Huzhou Central Hospital

Studies using animal models have shown that depression affects the stability of the microbiota, but the actual structure and composition in patients with major depressive disorder (MDD) are not well understood. Here, we analyzed fecal samples from 46 patients with depression (29 active-MDD and 17 responded-MDD) and 30 healthy controls (HCs). High-throughput pyrosequencing showed that, according to the Shannon index, increased fecal bacterial α-diversity was found in the active-MDD (A-MDD) vs. the HC group but not in the responded-MDD (R-MDD) vs. the HC group. Bacteroidetes, Proteobacteria, and Actinobacteria strongly increased in level, whereas that of Firmicutes was significantly reduced in the A-MDD and R-MDD groups compared with the HC group. Despite profound interindividual variability, levels of several predominant genera were significantly different between the MDD and HC groups. Most notably, the MDD groups had increased levels of Enterobacteriaceae and Alistipes but reduced levels of Faecalibacterium. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. These findings enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and depression and to evaluate the suitability of the microbiome as a biomarker.

BACKGROUND: During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. METHODS: Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. RESULTS: Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). CONCLUSIONS: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

Ischemic stroke after cerebral artery occlusion is one of the major causes of chronic disability worldwide. Interleukins (ILs) play a bidirectional role in ischemic stroke through information transmission, activation and regulation of immune cells, mediating the activation, multiplication and differentiation of T and B cells and in the inflammatory reaction. Crosstalk between different ILs in different immune cells also impact the outcome of ischemic stroke. This overview is aimed to roughly discuss the multiple roles of ILs after ischemic stroke. The roles of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-16, IL-17, IL-18, IL-19, IL-21, IL-22, IL-23, IL-32, IL-33, IL-34, IL-37, and IL-38 in ischemic stroke were discussed in this review.

on host metabolism and the underlying mechanism.

OBJECT Increased levels of H19 long noncoding RNA (lncRNA) have been observed in many cancers, suggesting that overexpression of H19 may be important in the development of carcinogenesis. However, the role of H19 in human glioblastoma is still unclear. The object of this study was to examine the level of H19 in glioblastoma samples and investigate the role of H19 in glioblastoma carcinogenesis. METHODS Glioblastoma and nontumor brain tissue specimens were obtained from tissue obtained during tumor resection in 30 patients with glioblastoma. The level of H19 lncRNA was detected by real-time quantitative reverse transcription polymerase chain reaction. The role of H19 in invasion, angiogenesis, and stemness of glioblastoma cells was then investigated using commercially produced cell lines (U87 and U373). The effects of H19 overexpression on glioblastoma cell invasion and angiogenesis were detected by in vitro Matrigel invasion and endothelial tube formation assay. The effects of H19 on glioblastoma cell stemness and tumorigenicity were investigated by neurosphere formation and an in vivo murine xenograft model. RESULTS The authors found that H19 is significantly overexpressed in glioblastoma tissues, and the level of expression was associated with patient survival. In the subsequent investigations, the authors found that overexpression of H19 promotes glioblastoma cell invasion and angiogenesis in vitro. Interestingly, H19 was also significantly overexpressed in CD133(+) glioblastoma cells, and overexpression of H19 was associated with increased neurosphere formation of glioblastoma cells. Finally, stable overexpression of H19 was associated with increased tumor growth in the murine xenograft model. CONCLUSIONS The results of this study suggest that increased expression of H19 lncRNA promotes invasion, angiogenesis, stemness, and tumorigenicity of glioblastoma cells. Taken together, these findings indicate that H19 plays an important role in tumorigenicity and stemness of glioblastoma and thus could be a therapeutic target for treatment of glioblastoma in the future.

