Improving the Purity of Extracellular Vesicles by Removal of Lipoproteins from Size Exclusion Chromatography- and Ultracentrifugation-Processed Samples Using Glycosaminoglycan-Functionalized Magnetic Beads.

Extracellular vesicles (EVs) are present in blood at much lower concentrations (5-6 orders of magnitude) compared to lipoprotein particles (LP). Because LP and EV overlap in size and density, isolating high-purity EVs is a significant challenge. While the current two-step sequential EV isolation process using size-expression chromatography (SEC) followed by a density gradient (DG) achieves high purity, the time-consuming ultracentrifugation (UC) step in DG hinders workflow efficiency. This paper introduces an optimized magnetic bead reagent, LipoMin, functionalized with glycosaminoglycans (GAGs), as a rapid alternative for LP removal during the second-step process in about 10 minutes. We evaluated LipoMin's efficacy on two sample types: (a) EV fractions isolated by size exclusion chromatography (SEC + LipoMin) and (b) the pellet obtained from ultracentrifugation (UC + LipoMin). The workflow is remarkably simple, involving a 10 min incubation with LipoMin followed by magnetic separation of the LP-depleted EV-containing supernatant. Results from enzyme-linked immunosorbent assay (ELISA) revealed that LipoMin removes 98.2% ApoB from SEC EV fractions, comparable to the LP removal ability of DG in the SEC + DG two-step process. Importantly, the EV yield (CD81 ELISA) remained at 93.0% and Western blot analysis confirmed that key EV markers, flotillin and CD81, were not compromised. Recombinant EV (rEV), an EV reference standard, was spiked into SEC EV fractions and recovered 89% of CD81 protein. For UC + LipoMin, ApoA1 decreased by 76.5% while retaining 90.7% of CD81. Notably, both colorectal cancer (CRC) and Alzheimer's disease (AD) samples processed by SEC + LipoMin and UC + LipoMin displayed clear expression of relevant EV and clinical markers. With a 10 min workflow (resulting in a 96% time saving compared to the traditional method), the LipoMin reagent offers a rapid and efficient alternative to DG for LP depletion, paving the way for a streamlined SEC + LipoMin two-step EV isolation process.

Advances in macrophage metabolic reprogramming in myocardial ischemia-reperfusion.

Acute myocardial infarction (AMI) is the leading cause of death worldwide, and reperfusion therapy is a critical therapeutic approach to reduce myocardial ischemic injury and minimize infarct size. However, ischemia/reperfusion (I/R) itself also causes myocardial injury, and inflammation is an essential mechanism by which it leads to myocardial injury, with macrophages as crucial immune cells in this process. Macrophages are innate immune cells that maintain tissue homeostasis, host defence during pathogen infection, and repair during tissue injury. During the acute phase of I/R, M1-type macrophages generate a pro-inflammatory milieu, clear necrotic myocardial tissue, and further recruit mononuclear (CCR2+) macrophages. Over time, the reparative (M2 type) macrophages gradually became dominant. In recent years, metabolic studies have shown a clear correlation between the metabolic profile of macrophages and their phenotype and function. M1-type macrophages are mainly characterized by glycolytic energy supply, and their tricarboxylic acid (TCA) cycle and mitochondrial oxidative phosphorylation (OXPHOS) processes are impaired. In contrast, M2 macrophages rely primarily on OXPHOS for energy. Changing the metabolic profile of macrophages can alter the macrophage phenotype. Altered energy pathways are also present in macrophages during I/R, and intervention in this process contributes to earlier and greater M2 macrophage infiltration, which may be a potential target for the treatment of myocardial I/R injury. Therefore, this paper mainly reviews the characteristics of macrophage energy metabolism alteration and phenotypic transition during I/R and its mechanism of mediating myocardial injury to provide a basis for further research in this field.

Arabidopsis thaliana MYC2 and MYC3 Are Involved in Ethylene-Regulated Hypocotyl Growth as Negative Regulators.

