Mechanisms of chondrocyte cell death in osteoarthritis: implications for disease progression and treatment.

Osteoarthritis (OA) is a chronic joint disease characterized by the degeneration, destruction, and excessive ossification of articular cartilage. The prevalence of OA is rising annually, concomitant with the aging global population and increasing rates of obesity. This condition imposes a substantial and escalating burden on individual health, healthcare systems, and broader social and economic frameworks. The etiology of OA is multifaceted and not fully understood. Current research suggests that the death of chondrocytes, encompassing mechanisms such as cellular apoptosis, pyroptosis, autophagy, ferroptosis and cuproptosis, contributes to both the initiation and progression of the disease. These cell death pathways not only diminish the population of chondrocytes but also exacerbate joint damage through the induction of inflammation and other deleterious processes. This paper delineates the morphological characteristics associated with various modes of cell death and summarizes current research results on the molecular mechanisms of different cell death patterns in OA. The objective is to review the advancements in understanding chondrocyte cell death in OA, thereby offering novel insights for potential clinical interventions.

Copper metabolism in osteoarthritis and its relation to oxidative stress and ferroptosis in chondrocytes.

Ferroptosis, an iron-ion-dependent process of lipid peroxidation, damages the plasma membrane, leading to non-programmed cell death. Osteoarthritis (OA), a prevalent chronic degenerative joint disease among middle-aged and older adults, is characterized by chondrocyte damage or loss. Emerging evidence indicates that chondrocyte ferroptosis plays a role in OA development. However, most research has concentrated on ferroptosis regulation involving typical iron ions, potentially neglecting the significance of elevated copper ions in both serum and joint fluid of patients with OA. This review aims to fill this gap by systematically examining the interplay between copper metabolism, oxidative stress, ferroptosis, and copper-associated cell death in OA. It will provide a comprehensive overview of copper ions' role in regulating ferroptosis and their dual role in OA. This approach seeks to offer new insights for further research, prevention, and treatment of OA.

Exploration of the potential mechanism of Yiyi Tongfeng Formula in the treatment of acute gouty arthritis based on network pharmacology and molecular docking: A review.

The global prevalence of gout is on the rise. Yiyi Tongfeng Formula (YTF), a traditional herbal compound, has gained recognition for its efficacy in managing acute gouty arthritis (AGA). Despite its widespread use, the underlying mechanisms of YTF in AGA treatment remain largely undefined. This study employed network pharmacology and molecular docking to elucidate these mechanisms. We utilized the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, SymMap database, and various literature sources to identify active components and corresponding targets of YTF. Relevant AGA-associated targets were identified through the Genecards, Drugbank, Therapeutic Target Database, and Online Mendelian Inheritance in Man databases. A protein-protein interaction network was constructed to delineate interactions between YTF targets and AGA. Key ingredients and central targets were further analyzed using Cytoscape. Functional enrichment analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, were conducted via Metascape. Additionally, molecular docking studies were performed using PyMOL and AutoDock4. It was found that quercetin, kaempferol, and luteolin may be the main active components of YTF for AGA treatment. Gene Ontology enrichment analysis shows that the main biological processes involved are cellular responses to lipids, and inflammatory responses. Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggests the involvement of the IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and so on. The findings suggest a multi-faceted therapeutic approach of YTF in treating AGA, involving multiple components, targets, biological processes, and signaling pathways. This comprehensive mechanism offers a foundation for further experimental validation.

Cytokine Storm in COVID-19: Insight into Pathological Mechanisms and Therapeutic Benefits of Chinese Herbal Medicines.