Aging is usually characterized with inflammation and disordered bile acids (BAs) homeostasis, as well as gut dysbiosis. The pathophysiological changes during aging are also sexual specific. However, it remains unclear about the modulating process among gut microbiota, BA metabolism, and inflammation during aging. In this study, we established a direct link between gut microbiota and BA profile changes in the liver, serum, and four intestinal segments of both sexes during aging and gut microbiota remodeling by co-housing old mice with young ones. We found aging reduced Actinobacteria in male mice but increased Firmicutes in female mice. Among the top 10 altered genera with aging, 4 genera changed oppositely between male and female mice, and most of the changes were reversed by co-housing in both sexes. Gut microbiota remodeling by co-housing partly rescued the systemically dysregulated BA homeostasis induced by aging in a sex- and tissue-specific manner. Aging had greater impacts on hepatic BA profile in females, but intestinal BA profile in males. In addition, aging increased hepatic and colonic deoxycholic acid in male mice, but reduced them in females. Moreover, muricholic acids shifted markedly in the intestine, especially in old male mice, and partially reversed by co-housing. Notably, the ratios of primary to secondary BAs in the liver, serum, and all four intestinal segments were increased in old mice and reduced by co-housing in both sexes. Together, the presented data revealed that sex divergent changes of gut microbiota and BA profile in multiple body compartments during aging and gut microbiota remodeling, highlighting the sex-specific prevention and treatment of aging-related disorders by targeting gut microbiota-regulated BA metabolism should particularly be given more attention.

Background Pancreatic cancer (PC) is a common malignancy of the digestive system and is characterized by poor prognosis and early metastasis. Tumor immune escape plays an important role in PC progression. Programmed death 1 (PD1) blockade therapy is a promising treatment for patients with PC, but is yet to achieve significant clinical effects so far. Interferon gamma (IFN-γ) is a soluble dimeric cytokine that is closely associated with tumor immune surveillance and cytotoxicity. IFN-γ suppresses a variety of tumor-derived cytokines in PC, such as CXCL8. In the present study, we investigated the therapeutic efficacy of combined anti-PD1 and IFN-γ treatment in PC. Methods BxPC-3 and Panc-1 human PC cell lines were used to construct a murine PC model. Blood samples (n=44) and surgical resection specimens (n=36) from human patients with PC were also collected. χ 2 test, two-tailed unpaired t-test or Kaplan-Meier survival analysis was used to calculate p values. Results PD1/PD-L1 signaling was overexpressed in PC tumor-bearing mice. Anti-PD1 prevented tumor growth if initiated early after tumor inoculation; however, delayed anti-PD1 treatment showed limited benefit. Murine PC model had a preferential expansion of CXCR2 + CD68 + macrophages, and these cells showed an immunosuppressive nature (M2 polarization). PC tumors overexpressed CXCL8 and tumor-derived CXCL8 deficiency prohibited the trafficking of CXCR2 + CD68 + macrophages. IFN-γ suppressed the expression of tumor-derived CXCL8, and combined with IFN-γ treatment, delayed anti-PD1 treatment showed significant antitumor effects. Thus, we conclude that murine CXCR2 + CD68 + macrophages traffic to PC tumors by tumor-derived CXCL8 and mediate local immunosuppression, which limits the efficacy of PD1 blockade therapy. IFN-γ suppresses tumor-derived CXCL8 and inhibits the tumor trafficking of CXCR2 + CD68 + macrophages by blocking the CXCL8–CXCR2 axis to enhance anti-PD1 efficacy. Human PC also produces high levels of CXCL8. Patients with PC present elevated CXCR2 expression on peripheral and tumor-infiltrating CD68 + macrophages, which are associated with advanced tumor stage and poor prognosis. Conclusion Our findings suggest that IFN-γ is a translatable, therapeutic option to improve the efficacy of PD1 blockade therapy by preventing trafficking of CXCR2 + CD68 + macrophages via blocking the CXCL8–CXCR2 axis.

