Global profiling of transcriptome, proteome and 2-hydroxyisobutyrylome in radioresistant lung adenocarcinoma cell.

Radioresistance contributes to metastasis and recurrence in non-small cell lung cancer (NSCLC) patients. However, the underlying mechanism remains unclear. To provide novel clues, a complete multi-omics map of a radioresistant cancer cell line has been profiled. In this article, a lung adenocarcinoma cell line, radioresistant A549 (RA549), was generated by exposure to a series of irradiation. Subsequently, we adopted transcriptome, quantitative proteome and lysine 2-hydroxyisobutyrylome to construct a differential profile on the transcriptional to post-tanslational levels on A549 and RA549 cell lines, respectively. Our analysis revealed 920 significantly differentially expressed genes and 699 proteins. Furthermore, 2-hydroxyisobutyrylome identified 30,089 Khib modified sites on 4635 proteins, indicating that Khib modifications play vital role in regulating NSCLC radioresistance. Multi-omics combined analysis identified 19 significantly differentially expressed genes/proteins in total. Meanwhile, we found that EGFR, a well-known lung cancer-related receptor, was upregulated at both the protein and Khib modification levels in RA549. Further gain/loss of function experiments showed that Khib modified EGFR level positively correlates with NSCLC cell radioresistance. Taken together, our findings report that Khib-modified proteins enhanced resistance to radiation and represent promising therapeutic targets.

The effectiveness of targeted therapy for recurrence or metastasis adenoid cystic carcinoma: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Several clinical studies have demonstrated the potential of molecular-targeted agents for the treatment of recurrent or metastatic adenoid cystic carcinoma (R/M ACC). However, there is currently no consensus regarding the efficacy of molecular-targeted agents for patients with R/M ACC. This study aimed to evaluate the therapeutic efficacy and safety of molecular-targeted agents in patients with R/M ACC and provide insights to guide clinical decision-making. MATERIALS AND METHODS: Five databases (PubMed, Embase, Cochrane, ProQuest, and Scopus) were searched based on the search strategy and selection criteria. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints were disease control rate (DCR), overall survival (OS), metastatic sites, and adverse events (AE). Pooled estimates were calculated using a random-effects meta-analysis. RESULTS: Finally, 28 studies, involving 849 patients, were included. The most common metastatic sites were the lungs, bones, liver, lymph nodes, and kidneys. The pooled ORR was 4.0% (95% CI, 0.7-8.8%), the pooled DCR was 80.5% (95% CI, 72.2%-87.7%). Compared with other-target drugs, multiple kinase inhibitors (MKIs) improved the ORR (pooled ORR for single-target drugs vs. MKIs: 5.9% vs. 0%). The combination of MKIs and immune checkpoint inhibitors (ICIs) had a significantly higher ORR (17.9% in the axitinib + avelumab group). The pooled median PFS and OS were 8.35 and 25.62 months, respectively. MKIs improved the median PFS compared to other-target drugs (9.43 months vs 5.06 months). In addition, the most common adverse events (AEs) were fatigue (51.6%), hypertension (44.2%), and nausea (40.0%), followed by hand-foot skin syndrome (36.8%), diarrhoea (34.4%), weight loss (34.2%), anorexia (31.8%), rash (31.7%), and headache (29.0%). CONCLUSION: The findings of this study suggest that MKIs have a better therapeutic efficacy than single-target drugs in patients with R/M ACC. Future studies are warranted to verify the synergistic role of the combination strategy of MKIs plus ICIs, given the limited number of studies on this topic conducted and published to date.

Spatial metabolomics reveals key features of hippocampal lipid changes in rats with postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is a common complication after cardiac surgery. Numerous evidence suggest that dysregulation of lipid metabolism is associated with cognitive impairment; however, its precise role in the development of POCD is still obscure. In this study, we established a cardiopulmonary bypass (CPB) model in rats and employed the Barnes maze to assess cognitive function, selecting POCD rats for subsequent experimentation. Utilizing mass spectrometry imaging, we detected plenty of lipids accumulates within the hippocampal CA1in the POCD group. Immunofluorescence staining revealed a significant reduction in the fluorescence intensity of calcium-independent phospholipases A2 (iPLA2) in the POCD group compared to the control, while serine palmitoyl transferase (SPT) was markedly increased in the POCD group. Transmission electron microscopy revealed that the number of synapses in hippocampal CA1decreased significantly and postsynaptic density became thinner in POCD group. Furthermore, after reversing the metabolic disorders of iPLA2 and SPT in the rat brain with docosahexaenoic acid and myriocin, the incidence of POCD after CPB was significantly reduced and the disrupted lipid metabolism in the hippocampus was also normalized. These findings may offer a novel perspective for exploring the etiology and prevention strategies of POCD after CPB.

