Background and Aims:N6-methyladenosine(m6A)epigenetic modification plays a crucial role in post-transcriptional gene expression regulation and various physiological and pathological processes,including tumorigenesis.The m6A reader IGF2BP2 significantly enhances mRNA stability and translation efficiency and is abnormally expressed in multiple cancers.However,the specific biological function of IGF2BP2 in pancreatic cancer remains unclear.Therefore,this study investigated the expression of the m6A reader IGF2BP2 in pancreatic cancer and its effects on pancreatic cancer cell functions.Methods:The expression levels of m6A-related writers,erasers,and readers were analyzed using The Cancer Genome Atlas(TCGA),the Genotype-Tissue Expression(GTEX)database,and the Gene Expression Omnibus(GEO).Kaplan-Meier survival analysis was conducted to assess the relationship between IGF2BP2 expression and the prognosis of pancreatic cancer patients.Immunohistochemistry was used to validate IGF2BP2 expression in clinical specimens of pancreatic cancer tissues and adjacent normal tissues.Functional experiments,including CCK-8 assay,flow cytometry for cell cycle analysis,colony formation assay,and Transwell migration assay,were performed to evaluate changes in cell proliferation,cell cycle distribution,colony formation ability,and migration capacity after IGF2BP2 knockdown in pancreatic cancer cells.Results:TCGA-GTEX and GEO database analyses showed that IGF2BP2 was highly expressed in pancreatic cancer tissues(both P<0.05)and that its high expression was associated with poor overall survival(both P<0.05).Immunohistochemical staining of clinical specimens confirmed that IGF2BP2 protein expression was higher in pancreatic cancer than in adjacent normal tissue.Functional experiments demonstrated that IGF2BP2 knockdown significantly reduced the proliferation ability of pancreatic cancer cells,arrested more cells in the G0-G1 phase,decreased colony formation,and impaired cell migration(all P<0.05).Conclusion:The m6A reader IGF2BP2 is highly expressed in pancreatic cancer tissues and is closely associated with poor prognosis in patients with this disease.Its mechanism of action may be related to the promotion of cancer cell growth and migration.

Background and Aims:N6-methyladenosine(m6A)epigenetic modification plays a crucial role in post-transcriptional gene expression regulation and various physiological and pathological processes,including tumorigenesis.The m6A reader IGF2BP2 significantly enhances mRNA stability and translation efficiency and is abnormally expressed in multiple cancers.However,the specific biological function of IGF2BP2 in pancreatic cancer remains unclear.Therefore,this study investigated the expression of the m6A reader IGF2BP2 in pancreatic cancer and its effects on pancreatic cancer cell functions.Methods:The expression levels of m6A-related writers,erasers,and readers were analyzed using The Cancer Genome Atlas(TCGA),the Genotype-Tissue Expression(GTEX)database,and the Gene Expression Omnibus(GEO).Kaplan-Meier survival analysis was conducted to assess the relationship between IGF2BP2 expression and the prognosis of pancreatic cancer patients.Immunohistochemistry was used to validate IGF2BP2 expression in clinical specimens of pancreatic cancer tissues and adjacent normal tissues.Functional experiments,including CCK-8 assay,flow cytometry for cell cycle analysis,colony formation assay,and Transwell migration assay,were performed to evaluate changes in cell proliferation,cell cycle distribution,colony formation ability,and migration capacity after IGF2BP2 knockdown in pancreatic cancer cells.Results:TCGA-GTEX and GEO database analyses showed that IGF2BP2 was highly expressed in pancreatic cancer tissues(both P<0.05)and that its high expression was associated with poor overall survival(both P<0.05).Immunohistochemical staining of clinical specimens confirmed that IGF2BP2 protein expression was higher in pancreatic cancer than in adjacent normal tissue.Functional experiments demonstrated that IGF2BP2 knockdown significantly reduced the proliferation ability of pancreatic cancer cells,arrested more cells in the G0-G1 phase,decreased colony formation,and impaired cell migration(all P<0.05).Conclusion:The m6A reader IGF2BP2 is highly expressed in pancreatic cancer tissues and is closely associated with poor prognosis in patients with this disease.Its mechanism of action may be related to the promotion of cancer cell growth and migration.

