Efficacy of DHA-enriched phosphatidylserine and its underlying mechanism in alleviating polystyrene nanoplastics-induced hepatotoxicity in mice.

OBJECTIVE: Plastic pollution has become a global pollution problem that cannot be ignored. As the main destination of human oral intake, the toxic effects of plastic on the digestive system represented by the intestine and liver are the focus of current research. Marine-derived DHA-PS has a variety of biological activities, mainly focusing on improving brain function and regulating lipid metabolism. However, whether it has an improvement effect on PS-NPs-induced hepato-intestinal injury and the underlying mechanism remain unclear. METHODS: A murine liver injury model was established by gavage of PS-NPs for six weeks. By integrating approaches from lipidomics, transcriptomics, and gut microbiota analysis, the molecular mechanism by which DHA-PS alleviates PS-NPs-induced murine hepatotoxicity was explored through the "gut-liver axis". RESULTS: Our findings reveal that prolonged exposure to PS-NPs results in significant murine liver damage and dysfunction, characterized by increased oxidative stress and inflammation, along with exacerbated hepatic lipid accumulation. Mechanistically, PS-NPs disrupt the hepatic SIRT1-AMPK pathway by suppressing the expression of SIRT1, AMPKα, and PPARα, while enhancing the expression of SREBP-1c, ultimately leading to disordered hepatic lipid metabolism. The sphingolipid and glycerophospholipid metabolic pathways were particularly affected. Additionally, in agreement with transcriptomic analyses, PS-NPs activate the hepatic TLR4/NF-κB pathway. At the same time, exposure to PS-NPs decreases the expression of ZO-1, occludin, and claudin-1, diminishes the relative abundance of beneficial gut bacteria (norank_f_Muribaculaceae, Akkermansia, and norank_f_norank_o_Clostridia_UCG-014), and increases the prevalence of pathogenic gut bacteria (Coriobacteriaceae_UCG-002 and Desulfovibrio), exacerbating liver injury through the gut-liver axis. However, administering DHA-PS (50 mg/kg) effectively alleviated these injuries. CONCLUSION: This study was the first to employ multi-omics techniques to elucidate the potential mechanisms underlying hepatotoxicity induced by PS-NPs, thereby supporting the use of DHA-PS as a dietary supplement to mitigate the effects of nanoplastic pollutants.

Insight into response mechanism of short-chain fatty acids to refined microbial transformation order of dissolved organic matter ranked by molecular weight during dry anaerobic digestion.

Dynamic transformation of dissolved organic matter (DOM) contributes to short-chain fatty acids (SCFAs) production during anaerobic digestion. However, the impact of refined transformation of DOM ranked by molecular weight (MW) on SCFAs has never been investigated. Results indicated that DOM conversion order was 3500-7000 Da>(MW>14000 Da) > 7000-4000 Da during hydrolysis stage, while it was independent of their MW in acidogenesis phase and followed a low to high MW order during methanogenesis stage. Proteins-like DOMs with different MW were closely related to SCFAs. Eight groups of microorganisms (e.g., Bacillus and Caldicoprobacter) responsible for the conversion of proteins-like DOMs to SCFAs. The possible routes linking environmental properties to microorganisms-proteins-like DOMs-SCFAs connections were constructed. Microbial activity modifications by regulating moisture, pH, NO3--N and NH4+-N can expedite the conversion of proteins-like DOMs to SCFAs. The study emphasizes the importance of MW-classification-based biotransformation of organic waste, offering a potential strategy to enhance anaerobic digestion performance.

Association between total body muscle-fat ratio and risk of thyroid disorders: a cross-sectional study.

