Therapeutic effect of Yinhuapinggan granules mediated through the intestinal flora in mice infected with the H1N1 influenza virus.

Objective: In this study, we examined the therapeutic effects of Yinhuapinggan granules (YHPGs) in influenza-infected mice. We also examined how YHPGs affect the composition of the intestinal flora and associated metabolites. Methods: We used the nasal drip method to administer the influenza A virus (IAV) H1N1 to ICR mice. Following successful model construction, the mice were injected with 0.9% sterile saline and low (5.5 g/kg), medium (11 g/kg), and high (22 g/kg) doses of YHPGs. The pathological changes in the lungs and intestines were evaluated by gavage for 5 consecutive days. Detection of sIgA, IL-6, TNF-α, INF-γ, and TGF-ß cytokine levels in serum by enzyme-linked immunosorbent assay. Real-time fluorescence quantitative polymerase chain reaction and Western blot were used to measure the mRNA and protein expression of the tight junction proteins claudin-1, occludin, and zonula occludens-1 (ZO-1) in the colon. To assess the influence of YHPGs on the intestinal microbiota, feces were obtained from the mice for 16s rRNA sequencing, and short-chain fatty acids (SCFAs) were measured in the feces. Results: By reducing the production of pro-inflammatory cytokines and increasing the relative expression of claudin-1, occludin, and ZO-1 in colon tissues, YHPGs had a protective effect in tissues from the lungs and colon. When YHPGs were administered to mice with IAV infection, the relative abundance of Lactobacillus, Coprobacillus, Akkermansia, Prevotella, Oscillospira, and Ruminococcus increased, whereas the relative abundance of Desulfovibrio decreased. Conclusion: The therapeutic mechanism of YHPGs against IAV infection in mice may be underpinned by modulation of the structural composition of colonic bacteria and regulation of SCFA production.

Synergistic promotion of angiogenesis after intracerebral hemorrhage by ginsenoside Rh2 and chrysophanol in rats.

BACKGROUND: Intracerebral hemorrhage (ICH) is a debilitating condition characterized by the rupture of cerebral blood vessels, resulting in profound neurological deficits. A significant challenge in the treatment of ICH lies in the brain's limited capacity to regenerate damaged blood vessels. This study explores the potential synergistic effects of Ginsenoside Rh2 and Chrysophanol in promoting angiogenesis following ICH in a rat model. METHODS: Network pharmacology was employed to predict the potential targets and pathways of Ginsenoside Rh2 and Chrysophanol for ICH treatment. Molecular docking was utilized to assess the binding affinity between these compounds and their respective targets. Experimental ICH was induced in male Sprague-Dawley rats through stereotactic injection of type VII collagenase into the right caudate putamen (CPu). The study encompassed various methodologies, including administration protocols, assessments of neurological function, magnetic resonance imaging, histological examination, observation of brain tissue ultrastructure, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunofluorescence staining, Western blot analysis, and statistical analyses. RESULTS: Network pharmacology analysis indicated that Ginsenoside Rh2 and Chrysophanol may exert their therapeutic effects in ICH by promoting angiogenesis. Results from animal experiments revealed that rats treated with Ginsenoside Rh2 and Chrysophanol exhibited significantly improved neurological function, reduced hematoma volume, and diminished pathological injury compared to the Model group. Immunofluorescence analysis demonstrated enhanced expression of vascular endothelial growth factor receptor 2 (VEGFR2) and CD31, signifying augmented angiogenesis in the peri-hematomal region following combination therapy. Importantly, the addition of a VEGFR2 inhibitor reversed the increased expression of VEGFR2 and CD31. Furthermore, Western blot analysis revealed upregulated expression of angiogenesis-related factors, including VEGFR2, SRC, AKT1, MAPK1, and MAPK14, in the combination therapy group, but this effect was abrogated upon VEGFR2 inhibitor administration. CONCLUSION: The synergistic effect of Ginsenoside Rh2 and Chrysophanol demonstrated a notable protective impact on ICH injury in rats, specifically attributed to their facilitation of angiogenesis. Consequently, this research offers a foundation for the utilization of Ginsenosides Rh2 and Chrysophanol in medical settings and offers direction for the advancement of novel pharmaceuticals for the clinical management of ICH.

