Effectiveness of nirmatrelvir-ritonavir versus azvudine for adult inpatients with severe or critical COVID-19.

BACKGROUND: In China, both nirmatrelvir-ritonavir (Paxlovid) and azvudine have been granted approval to treat adult SARS-CoV-2-infected patients with moderate symptoms. Information about the clinical effect of the two available agents among inpatients with severe or critical COVID-19 is scarce. PURPOSE: To compare the clinical outcomes of Paxlovid and azvudine among adult inpatients with severe or critical COVID-19. METHOD: We conducted a retrospective cohort study in two large medical centres after the epidemic control measures were lifted in China. A new propensity score matched-inverse probability of treatment weighting cohort was constructed to evaluate the in-hospital all-cause mortality, hospital length of stay, Sequential Organ Failure Assessment (SOFA) score and safety. RESULTS: A total of 955 individuals were in the cohort. The antiviral therapy strategies were decided by the senior physician and the supplies of the pharmacy. A total of 451 patients were in the Paxlovid group, and 504 patients were in the azvudine group. Compared with Paxlovid, the effects of azvudine on in-hospital all-cause mortality were not significantly different, and the OR (95% CI) was 1.084 (0.822 to 1.430), and the average hospital length of stay of patients discharged alive was also similar in the azvudine group, and the difference (day) and (95% CI) was 0.530 (-0.334 to 1.393). After 7 days of therapy, the degree of decline in the SOFA score was greater in the Paxlovid group than in the azvudine group (p<0.001). The change in glomerular filtration rate was not significantly different (p=0.824). CONCLUSION: Paxlovid and azvudine had similar effectiveness on in-hospital all-cause mortality and hospital length of stay. Compared with the azvudine group, after 7 days of therapy, the degree of decline in SOFA score was significantly higher in the Paxlovid group. These findings need to be verified in larger prospective studies or randomised controlled trials.

Role of LncRNA H19 in tumor progression and treatment.

As one of the earliest discovered lncRNA molecules, lncRNA H19 is usually expressed in large quantities during embryonic development and is involved in cell differentiation and tissue formation. In recent years, the role of lncRNA H19 in tumors has been gradually recognized. Increasing evidence suggests that its aberrant expression is closely related to cancer development. LncRNA H19 as an oncogene not only promotes the growth, proliferation, invasion and metastasis of many tumors, but also develops resistance to treatment, affecting patients' prognosis and survival. Therefore, in this review, we summarise the extensive research on the involvement of lncRNA H19 in tumor progression and discuss how lncRNA H19, as a key target gene, affects tumor sensitivity to radiotherapy, chemotherapy and immunotherapy by participating in multiple cellular processes and regulating multiple signaling pathways, which provides a promising prospect for further research into the treatment of cancer.

Killing two birds with one stone: Abscopal effect mechanism and its application prospect in radiotherapy.

Abscopal effects are characterized by the emergence of neoplasms in regions unrelated to the primary radiation therapy site, displaying a gradual attenuation or regression throughout the progression of radiation therapy, which have been of interest to scientists since Mole's proposal in 1953. The incidence of abscopal effects in radiation therapy is intricately linked to the immune system, with both innate and adaptive immune responses playing crucial roles. Biological factors impacting abscopal effects ultimately exert their influence on the intricate workings of the immune system. Although abscopal effects are rarely observed in clinical cases, the underlying mechanism remains uncertain. This article examines the biological and physical factors influencing abscopal effects of radiotherapy. Through a review of preclinical and clinical studies, this article aims to offer a comprehensive understanding of abscopal effects and proposes new avenues for future research in this field. The findings presented in this article serve as a valuable reference for researchers seeking to explore this topic in greater depth.

Gastrointestinal manifestations of critical ill heatstroke patients and their associations with outcomes: A multicentre, retrospective, observational study.

