First-Principles Calculate the Stability, Mechanical Properties and Electronic Structure of Carbide MC, M2C and M6C in M50NiL Steel.

In this paper, the stability, mechanical properties and electronic structure of carbides in steel were calculated using the first-principles method based on the density functional theory (DFT). Firstly, the MC, M2C, M6C (M = Cr, Mo, V, Fe) carbides models were established. Then, different interphases' lattice constants, formation enthalpy, binding energy and elastic modulus were calculated. The stability, hardness, ductility and anisotropy of each phase were finally analyzed. The results show that these phases are stable, and the stability is closely related to the electron loss ability of its metal elements. The stronger the electron loss ability of its metal elements, the more stable the formed phase. As for MC carbides, MoC has the largest bulk modulus and hardness. As for M2C carbides, the Poisson's ratio of Cr2C is the smallest, and all phases except for Cr2C show toughness and ductility. The anisotropy of M6C carbides is relatively poor.

Discriminating atypical parotid carcinoma and pleomorphic adenoma utilizing extracellular volume fraction and arterial enhancement fraction derived from contrast-enhanced CT imaging: A multicenter study.

OBJECTIVES: To investigate the added value of extracellular volume fraction (ECV) and arterial enhancement fraction (AEF) derived from enhanced CT to conventional image and clinical features for differentiating between pleomorphic adenoma (PA) and atypical parotid adenocarcinoma (PCA) pre-operation. METHODS: From January 2010 to October 2023, a total of 187 cases of parotid tumors were recruited, and divided into training cohort (102 PAs and 51 PCAs) and testing cohort (24 PAs and 10 atypical PCAs). Clinical and CT image features of tumor were assessed. Both enhanced CT-derived ECV and AEF were calculated. Univariate analysis identified variables with statistically significant differences between the two subgroups in the training cohort. Multivariate logistic regression analysis with the forward variable selection method was used to build four models (clinical model, clinical model+ECV, clinical model+AEF, and combined model). Diagnostic performances were evaluated using receiver operating characteristic (ROC) curve analyses. Delong's test compared model differences, and calibration curve and decision curve analysis (DCA) assessed calibration and clinical application. RESULTS: Age and boundary were chosen to build clinical model, and to construct its ROC curve. Amalgamating the clinical model, ECV, and AEF to establish a combined model demonstrated superior diagnostic effectiveness compared to the clinical model in both the training and test cohorts (AUC = 0.888, 0.867). There was a significant statistical difference between the combined model and the clinical model in the training cohort (p = 0.0145). CONCLUSIONS: ECV and AEF are helpful in differentiating PA and atypical PCA, and integrating clinical and CT image features can further improve the diagnostic performance.

Beneficial effects of the first case of washed microbiota transplantation for postorgasmic illness syndrome: a case report.

Introduction: Postorgasmic illness syndrome (POIS) is characterized by allergic symptoms and flu-like illness after ejaculation. There are still no effective treatments for POIS. Aim: To report the first case of washed microbiota transplantation (WMT) to treat patient with POIS. Methods: Data were collected from a patient with POIS who had received 3 courses of WMT: self-rating scale of POIS symptoms, Self-rating Anxiety Scale, Self-rating Depression Scale, and Symptom Checklist 90. The patient's stool samples for 16sDNA sequencing were collected 1 month after WMT. Results: POIS symptoms improved after WMT. Scores decreased from baseline after WMT: self-rating scale of POIS symptoms (before WMT, 16; after first, 16; after second, 8; after third, 9), Self-rating Anxiety Scale (45, 42.5, 37.5, 45), Self-rating Depression Scale (63.75, 58.75, 47.5, 50), and Symptom Checklist 90 (143, 140, 109, 149). Characteristics of the patient's gut microbiota changed. At the genus level, the relative abundance of beneficial bacteria increased, and some opportunistic pathogenic bacteria decreased. Conclusion: WMT may be an effective and safe choice for the treatment of patients with POIS by changing the gut microbiota of the host.

Devastating the Supply Wagons: Multifaceted Liposomes Capable of Exhausting Tumor to Death via Triple Energy Depletion.

