NMAAP1 regulated macrophage polarizion into M1 type through glycolysis stimulated with BCG.

Bacillus Calmette Guerin (BCG) perfusion is widely used as cancer adjuvant therapy, in which macrophages play an important role. Novel macrophage activated associated protein 1 (NMAAP1), upregulated after BCG's activation, was proved to promote macrophage polarization to the M1 type. We found that BCG could stimulate mice BMDM to the M1 type and kill tumor cells. After the deletion of NMAAP1, the tumor volume of mice became larger, and the number of M1 type macrophages in the tumor decreased significantly. When macrophages were induced into the M1 type, aerobic glycolysis, the Warburg effect manifested in the increased uptake of glucose and the conversion of pyruvate to lactic acid. NMAAP1 could bind with IP3R and regulate macrophage polarization to the M1 type. However, the specific mechanism of how NMAAP1 regulates macrophage polarization towards the M1 type and plays an antitumor role must be clarified. NMAAP1 could promote the release of lactic acid and pyruvate, enhance the glycolysis of macrophages, and affect the expression of HIF-1α. After inhibition of glycolysis by 2-DG and lactic acid generation by FX11, the effects of NMAAP1 promoting macrophage polarization to the antitumor M1 type were weakened. Furthermore, NMAAP1 upregulated the expression of HIF-1α, which is associated with glycolysis. Moreover, the Ca2+/NF-κB pathway regulated HIF-1α expression by NMAAP1 in the macrophages. NMAAP1 promotes the polarization of macrophages towards the M1 type by affecting the Warburg effect stimulated by BCG.

PDGFRA exhibits potential as an indicator of angiogenesis within the tumor microenvironment and is up-regulated in BLCA.

Bladder cancer (BLCA) is a common type of urogenital malignancy worldwide. The recurrence and metastasis of bladder cancer are closely related to angiogenesis, but the underlying mechanisms are unclear. In this study, we developed a method to predict survival outcomes among BLCA patients, which could be used to guide immunotherapy and chemotherapy. We obtained patient data from The Cancer Genome Atlas (TCGA) and identified angiogenesis-related genes from the GeneCards database. First, we used differential expression analysis and univariate Cox analysis to identify angiogenesis-related genes and used correlation analysis to generate molecular subtypes based on M2 macrophages. Next, we constructed a prognostic signature consisting of four genes (ECM1, EFEMP1, SLIT2, and PDGFRΑ), which was found to be an independent prognostic factor. Higher risk scores were associated with worse overall survival and higher expression of immune checkpoints. We also evaluated immune cell infiltration using the CIBERSORT and ssGSEA algorithms. Additionally, we performed stratification analyses, constructed a nomogram, and predicted chemotherapeutic responses based on the risk signature. Finally, we validated our findings by using qRT-PCR as well as IHC data to detect the expression levels of the four genes at mRNA and protein levels in BLCA patients and obtained results that were consistent with our predictions. Our study demonstrates the utility of a four-gene prognostic signature for prognostication in bladder cancer patients and designing personalized treatments, which could provide new avenues for personalized management of these patients.

Microbial signatures of neonatal bacterial meningitis from multiple body sites.

As a common central nervous system infection in newborns, neonatal bacterial meningitis (NBM) can seriously affect their health and growth. However, although metagenomic approaches are being applied in clinical diagnostic practice, there are some limitations for whole metagenome sequencing and amplicon sequencing in handling low microbial biomass samples. Through a newly developed ultra-sensitive metagenomic sequencing method named 2bRAD-M, we investigated the microbial signatures of central nervous system infections in neonates admitted to the neonatal intensive care unit. Particularly, we recruited a total of 23 neonates suspected of having NBM and collected their blood, cerebrospinal fluid, and skin samples for 2bRAD-M sequencing. Then we developed a novel decontamination method (Reads Level Decontamination, RLD) for 2bRAD-M by which we efficiently denoised the sequencing data and found some potential biomarkers that have significantly different relative abundance between 12 patients that were diagnosed as NBM and 11 Non-NBM based on their cerebrospinal fluid (CSF) examination results. Specifically, we discovered 11 and 8 potential biomarkers for NBM in blood and CSF separately and further identified 16 and 35 microbial species that highly correlated with the physiological indicators in blood and CSF. Our study not only provide microbiological evidence to aid in the diagnosis of NBM but also demonstrated the application of an ultra-sensitive metagenomic sequencing method in pathogenesis study.