Composite Aerogel Scaffolds Containing Flexible Silica Nanofiber and Tricalcium Phosphate Enable Skin Regeneration.

Poor hemostatic ability and less vascularization at the injury site could hinder wound healing as well as adversely affect the quality of life (QOL). An ideal wound dressing should exhibit certain characteristics: (a) good hemostatic ability, (b) rapid wound healing, and (c) skin appendage formation. This necessitates the advent of innovative dressings to facilitate skin regeneration. Therapeutic ions, such as silicon ions (Si4+) and calcium ions (Ca2+), have been shown to assist in wound repair. The Si4+ released from silica (SiO2) can upregulate the expression of proteins, including the vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA), which is conducive to vascularization; Ca2+ released from tricalcium phosphate (TCP) can promote the coagulation alongside upregulating the expression of cell migration and cell differentiation related proteins, thereby facilitating the wound repair. The overarching objective of this study was to exploit short SiO2 nanofibers along with the TCP to prepare TCPx@SSF aerogels and assess their wound healing ability. Short SiO2 nanofibers were prepared by electrospinning and blended with varying proportions of TCP to afford TCPx@SSF aerogel scaffolds. The TCPx@SSF aerogels exhibited good cytocompatibility in a subcutaneous implantation model and manifested a rapid hemostatic effect (hemostatic time 75 s) in a liver trauma model in the rabbit. These aerogel scaffolds also promoted skin regeneration and exhibited rapid wound closure, epithelial tissue regeneration, and collagen deposition. Taken together, TCPx@SSF aerogels may be valuable for wound healing.

Selenium and Bacillus proteolyticus SES increased Cu-Cd-Cr uptake by ryegrass: highlighting the significance of key taxa and soil enzyme activity.

Many studies have focused their attention on strategies to improve soil phytoremediation efficiency. In this study, a pot experiment was carried out to investigate whether Se and Bacillus proteolyticus SES promote Cu-Cd-Cr uptake by ryegrass. To explore the effect mechanism of Se and Bacillus proteolyticus SES, rhizosphere soil physiochemical properties and rhizosphere soil bacterial properties were determined further. The findings showed that Se and Bacillus proteolyticus SES reduced 23.04% Cu, 36.85% Cd, and 9.85% Cr from the rhizosphere soil of ryegrass. Further analysis revealed that soil pH, organic matter, soil enzyme activities, and soil microbial properties were changed with Se and Bacillus proteolyticus SES application. Notably, rhizosphere key taxa (Bacteroidetes, Actinobacteria, Firmicutes, Patescibacteria, Verrucomicrobia, Chloroflexi, etc.) were significantly enriched in rhizosphere soil of ryegrass, and those taxa abundance were positively correlated with soil heavy metal contents (P < 0.01). Our study also demonstrated that in terms of explaining variations of soil Cu-Cd-Cr content under Se and Bacillus proteolyticus SES treatment, soil enzyme activities (catalase and acid phosphatase) and soil microbe properties showed 42.5% and 12.2% contributions value, respectively. Overall, our study provided solid evidence again that Se and Bacillus proteolyticus SES facilitated phytoextraction of soil Cu-Cd-Cr, and elucidated the effect of soil key microorganism and chemical factor.

Single-cell RNA sequencing reveals recruitment of the M2-like CCL8high macrophages in Lewis lung carcinoma-bearing mice following hypofractionated radiotherapy.

