Surgical Myectomy and Myotomy for Refractory Blepharospasm in Meige Syndrome Patients: A Case Report.

Meige syndrome is a rare neurological disease characterized by segmental dystonia, specifically blepharospasm and oromandibular dystonia. These symptoms are often accompanied by complex movements of the eyelids, lower facial muscles, mandible, and neck muscles. Bilateral blepharospasm is the most common feature of this disease. In this case report, we present the successful treatment of refractory blepharospasm in a 72-year-old woman with Meige syndrome via 2 incisions resulting from myectomy and in situ surgery.

Network pharmacology analysis and experimental verification of the antithrombotic active compounds of trichosanthis pericarpium (Gualoupi) in treating coronary heart disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Trichosanthis pericarpium (TP; Gualoupi, pericarps of Trichosanthes kirilowii Maxim) has been used in traditional Chinese medicine (TCM) to reduce heat, resolve phlegm, promote Qi, and clear chest congestion. It is also an essential herbal ingredient in the "Gualou Xiebai" formula first recorded by Zhang Zhongjing (from the Eastern Han Dynasty) in the famous TCM classic "Jin-Guì-Yào-Lüe" for treating chest impediments. According to its traditional description, Gualou Xiebai is indicated for symptoms of chest impediments, which correspond to coronary heart diseases (CHD). AIM OF THE STUDY: This study aimed to identify the antithrombotic compounds in Gualoupi for the treatment of CHD. MATERIALS AND METHODS: A CHD rat model was established with a combination of high-fat diet and isoproterenol hydrochloride (ISO) administration via subcutaneous multi-point injection in the back of the neck. This model was used to evaluate the antithrombotic effect of two mainstream cultivars of TP ("HaiShi GuaLou" and "WanLou") by analyzing the main components and their effects. Network pharmacology, molecular docking-based studies, and a zebrafish (Danio rerio) thrombosis model induced by phenylhydrazine was used to validate the antithrombosis components of TP. RESULTS: TP significantly reduced the body weight of the CHD rats, improved myocardial ischemia, and reduced collagen deposition and fibrosis around the infarcted tissue. It reduced thrombosis in a dose-dependent manner and significantly reduced inflammation and oxidative stress damage. Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as candidate active TP compounds with antithrombotic effects. The key potential targets of TP in thrombosis treatment were initially identified by molecular docking-based analysis, which showed that the candidate active compounds have a strong binding affinity to the potential targets (protein kinase C alpha type [PKCα], protein kinase C beta type [PKCß], von Willebrand factor [vWF], and prostaglandin-endoperoxide synthase 1 [PTGS1], fibrinogen alpha [Fga], fibrinogen beta [Fgb], fibrinogen gamma [Fgg], coagulation factor II [F2], and coagulation factor VII [F7]). In addition, the candidate active compounds reduced thrombosis, improved oxidative stress damage, and down-regulated the expression of thrombosis-related genes (PKCα, PKCß, vWF, PTGS1, Fga, Fgb, Fgg, F2, and F7) in the zebrafish model. CONCLUSION: Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as the active antithrombotic compounds of TP used to treat CHD. Mechanistically, the active compounds were found to be involved in oxidative stress injury, platelet activation pathway, and complement and coagulation cascade pathways.

The efficacy of endoscopic dacryocystorhinostomy in the treatment of dacryocystitis: A systematic review and meta-analysis.