BACKGROUND: Extreme heat exposure is a growing health problem, and the effects of heat on the gastrointestinal (GI) tract is unknown. This study aimed to assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. AIM: To assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. METHODS: Patients admitted to the intensive care unit (ICU) due to heatstroke were included from 83 centres. Patient history, laboratory results, and clinically relevant outcomes were recorded at ICU admission and daily until up to day 15, ICU discharge, or death. GI symptoms, including nausea/vomiting, diarrhoea, flatulence, and bloody stools, were recorded. The characteristics of patients with heatstroke concomitant with GI symptoms were described. Multivariable regression analyses were performed to determine significant predictors of GI symptoms. RESULTS: A total of 713 patients were included in the final analysis, of whom 132 (18.5%) patients had at least one GI symptom during their ICU stay, while 26 (3.6%) suffered from more than one symptom. Patients with GI symptoms had a significantly higher ICU stay compared with those without. The mortality of patients who had two or more GI symptoms simultaneously was significantly higher than that in those with one GI symptom. Multivariable logistic regression analysis revealed that older patients with a lower GCS score on admission were more likely to experience GI symptoms. CONCLUSION: The GI manifestations of heatstroke are common and appear to impact clinically relevant hospitalization outcomes.

Clinical value of the red blood cell distribution width to albumin ratio in the assessment of prognosis in critically ill patients with sepsis: a retrospective analysis.

Background: Red blood cell (RBC) distribution width (RDW) to albumin ratio is a novel biomarker and its prognostic effect on critically ill patients with sepsis has not been extensively investigated. The objective of this study was to identify the prognostic value of the RDW to albumin ratio in these patients. Methods: Data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. A Cox proportional hazards model and restricted cubic spline model were used to determine the association of RDW to albumin ratio with mortality. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were applied, and the area under the curve (AUC) was used to compare the predictive value. Results: A total of 3,969 eligible patients were enrolled. The median RDW to albumin ratio was significantly higher in non-survivors than in survivors at 30 and 90 days. Patients were divided into groups according to the RDW to albumin ratio, and the risk of 30- and 90-day mortality markedly increased in the group with a higher ratio. The relationship between the RDW to albumin ratio as a continuous variable and 30-day mortality also showed an upward trend in the restricted cubic spline. The AUC of the RDW to albumin ratio was 0.633 in discriminating 30-day mortality which was similar to that of the lactate to albumin ratio (AUC =0.617; P=0.133) and higher than that of the neutrophil percentage to albumin ratio (AUC =0.559; P<0.001). Conclusions: The RDW to albumin ratio is a promising biomarker for assessing the prognosis of critically ill patients with sepsis. Its predictive value in determining mortality was found to be similar to that of the lactate to albumin ratio and superior to that of the neutrophil percentage to albumin ratio.

Carrier systems of radiopharmaceuticals and the application in cancer therapy.

Radiopharmaceuticals play a vital role in cancer therapy. The carrier of radiopharmaceuticals can precisely locate and guide radionuclides to the target, where radionuclides kill surrounding tumor cells. Effective application of radiopharmaceuticals depends on the selection of an appropriate carrier. Herein, different types of carriers of radiopharmaceuticals and the characteristics are briefly described. Subsequently, we review radiolabeled monoclonal antibodies (mAbs) and their derivatives, and novel strategies of radiolabeled mAbs and their derivatives in the treatment of lymphoma and colorectal cancer. Furthermore, this review outlines radiolabeled peptides, and novel strategies of radiolabeled peptides in the treatment of neuroendocrine neoplasms, prostate cancer, and gliomas. The emphasis is given to heterodimers, bicyclic peptides, and peptide-modified nanoparticles. Last, the latest developments and applications of radiolabeled nucleic acids and small molecules in cancer therapy are discussed. Thus, this review will contribute to a better understanding of the carrier of radiopharmaceuticals and the application in cancer therapy.

Pyroptotic cell death: an emerging therapeutic opportunity for radiotherapy.

