Research status and challenges of plant-derived exosome-like nanoparticles.

In recent years, there has been an increasing number of related studies on exosomes. Most studies have focused on exosomes derived from mammals, confirming the important role that exosomes play in cell communication. Plants, as a natural ingredient, plant-derived exosomes have been confirmed to have similar structures and functions to mammalian-derived exosomes. Plant-derived exosome-like nanoparticles (PELNs) are lipid bilayer membrane nanovesicles containing bioactive constituents such as miRNA, mRNA, protein, and lipids obtained from plant cells, that can participate in intercellular communication and mediate transboundary communication, have high bioavailability and low immunogenicity, are relatively safe, and have been shown to play an important role in maintaining cell homeostasis and preventing, and treating a variety of diseases. In this review, we describe the biogenesis, isolation and purification methods, structural composition, stability, safety, function of PELNs and challenges. The functions of PELNs in anti-inflammatory, antioxidant, antitumor and drug delivery are mainly described, and the status of research on exosome nanoparticles of Chinese herbal medicines is outlined. Overall, we summarized the importance of PELNs and the latest research results in this field and provided a theoretical basis for the future research and clinical application of PELNs.

Integrative polygenic risk score improves the prediction accuracy of complex traits and diseases.

Polygenic risk scores (PRSs) are an emerging tool to predict the clinical phenotypes and outcomes of individuals. We propose PRSmix, a framework that leverages the PRS corpus of a target trait to improve prediction accuracy, and PRSmix+, which incorporates genetically correlated traits to better capture the human genetic architecture for 47 and 32 diseases/traits in European and South Asian ancestries, respectively. PRSmix demonstrated a mean prediction accuracy improvement of 1.20-fold (95% confidence interval [CI], [1.10; 1.3]; p = 9.17 × 10-5) and 1.19-fold (95% CI, [1.11; 1.27]; p = 1.92 × 10-6), and PRSmix+ improved the prediction accuracy by 1.72-fold (95% CI, [1.40; 2.04]; p = 7.58 × 10-6) and 1.42-fold (95% CI, [1.25; 1.59]; p = 8.01 × 10-7) in European and South Asian ancestries, respectively. Compared to the previously cross-trait-combination methods with scores from pre-defined correlated traits, we demonstrated that our method improved prediction accuracy for coronary artery disease up to 3.27-fold (95% CI, [2.1; 4.44]; p value after false discovery rate (FDR) correction = 2.6 × 10-4). Our method provides a comprehensive framework to benchmark and leverage the combined power of PRS for maximal performance in a desired target population.

Injectable Hydrogels Including Magnetic Nanosheets for Multidisciplinary Treatment of Hepatocellular Carcinoma via Magnetic Hyperthermia.

Relapse and unresectability have become the main obstacle for further improving hepatocellular carcinoma (HCC) treatment effect. Currently, single therapy for HCC in clinical practice is limited by postoperative recurrence, intraoperative blood loss and poor patient outcomes. Multidisciplinary therapy has been recognized as the key to improving the long-term survival rate for HCC. However, the clinical application of HCC synthetic therapy is restricted by single functional biomaterials. In this study, a magnetic nanocomposite hydrogel (CG-IM) with iron oxide nanoparticle-loaded mica nanosheets (Iron oxide nanoparticles@Mica, IM) is reported. This biocompatible magnetic hydrogel integrated high injectability, magnetocaloric property, mechanical robustness, wet adhesion, and hemostasis, leading to efficient HCC multidisciplinary therapies including postoperative tumor margin treatment and percutaneous locoregional ablation. After minimally invasive hepatectomy of HCC, the CG-IM hydrogel can facilely seal the bleeding hepatic margin, followed by magnetic hyperthermia ablation to effectively prevent recurrence. In addition, CG-IM hydrogel can inhibit unresectable HCC by magnetic hyperthermia through the percutaneous intervention under ultrasound guidance.

[Aqueous extract of Epimedium sagittatum mitigates pulmonary fibrosis in mice].

