DNA response element-based smart drug delivery systems for precise drug release.

Smart drug delivery systems (DDSs) that respond to, interact with, or are actuated by biological signals or pathological abnormalities (e.g., the tumor microenvironment) for controllable drug release are appealing therapeutic platforms for cancer treatment. Owing to their inherent self-assembled nature, nucleic acids have emerged as programmable materials for the development of multifunctional structures. In response to external environmental stimuli, DNA response elements can serve as switches to trigger conformational changes in DNA structures. Their stimulus-responsive properties make them promising candidates for constructing smart DDSs, and advancements in DNA response element-based DDSs in the field of biomedicine have been made. This review summarizes different types of DNA response elements, including DNA aptamers, DNAzymes, disulfide bond-modified DNA, pH-responsive DNA motifs, and photocleavable DNA building blocks, and highlights the advancements in DNA response element-based smart DDSs for precise drug release. Finally, future challenges and perspectives in this field are discussed.

Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma.

Carnosine dipeptidase 1 (CNDP1), an enzyme integral to the hydrolysis of dipeptides containing histidine, plays an indispensable role in myriad physiological processes, including hydrolysis of proteins, maturation of specific biochemical functionalities within proteins, tissue regeneration, and regulation of cell cycle. However, the implications of CNDP1 in oncogenesis and its prognostic value are not yet fully elucidated. Initially, we procured the GSE40367 dataset from the Gene Expression Omnibus and established a protein-protein interaction network. Thereafter, we conducted functional and pathway enrichment analyses utilizing GO, KEGG, and GSEA. Moreover, we undertook an association analysis concerning the expression of CNDP1 with immune infiltration, along with survival analysis across various cancers and specifically in hepatocellular carcinoma (HCC). Our study uncovered a total of 2,248 differentially expressed genes, with a down-regulation of CNDP1 in HCC and other cancers. Our explorations into the relationship between CNDP1 and immune infiltration disclosed a negative correlation between CNDP1 expression and the presence of immune cells in HCC. Survival analyses revealed that diminished expression of CNDP1 correlates with an adverse prognosis in HCC and several other types of cancer. These observations intimate that CNDP1 holds promise as a novel prognostic biomarker for both pan-cancer and HCC.

Nomogram for preoperative estimation of microvascular invasion risk in hepatocellular carcinoma.

Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167-7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922-41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374-12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780-10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771-0.894) and 0.821 (95 % CI 0.720-0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively.

TBCRC 057: Survey about willingness to participate in cancer clinical trials during the pandemic.

BACKGROUND: Breast cancer patients experienced heightened anxiety during the pandemic. Also, modifications to clinical trial activities allowing for virtual platforms, local assessments, and greater flexibility were introduced to facilitate participation. We sought to evaluate the association between pandemic-related anxiety and willingness to participate in trials and how pandemic-era modifications to trial activities affect the decision to participate. METHODS: We conducted an online survey from August to September, 2021 of patients with breast cancer assessing pandemic-related anxiety; clinical trials knowledge and attitudes; willingness to participate during and before the pandemic; and how each modification affects the decision to participate. Fisher's exact tests evaluated differences in proportions and two-sample t-tests evaluated differences in means. The association of pandemic-related anxiety with a decline in willingness to participate during compared to prior to the pandemic was modeled using logistic regression. RESULTS: Among 385 respondents who completed the survey, 81% reported moderate-severe pandemic-related anxiety. Mean willingness to participate in a trial was lower during the pandemic than prior [2.97 (SD 1.17) vs. 3.10 (SD 1.09), (p < 0.001)]. Severe anxiety was associated with higher odds of diminished willingness to participate during the pandemic compared to prior (OR 5.07). Each of the modifications, with the exception of opting out of research-only blood tests, were endorsed by >50% of respondents as strategies that would increase their likelihood of deciding to participate. CONCLUSIONS: While pandemic-related anxiety was associated with diminished willingness to participate in trials, the leading reasons for reluctance to consider trial participation were unrelated to the pandemic but included worries about not getting the best treatment, side effects, and delaying care. Patients view trial modifications favorably, supporting continuation of these modifications, as endorsed by the National Cancer Institute and others.

