Combining single-cell RNA sequencing of peripheral blood mononuclear cells and exosomal transcriptome to reveal the cellular and genetic profiles in COPD.

BACKGROUND: It has been a long-held consensus that immune reactions primarily mediate the pathology of chronic obstructive pulmonary disease (COPD), and that exosomes may participate in immune regulation in COPD. However, the relationship between exosomes and peripheral immune status in patients with COPD remains unclear. METHODS: In this study, we sequenced plasma exosomes and performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) from patients with COPD and healthy controls. Finally, we constructed competing endogenous RNA (ceRNA) and protein-protein interaction (PPI) networks to delineate the interactions between PBMCs and exosomes within COPD. RESULTS: We identified 135 mRNAs, 132 lncRNAs, and 359 circRNAs from exosomes that were differentially expressed in six patients with COPD compared with four healthy controls. Functional enrichment analyses revealed that many of these differentially expressed RNAs were involved in immune responses including defending viral infection and cytokine-cytokine receptor interaction. We also identified 18 distinct cell clusters of PBMCs in one patient and one control by using an unsupervised cluster analysis called uniform manifold approximation and projection (UMAP). According to resultant cell identification, it was likely that the proportions of monocytes, dendritic cells, and natural killer cells increased in the COPD patient we tested, meanwhile the proportions of B cells, CD4 + T cells, and naïve CD8 + T cells declined. Notably, CD8 + T effector memory CD45RA + (Temra) cell and CD8 + effector memory T (Tem) cell levels were elevated in patient with COPD, which were marked by their lower capacity to differentiate due to their terminal differentiation state and lower reactive capacity to viral pathogens. CONCLUSIONS: We generated exosomal RNA profiling and single-cell transcriptomic profiling of PBMCs in COPD, described possible connection between impaired immune function and COPD development, and finally determined the possible role of exosomes in mediating local and systemic immune reactions.

Identification of Canine Pyometra-Associated Metabolites Using Untargeted Metabolomics.

Canine pyometra frequently occurs in middle-aged to older intact bitches, which seriously affects the life of dogs and brings an economic loss to their owners. Hence, finding a key metabolite is very important for the diagnosis and development of a new safe and effective therapy for the disease. In this study, dogs with pyometra were identified by blood examinations, laboratory analyses and diagnostic imaging, and fifteen endometrium tissues of sick dogs with pyometra and fifteen controls were collected and their metabolites were identified utilizing a UHPLC-qTOF-MS-based untargeted metabolomics approach. The results indicated that the elevated inflammatory cells were observed in dogs with pyometra, suggesting that sick dogs suffered systemic inflammation. In the untargeted metabolic profile, 705 ion features in the positive polarity mode and 414 ion features in the negative polarity mode were obtained in endometrium tissues of sick dogs with pyometra, with a total of 275 differential metabolites (173 in positive and 102 in negative polarity modes). Moreover, the multivariate statistical analyses such as PCA and PLS-DA also showed that the metabolites were significantly different between the two groups. Then, these differential metabolites were subjected to pathway analysis using Metaboanalyst 4.0, and Galactose metabolism, cAMP signaling pathway and Glycerophospholipid metabolism were enriched, proving some insights into the metabolic changes during pyometra. Moreover, the receiver operating characteristic curves further confirmed kynurenic acid was expected to be a candidate biomarker of canine pyometra. In conclusion, this study provided a new idea for exploring early diagnosis methods and a safe and effective therapy for canine pyometra.

The Relationship of Tumor Microbiome and Oral Bacteria and Intestinal Dysbiosis in Canine Mammary Tumor.

Canine mammary tumor (CMT) is the most common tumor in dogs, with 50% of malignant cases, and lacks an effective therapeutic schedule, hence its early diagnosis is of great importance to achieve a good prognosis. Microbiota is believed to play important roles in systemic diseases, including cancers. In this study, 91 tumors, 21 oral and fecal samples in total were collected from dogs with CMTs, and 31 oral and 21 fecal samples from healthy dogs were collected as control. The intratumoral, oral and gut bacterial community of dogs with CMTs and healthy dogs was profiled by 16S rRNA high-throughput sequencing and bioinformatic methods. The predominant intratumoral microbes were Ralstonia, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Pseudomonas, unidentified_Chloroplast and Bacteroides at the genus level. In addition, our findings demonstrated striking changes in the composition of the oral and gut bacterium community in the dogs suffered from CMTs compared to the healthy dogs, with a significant increase of Bacteroides which also was the significant microbial biomarker in the oral and gut bacterium community. It showed that the Bacteroides was shared in the intratumoral, oral and intestinal bacterial microbiomes, confirming that microbiota might travel from the mouth to the intestine and finally to the distant mammary tumor tissue. This study provides a new microbiological idea for the treatment of canine mammary tumors, and also provides a theoretical basis for the study of human breast cancer.