This study aims to investigate the intervention effect of the aqueous extract of Epimedium sagittatum Maxim on the mouse model of bleomycin(BLM)-induced pulmonary fibrosis, so as to provide data support for the clinical treatment of pulmonary fibrosis. Ninety male C57BL/6N mice were randomized into normal(n=10), model(BLM, n=20), pirfenidone(PFD, 270 mg·kg~(-1), n=15), and low-, medium-, and high-dose E. sagittatum extract(1.67 g·kg~(-1), n=15; 3.33 g·kg~(-1), n=15; 6.67 g·kg~(-1), n=15) groups. The model of pulmonary fibrosis was established by intratracheal instillation of BLM(5 mg·kg~(-1)) in the other five groups except the normal group, which was treated with an equal amount of normal saline. On the day following the modeling, each group was treated with the corresponding drug by gavage for 21 days. During this period, the survival rate of the mice was counted. After gavage, the lung index was calculated, and the morphology and collagen deposition of the lung tissue were observed by hematoxylin-eosin(HE) and Masson staining, respectively. The levels of reactive oxygen species(ROS) in lung cell suspensions were measured by flow cytometry. The levels of glutathione peroxidase(GSH-Px), total superoxide dismutase(T-SOD), and malondialdehyde(MDA) the in lung tissue were measured. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling(TUNEL) was employed to examine the apoptosis of lung tissue cells. The content of interleukin-6(IL-6), chemokine C-C motif ligand 2(CCL-2), matrix metalloproteinase-8(MMP-8), transforming growth factor-beta 1(TGF-ß1), alpha-smooth muscle actin(α-SMA), E-cadherin, collagen Ⅰ, and fibronectin in the lung tissue was measured by enzyme-linked immunosorbent assay(ELISA). The expression levels of F4/80, Ly-6G, TGF-ß1, and collagen Ⅰ in the lung tissue were determined by immunohistochemistry. The mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue were determined by qRT-PCR. The content of hydroxyproline(HYP) in the lung tissue was determined by alkaline hydrolysation. The expression of α-SMA and E-cadherin was detected by immunofluorescence, and the protein levels of α-SMA, vimentin, E-cadherin in the lung tissue were determined by Western blot. The results showed the aqueous extract of E. sagittatum increased the survival rate, decreased the lung index, alleviated the pathological injury, collagen deposition, and oxidative stress in the lung tissue, and reduced the apoptotic cells. Furthermore, the aqueous extract of E. sagittatum down-regulated the protein levels of F4/80 and Ly-6G and the mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue, reduced the content of IL-6, CCL-2, and MMP-8 in the alveolar lavage fluid. In addition, it lowered the levels of HYP, TGF-ß1, α-SMA, collagen Ⅰ, fibronectin, and vimentin, and elevated the levels of E-cadherin in the lung tissue. The aqueous extract of E. sagittatum can inhibit collagen deposition, alleviate oxidative stress, and reduce inflammatory response by regulating the expression of the molecules associated with epithelial-mesenchymal transition, thus alleviating the symptoms of bleomycin-induced pulmonary fibrosis in mice.

Berberine Protects Against Dihydrotestosterone-Induced Human Ovarian Granulosa Cell Injury and Ferroptosis by Regulating the Circ_0097636/MiR-186-5p/SIRT3 Pathway.

Polycystic ovarian syndrome (PCOS) is an endocrine syndrome in women of reproductive age. Berberine (BBR) is a Chinese herbal monomer that exhibits many pharmacological properties related to PCOS treatment. This study aims to analyze the effect of BBR on a cell model of PCOS and the underlying mechanism. Human ovarian granulosa (KGN) cells were treated with dihydrotestosterone (DHT) to mimic a PCOS cell model. The RNA expression of circ_0097636, miR-186-5p, and sirtuin3 (SIRT3) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was detected by western blotting. Cell viability was analyzed by CCK-8 assay. Cell proliferation and apoptosis were investigated by 5-ethynyl-2'-deoxyuridine (EdU) assay and flow cytometry assay, respectively. The levels of interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) were analyzed by enzyme-linked immunosorbent assays (ELISAs). Fe2+ concentration was assessed by an iron assay kit. Oxidative stress was assessed by detecting reactive oxygen species (ROS) level and malondialdehyde (MDA) level using commercial kits. The association of miR-186-5p with circ_0097636 and SIRT3 was identified by dual-luciferase reporter assay and RNA pull-down assay. Circ_0097636 expression was downregulated in the follicular fluid of PCOS patients and DHT-treated KGN cells when compared with control groups. BBR treatment partially relieved the DHT-induced inhibitory effect on cell proliferation and promoted effects on cell apoptosis, inflammation, ferroptosis, and oxidative stress in KGN cells. Additionally, circ_0097636 bound to miR-186-5p, and SIRT3 was identified as a target gene of miR-186-5p in KGN cells. BBR treatment ameliorated DHT-induced KGN cell injury by upregulating circ_0097636 and SIRT3 expression and downregulating miR-186-5p expression. Moreover, circ_0097636 overexpression protected KGN cells from DHT-induced injury by increasing SIRT3 expression. BBR ameliorated DHT-induced KGN cell injury and ferroptosis by regulating the circ_0097636/miR-186-5p/SIRT3 pathway.