BACKGROUND: Thyroid disorders(TD) poses a significant health threat to Americans due to its high incidence rate. Obesity, a common factor linked to thyroid disorders, has garnered increasing attention. While Body mass index (BMI) is a widely used obesity index, it fails to account for the distribution of muscle and fat in the body. Recently, tMFR has emerged as a crucial obesity index in clinical research, warranting further investigation into its association with TD. OBJECTIVE: Exploring the association between tMFR and thyroid disorders. METHOD: A comprehensive survey and data analysis were conducted using the NHANES database to investigate the relationship between tMFR and the risk of TD. This study utilized multiple logistic regression, smooth curve fitting, and subgroup analysis across four periods from 2011 to 2018. RESULT: A total of 11,912 subjects were included in the study, showing a prevalence of 7.14% for TD. The research indicated that tMFR had an inverse correlation with the risk of TD in a comprehensive model (OR = 0.90, 95% CI 0.82 to 1.00). When tMFR was divided into quartiles (Q1-Q4), individuals in the highest quartile had a 28% lower risk of TD than those in Q1 (OR = 0.72, 95% CI 0.57 to 0.91). Analysis using smoothed curve fitting demonstrated a nonlinear relationship between tMFR and TD risk, with the inflection point for tMFR saturation effect identified as 1.5. Subgroup analysis further confirmed the strong association between tMFR and TD risk. Receiver operating characteristic (ROC) curve analysis indicated that tMFR exhibited superior predictive ability for TD relative to BMI. CONCLUSION: The study found a negative association between tMFR and the risk of TD; however, additional prospective studies are required to validate these findings.

Efficacy and safety of Kegan Liyan oral liquid for patients with acute pharyngitis: A randomized, double-blinded, placebo-controlled, multi-center trial.

BACKGROUND: Alleviating the sore throat caused by acute pharyngitis is a primary patient concern. However, antibiotics are not commonly recommended drugs, and abuse can lead to serious consequences such as drug resistance. Therefore, seeking alternative treatments is necessary. PURPOSE: To investigate the efficacy and safety of Kegan Liyan (KGLY) oral liquid for patients with acute pharyngitis. STUDY DESIGN: Randomized, double-blinded, placebo-controlled, multi-center study. METHODS: Participants from 17 hospitals were randomly assigned 1:1 to receive KGLY oral liquid or placebo for five days. Assessments occurred at baseline, day 3, and day 6. The primary outcome was the recovery rate. Secondary outcomes included sore throat and cough visual analogue scale (VAS), the area under the curve (AUC) of sore throat VAS, time to sore throat relief and recovery, proportion of participants with sore throat relief and recovery, traditional Chinese medicine (TCM) syndrome score, single TCM manifestation score and use of acetaminophen. RESULTS: Involving 239 participants (120 in KGLY and 119 in placebo group), the study found a significantly higher recovery rate on day 6 in the KGLY group (between-group difference, 27.20 % [15.00 % to 39.40 %], p < 0.001). On day 3 and 6, the KGLY group showed significantly larger reductions in sore throat (-3.02 vs -2.37, p = 0.001; -4.66 vs -3.64, p < 0.001) and cough VAS scores (-1.55 vs -1.05, p = 0.004; -2.28 vs -1.56, p < 0.001) from baseline. KGLY oral liquid lowered the AUC of sore throat VAS score (-2.33 [-4.10 to -0.56], p = 0.011), shortened time to sore throat recovery (hazard ratio, 0.42 [0.30 to 0.59], p < 0.001), increased sore throat recovery rate at day 6 (75.00 % vs 42.86 %, p < 0.001), decreased the TCM syndrome score (-2.03 [-2.69 to -1.37], p < 0.001), and improved individual TCM symptoms compared to placebo. No significant differences between the groups in acetaminophen usage. KGLY oral liquid was safe and tolerated. CONCLUSION: KGLY oral liquid may be a beneficial and safe alternative treatment for acute pharyngitis, which can alleviate symptoms such as sore throat, swollen throat, cough, and phlegm production.

Tailor-made ammonia nitrogen risk management with machine learning models for aquatic environments in the Mainland of China.