BACKGROUND: This article aimed to discuss the efficacy and safety of endoscopic dacryocystorhinostomy (EDCR) versus external dacryocystorhinostomy (EX-DCR) for the treatment of dacryocystitis by meta-analysis. METHODS: All randomized controlled trials that met the inclusion and exclusion criteria were collected by searching the following databases: PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang, from the establishment of the database to June 2023. Meta-analysis was performed using Stata 17.0 software and review manager 5.4 software. In the collected trials, the observation group was treated with EDCR, whereas the control group was treated with EX-DCR. RESULTS: A total of 10 studies involving 969 patients were included in this analysis. There was a similar surgical success rate in the treatment of dacryocystitis between the 2 groups (RR = 1.021, 95% CI [0. 803, 1.297], P = 0. 865). However, compared with the control group, patients in the observation group had a higher total effective rate of treatment (RR = 1. 195, 95% CI [1. 063, 1.343], P = .003), and shorter operative time (WMD = -23.640, 95% CI [-35.533, -11.747], P < .001), and less intraoperative blood loss (WMD = -50.797, 95% CI [-80.339, -21.255], P = .001), shorter length of hospital stays (WMD = -4.570, 95% CI [-5.992, -3.148], P < .001), and lower incidence of adverse events (RR = 0.295, 95% CI [0.173, 0.504], P < .001). CONCLUSION: EDCR is an effective and safe surgical procedure for the treatment of dacryocystitis and can be used as an alternative to EX-DCR.

Unraveling the pharmacodynamic substances and possible mechanism of Trichosanthis Pericarpium in the treatment of coronary heart disease based on plasma pharmacochemistry, network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Coronary heart disease (CHD) is a chronic disease that seriously threatens people's health and even their lives. Currently, there is no ideal drug without side effects for the treatment of CHD. Trichosanthis Pericarpium (TP) has been used for several years in the treatment of diseases associated with CHD. However, there is still a need for systematic research to unravel the pharmacodynamic substances and possible mechanism of TP in the treatment of coronary heart. AIM OF THE STUDY: The purpose of current study was to explore the pharmacodynamic substances and potential mechanisms of TP in the treatment of CHD via integrating network pharmacology with plasma pharmacochemistry and experimental validation. MATERIALS AND METHODS: The effect of TP intervention in CHD was firstly assessed on high-fat diet combined with isoprenaline-induced CHD rats and H2O2-induced H9c2 cells, respectively. Then, the LC-MS was utilized to identify the absorbed components of TP in the plasma of CHD rats, and this was used to develop a network pharmacology prediction to obtain the possible active components and mechanisms of action. Molecular docking and immunohistochemistry were used to explore the interaction between TP and key targets. Subsequently, the efficacy of the active ingredients was investigated by in vitro cellular experiments, and their metabolic pathways in CHD rats were further analyzed. RESULTS: The effects of TP on amelioration of CHD were verified by in vivo and in vitro experiments. Plasma pharmacochemistry and network pharmacology screened six active components in plasma including apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin. The interaction of these compounds with potential key targets AKT1, IL-1ß, IL-6, TNF-α and VEGFA were preliminarily verified by molecular docking. And immunohistochemical results showed that TP reduced the expression of AKT1, IL-1ß, IL-6, TNF-α and VEGFA in CHD rat hearts. Then cellular experiments confirmed that apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin were able to reduce the ROS level in H2O2-induced HUVEC cells and promote the migration and tubule formation of HUVEC cells, indicating the pharmacodynamic effects of the active components. Meanwhile, the metabolites of TP in CHD rats suggested that the pharmacological effects of TP might be the result of the combined effects of the active ingredients and their metabolites. CONCLUSION: Our study found that TP intervention in CHD is characterized by multi-component and multi-target regulation. Apigenin, phenylalanine, linoleic acid, quercetin, luteolin, and tangeretin are the main active components of TP. TP could reduce inflammatory response and endothelial damage by regulating AKT1, IL-1ß, IL-6, TNF-α and VEGFA, reduce ROS level to alleviate the oxidative stress situation and improve heart disease by promoting angiogenesis to regulate endothelial function. This study also provides an experimental and scientific basis for the clinical application and rational development of TP.

Outer Membrane Vesicles Released from Garlic Exosome-like Nanoparticles (GaELNs) Train Gut Bacteria that Reverses Type 2 Diabetes via the Gut-Brain Axis.

