CPT1C-positive cancer-associated fibroblast facilitates immunosuppression through promoting IL-6-induced M2-like phenotype of macrophage.

Cancer-associated fibroblasts (CAFs) exhibit remarkable phenotypic heterogeneity, with specific subsets implicated in immunosuppression in various malignancies. However, whether and how they attenuate anti-tumor immunity in gastric cancer (GC) remains elusive. CPT1C, a unique isoform of carnitine palmitoyltransferase pivotal in regulating fatty acid oxidation, is briefly indicated as a protumoral metabolic mediator in the tumor microenvironment (TME) of GC. In the present study, we initially identified specific subsets of fibroblasts exclusively overexpressing CPT1C, hereby termed them as CPT1C+CAFs. Subsequent findings indicated that CPT1C+CAFs fostered a stroma-enriched and immunosuppressive TME as they correlated with extracellular matrix-related molecular features and enrichment of both immunosuppressive subsets, especially M2-like macrophages, and multiple immune-related pathways. Next, we identified that CPT1C+CAFs promoted the M2-like phenotype of macrophage in vitro. Bioinformatic analyses unveiled the robust IL-6 signaling between CPT1C+CAFs and M2-like phenotype of macrophage and identified CPT1C+CAFs as the primary source of IL-6. Meanwhile, suppressing CPT1C expression in CAFs significantly decreased IL-6 secretion in vitro. Lastly, we demonstrated the association of CPT1C+CAFs with therapeutic resistance. Notably, GC patients with high CPT1C+CAFs infiltration responded poorly to immunotherapy in clinical cohort. Collectively, our data not only present the novel identification of CPT1C+CAFs as immunosuppressive subsets in TME of GC, but also reveal the underlying mechanism that CPT1C+CAFs impair tumor immunity by secreting IL-6 to induce the immunosuppressive M2-like phenotype of macrophage in GC.

Inhibiting the "isolated island" effect in simulated bone defect repair using a hollow structural scaffold design.

The treatment of bone tissue defects remains a complicated clinical challenge. Recently, the bone tissue engineering (BTE) technology has become an important therapeutic approach for bone defect repair. Researchers have improved the scaffolds, cells, and bioactive factors used in BTE through various existing bone repair material preparation strategies. However, due to insufficient vascularization, inadequate degradation, and fibrous wrapping, most BTE scaffolds impede new bone ingrowth and the reconstruction of grid-like connections in the middle and late stages of bone repair. These non-degradable scaffolds become isolated and disordered like independent "isolated islands", which leads to the failure of osteogenesis. Consequently, we hypothesized that the "island effect" prevents successful bone repair. Accordingly, we proposed a new concept of scaffold modification-osteogenesis requires a bone temporary shelter (also referred to as the empty shell osteogenesis concept). Based on this concept, we consider that designing hollow structural scaffolds is the key to mitigating the "isolated island" effect and enabling optimal bone regeneration and reconstruction.

Three-Dimensional-Printed Spherical Hollow Structural Scaffolds for Guiding Critical-Sized Bone Regeneration.

The treatment of bone tissue defects continues to be a complex medical issue. Recently, three-dimensional (3D)-printed scaffold technology for bone tissue engineering (BTE) has emerged as an important therapeutic approach for bone defect repair. Despite the potential of BTE scaffolds to contribute to long-term bone reconstruction, there are certain challenges associated with it including the impediment of bone growth within the scaffolds and vascular infiltration. These difficulties can be resolved by using scaffold structural modification strategies that can effectively guide bone regeneration. This study involved the preparation of biphasic calcium phosphate spherical hollow structural scaffolds (SHSS) with varying pore sizes using 3D printing (photopolymerized via digital light processing). The chemical compositions, microscopic morphologies, mechanical properties, biocompatibilities, osteogenic properties, and impact on repairing critical-sized bone defects of SHSS were assessed through characterization analyses, in vitro cytological assays, and in vivo biological experiments. The results revealed the biomimetic properties of SHSS and their favorable biocompatibility. The scaffolds stimulated cell adhesion, proliferation, differentiation, and migration and facilitated the expression of osteogenic genes and proteins, including Col-1, OCN, and OPN. Furthermore, they could effectively repair a critical-sized bone defect in a rabbit femoral condyle by establishing an osteogenic platform and guiding bone regeneration in the defect region. This innovative strategy presents a novel therapeutic approach for assessing critical-sized bone defects.

