Effects of probiotic supplementation on 12 min run performance, mood management, body composition and gut microbiota in amateur marathon runners: A double-blind controlled trial.

Background: Probiotic supplementation has a positive effect on endurance exercise performance and body composition in athletes, but the underlying mechanisms remain unclear. Gut microbiota can provide measurable markers of immune function in athletes, and microbial composition analysis may be sensitive enough to detect stress and metabolic disorders caused by exercise. Methods: Nineteen healthy active amateur marathon runners (15 male and 4 female) with a mean age of 29.11 years volunteered to participate in this double-blind controlled study. Based on the performance of the Cooper 12-min running test (CRT), the participants were allocated into two groups to receive either a probiotic formulation comprising lactobacillus acidophilus and bifidobacterium longum (n = 10) or placebo containing maltodextrin (n = 9) for five weeks. Consistency of diet and exercise was ensured throughout the experimental period. Before and after the intervention, all participants were assessed for CRT, emotional stability and gastrointestinal symptoms, gut microbiota composition, body composition and magnetic resonance imaging (MRI) indicators of skeletal muscle microcirculation. Results: Compared to before the intervention, the probiotics group showed an increase in CRT score (2.88 ± 0.57 vs 3.01 ± 0.60 km, P＜0.05), significant improvement in GSRS and GIQLI (9.20 ± 4.64 vs 7.40 ± 3.24, 118.90 ± 12.30 vs 127.50 ± 9.85, P＜0.05), while these indicators remained unchanged in the control group, with a significant time-group interaction effect on gastrointestinal symptoms. Additionally, some MRI metabolic cycling indicators of the thigh skeletal muscle also changed in the probiotics group (P＜0.05). Regarding microbiota abundance, the probiotics group exhibited a significant increase in the abundance of beneficial bacteria and a significant decrease in the abundance of harmful bacteria post-intervention (P＜0.05). Conclusion: As a sports nutritional supplement, probiotics have the potential to improve athletic performance by optimizing the balance of gut microbiota, alleviating gastrointestinal symptoms.

Characteristics of the HIV/AIDS Epidemic among People Aged ≥ 50 Years in China during 2018-2021.

Objective: This study aimed to determine the current epidemiological status of PLWHA aged ≥ 50 years in China from 2018 to 2021. It also aimed to recommend targeted interventions for the prevention and treatment of HIV/AIDS in elderly patients. Methods: Data on newly reported cases of PLWHA, aged ≥ 50 years in China from 2018 to 2021, were collected using the CRIMS. Trend tests and spatial analyses were also conducted. Results: Between 2018 and 2021, 237,724 HIV/AIDS cases were reported among patients aged ≥ 50 years in China. The main transmission route was heterosexual transmission (91.24%). Commercial heterosexual transmission (CHC) was the primary mode of transmission among males, while non-marital non-CHC ([NMNCHC]; 60.59%) was the prevalent route in women. The proportion of patients with CHC decreased over time ( Z = 67.716, P < 0.01), while that of patients with NMNCHC increased ( Z = 153.05, P < 0.01). The sex ratio varied among the different modes of infection, and it peaked at 17.65 for CHC. The spatial analysis indicated spatial clustering, and the high-high clustering areas were mainly distributed in the southwestern and central-southern provinces. Conclusion: In China, PLWHA, aged ≥ 50 years, were predominantly infected through heterosexual transmission. The primary modes of infection were CHC and NMNCHC. There were variations in the sex ratio among different age groups, infected through various sexual behaviors. HIV/AIDS cases exhibited spatial clustering. Based on these results, the expansion of HIV testing, treatment, and integrated behavioral interventions in high-risk populations is recommended to enhance disease detection in key regions.

Follicular fluid exosome-derived miR-339-5p enhances in vitro maturation of porcine oocytes via targeting SFPQ, a regulator of the ERK1/2 pathway.