Cytokine storm (CS) is the main driver of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) in severe coronavirus disease-19 (COVID-19). The pathological mechanisms of CS are quite complex and involve multiple critical molecular targets that turn self-limited and mild COVID-19 into a severe and life-threatening concern. At present, vaccines are strongly recommended as safe and effective treatments for preventing serious illness or death from COVID-19. However, effective treatment options are still lacking for people who are at the most risk or hospitalized with severe disease. Chinese herbal medicines have been shown to improve the clinical outcomes of mild to severe COVID-19 as an adjunct therapy, particular preventing the development of mild to severe ARDS. This review illustrates in detail the pathogenesis of CS-involved ARDS and its associated key molecular targets, cytokines and signalling pathways. The therapeutic targets were identified particularly in relation to the turning points of the development of COVID-19, from mild symptoms to severe ARDS. Preclinical and clinical studies were reviewed for the effects of Chinese herbal medicines together with conventional therapies in reducing ARDS symptoms and addressing critical therapeutic targets associated with CS. Multiple herbal formulations, herbal extracts and single bioactive phytochemicals with or without conventional therapies demonstrated strong anti-CS effects through multiple mechanisms. However, evidence from larger, well-designed clinical trials is lacking and their detailed mechanisms of action are yet to be well elucidated. More research is warranted to further evaluate the therapeutic value of Chinese herbal medicine for CS in COVID-19-induced ARDS.

Disparate External Electric Field Effect on the Adsorption and Shear Behavior of Monovalent and Trivalent Ions in Electrolyte Solution.

Reducing friction is of great interest, and an external potential applied to the friction pair can regulate lubricity. Electrochemical atomic force microscopy (EC-AFM) is used to study the tribological and adsorption behavior of monovalent and trivalent ionic solutions between charged surfaces. An opposite trend of coefficient of friction (COF) and normal force that varies with the applied electric potential is witnessed. Direct force measurements and theoretical models have disclosed that, for the NaCl solution, the negative electric field reduces the COF by increasing cation adsorption. As for LaCl3 solution, the positive electric field promotes the primary adsorption of anions on HOPG, resulting in the disappearance of the attractive ion-ion correlation between the trivalent ions, thereby reducing the COF. The shear behavior of adsorbed ions in electrolyte solution is sensitive to their valence, because of their different surface force contribution. The study further provides a framework to optimize the design of hydration lubrication.

Data-driven approaches linking wastewater and source estimation hazardous waste for environmental management.

Industrial enterprises are major sources of contaminants, making their regulation vital for sustainable development. Tracking contaminant generation at the firm-level is challenging due to enterprise heterogeneity and the lack of a universal estimation method. This study addresses the issue by focusing on hazardous waste (HW), which is difficult to monitor automatically. We developed a data-driven methodology to predict HW generation using wastewater big data which is grounded in the availability of this data with widespread application of automatic sensors and the logical assumption that a correlation exists between wastewater and HW generation. We created a generic framework that used representative variables from diverse sectors, exploited a data-balance algorithm to address long-tail data distribution, and incorporated causal discovery to screen features and improve computation efficiency. Our method was tested on 1024 enterprises across 10 sectors in Jiangsu, China, demonstrating high fidelity (R² = 0.87) in predicting HW generation with 4,260,593 daily wastewater data.

Interpretable machine learning reveals microbiome signatures strongly associated with dairy cow milk urea nitrogen.

The gut microbiome plays an important role in the healthy and efficient farming of dairy cows. However, high-dimensional microbial information is difficult to interpret in a simplified manner. We collected fecal samples from 161 cows and performed 16S amplicon sequencing. We developed an interpretable machine learning framework to classify individuals based on their milk urea nitrogen (MUN) concentrations. In this framework, we address the challenge of handling high-dimensional microbial data imbalances and identify 9 microorganisms strongly correlated with MUN. We introduce the Shapley Additive Explanations (SHAP) method to provide insights into the machine learning predictions. The results of the study showed that the performance of the machine learning model improved (accuracy = 72.7%) after feature selection on high-dimensional data. Among the 9 microorganisms, g__Firmicutes_unclassified had the greatest impact in the model. This study provides a reference for precision animal husbandry.

Developing quality indicators for cancer hospitals in China: a national modified Delphi process.

