Can low-dose intravenous bevacizumab be as effective as high-dose bevacizumab for cerebral radiation necrosis?

Although intravenous bevacizumab (IVBEV) is the most promising treatment for cerebral radiation necrosis (CRN), there is no conclusion on the optimal dosage. Our retrospective study aimed to compare the efficacy and safety of high-dose with low-dose IVBEV in treating CRN associated with radiotherapy for brain metastases (BMs). This paper describes 75 patients who were diagnosed with CRN secondary to radiotherapy for BMs, treated with low-dose or high-dose IVBEV and followed up for a minimum of 6 months. The clinical data collected for this study include changes in brain MRI, clinical symptoms, and corticosteroid usage before, during, and after IVBEV treatment. At the 3-month mark following administration of IVBEV, a comparison of two groups revealed that the median percentage decreases in CRN volume on T2-weighted fluid-attenuated inversion recovery and T1-weighted gadolinium contrast-enhanced image (T1CE), as well as the signal ratio reduction on T1CE, were 65.8% versus 64.8% (p = 0.860), 41.2% versus 51.9% (p = 0.396), and 37.4% versus 35.1% (p = 0.271), respectively. Similarly, at 6 months post-IVBEV, the median percentage reductions of the aforementioned parameters were 59.5% versus 62.0% (p = 0.757), 39.1% versus 31.3% (p = 0.851), and 35.4% versus 28.2% (p = 0.083), respectively. Notably, the incidence of grade ≥3 adverse events was higher in the high-dose group (n = 4, 9.8%) than in the low-dose group (n = 0). Among patients with CRN secondary to radiotherapy for BMs, the administration of high-dose IVBEV did not demonstrate superiority over low-dose IVBEV. Moreover, the use of high-dose IVBEV was associated with a higher incidence of grade ≥3 adverse events compared with low-dose IVBEV.

LDLa containing C-type lectin mediates phagocytosis of V.anguillarum and regulates immune effector genes in shrimp.

C-type lectins (CTLs) function as pattern recognition receptors (PRRs) by recognizing invading microorganisms, thereby triggering downstream immune events against infected pathogens. In this study, a novel CTL containing a low-density lipoprotein receptor class A (LDLa) domain was obtained from Litopenaeus vannamei, designed as LvLDLalec. Stimulation by the bacterial pathogen Vibrio anguillarum (V. anguillarum) resulted in remarkable up-regulation of LvLDLalec, as well as release of LvLDLalec into hemolymph. The rLvLDLalec protein possessed broad-spectrum bacterial binding and agglutinating activities, as well as hemocyte attachment ability. Importantly, LvLDLalec facilitated the bacterial clearance in shrimp hemolymph and protected shrimp from bacterial infection. Further studies revealed that LvLDLalec promoted hemocytes phagocytosis against V. anguillarum and lysosomes were involved in the process. Meanwhile, LvLDLalec participated in humoral immunity through activating and inducing nuclear translocation of Dorsal to regulate phagocytosis-related genes and antimicrobial peptides (AMPs) genes, thereby accelerated the removal of invading pathogens in vivo and improved the survival rate of L. vannamei. These results unveil that LvLDLalec serves as a PRR participate in cellular and humoral immunity exerting opsonin activity to play vital roles in the immune regulatory system of L. vannamei.

Robust prognostic model based on immune infiltration-related genes and clinical information in ovarian cancer.

Immune infiltration of ovarian cancer (OV) is a critical factor in determining patient's prognosis. Using data from TCGA and GTEx database combined with WGCNA and ESTIMATE methods, 46 genes related to OV occurrence and immune infiltration were identified. Lasso and multivariate Cox regression were applied to define a prognostic score (IGCI score) based on 3 immune genes and 3 types of clinical information. The IGCI score has been verified by K-M curves, ROC curves and C-index on test set. In test set, IGCI score (C-index = 0.630) is significantly better than AJCC stage (C-index = 0.541, p < 0.05) and CIN25 (C-index = 0.571, p < 0.05). In addition, we identified key mutations to analyse prognosis of patients and the process related to immunity. Chi-squared tests revealed that 6 mutations are significantly (p < 0.05) related to immune infiltration: BRCA1, ZNF462, VWF, RBAK, RB1 and ADGRV1. According to mutation survival analysis, we found 5 key mutations significantly related to patient prognosis (p < 0.05): CSMD3, FLG2, HMCN1, TOP2A and TRRAP. RB1 and CSMD3 mutations had small p-value (p < 0.1) in both chi-squared tests and survival analysis. The drug sensitivity analysis of key mutation showed when RB1 mutation occurs, the efficacy of six anti-tumour drugs has changed significantly (p < 0.05).