Efficacy of electroacupuncture therapy in patients with functional anorectal pain: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Some Chinese scholars have initially explored the efficacy of electroacupuncture at Baliao acupoint in patients with functional anorectal pain (FAP). However, their studies are performed in a single center, or the sample size is small. Therefore, we aim to further explore the efficacy of electroacupuncture at Baliao acupoint on the treatment of FAP. METHODS: In this multicenter randomized controlled trial, 136 eligible FAP patients will be randomly allocated into an electroacupuncture group or sham electroacupuncture group at a 1:1 ratio. This trial will last for 34 weeks, with 2 weeks of baseline, 4 weeks and 8 weeks of treatment, and 1, 3, and 6 months of follow-up. Outcome assessors and statisticians will be blind. The primary outcome will be clinical treatment efficacy, and secondary outcomes will be pain days per month, quality of life, psychological state assessment, anorectal manometry, pelvic floor electromyography, and patient satisfaction. DISCUSSION: Results of this trial will be contributed to further clarify the value of electroacupuncture at Baliao acupoint as a treatment for FAP in the clinic. TRIAL REGISTRATION: This trial has been registered in Chinese Clinical Trial Registry  https://www.chictr.org.cn/  (ChiCTR2300069757) on March 24, 2023.

Real-world evidence on treatment pattern, effectiveness, and safety of blinatumomab in Chinese patients with B-cell acute lymphoblastic leukemia.

Blinatumomab is efficacious in patients with B-cell acute lymphoblastic leukemia (B-ALL), yet limited real-world data exists in this context. This retrospective study provided real-world data on the treatment pattern, effectiveness, and safety of blinatumomab in Chinese patients with newly diagnosed (ND) and relapsed/refractory (R/R) B-ALL. Patients with B-ALL who received at least one dose of blinatumomab in frontline or R/R settings between August 2021 and June 2023 were included. The primary outcome was the treatment pattern of blinatumomab. Key secondary outcomes included complete remission (CR)/CR with incomplete blood cell recovery (CRi) rate, minimal residual disease (MRD) negativity, median event-free survival (EFS), and safety. The study included 96 patients with B-ALL; 53 (55.2%) patients were in the ND group and 43 (44.8%) patients were in the R/R group. The median treatment duration was one cycle (range: 1-5). Most patients underwent chemotherapies, allo-HSCT, or experimental CAR-T following blinatumomab. The ND patients using blinatumomab induction therapy achieved 100% CR/CRi rate; 87.2% achieved MRD negativity within two cycles of blinatumomab. In R/R re-induction patients, the CR/CRi rate was 50%; MRD negativity rate was 64.2%. In R/R patients using blinatumomab for consolidation, MRD negativity rate was 90.9%. The median EFS was not reached in both ND and R/R patients; 1-year EFS rate was 90.8% (95% CI: 67%, 97%) and 55.1% (95% CI: 30%, 74%), respectively. Grade ≥ 3 adverse events were observed in 12.5% patients. Blinatumomab was found to be effective with a tolerable safety profile in real world setting.

Exploring the Potential Mechanisms of Guanxinshutong Capsules in Treating Pathological Cardiac Hypertrophy based on Network Pharmacology, Computer-Aided Drug Design, and Animal Experiments.

Cardiovascular diseases (CVDs) are significant causes of morbidity and mortality worldwide, and pathological cardiac hypertrophy (PCH) is an essential predictor of many heart diseases. Guanxinshutong capsule (GXST) is a Chinese patent medicine widely used in the clinical treatment of CVD, In our previous research, we identified 111 compounds of GXST. In order to reveal the potential molecular mechanisms by which GXST treats PCH, this study employed network pharmacology methods to screen for the active ingredients of GXST in treating PCH and predicted the potential targets. The results identified 26 active ingredients of GXST and 110 potential targets for PCH. Through a protein-protein interaction (PPI) network, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we confirmed AKT1, MAPK1, and MAPK3 as the core proteins in GXST treatment of PCH, thus establishing the PI3K/AKT and MAPK signaling pathways as the significant mechanisms of GXST in treating PCH. The results of molecular docking (MD) demonstrate that flavonoid naringenin and diterpenoid tanshinone iia have the highest binding affinity with the core protein. Before performing molecular dynamics simulations (MDSs), the geometric structure of naringenin and tanshinone iia was optimized using density functional theory (DFT) at the B97-3c level, and RESP2 atomic charge calculations were carried out at the B3LYP-D3(BJ)/def2-TZVP level. Further MDS results demonstrated that in the human body environment, the complex of naringenin and tanshinone iii with core proteins exhibited high stability, flexibility, and low binding free energy. Additionally, naringenin and tanshinone iia showed favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics and passed the drug similarity (DS) assessment. Ultrasound cardiograms and cardiac morphometric measurements in animal experiments demonstrate that GXST can improve the PCH induced by isoproterenol (ISO). Protein immunoblotting results indicate that GXST increases the expression of P-eNOS and eNOS by activating the PI3K/AKT signaling pathway and the MAPK signaling pathway, further elucidating the mechanism of action of GXST in treating PCH. This study contributes to the elucidation of the key ingredients and molecular mechanisms of GXST in treating PCH.