OBJECTIVE: Although demand and supply of cancer care have been rapidly increasing in recent decades, there is a lack of systemic quality measurement for cancer hospitals in China. This study aimed to develop a set of core indicators for measuring quality of care for cancer hospitals in China. DESIGN: The development of quality indicators was based on a literature review and a two-round modified Delphi survey. The theoretical framework and initial indicators were identified through the comprehensive literature review, and the selection of quality indicators relied on experts' consensus on the importance and feasibility of indicators by the modified Delphi process. In addition, indicator weight was identified using the analytical hierarchical process method and percentage weight method. SETTING AND PARTICIPANTS: A panel of leading experts including oncologists, cancer care nurses, quality management experts from various regions of China were invited to participate in the two-round modified Delphi process from October to December 2020. A total of 25 experts completed the two-round modified Delphi process. RESULTS: The experts reached consensus on a set of 47 indicators, comprising 17 structure indicators, 19 process indicators and 11 outcome indicators. Experts gave much higher weight to outcome indicators (accounting for 53.96% relative weight) than to structure (16.34%) and process (29.70%) indicators. In addition, experts also showed concerns and gave suggestions on data availability of specific outcome indicators. CONCLUSIONS: Drawing on the comprehensive literature review and the modified Delphi process, this study developed a core set of quality indicators that can be used to evaluate quality performance of cancer hospitals. This is helpful in supporting quality cancer care in China and will provide new insights into the systemic measurement of cancer care internationally.

Efficiency and safety of dual pathway inhibition for the prevention of femoropopliteal artery restenosis in repeated endovascular interventions.

OBJECTIVE: There is a lack of consensus regarding the optimal strategy for evaluating the efficiency and safety of dual-pathway inhibition (DPI) in preventing femoropopliteal restenosis in patients undergoing repeated endovascular interventions. Despite several therapeutic interventions available for preventing femoropopliteal restenosis post repeated endovascular interventions, the ideal strategy, particularly evaluating the efficacy and safety of DPI, remains a matter of debate. METHODS: From January 2015 to September 2021, patients who underwent repeated endovascular interventions for femoropopliteal restenosis were compared with those who underwent DPI or dual antiplatelet therapy (DAPT) after surgery using a propensity score-matched analysis. The primary outcome was clinically driven target lesion revascularization (CD-TLR). The principal safety outcome was a composite of major bleeding and clinically relevant non-major (CRNM) bleeding. To further enhance the rigor, Kaplan-Meier plots, Cox proportional hazards modeling, and sensitivity analyses, as well as subgroup analyses were employed, reducing potential confounders. RESULTS: A total of 441 patients were included in our study, of whom 294 (66.7%) received DAPT and 147 (33.1%) received DPI, with 114 matched pairs (mean age, 72.21 years; 84.2% male). Cumulative probability of CD-TLR at 36 months in the DPI group (17%) trended lower than that in the DAPT group (32%) (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.26-0.78; P =.004). The cumulative probability of freedom from CD-TLR at 36 months in the DPI group was 83%. No significant difference was observed in the composite outcome of major or CRNM bleeding between the DPI and DAPT groups (HR, 1.26; 95% CI, 0.34 to 4.69; P = .730). The DPI group was associated with significantly lower rates of CD-TLR in the main subgroup analyses of diabetes (P = .001), previous smoking history (P = .008), longer lesion length (>10 cm) (P = .003), and treatment with debulking strategy (P = .003). CONCLUSIONS: In our investigation focused on CD-TLR, we found that DPI exhibited a significant reduction in the risk of reintervention compared with other treatment modalities. This underscores the potential of DPI as a viable therapeutic strategy in preventing reinterventions. Moreover, our assessment of safety outcomes revealed that the bleeding risks associated with DPI were on par with DAPT, thereby not compromising patient safety. These findings pave the way for potential broader clinical implications, emphasizing the effectiveness and safety of DPI in the context of reducing reintervention risks.

Transbrachial Artery as Single or Combined Approach for Complex Interventions in Patients with Peripheral Artery Disease.