Finite-Time Thermodynamic Modeling and Optimization of Short-Chain Hydrocarbon Polymerization-Catalyzed Synthetic Fuel Process.

The short-chain hydrocarbon polymerization-catalyzed synthetic fuel technology has great development potential in the fields of energy storage and renewable energy. Modeling and optimization of a short-chain hydrocarbon polymerization-catalyzed synthetic fuel process involving mixers, compressors, heat exchangers, reactors, and separators are performed through finite-time thermodynamics. Under the given conditions of the heat source temperature of the heat exchanger and the reactor, the optimal performance of the process is solved by taking the mole fraction of components, pressure, and molar flow as the optimization variables, and taking the minimum entropy generation rate (MEGR) of the process as the optimization objective. The results show that the entropy generation rate of the optimized reaction process is reduced by 48.81% compared to the reference process; among them, the component mole fraction is the most obvious optimization variable. The research results have certain theoretical guiding significance for the selection of the operation parameters of the short-chain hydrocarbon polymerization-catalyzed synthetic fuel process.

Highly Integrated Nano-Platform for Breaking the Barrier between Chemotherapy and Immunotherapy.

Fighting metastasis is a major challenge in cancer therapy, and stimulation of the immune system is of particular importance in the treatment of metastatic cancers. Here, an integrated theranostic nanoplatform was developed for the efficient treatment of highly metastatic tumors. Versatile functions including "And" logically controlled drug release, prolonged circulation time, tumor targeting, and anti-metastasis were integrated into doxorubicin (DOX) loaded, highly integrated mesoporous silica nanoparticles (DOX@HIMSNs) for a systemic treatment of highly metastatic triple negative breast cancer (TNBC). It was found that the good therapeutic effect of DOX@HIMSN was only partially attributed to its anticancer cytotoxicity. Most importantly, DOX@HIMSN could induce anticancer immune responses including dendritic cell (DC) maturation and antitumor cytokine release. Compared with the traditional tumor chemotherapy, the integrated theranostic nanoplatform we developed not only improved the tumor specific cytotoxicity but also stimulated antitumor immune responses during the treatment.

Gold Nanocluster Decorated Polypeptide/DNA Complexes for NIR Light and Redox Dual-Responsive Gene Transfection.

Endo/lysosomal escape and subsequent nuclear translocation are recognized as the two major challenges for efficient gene transfection. Herein, nuclear localization signal (NLS) peptide sequences and oligomeric lysine sequences were crosslinked via disulfide bonds to obtain glutathione (GSH) reducible polypeptide (pNLS). The pNLS could condense DNA into compact positive-charged complexes with redox sensitivity, and then gold nanoclusters (AuNC) were further decorated to the surface via electrostatic interactions obtaining versatile pNLS/DNA/AuNC complexes. The AuNC could generate reactive oxygen species (ROS) under NIR-irradiation and accelerate the endo/lysosomal escape of the complexes, and then the pNLS sequence degraded by GSH in cytoplasm would release the DNA and facilitate the subsequent nuclear translocation for enhanced gene transfection.

Theranostic GO-based nanohybrid for tumor induced imaging and potential combinational tumor therapy.

Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function.

Aberrant PTPRO methylation in tumor tissues as a potential biomarker that predicts clinical outcomes in breast cancer patients.

