OBJECTIVE To investigate the mechanism by which Qiaobai cold compress solution （QBCS） improves acne vulgaris （AV） based on transcriptomics and animal experiments. METHODS Rats were randomly divided into a blank control group （ n ＝6） and a modeling group （ n ＝30）. AV models were established in the modeling group by topical application of oleic acid to the inner surface of both ears， combined with subcutaneous injection of Cutibacterium acnes suspension into the auricle. Successfully modeled rats were further divided into the model group， positive control group （Tretinoin cream， 0.045 g/kg）， and QBCS low-， medium-， high-dose groups [3.55， 7.11， 14.22 g/kg （calculated by the amount of crude drug） ] ， with 6 rats in each group. Rats in each d rug group were treated with the corresponding drugs once daily for 14 consecutive days. After the final administration， changes in the appearance of the ears and histopathological changes in the ear tissues were observed， and serum levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β， were measured. Auricular tissues from the blank control group， model group and QBCS medium-dose group were collected for transcriptome sequencing. Differential expressed genes （DEGs） were screened and subjected to Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis， followed by validation using real-time quantitative polymerase chain reaction and Western blot assay. RESULTS Compared with the model group， rats in all QBCS groups showed alleviated auricular acne symptoms， with reduced epidermal thickening， sebaceous gland hyperplasia， and inflammatory cell infiltration. Serum levels of TNF-α （except for the QBCS low-dose group）， IL-6 （except for the QBCS low-dose group） and IL-1β were significantly decreased （ P ＜0.05）. A total of 590 DEGs were identified （blank control group vs. model group）， and 596 DEGs were identified （model group vs. QBCS medium-dose group）. Above DEGs （blank control group vs. model group） were mainly enriched in Toll-like receptor （TLR） and nuclear factor-kappa B （NF-κB） signaling pathways， etc. Validation experiments showed that， compared with model group， low-， medium- and high-dose of QBCS reduced， to varying degrees， the mRNA expression of TNF-α， TLR2， interferon-γ and CXC chemokine ligand 8 in the auricular tissues of AV rats， increased the mRNA expression of peroxisome-proliferator-activated receptor gamma and tumor protein 53， and inhibited the phosphorylation of NF-κB p65 protein as well as the expressions of TLR2 and myeloid differentiation primary response protein 88（MyD88） （ P ＜0.05）. CONCLUSIONS QBCS can alleviate auricular inflammation and skin lesions in AV rats. This effect may be related to inhibition of the TLR/MyD88/NF-κB signaling pathway， thereby suppressing the expression of downstream inflammatory factors such as TNF-α.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

OBJECTIVE To analyze the specific risks and long-term toxicities of four BCR-ABL1 tyrosine kinase inhibitors （TKIs）（imatinib， dasatinib， nilotinib， and bosutinib） in pediatric patients with hematological malignancies. METHODS Adverse drug event （ADE） reports submitted to the the United States FDA Adverse Event Reporting System （FAERS） from January 2012 to December 2024， with imatinib， dasatinib， nilotinib， and bosutinib as the primary suspect drugs， were collected. Data mining was performed using the reporting odds ratio method and proportional reporting ratio method. ADE terms were classified and summarized by system organ class （SOC） and preferred term （PT） according to the Medical Dictionary for Drug Regulatory Activities （MedDRA， version 26.0）. Meanwhile， the ADE reports were divided by age into the adult group （≥18 years） and the pediatric group （＜18 years） to compare the differences in ADE between the two groups. RESULTS A total of 1 512 pediatric ADE reports were included： 993 for imatinib， 391 for dasatinib， 112 for nilotinib， and 16 for bosutinib. Among the reported ADEs， the patients were mainly aged 12-＜18 years； the reports mainly originated from the United States， France， and Japan； and the primary indications were chronic myeloid leukemia and acute lymphoblastic leukemia. A total of 5 256 ADE signals were mined， among which 235 were positive signals， involving 1 103 PT across 27 SOC. The top five PT ranked by the number of positive signals were nausea， febrile neutropenia， abdominal pain， neutropenia， and anemia. The top two SOC were general disorders and administration site conditions， and gastrointestinal disorders. Compared with the adult group， the pediatric group had relatively higher proportions of events related to infections and infestations as well as blood and lymphatic system disorders. Pediatric long-term toxicity signals primarily included growth retardation， accompanied by signals related to endocrine system abnormalities and bone metabolism abnormalities. Specific signals included imatinib-associated septic shock， dasatinib-associated chylothorax， and nilotinib-associated electrocardiographic QT interval prolongation. CONCLUSIONS When pediatric patients use BCR-ABL1 TKIs， priority monitoring of infection risk and hematologic parameters is required， along with long-term follow-up of height， endocrine， and bone metabolism parameters. Targeted screening and management of drug-specific signals should be performed to ensure the long-term safety of pediatric medication.

