Objective: To evaluate the diagnostic potential of fluid suppression (FS) techniques combined with amide proton transferweighted imaging (APTw) for assessment of isocitrate dehydrogenase (IDH) mutation status, glioma subtypes, and tumor proliferation. Materials and Methods: This retrospective study included 117 patients with adult-type diffuse gliomas. Conventional APTw, FSAPTw, and spillover-corrected FS-APTw (SCFS-APTw) metrics were calculated from 3T MRI data in tumor parenchyma, necrotic or cystic regions, and contralateral normal-appearing white matter. APTw signals were compared across the three techniques within each region, between IDH-mutant and IDH-wildtype gliomas, and among astrocytoma, oligodendroglioma, and glioblastoma subtypes. Diagnostic performance for distinguishing IDH mutation status and glioma subtypes was assessed using receiver operating characteristic (ROC) analysis. Correlations between APTw metrics and Ki-67 expression were also analyzed. Results: Both FS-APTw and SCFS-APTw significantly reduced signal intensity in tumor parenchyma and necrotic or cystic regions, with SCFS-APTw demonstrating a stronger suppression effect. IDH-wildtype gliomas showed significantly higher APTw metrics than IDH-mutant gliomas (all P < 0.001). Glioblastomas exhibited significantly higher metrics than oligodendrogliomas (all corrected P ≤ 0.015) and astrocytomas (all corrected P < 0.001). SCFS-APTw achieved the highest area under the ROC curve (AUC) of 0.846 for identification of IDH mutation status. For differentiation between astrocytomas and glioblastomas, the 90th percentile of APTw yielded the highest AUC (0.860), followed by SCFS-APTw (0.849). For discrimination between oligodendrogliomas and glioblastomas, the highest AUC (0.832) was obtained using the 90th percentile of SCFS-APTw. None of these metrics successfully differentiated oligodendrogliomas from astrocytomas. SCFS-APTw demonstrated the strongest correlation with Ki-67 expression (r = 0.451). Conclusion FS techniques effectively reduce elevated APTw signals originating from fluid compartments. Their combination with APTw imaging enables evaluation of IDH mutation status, glioma subtypes, and tumor proliferative activity in adulttype diffuse gliomas.

Objective: To investigate the role of butyric acid-producing bacteria in long bone homeostasis in mice with periodontitis under a high-fat/high-sugar diet and to provide new insights for the prevention and treatment of periodontitis and related bone metabolic diseases. Methods: This study has been approved by the Animal Welfare and Ethics Committee of the Experimental Animal Center. Initially, 14 mice were randomly divided into the CON group (the control group) and the LIG group (the periodontitis group). Mice in the LIG group had experimental periodontitis induced by ligating the second maxillary molars bilaterally and were fed a high-fat and high-sugar diet. After 8 weeks, samples were collected. Micro-computed tomography (Micro-CT) was used to analyze alveolar bone resorption and various parameters of the proximal tibia trabecular bone, including bone mineral density (BMD), bone volume per tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp). After decalcification, hematoxylin and eosin (HE) staining was performed on maxillary bone sections to assess periodontal tissue inflammation and connective tissue destruction. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect related genes in the distal femur and proximal tibia bone tissues, including osteocalcin (OCN), osteogenic transcription factor (Osterix), osteoprotegerin (OPG), tartrate resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), receptor activator of nuclear factor kappa-B (RANK), and receptor activator of nuclear factor kappa-B ligand (RANK-L). Subsequently, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + butyric acid-producing bacteria (BP) group, and LIG + BP group. The breeding, sampling, and sample detection methods remained the same. Finally, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + sodium butyrate (SB) group, and LIG + SB group. The breeding, sampling, and sample detection methods remained the same. Results: ①Periodontitis modeling was successful. Compared with the CON group, the LIG group exhibited significant alveolar bone resorption of the maxillary second molar, aggravated periodontal tissue inflammation, and connective tissue destruction. ②Periodontitis exacerbated long bone resorption in mice fed a high-fat high-sugar diet. Compared with the CON group, the LIG group had significantly lower BMD, BV/TV, Tb.N, and Tb.Th (P<0.05), and significantly higher Tb.Sp (P<0.05). HE staining of the proximal tibia showed that the trabeculae in the LIG group were sparse and disordered, with some areas showing fractures or dissolution. The expression of osteoblast markers (OCN, Osterix, OPG) was significantly lower in the LIG group (P<0.05), while the expression of the osteoclast marker TRAP showed an increasing trend (P>0.05). The ratio of RANK-L/OPG was significantly higher in the LIG group compared with the CON group (P<0.05). ③ Supplementation with butyric acid-producing bacteria alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BMD and Tb.Th were significantly higher in the LIG + BP group. HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + BP group compared with the LIG group. The expression of OCN and Osterix was significantly higher in the LIG + BP group, while the expression of osteoclast-specific genes (OSCAR, RANK, RANK-L) was significantly lower (P<0.05). ④ Supplementation with butyrate alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BV/TV and Tb.N were significantly higher in the LIG + SB group, and Tb.Sp was significantly lower (P<0.05). HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + SB group compared with the LIG group. The expression of Osterix, OPG, OSCAR, TRAP, and RANK was significantly lower in the LIG + SB group compared with the LIG group (P<0.05). Conclusion Periodontitis disrupts the long bone homeostasis of mice fed a high-fat high-sugar diet, aggravating long bone resorption. Supplementation with butyric acid-producing bacteria or butyrate can effectively alleviate the disruption of long bone homeostasis caused by periodontitis.