BACKGROUND: Unilateral biportal endoscopic discectomy (UBE) is a rapidly growing surgical method that uses arthroscopic system for treatment of lumbar disc herniation (LDH), while percutaneous endoscopic lumbar discectomy (PELD) has been standardized as a representative minimally invasive spine surgical technique for LDH. The purpose of this study was to compare the clinical outcomes between UBE and PELD for treatment of patients with LDH. METHODS: The subjects consisted of 54 patients who underwent UBE (24 cases) and PELD (30 cases) who were followed up for at least 6 months. All patients had lumber disc herniation for 1 level. Outcomes of the patients were assessed with operation time, incision length, hospital stay, total blood loss (TBL), intraoperative blood loss (IBL), hidden blood loss (HBL), complications, total hospitalization costs, visual analogue scale (VAS) for back and leg pain, the Oswestry disability index (ODI) and modified MacNab criteria. RESULTS: The VAS scores and ODI decreased significantly in two groups after operation. Preoperative and 1 day, 1 month, 6 months after operation VAS and ODI scores were not significantly different between the two groups. Compared with PELD group, UBE group was associated with higher TBL, higher IBL, higher HBL, longer operation time, longer hospital stay, longer incision length, and more total hospitalization costs. However, a dural tear occurred in one patient of the UBE group. There was no significant difference in the rate of complications between the two groups. CONCLUSIONS: Application of UBE for treatment of lumbar disc herniation yielded similar clinical outcomes to PELD, including pain control and patient satisfaction. However, UBE was associated with various disadvantages relative to PELD, including increased total, intraoperative and hidden blood loss, longer operation times, longer hospital stays, and more total hospitalization costs.

Exosomes are nano-sized membrane-bound vesicles and contain active substances (DNA, noncoding RNA [ncRNA], protein), which provide a novel method of transferring effector messages between cells. Circular RNAs (circRNAs), a kind of ncRNA, have attracted increasing attention over the last decade given advances in whole-genome and transcriptome sequencing technologies. It has become increasingly clear that circRNAs regulate gene expression through various actions and play diverse roles in many fields of human cancer biology. Notably, several studies reported that circRNAs are enriched in exosomes and that exosomal circRNAs play an important role in cancer biology. Exosomal circRNAs can be taken up by neighboring or distant cells and affect many aspects of physiological and pathological conditions of the recipient cells, potentially promoting cell communication and tumor metastasis. Herein, we briefly review the molecular mechanisms of circRNAs and recent findings regarding exosomal circRNAs, and highlight the specific roles of exosomal circRNAs in human cancer.

The aim of this study is to demonstrate the effect of extracellular calcium ion (Ca2+) and inorganic phosphate (Pi) concentrations on the growth and differentiation of bone-marrow-derived mesenchymal stem cells (MSCs), which is essential to understand the interaction between calcium phosphate ceramic (CPC) scaffolds and seeded cells during the construction of tissue-engineered bones. MSCs were separated from rabbits and cultured in media with different concentrations of Ca2+ and Pi supplements. Their proliferation, apoptosis, mineralization and osteogenic differentiation were determined by the MTT assay, TUNEL assay, Vonkossa stain and RT-PCR examination. A two-way ANOVA calculation with comparisons of estimated marginal means by LSD was used for statistical analysis. Results showed that the optimal extracellular Ca2+ and Pi concentrations for the cells to proliferate and differentiate were 1.8 mM and 0.09 mM, respectively, which are the concentrations supplied in many commonly used culture media such as DMEM and alpha-MEM. Cell proliferation and differentiation decreased significantly with greater or lower concentrations of the Pi supplement. Greater Pi concentrations also led to significant cell apoptosis. Greater Ca2+ concentrations did not change cell proliferation but significantly inhibited cell differentiation. In addition, greater Ca2+ concentrations could significantly enhance cell mineralization. In conclusion, extracellular Ca2+ and Pi significantly influence the growth and osteogenic differentiation of MSCs. It is important to take the cellular effect of Ca2+ and Pi into consideration when designing or constructing scaffolds for bone tissue engineering with CPC.

