Exosomal transfer leads to chemoresistance through oxidative phosphorylation-mediated stemness phenotype in colorectal cancer.

Background: Recently years have seen the increasing evidence identifying that OXPHOS is involved in different processes of tumor progression and metastasis and has been proposed to be a potential therapeutical target for cancer treatment. However, the exploration in oxidative phosphorylation-mediated chemoresistance is still scarce. In our study, we identify exosomal transfer leads to chemoresistance by reprogramming metabolic phenotype in recipient cells. Methods: RNA sequencing analysis was used to screen altered targets mediating exosome transfer-induced chemoresistance. Seahorse assay allowed us to measure mitochondrial respiration. Stemness was measured by spheroids formation assay. Serum exosomes were isolated for circ_0001610 quantification. Results: The induced oxidative phosphorylation leads to more stem-like properties, which is dependent on the transfer of exosomal circ_0001610. Exosome transfer results in the removal of miR-30e-5p-mediated suppression of PGC-1a, a master of mitochondrial biogenesis and function. Consequently, increased PGC-1a reshapes cellular metabolism towards oxidative phosphorylation, leading to chemoresistance. Inhibition of OXPHOS or exosomal si-circ_0001610 increases the sensitivity of chemotherapy by decreasing cell stemness in vitro and in vivo. Conclusion: Our data suggests that exosomal circ_0001610-induced OXPHOS plays an important role in chemoresistance and supports a therapeutical potential of circ_0001610 inhibitors in the treatment of oxaliplatin-resistant colorectal cancer by manipulating cell stemness.

Establishment of risk model for elderly CAP at different age stages: a single-center retrospective observational study.

Community-acquired pneumonia (CAP) is one of the main reasons of mortality and morbidity in elderly population, causing substantial clinical and economic impacts. However, clinically available score systems have been shown to demonstrate poor prediction of mortality for patients aged over 65. Especially, no existing clinical model can predict morbidity and mortality for CAP patients among different age stages. Here, we aimed to understand the impact of age variable on the establishment of assessment model and explored prognostic factors and new biomarkers in predicting mortality. We retrospectively analyzed elderly patients with CAP in Minhang Hospital, Fudan University. We used univariate and multiple logistic regression analyses to study the prognostic factors of mortality in each age-based subgroup. The prediction accuracy of the prognostic factors was determined by the Receiver Operating Characteristic curves and the area under the curves. Combination models were established using several logistic regressions to save the predicted probabilities. Four factors with independently prognostic significance were shared among all the groups, namely Albumin, BUN, NLR and Pulse, using univariate analysis and multiple logistic regression analysis. Then we built a model with these 4 variables (as ABNP model) to predict the in-hospital mortality in all three groups. The AUC value of the ABNP model were 0.888 (95% CI 0.854-0.917, p < 0.000), 0.912 (95% CI 0.880-0.938, p < 0.000) and 0.872 (95% CI 0.833-0.905, p < 0.000) in group 1, 2 and 3, respectively. We established a predictive model for mortality based on an age variable -specific study of elderly patients with CAP, with higher AUC value than PSI, CURB-65 and qSOFA in predicting mortality in different age groups (66-75/ 76-85/ over 85 years).

Prognostic Significance of Cuproptosis-Related Gene Signatures in Breast Cancer Based on Transcriptomic Data Analysis.

Breast cancer (BRCA) remains a serious threat to women's health, with the rapidly increasing morbidity and mortality being possibly due to a lack of a sophisticated classification system. To date, no reliable biomarker is available to predict prognosis. Cuproptosis has been recently identified as a new form of programmed cell death, characterized by the accumulation of copper in cells. However, little is known about the role of cuproptosis in breast cancer. In this study, a cuproptosis-related genes (CRGs) risk model was constructed, based on transcriptomic data with corresponding clinical information relating to breast cancer obtained from both the TCGA and GEO databases, to assess the prognosis of breast cancer by comprehensive bioinformatics analyses. The CRGs risk model was constructed and validated based on the expression of four genes (NLRP3, LIPT1, PDHA1 and DLST). BRCA patients were then divided into two subtypes according to the CRGs risk model. Furthermore, our analyses revealed that the application of this risk model was significantly associated with clinical outcome, immune infiltrates and tumor mutation burden (TMB) in breast cancer patients. Additionally, a new clinical nomogram model based on risk score was established and showed great performance in overall survival (OS) prediction, confirming the potential clinical significance of the CRGs risk model. Collectively, our findings revealed that the CRGs risk model can be a useful tool to stratify subtypes and that the cuproptosis-related signature plays an important role in predicting prognosis in BRCA patients.

Exploration of prognostic factors for prediction of mortality in elderly CAP population using a nomogram model.

Background: The incidence and mortality rate of community-acquired pneumonia (CAP) in elderly patients were higher than the younger population. The assessment tools including CURB-65 and qSOFA have been applied in early detection of high-risk patients with CAP. However, several disadvantages exist to limit the efficiency of these tools for accurate assessment in elderly CAP. Therefore, we aimed to explore a more comprehensive tool to predict mortality in elderly CAP population by establishing a nomogram model. Methods: We retrospectively analyzed elderly patients with CAP in Minhang Hospital, Fudan University. The least absolute shrinkage and selection operator (LASSO) logistic regression combined with multivariate analyses were used to select independent predictive factors and established nomogram models via R software. Calibration plots, decision curve analysis (DCA) and receiver operating characteristic curve (ROC) were generated to assess predictive performance. Results: LASSO and multiple logistic regression analyses showed the age, pulse, NLR, albumin, BUN, and D-dimer were independent risk predictors. A nomogram model (NB-DAPA model) was established for predicting mortality of CAP in elderly patients. In both training and validation set, the area under the curve (AUC) of the NB-DAPA model showed superiority than CURB-65 and qSOFA. Meanwhile, DCA revealed that the predictive model had significant net benefits for most threshold probabilities. Conclusion: Our established NB-DAPA nomogram model is a simple and accurate tool for predicting in-hospital mortality of CAP, adapted for patients aged 65 years and above. The predictive performance of the NB-DAPA model was better than PSI, CURB-65 and qSOFA.

Exploration of Aging-Care Parameters to Predict Mortality of Patients Aged 80-Years and Above with Community-Acquired Pneumonia.

Purpose: The study explores a clinical model based on aging-care parameters to predict the mortality of hospitalized patients aged 80-year and above with community-acquired pneumonia (CAP). Patients and methods: In this study, four hundred and thirty-five CAP patients aged 80-years and above were enrolled in the Central Hospital of Minhang District, Shanghai during 01,01,2018-31,12,2021. The clinical data were collected, including aging-care relevant factors (ALB, FRAIL, Barthel Index and age-adjusted Charlson Comorbidity Index) and other commonly used factors. The prognostic factors were screened by multivariable logistic regression analysis. Receiver operating characteristic (ROC) curves were used to predict the mortality risk. Results: Univariate analysis demonstrated that several factors, including gender, platelet distribution width, NLR, ALB, CRP, pct, pre-albumin, CURB-65, low-density, lipoprotein, Barthel Index, FRAIL, leucocyte count, neutrophil count, lymphocyte count and aCCI, were associated with the prognosis of CAP. Multivariate model analyses further identified that CURB-65 (p < 0.0001, OR = 5.44, 95% CI = 3.021-10.700), FRAIL (p < 0.0001, OR = 5.441, 95% CI = 2.611-12.25) and aCCI (p = 0.003, OR = 1.551, 95% CI = 1.165-2.099) were independent risk factors, whereas ALB (p = 0.005, OR = 0.871, 95% CI = 0.788-0.957) and Barthel Index (p = 0.0007, OR = 0.958, 95% CI = 0.933-0.981) were independent protective factors. ROC curves were plotted to further predict the in-hospital mortality and revealed that combination of three parameters (Barthel Index+ FRAI +CURB-65) showed the best performance. Conclusion: This study showed that CURB-65, frailty and aCCI were independent risk factors influencing prognosis. In addition, ALB and Barthel Index were protective factors for in CAP patients over 80-years old. AUC was calculated and revealed that combination of three parameters (Barthel Index+ FRAI +CURB-65) showed the best performance.

Aquifer flushing using a SDS/1-butanol based in-situ microemulsion: Performance and mechanism for the remediation of nitrobenzene contamination.

In-situ microemulsion flushing is an effective remediation technology for the removal of dense non-aqueous phase liquids (DNAPLs) from aquifers. Nitrobenzene (NB) is a typical DNAPL pollutant that is responsible for the serious contamination of many groundwater systems, while its removal using the flushing method has rarely been studied. In this study, bench scale, 1-D column and 2-D tank experiments were conducted to establish an efficient salt-free sodium dodecyl sulfate (SDS)/1-butanol based in-situ microemulsion flushing system for NB contaminated aquifers. Results showed that the NB/SDS/1-butanol/water microemulsion increased dissolved NB concentrations by more than 15-fold compared to the SDS-only solution. The formulation also presented good solubilization capacity at low temperature (5 â„ƒ) and with clay media. NB was effectively removed from the aquifer by solubilization and mobilization via the formation of the microemulsion with the injected SDS/1-butanol solution. The flushing system also reduced the tailing phenomenon in later remediation stages, and exhibited weak reagent adsorption onto aquifer media. Furthermore, the vertical DNAPL migration to deeper aquifer was effectively controlled. Therefore, the constructed in-situ microemulsion flushing system is a highly efficient treatment method for NB contaminated aquifers, with this study providing valuable reference information on the optimal reagent parameters and the remediation mechanism.

Comparison of Different Scoring Systems for Prediction of Mortality and ICU Admission in Elderly CAP Population.

BACKGROUND: The incidence and mortality rate of community-acquired pneumonia (CAP) in elderly patients were higher than the younger population. Different scoring systems, including The quick Sequential Organ Function Assessment (qSOFA), Combination of Confusion, Urea, Respiratory Rate, Blood Pressure, and Age ≥65 (CURB-65), Modified Early Warning Score (MEWS) and National Early Warning Score (NEWS), were used widely for predicting mortality and ICU admission of patients with community-acquired pneumonia (CAP). This study aimed to identify the most suitable score system for better hospitalization. METHODS: We retrospectively analyzed elderly patients with CAP in Minhang Hospital, Fudan University from 1 January 2018 to 1 January 2020. We recorded information of the patients including age, gender, underlying disease, consciousness state, vital signs, physiological and laboratory variables and further calculated the qSOFA, CURB-65, MEWS, and NEWS scores. Receiver operating characteristic (ROC) curves were used to predict the mortality risk and ICU admission. Kaplan-Meier survival curves were used in survival rate. RESULTS: In total, 1044 patients were selected for analysis and divided into two groups, namely survivor groups (902 cases) and non-survivor groups (142 cases). Depending on ICU admission enrolled patients were classified into ICU admission (n = 102) and non-ICU admission (n = 942) groups. Mortality expressed as AUC values were 0.844 (p < 0.001), 0.868 (p < 0.001), 0.927 (p < 0.001) and 0.892 (p < 0.001) for qSOFA, CURB 65, MEWS and NEWS, respectively. There were clear differences in MEWS vs CURB-65 (p < 0.0001), MEWS vs NEWS (p < 0.001), MEWS vs qSOFA (p < 0.0001). For ICU-admission, the AUC values of qSOFA, CURB-65, MEWS and NEWS scores were 0.866 (p < 0.001), 0.854 (p < 0.001), 0.922 (p < 0.001), 0.976 (p < 0.001), respectively. There were significant differences in NEWS vs CURB-65 (p < 0.0001), NEWS vs MEWS (p < 0.001), NEWS vs qSOFA (p < 0.0001). CONCLUSION: We explored the outcome prediction values of CURB65, qSOFA, MEWS and NEWS for patients aged 65-years and older with community-acquired pneumonia. We found that MEWS showed superiority over the other severity scores in predicting hospital mortality, and NEWS showed superiority over the other scores in predicting ICU admission.

Differential and Prognostic Significance of HOXB7 in Gliomas.

Diffuse glioma is the most common primary tumor of the central nervous system. The prognosis of the individual tumor is heavily dependent on its grade and subtype. Homeobox B7 (HOXB7), a member of the homeobox family, is abnormally overexpressed in a variety of tumors. However, its function in glioma is unclear. In this study, HOXB7 mRNA and protein expression levels were analyzed in 401 gliomas from the CGGA RNA-seq database (325 cases) and our hospital (76 cases). HOXB7 expression, at both mRNA and protein levels, were upregulated in glioblastoma (GBM) and isocitrate dehydrogenase 1 (IDH1) wild-type glioma tissues. Kaplan-Meier with log-rank test showed that patients with high HOXB7 expression had a poor prognosis (p < 0.0001). Moreover, HOXB7 protein was deleted in 90.9% (20/22) of oligodendrogliomas and 13.0% (3/23) of astrocytomas. The sensitivity and specificity of HOXB7 protein deletion in oligodendroglioma were 90.9% (20/22) and 87.0% (20/23), respectively. To verify the reliability of using HOXB7 in differentiating oligodendroglioma, we used 1p/19q fluorescence in situ hybridization (FISH) testing as a positive control. The Cohen's kappa coefficient of HOXB7 immunohistochemistry staining and 1p/19q FISH testing was 0.778 (95% CI: 0.594-0.962, p < 0.001). In conclusion, HOXB7 is an independent predictor of poor prognosis in all grade gliomas. Additionally, HOXB7 is also a highly sensitive and specific indicator to differentiate oligodendroglioma from astrocytoma.

Analysis of topoisomerase I expression and identification of predictive markers for efficacy of topotecan chemotherapy in small cell lung cancer.

BACKGROUND: We evaluated topoisomerase I (TOPO1) expression in patients with small cell lung cancer (SCLC) and identified predictive factors for the efficacy of second-line topotecan chemotherapy. METHODS: We retrospectively evaluated the records of SCLC patients treated in our department from January 2007 to December 2016 who received second-line topotecan chemotherapy. Patients with archived tumor samples were enrolled. TOPO1 expression levels were evaluated by immunohistochemistry, and the relationships between TOPO1 expression, clinical factors, chemotherapy efficacy, and survival were analyzed. RESULTS: Of the 78 patients enrolled, 67 showed TOPO1 expression (85.9%). Patients were divided into strong (n = 43) or weak (n = 35) expression groups based on staining intensity. Disease control rates for topotecan were 39.5% and 14.3% in the strong and weak groups, respectively (P = 0.014). Second-line median progression-free survival was 2.2 and 2.0 months (P = 0.057), and median overall survival was 8.1 and 6.0 months (P = 0.199) in the strong and weak positive groups, respectively. Patients were also divided into sensitive (n = 47) and refractory (n = 31) disease groups according to the duration from the onset of first-line therapy to relapse. Median second-line progression-free survival was 2.2 and 1.8 months in the sensitive and refractory relapse groups, respectively (P = 0.005). CONCLUSIONS: TOPO1 expression was prevalent in SCLC patients. Strong expression was associated with an elevated disease control rate after second-line topotecan chemotherapy. Patients with sensitive disease that relapsed after first-line chemotherapy had better survival than refractory patients who received second-line topotecan chemotherapy.

Preparation of Hierarchical Highly Ordered Porous Films of Brominated Poly(phenylene oxide) and Hydrophilic SiO2/C Membrane via the Breath Figure Method.

Porous permeable films materials have very broad prospects in the treatment of sludge-containing waste water due to their large surface area and good microfiltration. In this work, highly ordered porous membranes have been prepared successfully on ice substrates using a poly(phenylene oxide) (BPPO)-SiO2 nanoparticle (NP) mixture by the brePorous permeable films materials have very broad prospects in the treatment of sludge-containing waste water due to their large surface area and good microfiltration. In this work, highly ordered porous membranes have been prepared successfully on ice substrates using aath figure method. Based on the theory of Pickering emulsion system and capillary flow, particle assisted membrane formation was analyzed. Another two sorts of new membranes SiO2/C membrane and hierarchical porous polymer (HPP) membrane, which were obtained by modification of the BPPO-SiO2 membrane by calcination and etching, were set up in a further study. Their properties were investigated through the methods of scanning electron microscopy (SEM), fourier transform infrared spectrometry (FTIR), ultraviolet spectrum (UV), capillary electrophoresis (CE), contact angle, and water flux tests. All these results demonstrate that both surface hydrophilicity and fouling resistance of the membrane would be improved by using SiO2 as a filler. The membranes with high permeability and antifouling properties were used for microfiltration applications.