Objective: To investigate the impact of milk and egg supplementation on body composition and bone mineral density of rural primary school students in Yunnan Province, so as to provide a reference for developing targeted nutritional intervention strategies. Methods: In December 2023, a cluster sampling method was adopted to select students from grades one to three in four primary schools each from Jinggu and Shidian countys of Yunnan Province, as the intervention group (662 students). Additionally, two boarding primary schools were selected from each county based on the principle of matching scale and student numbers as the control group (455 students). Starting from April 2023, the intervention group received 200 mL milk and 50 g eggs during the break on school days for 8 months, while the control group maintained their usual diet behavior. Body composition was measured by using bioelectrical impedance analysis, and distal radial bone mineral density was assessed via dual energy X-ray absorptiometry in April and December 2023. The intervention effects were analyzed by using a difference in-differences approach. Results: The final measurements of body fat percentage, skeletal muscle mass and fat free mass of the intervention group and the control group of primary school students were significantly higher than the baseline values, and the net effect of milk and egg intervention on these body composition indicators was not statistically significant ( P >0.05, both before and after adjustment). In contrast, bone mineral density increased significantly by 0.02 g/cm 2 in the intervention group. The net intervention effect on bone mineral density was statistically significant ( β=0.02, 95%CI =0.00-0.04), and remained significant after model adjustment ( β=0.02, 95%CI =0.00-0.04) (both P < 0.05). Subgroup analysis showed statistically significant effects of the intervention among girls ( β=0.02, 95%CI =0.00-0.04), day students ( β=0.04, 95%CI =0.01-0.07), and students with normal nutritional status ( β=0.02, 95%CI =0.00-0.04) (all P <0.05). No significant effect of milk and egg supplementation was observed on body composition indicators (all P <0.05). Conclusions Milk and egg supplementation can improve bone mineral density among rural primary school students in Yunnan Province. It is recommended that rural school aged children should increase intake of milk and eggs to support growth and development.

Flavonoid 3-O-glucosyltransferase (3GT) is a key enzyme in the glucosidation of anthocyanins. To investigate the 3GT gene in rhododendron, we cloned an open reading frame (ORF) of 3GT gene (named Rh3GT) from Rhododendron hybridum Hort (Red cultivar) and then characterized this gene and the deduced protein in terms of the biochemical characteristics, expression level, and enzymatic function. The results showed that Rh3GT had a full length of 993 bp and encoded 330 amino acid residues. The deduced protein was hydrophilic, stable, weak acid, belonging to the glycosyltransferase family (GT-B type), with glutamine (Q) at position 44 in the PSPG box. The phylogenetic analysis showed that Rh3GT was most closely related to Vc3GT from Vaccinium corymbosum and Vm3GT from Vaccinium myrtillus. Rh3GT was expressed in the stems, leaves, and flowers and almost not expressed in the roots, with the highest expression level in petals during full blooming stage. Introduction of pCAMBIAL1302-Rh3GT into petals significantly up-regulated the expression level of Rh3GT and increased the total anthocyanin accumulation. Rh3GT was successfully expressed in Escherichia coli BL21 in the form of inclusion bodies with a size of about 36 kDa. The results of HPLC showed that the recombinant Rh3GT after denaturation, purification, and dilution could catalyze the synthesis of cyanidin and UDP-glucose to synthesize cyanidin 3-O-glucoside, indicating that the expressed protein had 3GT activity. This study provides basic data for further studying the molecular regulation mechanism of anthocyanin biosynthesis and theoretical support for molecular breeding of rhododendron.
Rhododendron/classification* ; Glucosyltransferases/metabolism* ; Cloning, Molecular ; Escherichia coli/metabolism* ; Recombinant Proteins/biosynthesis* ; Anthocyanins/biosynthesis* ; Phylogeny ; Plant Proteins/metabolism* ; Amino Acid Sequence