Hederasaponin C inhibits LPS-induced acute kidney injury in mice by targeting TLR4 and regulating the PIP2/NF-κB/NLRP3 signaling pathway.

Acute kidney injury (AKI) is a common clinical condition associated with increased incidence and mortality rates. Hederasaponin C (HSC) is one of the main active components of Pulsatilla chinensis (Bunge) Regel. HSC possesses various pharmacological activities, including anti-inflammatory activity. However, the protective effect of HSC against lipopolysaccharide (LPS)-induced AKI in mice remains unclear. Therefore, we investigated the protective effect of HSC against LPS-induced renal inflammation and the underlying molecular mechanisms. Herein, using MTT and LDH assays to assess both cell viability and LDH activity; using dual staining techniques to identify different cell death patterns; conducting immunoblotting, QRT-PCR, and immunofluorescence analyses to evaluate levels of protein and mRNA expression; employing immunoblotting, molecular docking, SPR experiments, and CETSA to investigate the interaction between HSC and TLR4; and studying the anti-inflammatory effects of HSC in the LPS-induced AKI. The results indicate that HSC inhibits the expression of TLR4 and the activation of NF-κB and PIP2 signaling pathways, while simultaneously suppressing the activation of the NLRP3 inflammasome. In animal models, HSC ameliorated LPS-induced AKI and diminished inflammatory response and the level of renal injury markers. These findings suggest that HSC has potential as a therapeutic agent to mitigate sepsis-related AKI.

China's application of the One Health approach in addressing public health threats at the human-animal-environment interface: Advances and challenges.

Background: Due to emerging issues such as global climate change and zoonotic disease pandemics, the One Health approach has gained more attention since the turn of the 21st century. Although One Health thinking has deep roots and early applications in Chinese history, significant gaps exist in China's real-world implementation at the complex interface of the human-animal-environment. Methods: We abstracted the data from the global One Health index study and analysed China's performance in selected fields based on Structure-Process-Outcome model. By comparing China to the Belt & Road and G20 countries, the advances and gaps in China's One Health performance were determined and analysed. Findings: For the selected scientific fields, China generally performs better in ensuring food security and controlling antimicrobial resistance and worse in addressing climate change. Based on the SPO model, the "structure" indicators have the highest proportion (80.00%) of high ranking and the "outcome" indicators have the highest proportion (20.00%) of low ranking. When compared with Belt and Road countries, China scores above the median in almost all indicators (16 out of 18) under the selected scientific fields. When compared with G20 countries, China ranks highest in food security (scores 72.56 and ranks 6th), and lowest in climate change (48.74, 11th). Conclusion: Our results indicate that while China has made significant efforts to enhance the application of the One Health approach in national policies, it still faces challenges in translating policies into practical measures. It is recommended that a holistic One Health action framework be established for China in accordance with diverse social and cultural contexts, with a particular emphasis on overcoming data barriers and mobilizing stakeholders both domestically and globally. Implementation mechanisms, with clarified stakeholder responsibilities and incentives, should be improved along with top-level design.

Effects of Liver-Regulating Herb Compounds on Varicocele-Associated Testicular Dysfunction Through Restoring Hormones and Spermatocytes Apoptosis.