Efficient management of pollutant risks in water bodies is crucial for public health and aquatic ecosystem sustainability. However, the toxicities of pollutants, such as ammonia nitrogen (NH3-N), are often affected by multiple water quality factors, including the pH and water temperature. Extensive spatial and temporal variability in these factors hinders tailor-made management of risk. This study used high-frequency monitoring data collected over 1 year to evaluate the long-term NH3-N risk in China's aquatic ecosystems. High accuracy and interpretability were achieved by decomposing NH3-N risk into the contributions of key influencing factors using random forest models and Shapley Additive Explanations. Two distinct types of NH3-N risk hotspots were identified across 18 cities: 15 cities with high NH3-N concentrations and 3 cities with low environmental carrying capacity due to high pH levels or elevated water temperatures. For the former, rapid NH3-N abatement measures are necessary to bring NH3-N concentrations back below the environmental capacity. For the latter, it is recommended that NH3-N related industries are relocated to regions with high environmental capacities because fragile environments are not suitable for such industries. Importantly, this study investigated methods for attributing pollutant risks in the context of non-linear influencing factors, and the risk of NH3-N was predicted to increase by 6.1 % by the end of 2100 in the context of increasing temperatures under the SSP 2-4.5 scenario. The methodology is also adaptable and suitable for integration into global ecosystem risk management efforts to balance development and aquatic ecological sustainability.

Efficacy and safety of Tongxin formula in the treatment of coronary microvascular disease: A randomized, double-blind, placebo-controlled clinical trial study.

Objective: The objective of this study was to evaluate the efficacy and safety of Tongxin Formula in the treatment of coronary microvascular disease. Methods: We conducted a randomized, double-blind, placebo-controlled study simultaneously in two hospitals, consisting of 80 participants. Using a random number table, we assigned patients to the treatment and control groups. Patients in both groups received conventional Western medicine for coronary microvascular disease. In addition, those in the treatment group received Tongxin formula granules, while those in the control group received a placebo. The treatment course for both groups was three months, and the follow-up duration was six months. The primary efficacy indicators were coronary blood flow reserve and cardiovascular adverse events; the secondary efficacy indicators were the traditional Chinese medicine (TCM) syndrome score, the angina symptom score, the Seattle Angina Questionnaire (SAQ) score, left ventricular function, and adverse reactions. Results: After treatment, patients in the treatment group showed significantly higher variation in the coronary flow reserve (CFR) levels (CFR >2) and improvement of diastolic function (peak filling rate, or PFR >2.5) than those in the control group (P < 0.05). After 6 months of follow-up, the incidence of cardiovascular events in the treatment group was significantly lower than that in the control group (P < 0.05). After 3 months of treatment and 6 months of follow-up, the total effective rates of TCM symptoms and angina symptoms, as well as the total SAQ standard scores, in the treatment group were higher than those in the control group (P < 0.05). There were no serious adverse reactions in either group before or after treatment, and there was no significant change (P > 0.05). Conclusion: We found that Tongxin Formula combined with conventional Western medicine can significantly improved the level of coronary blood flow reserve, reduced the occurrence of cardiovascular adverse events, improved the clinical symptoms of patients, and enhanced the quality of life of patients with coronary microvascular disease with favorable safety.

Case Report: Diagnosis of Hemolytic Anemia from Babesia and Secondary Multi-Pathogen Pneumonia Using a Metagenomic Next-Generation Sequencing Approach.

Babesiosis, as a vector-borne infectious disease, remains relatively rare and is prone to being overlooked and misdiagnosed. Therefore, understanding the epidemiological characteristics and clinical manifestations of babesiosis is crucial for the prompt detection and treatment of the disease. We reported a 63-year-old male patient presenting with spontaneous fever and chills. Laboratory investigations revealed erythrocytopenia, reduced hemoglobin levels, and increased reticulocytes and total bilirubin. Bone marrow examination indicated vigorous cell proliferation, a decreased granulocyte to red cell ratio, and predominant erythroid cell proliferation, with a higher prevalence of intermediate and late-stage juvenile granulocyte and erythroid cells. Initial treatment focused on hemophagocytic syndrome triggered by Epstein-Barr virus infection yielded unsatisfactory results, leading to secondary multiple pulmonary infections. Metagenomic next-generation sequencing (mNGS) of sputum samples pointed to hemolytic anemia induced by Babesia infection, which was subsequently confirmed through peripheral blood smear analysis. The patient responded well to prompt administration of atovaquone and azithromycin, with symptoms resolving and laboratory parameters normalizing. Hemolytic anemia resulting from babesiosis should be distinguished from hemophagocytic syndrome caused by Epstein-Barr virus and other hematologic conditions. mNGS represents an efficient technique for Babesia detection.