Objective:To construct a recommended list of high-alert medication (HAM) based on big data from medication error (ME) reports in China, providing reference for preventing and reducing HAM-related risks.Methods:The drugs involved in the serious ME reports of the National Monitoring Network for Clinical Safe Medication (Monitoring Network) were collected (as of December 31, 2023), and the candidate drugs were preliminarily determined referring to the HAM list of China 2023 (Chinese list) and the latest three lists of American Institute for Safe Medication Practices (ISMP). Candidate drugs that were included in both the Chinese list and ISMP lists, as well as those existed in the Chinese list but had never been included in the ISMP lists were included in the current list, and their risk levels followed the original risks in the Chinese list. Candidate drugs that existed in the Chinese list but had been excluded from the ISMP lists, and those existed in the ISMP lists but had not been included in the Chinese list were listed as suspected drugs. For the other candidate drugs, those did not meet the definition of HAM were excluded firstly, and those related to ME that had caused serious harm were listed as suspected drugs, according to the judicial cases on ME of China Judgements Online and PKULAW database. Two methods, including Delphi expert consultation and questionnaire survey, were used to determine whether the above suspected drugs were included in the HAM list and their risk levels.Results:A total of 138 drugs were obtained through the initial screening, 106 of which were directly included in the current list, and 32 of which were listed as drugs requiring further assessment. After 2 rounds of Delphi expert consultation by 18 experts and surveys with 136 valid questionnaires, 32 suspected drugs did not meet the inclusion criteria. Finally, a total of 106 drugs were included in the current list, including 51 A-class drugs in 9 categories, 33 B-class drugs in 9 categories, and 22 C-class drugs in 5 categories.Conclusion:Based on the big data of the ME reports in China, a HAM list is constructed, which is accurate and concise and better fits the actual clinical drug risks in China, helping to improve the drug safety management.

Objective:To investigate the relationship between screen time and content, and the mental health status of adolescents. The findings will inform the formulation of targeted intervention policies to enhance adolescent mental health.Methods:Between September and November 2023, 5 197 students from 64 junior high, senior high, and vocational schools across 13 districts in Wuhan were recruited, using the stratified whole-cluster random sampling to investigate their screen behavior and mental health status. Mental health status was measured using the Mental Health Inventory for Chinese Middle School Students (MMHI-60). A generalized additive model was used to explore the nonlinear association between screen time and mental health status. Additionally, a mixed-effects model was utilized to explore the dose-response associations between average daily total screen time, screen time for different content types, and adolescents' mental health status and the impact of the proportion of different screen contents on mental health outcomes.Results:The age of the participants was (14.40±1.48) years, with 56.07% being boys. The MMHI-60 score averaged 1.73±0.70. The M( Q1,Q3) for daily total screen time was 50.00 (0.00,128.57) minutes. The M( Q1,Q3) for screen time dedicated to gaming, studying, socializing, and watching videos were 0.00 (0.00, 20.00), 8.57 (1.64, 44.50), 4.28 (0.00, 30.00), and 0.00 (0.00, 25.71) minutes, respectively. A non-linear association was observed between average daily screen time and adolescent mental health problem score, 0-1 hour of daily screen time was beneficial for adolescent mental, compared to no screen time. However, screen time exceeding 1 hour was detrimental, with the negative impact increasing alongside screen time duration. When total daily screen time was held constant, the proportion of time spent on gaming ( β=0.14, 95% CI: 0.05-0.23, P=0.003) and video ( β=0.21, 95% CI: 0.09-0.28, P<0.001) was positively correlated with mental health problems, whereas the proportion of time spent on studying was negatively correlated with mental health problems ( β=-0.17, 95% CI: -0.24 - -0.11, P<0.001). Conclusions:Moderate screen time is advantageous for adolescent mental health. However, it is crucial to minimize the proportion of screen time dedicated to video and gaming activities to mitigate potential adverse effects.