Auto-brewery syndrome(ABS)is a rare and easily overlooked disease.Overgrowth of certain high-alcohol-producing fungi and bacteria in the intestine leads to the production of endogenous ethanol that ex-ceeds the liver's maximum metabolic capacity,resulting in an elevated ethanol concentration in the patient's peripheral blood.Even without alcohol intake,patients may exhibit symptoms similar to intoxication,causing various social,occupational,and health-related distress.This article provides an overview of the diagnosis and differential diagnosis of ABS,reveals that gut microbiota dysbiosis is the core of ABS,and introduces multiple intervention strategies involving the regulation of the gut microbiota,including dietary intervention,pharmaco-therapy,probiotic therapy,fecal microbiota transplantation,and phage therapy,with the aim of assisting clini-cians in the early identification and treatment of ABS.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.

Objective To explore the effect of galangin(GAL)on bone metabolism by regulating Hippo/Yes associated protein(YAP)signaling pathway in rats with diabetic osteoporosis(DOP).Methods 90 female SD rats were randomly divided into normal control(NC)group,model(Mod)group,low-dose GAL(GAL-L)group,high-dose GAL(GAL-H)group,and high-dose GAL+YAP inhibitor Verteporfin(GAL-H+Verteporfin)group,with 18 rats in each group.Dual energy X-ray was used to detect bone mineral density(BMD).Three-point bending assay was used to evaluate the biomechanics of femur.HE staining was used to test the pathological changes in femoral tissue.ELISA was used to detect serum levels of osteocalcin(OC),alkaline phosphatase(ALP),and tartaric-resistant acid phosphatase(TRAP).Western blot was used to evaluate the expression of YAP protein in femoral tissue.Results Compared with NC group,the BMD,maximum load,elastic modulus,OC,ALP,and YAP protein expression of femur were reduced(P<0.05),and the TRAP was increased in Mod group(P<0.05).Compared with Mod group,BMD,maximum load,elastic modulus,OC,ALP and YAP protein expressions of femur were increased(P<0.05),while TRAP was decreased in GAL-L and GAL-H groups(P<0.05),and the improvement was better in GAL-H group.Compared with GAL-H group,femur BMD,maximum load,elastic modulus,OC,ALP and YAP protein expressions of femur were decreased(P<0.05),while TRAP was increased in GAL-H+Verteporfin group(P<0.05).Conclusions GAL may regulate the Hippo/YAP signaling pathway,increase the expression of YAP,regulate bone metabolism in DOP rats,and inhibit bone resorption.

Epstein-Barr virus(EBV)has a high prevalence of infection worldwide,with early onset of a-symptomatic latent infection,and has been shown to be closely associated with the development of many lym-phomas and lymphoproliferative disorders.These diseases are characterized by both viral infection and involve-ment of the blood and lymphatic system,with complex clinical manifestations and poor prognosis,which pose problems in the diagnosis and selection of treatment options.Early detection and intervention are essential for the prevention and treatment of EBV-related diseases.However,traditional detection methods face the diffi-culties of viral leakage and the complex genetic features of EBV-associated lymphomas,and there is an urgent need for new detection techniques to assist in the diagnosis of the disease.This article mainly focuses on the clinical features of common EBV-associated lymphomas and the research progress of the corresponding detec-tion technologies.

OBJECTIVES: To investigate the expression of parathyroid hormone-like hormone (PTHLH) in hepatocellular carcinoma (HCC) and analyze its correlation with clinical prognosis, its regulatory effects on HCC cell behaviors, and the signaling pathways mediating its effects. METHODS: We analyzed the differential expression of PTHLH in HCC and adjacent tissues and its association with patient prognosis based on data from TCGA and GEO databases and from 70 HCC patients treated in our hospital. The effects of PTHLH knockdown and overexpression on proliferation, migration, and invasion of cultured HCC cells were investigated using CCK-8 assay, colony formation assay, Transwell migration and invasion assays, and the signaling pathways activated by PTHLH were detected using Western blotting. RESULTS: TCGA and GEO database analysis showed significant overexpression of PTHLH mRNA in HCC tissues, which was associated with poor prognosis of the patients (P<0.05). High PTHLH mRNA expression was a probable independent prognostic risk factor for HCC (P<0.05). In the clinical samples, PTHLH mRNA and protein expressions were significantly higher in HCC tissues than in the adjacent tissues (P<0.001 or 0.01). Univariate and multivariate Cox regression analyses suggested that high PTHLH mRNA expression was an independent risk factor to affect postoperative disease-free survival of HCC patients (P<0.05). The prognostic prediction model based on PTHLH mRNA expression showed an improved accuracy for predicting the risk of postoperative recurrence in HCC patients. In cultured HCC cells, PTHLH overexpression significantly promoted cell proliferation, colony formation, migration and invasion, and caused activation of the ERK/JNK signaling pathway in Huh7 and Hep3B cells. CONCLUSIONS High PTHLH expression promotes HCC progression and is associated with poor patient prognosis. Its pro-tumor effects may be mediated by activation of the ERK/JNK signaling pathway.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Prognosis ; Cell Proliferation ; Parathyroid Hormone-Related Protein/genetics* ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; Signal Transduction ; Male ; RNA, Messenger/genetics* ; Female