Developing a plant microbial fuel cell by planting water spinach in a hanging-submerged plant pot system.

To plant crops (especially dry crops such as water spinach) with concomitant electricity recovery, a hanging-submerged-plant-pot system (HSPP) is developed. The HSPP consists of a soil pot (anodic) partially submerged under the water surface of a cathode tank. The microbial communities changed with conditions were also investigated. It was found that with chemical fertilizers the closed-circuit voltage (CCV, with 1 kΩ) was stable (approximately 250 mV) within 28 d; however, without fertilizer, the water spinach could adjust to the environment to obtain a better power output (approximately 3 mW m-2) at day 28. The microbial-community analyses revealed that the Pseudomonas sp. was the only exoeletrogens found in the anode pots. Using a secondary design of HSPP, for a better water-level adjustment, the maximum power output of each plant was found to be approximately 27.1 mW m-2. During operation, high temperature resulted in low oxygen solubility, and low CCV as well. At this time, it is yet to be concluded whether the submerged water level significantly affects electricity generation.

A novel intervention of molecular hydrogen on the unbalance of the gut microbiome in opioid addiction: Experimental and human studies.

The gut-brain axis mediates the interaction pathway between microbiota and opioid addiction. In recent years, many studies have shown that molecular hydrogen has therapeutic and preventive effects on various diseases. This study aimed to investigate whether molecular hydrogen could serve as pharmacological intervention agent to reduce risks of reinstatement of opioid seeking and explore the mechanism of gut microbiota base on animal experiments and human studies. Morphine-induced conditioned place preference (CPP) was constructed to establish acquisition, extinction, and reinstatement stage, and the potential impact of H2 on the behaviors related to morphine-induced drug extinction was determined using both free accessible and confined CPP extinction paradigms. The effects of morphine on microbial diversity and composition of microbiota, as well as the subsequent changes after H2 intervention, were assessed using 16 S rRNA gene sequencing. Short-Chain Fatty Acids (SCFAs) in mice serum were detected by gas chromatography-mass spectrometry (GC-MS). Meanwhile, we also conducted molecular hydrogen intervention and gut microbiota testing in opioid-addicted individuals. Our results revealed that molecular hydrogen could enhance the extinction of morphine-related behavior, reducing morphine reinstatement. Gut microbes may be a potential mechanism behind the therapeutic effects of molecular hydrogen on morphine addiction. Additionally, molecular hydrogen improved symptoms of depression and anxiety, as well as gut microbial features, in individuals with opioid addiction. This study supports molecular hydrogen as a novel and effective intervention for morphine-induced addiction and reveals the mechanism of gut microbiota.

Antibiotic-induced severe cutaneous adverse reactions: a single-center retrospective study over ten years.

Objective: Severe cutaneous adverse reactions (SCARs) are rare but life-threatening, with antibiotics being the main cause. This retrospective study from a single center was designed to analyze the culprit drugs, clinical features and treatment outcomes of antibiotic-induced SCARs. Methods: We analyzed cases of antibiotic-induced SCARs in a tertiary hospital in China between January 2013 and January 2024, including Steven-Johnson syndrome (SJS) or Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) overlap, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). Descriptive analysis of the demographic characteristics, clinical manifestations, treatment and prognosis were carried out. Results: Among 354 cases of SCARs, 63 validated antibiotic-related cases were included. Cephalosporins (31.7%), penicillins (25.4%), and quinolones (19.0%) were the most common triggers for SCARs. Overall, liver (50.8%), lungs (31.7%), and kidneys (23.8%) were the most frequently affected organ in SCARs cases. Eight patients (28.6%) in the SJS/SJS-TEN overlap group and 8 patients (80.0%) in the TEN group received combination therapy of corticosteroids and IVIG. Patients with SCARs caused by penicillins or cephalosporins could receive alternative treatments such as lincomamides, quinolones, and tetracyclines. The mortality rate in the TEN group was the highest at 20.0%, followed by the SJS/SJS-TEN overlap group (7.1%), and no deaths were observed in the DRESS and AGEP groups. Conclusion: The identification of the culprit antibiotics and the application of alternative antibiotic therapies are crucial for the management of antibiotic-induced SCARs. If complicated underlying conditions and complications like advanced age, cancer and pneumonia coexist with SCARs, patients might be more at risk for mortality.