Objective: To compare the consistency between bioelectrical impedance analysis (BIA) and dual energy X ray absorptiometry (DXA) in measuring body composition among Tibetan children and adolescents and to explore the applicability of BIA in plateau region, so as to provide scientific and convenient body composition measurement support among children and adolescents. Methods: From May to June, 2022, a total of 344 Tibetan children and adolescents aged 6-17 years were selected from Golmud Municipal National Middle School and Changjiangyuan Nationality Primary School in Qinghai Province by cluster sampling method, and their fat mass, fat mass percentage and lean mass were measured by DXA and BIA. The consistency and correlation between the two methods were assessed by using the Wilcoxon rank-sum test, Spearman correlation analysis, intraclass correlation coefficient (ICC), and Bland-Altman analysis. Results: DXA measured fat mass and fat mass percentage were significantly higher than those obtained by BIA (6-12 years old: Z =9.91, 11.28; 13-17 years old: Z =9.02, 10.21), while lean mass and lean mass percentage were significantly lower than BIA results (6-12 years old: Z =-11.60, -11.30; 13-17 years old: Z =-10.77, -10.36) (all P < 0.05 ). The two methods showed strong correlations in fat mass and lean mass (all r >0.80, all ICC >0.90), but exhibited poor agreement in fat mass percentage and lean mass percentage (6-12 years old: Lin s CCC =0.64, 0.41; 13-17 years old: Lin s CCC = 0.79 , 0.35). Bland-Altman analysis showed that the difference between the two methods was negatively correlated with the average value in FM%(6-12 years old: r =-0.75, 13-17 years old: r =-0.79, both P <0.01). Conclusion BIA and DXA show high consistency in measuring body fat mass and lean body mass in Tibetan children and adolescents, although some bias is still present in certain individuals.

Objective: To analyze the characteristics of latent classes of dietary patterns among children and adolescents in Qinghai Province, and their association with overweight and obesity, so as to provide a scientific basis for conducting targeted nutritional interventions and weight management for the local population. Methods: From May to October 2025, a multi stage stratified cluster random sampling method was employed to recruit 1 611 children and adolescents aged 6-17 years from Chengdong District of Xining City and Gonghe County of Hainan Tibetan Autonomous Prefecture in Qinghai Province. Questionnaire survey was conducted using a questionnaire developed by the Chinese Center for Disease Control and Prevention, and physical examination was conducted by using unified measurement standards. Latent class analysis (LCA) was performed on the food intake frequency of the participants. The χ 2 test and Logistic regression analysis were applied to explore the relationship between dietary patterns and overweight/obesity. Results: The detection rates of overweight, obesity, and overall overweight/obesity among the participants were 10.4%, 5.8%, and 16.2%, respectively. Latent class analysis identified three dietary patterns: modern mixed pattern ( n =399, 24.8%), low diversity pattern ( n =476, 29.5%), and traditional dietary pattern ( n =736, 45.7%). The potential category distribution differences of three dietary patterns among children and adolescents with and without overweight or obesity were statistically significant (non overweight and obesity: 22.5%, 29.1%, 48.4%; overweight and obesity: 36.4%, 31.8%, 31.8%) ( χ 2=30.69, P <0.01). Logistic regression showed that, compared with the traditional dietary pattern, the modern mixed pattern was associated with a higher risk of overweight and obesity ( OR =1.68, 95% CI =1.13-2.49); female sex was associated with a lower risk of overweight/obesity compared with male sex ( OR =0.66, 95% CI =0.50-0.86) (both P <0.05). Conclusions A positive association exists between the modern mixed dietary pattern and obesity in children and adolescents. It is recommended to reduce the intake of grains and unhealthy foods among overweight and obese children and adolescents, while increasing the consumption of legumes, fish, and shrimp, in order to cultivate healthy and rational dietary habits.