Abstract Lipidomics research could provide insights of pathobiological mechanisms in Alzheimer’s disease. This study explores a battery of plasma lipids that can differentiate Alzheimer’s disease (AD) patients from healthy controls and determines whether lipid profiles correlate with genetic risk for AD. AD plasma samples were collected from the Sydney Memory and Ageing Study (MAS) Sydney, Australia (aged range 75–97 years; 51.2% male). Untargeted lipidomics analysis was performed by liquid chromatography coupled–mass spectrometry (LC–MS/MS). We found that several lipid species from nine lipid classes, particularly sphingomyelins (SMs), cholesterol esters (ChEs), phosphatidylcholines (PCs), phosphatidylethanolamines (PIs), phosphatidylinositols (PIs), and triglycerides (TGs) are dysregulated in AD patients and may help discriminate them from healthy controls. However, when the lipid species were grouped together into lipid subgroups, only the DG group was significantly higher in AD. ChEs, SMs, and TGs resulted in good classification accuracy using the Glmnet algorithm (elastic net penalization for the generalized linear model [glm]) with more than 80% AUC. In general, group lipids and the lipid subclasses LPC and PE had less classification accuracy compared to the other subclasses. We also found significant increases in SMs, PIs, and the LPE/PE ratio in human U251 astroglioma cell lines exposed to pathophysiological concentrations of oligomeric Aβ 42 . This suggests that oligomeric Aβ 42 plays a contributory, if not causal role, in mediating changes in lipid profiles in AD that can be detected in the periphery. In addition, we evaluated the association of plasma lipid profiles with AD-related single nucleotide polymorphisms (SNPs) and polygenic risk scores (PRS) of AD. We found that FERMT2 and MS4A6A showed a significantly differential association with lipids in all lipid classes across disease and control groups. ABCA7 had a differential association with more than half of the DG lipids (52.63%) and PI lipids (57.14%), respectively. Additionally, 43.4% of lipids in the SM class were differentially associated with CLU . More than 30% of lipids in ChE, PE, and TG classes had differential associations with separate genes (ChE- PICALM , SLC24A4 , and SORL1 ; PE- CLU and CR1 ; TG- BINI ) between AD and control group. These data may provide renewed insights into the pathobiology of AD and the feasibility of identifying individuals with greater AD risk.

BACKGROUND: Chronic hepatitis C (CHC) is a contagious liver disease that results from infection with the hepatitis C virus (HCV). The most serious consequence of CHC is HCV-related hepatocellular carcinoma (HCC). OBJECTIVE: To illustrate the clinical significance of lncRNA HEIH expression in serum and exosomes in the development of HCV-related HCC. METHODS: Thirty-five CHC, twenty-two HCV-induced cirrhosis and ten HCV-related HCC patients in Huzhou Central Hospital from January 2016 to September 2016 were recruited in the present study. Basic patient information, clinical serological indicators, and clinical imaging data were investigated and analyzed. Serum samples were collected from patients after receiving informed consent. Exosomes were extracted from the serum, and electron microscopy was used to observe the ultrastructure of exosomes. Quantitative PCR was used to detect lncRNA HEIH gene expression in serum and exosomes. RESULTS: The changes in the ALT, GGT, HDL, INR, Alb and AFP levels in the patients with HCV-induced cirrhosis and HCV-related HCC were statistically significant. In patients with HCV-related HCC, lncRNA-HEIH expression in serum and exosomes was increased, but the ratio of lncRNA-HEIH expression in serum versus exosomes was decreased compared to patients with CHC.