Investigating the Mechanistic of Danhong Injection in Brain Damage Caused by Cardiac I/R Injury via Bioinformatics, Computer Simulation, and Experimental Validation.

OBJECTIVE: Cardiac ischemia-reperfusion (I/R) injury has negative effects on the brain and can even lead to the occurrence of ischemic stroke. Clinical evidence shows that Danhong injection (DHI) protects the heart and brain following ischemic events. This study investigated the mechanisms and key active compounds underlying the therapeutic effect of DHI against brain damage induced by cardiac I/R injury. METHODS: The gene expression omnibus database provided GSE66360 and GSE22255 data sets. The R programming language was used to identify the common differentially expressed genes (cDEGs). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed, and protein-protein interaction network was constructed. Active compounds of DHI were collected from the Traditional Chinese Medicine Systems Pharmacology database. Molecular docking and molecular dynamics simulations were performed. The MMPBSA method was used to calculate the binding-free energy. The pkCSM server and DruLiTo software were used for Absorption, Distribution, metabolism, excretion, and toxicity (ADMET) analysis and drug-likeness analysis. Finally, in vitro experiments were conducted to validate the results. RESULTS: A total of 27 cDEGs had been identified. The PPI and enrichment results indicated that TNF-α was considered to be the core target. A total of 80 active compounds were retrieved. The molecular docking results indicated that tanshinone I (TSI), tanshinone IIA (TSIIA), and hydroxyl safflower yellow A (HSYA) were selected as core active compounds. Molecular dynamics verification revealed that the conformations were relatively stable without significant fluctuations. MMPBSA analysis revealed that the binding energies of TSI, TSIIA, and HSYA with TNF-α were -36.01, -21.71, and -14.80 kcal/mol, respectively. LEU57 residue of TNF-α has the highest contribution. TSI and TSIIA passed both the ADMET analysis and drug-likeness screening, whereas HSYA did not. Experimental verification confirmed that DHI and TSIIA reduced the expression of TNF-α, NLRP3, and IL-1ß in the injured H9C2 and rat brain microvascular endothelial cells. CONCLUSION: TNF-α can be considered to be a key target for BD-CI/R. TSIIA in DHI exerts a significant inhibitory effect on the inflammatory damage of BD-CI/R, providing new insights for future drug development.

Acupuncture Versus Biofeedback for Treatment of Functional Anorectal Pain.

BACKGROUND/AIMS: Functional anorectal pain is one of several types of functional anorectal disorders. In this study, we compared the effectiveness of acupuncture (intervention) and biofeedback (control) as treatment for patients with functional anorectal pain. MATERIALS AND METHODS: This prospective, single-center, randomized, and comparative study examined 68 patients with functional anorectal pain who were recruited from June 2017 to January 2019 at the Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Patients were randomly assigned to receive acupuncture or biofeedback. Patients in the acupuncture group received acupuncture at Zhongliao (BL33), Xialiao (BL34), Ganshu (BL18), Shenshu (BL23), and Dachangshu (BL25). Patients in the biofeedback group received pelvic floor biofeedback therapy, consisting of Kegel pelvic floor muscle training and electrical stimulation. Patients in both groups received 20 treatments over 4 weeks. The primary outcome was pain score on a visual analog scale, and the secondary outcomes were results from the MOS 36-item short-form health survey (SF-36) quality of life questionnaire, the self-rating depression scale, and the self-rating anxiety scale. RESULTS: Visual analog scale pain scores significantly decreased in both of the groups with treatment (both P < .01). The final visual analog scale score was significantly lower in patients with pelvic floor dyssynergia who were treated with biofeedback (1.40 ± 0.97 vs. 5.30 ± 1.70) (P < .05). The 2 groups had similar decreases in self-rating depression scale and self-rating anxiety scale scores. Intriguingly, the acupuncture group had better mental health outcomes (P <.05). CONCLUSION: Both acupuncture and biofeedback therapy reduced the pain of patients with functional anorectal pain. Biofeedback provided more relief in patients with pelvic floor dyssynergia, and acupuncture provided greater improvements in mental health status.