Clinicopathological characteristics of 3 probable pediatric cases with acute severe hepatitis of unknown aetiology.

Background: Acute severe hepatitis with unknown aetiology in children (ASHep-UA) has become a global health alert. This article reported clinicopathological characteristics of 3 probable ASHep-UA cases. Methods: We respectively collected serological data and liver biopsies of 3 suspected cases of ASHep-UA. Neutralizing antibodies titer for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants were determined by virus neutralization test (VNT). Histological assessment, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for cytomegalovirus (CMV), Epstein-Barr virus (EBV), human adenoviruses (HAdV), adeno-associated virus (AAV2), human herpes virus type 6 (HHV-6) were performed to identify possible aetiologies. Results: Remarkable elevation of transaminase (median ALT level, 1100 IU/liter; median AST level, 500 IU/liter) were revealed with undetectable hepatitis A-E and non-hepatotropic virus in both sera and tissues. Weakness, jaundice, pale stools and splenomegaly were observed. Interestingly, two individuals had SARS-CoV-2 Omicron variants infection. Histologically, moderate or severe lobular necroinflammation, active interface hepatitis and portal inflammatory infiltrate with lymphocytic, plasma cells, neutrophils and eosinophilic cells were noted. Conclusions: The exact aetiology of ASHep-UA was still unknown. By reporting the 3 probable cases, we expect to enrich the clinical experience in diagnosis and treatment of ASHep-UA as well as the pathological characteristics.

Risk factors for surgical site infections following open reduction and internal fixation in patients with tibial plateau fractures.

This retrospective cohort study aimed to identify the risk factors associated with postoperative wound infections in patients undergoing open reduction and internal fixation for tibial plateau fractures. The study was conducted between January 2019 and December 2022, with stringent inclusion and exclusion criteria. Data were collected from the Electronic Health Record system, including demographic information, lifestyle habits, comorbid conditions and surgical variables like preoperative American Society of Anesthesiologists (ASA) scores. The IBM Statistical Package for the Social Sciences, version 27.0, was utilized for rigorous statistical analyses. Univariate analysis identified several factors, such as body mass index (BMI), smoking status and diabetes mellitus, as significant predictors of postoperative wound infection. Multivariate logistic regression revealed that BMI, type of fracture (open vs. closed), surgery duration exceeding 150 min, preoperative albumin levels below 35 g/L and preoperative ASA score of 3 or higher were significant independent risk factors (p < 0.05). Patients with open fractures, preoperative malnutrition, elevated preoperative ASA scores and a history of smoking are at a heightened risk of developing postoperative wound infections. Timely preoperative evaluation of these risk factors is crucial for minimizing the risk of surgical site infections and optimizing clinical management.

Levels of Matrix Metalloproteinase 9 Are Elevated in Persons With Schizophrenia or Bipolar Disorder: The Role of Modifiable Factors.

Background: Matrix metalloproteinases (MMPs) are a diverse set of enzymes associated with inflammation. MMP-9 is of particular interest because it has been associated with autoimmune and cardiopulmonary disorders, tobacco smoking, and obesity, prevalent in psychiatric populations. Methods: Sensitive enzyme immunoassays measured MMP-9 in blood samples from 1121 individuals (mean age = 35.6 [SD = 13.0] years; 47.7% male; 440 with schizophrenia, 399 with bipolar disorder, and 282 without a psychiatric disorder). We estimated the odds of diagnosis associated with MMP-9, demographic variables, tobacco smoking, and obesity, and also the partial explained variance using regression methods. We also determined the association between psychiatric medications and MMP-9 levels. Results: Individuals with elevated MMP-9 levels had higher odds of schizophrenia or bipolar disorder compared with the nonpsychiatric group adjusted for demographic variables. Partial correlation analyses indicated the demographic-adjusted variance associated with MMP-9, smoking, obesity, and their interaction explained 59.6% for schizophrenia and 39.9% for bipolar disorder. Levels of MMP-9 were substantially lower in individuals receiving valproate, particularly relatively high doses. Conclusions: Individuals with higher levels of MMP-9 have significantly higher odds of schizophrenia or bipolar disorder. Individuals receiving valproate had substantially lower levels of MMP-9, possibly related to its ability to inhibit histone deacetylation. A substantial portion of the variance in clinical disorders associated with MMP-9 can be attributed to smoking or obesity. Interventions to reduce smoking and obesity might reduce the morbidity and mortality associated with elevated MMP-9 levels and improve the health outcomes of individuals with these disorders.

