Clinical significance of the lactate-to-albumin ratio on prognosis in critically ill patients with acute kidney injury.

OBJECTIVE: To explore the relationship between lactate-to-albumin ratio (LAR) at ICU admission and prognosis in critically ill patients with acute kidney injury (AKI). METHODS: A retrospective analysis was conducted. Patients were divided into low (<0.659) LAR and high LAR (≥0.659) groups. Least absolute shrinkage and selection operator regression analysis was conducted to select variables associated with the 30-day prognosis. Cox regression analyses were performed to assess the association between LAR and mortality. Kaplan-Meier curves were plotted to compare cumulative survival rates between high and low LAR groups. Subgroup analysis was employed to assess the stability of the results. ROC curve was used to determine the diagnostic efficacy of LAR on prognosis. RESULTS: A nonlinear relationship was observed between LAR and the risk of 30-day and 360-day all-cause mortality in AKI patients (p < 0.001). Cox regulation showed that high LAR (≥ 0.659) was an independent risk factor for 30-day and 360-day all-cause mortality in patients with AKI (p < 0.001). The Kaplan-Meier survival curves demonstrated a noteworthy decrease in cumulative survival rates at both 30 and 360 days for the high LAR group in comparison to the low LAR group (p < 0.001). Subgroup analyses demonstrated the stability of the results. ROC curves showed that LAR had a diagnostic advantage when compared with lactate or albumin alone (p < 0.001). CONCLUSION: High LAR (≥0.659) at ICU admission was an independent risk factor for both short-term (30-day) and long-term (360-day) all-cause mortality in patients with AKI.

The association between albumin-corrected calcium and prognosis in patients with cardiac arrest: a retrospective study based on the MIMIC-IV database.

BACKGROUND: Cardiac arrest (CA) is one of the leading causes of death globally, characterized by high incidence and mortality. It is of particular significance to determine the prognosis of patients with CA early and accurately. Therefore, we aim to investigate the correlation between albumin-corrected calcium (ACC) and the prognosis in patients diagnosed with CA. METHODS: We retrospectively collected data from medical information mart for intensive care IV database. Patients were divided into two groups (survival and non-survival groups), according to the 90-day prognosis. In the Restricted cubic spline (RCS) analysis, the cut-off values (8.86 and 10.32) were obtained to categorize patients into three groups: low ACC group (< 8.86), moderate ACC group (8.86-10.32), and high ACC group (> 10.32). The least absolute shrinkage and selection operator with a ten-fold cross-validation regression analysis was performed to identify variables linked to the mortality. The inverse probability treatment weighting (IPTW) was used to address the confounding factors, and a weighted cohort was generated. RCS, Kaplan-Meier curve, and Cox regression analyses were used to explore the relationship between ACC and the mortality. Sensitivity analysis was employed to validate the stability of the results. RESULTS: Cut-off values for ACC of 8.86 and 10.32 were determined. RCS analyses showed that there was an overall non-linear trend relationship between ACC and the risk of 90-day and 360-day mortalities. After IPTW adjustment, compared to the moderate ACC group, the 90-day and 360-day mortalities in the high ACC group were higher (P < 0.05). The Cox analyses before and after IPTW adjustment showed that both low ACC and high ACC group were independent risk factors for 90-day and 360-day all-cause mortality in patients with CA (P < 0.05). The results obtained from sensitivity analyses indicated the stability of the findings. The Kaplan-Meier survival curves indicated that 90- and 360-day cumulative survival rates in the low ACC and high ACC groups were lower than that in the moderate ACC group (χ2 = 11.350, P = 0.003; χ2 = 14.110, P = 0.001). CONCLUSION: Both low ACC (< 8.86) and high ACC groups (> 10.32) were independent risk factors for 90-day and 360-day all-cause mortality in patients with CA (P < 0.05). For those CA patients with high and low ACC, it deserved the attention of clinicians.

The Antitumor Effects of α-Linolenic Acid.