In this study, we aimed to investigate cytoplasmic maturation and miRNA expression of mature oocytes cultured in porcine follicular fluid exosomes. We also examined the effect of miR-339-5p on oocyte maturation. Twenty eight differentially expressed miRNAs were detected using miRNA-seq. We then transfected cumulus oocyte complexes with miR-339-5p mimics and inhibitor during culture. The results showed that exosomes increased endoplasmic reticulum levels and the amount of lipid droplets, and decreased ROS levels, lipid droplet size, and percentage of oocytes with abnormal cortical granule distribution. Overexpressing miR-339-5p significantly decreased cumulus expansion genes, oocyte maturation-related genes, target gene proline/glutamine-rich splicing factor (SFPQ), ERK1/2 phosphorylation levels, oocyte maturation rate, blastocyst rate, and lipid droplet number, but increased lipid droplet size and the ratio of oocytes with abnormal cortical granule distribution. Inhibiting miR-339-5p reversed the decrease observed during overexpression. Mitochondrial membrane potential and ROS levels did not differ significantly between groups. In summary, exosomes promote oocyte cytoplasmic maturation and miR-339-5p regulating ERK1/2 activity through SFPQ expression, thereby elevating oocyte maturation and blastocyst formation rate in vitro.

Identification of the CD8+ T-cell Related Signature for Predicting the Prognosis of Gastric Cancer Based on Integrated Analysis of Bulk and Single-cell RNA Sequencing Data.

The infiltration of CD8+ T cells in the tumor microenvironment is associated with better survival and immunotherapy response. However, their roles in gastric cancer have not been explored so far. In here, the profiles of GC gene expression were collected from The Cancer Genome Atlas database. Single-cell transcriptomic data originated from GSE134520. Cell clustering, annotation, and CD8+ T-cell differential genes were from the TISCH database. We determined 896 CD8+ T-cell differential genes by scRNA-seq analysis. After integrating immune-related genes, 174 overlapping genes were obtained and a novel risk model was subsequently built. The performance of CD8+ T-cell-associated gene signature was assessed in the training and external validation sets. The gene signature showed independent risk factors of overall survival for GC. A quantitative nomogram was built to enhance the clinical efficacy of this signature. Furthermore, low-risk individuals showed higher mutation status, higher immune checkpoint expression, low Tumour Immune Dysfunction and Exclusion (TIDE) scores, and higher IPS-PD-1 combined IPS-CTLA4 scores, indicating a greater response to immunotherapy. In addition, analysis of IMvigor210 immunotherapy cohort demonstrated that low-risk individuals had a favorable response to prognosis and immunotherapy. In conclusion, we generated a CD8+ T-cell-related signature that can serve as a promising tool for personalized prognosis prediction and guiding decisions regarding immunotherapy in GC patients.

Proteomics Study of Benzene Metabolite Hydroquinone Induced Hematotoxicity in K562 Cells.

Objective: Hydroquinone (HQ), one of the phenolic metabolites of benzene, is widely recognized as an important participant in benzene-induced hematotoxicity. However, there are few relevant proteomics in HQ-induced hematotoxicity and the mechanism hasn't been fully understood yet. Methods: In this study, we treated K562 cells with 40 µmol/L HQ for 72 h, examined and validated protein expression changes by Label-free proteomic analysis and Parallel reaction monitoring (PRM), and performed bioinformatics analysis to identify interaction networks. Results: One hundred and eighty-seven upregulated differentially expressed proteins (DEPs) and 279 downregulated DEPs were identified in HQ-exposed K562 cells, which were involved in neutrophil-mediated immunity, blood microparticle, and other GO terms, as well as the lysosome, metabolic, cell cycle, and cellular senescence-related pathways. Focusing on the 23 DEGs and 5 DEPs in erythroid differentiation-related pathways, we constructed the network of protein interactions and determined 6 DEPs (STAT1, STAT3, CASP3, KIT, STAT5B, and VEGFA) as main hub proteins with the most interactions, among which STATs made a central impact and may be potential biomarkers of HQ-induced hematotoxicity. Conclusion: Our work reinforced the use of proteomics and bioinformatic approaches to advance knowledge on molecular mechanisms of HQ-induced hematotoxicity at the protein level and provide a valuable basis for further clarification.

Arginine Kinase Activates Arginine for Phosphorylation by Pyramidalization and Polarization.

Arginine phosphorylation plays numerous roles throughout biology. Arginine kinase (AK) catalyzes the delivery of an anionic phosphoryl group (PO3-) from ATP to a planar, trigonal nitrogen in a guanidinium cation. Density functional theory (DFT) calculations have yielded a model of the transition state (TS) for the AK-catalyzed reaction. They reveal a network of over 50 hydrogen bonds that delivers unprecedented pyramidalization and out-of-plane polarization of the arginine guanidinium nitrogen (Nη2) and aligns the electron density on Nη2 with the scissile P-O bond, leading to in-line phosphoryl transfer via an associative mechanism. In the reverse reaction, the hydrogen-bonding network enforces the conformational distortion of a bound phosphoarginine substrate to increase the basicity of Nη2. This enables Nη2 protonation, which triggers PO3- migration to generate ATP. This polarization-pyramidalization of nitrogen in the arginine side chain is likely a general phenomenon that is exploited by many classes of enzymes mediating the post-translational modification of arginine.