The anabolism of tumor cells can not only support their proliferation, but also endow them with a steady influx of exogenous nutrients. Therefore, consuming metabolic substrates or limiting access to energy supply can be an effective strategy to impede tumor growth. Herein, a novel treatment paradigm of starving-like therapy-triple energy-depleting therapy-is illustrated by glucose oxidase (GOx)/dc-IR825/sorafenib liposomes (termed GISLs), and such a triple energy-depleting therapy exhibits a more effective tumor-killing effect than conventional starvation therapy that only cuts off one of the energy supplies. Specifically, GOx can continuously consume glucose and generate toxic H2O2 in the tumor microenvironment (including tumor cells). After endocytosis, dc-IR825 (a near-infrared cyanine dye) can precisely target mitochondria and exert photodynamic and photothermal activities upon laser irradiation to destroy mitochondria. The anti-angiogenesis effect of sorafenib can further block energy and nutrition supply from blood. This work exemplifies a facile and safe method to exhaust the energy in a tumor from three aspects and starve the tumor to death and also highlights the importance of energy depletion in tumor treatment. It is hoped that this work will inspire the development of more advanced platforms that can combine multiple energy depletion therapies to realize more effective tumor treatment.

Identification of multiomics map and key biomarkers in uveal melanoma with chromosome 3 loss.

Purpose: Chromosome 3 loss is an independent risk factor for uveal melanoma (UM), but its exact molecular mechanisms remain unclear. This study was designed to investigate the relationship between chromosome 3 loss and molecular alterations at multiple levels to construct a prognostic model. Methods: Forty-four UM cases with chromosome 3 loss (chr3 del group) and 36 UM cases without copy number variation on chromosome 3 (chr3 wt group) were collected from the Cancer Genome Atlas (TCGA). The TCGA dataset was subjected to a univariate Cox regression analysis to identify different expressed genes, and a subsequent random forest algorithm analysis revealed significant changes in different expressed genes, which were used to develop key biomarkers for UM. Following that, the immune cell infiltration analysis and drug sensitivity analyses were carried out. The UM cell line was then utilized to investigate the potential functions of the key biomarker via cell apoptosis, proliferation, cycle assays, WB, and RT-qPCR. Results: By analyzing the 80 cases data in TCGA, the authors unveiled molecular changes relevant to loss of chromosome 3 in UM as well as their poor survival. In addition, machine learning analysis identified three hub genes (GRIN2A, ACAN, and MMP9) as potential therapeutic targets. The differentially enriched pathways between the two groups were mainly about immune-system activity, and hub genes expression was also highly correlated with immune infiltration levels. Conclusion: Chromosome 3 loss has considerable clinical significance for UM, and GRIN2A may be useful in diagnosing, treating, and prognosticating the condition.

Immunomodulatory effect of Liangyi paste on the gut microbiota of mice.

Liangyi paste (LY) is a traditional Chinese medicine made from a mixture of Ginseng and Rehmanniae radix praeparata. The present study aimed to investigate the effects of LY on gut microbiota diversity in immunocompromised mice. The chemical composition of LY extract was analyzed using UPLC-Q-Orbitrap-MS/MS, and the differences in the structure and diversity of the intestinal microbiota of LY extract were examined using 16S rRNA. In this study, identified and analyzed 66 compounds from the LY. These compounds included 11 iridoids, 6 oligosaccharides, 21 protopanaxtriols, 23 protopanaxadiols, 2 OLE, 1 Ionone and 2 phenylethanoside, using advanced UPLC-Q-Orbitrap-MS/MS technology. Through the use of 16S rRNA analysis, the study found that LY significantly increased the relative abundance of the Firmicutes phylum in immunocompromised mice, while decreasing the abundance of the Proteobacteria and Actinobacteria phyla. At the genus level, LY significantly increased the relative abundance of beneficial bacteria such as Clostridium_sensu_stricto_l, Lactobacillus, and Limosilactobacillus in immunocompromised mice. Conversely, the paste extract decreased the relative abundance of harmful bacteria such as Enterococcus and Escherichia Shigella in immunocompromised mice. These findings highlight the potential of LY to serve as a natural dietary supplement for enhancing gut microbiota diversity and promoting gut health. The identification of numerous compounds within the paste extract demonstrates its complexity and potential as a source for further research and development. Additionally, the LY extract exerted a significant influence on both nucleotide and amino acid metabolism. To sum up, the findings suggest that the LY extract has the potential to modulate the structure and diversity of gut microbiota, as well as promote metabolic balance in immunocompromised mice.

