Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

Objective: To explore the comorbidity and associated factors of dental caries and overweight/obesity among primary and secondary school students in Guangxi, so as to provide a scientific basis for the development of targeted prevention strategies. Methods: A stratified cluster random sampling method was used to survey 178 700 students from the fourth grade of primary school to the third year of high school in Guangxi Zhuang Autonomous Region from September to November 2023, including physical examination, oral screening, and questionnaire survey. Chisquare tests and binary Logistic regression analysis were employed to investigate the related factors of the cooccurrence of dental caries and overweight/obesity among students. Results: The comorbidity rate of dental caries and overweight/obesity was 9.55%, with urban areas (9.95%) higher than rural counties (9.24%), boys (10.54%) higher than girls (8.54%), primary school students (11.49%) higher than senior high school students (8.92%) and junior high school students (8.05%), and nonboarding students (11.44%) higher than boarding students (7.94%), and all differences were statistically significant (χ2=26.07, 207.91, 471.54, 629.14,P<0.01). Multivariate Logistic regression analysis showed that consuming cereal for breakfast (OR=0.91, 95%CI=0.88-0.94), drinking milk in the past week (OR=0.89, 95%CI=0.83-0.95), meeting sleep standards (OR=0.95, 95%CI=0.91-0.99), and brushing teeth at least once a day (OR=0.82, 95%CI=0.73-0.93) had a lower risk of the comorbidity of dental caries and overweight/obesity. In contrast, drinking beverages in the past week (OR=1.14, 95%CI=1.09-1.20), consuming fried foods in the past week (OR=1.11, 95%CI=1.06-1.17), eating fruit ≥1 time every day (OR=1.06, 95%CI=1.02-1.11), consuming fruit ≥1 type every day (OR=1.07, 95%CI=1.01-1.12), and having fish, poultry, meat, or eggbased breakfasts (OR=1.03, 95%CI=1.05-1.13) had a higher risk of the comorbidity of dental caries and overweight/obesity (P<0.05). Conclusions Dietary habits and lifestyle behaviors are associated with the comorbidity of dental caries and overweight/obesity among primary and secondary school students in Guangxi. Guiding students to form healthy living habits is helpful to preven dental caries and overweight/obesity.

The innate immune system detects cellular stressors and microbial infections, activating programmed cell death (PCD) pathways to eliminate intracellular pathogens and maintain homeostasis. Among these pathways, pyroptosis, apoptosis, and necroptosis represent the most characteristic forms of PCD. Although initially regarded as mechanistically distinct, emerging research has revealed significant crosstalk among their signaling cascades. Consequently, the concept of PANoptosis has been proposed—an inflammatory cell death pathway driven by caspases and receptor-interacting protein kinases (RIPKs), and regulated by the PANoptosome, which integrates key features of pyroptosis, apoptosis, and necroptosis. The core mechanism of PANoptosis involves the assembly and activation of the PANoptosome, a macromolecular complex composed of three structural components: sensor proteins, adaptor proteins, and effector proteins. Sensors detect upstream stimuli and transmit signals downstream, recruiting critical molecules via adaptors to form a molecular scaffold. This scaffold activates effectors, triggering intracellular signaling cascades that culminate in PANoptosis. The PANoptosome is regulated by upstream molecules such as interferon regulatory factor 1 (IRF1), transforming growth factor beta-activated kinase 1 (TAK1), and adenosine deaminase acting on RNA 1 (ADAR1), which function as molecular switches to control PANoptosis. Targeting these switches represents a promising therapeutic strategy. Furthermore, PANoptosis is influenced by organelle functions, including those of the mitochondria, endoplasmic reticulum, and lysosomes, highlighting organelle-targeted interventions as effective regulatory approaches. Cardiovascular diseases (CVDs), the leading global cause of morbidity and mortality, are profoundly impacted by PCD. Extensive crosstalk among multiple cell death pathways in CVDs suggests a complex regulatory network. As a novel cell death modality bridging pyroptosis, apoptosis, and necroptosis, PANoptosis offers fresh insights into the complexity of cell death and provides innovative strategies for CVD treatment. This review summarizes current evidence linking PANoptosis to various CVDs, including myocardial ischemia/reperfusion injury, myocardial infarction, heart failure, arrhythmogenic cardiomyopathy, sepsis-induced cardiomyopathy, cardiotoxic injury, atherosclerosis, abdominal aortic aneurysm, thoracic aortic aneurysm and dissection, and vascular toxic injury, thereby providing critical clinical insights into CVD pathophysiology. However, the current understanding of PANoptosis in CVDs remains incomplete. First, while PANoptosis in cardiomyocytes and vascular smooth muscle cells has been implicated in CVD pathogenesis, its role in other cell types—such as vascular endothelial cells and immune cells (e.g., macrophages)—warrants further investigation. Second, although pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are known to activate the PANoptosome in infectious diseases, the stimuli driving PANoptosis in CVDs remain poorly defined. Additionally, methodological challenges persist in identifying PANoptosome assembly in CVDs and in establishing reliable PANoptosis models. Beyond the diseases discussed, PANoptosis may also play a role in viral myocarditis and diabetic cardiomyopathy, necessitating further exploration. In conclusion, elucidating the role of PANoptosis in CVDs opens new avenues for drug development. Targeting this pathway could yield transformative therapies, addressing unmet clinical needs in cardiovascular medicine.