Coculturing scaffolds with seeded cells in vitro is an indispensable process for construction of engineered tissues. It is essential to understand effects of the constituent particles of scaffold on seeded cells. In this study, we investigated the influence of nano-sized hydroxyapatite (nHAP) particles on the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (MSCs). nHAP particles were cocultured with MSCs separated from rabbit. Cellular effects of particles were determined by cell counts, Vonkossa stains, and reverse transcription-polymerase chain reaction (RT-PCR) examinations. Results showed that nHAP particles could promote the MSCs growth when particle concentrations were lower than 20 microg/10(4) cells. This effect disappeared when the particles and the cells were cocultured in serum-free media. Higher particle concentrations could significantly inhibit the cell growth. Under the standard culture condition, the only effect of nHAP particles on osteogenic differentiation of MSCs was to enhance the expression of collagen I. Under the osteogenic-inductive culture condition, nHAP particles could inhibit mineralization of cells but promote their osteogenic differentiation. These cellular effects of particles still existed when the particles and the cells were cultured in indirect coculture system. nHAP particles could decrease calcium and phosphate concentrations of culture media, which possibly contributed to the cellular effects of nHAP particles.

BACKGROUND: Pancreatic cancer is a devastating disease that is characterized by persistent hypoxia. The roles of hypoxia-inducible factor-2α (hif-2α) are different to those of hif-1α, although both are critical for tumor cells to adapt to the hypoxic microenvironment. However, unlike the well-studied hif-1α, the role of hif-2α in tumors, including pancreatic cancer, is poorly understood. METHODS: Herein, we used a mutated hif-2α (A530T) to figure out the problem that wild-type hif-2α is quickly degraded which limits the study of its function. Using several cell lines, mouse models, and human tissues, we obtained a general picture of hif-2α in pancreatic cancer progression. RESULTS: Functional assays revealed that hif-2α promotes epithelial-to-mesenchymal transition, enhances tumor proliferation and invasion, increases stemness, facilitates angiogenesis, and up-regulates aerobic glycolysis. We identified an interaction between hif-2α and β-catenin, and found that hif-2α/β-catenin complex formation increased the activity of β-catenin and the protein stability of hif-2α. In vivo study confirmed the pro-oncogenic role of hif-2α, whose expression correlated with those of E-cadherin, vimentin, Ki-67, and CD31, but not hif-1α. A human tissue study showed that hif-2α was associated with lymph node metastasis, pathological grade, stroma abundance, vascularization and patient survival. High expression of hif-2α was also identified as an independent indicator of poor prognosis in patients with pancreatic cancer. CONCLUSIONS: Our systematic study revealed the roles of hif-2α in pancreatic cancer, and may provide a novel target for this highly malignant disease.

OBJECTIVE: Breast cancer (BC) is one of the most common cancers in females. Abnormal proliferation and metastasis are key reasons that cause mortality in BC patients. More and more evidence showed that lncRNA played an important role in the BC development, but the mechanism was not well established. PATIENTS AND METHODS: The expression of lncRNA NEAT1 was detected in 40 BC patients by qRT-PCR technology. MTT and Wound Healing assays were applied to detect the effect of lncRNA NEAT1 in proliferation and metastasis in BC. Western blot was used to detect possible protein, which was regulated by lncRNA NEAT1. RESULTS: lncRNA NEAT1 was highly expressed in BC tissue, and the expression was also closely related to the tumor size and lymph node metastasis. Survival study also showed that the expression of lncRNA NEAT1 was closely related with prognosis of BC patients. MTT and Wound Healing assays showed that suppression of lncRNA NEAT1 could lead to decreased proliferation and metastasis in BC cell lines. Western blot also showed that β-catenin and N-cad were decreased while E-cad was increased after lncRNA NEAT1 being suppressed. CONCLUSIONS: lncRNA NEAT1 may act as an oncogene in BC, which can promote proliferation and metastasis of BC.