Design, synthesis and bioevaluation of PI3Kα-selective inhibitors as potential colorectal cancer drugs.

The dysregulation of the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin signaling pathway has been implicated in various human cancers, and isoform-selective inhibitors targeting PI3Kα have received significant interest in recent years. In this study, we have designed and synthesized three series of substituted benzoxazole derivatives based on the clinical candidate TAK-117 (8a). A detailed structure-activity relationship (SAR) study has identified the optimal compound 18a bearing a quinoxaline scaffold. Compared to the control 8a, 18a exhibited 4.4-fold more potent inhibitory activity against PI3Kα (IC50: 2.5 vs 11 nM) and better isoform-selective profiles over other PI3Ks. In addition, 18a showed a 1.5-fold more potent antiproliferative effect against HCT-116 cell lines (IC50: 3.79 vs 5.80 µM) and a better selectivity over the normal tissue cells. The potential antitumor mechanism and in vitro metabolic stability of 18a were also investigated. Notably, pharmacokinetic assays indicated that 18a had a higher plasma exposure, a higher maximum concentration and shorter elimination time compared to 8a.

Virtual screening of novel mTOR inhibitors for the potential treatment of human colorectal cancer.

The abnormal activation of the mTOR pathway is closely related to the occurrence and progression of cancer, especially colorectal cancer. In this study, a rational virtual screening strategy has been established and MT-5, a novel mTOR inhibitor with a quinoline scaffold, was obtained from the ChemDiv database. MT-5 showed potent kinase inhibitory activity (IC50: 8.90 µM) and antiproliferative effects against various cancer cell lines, especially HCT-116 cells (IC50: 4.61 µM), and this was 2.2-fold more potent than that of the cisplatin control (IC50: 9.99 µM). Western blot, cell migration, cycle arrest, and apoptosis assays were performed with HCT-116 cells to investigate the potential anticancer mechanism of MT-5. Metabolic stability results in vitro indicated that MT-5 exhibited good stability profiles in artificial gastrointestinal fluids, rat plasma, and liver microsomes. In addition, the key contribution of the residues around the binding pocket of MT-5 in binding to the mTOR protein was also investigated from a computational perspective.

Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis.

Peritoneal metastasis is the leading cause of death for gastrointestinal cancers. The native and therapy-induced ascites ecosystems are not fully understood. Here, we characterize single-cell transcriptomes of 191,987 ascites cancer/immune cells from 35 patients with/without gastric cancer peritoneal metastasis (GCPM). During GCPM progression, an increase is seen of monocyte-like dendritic cells (DCs) that are pro-angiogenic with reduced antigen-presenting capacity and correlate with poor gastric cancer (GC) prognosis. We also describe the evolution of monocyte-like DCs and regulatory and proliferative T cells following therapy. Moreover, we track GC evolution, identifying high-plasticity GC clusters that exhibit a propensity to shift to a high-proliferative phenotype. Transitions occur via the recently described, autophagy-dependent plasticity program, paligenosis. Two autophagy-related genes (MARCKS and TXNIP) mark high-plasticity GC with poorer prognosis, and autophagy inhibitors induce apoptosis in patient-derived organoids. Our findings provide insights into the developmental trajectories of cancer/immune cells underlying GCPM progression and therapy resistance.

New cycloalkyl[b]thiophenylnicotinamide-based α-glucosidase inhibitors as promising anti-diabetic agents: Synthesis, in silico study, in vitro and in vivo evaluations.

