When inflammation is continuously activated or dysregulated， it can induce chronic tissue injury and organ dysfunction， and participate in the occurrence and development of various inflammatory diseases such as atherosclerosis and inflammatory bowel disease. Owing to high targeting， long-acting efficacy and programmability， nucleic acid drugs provide a new direction for the treatment of inflammatory diseases. This article reviews the classification， mechanism of action and application progress of nucleic acid drugs in inflammatory diseases. It is found that small interfering RNA （siRNA） can specifically cut target mRNA through RNA interference to achieve inhibiting the expression of the target protein； antisense oligonucleotide （ASO） can inhibit target protein expression by inducing microRNA （miRNA） degradation or regulating splicing processes； miRNA can achieve network intervention by regulating multiple inflammatory target genes. At present， important breakthroughs have been made in the field of inflammatory diseases with siRNA drugs including Lumasiran， Nedosiran （for primary hyperoxaluria 1） and Inclisiran （for atherosclerosis）， ASO drugs including Donidalorsen （for hereditary angioedema）， Volanesorsen and Olezarsen （for familial chylomicronemia syndrome） and Lademirsen （for Alport syndrome）， as well as miRNA drugs including Obefazimod （for inflammatory bowel disease） and Remlarsen （for pathological fibrosis）. These drugs are expected to become a new generation of anti-inflammatory therapeutic strategies and bring more precise and efficient treatment options for patients with chronic inflammation and fibrotic diseases.

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

Objective To evaluate the efficacy and safety of transcatheter aortic valve implantation(TAVI)for the treatment of primary aortic valve regurgitation(NAVR)and to compare the difference in the choice of prosthetic valve size and the difference in complications with aortic stenosis(AS).Methods According to the definition of Valve Academic Research Consortium(VARC-3),143 patients with NAVR/AS treated with TAVI and patients with NAVR treated with surgical aortic valve replacement(SAVR)at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,China,from March 2019 to September 2024 were selected,and clinical data on baseline,perioperative,and primary endpoint events were were retrospectively collected and compared.Results Forty-three patients with NAVR were treated with TAVI,with a device success rate of 86.0％and a surgical success rate of 95.3％.Subgroup comparisons:(1)NAVR-TAVI group than NAVR-SAVR group:patients in the TAVI group had a significantly shorter operative time than those in the SAVR group(P＜0.001);complete left bundle branch block was more likely to occur after TAVI(P=0.042),and complete right bundle branch block was more likely to occur after SAVR(P=0.044).SAVR postoperatively The incidence of congestive heart failure was higher(P=0.013),and the mortality rate was significantly higher in the SAVR group than in the TAVI group(P=0.019).(2)NAVR-TAVI group than AS-TAVI group:the differences in access selection,THV size[28(22,34)mm vs.24(22,32)mm,P=0.044]and proportion of THV overdiameter[14％(7％,20％)vs.7％(3％,11％),P＜0.001]were statistically significant.patients in AS and NAVR groups had 1 case of permanent pacing after TAVI treatment.In the AS and NAVR groups,there was 1 case of permanent pacemaker implantation after TAVI.2 patients in the AS group were converted to surgical treatment,and 6 patients died.Conclusions The use of"off-label"(transfemoral)and"on-label"(transapical)TAVI devices(both from domestic sources)is safer than SAVR for the treatment of NAVR,especially in elderly and high-risk patients.Compared with patients with AS treated with TAVI,larger diameter annulas are usually selected for NAVR,with higher rates of valve migration,but overall safety and efficacy are comparable to AS.

Objective To develop an automated system that can accurately determine the relationship between the mandibular third molar and the mandibular nerve canal from panoramic images.Methods A dataset consisting of 600 panoramic images of the oral cavi-ty was selected,and the positions of the mandibular third molar and the mandibular nerve canal were accurately labeled.We compared the research designed TI-YOLOv5 with PANet,Faster R-CNN,Mask R-CNN,ResNeSt-101,and the original YOLOv5 in image seg-mentation tasks,with evaluation metrics of AP and AP50.Results TI-YOLOv5 achieved AP(average precision)54.0％and AP5094.9％,an increase of 4.9 and 6.7 percentage points respectively compared to the original YOLOv5(AP 49.1％,AP50 88.2％),and surpassed other SOTA methods such as Mask R-CNN(AP 45.1％,AP50 84.2％).Conclusion TI-YOLOv5 is significantly superior to mainstream networks in automatic positioning and relationship classification of mandibular wisdom teeth and neural tubes,with high de-tection accuracy and discrimination accuracy,and can provide reliable technical support for preoperative risk assessment of mandibular wisdom tooth extraction.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