BACKGROUND: This study aimed to assess the safety and efficacy of the transbrachial approach as a single or combined procedure for complex interventions in peripheral artery disease (PAD). METHODS: Between March 2011 and April 2021, 169 patients with PAD underwent endovascular therapy via the transbrachial approach as a single or dual procedure. Univariate and multivariate analyses were performed to evaluate the predictors of adverse events at the brachial puncture site. All demographic, clinical, and perioperative data were acquired from electronic medical records and retrospectively analyzed. RESULTS: Brachial artery access was used alone and in combination in 87 and 82 patients, respectively. Patients in the combined-approach group underwent more intraoperative stent implantations and had more vascular closure devices (VCD). Multivariate logistic regression analysis revealed that hypertension was an independent factor for higher rates of brachial puncture site adverse events (odds ratio, 4.76; 95% confidence interval, 1.33-16.97; P = 0.016). Brachial artery access-site complications occurred in 26 patients, including 6 (23.1%) major and 20 (76.9%) minor entry-site complications. Entry-site complications were observed in 21 (16.8%) and 5 (11.4%) patients assigned to manual compression and VCD groups, respectively. There were no significant intergroup differences in the incidence of major or minor complications. Interestingly, patients assigned to the VCD group did not experience major entry-site complications. CONCLUSIONS: The transbrachial approach, as a single or combined procedure, is a safe alternative to complex interventions in patients with PAD. Complications of brachial access progressively decrease with improved blood pressure control.

Rumen Fermentation Parameters Prediction Model for Dairy Cows Using a Stacking Ensemble Learning Method.

Volatile fatty acids (VFAs) and methane are the main products of rumen fermentation. Quantitative studies of rumen fermentation parameters can be performed using in vitro techniques and machine learning methods. The currently proposed models suffer from poor generalization ability due to the small number of samples. In this study, a prediction model for rumen fermentation parameters (methane, acetic acid (AA), and propionic acid (PA)) of dairy cows is established using the stacking ensemble learning method and in vitro techniques. Four factors related to the nutrient level of total mixed rations (TMRs) are selected as inputs to the model: neutral detergent fiber (NDF), acid detergent fiber (ADF), crude protein (CP), and dry matter (DM). The comparison of the prediction results of the stacking model and base learners shows that the stacking ensemble learning method has better prediction results for rumen methane (coefficient of determination (R2) = 0.928, root mean square error (RMSE) = 0.968 mL/g), AA (R2 = 0.888, RMSE = 1.975 mmol/L) and PA (R2 = 0.924, RMSE = 0.74 mmol/L). And the stacking model simulates the variation of methane and VFAs in relation to the dietary fiber content. To demonstrate the robustness of the model in the case of small samples, an independent validation experiment was conducted. The stacking model successfully simulated the transition of rumen fermentation type and the change of methane content under different concentrate-to-forage (C:F) ratios of TMR. These results suggest that the rumen fermentation parameter prediction model can be used as a decision-making basis for the optimization of dairy cow diet compositions, rapid screening of methane emission reduction, feed beneficial to dairy cow health, and improvement of feed utilization.

Replacing alfalfa hay with industrial hemp ethanol extraction byproduct and Chinese wildrye hay: Effects on lactation performance, plasma metabolites, and bacterial communities in Holstein cows.