Metagenomics next-generation sequencing (mNGS) reveals emerging infection induced by Klebsiella pneumoniaeniae.

OBJECTIVES: The increasing emergence of hypervirulent Klebsiella pneumoniae (hv-Kp) and carbapenem-resistant K. pneumoniae (CR-Kp) is a serious and substantial public health problem. The use of the last resort antimicrobials, tigecycline and polymyxin to combat infections is complicated by the expanding repertoire of newly-identified CR-hvKp. The transmission and co-occurrence of the corresponding antimicrobial resistance and virulence determinants are largely unknown. The aim of this study was to investigate the dissemination and dynamics of CR-Kp and its antibiotic resistance in a hospitalised patient. METHODS: Metagenomic next-generation sequencing (mNGS) was conducted for different specimens collected from an elderly male hospitalised patient. CR-Kp strains were examined using antibiotic susceptibility and string testing. Antimicrobial and virulence genes were annotated using whole-genome sequencing (WGS). RESULTS: A clinical case of a patient infected with a variety of CR-Kp isolates was reported. The co-occurrence of KPC-2 and NDM-1 in the patient was revealed. The CR-Kp isolates, such as BALF2, and Sputum T1 and T3, were classified into ST11 and ST147, respectively. The genetic signature (iuc operon) of hypervirulence was identified in strain T1, although string testing indicated its intermediate virulence. CONCLUSIONS: In this study, multiple infections of CR-Kp isolates were revealed by mNGS, and their dissemination was attributed to plasmid variations, mgrB inactivation and integrative conjugative elements (ICEs). Furthermore, the finding indicated one likely convergence to form CR-hvKp, different from acquisition of carbapenem-resistance determinants in hvKp. A combination of mNGS and WGS is beneficial for clinical diagnosis and anti-infection therapy, and facilitates a better understanding of genetic variants conferring antimicrobial and virulence properties.

Dysbiosis of lower respiratory tract microbiome are associated with proinflammatory states in non-small cell lung cancer patients.

BACKGROUND: The lung has a sophisticated microbiome, and respiratory illnesses are greatly influenced by the lung microbiota. Despite the fact that numerous studies have shown that lung cancer patients have a dysbiosis as compared to healthy people, more research is needed to explore the association between the microbiota dysbiosis and immune profile within the tumor microenvironment (TME). METHODS: In this study, we performed metagenomic sequencing of tumor and normal tissues from 61 non-small cell lung cancer (NSCLC) patients and six patients with other lung diseases. In order to characterize the impact of the microbes in TME, the cytokine concentrations of 24 lung tumor and normal tissues were detected using a multiple cytokine panel. RESULTS: Our results showed that tumors had lower microbiota diversity than the paired normal tissues, and the microbiota of NSCLC was enriched in Proteobacteria, Firmicutes, and Actinobacteria. In addition, proinflammatory cytokines such as IL-8, MIF, TNF- α, and so on, were significantly upregulated in tumor tissues. CONCLUSION: We discovered a subset of bacteria linked to host inflammatory signaling pathways and, more precisely, to particular immune cells. We determined that lower airway microbiome dysbiosis may be linked to the disruption of the equilibrium of the immune system causing lung inflammation. The spread of lung cancer may be linked to specific bacteria.

Comparison between Novel Anatomical Locking Guide Plate and Conventional Locking Plate for Acetabular Fractures: A Finite Element Analysis.

The treatment of complex acetabular fractures remains a complicated clinical challenge. Our self-designed novel anatomical locking guide plate (NALGP) has previously shown promising potential in T-shaped acetabular fractures (TAF), but a direct comparison with conventional fixations is yet to be made. The TAF model was established based on a volunteer's computer tomography data and then fixed with double column locking plates (DLP), a posterior column locking plate with anterior column screws (LPACS), and our NALGP. Forces of 200 N, 400 N, and 600 N were then loaded on the model vertically downward, respectively. The stress distribution and peaks and maximum displacements at three sites were assessed. We found that the stress area of all three plates was mainly concentrated around the fracture line, while only the matching screws of the NALGP showed no obvious stress concentration points. In addition, the NALGP and DLP showed significantly less fracture fragment displacement than the LPACS at the three main fracture sites. The NALGP was found to have less displacement than DLP at the posterior column and ischiopubic branch sites, especially under the higher loading forces of 400 N and 600 N. The fixation stability of the NALGP for TAF was similar to that of DLP but better than that of LPACS. Moreover, the NALGP and its matching screws have a more reasonable stress distribution under different loads of force and the same strength as the LPACS.