Gut microbiota function has numerous effects on humans and the diet humans consume has emerged as a pivotal determinant of gut microbiota function. Here, a new concept that gut microbiota can be trained by diet-derived exosome-like nanoparticles (ELNs) to release healthy outer membrane vesicles (OMVs) is introduced. Specifically, OMVs released from garlic ELN (GaELNs) trained human gut Akkermansia muciniphila (A. muciniphila) can reverse high-fat diet-induced type 2 diabetes (T2DM) in mice. Oral administration of OMVs released from GaELNs trained A. muciniphila can traffick to the brain where they are taken up by microglial cells, resulting in inhibition of high-fat diet-induced brain inflammation. GaELNs treatment increases the levels of OMV Amuc-1100, P9, and phosphatidylcholines. Increasing the levels of Amuc-1100 and P9 leads to increasing the GLP-1 plasma level. Increasing the levels of phosphatidylcholines is required for inhibition of cGas and STING-mediated inflammation and GLP-1R crosstalk with the insulin pathway that leads to increasing expression of Insulin Receptor Substrate (IRS1 and IRS2) on OMV targeted cells. These findings reveal a molecular mechanism whereby OMVs from plant nanoparticle-trained gut bacteria regulate genes expressed in the brain, and have implications for the treatment of brain dysfunction caused by a metabolic syndrome.

Sophocarpine alleviates doxorubicin-induced heart injury by suppressing oxidative stress and apoptosis.

Doxorubicin (DOX) is an effective anti-tumor drug accompanied with many side effects, especially heart injury. To explore what effects of sophocarpine (SOP) on DOX-induced heart injury, this study conducted in vivo experiment and in vitro experiment, and the C57BL/6J mice and the H9C2 cells were used. The experimental methods used included echocardiography, enzyme-linked immunosorbent assay (ELISA), dihydroethidium (DHE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, western blotting and so on. Echocardiography showed that SOP alleviated DOX-induced cardiac dysfunction, as evidenced by the improvements of left ventricle ejection fraction and left ventricle fractional shortening. DOX caused upregulations of creatine kinase (CK), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), while SOP reduced these indices. The relevant stainings showed that SOP reversed the increases of total superoxide level induced by DOX. DOX also contribute to a higher level of MDA and lower levels of SOD and GSH, but these changes were suppressed by SOP. DOX increased the pro-oxidative protein level of NOX-4 while decreased the anti-oxidative protein level of SOD-2, but SOP reversed these effects. In addition, this study further discovered that SOP inhibited the decreases of Nrf2 and HO-1 levels induced by DOX. The TUNEL staining revealed that SOP reduced the high degree of apoptosis induced by DOX. Besides, pro-apoptosis proteins like Bax, cleaved-caspase-3 and cytochrome-c upregulated while anti-apoptosis protein like Bcl-2 downregulated when challenged by DOX, but them were suppressed by SOP. These findings suggested that SOP could alleviate DOX-induced heart injury by suppressing oxidative stress and apoptosis, with molecular mechanism activating of the Nrf2/HO-1 signaling pathway.

The impact of superselective adrenal artery embolization on renal function in patients with primary aldosteronism: a prospective cohort study.

Superselective adrenal artery embolization (SAAE) is an effective treatment for patients with primary aldosteronism (PA). However, the impact of SAAE on renal function in the PA population remains uncertain. We investigated the estimated glomerular filtration rate (eGFR) and age, sex, body mass index, and diabetes-specific percentiles of eGFR residuals in 182 PA patients treated with SAAE in a prospective cohort from Nanchang SAAE in treating PA registry study. Data suggest that SAAE caused a significant decrease in eGFR from 91.9 ± 26.1 to 88.7 ± 24.1 ml/min/1.73 m2 (p < 0.05) after a median follow-up of 8 months in PA patients. Patients experienced a significant decrease in eGFR from 110.6 ± 18.9 to 103.8 ± 18.2 ml/min/1.73 m2 (p < 0.001) and a very slight increase from 71.1 ± 14.8 to 71.8 ± 17.8 ml/min/1.73 m2 (p = 0.770) with baseline eGFR ≥90 and <90 ml/min/1.73 m2, respectively. Patients with high eGFR residuals (glomerular hyperfiltration) experienced a significant decrease in their eGFR levels from 123.1 ± 22.6 to 105.0 ± 18.6 ml/min/1.73 m2 (p < 0.001). In contrast, there was no significant impact of SAAE on the eGFR of patients with normal or low eGFR residuals. The very early eGFR changes (24 h after SAAE) best predicted the effect of SAAE on eGFR changes after median of eight months in PA patients. On the whole, SAAE seems to have a beneficial impact on renal function in patients with PA, the results of which vary depending on the patient's baseline eGFR and glomerular hyperfiltration status.