This trial was designed to investigate the effects of industrial hemp ethanol extraction byproduct (IHEEB) and Chinese wildrye hay (CWH) replacement of alfalfa hay (AH) on digestibility, and lactation performance, plasma metabolites, ruminal fermentation, and bacterial communities in Holstein dairy cows. Nine healthy multiparous Holstein cows (parity = 3) with similar body weights (584 ± 12.3 kg), days in milk (108 ± 11.4), and milk yields (30 ± 1.93 kg; all mean ± standard deviation) were used in a replicated 3 × 3 Latin square design with 3 periods of 21 d. During each period, each group consumed 1 of 3 diets: (1) 0% IHEEB (0IHEEB); (2) 6.0% IHEEB and 1.7% Chinese wildrye hay (6IHEEB); (3) 10.8% IHEEB and 4.3% Chinese wildrye hay (11IHEEB). The diets in each group were isocaloric and isonitrogenous, with similar contents of concentrate and silage but different ratios of IHEEB and CWH to replace AH. The results showed that increasing the substitute did not affect the total-tract apparent nutrient digestibility. There was no difference in lactation performance of dairy cows fed the three diets, except for the cows' somatic cell count (SCC), which decreased with the increase in the amount of the substitute. Cannabidiol and tetrahydrocannabinol were not detected in milk samples of dairy cows in the different treatment groups. 6IHEEB and 11IHEEB-fed cows showed a linear decrease in total volatile fatty acids (VFA) and butyrate compared to the 0IHEEB cows. Plasma IL-1ß content quadratically decreased with feeding IHEEB and CWH, and other blood parameters were unaffected. The rumen fluid's relative abundances of Bacteroidota, Fibrobacterota, and Prevotellaceae quadratically increased, while Firmicutes tended to decrease quadratically as the substitution increased. Feeding IHEEB and CWH linearly increased the relative abundances of Firmicutes, Lachnospiraceae, Monoglobaceae, and Butyricicoccaceae in the feces. As the substitution increased, the cost of dairy farming was reduced. In summary, substituting AH with IHEEB and CWH in diets did not affect the total-tract apparent nutrient digestibility, improved milk composition, and plasma immune indices. It changed the bacterial composition in rumen fluid and feces and improved dairy farming benefits.

Clostridium butyricum alleviates LPS-induced acute immune stress in goats by regulating bacterial communities and blood metabolites.

The mitigation and prevention of acute immune stress are essential for livestock production. Clostridium butyricum (C. butyricum) has shown positive effects in stabilizing intestinal microbiota disorders, improving immune function and inhibiting disease development, but its effects on ruminants are unclear. Therefore, the current trial hypothesized that C. butyricum could improve goats' immune function and antioxidant capacity by regulating bacterial communities and blood metabolism and effectively alleviating the acute immune stress induced by Lipopolysaccharides (LPS). Sixteen healthy goats were fed C. butyricum for 70 days, and the goats were challenged with LPS on day 71. Blood and feces were collected at 0 h and 6 h after the challenge to evaluate the effects of C. butyricum on their intestinal microbiota, immune function, antioxidant function, and plasma metabolites. The results showed that C. butyricum had no significant effect on plasma biochemical parameters at the beginning of the LPS challenge. However, supplementation with C. butyricum increased plasma levels of IgA, IgG, T-SOD, and T-AOC (P < 0.05), but TNF-α, IL-6, and MDA were decreased (P < 0.05). In contrast, IL-10 showed an increasing trend (P < 0.10). Rectal microbiota analysis showed that C. butyricum significantly increased the relative abundance of Epsilonbacteraeota at the phylum level of goats; at the genus level, the relative abundances of Campylobacter and Anaerorhabdus]_furcosa_group were also significantly increased (P < 0.05). Christensenellaceae_R-7_group as the dominant microbiota also showed a significant increase in their abundance values, while Clostridium and Lachnospiraceae_UCG-001 were significantly lower (P < 0.05). When the LPS challenge continued up to 6 h, dietary supplementation with C. butyricum still resulted in significantly higher plasma concentrations of IgA, IL-10, and T-SOD in goats than in the control group, reducing TNF-α levels (P < 0.05). In addition, plasma levels of T-CHOL and LDL were significantly reduced, and the expression of d-proline was significantly upregulated according to metabolomic analysis (P < 0.05). In conclusion, dietary supplementation with C. butyricum helped optimize the expression of bacterial communities and plasma metabolites to enhance the ability of goats to alleviate acute immune stress.

Assessment of factors affecting the diurnal variations of atmospheric PAHs based on a numerical simulation.