Four pyrazines were isolated from the n-butanol fraction of Hypecoum erectum L. by using various chromatographic methods, including MCI gel, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified as hyperectpyrazin A (1), 1′S-(6-methylpyrazin-2-yl)-ethane-1′,2′-diol (2), 2-hydroxymethyl-6-methylpyrazin (3) and pyrazine-2-carboxylic acid (4) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, MS, etc.). The absolute configuration of compound 2 was determined by using the Mo₂(OAc)₄ induced CD analysis for the first time. Compound 1 was a new compound, compounds 2-4 were isolated from H. erectum for the first time. Compounds 1-4 were evaluated for their inhibition against acetylcholinesterase and nitric oxide generation induced by lipopolysaccharide-RAW264.7 macrophage cells. At a concentration of 50 μmol·L^-1, compounds 2 and 4 displayed inhibitory effects on acetylcholinesterase with the inhibition rates of 44.40% and 43.99%, respectively.

Objective To evaluate the bioequivalence of oral sidenafil citrate tablets manufactured(100 mg)test preparations and reference preparations in healthy subjects under fasting and fed conditions.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design,36 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test 100 mg with 7-day washout period.Plasma concentration of sidenafil and N-demethylsildenafil was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by Analyst 1.6.3(AB Scie)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The main pharmacokinetic parameters of sidenafil after a single oral dose of sidenafil citrate tablets under fasting condition for test and reference were as follows:Cmax were(494.69±230.94)and(558.78±289.83)ng·mL-1,AUC0-t were(1 336.21±509.78)and(1 410.82±625.99)h·ng·mL-1,AUC0-were(1 366.49±512.16)and(1 441.84±628.04)h·ng·mL-1,respectively.The main pharmacokinetic parameters of sidenafil under fed condition for T and R were as follows:Cmax were(381.89±126.53)and(432.47±175.91)ng·mL-1,AUC0-t were(1 366.34±366.99)and(1 412.76±420.37)h·ng·mL-1,AUC0-were(1 403.28±375.32)and(1 454.13±429.87)h·ng·mL-1,respectively.The results demonstrated the bioequivalence of sidenafil citrate tablets between T and R.The incidence of adverse events in fasting and fed tests were 33.33％and 25.00％,respectively.No serious adverse event was reported.Conclusion The test and reference formulation of sidenafil citrate tablets were equivalent and was safe.