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

OBJECTIVES: To investigate pharmacologically active components of Yiqi Zishen Formula (YZF) and their mechanisms for alleviating airway inflammation in mice with chronic obstructive pulmonary disease (COPD). METHODS: Ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry was employed to characterize the chemical components in YZF and YZF-medicated rat serum. A compound-disease target network was constructed based on serum components of YZF to screen the key pathways and targets using enrichment analysis. A mouse model of cigarette smoke-induced COPD was used to evaluate the anti-inflammatory effect of YZF and validate the expression of key proteins in network pharmacology-enriched pathways. Fifty male C57BL/6J mice were randomized equally into control group, COPD model group, high- and low-dose YZF treatment groups, and N-acetylcysteine treatment group. Pulmonary function of the mice was assessed using whole-body plethysmography, and lung histopathology, alveolar structure, and airway remodeling were analyzed using HE staining. The levels of IL-1β, IL-6, and TNF‑α in bronchoalveolar lavage fluid (BALF) were determined with ELISA, and pulmonary expressions of PI3K, Akt, phosphorylated Akt (p-Akt), p65, and phosphorylated p65 (p-p65) were detected using immunohistochemistry. RESULTS: We identified a total of 156 chemical components (including 26 flavonoids or flavonoid glycosides, 27 alkaloids, and 11 saponins) in YZF and 43 prototype components in medicated rat serum. Network pharmacology revealed 704 YZF-related targets and 1199 COPD-associated targets. Integrated analysis suggested that the anti-COPD effects of YZF were associated with the PI3K-Akt signaling pathway. In mouse models of COPD, YZF treatment significantly increased mean alveolar number and peak expiratory flow (P<0.05), reduced mean linear intercept, bronchial wall thickness, lung coefficient, and BALF cytokine levels, and suppressed the expressions of PI3K, Akt, p-Akt, p65, and p-p65 in the lung tissues. CONCLUSIONS YZF alleviates COPD symptoms and airway inflammation in mice possibly by inhibiting the PI3K/Akt/NF‑κB pathway through its multiple components that interact with multiple targets.
Animals ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Male ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; NF-kappa B/metabolism* ; Inflammation/drug therapy* ; Rats

BACKGROUND: Epidemiological data on chronic diarrhea in the Chinese population are lacking, and the association between obesity and chronic diarrhea in East Asian populations remains inconclusive. This study aimed to investigate the prevalence of chronic diarrhea and its association with obesity in a representative community-dwelling Chinese population. METHODS: This cross-sectional study was based on a multistage, randomized cluster sampling involving 3503 residents aged 20-69 years from representative urban and rural communities in Beijing. Chronic diarrhea was assessed using the Bristol Stool Form Scale (BSFS), and obesity was determined based on body mass index (BMI). Logistic regression analysis and restricted cubic splines were used to evaluate the relationship between obesity and chronic diarrhea. RESULTS: The standardized prevalence of chronic diarrhea in the study population was 12.88%. The average BMI was 24.67 kg/m 2 . Of all the participants, 35.17% (1232/3503) of participants were classified as overweight and 16.13% (565/3503) as obese. After adjustment for potential confounders, individuals with obesity had an increased risk of chronic diarrhea as compared to normal weight individuals (odds ratio = 1.58, 95% confidence interval: 1.20-2.06). A nonlinear association between BMI and the risk of chronic diarrhea was observed in community residents of males and the overall participant group ( P  = 0.026 and 0.017, respectively). CONCLUSIONS This study presents initial findings on the prevalence of chronic diarrhea among residents of Chinese communities while offering substantiated evidence regarding the significant association between obesity and chronic diarrhea. These findings offer a novel perspective on gastrointestinal health management.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Body Mass Index ; China/epidemiology* ; Chronic Disease/epidemiology* ; Cross-Sectional Studies ; Diarrhea/epidemiology* ; Obesity/complications* ; Prevalence ; East Asian People/statistics & numerical data*