Reduced-dose chemotherapy followed by blinatumomab in induction therapy for newly diagnosed B-cell acute lymphoblastic leukemia.

BACKGROUND: Blinatumomab early-line treatment in B-cell precursor acute lymphoblastic leukemia (B-ALL) might improve clinical outcomes. METHODS: We conducted a retrospective real-world cohort analysis in 20 newly diagnosed B-ALL patients who received reduced-dose chemotherapy (idarubicin, vindesine, and dexamethasone) for 1-3 weeks, followed by blinatumomab for 1-4 weeks as an induction therapy. RESULTS: At the end of the induction therapy, a complete remission rate of 100% was achieved; 17 (85%) patients were minimal residual disease (MRD) negative (<1 × 10-4 ). Adverse events (AEs) were reported in 12 (60%) patients-43.8% were grade 1-2 and 56.2% were grade 3-4. No incidence of neurotoxicity or grade ≥3 cytokine release syndrome was reported. CONCLUSIONS: Blinatumomab demonstrated a significant improvement in clinical outcomes in patients with newly diagnosed B-ALL irrespective of their poor-risk factor status and the pretreatment blast burden.

Exploring the Mechanism of Salvianolic Acid B against Myocardial Ischemia-Reperfusion Injury Based on Network Pharmacology.

This study aimed to explore the mechanisms through which salvianolic acid B (Sal-B) exerts its effects during myocardial ischemia-reperfusion injury (MI/RI), aiming to demonstrate the potential pharmacological characteristics of Sal-B in the management of coronary heart disease. First, Sal-B-related targets and MI/RI-related genes were compiled from public databases. Subsequent functional enrichment analyses using the protein-protein interaction (PPI) network, gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) predicted the core targets and approaches by which Sal-B counters MI/RI. Second, a Sal-B-treated MI/RI mouse model and oxygen-glucose deprivation/reoxygenation (OGD/R) H9C2 cell model were selected to verify the main targets of the network pharmacological prediction. An intersectional analysis between Sal-B and MI/RI targets identified 69 common targets, with a PPI network analysis highlighting caspase-3, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38) as central targets. GO and KEGG enrichment analyses indicated remarkable enrichment of the apoptosis pathway among these targets, suggesting their utility in experimental studies in vivo. Experimental results demonstrated that Sal-B treatment not only mitigated myocardial infarction size following MI/RI injury in mice but also modulated the expression of key apoptotic regulators, including Bcl-2-Associated X (Bax), caspase-3, JNK, and p38, alongside enhancing the B-cell lymphoma-2 (Bcl-2) expression, thereby inhibiting myocardial tissue apoptosis. This study leveraged an integrative network pharmacology approach to predict Sal-B's potential targets in MI/RI treatment and verified the involvement of key target proteins within the predicted signaling pathways through both in vivo and in vitro experiments, offering a comprehensive insight into Sal-B's pharmacological mechanism in MI/RI management.

Lipid regulation of protocatechualdehyde and hydroxysafflor yellow A via AMPK/SREBP2/PCSK9/LDLR signaling pathway in hyperlipidemic zebrafish.