Comparison of effects of HucMSCs, exosomes, and conditioned medium on NASH.

To investigate the effects and potential mechanisms of human umbilical cord mesenchymal stem cells, exosomes, and their conditioned media on lipid storage in oleic acid (OA) and palmitic acid (PA) treated hepatocytes and high-fat methionine- choline deficient diet (HFMRCD) induced non-alcoholic steatohepatitis (NASH) mice. AML12 cells were stimulated with OA and PA to establish the lipid storage cell model. HucMSCs, exosomes, and culture medium were then co-cultured. At the same time, C57BL/6 mice were fed an HFMRCD for 6 or 8 weeks to establish a NASH mouse model. The effect of HucMSCs, exosomes, and culture medium on lipid droplet repair of hepatocytes or NASH mice was then assessed. The weight of hepatocytes or liver tissue, Oil Red O, hematoxylin-eosin staining, Masson staining, Western blot, and qPCR were used to detect the related IL-6, TNF-α, TGF-ß1 andEI24/AMPK/mTOR pathway expression in hepatocytes and liver tissue. Compared with the model group, the effect of HucMSCs-Ex on inhibiting the accumulation of lipid droplets was more obvious at the cell level. In vivo study showed that HucMSCs-Ex reduces activity scores in NASH mice and improves liver tissue morphology by reducing vacuolar degeneration, fat deposition, and collagen deposition of liver tissue. Western blot and qPCR results showed that inflammatory factors and AMPK/mTOR or EI24-related autophagy pathways were altered before and after treatment. HucMSCs, HucMSC-Ex, and CM can promote autophagy in hepatocytes or NASH mice through the AMPK/mTOR or EI24-related autophagy pathway and alleviate injury associated with lipid deposition, collagen deposition or inflammation, reversing the progression of NASH.

Direct prediction of carbapenem resistance in Pseudomonas aeruginosa by whole genome sequencing and metagenomic sequencing.

Carbapenem resistance is a major concern in the management of antibiotic-resistant Pseudomonas aeruginosa infections. The direct prediction of carbapenem-resistant phenotype from genotype in P. aeruginosa isolates and clinical samples would promote timely antibiotic therapy. The complex carbapenem resistance mechanism and the high prevalence of variant-driven carbapenem resistance in P. aeruginosa make it challenging to predict the carbapenem-resistant phenotype through the genotype. In this study, using whole genome sequencing (WGS) data of 1,622 P. aeruginosa isolates followed by machine learning, we screened 16 and 31 key gene features associated with imipenem (IPM) and meropenem (MEM) resistance in P. aeruginosa, including oprD(HIGH), and constructed the resistance prediction models. The areas under the curves of the IPM and MEM resistance prediction models were 0.906 and 0.925, respectively. For the direct prediction of carbapenem resistance in P. aeruginosa from clinical samples by the key gene features selected and prediction models constructed, 72 P. aeruginosa-positive sputum samples were collected and sequenced by metagenomic sequencing (MGS) based on next-generation sequencing (NGS) or Oxford Nanopore Technology (ONT). The prediction applicability of MGS based on NGS outperformed that of MGS based on ONT. In 72 P. aeruginosa-positive sputum samples, 65.0% (26/40) of IPM-insensitive and 63.2% (24/38) of MEM-insensitive P. aeruginosa were directly predicted by NGS-based MGS with positive predictive values of 0.897 and 0.889, respectively. By the direct detection of the key gene features associated with carbapenem resistance of P. aeruginosa, the carbapenem resistance of P. aeruginosa could be directly predicted from cultured isolates by WGS or from clinical samples by NGS-based MGS, which could assist the timely treatment and surveillance of carbapenem-resistant P. aeruginosa.