Pyroptotic cell death, an inflammatory form of programmed cell death (PCD), is emerging as a potential therapeutic opportunity for radiotherapy (RT). RT is commonly used for cancer treatment, but its effectiveness can be limited by tumor resistance and adverse effects on healthy tissues. Pyroptosis, characterized by cell swelling, membrane rupture, and release of pro-inflammatory cytokines, has been shown to enhance the immune response against cancer cells. By inducing pyroptotic cell death in tumor cells, RT has the potential to enhance treatment outcomes by stimulating anti-tumor immune responses and improving the overall efficacy of RT. Furthermore, the release of danger signals from pyroptotic cells can promote the recruitment and activation of immune cells, leading to a systemic immune response that may target distant metastases. Although further research is needed to fully understand the mechanisms and optimize the use of pyroptotic cell death in RT, it holds promise as a novel therapeutic strategy for improving cancer treatment outcomes. This review aims to synthesize recent research on the regulatory mechanisms underlying radiation-induced pyroptosis and to elucidate the potential significance of this process in RT. The insights gained from this analysis may inform strategies to enhance the efficacy of RT for tumors.

Gadolinium Oxide Nanoparticles Reinforce the Fractionated Radiotherapy-Induced Immune Response in Tri-Negative Breast Cancer via cGAS-STING Pathway.

Introduction: Radiotherapy is a widely recognized first-line clinical treatment for cancer, but its efficacy may be impeded by the radioresistance of advanced tumors. It is urgent to improve the sensitivity of radioresistant tumors to radiotherapy. In this work, gadolinium oxide nanocrystals (GONs) were utilized as radiosensitizers to enhance the killing effect and reinforce the immune activation of X-ray irradiation on 4T1 breast cancer cells in vitro and in vivo. Methods: 1.0 T small animal MR imaging (MRI) system was employed to trace GONs in vivo, while 225 kVp X-ray irradiation equipment was utilized for investigating the radiosensitization of GONs in 4T1 breast cancer cells in vitro and in vivo. Western blot, quantitative real-time PCR (RT-qPCR), immunohistochemistry, immunofluorescence, clonal survival assay, flow cytometry and reactive oxygen species assay were used to explore the biological mechanism of GON sensitization. Results: GONs exhibited exceptional utility as contrast agents for both in vivo and in vitro MRI imaging. Interestingly, a single dose of 8.0 Gy X-rays together with GONs failed to confer superior therapeutic effects in tumor-bearing mice, while only 3.0 Gy × 3 fractions X-rays combined with GONs exhibited effective tumor growth inhibition. Moreover, fractionated X-ray irradiation with GONs demonstrated a superior capacity to activate the cGAS-STING pathway. Discussion: Fractionated X-ray irradiation in the presence of GONs has demonstrated the most significant activation of the anti-tumor immune response by boosting the cGAS-STING pathway.

Prediction of prokinetic agents in critically ill patients with feeding intolerance: a prospective observational clinical study.

Background: Prokinetic agents are currently considered the first-line therapy to improve gastric emptying when feeding intolerance occurred in critically ill adults. In this study, we developed a technique to assess the feasibility of predicting prokinetic agent efficacy in critically ill patients. Methods: The first images of each patient were obtained after EFI had occurred but before the first dose of prokinetic agents was administered and additional images were obtained every morning until the seventh day. The gastric antrum echodensity was recorded based on grayscale values (50th percentile, ED50; 85th percentile, ED85; mean, EDmean) and daily energy and protein intake was collected as the judgment for effective and ineffective group. A receiver operating characteristic curve was analyzed to distinguish the thresholds between the two groups and thus determine the ability of the gastric antrum echodensity to predict the efficacy of prokinetic agents. Results: In total, 83 patients were analyzed. Patients in the ineffective group had a higher ED50 (58.13 ± 14.48 vs. 49.88 ± 13.78, p < 0.001, difference 95% CI: 5.68, 10.82), ED85 (74.81 ± 16.41 vs. 65.70 ± 16.05, p < 0.001, difference 95% CI:6.16, 12.05), and EDmean (60.18 ± 14.31 vs. 51.76 ± 14.08, p < 0.001, difference 95% CI: 5.85, 11.00) than those in the effective group. Patients in the effective group more easily reached the target energy 16.21 ± 7.98 kcal/kg vs. 9.17 ± 6.43 kcal/kg (p < 0.001), 0.72 ± 0.38 g/kg vs. 0.42 ± 0.31 g/kg (p < 0.001) than in the ineffective group intake by day. Conclusion: The gastric antrum echodensity might serve as a tool for judging the efficacy of prokinetic agents, helping clinicians to decide whether to use prokinetic agents or place a post-pyloric tube when feeding intolerance occurs in critically ill patients.Clinical trial registration:http://www.chictr.org.cn/addproject2.aspx, ChiCTR2200058373. Registered 7 April 2022.