L-arabinose Attenuates LPS-Induced Intestinal Inflammation and Injury through Reduced M1 Macrophage Polarization.

BACKGROUND: L-arabinose has anti-inflammatory and metabolism-promoting properties, and macrophages participate in the alleviation of inflammation; however, the mechanism by which they contribute to the anti-inflammatory effects of L-arabinose is unknown. OBJECTIVES: To investigate the involvement of macrophages in the mitigation of L-arabinose in an intestinal inflammation model induced by lipopolysaccharide (LPS). METHODS: Five-week-old male C57BL/6 mice were divided into 3 groups: a control and an LPS group that both received normal water supplementation, and an L-arabinose (ARA+LPS) group that received 5% L-arabinose supplementation. Mice in the LPS and ARA+LPS groups were intraperitoneally injected with LPS (10 mg/kg body weight), whereas the control group was intraperitoneally injected with the same volume of saline. Intestinal morphology, cytokines, tight junction proteins, macrophage phenotypes, and microbial communities were profiled at 6 h postinjection. RESULTS: L-arabinose alleviated LPS-induced damage to intestinal morphology. L-arabinose down-regulated serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6, and messenger RNA (mRNA) levels of TNF-α, IL-1ß, interferon-γ (IFN-γ), and toll-like receptor-4 in jejunum and colon compared with those of the LPS group (P < 0.05). The mRNA and protein levels of occludin and claudin-1 were significantly increased by L-arabinose (P < 0.05). Interferon regulatory factor-5 (IRF-5) and signal transducer and activator of transcription-1 (STAT-1), key genes characterized by M1 macrophages, were elevated in the jejunum and colon of LPS mice (P < 0.05) but decreased in the ARA+LPS mice (P < 0.05). In vitro, L-arabinose decreased the proportion of M1 macrophages and inhibited mRNA levels of TNF-α, IL-1ß, IL-6, IFN-γ, as well as IRF-5 and STAT-1 (P < 0.01). Moreover, L-arabinose restored the abundance of norank_f__Muribaculaceae, Faecalibaculum, Dubosiella, Prevotellaceae_UCG-001, and Paraasutterella compared with those of LPS (P < 0.05) and increased the concentration of short-chain fatty acids (P < 0.05). CONCLUSION: The anti-inflammatory effects of L-arabinose are achieved by reducing M1 macrophage polarization, suggesting that L-arabinose could be a candidate functional food or nutritional strategy for intestinal inflammation and injury.

A comparison of the impact on neuronal transcriptome and cognition of rAAV5 transduction with three different doses in the mouse hippocampus.