Identification of metabolic biomarkers associated with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease. Metabolism-related genes significantly influence the onset and progression of the disease. Hence, it is necessary to screen metabolism-related biomarkers for the diagnosis and treatment of NAFLD patients. METHODS: GSE48452, GSE63067, and GSE89632 datasets including nonalcoholic steatohepatitis (NASH) and healthy controls (HC) analyzed in this study were retrieved from the Gene Expression Omnibus (GEO) database. First, differentially expressed genes (DEGs) between NASH and HC samples were obtained. Next, metabolism-related DEGs (MR-DEGs) were identified by overlapping DEGs and metabolism-related genes (MRG). Further, a protein-protein interaction (PPI) network was developed to show the interaction among MR-DEGs. Subsequently, the "Least absolute shrinkage and selection operator regression" and "Random Forest" algorithms were used to screen metabolism-related genes (MRGs) in patients with NAFLD. Next, immune cell infiltration and gene set enrichment analyses (GSEA) were performed on these metabolism-related genes. Finally, the expression of metabolism-related gene was determined at the transcription level. RESULTS: First, 129 DEGs related to NAFLD development were identified among patients with nonalcoholic steatohepatitis (NASH) and healthy control. Next, 18 MR-DEGs were identified using the Venn diagram. Subsequently, four genes, including AMDHD1, FMO1, LPL, and P4HA1, were identified using machine learning algorithms. Moreover, a regulatory network consisting of four genes, 25 microRNAs (miRNAs), and 41 transcription factors (TFs) was constructed. Finally, a significant increase in FMO1 and LPL expression levels and a decrease in AMDHD1 and P4HA1 expression levels were observed in patients in the NASH group compared to the HC group. CONCLUSION: Metabolism-related genes associated with NAFLD were identified, containing AMDHD1, FMO1, LPL, and P4HA1, which provide insights into diagnosing and treating patients with NAFLD.

Functionalized 3D-Printed PLA Biomimetic Scaffold for Repairing Critical-Size Bone Defects.

The treatment of critical-size bone defects remains a complicated clinical challenge. Recently, bone tissue engineering has emerged as a potential therapeutic approach for defect repair. This study examined the biocompatibility and repair efficacy of hydroxyapatite-mineralized bionic polylactic acid (PLA) scaffolds, which were prepared through a combination of 3D printing technology, plasma modification, collagen coating, and hydroxyapatite mineralization coating techniques. Physicochemical analysis, mechanical testing, and in vitro and animal experiments were conducted to elucidate the impact of structural design and microenvironment on osteogenesis. Results indicated that the PLA scaffold exhibited a porosity of 84.1% and a pore size of 350 µm, and its macrostructure was maintained following functionalization modification. The functionalized scaffold demonstrated favorable hydrophilicity and biocompatibility and promoted cell adhesion, proliferation, and the expression of osteogenic genes such as ALP, OPN, Col-1, OCN, and RUNX2. Moreover, the scaffold was able to effectively repair critical-size bone defects in the rabbit radius, suggesting a novel strategy for the treatment of critical-size bone defects.

Regulatory effects of different anionic surfactants on the transformation of heavy metal fractions and reduction of heavy metal resistance genes in chicken manure compost.

Surfactants are widely used as a passivating agent in heavy metal passivation process, but their effect on transformation of heavy metal fraction and reduction of heavy metal resistance genes (MRGs) in composting process is still unknown. The aim of this study was to compare the effects of two anionic surfactants (rhamnolipid and sodium dodecyl sulfate) on heavy metal passivation and resistance gene reduction in chicken manure composting. The results showed that the addition of surfactant can effectively enhance degradation of organic matter (OM). Both surfactants could effectively reduce the bioavailability of heavy metals (HMs) and the relative abundance of resistance genes, especially rhamnolipids. The potential functional bacteria affecting heavy metal passivation were identified by the changes of microbial community. Redundancy analysis (RDA) showed that protease (PRT) activity was the key factor affecting the fractions of the second group of HMs including ZnF1, CuF1, CuF2, PbF1 and PbF3. These findings indicate that addition of anionic surfactants can reduce the bioavailability of HMs and the abundance of resistance genes in compost products, which is of guiding significance for the reduction of health risks in the harmless utilization of livestock and poultry manure.

Early-phase rotator training impairs tissue repair and functional recovery after spinal cord injury.