BACKGROUND: Aberrant hypermethylation of gene promoter regions is a primary mechanism by which tumor suppressor genes become inactivated in breast cancer. Epigenetic inactivation of the protein tyrosine phosphatase receptor-type O gene (PTPRO) has been described in several types of cancer. RESULTS: We screened primary breast cancer tissues for PTPRO promoter hypermethylation and assessed potential associations with pathological features and patient outcome. We also evaluated its potential as a breast cancer biomarker. PTPRO methylation was observed in 53 of 98 (54%) breast cancer tissues but not in adjacent normal tissue. Among matched peripheral blood samples from breast cancer patients, 33 of 98 (34%) exhibited methylated PTPRO in plasma. In contrast, no methylated PTPRO was observed in normal peripheral blood from 30 healthy individuals. PTPRO methylation was positively associated with lymph node involvement (P = 0.014), poorly differentiated histology (P = 0.037), depth of invasion (P = 0.004), and HER2 amplification (P = 0.001). Multivariate analysis indicated that aberrant PTPRO methylation could serve as an independent predictor for overall survival hazard ratio (HR): 2.7; 95% CI: 1.1-6.2; P = 0.023), especially for patients with HER2-positive (hazard ratio (HR): 7.5; 95% CI: 1.8-31.3; P = 0.006), but not in ER + and PR + subpopulation. In addition, demethylation induced by 5-azacytidine led to gene reactivation in PTPRO-methylated and -silenced breast cancer cell lines. CONCLUSIONS: Here, we report that tumor PTPRO methylation is a strong prognostic factor in breast cancer. Methylation of PTPRO silences its expression and plays an important role in breast carcinogenesis. The data we present here may provide insight into the development of novel therapies for breast cancer treatment. Additionally, detection of PTPRO methylation in peripheral blood of breast cancer patients may provide a noninvasive means to diagnose and monitor the disease.

The protective effect of fasciotomy combined with hypertonic saline flushing for crush syndrome in rats.

ABSTRACT: In natural disasters such as earthquakes and landslides, the main problem that wounded survivors are confronted with is Crush Syndrome (CS). The aim of this study was to explore more convenient and effective early treatment measures for it.In the present study, we investigated the protective effect of fasciotomy combined with different concentration of hypertonic saline flushing with CS rats. CS model was prepared by compressing the buttocks and both lowering limbs of rats with 7.5 kg dumbbell for 4 hours. The rats were divided into 10 groups, which were normal control group, model group, incision without flushing group, 0.45%, 0.9%, 3%, 5%, 7% saline group, 3%-0.45% and 7%-0.45% saline alternating flushing group respectively. 6 hours after the treatment, the blood was sampled for measurement of the potassium, calcium, AST, ALT, Cr, Urea, myoglobin, and lactic acid content. The blood flow of the compressed tissue and kidneys, the pathological changes of the kidneys and the survival rate of 3%-0.45% saline alternating flushing group were also observed.The experimental results showed that fasciotomy alone for treatment cannot improve the presentation of CS of rats. Instead, hypertonic saline flushing significantly improved the AST, ALT, Cr, Urea indices, blood flow of muscles and kidneys. It also enormously decreased the blood K+, myoglobin, lactic acid concentration and slight increased the blood Ca2+. Among them, alternating flushing with 3%-0.45% saline had the best therapeutic effect on CS. Finally, it can be found that 3%-0.45% saline treatment regimen dramatically raised the survival rate of CS rats.All in all, this study suggests that fasciotomy combined with hypertonic saline flushing is a good therapeutic approach for CS.

Trap & kill: a neutrophil-extracellular-trap mimic nanoparticle for anti-bacterial therapy.

Fenton chemistry-mediated antimicrobials have demonstrated great promise in antibacterial therapy. However, the short life span and diffusion distance of hydroxyl radicals dampen the therapeutic efficiency of these antimicrobials. Herein, inspired by the neutrophil extracellular trap (NET), in which bacteria are trapped and agglutinated via electronic interactions and killed by reactive oxygen species, we fabricated a NET-mimic nanoparticle to suppress bacterial infection in a "trap & kill" manner. Specifically, this NET-mimic nanoparticle was synthesized via polymerization of ferrocene monomers followed by quaternization with a mannose derivative. Similar to the NET, the NET-mimic nanoparticles trap bacteria through electronic and sugar-lectin interactions between their mannose moieties and the lectins of bacteria, forming bacterial agglutinations. Therefore, they confine the spread of the bacteria and restrict the bacterial cells to the destruction range of hydroxyl radicals. Meanwhile, the ferrocene component of the nanoparticle catalyzes the production of highly toxic hydroxyl radicals at the H2O2 rich infection foci and effectively eradicates the agglutinated bacteria. In a mouse model of an antimicrobial-resistant bacteria-infected wound, the NET-mimic nanoparticles displayed potent antibacterial activity and accelerated wound healing.