Long noncoding RNA (lncRNA) plays pivotal roles in cancer development. To date, only a small number of lncRNAs have been characterized at functional level. Here, we discovered a novel lncRNA termed GAS5-AS1 as a tumor suppressor in non-small cell lung cancer (NSCLC). The expression of GAS5-AS1 in NSCLC tumors was much lower than that in the adjacent normal lung tissues. The reduced GAS5-AS1 was significantly correlated with larger tumors, higher TNM stages, and lymph node metastasis in NSCLC patients. While ectopic expression or specific knockdown of GAS5-AS1 had no effect on proliferation, cell cycle progression, and apoptosis, it dramatically decreased or increased, respectively, NSCLC cell migration and invasion. Overexpression of GAS5-AS1 in NSCLC cells reduced a cohort of molecules (ZEB1, N-cadherin, Vimentin, and/or Snail1) critical for epithelial-mesenchymal transition (EMT). Furthermore, the DNA demethylating agent 5-aza-2-deoxycytidine failed to upregulate GAS5-AS1 in NSCLC cells, whereas the pan-HDAC inhibitors panobinostat and SAHA significantly induced GAS5-AS1 in a dose-dependent manner. In addition, GAS5-AS1 can be upregulated by specific knockdown of HDAC1 or HDAC3. Collectively, our data suggest that histone modifications play a major role leading to epigenetic silencing of GAS5-AS1 in NSCLC and subsequently promote tumor metastasis via upregulation of several key EMT markers.

In 2012, the European Society of Intensive Care Medicine proposed a definition for acute gastrointestinal injury (AGI) based on current medical evidence and expert opinion. The aim of the present study was to evaluate the feasibility of using the current AGI grading system and to investigate the association between AGI severity grades with clinical outcome in critically ill patients. Adult patients at 14 general intensive care units (ICUs) with an expected ICU stay ≥24 h were prospectively studied. The AGI grade was assessed daily on the basis of gastrointestinal (GI) symptoms, intra-abdominal pressures, and feeding intolerance (FI) in the first week of admission to the ICU. Among the 550 patients enrolled, 456 patients (82.9%) received mechanical ventilation, and 470 patients were identified for AGI. The distribution of the global AGI grade was 24.5% with grade I, 49.4% with grade II, 20.6% with grade III, and 5.5% with grade IV. AGI grading was positively correlated with 28- and 60-day mortality (P < 0.0001). Univariate Cox regression analysis showed that age, sepsis, diabetes mellitus, coronary artery disease, the use of vasoactive drugs, serum creatinine and lactate levels, mechanical ventilation, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and the global AGI grade were significantly (P ≤ 0.02) associated with 60-day mortality. In a multivariate analysis including these variables, diabetes mellitus (HR 1.43, 95% CI 1.03–1.87; P = 0.05), the use of vasoactive drugs (HR 1.56, 95% CI 1.12–2.11; P = 0.01), serum lactate (HR 1.15, 95% CI 1.06–1.24; P = 0.03), global AGI grade (HR 1.65, 95% CI 1.28–2.12; P = 0.008), and APACHE II score (HR 1.04, 95% CI 1.02–1.06; P < 0.001) were independently associated with 60-day mortality. In a subgroup analysis of 402 patients with 7-day survival, in addition to clinical predictors and the AGI grade on the first day of ICU stay, FI within the first week of ICU stay had an independent and incremental prognostic value for 60-day mortality (χ2 = 41.9 vs. 52.2, P = 0.007). The AGI grading scheme is useful for identifying the severity of GI dysfunction and could be used as a predictor of impaired outcomes. In addition, these results support the hypothesis that persistent FI within the first week of ICU stay is an independent determinant for mortality. Chinese Clinical Trial Registry identifier: ChiCTR-OCS-13003824 . Registered on 29 September 2013.