BACKGROUND: Tumor-associated macrophages (TAMs) play a pivotal role in reshaping the tumor microenvironment following radiotherapy. The mechanisms underlying this reprogramming process remain to be elucidated. METHODS: Subcutaneous Lewis lung carcinoma (LLC) murine model was treated with hypofrationated radiotherapy (8 Gy × 3F). Single-cell RNA sequencing was utilized to identify subclusters and functions of TAMs. Multiplex assay and enzyme-linked immunosorbent assay (ELISA) were employed to measure serum chemokine levels. Bindarit was used to inhibit CCL8, CCL7, and CCL2. The infiltration of TAMs after combination treatment with hypofractionated radiotherapy and Bindarit was quantified with flow cytometry, while the influx of CD206 and CCL8 was assessed by immunostaining. RESULTS: Transcriptome analysis identified a distinct subset of M2-like macrophages characterized by elevated Ccl8 expression level following hypofractionated radiotherapy in LLC-bearing mice. Remarkbly, hypofractionated radiotherapy not only promoted CCL8high macrophages infiltration but also reprogrammed them by upregulating immunosuppressive genes, thereby fostering an immunosuppressive tumor microenvironment. Additioinally, hypofractionated radiotherapy enhanced the CCL signaling pathway, augmenting the pro-tumorigenic functions of CCL8high macrophages and boosting TAMs recruitment. The adjunctive treatment combining hypofractionated radiotherapy with Bindarit effectively reduced M2 macrophages infiltration and prolonged the duration of local tumor control. CONCLUSIONS: Hypofractionated radiotherapy enhances the infiltration of CCL8high macrophages and amplifies their roles in macrophage recruitment through the CCL signaling pathway, leading to an immunosuppressive tumor microenvironment. These findings highlight the potential of targeting TAMs and introduces a novel combination to improve the efficacy of hypofractionated radiotherapy.

Gastrointestinal manifestations of critical ill heatstroke patients and their associations with outcomes: A multicentre, retrospective, observational study.

BACKGROUND: Extreme heat exposure is a growing health problem, and the effects of heat on the gastrointestinal (GI) tract is unknown. This study aimed to assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. AIM: To assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. METHODS: Patients admitted to the intensive care unit (ICU) due to heatstroke were included from 83 centres. Patient history, laboratory results, and clinically relevant outcomes were recorded at ICU admission and daily until up to day 15, ICU discharge, or death. GI symptoms, including nausea/vomiting, diarrhoea, flatulence, and bloody stools, were recorded. The characteristics of patients with heatstroke concomitant with GI symptoms were described. Multivariable regression analyses were performed to determine significant predictors of GI symptoms. RESULTS: A total of 713 patients were included in the final analysis, of whom 132 (18.5%) patients had at least one GI symptom during their ICU stay, while 26 (3.6%) suffered from more than one symptom. Patients with GI symptoms had a significantly higher ICU stay compared with those without. The mortality of patients who had two or more GI symptoms simultaneously was significantly higher than that in those with one GI symptom. Multivariable logistic regression analysis revealed that older patients with a lower GCS score on admission were more likely to experience GI symptoms. CONCLUSION: The GI manifestations of heatstroke are common and appear to impact clinically relevant hospitalization outcomes.

Fisetin suppresses chondrocyte senescence and attenuates osteoarthritis progression by targeting sirtuin 6.

Osteoarthritis (OA) is the most common type of arthritis and is an age-related joint disease that is particularly prevalent in subjects over 65 years old. The chronic rise of senescent cells has a close correlation with age-related diseases such as OA, and the senescence-associated secretory phenotype (SASP) is implicated in OA cartilage degeneration pathogenesis. Sirtuin 6 (SIRT6) is likely to be a key senescence-related regulator. Fisetin (FST) is a natural flavonol of the flavonoid family that is recommended as a senolytic drug to extend health and lifespan. However, the potential chondroprotective effects of FST on OA rats are largely unclarified. The aim of this study is to investigate the ameliorative effects of FST on OA joint cartilage and the relationship with SIRT6 and the detailed mechanisms from anti-inflammatory and anti-senescent perspectives. Rats were subjected to destabilization of the medial meniscus (DMM) surgery as a means of inducing the experimental OA model in vivo. Chondrocytes treated with IL-1ß were utilized for mimicking the OA cell model in vitro. Intra-articular injection of FST, OSS_128,167 (OSS, SIRT6 inhibitor), and MDL800 (MDL, SIRT6 agonist) in vivo or administering them in IL-1ß-induced rat chondrocytes in vitro were performed in order to determine the effects FST has on OA and the link with SIRT6. This study found SIRT6 level to be negatively correlated with OA severity. SIRT6 downregulation was validated in the joint cartilages of DMM rats and IL-1ß-treated chondrocytes. It was also notably demonstrated that FST can activate SIRT6. Both the administration of FST and activation of SIRT6 using MDL were found to rescue cartilage erosion, decrease extracellular matrix (ECM) degradation, prevent cartilage from apoptosis, and improve detrimental senescence-related phenotype. The alleviative effects of FST against inflammation, ECM degradation, apoptosis, and senescence in IL-1ß-stimulated chondrocytes were also confirmed. SIRT6 loss occurs in articular cartilage in OA pathogenesis, which is linked to aging. FST attenuates injury-induced aging-related phenotype changes in chondrocytes through the targeting of SIRT6.

