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.

OBJECTIVE To elucidate the mechanisms responsible for the inhibitory effects of limonene on the proliferation of non-small cell lung cancer(NSCLC) by non-targeted metabolomics and additional approaches. METHODS The CCK-8 assay was utilized to evaluate the inhibitory effects of limonene on NSCLC A549 cell viability and to ascertain the IC50. In vitro experiments, encompassing colony formation, flow cytometry, iron content assessment, and mitochondrial staining, were conducted to assess the anti-lung cancer and iron-induced cell death effects of limonene. Metabolomic analysis was employed to identify potential pathways influenced by limonene, and Western blotting was carried out to validate pivotal proteins within these pathways. RESULTS In comparison to the control group, the limonene-treated group demonstrated a significant, dose-dependent reduction in A549 cell proliferation and colony formation. Optical microscopy revealed cellular detachment and pronounced changes in cellular morphology following exposure to limonene. Limonene induced apoptosis in A549 cells and arrested them in the G0-G1 phase of the cell cycle. Confocal microscopy unveiled diminished mitochondrial fluorescence and an augmented intracellular iron content, indicative of the classical phenomenon of ferroptosis. Metabolomic investigations unveiled divergent metabolic pathways, including glutathione(GSH) metabolism, arginine biosynthesis, D-glutamine and D-glutamate metabolism, as well as cysteine and methionine metabolism, with many of them intricately linked to intracellular GSH synthesis. Western blotting experiments underscored a marked reduction in the levels of SLC40A1, SLC7A11(xCT), and GPX4 proteins within the cells post-limonene treatment. CONCLUSION Limonene may induce ferroptosis in lung cancer cells by reducing GSH synthesis and increasing Fe2+ levels.

Cinnamomi Ramulus and Alismatis Rhizoma are commonly used in the treatment of external-contraction diseases. Cinnamomi Ramulus is pungent， sweet， and warm， with the effects of ventilating lung and dispersing cold， warming Yang and transforming Qi， and promoting water and liquid flow from Taiyang meridian to remove dampness. Alismatis Rhizoma is sweet and cold， with the effects of draining dampness and promoting urination， regulating the waterway， removing water retention in lung， and promoting urination to remove dampness and heat. Herbal pairs are extracted from the accumulated experience of medical practitioners over the ages in the use of medicines and have been proved by clinical application to be composed of simple and effective combinations for specific diseases. The herb pair Cinnamomi Ramulus-Alismatis Rhizoma is an important part in ancient classic formulas such as Wulingsan. Both herbs play a role in draining dampness and promoting urination， warming Yang and transforming Qi， being a representative herb pair used for treating external-contraction exterior syndrome and water retention inside. The review of ancient medical publications revealed that there were a large number of compound formulas containing Cinnamomi Ramulus-Alismatis Rhizoma for dispersing cold and removing dampness， which were widely used for thousands of years in clinical practice. Modern pharmacological studies have shown that the active pharmacological components of Cinnamomi Ramulus （cinnamaldehyde and cinnamic acid） and Alismatis Rhizoma （alisol A and 23-acetate alisol B） have anti-inflammatory， antiviral， and immunoregulatory effects and high safety. Qingfei Paidu decoction containing this herbal pair played an important role in fighting against COVID-19. Despite the extensive pharmacological studies on Cinnamomi Ramulus and Alismatis Rhizoma， few studies have been carried out regarding this herb pair. This paper summarizes the traditional Chinese medicine knowledge about Cinnamomi Ramulus and Alismatis Rhizoma in the treatment of external-contraction diseases and summarizes the chemical composition， pharmacological effects， toxicology and other aspects of the two herbs before and after compatibility， aiming to provide a reference for further research and clinical application.

Purpose To investigate the relationship be-tween the expressions of CD3,CD4,CD8,CD20,CD68,PD-1 and PD-L1 and the clinical prognosis of peritoneal mesothelioma(PM).Methods Clinical data of 69 PM patients were collect-ed.EnVision two-step immunohistochemical method was used to detect the expression of CD3,CD4,CD8,CD20,CD68,PD-1 and PD-L1 in PM.Associations between expression levels and survival were estimated by univariate and multivariate Cox pro-portional-hazards models.Results There were no significant differences in the expressions of CD3,CD4,CD8,CD20,CD68,and PD-1 in tumor infiltrating lymphocytes(TILs)of ep-ithelioid and non-epithelioid PM.The expression of PD-L1 in non-epithelioid PM TILs was higher than that in epithelioid PM TILs,but the difference was not statistically significant.The median overall survival(mOS)time of PM was 19.1 months.Multivariate models identified asbestos exposure(P=0.002),PCI score(P=0.034),histological type(P=0.036),and CD4 expression(P=0.043)was independent prognostic factors for PM.Conclusion Asbestos exposure,PCI score,histologi-cal type and CD4 expression in TILs may exert significant im-pacts on survival of PM patients.