α-linolenic acid (ALA), which is a member of the n-3 polyunsaturated fatty acid (n-3 PUFA) family, has often been ignored due to a lack of information. ALA has gradually attracted increased attention due to its nutritional and medicinal advantages. Studies have shown that ALA exerts beneficial effects on a variety of diseases, including cancer. In this review, we summarize the antitumor effects of ALA in the context of cell biology, including the inhibition of proliferation, the induction of apoptosis, the inhibition of metastasis and angiogenesis, and antioxidant effects. In addition, studies have shown that ALA can be used as a drug carrier or exert positive clinical effects when combined with drugs. Therefore, the use of ALA in clinical treatments is very promising and valuable.

The Global Environmental Impacts of China's Accession to the WTO: A 20-Year Review.

Robust empirical assessments of the long-term cumulative global effects of free trade and economic globalization on the environment are limited. This account fills this gap by constructing a dynamic computable general equilibrium model to estimate the environmental effects of a milestone in the recent history of trade liberalization: China's 20-year World Trade Organization (WTO) accession. The modeling shows that China's accession could have resulted in an increase in the global cumulative greenhouse gases (GHGs), sulfur dioxide (SO2), and nitrogen oxide (NOx) emissions by roughly 14,000 Mt CO2-eq, 64 Mt, and 46 Mt, respectively. The global production scale effect contributed to most of these estimated increases. The regional total output composition effect also caused higher emissions. Meanwhile, the sectoral output composition effect helped reduce total emissions to a limited extent. Fortunately, a package of emission abatement measures led to a decrease in emission factors and a drop in the global cumulative emissions of GHGs, SO2, and NOx. The findings suggest that to enjoy the free trade and economic globalization benefits and minimize the induced emission increases, it is vitally important to systemically reduce emissions across the entire economy and nurture a low-carbon trade regime.

The relationship between lactate dehydrogenase to albumin ratio and all-cause mortality during ICU stays in patients with sepsis: A retrospective cohort study with propensity score matching.

Background: Sepsis is a prevalent and severe medical condition which is frequently observed in the intensive care unit (ICU). Although numerous biomarkers have been identified to predict the prognosis of sepsis, the lactate dehydrogenase to albumin ratio (LDH/ALB ratio) has not been extensively investigated. The principal objective of this study is to assess the relationship between LDH/ALB ratio and all-cause mortality in patients with sepsis. Methods: This study included all adult critically ill patients with sepsis from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.0) database. Propensity score matching (PSM) analysis was conducted to mitigate bias, and Kaplan-Meier curves were performed to evaluate the cumulative survival across different groups. The association between the LDH/ALB ratio and mortality was examined through restricted cubic spline (RCS) analysis and Cox regression analysis. The robustness of the findings was confirmed through subgroup analyses. Additionally, the prognostic capability of the LDH/ALB ratio was further evaluated using receiver operating characteristic (ROC) curve analysis. Results: There were 6059 adult patients with sepsis enrolled in the final analysis. RCS revealed a non-linear relationship between the LDH/ALB ratio and an increased risk of ICU all-cause mortality (χ2 = 46.900, P < 0.001). Following PSM analysis, 1553 matched pairs were obtained. As comparison to the low LDH/ALB ratio group, the mortality rate in the high LDH/ALB ratio group was significantly higher (P < 0.001). Kaplan-Meier curves, both before and after PSM, revealed that the ICU cumulative survival rate for patients with sepsis was significantly lower in the high LDH/ALB ratio group compared to the low LDH/ALB ratio group (χ2 = 93.360, P < 0.001; χ2 = 14.400, P < 0.001). Even after adjusting for a range of potential confounders, multivariate Cox regression analysis indicated that an elevated LDH/ALB ratio was a significant predictor of all-cause mortality in these patients. ROC curve analysis demonstrated that the LDH/ALB ratio had an area under the ROC curve (AUC) of 0.688 for predicting ICU mortality, with a sensitivity of 69.2% and a specificity of 58.6%. Conclusions: An elevated LDH/ALB ratio (≥10.57) was associated with all-cause mortality in critically ill patients with sepsis, and it might serve as a prognostic marker. Clinicians should pay closer attention to sepsis patients presenting with an LDH/ALB ratio of 10.57 or higher.

The correlation between albumin-corrected anion gap and prognosis in patients with acute myocardial infarction.

