ObjectiveTo investigate the effect and mechanism of total saponins from Panax japonicus （TSPJ） on white adipose tissue （WAT） browning/brown adipose tissue （BAT） activation in C57BL6/J male mice fed on a high-fat diet （HFD）. MethodThirty-two C57BL6/J male mice （8-week-old） were randomly divided into a normal group， a model group， a low-dose TSPJ group， and a high-dose TSPJ group. The mice in the low-dose and high-dose TSPJ groups were given TSPJ for four months by gavage at 25， 75 mg·kg^-1·d^-1， respectively， and those in the other groups were given 0.5% sodium carboxymethyl cellulose （CMC-Na） accordingly. After four months of feeding， all mice were placed at 4 ℃ for acute cold exposure， and the core body temperature was monitored. Subsequently， all mice were sacrificed， and BAT and inguinal WAT （iWAT） were separated rapidly to detect the corresponding indexes. Hematoxylin-eosin （HE） staining was used to observe the morphological changes in each group. The effect of TSPJ on the mRNA expression of uncoupling protein 1 （UCP1）， fatty acid-binding protein 4 （FABP4）， cytochrome C （CytC）， PR domain-containing protein 16 （PRDM16）， elongation of very long chain fatty acids protein 3 （ELOVL3）， peroxisome proliferator-activated receptor γ （PPARγ）， and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） in iWAT and BAT was detected by Real-time polymerase chain reaction （Real-time PCR）. Western blot was also used to detect the protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in BAT and iWAT of each group. The effect of TSPJ on UCP1 expression in BAT and iWAT was detected by immunohistochemistry. Result① Compared with the model group， TSPJ could decrease the body weight and proportions of iWAT and BAT in the HFD-induced mice （P<0.05， P<0.01）. ② The body temperature of mice in the model group decreased compared with that in the normal group in the acute cold exposure tolerance test （P<0.05）. The body temperature in the high-dose TSPJ group increased compared with that in the model group （P<0.01）. ③ Compared with the normal group， the model group showed increased adipocyte diameter in iWAT and BAT and decreased number of adipocytes per unit area. Compared with the model group， the TSPJ groups showed significantly reduced cell diameter and increased number of cells per unit area， especially in the high-dose TSPJ group. ④ Compared with the normal group， the model group showed decreased mRNA expression of FABP4， UCP1， CytC， PRDM16， ELOVL3， PGC-1α， and PPARγ in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the mRNA expression was significantly up-regulated （P<0.05， P<0.01）. ⑤ Compared with the normal group， the model group showed decreased protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the protein expression increased significantly （P<0.05， P<0.01）. ConclusionTSPJ could induce the browning of iWAT/BAT activation and enhance adaptive thermogenesis in obese mice induced by HFD. The underlying mechanism may be attributed to the activation of the PPARγ/PGC-1α signaling pathway.

Objective:To investigate whether long non-coding RNA(lncRNA) AW112010 can improve insulin resistance in aging adipocytes through the miR-204/POU2F2 signaling pathway.Methods:In vivo experiment: C57BL/6 mice were divided into young control group(4 months old) and aging model group(18 months old) based on body weight. The expression levels of AW112010, miR-204-5p, POU2F2, aging related indicators(p16, p21), and insulin signaling pathway genes [insulin receptor(INSR), insulin receptor substrate 1(IRS1), phosphatidylinositol kinase(PI3K), protein kinase B(AKT)] in epididymal adipose tissue were detected using real-time fluorescence quantitative PCR(RT-qPCR) and Western blotting. In vitro experiment: Using adriamycin(ADR) to induce 3T3-L1 aging adipocyte model, β-gal staining was used to observe cellular senescence, and miR-204 inhibitor and miR-204 mimic small interfering RNA were successfully constructed and transfected into 3T3-L1 adipocytes. Results:RT-qPCR and Western blot results showed that compared with the young group, the expression of AW112010 in the adipose tissue of aging mice was increased, while the expression of miR-204-5p was decreased. The expressions of POU2F2, p16, and p21 in the adipose tissue of aging mice were increased, while the expressions of INSR, IRS1, PI3K, GLUT4 mRNA and protein were decreased. The β-gal stainging results showed that the number of 3T3-L1 senescent adipocytes induced by ADR was significantly increased, and the expression levels of AW112010, POU2F2, p16, and p21 in ADR-induced senescent adipocytes were increased compared with the control group, while the expression levels of miR-204-5p, INSR, IRS1, PI3K, GLUT4 were decreased, and remaining glucose in the culture medium was increased. Compared with control, overexpression of miR-204 resulted in decreased expressions of aging indicators p16, p21, and target gene POU2F2 while the expressions of INSR and GLUT4 were increased.Conclusion:Upregulation of lncRNA AW112010 in adipocytes of aging mice may induce insulin resistance by targeting miR-204-5p/POU2F2/IRS1.