The consumption of a high-cholesterol diet is known to cause hyperlipidemia, which is one of the main risk factors for cardiovascular disease. Protocatechualdehyde (PCA) and hydroxysafflor yellow A (HSYA) are the active components of Salvia miltiorrhiza and safflower, respectively. However, their exact mechanism is still unclear. The aim of this study is to investigate its effects on lipid deposition and liver damage in hyperlipidemic zebrafish and its mechanism of anti-hyperlipidemia. The results showed that the use of PCA and HSYA alone and in combination can improve lipid deposition, slow behavior, abnormal blood flow and liver tissue damage, and the combined use is more effective. Further RT-qPCR results showed that PCA + HSYA can regulate the mRNA levels of PPAR-γ, SREBP2, SREBP1, HMGCR, PCSK9, mTOR, C/EBPα, LDLR, AMPK, HNF-1α and FoxO3a. The PCA + HSYA significantly improves lipid deposition and abnormal liver function in hyperlipidemic zebrafish larvae, which may be related to the AMPK/SREBP2/PCSK9/LDLR signaling pathway.

Chlorogenic acid inhibits macrophage PANoptosis induced by cefotaxime-resistant Escherichia coli.

Antibiotics are commonly used in clinical practice to treat bacterial infections. Due to the abuse of antibiotics, the emergence of drug-resistant strains, such as cefotaxime sodium-resistant Escherichia coli (CSR-EC), has aggravated the treatment of diseases caused by bacterial infections in the clinic. Therefore, discovering new drug candidates with unique mechanisms of action is imperative. Chlorogenic acid (CGA) is an active component of Yinhua Pinggan Granule, which has antioxidant and anti-inflammatory effects. We chose the CGA to explore its effects on PANoptosis in cultured macrophages infected with CSR-EC. In this study, we explored the protective impact of CGA on macrophage cell damage generated by CSR-EC infection and the potential molecular mechanistic consequences of post-infection therapy with CGA on the PANoptosis pathway. Our findings demonstrated that during CSR-EC-induced macrophage infection, CGA dramatically increased cell survival. CGA can inhibit pro-inflammatory cytokine expression of IL-1ß, IL-18, TNF-α, and IL-6. CGA decreased ROS generation and increased Nrf-2 expression at the gene and protein levels to lessen the cell damage and death brought on by CSR-EC infection. Additionally, we discovered that the proteins Caspase-3, Caspase-7, Caspase-8, Caspase-1, GSDMD, NLRP-3, RIPK-3, and MLKL were all inhibited by CGA. In summary, our research suggests that CGA is a contender for reducing lesions brought on by CSR-EC infections and that it can work in concert with antibiotics to treat CSR-EC infections clinically. However, further research on its mechanism of action is still needed.

Network Analysis and Experimental Verification of the Mechanisms of Hydroxysafflor Yellow A in Ischemic Stroke Following Atherosclerosis.

Hydroxysafflor yellow A (HSYA) is derived from Carthamus tinctorius L. (Honghua in Chinese) and is used to treat cardiovascular and cerebrovascular disease. However, the mechanism by which HSYA treats ischemic stroke following atherosclerosis (ISFA) remains unclear. The targets and pathways of HSYA against ISFA were obtained using network analysis. A total of 3335 potential IFSA-related targets were predicted using the GenCards and Drugbank databases, and a total of 88 potential HSYA-related targets were predicted using the Swiss Target Prediction database. A total of 62 HSYA-related targets against IFSA were obtained. The network was composed of HSYA, 62 targets, and 20 pathways. The top 20 targets were constructed via the protein-protein interaction (PPI) network. Gene Ontology analysis revealed that the targets were involved in signal transduction, protein phosphorylation, the cytoplasm, the plasma membrane, the cytosol, zinc ion binding, ATP binding, protein kinase binding/activity, and enzyme binding. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the pathways were associated with cancer, inflammatory mediator regulation of the transient receptor potential channels, and microRNA in cancer. Additionally, molecular docking indicated that HSYA mainly interacts with five targets, namely interleukin 1 beta (IL-1ß), signal transducer and activator of transcription 3 (STAT3), E1A-binding protein p300 (EP300), protein kinase C alpha (PRKCA), and inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB). In animal experiments, HSYA administration ameliorated the infarct size, neurological deficit score, histopathological changes, carotid intima-media thickness (IMT), and blood lipid level (total cholesterol and triglycerides). Immunochemistry and quantitative PCR showed that HSYA intervention downregulated the expression of STAT3, EP300, PRKCA, and IKBKB, and the enzyme-linked immunoassay showed reduced IL-1ß levels. The findings of this study provide a reference for the development of anti-ISFA drugs.

Yinhuapinggan granule ameliorates lung injury caused by multidrug-resistant Acinetobacter baumannii via inhibiting NF-κB/NLRP3 pathway.