Spinal cord injury (SCI) is a devastating disorder that often results in severe sensorimotor function impairment with limited recovery of function. In recent years, rehabilitation training for spinal cord injury has gradually emerged, and some of them play an important role in the repair of spinal cord injury However, the optimal training regimen for SCI remains to be determined. In this study, we explore the effects of rotarod training (began at 7 days post-injury) on the recovery of motor function after SCI, as well as its possible repair mechanism from the aspects of function and histopathological changes, the behaviors of specific trophic factors and cytokines, and the expression profile of specific genes. Multiple functional assessments showed that rotarod training initiated at 7 days post-injury is unsuitable for promoting neuro-electrophysiological improvement and trunk stability, but impaired functional coordination and motor recovery. In addition, rotarod training has negative effects on spinal cord repair after SCI, which is manifested as an increase of lesion area, a decrease in neuronal viability, a deterioration in immuno-microenvironment and remyelination, a significant reduction in the expression of trophic factors and an increase in the expression of pro-inflammatory factors. RNA sequencing suggested that the genes associated with angiogenesis and synaptogenesis were significantly downregulated and the PI3K-AKT pathway was inhibited, which was detrimental to spinal cord repair and impeded nerve regeneration. These results indicate that immediate rotarod training after SCI is currently unsuitable for rehabilitation in mice.

DLP-printed GelMA-PMAA scaffold for bone regeneration through endochondral ossification.

Intramembranous ossification (IMO) and endochondral ossification (ECO) are two pathways of bone regeneration. The regeneration of most bone, such as limb bone, trunk bone, and skull base bone, mainly occurs in the form of endochondral ossification, which has also become one of the effective ways for bone tissue engineering. In this work, we prepared a well-structured and biocompatible methacrylated gelatin/polymethacrylic acid (GelMA/PMAA) hydrogel by digital light processing (DLP) printing technology, which could effectively chelate iron ions and continuously activate the hypoxia-inducible factor-1 alpha (HIF-1α) signaling pathway to promote the process of endochondral ossification and angiogenesis. The incorporation of PMAA endowed the hydrogel with remarkable viscoelasticity and high efficacy in chelation of iron ions, giving rise to the activation of HIF-1α signaling pathway, improving chondrogenic differentiation in the early stage, and facilitating vascularization in the later stage and bone remodeling. Therefore, the findings have significant implications on DLP printing technology of endochondral osteogenesis induced by the iron-chelating property of biological scaffold, which will provide an effective way in the development of novel bone regeneration.

First-Aid Hydrogel Wound Dressing with Reliable Hemostatic and Antibacterial Capability for Traumatic Injuries.

First-aid for severe traumatic injuries in the battlefield or pre-hospital environment, especially for skin defects or visceral rupture, remains a substantial medical challenge even in the context of the rapidly evolving modern medical technology. Hydrogel-based biomaterials are highly anticipated for excellent biocompatibility and bio-functional designability. Yet, inadequate mechanical and bio-adhesion properties limit their clinical application. To address these challenges, a kind of multifunctional hydrogel wound dressing is developed with the collective multi-crosslinking advantages of dynamic covalent bonds, metal-catechol chelation, and hydrogen bonds. The mussel-inspired design and zinc oxide-enhanced cohesion strategy collaboratively reinforce the hydrogel's bio-adhesion in bloody or humoral environments. The pH-sensitive coordinate Zn2+ -catechol bond and dynamic Schiff base with reversible breakage and reformation equip the hydrogel dressing with excellent self-healing and on-demand removal properties. In vivo evaluation in a rat ventricular perforation model and Methicillin-resistant Staphylococcus aureus (MRSA)-infected full-thickness skin defect model reveal excellent hemostatic, antibacterial and pro-healing effectiveness of the hydrogel dressing, demonstrating its great potential in dealing with severe bleeding and infected full-thickness skin wounds.

Application of photocrosslinkable hydrogels based on photolithography 3D bioprinting technology in bone tissue engineering.

Bone tissue engineering (BTE) has been proven to be an effective method for the treatment of bone defects caused by different musculoskeletal disorders. Photocrosslinkable hydrogels (PCHs) with good biocompatibility and biodegradability can significantly promote the migration, proliferation and differentiation of cells and have been widely used in BTE. Moreover, photolithography 3D bioprinting technology can notably help PCHs-based scaffolds possess a biomimetic structure of natural bone, meeting the structural requirements of bone regeneration. Nanomaterials, cells, drugs and cytokines added into bioinks can enable different functionalization strategies for scaffolds to achieve the desired properties required for BTE. In this review, we demonstrate a brief introduction of the advantages of PCHs and photolithography-based 3D bioprinting technology and summarize their applications in BTE. Finally, the challenges and potential future approaches for bone defects are outlined.

Application of metagenomic next-generation sequencing in the diagnosis of urinary tract infection in patients undergoing cutaneous ureterostomy.