Objective To investigate the inhibitory effect of quercetin on Gastro entero pancreatic NEN(GEP-NEN).Methods Human pancreatic neuroendocrine tumor BON-1 cells were randomly divided into control group,quercetin group(80 μmol·L-1 quercetin),quercetin+si-NC group(transfected with si-NC+80 μmol·L-1 quercetin),quercetin+si-growth arrest-specific+ranscript 5(GAS5)group(transfected with si-GAS5+80 μmol·L-1 quercetin).Dual luciferase reporter gene assay was used to verify the targeted binding of GASS5 to miR-18b-5p;real-time quantitative fluorescent PCR(qRT-PCR)was used to detect the mRNA expression levels of B-cell lymphoma-2(Bcl-2)and Bel-2 associated X protein(Bax);positive expression of GAS5 and miR-18b-5p in cells was detected by fluorescence in situ hybridization(FISH)assay.Results Dual luciferase reporter gene results showed that GAS5 was targeted to miR-18b-5p.The GAS5 expression levels of control group,quercetin group,quercetin+si-NC group and quercetin+si-GAS5 group were 1.00±0.13,1.72±0.19,1.78±0.14 and 1.16±0.11,respectively;the expression levels of miR-18b-5p were 1.00±0.15,0.67±0.08,0.72±0.06 and 0.95±0.11 respectively;Bax mRNA expression levels were 1.00±0.12,2.17±0.25,2.32±0.28 and 1.37±0.15,respectively;Bcl-2 mRNA expression levels were 1.00±0.15,0.41±0.05,0.37±0.06 and 1.21±0.13,respectively.The above indexes were significantly different between quercetin group and control group(all P＜0.05);the above indexes were significantly different between quercetin+si-NC group and quercetin+si-GAS5 group(all P＜0.05).Conclusion Quercetin may slow down the development of GEP-NEN by targeting GAS5/miR-18b-5p molecular axis to inhibit cell growth.

S100 calc-binding protein A8/A9(S100A8/A9)can induce the migration of primary tumor cells to distant target organs by binding multiple channel proteins,promote the formation of tumor metastasis microenvironment,and play an important role in the immune and inflammatory response of the body.It provides a new target and idea for the prevention and treatment of tumor metastasis and invasion.This paper mainly reviewed the expression and mechanism of S100A8/A9 on related channel proteins in a variety of high incidence tumors,in order to provide a new strategy for tumor prevention,diagnosis and treatment.

Abstract Spinal curvatures has emerged as the third major chronic condition seriously threatening the physical and mental health of Chinese children and adolescents, with significant regional differences. Its etiology is complex and diverse, and early prevention and treatment are feasible, whereas treatment in later stages entails considerable difficulty and economic burden. Currently, the prevention and control of student spinal curvatures has been elevated to a national health strategy. A series of policy documents have been successively issued, and it has greatly facilitated the institutionalization and normalization of national routine screening for student spinal curvatures. However, it is still inadequate considering current prevention and control system for spinal curvatures in children and adolescents. There is an urgent need to establish a closed loop model based on China s institutional advantages, comprising Initial Screening-Diagnosis-Treatment-Preventive Control-Followup Assessment, to strengthen the safeguarding of spinal health in children and adolescents.

The present analysis was based on the iteration of the 2023 WHO Essential Medicines Model List(23rd list)and Essential Medicines Model List for Children(9th list).In a methodological fashion,the adjustment procedure of the basic drug list and the materials required to submit the application were sorted out.Subsequently,a comprehensive synthesis of predominant features characterizing the 2023 edition of the EML and EMLc are summarized(offered).Notably,this edition boasts the highest count of medicines ever included featuring extensive inclusion of innovative drugs to fill the gap,select medicines for children carefully,and the emphasizing on clinical benefit evidence and public health affordability.It is suggested that China should update the NEML according to the national conditions and the experience of WHO as soon as possible,pay attention to the difference and connection between the list of essential medicines and the list of medical insurance,and play a meticulous role for establishing effective linkages between two lists.Such measures are envisaged to meet the basic drug needs,and ensure the accessibility and affordability of drugs,thereby optimizing the allocation of health resources.

Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners