Implications of cardiac markers in risk-stratification and management for COVID-19 patients.

BACKGROUND: COVID-19 has resulted in high mortality worldwide. Information regarding cardiac markers for precise risk-stratification is limited. We aim to discover sensitive and reliable early-warning biomarkers for optimizing management and improving the prognosis of COVID-19 patients. METHODS: A total of 2954 consecutive COVID-19 patients who were receiving treatment from the Wuhan Huoshenshan Hospital in China from February 4 to April 10 were included in this retrospective cohort. Serum levels of cardiac markers were collected after admission. Coronary artery disease diagnosis and survival status were recorded. Single-cell RNA-sequencing and bulk RNA-sequencing from different cohorts of non-COVID-19 were performed to analyze SARS-CoV-2 receptor expression. RESULTS: Among 2954 COVID-19 patients in the analysis, the median age was 60 years (50-68 years), 1461 (49.5%) were female, and 1515 (51.3%) were severe/critical. Compared to mild/moderate (1439, 48.7%) patients, severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. In severe/critical COVID-19 patients, those with abnormal serum levels of BNP (42 [24.6%] vs 7 [1.1%]), hs-TNI (38 [48.1%] vs 6 [1.0%]), α- HBDH (55 [10.4%] vs 2 [0.2%]), CK-MB (45 [36.3%] vs 12 [0.9%]), and LDH (56 [12.5%] vs 1 [0.1%]) had a significantly higher mortality rate compared to patients with normal levels. The same trend was observed in the ICU admission rate. Severe/critical COVID-19 patients with pre-existing coronary artery disease (165/1,155 [10.9%]) had more cases of BNP (52 [46.5%] vs 119 [16.5%]), hs-TNI (24 [26.7%] vs 9.6 [%], α- HBDH (86 [55.5%] vs 443 [34.4%]), CK-MB (27 [17.4%] vs 97 [7.5%]), and LDH (65 [41.9%] vs 382 [29.7%]), when compared with those without coronary artery disease. There was enhanced SARS-CoV-2 receptor expression in coronary artery disease compared with healthy controls. From regression analysis, patients with five elevated cardiac markers were at a higher risk of death (hazards ratio 3.4 [95% CI 2.4-4.8]). CONCLUSIONS: COVID-19 patients with pre-existing coronary artery disease represented a higher abnormal percentage of cardiac markers, accompanied by high mortality and ICU admission rate. BNP together with hs-TNI, α- HBDH, CK-MB and LDH act as a prognostic biomarker in COVID-19 patients with or without pre-existing coronary artery disease.

Expression profile and prognostic value of SAV1 in patients with pancreatic ductal adenocarcinoma.

SAV1 is a human homolog of salvador that contains two protein-protein interaction modules known as WW domains and acts as a scaffolding protein for Hpo and Warts. SAV1 is known to be a tumor suppressor, but its clinical and prognostic implications remain elusive. This study aimed at evaluating the prognostic significance and associated expression of SAV1 in pancreatic ductal adenocarcinoma (PDAC) patients. The expression of SAV1 in tissue specimens of PDAC patients were assayed with immunohistochemistry on a tissue microarray. The correlations between SAV1 expression and clinicopathological characteristics were analyzed by Pearson's chi-square test, Fisher's exact test, and Spearman's rank. The prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. The percentage of SAV1 expression in PDAC (50.6 %) was significantly lower than those in paratumor tissues (69.9 %) (P = 0.017). Expression of SAV1 was only significantly correlated with histological differentiation (P = 0.025) and N classification (P = 0.009). On multivariate analysis, elevated expression of SAV1 and N0 was a significant favorable prognostic factor of OS. Our study demonstrated for the first time that lower expression of SAV1 might be involved in the progression of PDAC, suggesting that SAV1 may be a potential prognostic marker and target for PDAC therapy.

Identification of potential biomarkers to differentially diagnose solid pseudopapillary tumors and pancreatic malignancies via a gene regulatory network.

BACKGROUND: Solid pseudopapillary neoplasms (SPN) are pancreatic tumors with low malignant potential and good prognosis. However, differential diagnosis between SPN and pancreatic malignancies including pancreatic neuroendocrine tumor (PanNET) and ductal adenocarcinoma (PDAC) is difficult. This study tried to identify candidate biomarkers for the distinction between SPN and the two malignant pancreatic tumors by examining the gene regulatory network of SPN. METHODS: The gene regulatory network for SPN was constructed by a co-expression model. Genes that have been reported to be correlated with SPN were used as the clues to hunt more SPN-related genes in the network according to a shortest path approach. By means of the K-nearest neighbor algorithm (KNN) classifier evaluated by the jackknife test, sets of genes to distinguish SPN and malignant pancreatic tumors were determined. RESULTS: We took a new strategy to identify candidate biomarkers for differentiating SPN from the two malignant pancreatic tumors PanNET and PDAC by analyzing shortest paths among SPN-related genes in the gene regulatory network. 43 new SPN-relevant genes were discovered, among which, we found hsa-miR-194 and hsa-miR-7 along with 7 transcription factors (TFs) such as SOX11, SMAD3 and SOX4 etc. could correctly differentiate SPN from PanNET, while hsa-miR-204 and 4 TFs such as SOX9, TCF7 and PPARD etc. were demonstrated as the potential markers for SPN versus PDAC. 14 genes were demonstrated to serve as the candidate biomarkers for distinguishing SPN from PanNET and PDAC when considering them as malignant pancreatic tumors together. CONCLUSION: This study provides new candidate genes related to SPN and the potential biomarkers to differentiate SPN from PanNET and PDAC, which may help to diagnose patients with SPN in clinical setting. Furthermore, candidate biomarkers such as SOX11 and hsa-miR-204 which could cause cell proliferation but inhibit invasion or metastasis may be of importance in understanding the molecular mechanism of pancreatic oncogenesis and could be possible therapeutic targets for malignant pancreatic tumors.

Pb(II) Adsorption Properties of a Three-Dimensional Porous Bacterial Cellulose/Graphene Oxide Composite Hydrogel Subjected to Ultrasonic Treatment.

A three-dimensional porous bacterial cellulose/graphene oxide (BC/GO) composite hydrogel (BC/GO) was synthesized with multi-layer graphene oxide (GO) as the modifier and bacterial cellulose as the skeleton via an ultrasonic shaking process to absorb lead ions effectively. The characteristics of BC/GO were investigated through TEM, SEM, FT-IR, NMR and Zeta potential experiments. Compared to bacterial cellulose, the ultrasonic method and the carboxyl groups stemming from GO helped to enhance the availability of O(3)H of BC, in addition to the looser three-dimensional structure and enriched oxygen-containing groups, leading to a significantly higher adsorption capacity for Pb(II). In this paper, the adsorption behavior of BC/GO is influenced by the GO concentration, adsorption time, and initial concentration. The highest adsorption capacity for Pb(II) on BC/GO found in this study was 224.5 mg/g. The findings implied that the pseudo-second-order model explained the BC/GO adsorption dynamics and that the data of its adsorption isotherm fit the Freundlich model. Because of the looser three-dimensional structure, the complexation of carboxyl groups, and the enhanced availability of O(3)H, bacterial cellulose exhibited a much better adsorption capacity.

Construction of disulfidptosis-based immune response prediction model with artificial intelligence and validation of the pivotal grouping oncogene c-MET in regulating T cell exhaustion.

Background: Given the lack of research on disulfidptosis, our study aimed to dissect its role in pan-cancer and explore the crosstalk between disulfidptosis and cancer immunity. Methods: Based on TCGA, ICGC, CGGA, GSE30219, GSE31210, GSE37745, GSE50081, GSE22138, GSE41613, univariate Cox regression, LASSO regression, and multivariate Cox regression were used to construct the rough gene signature based on disulfidptosis for each type of cancer. SsGSEA and Cibersort, followed by correlation analysis, were harnessed to explore the linkage between disulfidptosis and cancer immunity. Weighted correlation network analysis (WGCNA) and Machine learning were utilized to make a refined prognosis model for pan-cancer. In particular, a customized, enhanced prognosis model was made for glioma. The siRNA transfection, FACS, ELISA, etc., were employed to validate the function of c-MET. Results: The expression comparison of the disulfidptosis-related genes (DRGs) between tumor and nontumor tissues implied a significant difference in most cancers. The correlation between disulfidptosis and immune cell infiltration, including T cell exhaustion (Tex), was evident, especially in glioma. The 7-gene signature was constructed as the rough model for the glioma prognosis. A pan-cancer suitable DSP clustering was made and validated to predict the prognosis. Furthermore, two DSP groups were defined by machine learning to predict the survival and immune therapy response in glioma, which was validated in CGGA. PD-L1 and other immune pathways were highly enriched in the core blue gene module from WGCNA. Among them, c-MET was validated as a tumor driver gene and JAK3-STAT3-PD-L1/PD1 regulator in glioma and T cells. Specifically, the down-regulation of c-MET decreased the proportion of PD1+ CD8+ T cells. Conclusion: To summarize, we dissected the roles of DRGs in the prognosis and their relationship with immunity in pan-cancer. A general prognosis model based on machine learning was constructed for pan-cancer and validated by external datasets with a consistent result. In particular, a survival-predicting model was made specifically for patients with glioma to predict its survival and immune response to ICIs. C-MET was screened and validated for its tumor driver gene and immune regulation function (inducing t-cell exhaustion) in glioma.

LINC01133 can induce acquired ferroptosis resistance by enhancing the FSP1 mRNA stability through forming the LINC01133-FUS-FSP1 complex.

Due to a lack of research on the critical non-coding RNAs in regulating ferroptosis, our study aimed to uncover the crucial ones involved in the process. We found that LINC01133 could make pancreatic cancer cells more resistant to ferroptosis. A higher expression of LINC01133 was associated with a higher IC50 of sorafenib in clinical samples. Furthermore, we discovered that LINC01133 induced this process through enhancing the mRNA stability of FSP1. CEBPB was the transcription factor to increase the expression of LINC01133. A higher CEBPB could also indicate a higher IC50 of sorafenib in patients with cancer. Moreover, we confirmed that LINC01133 could form a triple complex with FUS and FSP1 to increase the mRNA stability of FSP1.

Designing a solar interfacial evaporator based on tree structures for great coordination of water transport and salt rejection.

Solar interfacial evaporation has been receiving increasing attention but it is still a huge challenge to achieve excellent coordination between efficient water transport and salt rejection. Here, unlike the common wood-inspired evaporators with equal-diameter directional pores, we have constructed an integrated structure with highly connected gradient pores that mimic the xylem vessels and phloem sieve tubes found in trees. The bio-inspired structure can reduce the resistance of water transport and salt rejection in the same channel. The average transport speed of the 6.5 cm high (2 cm in diameter) porous structure reached 1.504 g s-1, and water was transported 16 cm after 100 seconds. Using multilayer graphene oxide as the photothermal conversion material, the evaporators with different heights can work for more than 9 hours under the condition of 1 sun illumination and 23 wt% brine without any salt crystallization, and the evaporation rates range from 3.28 to 4.51 kg m-2 h-1, with the highest energy utilization efficiency of about 80%. When used in heavy metal treatment, the rejection was greater than 99.99%. This research provides a simple but innovative design idea for evaporators and is expected to further expand the application of solar interfacial evaporation.

PTPRC promoted CD8+ T cell mediated tumor immunity and drug sensitivity in breast cancer: based on pan-cancer analysis and artificial intelligence modeling of immunogenic cell death-based drug sensitivity stratification.

Background: Immunogenic cell death (ICD) is a result of immune cell infiltration (ICI)-mediated cell death, which is also a novel acknowledgment to regulate cellular stressor-mediated cell death, including drug therapy and radiotherapy. Methods: In this study, TCGA and GEO data cohorts were put into artificial intelligence (AI) to identify ICD subtypes, and in vitro experiments were performed. Results: Gene expression, prognosis, tumor immunity, and drug sensitivity showed significance among ICD subgroups, Besides, a 14-gene-based AI model was able to represent the genome-based drug sensitivity prediction, which was further verified in clinical trials. Network analysis revealed that PTPRC was the pivotal gene in regulating drug sensitivity by regulating CD8+ T cell infiltration. Through in vitro experiments, intracellular down-regulation of PTPRC enhanced paclitaxel tolerance in triple breast cancer (TNBC) cell lines. Meanwhile, the expression level of PTPRC was positively correlated with CD8+ T cell infiltration. Furthermore, the down-regulation of PTPRC increased the level of TNBC-derived PD-L1 and IL2. Discussion: ICD-based subtype clustering of pan-cancer was helpful to evaluate chemotherapy sensitivity and immune cell infiltration, and PTPRC was a potential target to against drug resistance of breast cancer.

Transfer Parameter Analysis of Chloride Ingress into Concrete Based on Long-Term Exposure Tests in China's Coastal Region.

Chloride penetration resistance is one of the most important performance measures for the evaluation of the durability of concrete under a chloride environment. Due to differences in theory and experimental conditions, the durability index (chloride diffusion coefficient) obtained from laboratory accelerated migration tests cannot reflect the real process of chloride ingress into concrete in the natural environment. The difference in test methods must be considered and the transfer parameter kt should be introduced into the service life prediction model when the test results of accelerated methods are used. According to the test data of coastal exposure in South China, the attenuation rule of the chloride diffusion coefficient of different cement-based materials changed with time and was analyzed in this paper. Based on the diffusion coefficient-time curve, the theoretical natural diffusion coefficients of 28 d and 56 d were deduced, which were compared with the chloride diffusion coefficients obtained from the non-steady-state rapid migration method (RCM) at the same age. Therefore, the transfer parameter kt that expounds the relationship between concrete resistance to chloride permeability under a non-stationary electrical accelerated state and natural diffusion in the marine environment can be calculated; thus, the RCM testing index can be used to evaluate the long-term performance of the concrete structure in the marine environment. The results show that the value of kt was related to environmental conditions, test methods, and binder systems.

Phosphogypsum-Based Ultra-Low Basicity Cementing Material.

Traditional Portland cement is widely used in the preparation of various hydraulic concrete. However, the high alkalinity produced by cement hydration threatens the survival of aquatic animals and plants. In this paper, a new eco-friendly, ultra-low alkalinity, cementitious material was prepared with industrial waste phosphogypsum, granulated ground blast slag (GGBS) and sulphoaluminate cement. When appropriate proportions are used, the pH value of the test blocks' pore solutions at different ages were all less than 9, showing the remarkable characteristic of ultra-low alkalinity. The XRD and SEM analyses showed that the 56 d hydration products were mainly ettringite and hydrated calcium silicate, and the content of Ca(OH)2 was not detected. The new cementitious material also has the advantages of short setting time, low heat of hydration, high strength of cement mortar and the ability to fix harmful substances in phosphogypsum, such as phosphate, fluoride and Cr and Ba elements. It has a broad application prospect in the construction of island and reef construction, river restoration and so on.

Detection and Localization of Solid Tumors Utilizing the Cancer-Type-Specific Mutational Signatures.

Accurate detection and location of tumor lesions are essential for improving the diagnosis and personalized cancer therapy. However, the diagnosis of lesions with fuzzy histology is mainly dependent on experiences and with low accuracy and efficiency. Here, we developed a logistic regression model based on mutational signatures (MS) for each cancer type to trace the tumor origin. We observed MS could distinguish cancer from inflammation and healthy individuals. By collecting extensive datasets of samples from ten tumor types in the training cohort (5,001 samples) and independent testing cohort (2,580 samples), cancer-type-specific MS patterns (CTS-MS) were identified and had a robust performance in distinguishing different types of primary and metastatic solid tumors (AUC:0.76 ∼ 0.93). Moreover, we validated our model in an Asian population and found that the AUC of our model in predicting the tumor origin of the Asian population was higher than 0.7. The metastatic tumor lesions inherited the MS pattern of the primary tumor, suggesting the capability of MS in identifying the tissue-of-origin for metastatic cancers. Furthermore, we distinguished breast cancer and prostate cancer with 90% accuracy by combining somatic mutations and CTS-MS from cfDNA, indicating that the CTS-MS could improve the accuracy of cancer-type prediction by cfDNA. In summary, our study demonstrated that MS was a novel reliable biomarker for diagnosing solid tumors and provided new insights into predicting tissue-of-origin.

Association of blood glucose level and prognosis of inpatients with coexistent diabetes and COVID-19.

Type 2 diabetes (T2D) increases the risk of coronavirus disease (COVID-19). This study investigates the association between glucose control of COVID-19 patients with T2D in first 7 days after hospital admission and prognosis. A total of 252 infected inpatients with T2D in China were included. Well-controlled blood glucose was defined as stable fasting blood glucose (FBG) levels in the range of 3.9-7.8 mmol/L during first 7 days using indicators of average (FBGA), maximum (FBGM) or first-time (FBG1) FBG levels. The primary endpoint was admission to intensive care unit or death. Hazard ratio (HR) of poorly controlled glucose level group compared with well-controlled group were 4.96 (P = 0.021) for FBGM and 5.55 (P = 0.014) for FBGA. Well-controlled blood glucose levels in first 7 days could improve the prognosis of COVID-19 inpatients with diabetes.

LncRNA OTUD6B-AS1 promotes paclitaxel resistance in triple negative breast cancer by regulation of miR-26a-5p/MTDH pathway-mediated autophagy and genomic instability.

Genomic instability (GIN) is pivotal in regulating tumor drug resistance, which blocked the treatment of triple negative breast cancer (TNBC). Although recent studies implied that non-coding RNA (ncRNA)-mediated autophagy abolishment promoted tumorigenesis by up-regulation of GIN, autophagy was known as a risk factor in tumor drug resistance. However, previous study also pointed that up-regulation of autophagy promoted GIN. Therefore, the relationship between autophagy and GIN is not clear, and more work is needed. And, if an ncRNA is identified to be a co-regulator of autophagy and GIN, it will be a potential therapy target of chemotherapy resistance in TNBC. In our study, we recognized both autophagy-GIN-associated microRNA (mi-26a-5p) by big data analysis, which was prognosis-correlated in breast cancer. Next, we identified the up-stream regulators (long non-coding RNA, lncRNA) and down-stream targets of miR-26a-5p by bioinformatics analysis (online public databases). Finally, we established lncRNA OTUD6B-AS1/miR-26a-5p/MTDH signaling pathway, and verified their functions by cytological, molecular biological and zoological experiments. In general, our study found (1) miR-26a-5p was a protective factor of breast cancer, while OTUD6B-AS1 and MTDH were risk factors; (2) OTUD6B-AS1 was the up-stream regulator of miR-26a-5p verified by luciferase; (3) up-regulation of miR-26a-5p and down-regulation of MTDH promoted cellular cytotoxicity of paclitaxel (PTX) in vitro and in vivo. (4) down-regulation of miR-26a-5p, overexpression of MTDH and OTUD6B-AS1 promoted autophagy and DNA damage; (5) up-regulation of OTUD6B-AS1 and MTDH inhibited DNA damage response (DDR) by inhibiting the phosphorylated activation of RAD51, ATR and ATM.

FHL3 Contributes to EMT and Chemotherapy Resistance Through Up-Regulation of Slug and Activation of TGFß/Smad-Independent Pathways in Gastric Cancer.