AIMS: Acute myocardial infarction (AMI) is a cardiovascular disease with high morbidity and mortality. We collected patients with AMI from the Medical Information Mart for Intensive Care IV (v2.0) database and explored the association between serum albumin-corrected anion gap (ACAG) level and mortality in patients with AMI. METHODS AND RESULTS: Data of adult patients with AMI were collected. According to the 360 day prognosis, patients were divided into survival and non-survival groups. Based on the ACAG level, patients were then divided into normal and high ACAG groups. Cox hazard proportional models and restricted cubic splines (RCSs) were used to investigate the correlation between ACAG and mortality. Kaplan-Meier curves were created to compare the cumulative survival rates between the high and normal ACAG groups. The receiver operating characteristic (ROC) curve was used to analyse the predictive value of ACAG for the prognosis of patients with AMI. Sensitivity and subgroup analyses were conducted to revalidate the results. Finally, 1783 patients were included. Elevated ACAG (>20 mmol/L) was significantly associated with 30 and 360 day mortality (P < 0.001). Adjusted for multiple confounding factors, the Cox proportional hazard analysis showed that elevated ACAG (>20 mmol/L) was an independent risk factor of increased all-cause mortality in patients with AMI (hazard ratio 1.423, 95% confidence interval 1.206-1.678, P < 0.001). RCS analysis further showed that there was a non-linear trend relationship between ACAG and the risk of all-cause mortality at 30 and 360 days (χ2 = 10.750, P = 0.013; χ2 = 13.960, P = 0.003). Kaplan-Meier survival curves showed that the 30 and 360 day cumulative survival rates of patients with AMI were significantly lower (log-rank test, χ2 = 98.880, P < 0.001; χ2 = 105.440, P < 0.001) in the high ACAG group. ROC curve analysis showed that the area under the curve (AUC) of ACAG was 0.651, while the AUC of anion gap (AG) was 0.609, indicating that ACAG had a higher predictive value for 360 day mortality than AG. When combined with Sequential Organ Failure Assessment score, the predictive performance of ACAG for 360 day mortality was better, with an AUC of 0.699. Sensitivity and subgroup analyses were conducted suggesting the stability of our results. CONCLUSIONS: Elevated serum ACAG (≥20 mmol/L) is an independent risk factor for short-term and long-term mortality in critically ill patients with AMI, and it may assist clinicians and nurses identifying high-risk patients.

IFIT3 inhibits Epstein-Barr virus reactivation via upregulating innate immunity.

Epstein-Barr virus (EBV), a member of the γ-herpesvirus family, can establish latent infection in B lymphocytes and certain epithelial cells after primary infection. Under certain circumstances, EBV can enter into lytic replication. However, the regulation of EBV latent-lytic infection remains largely unclear. The important immune molecule, interferon-induced protein with tetratricopeptide repeats 3 (IFIT3), was upregulated in EBV latently infected cells. When the lytic replication of EBV was induced, the expression of IFIT3 was further increased. In turn, IFIT3 overexpression dramatically inhibited the lytic replication of EBV, while IFIT3 knockdown facilitated EBV lytic replication. Moreover, upon the lytic induction, the ectopic IFIT3 expression promoted the activation of the interferon (IFN) pathway, including the production of IFN-stimulated genes (ISGs), IFNB1, and the phosphorylation of IFN-regulatory factor 3 (IRF3). In contrast, the depletion of IFIT3 led to decreased ISGs and IFNB1 expression. Mechanically, IFIT3 inhibited EBV lytic replication through IFN signaling. This study revealed that the host innate immune-related factor IFIT3 played an important role in regulating EBV latent-lytic homeostasis. The results implied that EBV has evolved well to utilize host factors to maintain latent infection.

Association between serum anion gap and all-cause mortality in patients with acute myocardial infarction: A retrospective study based on MIMIC-IV database.

Background: Although previous studies have reported that many biomarkers can determine the prognosis of patients with acute myocardial infarction (AMI), serum anion gap (AG) has not been well studied. We aimed to investigate the association between serum AG and mortality in patients with AMI. Methods: Adult patients first admitted to the ICU and diagnosed with AMI from 2008 to 2019 in the MIMIC-IV database were included. Patients were divided into the survival and non-survival groups based on 30-day and 90-day outcomes. According to the AG value (15.12 mmol/L) with a hazard ratio of 1 in the restricted cubic spline (RCS) analysis, patients were further divided into high and low AG groups. The Kaplan-Meier survival curve was plotted, and all-cause mortality was compared between the high and low groups using the log-rank test. Multivariate Cox regression analysis and RCS analysis were constructed to assess the relationship between AG and recent all-cause mortality in patients with AMI. Results: 4446 patients were enrolled. The 30-day and 90-day mortality rates in the high AG group (25.53%, 31.75%) were higher than that in the low AG group (9.73%, 14.01%, P < 0.001) independently. The Kaplan-Meier curve showed that the 30-day and 90-day cumulative survival rates were lower in the high AG group than that in the low AG group (P < 0.001). RCS analysis showed that there was a non-linear relationship between AG and the risk of 90-day all-cause mortality in patients with AMI (χ2 = 18.680 P < 0.001). When AG was 15.12 mmol/L, its HR was about 1. Multivariable Cox regression analysis confirmed that increased AG was associated with higher 30-day and 90-day mortality. Conclusion: Elevated serum AG (≥15.12 mmol/L) is an independent predictor for short-term mortality in patients with AMI, and it may provide a basis for clinicians to identify patients with poor prognosis as early as possible.

Association between anion gap and all-cause mortality of critically ill surgical patients: a retrospective cohort study.

BACKGROUND: There are few widely accepted and operationally feasible models for predicting the mortality risk of patients in surgical intensive care unit (SICU). Although serum anion gap (AG) is known to be correlated with severe metabolic acidosis, no investigations have been reported about the association between AG level and the outcome during hospitalization in SICU. This study aimed to explore the predictive power of AG for 90-day all-cause mortality in SICU. METHODS: Data of the eligible patients in SICU from 2008 to 2019 was obtained from the Medical Information Mart for Intensive Care IV version 2.0 (MIMIC-IV v2.0) database. Baseline clinical data of the selected patients was compared in different groups stratified by the outcome during their admission via univariate analysis. Restricted cubic spline (RCS) was drawn to confirm the relationship of AG and the short-term mortality. Kaplan-Meier survival curve was plotted in different AG level groups. Univariate and multivariate Cox analyses were performed, and Cox proportional-hazards models were built to investigate an independent role of AG to predict 90-day all-cause mortality risk in SICU. Receiver operating characteristics (ROC) curves analysis was performed to evaluate the predictive value of AG on the 90-day prognosis of patients. RESULTS: A total of 6,395 patients were enrolled in this study and the 90-day all-cause mortality rate was 18.17%. Univariate analysis showed that elevated serum AG was associated with higher mortality (P < 0.001). RCS analysis indicated a positively linear relationship between serum AG and the risk of 90-day all-cause mortality in SICU (χ2 = 4.730, P = 0.193). Kaplan-Meier survival analysis demonstrated that low-AG group (with a cutoff value of 14.10 mmol/L) had a significantly higher cumulative survival rate than the counterpart of high-AG group (χ2 = 96.370, P < 0.001). Cox proportional-hazards models were constructed and confirmed the independent predictive role of AG in 90-day all-cause mortality risk in SICU after adjusting for 23 confounding factors gradually (HR 1.423, 1.246-1.625, P < 0.001). In the further subgroup analyses, a significant interaction was confirmed between AG and sepsis as well as surgery on the risk for the 90-day mortality. The ROC curve showed that the optimal cut-off value of AG for predicting 90-day mortality was 14.89 with sensitivity of 60.7% and specificity of 54.8%. The area under curve (AUC) was 0.602. When combined with SOFA score, the AUC of AG for predicting 90-day prognosis was 0.710, with a sensitivity and specificity of 70% and 62.5% respectively. CONCLUSIONS: Elevated AG (≥ 14.10 mmol/L) is an independent risk factor for predicting severe conditions and poor prognosis of critical ill surgical patients.

TIPE2 deficiency prolongs mouse heart allograft survival by facilitating immature DCs-induced Treg generation.