Risk of dietary intake of organochlorine pesticides among the childbearing-age women: A multiple follow-up study in North China.

Exposure to organochlorine pesticides (OCPs) can cause adverse health effects in the female population. We investigated the dietary OCP intake of childbearing-age women living in large agricultural areas of Northern China, as well as their associated health risks. Ten childbearing-age women were recruited during 2015-2016. Their weekly dietary intake diaries and food samples were collected over the course of five visits. The OCP residues of 322 food samples from seven categories (i.e., cereal, vegetable, fruit, fish, meat, egg, and milk) were analyzed by gas chromatography-mass spectrometry. The average concentrations of the total hexachlorocyclohexanes (ΣHCH), dichlorodiphenyltrichloroethanes and their metabolites (ΣDDX), endosulfans (ΣES), and dieldrin and endrin (ΣDrin) in all food categories were, overall, much lower than the maximum residue limits. Relative high mean residues of ΣDrin and ΣES were found in fruits (ΣDrin: 0.687 ng g-1 wet weight (w.w.), ΣES: 2.24 ng g-1 w.w.) and vegetables (ΣDrin: 0.690 ng g-1 w.w., ΣES: 2.11 ng g-1 w.w.). The estimated daily dietary intake (EDI) of these compounds was calculated, with mean levels of 10.6 (ΣES) > 4.37 (ΣDrin) > 1.51 (ΣHCH) > 0.850 (ΣDDX) ng kg-1 day-1. Women during the heating period (from January to March) tended to ingest more ΣHCH, ΣDDX, ΣDrin, and ΣES. Overall, women had no obvious non-carcinogenic and carcinogenic risks due to intake of OCPs, but 83.9% of them has potential carcinogenic risk, with estimated life carcinogenic risk (LCR) exceeding 10-6. Furthermore, women had a higher potential carcinogenic risk during the heating period (mean LCR: 1.33 × 10-5) than during the non-heating period (mean LCR: 8.50 × 10-6). ΣDrin was the dominant OCP responsible for health risks, followed by ΣHCH. We concluded that women in North China still have some dietary OCP intake, especially during the heating period.

Associations of Dietary Exposure to Organochlorine Pesticides from Plant-Origin Foods with Lipid Metabolism and Inflammation in Women: A Multiple Follow-up Study in North China.

This study explored effects of dietary OCP intake from plant-origin foods (cereals, fruits, and vegetables) consumption on lipid metabolism and inflammation of women using a multiple follow-up study. The results showed that dietary intake of p,p'-dichlorodiphenyltrichloroethane (DDT) [ß = - 10.11, 95% confidence interval (95%CI): - 17.32, - 2.905] and o,p'-dichlorodiphenyldichloroethylene (DDE) (ß = - 6.077, 95%CI: - 9.954, - 2.200) were overall negatively associated with serum high-density lipoprotein cholesterol (HDL), whereas other OCPs were not. Serum interleukin (IL)-8 was positively associated with intake of dieldrin (ß = 0.390, 95%CI: 0.105, 0.674), endosulfan-ß (ß = 0.361, 95%CI: 0.198, 0.523), total endosulfan (ß = 0.136, 95%CI: 0.037, 0.234), and total OCPs (ß = 0.084, 95%CI: 0.016, 0.153), and negatively correlated with intake of p,p'-DDE (ß = - 2.692, 95%CI: - 5.185, - 0.198). We concluded that dietary intake of some individual DDT-, DDE- dieldrin-, and endosulfan-class chemicals from plant-origin foods may interfere with lipid metabolism and inflammation responses.

Identification of Key Genes Related to Lung Squamous Cell Carcinoma Using Bioinformatics Analysis.