Introduction: Recombinant adeno-associated viruses (rAAVs) are widely used in genetic therapeutics. AAV5 has shown superior transduction efficiency, targeting neurons and glial cells in primate brains. Nonetheless, the comprehensive impact of AAV5 transduction on molecular and behavioral alterations remains unexplored. This study focuses on evaluating the effects of AAV5 transduction in the hippocampus, a critical region for memory formation and emotional processes. Methods: In this experiment, fluorescence-activated cell sorting (FACS) was utilized to isolate the mCherry-labeled pyramidal neurons in the hippocampus of CaMkIIα-cre mice following three different doses rAAV5-mCherry infusion after 3 weeks, which were then subjected to RNA sequencing (RNA-seq) to assess gene expression profiles. The cytokines concentration, mRNA expression, and glial response in hippocampi were confirmed by ELASA, digital droplet PCR and immunohistochemistry respectively. Locomotion and anxiety-like behaviors were elevated by Open Field Test and Elevated Plus Maze Test, while the Y-Maze were used to assessed spatial working memory. Recognition memory and fear responses were examined by the Novel Object Recognition Test and Fear Conditioning Test, respectively. Results: We found that 2.88 × 1010 v.g rAAV5 transduction significantly upregulated genes related to the immune response and apoptosis, and downregulated genes associated with mitochondrial function and synaptic plasticity in hippocampal pyramidal neurons, while did not induce neuronal loss and gliosis compared with 2.88 × 109 v.g and 2.88 × 108 v.g. Furthermore, the same doses impaired working memory and contextual fear memory, without effects on locomotion and anxiety-related behaviors. Discussion: Our findings highlight the detrimental impact of high-dose administration compared to median-dose or low-dose, resulting in increased neural vulnerability and impaired memory. Therefore, when considering the expression effectiveness of exogenous genes, it is crucial to also take potential side effects into account in clinical settings. However, the precise molecular mechanisms underlying these drawbacks of high-dose rAAV5-mCherry still require further investigation in future studies.

TEAD4 predicts poor prognosis and transcriptionally targets PLAGL2 in serous ovarian cancer.

The oncogenic function of TEA domain transcription factor 4 (TEAD4) has been confirmed in multiple human malignancies, while its potential role and regulatory mechanism in serous ovarian cancer progression are left unknown. By the gene expression analyses from Gene Expression Profiling Interactive Analysis (GEPIA) database, TEAD4 expression is shown to be up-regulated in serous ovarian cancer samples. Here, we confirmed the high expression of TEAD4 in clinical serous ovarian cancer specimens. In the following functional experiments, we found that TEAD4 overexpression promoted serous ovarian cancer malignant phenotypes, including proliferation, migration and invasion in serous ovarian cancer SK-OV-3 and OVCAR-3 cells, while TEAD4 knockout exerted the opposite function. The tumor growth inhibition of TEAD4 depletion was also affirmed by a Xenograft model in mice. In addition, this phenotypic deterioration induced by TEAD4 overexpression was diminished by PLAG1 like zinc finger 2 (PLAGL2) silencing. More importantly, combined with the results of the dual-luciferase assay, the transcriptional regulation of TEAD4 on PLAGL2 promoter was evidenced. Our results showed that the cancer-promoting gene TEAD4 was involved in serous ovarian cancer progression via targeting PLAGL2 at the transcriptional level.

Proinflammatory Polarization of Macrophages Causes Intestinal Inflammation in Low-Birth-Weight Piglets and Mice.

BACKGROUND: Low-birth-weight (LBW) animals suffer from intestinal damage and inflammation in their early life. OBJECTIVES: The aim of this study was to investigate the role of macrophages in intestinal inflammation in LBW piglets and mice. METHODS: Major genes involved in intestinal barrier function such as claudin-1, zonula occludens-1 (ZO-1), occludin, and mucin 2 and inflammatory cytokines such as IL-1ß, TNF-α, IL-10, and IL-13 were evaluated in 21-day-old, normal-birth-weight (NBW) and LBW piglets and mice. Macrophage markers such as CD16/32, CD163, and CD206 were also assessed by immunofluorescence and flow cytometry. Polarized and unpolarized macrophages were further transferred into NBW and LBW mice, followed by an evaluation of intestinal permeability and inflammation. RESULTS: Claudin-1 mRNA in LBW piglets as well as claudin-1, occludin, ZO-1, and mucin 2 mRNAs in LBW mice, was significantly downregulated. IL-1ß and TNF-α were significantly upregulated in LBW piglets (P < 0.05). LBW mice showed a reduced expression of IL-10 and IL-13 (P < 0.05), with a heightened IL-6 level (P < 0.01) in the jejunum. CD16, a marker for M1 macrophages, was significantly elevated in the jejunum of LBW piglets, whereas CD163, a marker for M2 macrophages, was significantly decreased (P < 0.05). Similarly, LBW mice had more CD11b+CD16/32+ M1 macrophages (P < 0.05) and fewer CD206+ M2 macrophages (P < 0.01) than NBW mice. Moreover, the transfer of M1 macrophages exacerbated intestinal inflammation in LBW mice. Furthermore, 2 major glycolysis-associated genes, hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA), were significantly upregulated in LBW piglets and mice (P < 0.05). CONCLUSIONS: This study revealed for the first time that the intestinal macrophages are polarized toward a proinflammatory phenotype in LBW piglets and mice, contributing to intestinal inflammation. The findings of this study provide new options for the management of intestinal inflammation in LBW animals.