Rosuvastatin plus ticagrelor decreases the risk of major adverse cardiovascular events and elevates cardiac function compared with ticagrelor alone in patients undergoing percutaneous coronary intervention: A meta­analysis.

Several previous studies have reported that rosuvastatin plus ticagrelor is superior to ticagrelor monotherapy in patients receiving percutaneous coronary intervention (PCI); several others, however, dispute this. The present meta-analysis summarized relevant studies, aiming to comprehensively explore the efficacy of rosuvastatin plus ticagrelor vs. ticagrelor monotherapy in patients receiving PCI. Published studies comparing the efficacy between rosuvastatin plus ticagrelor and ticagrelor alone among patients receiving PCI were searched in the CNKI, Wanfang, CQVIP, EMBASE, Cochrane and PubMed databases until January 2023. The present meta-analysis included 3 cohort studies and 4 randomized controlled trials with 426 patients receiving rosuvastatin plus ticagrelor and 424 patients receiving ticagrelor monotherapy. Rosuvastatin plus ticagrelor decreased the occurrence of major adverse cardiovascular events (MACE) compared with ticagrelor [relative risk (RR), 0.29; 95% confidence interval (CI), 0.18-0.47]. Subgroup analysis revealed similar findings in studies with a follow-up of <6 months (RR, 0.24; 95% CI, 0.13-0.47) and ≥6 months (RR, 0.36; 95% CI, 0.18-0.70), as well as in studies using 10 mg rosuvastatin (RR, 0.27; 95% CI, 0.15-0.50) and 20 mg rosuvastatin (RR, 0.33; 95% CI, 0.16-0.69). In addition, rosuvastatin plus ticagrelor decreased the left ventricular (LV) end-systolic diameter [mean difference (MD), -0.71; 95% CI, -(1.36-0.07)], LV end-diastolic diameter [MD, -1.17; 95% CI, -(1.91-0.43)] and N-terminal pro-B-type natriuretic peptide [MD, -2.97; 95% CI, -(4.55-1.38)], and increased the LV ejection fraction (MD, 0.99; 95% CI, 0.74-1.25). In conclusion, rosuvastatin plus ticagrelor was shown to decrease the risk of MACE and elevate cardiac function compared with ticagrelor monotherapy in patients receiving PCI.

Bempedoic Acid can Reduce Cardiovascular Events in Combination with Statins or As Monotherapy: A Systematic Review and Meta-analysis.