Disease spectrum and pathogenic genes of inherited metabolic disorder in Gansu Province of China / 中国当代儿科杂志

OBJECTIVES@#To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder (IMD) among neonates in Gansu Province of China.@*METHODS@#A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021. A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.@*RESULTS@#A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates, and the overall prevalence rate of IMD was 0.63 (1/1 593), among which phenylketonuria showed the highest prevalence rate of 0.32 (1/3 083), followed by methylmalonic acidemia (0.11, 1/8 959) and tetrahydrobiopterin deficiency (0.06, 1/15 927). In this study, 166 variants were identified in the 28 pathogenic genes, with 13 novel variants found in 9 genes. According to American College of Medical Genetics and Genomics guidelines, 5 novel variants were classified as pathogenic variants, 7 were classified as likely pathogenic variants, and 1 was classified as the variant of uncertain significance.@*CONCLUSIONS@#This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Analysis of effects of trastuzumab assisted modified DOF fortnightly regimen on serum tumor markers and survival rate in patients with cisplatin-resistant gastric cancer / 中国癌症杂志

Background and purpose:Trastuzumab has a relatively low incidence of drug resistance,which can be used as an adjuvant treatment to improve clinical efficacy.It has been used to treat breast cancer in the past,but its application in other cancers has been less studied.This study aimed to explore the effects of trastuzumab assisted modified DOF fortnightly regimen on serum tumor markers and survival rate in cisplatin-resistant gastric cancer patients,in order to provide more references for the selection of clinical treatment methods for cisplatin-resistant gastric cancer.Methods:Eighty patients with cisplatin-resistant gastric cancer treated in Harison International Peace Hospital from January 2017 to January 2019 were selected as the study objects,and they were divided into observation group and control group according to random number table method.All of them received improved DOF fortnightly treatment,and trastuzumab adjuvant treatment was added to the observation group on this basis.The serum tumor markers[serum carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9),CA72-4],serum neovascular markers[vascular endothelial growth factor(VEGF),pigment epithelial derived factor(PEDF),angiopoietin-2(Ang-2)],biochemical indicators[N-terminal pro B type natriuretic peptide(NT proBNP),aspartate transaminase(AST),blood urea nitrogen(BUN),alanine aminotransferase(ALT)],adverse reactions and survival rate were compared between two groups.This study was approved by the Ethics Committee of Harison International Peace Hospital(number:20160511).Results:After treatment,CEA,CA19-9 and CA72-4 in both groups decreased,and CEA,CA19-9 and CA72-4 levels were lower in the observation group than in the control group with statistical significance(P＜0.01).After treatment,VEGF,PEDF and Ang-2 in two groups decreased,and the difference was statistically significant(P＜0.01).The levels of VEGF,PEDF and Ang-2 were compared between the two groups before and after treatment,and there was no significant difference(P＞0.05).The levels of NT-proBNP,AST,BUN and ALT were compared between the two groups before and after treatment,and there was no statistically significant difference(P＞0.05).The number of patients with fatigue,gastrointestinal reaction and myelosuppression and the total incidence of adverse reactions were compared between the two groups,and there was no statistically significant difference(P＞0.05).At 5 years after treatment,11 cases(27.5%)survived and 29 cases(72.5%)died in the observation group.There were 3 cases(7.5%)of survival and 37 cases(92.5%)of death in the control group.The median survival was 2 years(95%CI:1.8-2.2)in the observation group and 1 year(95%CI:0.6-1.4)in the control group.The survival rate of 1-5 years was higher in the observation group than in the control group.The difference was statistically significant(log-rank χ2 = 13.853,P = 0.001).Conclusion:In the clinical treatment of cisplatin-resistant gastric cancer,trastuzumab assisted modified DOF fortnightly regimen suggests that it can reduce the expression levels of serum tumor markers,improve the 5-year survival rate of patients,and has certain drug safety.