Objective To mine adverse drug event(ADE)signals of doxycycline using the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,and provide scientific evidence for clinical medication safety.Methods The data from the FAERS database between the first quarter of 2004 and the first quarter of 2024 were extracted.After data cleaning and standardization,ADE reports with doxycycline as the main suspected drug were screened.The system organ class(SOC)of ADE was performed using MedDRA,and the reporting odds ratio method and Medicines and Healthcare products Regulatory Agency method were used to mine ADE signals.The information component method was also used to evaluate signal strength.Results A total of 43 126 ADE reports with doxycycline as the primary suspected drug were collected,involving 14 642 patients,with a higher proportion of female patients(57.32％).There were 555 related ADE signals involving 26 SOC,with the top 5 SOC being gastrointestinal disorders,skin and subcutaneous tissue disorders,injuries,poisonings,and procedural complications,psychiatric disorders,and infections and infestations.The top 5 ADE signals with the highest signal intensity were Hatch reaction,sclerosing cholangitis,esophageal ulcer,gastrointestinal mucosal necrosis,and gastrointestinal injury.Among the ADE signals with the strongest signal strength not listed in the package insert,the top five were sclerosing cholangitis,nephrogenic diabetes insipidus,minimal change glomerular nephritis,diabetes insipidus and Sixth cranial nerve paralysis.Conclusion In clinical practice,particular attention should be paid to the frequent ADEs caused by doxycycline,as well as those not yet documented in the package insert,which involve multiple SOC such as renal and urinary disorders,hepatobiliary diseases,blood and lymphatic system disorders,and endocrine disorders.Therefore,clinical pharmacists should play a key role in assisting clinicians to develop and implement prevention plans for ADEs,thereby improving the safety of doxycycline in clinical use.

The standardization of classification methods of Traditional Chinese Medicine(TCM) ancient books can provide a clear and reliable reference for all kinds of TCM ancient books collection units, which can also promote the sharing and utilization of TCM ancient books. We studied and investigated the classification methods of TCM ancient books in past dynasties. The standard on classification of TCM ancient books was formulated by compared with the classification table of Zhongguo Zhongyi Guji Zongmu, and referred to the classification table of Zhonghua Guji Zongmu. This standard specified three-level categories and classification principles of TCM ancient books, and mainly composed of basic categories, three-level category table, classification principles and examples, and instructions for use.

Objective:To evaluate the efficacy and safety of acupuncture combined with antihypertensive drugs in the treatment of essential hypertension through meta-analysis.Methods:RCTs about acupuncture combined with antihypertensive drugs in the treatment of essential hypertension were retrieved from CNKI, VIP, WANFANG, CBM, PubMed, Embase and Web of Science from the establishment of the databases to January 28, 2022. The risk and quality of literature publication bias were evaluated according to Cochrane 5.1.0 System Evaluation Manual, and relevant data were extracted. RevMan 5.4 software was used for meta-analysis.Results:A total of 36 RCTs involving 2 905 patients were included. Meta-analysis results showed that compared with antihypertensive drugs, acupuncture alone demonstrated advantages in reducing systolic blood pressure [ SMD=-0.70 (-1.05, -0.36), P<0.01], diastolic blood pressure [ SMD=-0.69(-1.06, -0.32), P<0.01], antihypertensive efficacy [ RR=1.11 (1.04, 1.19), P<0.01], symptomes efficacy [ RR=1.21 (1.11, 1.31), P<0.01] and comprehensive efficacy [ RR=1.35 (1.16, 1.57), P<0.01], without serious adverse reactions. Conclusion:Acupuncture alone has good clinical efficacy and safety in the treatment of essential hypertension, compared with antihypertensive drugs alone. However, researches with large samples and high quality are still needed to support the conclusion.