Atmospheric polycyclic aromatic hydrocarbons (PAHs) are a type of organic pollutants that seriously endanger human health. Obtaining the diurnal variations of PAHs and clarifying their impact mechanisms are significant for the government to formulate targeted prevention and control measures. However, the influencing factors that dominate the diurnal variations of common PAHs are currently unclear. In order to solve this problem, 16 PAHs selected by the United States Environmental Protection Agency (EPA) as priority-controlled pollutants were simulated with high resolution. The simulation results were validated based on diurnal observations in the vertical direction. Although the model underestimated the particle-phase concentrations of most components, it captured their diurnal variations fairly well. In addition, we assessed the factors affecting the diurnal variations of PAHs with sensitivity tests, including chemical reactions and atmospheric diffusion. The results showed that the transforming ratios of PAHs by oxidants were higher during the day than that at night due to the dominant reactions with OH radical. Atmospheric dispersion affected the vertical distribution of PAHs, which resulted in higher day/night ratios at high altitudes than near the ground. We also compared the strength of atmospheric diffusion and chemical reaction on the diurnal trends of PAHs. Near the ground, atmospheric diffusion was the most dominant factor in determining their diurnal trends. At high altitudes, their diurnal trends were determined by a combination of atmospheric diffusion and chemical reactions. These findings can provide a comprehensive understanding of the diurnal variations of common PAHs, which are informative for the prevention and control of PAHs pollution.

Sex-related differences in the effect of rotational thrombectomy for thrombus-containing lower limbs ischemic lesions.

BACKGROUND: To assess the immediate effect and factors affecting the efficacy of rotational thrombectomy (RT) in patients with thrombus-containing lower-limb ischaemic lesions. METHODS: Patients were retrospectively divided into two groups: RT and RT+ CDT (Catheter-directed thrombolysis). The RT group included patients in whom intraoperative thrombus aspiration was successful, while the RT + CDT group included patients in whom intraoperative thrombus aspiration was less effective and remedial CDT treatment was used. The primary outcome was the immediate effect of RT on thrombus-containing lower-limb ischaemic lesions. RESULTS: From May 2015 to July 2021, 170 patients (113 men, 57 women; mean age, 74.0 years) with thrombus-containing lower-limb ischaemic lesions were treated in our centre. Of these patients, 113 received RT only, while 57 received RT + CDT. There were no significant intergroup differences in terms of age, disease duration, or comorbidities, but a higher proportion of male patients and higher preoperative plasma D-dimer levels (1.23 vs. 0.84; p = .017) was observed in the RT + CDT group. There were no significant intergroup differences in terms of diagnosis, lesion characteristics, lesion location, or lesion length. Multivariate logistic regression analysis revealed that male sex (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.098-6.410; p = .030) and poor distal runoff (OR, 2.94; 95% CI, 1.439-5.988; p = .003) were associated with higher rates of additional CDT. Male patients also had a significantly longer onset time, more thrombotic occlusions, and a greater frequency of in-stent restenosis. CONCLUSIONS: RT alone or with CDT is a feasible primary treatment option for thrombus debulking. Sex significantly influences the effect of RT on thrombus-containing lower-limb ischaemic lesions.

Genesis of Superlow Friction in Strengthening Si-DLC/PLC Nanostructured Multilayer Films for Robust Superlubricity at Ultrahigh Contact Stress.

Diamond-like carbon (DLC) films have significant potential to provide solutions for the friction reduction and the lubricity problem of mechanical moving friction pairs. However, the realization of excellent lubrication or even superlubricity and long lifetime under heavy loading conditions is still a great challenge, which is crucial for the applications of DLC in harsh environments. Here, we construct a group of property-strengthening Si-DLC/PLC multilayer films that could withstand ultrahigh contact stresses and achieve robust superlubricity. Under a peak Hertz contact stress of up to 2.37 GPa, the setup of a bilayer thickness of 324 nm enables the multilayered film (an overall film thickness of 1.53 µm) to achieve a superlow coefficient of friction toward 0.001 and an ultralow wear rate of 3.13 × 10-9 mm3/Nm. An alternating load reciprocating friction test emphasizes that this strengthening nanostructured Si-DLC/PLC multilayer possesses a kind of load self-adaptation because of its in situ nanoclustering transformation and local ordering of sp2-C phases at the sliding interface. The genesis of self-adaptation to the applied load is evaluated comprehensively to reveal its strengthening and toughening structural characteristics and robustness of the near-zero friction and wear features. The findings provide a significant design criterion for carbon-based solid lubricants applicable to harsh loading environments.

Clostridium butyricum improves the intestinal health of goats by regulating the intestinal microbial community.

