Moutai Distiller's grains Polyphenol extracts and rutin alleviate DSS-induced colitis in mice: Modulation of gut microbiota and intestinal barrier function （R2）.

Distiller's grains, byproducts of the brewing process, represent a valuable resource for extracting natural phenolic compounds due to their significant global production. This study presents the first evidence of the protective effects of Moutai distiller's grain polyphenol extract (MDGP) on dextran sulfate sodium (DSS)-induced colitis in mice. These protective effects manifest predominantly through the amelioration of general colitis indices and histopathological improvements. Utilizing liquid chromatography-high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS), the main components of MDGP were identified as rutin, quercetin, naringenin, and dihydroquercetin. Moreover, a novel mechanism was elucidated by which rutin, the primary active component of MDGP, alleviates DSS-induced colitis. Assessment of intestinal barrier function, microbial sequencing, fecal transplantation, and antibiotic depletion experiments revealed that rutin suppresses the abundance of pathogenic bacteria (Helicobacter, Klebsiella, and Veillonella) while promoting the proliferation of beneficial bacteria (Ruminococcus_torques_group, Lachnoclostridium, and norank_f__Muribaculaceae). This modulation culminates in elevated butyric acid concentrations within short-chain fatty acids (SCFAs), amplified integrity of tight (ZO-1, occludin) and adherent (E-cadherin, ß-catenin) junctional complexes, fortified intestinal barrier function, and diminished intestinal inflammation.This investigation accentuates the innovative therapeutic potential of MDGP and its main active component, rutin, in assuaging DSS-induced intestinal inflammation and fortifying the intestinal barrier through a mechanism predominantly mediated by the intestinal microbiota. Such insights potentially elevate the prominence of distiller's grains in the realm of functional food development.

Determining the survival benefit of postoperative radiotherapy in patients with pT1-3N1M0 rectal cancer undergoing total mesorectal excision: a retrospective analysis.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend routine postoperative adjuvant radiotherapy and chemotherapy for patients with stage III rectal cancer who do not receive neoadjuvant therapy before surgery. The present study aimed to evaluate the value of postoperative radiotherapy in patients with low-risk disease (pT1-3N1M0) who did not receive neoadjuvant therapy prior to total mesorectal excision. METHODS: We used the Surveillance, Epidemiology, and End Results database (2004-2016) to retrospectively recruit patients with pT1-3N1M0 rectal cancer whose initial treatment was radical surgery with postoperative adjuvant chemotherapy. A propensity score model was used to balance the baseline covariates. RESULTS: Of the 2012 patients included in the present study, 1384 received adjuvant chemoradiotherapy (radio group), whereas the remaining 718 received chemotherapy alone (no-radio group). There was no significant difference in cancer-specific survival rate between the two groups (log-rank test χ2 = 2.372, P = 0.124) in the overall sample. Additionally, in the propensity score-matched cohort, adjuvant radiotherapy did not improve cancer-specific survival. Subgroup analysis showed that having three positive lymph nodes and a tumor > 50 mm, combined with postoperative adjuvant chemotherapy, could lead to an improved tumor-specific survival rate, while other cases did not benefit from postoperative radiotherapy. CONCLUSIONS: For patients with pT1-3N1M0 rectal cancer who did not receive neoadjuvant therapy before surgery, postoperative radiotherapy in addition to adjuvant chemotherapy did not significantly improve survival rates. The number of positive nodes (n = 3) and tumor size (> 50 mm) were found to be potential screening indicators for postoperative adjuvant radiotherapy.

Cumulative dose of radiation therapy of hepatocellular carcinoma patients and its deterministic relation to radiation-induced liver disease.

