Traditional Chinese medicine(TCM) capable of clearing heat and removing toxin is most commonly used in clinical practice and has the effect of removing fire-heat and toxin. Studies have shown that most of the Ilex plants have the effect of clearing heat and removing toxin, among which the varieties of I. cornuta, I. pubescens, I. rotunda, I. latifolia, and I. chinensis are most widely used. These plants generally contain triterpenoids and their glycosides, alkaloids, flavonoids, phenylpropanoids, and other chemical components, especially pentacyclic triterpenoids. According to their skeletons, pentacyclic triterpenoids can be divided into the oleanane type, the ursane type, the lupinane type, etc. Among them, ursane-type components are the most abundant, and 136 species have been found so far. These components have been proved to have pharmacological effects such as anti-inflammatory, anti-tumor, hypolipidemic, anti-thrombosis, cardiomyocyte-protective, antibacterial, and hepatoprotective effects. Therefore, this paper systematically reviews the domestic and foreign literature on Ilex plants with a focus on the research progress on pentacyclic triterpenoids and their pharmacological activities, aiming to provide reference for the development of TCM resources with the effect of clearing heat and removing toxin.
Ilex/chemistry* ; Plants, Medicinal/chemistry* ; Pentacyclic Triterpenes/pharmacology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Animals

Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective:To retrospectively analyze the clinical and genetic characteristics of six patients with Acromicric dysplasia due to variants of the FBN1 gene. Methods:Six patients who had visited the Affiliated Hospital of Qingdao University between February 2018 and October 2020 were selected as the study subjects. Clinical data of the patients were collected. High-throughput sequencing was carried out. And candidate variants were verified by Sanger sequencing.Results:All of the six patients had presented with severe short stature (< 3 s), brachydactyly, short and broad hands and feet. Other manifestations included joint stiffness, facial dysmorphism, delayed bone age, liver enlargement, coracoid femoral head, and lumbar lordosis. Genetic testing revealed that all had harbored heterozygous variants of the FBN1 gene. Patient 1 had harbored a c. 5183C>T (p.A1728V) missense variant in exon 42, which had derived from his father (patient 2). Patient 3 had harbored a c. 5284G>A (p.G1762S) missense variant in exon 43, which had derived from her mother (patient 4). Patient 5 had harbored a c. 5156G>T (p.C1719F) missense variant in exon 42, which was de novo in origin. Patient 6 had harbored a c. 5272G>T (p.D1758Y) missense variant in exon 43, which was also de novo in origin. The variants carried by patients 1, 3 and 6 were known to be pathogenic. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the FBN1: c. 5156G>T was rated as a pathogenic variant (PS2+ PM1+ PM2_Supporting + PM5+ PP3). Conclusion:All of the six patients had severe short stature and a variety of other clinical manifestations, which may be attributed to the variants of the FBN1 gene.

Objective:To construct a medical equipment management system based on improved evidence theory,and to analyze its application effect in the equipment management of geriatric gastroenterology department in hospitals.Methods:With the help of improved evidence theory,the risk of medical equipment management in geriatric gastroenterology department was identified,dynamic weights and static weights were introduced,and a medical equipment management system based on improved evidence theory was constructed by combining the game idea with the portfolio empowerment approach.A total of 60 medical devices in clinical use in the department of geriatric gastroentero1ogy of Xi'an No.1 Hospital from 2021 to 2023 were selected,and the medical devices used from 2021 to 2022 were managed by conventional methods,and the medical devices used from 2022 to 2023 were managed by using the improved evidence theory(improved evidence theory management).The equipment management quality,equipment data integrity score and comprehensive assessment score of equipment management team were compared between the two management methods.Results:The average failure rate and scrap rate of equipment managed by the improved evidence theory method were(12.36±3.65)％and(2.65±0.54)％,respectively,which were lower than those of the conventional management method(t=9.897,15.877,P＜0.05),the average self-maintenance rate and upgrade rate of faults were(90.69±6.25)％and(91.25±5.25)％,respectively,which were higher than those of the conventional management method,the difference was statistically significant(t=13.191,14.828,P＜0.05).The average scores of equipment data management,diagnosis and treatment data analysis and clinical application data integrity using the improved evidence theory method were(92.36±2.36)points,(93.69±2.36)points and(94.39±3.26)points,respectively,which were higher than those of the conventional management method,the difference was statistically significant(t=13.044,13.893,15.036,P＜0.05).The average comprehensive assessment scores of technical support team,technical development team,technical practice team and auxiliary management team members adopting the improved evidence theory method were(91.36±3.26)points,(94.26±3.59)points,(95.36±4.36)points and(96.36±3.26)points,respectively,which were higher than those of the conventional management method,the difference was statistically significant(t=8.224,14.796,14.129,19.005,P＜0.05).Conclusion:The medical equipment management system based on the improved evidence theory can evaluate the risks in the application of equipment,improve the quality of equipment management,enhance the level of equipment management team,and provide decision-making assistance for the equipment management in geriatric gastroenterology department.

