ObjectiveTo investigate the impacts of three types of acupuncture timing factors， including intervention initiation time， needle retention duration， and treatment intervals， on the treatment efficacy of ischemic stroke （IS） and provide evidence-based support for optimizing acupuncture timing strategies. MethodsA systematic search was conducted in both Chinese and English databases， including CNKI， Wanfang Data， VIP， CBM， PubMed， Web of Science， Cochrane Library， and Embase. The randomized controlled trials involving multiple acupuncture intervention time groups were included to reduce inter-study heterogeneity. A network meta-analysis model was constructed to compare the effects of different intervention initiation time， needle retention duration， and treatment intervals on primary IS outcomes， including total clinical response rate， neurological and limb function scores， quality of life score， and hemorheological parameters. Adverse events were also assessed. ResultsA total of 32 studies were included. The results showed that early acupuncture intervention （1-3 days and 4-7 days after onset） outperformed late intervention （>14 days） in terms of response rate， neurological function improvement， and quality of life （P<0.05， P<0.01）. Extending needle retention time to 40-60 min was associated with improved response rates and hemorheological parameters （P<0.01）. No significant differences were observed among different treatment intervals. The evidence of key outcomes showed high overall certainty， with low heterogeneity and inconsistency. Sensitivity analyses and publication bias assessments indicated the stability of the main results and a low risk of publication bias. No significant adverse reaction was reported. ConclusionDifferent timing factors significantly influence the efficacy of acupuncture treatment for IS. Early intervention and appropriately extended needle retention time result in better clinical outcomes， while treatment interval has no significant effect on efficacy. The inclusion of studies with multiple acupuncture timing groups helps control methodological heterogeneity and enhances the robustness of the analysis， providing evidence-based guidance for optimizing acupuncture timing strategies in IS management.

ObjectiveTo construct a comprehensive evaluation indicator system for clinical practice guidelines of traditional Chinese medicine （TCM） that is scientific， systematic， and reflects the characteristics of TCM. MethodsA systematic search was conducted in Chinese and English databases， including CNKI， Wanfang， VIP， SinoMed， PubMed， Embase， and Cochrane Library， to include literature on domestic and international guideline evaluation tools and TCM-related research. Document analysis and CiteSpace were utilized for keyword co-occurrence and clustering analysis. ResultsA total of 65 relevant studies were included， from which seven core thematic domains were identified. Based on the research objectives， a two-step construction strategy was adopted： first， an external evaluation framework was established by referencing international tools to cover methodological rigor and procedural standardization； second， an internal evaluation framework was developed to reflect the distinctive features of TCM clinical practice， including syndrome differentiation and efficacy feedback. Through expert consensus， the indicator system was refined， resulting in a dual-layered structure comprising 8 primary indicators， 22 secondary indicators， and 62 evaluation criteria. ConclusionThe comprehensive evaluation system for TCM clinical practice guidelines， based on bibliometric analysis and core element extraction， integrates both theoretical integrity and practical applicability. This study provides a preliminary research foundation for further optimization， validation， and development of a refined comprehensive evaluation system.

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.

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.

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.

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.