Comprehensive metabolomics profiling of seminal plasma in asthenozoospermia caused by different etiologies.

BACKGROUND: Asthenozoospermia (AZS) is a disease characterized by decreased sperm motility induced by multiple etiologies, and the pathological mechanisms of various AZS are unclear. We simultaneously analyzed the metabolic profiling of four representative AZS to provide new insights into the etiologies of AZS. METHOD: Seminal plasma samples were collected from healthy control (HC; n = 30) and four AZS induced by varicocele (VA, n = 30), obesity (OA, n = 22), reproductive system infections (RA; n = 17) and idiopathic (IA, n = 30), respectively, and were analyzed using gas chromatography-mass spectrometry. Disturbed metabolites and metabolic pathways were compared between AZS and HC, as well as IA and the other three AZS. RESULTS: A total of 40 different metabolites were identified in the seminal plasma of AZS and HC, of which lactic acid, fructose, citric acid, glutamine and pyruvic acid metabolic abnormalities associated with all the AZS groups, while each AZS group had unique metabolic changes. RA was significantly separated from the other three AZS, and metabolites such as cholesterol, octadecanoic acid and serine mainly contributed to the separation. CONCLUSION: The comprehensive metabolomic analysis and comparison of four various AZS provided evidence and clues for the mechanism mining, which will benefit future etiology, diagnosis and treatment of AZS.

Is glucocorticoid use associated with a higher clinical pregnancy rate of in vitro fertilization and embryo transfer? A meta-analysis.

Background: It has been reported that the use of glucocorticoids may be able to improve clinical pregnancy rates in patients receiving in vitro fertilization and embryo transfer (IVF-ET). The purpose of this study was to investigate the association between glucocorticoid use and clinical pregnancy rate in IVF-ET patients. Methods: This study has been registered on the International Register of Prospective Systems Evaluation (PROSPERO) (ID: CRD42022375427). A thorough and detailed search of databases including PubMed, Web of Science, Embase, and Cochrane Library was conducted to identify eligible studies up to October 2022. Quality assessment was conducted on the modified Jadad Scoring Scale and Newcastle-Ottawa Scale, and the inter-study heterogeneity was estimated by Q test and I2 test. Combined hazard ratios with 95% CI were calculated using random effects or fixed effects models based on heterogeneity. Meanwhile, Begg's and Egger's tests were used to detect the existence of publication bias, the leave-one-out method was used for sensitivity analysis and multiple subgroup analyses were conducted. Results: Seventeen studies involving 3056 IVF-ET cycles were included. We found that glucocorticoid use was associated with a higher IVF-ET pregnancy rate (OR = 1.86, 95% CI = 1.27-2.74, P = 0.002). In the subgroup analysis, studies of different regions and different study types all showed similar results that glucocorticoid is beneficial to improve the clinical pregnancy rate of patients with IVF-ET, and patients with positive autoantibodies and patients receiving IVF-ET multiple times also showed the same results. However, there was no significant change in clinical pregnancy rates in the seven studies with negative autoantibodies and in the seven studies with initial IVF-ET treatment. The results of the 12 medium-acting glucocorticoids and 4 long-acting glucocorticoids were also generally consistent with each other. There was no statistical difference in subgroup analysis of whether patients had endometriosis or not. Conclusion: Appropriate use of glucocorticoids is beneficial for improving the clinical pregnancy rate in women receiving IVF-ET, but this result still needs to be verified by more high-quality and large sample size randomized controlled trials (RCTs).

Prognostic capacity of the systemic inflammation response index for functional outcome in patients with aneurysmal subarachnoid hemorrhage.