PURPOSE: Varicocele is considered one of the causes of male infertility. Though varicocelectomy is supposed to improve semen parameters in adult infertile men, some patients with varicocele were still infertile after varicocelectomy. Previous studies showed Traditional Chinese Medicine, Liver-regulating herb compounds (LRHC) could improve the semen quality and increase fertility rates of infertile patients with varicocele. This study aimed to throw light on the mechanism of LRHC on varicocele-associated infertility. MATERIALS AND METHODS: Rats with varicocele-induced were treated with LRHC at dosage of 1mL/100g by intragastric administration for 90 days. The effects of LRHC on hormones and spermatocytes apoptosis were examined using ELISA assay, Western blotting, and flow cytometry. RESULTS: Rats induced with varicocele showed a higher level of follicle stimulating hormone (FSH) in serum, which was brought back to normal level by LRHC. After treatment with LRHC, both testicular tissue in vivo and Sertoli cell TM4 cells in vitro showed elevated expressions of FSHR. Cell viabilities of TM4 cells and spermatocyte GC-2 cells were improved by LRHC treatment under normoxia and hypoxia conditions. Moreover, LRHC protected GC-2 cells from apoptosis induced by hypoxia. The expression of Bax reduced, while that of Bcl-2 increased after treatment with LRHC. CONCLUSION: This study revealed that LRHC had protective effects on spermatogenic disturbance caused by varicocele through regulating hormones and reducing spermatogenic cell apoptosis under hpoxia conditions.

Case report and literature review on a large MBC with ulceration.

RATIONALE: Metaplastic breast cancer (MBC) is a rare tumor of the breast, and skin ulceration of breast tumors is a difficult clinical problem that reduces the patient's quality of life. PATIENT CONCERNS: There are currently no Standard Treatment Guidelines for MBC at present, and the treatment for the skin ulceration of breast tumors is limited in clinics. DIAGNOSIS: Here, we report the case of a patient with a large MBC and skin ulceration, accompanied by exudation and odor. INTERVENTION: The combined treatment of albumin paclitaxel and carrelizumab (anti-PD-1 immunotherapy) was effective in reducing the tumor, but it increased the severity of the skin ulceration. After taking traditional Chinese medicine, the skin ulceration healed completely. Then the patient underwent a mastectomy and radiotherapy. OUTCOMES: The patient has a high quality of life and was in good condition after the comprehensive treatment. LESSONS: This suggests that traditional Chinese medicine may have a good auxiliary therapeutic effect on the skin ulceration of MBC.

Diterpenoid quinones from the Salvia miltiorrhiza and their lung protective activity.

Seven new diterpenoids quinones (1-6), together with five known ones (7-11), were isolated from the roots of Salvia miltiorrhiza Bunge. Their structures were elucidated by using 1D and 2D NMR data, while the relative and absolute configurations were confirmed by interpretations of the NOESY correlations and comparison of the experimental and calculated ECD spectra. In the evaluation of bioactivities, salviamilthiza C (3), significantly increased cell viability and decreased the expression of IL-1ß in LPS-induced BEAS-2B cells.

Long-term effect of a large dose of iodinated contrast in patients with mild thyroid dysfunction: a prospective cohort study.

BACKGROUND: More than 75 million procedures with intravascular iodine-based contrast media (ICM) are performed worldwide every year, and some patients undergoing these procedures do not have normal thyroid function. The long-term effects of ICM in patients with mild thyroid dysfunction (TD) are unclear. METHODS: This prospective cohort study was conducted in China. Patients with stable angina pectoris with total triiodothyronine (TT3) reduction, normal thyroid-stimulating hormone, and reverse triiodothyronine (rT3) were enrolled and divided into high-dose (≥100 mL ICM) and low-dose groups (<100 mL ICM). We dynamically investigated the trends in thyroid function, rT3, and thyroid antibodies one year after ICM exposure. RESULTS: A total of 154 patients completed 6 months of follow-up and 149 completed 1 year of follow-up. Thyroglobulin antibody (TGAB) levels were elevated in 41 (26.6%) patients before ICM exposure, 11 (7.1%) of whom also had elevated thyroid peroxidase antibody levels. Transient subclinical TD occurred 6 months after ICM exposure; 75.5% (34/45) of post-operative TD occurred in the high-dose group. One patient developed severe hypothyroidism with myxedema, requiring drug intervention 1 year after ICM exposure. The level of rT3 showed no statistically significant changes during post-operative follow-up ( P  = 0.848). The TGAB level decreased at 6th month ( P  < 0.001), but increased at 1 year after ICM exposure ( P  = 0.002). CONCLUSIONS: Patients with T3 reduction are at a risk of transient subclinical TD and hypothyroidism after a single large dose of ICM. Follow-up of this population at 9-12 months after ICM exposure is warranted.