It has been reported that deletion of tumor necrosis factor-α-induced protein-8 like 2 (TNFAIP8L2, TIPE2) facilitates the activation of T-cell receptors. However, the role of TIPE2 in T-cell-mediated acute transplant rejection remains unclear. To illustrate the underlying cellular mechanisms, we transplanted BALB/c hearts into C57BL/6 wild-type (WT) or C57BL/6 mice deficient for TIPE2 (TIPE2-/-) and found that TIPE2-/- recipient mice showed significantly prolonged survival of heart allografts and suppressed maturation of CD11c+ dendritic cells (DCs), which largely abolished the activation and proliferation of alloreactive T cells and their cytotoxic activity. TIPE2-/- DCs increased CD4+CD25+Foxp3+CD127- regulatory T cells (Tregs)generation, likely by inhibiting DCs maturation and CD80 and CD86 expression. Administration of anti-CD25 abolished the allograft survival induced by TIPE2 deficiency. Moreover, TIPE2 deficiency increased IL-10 production in T cells and in recipient serum and allografts. Mechanistic studies revealed that TIPE2-/- restrained the maturation of DCs via inhibition of PI3K/AKT phosphorylation during alloantigen stimulation. Taken together, TIPE2 deficiency in recipient mice inhibited acute rejection by increasing Tregs generated by immature DCs. Thus, TIPE2 could be a therapeutic target for suppressing rejection in organ transplantation.

Evaluation of the knowledge, awareness, and attitudes toward epilepsy among general practitioners in Eastern China.

OBJECTIVE: We aimed to assess the knowledge, awareness, and attitudes toward epilepsy among general practitioners (GPs) from community health service centers (CHCs) in Hangzhou, Eastern China. METHODS: One hundred twenty three GPs working at CHCs participated in this cross-sectional study in 2022. A custom-built electronic questionnaire, which comprised four domains, including 12 items for general condition data, 10 items for awareness (including first aid), a 16-item scale for attitudes, and 6 items for demographic data, was administered to the GPs. Descriptive statistics, the Mann-Whitney U test, the Kruskal-Wallis H test, and Spearman's rank correlation analysis were used to analyze the non-normal distribution of the data set. RESULTS: The GPs' average score on the awareness of epilepsy section was 18.14 ± 3.34 (aggregate score: 34), the first aid knowledge of epilepsy section scored 4.89 ± 1.54 (aggregate score: 7), and the epilepsy attitude section scored 62.28 ± 10.15 (aggregate score: 80). Age (rs = 0.218, P = 0.015), professional title (rs = 0.215, P = 0.017), and length of service (rs = 0.240, P = 0.008) correlated significantly with mean awareness of epilepsy scores. Age (rs = -0.234, P = 0.009) and educational background (rs = 0.199, P = 0.028) correlated significantly with attitudes toward epilepsy. Furthermore, when GPs faced newly diagnosed people with epilepsy (PWE), a referral was usually recommended (89.43%) and some would give Chinese traditional treatment (13.01%). In addition, the difficulties the GPs encountered in managing included PWE rarely appearing in the community (82.93%), the community lacking corresponding medical equipment (82.11%), and GPs lacking epilepsy-related experience (73.17%). CONCLUSION: The awareness and attitudes of GPs toward epilepsy in the CHCs were suboptimal. General practitioners age, professional title, length of service, and educational background influenced awareness and attitudes toward PWE. Effective public intervention programs, epilepsy training based on National Guidelines, and referral routes need to improve in China to enhance the care of PWE.

Elevated albumin corrected anion gap is associated with poor in-hospital prognosis in patients with cardiac arrest: A retrospective study based on MIMIC-IV database.