ObjectiveTo investigate the effect of icariin （ICA） on the phenotype of dendritic cells （DCs） in heart tissue of the Dahl salt-sensitive myocardial remodeling model of rats and its regulation on the vitamin D system. MethodsMale Dahl salt-resistant rats were divided into a normal group， and male Dahl salt-sensitive rats were divided into a model group， low-， medium-， and high-dose ICA groups （30， 60， 120 mg·kg^-1·d^-1）， and Vitamin D group （3×10^-5 mg·kg^-1·d^-1）. In addition to the normal group， the other groups were given an 8% high salt diet to establish a myocardial remodeling model and received intragastric administration after successful modelling once a day for six weeks. The dynamic changes in tail artery blood pressure were monitored， and detection of cardiac ultrasound function in rats was performed. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the morphological changes in rat heart tissue. The phenotype of DCs and T helper cell 17 （Th17）/regulatory T cell （Treg） ratio were detected by flow cytometry. The mRNA and protein expression of vitamin D receptor （VDR）， 1α-hydroxylase （CYP27B1）， 24-hydroxylase （CYP24A1）， forkhead frame protein 3 （FoxP3）， solitaire receptor γt （RORγt）， myocardial type Ⅰ collagen （ColⅠ）， and type collagen （ColⅢ） in heart tissue was detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the normal group， the model group showed disordered arrangement and rupture of myocardial cells， nuclear condensation， significant edema of myocardial tissue， significant proliferation of collagen fibers in a network distribution， and a significant increase in tail artery blood pressure， left ventricular end diastolic diameter （LVEDD）， and left ventricular end systolic diameter （LVESD） （P<0.05）. The phenotype of cardiac DCs was CD40， CD80， and CD86， and the levels of major histocompatibility complex Ⅱ （MHC-Ⅱ）， Th17 cells， and Th17/Treg were significantly increased （P<0.05）. The mRNA and protein expression of CYP24A1 and RORγt in the heart， as well as the mRNA expression of ColⅠ and ColⅢ， were significantly increased （P<0.05）. The left ventricular ejection fraction （LVEF）， interventricular septal thickness （IVSD）， and left ventricular posterior wall thickness （LVPWD） were significantly decreased （P<0.05）. The phenotype of cardiac DCs such as CD11， CD11b， and Treg cells， were significantly reduced （P<0.05）， while the mRNA and protein expression of cardiac VDR， CYP27B1， and FoxP3 were significantly decreased （P<0.05）. Compared with the model group， the low-， medium-， and high-dose ICA groups and vitamin D group significantly reduced myocardial cell rupture and nuclear consolidation in rats. The high-dose ICA group and vitamin D group showed a small amount of myocardial cell rupture and nuclear consolidation， improving myocardial fiber arrangement to varying degrees and significantly reducing myocardial fiber rupture and proliferation. The tail artery blood pressure， LVEDD， and LVESD were significantly decreased in the low-， medium-， and high-dose ICA groups and vitamin D group （P<0.05）， and the phenotype of cardiac DCs including CD40， CD80， CD86， MHC-Ⅱ， Th17 cells， and Th17/Treg were significantly decreased （P<0.05）. The mRNA and protein expression of CYP24A1 and RORγt， and the mRNA expression of ColⅠ and ColⅢ in the heart were significantly decreased in the medium- and high-dose ICA groups and vitamin D group （P<0.05）. The LVEF， IVSD， and LVPWD of myocardial remodeling model rats in the low-， medium-， and high-dose ICA groups and vitamin D group were significantly increased （P<0.05）. The phenotypes of cardiac DCs including CD11， CD11b， and Treg cells were significantly increased in the medium- and high-dose ICA groups and the Vitamin D group （P<0.05）. The mRNA and protein expressions of VDR， CYP27B1， and FoxP3 in the heart were significantly increased in the medium- and high-dose ICA groups and vitamin D group （P<0.05）. ConclusionICA can regulate tail artery blood pressure， cardiac structural and functional damage， and myocardial tissue fibrosis and inhibit phenotype and functional maturation of DCs in heart tissue in the myocardial remodeling model of Dahl salt-sensitive rats. It can also affect the gene and protein expression of VDR， CYP24A1， and CYP27B1， achieving its intervention in Th17/Treg balance in the immune process of myocardial remodeling possibly by regulating vitamin D/VDR in heart tissue.

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.

Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 ( CFAP300 ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous CFAP300 loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in CFAP300 -mutant individual, whereas immunofluorescence demonstrated markedly reduced CFAP300 expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the CFAP300 mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband's sperm. Overall, this study expands the known CFAP300 mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.
Humans ; Male ; Infertility, Male/pathology* ; Acrosome/pathology* ; Sperm Tail/pathology* ; Pedigree ; Spermatozoa ; Adult ; Loss of Function Mutation ; Ciliary Motility Disorders/genetics* ; Spermatogenesis/genetics* ; Female