In the present study, a series of cycloalkyl[b]thiophenylnicotinamide derivatives against α-glucosidase were synthesized, and evaluated for their in vitro and in vivo anti-diabetic potential. Most of the synthetic analogues exhibited superior α-glucosidase inhibitory effects than the standard drug acarbose (IC50 = 258.5 µM), in which compound 11b with cyclohexyl[b]thiophene core demonstrated the highest activity with an IC50 value of 9.9 µM and showed higher selectivity towards α-glucosidase over α-amylase by 7.4-fold. Fluorescence quenching experiment confirmed the direct binding of 11b with α-glucosidase, kinetics study revealed that 11b was a mixed-type inhibitor, and its binding mode was analyzed using molecular docking. Moreover, analogs compounds 6a-9b, 11b, 12b did not show in vitro cytotoxicity against LO2 and HepG2 cells. Finally, compound 11b exhibited in vivo hypoglycemic activity by reducing the blood glucose levels in sucrose-loaded rats.

Silencing METTL3 Stabilizes Atherosclerotic Plaques by Regulating the Phenotypic Transformation of Vascular Smooth Muscle Cells via the miR-375-3p/PDK1 Axis.

PURPOSE: Atherosclerosis (AS) is a primary cause of cardiovascular diseases. This study investigated the mechanism of methyltransferase-like 3 (METTL3) in AS plaques via modulating the phenotypic transformation of vascular smooth muscle cells (VSMCs). METHODS: AS mouse models and MOVAS cell models were established through high-fat diet and the treatment of ox-LDL, respectively. METTL3 expression in AS models was detected via RT-qPCR and Western blot. The AS plaques, lipid deposition, and collagen fibers were examined via histological staining. The levels of Ly-6c, α-SMA, and OPN were examined via Western blot. The blood lipid indexes in mouse aortic tissues were determined using kits. The proliferation and migration of MOVAS cells were detected via CCK-8 and Transwell assays. The m6A modification level of mRNA was quantified. The binding relationship between pri-miR-375 and DGCR8, and the enrichment of m6A on pri-miR-375 were detected via RIP. The binding relationship between miR-375-3p and 3-phosphoinositide-dependent protein kinase-1 (PDK1) was verified via dual-luciferase assay. Joint experiments were designed to investigate the role of miR-375-3P/PDK1 in the phenotypic transformation of VSMCs. RESULTS: METTL3 was highly expressed in AS. Silencing METTL3 alleviated AS progression and stabilized AS plaques in mice, and limited the phenotypic transformation of VSMCs induced by ox-LDL. Silencing METTL3 inhibited m6A level and decreased the binding of DGCR8 to pri-miR-375 and further limited miR-375-3p expression. miR-375-3p targeted PDK1 transcription. miR-375-3p upregulation or PDK1 downregulation facilitated the phenotypic transformation of VSMCs. CONCLUSION: METTL3-mediated m6A modification promoted VSMC phenotype transformation and made AS plaques more vulnerable via the miR-375-3p/PDK1 axis.

CD206+CD68+ mono-macrophages and serum soluble CD206 level are increased in antineutrophil cytoplasmic antibodies associated glomerulonephritis.

BACKGROUND: Antineutrophil Cytoplasmic Antibodies (ANCA) associated glomerulonephritis (AGN) is a group of autoimmune diseases and mono-macrophages are involved in its glomerular injuries. In this study, we aim to investigate the role of CD206+ mono-macrophages in AGN. METHODS: 27 AGN patients (14 active AGN, 13 remissive AGN) together with healthy controls (n = 9), disease controls (n = 6) and kidney function adjusted controls (n = 9) from Department of Nephrology, Ruijin hospital were recruited. Flow cytometry was used to study proportion of CD206+ cells in peripheral blood. Immunohistochemistry for CD206 staining was performed and CD206 expression was scored in different kidney regions. Serum soluble CD206 (sCD206) was measured by enzyme-linked immunosorbent assay (ELISA). We also generated murine myeloperoxidase (MPO) (muMPO) ANCA by immunizing Mpo-/- mice. Mouse bone marrow-derived macrophages (BMDMs) from wild C57BL/6 mice and peripheral blood mononuclear cell (PBMC) derived macrophages from healthy donors were treated with MPO ANCA with or without its inhibitor AZD5904 to investigate the effects of MPO-ANCA on CD206 expression. RESULTS: The proportion of peripheral CD206+CD68+ cells in active AGN patients were significantly higher than that in remissive patients (p < 0.001), healthy controls (p < 0.001) and kidney function adjusted controls (p < 0.001). Serum sCD206 level in active AGN patients was higher than that in healthy controls (p < 0.05) and remissive patients (p < 0.01). Immunohistochemistry showed CD206 was highly expressed in different kidney regions including fibrinoid necrosis or crescent formation, glomeruli, periglomerular and tubulointerstitial compartment in active AGN patients in comparison with disease controls. Further studies showed MPO ANCA could induce CD206 expression in BMDMs and PBMC derived macrophages and such effects could be reversed by its inhibitor AZD5904. CONCLUSION: ANCA could induce CD206 expression on mono-macrophages and CD206+ mono-macrophages are activated in AGN. CD206 might be involved in the pathogenesis of AAV and may be a potential target for the disease.