Enhancement, integration, expansion: Activating representation of detailed features for occluded person re-identification.

A proposed method, Enhancement, integration, and Expansion, aims to activate the representation of detailed features for occluded person re-identification. Region and context are two important and complementary features, and integrating them in an occluded environment can effectively improve the robustness of the model. Firstly, a self-enhancement module is designed. Based on the constructed multi-stream architecture, rich and meaningful feature interference is introduced in the feature extraction stage to enhance the model's ability to perceive noise. Next, a collaborative integration module similar to cascading cross-attention is proposed. By studying the intrinsic interaction patterns of regional and contextual features, it adaptively fuses features across streams and enhances the diverse and complete representation of internal information. The module is not only robust to complex occlusions, but also mitigates the feature interference problem due to similar appearances or scenes. Finally, a matching expansion module that enhances feature discriminability and completeness is proposed. Providing more stable and accurate features for recognition. Compared with state-of-the-art methods on two occluded and holistic datasets, the proposed method is proved to be advanced and the effectiveness of the module is proved by extensive ablation studies.

Comparative effectiveness of nonpharmacological interventions in reducing psychological symptoms among patients with chronic low back pain.

OBJECTIVES: Chronic low back pain (CLBP) can seriously impair the quality of life of patients and has a remarkable comorbidity with psychological symptoms, which, in turn, can further exacerbate the symptoms of CLBP. Psychological treatments are critical and nonnegligent for the management of CLBP, and thus, should attract sufficient attention. However, current evidence does not suggest the superiority and effectiveness of nonpharmacological interventions in reducing psychological symptoms among patients with CLBP.Thus, this study was designed to compare the effectiveness of nonpharmacological interventions for depression, anxiety, and mental health among patients with CLBP and to recommend preferred strategies for attenuating psychological symptoms in clinical practice. METHODS: In this systematic review and network meta-analysis (NMA), PubMed, Embase Database, Web of Science, and Cochrane Library were searched from database inception until March 2022. Randomized clinical trials (RCTs) that compare different nonpharmacological interventions for depression, anxiety, and mental health among patients with CLBP were eligible. The Preferred Reporting Items for Systematic Reviews and Meta-analyses statement was used. Four reviewers in pairs and divided into two groups independently performed literature selection, data extraction, and risk of bias, and certainty of evidence assessments. This NMA was conducted with a random effects model under a frequentist framework. The major outcomes were depression, anxiety, and mental health presented as the standardized mean difference (SMD) with the corresponding 95% CI. RESULTS: A total of 66 RCTs that randomized 4806 patients with CLBP met the inclusion criteria. The quality of evidence was typically low or some risks of bias (47 out of 66 trials, 71.3%), and the precision of summary estimates for effectiveness varied substantially. In addition, 7 categories of interventions with 26 specific treatments were evaluated. For depression, mind body therapy (pooled SMD = -1.20, 95% CI: -1.63 to -0.78), biopsychosocial approach (pooled SMD = -0.41, 95% CI: -0.70 to -0.12), and physical therapy (pooled SMD = -0.26, 95% CI: -0.50 to -0.02) exhibited remarkable effectiveness in reducing depression compared with the control group. For managing anxiety, mind body therapy (pooled SMD = -1.35, 95% CI: -1.90 to -0.80), multicomponent intervention (pooled SMD = -0.47, 95% CI: -0.88 to -0.06), and a biopsychosocial approach (pooled SMD = -0.46, 95% CI: -0.79 to -0.14) were substantially superior to the control group. For improving mental health, multicomponent intervention (pooled SMD = 0.77, 95% CI: 0.14 to 1.39), exercise (pooled SMD = 0.60, 95% CI: 0.08 to 1.11), and physical therapy (pooled SMD = 0.47, 95% CI: 0.02-0.92) demonstrated statistically substantial effectiveness compared with the control group. The rank probability indicated that mind body therapy achieved the highest effectiveness in reducing depression and anxiety among patients with CLBP. Besides, the combined results should be interpreted cautiously based on the results of analyses evaluating the inconsistency and certainty of the evidence. CONCLUSION: This systemic review and NMA suggested that nonpharmacological interventions show promise for reducing psychological symptoms among patients with CLBP. In particular, mind body therapy and a biopsychosocial approach show considerable promise, and mind body therapy can be considered a priority choice in reducing depression and anxiety. These findings can aid clinicians in assessing the potential risks and benefits of available treatments for CLBP comorbidity with psychological symptoms and provide evidence for selecting interventions in clinical practice. More RCTs involving different interventions with rigorous methodology and an adequate sample size should be conducted in future research.