Objective: We aimed to investigate the relationship between systemic inflammatory response index (SIRI) and functional outcome after aneurysmal subarachnoid hemorrhage (aSAH). Methods: A retrospective cohort study was performed involving all consecutive aSAH patients admitted to our institution. The modified Rankin Scale (mRS) score was performed to determine the functional outcomes of all patients at 3 months after aSAH. Results were categorized as favorable (mRS score 0-2) and unfavorable (mRS score 3-6). Univariate and multivariate logistic regressive analyses were utilized to identify the prognostic significance of SIRI. To minimize the effects of confounding factors, patients were stratified according to the optimal cut-off value of SIRI with propensity score matching (PSM). Further subgroup analysis was conducted to verify the consistency of our findings and Pearson's correlation analysis was used to assess the relationship between SIRI and the severity of aSAH. Results: In this study, 350 patients were enrolled and 126 (36.0%) of them suffered unfavorable outcomes. The SIRI of 5.36 × 109/L was identified as the optimal cut-off value. Two score-matched cohorts (n = 100 in each group) obtained from PSM with low SIRI and high SIRI were used for analysis. A significantly higher unfavorable functional outcome rate was observed in patients with high SIRI before and after PSM (p < 0.001 and 0.017, respectively). Multivariate logistic regression analysis demonstrated that SIRI value ≥ 5.36 × 109/L was an independent risk factor for poor outcomes (OR 3.05 95% CI 1.37-6.78, p = 0.006) after adjusting for possible confounders. A identical result was discovered in the PSM cohort. In ROC analysis, the area under the curve (AUC) of SIRI was 0.774 which shown a better predictive value than other inflammatory markers observed in previous similar studies. Pearson's correlation analysis proved the positive association between SIRI and aSAH severity. Conclusions: Elevated SIRI at admission is associated with worse clinical status and poorer functional outcomes among patients with aSAH. SIRI is a useful inflammatory marker with prognostic value for functional outcomes after aSAH.

Metabolomics profiling of seminal plasma in obesity-induced asthenozoospermia.

BACKGROUND: Asthenozoospermia is one of the essential causes of male infertility, and its incidence is significantly higher in obese men. Due to its complex etiology and unknown pathomechanism, the diagnosis and treatment of obesity-induced asthenozoospermia is a prevalent problem in reproductive medicine. OBJECTIVE: This study aims to explore major differential metabolites and metabolic pathways in seminal plasma and pathological mechanisms for obesity-induced asthenozoospermia. MATERIALS AND METHODS: We performed non-target metabolomic studies on the seminal plasma of healthy men with normal semen parameters (HN group, n = 20), obese men with normal semen parameters (ON group, n = 20), and men with obesity-induced asthenozoospermia (OA group, n = 20) based on gas chromatography-mass spectrometry. Metabolic profilings and related pathway analyses were conducted to discriminate differential metabolites and metabolic pathways. RESULTS: A total of 20 differential metabolites including fructose, succinic acid, aconitic acid, methylmaleic acid, glucopyranose, serine, valine, leucine, phenylalanine, glycine, glutamic acid, alanine, proline and threonine were identified in HN group and ON group; 24 differential metabolites including glucose, fructose, pyruvic acid, citric acid, succinic acid, aconitic acid, glucopyranose, glutamic acid, valine, leucine, glycine, phenylalanine, lysine, citrulline, proline and alanine were produced in OA group and ON group; and 28 differential metabolites including glucose, fructose, citric acid, succinic acid, glucopyranose, valine, glycine, serine, leucine, phenylalanine, alanine, threonine, proline, glutamic acid, citrulline, lysine and tyrosine were produced in OA group and HN group. In addition, abnormal energy metabolism including carbohydrate metabolism (TCA cycle, glycolysis/gluconeogenesis, and pyruvate metabolism) and amino acid metabolism (phenylalanine, tyrosine, and tryptophan biosynthesis, D-glutamine and D-glutamate metabolism; phenylalanine metabolism, etc.) were found in ON group and OA group. CONCLUSION: Obesity could affect the metabolite composition in seminal plasma and abnormal energy metabolism in seminal plasma mainly including carbohydrate metabolism and amino acid metabolism were closely related to obesity-induced asthenozoospermia.

RuO2-Incorporated Co3O4 Nanoneedles Grown on Carbon Cloth as Binder-Free Integrated Cathodes for Tuning Favorable Li2O2 Formation.