Combined use of dexmedetomidine and nalbuphine in laparoscopic radical gastrectomy for gastric cancer.

BACKGROUND: Radical laparoscopic gastrectomy is an important treatment modality for gastric cancer. Surgery requires general anesthesia, and patients are susceptible to the effects of anesthetic drugs and carbon dioxide insufflation during the procedure, leading to inflammation or severe pain, which can affect patient outcome. AIM: To explore the efficacy of combining dexmedetomidine (DEX) with nalbuphine in patients underwent laparoscopic radical gastrectomy for gastric cancer. METHODS: Patients scheduled to undergo laparoscopic radical gastrectomy were selected and randomly assigned to A or B group. In A group, patients received an intravenous injection of nalbuphine 0.2 mg/kg + DEX 0.4 µg/kg 10 min before the end of surgery; in B group, patients received only an intravenous injection of nalbuphine. The trends in hemodynamic parameter fluctuations, awakening quality during the recovery period, serum inflammatory markers, agitation scores, cough severity, incidence, and duration of postoperative delirium (POD) were compared. RESULTS: The mean arterial pressure and heart rate in the A group were more stable (P < 0.05). The A group had a lower average awakening time, extubation time, and agitation scores during recovery than the B group. Agitation control in the A group was more effective at different time points (P < 0.05). Patients in the A group had lower serum interleukin (IL)-6, tumour necrosis factor alpha, and IL-10 levels at 1 h after surgery than the B group. The incidence of coughing and duration of POD were lower and shorter in the A group than in the B group. Adverse reactions caused by the two anesthesia methods were less frequent in the A group than in the B group (P < 0.05). CONCLUSION: The use of DEX and nalbuphine in patients undergoing laparoscopic radical gastrectomy for gastric cancer help reducing the inflammatory response, cough severity, and agitation and helps maintain hemodynamic stability.

Post-COVID-19 Pandemic Rebound of Macrolide-Resistant Mycoplasma pneumoniae Infection: A Descriptive Study.

The rebound characteristics of respiratory infections after lifting pandemic control measures were uncertain. From January to November 2023, patients presenting at a teaching hospital were tested for common respiratory viruses and Mycoplasma pneumoniae using a combination of antigen, nucleic acid amplification, and targeted next-generation sequencing (tNGS) tests. The number and rate of positive tests per month, clinical and microbiological characteristics were analyzed. A rapid rebound of SARS-CoV-2 was followed by a slower rebound of M. pneumoniae, with an interval of 5 months between their peaks. The hospitalization rate was higher, with infections caused by respiratory viruses compared to M. pneumoniae. Though the pediatric hospitalization rate of respiratory viruses (66.1%) was higher than that of M. pneumoniae (34.0%), the 4094 cases of M. pneumoniae within 6 months posed a huge burden on healthcare services. Multivariate analysis revealed that M. pneumoniae-infected adults had more fatigue, comorbidities, and higher serum C-reactive protein, whereas children had a higher incidence of other respiratory pathogens detected by tNGS or pathogen-specific PCR, fever, and were more likely to be female. A total of 85% of M. pneumoniae-positive specimens had mutations detected at the 23rRNA gene, with 99.7% showing A2063G mutation. Days to defervescence were longer in those not treated by effective antibiotics and those requiring a change in antibiotic treatment. A delayed but significant rebound of M. pneumoniae was observed after the complete relaxation of pandemic control measures. No unusual, unexplained, or unresponsive cases of respiratory infections which warrant further investigation were identified.

A study on the correlation between intrauterine microbiota and uterine pyogenesis in dogs.

