Objective: To define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective To analyze the association between eye-related behaviors and myopia among preschool chil-dren in Ningxia Hui Autonomous Region,and to develop a predictive nomogram model.Methods Using stratified cluster random sampling,36 062 preschool children from 400 randomly selected kindergartens in Ningxia Hui Autonomous Region were enrolled between October and December 2023.Primary caregivers of participants completed structured question-naires.Data were randomly split into a training set(n=25 243,70％)and a validation set(n=10 819,30％)in a ratio of 7∶3.The training set was used for model construction,and the validation set for external validation.Calibration plots and the Hosmer-Lemeshow(H-L)goodness-of-fit test assessed agreement between predicted and observed risks.Decision curve analysis(DCA)and clinical impact curve analysis(CICA)evaluated clinical utility.Results The myopia preva-lence among preschool children in Ningxia Hui Autonomous Region was 3.8％.A nomogram model based on binary Logistic regression showed area under the curve(AUC)values of 0.88(95％CI:0.87-0.89)for the training set and 0.89(95％CI:0.87-0.90)for the validation set,indicating strong discriminative ability.Calibration curves and H-L tests revealed good model fit(training set:x2=4.92,P=0.766;validation set:x2=5.52,P=0.961),with all P＞0.05.DCA and CICA confirmed clinical utility.The nomogram identified parental myopia,academic pressure,frequency of eye fatigue,daily screen time,and regular vision checks as the top five predictors of myopia.Conclusion The nomogram demonstrates promising potential for predicting myopia risk in preschool children in Ningxia Hui Autonomous Region,serving as a robust tool for clinical and educational myopia risk assessment.

Objective To investigate the relationship between the threonine and tyrosine kinase(TTK)gene and eyelid basal cell carcinoma(BCC).Methods Bioinformatics methods were used to screen the core gene(namely,TTK)associated with the occurrence and development of BCC from the Gene Expression Omnibus(GEO)database.Surgically removed eyelid BCC tissue specimens(BCC cells were divided into BBC Grade Ⅰ,Ⅱ and Ⅲ groups by tumor grade)and be-nign tumor tissue specimens(Control group)were collected from Ziyang Central Hospital for subsequent experiments.Cel-lular immunofluorescence assay(CIA)was used to detect the expression of the TTK gene in benign and malignant eyelid tumor cells.After knocking down TTK in BCC cells through transfection with lentiviruses(the cells transfected with LV-TTK-shRNA were taken as the TTK-shRNA group,and those transfected with LV-BBC-shRNA were taken as the BBC nega-tive control group),CIA was used to detect the expression of key proteins Bcl-2 and Bax in the apoptotic signaling pathway of each group of cells.Results The bioinformatics analysis showed that the TTK gene was the core gene associated with the occurrence and development of eyelid BCC.CIA detection results revealed that the fluorescence signal intensities in the tumor cytoplasm of Control,BCC Grade Ⅰ,Ⅱ,and Ⅲ groups were 1.03±0.07,1.28±0.11,1.58±0.13 and 1.92±0.17,respectively.The fluorescence signal intensity gradually increased,and the difference in fluorescence signal intensity among the four groups was statistically significant(all P＜0.05).Compared with that in the Control group(1.02±0.05),the cell fluorescence intensity was increased in the BCC negative control group(1.74±0.12)and decreased in the TTK-shRNA group(1.31±0.09)(P＜0.05).The difference in cell fluorescence intensity was significant among the Control,BCC nega-tive control and TTK-shRNA groups(all P＜0.05).The fluorescence intensity of the anti-apoptotic protein Bcl-2 was 1.04±0.12 in the Control group,2.12±0.23 in the BCC negative control group,and 1.43±0.15 in the TTK-shRNA group.The fluorescence intensity of the pro-apoptotic protein Bax was 1.02±0.08 in the Control group,0.64±0.11 in the BCC negative control group,and 1.47±0.16 in the TTK-shRNA group.After TTK knockdown,the expression level of BcL-2 in BCC cells decreased,and that of Bax increased.The fluorescence intensities of BcL-2 and Bax were significantly different among the Control,BCC negative control and TTK-shRNA groups(all P＜0.05).Conclusion The TTK gene plays a role in the regulation of eyelid BCC cell proliferation,and this effect is closely related to the PI3K-AKT-Bcl-2/Bax signaling path-way.