Objective: Urinary tract infection (UTI) is an inflammatory response of the urothelium to bacterial invasion and is a common complication in patients with cutaneous ureterostomy (CU). For such patients, accurate and efficient identification of pathogens remains a challenge. The aim of this study included exploring utility of metagenomic next-generation sequencing (mNGS) in assisting microbiological diagnosis of UTI among patients undergoing CU, identifying promising cytokine or microorganism biomarkers, revealing microbiome diversity change and compare virulence factors (VFs) and antibiotic resistance genes (ARGs) after infection. Methods: We performed a case-control study of 50 consecutive CU patients from December 2020 to January 2021. According to the clinical diagnostic criteria, samples were divided into infected group and uninfected group and difference of urine culture, cytokines, microorganism, ARGs and VFs were compared between the two groups. Results: Inflammatory responses were more serious in infected group, as evidenced by a significant increase in IFN-α (p=0.031), IL-1ß (0.023) and IL-6 (p=0.018). Clinical culture shows that there is higher positive rate in infected group for most clinical pathogens like Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Candida auris etc. and the top three pathogens with positive frequencies were E. coli, K. pneumoniae, and Enterococcus faecalis. Benchmarking clinical culture, the total sensitivity is 91.4% and specificity is 76.3% for mNGS. As for mNGS, there was no significant difference in microbiome α- diversity between infected and uninfected group. Three species biomarkers including Citrobacter freundii, Klebsiella oxytoca, and Enterobacter cloacae are enriched in infected group based on Lefse. E. cloacae were significantly correlated with IL-6 and IL-10. K. oxytoca were significantly correlated with IL-1ß. Besides, the unweighted gene number and weighted gene abundance of VFs or ARGs are significantly higher in infected group. Notablely, ARGs belonging to fluoroquinolones, betalatmas, fosfomycin, phenicol, phenolic compound abundance is significantly higher in infected group which may have bad effect on clinical treatment for patients. Conclusion: mNGS, along with urine culture, will provide comprehensive and efficient reference for the diagnosis of UTI in patients with CU and allow us to monitor microbial changes in urine of these patients. Moreover, cytokines (IL-6, IL-1ß, and IFN-a) or microorganisms like C. freundii, K. oxytoca or E. cloacae are promising biomarkers for building effective UTI diagnostic model of patients with CU and seriously the VFs and ARGs abundance increase in infected group may play bad effect on clinical treatment.

3D-Printed GelMA/PEGDA/F127DA Scaffolds for Bone Regeneration.

Tissue-engineered scaffolds are an effective method for the treatment of bone defects, and their structure and function are essential for bone regeneration. Digital light processing (DLP) printing technology has been widely used in bone tissue engineering (BTE) due to its high printing resolution and gentle printing process. As commonly used bioinks, synthetic polymers such as polyethylene glycol diacrylate (PEGDA) and Pluronic F127 diacrylate (F127DA) have satisfactory printability and mechanical properties but usually lack sufficient adhesion to cells and tissues. Here, a compound BTE scaffold based on PEGDA, F127DA, and gelatin methacrylate (GelMA) was successfully prepared using DLP printing technology. The scaffold not only facilitated the adhesion and proliferation of cells, but also effectively promoted the osteogenic differentiation of mesenchymal stem cells in an osteoinductive environment. Moreover, the bone tissue volume/total tissue volume (BV/TV) of the GelMA/PEGDA/F127DA (GPF) scaffold in vivo was 49.75 ± 8.50%, higher than the value of 37.10 ± 7.27% for the PEGDA/F127DA (PF) scaffold and 20.43 ± 2.08% for the blank group. Therefore, the GPF scaffold prepared using DLP printing technology provides a new approach to the treatment of bone defects.

Construction of ovarian metastasis-related immune signature predicting prognosis of gastric cancer patients.