Identification and experimental validation of programmed cell death- and mitochondria-associated biomarkers in osteoporosis and immune microenvironment.

Background: Prior research has demonstrated that programmed cell death (PCD) and mitochondria assume pivotal roles in controlling cellular metabolism and maintaining bone cell equilibrium. Nonetheless, the comprehensive elucidation of their mode of operation in osteoporosis (OP) warrants further investigation. Therefore, this study aimed at analyzing the role of genes associated with PCD (PCD-RGs) and mitochondria (mortality factor-related genes; MRGs) in OP. Methods: Differentially expressed genes (DEGs) were identified by subjecting the GSE56815 dataset obtained from the Gene Expression Omnibus database to differential expression analysis and comparing OP patients with healthy individuals. The genes of interest were ascertained through the intersection of DEGs, MRGs, and PCD-RGs; these genes were filtered using machine learning methodologies to discover potential biomarkers. The prospective biomarkers displaying uniform patterns and statistically meaningful variances were identified by evaluating their levels in the GSE56815 dataset and conducting quantitative real-time polymerase chain reaction-based assessments. Moreover, the functional mechanisms of these biomarkers were further delineated by constructing a nomogram, which conducted gene set enrichment analysis, explored immune infiltration, generated regulatory networks, predicted drug responses, and performed molecular docking analyses. Results: Eighteen candidate genes were documented contingent upon the intersection between 2,354 DEGs, 1,136 MRGs, and 1,548 PCD-RGs. The biomarkers DAP3, BIK, and ACAA2 were upregulated in OP and were linked to oxidative phosphorylation. Furthermore, the predictive ability of the nomogram designed based on the OP biomarkers exhibited a certain degree of accuracy. Correlation analysis revealed a strong positive correlation between CD56dim natural killer cells and ACAA2 and a significant negative correlation between central memory CD4+ T cells and DAP3. DAP3, BIK, and ACAA2 were regulated by multiple factors; specifically, SETDB1 and ZNF281 modulated ACAA2 and DAP3, whereas TP63 and TFAP2C governed DAP3 and BIK. Additionally, a stable binding force was observed between the drugs (estradiol, valproic acid, and CGP52608) and the biomarkers. Conclusion: This investigation evidenced that the biomarkers DAP3, BIK, and ACAA2 are associated with PCD and mitochondria in OP, potentially facilitate the diagnosis of OP in clinical settings.

Application of the Biological Toxicity Effect Ratio (BER) Method for Advancing Water Quality Criteria Derivation.

Water quality criteria (WQC) serve as a scientific foundation for pollutant risk assessment and control in aquatic ecosystems. The development of regionally differentiated WQC tailored to specific regional characteristics has become an emerging trend. However, the current WQC is constrained by a lack of regional species toxicity data. To address these limitations, this study proposes the biological toxicity effect ratio (BER) method, which indirectly reflects the toxicity sensitivity of the overall aquatic ecosystem through the toxicity information on a limited number of species, enabling rapid WQC prediction. Using the established WQC in China and the USA as a case study, we combined mathematical derivation and data validation to evaluate the BER method. Among various species-taxon groups of freshwater organisms, planktonic crustaceans demonstrated the highest predictive accuracy. Our analysis further revealed that species toxicity sensitivity and regional variability jointly influence the prediction accuracy. Regardless of the evaluation indexes, planktonic crustaceans emerged as the most suitable species-taxon group for the BER method. Additionally, the BER method is particularly applicable to pollutants with conserved mechanisms across species. This study systematically explores the feasibility of using the BER method and offers new insights for deriving regionally differentiated WQC.

Prediction of CD8+T lymphocyte infiltration levels in gastric cancer from contrast-enhanced CT and clinical factors using machine learning.