Non-small cell lung cancer(NSCLC)constitutes the largest portion of lung cancer overall,with high incidence and mortality rates.Apoptosis,is a hot focus in the clinical treatment of NSCLC,its main pathways include the extrinsic death receptor pathway,intrinsic mitochondrial apoptosis pathway and endoplasmic reticulum stress pathway,collectively regulating the cellular apoptosis process.Traditional Chinese medicine(TCM)has significant efficacy in the treatment and prognosis of NSCLC,with advantages such as boosting the body's resistance and less adverse drug reactions.Studies have shown that various individual Chinese herbal medicines and compound formulas can treat NSCLC through the apoptosis pathway,alleviating the adverse drug reaction of radiotherapy and chemotherapy.Based on this,this article summarizes recent domestic and international literature,focusing on apoptosis,to summarize the research progress of TCM in treating NSCLC by regulating apoptosis,aiming to provide reference for clinical treatment for NSCLC.

This study was aimed at determining the molecular characteristics of Yersinia pestis in the natural plague foci around Qinghai Lake through single nucleotide polymorphism technology,to lay a foundation for molecular epidemiological and source-tracing analysis of Y.pestis in this area.Using the whole genome sequencing technology,we obtained the whole genome sequences of 84 representative Y.pestis strains.Using the sequences of Y.pestis and Yersinia pseudotuberculosis IP32953 from the NCBI database as references,we compared and analyzed the 2 298 SNP loci of these strains.From 1957 to 2020,84 representative strains of Y.pestis from the natural plague foci around Qinghai Lake were divided into two clades:1.IN2 and 3.ANT1.The 1.IN2 clade was the characteristic population of Y.pestis throughout all epidemic years in this area.Additionally,analysis of the SNP distribution and hosts in the region indicated that the 1.IN2 clade was located in five counties except Wulan,whereas the 3.ANT1 clade was isolated from Himalayan marmot and dog in two counties.In conclusion,the population structure of SNP of Y.pestis in the natural plague foci around Qinghai Lake is relatively simple,and SNP analysis of Y.pestis provided a scientific basis for tracing plague epidemic sources and formulating plague prevention and control measures in this area.

OBJECTIVE: To investigate the relationship between serum levels of fibroblast growth factor-23 (FGF-23), heparanase (HPSE) and early renal impairment (RI) in patients with multiple myeloma (MM). METHODS: A retrospective analysis was conducted on the clinical data of 125 MM patients who were initially diagnosed in the Department of Hematology of the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology from June 2020 to June 2023. The patients were divided into RI group (>176.80 μmol/L) and non-RI group (≤176.80 μmol/L) based on their serum creatinine levels when diagnosed. The baseline data and laboratory indexes of the two groups were compared. The relationship between serum FGF-23, HPSE and early RI in MM patients was analyzed. RESULTS: Among 125 newly diagnosed MM patients, 33 cases developed early RI, accounting for 26.40%. The proportion of light chain type, blood urea nitrogen (BUN), blood uric acid, lactate dehydrogenase, FGF-23, and HPSE levels in RI group were higher than those in non-RI group (all P <0.05). There was no statistical significant difference in other data between the two groups (P >0.05). Multivariate logistic regression analysis showed that BUN, FGF-23 and HPSE were associated with early RI in MM patients (all P <0.05). The serum FGF-23 level was divided into Q1-Q4 groups by quartile, and the serum HPSE level was divided into q1-q4 groups. The correlation analysis showed that with the increase of serum FGF-23 and HPSE levels, the incidence of early RI increased (r =0.668, 0.592). Furthermore, logistic regression analysis showed that after controlling for confounding factors, elevated levels of serum FGF-23 and HPSE were still influencing factors for early RI in MM patients (OR>1, P <0.05). According to Pearson's linear correlation test, there was a positive correlation between serum FGF-23 level and HPSE level (r =0.373). CONCLUSION There is a certain correlation between serum levels of FGF-23, HPSE and early RI in MM patients, and the incidence of early RI is higher in patients with abnormally high levels of both.
Humans ; Multiple Myeloma/complications* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/blood* ; Glucuronidase/blood* ; Male ; Female ; Middle Aged ; Renal Insufficiency/blood* ; Aged

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.