Neutrophils in pancreatic ductal adenocarcinoma: bridging preclinical insights to clinical prospects for improved therapeutic strategies.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by a dismal five-year survival rate of less than 10%. Neutrophils are key components of the innate immune system, playing a pivotal role in the PDAC immune microenvironment. AREAS COVERED: This review provides a comprehensive survey of the pivotal involvement of neutrophils in the tumorigenesis and progression of PDAC. Furthermore, it synthesizes preclinical and clinical explorations aimed at targeting neutrophils within the milieu of PDAC, subsequently proposing a conceptual framework to propel further inquiry focused on enhancing the therapeutic efficacy of PDAC through neutrophil-targeted strategies. PubMed and Web of Science databases were utilized for researching neutrophils in pancreatic cancer publications prior to 2024. EXPERT OPINION: Neutrophils play roles in promoting tumor growth and metastasis in PDAC and are associated with poor prognosis. However, the heterogeneity and plasticity of neutrophils and their complex relationships with other immune cells and extracellular matrix also provide new insights for immunotherapy targeting neutrophils to achieve a better prognosis for PDAC.

From intramuscular to nasal: unleashing the potential of nasal spray vaccines against coronavirus disease 2019.

Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected 700 million people worldwide since its outbreak in 2019. The current pandemic strains, including Omicron and its large subvariant series, exhibit strong transmission and stealth. After entering the human body, the virus first infects nasal epithelial cells and invades host cells through the angiotensin-converting enzyme 2 receptor and transmembrane serine protease 2 on the host cell surface. The nasal cavity is an important body part that protects against the virus. Immunisation of the nasal mucosa produces immunoglobulin A antibodies that effectively neutralise viruses. Saline nasal irrigation, a type of physical therapy, can reduce the viral load in the nasal cavity and prevent viral infections to some extent. As a commonly used means to fight SARS-CoV-2, the intramuscular (IM) vaccine can induce the human body to produce a systemic immune response and immunoglobulin G antibody; however, the antibody is difficult to distribute to the nasal mucosa in time and cannot achieve a good preventive effect. Intranasal (IN) vaccines compensate for the shortcomings of IM vaccines, induce mucosal immune responses, and have a better effect in preventing infection. In this review, we discuss the nasal defence barrier, the harm caused by SARS-CoV-2, the mechanism of its invasion into host cells, nasal cleaning, IM vaccines and IN vaccines, and suggest increasing the development of IN vaccines, and use of IN vaccines as a supplement to IM vaccines.

RNF31 alleviates liver steatosis by promoting p53/BNIP3-related mitophagy in hepatocytes.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is one of the liver illnesses that may be affected by mitophagy, which is the selective removal of damaged mitochondria. RNF31, an E3 ubiquitin ligase, is carcinogenic in many malignancies. However, the influence of RNF31 on mitochondrial homeostasis and NAFLD development remains unknown. METHODS: Oleic-palmitic acid treated hepatocytes and high-fat diet (HFD)-fed mice were established to observe the effect of RNF31 on hepatocyte mitophagy and steatosis. Mitophagy processes were comprehensively assessed by mt-Keima fluorescence imaging, while global changes in hepatic gene expression were measured by RNA-seq. RESULTS: The present study discovered a reduction in RNF31 expression in lipotoxic hepatocytes with mitochondrial dysfunction. The observed decrease in RNF31 expression was associated with reduced mitochondrial membrane potential, disturbed mitophagy, and increased steatosis. Additionally, the findings indicated that RNF31 is a pivotal factor in the initiation of mitophagy and the facilitation of mitochondrial homeostasis, resulting in a decrease in steatosis in lipotoxic hepatocytes. Mechanistically, RNF31 enhanced p53 ubiquitination and subsequent proteasomal degradation. Down-regulation of p53 led to increased expression of the mitophagy receptor protein BCL2 and adenovirus E1B 19 kDa-interacting protein 3 (BNIP3), thereby promoting mitophagy in hepatocytes. Furthermore, it was demonstrated that the transportation of RNF31 via small extracellular vesicles derived from mesenchymal stem cells (referred to as sEV) had a substantial influence on reducing hepatic steatosis and restoring liver function in HFD-fed mice. CONCLUSIONS: The findings highlight RNF31's essential role in the regulation of mitochondrial homeostasis in hepatocytes, emphasizing its potential as a therapeutic target for NAFLD.

The factors affecting the performance of the tunnel wall drilling task and their priority.

Clarifying the relationship between the man-machine environment and its impact on the tunnel wall drilling task performance (TWDTP) is crucial for enhancing the task performance. Based on a questionnaire survey, indicators of the man-machine environment that affect the TWDTP were proposed in this study, and exploratory factor analysis and a structural equation model were employed to examine the potential factors influencing the task performance and their degrees of influence. By comparing the discrepancy between the perceived performance and importance, the satisfaction of potential factors was evaluated, and the priority order for optimizing these factors was determined by considering the degree of influence and dissatisfaction. The results of survey data analysis based on actual tunnel drilling operation scenarios indicated that tools had the greatest impact on the TWDTP, followed by the quality of the physical environment, while human factors had the least influence on the task performance. Convenient functional maintenance is the key to improving the TWDTP, along with enhancing the quality of the working environment. Once these main aspects are optimized, it is important to consider additional factors such as availability of spare tools, efficient personnel organization, man-tool matching, and safety and health assurance. This research approach provides significant guidance in understanding the relationships between the man-machine environmental factors affecting the performance of complex engineering tasks and identifying key influencing factors, thus providing essential insights for optimizing the TWDTP.

Clinical Outcomes of Severe Rhinosinusitis Complicated with Cavernous Sinus Syndrome.

Background: Various diseases involving the cavernous sinus can cause a condition called cavernous sinus syndrome (CSS), which is characterized by ophthalmoplegia or sensory deficits over the face resulting from the compression effect of internal structure. While tumor compression is the most reported cause of CSS, statistical data on CSS caused by infections are limited. Its risk factors, treatment methods, and clinical outcomes are not well-documented. Methods: In this retrospective study, we reviewed the data of patients admitted to a tertiary medical center from 2015 to 2022 with a diagnosis of acute and chronic sinusitis and at least one diagnostic code for CSS symptoms. We manually reviewed whether patients were involved in two or more of the following cranial nerves (CN): CN III, CN IV, CN V, or CN VI, or at least one of these nerves with a neuroimaging-confirmed lesion in the cavernous sinus. Results: Nine patients were diagnosed with rhinosinusitis-related CSS. The most common comorbidity was type 2 diabetes, and the most common clinical manifestations were diplopia and blurred vision. The sphenoid sinus was the most affected sinus. One patient expired due to a severe brain abscess infection without surgery. The remaining patients underwent functional endoscopic sinus surgery, and 50% of the pathology reports indicated fungal infections. Staphylococcus spp. was the most cultured bacteria, and Amoxycillin/Clavulanate was the most used antibiotic. Only four patients had total recovery during the follow-up one year later. Conclusions: CSS is a rare but serious complication of rhinosinusitis. Patients with diabetes and the elderly may be at a higher risk for this complication. Even after treatment, some patients may still have neurological symptoms.

Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis.

OBJECTIVE: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN: Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed. RESULTS: Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial. CONCLUSIONS: This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation. TRIAL REGISTRATION NUMBER: NCT03202498.

Deficiency of neutral cholesterol ester hydrolase 1 (NCEH1) impairs endothelial function in diet-induced diabetic mice.