BACKGROUND: CD8+ T lymphocyte infiltration is closely associated with the prognosis and immunotherapy response of gastric cancer (GC). For now, the examination of CD8 infiltration levels relies on endoscopic biopsy, which is invasive and unsuitable for longitude assessment during anti-tumor therapy. PURPOSE: This work aims to develop and validate a noninvasive workflow based on contrast-enhanced CT (CECT) images to evaluate the CD8+ T-cell infiltration profiles of GC. METHODS: GC patients were retrospectively and consecutively enrolled and randomly assigned to the training (validation) or test cohort at a 7:3 ratio. All patients were binary classified into the CD8-high (infiltrated proportion ≥ 20%) or CD8-low group (infiltrated proportion < 20%) group. A total of 1170 radiomics features were extracted from each presurgical CECT series. After feature selection, fifteen radiomics features were transmitted to three independent machine-learning models for the computation of predictive radiological scores. Multilayer perceptron (MLP) was applied to merge the radiological scores with clinical factors. The predictive efficacy of the radiological scores and of the combined model was evaluated by receiver operating characteristic curve, calibration curve, and decision curve analysis in both the training and test cohorts. RESULTS: A total of 210 patients were enrolled in this study (mean age: 63.22 ± 8.74 years, 151 men), and were randomly assigned to the training set (n = 147) or the test set (n = 63). The merged radiological score was correlated with CD8 infiltration in both the training (p = 1.8e-10) and test cohorts (p = 0.00026). The combined model integrating the radiological scores and clinical features achieved an area under the curve (AUC) value of 0.916 (95% CI: 0.872-0.960) in the training set and 0.844 (95% CI: 0.742-0.946) in the test set for classifying CD8-high GCs. The model was well-calibrated and exhibited net benefit over "treat-all" and"treat-none" strategies in decision curve analysis. CONCLUSIONS: Artificial intelligent systems combining radiological features and clinical factors could accurately predict CD8 infiltration levels of GC, which may benefit personalized treatment of GC in the context of immunotherapy.

DHA-enriched phosphatidylserine alleviates bisphenol A-induced liver injury through regulating glycerophospholipid metabolism and the SIRT1-AMPK pathway.

To investigate the alleviating effect and mechanism of the docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on bisphenol A (BPA)-induced liver injury in mice, the murine liver injury model was established by gavage of BPA (5 mg/kg) or co-administration of BPA and DHA-PS (50 mg/kg or 100 mg/kg) for 6 weeks. The results showed that after administration of 100 mg/kg DHA-PS, the liver index, serum levels of AST, ALT, TC, TG, NEFA, and LDL-C in mice were significantly decreased, while HDL-C was significantly increased. The LPS, IL-6, IL-1ß, TNF-α, and MDA levels in liver tissues were effectively down-regulated, and IL-10, SOD, GSH-Px, and CAT levels were effectively up-regulated. The H&E and Oil Red O staining results showed that liver damage was notably repaired and lipid deposition was notably reduced after DHA-PS administration. Furthermore, metabolomics and immunohistochemical studies revealed that DHA-PS mainly regulates glycerophospholipid metabolism and the SIRT1-AMPK pathway to improve metabolic disorders of the liver caused by BPA. Therefore, DHA-PS could potentially alleviate BPA-induced murine liver injury through suppressing inflammation and oxidative stress, and modulating lipid metabolism disorders.

DHA-enriched phosphatidylserine ameliorates cyclophosphamide-induced liver injury via regulating the gut-liver axis.