AIM: Bempedoic acid has shown noteworthy progress in the prevention and management of atherosclerotic cardiovascular disease (ASCVD) in recent years. However, there has been a lack of high-quality evidence regarding the risk reduction of clinical events with bempedoic acid. Therefore, the aim of this article is to conduct a comprehensive evaluation of the impact of bempedoic acid on the incidence of cardiovascular events. METHODS: A systematic review and meta-analysis of randomized controlled trials pertaining to bempedoic acid was carried out. We conducted a systematic search across the Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases to identify relevant studies published from inception to 23 April 2023. A total of four trials comparing the clinical benefit achieved with bempedoic acid versus placebo were included. RESULTS: Our analysis comprised four trials that encompassed a total of 17,323 patients. In comparison to the placebo, bempedoic acid showed a significant reduction in the risk of major adverse cardiovascular events (MACE) [relative risk (RR), 0.86, 95% confidence interval (CI) 0.87-0.94]. Additionally, bempedoic acid substantially lowered the occurrence of fatal or nonfatal myocardial infarction (RR 0.76, 95% CI 0.66-0.89), hospitalization for unstable angina (RR 0.70, 95% CI 0.55-0.89), and coronary revascularization (RR 0.82, 95% CI 0.73-0.92). There was also a similar reduction in MACE in patients on the maximally tolerated statin therapy. CONCLUSION: Bempedoic acid may reduce the risk of cardiovascular events regardless of whether the patient is taking stains or not. REGISTRATION: PROSPERO registration number CRD42023422932.

Associations of the Geriatric Nutritional Risk Index with high risk for prostate cancer: A cross-sectional study.

OBJECTIVES: The geriatric Nutritional Risk Index (GNRI) is an effective tool to assess the nutritional status of the elderly. However, the relationship between the GNRI and the risk for prostate cancer (PCa) remains uncertain in middle-aged and older men. The aim of this study was to investigate the association between the GNRI and the risk for PCa by analyzing the serum total (tPSA) and free prostate-specific antigen (fPSA) levels (including percent fPSA [%fPSA]). METHODS: Data for this study were obtained from 7396 men ≥40 y of age from the 2001-2010 National Health and Nutrition Survey (NHANES). We obtained the tPSA and fPSA and calculated the %fPSA and the GNRI. Participants with %fPSA >25% and tPSA <4 ng/mL were defined as high PCa risk. The relationship between the GNRI and serum PSA levels was investigated using a linear regression model. The odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the GNRI and PCa risk were estimated by a logistic regression model. The non-linear relationship was also characterized by a restricted cubic spline regression model. RESULTS: The median of tPSA, fPSA, and %fPSA was 0.90, 0.26, and 29%, respectively. The mean of the GNRI was 29. The proportion of participants in the low PCa- and high PCa-risk groups was 93% and 7%, respectively. There was a negative and linear correlation between the GNRI and serum tPSA and fPSA levels in all models. However, no association between the GNRI and the %fPSA was observed. In the adjusted model, lower GNRI was associated with higher PCa risk (OR, 0.570; 95% CI, 0.415-0.784; Ptrend = 0.001). The restricted cubic spline regression model showed a non-linear and negative association between the GNRI and PCa risk (Pnon-linearity = 0.020), with inflection points of 109.148. CONCLUSION: The results of this study suggest that nutritional status, as represented by the GNRI, is associated with the risk for PCa.

Ferroptosis: a novel regulated cell death participating in cellular stress response, radiotherapy, and immunotherapy.

BACKGROUND: Ferroptosis is a regulated cell death mode triggered by iron-dependent toxic membrane lipid peroxidation. As a novel cell death modality that is morphologically and mechanistically different from other forms of cell death, such as apoptosis and necrosis, ferroptosis has attracted extensive attention due to its association with various diseases. Evidence on ferroptosis as a potential therapeutic strategy has accumulated with the rapid growth of research on targeting ferroptosis for tumor suppression in recent years. METHODS: We summarize the currently known characteristics and major regulatory mechanisms of ferroptosis and present the role of ferroptosis in cellular stress responses, including ER stress and autophagy. Furthermore, we elucidate the potential applications of ferroptosis in radiotherapy and immunotherapy, which will be beneficial in exploring new strategies for clinical tumor treatment. RESULT AND CONCLUSION: Based on specific biomarkers and precise patient-specific assessment, targeting ferroptosis has great potential to be translated into practical new approaches for clinical cancer therapy, significantly contributing to the prevention, diagnosis, prognosis, and treatment of cancer.