Background: Cardiac arrest(CA) is one of the most leading causes of death. Most of the indicators which used to predict the prognosis of patients with CA are not recognized. Previous studies have suggested that albumin corrected anion gap (ACAG) is associated with recovery of spontaneous circulation in patients with CA, but the predictive value of ACAG for prognosis has not been investigated. This study aims to explore the relationship between ACAG and prognosis during hospitalization in patients with CA. Methods: The baseline data of adult patients with CA hospitalized in the intensive care unit (ICU) from 2008 to 2019 in the American Intensive Care Database (MIMIC-IV, version v2.0) were collected. According to the in-hospital prognosis, patients were divided into survival and non-survival group. Based on the criteria of ACAG level in the previous literature, patients enrolled were divided into normal ACAG (12-20 mmol/L) and high ACAG (>20 mmol/L) group. The basic information of patients during hospitalization were compared and analyzed between the two groups with propensity score matching (PSM). The Kaplan-Meier method was used to compare the cumulative survival rates of normal ACAG and high ACAG groups before and after matching. Restricted cubic spline (RCS) method and multivariate COX proportional hazards regressions were used to analyze whether elevated ACAG was associated with all-cause mortality during hospitalization. Results: A total of 764 patients were included. A matched cohort (n = 310) was obtained after PSM analysis. The mortality rate before and after matching in the high ACAG group was higher than that in the normal ACAG group (χ 2 = 25.798; P < 0.001; χ 2 = 6.258; P = 0.012) The Kaplan-Meier survival analysis before and after matching showed that the cumulative survival rate of the high ACAG group was lower (P < 0.05). RCS analysis showed that ACAG had a non-linear relationship with the risk of in-hospital all-cause mortality (χ 2 = 6.060, P < 0.001). Multivariate COX regression analysis before and after PSM suggested that elevated ACAG was an independent risk factor for all-cause mortality in patients with CA during hospitalization (P < 0.01). Conclusions: Elevated ACAG is associated with increased all-cause mortality in patients with CA during hospitalization, it can be an independent risk factor for poor prognosis in patients with CA and remind clinicians to pay more attention to these patients.

Epstein-Barr Virus Synergizes with BRD7 to Conquer c-Myc-Mediated Viral Latency Maintenance via Chromatin Remodeling.

Epstein-Barr virus (EBV) switches between latent and lytic phases in hosts, which is important in the development of related diseases. However, the underlying mechanism of controlling the viral biphasic life cycle and how EBV mediates this regulation remain largely unknown. This study identified bromodomain-containing protein 7 (BRD7) as a crucial host protein in EBV latent infection. Based on the chromatin immunoprecipitation (ChIP) sequencing of endogenous BRD7 in Burkitt lymphoma cells, we found that EBV drove BRD7 to regulate cellular and viral genomic loci, including the transcriptional activation of c-Myc, a recently reported regulator of EBV latency. Additionally, EBV-mediated BRD7 signals were enriched around the FUSE (far-upstream sequence element) site in chromosome 8 and the enhancer LOC108348026 in the lgH locus, which might activate the c-Myc alleles. Mechanically, EBV-encoded nuclear antigen 1 (EBNA1) bound to BRD7 and colocalized at promoter regions of the related genes, thus serving as cofactors for the maintenance of viral latency. Moreover, the disruption of BRD7 decreased the c-Myc expression, induced the BZLF1 expression, and reactivated the lytic cycle. Our findings reveal the unique role of BRD7 to synergize with EBV in maintaining the viral latency state via chromatin remodeling. This study paves the way for understanding the new molecular mechanism of EBV-induced chromatin remodeling and latent-lytic switch, providing novel therapeutic candidate targets for EBV persistent infection. IMPORTANCE When establishing persistent infection in most human hosts, EBV is usually latent. How the viral latency is maintained in cells remains largely unknown. c-Myc was recently reported to act as a controller of the lytic switch, while whether and how EBV regulates it remain to be explored. Here, we identified that BRD7 is involved in controlling EBV latency. We found that EBV-mediated BRD7 was enriched in both the normal promoter regions and the translocation alleles of c-Myc, and disruption of BRD7 decreased c-Myc expression to reactivate the lytic cycle. We also demonstrated that EBV-encoded EBNA1 bound to and regulated BRD7. Therefore, we reveal a novel mechanism by which EBV can regulate its infection state by coordinating with host BRD7 to target c-Myc. Our findings will help future therapeutic intervention strategies for EBV infection and pathogenesis.

The emerging roles of IFIT3 in antiviral innate immunity and cellular biology.

The interferon-inducible protein with tetrapeptide repeats 3 (IFIT3) is one of the most important members in both the IFIT family and interferon-stimulated genes family. IFIT3 has typical features of the IFIT family in terms of gene and protein structures, and is able to be activated through the classical PRRs-IFN-JAK/STAT pathway. A variety of viruses can induce the expression of IFIT3, which in turn inhibits the replication of viruses, with the underlying mechanism showing its crucial role in antiviral innate immunity. Emerging studies have also identified that IFIT3 is involved in cellular biology changes, including cell proliferation, apoptosis, differentiation, and cancer development. In this review, we summarize the characteristics of IFIT3 with respect to molecular structure and regulatory pathways, highlighting the role of IFIT3 in antiviral innate immunity, as well as its diverse biological roles. We also discuss the potential of IFIT3 as a biomarker in disease diagnosis and therapy.