OBJECTIVE: This study explores the therapeutic effects and mechanisms of DHA-enriched phosphatidylserine (DHA-PS) on liver injury induced by cyclophosphamide (CTX) in mice, focusing on the gut-liver axis. METHODS: A mouse model was established by administering CTX (80 mg/kg) intraperitoneally for 5 days. DHA-PS (50 or 100 mg/kg) was administered for the next 7 days to assess its reparative impact on liver damage. RESULTS: The findings revealed significant improvements in liver biochemical indices, inflammatory markers, and oxidative stress levels in the mice treated with DHA-PS. Through non-targeted metabolomics analysis, DHA-PS mitigated CTX-induced metabolic disruptions by modulating lipid, amino acid, and pyrimidine metabolism. Immunofluorescence analysis further confirmed that DHA-PS reduced the expression of liver-associated inflammatory proteins by inhibiting the TLR4/NF-κB pathway. Additionally, DHA-PS restored the intestinal barrier, evidenced by adjustments in the levels of intestinal lipopolysaccharide (LPS), secretory immunoglobulin A (sIgA), and tight junction proteins (Claudin-1, Occludin, and ZO-1). It also improved gut microbiota balance by enhancing microbial diversity, increasing beneficial bacteria, and altering community structures. CONCLUSION: These results suggest that DHA-PS could be a potential therapeutic agent or functional food for CTX-induced liver injury through its regulation of the gut-liver axis.

Bitongqing Attenuates CIA Rats by Suppressing Macrophage Pyroptosis and Modulating the NLRP3/Caspase-1/GSDMD Pathway.

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis and inflammatory cell infiltration. The traditional Chinese medicine prescription, Bitongqing (BTQ) exhibited significant efficacy in the clinical treatment of RA. However, the potential therapeutic mechanisms of BTQ in treating RA have not been fully investigated. This study aims to elucidate the effect of BTQ on collagen-induced arthritis (CIA) rat macrophage pyroptosis, providing a theoretical basis for treating RA. Methods: This research employed liquid chromatography-mass spectrometry (LC-MS) to identify the primary components of BTQ. The therapeutic effects of BTQ were evaluated in a rat model of CIA. In vivo experiments were conducted using pathohistological staining, immunofluorescence, micro-CT, and Western blotting. Next, Mouse leukemia cells of monocyte macrophage cells (RAW264.7) were induced to undergo pyroptosis using lipopolysaccharide (LPS) and adenosine triphosphate (ATP), and the impact of BTQ on RAW264.7 macrophages was assessed through cell viability, immunofluorescence analysis, lactate dehydrogenase (LDH) secretion measurement, and Western blotting. Results: BTQ had a therapeutic effect on CIA rats, which was mainly manifested as a reduction in joint inflammation, foot swelling, bone erosion, and amelioration of pathological changes in these rats. Further studies revealed that BTQ inhibited the levels of cytokine production interleukin-18 (IL-18) and interleukin-1ß (IL-1ß), and likewise, it inhibited the expression of key proteins in the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) mediated pyroptosis in the synovial tissues of CIA rats. The results of in vitro experiments demonstrated that BTQ attenuated LDH secretion, decreased IL-18 and IL-1ß cytokine production, and downregulated expression of key proteins involved in the NLRP3-mediated pyroptosis on RAW264.7 macrophages. Conclusion: The therapeutic potential of BTQ in CIA lies in its ability to inhibit NLRP3-mediated macrophage pyroptosis, thereby suggesting a promising strategy for the treatment of RA.

Efficacy, Safety, and Immunogenicity of Subunit Respiratory Syncytial Virus Vaccines: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Respiratory syncytial virus (RSV) is garnering increasing attention, with a growing number of subunit RSV vaccines under active clinical investigation. However, comprehensive evidence is limited. METHODS: We conducted a comprehensive search across PubMed, Embase, the Cochrane Library, Web of Science, and ClinicalTrials.gov from database inception to 12 January 2024, focusing on published randomized controlled trials (RCTs). RESULTS: A total of 17 studies were included, encompassing assessments of efficacy (5 studies), safety (17 studies), and immunogenicity (12 studies) of RSV subunit vaccines. The pooled risk ratio (RR) for RSV-associated acute respiratory infection (RSV-ARI) with subunit vaccines was 0.31 (95% CI: 0.23-0.43), for RSV-associated lower respiratory tract infection (RSV-LRTI), it was 0.32 (95% CI: 0.22-0.44), and for severe RSV-LRTI (RSV-SLRTI), it was 0.13 (95% CI: 0.06-0.29). There was no significant difference in serious adverse events (SAEs) between the vaccine and placebo groups, with a pooled RR of 1.05 (95% CI: 0.98-1.14). The pooled standardized mean difference (SMD) for the geometric mean titer (GMT) of neutralizing antibodies was 2.89 (95% CI: 2.43-3.35). CONCLUSION: Subunit RSV vaccines exhibit strong efficacy, favorable safety profiles, and robust immunogenicity. Future research should focus on the cost-effectiveness of various vaccines to enhance regional and national immunization strategies.