Developing ideal Li-O2 batteries (LOBs) requires the discharge product to have a large quantity, have large contact area with the cathode, and not passivate the porous surface after discharge, which put forward high requirement for the design of cathodes. Herein, combining the rational structural design and high activity catalyst selection, minor amounts of RuO2-incorporated Co3O4 nanoneedles grown on carbon cloth are successfully synthesized as binder-free integrated cathodes for LOBs. With this unique design, plenty of electron-ion-oxygen tri-phase reaction interface is created, the side reaction from carbon is isolated, and oxygen reduction reaction/oxygen evolution reaction (OER) kinetics are significantly facilitated. Upon discharge, film-like Li2O2 is observed growing on the needle surface first and eventually ball-like Li2O2 particles form at each tip of the needle. The cathode surface remains porous after discharge, which is beneficial to the OER and is rare in the previous reports. The battery exhibits a high specific discharge capacity (7.64 mAh cm-2) and a long lifespan (500 h at 0.1 mA cm-2). Even with a high current of 0.3 mA cm-2, the battery achieves a cycling life of 200 h. In addition, punch-type LOBs are fabricated and successfully operated, suggesting that the cathode material can be utilized in ultralight, flexible electronic devices.

Morphological evaluation of the risk of posterior communicating artery aneurysm rupture: a mirror aneurysm model.

OBJECTIVE: The aim of this study was to use morphological parameters of mirror posterior communicating artery (PCoA) aneurysms to evaluate aneurysm rupture risk. METHODS: The morphological parameters of 45 pairs of ruptured mirror PCoA aneurysms were analyzed. Conditional univariate and multivariate logistic regression of the following paired morphological parameters was performed: aneurysm with a daughter sac, aneurysm height, aneurysm width, neck width, internal carotid artery diameter, PCoA diameter, flow angle, PCoA angle, aspect ratio, bottleneck factor, size ratio, height/width ratio, fetal posterior cerebral artery, and aneurysm with height > width. A scoring system was established according to the odds ratios (ORs). The receiver operating characteristic was used to test the prediction accuracy of this scoring system in the authors' database of 523 PCoA aneurysms and the threshold value was used to define higher risk. RESULTS: Aneurysm width (OR 1.676, p = 0.014), aneurysm with daughter sac (OR 7.775, p = 0.016), and aneurysm with height > width (OR 9.067, p = 0.012) were independent risk factors for rupture. The scoring system consisted of aneurysm width (1 point per mm), aneurysm with a daughter sac (5 points), and aneurysm with height > width (5 points). The area under the curve (AUC) of the scoring system was 0.842, and its threshold value was 7.97. A score ≥ 8 points was defined as higher risk. The AUC using this definition was 0.802. CONCLUSIONS: Aneurysm width, aneurysms with height > width, and aneurysms with a daughter sac were independent risk factors for PCoA aneurysm rupture. The scoring system devised in this study accurately predicts rupture risk.

Study on the preparation and properties of CaCO3 ultrafine powder derived from waste eggshell.

In this study, eggshell-derived CaCO3 ultrafine powder was prepared from waste eggshell with the method of omnidirectional planetary ball mill. The particle size distribution was measured by laser particle size analyzer. Then, the parameters of grinding kinetic equation of eggshell powder were obtained by software fitting, and the grinding model and characteristic equation of particle-size distribution of the eggshell-derived CaCO3 powder were discussed. The results showed that the best grinding conditions were as follows: using 3 mm zirconia grinding ball, 400 rpm, 50% filling rate, 50% slurry concentration, and ball-milling time of 30 min. The grinding kinetic equation can well simulate the eggshell crushing process. The equation showed that with the prolongation of milling time, the large particle size of the eggshell powder gradually decreased, and the milling efficiency was 0 after 60 min. The Rosin-Rammler-Bennet distribution model could be used to describe the distribution characteristics of the cumulative particle size of the eggshell powder, and the fitting degree of particle size distribution at each milling time could reach R2 > 0.99. No chemical change occurred in the eggshell powder before and after grinding. However, the calcite crystal structure of eggshell-derived CaCO3 ultrafine powder becomes incomplete.

Prognostic significance of combined score of fibrinogen and neutrophil-lymphocyte ratio for functional outcome in patients with aneurysmal subarachnoid hemorrhage.