Insights into starch-based gels: Selection, fabrication, and application.

Starch a natural polymer, has made significant advancements in recent decades, offering superior performance and versatility compared to synthetic materials. This review discusses up-to-date diverse applications of starch gels, their fabrication techniques, and their advantages over synthetic materials. Starch gels renewability, biocompatibility, biodegradability, scalability, and affordability make them attractive. Also, advanced theoretical foundations and emerging industrial technologies could further expand their scope and functions inspiring new applications.

Rational Design of Guanidinium-Based Bio-MCOF as a Multifunctional Nanocatalyst in Tumor Cells for Enhanced Chemodynamic Therapy.

Chemodynamic therapy (CDT) has emerged as a promising approach to cancer treatment, which can break the intracellular redox state balance and result in severe oxidative damage to biomolecules and organelles with the advantages of being less dependent on external stimulation, having deep tissue-healing abilities, and being resistant to drug resistance. There is considerable interest in developing CDT drugs with high efficiency and low toxicity. In this study, a new guanidinium-based biological metal covalent organic framework (Bio-MCOF), GZHMU-1@Mo, is rationally designed and synthesized as a multifunctional nanocatalyst in tumor cells for enhanced CDT. The DFT calculation and experimental results showed that due to the ability of MoO42- ion to promote electron transfer and increase the redox active site, Cu3 clusters and MoO42- ions in GZHMU-1@Mo can synergistically catalyze the production of reactive oxygen species (ROS) from oxygen and H2O2 in tumor cells, as well as degrade intracellular reducing substances, GSH and NADH, so as to disrupt the redox balance in tumor cells. Moreover, GZHMU-1@Mo exhibits a potent killing effect on tumor cells under both normal oxygen and anaerobic conditions. Further in vitro and in vivo antiproliferation studies revealed that the GZHMU-1@Mo nanoagent displays a remarkable antiproliferation effect and effectively inhibits tumor growth. Taken together, our study provides an insightful reference benchmark for the rational design of Bio-MCOF-based nanoagents with efficient CDT.

Establishment of a Rapid LAMP Assay for Aeromonas hydrophila and Comparison with the Application of qPCR.