Towards an integrated health risk assessment framework of soil heavy metals pollution: Theoretical basis, conceptual model, and perspectives.

The health risk of soil heavy metals pollution has been gaining increasing public concern. However, many countries have not set their own health risk assessment (HRA) framework and most of the existing studies directly referred to the USEPA risk assessment model and parameters. For those countries that do not propose an original HRA framework, the experience of developed countries is crucial for advancing their own HRA system. This study systematically reviewed the development of HRA framework in some representative developed countries. The theoretical basis, conceptual model, progress, and challenges of HRA researches concerning soil heavy metals pollution were summarized. By recalling and comparing the health risk-related laws and guidance in the USA, UK, and Japan, results showed that the construction of HRA framework varied between these countries, but HRA has become the main method for deriving their soil environmental criteria. We further summarized the evaluation scales, land use types, exposure pathways, and sensitive receptors of HRA studies, and highlighted the key parameters affecting health risk outputs. There has been a shift toward the incorporation of probabilistic modeling, metals bioavailability, and sources emission characteristics into recent HRA studies. Nonetheless, challenges remained on how to minimize the uncertainty of generating probability distribution and detecting metal bioavailability. To facilitate the development of HRA framework, it was advised that developing countries should strengthen the theoretical researches of health risk and localization researches of exposure factors. Future directions are suggested to tend to: 1) promote sensitive analysis to quantify the impact of distribution assumptions on health risk outputs, 2) derive reasonable risk threshold and consistent evaluation protocol for bioavailability-based health risk assessment method, and 3) strive to explore the combined health effect of exposure to heavy metals in soil through source-media-receptor integrated studies.

Effects of fertilizer application on phthalate ester pollution and the soil microbial community in plastic-shed soil on long-term fertilizer experiment.

Due to the use of agricultural film, the pollution of phthalate esters (PAEs) in plastic-shed soils has attracted increasing attention. In this study, we used watermelon as a planting system and investigated the effects of organic fertilizer and chemical fertilizer application on the degradation of PAEs by evaluating soil nutrients and soil bacterial communities in plastic-shed soil. The dibutyl phthalate (DBP) concentration in the organic fertilizer soil was only 58.2% in the zero-fertilization control (CK) soil, but the concentrations of monohexyl phthalate (MEHP) and mono-n-butyl ester (MBP), the metabolites of PAEs, were found to be higher. The concentration of MBP is ten times that of DBP. The results showed that fertilization, especially the application of organic fertilizers, had a significant effect on the degradation of PAEs. There were specific biomarkers in different fertilization treatments. Among the microbiome community, Planifilum had the highest relative abundance in the organic fertilizer (OF) soil, and the highest proportion of Thermodesulfovibrionia was detected in the chemical fertilizer (CF) soil. These biomarkers were significantly correlated with PAEs and their metabolites. The relative abundance of Thermomonosporaceae was significantly positively correlated with DBP. Planifilum and Thermaerobacter, which significantly increased in organic fertilizer soil, showed a significant negative correlation with DBP and a significant positive correlation with MBP. The relative abundances of Planifilum and Geobacillus were elevated in the OF soil and may be able to co-metabolize soil nitrogen and PAEs. PAEs and their metabolites in soils had significant effects on soil microbes, as did the soil nutrients including available phosphorus (AP), alkali-hydrolysable nitrogen (Alkali-N), and organic matter (OM). Our research provides scientific support for the use of fertilizers to reduce PAE contamination but also warns of the potential risks of PAE metabolites.

[Mechanism of "Ephedrae Herba-Descurainiae Semen Lepidii Semen" combination in treatment of bronchial asthma based on network pharmacology and experimental verification].

