Objective: To investigate the environmental contamination of norovirus in nurseries and primary/secondary schools, so as to provide a scientific basis for effective prevention and control measures. Methods: A total of 483 external environmental samples were collected from 34 cluster outbreaks of norovirus gastroenteritis in kindergartens and primary/secondary schools in Linhai City from 2021 to 2024. Pathogen detection was conducted using a rapid nucleic acid extraction kit and realtime fluorescence RT-PCR, and the results were analyzed using the χ2 test or Fishers exact test. Results: Among the collected external environmental samples, the total positive rate of surface contamination was 13.66%. The positive rates in kindergartens and primary/secondary schools were 12.20% and 15.82%, respectively. In kindergartens, the five surfaces with the highest detection rates were desks/chairs (23.33%), toilet stool troughs (20.69%), urinal troughs (12.00%), washbasins/sinks (11.11%), and toilet mops (9.38%). In primary/secondary schools, the top five were toilet stool troughs (38.30%), urinal troughs (23.53%), toilet door handles (13.04%), toilet mops (12.50%), and drinking cups (11.11%). The difference in positive detection rates among different external environments in primary/secondary schools was statistically significant (Fishers exact probability test, P<0.01). The positive detection rate in sanitary toilets was higher than that in classroom environments (χ2=17.38), while the positive detection rate in classroom environments of kindergartens was higher than that in primary/secondary schools (χ2=5.42)(P<0.05). Conclusions Norovirus exhibits a high contamination rate in nurseries and schools, particularly in restroom areas. Strengthening sanitation and disinfection in highrisk environments, and improving hygiene awareness among children and staff, are essential for the effective prevent and control of norovirus.

AIM:To investigate the effect of 3% diquafosol sodium eye drops on tear film homeostasis in patients wearing overnight orthokeratology lenses.METHODS:Retrospective study. A total of 340 patients(564 eyes)fitted with night-worn orthokeratology lenses from June to December 2022 were respectively divided into a diquafosol sodium group(200 cases, 323 eyes, treated with 3% diquafosol sodium eye drops)and a sodium hyaluronate group(140 cases, 241 eyes, treated with sodium hyaluronate eye drops). The uncorrected visual acuity(LogMAR), ocular surface disease index(OSDI), non-invasive tear film break-up time(NIBUT), meibomian gland infrared imaging score, and corneal epithelial fluorescein staining were analyzed and compared between the two groups.RESULTS:Compared to baseline, both groups showed significant improvements in uncorrected visual acuity(LogMAR)at 1 wk, 1, and 3 mo after lens wear(all P<0.01). However, no statistically significant difference in uncorrected visual acuity(LogMAR)was observed between the two groups at any time point(all P>0.05). No significant differences in NIBUT or OSDI scores were found between the groups before and at 1 wk after lens wear(all P>0.05). At the 1- and 3 mo follow-ups, the 3% diquafosol sodium group demonstrated significantly longer NIBUT(all P<0.001)and lower OSDI scores(all P<0.001)compared to the sodium hyaluronate group. After wearing lens for 3 mo, the meibomian gland infrared imaging scores were significantly better in the diquafosol sodium group(P<0.001), whereas no significant intergroup difference was observed in corneal fluorescein staining(P>0.05). Furthermore, the incidence of adverse events during the study period did not differ significantly between the two groups(P>0.05).CONCLUSION:Compared with sodium hyaluronate, 3% diquafosol sodium eye drops were more effective in maintaining tear film homeostasis in patients wearing overnight orthokeratology lenses.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Background Atmospheric fine particulate matter (PM_2.5) can disrupt the metabolic homeostasis of the liver and accelerate the progression of liver diseases, but there are few studies on the effects of sub-chronic PM_2.5 exposure on the liver metabolome. Objectives To investigate the effects of sub-chronic exposure to concentrated PM_2.5 on hepatic metabolomics in mice by liquid chromatography-mass spectrometry (LC-MS), and to identify potentially affected metabolites and metabolic pathways. Methods Twelve male C57BL/6J (6 weeks old) mice were randomly divided into two groups: a concentrated PM_2.5 exposure group and a clean air exposure group. The mice were exposed to concentrated PM_2.5 using the "Shanghai Meteorological and Environmental Animal Exposure System" at Fudan University. The exposure duration was 8 h per day, 6 d per week, for a total of 8 weeks. The mice's liver tissues were collected 24 h after the completion of exposure. LC-MS was performed to assess changes in the hepatic metabolome. Orthogonal partial least squares discriminant analysis and t-test were employed to identify differentially regulated metabolites between the two groups under the conditions of variable important in projection (VIP)≥1.0 and P<0.05. Metabolic pathway enrichment analysis was performed using MetaboAnalyst 5.0 software and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results A total of 297 differentially regulated metabolites were identified between the concentrated PM_2.5 exposure group and the clean air group. Among these metabolites, 142 were upregulated and 155 were downregulated. A total of 38 metabolic pathways were altered, with 7 pathways showing significant perturbation (P<0.05). These pathways involved amino acid metabolism, glucose metabolism, nucleotide metabolism, as well as cofactor and vitamin metabolism. The 7 significant metabolic pathways were pantothenic acid and coenzyme A biosynthesis; purine metabolism; amino sugar and nucleotide sugar metabolism; arginine biosynthesis; alanine, aspartate and glutamate metabolism; aminoacyl-tRNA biosynthesis; and fructose and mannose metabolism. Conclusion The results from metabolomics analysis suggest that sub-chronic exposure to PM_2.5 may disrupt hepatic energy metabolism and induce oxidative stress damage. Aspartic acid, succinic acid, ornithine, fumaric acid, as well as purine and xanthine derivatives, were identified as potential early biomarkers of hepatic response to sub-chronic PM_2.5 exposure.