The ethylene-regulated hypocotyl elongation of Arabidopsis thaliana involves many transcription factors. The specific role of MYC transcription factors in ethylene signal transduction is not completely understood. The results here revealed that two MYCs, MYC2 and MYC3, act as negative regulators in ethylene-suppressed hypocotyl elongation. Etiolated seedlings of the loss-of-function mutant of MYC2 or MYC3 were significantly longer than wild-type seedlings. Single- or double-null mutants of MYC2 and MYC3 displayed remarkably enhanced response to ACC(1-aminocyclopropane-1-carboxylate), the ethylene precursor, compared to wild-type seedlings. MYC2 and MYC3 directly bind to the promoter zone of ERF1, strongly suppressing its expression. Additionally, EIN3, a key component in ethylene signaling, interacts with MYC2 or MYC3 and significantly suppresses their binding to ERF1's promoter. MYC2 and MYC3 play crucial roles in the ethylene-regulated expression of functional genes. The results revealed the novel role and functional mechanism of these transcription factors in ethylene signal transduction. The findings provide valuable information for deepening our understanding of their role in regulating plant growth and responding to stress.

Benefits of NGS in Advanced Lung Adenocarcinoma Vary by Populations and Timing of Examination.

Despite the widespread application of next-generation sequencing (NGS) in advanced lung adenocarcinoma, its impact on survival and the optimal timing for the examination remain uncertain. This cohort study included advanced lung adenocarcinoma patients who underwent NGS testing. We categorized patients into four groups: Group 1: treatment-naïve, upfront NGS; Group 2: Treatment-naïve, exclusionary EGFR/ALK/ROS1; Group 3: post-treatment, no known EGFR/ALK/ROS1; Group 4: known driver mutation and post-TKI treatment. A total of 424 patients were included. There were 128, 126, 90, and 80 patients in Groups 1, 2, 3, and 4, respectively. In Groups 1, 2, 3, and 4, targetable mutations were identified in 76.6%, 49.2%, 41.1%, and 33.3% of the patients, respectively (p < 0.001). Mutation-targeted treatments were applied in 68.0%, 15.1%, 27.8%, and 22.5% of the patients, respectively (p < 0.001). In the overall population, patients receiving mutation-targeted treatments exhibited significantly longer overall survival (OS) (aHR 0.54 [95% CI 0.37-0.79], p = 0.001). The most profound benefit was seen in the Group 1 patients (not reached vs. 40.4 months, p = 0.028). The median OS of patients with mutation-targeted treatments was also significantly longer among Group 2 patients. The median post-NGS survival of patients receiving mutation-targeted treatments was numerically longer in Group 3 and Group 4 patients. In conclusion, mutation-targeted therapy is associated with a favorable outcome. However, the opportunities of NGS-directed treatment and the survival benefits of mutation-targeted treatment were various among different populations.

Hepatic decompensation is the major driver of mortality in patients with HCC treated with atezolizumab plus bevacizumab: The impact of successful antiviral treatment.

BACKGROUND AND AIMS: Unlike other malignancies, hepatic functional reserve competes with tumor progression in determining the risk of mortality from hepatocellular carcinoma (HCC). However, the relative contribution of hepatic decompensation over tumor progression in influencing overall survival (OS) has not been assessed in combination immunotherapy recipients. APPROACH AND RESULTS: From the AB-real observational study (n = 898), we accrued 571 patients with advanced/unresectable hepatocellular carcinoma, Child-Pugh A class treated with frontline atezolizumab + bevacizumab (AB). Hepatic decompensation and tumor progression during follow-up were studied in relationship to patients' OS using a time-dependent Cox model. Baseline characteristics were evaluated as predictors of decompensation in competing risks analysis. During a median follow-up of 11.0 months (95% CI: 5.1-19.7), 293 patients (51.3%) developed tumor progression without decompensation, and 94 (16.5%) developed decompensation. In multivariable time-dependent analysis, decompensation (HR: 19.04, 95% CI: 9.75-37.19), hepatocellular carcinoma progression (HR: 9.91, 95% CI: 5.85-16.78), albumin-bilirubin (ALBI) grade 2/3 (HR: 2.16, 95% CI: 1.69-2.77), and number of nodules >3(HR: 1.63, 95% CI: 1.28-2.08) were independently associated with OS. Pretreatment ALBI grade 2/3 (subdistribution hazard ratio [sHR]: 3.35, 95% CI: 1.98-5.67) was independently associated with decompensation, whereas viral etiology was protective (sHR: 0.55, 95% CI: 0.34-0.87). Among patients with viral etiology, effective antiviral treatment was significantly associated with a lower risk of decompensation (sHR: 0.48, 95% CI: 0.25-0.93). CONCLUSIONS: Hepatic decompensation identifies patients with the worst prognosis following AB and is more common in patients with baseline ALBI >1 and nonviral etiology. Effective antiviral treatment may protect from decompensation, highlighting the prognostic disadvantage of patients with nonviral etiologies and the importance of multidisciplinary management to maximize OS.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