This study aimed to investigate the relationship between dose and radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) receiving 3-dimensional conformal radiotherapy (3DCRT). Twenty-three patients with HCC who received conventional fractionated 3DCRT, including 7 who were diagnosed with classic RILD, were enrolled in this retrospective investigation. Cone-beam computed tomography (CBCT) scans were acquired at the time of treatment for each patient. The beams from each patient's treatment plan were applied to each pretreatment CBCT (the modified CBCT or mCBCT) to construct the delivered dose distribution of the day considering inter-treatment anatomy changes. The daily doses were summed together with the help of deformable image registration (DIR) to obtain the adjusted cumulative dose (Dadjusted). The dose changes to the normal liver between the original planned dose (Dplan) and Dadjusted were evaluated by V20, V30, V40, and the mean dose to normal liver (MDTNL). Univariate analysis was performed to identify the significant dose changes. Among the 23 patients, the liver V20, V30, V40, and MDTNL showed significant differences between Dplan and Dadjusted, with average values of these parameters increased by 4.1%, 4.7%, 4.5%, and 3.9 Gy, respectively (p < 0.05). The adjusted liver dose in 21 patients (91%) was higher than the planned value. For patients without and with RILD,the MDTNL was increased on average by 3.5 Gy and 4.7 Gy, and normal tissue complication probability (NTCP) increased on average by 2.8% and 7.5%, respectively. Our study found that the adjusted cumulative dose based on calculations using pretreatment mCBCT differs significantly from planned dose; the use of the dosimetric results of the initial plan was found to be less predictive of RILD as compared with Dadjusted. Determination of a reconstructed Dadjusted using the mCBCT scans are more accurate in predicting RILD and has the potential to reduce the risk of RILD.

Determining the Optimal Dose Prescription for the Planning Target Volume with Stereotactic Body Radiotherapy for Non- Small Cell Lung Cancer Patients.

OBJECTIVE: The aim of this study was to determine a method of dose prescription that minimizes normal tissue irradiation outside the planning target volume (PTV) during stereotactic body radiotherapy (SBRT) for patients with non-small cell lung cancer. METHODS: Previous research and patients with typical T1 lung tumors with peripheral lesions in the lung were selected for analysis. A PTV and several organs at risk (OARs) were constructed for the dose calculated; six treatment plans employing intensity modulated radiotherapy (IMRT) were produced, in which the dose was prescribed to encompass the PTV, with the prescription isodose level (PIL) set at 50, 60, 70, 80, 90 or 95% of the isocenter dose. Additionally, four OARs around the PTV were constructed to evaluate the dose received in adjacent tissues. RESULTS: The use of higher PILs for SBRT resulted in improved sparing of OARs, with the exception of the volume of lung treated with a lower dose. CONCLUSIONS: The use of lower PILs is likely to create significant inhomogeneity of the dose delivered to the target, which may be beneficial for the control of tumors with poor conformity indices.

Influence of intravenous contrast medium on dose calculation using CT in treatment planning for oesophageal cancer.

OBJECTIVE: To evaluate the effect of intravenous contrast on dose calculation in radiation treatment planning for oesophageal cancer. METHODS: A total of 22 intravein-contrasted patients with oesophageal cancer were included. The Hounsfield unit (HU) value of the enhanced blood stream in thoracic great vessels and heart was overridden with 45 HU to simulate the non-contrast CT image, and 145 HU, 245 HU, 345 HU, and 445 HU to model the different contrast-enhanced scenarios. 1000 HU and -1000 HU were used to evaluate two non-physiologic extreme scenarios. Variation in dose distribution of the different scenarios was calculated to quantify the effect of contrast enhancement. RESULTS: In the contrast-enhanced scenarios, the mean variation in dose for planning target volume (PTV) was less than 1.0%, and those for the total lung and spinal cord were less than 0.5%. When the HU value of the blood stream exceeded 245 the average variation exceeded 1.0% for the heart V40. In the non-physiologic extreme scenarios, the dose variationof PTV was less than 1.0%, while the dose calculations of the organs at risk were greater than 2.0%. CONCLUSIONS: The use of contrast agent does not significantly influence dose calculation of PTV, lung and spinal cord. However, it does have influence on dose accuracy for heart.

Mitofusin-2 ameliorates high-fat diet-induced insulin resistance in liver of rats.