The Efficacy and Safety of Celecoxib in Addition to Standard Cancer Therapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The purpose of this meta-analysis was to evaluate the efficacy and safety of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in addition to standard anticancer therapy. Randomized controlled trials (RCTs) that evaluated the efficacy and safety of celecoxib-combined cancer therapy were systematically searched in PubMed and Embase databases. The endpoints were overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), objective response rate (ORR), disease control rate (DCR), pathological complete response (pCR), and adverse events (AEs). The results of 30 RCTs containing 9655 patients showed limited benefits in celecoxib-combined cancer therapy. However, celecoxib-combined palliative therapy prolonged PFS in epidermal growth factor receptor (EGFR) wild-type patients (HR = 0.57, 95%CI = 0.35-0.94). Moreover, despite a slight increase in thrombocytopenia (RR = 1.35, 95%CI = 1.08-1.69), there was no increase in other toxicities. Celecoxib combined with adjuvant therapy indicated a better OS (HR = 0.850, 95%CI = 0.725-0.996). Furthermore, celecoxib plus neoadjuvant therapy improved the ORR in standard cancer therapy, especially neoadjuvant therapy (overall: RR = 1.13, 95%CI = 1.03-1.23; neoadjuvant therapy: RR = 1.25, 95%CI = 1.09-1.44), but not pCR. Our study indicated that adding celecoxib to palliative therapy prolongs the PFS of EGFR wild-type patients, with good safety profiles. Celecoxib combined with adjuvant therapy prolongs OS, and celecoxib plus neoadjuvant therapy improves the ORR. Thus, celecoxib-combined cancer therapy may be a promising therapy strategy.

Cobalt-promoted synthesis of sulfurated oxindoles via radical annulation of N-arylacrylamides with disulfides.

An efficient radical annulation of N-arylacrylamides with disulfides is developed for the synthesis of sulfurated oxindoles. The reaction occurs in a facile manner using CoBr2 as both an initiator and a promoter for the first time and (NH4)2S2O8 as the oxidant. By controlling the CoBr2/(NH4)2S2O8 ratio, a wide range of sulfurated and brominated/sulfurated oxindoles are selectively prepared in good to excellent yields. The present protocol is simple and highly atom economical, and can tolerate a broad range of substrates.

Influence of impact velocity and impact attack angle of bullets on damage of human tissue surrogate -- ballistic gelatin.

PURPOSE: Terminal performance of a bullet in human body is critical for the treatment of gunshot injury and optimization of bullet design. The effects of the impact velocity (v0) and the impact attack angle (δ0) of the bullet on its terminal performance was investigated, using a new evaluation method (called expansion method) based on the expansion of cracks and the permanent cavity wall in ballistic gelatin. METHODS: Ballistic gelatin was used to simulate human body. The 7.62 mm × 39 mm rifle bullets with different v0 (600-760 m/s) and δ0 (0°-6°) were fired into the gelatin blocks. The gelatin block was cut into slices of about 20 mm thickness. The cracks and the permanent cavity on each slice were obtained manually. The damaged gelatin was determined using two methods: expanding the permanent cavity but ignoring the cracks, and expanding both the permanent cavity and the cracks. The relations between the damaged gelatin and v0 and δ0 were obtained using linear fitting method. RESULTS: According to the distribution of the damaged gelatin along the penetration depth, the damaged gelatin block could be divided into two parts: the less damaged part and the severely damaged part. The length of the less damaged part depends mostly on δ0; while the average damaged area of this part depends on both δ0 as well as v0. The cracks contributed significantly to the total volume of damaged gelatin, particularly when the expansion was larger than 1.9 mm. The total damaged gelatin increases with v0, δ0 and the expansion extent. The average length of equivalent cracks grew with v0 and δ0 when considering the cracks, and decreased with v0 when ignoring the cracks. CONCLUSION: The expansion method is suitable to investigate the influence of different factors of bullets on their terminal performance. The characteristics of the damaged gelatin have a linear relationship with the initial attack angle (δ0) and the initial velocity (v0) of the bullet.