BACKGROUND: Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored. The present study sought to investigate whether NCEH1 improved endothelial function in diabetes, and the underlying mechanisms were explored. METHODS: The expression and activity of NCEH1 were determined in obese mice with high-fat diet (HFD) feeding, high glucose (HG)-induced mouse aortae or primary endothelial cells (ECs). Endothelium-dependent relaxation (EDR) in aortae response to acetylcholine (Ach) was measured. RESULTS: Results showed that the expression and activity of NCEH1 were lower in HFD-induced mouse aortae, HG-exposed mouse aortae ex vivo, and HG-incubated primary ECs. HG exposure reduced EDR in mouse aortae, which was exaggerated by endothelial-specific deficiency of NCEH1, whereas NCEH1 overexpression restored the impaired EDR. Similar results were observed in HFD mice. Mechanically, NCEH1 ameliorated the disrupted EDR by dissociating endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to eNOS activation and nitric oxide (NO) release. Moreover, interaction of NCEH1 with the E3 ubiquitin-protein ligase ZNRF1 led to the degradation of Cav-1 through the ubiquitination pathway. Silencing Cav-1 and upregulating ZNRF1 were sufficient to improve EDR of diabetic aortas, while overexpression of Cav-1 and downregulation of ZNRF1 abolished the effects of NCEH1 on endothelial function in diabetes. Thus, NCEH1 preserves endothelial function through increasing NO bioavailability secondary to the disruption of the Cav-1/eNOS complex in the endothelium of diabetic mice, depending on ZNRF1-induced ubiquitination of Cav-1. CONCLUSIONS: NCEH1 may be a promising candidate for the prevention and treatment of vascular complications of diabetes.

Virtual Water Embodied in Interregional Energy Trade in China: A City-Level Analysis.

Large volumes of water are used in energy production for both primary (e.g., fuel extraction) and secondary energy (e.g., electricity). In countries such as China, with a large internal trade in fuels and long-distance transmission grids, this can result in considerable water inequalities. Previous research focused on the water impacts of energy production at the national and provincial levels, which is too coarse to identify the spatial differences and make specific case studies. Here, we take the next step toward a spatially explicit economically integrated water-use for energy assessment by combining a bottom-up assessment approach with a city-level multiregional input-output model. Specifically, we examine the water consumption of energy production in China, distinguishing between water for primary and secondary energy at the level of coal mines, oil and gas fields, and power plants for the first time. Of the total energy-related freshwater consumption of 4.9 Gm3 in 2017, primary energy accounted for 19% (940 Mm3) and secondary energy accounted for 81% (3955 Mm3). Coal was the largest water consumer for both primary and secondary energy (540 and 3880 Mm3, respectively), with both oil (361, and 0.5 Mm3, respectively) and gas (7 and 69 Mm3, respectively) also consuming large amounts. Intercity virtual water, that is, water embodied in energy trade across cities, reached 54% (2.6 Gm3) of energy-related freshwater consumption. Across China, 32% of cities see a bilateral trade in secondary- and primary-energy-related virtual water (e.g., Daqing city exports virtual water embodied in primary fuel to other cities that is then used to produce electricity in those cities, part of which is used back in Daqing via transmission). For these 32% of cities, 73% export more virtual water than import and 27% import more virtual water than export. This study reveals significant differences in city-level virtual water patterns (e.g., scale and direction) between primary and secondary energy to provide information for cities about their virtual water inflow and outflow and the potential collaboration partners for water management.

Association between holiday and weekend admissions and mortality outcomes among patients with acute myocardial infarction receiving percutaneous coronary intervention in Taiwan.

There is a lack of studies that concurrently differentiate the effect of the holiday season from the weekend effect on mortality risk in patients with acute myocardial infarction (AMI). We evaluated the mortality risk among patients admitted with AMI who underwent percutaneous coronary intervention, using data from the Taiwan National Health Insurance Research Database. Adult AMI patients admitted during January and February between 2013 and 2020 were enrolled and classified into the holiday season (using the Chinese New Year holiday seasons as an indicator) (n = 1729), weekend (n = 4725), and weekday (n = 14,583) groups according to the first day of admission. A multivariable logistic regression model was used to assess the risk. With the weekday group or the weekend group as the reference, the holiday season group did not have increased risks of in-hospital mortality (adjusted odds ratio [aOR] 1.15; 95% confidence intervals [CI] 0.93-1.42 or aOR 1.23; 95% CI 0.96-1.56) and 7-day mortality (aOR 1.20; 95% CI 0.90-1.58 or aOR 1.24; 95% CI 0.90-1.70). Stratified and subgroup analyses showed similar trends. We conclude that holiday season-initiated admissions were not associated with higher mortality risks in AMI admission cases than weekday or weekend admissions.

Preliminary exploration of animal models of congenital choledochal cysts.