The correlation study between blood urea nitrogen to serum albumin ratio and prognosis of patients with sepsis during hospitalization.

BACKGROUND: Sepsis is a common critical illness in intensive care unit (ICU) and seriously threatens the life of patients. Therefore, to identify a simple and effective clinical indicator to determine prognosis is essential for the management of sepsis patients. This study was mainly based on blood urea nitrogen to albumin ratio (B/A), a comprehensive index, to explore its correlation with the prognosis of sepsis patients during hospitalization. METHODS: Totally, adult patients in ICU who were diagnosed with sepsis in Medical Information Mart for Intensive Care IV(MIMIC-IV) database from 2008 to 2019 were involved in this study. The study population were divided into survivors group and non-survivors group based on the prognosis during hospitalization. Restricted cubic spline (RCS) was utilized to analyze the association between B/A level and the risk of ICU all-cause mortality in patients with sepsis and determine the optimal cut-off value of B/A. The study population was divided into low B/A group and high B/A group based on the optimal cut-off value. The survival curve of ICU cumulative survival rate was draw through Kaplan-Meier method. The correlation between B/A and the prognosis of patients was conducted by multivariate Cox regression analysis. Furthermore, we performed sensitivity analyses to assess the robustness of the results. RESULTS: A total of 10,578 patients with sepsis were enrolled, and the ICU all-cause mortality was 15.89%. The patients in the non-survivors group had higher B/A values and more comorbidities than those in the survivors group. RCS showed that the risk of ICU all-cause mortality increased with the B/A level, showing a non-linear trend (χ2 = 66.82, p < 0.001). The mortality rate in the high B/A group was significantly higher than that in the low B/A group (p < 0.001). Kaplan-Meier curves revealed that compared with the low B/A group, the ICU cumulative survival rate of patients with sepsis was significantly lower in the high B/A group (log-rank test, χ2 = 148.620, p < 0.001). Further analysis of multivariate Cox proportional hazards regression showed that an elevated B/A (≥ 7.93) was an independent factor associated with ICU mortality among patients with sepsis. CONCLUSIONS: An elevated B/A might be a useful prognostic indicator in patients with sepsis. This study could offer a deeper insight into treating sepsis.

Insight into LncRNA- and CircRNA-Mediated CeRNAs: Regulatory Network and Implications in Nasopharyngeal Carcinoma-A Narrative Literature Review.

Nasopharyngeal carcinoma (NPC) is a kind of head-and-neck malignant tumor, and distant metastasis treatment resistance is the leading cause of patient death. In-depth understanding of NPC progression and treatment failure remains to be explored. Long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are noncoding RNAs that play key regulatory role in shaping tumor cell activities. Recent studies have revealed that lncRNA and circRNA function as competitive endogenous RNAs (ceRNAs) by regulating the posttranscriptional expression of genes as miRNA baits. The imbalanced ceRNA networks derived from lncRNA/circRNA-miRNA-mRNA interaction are widely found to contribute to NPC development. Herein, we summarize typical examples of lncRNA/circRNA-associated ceRNAs in recent years, which involved the potential molecular mechanisms in the regulation of proliferation, apoptosis, treatment resistance and metastasis of NPC, and discuss their potential clinical significance in the prognosis and treatment of NPC. Interpreting the involvement of ceRNAs networks will provide new insight into the pathogenesis and treatment strategies of NPC. However, ceRNA regulatory mechanism has some limitations currently. Screening the most effective ceRNA targets and the clinical application of ceRNA still has many challenges.

Cyclophilin A binds to AKT1 and facilitates the tumorigenicity of Epstein-Barr virus by mediating the activation of AKT/mTOR/NF-κB positive feedback loop.