Objective:To explore the effects of tigacycline-based combination therapy on procalcitonin (PCT), high sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) in patients with multiple drug-resistant acinetobacterbaumannii post-operative abdominal infection in intensive care unit (ICU).Methods:Seventy-five patients with multiple drug-resistant acinetobacter baumannii post-operative abdominal infection in ICU admitted to West Central Hospital of Hainan Prorvincefrom October 2015 to October 2018 were selected and divided into the control group (37cases) and the observation group (38 cases) according to random number table method. The control group was treated with cefoperazone-sulbactam on the basis of routine treatment, while the observation group was treated with tegacycline on the basis of the control group. Both groups were treated for 1 week. The clearance of acinetobacterbaumannii and clinical efficacy of the two groups were counted; the levels of serum PCT, hs-CRP and IL-6 and ummune function were compared.Results:The clearance rate of acinetobacterbaumannii in the observation group was significantly higher than that in the control group: 76.32%(29/38) vs. 54.05%(20/37), χ2 = 4.10, P = 0.043. Compared with before treatment, the levels of serum PCT, hs-CRP and IL-6 in the two groups were decreased after 1 week of treatment, and the levels of serum PCT, hs-CRP and IL-6 in the observation group were lower than those in the control group ( P<0.05). Compared with before treatment, the levels of peripheral blood CD 3+, CD 4+, CD 4+/CD 8+ were increased and peripheral blood CD 8+ was decreased in both groups, and the levels of peripheral blood CD 3+, CD 4+, CD 4+/CD 8+ in the observation group were higher than those in the control group ( P<0.05), while the level of peripheral blood CD 8+ in the observation group was lower than that in the control group ( P<0.05). The total effective rate in the observation group was significantly higher than that in the control group: 89.47% (34/38) vs. 67.57% (25/37), χ2 = 4.13, P<0.05. Conclusions:Tigacycline combined with cefoperazone-sulbactam in the treatment of intra-abdominal infection after surgery of acinetobacterbaumannii in ICU could reduce the levels of serum PCT, hs-CRP, IL-6, reduce the body′s inflammatory response and improve the immune function, and improve the treatment efficiency of intra-abdominal infection.

OBJECTIVE：To study the effects of limonin on immune function and apo ptosis-related factors expression in MFC gastric cancer bearing model mice. METHODS ：MFC gastric cancer bearing model was established by inoculating MFC gastric cancer cells into the right armpit of mice. After modeling ，model mice were divided into model group ，cyclophosphamide group （positive control ，25 mg/kg）and limonin high-dose ，medium-dose and low-dose groups （100，50 and 25 mg/kg），with 10 mice in each group. Other groups were given relevant medicine intragastrically ，once a day ，for consecutive 14 days，except that model group was given 0.5％ sodium carboxymethyl cellulose intragastrically. Before administration and after last administration ，the body weight of mice was measured ；spleen，thymus and tumor tissue were taken after the last administration to calculate the spleen index，thymus index and tumor inhibition rate. The percentage of CD 4+ and CD 8+ T lymphocytes ，CD4+/CD8+ ratio were detected by flow cytometry. The expression of immune function related indexes （IL-2，IL-10，IFN-γ）in serum were detected by ELISA. RT-PCR and Western blot assay were adopted to detect relative mRNA and protein expression of apoptosis-related factors [cytochrome C （Cyt-C），Bcl-2，Bax] in tumor tissue of mice. RESULTS ：There was no significant difference in body weight among the other groups except that of cyclophosphamide group was decreased significantly ，compared with model group （P＜0.05）. Inhibitory rate of tumor were （58.16 ± 7.07）％ ，（37.09 ± 4.26）％ ，（27.30 ± 3.64）％ ，（15.13 ± 2.95）％ in cyclophosphamide group ，limonin high-dose ，medium-dose and low-dose groups. Compared with model group ，spleen index ， thymus index ，the percentages of CD 4+ and CD 8+T lymphocyte cells ，CD4+/CD8+ ratio，serum levels of IL- 2 and IL- 10，relative mRNA and protein expression of Bcl- 2 in tumor of mice in cyclophosphamide group as well as the expression of IL- 10，relative mRNA and protein expression of Bcl- 2 in limonin groups were decreased significantly （P＜0.05）. The expression of IFN-γ，relative mRNA and protein expression of Cyt-C and Bax of cyclophosphamide group as well as spleen index （except for low-dose group ）， thymus index ， the percentage of CD 4 + and CD 8 + T lymphocytes，CD4+/CD8+ ratio，the expression of IL- 2 and IFN-γ，and relative mRNA and protein expression of Cyt-C and Bax in limonin groups were increased significantly （P＜0.05）. CONCLUSIONS ：Limonin can inhibit tumor growth in MFC gastric cancer bearing model mice ，and the side effects are relatively weak. Its mechanism is related to the improvement of immune function and the induction of apoptosis.