AIM: To investigate the effects of mitofusin-2 (MFN2) on insulin sensitivity and its potential targets in the liver of rats fed with a high-fat diet (HFD). METHODS: Rats were fed with a control or HFD for 4 or 8 wk, and were then infected with a control or an MFN2 expressing adenovirus once a week for 3 wk starting from the 9(th) wk. Blood glucose (BG), plasma insulin and insulin sensitivity of rats were determined at end of the 4(th) and 8(th) wk, and after treatment with different amounts of MFN2 expressing adenovirus (10(8), 10(9) or 10(10) vp/kg body weight). BG levels were measured by Accu-chek Active Meter. Plasma insulin levels were analyzed by using a Rat insulin enzyme-linked immunosorbent assay kit. Insulin resistance was evaluated by measuring the glucose infusion rate (GIR) using a hyperinsulinemic euglycemic clamp technique. The expression or phosphorylation levels of MFN2 and essential molecules in the insulin signaling pathway, such as insulin receptor (INSR), insulin receptor substrate 2 (IRS2), phosphoinositide-3-kinase (PI3K), protein kinase beta (AKT2) and glucose transporter type 2 (GLUT2) was assayed by quantitative real-time polymerase chain reaction and Western-blotting. RESULTS: After the end of 8 wk, the body weight of rats receiving the normal control diet (ND) and the HFD was not significantly different (P > 0.05). Compared with the ND group, GIR in the HFD group was significantly decreased (P < 0.01), while the levels of BG, triglycerides (TG), total cholesterol (TC) and insulin in the HFD group were significantly higher than those in the ND group (P < 0.05). Expression of MFN2 mRNA and protein in liver of rats was significantly down-regulated in the HFD group (P < 0.01) after 8 wk of HFD feeding. The expression of INSR, IRS2 and GLUT2 were down-regulated markedly (P < 0.01). Although there were no changes in PI3K-P85 and AKT2 expression, their phosphorylation levels were decreased significantly (P < 0.01). After intervention with MFN2 expressing adenovirus for 3 wk, the expression of MFN2 mRNA and protein levels were up-regulated (P < 0.01). There was no difference in body weight of rats between the groups. The levels of BG, TG, TC and insulin in rats were lower than those in the Ad group (P < 0.05), but GIR in rats infected with Ad-MFN2 was significantly increased (P < 0.01), compared with the Ad group. The expression of INSR, IRS2 and GLUT2 was increased, while phosphorylation levels of PI3K-P85 and AKT2 were increased (P < 0.01), compared with the Ad group. CONCLUSION: HFDs induce insulin resistance, and this can be reversed by MFN2 over-expression targeting the insulin signaling pathway.

RapidArc radiotherapy for whole pelvic lymph node in cervical cancer with 6 and 15 MV: a treatment planning comparison with fixed field IMRT.

Dosimetric differences were investigated among single and dual arc RapidArc and fixed-field intensity-modulated radiotherapy (f-IMRT) treatment plans for whole pelvic irradiation of lymph nodes. A total of 12 patients who had undergone radical surgery for cervical cancer and who had demonstrated multiple pelvic lymph node metastases were treated with radiotherapy. For all 12 cases, 7-field IMRT, single-arc RapidArc and dual-arc RapidArc were applied with 6 MV and 15 MV X-ray energies. The radiation dosimetric parameters for the different plans were compared with one another. All the plans met the clinical requirements. The homogeneity, conformity and external volume indices of f-IMRT and dual-arc RapidArc were better than for single-arc RapidArc (P < 0.05), while the differences between f-IMRT and dual-arc RapidArc were not significant. There were no significant differences in the radiation dose to organs at risk, except for the small bowel receiving >40 Gy (f-IMRT and dual-arc < single-arc, P < 0.05). The differences in dose distributions between the two applied X-ray energies for each of the modality plans were not significant. RapidArc plans resulted in fewer monitor units than the corresponding f-IMRT plans. Also, there were no differences between the two photon energies, except for a reduction in the number of MUs for 15 MV (P > 0.05). Compared to f-IMRT, no significant dosimetric benefits were found using RapidArc for whole pelvic lymph node irradiation. However, RapidArc has been associated with shorter treatment time and fewer monitor units, supporting the case for its safety and efficacy for pelvic irradiation.

Evaluation of the geometric accuracy of anatomic landmarks as surrogates for intrapulmonary tumors in image-guided radiotherapy.