BACKGROUND: Ovarian metastasis (OM) results in poor survival of gastric cancer (GC) patients. While immunotherapy has emerged as a promising approach for late-stage GC, validated immune-related prognostic signatures still remain in need. In this study, we constructed an ovarian metastasis- and immune-related prognostic signature (OMIRPS), characterized the molecular and immune features of OMIRPS-categorized subgroups and predicted their potential response to immunotherapy. METHODS: Three individual cohorts were used to construct and evaluate OMIRPS: RNA-seq of matched primary GC and OM from Fudan University Shanghai Cancer Center (FUSCC) (discovery cohort, n = 4), The Cancer Genome Atlas (TCGA) (training cohort, n = 544) and GSE84437 (validation cohort, n = 433). Differentially expressed genes (DEGs) identified between primary GC and OM and immune-related genes (IRGs) from the ImmPort and InnateDB databases were used to identify immune-related prognostic hub genes, which were further used to construct OMIRPS by using LASSO regression analysis. Prognosis, molecular characteristics, immune features, and differential immunotherapy efficacy between different OMIRPS subgroups were analyzed. RESULTS: Functional analyses of DEGs revealed the significance of immune-related signatures and pathways in the OM. Immune-related prognostic hub genes including TNFRSF18, CARD11, BCL11B, NRP1, BNIP3L, and ATF3 were utilized to construct OMIRPS, which was identified as an independent prognostic factor. Comprehensive analyses unveiled the distinctive molecular and immune characteristics of OMIRPS-high and -low subgroup in regard to enriched pathways, mutation rate, tumor mutation burden, microsatellite instability status, infiltrated immune cell, immune exclusion score, and the prediction of immunotherapy efficacy. Additionally, OMIRPS was associated with Immune Subtypes with borderline significance. CONCLUSIONS: RNA-seq of paired primary and ovarian metastatic tumors unveiled the significance of immune-related pathways and tumor immune microenvironment in OM. OMIRPS served as a promising biomarker to predict the prognosis of GC patients and distinguish the molecular features, immune characteristics, and efficacy of immunotherapy between different subgroups.

Partial omentectomy maybe practicable for T3 or shallower gastric cancer patients.

BACKGROUND: Total omentectomy is often performed with gastrectomy as radical surgery for gastric cancer (GC) patients. However, it remains controversial whether GC patients can benefit from omentectomy. The aim of this study was to analyze the incidence and clinical significance of tumor deposits (TDs) in different anatomical subregions of perigastric omentum in GC patients undergoing gastrectomy with total omentectomy. METHODS: From October 2011 to December 2013, 1253 patients who underwent gastrectomy with total omentectomy for GC were retrospective reviewed. The TDs in different anatomical subregions of perigastric omentum were examined. RESULTS: Of 1253 patients, TDs positivity was 11.2%. Tumor deposits in the omentum of greater curvature and in the omentum of lesser curvature were associated with lymphovascular invasion, perineural invasion, advanced tumor node metastasis stages, and unfavorable survival. Besides, TDs in the proximal omentum of greater curvature and in the omentum of lesser curvature correlated with older patients and larger tumors. Kaplan-Meier curves showed that patients with TDs had worser overall survival (OS) than those without, regardless of TD positions. Patients with TDs in the omentum of greater curvature had the worst prognosis, followed by patients with TDs in the omentum of lesser curvature and patients with no TDs. Tumor deposits in the proximal omentum of greater curvature was an independent prognostic factor for OS. Moreover, only patients classified as pT4 had TDs in the distal omentum of greater curvature. CONCLUSIONS: Patients with TDs in the omentum of greater curvature had the worst prognosis, followed by patients with TDs in the omentum of lesser curvature and patients with no TDs. In addition, partial omentectomy might be practicable for gastric cancer patients classified as T3 or shallower tumors.

The Key Drivers of Brain Injury by Systemic Inflammatory Responses after Sepsis: Microglia and Neuroinflammation.

Sepsis is a leading cause of intensive care unit admission and death worldwide. Most surviving patients show acute or chronic mental disorders, which are known as sepsis-associated encephalopathy (SAE). Although accumulating studies in the past two decades focused on the pathogenesis of SAE, a systematic review of retrospective studies which exclusively focuses on the inflammatory mechanisms of SAE has been lacking yet. This review summarizes the recent advance in the field of neuroinflammation and sheds light on the activation of microglia in SAE. Activation of microglia predominates neuroinflammation. As the gene expression profile changes, microglia show heterogeneous characterizations throughout all stages of SAE. Here, we summarize the systemic inflammation following sepsis and also the relationship of microglial diversity and neuroinflammation. Moreover, a collection of neuroinflammation-related dysfunction has also been reviewed to illustrate the possible mechanisms for SAE. In addition, promising pharmacological or non-pharmacological therapeutic strategies, especially those which target neuroinflammation or microglia, are also concluded in the final part of this review. Collectively, clarification of the vital relationship between neuroinflammation and SAE-related mental disorders would significantly improve our understanding of the pathophysiological mechanisms in SAE and therefore provide potential targets for therapies of SAE aimed at inhibiting neuroinflammation.