Uric acid (UA), the final product of human purine metabolism, can cause hyperuricemia (HUA) when excessively accumulated. HUA is closely linked to chronic kidney diseases (CKD) and is considered an independent risk factor. Hyperuricemic nephropathy, a form of CKD induced by HUA, has seen significant advances in understanding through research into the pathogenic roles of uric acid and the development of HUA animal models. Although progress has been made in understanding the pathophysiological mechanisms by which UA induces CKD, much remains to be learned about its pathological molecular mechanisms. New approaches in animal modeling or the selection of model animals may potentially lead to significant breakthroughs in research on hyperuricemia as well as related CKD. This paper reviews the research progress on the molecular mechanisms of hyperuricemic nephropathy, focusing on oxidative stress, inflammation, autophagy, fibrosis, and gut microbiota. Oxidative stress is induced by uric acid intracellularly through xanthine oxidase, NADPH oxidases, and mitochondria, leading to cellular damage. In terms of inflammation, uric acid crystals can activate the NLRP3 inflammasome, triggering an inflammatory cascade. The role of free uric acid as a pro-inflammatory agent, however, remains controversial. Depending on the study conducted, autophagy has been found to either alleviate or exacerbate inflammation induced by uric acid. Fibrosis, particularly through epithelial-mesenchymal transition (EMT), is a major mechanism by which uric acid causes glomerulosclerosis and tubulointerstitial fibrosis. Extensive research has explored various signaling pathways involved in uric acid-induced EMT. Beneficial gut microbiota protect the kidneys by synthesizing short-chain fatty acids, reducing urea’s enterohepatic circulation, and decreasing uric acid production. This paper aims to enhance understanding of the complex relationships between HUA and CKD, serving as a reference for further research and new drug development.

This study used the Appraisal of Guidelines Research & Evaluation-Health Systems （AGREE-HS） to demonstratively compare 34 global coronavirus disease-2019 （COVID-19） health systems guidance documents （HSGs） and 6 World Health Organization （WHO） standard HSGs. The comparison involved topic， participants， methods， recommendations， and implementability， with the aim of exploring the characteristics of emergency HSGs. The results showed that the emergency HSGs had an overall average score of 49%， with topic having the highest score， recommendations having the second highest score， and participants having the lowest score. The standard HSGs had an overall average score of 79%， with high scores in all items. The emergency HSGs had lower scores in participants， methods， recommendations， and implementability than the standard HSGs （P<0.001）， while the COVID-19 emergency HSGs developed by the WHO had higher score in topic than the standard HSGs （P<0.05）. Compared with those released by countries， the COVID-19 emergency HSG developed by the WHO showed superiority in all items and overall scores （P=0.000 2）. This indicates that emergency HSGs， represented by the COVID-19 emergency HSG， place equal emphasis on topic and recommendations as standard HSGs but have low requirements in terms of expert participation， evidence support， and comprehensive consideration in the time- and resource-limited context. They have the characteristics of prominent topics， clear purposes， orientation to demand， keeping up with the latest evidence， flexible adjustment， and timeliness， emphasizing immediate implementation effects， weakening long-term effects， and focusing on comprehensive benefits. Additionally， developers， types， and report completeness are important influencing factors.