Pyometra is a common and high-incidence reproductive system disease in female dogs, and its development involves both hormonal and bacterial factors. Characterization of the endometrial microbiome in healthy dogs and diseased dogs with pyometra remains unclear at present, however. In this study, dogs with pyometra were identified based on the clinical examinations, hematology examinations, vaginal smears and uterine histopathology. The endometrial samples of healthy dogs (n = 30) and diseased dogs (n = 41) were then collected and sequenced by 16S rRNA high-throughput sequencing technology. Dogs with pyometra suffered from inflammation, and their endometrial microbial diversity (ACE and Chao 1 indices) was significantly lower than that of healthy dogs (P < 0.05). The endometrial samples of both groups were enriched in four phyla (Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria), with a greater abundance of Firmicutes in diseased dogs (P < 0.05). At the genus level, the most prevalent microbes in diseased dogs belonged to Pseudomonas, Escherichia-Shigella, Mycoplasma, Enterococcus, Haemophilus, Vibrio and Ralstonia, with lower levels of Mycoplasma, Enterococcus and Haemophilus in the healthy control. Principal co-ordinates analysis and non-metric multi-dimensional scaling showed that the endometrial microbiome of diseased dogs clustered separately from that of the healthy controls (P < 0.05). In the LDA effect size analysis, 18 members of the endometrial microbiome were screened. Of these, the bacterial species Pseudomonas_aeruginosa and microbes within the genera Mycoplasma, Enterococcus and Haemophilus were found to be enriched in the uteruses of diseased dogs. Furthermore, the Random Forests model further confirmed that Mycoplasma and Haemophilus could be considered as biomarkers of diseased endometrium. In conclusion, this study provided a theoretical basis for the development of probiotic preparation in the future.

MicroRNA-128 suppresses tau phosphorylation and reduces amyloid-beta accumulation by inhibiting the expression of GSK3ß, APPBP2, and mTOR in Alzheimer's disease.

INTRODUCTION AND AIMS: Alzheimer's disease (AD) is characterized by the abnormal accumulation of hyperphosphorylated tau proteins and amyloid-beta (Aß) peptides. Recent studies have shown that many microRNAs (miRNAs) are dysregulated in AD, and modulation of these miRNAs can influence the development of tau and Aß pathology. The brain-specific miRNA miR-128, encoded by MIR128-1 and MIR128-2, is important for brain development and dysregulated in AD. In this study, the role of miR-128 in tau and Aß pathology as well as the regulatory mechanism underlying its dysregulation were investigated. METHODS: The effect of miR-128 on tau phosphorylation and Aß accumulation was examined in AD cellular models through miR-128 overexpression and inhibition. The therapeutic potential of miR-128 in AD mouse model was assessed by comparing phenotypes of 5XFAD mice administered with miR-128-expressing AAVs with 5XFAD mice administered with control AAVs. Phenotypes examined included behavior, plaque load, and protein expression. The regulatory factor of miR-128 transcription was identified through luciferase reporter assay and validated by siRNA knockdown and ChIP analysis. RESULTS: Both gain-of-function and loss-of-function studies in AD cellular models reveal that miR-128 represses tau phosphorylation and Aß secretion. Subsequent investigations show that miR-128 directly inhibits the expression of tau phosphorylation kinase GSK3ß and Aß modulators APPBP2 and mTOR. Upregulation of miR-128 in the hippocampus of 5XFAD mice ameliorates learning and memory impairments, decreases plaque deposition, and enhances autophagic flux. We further demonstrated that C/EBPα transactivates MIR128-1 transcription, while both C/EBPα and miR-128 expression are inhibited by Aß. CONCLUSION: Our findings suggest that miR-128 suppresses AD pathogenesis, and could be a promising therapeutic target for AD. We also find a possible mechanism underlying the dysregulation of miR-128 in AD, in which Aß reduces miR-128 expression by inhibiting C/EBPα.

hsa_circ_0003176 Suppresses the Progression of Non-Small-Cell Lung Cancer via Regulating miR-182-5p/RBM5 Axis.