[Corrigendum] Altered expression of miR­152 and miR­148a in ovarian cancer is related to cell proliferation.

Following the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 5D, the data panels selected to represent the 'SKOV3 with miR­148a mimics' and 'SKOV3 with Negative Control' experiments appeared to contain overlapping data, such that they may have been derived from the same original source. The authors have re­examined their original data, and realized how the errors in the compilation of Fig. 5 arose. The corrected version of Fig. 5, showing the correct data for the 'SKOV3 with miR­148a mimics' panel in Fig. 5D and the 'SKOV3 with Negative Control' panel in Fig. 5C, is shown on the next page. Note that these errors did not affect the overall conclusions reported in the study. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize for any inconvenience caused to the readership of the Journal. [the original article was published in Oncology Reports 27: 447-454, 2012; DOI: 10.3892/or.2011.1482].

Design, synthesis and biological evaluation of marine phidianidine-inspired derivatives against oxidized ldl-induced endothelial injury by activating Nrf2 anti-oxidation pathway.

Inhibition of oxidized low-density lipoprotein (oxLDL)-induced vascular endothelial cell (VEC) injury is one of the effective strategies for treating atherosclerosis. In the present study, a series of novel marine phidianidine-inspired indole-1,2,4-oxadiazoles was designed, synthesized, and evaluated for their effects against oxLDL-induced injury in VECs. Among them, compound D-6, displaying the most effective protective activity, was found to inhibit oxLDL-induced apoptosis and the expression of ICAM-1 and VCAM-1 in VECs. Mechanistic studies showed that D-6 could trigger Nrf2 nuclear translocation, subsequently resulting in increased expression of Nrf2 target gene HO-1. Meanwhile, D-6 suppressed the increase of ROS level and nuclear translocation of NF-κB induced by oxLDL. Importantly, Nrf2 knockdown attenuated the inhibition effects of D-6 on oxLDL-induced apoptosis, ROS production and NF-κB nuclear translocation. Collectively, our studies demonstrated that compound D-6 protected against oxLDL-induced endothelial injury by activating Nrf2/HO-1 anti-oxidation pathway.

Reliability and validity of the Pittsburgh Sleep Quality Index among frontline COVID-19 health care workers using classical test theory and item response theory.

STUDY OBJECTIVES: The applicability of sleep-related scales to frontline medical staff for the COVID-19 pandemic has not been fully proved, so sleep survey results lack credibility and accuracy, creating difficulties for the guidance and treatment of frontline medical staff with sleep disorders, which is not conducive to the prevention and control of COVID-19. This study sought to analyze the reliability and validity of the Pittsburgh Sleep Quality Index (PSQI) among frontline medical staff fighting the COVID-19 pandemic. METHODS: A network questionnaire survey was used to investigate the PSQI among frontline medical staff who fought COVID-19 in Wuhan, China from March 19 to April 15, 2020. Combined with classical test theory and item response theory, the content validity, internal consistency, construct validity, and other aspects of the PSQI were evaluated. RESULTS: According to classical test theory, content validity, criterion validity, and construct validity of the PSQI were good. But the internal consistency was better after the deletion of the "daytime dysfunction" subscale. With regard to item response theory, difficulty, the differential item function, and the Wright map performed well. CONCLUSIONS: The original PSQI showed acceptable applicability in frontline COVID-19 medical staff, and its characteristics moderately improved after the "daytime dysfunction" subscale was removed. CITATION: Wang L, Wu Y-X, Lin Y-Q, et al. Reliability and validity of the Pittsburgh Sleep Quality Index among frontline COVID-19 health care workers using classical test theory and item response theory. J Clin Sleep Med. 2022;18(2):541-551.