Lung squamous cell carcinoma (LUSC) is often diagnosed at the advanced stage with poor prognosis. The mechanisms of its pathogenesis and prognosis require urgent elucidation. This study was performed to screen potential biomarkers related to the occurrence, development and prognosis of LUSC to reveal unknown physiological and pathological processes. Using bioinformatics analysis, the lung squamous cell carcinoma microarray datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were analyzed to identify differentially expressed genes (DEGs). Furthermore, PPI and WGCNA network analysis were integrated to identify the key genes closely related to the process of LUSC development. In addition, survival analysis was performed to achieve a prognostic model that accomplished good prediction accuracy. Three hundred and thirty-seven up-regulated and 119 down-regulated genes were identified, in which four genes have been found to play vital roles in LUSC development, namely CCNA2, AURKA, AURKB, and FEN1. The prognostic model contained 5 genes, which were all detrimental to prognosis. The AUC of the established prognostic model for predicting the survival of patients at 1, 3, and 5 years was 0.692, 0.722, and 0.651 in the test data, respectively. In conclusion, this study identified several biomarkers of significant interest for additional investigation of the therapies and methods of prognosis of lung squamous cell carcinoma.

Immobilized bacteria with pH-response hydrogel for self-healing of concrete.

Concrete is significant for construction. A problem in application is the appearance of cracks that will damage its strength. An autogenous crack-healing mechanism based on bacteria receives increasing attention in recent years. The bacteria are able to form calcium carbonate (CaCO3) precipitations in suitable conditions to protect and reinforce the concrete. However, a large number of spores are crushed in aged specimens, resulting in a loss of viability. A new kind of hydrogel crosslinked by alginate, chitosan and calcium ions was introduced in this study. It was observed that the addition of chitosan improved the swelling properties of calcium alginate. Opposite pH response to calcium alginate was observed when the chitosan content in the solution reached 1.0%. With an addition of 1.0% chitosan in hydrogel beads, 10.28% increase of compressive strength and 13.79% increase of flexural strength to the control were observed. The results reveal self-healing properties of concretes. A healing crack of 4 cm length and 1 mm width was observed when using cement PO325, with the addition of bacterial spores (2.54-3.07 × 105/cm3 concrete) encapsulated by hydrogel containing no chitosan.

Granulocytic myeloid-derived suppressor cell population increases with the severity of alcoholic liver disease.

Alcoholic liver disease (ALD) is a progressive liver disease that can cause a series of complications, including cirrhosis, liver failure and hepatocellular carcinoma. Granulocytic myeloid-derived suppressor cell (gMDSC) populations have been observed to expand in various liver diseases and to inhibit innate and adaptive immunity in patients with liver disease. However, the characteristics of gMDSCs in patients with ALD have not been studied. We studied 24 healthy controls (HCs) and 107 patients with ALD and found an accumulation of gMDSCs in the peripheral blood of patients with alcoholic liver cirrhosis (ALC). Furthermore, ALC patients with a poor prognosis displayed a significant increase in peripheral gMDSCs and showed an increased capacity for arginase I production compared to HCs. In contrast, plasma arginase I levels in ALC patients were negatively correlated with total bilirubin and international normalized ratio, two key parameters of liver damage. Importantly, gMDSCs accumulated in the livers of ALC patients, and the frequency of liver gMDSCs significantly correlated with that of peripheral gMDSCs. In addition, gMDSC enrichment in vitro significantly inhibited the function of natural killer (NK) cells, perhaps preventing the NK-induced apoptosis of hepatic stellate cells. In summary, increased peripheral and intrahepatic gMDSC populations are present in patients with ALC and may contribute to enhancing the severity of liver cirrhosis.

Plasma levels of soluble ST2, but not IL-33, correlate with the severity of alcoholic liver disease.

Alcoholic liver disease (ALD) is a complication that is a burden on global health and economy. Interleukin-33 (IL-33) is a newly identified member of the IL-1 cytokine family and is released as an "alarmin" during inflammation. Soluble suppression of tumourigenicity 2 (sST2), an IL-33 decoy receptor, has been reported as a new biomarker for the severity of systemic and highly inflammatory diseases. Here, we found the levels of plasma sST2, increased with the disease severity from mild to severe ALD. Importantly, the plasma sST2 levels in ALD patients not only correlated with scores for prognostic models (Maddrey's discriminant function, model for end-stage liver disease and Child-Pugh scores) and indexes for liver function (total bilirubin, international normalized ratio, albumin, and cholinesterase) but also correlated with neutrophil-associated factors as well as some proinflammatory cytokines. In vitro, lipopolysaccharide-activated monocytes down-regulated transmembrane ST2 receptor but up-regulated sST2 mRNA and protein expression and produced higher levels of tumour necrosis factor-α (TNF-α). By contrast, monocytes pretreated with recombinant sST2 showed decreased TNF-α production. In addition, although plasma IL-33 levels were comparable between healthy controls and ALD patients, we found the IL-33 expression in liver tissues from ALD patients was down-regulated at both RNA and protein levels. Immunohistochemical staining further showed that the decreased of IL-33-positive cells were mainly located in liver lobule area. These results suggested that sST2, but not IL-33, is closely related to the severity of ALD. Consequently, sST2 could be used as a potential biomarker for predicting the prognosis of ALD.