BACKGROUND: Various animal models have been used to explore the pathogenesis of choledochal cysts (CCs), but with little convincing results. Current surgical techniques can achieve satisfactory outcomes for treatment of CCs. Consequently, recent studies have focused more on clinical issues rather than basic research. Therefore, we need appropriate animal models to further basic research. AIM: To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs. METHODS: Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group, sham surgical group, or control group. A rat model of CC was established by partial ligation of the bile duct. The reliability of the model was confirmed by measurements of serum biochemical indices, morphology of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues. RESULTS: Dilation classified as mild (diameter, ≥ 1 mm to < 3 mm), moderate (≥ 3 mm to < 10 mm), and severe (≥ 10 mm) was observed in 17, 17, and 2 rats in the surgical group, respectively, while no dilation was observed in the control and sham surgical groups. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery, while direct bilirubin, total bilirubin, and gamma-glutamyltransferase were further increased 14 d after surgery. Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery. The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues. CONCLUSION: The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC, which may contribute to investigating the pathogenesis of CC.

Progress of uric acid in cardiovascular disease.

Due to the global prevalence of hyperuricemia (HUA), there is growing interest in research on uric acid (UA). HUA is a common condition that has various adverse consequences, including gout and kidney disease. However, recent studies have also implicated UA in the development of cardiovascular diseases (CVD) such as atrial fibrillation (AF) and coronary heart disease (CHD). Experimental and clinical research has extensively demonstrated the detrimental effects of elevated serum UA levels on cardiovascular health. Furthermore, serum UA levels have been identified as predictors of CVD outcomes following percutaneous coronary intervention (PCI) and catheter ablation. Additionally, the use of UA-lowering therapy holds important implications for the management of CVD. This review aims to consolidate the current evidence on the relationship between serum UA and CVD.

Long-term Efficacy and Safety of High-frequency Spinal Stimulation for Chronic Pain: A Meta-analysis of Randomized Controlled Trial.

OBJECTIVE: The aim of our meta-analysis was to systematically assess the enduring effectiveness and safety of high-frequency spinal stimulation (HF-SCS) in the management of chronic pain. METHODS: We developed a comprehensive literature search strategy to identify clinical trials investigating the efficacy of high-frequency spinal stimulation for chronic pain. The search was conducted in multiple databases, including Web of Science, Cochrane, PubMed, and Embase, covering the period from 2004 to 2023. The inclusion and exclusion criteria established for this study were applied to screen the eligible literature by carefully reviewing abstracts and, when necessary, examining the full text of selected articles. To assess the quality of the included studies, we utilized the risk of bias assessment tool provided by the Cochrane Collaboration.The PRISMA method was followed for the selection of articles, and the quality of the articles was evaluated using the risk assessment table for bias provided by the Cochrane Collaboration.Meta-analysis of the selected studies was performed using Review Manager 5.4 and STATA 16.0. Effect sizes for continuous data were reported as mean differences (MD) or standardized mean differences (SMD), while categorical data were analyzed using relative risks (RR). RESULTS: According to our predefined literature screening criteria, a total of seven English-language randomized controlled trials (RCTs) were included in the meta-analysis. The findings from the meta-analysis demonstrated that high-frequency spinal cord stimulation (HF-SCS) exhibited superior efficacy in the long-term treatment of chronic pain when compared to the control group (RR = 2.44, 95% CI [1.20, 4.96], P = 0.01). Furthermore, HF-SCS demonstrated a statistically significant improvement in the Oswestry Disability Index score (mean difference MD = 3.77, 95% CI [1.17, 6.38], P = 0.005).However, for pain assessment (standardized mean difference SMD = -0.59, 95% CI [-1.28, 0.10], P = 0.09), Patient Global Impression of Improvement (PGI-I) score (MD = 0.11, 95% CI [-0.66, 0.88], P = 0.78 for 6 months; MD = 0.02, 95% CI [-0.42, 0.43], P = 0.97 for 12 months), Clinical Global Impression of Improvement (CGI-I) score (MD = -0.58, 95% CI [-1.62, 0.43], P = 0.27 for 6 months; MD = -0.23, 95% CI [-0.94, 0.48], P = 0.52 for 12 months), and occurrence of adverse effects (odds ratio OR = 0.77, 95% CI [0.23, 2.59], P = 0.67) from a statistical point of view, HF-SCS did not show sufficient effect compared with the control group. Not significant enough to consider it. CONCLUSIONS: The findings from our comprehensive review and meta-analysis, encompassing research from 2004 to 2023, offer encouraging data about the prolonged efficacy and safety of HF-SCS in chronic pain management. Nonetheless, recognizing the constraints of the existing evidence is crucial. Upcoming clinical trials, meticulously planned and stringent, are essential to bolster the current body of evidence and reach more conclusive findings.