The development of an exceptionally sensitive diagnostic technique for early identification of aquaculture diseases, specifically Aeromonas hydrophila, is essential for efficient management of disease outbreaks at aquaculture locations. In this research, a swift and sensitive diagnostic assay employing Loop-mediated isothermal amplification (LAMP) of Aeromonas hydrophila was devised and compared to the conventional qPCR method documented by Rong Wang. Validation of the diagnostic assay was carried out using actual samples obtained from aquaculture fish. The findings revealed that based on the rapid detection of crude bacterial genomic DNA, the fluorescent LAMP assay possessed a lower limit of detection (LOD) of 0.559 ng/µL (0.315-1.693, 95% CI), while the LOD for qPCR stood at 4.301 ng/µL (2.084-8.876, 95% CI). Both techniques demonstrated outstanding specificity, exhibiting no cross-reactivity with bacteria from the same or closely related genera. A total of 74 fish samples suspected to be infected with the fish disease were gathered, with 26 and 23 samples testing positive for Aeromonas hydrophila via LAMP and qPCR, respectively. The concordance analysis for LAMP and qPCR methods generated a Kappa value of 0.909 (0.778-1.000, 95% CI), signifying a high degree of diagnostic consensus. This study highlights that the LAMP assay eliminates the thermal cycle temperature change process of qPCR, uses lysate to crudely extract bacterial genomic DNA, and can complete the detection within 40 min, rendering it a practical and efficient alternative for monitoring disease outbreaks at aquaculture sites.

Electrolyte Strategies Facilitating Anion-Derived Solid-Electrolyte Interphases for Aqueous Zinc-Metal Batteries.

Rechargeable aqueous zinc-metal batteries (AZBs) are a promising complimentary technology to the existing lithium-ion batteries and the re-emerging lithium-metal batteries to satisfy the increasing demands on energy storage. Despite considerable progress achieved in the past years, the fundamental understanding of the solid-electrolyte interphase (SEI) formation and how its composition influences the SEI properties are limited. This review highlights the functionalities of anion-tuned SEI on the reversibility of zinc-metal anode, with a specific emphasis on new structural insights obtained through advanced characterizations and computational techniques. Recent efforts in terms of key variables that govern the interfacial behaviors to improve the long-term stability of zinc anode, i.e., Coulombic efficiency, plating morphology, dendrite formation, and side-reactions, are comprehensively reviewed. Lastly, the remaining challenges and future perspectives are presented, providing insights into the rational design of practical high-performance AZBs.

Survey of Colistin Resistance in Commensal Bacteria from Penaeus vannamei Farms in China.

Aquatic environments are important reservoirs for drug resistance. Aquatic foods may act as carriers to lead antibiotic-resistant commensal bacteria into the human gastrointestinal system, then contacting gut microbiota and spreading antibiotic resistance. Here, several shrimp farms were investigated to identify colistin resistance among commensal bacteria of aquaculture. A total of 884 (41.6%) colistin-resistant isolates were identified among 2126 strains. Electroporation demonstrated that colistin-resistant fragments were present in some commensal bacteria that could be transferred to other bacteria. Most of the resistant bacteria were Bacillus spp., with 69.3% of the Bacillus species exhibiting multiple drug resistance. Bacillus licheniformis was prevalent, with 58 strains identified that comprised six sequence types (ST) based on multilocus sequence typing. Whole-genome sequencing and comparisons with previous B. licheniformis genomes revealed a high degree of genomic similarity among isolates from different regions. Thus, this species is widely distributed, and this study provides new insights into global antibiotic-resistant characteristics of B. licheniformis. Sequence analyses further revealed some of these strains are even pathogenic and virulent, suggesting the antibiotic resistance and hazards of commensal bacteria in aquaculture should be considered. Considering the "One Health" perspective, improved monitoring of aquatic food is needed to prevent the spread of drug-resistant commensal bacteria from food-associated bacteria to humans.