Immunotherapy vs Best Supportive Care for Patients With Hepatocellular Cancer With Child-Pugh B Dysfunction.

Importance: Whether patients with Child-Pugh class B (CP-B) cancer with unresectable hepatocellular carcinoma (uHCC) benefit from active anticancer treatment vs best supportive care (BSC) is debated. Objective: To evaluate the association of immune checkpoint inhibitor (ICI)-based therapies vs BSC with overall survival (OS) of patients with uHCC and CP-B liver dysfunction. Design, Setting, and Participants: This retrospective, multicenter, international clinical case series examined data of patients with CP-B with uHCC who were receiving first-line ICI-based regimens from September 2017 to December 2022 whose data were extracted from an international consortium and compared with a cohort of patients with CP-B receiving BSC. Patients were treated in tertiary care centers across Europe, US, and Asia in routine clinical practice. After applying the inclusion criteria, 187 and 156 patients were left in the ICI and BSC groups, respectively. The propensity score was calculated for the following variables: age, alpha-fetoprotein levels, Child-Pugh score, extrahepatic spread, portal vein tumor thrombosis, cirrhosis, ascites, and baseline Eastern Cooperative Oncology Group performance status. Exposures: Patients in the ICI group received first-line systemic therapy with either atezolizumab plus bevacizumab (A+B) (n = 141) or nivolumab (n = 46). Main Outcomes and Measures: OS in the inverse probability of treatment weighting (IPTW) populations was the main outcome, and it was estimated with Kaplan-Meier method; univariable Cox regression test was used to make comparisons between the 2 groups. Results: The median age was 66 (IQR, 61-72) and 73 (IQR, 66-81) years in the ICI (33 women [18%]) and BSC groups (41 women [26%]), respectively. In the IPTW populations, median OS was significantly longer in the ICI group (7.50 months; 95% CI, 5.62-11.15) compared with BSC (4.04 months; 95% CI, 3.03-5.03; hazard ratio, 0.59; 95% CI, 0.43-0.80; P < .001). Multivariable analysis confirmed that ICI exposure was associated with a reduction of approximately 50% in the risk of death (hazard ratio, 0.55; 95% CI, 0.35-0.86; P < .001), and the presence of portal vein tumor thrombosis, an Eastern Cooperative Oncology Group performance score of greater than 1, and alpha-fetoprotein levels of 400 ng/mL or greater were associated with increased risk of death. Conclusions and Relevance: The results of this case series provide comparative evidence of improved survival in association with ICI treatment compared with BSC in patients with uHCC with CP-B liver dysfunction.

Analysis of the Spatholobus suberectus full-length transcriptome identified an R2R3-MYB transcription factor-encoding gene SsMYB158 that regulates flavonoid biosynthesis.

Spatholobus suberectus Dunn (Leguminosae) has been used for medicinal purposes for a long period. Flavonoids are the major bioactive components of S. suberectus. However, there is still limited knowledge of the exact method via which transcription factors (TFs) regulate flavonoid biosynthesis. The full-length transcriptome of S. suberectus was analyzed using SMRT sequencing; 61,548 transcripts were identified, including 12,311 new gene loci, 53,336 novel transcripts, 44,636 simple sequence repeats, 36,414 complete coding sequences, 871 long non-coding RNAs and 6781 TFs. The SsMYB158 TF, which is associated with flavonoid biosynthesis, belongs to the R2R3-MYB class and is localized subcellularly to the nucleus. The overexpression of SsMYB158 in Nicotiana benthamiana and the transient overexpression of SsMYB158 in S. suberectus resulted in a substantial enhancement in both flavonoids and catechin levels. In addition, there was a remarkable upregulation in the expression of essential enzyme-coding genes associated with the flavonoid biosynthesis pathways. Our study revealed SsMYB158 as a critical regulator of flavonoid biosynthesis in S. suberectus and laying the foundation for its molecular breeding.