ObjectiveTo investigate the effects of Tongluo Juanbi granules on chondrocyte apoptosis and Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway of rabbits with knee osteoarthritis （KOA） and study the mechanism of Tongluo Juanbi granules in the prevention and treatment of KOA. MethodThirty New Zealand rabbits were randomly assigned to the following five groups （n=6）： sham group， model group， low-dose and high-dose groups of Tongluo Juanbi granules （4.1 and 8.2 g·kg^-1·d^-1）， and celecoxib group （10.9 mg·kg^-1·d^-1）. The KOA model was established by destabilization of the medial meniscus （DMM） for six weeks. Six weeks after the modeling， the drug was given once a day for eight weeks. The pathological changes of cartilago articularis were observed by hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was performed to detect chondrocyte apoptosis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in synovial fluid. The mRNA and protein expression levels of genes related to the TLR4/MyD88/NF-κB signaling pathway were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the sham group， the cartilago articularis of the model group significantly degenerated. Mankin's score was increased （P<0.01）， and the contents of IL-1β and TNF-α in synovial fluid were increased （P<0.01）. The number of apoptosis of chondrocytes was increased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were up-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were down-regulated （P<0.01）. Compared with the model group， chondrocyte degeneration in both low-dose and high-dose groups of Tongluo Juanbi granules was improved， and Mankin's score was decreased （P<0.01）. The contents of IL-1β and TNF-α were decreased （P<0.01）， and the number of apoptosis of chondrocytes was decreased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were down-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were up-regulated （P<0.01）. In addition， in the above observation indicators， the high-dose group of Tongluo Juanbi granules was significantly superior to the low-dose group of Tongluo Juanbi granules. ConclusionTongluo Juanbi granules could inhibit chondrocyte apoptosis in rabbits with KOA and improve cartilage degeneration， which may be related to inhibiting inflammatory responses mediated by TLR4/MyD88/NF-κB signaling pathway.