Modified Palmer classification of traumatic triangular fibrocartilage complex injury based on MRI / 实用放射学杂志

Objective To classify traumatic triangular fibrocartilage complex(TFCC)injury based on 3.0T MR.Methods A total of 46 patients with definite history of wrist trauma admitted were collected.All patients underwent MRI scanning within 3 days after trauma,and the MRI findings were classified as follows according to the Palmer classification criteria:the focal structures of triangular fibro-cartilage(articular disc)(TFC)injury,the horizontal of the articular disc tear,injuries of ulnar styloid attachment and ulnar fovea attach-ment in TFC,ulnolunate and ulnotriquetral ligaments injuries,injury of the radial sigmoid notch junction,meniscal homologous inju-ry.The presence of TFCC injury was eventually confirmed by surgery in all patients.Results Of 46 patients,38 patients could be classified by Palmer,and there were 10 cases with type ⅠA,23 cases with type ⅠB,3 cases with type ⅠC and 2 cases with type ⅠD.A total of 8 patients were not suitable for Palmer type,and there were 3 patients with horizontal tears in the articular disc and 5 patients with meniscus homologous injuries.Conclusion The 3.0T MR can not only show various subtypes of Palmer classification,but also refine and supplement the classification based on the original classification,such as the injuries of ulnar styloid attachment and ulnar fovea attachment at the ulnar end of the articular disc,horizontal tear of the articular disc,meniscus homologous injury,etc.

Application of the second generation snap shot freeze combined with artificial intelligence in free heart rate coronary CT angiography / 实用放射学杂志

Objective To evaluate the application value of the second generation snap shot freeze(SSF2)combined with artificial intelligence reconstruction in free heart rate coronary computed tomography angiography(CCTA).Methods The examination data of 37 patients undergoing CCTA were divided into two groups for reconstruction.Group A,reconstruction by artificial intelligence after SSF2 algorithm correction;group B,original images automatically split and multi-phase reconstruction by artificial intelligence.Image quality were compared on volume rendering(VR),curve planar reformation(CPR),maximum intensity projection(MIP)image,subjective evaluation,objective scoring,and signal-to-noise ratio(SNR).Independent samples t-test and Chi-square test were used,and P<0.05 was considered statistically significant.Results There were statistically significant differences in the image quality score and SNR of the two reconstruction methods(P=0.009).Group A scored better,with higher signal intensity,lower noise intensity,and better SNR.The difference in the number of right coronary artery(RCA)analyzable segments between the two groups was statistically significant(P<0.05).The excellent and good rate of subjective evaluation of coronary artery segments in group A RCA(98.6%)was higher than that in group B(69.6%).Conclusion Using SSF2 combined with artificial intelligence reconstruction technology can significantly improve the image quality of CCTA,improve the success rate of CCTA examination,and improve the overall work efficiency.

PDCA cycle helps the continuous improvement of laboratory diagnostics teaching / 中华医学教育探索杂志

In the context of "New Era" and "New Medicine", the teaching team of laboratory diagnostics proposed a new teaching method of PDCA (Plan, Do, Check, Action) cycle to innovate the instructional design and implementation of laboratory diagnosis on the base of traditional teaching model. Through optimizing the curriculum system, integrating superior resources, taking full advantage of information technology, mobilizing the virtual simulation laboratory, implementing moral education and multiple comprehensive evaluation results, the self-learning enthusiasm, innovation and development ability of students were improved significantly, accompanied with high humanistic care spirit. Moreover, the enthusiasm of participating in scientific research activities and professional competitions was enhanced obviously. Therefore, we believe that the PDCA cycle, with notable successes, deserves high promotion value and wide application.

Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition) / 中草药·英文版

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Selenium-induced rhizosphere microorganisms endow salt-sensitive soybeans with salt tolerance.

Soil salinization is a prevalent abiotic stress that adversely affects soybean production. Rhizosphere microorganisms have been shown to modulate the rhizosphere microenvironment of plants, leading to improved stress resistance. Selenium is known to optimize the rhizosphere microbial community, however, it remains uncertain whether selenium-induced rhizosphere microorganisms can enhance plant salt tolerance. In this study, we selected two soybean varieties, including salt-tolerant and salt-sensitive, and conducted pot experiments to explore the impact of selenium application on the structure and composition of the rhizosphere microbial community of soybean plants under salt stress. Four salt-tolerant bacteria from salt-tolerant soybean rhizosphere soil fertilized with selenium under salt stress were isolated, and their effects on improving salt tolerance in salt-sensitive soybean were also investigated. Our results showed that selenium application enhanced soybean salt tolerance by optimizing the structure of the plant rhizosphere microbial community and improving soil enzyme activities in both salt-tolerant and salt-sensitive varieties. Moreover, compared with salt-only treatment, inoculation of the four bacteria led to a significant increase in the plant height (7.2%-19.8%), aboveground fresh weight (57.3%-73.5%), SPAD value (8.4%-30.3%), and K+ content (4.5%-12.1%) of salt-sensitive soybean, while reducing the content of proline (84.5%-94%), MDA (26.5%-49.3%), and Na+ (7.1%-21.3%). High-throughput sequencing of the 16 S ribosomal RNA gene indicated that the four bacteria played a crucial role in changing the community structure of salt-sensitive soybean and mitigating the effects of salt stress. This study highlighted the importance of selenium combined with beneficial microorganisms in the plant rhizosphere in alleviating salinity stress.

Dietary resveratrol supplementation on growth performance, immune function and intestinal barrier function in broilers challenged with lipopolysaccharide.

This study discusses the effects of resveratrol (RES) on the productive performance, immune function and intestinal barrier function of broiler chickens challenged with lipopolysaccharide (LPS). Two hundred and forty 1-day-old male Arbor Acres broilers were randomly divided into 4 groups of 6 replicates each, with 10 broilers per replicate. This experiment used a 2 × 2 factorial design with dietary factors (basal diets or basal diets supplemented with 400 mg/kg RES were administered from d 1 to 21) and stress factors (intraperitoneal injection of 0.5 mg/kg BW of saline or LPS at 16, 18 and 20 d of age). The results showed that LPS challenge had a significant adverse effect on average daily gain (ADG) in broilers at 16 to 21 d of age (P < 0.05), whereas the addition of RES to the diet inhibited the LPS-induced decrease in ADG (P < 0.05). RES also alleviated LPS-induced immune function damage in broilers, which was manifested by the decrease of spleen index (P < 0.05) and the recovery of serum immunoglobulin M and ileal secretory immunoglobulin A content (P < 0.05). The LPS challenge also disrupts intestinal barrier function and inflammation, and RES mitigates these adverse effects in different ways. RES attenuated LPS-induced reduction of villus height in the jejunum and ileum of broilers (P < 0.05). LPS also caused an abnormal increase in plasma D-lactic acid levels in broilers (P < 0.05), which was effectively mitigated by RES (P < 0.05). LPS challenge resulted in a significant decrease in mRNA expression of occludin in the intestinal mucosa (P < 0.05), which was mitigated by the addition of RES (P < 0.05). RES significantly decreased the mRNA expression of toll-like receptor 4, nuclear factor kappa-B and tumor necrosis factor alpha in the ileum tissue stimulated by LPS (P < 0.05). Taken together, this study shows that RES exerts its beneficial effect on broilers challenged with LPS by alleviating immune function damage, relieving intestinal inflammation and barrier damage, and thus improving growth performance.

Phagocyte extracellular traps formation contributes to host defense against Clostridium perfringens infection.