This study aims to investigate mechanism of "Ephedrae Herba-Descurainiae Semen Lepidii Semen" combination(MT) in the treatment of bronchial asthma based on network pharmacology and in vivo experiment, which is expected to lay a theoretical basis for clinical application of the combination. First, the potential targets of MT in the treatment of bronchial asthma were predicted based on network pharmacology, and the "Chinese medicine-active component-target-pathway-disease" network was constructed, followed by Gene Oncology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the potential targets. Molecular docking was used to determine the binding activity of key candidate active components to hub genes. Ovalbumin(OVA, intraperitoneal injection for sensitization and nebulization for excitation) was used to induce bronchial asthma in rats. Rats were classified into control group(CON), model group(M), dexamethasone group(DEX, 0.075 mg·kg~(-1)), and MT(1∶1.5) group. Hematoxylin and eosin(HE), Masson, and periodic acid-Schiff(PAS) staining were performed to observe the effect of MT on pathological changes of lungs and trachea and goblet cell proliferation in asthma rats. The levels of transforming growth factor(TGF)-ß1, interleukin(IL)6, and IL10 in rat serum were detected by enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein levels of mitogen-activated protein kinase 8(MAPK8), cyclin D1(CCND1), IL6, epidermal growth factor receptor(EGFR), phosphatidylinositol 3-kinase(PI3 K), and protein kinase B(Akt) by qRT-PCR and Western blot. Network pharmacology predicted that MAPK8, CCND1, IL6, and EGFR were the potential targets of MT in the treatment of asthma, which may be related to PI3 K/Akt signaling pathway. Quercetin and ß-sitosterol in MT acted on a lot of targets related to asthma, and molecular docking results showed that quercetin and ß-sitosterol had strong binding activity to MAPK, PI3 K, and Akt. In vivo experiment showed that MT could effectively alleviate the symptoms of OVA-induced asthma rats, improve the pathological changes of lung tissue, reduce the production of goblet cells, inhibit the inflammatory response of asthma rats, suppress the expression of MAPK8, CCND1, IL6, and EGFR, and regulate the PI3 K/Akt signaling pathway. Therefore, MT may relieve the symptoms and inhibit inflammation of asthma rats by regulating the PI3 K/Akt signaling pathway, and quercetin and ß-sitosterol are the candidate active components.

Guanxinning tablet inhibits the interaction between leukocyte integrin Mac-1 and platelet GPIbα for antithrombosis without increased bleeding risk.

Recent studies have showed that thrombosis is closely related to leucocytes involved in immunity. Interfering with the binding of leukocyte integrin Mac-1 and platelet GPIbα can inhibit thrombosis without affecting physiological coagulation. Mac-1-GPIbα is proposed as a potential safety target for antithrombotic agents. Guanxinning tablet (GXNT) is an oral Chinese patent medicine used for the treatment of angina pectoris, which contains phenolic acid active ingredients, such as salvianolic acids, ferulic acid, chlorogenic acid, caffeic acid, rosmarinic acid, tanshinol, and protocatechualdehyde. Our previous studies demonstrated that GXN exhibited significant antithrombotic effects, and clinical studies suggested that it did not increase bleeding risk. In addition, GXN exerted a significantly regulatory effect on immune inflammation. In the current study, we intended to evaluate the effects of GXN on bleeding events and explore the safety antithrombotic mechanism of GXN based on leukocyte-platelet interaction. First, we established a gastric ulcer model induced by acetic acid in rats and found that GXN not only did not increase the degree of gastrointestinal bleeding when gastric ulcer occurred, but also had a certain promoting effect on the healing of gastric ulcer. Second, in vitroexperiments showed that after pretreatment with GXN and activation by phorbol 12-myristate-13-acetate (PMA), the adhesion and aggregation of leukocytes with human platelets were reduced. It was also found that GXN reduced the expression and activation of Mac-1 in leucocytes, and inhibited platelet activation due to leukocyte engagement via Mac-1. Overall, the results suggest that GXN may be a safe antithrombotic agent, and its low bleeding risk mechanism is probably related to inhibited leukocyte-platelet aggregation and its interaction target Mac-1-GPIbα.

Effects of WB-EMS and protein supplementation on body composition, physical function, metabolism and inflammatory biomarkers in middle-aged and elderly patients with sarcopenic obesity: A meta-analysis of randomized controlled trials.

