocarcinoma, who received direct surgical resection and underwent preoperative rectal MRIs, were enrolled retrospectively. Based on pathological analysis of surgical specimen, patients were classified into negative LN (LN−) and positive LN (LN+) groups. The degree of differentiation and pathological T stage were recorded. Clinical T stage, tumor location, and maximum diameter of tumor were evaluated of each patient. Whole-tumor texture analysis was independently performed by two radiologists on axial T2WI, including skewness, kurtosis, energy, and entropy. The interobserver agreement was overall good for texture analysis between two radiologists, with intraclass correlation coefficients (ICCs) ranging from 0.626 to 0.826. The LN− group had a significantly higher skewness (p

The purpose of this study is to determine the performance of the apparent diffusion coefficient (ADC) value calculated from high-resolution DWI using readout-segmented echo-planar imaging (rs-EPI) and to assess the texture parameters of T2-weighted MR images in identifying pathologic complete response (pCR) after patients with locally advanced rectal cancer (LARC) undergo preoperative chemoradiotherapy (CRT).A total of 76 patients with LARC who underwent preoperative CRT and subsequent surgery were enrolled in the study retrospectively. All patients underwent post-CRT MRI, which included acquisition of a DWI sequence with use of the rs-EPI technique. The histopathologic tumor regression grade was the reference standard. Patients were subdivided into pCR and non-pCR groups. Two radiologists independently drew whole-tumor ROIs on DW images and T2-weighted MR images to calculate the mean ADC value and first-order texture parameters.Interobserver agreement was good to excellent (intraclass correlation coefficient [ICC], 0.79-0.993) for imaging analysis. Calculated from high-resolution DWI, the mean post-CRT ADC value was significantly higher in the pCR group (p0.001). The pCR group also showed lower uniformity (p0.001) of the T2-weighted image. The mean ADC value and uniformity were significantly correlated with the tumor regression grade. The mean ADC value was a good indicator for differentiating pCR from absence of pCR (ROC AUC value, 0.912). Uniformity (ROC AUC value, 0.776) showed a moderate ability to identify pCR. Combining the mean ADC value and uniformity yielded an ROC AUC value comparable to that of the mean ADC value (p = 0.125).Mean post-CRT ADC values calculated from high-resolution DWI using rs-EPI could effectively select for patients with LARC who have a pCR after preoperative CRT. First-order texture parameters of T2-weighted MR images could also identify patients with pCR by reflecting tumor heterogeneity, even though they could not significantly improve the diagnostic performance.

ObjectiveThis study assessed the association between body composition and prognosis of patients with upper urinary tract urothelial carcinoma (UTUC) patients treated by radical nephroureterectomy.MethodsWe retrospectively collected baseline data on age, sex, body mass index (BMI), hypertension, diabetes, and tumor-related factors. Computed tomography (CT) scans were performed to measure body composition parameters such as muscle attenuation (MA), total abdominal muscle area (TAMA), visceral fat area (VFA), intermuscular fat area (IMF), and lateral/posterior perirenal fat thickness (L/P PNF), visceral fat density (VD), and subcutaneous fat density (SD). Patient follow-up was conducted via telephone or in the clinic. The endpoints of follow-up were all-cause death, local progression or distant metastasis. Survival analysis was analyzed using the Kaplan-Meier method, and risk factors associated with prognosis were identified using univariate and multivariate Cox proportional hazard analyses.ResultsAmong the 273 UTUC patients (median age, 68 years) enrolled in our study, 102 had a BMI > 24.0, 100 suffered from diabetes, and 120 had hypertension. A large proportion of patients (189) had high grade tumors. Across all patients, 1- and 3-year rates for overall survival were 86.45% and 75.55%; local progression-free survival, 92.11% and 89.67%; and distant metastasis-free survival, 85.23% and 80.17%. Based on the Cox regression analysis, MA, IMF, TAMA, TPA, TPT, APT, SMI and PMI significantly reduced the risk of local progression (p < 0.05), while PPNF = 1 point reduced the risk of distant metastasis (p < 0.05). Overall survival was significantly associated with MA, TAMA, and SMI (p < 0.05).ConclusionOur findings illustrate that body composition parameters can act as independent predictors of prognosis in UTUC patients who underwent RNU. These results can help improve stratification of patients and optimize postoperative treatment.

Background: To develop a radiomics model for bounding box-based region of interest (ROI) annotation for the preoperative diagnosis of occult peritoneal metastasis (OPM) in advanced gastric cancer (AGC) patients. Methods: 599 AGC patients from 3 centers were retrospectively enrolled and were divided into training, validation, and testing cohorts. The ROIs for the largest tumor area, the minimum circumscribed rectangle of the ROIs (BBOX), the nonoverlapping area between the ROIs and BBOX (peritumoral area; PERI) and the smallest rectangle that could completely contain the lesion determined by a radiologist (M_BBOX) were used as inputs to extract radiomic features. Multivariate logistic regression was used to construct a radiomics model to estimate the preoperative probability of OPM in GC patients. Findings: The BBOX radiomics model had the highest area under the receiver operating characteristic curve (AUC) of 0.873 [0.820-0.940], outperforming the other radiomics models. The M_BBOX model was not significantly different from BBOX in the validation cohort (AUC: M_BBOX model 0.871 [0.814-0.940] vs. BBOX model 0.873 [0.820-0.940]; p = 0.937). M_BBOX was selected as the final radiomics model because of its extremely low annotation cost and superior OPM discrimination performance (sensitivity of 85.7% and specificity of 82.8%) over the clinical model, and this radiomics model showed comparable diagnostic efficacy in the testing cohort. Interpretation: The radiomics model based on bounding box annotation achieved higher OPM detection accuracy in AGC patients than the clinical model and had potential generalizability. Funding Information: This work was supported by the 1*3*5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (No. ZY2017304). Declaration of Interests: The authors have no relevant conflicts of interest to disclose. Ethics Approval Statement: This multicenter retrospective study was approved by the institutional review board of each center, and the informed consent requirement was waived.

To evaluate the role of IVIM and diffusion kurtosis imaging (DKI) in identifying pathologic complete response (pCR) and T stages after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC).Forty-two patients with biopsy-proven rectal adenocarcinoma, who underwent both pre-and post-CRT MRI with IVIM and DKI sequences on a 3 T scanner, were enrolled prospectively. According to the pathologic ypTNM stages and tumor regression grade (TRG), patients were grouped into pCR (TRG0) and non-pCR (TRG1-3) groups and low T stage (ypT0-2) and high T stage (ypT3-4) groups. IVIM parameters (the slow diffusion coefficient [D], fast diffusion coefficient [D*], perfusion fraction [f]), DKI parameters (mean diffusivity [MD] and mean kurtosis [MK]), and mono-exponential ADC were calculated and analyzed between groups.The pCR group had significantly higher post-CRT ADC, D*, f, and MD values than non-pCR group, and higher percent changes in the ADC, f, and MD values (all P 0.05). The post-CRT MD values yielded the highest AUC (0.788) with higher sensitivity than post-ADC values (82.9 % vs. 77.1 %, respectively). Post-CRT ADC and MD values and the percent changes in the ADC and MD values were also negatively correlated with TRG (all P 0.05). Besides, negative correlations were found among the pre-CRT MD, post-CRT ADC, D, f, and MD values and the ypT stages (all P 0.05).Both IVIM and DKI parameters could provide more information when evaluating pCR and T stages after nCRT. In particular, the diagnostic performance of the MD values was more valuable than ADC values in being able to determine pCR.