The scientific rigor and efficacy of methodologies employed in drafting emergency health systems guidance documents （HSGs） are paramount in guaranteeing the quality， reliability， and applicability of HSGs. According to the Appraisal of Guidelines for Research and Evaluation- Health Systems （AGREE-HS）， we demonstratively assessed both global coronavirus disease-2019 （COVID-19） emergency HSGs and World Health Organization （WHO） standard HSGs to uncover the core attributes of methods employed in the development of emergency HSGs. Our evaluation findings revealed that across the five assessment items of AGREE-HS， methods in the 34 emergency HSGs evaluated ranked third， trailing behind topic and recommendations. Notably， criterion 2 （the best available and most contextually relevant evidence is considered） received the highest score， whereas criterion 5 （evidence of cost and cost-effectiveness of the potential options is described） scored the lowest. Compared with the WHO standard HSGs， the COVID-19 emergency HSGs exhibited low scores in methods （P<0.05）， which was reflected in nine criteria （P<0.05）， especially in criteria 1 （systematic and transparent methods are used to identify and review the evidence） and 9 （systematic and transparent methods are used to agree upon the final recommendations）. Among the COVID-19 emergency HSGs， that developed by the WHO achieved higher scores in eight out of all nine criteria， excluding criterion 8 （P<0.05）. The clinically relevant emergency HSGs had higher scores in the criteria 3 （the evidence base is current） and 8 （the rationale behind the recommendations is clear） than other types of emergency HSGs. Collectively， the methodology for developing emergency HSGs， represented by the COVID-19 emergency HSG， underscores evidence orientation and integrates expert consensus. It is characterized by adaptable evidence synthesis strategies， streamlined evidence review protocols， and contextual relevance， all of which are influenced by external， internal， and implementation-specific factors.

The formulation method of emergency health systems guidance （HSG） is crucial， directly impacting the efficiency and effectiveness of responses in emergencies. A scientifically sound， systematic， and easily executable guidance document can assist health institutions at all levels in quickly coordinating resources， standardizing emergency response processes， and safeguarding public health. This study employed the Appraisal of Guidelines for Research and Evaluation for Health Systems （AGREE-HS） to analyze the characteristics of participants in developing emergency HSGs represented by the COVID-19 emergency HSG. The results showed that in the 34 HSGs included in this study， the item participants received the lowest score. Within this item， criterion 1 （diversity of development group） scored the highest （3.13±1.55）， while criterion 5 （prevention of funding agency influence） scored the lowest （1.21±0.47）. There were differences （P<0.05） in measures taken to mitigate funding agency influence between the six standard HSGs developed by the World Health Organization （WHO） and the four emergency HSGs. Additionally， differences （P<0.05） existed in the development group members， background， conflicts of interest， and preventive measures between the six WHO standard HSGs and the 34 emergency HSGs， as well as between the HSGs developed by the WHO and those developed by countries. The participants in developing emergency HSGs were influenced by various factors， including limited time for guideline development， modes of participation， scarce evidence， and uncertainties in expected outcomes. There is a need to downplay extensive requirements concerning the composition of group members， institutional diversity， and conflicts of interest， emphasizing the roles of key participants like government officials and professionals who can provide rapid， practical guidance in emergency situations.

Recommendations， consensus-based syntheses of the best available evidence， constitute the core content of a guideline. This paper analyzes the characteristics of emergency health systems guidance documents （HSGs）， represented by the coronavirus disease-2019 （COVID-19） emergency HSG， regarding the item "recommendations" and its eight evaluation criteria in the Appraisal of Guidelines for Research and Evaluation for Health Systems （AGREE-HS）. The World Health Organization （WHO） standard HSGs were used as reference to explore the characteristics of emergency HSGs that are different from non-emergency HSGs. The results showed that the “recommendations” scored second after “topic” among the five items. Criterion 7 relating to operability scored higher than others among the eight criteria， and criterion 3 dealing with ethical principles scored lower than other criteria. Compared with the standard HSGs， the emergency HSGs showed decreased scores （P<0.05） of the item recommendations and the criteria of this item except criterion 4 concerning equity promotion. Among the HSGs with different developers， those developed by the WHO had higher （P<0.05） scores of recommendations than nationally developed HSGs， as evidenced by criterion 4， criterion 5 involving acceptability to and alignment with sociocultural and political interests， and criterion 8 for updating plans. The HSGs regarding global or country strategy scored higher （P<0.05） on criterion 2 relating to comprehensiveness than those involving specific guidance on clinical or material issues. Overall， the emergency HSGs， represented by the COVID-19 emergency HSGs， differ from the standard HSGs in a number of ways in terms of their recommendations. Emergency HSGs have more condensed content and weaker articulation of expected outcomes. They incline to put more emphasis on updating plans， rather than comprehensiveness or integrative requirements in terms of ethics， equity， and sociocultural and political interests.