Utilization of a primary care-based cancer survivorship clinic: patterns and patient characteristics.

PURPOSE: The Johns Hopkins Primary Care for Cancer Survivors (PCCS) Clinic was established in 2015 to improve care delivery for the growing cancer survivor population. We aim to describe areas of care addressed by PCCS and factors associated with clinic utilization. METHODS: We conducted a retrospective chart review of the first 301 patients' clinic visits. We used negative binomial regression models to identify factors associated with the rate of PCCS clinic visits overall and for cancer surveillance and treatment-related effects. RESULTS: There were 1702 clinic visits across 301 patients during the study period (77% female, median age 61). The most common areas of care addressed were chronic medical problems (80%), preventive health care (62%), cancer surveillance (59%), treatment-related effects (50%), and new/acute problems (46%). Multivariate analyses found that age > 60 years (IRR = 1.9, 95% CI = 1.2-3.0, p = 0.007) and higher number of comorbidities (IRR = 1.2, 95% CI = 1.1 - 1.2, p < 0.001) were associated with more overall PCCS visits, while female gender was associated with fewer visits (IRR = 0.6, CI = 0.4 - 0.8, p = 0.001). Gastrointestinal cancer type, shorter length of survivorship, male gender, and higher number of comorbidities were associated with a higher rate of visits addressing both surveillance and treatment-related effects (p < 0.05). CONCLUSIONS: The PCCS clinic addressed cancer and non-cancer related needs. Older patients and survivors with more comorbidities had significantly increased clinic utilization. IMPLICATIONS FOR CANCER SURVIVORS: As the cancer survivor population grows, increasing access to survivorship clinics based in primary care may help meet these patients' diverse oncologic and general health needs.

RelB represses miR-193a-5p expression to promote the phenotypic transformation of vascular smooth muscle cells in aortic aneurysm.

Aortic aneurysm (AA) is a potentially fatal disease with the possibility of rupture, causing high mortality rates with no effective drugs for the treatment of AA. The mechanism of AA, as well as its therapeutic potential to inhibit aneurysm expansion, has been minimally explored. Small non-coding RNA (miRNAs and miRs) is emerging as a new fundamental regulator of gene expression. This study aimed to explore the role and mechanism of miR-193a-5p in abdominal aortic aneurysms (AAA). In AAA vascular tissue and Angiotensin II (Ang II)-treated vascular smooth muscle cells (VSMCs), the expression of miR-193a-5 was determined using real-time quantitative PCR (RT-qPCR). Western blotting was used to detect the effects of miR-193a-5p on PCNA, CCND1, CCNE1, and CXCR4. To detect the effect of miR-193a-5p on the proliferation and migration of VSMCs, CCK-8, and EdU immunostaining, flow cytometry, wound healing, and Transwell Chamber analysis were performed. In vitro results suggest that overexpression of miR-193a-5p inhibited the proliferation and migration of VSMCs, and its inhibition aggravated their proliferation and migration. In VSMCs, miR-193a-5p mediated proliferation by regulating CCNE1 and CCND1 genes and migration by regulating CXCR4. Further, in the Ang II-induced abdominal aorta of mice, the expression of miR-193a-5p was reduced and significantly downregulated in the serum of patients with aortic aneurysm (AA). In vitro studies confirmed that Ang II-induced downregulation of miR-193a-5p in VSMCs by upregulation of the expression of the transcriptional repressor RelB in the promoter region. This study may provide new intervention targets for the prevention and treatment of AA.