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Stress granules are highly dynamic, membrane-free organelles that form in cells under stress conditions through liquid-liquid phase separation.Their main components are RNA and proteins, and they play a role in RNA metabolism, among other functions.The formation, dispersion, and removal of stress granules are regulated by the rapamycin pathway, the eukaryotic translation initiation factor pathway, and modifications of RNA-binding proteins.While physiological stress granules are typically transient, chronic stress associated with aging can lead to homeostatic imbalance and persistence of these granules.This aberrant RNA metabolism can result in the pathological aggregation of RNA-binding proteins, cellular damage, and the formation of pathological stress granules, which may accelerate the progression of aging-related diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, and tumors.In this paper, we will summarize the connection between stress granules and aging-related diseases to provide new insights for disease diagnosis and research.

Objective:To investigate the effect of "four-staff co-management" follow-up mode on risk factor control and medium-term prognosis improvement in patients with coronary heart disease after percutaneous coronary intervention (PCI).Methods:This was a intervention study. Patients with coronary heart disease who were admitted to the Xiamen Cardiovascular Hospital of Xiamen University from June 2021 to January 2022 and successfully discharged after PCI were included. According to the different types of follow-up after discharge, patients were divided into the traditional follow-up group and the "four-staff co-management" follow-up group. The "four-staff co-management" follow-up mode means that specialists, specialist managers in third-level A hospitals and general practitioners and health managers in basic hospitals were jointly responsible for post-discharge follow-up of PCI patients. Baseline clinical data were collected. The primary endpoints were the rate of compliance of coronary heart disease risk factor control at 12 months after surgery, the rate of secondary surgery, and the incidence of mid-term major adverse cardiovascular and cerebrovascular events (MACCE). Unplanned secondary PCI included symptom-driven secondary PCI and asymptomatic secondary PCI. MACCE includes myocardial infarction, hospitalization for heart failure, stroke, major bleeding, all-cause death, and composite endpoints including these events.Results:A total of 2 181 patients were enrolled, including 1 097 patients in the traditional follow-up group and 1 084 patients in the "four-staff co-management" follow-up group. At baseline, there were no statistically significant differences in gender, age, discharge diagnosis, co-existing diseases, echocardiographic indexes, and coronary artery lesions between the two groups (all P>0.05). There were no significant differences between the two groups in total PCI stent length, maximum internal diameter of stent, proportion of patients using drug balloon, proportion of patients with a planned second surgery during hospitalization, and discharge with drugs (all P>0.05). Twelve months after PCI, the reduction in HbA1c and low-density lipoprotein cholesterol was greater in the "four-staff co-management " follow-up group than that in the traditional follow-up group (all P<0.05), and the rate of reaching the standard for low-density lipoprotein cholesterol was higher than that in the traditional follow-up group ( P=0.001), but there was no statistical significance between the two groups for blood pressure and blood glucose (all P>0.05). During the follow-up period, the proportion of symptom-driven second operation patients was lower in the "four-staff co-management" follow-up group than that in the traditional follow-up group ( P<0.001), and there was no significant difference in the proportion of asymptomatic second operation patients between the two groups ( P=0.191). The proportion of hospitalized patients with heart failure in the "four-staff co-management" follow-up group was lower than that in the traditional follow-up group ( P=0.029), and there was no significant difference in the proportion of myocardial infarction, cerebral infarction, cerebral hemorrhage, massive hemorrhage, death and complex endpoint events between the two groups (all P>0.05). Conclusion:The "four-staff co-management" follow-up mode can effectively improve the control of risk factors and medium-term prognosis in patients with coronary heart disease after PCI.