Antibiotic prophylaxis for surgical wound infections in clean and clean-contaminated surgery: an updated systematic review and meta-analysis.

BACKGROUND: The efficacy and necessity of prophylactic antibiotics in clean and clean-contaminated surgery remains controversial. METHODS: The studies were screened and extracted using databases including PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials.gov according to predefined eligibility criteria. Randomized controlled trials (RCTs) comparing the effect of preoperative and postoperative prophylactic antibiotic use on the incidence of surgical site infections (SSIs) in patients undergoing any clean or clean-contaminated surgery. RESULTS: A total of 16 189 participants in 48 RCTs were included in the primary meta-analysis following the eligibility criteria. The pooled odds ratio (OR) for SSI with antibiotic prophylaxis versus placebo was 0.60 (95% CI: 0.53-0.68). The pooled OR among gastrointestinal, oncology, orthopedics, neurosurgery, oral, and urology surgery was 3.06 (95% CI: 1.05-8.91), 1.16 (95% CI: 0.89-1.50), 2.04 (95% CI: 1.09-3.81), 3.05 (95% CI: 1.25-7.47), 3.55 (95% CI: 1.78-7.06), and 2.26 (95% CI: 1.12-4.55), respectively. Furthermore, the summary mean difference (MD) for patients' length of hospitalization was -0.91 (95% CI: -1.61, -0.16). The results of sensitivity analyses for all combined effect sizes showed good stability. CONCLUSION: Antibiotics are both effective, safe, and necessary in preventing surgical wound infections in clean and clean-contaminated procedures, attributed to their reduction in the incidence of surgical site infections as well as the length of patient hospitalization.

Embolization treatment of right pulmonary artery agenisis with patent ductus arteriosus causing pulmonary hypertension and hemoptysis: a case report and literature review.

As the pediatric patient with right pulmonary artery agenesis (PAA) matured, she progressively presented symptoms of pulmonary hypertension and hemoptysis. There is limited clinical literature on this condition, and currently, there is no consensus regarding its diagnosis and treatment. This article presents a case study of a 16-year-old female patient with right pulmonary artery hypoplasia, providing a comprehensive summary and analysis of her developmental progression, pathology, diagnosis, and treatment.

Wheat peptide alleviates DSS-induced colitis by activating the Keap1-Nrf2 signaling pathway and maintaining the integrity of the gut barrier.

Inflammatory bowel disease (IBD) is difficult to cure, and formulating a dietary plan is an effective means to prevent and treat this disease. Wheat peptide contains a variety of bioactive peptides with anti-inflammatory and antioxidant functions. The results of this study showed that preventive supplementation with wheat peptide (WP) can significantly alleviate the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice. WP can increase body weight, alleviate colon shortening, and reduce disease activity index (DAI) scores. In addition, WP improved intestinal microbial disorders in mice with colitis. Based on LC-MS, a total of 313 peptides were identified in WP, 4 of which were predicted to be bioactive peptides. The regulatory effects of WP and four bioactive peptides on the Keap1-Nrf2 signaling pathway were verified in Caco-2 cells. In conclusion, this study demonstrated that WP alleviates DSS-induced colitis by helping maintain gut barrier integrity and targeting the Keap1-Nrf2 axis; these results provided a rationale for adding WP to dietary strategies to prevent IBD.

GnRH-driven FTO-mediated RNA m6A modification promotes gonadotropin synthesis and secretion.