Clostridium butyricum, as a probiotic with a variety of active products, has been widely used to improve the intestinal health of humans and animals. Previous studies had demonstrated that Clostridium butyricum exhibited potential protective and positive effects in human disease research and animal production by producing a variety of beneficial substances, such as intestinal inflammation, the intestinal epithelial barrier, metabolic diseases, and regulation of the gut microbiota. Therefore, we hypothesized that dietary Clostridium butyricum supplementation could improve gut health in fattening goats by modulating gut microbiota. However, it is unclear whether Clostridium butyricum can reach the intestine through the rumen, so 15 healthy Albas goats were selected and randomly divided into 3 treatments with 5 replicates in each group. The groups were divided as follows: control group (CON: basal diet), rumen-protected Clostridium butyricum group (RPCB: basal diet plus 1.0 × 109 CFU/kg Clostridium butyricum coated with hydrogenated fat), and Clostridium butyricum group (CB: basal diet plus 1.0 × 109 CFU/kg Clostridium butyricum). The experiment was slaughtered after a 70-day growth test, and the jejunal mucosa and intestinal contents of the goats were collected to determine tight junction proteins related genes expression and 16S rDNA microbial sequencing analysis to evaluate the intestine health. The results showed that dietary supplementation with Clostridium butyricum significantly increased the expression of the Claudin-4 gene of the jejunal mucosa (P < 0.05) and had a trend toward a significant increase in the Occludin gene (0.05 < P < 0.10). However, Clostridium butyricum had no significant effect on the expression of intestinal inflammatory factors (P > 0.10). In addition, the relative fractionation of Clostridium and Clostridiaceae_unclassified in the gut microbiota at the genus level decreased significantly compared with controls (P < 0.05). The results of the analysis of the level of Clostridium species showed that Clostridium butyricum only existed in the treatment group. And the correlation results showed that Occludin and Claudin-4 genes were positively correlated with Sharppea and Clostridium butyricum, and negatively correlated with Clostridium (P < 0.05). Supplementing Clostridium butyricum in the diet did not significantly affect the intestinal immune function of goats, while regulation of the intestinal microbiota was associated with improving the intestinal epithelial barrier.

Efficacy and safety evaluation of rivaroxaban vs. warfarin among non-valvular atrial fibrillation patients undergoing lower extremity revascularization.

Introduction: The efficacy and safety of antithrombotic strategies remain uncertain in patients with atrial fibrillation undergoing lower-extremity revascularisation. Materials and methods: Between January 2011 and November 2021, 319 patients with atrial fibrillation after lower-extremity revascularisation received rivaroxaban or warfarin treatment as anticoagulation regimens with different antiplatelet therapy strategies. The primary efficacy outcome was the composite of acute limb ischaemia, major amputation for vascular causes, myocardial infarction, ischaemic stroke, clinically driven target lesion revascularisation, and death from vascular causes. The safety outcomes were major bleeding events according to the International Society on Thrombosis and Haemostasis classification criteria. Results: A total of 178 and 141 patients received rivaroxaban and warfarin treatments, respectively, after revascularisation with or without antiplatelet regimens. The incidence of the primary efficacy outcome at 36 months in the rivaroxaban group (44 patients, 24.7%) tended to be lower than that in the warfarin group (43 patients, 30.5%) (hazard ratio, 0.870; 95% confidence interval, 0.565-1.339; P = 0.527). The incidence of the secondary efficacy outcomes decreased in the rivaroxaban group (56 patients, 31.6%) compared with that in the warfarin group (61 patients, 43.2%). Major bleeding events occurred in three patients (1.7%) in the rivaroxaban group and five patients (3.5%) in the warfarin group; no significant difference in fatal or intracranial bleeding was observed between the groups. Conclusion: This study describes practical experience regarding the use of rivaroxaban and warfarin in patients with peripheral arterial disease complicated by non-valvular atrial fibrillation following endovascular intervention. The efficacy and safety outcomes do not differ significantly between rivaroxaban and warfarin.

[Research on function of Feilike Mixture in stopping cough, eliminating phlegm and relieving asthma based on animal experiments and network pharmacology].