Myeloperoxidase in the pericardial fluid improves the performance of prediction rules for postoperative atrial fibrillation.

OBJECTIVES: After surgery, inflammation is a prominent factor influencing postoperative atrial fibrillation. Myeloperoxidase is a major contributor to inflammatory responses after surgical tissue damage. We evaluated whether myeloperoxidase is associated with postoperative atrial fibrillation clinically and in an animal model. METHODS: This prospective cohort study included patients undergoing isolated coronary artery bypass grafting. Myeloperoxidase concentrations in blood and pericardial fluid were determined at baseline and 6, 12, and 18 hours after coronary artery bypass grafting. Myeloperoxidase activity in blood, pericardial fluid, and atrium were also evaluated in a canine coronary artery bypass grafting model. Electrophysiologic, histologic, and immunohistochemistry analyses were performed to explore underlying mechanisms. RESULTS: Postoperative atrial fibrillation occurred in 45 of 137 patients (32.8%). Patients with postoperative atrial fibrillation had significantly higher serum and pericardial myeloperoxidase levels. Individual clinical and surgical factors had moderate predictive value (area under the curve, 0.760) for postoperative atrial fibrillation. Discrimination improved remarkably when myeloperoxidase was combined with other parameters (area under the curve, 0.901). Pericardial myeloperoxidase at 6 hours postoperatively was the strongest independent predictor of postoperative atrial fibrillation (odds ratio, 19.215). The rate of postoperative atrial fibrillation increased exponentially across pericardial myeloperoxidase grades. Compared with controls, coronary artery bypass grafting-treated dogs showed higher atrial fibrillation vulnerability and maintenance, shorter atrial effective refractory period, attenuated connexin 43 expression, and increased myocardial and pericardial myeloperoxidase activity. Connexin 43 expression and atrial effective refractory period were strongly negatively correlated with myocardial and pericardial myeloperoxidase activity. CONCLUSIONS: Myeloperoxidase is linked to postoperative atrial fibrillation, and the ability to predict postoperative atrial fibrillation was remarkably improved by adding pericardial myeloperoxidase. Myeloperoxidase-related atrial structural and electrical remodeling is a physiologic substrate for this arrhythmia.

Clinical study of hepatitis B vaccine in achieving hepatitis B surface antibody seroconversion in patients with functional cure

Abstract Hepatitis B Surface Antigen (HBsAg) seroclearance is the highest treatment goal recommended by the current guidelines for hepatitis B. Levels of antibodies to HBsAg (anti-HBs) are strongly associated with HBsAg recurrence, but hepatitis B vaccination may increase the anti-HBs seroconversion rate and reduce recurrence. We conducted a retrospective clinical study to ascertain the effect of this vaccination on the seroconversion rate and levels of protective anti-HBs after HBsAg. In this retrospective study, we distributed a questionnaire through an online survey platform to collect information related to hepatitis B vaccination in patients with functional cure of hepatitis B with Interferon-α (IFNα) therapy. We enrolled 320 patients who achieved functional cure from IFNα therapy. Of these, 219 patients had received hepatitis B vaccination according to their personal preference and drug accessibility after HBsAg seroclearance, whereas the remaining 101 patients did not receive hepatitis B vaccination. The anti-HBs seroconversion rate of 78.1% in the vaccinated group was significantly greater than that in the unvaccinated group (41.6%) (p < 0.001). Stratified comparisons with anti-HBs of ≥ 100 IU/L and ≥ 300 IU/L showed that both proportions in the vaccinated group were greater than those in the unvaccinated group (71.2% vs. 32.7% and 56.2% vs. 17.8%, respectively, all p-values < 0.001). Logistic regression analysis showed that the odds ratio of vaccination was 4.427, which was the strongest influencing factor for anti-HBs, reaching 100 IU/L or higher. Hepatitis B vaccination in patients after HBsAg seroclearance not only increased the anti-HBs seroconversion rate but also significantly increased antibody levels, with good safety, indicating the clinical value of vaccine therapy for patients with functional cure.