Survival landscape of different tumor regression grades and pathologic complete response in rectal cancer after neoadjuvant therapy based on reconstructed individual patient data.

BACKGROUND: Neoadjuvant therapy can lead to different tumor regression grades (TRG) in rectal cancer after neoadjuvant therapy. The purposes of this study are to investigate the relationships among TRG, pathologic complete response (pCR) and long-term survival, on the basis of reconstructed individual patient data (IPD). METHODS: The PubMed, Embase, Ovid and Cochrane CENTRAL databases were searched. The primary endpoint was to evaluate the survival landscape of different TRGs after neoadjuvant therapy and the secondary endpoint was to evaluate the associations between pCR and survival. IPD were reconstructed with Kaplan-Meier curves. RESULTS: The 10-year overall survival (OS) and 5-year disease-free survival (DFS) were clearly higher in the pCR group than in the non-pCR (npCR) group (80.5% vs. 48.3, 90.1% vs. 69.8%). Furthermore, the OS and DFS increased with improvement in tumor regression after neoadjuvant therapy. According to the IPD, the pCR group had longer OS (HR = 0.240, 95% CI = 0.177-0.325, p < 0.001) and DFS (HR = 0.274, 95% CI = 0.205-0.367, p < 0.001) than the npCR group. Better tumor regression was associated with better survival outcomes (p < 0.005). Direct calculation of published HR values yielded similar results. CONCLUSIONS: Our results indicate a positive relationship between better tumor regressions and improved survival benefits among the npCR group and patients with rectal cancer achieving pCR had much longer OS and DFS than patients achieving npCR, presenting a survival landscape of different TRGs and pCR in rectal cancer after neoadjuvant therapy.

Effect of stabilization malvids anthocyanins on the gut microbiota in mice with oxidative stress.

Malvids anthocyanins have been proven to have a significant antioxidant activity. However, natural anthocyanins are unstable as they are easily affected by temperature, light, and pH. They can produce copigmentation with caffeic acids, leading to the improvement of color stability. The objective of this research was to survey the anti-oxidative stress functional role of stabilization malvids anthocyanins (SMA) in vivo. Changes on the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), total antioxidant capacity (T-AOC) and malondialdehyde (MDA) in the serum and liver of oxidatively damaged mice of SMA were investigated. The effects of SMA on the diversity of gut microbiota in mice with oxidatively damage were also evaluated. Compared to oxidative damaged mice, SMA increased the activities of SOD, GSH-Px, CAT and T-AOC but decreased the levels of MDA in the serum and liver. SMA significantly changed the composition and diversity of the gut microbiota. Specifically, SMA increased the relative abundance of the phylum Firmicutes and decreased the relative abundance of the phyla Bacteroidetes. At the genus level, SMA significantly increased the relative abundance of Lactobacillus, but decreased the relative abundance of Bacteroides. In addition, SMA also reversed carbohydrate metabolism and amino acid metabolism to normal levels. It indicates that SMA could protect the body from oxidative damage and be used as a potential functional food to prevent diseases related to oxidative stress. PRACTICAL APPLICATIONS: Anthocyanins provide protective effects against harmful effect of oxidative stress. Natural anthocyanins are safer and nutritious as compared to synthetic pigments. However, their stability is poor. The previous research done by this group showed that the anthocyanins content of variety of Vitis amurensis Rupr was as high as 180 mg/(100 g·FW), and the content of malvids anthocyanidin in its ingredients was the highest of all. Malvids anthocyanin and caffeic acid are bonded to produce stabilized malvids anthocyanins (SMA) high hydrostatic pressure technology, which has better stability. Our results indicate that SMA could increased the activities of antioxidant enzymes and altered the composition and diversity of the gut microbiota in mice with oxidative damage. The study will help to deepen the understanding of antioxidative stress mechanism of SMA and lay a foundation for the application of natural anthocyanidin in health aspect.