Management of urinary incontinence after radical cystectomy and orthotopic neobladder: A scoping review of international practices.

OBJECTIVES: To identify and describe international practice in incontinence management after radical cystectomy and orthotopic neobladder. MATERIALS AND METHODS: A systematic scoping review following the methodology of the Joanne Briggs Institute was conducted in which the application searched 15 data sources to identify papers published in English, from 1979 to 2022. RESULTS: Of the 16 papers that met the eligibility criteria, articles in Eastern countries mainly focus on the effect of conservative treatment, while in Western countries, more attention is paid to the effect of surgical treatment. Clinical characteristics of patients included conservative treatment failure, duration of post-operative intervention and unique differential treatment of male and female patients. Reported factors influencing the achievement of urinary incontinence (UI) include lack of evidence to guide management practice, limited value of conservative treatment, high risk of surgical treatment and uncertainty of efficacy; currently, early behavioural research and multimodal rehabilitation training have good results. CONCLUSIONS: UI in neobladder patients is a distressing condition that is difficult to treat and often requires high-quality rehabilitation guidance and surgical intervention. Further research to address current knowledge gaps is important to inform practice.

Disparities between randomized clinical trial participants and sepsis patients in real-world.

BACKGROUND: The external validity or "generalizability" of randomized controlled trials (RCTs) often needs be considered when making treatment decisions. We evaluate whether participants in large multicenter RCTs investigating sepsis were similar in age, disease severity, comorbidities, and mortality to the general population of sepsis patients. METHODS: Using MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials, RCTs that enrolled 100 or more adult sepsis patients from two or more sites published from 01 January 2000 to 04 August 2019 were identified. The weighted mean age of trial participants was calculated as the main variable, and it was compared with the mean ages of the overall populations derived from the MIMIC database and the EICU database. Two researchers independently screened all abstracts and performed data extraction, then aggregated the data using a random effects model. Multiple linear regression was used to determine whether any factors were significantly associated with age disparities. RESULTS: The mean age of the 60,577 participants in the 94 trials included in the analysis was significantly lower than those of the patients in the MIMIC and EICU databases (weighted mean age 62.28 years vs. 64.47 years for MIMIC and 65.20 years for EICU; both p < 0.001). Trial participants were less likely to have known comorbidities such as diabetes (13.96% vs. 30.64% for MIMIC and 35.75% for EICU; both p < 0.001). The weighted mortality rate in trial participants was higher than that in patients in the MIMIC and EICU databases (29.33% vs. 20.72% for MIMIC and 17.53% for EICU; both p < 0.001). Differences in age, severity score, and comorbidities remained statistically significant in sensitivity analyses. Multivariable regression suggested that commercially supported trials were more likely to include patients with higher severity scores (p = 0.002), but after adjustment for study region and sepsis diagnosis inclusion in such trials was not significantly associated with age. CONCLUSIONS: On average, trial participants were younger than the general sepsis patient population. Commercial support influenced patient selection. Efforts to understand and address the above-described patient disparities are necessary to improve the generalizability of RCT results. TRIAL REGISTRATION: PROSPERO CRD42019145692.

Comparison of laparoscopic, robotic, and open retroperitoneal lymph node dissection for non-seminomatous germ cell tumor: a single-center retrospective cohort study.