This study observed the pharmacological effects of Feilike Mixture(FLKM) in stopping cough, eliminating phlegm, and relieving asthma through animal experiments, and explored its mechanism using network pharmacology. The antitussive effect was detected by citric acid-induced guinea pig cough model, the expectorant effect by mouse phenol red excretion experiment and lipopolysaccharide-induced mucus hypersecretion rat model, and the antiasthmatic effect by histamine phosphate-induced guinea pig asthma model. The chemical components of FLKM were collected by TCMSP, TCMID, TCMIP, and BATMAN-TCM databases and literature search, and the potential active components were screened through ADMETlab 2.0. The targets of FLKM were obtained by STITCH, SwissTargetPrediction, and TCMSP, and the symptom targets of cough, phlegm, and asthma were acquired through SymMap database. After taking the intersection of FLKM targets and symptom targets, this study used the OECloud tool to perform Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. RESULTS:: demonstrated that FLKM 0.43-1.74 g·kg~(-1) reduced the number of coughs in guinea pigs within 3 min(P<0.05, P<0.01), and FLKM 6-12 g·kg~(-1) increased the tracheal phenol red excretion in mice(P<0.01). Moreover, FLKM 2-8 g·kg~(-1) inhibited the number of goblet cells(P<0.05, P<0.01), and FLKM 7-11.2 g·kg~(-1) prolonged the incubation period of asthma(P<0.05). A total of 115 potential active components and 910 targets of FLKM were obtained through network pharmacological analysis. FLKM had 27, 12, and 7 targets for stopping cough, eliminating phlegm, and relieving asthma, respectively. The GO and KEGG enrichment analysis found that there were commonalities and characteristics, among which cytokine-cytokine receptor interaction and infectious disease-related signaling pathway were shared. FLKM has a good effect of stopping cough, eliminating phlegm, and relieving asthma through animal experiments and network pharmacology.

Effects of Dietary Supplementation With Clostridium butyricum on Growth Performance, Apparent Digestibility, Blood Metabolites, Ruminal Fermentation and Bacterial Communities of Fattening Goats.

Clostridium butyricum (C. butyricum) is currently widely used to improve the body health and productive performance of monogastric animals. However, there have been few reports on the effects and specific mechanism of action of Clostridium butyricum in ruminants. This study aimed to investigate the effects of Clostridium butyricum supplementation on the growth performance and digestive microbiota of fattening goats. Twenty-four healthy male Albas goats (body weight = 22 ± 2.03 kg) were randomly divided into 3 treatment groups with eight goats in each group. The treatments were as follows: control group (CON) (basal diet, concentrate to forage ratio = 65:35); low-dose Clostridium butyricum (LCB) (basal diet plus 2.0 × 108 CFU/kg Clostridium butyricum); and high-dose Clostridium butyricum (HCB) (basal diet plus 1.0 × 109 CFU/kg Clostridium butyricum). The experiment lasted for 8 weeks after a 2-week adaptation period. Therefore, growth performance and rumen and rectum microbiota were evaluated in goats supplemented with Clostridium butyricum and its metabolites. The results showed that dietary supplementation with Clostridium butyricum significantly increased the pH (P < 0.05), but had no significant effect on growth performance (P > 0.05). Compared with the control group, dietary Clostridium butyricum supplementation significantly increased the relative abundance of Prevotella_1, Christensenellaceae AE_R-7_Group and Prevotellaceae AE_UCG-003 (P < 0.05), and significantly decreased Succiniclasticum and Muribaculaceae_unclassified (P < 0.05). The relative abundance of Clostridium in the rumen was <1.0%. Moreover, 16S rDNA analysis showed that the fecal Clostridium or Clostridium butyricum count was significantly decreased (P < 0.05), and the relative abundance of Alistipes and Akkermansia was increased (P < 0.10) in the low-dose group compared with the control group. Supplementing Clostridium butyricum in a high-concentrate diet did not significantly affect the performance of goats, while regulation of the gastrointestinal microbiota and related metabolites was associated with rumen fermentation.