Objective: To explore the relationship between fibrinogen and neutrophil to lymphocyte ratio (F-NLR) score and functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Method: A retrospective study was conducted that involved all consecutive patients with aSAH admitted to our institution from March 2018 to October 2021. Factors, such as demographics, comorbidities, clinical characteristics, neuroradiological data, and laboratory parameters, were collected from institutional databases. All patients achieved neurological assessment using the modified Rankin Scale (mRS) score 3 months after discharge to clarify the functional outcomes. The results were classified as favorable (mRS score 0-2) and unfavorable (mRS score 3-6). Univariate and multivariable analyses were performed to identify the relevant factors between inflammatory markers and functional outcomes after aSAH. Subsequently, a receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predicting performance of variables. A propensity score match (PSM) was performed to correct imbalances in patients' baseline characteristics. Results: Finally, 256 patients with aSAH were included in the study cohort. A total of 94 (36.7%) patients had an unfavorable outcome. F-NLR scores were 0 [interquartile range (IQR) 0-1] and 1 (IQR 1-2) in patients with favorable and unfavorable outcomes, respectively (p < 0.001). After adjustment, the F-NLR score on admission remained significantly associated with unfavorable outcomes in patients with aSAH. In the multivariable analysis, the F-NLR score was regarded as an independent risk factor of unfavorable outcomes [odds ratio (OR) 3.113, 95% CI 1.755-5.523, p < 0.001]. In ROC analysis, the optimal cutoff value of the F-NLR score was 0.5 points. Two cohorts (n = 86 in each group) obtained from PSM with low F-NLR scores (0 points) and high F-NLR scores (1-2 points) were used for analysis. A significantly higher unfavorable functional outcome rate was observed in patients with high F-NLR scores (33.7 vs. 9.3%, p < 0.001). The area under the curve (AUC) values of F-NLR scores before and after PSM were 0.767 and 0.712, respectively. Conclusion: Fibrinogen and neutrophil to lymphocyte ratio score was an independent risk parameter associated with unfavorable functional outcomes at 3 months after aSAH. A higher F-NLR score predicts the occurrence of poor functional outcomes.

Strategies toward anode stabilization in nonaqueous alkali metal-oxygen batteries.

Alkali metal-O2 batteries exhibit ultra-high theoretical energy density which is even on par with fossil energy and are expected to become the next generation energy storage devices. However, to maintain the advantages of high energy density of alkali metal-O2 batteries, the reversibility of alkali metal anodes with high capacity is of vital importance. But the alkali metal anode with high chemical activity often faces a variety of challenges, including various side reactions, dendrite formation and volume expansion. In this highlight, we focus on the challenges faced by alkali metal anodes in alkali metal-O2 batteries and introduce the latest strategies to effectively stabilize the metal anode. Future perspectives are pointed out, which are valuable for the further development of nonaqueous alkaline metal-O2 batteries.

Architectural Narrative Shapes Brain Activities Underlying Approach-Avoidance Response: A Case Study of the Stadium.

Each great architecture tells a story to make its space meaningful. What the stadium tells matters how the individual interacts with it. The potent influence of narrative in shaping our cognitive processing has been revealed and widely used. This influence, however, has not been the focus of researchers in stadium operations. The present study aimed at investigating the influence of the stadium narrative on approach-avoidance responses and the corresponding neural correlates. Participants were presented with a sequence of pictures expressing a story congruent or incongruent with the general profile of the stadium, and were required to make an enter or exit response. Results showed larger amplitudes of N400 for incongruent trials than congruent trials at the end of the narrative, indicating the feasibility of continuity editing procedure for the study of narratives. Moreover, larger amplitudes of LPP were observed in response to the stadium preceded by congruent trials than incongruent trials. This effect was more pronounced in the left than right frontal sites. The LPP suggested that a congruent narrative imparted the stadium approaching affective features, and induced approaching responses, which was consistent with the behavioral and correlational results. Our findings suggested that changes in narrative were sufficient to shape the approach-avoidance responses and the underlying neural correlates. Implications for stadium management and buildings are provided.

Additive-Assisted Hydrophobic Li+ -Solvated Structure for Stabilizing Dual Electrode Electrolyte Interphases through Suppressing LiPF6 Hydrolysis.

Lithium-metal batteries have attracted much attention due to their high energy density. However, the hydrolysis of LiPF6 leads to uncontrollable Li dendrites growth and fast capacity fading. Herein, a hydrophobic Li+ -solvated structure is designed by inducing the hexafluoroisopropyl acrylate into the electrolyte system. Due to the alkene groups and non-polar perfluorocarbon (-CF2 CF2 CF3 ) chain, a hydrophobic surface around Li-ion solvated aggregates can be obtained to protect the LiPF6 against the attack from trace H2 O. Moreover, the additive could also help to form an organic solid electrolyte interphase with rich polar C-F bonds, which can capture Li ions to restrain the dendrite growth. Therefore, the Li||Li symmetric cells show a stable cycling performance up to 500 h at a current density of 1 mA cm-2 . The Li||LiNi0.6 Co0.2 Mn0.2 O2 cells show good cycling stability, exhibiting a specific capacity of 111 mAh g-1 at 1 C with a capacity retention of 74 % after 200 cycles.