BACKGROUND: Gonadotropin precisely controls mammalian reproductive activities. Systematic analysis of the mechanisms by which epigenetic modifications regulate the synthesis and secretion of gonadotropin can be useful for more precise regulation of the animal reproductive process. Previous studies have identified many differential m6A modifications in the GnRH-treated adenohypophysis. However, the molecular mechanism by which m6A modification regulates gonadotropin synthesis and secretion remains unclear. RESULTS: Herein, it was found that GnRH can promote gonadotropin synthesis and secretion by promoting the expression of FTO. Highly expressed FTO binds to Foxp2 mRNA in the nucleus, exerting a demethylation function and reducing m6A modification. After Foxp2 mRNA exits the nucleus, the lack of m6A modification prevents YTHDF3 from binding to it, resulting in increased stability and upregulation of Foxp2 mRNA expression, which activates the cAMP/PKA signaling pathway to promote gonadotropin synthesis and secretion. CONCLUSIONS: Overall, the study reveals the molecular mechanism of GnRH regulating the gonadotropin synthesis and secretion through FTO-mediated m6A modification. The results of this study allow systematic interpretation of the regulatory mechanism of gonadotropin synthesis and secretion in the pituitary at the epigenetic level and provide a theoretical basis for the application of reproductive hormones in the regulation of animal artificial reproduction.

Correlating Reiff scores with clinical, functional, and prognostic factors: characterizing noncystic fibrosis bronchiectasis severity: validation from a nationwide multicenter study in Taiwan.

BACKGROUND: Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB). METHODS: This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores. RESULTS: Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p < 0.001), heightened clinical symptoms (p < 0.001), elevated pathogen colonization (pseudomonas aeruginosa) (p < 0.001), and an increased annual hospitalization rate (p < 0.001). In the following multivariate analysis, elderly age, pseudomonas aeruginosa pneumonia, and hospitalizations per year emerged as the only independent predictors of mortality. CONCLUSION: Based on our large cohort study, the simplified CT scoring system (Reiff score) can serve as a useful adjunct to clinical factors in predicting disease severity and prognosis among Taiwanese patients with NCFB.

Echinacea purpurea Polysaccharide Ameliorates Dextran Sulfate Sodium-Induced Colitis by Restoring the Intestinal Microbiota and Inhibiting the TLR4-NF-κB Axis.

Ulcerative colitis (UC) is a chronic intestinal ailment which cannot be completely cured. The occurrence of UC has been on the rise in recent years, which is highly detrimental to patients. The effectiveness of conventional drug treatment is limited. The long-term usage of these agents can lead to substantial adverse effects. Therefore, the development of a safe and efficient dietary supplement is important for the prevention of UC. Echinacea purpurea polysaccharide (EPP) is one of the main bioactive substances in Echinacea purpurea. EPP has many favorable effects, such as antioxidative, anti-inflammatory, and antitumor effects. However, whether EPP can prevent or alleviate UC is still unclear. This study aims to analyze the effect and mechanism of EPP on UC in mice using a 3% dextran sulfate sodium (DSS)-induced UC model. The results showed that dietary supplementation with 200 mg/kg EPP significantly alleviated the shortening of colon length, weight loss, and histopathological damage in DSS-induced colitis mice. Mechanistically, EPP significantly inhibits the activation of the TLR4/NF-κB pathway and preserves the intestinal mechanical barrier integrity by enhancing the expression of claudin-1, ZO-1, and occludin and reducing the loss of goblet cells. Additionally, 16S rRNA sequencing revealed that EPP intervention reduced the abundance of Bacteroides, Escherichia-Shigella, and Klebsiella; the abundance of Lactobacillus increased. The results of nontargeted metabonomics showed that EPP reshaped metabolism. In this study, we clarified the effect of EPP on UC, revealed the potential function of EPP, and supported the use of polysaccharide dietary supplements for UC prevention.

Effect of metabolic dysfunction on the risk of liver-related events in patients cured of hepatitis C virus.

The impact of metabolic dysfunction or metabolic dysfunction-associated fatty liver disease (MAFLD) on liver-related events (LREs) in patients with chronic hepatitis C (CHC) who had achieved a sustained virologic response (SVR) to direct-acting antiviral agents (DAAs) is unknown. A total of 924 patients with cured CHC and documented body mass index (BMI) were included in the analysis, and the data period was from September 2012 to April 2022. Hepatic steatosis was identified either through ultrasonography or blood biomarkers. Metabolic dysfunction was defined as the presence of overweight or obesity (BMI ≥ 23 kg/m2), type 2 diabetes mellitus (DM), and metabolic dysregulation. Patients may have more than one metabolic dysfunction. Variables at 12 or 24 weeks after DAA therapy (PW12) were used to identify predictors of LREs. The median age of the 924 patients was 58 (49-65) years. Of the participants, 418 (45.2%) were male. The median BMI was 24.01 (21.78-26.73) kg/m2, and 174 (18.8%) patients had DM. A multivariable Cox regression analysis revealed that age, male, albumin, total bilirubin, alpha-fetoprotein (AFP), metabolic dysfunction (hazard ratio: 1.709, 95% confidence interval: 1.128-2.591, P = .011), and FIB-4 > 3.25 were independent predictors of LREs. Type 2 DM and metabolic dysregulation exhibited a larger time-dependent area under the receiver operating characteristic curve for LREs than did overweight or obesity. Moreover, metabolic dysfunction was identified to be an independent predictor of hepatocellular carcinoma. Metabolic dysfunction increased the risk of LREs and HCC in patients with CHC who had achieved an SVR to DAA therapy.