LIST OF ABBREVIATIONS: EMBL-EBI The European Bioinformatics Institute; E. coli Escherichia coli; E. faecalis Enterobacter faecalis; B. fragilis Bacteroides fragilis; B. vulgatus Bacteroides vulgatus; SaPIs Staphylococcus aureus pathogenicity islands; ARGs Antibiotic resistance genes; STEC Shiga toxigenic E. coli; Stx Shiga toxin; BLAST Basic Local Alignment Search Tool; TSST-1 Toxic shock toxin 1; RBPs Receptor-binding proteins; LPS lipopolysaccharide; OMVs Outer membrane vesicles; PT Phosphorothioate; BREX Bacteriophage exclusion; OCR Overcome classical restriction; Pgl Phage growth limitation; DISARM Defense island system associated with restrictionmodification; R-M system Restriction-modification system; BREX system Bacteriophage exclusion system; CRISPR Clustered regularly interspaced short palindromic repeats; Cas CRISPR-associated; PAMs Prospacer adjacent motifs; crRNA CRISPR RNA; SIE; OMPs; Superinfection exclusion; Outer membrane proteins; Abi Abortive infection; TA Toxin-antitoxin; TLR Toll-like receptor; APCs Antigen-presenting cells; DSS Dextran sulfate sodium; IELs Intraepithelial lymphocytes; FMT Fecal microbiota transfer; IFN-γ Interferon-gamma; IBD Inflammatory bowel disease; AgNPs Silver nanoparticles; MDSC Myeloid-derived suppressor cell; CRC Colorectal cancer; VLPs Virus-like particles; TMP Tape measure protein; PSMB4 Proteasome subunit beta type-4; ALD Alcohol-related liver disease; GVHD Graft-versus-host disease; ROS Reactive oxygen species; RA Rheumatoid arthritis; CCP Cyclic citrullinated protein; AMGs Accessory metabolic genes; T1DM Type 1 diabetes mellitus; T2DM Type 2 diabetes mellitus; SCFAs Short-chain fatty acids; GLP-1 Glucagon-like peptide-1; A. baumannii Acinetobacter baumannii; CpG Deoxycytidylinate-phosphodeoxyguanosine; PEG Polyethylene glycol; MetS Metabolic syndrome; OprM Outer membrane porin M.

AIM: ). METHODS: . Five-year disease-free survival (DFS) and overall survival (OS) were compared. SPSS 21.0 software was used for all data. DFS and OS were compared and analyzed by Kaplan-Meier and Log-rank test. RESULTS: = 0.012) in stage IVC patients compared to stage IVB patients. CONCLUSION: has shown that peritoneal metastasis has a worse prognosis than distant organ metastasis in our institution's CRC cohort. Additional datasets should be analyzed to confirm these findings.

Tendon-bone insertion injuries (TBI), such as anterior cruciate ligament (ACL) and rotator cuff injuries, are common degenerative or traumatic pathologies with a negative impact on the patient's daily life, and they cause huge economic losses every year. The healing process after an injury is complex and is dependent on the surrounding environment. Macrophages accumulate during the entire process of tendon and bone healing and their phenotypes progressively transform as they regenerate. As the "sensor and switch of the immune system", mesenchymal stem cells (MSCs) respond to the inflammatory environment and exert immunomodulatory effects during the tendon-bone healing process. When exposed to appropriate stimuli, they can differentiate into different tissues, including chondrocytes, osteocytes, and epithelial cells, promoting reconstruction of the complex transitional structure of the enthesis. It is well known that MSCs and macrophages communicate with each other during tissue repair. In this review, we discuss the roles of macrophages and MSCs in TBI injury and healing. Reciprocal interactions between MSCs and macrophages and some biological processes utilizing their mutual relations in tendon-bone healing are also described. Additionally, we discuss the limitations in our understanding of tendon-bone healing and propose feasible ways to exploit MSC-macrophage interplay to develop an effective therapeutic strategy for TBI injuries. The Translational potential of this article: This paper reviewed the important functions of macrophages and mesenchymal stem cells in tendon-bone healing and described the reciprocal interactions between them during the healing process. By managing macrophage phenotypes, mesenchymal stem cells and the interactions between them, some possible novel therapies for tendon-bone injury may be proposed to promote tendon-bone healing after restoration surgery.