Objective:To design and develop a molecular imaging probe of 68Ga-labeled bombesin (BBN) analogue, 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-polyethylene glycol (PEG) 4-BBN, and investigate its potential to target prostate cancer with high expression of gastrin-releasing peptide receptor (GRPR) while minimizing uptake in pancreatic tissue. Methods:Based on the amino acid sequence of BBN peptides, the precursor DOTA-PEG 4-BBN was designed and prepared, followed by labeling with 68Ga and conducting to quality control analysis. The tumor uptake of 68Ga-DOTA-PEG 4-BBN was assessed by microPET/CT imaging on tumor-bearing nude mice models with PC3 of high GRPR expression or HT29 of low GRPR expression (3 mice per group). 68Ga-DOTA-PEG 4-BBN microPET/CT imaging was also performed on 6 tumor-bearing nude mice models with PC3, among which 3 mice were treated with gastrin-releasing peptide antagonist 1 h prior to injection of the tracer (blocked group). After imaging, the ex vivo tissues of 3 PC3 tumor-bearing nude mice of the non-blocked group were examined for radioactivity counting to evaluation the biodistribution of 68Ga-DOTA-PEG 4-BBN, and the percentage injected dose per gram of tissue (%ID/g) was calculated. Independent-sample t test was used for data analysis. Results:The synthesis of 68Ga-DOTA-PEG 4-BBN took 40 min, with the radiochemical yield of 50%-60% (no decay correction) and the radiochemical purity of over 95%. After incubation in the serum at 37 ℃ for 4 h, the radiochemical purity remained more than 95%. The microPET/CT imaging results indicated that the uptake in the PC3 tumor was 3.2 times higher than the uptake in the tumor after GRPR blockade ((1.34±0.24) vs (0.42±0.03) %ID/g; t=5.47, P=0.005). After the injection of 68Ga-DOTA-PEG 4-BBN at 1 h and following imaging for 15 min, the PC3 tumor-bearing nude mice models of the non-blocked group showed that the pancreatic uptake ((0.150±0.058) %ID/g) was significantly lower than that in kidneys, lungs and liver ((9.452±0.234), (0.720±0.041), (1.572±0.213) %ID/g) with a profound statistical distinction ( t values: 11.28-53.02, all P<0.001). The tumor/pancreas uptake ratio could reach 16.92 in the tumor-bearing nude mice models with high GRPR expression. Conclusion:A novel molecular imaging probe 68Ga-DOTA-PEG 4-BBN demonstrates specific recognition of tumors with high GRPR expression while exhibiting low uptake in the pancreas, which shows its potential in prostate cancer molecular imaging.

