ObjectiveTo investigate the intervention effect of heat shock protein 60 (HSP60) on learning and memory impairment induced by combined exposure to lead and hypertension in mice, and the relative mechanism of triggering receptor expressed on myeloid cells 2 (TREM2). Methods Specific pathogen-free C57BL/6J male mice were randomly divided into control group, hypertension group, lead-exposed group and lead-exposed + hypertension group, or into control group, heat shock protein 60 (HSP60) control group, lead-exposed + hypertension group and HSP60 intervention group, with 10 mice in each group. Mice of hypertension group and lead-exposed + hypertension group were intraperitoneally injected with angiotensin Ⅱ at a dose of 0.5 mg/(kg·d) for seven consecutive days to induce hypertension model. Mice of the lead-exposed group, lead-exposed + hypertension group, and HSP60 intervention group were given lead acetate drinking water with a mass concentration of 250.0 mg/L, while mice in the control group, hypertension group, and HSP60 control group were given purified water for 12 weeks. Mice of the HSP60 control group and HSP60 intervention group were intraperitoneally injected with a solution of HSP60 at a dose of 4 mg/kg body weight, every other day for a total of three times at the 12th week. The learning and memory ability of mice was detected using the Morris water maze test. The enzyme-linked immunosorbent assay was used to detect the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the hippocampal tissues of the mice. The relative expression of ionized calcium binding adaptor molecule-1 (IBA1) and TREM2 protein in the hippocampus of mice was detected using Western blot. Results i) The number of platform crossings of the mice in the hypertension group and the lead-exposed group was lower than that in the control group (both P<0.05). The escape latency of the mice on the third day was longer and the number of platform crossings was lower in the lead-exposed + hypertension group compared with the control group, hypertension group and lead-exposed group (all P<0.05). The levels of IL-1β, IL-6, and TNF-α in the hippocampus of the other three groups increased compared with the control group (all P<0.05). The relative expression of IBA1 protein in the hippocampus of lead-exposed group and lead-exposed + hypertension group increased (all P<0.05), while the relative protein expression of TREM2 decreased compared with the control group (all P<0.05). The levels of IL-1β, IL-6, TNF-α, and the relative protein expression of IBA1 protein in the hippocampus of the lead-exposed+hypertension group were higher (all P<0.05), and relative expression of TREM2 protein was lower (P<0.05) than those in the hypertension group. The level of TNF-α and the relative expression of IBA1 protein in the hippocampus of lead-exposed+hypertension group were higher than those in lead-exposed group (all P<0.05). ii) The escape latency of mice in the lead-exposed + hypertension group was longer than that in the control group (P<0.05), and the number of platform crossings was fewer than that in the control group (P<0.05). The escape latency of mice in the HSP60 intervention group was shortened (P<0.05), the number of platform crossings increased (P<0.05), and the levels of IL-1β, IL-6, TNF-α and relative expression of IBA1 protein decreased in the hippocampus (all P<0.05), while the relative expression of TREM2 protein increased (P<0.05) compared with the lead-exposed+hypertension group. Conclusion Combined exposure of lead and hypertension has a synergistic effect on learning and memory impairment in mice. The mechanism may be related to the inhibition of TREM2 expression by lead in the hippocampus of hypertensive mice and aggravating the neuroinflammatory response. Intervention with TREM2 receptor agonist HSP60 can alleviate learning and memory impairment in mice exposed to lead and hypertension by up-regulating TREM2 expression in the hippocampus.

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.

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 To analyze the secondary metabolites of Abrus cantoniensis Hance based on plant metabolomics,and the quality marker(Q-marker)of Abrus cantoniensis Hance by multivariate statistics and network pharmacology prediction.Methods The chemical constituents of 11 batches of Abrus cantoniensis Hance were analyzed by UPLC-Q-TOF-MS methods established and their common components were confirmed.At the same time,cluster analysis(HCA),principal component analysis(PCA)and partial least squares discriminant analysis(OPLS-DA)were carried out to identify the main differential components that caused the classification of the multi-batch medicinal materials of Abrus cantoniensis Hance.Then,the network of"core components-core target-core pathway"was constructed through network pharmacology to screen and predict the potential Q-marker of Abrus cantoniensis Hance,and molecular docking verification was applied to further predict the activity.Results 39 common components were identified in 11 batches of Abrus cantoniensis Hance,mainly containing triterpenoid saponins,flavonoids,alkaloids,etc.HCA and PCA analysis showed that 11 batches of Abrus cantoniensis Hance were divided into 4 categories,and OPLS-DA analysis showed that 9 chemical components played an important role in the classification.The results of network pharmacology analysis showed that the above 9 components which acted on 166 targets were active components,and 29 core targets were obtained by protein interaction(PPI)screening.Among them,four chemical components,Abrine,Hypaphorine,SoyasaponinⅠ and Arginine,were highly correlated with the core targets.Combined with the concept of Q-marker and molecular docking results,it was preliminarily predicted that Abrine and Hypaphorine would be the Q-markers of Abrus cantoniensis Hance.Conclusion The Q-marker of Abrus cantoniensis Hance can be predicted and analyzed by plant metabolomics combined with multivariate statistics and network pharmacology.This study provided data reference for the quality control and evaluation of Abrus cantoniensis Hance and research ideas for further scientific development of Abrus cantoniensis Hance.