CopA Protects Streptococcus suis against Copper Toxicity.

Streptococcus suis is a zoonotic pathogen that causes great economic losses to the swine industry and severe threats to public health. A better understanding of its physiology would contribute to the control of its infections. Although copper is an essential micronutrient for life, it is toxic to cells when present in excessive amounts. Herein, we provide evidence that CopA is required for S. suis resistance to copper toxicity. Quantitative PCR analysis showed that copA expression was specifically induced by copper. Growth curve analyses and spot dilution assays showed that the ΔcopA mutant was defective in media supplemented with elevated concentrations of copper. Spot dilution assays also revealed that CopA protected S. suis against the copper-induced bactericidal effect. Using inductively coupled plasma-optical emission spectroscopy, we demonstrated that the role of CopA in copper resistance was mediated by copper efflux. Collectively, our data indicated that CopA protects S. suis against the copper-induced bactericidal effect via copper efflux.

IL-33-ST2 Axis in Liver Disease: Progression and Challenge.

The new member of the IL-1 family, interleukin-33 (IL-33), participates in the progression of a variety of diseases through binding with its receptor ST2. Recently, much clinical evidence and experimental data have indicated that IL-33 is associated with various liver diseases. This review primarily addresses the relationship between IL-33 and several hepatic diseases. IL-33 can alleviate high-fat diet- (HFD-) induced hepatic steatosis and insulin resistance, and IL-33 acts as an alarmin, which quickly triggers the immune system to respond to virus invasion and toxic damage to the liver. However, when liver injury is chronic, IL-33 promotes Th2 reactions and hepatic stellate cell (HSC) activity, facilitating progression to liver fibrosis. The complicated functions of IL-33 should be considered before its clinical application.

LAPTM4B counteracts ferroptosis via suppressing the ubiquitin-proteasome degradation of SLC7A11 in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide, necessitating the identification of novel therapeutic targets. Lysosome Associated Protein Transmembrane 4B (LAPTM4B) is involved in biological processes critical to cancer progression, such as regulation of solute carrier transporter proteins and metabolic pathways, including mTORC1. However, the metabolic processes governed by LAPTM4B and its role in oncogenesis remain unknown. In this study, we conducted unbiased metabolomic screens to uncover the metabolic landscape regulated by LAPTM4B. We observed common metabolic changes in several knockout cell models suggesting of a role for LAPTM4B in suppressing ferroptosis. Through a series of cell-based assays and animal experiments, we demonstrate that LAPTM4B protects tumor cells from erastin-induced ferroptosis both in vitro and in vivo. Mechanistically, LAPTM4B suppresses ferroptosis by inhibiting NEDD4L/ZRANB1 mediated ubiquitination and subsequent proteasomal degradation of the cystine-glutamate antiporter SLC7A11. Furthermore, metabolomic profiling of cancer cells revealed that LAPTM4B knockout leads to a significant enrichment of ferroptosis and associated metabolic alterations. By integrating results from cellular assays, patient tissue samples, an animal model, and cancer databases, this study highlights the clinical relevance of the LAPTM4B-SLC7A11-ferroptosis signaling axis in NSCLC progression and identifies it as a potential target for the development of cancer therapeutics.

Pd-Decorated Cu2O-Ag Catalyst Promoting CO2 Electroreduction to C2H4 by Optimizing CO Intermediate Adsorption and Hydrogenation.