Objective:To explore the categories of benefit finding among gastric cancer patients, analyze the differences and influencing factors among different groups, and provide reference for clinical nursing.Methods:A convenience sampling method was used to select 279 hospitalized gastric cancer patients admitted to the First Affiliated Hospital of Anhui Medical University from January 2024 to May 2024. The general information investigation, Benefit Finding Scale, Health-Related Hardiness Scale, Chronic Diseases Risk Perception Questionnaire and Distress Disclosure Index were used for cross-sectional survey. Latent profile analysis was used to identify the potential categories of benefit finding in patients with gastric cancer, and multivariate Logistic regression was used to analyze the related influencing factors.Results:A total of 266 valid questionnaires were returned, including 195 males and 71 females, with an age of (63.77 ± ?9.36) years. And three latent profiles of benefit finding were identified: low benefit-low growth group (31.96%, 85/266), moderate benefit group (37.59%, 100/266), and high benefit-health behavior group (30.45%, 81/266). The results of multiple Logistic regression analysis showed that compared with the moderate benefit group, the patients with course of disease<6 months ( OR = 0.344, 95% CI 0.160-0.737), cancer stage Ⅰ ( OR = 0.050, 95% CI 0.004-0.589), and highrisk perception ( OR = 0.935, 95% CI 0.878-0.996) were more likely to enter the low benefit-low growth group, and the patients without comorbidities ( OR = 2.520, 95% CI 1.250-5.081) and high self-disclosure ( OR = 1.137, 95% CI 1.007-1.283) were more likely to enter the moderate benefit group (all P<0.05). Compared with the high benefit-health behavior group, patients withcourse of disease<6 months ( OR = 0.108, 95% CI 0.039-0.301) were more likely to enter the low benefit-low growth group, male ( OR = 3.088, 95% CI 1.407-9.106), chemotherapy only ( OR = 6.515, 95% CI 2.034-20.864) and high health-related hardiness ( OR = 1.146, 95% CI 1.096-1.199) were more likely to enter the high benefit-health behavior group (all P<0.05). Conclusions:The benefit finding of gastric cancer patients has obvious classification characteristics. Clinical nursing staff should consider targeted interventions according to the characteristics of different categories of gastric cancer patients, encourage patients to face the disease with a positive attitude, and enhance patients′mental health literacy.

Objective : To explore the utility of a nomogram integrating contrast-enhanced CT radiomics with clinical features in the preoperative prediction of WHO/ISUP grade for clear cell renal cell carcinoma(ccRCC). Methods: A total of 214 patients with pathologically proven ccRCC who underwent enhanced CT scan before surgery were retrospectively included. According to the WHO/ISUP grade system, the cases were classified into low-grade(grades Ⅰ-Ⅱ) and high-grade(grades Ⅲ-Ⅳ), and then randomly divided into training and test set with a ratio of 4 ∶1. Regions of interest were segmented from both unenhanced and three-phase enhanced images, and radiomic features were extracted. Feature selection and dimensionality reduction were performed using Spearman rank correlation coefficients and LASSO regression, followed by the construction of the radiomic model with the KNN algorithm. Clinical and semantic imaging features were selected through univariate and multivariate analyses, and a clinical model was developed using the KNN algorithm. The clinical and radiomics signatures were used to construct a combined model and a nomogram was developed. The ROC curve and delong test were used to evaluate the diagnostic performance of the model, while calibration and decision curve analyses assessed its accuracy and clinical applicability. Results: 8 clinical features and 11 radiomic features were selected. The combined model, integrating these clinical and radiomics signatures, exhibited robust predictive performance with AUC values of 0.887 in the training set and 0.800 in the test set. The calibration curve demonstrated good consistency between the nomogram model and actual outcomes, while decision curve analysis indicated a favorable net benefit for the nomogram. Conclusion The nomogram constructed by combining radiomics and clinical signatures can provide evidence for preoperative prediction of ccRCC grade and guide clinical decision-making.

Objective:To investigate the current situation of water-borne endemic fluorosis in Anhui Province, and provide basic data for the adjusting the prevention and control measures.Methods:Using cross-sectional survey method, all villages in the water-borne endemic fluorosis areas were investigated in Anhui Province from 2019 to 2022. In water-borne endemic fluorosis village, the situation of water improvement project and the fluoride level of drinking water were investigated, and dental fluorosis of all children aged 8 - 12 was examined. The criteria for determining the achievement of control targets for water-borne endemic fluorosis in affected counties were based on the "Evaluation Measures for Control and Elimination of Key Endemic Diseases (2019 Edition)".Results:From 2019 to 2022, the rate of water improvement village in water-borne endemic fluorosis areas were 88.47% (1 527/1 726), 100% (1 726/1 726), 100% (1 726/1 726) and 100% (1 726/1 726), respectively. The qualified proportion of water fluoride in water-borne endemic fluorosis villages was 33.84% (584/1 726), 63.09% (1 089/1 726), 70.74% (1 221/1 726) and 74.33% (1 283/1 726), respectively. The prevalence rates of dental fluorosis in children aged 8 - 12 were 25.48% (45 461/178 440), 15.78% (27 959/177 200), 13.68% (23 505/171 880) and 12.66% (23 315/184 200), respectively. The proportion of affected counties that had achieved the control target of water-borne endemic fluorosis was 16% (4/25), 60% (15/25), 36% (9/25) and 40% (10/25), respectively.Conclusions:The water-borne endemic fluorosis areas in Anhui Province have improved the water fluoride qualification rate and reduced the incidence of fluorosis in children through prevention and control measures such as water improvement and fluoride reduction. However, the prevention and control efforts in key areas and counties need to be further improved.

Objective:To systematically evaluate and integrate the disease experience and needs of gastric cancer patients, so as to provide an evidence-based basis for clinical nursing.Methods:Qualitative studies on gastric cancer patients' experiences and needs during the disease process were electronically searched in PubMed, Web of Science, Embase, CINAHL, Cochrane Library, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biomedical Database. The search period was from database establishment to February 2024. The quality of the literature was evaluated using the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center. Meta-synthesis of results was performed using the aggregative synthesis.Results:A total of 13 papers were included, and 50 themes were distilled and summarized to form 11 new categories and three integrative results, including suffering and challenges from illness, self-adjustment and the search for a new normal in life, and undermet needs.Conclusions:Gastric cancer patients face a variety of significant challenges and changes during the course of their disease. Healthcare professionals should pay attention to the patients' disease experience and physical and mental needs, and construct personalized care plans for gastric cancer patients to help them coexist with the disease and achieve life reconstruction.