Objective To investigate the expressions of extracellular matrix metalloproteinase inducer(EMMPRIN),matrix metalloproteinase-9(MMP-9),lysine demethylase 6B(KDM6B)proteins and their correlation with clinicopathologic features in invasive breast cancer,and analyze the correlation among the three proteins and their value in pathological diagnosis of invasive breast cancer.Methods The surgical biopsy specimens of 124 patients with invasive breast cancer who were admitted to the Department of Pathology,the Fifth Clinical Medical College of Henan University of Chinese Medicine/People's Hospital of Zhengzhou from January 2014 to December 2017 were selected as research subjects,and 20 low-grade intraductal carcinoma tissue specimens,27 high-grade intraductal carcinoma tissue specimens,and 22 adjacent tissue specimens＞1 cm away from the invasive breast cancer were selected as controls.The expressions of EMMPRIN,MMP-9 and KDM6B proteins in cancer-adjacent tissues,low-grade intraductal carcinoma tissues,high-grade intraductal carcinoma tissues and invasive breast cancer tissues were detected by immunohistochemistry.The relationship between the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins and clinicopathologic features of invasive breast cancer was analyzed,Spearman correlation analysis was used to evaluate the correlation of EMMPRIN,MMP-9 and KDM6B proteins in breast cancer tissues,and receiver operating characteristic(ROC)curve was adopted to evaluate the diagnostic value of EMMPRIN,MMP-9 and KDM6B for invasive breast cancer.Results The relative expressions of EMMPRIN and MMP-9 proteins in high-grade intraductal carcinoma and invasive breast cancer tissues were significantly higher those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than those in cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in invasive breast cancer tissues were significantly higher those in high-grade intraductal carcinoma tissues,and the relative expression of KDM6B protein was significantly lower than that in high-grade intraductal carcinoma tissues(P＜0.05);there was no statistically significant difference in the relative expressions of EMMPRIN,MMP-9 and KDM6B proteins between cancer-adjacent tissues and low-grade intraductal carcinoma tissues(P＞0.05).The relative expressions of EMMPRIN and KDM6B proteins were not related to the age,tumor location and tumor diameter of patients with invasive breast cancer(P＞0.05),and the relative expression of MMP-9 protein was not related to the age and tumor location of patients with invasive breast cancer(P＞0.05).Relative expressions of EMMPRIN,MMP-9 and KDM6B proteins were correlated with WHO grading,lymph node metastasis,and tumor,node and metastasis(TNM)staging of invasive breast cancer(P＜0.05),and the relative expression of MMP-9 protein was correlated with the tumor diameter(P＜0.05).In the WHO grades Ⅰ,Ⅱ,and Ⅲ of invasive breast cancer,the relative expressions of EMMPRIN and MMP-9 proteins increased sequentially,while the relative expression of KDM6B protein decreased sequentially(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in the lymph node metastasis group were significantly higher than those in the non-lymph node metastasis group,and the relative expression of KDM6B protein was significantly lower than that in the non-lymph node metastasis group(P＜0.05);the relative expressions of EMMPRIN and MMP-9 proteins in TNM stages Ⅲ-Ⅳ were significantly higher than those in stages Ⅰ-Ⅱ(P＜0.05),while the relative expression of KDM6B protein was significantly lower than that in stages Ⅰ-Ⅱ(P＜0.05).In the group of invasive breast cancer with diameter≤2 cm,2 to 5 cm,and＞5 cm,the relative expression of MMP-9 protein increased sequentially(P＜0.05).Spearman correlation analysis showed that the expression of EMMPRIN was positively correlated with MMP-9 protein in invasive breast cancer tissues(r=0.990,P=0.000),the expression of EMMPRIN was negatively correlated with KDM6B protein(r=-0.606,P=0.000),and the expression of MMP-9 was negatively correlated with KDM6B protein(r=-0.612,P=0.000).ROC curve analysis showed that the area under the curve(AUC)of EMMPRIN protein for diagnosing invasive breast cancer was 0.875[95％confidence interval(CI):0.823-0.926,P＜0.05],with an optimal threshold of 10.043,sensitivity of 79.0％,and specificity of 76.8％;the AUC of MMP-9 protein in diagnosing invasive breast cancer was 0.863(95％CI:0.808-0.917,P＜0.05),with an optimal threshold of 10.070,sensitivity of 74.2％,and specificity of 76.8％;the AUC of KDM6B protein in diagnosing invasive breast cancer was 0.267(95％CI:0.196-0.338,P＜0.05),with an optimal threshold of 11.003,sensitivity of 71.0％,and specificity of 98.6％.Conclusion EMMPRIN,MMP-9 and KDM6B are related to the occurrence and development of invasive breast cancer.Detection of the expressions of EMMPRIN,MMP-9 and KDM6B is helpful to the pathological diagnosis of invasive breast cancer and clinical judgment of invasion and metastasis of breast cancer.

Objective To investigate the knowledge,demand,and use of clinical practice guide-lines(CPGs)among anesthesia professionals in Gansu province,and to explore the strategies and barriers during the implementation process.Methods A questionnaire survey was conducted to investigated the knowledge,demand,and use of CPGs,as well as the strategies and barriers during the process of guideline implementation.Statistical analysis was applied to the collected data.Results A total of 339 valid question-naires were collected,96.8%of the respondents were aware of the guidelines,and the majority of the re-spondents(86.4%)consulted the guidelines when they encountered problems in clinical practice.The main barriers for guideline utilization were identified as lack of convenience(70.2%),limited availability chan-nels(64.3%)or restricted access rights(56.9%)to obtain the guidelines,inadequate training(31.3%),and language barriers(21.5%).Multiple forms of assisting guideline use and opening up guideline access were considered by most respondents as important ways to promote guideline implementation.Conclusion Anesthesia professionals in Gansu province demonstrated good levels of awareness and compliance with guidelines.However,the primary barriers to utilization were attributed to the guidelines themselves or diffi-culties in accessing them.It is recommended to establish a national guideline clearinghouse,provide imple-mentation tools,and enhance healthcare professional training to facilitate the promotion and application of guidelines in the future.