Predictors of complete recovery of oculomotor nerve palsy induced by posterior communicating artery aneurysms in patients aged eighteen to sixty.

OBJECTIVE: To explore prognostic factors of complete recovery of oculomotor nerve palsy (ONP) induced by posterior communicating artery aneurysm (PcomAA). METHOD: PcomAA patients aged 18-60 years combined with ONP who underwent surgical clipping or endovascular embolization at our institution between January 2014 and January 2020 were enrolled. Characteristics included maximum diameter of aneurysm, width of aneurysm, subarachnoid hemorrhage (SAH), duration of ONP, age, sex, ONP type, treatment method were compared. Based on the recovery of ONP, patients were separated into two groups: complete recovery group, partial and no recovery group. Analyzing by univariate and multivariate logistic regressions to identify the independent prognostics for complete ONP recovery. We established a score based on these prognostics. Receiver operating characteristics (ROC) were conducted to under the performance of the predictors and score. RESULTS: Finally, ONP type (OR 6.457 95% CI 1.664-25.052, p = 0.007), treatment method (OR 5.051, 95% CI 1.332-19.158, p = 0.017), and interval to treatment ≤2 weeks (OR 25.601 95% CI 6.222-105.340, p < 0.001) were independent predictors of complete ONP recovery. The score had an area under the curve (AUC) value of 0.870. We defined that the score higher than 5 points as easier to achieve complete ONP recovery, and the AUC value of this definition was 0.821. CONCLUSIONS: For ONP induced by PcomAA in patients aged 18-60 years, the best prognostic factor for complete ONP recovery was timely treatment. The ONP type and treatment methods were correlated with complete ONP recovery.

Li2 O2 Formation Electrochemistry and Its Influence on Oxygen Reduction/Evolution Reaction Kinetics in Aprotic Li-O2 Batteries.

Aprotic Li-O2 batteries are regarded as the most promising technology to resolve the energy crisis in the near future because of its high theoretical specific energy. The key electrochemistry of a nonaqueous Li-O2 battery highly relies on the formation of Li2 O2 during discharge and its reversible decomposition during charge. The properties of Li2 O2 and its formation mechanisms are of high significance in influencing the battery performance. This review article demonstrates the latest progress in understanding the Li2 O2 electrochemistry and the recent advances in regulating the Li2 O2 growth pathway. The first part of this review elaborates the Li2 O2 formation mechanism and its relationship with the oxygen reduction reaction/oxygen evolution reaction electrochemistry. The following part discusses how the cycling parameters, e.g., current density and discharge depth, influence the Li2 O2 morphology. A comprehensive summary of recent strategies in tailoring Li2 O2 formation including rational design of cathode structure, certain catalyst, and surface engineering is demonstrated. The influence resulted from the electrolyte, e.g., salt, solvent, and some additives on Li2 O2 growth pathway, is finally discussed. Further prospects of the ways in making advanced Li-O2 batteries by control of favorable Li2 O2 formation are highlighted, which are valuable for practical construction of aprotic lithium-oxygen batteries.

The role of HIF-1α in BCG-stimulated macrophages polarization and their tumoricidal effects in vitro.

BCG is widely used for cancer treatment, where macrophages play an important role. However, the mechanism of BCG affecting macrophages remains poorly understood. In this study, we used BCG to stimulate myeloid-derived macrophages lacking HIF-1α, the levels of TNF-α, IL-1ß, CD86 of macrophages and their effects on the growth of tumor cells MCA207 and B16-F10 were detected. We found that the absence of HIF-1α prevents BCG-stimulated macrophages from polarizing towards the M (BCG) and attenuating its killing effect on tumor cells. In addition, we demonstrated that the tumors of mice lacking HIF-1α in macrophages were significantly increased by the experiment of mice transplantation. Our study provides relevant evidence for exploring the mechanism of the BCG vaccine in the prevention and treatment of related diseases.

Inflammation-associated factors for predicting in-hospital mortality in patients with COVID-19.