BACKGROUND: The patients with sarcopenic obesity (SO) have the characteristics of both sarcopenia and obesity, that is, less muscle mass and increased fat mass, and their morbidity, disability and mortality are higher than patients with sarcopenia or obesity alone. OBJECTIVES: To investigate the effects of whole-body electromyostimulation (WB-EMS) training and protein supplementation intervention on body composition, physical function, metabolism and inflammatory biomarkers in middle-aged and elderly patients with SO. METHODS: We searched for randomized controlled trials in seven databases, including PubMed, Web of Science, Embase, Cochrane Library, Scopus, SinoMed, and CNKI as of July 3, 2021. The methodological quality of each included study was assessed using the Physiotherapy Evidence Database (PEDro) scale. The Cochrane Risk of Bias Tool was used to assess the risk of bias. Statistical analysis was performed using Review Manager 5.3. RESULTS: Eleven randomized controlled studies with a total of 779 participants were included in this meta-analysis. WB-EMS training improved sarcopenia Z-score (MD = -1.52, 95 % CI: -2.27, -0.77, P < 0.0001) and waist circumference (WC) (MD = -1.41, 95 % CI: -2.62, -0.20, P = 0.02), and increased skeletal muscle mass index (SMI) (MD = 1.27, 95 % CI: 0.66,1.88, P < 0.0001) and appendicular skeletal muscle mass (ASMM) (MD = 0.68, 95 % CI: 0.08, 1.27, P = 0.03). Protein supplementation intervention reduced body fat rate (BF%) (MD = -1.28, 95 % CI: -1.88, -0.68, P < 0.0001, I2 = 0 %), total body fat (TBF) (MD = -0.98, 95 % CI: -1.65, -0.31, P = 0.004, I2 = 0 %) and trunk body fat mass (TBFM) (MD = -0.50, 95 % CI: -0.94, -0.06, P = 0.03, I2 = 0 %), and increased grip strength (GS) (MD = 1.13, 95 % CI: 0.06, 2.21, P = 0.04, I2 = 0 %). The combination of WB-EMS and protein supplements is beneficial to most body components and physical functions, such as SMI (MD = 1.21, 95 % CI: 0.73, 1.51, P < 0.00001, I2 = 0 %), GS (MD = 1.60, 95 % CI: 0.80, 2.40, P < 0.0001, I2 = 45 %) and walking speed (WS) (MD = 0.04, 95 % CI: 0.02, 0.06, P < 0.0001, I2 = 49 %). Compared with protein supplementation alone, WB-EMS could have an additional beneficial effect on BF% (MD = -0.92, 95 % CI: -1.80, -0.04, P = 0.04) and WC (MD = -1.03, 95 % CI: -1.70, -0.36, P = 0.003). Nevertheless, the addition of protein supplements did not provide any additional benefit compared with WB-EMS alone. In addition, there was almost no positive effect of WB-EMS and protein supplements on metabolic and inflammatory biomarkers. CONCLUSIONS: As things stand, protein supplementation intervention can effectively reduce body fat percentage, fat mass, and increase grip strength in SO patients. Both WB-EMS and protein supplementation intervention had no significant effects on metabolic and inflammatory biomarkers. WB-EMS combined with protein supplementation intervention was beneficial for SO patients in many ways. Due to the small number of studies, further studies are needed to confirm the efficacy of WB-EMS alone or in combination with protein supplementation intervention in SO patients. REGISTRATION NUMBER: INPLASY202190096 DOI:10.37766/inplasy2021.9.0096.

Towards a global One Health index: a potential assessment tool for One Health performance.

BACKGROUND: A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed. METHODS: We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators. RESULTS: The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8-65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible. CONCLUSIONS: GOHI-subject to rigorous validation-would represent the world's first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge.

[Volatile Organic Compound Emission Characteristics and Influences Assessment of a Petrochemical Industrial Park in the Pearl River Delta Region].