The clear definition of the topic in emergency health systems guidance （HSG） ensures the relevance， scientific rigor， and practicality of the guidance， providing a clear direction and a framework for a rapid and effective public health response. This study used the Appraisal of Guidelines for Research & Evaluation-Health Systems （AGREE-HS） to demonstratively evaluate the global COVID-19 emergency HSGs and World Health Organization （WHO） standard HSGs， aiming to explore the characteristics of topic in emergency HSGs. The results showed that in the 34 HSGs included， the item topic received the highest score. Specifically， criterion 4 relating to relevant and applicable factors scored the highest （5.59）， while criterion 3 concerning the prioritization of health system challenges scored the lowest （2.76）. There were differences （P<0.05） in criterion 1 between standard HSGs and overall emergency HSGs， as well as between WHO and national emergency HSGs. Criterion 3 also showed differences （P<0.05） between standard HSGs and emergency HSGs， as well as between WHO and national emergency HSGs. Criterion 4 displayed differences （P<0.000 1） between WHO and national emergency HSGs. No differences were observed in intra-group or inter-group comparisons of different emergency HSG subcategories （P<0.05）. Overall， emergency HSGs represented by the COVID-19 emergency HSG focus on detailing the challenges faced by the health system， including the natures of challenges， affected populations， and other relevant and applicable factors， while aligning with stakeholder concerns. The prioritization is downplayed， with emphasis placed on rapid responses to and flexible handling of urgent issues. Influenced by factors such as the evidence base， phase timing， and effectiveness， the topic setting shows variations.

Guidance implementation acts as a bridge between theory and practice，enabling the rapid expansion of their impact and application. This study demonstratively evaluated emergency health systems guidance documents （HSG），represented by the COVID-19 emergency HSG，based on the item implementability of the Appraisal of Guidelines for Research and Evaluation-Health Systems （AGREE-HS），aiming to explore the characteristics of implementability in emergency HSG. The evaluation results indicated that the COVID-19 emergency HSG had a low mean score in implementability，which ranked just above the item participants. Criterion 2 （costs and resource considerations for implementing the recommendations） received the highest mean score of 4.29，while criterion 9 （systematic evaluation of implementation） received the lowest mean score of 1.34. The emergency HSG formulated by the World Health Organization（WHO） and those formulated by various countries showed no difference （P=0.114） in criterion 1 （barriers and facilitators to implementation） but had differences （P<0.05） regarding the average item scores and the scores of the remaining criteria. The WHO standard HSG had high overall scores and had differences （P<0.05） in both the mean item scores and the scores of the nine criteria when compared with the emergency HSG. The global/national HSG showed differences in scores of criterion 1 （barriers and facilitators to implementation） compared with the both clinically relevant HSG and material support HSG （P<0.05）. Emergency HSG prioritized considerations of implementation costs，resources，and flexibility in terms of implementability，while de-emphasizing aspects such as stakeholder opinions，dissemination strategies，and evaluation of HSG. This may be attributed to the context in which emergency HSG are formulated，given the inherent flexibility and variability of emergency health events. The developers should comprehensively consider the needs and characteristics related to the implementability of emergency HSG during the formulation process.

Objective This study aimed to investigate the role and mechanism of atractylenolide Ⅰ in inhibiting XPOT proliferation and invasion in gastric cancer cells.Methods This study included exploration of XPOT expression in gastric cancer tissues,analysis of gene expression data from GC patients in TCGA and GEO databases,as well as various cellular assays to detect the ability of cancer cells to proliferate,migrate,and invade.Protein expression levels of XPOT,SKP2,CyclinA,and P27 mRNA were also detected by qPCR and Western Blot.Results Analysis confirmed that XPOT was highly expressed in gastric cancer tissues,indicating a poor prognosis.In vitro studies revealed that AT-1 inhibits the proliferation and invasion ability of GC cells;XPOT down-regulation also inhibits these abilities.Furthermore,AT-1 down-regulates the expression of XPOT which then regulates SKP2,P27,and CyclinA-ultimately inhibiting the proliferation and invasion of gastric cancer cells through the regulation of the XPOT pathway.Conclusion The overexpression of XPOT in gastric cancer tissues can indicate a poor prognosis.Atractylenolide Ⅰ down-regulates the XPOT-regulated ubiquitination-proteasome pathway to inhibit proliferation and invasion of gastric cancer cells.