BACKGROUND: Gastric cancer presents high risk of metastasis and chemotherapy resistance. Hence, it is important to understand the mechanisms of gastric cancer distant metastasis and chemotherapeutic resistance. Our previous study has revealed Four and a Half LIM Domains 3 (FHL3) plays as a binding partner of Glycogen Synthase Kinase 3 Beta (GSK3ß), promoted tumor metastasis in pancreatic cancer. However, the role of FHL3 in gastric cancer still remains unclear. METHODS: TCGA database and clinical samples are used for exploring the role of FHL3 in disease progression and prognosis. Oxaliplatin (OHP) resistance cell lines were established to study the role of FHL3 in chemotherapy resistance. The experiments about cell proliferation, apoptosis, and metastasis were performed to measure the chemotherapy effects of sh-FHL3 on gastric cancer cell lines and in vivo. That FHL3 changed the EMT phenotype was verified by western blot. Finally, we explored the mechanism of FHL3-mediated EMT and chemotherapy resistance. RESULTS: mRNA and protein level of FHL3 were significantly up-regulated in gastric cancer tissues when compared with adjacent tissue. FHL3 higher expression is always accompanied with higher TNM stage and worse overall survival. FHL3 over-expressed could lead to OHP resistance. Knockdown of FHL3 slightly inhibited the cell growth, while it obviously sensitized the chemotherapy in vivo and in vitro. In addition, down-regulation of FHL3 increased the mesenchymal markers, such as Slug, Snail, Twist Family BHLH Transcription Factor 1 (Twist1), and Vimentin, while it decreased the epithelial marker E-cadherin. Cell and animal experiments also proved that down-regulation of FHL3 can decrease cancer cell metastasis. For mechanism study, FHL3 knockdown down-regulated the expression level of Mitogen-Activated Protein Kinase (MAPK)/Extracellular Regulated Protein Kinase (ERK) pathway and Transforming Growth Factor-ß (TGFß)/Phosphatidylinositol 3-Kinase (PI3K)/protein kinase B(Akt)/GSK3ß-(Ring Finger Protein 146) RNF146/ubiquitin pathway. FHL3 competitively bonded the ubiquitin complex (Slug/GSK3ß/RNF146) with Slug and inhibited ubiquitination of Slug. Mesenchymal phenotype cells hold higher level of Multidrug Resistance Gene1 (MDR1), and the FHL3 knockdown reverts the MDR1 in this type cell. CONCLUSION: FHL3 high expression contributed to EMT and chemotherapy resistance via MAPK, and PI3K pathways were activated. FHL3 competitively bonded the ubiquitin complex with Slug, resulting in the up-regulation of Slug and leading to metastasis of gastric cancer.

High Expression of ACE2 and TMPRSS2 at the Resection Margin Makes Lung Cancer Survivors Susceptible to SARS-CoV-2 With Unfavorable Prognosis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide. Systematic analysis of lung cancer survivors at molecular and clinical levels is warranted to understand the disease course and clinical characteristics. METHODS: A single-center, retrospective cohort study was conducted in 65 patients with COVID-19 from Wuhan Huoshenshan Hospital, of which 13 patients were diagnosed with lung cancer. The study was conducted from February 4 to April 11, 2020. RESULTS: During the course of treatment, lung cancer survivors infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) had shorter median time from symptom onset to hospitalization (P = 0.016) and longer clinical symptom remission time (P = 0.020) than non-cancer individuals. No differences were observed among indicators such as time from symptom onset to hospitalization and symptom remission time between medium-term and short-term survivors. The expression of ACE2 (P = 0.013) and TMPRSS2 (P <0.001) was elevated in lung cancer survivors as compared with that in non-cancer individuals. CONCLUSIONS: ACE2 and TMPRSS2 levels were higher at resection margins of lung cancer survivors than those in normal tissues of non-cancerous individuals and may serve as factors responsible for the high susceptibility to COVID-19 among lung cancer survivors. Lung cancer patients diagnosed with COVID-19, including medium-term survivors, have worse outcomes than the general population.

Laboratory Testing Implications of Risk-Stratification and Management of COVID-19 Patients.

