Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer

OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >;7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >;7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical factors could be valuable for post-operative assessment of pathological complete response

Duck TRIM29 negatively regulates type I IFN production by targeting MAVS

The innate immune response is a host defense mechanism that induces type I interferon and proinflammatory cytokines. Tripartite motif (TRIM) family proteins have recently emerged as pivotal regulators of type I interferon production in mammals. Here, we first identified duck TRIM29, which encodes 571 amino acids and shows high sequence homology with other bird TRIM29 proteins. DuTRIM29 inhibited IFN-β and IRF7 promoter activation in a dose-dependent manner and downregulated the mRNA expression of IFN-β, IRF7, Mx and IL-6 mediated by duRIG-I. Moreover, duTRIM29 interacted and colocalized with duMAVS in the cytoplasm. DuTRIM29 interacted with duMAVS via its C-terminal domains. In addition, duTRIM29 inhibited IFN-β and IRF7 promoter activation and significantly downregulated IFN-β and immune-related gene expression mediated by duMAVS in ducks. Furthermore, duTRIM29 induced K29-linked polyubiquitination and degradation of duMAVS to suppress the expression of IFN-β. Overall, our results demonstrate that duTRIM29 negatively regulates type I IFN production by targeting duMAVS in ducks. This study will contribute to a better understanding of the molecular mechanism regulating the innate immune response by TRIM proteins in ducks

Locally advanced rectal cancer with dMMR/MSI-H may be excused from surgery after neoadjuvant anti-PD-1 monotherapy: a multiple-center, cohort study

ObjectiveExamine patients with locally advanced rectal cancer (LARC) with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) who received neoadjuvant immunotherapy (nIT), and compare the outcomes of those who chose a watch-and-wait (WW) approach after achieving clinical complete response (cCR) or near-cCR with those who underwent surgery and were confirmed as pathological complete response (pCR).MethodsLARC patients with dMMR/MSI-H who received nIT were retrospectively examined. The endpoints were 2-year overall survival (OS), 2-year disease-free survival (DFS), local recurrence (LR), and distant metastasis (DM). The efficacy of programmed cell death protein-1 (PD-1) inhibitor, immune-related adverse events (irAEs), surgery-related adverse events (srAEs), and enterostomy were also recorded.ResultsTwenty patients who received a PD-1 inhibitor as initial nIT were examined. Eighteen patients (90%) achieved complete response (CR) after a median of 7 nIT cycles, including 11 with pCR after surgery (pCR group), and 7 chose a WW strategy after evaluation as cCR or near-cCR (WW group). Both groups had median follow-up times of 25.0 months. Neither group had a case of LR or DM, and the 2-year DFS and OS in each group was 100%. The two groups had similar incidences of irAEs (P=0.627). In the pCR group, however, 2 patients (18.2%) had permanent colostomy, 3 (27.3%) had temporary ileostomy, and 2 (18.2%) had srAEs.ConclusionNeoadjuvant PD-1 blockade had high efficacy and led to a high rate of CR in LARC patients with dMMR/MSI-H. A WW strategy appears to be a safe and reliable option for these patients who achieve cCR or near-cCR after nIT

Delineating the molecular landscape of different histopathological growth patterns in colorectal cancer liver metastases

BackgroundHistopathological growth patterns (HGPs) have shown important prognostic values for patients with colorectal cancer liver metastases, but the potential molecular mechanisms remain largely unknown.MethodsWe performed an exploratory analysis by conducting the RNA sequencing of primary colorectal lesions, colorectal liver metastatic lesions and normal liver tissues.FindingsWe found that desmoplastic HGPs of the metastatic lesions were significantly enriched in EMT, angiogenesis, stroma, and immune signaling pathways, while replacement HGPs were enriched in metabolism, cell cycle, and DNA damage repair pathways. With the exception of immune-related genes, the differentially expressed genes of the two HGPs from colorectal liver metastases were mostly inherited from the primary tumor. Moreover, normal liver tissue in the desmoplastic HGP subgroup was markedly enriched in the fibrinous inflammation pathway.ConclusionsWe surmised that HGPs are observable morphological changes resulting from the regulation of molecular expressions, which is the combined effect of the heterogeneity and remodeling of primary tumors seeds and liver soils

Investigation of Electronic and Optical Properties of Al/Ag and Al/N Co-Implanted ZnO Thin Films

Either metal/metal or metal/non-metal co-doping is one of the most effective methods to modulate the visible emission of ZnO. In this paper, ZnO, aluminum-doped ZnO (Al-ZnO), aluminum and silver co-doped ZnO (Al/Ag-ZnO), and aluminum and nitrogen co-doped ZnO (Al/N-ZnO) are deposited. Combining the substitution of zinc ions using Al and/or Ag doping and the substitution of oxygen ions using N doping is expected to introduce more interstitial zinc and oxygen vacancy defects related to visible light emission in ZnO films. The results indicate that the PL spectrum of ZnO shows a violet emission peak at 406 nm and other weak visible emission peaks. After Al doping, we observe a strong blue emission at 421 nm, and its intensity is further enhanced and attains the maximum for Al/N-ZnO. However, for Al/Ag-ZnO, the blue emission shifts toward a longer wavelength, and the intensity of the blue emission conversely decreases. Then, the band structures, the density of states (DOS), the partial density of states (PDOS), and the optical constant of doped ZnO are calculated using density functional theory (DFT). Based on the experimental and theoretical results, the enhancement mechanism of visible light is discussed