The AKT/mTOR and NF-κB signalings are crucial pathways activated in cancers including nasopharyngeal carcinoma (NPC), which is prevalent in southern China and closely related to Epstein-Barr virus (EBV) infection. How these master pathways are persistently activated in EBV-associated NPC remains to be investigated. Here we demonstrated that EBV-encoded latent membrane protein 1 (LMP1) promoted cyclophilin A (CYPA) expression through the activation of NF-κB. The depletion of CYPA suppressed cell proliferation and facilitated apoptosis. CYPA was able to bind to AKT1, thus activating AKT/mTOR/NF-κB signaling cascade. Moreover, the use of mTOR inhibitor, rapamycin, subverted the activation of the positive feedback loop, NF-κB/CYPA/AKT/mTOR. It is reasonable that LMP1 expression derived from initial viral infection is enough to assure the constant potentiation of AKT/mTOR and NF-κB signalings. This may partly explain the fact that EBV serves as a tumor-promoting factor with minimal expression of the viral oncoprotein LMP1 in malignancies. Our findings provide new insight into the understanding of causative role of EBV in tumorigenicity during latent infection.

Dairy Trade Helps to Alleviate Global Carbon Emission Pressure.

Global dairy production, consumption, and trade are growing rapidly, driven by population and per capita income growth and increasing health concerns mainly from developing countries, which has aroused concerns about the related carbon emission (mostly in the form of methane) increase. If all of the dairy products consumed were produced locally/domestically in the developing countries/economies (a counterfactual scenario), the carbon emissions in 2018 would be 28 Mt CO2-equiv higher than its status quo (a factual scenario). The present study indicates that unlike in many global trade cases in which carbon leakages are from developed to developing countries, global dairy trade is characterized by net embodied carbon flows from developed to developing countries/economies due to the fact that there is an overwhelming one-way-flow of dairy products from developed to developing countries/economies. The differences in the carbon emission factors between the developed and developing countries/economies provide an opportunity that global dairy trade and production specialization can help to reduce carbon emissions from increasing dairy product demand, and the total reduction potential is estimated to be about 414 Mt CO2-equiv from 2018 to 2030. Free trade agreements such as the Regional Comprehensive Economic Partnership will incentivize larger carbon emission reduction benefits through promoting dairy trade.

Construction of a novel two-dimensional AgBiO3/BiOBr step-scheme heterojunction for enhanced broad-spectrum photocatalytic performance.

Efficient S-scheme heterojunction photocatalysts were prepared through in situ growth of AgBiO3 on BiOBr. The self-assembled hierarchical structure of AgBiO3/BiOBr was formed from flower-like AgBiO3 and plate-like BiOBr. The optimized AgBiO3/BiOBr heterojunction possessed excellent visible-light photocatalytic degradation efficiency (83%) for ciprofloxacin (CIP) after 120 min, with 1.46- and 4.15-times higher activity than pure AgBiO3 and BiOBr, respectively. Furthermore, the removal ratio of multiple organic pollutants including tetracycline, Rhodamine B, Lanasol Red 5B and methyl orange was also investigated. Environmental interference experiments demonstrated that high pollutant concentrations, low photocatalyst dose and the addition of ions (SO4 2-, PO4 3-, HPO4 2-, H2PO4 -) inhibited the photocatalytic activities. Subsequently, a simultaneous degradation experiment showed the competitive actions between CIP and RhB for radicals, decreasing the photocatalytic activity of CIP. Furthermore, trapping and electron spin resonance experiments showed that h+ and ˙O2 - played a certain role in the degradation process and that ˙OH acted as assistant.

The implications of cell-free DNAs derived from tumor viruses as biomarkers of associated cancers.

Cancer is still ranked as a leading cause of death according to estimates from the World Health Organization (WHO) and the strong link between tumor viruses and human cancers have been proved for almost six decades. Cell-free DNA (cfDNA) has drawn enormous attention for its dynamic, instant, and noninvasive advantages as one popular type of cancer biomarker. cfDNAs are mainly released from apoptotic cells and exosomes released from cancer cells, including those infected with viruses. Although cfDNAs are present at low concentrations in peripheral blood, they can reflect tumor load with high sensitivity. Considering the relevance of the tumor viruses to the associated cancers, cfDNAs derived from viruses may serve as good biomarkers for the early screening, diagnosis, and treatment monitoring. In this review, we summarize the methods and newly developed analytic techniques for the detection of cfDNAs from different body fluids, and discuss the implications of cfDNAs derived from different tumor viruses in the detection and treatment monitoring of virus-associated cancers. A better understanding of cfDNAs derived from tumor viruses may help formulate novel antitumoral strategies to decrease the burden of cancers that attributed to viruses.