Uncovering the key pharmacodynamic material basis and possible molecular mechanism of extract of Epimedium against liver cancer through a comprehensive investigation.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver cancer is a worldwide malignant tumor, and currently lacks effective treatments. Clinical studies have shown that epimedium (YYH) has therapeutic effects on liver cancer, and some of its prenylflavonoids have demonstrated anti-liver cancer activity through multiple mechanisms. However, there is still a need for systematic research to uncover the key pharmacodynamic material basis and mechanism of YYH. AIM OF THE STUDY: This study aimed to screen the anti-cancer material basis of YYH via integrating spectrum-effect analysis with serum pharmacochemistry, and explore the multi-target mechanisms of YYH against liver cancer by combining network pharmacology with metabolomics. MATERIALS AND METHODS: The anti-cancer effect of the extract of YYH (E-YYH) was first evaluated in mice with xenotransplantation H22 tumor cells burden and cultured hepatic cells. Then, the interaction between E-YYH compounds and the cytotoxic effects was revealed through spectrum-effect relationship analysis. And the cytotoxic effects of screened compounds were verified in hepatic cells. Next, UHPLC-Q-TOF-MS/MS was employed to identify the absorbed components of E-YYH in rat plasma to distinguish anti-cancer components. Subsequently, network pharmacology based on anti-cancer materials and metabolomics were used to discover the potential anti-tumor mechanisms of YYH. Key targets and biomarkers were identified and pathway enrichment analysis was performed. RESULTS: The anti-cancer effect of E-YYH was verified through in vitro and in vivo experiments. Six anti-cancer compounds in plasma (icariin, baohuoside Ⅰ, epimedin C, 2″-O-rhamnosyl icariside Ⅱ, epimedin B and sagittatoside B) were screened out by spectrum-effect analysis. Forty-five liver-cancer-related targets were connected with these compounds. Among these targets, PTGS2, TNF, NOS3 and PPARG were considered to be the potential key targets preliminarily verified by molecular docking. Meanwhile, PI3K/AKT signaling pathway and arachidonic acid metabolism were found to be associated with E-YYH's efficacy in network pharmacology and metabolomics analysis. CONCLUSIONS: Our research revealed the characteristics of multi-component, multi-target and multi-pathway mechanism of E-YYH. This study also provided an experimental basis and scientific evidence for the clinical application and rational development of YYH.

Natural γδT17 cell development and functional acquisition is governed by the mTORC2-c-Maf-controlled mitochondrial fission pathway.

Natural IL-17-producing γδ T cells (γδT17 cells) are unconventional innate-like T cells that undergo functional programming in the fetal thymus. However, the intrinsic metabolic mechanisms of γδT17 cell development remain undefined. Here, we demonstrate that mTORC2, not mTORC1, selectively controls the functional fate commitment of γδT17 cells through regulating transcription factor c-Maf expression. scRNA-seq data suggest that fetal and adult γδT17 cells predominately utilize mitochondrial metabolism. mTORC2 deficiency results in impaired Drp1-mediated mitochondrial fission and mitochondrial dysfunction characterized by mitochondrial membrane potential (ΔΨm) loss, reduced oxidative phosphorylation (OXPHOS), and subsequent ATP depletion. Treatment with the Drp1 inhibitor Mdivi-1 alleviates imiquimod-induced skin inflammation. Reconstitution of intracellular ATP levels by ATP-encapsulated liposome completely rescues γδT17 defect caused by mTORC2 deficiency, revealing the fundamental role of metabolite ATP in γδT17 development. These results provide an in-depth insight into the intrinsic link between the mitochondrial OXPHOS pathway and γδT17 thymic programming and functional acquisition.

The Prognostic Model Established by the Differential Expression Genes Based on CD8+ T Cells to Evaluate the Prognosis and the Response to Immunotherapy in Osteosarcoma.