Huaier Polysaccharide Alleviates Dextran Sulphate Sodium Salt-Induced Colitis by Inhibiting Inflammation and Oxidative Stress, Maintaining the Intestinal Barrier, and Modulating Gut Microbiota.

The incidence of ulcerative colitis (UC) is increasing annually, and UC has a serious impact on patients' lives. Polysaccharides have gained attention as potential drug candidates for treating ulcerative colitis (UC) in recent years. Huaier (Trametes robiniophila Murr) is a fungus that has been used clinically for more than 1000 years, and its bioactive polysaccharide components have been reported to possess immunomodulatory effects, antitumour potential, and renoprotective effects. In this study, we aimed to examine the protective effects and mechanisms of Huaier polysaccharide (HP) against UC. Based on the H2O2-induced oxidative stress model in HT-29 cells and the dextran sulphate sodium salt (DSS)-induced UC model, we demonstrated that Huaier polysaccharides significantly alleviated DSS-induced colitis (weight loss, elevated disease activity index (DAI) scores, and colonic shortening). In addition, HP inhibited oxidative stress and inflammation and alleviated DSS-induced intestinal barrier damage. It also significantly promoted the expression of the mucin Muc2. Furthermore, HP reduced the abundance of harmful bacteria Escherichia-Shigella and promoted the abundance of beneficial bacteria Muribaculaceae_unclassified, Anaerotruncus, and Ruminococcaceae_unclassified to regulate the intestinal flora disturbance caused by DSS. Nontargeted metabolomics revealed that HP intervention would modulate metabolism by promoting levels of 3-hydroxybutyric acid, phosphatidylcholine (PC), and phosphatidylethanolamine (PE). These results demonstrated that HP had the ability to mitigate DSS-induced UC by suppressing oxidative stress and inflammation, maintaining the intestinal barrier, and modulating the intestinal flora. These findings will expand our knowledge of how HP functions and offer a theoretical foundation for using HP as a potential prebiotic to prevent UC.

Transarterial chemoembolization plus stent placement for hepatocellular carcinoma with main portal vein tumor thrombosis: A meta-analysis.

BACKGROUND: Portal vein tumor thrombus is an important indicator of poor prognosis in patients with hepatocellular carcinoma. Transarterial chemoembolization is recommended as the standard first-line therapy for unresectable hepatocellular carcinoma. Portal vein stent placement is a safe and effective therapy for promptly restoring flow and relieving portal hypertension caused by tumor thrombus. AIM: To assess the clinical significance of transarterial chemoembolization plus stent placement for the treatment of hepatocellular carcinoma with main portal vein tumor thrombosis. METHODS: We searched English and Chinese databases, assessed the quality of the included studies, analyzed the characteristic data, tested heterogeneity, explored heterogeneity, and tested publication bias. RESULTS: In total, eight clinical controlled trials were included. The results showed that the pressure in the main portal vein after stent placement was significantly lower than that with no stent placement. The cumulative stent patency and survival rates at 6 and 12 months were lower in the transarterial chemoembolization + stent placement group than in the transarterial chemoembolization + stent placement + brachytherapy/radiotherapy group. The survival rates of patients treated with transarterial chemoembolization + stent placement for 6 and 12 months were higher than those of patients treated with transarterial chemoembolization alone. CONCLUSION: For Chinese patients with hepatocellular carcinoma with main portal vein tumor thrombosis, transarterial chemoembolization plus stenting is effective. Transarterial chemoembolization + stent placement is more effective than transarterial chemoembolization alone. Transarterial chemoembolization + stent placement + brachytherapy/radiotherapy is more effective than transarterial chemoembolization + stenting.