Electrocatalytic CO2 reduction reaction (CO2RR) to high value-added products, such as ethylene (C2H4), offers a promising approach to achieve carbon neutrality. Although recent studies have reported that a tandem catalyst (for example, Cu-Ag systems) exhibits advantage in C2H4 production, its practical application is largely inhibited by the following: (1) a traditional tandem catalyst cannot effectively stabilize the *CO intermediate, resulting in sluggish C-C coupling, and (2) inadequate H2O activation ability hinders the hydrogenation of intermediates. To break through the above bottleneck, herein, palladium (Pd) was introduced into Cu2O-Ag, a typical conventional tandem catalyst, to construct a Cu2O-Pd-Ag ternary catalyst. Extensive experiment and density functional theory calculation prove that Pd can efficiently stabilize the *CO intermediate and promote the H2O activation, which contributes to the C-C coupling and intermediate hydrogenation, the key steps in the conversion of CO2 to C2H4. Beneficial to the efficient synergy of Cu2O, Pd, and Ag, the optimal Cu2O-Pd-Ag ternary catalyst achieves CO2RR toward C2H4 with a faradaic efficiency of 63.2% at -1.2 VRHE, which is higher than that achieved by Cu2O-Ag and most of other reported catalysts. This work is a fruitful exploration of a rare ternary catalyst, providing a new route for constructing an efficient CO2RR electrocatalyst.

Multiomics profiling reveals the benefits of gamma-delta (γδ) T lymphocytes for improving the tumor microenvironment, immunotherapy efficacy and prognosis in cervical cancer.

BACKGROUND: As an unconventional subpopulation of T lymphocytes, γδ T cells can recognize antigens independently of major histocompatibility complex restrictions. Recent studies have indicated that γδ T cells play contrasting roles in tumor microenvironments-promoting tumor progression in some cancers (eg, gallbladder and leukemia) while suppressing it in others (eg, lung and gastric). γδ T cells are mainly enriched in peripheral mucosal tissues. As the cervix is a mucosa-rich tissue, the role of γδ T cells in cervical cancer warrants further investigation. METHODS: We employed a multiomics strategy that integrated abundant data from single-cell and bulk transcriptome sequencing, whole exome sequencing, genotyping array, immunohistochemistry, and MRI. RESULTS: Heterogeneity was observed in the level of γδ T-cell infiltration in cervical cancer tissues, mainly associated with the tumor somatic mutational landscape. Definitely, γδ T cells play a beneficial role in the prognosis of patients with cervical cancer. First, γδ T cells exert direct cytotoxic effects in the tumor microenvironment of cervical cancer through the dynamic evolution of cellular states at both poles. Second, higher levels of γδ T-cell infiltration also shape the microenvironment of immune activation with cancer-suppressive properties. We found that these intricate features can be observed by MRI-based radiomics models to non-invasively assess γδ T-cell proportions in tumor tissues in patients. Importantly, patients with high infiltration levels of γδ T cells may be more amenable to immunotherapies including immune checkpoint inhibitors and autologous tumor-infiltrating lymphocyte therapies, than to chemoradiotherapy. CONCLUSIONS: γδ T cells play a beneficial role in antitumor immunity in cervical cancer. The abundance of γδ T cells in cervical cancerous tissue is associated with higher response rates to immunotherapy.

Dosimetric analysis of brachial plexopathy after stereotactic body radiotherapy: Significance of organ delineation.

OBJECTIVES: Examine the significance of contouring the brachial plexus (BP) for toxicity estimation and select metrics for predicting radiation-induced brachial plexopathy (RIBP) after stereotactic body radiotherapy. MATERIALS AND METHODS: Patients with planning target volume (PTV) ≤ 2 cm from the BP were eligible. The BP was contoured primarily according to the RTOG 1106 atlas, while subclavian-axillary veins (SAV) were contoured according to RTOG 0236. Apical PTVs were classified as anterior (PTV-A) or posterior (PTV-B) PTVs. Variables predicting grade 2 or higher RIBP (RIBP2) were selected through least absolute shrinkage and selection operator regression and logistic regression. RESULTS: Among 137 patients with 140 BPs (median follow-up, 32.1 months), 11 experienced RIBP2. For patients with RIBP2, the maximum physical dose to the BP (BP-Dmax) was 46.5 Gy (median; range, 35.7 to 60.7 Gy). Of these patients, 54.5 % (6/11) satisfied the RTOG limits when using SAV delineation; among them, 83.3 % (5/6) had PTV-B. For patients with PTV-B, the maximum physical dose to SAV (SAV-Dmax) was 11.2 Gy (median) lower than BP-Dmax. Maximum and 0.3 cc biologically effective doses to the BP based on the linear-quadratic-linear model (BP-BEDmax LQL and BP-BED0.3cc LQL, α/ß = 3) were selected as predictive variables with thresholds of 118 and 73 Gy, respectively. CONCLUSION: Contouring SAV may significantly underestimate the RIBP2 risk in dosimetry, especially for patients with PTV-B. BP contouring indicated BP-BED0.3cc LQL and BP-BEDmax LQL as potential predictors of RIBP2.