OBJECTIVES: The purpose of this study was to evaluate the geometric accuracy of thoracic anatomic landmarks as target surrogates of intrapulmonary tumors for manual rigid registration during image-guided radiotherapy (IGRT). METHODS: Kilovolt cone-beam computed tomography (CBCT) images acquired during IGRT for 29 lung cancer patients with 33 tumors, including 16 central and 17 peripheral lesions, were analyzed. We selected the "vertebrae", "carina", and "large bronchi" as the candidate surrogates for central targets, and the "vertebrae", "carina", and "ribs" as the candidate surrogates for peripheral lesions. Three to six pairs of small identifiable markers were noted in the tumors for the planning CT and Day 1 CBCT. The accuracy of the candidate surrogates was evaluated by comparing the distances of the corresponding markers after manual rigid matching based on the "tumor" and a particular surrogate. Differences between the surrogates were assessed using 1-way analysis of variance and post hoc least-significant-difference tests. RESULTS: For central targets, the residual errors increased in the following ascending order: "tumor", "bronchi", "carina", and "vertebrae"; there was a significant difference between "tumor" and "vertebrae" (p=0.010). For peripheral diseases, the residual errors increased in the following ascending order: "tumor", "ribs", "vertebrae", and "carina". There was a significant difference between "tumor" and "carina" (p=0.005). CONCLUSIONS: The "bronchi" and "carina" are the optimal surrogates for central lung targets, while "ribs" and "vertebrae" are the optimal surrogates for peripheral lung targets for manual matching of online and planned tumors.

[Role of JNK signal transduction pathway in nonalcoholic fatty liver disease].

OBJECTIVE: To investigate the role of c-Jun N-terminal kinase (JNK) signal transduction pathway in the rats of nonalcoholic fatty liver disease (NAFLD). METHODS: Sixty four Sprague-Dawley rats were randomly divided into four groups: 8-week control group (NG8w), 12-week control group (NG12 w), 8-week high-fat diet (HG8w), and 12-week high-fat diet group (HG12w), with 16 rats in each group. Glucose infusion rate (GIR) was tested by euglycemic hyperinsulinemic clamp; aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), free fatty acid (FFAs), fast insulin (FIns), tumor necrosis factor alpha (TNF alpha), superoxide dismutase (SOD) and malondialdehyde (MDA) were tested by biochemistry automatic analyzer or RIA; The expression of JNK1, insulin receptor substrate-1 (IRS-1), phospho-IRS-1 Ser307 (p-IRS-1 Ser307), Protein kinase B (PKB) and phospho-PKB Ser473 (p- PKB Ser473) were detected by Western blot. RESULTS: Compared to control group, body weight, liver index, serum levels of ALT, AST, TG, TC, FIns, FFAs, TNF alpha, and TC, TG FFAs, MDA in liver homogenates were increased, while the level of SOD, and GIR were decreased. The expression of JNK1 protein and p-IRS-1 Ser307 in liver tissue was up-regulated, while expression of p-PKB Ser473 was decreased (P < 0.05). A positive correlation was found between the expression intensity of JNK1 and IR (Pearson correlation: 0.718, P < 0.01). CONCLUSION: The high-fat could induce the expression of JNK1, which in turn modulates the phosphorylation of proteins in the insulin signaling pathway, and induces insulin resistant.

Protection of lung function by introducing single photon emission computed tomography lung perfusion image into radiotherapy plan of lung cancer.

BACKGROUND: The lung functional status could be displayed on lung perfusion images. With the images, the radiotherapy plans of lung cancer could be guided to more optimized. This study aimed to assess quantitatively the impact of incorporating functional lung imaging into 3-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT) planning for non-small cell lung cancer (NSCLC). METHODS: Ten patients with NSCLC who had undergone radiotherapy were included in this study. Before radiotherapy, each patient underwent CT simulation and lung perfusion imaging with single photon emission computed tomography (SPECT). The SPECT images were registered with simulation planning CT and used to contour functional lung (lung-F) and non-functional lung (lung-NF). Two 3DCRT plans and two IMRT plans were designed and compared in each patient: two anatomic plans using simulation CT alone and two functional plans using SPECT-CT in addition to the simulation CT. Dosimetric parameters of the four types of plans were compared in terms of tumor coverage and avoidance of normal tissues. Total radiation dose was set at 66 Gy (2 Gy x 33 fractions). RESULTS: In incorporating perfusion information in 3DCRT and IMRT planning, the reductions on average in the mean doses to the functional lung in the functional plan were 168 cGy and 89 cGy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with > 5 Gy, > 10 Gy, > 20 Gy, > 30 Gy and > 40 Gy for functional lung in the functional plans were 6.50%, 10.21%, 14.02%, 22.30% and 23.46% in 3DCRT planning, respectively, and 3.05%, 15.52%, 14.16%, 4.87%, and 3.33% in IMRT planning, respectively. No greater degree of sparing of the functional lung was achieved in functional IMRT than in 3DCRT. CONCLUSION: Function-guided 3DCRT and IMRT plannings both appear to be effective in preserving functional lung in NSCLC patients.