Objective To systematically evaluate the efficacy and safety of electroacupuncture(EA)in the treatment of postoperative nausea and vomiting(PONV)after gynecological surgery.Methods PubMed,Cochrane Library,Web of Science,Embase,China national knowledge infrastructure(CNKI),Wanfang database,and China biomedical literature database(CBM)were systematically searched.The re-trieval period was from the establishment of the database to December 2022.Relevant randomized controlled trials on EA for the treatment of PONV in gynecological surgery were collected.RevMan 5.3 software was used for meta-analysis.Results Fourteen randomized controlled trials were accommodated,including 958 patients,477 patients in the EA group and 481 patients in the control group.Compared with the control group,the incidence of PONV was significantly lower in group EA at 0-48 hours postoperatively(RR=0.55,95％CI 0.47 to 0.65,P＜0.001),and the PONV scores were significantly lower in the postopera-tive period within 48 hours in group EA(MD=-0.40 scores,95％CI-0.65 to-0.16 scores,P=0.004),the incidence of postoperative remedial antiemetic were significantly lower(RR=0.28,95％CI 0.16 to 0.51,P＜0.001).Conclusion EA can reduce the incidence of PONV and the incidence of re-medial antiemetic after gynecologic surgery.

Objective To evaluate the efficacy of preoperative electroacupuncture intervention in promoting postoperative gastrointestinal functional recovery by meta-analysis.Methods The databases of PubMed,Cochrane Library,Web of Science,Embase,CBM,CNKI,VIP,and WanFang were searched systematically.The search period ranged from the inception of the databases to March 2024.Two researchers screened the literature independently,extracted the data,used Cochrane Risk of Bias tools to evaluate the quality of the inclusion study,and used RevMan 5.3 software for meta-analysis.Results Twelve RCTs were included,with 773 patients.There were 421 patients in the preoperative electroacupuncture group and 352 patients in the control group.The results of the meta-analysis showed that,time to first flatus(SMD=-0.56,95%CI-0.84 to-0.28,P＜0.001),time to first defecation(MD=-6.40 hours,95%CI-9.27 to-3.53,P＜0.001),time to bowel sound recovery(MD=-8.45 hours,95%CI-10.37 to-6.52,P＜0.001),time to first oral feeding(MD=-16.88 hours,95%CI-23.92 to-9.83,P＜0.001),the incidence of PONV(RR=0.75,95%CI 0.57 to 0.98,P=0.04)and length of hospital stay(MD=-0.78 d,95%CI-1.38 to-0.19,P=0.010)were significantly lower than the control group.Conclusion Electroacupuncture intervention before operation can effectively promote the recovery of post-operative exhaust,defecation,and bowel sound,shorten the time of fasting and drinking,reduce the inci-dence of PONV,shorten the length of hospital stay,and has good clinical value in promoting the recovery of postoperative gastrointestinal function.

Objective To systematically evaluate the effect of transcutaneous electrical acupoint stimulation(TEAS)in the treatment of postoperative nausea and vomiting(PONV)after laparoscopic non-gastrointestinal surgery.Methods Databases such as PubMed,Cochrane library,Web of Science,Embase,CNKI,Wanfang,and Chinese biomedical database(CBM)were searched to find and screen ran-domized controlled trials(RCTs)of TEAS in the prevention and treatment of PONV after laparoscopic non-gastrointestinal surgery.The retrieval time was from the establishment of the database to July 2023.Meta-a-nalysis was performed using RevMan 5.3 software.Results Twenty-two RCTs involving 3 538 patients were included,including 1 799 in the TEAS group and 1 739 in the control group.The results of meta-analysis showed that the total incidence of PONV in the TEAS group was significantly lower than that in the control group 0-24 hours after operation(RR=0.54,95％CI 0.44-0.68,P＜0.001),and the incidence of postoperative remedial antiemetic was significantly reduced(RR=0.54,95％CI 0.38-0.77,P＜0.001).There was no significant difference in the incidence of postoperative acupoint stimulation-related adverse reactions between the two groups(RR=0.62,95％CI 0.15-2.51,P=0.500).Conclusion TEAS has good clinical efficacy and safety in the treatment of PONV after laparoscopic non-gastrointestinal surgery.