ELM-Based Adaptive Faster Fixed-Time Control of Robotic Manipulator Systems.

This article addresses the problem of fast fixed-time tracking control for robotic manipulator systems subject to model uncertainties and disturbances. First, on the basis of a newly constructed fixed-time stable system, a novel faster nonsingular fixed-time sliding mode (FNFTSM) surface is developed to ensure a faster convergence rate, and the settling time of the proposed surface is independent of initial values of system states. Subsequently, an extreme learning machine (ELM) algorithm is utilized to suppress the negative influence of system uncertainties and disturbances. By incorporating fixed-time stable theory and the ELM learning technique, an adaptive fixed-time sliding mode control scheme without knowing any information of system parameters is synthesized, which can circumvent chattering phenomenon and ensure that the tracking errors converge to a small region in fixed time. Finally, the superior of the proposed control strategy is substantiated with comparison simulation results.

Impact of aluminum exposure on oxidative stress, intestinal changes and immune responses in red swamp crayfish (Procambarus clarkii).

Aluminum (Al) is an abundant metal that has been classified as a threatening pollutant due to indiscriminate use and anthropogenic activities. This study aimed to evaluate the impacts of Al on crayfish (Procambarus clarkii), including biochemical change, histological alteration, gut microbial community diversification, and immune changes. The bioaccumulation of Al was detected in the hemolymph and intestine of crayfish after Al exposure at different time points. Results showed that Al exposure significantly induced oxidative stress and caused pathohistological changes on intestinal barrier structures in crayfish. It was found that the intestinal microbiota was affected by retained Al and the intestinal community diversity was changed after Al treated in the crayfish. Furthermore, Al exposure affected the immunity in crayfish, by altering the expression of a set of immune-related genes, as well as reducing the phenoloxidase and lysozyme activities. Moreover, Al exposure promoted hemocytes apoptosis and impaired hemophagocytic capacity against Vibro parahamolyticus, resulting in higher mortality of crayfish upon bacterial infection. Taken these results together, we conclude that excessive Al exposure caused adverse effects on multiple biological processes of crayfish and Al pollution is a potential threat to crayfish culture.

Antibacterial and immunoregulatory activity of an antimicrobial peptide hepcidin in loach (Misgurnus anguillicaudatus).

Antimicrobial peptides (AMPs) are members of humoral immunity and particpate in resisting microbial invasion. In this study, an AMP gene hepcidin was obtained from the oriental loach Misgurnus anguillicaudatus and named Ma-Hep. This Ma-Hep encodes a peptide of 90 amino acids, with a predicted active peptide segment (Ma-sHep) of 25 amino acids at C terminus. Stimulation by a bacterial pathogen Aeromonas hydrophila resulted in significant up-regulation of Ma-Hep transcripts in loach midgut, head kidney, and gill. Ma-Hep and Ma-sHep proteins were expressed in Pichia pastoris and their antibacterial activity was examined. Results showed that Ma-sHep possessed stronger antibacterial activity against various Gram-positive and Gram-negative bacteria, compared to Ma-Hep. Scanning electron microscopy showed that Ma-sHep might kill bacteria by destroying bacterial cell membranes. Moreover, we found that Ma-sHep had an inhibitory effect on blood cell apoptosis induced by A. hydrophila and facilitated the bacterial phagocytosis and clearance in loach. Histopathological analysis indicated Ma-sHep could protect liver and gut of loach from bacterial infection. Ma-sHep has high thermal stability and PH stability, which is conducive to further feed addition. Feed supplemented with Ma-sHep expressing yeast improved the intestinal flora of loach by increasing the dominant bacteria and decreasing the harmful bacteria. Feed supplemented with Ma-sHep expressing yeast also regulated the expression of inflammatory related factors in various tissues of loach and reduced the mortality of loach upon bacterial infection. These findings show that the antibacterial peptide Ma-sHep is involved in the antibacterial defense of loach and can be used as a candidate for new antimicrobial agents in aquaculture.

[Prognosis Analysis of Early-stage Non-small Cell Lung Cancer Patients Treated with Stereotactic Body Radiotherapy].