Suicidal incidence and gender-based discrepancies in prolonged grief disorder: insights from a meta-analysis and systematic review.

Background: In the aftermath of bereavement, our research explores the subtleties of Prolonged Grief Disorder (PGD), focusing particularly on its correlation with suicidal behaviors and their variation across genders. This study seeks to elucidate the impact of gender on these behaviors among individuals suffering from PGD, thereby enhancing our understanding and facilitating the development of tailored therapeutic interventions. Methods: By November 24th, 2023, we had rigorously reviewed key databases such as PubMed, Web of Science, Cochrane Library, PsycINFO, and Embase. Independently, two researchers conducted detailed interviews and filled out questionnaires with participants to gather demographic information and record instances of prolonged grief disorder. The study also meticulously tracked occurrences of suicidal ideation, suicide attempts, suicide deaths, and self-injury among the participants. Results: The findings indicate that 22.34% of males reported suicidal ideation (95% CI: 21.33-23.35), a figure that rises to 26.84% among females (95% CI: 25.99-27.69). Notably, 12.11% of males attempted suicide (95% CI: 11.49-12.72), marginally surpassing the 9.60% observed in females (95% CI: 9.17-10.04). More striking disparities were observed in suicide deaths, with rates for males at 3.66% (95% CI: 3.32-4.00) compared to a notably higher 7.12% for females (95% CI: 6.44-7.81). Furthermore, the incidence of self-injury was lower among males, at 2.48% (95% CI: 2.03-2.94), than in females, who reported a rate of 5.09% (95% CI: 4.69-5.49). These patterns underscore the critical need for gender-specific interventions aimed at reducing these significant disparities. Conclusion: This study distinctly underscores the profound impact of gender on the manifestation of suicidal behaviors in individuals afflicted with prolonged grief disorder. It reveals that females are more prone to suicidal ideation, self-injury, and suicide deaths, while males predominantly exhibit a higher incidence of suicide attempts and risk-taking behaviors. These unmediated trends highlight the necessity for gender-specific clinical interventions tailored to address particular behaviors and modify prevalent patterns that typically resist conventional approaches. Systematic review registration: PROSPERO (york.ac.uk), identifier CRD42023480035.

Chinese national clinical practice guidelines on prevention, diagnosis and treatment of early colorectal cancer.

BACKGROUND: The incidence and mortality of colorectal cancer (CRC) in China are increasing in recent years. The clarified pathogenesis and detectable precancerous lesions of CRC make it possible to prevent, screen, and diagnose CRC at an early stage. With the development of endoscopic and surgical techniques, the choice of treatment for early CRC is also worth further discussion, and accordingly, a standard follow-up program after treatment needs to be established. METHODS: This clinical practice guideline (CPG) was developed following the recommended process of the World Health Organization, adopting Grading of Recommendations Assessment, Development and Evaluation (GRADE) in assessing evidence quality, and using the Evidence to Decision framework to formulate clinical recommendations, thereby minimizing bias and increasing transparency of the CPG development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guides to ensure the guideline's completeness and transparency. RESULTS: This CPG comprises 46 recommendations concerning prevention, screening, diagnosis, treatment, and surveillance of CRC. In these recommendations, we have indicated protective and risk factors for CRC and made recommendations for chemoprevention. We proposed a suitable screening program for CRC based on the Chinese context. We also provided normative statements for the diagnosis, treatment, and surveillance of CRC based on existing clinical evidence and guidelines. CONCLUSIONS: The 46 recommendations in this CPG are formed with consideration for stakeholders' values and preferences, feasibility, and acceptability. Recommendations are generalizable to resource-limited settings with similar CRC epidemiology pattern as China.