Risk of Severe Illness and Risk Factors of Outcomes of COVID-19 in Hospitalized Patients with Chronic Liver Disease in a Major U. S. Hospital Network.

Methods: We studied 2731 patients with known CLD who were hospitalized at the Johns Hopkins Health System with COVID-19 between March 1, 2020, and December 15, 2021. The primary outcome was all-cause mortality, and secondary outcomes were MV and vasopressors. Multivariable Cox regression models were performed to explore factors associated with the outcomes. Results: Overall, 80.1% had severe COVID-19, all-cause mortality was 8.9%, 12.8% required MV, and 11.2% received vasopressor support. Older patients with underlying comorbidities were more likely to have severe COVID-19. There was association between elevated aminotransferases and total bilirubin with more severe COVID-19. Hepatic decompensation was independently associated with all-cause mortality (HR 2.94; 95% CI 1.23-7.06). Alcohol-related liver disease (ALD, HR 2.79, 95% CI, 1.00-8.02) was independently associated with increased risk for MV, and independent factors related to vasopressor support were chronic pulmonary disease and underlying malignancy. Conclusions: COVID-19 infection in patients with CLD is associated with poor outcomes. SARS-CoV-2 infection in patients with hepatic decompensation was associated with an increased risk of in-hospital mortality hazard, and ALD among patients with COVID-19 was associated with an increased hazard for MV.

Bifidobacterium animalis Promotes the Growth of Weaning Piglets by Improving Intestinal Development, Enhancing Antioxidant Capacity, and Modulating Gut Microbiota.

Probiotics are widely used to promote performance and improve gut health in weaning piglets. Therefore, the objective of this study was to investigate the effects of dietary supplementation with Bifidobacterium animalis subsp. lactis (B. animalis) JYBR-190 on the growth performance, intestine health, and gut microbiota of weaning piglets. The results showed that the dietary addition of B. animalis significantly improved growth performance and decreased diarrhea incidence. B. animalis increased villus height in the duodenum and elevated goblet cell numbers and amylase activity in the jejunum. Additionally, B. animalis supplementation markedly increased total antioxidant capacity in jejunal mucosa but declined the malondialdehyde content. B. animalis treatment did not affect the mRNA expressions associated with the intestinal barrier and inflammatory cytokine in various intestinal segments. Microbiota analysis indicated that a diet supplemented with B. animalis significantly increased the relative abundances of health-promoting bacteria in the lumen, such as Streptococcus, Erysipelotrichaceae, Coprococcus, and Oscillibacter. There was a trend for B. animalis fed piglets to have a higher relative abundance of B. animalis in ileal digesta. Moreover, B. animalis-treated pigs decreased the abundance of Helicobacter and Escherichia-Shigella in ileal mucosa-associated microbiota. In summary, this study showed that B. animalis supplementation stimulated growth performance, improved gut development, enriched beneficial bacteria abundances, and declined intestinal pathogens populations, while B. animalis had limited effects on the intestinal barrier and immune function. IMPORTANCE In the modern swine industry, weaning is a critical period in the pig's life cycle. Sudden dietary, social, and environmental changes can easily lead to gut microbiota dysbiosis, diarrhea, and a decrease in growth performance. To stabilize intestinal microbiota and promote animal growth, antibiotics were widely applied in swine diets during the past few decades. However, the side effects of antibiotics posed a great threat to public health and food safety. Therefore, it is urgent to find and develop antibiotic alternatives. The growing evidence suggested that probiotics can be preferable alternatives to antibiotics because they can modulate microbiota composition and resist pathogens colonization. In this study, our results indicated that dietary supplementation with Bifidobacterium animalis promoted growth in weaning piglets by improving gut development, increasing beneficial bacteria abundances, and declining pathogens populations.

Circulating exosome-derived miR-122-5p is a novel biomarker for prediction of postoperative atrial fibrillation.