Osteosarcoma (OS) is a malignant tumor with an extremely poor prognosis, especially in progressive patients. Immunotherapy based on immune checkpoint inhibitors (ICIs) is considered to be a promising treatment option for OS. Due to tumor heterogeneity, only a minority of patients benefit from immunotherapy. Therefore, it is urgent to explore a model that can accurately assess the response of OS to immunotherapy. In this study, we obtained the single-cell RNA sequencing datasets of OS patients from public databases and defined 34 cell clusters by dimensional reduction and clustering analysis. PTPRC was applied to identify immune cell clusters and nonimmune cell clusters. Next, we performed clustering analysis on the immune cell clusters and obtained 25 immune cell subclusters. Immune cells were labeled with CD8A and CD8B to obtain CD8+ T cell clusters. Meanwhile, we extracted the differentially expressed genes (DEGs) of CD8+ T cell clusters and other immune cell clusters. Furthermore, we constructed a prognostic model (CD8-DEG model) based on the obtained DEGs of CD8+ T cells, and verified the excellent predictive ability of this model for the prognosis of OS. Moreover, we further investigated the value of the CD8-DEG model. The results indicated that the risk score of the CD8-DEG model was an independent risk factor for OS patients. Finally, we revealed that the risk score of the CD8-DEG model correlates with the immune profile of OS and can be used to evaluate the response of OS to immunotherapy. In conclusion, our study revealed the critical role of CD8 cells in OS. The risk score model based on CD8-DEGs can provide guidance for prognosis and immunotherapy of OS.

Association Between the Metabolic Score for Insulin Resistance and Hypertension in Adults: A Meta-Analysis.

The metabolic score for insulin resistance (METS-IR) is a recently developed parameter for screening of metabolic disorder. However, the association between METS-IR and risk of hypertension in general adult population remains not fully determined. A meta-analysis was therefore performed. Observational studies evaluating the association between METS-IR and hypertension in adults were retrieved by searching PubMed, Embase, and Web of Science databases from inception to October 10, 2022. A random-effects model, which incorporates the potential influence of heterogeneity, was used to pool the results. Eight studies with 305 341 adults were included in the meta-analysis, and 47 887 (15.7%) of them had hypertension. Pooled results showed that a higher METS-IR was associated with hypertension after adjusting for multiple conventional risk factors [relative risk (RR) for highest versus lowest category of METS-IR: 1.67, 95% confidence interval (CI): 1.53 to 1.83, p<0.001, I2=8%]. The results were consistent in subgroup analyses according to study design, source of the cohort, age, sex, body mass index of the participants, and quality scores of the study (p for subgroup difference all>0.05). Results of meta-analysis with METS-IR analyzed in continuous variables also showed that METS-IR was associated with the risk of hypertension (RR for 1-unit increment of METS-IR: 1.15, 95% CI: 1.08 to 1.23, p<0.001, I2=79%). In conclusion, a high METS-IR is associated with hypertension in general adult population. Measuring METS-IR may be useful for screening participants at high risk of hypertension.

An extracellular vesicular mutant KRAS-associated protein complex promotes lung inflammation and tumor growth.

Extracellular vesicles (EVs) contain more than 100 proteins. Whether there are EVs proteins that act as an 'organiser' of protein networks to generate a new or different biological effect from that identified in EV-producing cells has never been demonstrated. Here, as a proof-of-concept, we demonstrate that EV-G12D-mutant KRAS serves as a leader that forms a protein complex and promotes lung inflammation and tumour growth via the Fn1/IL-17A/FGF21 axis. Mechanistically, in contrast to cytosol derived G12D-mutant KRAS complex from EVs-producing cells, EV-G12D-mutant KRAS interacts with a group of extracellular vesicular factors via fibronectin-1 (Fn1), which drives the activation of the IL-17A/FGF21 inflammation pathway in EV recipient cells. We show that: (i), depletion of EV-Fn1 leads to a reduction of a number of inflammatory cytokines including IL-17A; (ii) induction of IL-17A promotes lung inflammation, which in turn leads to IL-17A mediated induction of FGF21 in the lung; and (iii) EV-G12D-mutant KRAS complex mediated lung inflammation is abrogated in IL-17 receptor KO mice. These findings establish a new concept in EV function with potential implications for novel therapeutic interventions in EV-mediated disease processes.