Translation and validation of chinese version of MDASI immunotherapy for early-phase trials module: a cross-sectional study

Abstract Background During immunotherapy treatment and survival, identifying symptoms requires a standardized and validated assessment tool. The aim of this study was to translate, validate and use the Chinese version of the Immunotherapy of the M.D. Anderson Symptom Inventory for Early-Phase Trials module (MDASI-Immunotherapy EPT) to assess the symptom burden of cancer patients receiving immunotherapy in China. Methods The MDASI-Immunotherapy EPT was translated into Chinese using Brislin’s translation model and the back-translation method. In total, 312 Chinese-speaking colorectal cancer patients receiving immunotherapy were enrolled in the trial from August 2021 to July 2022 after receiving definitive diagnoses in our cancer center. The reliability and validity of the translated version was evaluated. Results Cronbach’s α values were 0.964 and 0.935 for the symptom severity and interference scales, respectively. Significant correlations were found between the MDASI-Immunotherapy EPT-C and FACT-G scores (-0.617–0.732, P < 0.001). Known-group validity was supported by significant differences in the scores of the four scales grouped by ECOG PS (all P < 0.01). The overall mean subscale scores for the core and interference subscales were 1.92 ± 1.75 and 1.46 ± 1.87, respectively. Fatigue, numbness/tingling, and disturbed sleep had the highest scores for the most serious symptoms. Conclusion The MDASI-Immunotherapy EPT-C showed adequate reliability and validity for measuring symptoms among Chinese-speaking colorectal cancer patients receiving immunotherapy. The tool could be used in clinical practice and clinical trials to gather patients’ health and quality of life data and manage their symptoms in a timely manner in the future

Preparation of Carbon-Based Solid Acid Catalysts Using Rice Straw Biomass and Their Application in Hydration of α-Pinene

Carbon-based solid acid catalysts were prepared using rice straw (RS) waste, and the effects of carbonization temperature and sulfonation temperature on the catalytic activity were investigated. The properties of the catalysts were characterized using thermo gravimetric (TG), scanning electron microscope (SEM), Brunauer&ndash;Emmet&ndash;Teller (BET), Fourier transform infrared spectroscopy (FT-IR), temperature-programmed desorption (TPD), and X-ray photoelectron spectroscopy (XPS), and their activities were investigated through the hydration of &alpha;-pinene. The conversion of &alpha;-pinene and the selectivity of &alpha;-terpineol reached 67.60% and 57.07% at 80 &deg;C and atmospheric pressure in 24 h, respectively. The high catalytic capacity of the catalyst is attributed to the high acid site density and high porosity of the catalyst. TPD analysis and FT-IR spectroscopy showed that the catalyst produced by low-temperature carbonization at 300 &deg;C followed by low-temperature sulfonation at 80 &deg;C had abundant strong acid sites (0.82 mmol/g), which can effectively inhibit the side reactions of hydrated &alpha;-pinene. The total acidity reached 2.87 mmol/g. N2-physisorption analysis clearly indicated that the obtained catalysts were mesopore-predominant materials, and the SBET and VTotal of catalysts reached 420.9 m2/g and 4.048 cm3/g, respectively. Preparation of the catalyst involves low energy consumption, and its cheap raw materials make the whole process simple, economical, and environmentally friendly

Preparation of Cu2+/TA/HAP composite coating with anti-bacterial and osteogenic potential on 3D-printed porous Ti alloy scaffolds for orthopedic applications

Because of stress shielding effects, traditional titanium (Ti) alloy scaffolds have a high elastic modulus, which might promote looseness and bone disintegration surrounding the implant, increasing the likelihood of a second surgery. In contrast, 3D-printed porous Ti alloy scaffolds can reduce the scaffold weight while enhancing biocompatibility. Further, these scaffolds’ porous nature allows bone tissue ingrowth as well as strong pore connectivity, which can improve nutrient absorption. Nevertheless, bare Ti alloy implants may fail because of inadequate bone integration; hence, adding a coating on the implant surface is an effective technique for improving implant stability. In this study, a composite coating comprising hydroxyapatite (HAP), chitosan (CS), tannic acid (TA) and copper ions (Cu2+) (Cu2+/TA/HAP composite coating) was prepared on the surface of 3D printed porous Ti alloy scaffolds using electrophoretic deposition. Using the standard plate count method, Live/Dead bacteria staining assay, FITC Phalloidin and 4′,6-diamidino-2-phenylindole staining assay, and live/dead staining of cells we determined that the composite coating has better antibacterial properties and cytocompatibility as well as lower cytotoxicity. The Alkaline Phosphatase assay revealed that the coating results showed good osteogenesis potential. Overall, the composite coatings produced in this investigation give new potential for the application of Ti alloys in clinics