PURPOSE: To compare the perioperative outcomes of L-RPLND, R-RPLND and O-RPLND, and determine which one can be the mainstream option. METHODS: We retrospectively reviewed medical records of 47 patients undergoing primary RPLND by three different surgical techniques for stage I-II NSGCT between July 2011 and April 2022 at our center. Standard open and laparoscopic RPLND was performed with usual equipment, and robotic RPLND was operated with da Vinci Si system. RESULTS: Forty-seven patients underwent RPLND during 2011-2022, and 26 (55.3%) of them received L-RPLND, 14 (29.8%) were operated with robot, while 7 (14.9%) were performed O-RPLND. The median follow-up was 48.0 months, 48.0 months, and 60.0 months, respectively. The oncological outcomes were comparable among all groups. In L-RPLND group, there were 8 (30.8%) cases of low grade (Clavien I-II) complications, and 3 (11.5%) cases of high-grade (Clavien III-IV) complications. In R-RPLND group, one (7.1%) low-grade complication and four (28.6%) high-grade complications were observed. In O-RPLND group, there were 2 (28.5%) cases of low-grade complications and one case (14.2%) of high-grade one. The operation duration of L-RPLND was the shortest. In O-RPLND group, the number of positive lymph nodes were higher than other two groups. Patients undergoing open surgery had lower (p < 0.05) red blood cell count, hemoglobin level, and higher (p < 0.05) estimated blood loss, white blood cell count than those receiving either laparoscopic or robotic surgery. CONCLUSION: All three surgical techniques are comparable in safety, oncological, andrological, and reproductive outcomes under the circumstance of not using primary chemotherapy. L-RPLND might be the most cost-effective option.

Sirt4 deficiency promotes the development of atherosclerosis by activating the NF-κB/IκB/CXCL2/3 pathway.

BACKGROUND AND AIMS: As a member of mitochondrial sirtuins, Sirt4 plays a vital role in cellular metabolism and intracellular signal transduction; however, its effect on atherosclerosis is unclear. This study aimed to explore the effect of Sirt4 on atherosclerosis and its underlying mechanism. METHODS: In vivo, Apoe-/- and Apoe-/-/Sirt4-/- mice were fed a high-fat diet to induce atherosclerosis. In vitro, peritoneal macrophages from two mouse types were extracted and treated with oxidized low-density lipoprotein to establish a cell model, THP-1 cells were used to observe the effect of Sirt4 on the adhesion ability of monocytes. The growth and composition of aortic plaques in two mouse types were analyzed by H&E staining, Oil Red O staining, Dil oxidized low-density lipoprotein, immunohistochemistry, real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Transcriptome analysis and Western blotting were performed to explore the specific mechanism. RESULTS: Sirt4 deficiency aggravated atherosclerosis in mice. In vivo, aortic plaque size, lipid content, and expression of related inflammatory factors in Apoe-/-/Sirt4-/- mice were higher than those in the control group, whereas the content of collagen Ⅰ and smooth muscle actin-α was significantly lower. Sirt4-deficient macrophages exhibited stronger lipid phagocytosis in vitro, and the adhesion ability of monocytes increased when Sirt4 expression decreased. Transcriptome analysis showed that the expression of CXCL2 and CXCL3 in Sirt4-deficient peritoneal macrophages increased significantly, which may play a role by activating the NF-κB pathway. In further analysis, the results in vitro and in vivo showed that the expression of VCAM-1 and pro-inflammatory factors, such as IL-6, TNF-α and IL-1ß, increased, whereas the expression of anti-inflammatory factor IL-37 decreased in Sirt4-deficient peritoneal macrophages and tissues. After blocking the effect with NK-κB inhibitor BAY11-7082, the inflammatory reaction in sirt4 deficient macrophages was also significantly decreased. CONCLUSIONS: This study demonstrates that Sirt4 deficiency promotes the development of atherosclerosis by activating the NF-κB/IκB/CXCL2/3 pathway, suggesting that Sirt4 may exhibit a protective effect in atherosclerosis, which provides a new strategy for clinical prevention and treatment of atherosclerosis.

R-spondin family biology and emerging linkages to cancer.