The aim is to explore the relation between inflammation-associated factors and in-hospital mortality and investigate which factor is an independent predictor of in-hospital death in patients with coronavirus disease-2019. This study included patients with coronavirus disease-2019, who were hospitalized between February 9, 2020, and March 30, 2020. Univariate Cox regression analysis and least absolute shrinkage and selection operator regression (LASSO) were used to select variables. Multivariate Cox regression analysis was applied to identify independent risk factors in coronavirus disease-2019. A total of 1135 patients were analyzed during the study period. A total of 35 variables were considered to be risk factors after the univariate regression analysis of the clinical characteristics and laboratory parameters (p < .05), and LASSO regression analysis screened out seven risk factors for further study. The six independent risk factors revealed by multivariate Cox regression were myoglobin (HR, 5.353; 95% CI, 2.633-10.882; p < .001), C-reactive protein (HR, 2.063; 95% CI, 1.036-4.109; p = .039), neutrophil count (HR, 2.015; 95% CI, 1.154-3.518; p = .014), interleukin 6 (Il-6; HR, 9.753; 95% CI, 2.952-32.218; p < .001), age (HR, 2.016; 95% CI, 1.077-3.773; p = .028), and international normalized ratio (HR, 2.595; 95% CI, 1.412-4.769; p = .002). Our results suggested that inflammation-associated factors were significantly associated with in-hospital mortality in coronavirus disease-2019 patients. C-reactive protein, neutrophil count, and interleukin 6 were independent factors for predicting in-hospital mortality and had a better independent predictive ability. We believe these findings may allow early identification of the patients at high risk for death, and can also assist in better management of these patients.

The novel target：exosoms derived from M2 macrophage.

More and more exosome-based therapeutics are being developed with advances in nanotechnology and precision medicine. Exosome is a kind of tiny vesicles with a bilayer of phospholipids, which can transfer biological macromolecules to recipients to influence the biological process. M2 macrophages are closely related to the occurrence and development of serious diseases such as tumor. In addition to the traditional concept of macrophage functions such as opsonization, secretion of cytokines and other soluble factors, some studies have found that the exosome derived from M2 macrophages can influence the development of disease by carrying microRNA, long noncodingRNA and functional proteins to regulate target gene expression as well as related proteins synthesis recently. Here, we outlined the biogenesis of the exosome and its biological functions in disease. Then we focused on elucidating the effects of the exosome derived from M2 macrophages on several diseases and its mechanisms. Finally, we discussed the appropriateness and inappropriateness in existing potential applications based on exosomes and macrophages.

Development and validation of a nomogram using on admission routine laboratory parameters to predict in-hospital survival of patients with COVID-19.

To develop and validate a nomogram using on admission data to predict in-hospital survival probabilities of coronavirus disease 2019 (COVID-19) patients. We analyzed 855 COVID-19 patients with 52 variables. The least absolute shrinkage and selection operator regression and multivariate Cox analyses were used to screen significant factors associated with in-hospital mortality. A nomogram was established based on the variables identified by Cox regression. The performance of the model was evaluated by C-index and calibration plots. Decision curve analysis was conducted to determine the clinical utility of the nomogram. Six variables, including neutrophil (hazard ratio [HR], 1.088; 95% confidence interval [CI], [1.0004-1.147]; p < .001), C-reactive protein (HR, 1.007; 95% CI, [1.0026-1.011]; p = .002), IL-6 (HR, 1.001; 95% CI, [1.0003-1.002]; p = .005), d-dimer (HR, 1.034; 95% CI, [1.0111-1.057]; p = .003), prothrombin time (HR 1.086, 95% CI [1.0369-1.139], p < .001), and myoglobin (HR, 1.001; 95% CI, [1.0007-1.002]; p < .001), were identified and applied to develop a nomogram. The nomogram predicted 14-day and 28-day survival probabilities with reasonable accuracy, as assessed by the C-index (0.912) and calibration plots. Decision curve analysis showed relatively wide ranges of threshold probability, suggesting a high clinical value of the nomogram. Neutrophil, C-reactive protein, IL-6, d-dimer, prothrombin time, and myoglobin levels were significantly correlated with in-hospital mortality of COVID-19 patients. Demonstrating satisfactory discrimination and calibration, this model could predict patient outcomes as early as on admission and might serve as a useful triage tool for clinical decision making.