The paper reported a case of a young male patient, with graft-versus-host disease (GVHD) multi-organ involvement lesions after allo-hematopoietic stem cell transplantation. The patient had diverse clinical manifestations, and overlapping acute and chronic disease processes. Acute GVHD were mainly hyperbilirubinemia, with or without elevated transaminase, bloody watery stools; chronic GVHD were highlighted by extensive skin depigmentation, oral mucosal ulcer, sick nails, etc., and chronic signs, such as membranous nephropathy, polyserositis and pulmonary restrictive ventilatory insufficiency. The diagnosis of chronic GVHD mainly relies on medical history combined with clinical manifestations, and it's needed to exclude infections, drugs and tumors. Besides, the rate of missed diagnosis and misdiagnose is high, and it requires multidisciplinary diagnosis and treatment. Combined with the literature review, it indicates that there is a greater risk of GVHD in the male recipient with female donor, and peripheral blood stem cell transplant patients have a higher incidence than bone marrow transplant patients after hematopoietic stem cell transplantation, but the effect of the graft-versus-leukemia exists. Currently, glucocorticoids therapy with or without calcineurin inhibitors are the first-line treatment for GVHD, but the overall prognosis is poor.

Clear cell renal cell carcinoma(ccRCC)is a frequently occurring renal cancer.The Von Hippel-Lindau disease tumor suppressor VHL,a known tumor suppressor gene,is frequently mutated in about 50％of patients with ccRCC.However,it is unclear whether VHL influences the progression of ccRCC tumors expressing wild-type VHL.In the present study,we found that higher expression of VHL was correlated with the better disease-free survival(DFS)in ccRCC patients using The Cancer Genome Atlas(TCGA)datasets.We revealed that VHL overexpression in ccRCC cells inhibited epithelial-mesenchymal transition(EMT),sterol regulatory element-binding protein 1(SREBP1)-regulated triglyceride synthesis,and cell proliferation.Proteomic anal-ysis provided us a global view that VHL regulated four biological processes,including metabolism,immune regulation,apoptosis,and cell movement.Importantly,we found that VHL overexpression led to up-regulated expression of proteins associated with antigen processing and interferon-responsive proteins,thus rendering ccRCC cells more sensitive to interferon treatment.We defined an interferon-responsive signature(IRS)composed of ten interferon-responsive proteins,whose mRNA expression levels were positively correlated with DFS in ccRCC patients.Taken together,our results propose that the subset of ccRCC patients with high VHL expression benefit from immunotherapy.

Objective To investigate the clinical and epidemiological characteristics of crayfish associated rhabdomyolysis syndrome in Baiyun District, Guangzhou, and explore the related factors, and to provide evidence for the prevention of crayfish rhabdomyolysis syndrome. Methods The cases of crawfish associated rhabdomyolysis syndrome were found through the foodborne disease surveillance and reporting system, and a field epidemiological investigation was carried out to analyze the clinical and epidemiological characteristics of the cases. Results A total of 25 cases of crayfish associated rhabdomyolysis syndrome occurred in 2020. The intake of crayfish of the cases ranged from 5 to 25, the incubation period was 1 to 9.5h, and the interval from onset to medical treatment was 0.17 to 9h. All the cases had muscle pain, and the content of creatine kinase (CK) in the cases increased to varying degrees (128-17851 U/L). Retrospective cohort analysis of 10 crayfish events found no correlation between the consumption of different parts of crayfish and the incidence of crayfish-related rhabdomyolysis syndrome. Conclusion The incidence of rhabdomyolysis syndrome reported in Baiyun District of Guangzhou is related to the consumption of crayfish, but the pathogenic factors need to be further studied. It is suggested to strengthen the supervision of crayfish breeding, transportation, sales, and processing to ensure the health of consumers.

Objective To investigate the disinfection effect and cytotoxicity of intelligent water treatment system on dental unit waterlines (DUWLs), so as to provide basis for the safe and intelligent treatment of DUWLs.Methods From September to October 2017, 4 dental units with intelligent water treatment system were selected as the experimental group, and 4 dental units with municipal water as the source of water supply were used as the control group. The microbiological quality of water samples collected from DUWLs was assessed before and after installation of the intelligent water disinfection system in terms of the total viable counts of microorganisms. Studentt was used to detect the inhibitory effect of water samples on oral microorganism and its toxicity on human oral normal clone.Results After thoroughly disinfecting the waterlines of the dental unit, the bacteria of dental unit in the control group could rapidly grow up to (3.2±1.02) ×103 CFU/ml within 1 weeks, and the experimental group could be maintained at <100 CFU/ml, the difference was statistically significant (P<0.05); In the control group, Pseudomonas aeruginosa, non tuberculous mycobacteria and Acinetobacter baumannii could be detected in the water samples of the control group, while the above pathogens were not be detected in the experimental group. The water samples in the experimental group had significant inhibitory effects on the common bacteria in the dental unit waterlines and in the human oral cavity (P< 0.05), but only a lower cytotoxicity was shown to the epithelial cells of the human oral cavity.Conclusions The intelligent water treatment system can effectively reduce microbial contamination in dental waterlines and provide safe water for patients.