Safety and efficacy of transcatheter arterial embolization in autosomal dominant polycystic kidney patients with gross hematuria: Six case reports.

BACKGROUND: To retrospectively report the safety and efficacy of renal transcatheter arterial embolization for treating autosomal dominant polycystic kidney disease (ADPKD) patients with gross hematuria. CASE SUMMARY: The purpose of this study is to retrospectively report the safety and efficacy of renal transcatheter arterial embolization for treating ADPKD patients with gross hematuria. Materials and methods: During the period from January 2018 to December 2019, renal transcatheter arterial embolization was carried out on 6 patients with polycystic kidneys and gross hematuria. Renal arteriography was performed first, and then we determined the location of the hemorrhage and performed embolization under digital subtraction angiography monitoring. Improvements in routine blood test results, routine urine test results, urine color and postoperative reactions were observed and analyzed. Results: Renal transcatheter arterial embolization was successfully conducted in 6 patients. The indices of 5 patients and the color of gross hematuria improved after surgery compared with before surgery. No severe complication reactions occurred. CONCLUSION: For autosomal dominant polycystic kidney syndrome patients with gross hematuria, transcatheter arterial embolization was safe and effective.

Liver stiffness and spleen stiffness predict distinct liver-related events after hepatitis C eradication with direct-acting antivirals.

BACKGROUND: /Purpose: This study aimed to directly compare the utility of liver stiffness (LS) and spleen stiffness (SS) at sustained virologic response (SVR) for predicting hepatocellular carcinoma (HCC) and non-HCC events in patients with chronic hepatitis C (CHC) after direct-acting antiviral therapy. METHODS: This retrospective study included 695 CHC patients who achieved SVR and underwent LS and SS measurements. LS and SS were measured using point shear wave elastography and compared head-to-head. RESULTS: During a median follow-up of 29.5 months, 49 (7.1%) patients developed liver-related events (LREs), including 28 HCC and 22 non-HCC events after SVR. Multivariable Cox regression analysis revealed that age, albumin level, and LS (≥ versus <1.46 m/s) at SVR (adjusted hazard ratio [aHR]: 5.390; 95% confidence interval [CI]: 2.349-12.364; p < 0.001), but not SS at SVR, significantly predicted the overall risk of post-SVR LREs (n = 49). Furthermore, age and LS (≥ versus <1.46 m/s) at SVR (aHR: 6.759; 95% CI: 2.317-19.723; p < 0.001), but not SS at SVR, independently predicted the risk of post-SVR incident HCC. In contrast, SS (≥ versus <2.87 m/s) at SVR (aHR: 11.212; 95% CI: 1.564-20.132; p = 0.021) and albumin level, but not LS at SVR, significantly predicted the risk of post-SVR non-HCC events. CONCLUSION: Post-SVR LS better predicts HCC risk. Post-SVR SS helps predict non-HCC risk after antiviral therapy for CHC. LS and SS at SVR provide complementary prognostic information regarding risks of HCC and non-HCC events in the post-SVR setting. Further validation is warranted in larger cohorts.

EGF-driven EGFR/miR-27b-3p/FOXO1 promotes rat FSH synthesis and secretion.

The adenopituitary secretes follicle-stimulating hormone (FSH), which plays a crucial role in regulating the growth, development, and reproductive functions of organisms. Investigating the process of FSH synthesis and secretion can offer valuable insights into potential areas of focus for reproductive research. Epidermal growth factor (EGF) is a significant paracrine/autocrine factor within the body, and studies have demonstrated its ability to stimulate FSH secretion in animals. However, the precise mechanisms that regulate this action are still poorly understood. In this research, in vivo and in vitro experiments showed that the activation of epidermal growth factor receptor (EGFR) by EGF induces the upregulation of miR-27b-3p and that miR-27b-3p targets and inhibits Foxo1 mRNA expression, resulting in increased FSH synthesis and secretion. In summary, this study elucidates the precise molecular mechanism through which EGF governs the synthesis and secretion of FSH via the EGFR/miR-27b-3p/FOXO1 pathway.