The R-spondin protein family comprises four members (RSPO1-4), which are agonists of the canonical Wnt/ß-catenin pathway. Emerging evidence revealed that RSPOs should not only be viewed as agonists of the Wnt/ß-catenin pathway but also as regulators for tumor development and progression. Aberrant expression of RSPOs is related to tumorigenesis and tumor development in multiple cancers and their expression of RSPOs has also been correlated with anticancer immune cell signatures. More importantly, the role of RSPOs as potential target therapies and their implication in cancer progressions has been studied in the preclinical and clinical settings. These findings highlight the possible therapeutic value of RSPOs in cancer medicine. However, the expression pattern, effects, and mechanisms of RSPO proteins in cancer remain elusive. Investigating the many roles of RSPOs is likely to expand and improve our understanding of the oncogenic mechanisms mediated by RSPOs. Here, we reviewed the recent advances in the functions and underlying molecular mechanisms of RSPOs in tumor development, cancer microenvironment regulation, and immunity, and discussed the therapeutic potential of targeting RSPOs for cancer treatment. In addition, we also explored the biological feature and clinical relevance of RSPOs in cancer mutagenesis, transcriptional regulation, and immune correlation by bioinformatics analysis.KEY MESSAGESAberrant expressions of RSPOs are detected in various human malignancies and are always correlated with oncogenesis.Although extensive studies of RSPOs have been conducted, their precise molecular mechanism remains poorly understood.Bioinformatic analysis revealed that RSPOs may play a part in the development of the immune composition of the tumor microenvironment.

Fabrication and application of chitosan-based biomass composites with fire safety, water treatment and antibacterial properties.

In this work, a biomass composite material (CS@NC@PA-Na) was prepared from chitosan (CS), nano-cellulose (NC) and sodium phytate (PA-Na). The prepared products were characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectrometry (XPS) and X-ray diffraction (XRD). The fire/water safety and antimicrobial properties of the CS@NC@PA-Na were fully studied. The results indicated CS@NC@PA-Na (50 mg) could effectively reduce the concentration of methyl orange by 85 % under 30 min adsorption. Meanwhile, only 5 wt% CS@NC@PA-Na could increase the limiting oxygen index (LOI) value of epoxy resin composite from 24.5 to 30.1 %, and decrease the peak heat/smoke release rate by 29.5 and 33.3 %, respectively. Moreover, CS@NC@PA-Na also exhibited excellent antibacterial effect. This work provides an efficient, feasible and eco-friendly route for large-scale production of multi-functional CS-based biomass materials that could be used in the fields of fire safety and environmental conservation.

Association of Vasopressors Dose Trajectories with Enteral Nutrition Tolerance in Patients with Shock: A Prospective Observational Study.

(1) Background: Studies on the long-term patterns of using vasopressors in patients with shock and their correlations with the risk of feeding intolerance (FI) are limited. This study aimed to characterize the norepinephrine equivalent dose (NEQ) trajectories and explore its correlations with FI in patients with shock. (2) Methods: This study prospectively enrolled patients with shock, who received vasopressors from August 2020 to June 2022. The Growth Mixed Model (GMM) was used to traverse longitudinal NEQ data at six-hour intervals and identify the latent trajectories of NEQ use in these patients. Cox proportional hazards regression models were used to examine the correlations of NEQ trajectories with FI. (3) Results: This study included a total of 210 patients with shock recruited from August 2020 to June 2022. Four trajectories of NEQ dose were identified and characterized by low-dose stable NEQ (L-NEQ, n = 98), moderate-dose stable NEQ (M-NEQ, n = 74), high-dose stable NEQ (H-NEQ, n = 21), and rapidly rising NEQ (R-NEQ, n = 17), with NEQ doses of 0.2, 0.4, 0.4, and 0.5 µg/kg/min at enteral nutrition (EN) initiation, respectively. The incidences of FI were 37.76%, 67.57%, 80.95%, and 76.47% in the L-NEQ, M-NEQ, H-NEQ, and R-NEQ groups, respectively (p < 0.001). As compared to the L-NEQ group, the risk of FI occurrence increased in the M-NEQ, H-NEQ, and R-NEQ groups (all p < 0.05). (4) Conclusions: The risk of FI was significantly associated with NEQ trajectories. It might be appropriate to initiate EN when the NEQ dose is stabilized below 0.2 µg/kg/min in patients with shock.