The petrochemical industry is one of the major emission sources of volatile organic compounds (VOCs). However, the current studies have mostly focused on the identification of the chemical characteristics of non-methane hydrocarbon (NMHC) VOCs species from the petroleum refining sub-sector. Research on the characteristics of VOCs components in oxygenated VOCs (OVOCs) species and other important sub-sectors is still lacking. Therefore, eight enterprises at a petrochemical industrial park in the Pearl River Delta region were carefully selected to represent three major subsectors, namely petroleum refining, synthetic materials, and organic chemicals, for the petrochemical industry. The VOCs (including 22 OVOCs species) from stack emissions and fugitive emissions, as well as nearby sensitive sites, were sampled, and the source reactivity (SR), the thresholds of malodor, and the carcinogenic and non-carcinogenic risks were assessed. The main results were as follows:① the VOCs concentrations of the stack emissions from the petrochemical industrial park were between 0.2-46.3 mg·m-3. The VOCs species were greatly affected by the type of after-treatment technology. A major VOC species emitted from the combustion-based after treatments was formaldehyde, whereas the species emitted from the non-combustion-based equipment were acetone, 1,3-butadiene, acrylic, and isobutane. ② The fugitive VOCs emissions from the petroleum storage tank area were dominated by alkanes, whereas the other fugitive emission sites and the sensitive sites were dominated by OVOCs such as acetone, formaldehyde, and ethyl acetate. ③ The SRs were mainly contributed by OVOCs, aromatics, and olefins, with average proportions of 43.1%, 24.2%, and 21.1%, respectively, with the major species being formaldehyde, acetaldehyde, m/p-xylene, ethylene, and toluene. ④ The malodor appeared both in fugitive emission areas and the sensitive sites. The main odor components were OVOCs such as n-butyraldehyde, propionaldehyde, hexanal, and valeraldehyde. ⑤ The non-carcinogenic risks occurred in the fugitive emission areas and the sensitive sites of resin, alcohol, and aldehyde production, which were mainly caused by OVOCs such as free acetaldehyde, acrolein, and propionaldehyde. No carcinogenic risk was found in any of the sampled sites. This research can provide scientific support for the formulation of priority VOCs species-based precise control strategies in petrochemical industrial parks.

Metabolomic Profiling of Poor Ovarian Response Identifies Potential Predictive Biomarkers.

Objective: To characterize the serum metabolomic profile and its role in the prediction of poor ovarian response (POR). Patients: Twenty-five women with normal ovarian reserve (24-33 years, antral follicle count [AFC] ≥5, anti-Müllerian hormone [AMH] ≥1.2 ng/ml) as the control group and another twenty-five women with POR (19-35 years, AFC <5, AMH < 1.2 ng/ml) as the study group were collected in our study. The serum levels of the women in both groups were determined from their whole blood by untargeted liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical analysis and cell signal pathways analysis were used to reveal the results. Results: A total of 538 different metabolites were finally identified in the two groups. Tetracosanoic acid, 2-arachidonoylglycerol, lidocaine, cortexolone, prostaglandin H2,1-naphthylamine, 5-hydroxymethyl-2-furancarboxaldehyde, 2,4-dinitrophenol, and D-erythrulose1-phosphate in POR were significantly different from control as were most important metabolites in support vector machines (p <0.05). Metabolomic profiling, together with support vector machines and pathway analysis found that the nicotinate and nicotinamide metabolism pathway, including L-aspartic acid, 6-hydroxynicotinate, maleic acid, and succinic acid semialdehyde, was identified to have significant differences in POR women compared to control women, which may be associated with ovarian reserve. Conclusion: This study indicated that LC-MS-based untargeted metabolomics analysis of serum provided biological markers for women with POR. The nicotinate and nicotinamide metabolism pathway may offer new insight into the complementary prediction and therapeutic potential of POR. The functional associations of these metabolites need further investigation.

Curdione and Schisandrin C Synergistically Reverse Hepatic Fibrosis via Modulating the TGF-ß Pathway and Inhibiting Oxidative Stress.

Hepatic fibrosis is the final pathway of several chronic liver diseases, which is characterized by the accumulation of extracellular matrix due to chronic hepatocyte damage. Activation of hepatic stellate cells and oxidative stress (OS) play an important role in mediating liver damage and initiating hepatic fibrosis. Hence, hepatic fibrosis can be reversed by inhibiting multiple channels such as oxidative stress, liver cell damage, or activation of hepatic stellate cells. Liuwei Wuling Tablets is a traditional Chinese medicine formula with the effect of anti- hepatic fibrosis, but the composition and mechanism of reversing hepatic fibrosis are still unclear. Our study demonstrated that one of the main active components of the Chinese medicine Schisandra chinensis, schisandrin C (Sin C), significantly inhibited oxidative stress and prevented hepatocyte injury. Meanwhile one of the main active components of the Chinese medicine Curdione inhibited hepatic stellate cell activation by targeting the TGF-ß1/Smads signaling pathway. The further in vivo experiments showed that Sin C, Curdione and the combination of both have the effect of reversing liver fibrosis in mice, and the combined effect of inhibiting hepatic fibrosis is superior to treatment with Sin C or Curdione alone. Our study provides a potential candidate for multi-molecular or multi-pathway combination therapies for the treatment of hepatic fibrosis and demonstrates that combined pharmacotherapy holds great promise in the prevention and treatment of hepatic fibrosis.