Yinhuapinggan granule (YHPG) is a traditional Chinese medicine prescription with rich clinical experience for the treatment of colds and coughs. The aim of this study is to investigate the protective effect of YHPG on multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infection in vivo and its potential anti-inflammatory mechanism. BALB/c mice were intranasally inoculated with MDR A. baumannii strain to establish the pneumonia infection model, and received intraperitoneally cyclophosphamide to form immunosuppression before attack. YHPG (6, 12 and 18 g/kg) was administered by gavage once a day for 3 consecutive days after infection. The protective effect of YHPG was evaluated by lung index, spleen index, thymus index, pathological changes of lung tissue and inflammatory factors (IL-1ß, IL-6 and TNF-α) in serum. The expression of key targets of NF-κB/NLRP3 signaling pathway in vivo was analyzed by immunohistochemistry, immunofluorescence, reverse transcription quantitative PCR (RT-qPCR) and Western blot. The results showed that YHPG improved the lung index and its inhibition rate, immune organ indexes and lung pathological changes in infected mice, and significantly reduced IL-1ß, IL-6 and TNF-α levels in serum. In addition, YHPG significantly down-regulated the mRNA and protein expression of NF-κB p65, NLRP3, ASC, Caspase-1, TNF-α, IL-6 and IL-1ß in mice lung tissue. The results of the current study demonstrated that YHPG has significant protective effects on mice infected with MDR A.baumannii, which may be related to the regulation of inflammatory factors and NF-κB/NLRP3 signaling pathway, indicating that YHPG has a wide range of clinical application value and provides a theoretical basis for its treatment of MDR A.baumannii infection.

Effect of Galactooligosaccharide on PPARs/PI3K/Akt Pathway and Gut Microbiota in High-Fat and High-Sugar Diet Combined with STZ-Induced GDM Rat Model.

Gestational diabetes mellitus (GDM) is a metabolic disorder, characterized by underlying glucose intolerance, diabetes onset or first diagnosis during pregnancy. Galactooligosaccharide (GOS) is essential for consumer protection as food supplementation. However, there is limited understanding of the effects of GOS on GDM. We successfully established a GDM rat model to explore GOS whether participated in PPARs/PI3K/Akt pathway and gut microbiota metabolites to treat for GDM. In this study, compared with the GDM group, GOS administration lowered the levels of TG, LDL-C, and HDL-C in rat serum, as well as improved the pathological changes pancreatic, liver, and kidney tissues. Compared with the GDM group, the protein expressions of PPARα, PPARγ, and PPARß/δ markedly enhanced in GOS-treated groups (P < 0.01). Moreover, GOS administration upregulated the protein expressions of PPARα, PPARß, PPARγ, PI3K, Akt, GLUT4, Bax, and Bcl2. GOS administration altered gut microbiota metabolites, including both SCFAs and BAs. Correlation analysis revealed close relationships between gut microbiota and experimental indicators. This study indicated that GOS effectively improved GDM in rats through the modulation of PPARs/PI3K/Akt pathway and gut microbiota. Thus, the GOS could be recommended as a candidate for novel therapy of GDM.

Polydatin prevent lung epithelial cell from Carbapenem-resistant Klebsiella pneumoniae injury by inhibiting biofilm formation and oxidative stress.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes severe inflammation in various infectious diseases, such as bloodstream infections, respiratory and urinary tract infections, which leads to high mortality. Polydatin (PD), an active ingredient of Yinhuapinggan granule, has attracted worldwide attention for its powerful antioxidant, anti-inflammatory, antitumor, and antibacterial capacity. However, very little is known about the effect of PD on CRKP. In this research, we evaluated the inhibitory effects of PD on both the bacterial level and the bacterial-cell co-culture level on anti-biofilm and efflux pumps and the other was the inhibitory effect on apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) after CRKP induction. Additionally, we validated the mechanism of action by qRT-PCR and western blot in human lung epithelial cells. Firstly, PD was observed to have an inhibitory effect on the biofilm of CRKP and the efflux pump AcrAB-TolC. Mechanically, CRKP not only inhibited the activation of Nuclear Factor erythroid 2-Related Factor 2 (Nrf-2) but also increased the level of ROS in cells. These results showed that PD could inhibit ROS and activate Nrf-2 production. Together, our research demonstrated that PD inhibited bacterial biofilm formation and efflux pump AcrAB-TolC expression and inhibited CRKP-induced cell damage by regulating ROS and Nrf-2-regulated antioxidant pathways.