Objective To investigate the characteristics of gut flora related to dampness syndrome in the population at risk of cerebrovascular disease and to explore their influencing factors.Methods Based on the results of epidemiological investigation of damp syndrome in at-risk population of cerebrovascular disease in Guangdong from October 2021 to February 2023,60 subjects(including 41 at-risk cases of cerebrovascular disease and 19 healthy controls)were included in the study.The identification of dampness syndrome and the risk rating of stroke were carried out for the subjects,and fecal samples were collected.High-throughput 16S rRNA sequencing technology and bioinformatics methods were used to analyze the characteristics of gut flora.Results(1)A total of 53 cases(88.33％)were identified as dampness syndrome.There was significant difference in the quantitative score of dampness syndrome between the risk group and the healthy group,and between the low-,medium-and high-risk groups(P=0.016;P=0.041).(2)There was no statistical difference in the species and abundance of gut flora between the dampness syndrome group and the non-dampness syndrome group.(3)In the population identified as dampness syndrome,there was no significant difference in Alpha diversity between the healthy group and the risk group,but there was significant difference in Beta diversity analysis;LEfSe analysis found that Fusobacterium and Lactobacillus were enriched in the risk group;correlation analysis showed that the differential bacteria were related to the three risk factors of diabetes,dyslipidemia and obesity and carotid intima-media thickness(IMT).(4)In the population identified as dampness syndrome and having the risk of cerebrovascular disease,there was no significant difference in Alpha diversity among three groups with different levels of risks,while significant difference in Beta diversity was observed;LEfSe analysis showed that Acidaminococcaceae,Phascolarctobacterium and Butyricimonas were enriched in the low-risk group,Veillonellaceae was enriched in the medium-risk group,and Ruminococcus 2 and Alloprevotella were enriched in the high-risk group;correlation analysis showed that the differential bacteria were associated with high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),white blood cell count(WBC),and neutrophil count(NEUT).Conclusion In the Guangdong population predominated by dampness syndrome,the severity of dampness syndrome is related to the risk of stroke,and the specific flora associated with sub-clinical atherosclerosis,inflammatory response and lipid metabolism are presented.

Objective To investigate whether microRNA(miR)-199a-5p regulates blood-brain barrier(BBB)integrity through PI3K/Akt pathway after cerebral ischemia.Methods A permanent middle cerebral artery occlusion(MCAO)model was established in SPF adult male SD rats.Totally 48 rats were randomly divided into sham group(n=12),model group(n=12),MCAO+miR-199a-5p group(n=12),and MCAO+miR-199a-5p negative control group(n=12).The Ludmila Bellayev 12 point score was used to evaluate the neurobehavioral performance of rats;The integrity of the BBB after ischemia stroke was detected through Evans blue staining;Immunofluorescent staining was used to determine apoptosis after cerebral ischemia;Western blotting technology was used to detect the protein expression of claudin-5,phosphatidylinositol-3 kinase regulatory subunit 2(PIK3R2),p-Akt,Akt,and vascular endothelial growth factor(VEGF)-A;Real-time PCR was used to investigate the expression levels of miR-199a-5p,claudin-5,and VEGF-A in the ischemic penumbra and infarcted area of the brain.Results The result showed that miR-199a-5p mimic intervention improved proprioception and motor ability in MCAO rats.MiR-199a-5p mimic reduced the expression of PIK3R2 following ischemia stroke,activated the Akt signaling pathway,and increased the expression of claudin-5 and VEGF-A in the ischemic penumbra.In addition,miR-199a-5p alleviated inflammation after cerebral ischemia.MiR-199a-5p mimic reduced BBB permeability and reduced neuronal apoptosis after cerebral ischemia.Conclusion MiR-199a-5p can reduce the expression of PIK3R2 following ischemic stroke,activate the Akt signaling pathway,reduce the expression of inflammatory cytokines,and alleviate the damage to the blood-brain barrier.

Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.

The influence of bed sharing on children′s physical and psychological health has been concerned as one of the main types of sleep arrangements.At present, there are significant differences in bed sharing among children of different ages, groups, regions and races.There are also studies on the impact of bed sharing sleep on children′s health, on the one hand, it is conducive to breastfeeding, where infants get enough security; on the other hand, it leads to an increase in the incidence of sudden infant death syndrome, and an increase in the number of night awakenings.Therefore, it is important to understand the current research situation of bed sharing and its influences on children, thus to better promote children healthy growth.