Objective: To distinguish COVID-19 patients and non-COVID-19 viral pneumonia patients and classify COVID-19 patients into low-risk and high-risk at admission by laboratory indicators. Materials and methods: In this retrospective cohort, a total of 3,563 COVID-19 patients and 118 non-COVID-19 pneumonia patients were included. There are two cohorts of COVID-19 patients, including 548 patients in the training dataset, and 3,015 patients in the testing dataset. Laboratory indicators were measured during hospitalization for all patients. Based on laboratory indicators, we used the support vector machine and joint random sampling to risk stratification for COVID-19 patients at admission. Based on laboratory indicators detected within the 1st week after admission, we used logistic regression and joint random sampling to develop the survival mode. The laboratory indicators of COVID-10 and non-COVID-19 were also compared. Results: We first identified the significant laboratory indicators related to the severity of COVID-19 in the training dataset. Neutrophils percentage, lymphocytes percentage, creatinine, and blood urea nitrogen with AUC >0.7 were included in the model. These indicators were further used to build a support vector machine model to classify patients into low-risk and high-risk at admission in the testing dataset. Results showed that this model could stratify the patients in the testing dataset effectively (AUC = 0.89). Our model still has good performance at different times (Mean AUC: 0.71, 0.72, 0.72, respectively for 3, 5, and 7 days after admission). Moreover, laboratory indicators detected within the 1st week after admission were able to estimate the probability of death (AUC = 0.95). We identified six indicators with permutation p < 0.05, including eosinophil percentage (p = 0.007), white blood cell count (p = 0.045), albumin (p = 0.041), aspartate transaminase (p = 0.043), lactate dehydrogenase (p = 0.002), and hemoglobin (p = 0.031). We could diagnose COVID-19 and differentiate it from other kinds of viral pneumonia based on these laboratory indicators. Conclusions: Our risk-stratification model based on laboratory indicators could help to diagnose, monitor, and predict severity at an early stage of COVID-19. In addition, laboratory findings could be used to distinguish COVID-19 and non-COVID-19.

Comparative Characterization and Risk Stratification of Asymptomatic and Presymptomatic Patients With COVID-19.

The identification of asymptomatic, non-severe presymptomatic, and severe presymptomatic coronavirus disease 2019 (COVID-19) in patients may help optimize risk-stratified clinical management and improve prognosis. This single-center case series from Wuhan Huoshenshan Hospital, China, included 2,980 patients with COVID-19 who were hospitalized between February 4, 2020 and April 10, 2020. Patients were diagnosed as asymptomatic (n = 39), presymptomatic (n = 34), and symptomatic (n = 2,907) upon admission. This study provided an overview of asymptomatic, presymptomatic, and symptomatic COVID-19 patients, including detection, demographics, clinical characteristics, and outcomes. Upon admission, there was no significant difference in clinical symptoms and CT image between asymptomatic and presymptomatic patients for diagnosis reference. The mean area under the receiver operating characteristic curve (AUC) of the differential diagnosis model to discriminate presymptomatic patients from asymptomatic patients was 0.89 (95% CI, 0.81-0.98). Importantly, the severe and non-severe presymptomatic patients can be further stratified (AUC = 0.82). In conclusion, the two-step risk-stratification model based on 10 laboratory indicators can distinguish among asymptomatic, severe presymptomatic, and non-severe presymptomatic COVID-19 patients on admission. Moreover, single-cell data analyses revealed that the CD8+T cell exhaustion correlated to the progression of COVID-19.

Interferon-α2b enhances survival and modulates transcriptional profiles and the immune response in melanoma patients treated with dendritic cell vaccines.

Malignant melanoma (MM) is the most lethal cutaneous cancer and is associated with 80 % of skin cancer deaths. Recent progress into elucidating the role of the immune system in melanoma development and progression has led to promising treatments for patients with MM, including dendritic cell (DC) vaccination. Interferon-α2b is a commonly used adjuvant for MM that prolongs overall survival (OS) and progression-free survival (PFS). In the present study, we examined the impact of a DC-based vaccine with subsequent delivery of high-dose systemic interferon-α2b (HDI) on gene expression profiles and the immune response in MM patients. The results indicated that patients who were randomized to receive an HDI boost following DC vaccination had significantly higher OS and PFS rates compared with patients that received DC vaccination alone. Further analysis revealed that intradermal DC immunization did not significantly alter transcriptional profiles, whereas subsequent HDI injections enhanced B cell, T cell and natural killer cell-related gene expression. Analysis of the abundance of tumor-infiltrating immune cells revealed that HDI altered the immune cell profiles. Moreover, we determined that follicular helper T (Tfh) cells and eosinophils were associated with prolonged PFS in MM patients treated with the DC vaccine.

siMTA1-Loaded Exosomes Enhanced Chemotherapeutic Effect of Gemcitabine in Luminal-b Type Breast Cancer by Inhibition of EMT/HIF-α and Autophagy Pathways.