Background: Non-small-cell lung cancer (NSCLC) is one of the major diseases that threaten human health, and there is still no fundamental treatment method. Emerging evidences suggested that circRNAs might be an effective target to treatment NSCLC. However, the roles and detailed mechanisms of hsa_circ_0003176 in NSCLC still not clear. Methods: hsa_circ_0003176 was identified from GSE101684 and GSE112214 datasets of Gene Expression Omnibus (GEO) database. The expression of hsa_circ_0003176 was detected by RT-qPCR in NSCLC tissues, paired adjacent nontumor tissues, and cell lines. RNA fluorescence in situ hybridization and nuclear and cytoplasmic RNA fractionation analysis was used to detect the subcellular localization of hsa_circ_0003176 in H1299 and A549 cells. Dual-luciferase reporter and RNA pull-down assay were used to confirm the regulatory of miR-182-5p to hsa_circ_0003176 and RBM5. The roles of hsa_circ_0003176 in NSCLC progression was evaluated both in vitro by CCK-8 assay, colony formation assay, wound-healing assay, and matrigel transwell assay and in vivo by the subcutaneous xenograft nude mouse experiment and lung metastasis nude mouse experiment. In addition, RNA pull down and luciferase reporter assays were carried out to investigate the interaction between hsa_circ_0003176 or RBM5 and miR-182-5p. Results: Our results indicated that hsa_circ_0003176 showed typical characteristic of circRNAs, which was downregulated in both NSCLC tissues and cell lines. Functionally, overexpression of hsa_circ_0003176 suppressed the proliferation, migration, and invasion of NSCLC cells in vitro and inhibited NSCLC growth and metastasis in vivo. Furthermore, we found that hsa_circ_0003176 acts as sponge of miR-182-5p to regulate RBM5 expression. Further, in vitro rescue experiments demonstrated that hsa_circ_0003176 suppressed the proliferation, migration, and invasion of NSCLC cells by regulating miR-182-5p/RBM5 axis. Conclusion: We demonstrated that hsa_circ_0003176 suppressed the NSCLC progression via regulating miR-182-5p/RBM5 axis. These data indicated that hsa_circ_0003176 might be a novel molecular target for NSCLC treatment.

Analogous comparison unravels heightened antiviral defense and boosted viral infection upon immunosuppression in bat organoids.

Horseshoe bats host numerous SARS-related coronaviruses without overt disease signs. Bat intestinal organoids, a unique model of bat intestinal epithelium, allow direct comparison with human intestinal organoids. We sought to unravel the cellular mechanism(s) underlying bat tolerance of coronaviruses by comparing the innate immunity in bat and human organoids. We optimized the culture medium, which enabled a consecutive passage of bat intestinal organoids for over one year. Basal expression levels of IFNs and IFN-stimulated genes were higher in bat organoids than in their human counterparts. Notably, bat organoids mounted a more rapid, robust and prolonged antiviral defense than human organoids upon Poly(I:C) stimulation. TLR3 and RLR might be the conserved pathways mediating antiviral response in bat and human intestinal organoids. The susceptibility of bat organoids to a bat coronavirus CoV-HKU4, but resistance to EV-71, an enterovirus of exclusive human origin, indicated that bat organoids adequately recapitulated the authentic susceptibility of bats to certain viruses. Importantly, TLR3/RLR inhibition in bat organoids significantly boosted viral growth in the early phase after SARS-CoV-2 or CoV-HKU4 infection. Collectively, the higher basal expression of antiviral genes, especially more rapid and robust induction of innate immune response, empowered bat cells to curtail virus propagation in the early phase of infection.

Epidemiological Investigation of Canine Mammary Tumors in Mainland China Between 2017 and 2021.

Epidemiological studies enable us to analyze disease behavior, define risk factors, and establish fundamental prognostic criteria. This study aimed to determine the epidemiological and clinical characteristics of canine tumors diagnosed during the years 2017-2021. The results showed that canine mammary tumors were the most common tumors, and their relative incidence for 5-years-total was 46.71% (504/1,079), with 48.41% (244/504) of benign, and 51.59% (260/504) of malignant. Pure breeds accounted for 84.13% (424/504) of submissions, and adult female dogs (9-12 years old) were most frequently involved, followed by 5-8-year-old females. Remarkably, 2.58% (13/504) occurred in the male dogs. In addition, a high prevalence of mammary tumors (77.38%, 390/504) was diagnosed in unneutered dogs, and different incidence rates were observed in different regions (Northeast, Southeast, Northwest and Southwest China). For clinical factors, the tumor size ranged from 0.5 to 28 cm, with the 0-5 cm being the most common tumor size (47.82%, 241/504), and malignant tumors (4.33 ± 2.88 cm, mean ± SD) were bigger than benign ones (3.06 ± 1.67 cm, mean ± SD) (p < 0.001). The incidence of single tumor (55.36%, 279/504) was higher than that of multiple tumors in dogs, while the latter had a higher incidence of malignant tumors (74.67%, 168/225). According to this study, we also found that canine mammary tumors were more common in the last two pairs of mammary glands. In addition, multiple linear regression analysis showed that there was linear significant relationship between three independent variables (age, tumor size, and tumor number) and histological properties of canine mammary tumor [(p>|t|) < 0.05]. This is the first retrospective statistical analysis of such a large dataset in China to reveal the link between epidemiological clinical risks and histological diagnosis. It aids in the improvement of the host's knowledge of canine tumor disorders and the early prevention of canine mammary tumors.