Metabolomics: A useful tool for ischemic stroke research.

Ischemic stroke (IS) is a multifactorial and heterogeneous disease. Despite years of studies, effective strategies for the diagnosis, management and treatment of stroke are still lacking in clinical practice. Metabolomics is a growing field in systems biology. It is starting to show promise in the identification of biomarkers and in the use of pharmacometabolomics to help patients with certain disorders choose their course of treatment. The development of metabolomics has enabled further and more biological applications. Particularly, metabolomics is increasingly being used to diagnose diseases, discover new drug targets, elucidate mechanisms, and monitor therapeutic outcomes and its potential effect on precision medicine. In this review, we reviewed some recent advances in the study of metabolomics as well as how metabolomics might be used to identify novel biomarkers and understand the mechanisms of IS. Then, the use of metabolomics approaches to investigate the molecular processes and active ingredients of Chinese herbal formulations with anti-IS capabilities is summarized. We finally summarized recent developments in single cell metabolomics for exploring the metabolic profiles of single cells. Although the field is relatively young, the development of single cell metabolomics promises to provide a powerful tool for unraveling the pathogenesis of IS.

Study on Job Burnout of Staff with Different Qualifications in Disinfection Supply Center of Public Hospitals.

Objective: To investigate the job burnout situation in different seniority staff in a public hospital disinfection supply center. Methods: The hospital Disinfection supply center staff in 4 grade 3 A public hospitals received a questionnaire From January 1st to 7th, 2023 including Maslach Burnout Inventory-General Survey, MBI-GS, and other programs. 158 subjects were included in this study. They were divided into three groups according to working years: A short seniority group of 68 cases (≤5 years), middle seniority: 49 cases (5 ~15 years), and long seniority: 41 cases (≥15 years). The correlation between seniority and job burnout was explored by comparing the job burnout scores of three groups. MBI-GS is divided into three parts: the sense of achievement, work attitude, and emotional failure. The full score of achievement is 36 (reverse scored). Higher scores indicate lower achievement from work and severe burnout. Besides, the gender rate, educational background, and job title, as well as the scores in achievability, job attitude, emotional exhaustion, and job burnout were compared among the three groups. Results: By comparing with the short seniority group, the proportion of men in the long seniority group (41.4%) and the middle seniority group (44.8%) were higher. Compared with the long seniority group (39%), the highly educated rate of the short seniority group (92.6%) and middle seniority group (77.5%) was higher. Compared with the long seniority group (63.5%), the proportion of low job titles including primary nurse and no job title in the short seniority group (95.6%) and middle seniority group (77.6%) were higher. The achievability of the short seniority group (19.4 ± 4.2) was significantly lower than those of the middle (11.4 ± 3.6) and long seniority group (9.4 ± 4.0). Compared with the short (10.2 ± 2.3) and long subgroups group (13.5 ± 3.1), the job attitude of the middle seniority group (9.7 ± 3.3) was poorer. Compared with the short (9.7 ± 3.3) and long seniority group (12.3 ± 4.2), the emotional control ability and thus emotional exhaustion of the middle seniority group (14.2 ± 3.8) was poorer. In contrast with the long-seniority group, job burnout situations in the short and middle-seniority groups were more serious. Conclusion: There was a significant difference in the job burnout of different seniority staff in public hospital disinfection supply centers, with lower achievability for short seniority, emotional exhaustion, and poorer job attitude for middle seniority staff.

Salvianolic acid B inhibits atherosclerosis and TNF-α-induced inflammation by regulating NF-κB/NLRP3 signaling pathway.