Postoperative atrial fibrillation (POAF) is a frequent complication associated with increased periprocedural mortality and morbidity after cardiac surgery. Our study aimed to identify the difference in exosomal miRNA and further explore its role in the diagnosis of POAF. First, the differentially expressed miRNAs (DEMs) were obtained by high-throughput RNA sequencing. Second, the DEMs target genes were put into gene ontology (GO) and KEGG pathway analysis. Third, real-time quantification PCR (RT-qPCR) was used to verify the DEMs. Finally, we revealed 23 DEMs in POAF patients. Furthermore, analysis of gene function revealed that DEMs may affect atrial structure through many signaling pathways. We also found that miR-122-5p was up-regulated in POAF patients, but there are no significant changes in miR-191-5p, miR-181a-5p, miR-155-5p and miR-151a-5p. Our study revealed that exosomal miRNAs exert enormous potential in evaluating the severity or prognostic of POAF.

Controversy on Positive Peritoneal Cytology of Endometrial Carcinoma.

Endometrial carcinoma (EC) is one of the most common gynecological malignancies. Its incidence rate has been increasing year by year. The prognostic factors and treatment strategies of EC have aroused wide concern. The effects of peritoneal cytology on the prognosis and treatment of EC remain controversial. Some factors, such as differentiation degree, muscle invasion, and tumor size, are related to positive peritoneal cytology. Hysteroscopy is commonly used in the diagnosis and treatment of endometrial cancer, but hysteroscopic surgery may cause the tumor to spread into the abdominal cavity, resulting in positive peritoneal cytology. In this review, we discuss the factors related to positive peritoneal cytology and the influence of positive peritoneal cytology on the prognosis of endometrial cancer. Suspicious positive peritoneal cytology may be an independent risk factor for endometrial cancer. The positive rate of peritoneal tumor cells in type II endometrial cancer is higher than other cells and is an independent risk factor for type II endometrial cancer. We also discuss the effects of peritoneal cytology on treatment decisions. Aggressive treatments seem to be more beneficial for patients with positive ascites cytology, but there is a lack of large-scale prospective clinical studies on their effectiveness and safety. The application of peritoneal cytology for endometrial cancer has been decreased in recent years. We believe that peritoneal cytology is necessary for this type of cancer. However, more studies on peritoneal cytology in endometrial cancer should be carried out.

Nocardia rubra cell-wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells.

BACKGROUND: As an immune enhancer, Nocardia rubra cell-wall skeleton (Nr-CWS) has been used to treat persistent human papillomavirus infection and cervical precancerous lesions. However, it is still unclear whether it can be used to treat cervical carcinoma. METHODS: In our study, the aim was to determine whether Nr-CWS affects the apoptosis of cervical carcinoma cells by enhancing the antitumor effect of dendritic cells and macrophages in vivo and in vitro. RESULTS: The experimental results showed that Nr-CWS can promote the activity of dendritic cells and macrophages and reduce their apoptosis. It also increased the cytokines IL-6, IL-12, TNF-ɑ, and IL-1ß secreted by dendritic cells and macrophages and reduced their PD-L1 expression. In vitro, Nr-CWS inhibited the proliferation, colony forming ability of HeLa and SiHa cervical carcinoma cell lines cultured with macrophages, and more cells were blocked in G2/M phase. Nr-CWS promoted TNF-ɑ/TNFR1/caspase-8-mediated apoptosis by increasing macrophages secretion of TNF-ɑ and inhibited cell migration and invasion regulated by the WNT/ß-catenin-EMT pathway. Nr-CWS also reduced the expression of the cervical carcinoma genes E6 and E7 thereby increasing expression of p53 gene and decreasing expression of PD-L1 gene. In vivo, Nr-CWS inhibited tumor growth and decreased the expression of E6, E7, PD-L1, P16, Ki67, and PCNA in tumors. CONCLUSIONS: Therefore, our results suggest that Nr-CWS can promote apoptosis of cervical carcinoma cells by enhancing the antitumor effect of dendritic cells and macrophages.