Association between comorbid sleep apnoea-hypopnoea syndrome and prognosis of intensive care patients: a retrospective cohort study.

OBJECTIVE: In this study, we investigated the association between comorbid sleep apnoea-hypopnoea syndrome (SAHS) and the prognosis of patients in an intensive care unit (ICU) to determine whether this relationship varies between different disease subgroups. METHODS: We conducted a retrospective cohort study using publicly available information from the critical care database Medical Information Mart for Intensive Care III. Adults (≥18 years of age) who attended the ICU for the first time were enrolled. Demographic information and clinical data were obtained from each patient. The primary outcome was 30-day mortality after ICU admission, and the secondary outcomes were in-hospital and ICU mortality. Multivariate logistic regression and Cox regression analyses were used to examine the associations between SAHS comorbidities and the research outcomes. Propensity score matching was used to adjust for potential confounding variables. RESULTS: Of the 32 989 patients enrolled, 1918 (5.81%) were diagnosed with SAHS as a comorbid condition. Patients with SAHS had a significantly lower 30-day mortality rate compared with those without SAHS (5.27% vs 13.65%, respectively; p<0.001). The frequency of chronic obstructive pulmonary disease, cerebral disease, cardiovascular disease, hypertension, diabetes mellitus and renal failure was significantly different between the two groups. Patients with SAHS demonstrated significantly longer survival compared with patients without SAHS. Multivariate Cox proportional hazards regression identified a significant relationship between SAHS and mortality within 30 days (adjusted HR=0.610, 95% CI 0.499 to 0.747, p<0.0001). CONCLUSION: SAHS as a comorbid condition decreases the risk of 30-day mortality, in-hospital mortality and ICU mortality among ICU patients.

Engineering Living Bacteria for Cancer Therapy.

Bacteria possess many unique properties in treating cancer that are unachievable with standard methods, including specific tumor targeting, deep tissue penetration, and programmable therapeutic efficacy. Bacteria species such as Salmonella, Escherichia, Clostridium, and Listeria have been demonstrated to restrict tumor growth with improved prognosis in mice models. Moreover, some bacterial strains were advanced to clinical trials. This Spotlight on Applications summarizes general strategies for engineering living bacteria to fight cancer and provides examples to illustrate different approaches to engineer bacteria for safety and therapeutic index improvement.

Differences in Clinical Features and Laboratory Results between Adults and Children with SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children accounts for a small proportion of all infections and is usually mild or asymptomatic. There are few studies on the clinical characteristics of SARS-CoV-2 infection in children, and the causes of the low prevalence in children remain unclear. Herein, we compared the epidemiological and clinical characteristics of SARS-CoV-2 infection between adults and children. Fifty-two patients with Coronavirus Disease 2019 (COVID-19) were retrospectively analyzed, including 38 adults and 14 children. Their clinical information such as epidemiological exposure history, laboratory indicators, chest computed tomography (CT) performance, and number of SARS-CoV-2 positive days were analyzed and compared. In children, 5 (35.71%) had mild COVID-19 and 9 (64.29%) had common type, while, in adults, 9 (23.68%) cases were mild, and 29 (76.32%) were common COVID-19. Among them, family clustering infection accounted for 50% (7/14) of child cases and 23.68% (9/36) of adult cases. Epidemiological exposure history, clinical classification, clinical symptoms, chest CT manifestations, and number of SARS-CoV-2-positive days were not significantly different between children and adults. However, the percentage of neutrophils in adults was significantly higher than that in children (P < 0.05). The percentage and absolute value of lymphocytes, platelet counts, aspartate aminotransferase, and aspartate aminotransferase/alanine aminotransferase in adults were lower than those in children (P < 0.05). Conclusively, children infected with SARS-CoV-2 show the characteristics of family clustering, and the proportion of mild and asymptomatic infections is higher. For families with a history of epidemiological exposure, routine SARS-CoV-2 nucleic acid testing and chest CT examination should be performed in asymptomatic children to determine whether they are infected. Unlike adults, although the reduction of lymphocytes and platelets in children is not common, it is necessary to be alert to the increased risk of liver damage in children.