BACKGROUND: Inflammation is critical in the pathophysiology of atherosclerosis (AS). The aim of this study was to investigate the protective effect of salvianolic acid B (Sal B) on AS and to explore the molecular mechanism of tumor necrosis factor-α (TNF-α)-induced damage in human umbilical vein endothelial cells (HUVECs). METHODS: In vivo studies, LDLR-/- mice were fed a high-fat diet (HFD) for 14 weeks to establish an AS model to evaluate the protective effect of Sal B on the development of AS. Total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels were determined in the blood serum. En face and cross section lipid deposits were measured and quantified with Oil Red O staining. Hematoxylin and eosin (H&E) and Masson's trichrome staining were used to quantify atherosclerotic plaque size and collagen fiber content in aortic root sections. Reactive oxygen species (ROS) were detected in aortic root using dihydroethylenediamine (DHE) staining. Apoptosis rate was determined by TdT-mediated dUTP nick end labeling (TUNEL) staining. Immunofluorescence (IF) staining was used to detect the expression of the nuclear factor kappa-B (NF-κB) p65 and NOD-like receptor family pyrin domain containing 3 (NLRP3). To further investigate the protective effect of Sal B, we used TNF-α induced HUVECs inflammation model. We examined cell viability, lactate dehydrogenase (LDH) content, and ROS production. The transcription of NF-κB was evaluated by immunofluorescence. The mRNA levels of NLRP3, caspase-1, and IL-1ß were detected by RT-PCR. Pyroptosis related proteins were detected by Western blot. RESULTS: The change in the weight of the mice over time was an indication that Sal B had an effect on weight gain. IN VIVO STUDIES: we were able to show that the serum lipids TC, TG and LDL-C were increased in the model group and that the treatment with Sal B reduced the levels of serum lipids. Histological staining showed that the LDLR-/- mice had a large amount of foam cell deposition accompanied by inflammatory cell infiltration and the formation of atherosclerotic plaques in theMOD group. The pathological abnormalities were significantly improved by Sal B treatment. ROS release and apoptosis were significantly increased after HFD in aortic root, which was attenuated by Sal B. IF results showed that the expression of NF-κB p65 and NLRP3 was significantly increased in the MOD group and significantly decreased in the Sal B group, suggesting that Sal B may act through the NF-κB/NLRP3 pathway. And in vitro studies: inflammatory damage of HUEVCs was induced by TNF-α, and Sal B treatmented significantly increased cell viability and reduced LDH release. It was also found that Sal B inhibited ROS level increase after TNF-α-induced HUEVCs. Activation of NF-κB p65 by TNF-α stimulation, NF-κB p65 is transferred to the nucleus. Sal B treatment could reverse this effect. RT-PCR and Western blot showed that Sal B affected NF-κB transcription and NLRP3 inflammasome activation and could significantly inhibit TNF-α-induced NLRP3 inflammasome activation. These results suggest that Sal B may participate in antiatherosclerotic and inflammatory responses through the NF-κB/NLRP3 pathway. CONCLUSIONS: This study shows that Sal B ameliorates the development of AS lesions in HFD-induced LDLR-/- mice. Furthermore, under TNF-α conditions, Sal B reduced ROS release and reversed nuclear translocation of NF-κB, and inhibited atherosclerosis and inflammation by modulating the NF-κB/NLRP3 pathway.

Amygdalin Reverses Macrophage PANoptosis Induced by Drug-Resistant Escherichia coli.

Infectious diseases caused by drug-resistant Escherichia coli (E. coli) pose a critical concern for medical institutions as they can lead to high morbidity and mortality rates. In this study, amygdalin exhibited anti-inflammatory and antioxidant activities, as well as other potentials. However, whether it could influence the drug-resistant E. coli-infected cells remained unanswered. Amygdalin was therefore tested in a cellular model in which human macrophages were exposed to resistant E. coli. Apoptosis was measured by flow cytometry and the lactate dehydrogenase (LDH) assay. Western immunoblotting and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to quantify interleukin-18 (IL-18), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). The production of reactive oxygen species (ROS) in macrophages was detected by ROS kit. The expression of panapoptotic proteins in macrophages was measured by qRT-PCR and Western immunoblotting. Drug-Resistant E. coli inhibited cell viability and enhanced apoptosis in the cellular model. In cells treated with amygdalin, this compound can inhibit cell apoptosis and reduce the expression of pro - inflammatory cytokines such as IL-1ß, IL-18 and IL-6. Additionally, it decreases the production of PANoptosis proteins, Furthermore, amygdalin lowered the levels of reactive oxygen species induced by drug-resistant E. coli, in cells, demonstrating its antioxidant effects. Amygdalin, a drug with a protective role, alleviated cell damage caused by drug-resistant E. coli in human macrophages by inhibiting the PANoptosis signaling pathway.