BACKGROUND: With the aging of the population and the increased importance of lung cancer screening, the number of early-stage lung cancer patients has been on the rise in recent years, which can be classified into operable early-stage lung cancer and inoperable early-stage lung cancer. The most common pathological type is non-small cell lung cancer (NSCLC). Stereotactic body radiation therapy (SBRT) is the optimal treatment for inoperable early-stage NSCLC. The aim of this study was to investigate the prognosis of early-stage NSCLC patients treated with SBRT and its influencing factors in order to reduce the side effects of radiotherapy and improve the survival and quality of life. METHODS: Clinical data and follow-up outcomes of early-stage NSCLC patients treated with SBRT in our hospital from August 2010 to August 2020 were collected. Kaplan-Meier method was used to assess the prognosis, and the Cox proportional risk model was used for multivariate prognostic analysis. RESULTS: A total of 165 patients were included with a median follow-up time of 43.2 (range: 4.8-132.1) mon. The local control (LC) rates at 1-yr, 2-yr and 5-yr were 98.1%, 94.8% and 86.5% respectively. Karnofsky performance status (KPS) score greater than 80 was an independent prognostic factor for LC (P=0.02). The overall survival (OS) rates at 1-yr, 2-yr and 5-yr were 97.6%, 93.0% and 68.9% respectively. A biological equivalent dose when α/ß=10 (BED10) greater than 132 Gy was an independent prognostic factor for OS (P=0.04). Progression-free survival (PFS) rates at 1-yr, 2-yr and 5-yr were 93.3%, 79.5% and 55.3% respectively. The distance metastasis free survival (DMFS) rates at 1-yr, 2-yr and 5-yr were 94.5%, 83.2% and 58.4% respectively. BED10 greater than 150 Gy was an independent prognostic factor for DMFS (P=0.02). The regional control (RC) rates at 1-yr, 2-yr and 5-yr were 98.8%, 95.4% and 87.9% respectively. CONCLUSIONS: SBRT is effective in treating early-stage NSCLC. KPS greater than 80 is an independent prognostic factor for LC; BED10 greater than 132 Gy is an independent prognostic factor for OS; BED10 greater than 150 Gy is an independent prognostic factor for DMFS.

Impact of radiation dose to the immune system on disease progression and survival for early-stage non-small cell lung cancer treated with stereotactic body radiation therapy.

OBJECTIVES: Although the effects of estimated dose of radiation to immune cells (EDRIC) in stage III NSCLC, LA-NSCLC, LS-SCLC and esophageal cancer on clinical outcomes have been studied, its impact in early-stage non-small cell lung cancer (ES-NSCLC) is unknown. In this study, we evaluated the role of EDRIC and identified the factors influencing EDRIC in this population. METHODS AND MATERIALS: We retrospectively analyzed 211 pathologically confirmed ES-NSCLC patients who were treated with SBRT between 2007 and 2020. EDRIC was calculated based on the model developed by Jin et al. and improved by Ladbury et al. Kaplan-Meier method and Cox proportional hazards regression were adopted to estimate CSS, PFS, LPFS, and DMFS. Pearson correlation was used to assess the correlation between variables. We further validated our findings in an independent cohort of 119 patients with ES-NSCLC. RESULTS: A total of 211 patients were included with median follow-up of 48 months in the training cohort. The median EDRIC was 2.178 Gy (range: 0.426-6.015). GTV showed a positive correlation with EDRIC (r = 0.707, P = 0.000). In multivariate analysis, higher EDRIC was significantly associated with worse CSS (HR = 1.468, P = 0.009) and DMFS (HR = 1.491, P = 0.016). Considering each EDRIC quartile, there was a significant difference in CSS between 1st and 4th and 1st and 3rd quartile (P = 0.000, P = 0.004, respectively); and DMFS between 1st and 4th,1st and 3rd, and 1st and 2nd quartile (P = 0.000, P = 0.000, P = 0.008, respectively). In the subgroup and validation cohort, EDRIC was also the important prognostic predictor of CSS and DMFS using multivariate analysis. CONCLUSION: EDRIC was an independent predictor of CSS and DMFS in ES-NSCLC, and it was affected by GTV and tumor location. Though EDRIC is a critical determinant of treatment outcomes, it is quantifiable and potentially modifiable. Additional researches exploring the feasibility of achieving lower EDRIC while maintaining adequate tumor coverage during radiotherapy are warranted.