Advanced breast cancer holds a poor prognosis for chemotherapy and endocrine therapy resistance. Autophagy is one of the main causes of tumor drug-therapy failure, and increasing evidence shows that EMT also is responsible for that. Metastasis-associated protein1 (MTA1) is up regulated in lots of tumors, which leads to tumor progression and drug resistance. However, the role of MTA1 in chemotherapeutic resistance in luminal-b breast cancer is still unclear. In this paper, our research shows that higher expression of MTA1 accompanies with worse prognosis in luminal-b breast cancer. Knockdown of MTA1 enhances the sensitivity of MCF-7 to gemcitabine and weakens the metastasis ability of MCF-7 in vitro and in vivo. Further, we find that knockdown of MTA1 strengthens the gemcitabine-mediated tumor growth inhibition effect in vivo, through reversion of the EMT process and inhibition of the autophagy process. Furthermore, our research builds the siMTA1-loaded exosomes, which increases the gemcitabine-mediated tumor growth inhibition effect in vivo.

Expression and Prognostic Significance of Metastasis-Associated Protein 1 in Gastrointestinal Cancer.

BACKGROUND: Metastasis-associated protein 1 (MTA1) has been considered as a transcriptional regulator, which is significantly related to the prognosis in various types of tumors. However, whether MTA1 is a potential prognostic index of gastrointestinal cancer (GIC) remains controversial. The current meta-analysis was performed to evaluate the role of MTA1 expression in the prediction of the clinicopathological features and survival in GIC cases. And the results of gastric cancer were verified by immunohistochemistry (IHC). METHODS: Eligible studies assessing the relationship between MTA1 and GIC by IHC were searched in the PubMed, Cochrane, Ovid, Web of Science and CNKI databases by various search strategies. The STATA 16.0 software was applied to gather data and to analyze the potential relationship between MTA1 and GIC. The expression level of MTA1 was examined in 80 GC samples by IHC assay. SPSS 20.0 was applied for statistical analysis, and the survival curves were calculated by the Kaplan-Meier method. The data of 95% CI was displayed as "[a-b]". RESULTS: According to the meta-analysis, the expression level of MTA1 was tightly associated with the tumor size (OR=1.82 [1.16-2.84], P=0.009), tumor tissue differentiation (OR=1.71 [1.24-2.37], P=0.001), depth of invasion (OR=3.12 [2.55-3.83], P<0.001), lymphatic metastasis (OR=2.99 [2.02-4.43], P<0.001), distant metastasis (OR=4.66 [1.13-19.24], P=0.034), TNM stage (OR=4.28 [2.76-6.63], P<0.001). In addition, MTA1 played the negative effects in 1- (RR=2.48 [1.45-4.25], P=0.001), 3- (RR=1.66 [1.30-2.11], P<0.001) and 5-year (RR=1.73 [1.37-2.20], P<0.001). Study in subgroup, grouped by language and tumor type, we reached similar conclusions. Further validation by IHC yielded similar conclusions. Tumor size (P=0.008), lymph node metastasis (P=0.007) and distant metastasis (P=0.023) significantly accompanied with higher expression of MAT1 in GC cases. Besides, the expression level of MTA1 was statistically significantly correlated with OS in GC cases (HR=2.061 [1.066-3.986], P=0.032), which suggested that MTA1 might be an independent prognostic marker for GC. Finally, we verified the correlation between the expression level of MTA1 and prognosis of GC in 80 GC samples. CONCLUSIONS: MTA1 is tightly associated with metastasis-related factors and may constitute a promising prognostic factor of GIC.