Clostridium perfringens (C. perfringens) is an important Gram-positive anaerobic spore-forming pathogen that provokes life-threatening gas gangrene and acute enterotoxaemia, although it colonizes as a component of the symbiotic bacteria in humans and animals. However, the mechanisms by which C. perfringens is cleared from the host remains poorly understood, thereby impeding the development of novel strategies for control this infection. Here, we uncover a beneficial effect of extracellular traps (ETs) formation on bacterial killing and clearance by phagocytes. C. perfringens strain ATCC13124, and wild-type isolates CP1 and CP3 markedly trigger ETs formation in macrophages and neutrophils. As expected, visualization of DNA decorated with histone, myeloperoxidase (MPO) and neutrophils elastase (NE) in C. perfringens-triggered classical ETs structures. Notably, the bacteria-induced ETs formation is an ERK1/2-, P38 MAPK-, store-operated calcium entry (SOCE)-, NADPH oxidase-, histone-, NE-, and MPO-dependent process, and is independent of LDH activity. Meanwhile, the defect of bactericidal activity is mediated by impairing ETs formation in phagocytes. Moreover, In vivo studies indicated that degradation of ETs by DNase I administration leads to a defect in the protection against experimental gas gangrene, with higher mortality rates, exacerbated tissue damage, and more bacterial colonization. Together, these results suggest that phagocyte ETs formation is essential for the host defense against C. perfringens infection.

Preoperative frailty assessment could be a predictive factor for the prognosis of elderly patients undergoing coronary artery bypass grafting: a retrospective case-control study.

BACKGROUND: Frailty has been considered to be associated with major mortality and increased length of stay after cardiac surgery. This study aimed to explore the predictive potential of frailty assessment in the prognosis of elderly patients undergoing bypass surgery. METHODS: This study assessed the preoperative frailty according to the Fried's frailty phenotype, and included 150 frail and 150 non-frail elderly patients (≥ 65 y) who underwent bypass surgery. The present study evaluated the prognosis of elderly patients based on sequential organ failure assessment (SOFA) score, and collected clinical indicators to construct logistic regression models with the prognosis as the dependent variable, to explore the potential predictive ability of preoperative frailty. Moreover, this study focused on the complications and analyzed the relationship between preoperative frailty and postoperative complications. RESULTS: In the present study, 244 patients were divided into the favorable prognosis group and 56 patients were divided into the unfavorable prognosis group. Logistic regression analysis showed that increased myoglobin and high cardiac function classification were independent risk factors for unfavorable prognosis in elderly patients undergoing bypass surgery. The discrimination of the clinical prediction model was determined by the receiver operating characteristic (ROC) curve, and the area under curve (AUC) was 0.928. After adding preoperative frailty assessment, the AUC was improved to 0.939. This study found a significant correlation between preoperative frailty and postoperative complications, mainly in the circulatory system. CONCLUSION: Preoperative frailty assessment could be a predictive factor for the prognosis of elderly patients undergoing coronary artery bypass grafting. According to our study, frailty assessment and appropriate intervention before bypass surgery may be beneficial to the enhanced recovery after cardiac surgery. TRIAL REGISTRATION: The clinical study was approved by the Medical Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (2021-SR-393). All patients signed an informed consent form.

Express delivery logistics with high-speed railway: a perspective of payment scheme and forecast information sharing.

This paper investigates the payment scheme and forecast information sharing issues in the express delivery logistics with the high-speed railway. The HSR carriers need to coordinate the transportation capacity between passenger and freight. It is widely recognized that the advance payment scheme (APS) using as deposit is a beneficial way for the HSR carriers to make decisions on the transportation capacity preserved for express delivery. However, the express service providers, who possess private forecast information of express delivery demand, may share inaccurate information with the HSR carriers to acquire sufficient preserved transportation capacity. This paper discusses what payment scheme is preferred by the HSR carrier, the express service provider through discussing the deposit decisions with or without forecast information sharing. We show that sharing demand forecast information can reduce the prereserved capacity and increase the profits of the HSR carrier. With the delayed payment scheme (DPS), the express service provider has no motivation to share the information; while with the APS, the HSR carrier can reasonably choose the deposit to encourage the express service provider to share the demand information. Our analysis also shows that the HSR carrier's profits with the APS is restricted by the investment returns and the express service provider's information sharing decisions. We also analyze the value range of the deposit, which is a proportion of the overall payment, that allows both the HSR carrier and the express service provider to prefer the APS, as well as to encourage the express service provider to share the demand information.