Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Objective: To explore the association between CDKAL1 rs35261542, FAIM2 rs 3205718, and VGLL4 rs 2574704 polymorphisms with childhood obesity and related metabolic phenotypes to provide evidence for personalized prevention and management strategies. Methods: Based on the 2023 Long term Nutritional Health Effects of Early Childhood Nutrition Package Intervention project, the study enrolled 1 078 children aged 5-7 years from four counties in Henan (Songxian and Ruyang countries) and Guizhou (Guiding and Fuquan countries) provinces. Using BMI Z scores, 87 overweight and obese(OVOB) children were selected and matched by sex, age, and BMI Z score with 117 normal weight controls. Participants were further stratified into four metabolic phenotype groups: metabolically healthy normal weight (MHNW, n =51), metabolically unhealthy normal weight (MUNW, n =66), metabolically healthy obesity (MHO, n =31) and metabolically unhealthy obesity (MUO, n =56) based on four conventional cardiometabolic risk factor (CR) criteria. Data were collected through questionnaires, anthropometric measurements, serum biochemical tests, and KASP genotyping. The distribution of three genetic polymorphisms ( CDKAL1 rs35261542, FAIM2 rs3205718, VGLL4 rs 2574704) across metabolic subgroups was analyzed. Multivariate Logistic regression models assessed associations between these polymorphisms and obesity/metabolic phenotypes. Results: Multivariate Logistic regression analysis showed that Homozygous mutant AA genotype of CDKAL1 rs 35261542 was positively associated with OVOB( OR =3.63), MHO ( OR =11.04), MUO ( OR = 4.88 ) ( P <0.05). Homozygous TT genotype of FAIM2 rs 3205718 increased OVOB risk ( OR =4.44, P <0.05) but showed no association with metabolic phenotypes ( P >0.05). Homozygous mutant TT of VGLL4 rs 2574704 reduced the risks of MHO and MUO ( OR = 0.30, 0.24， P <0.05). Cumulative genetic effects analysis demonstrated carriers of 1 or 2 risk genotypes of rs 35261542 and rs 3205718 had progressively higher OVOB risk ( OR =2.53, 20.79), and the combination of rs 35261542 and rs 2574704 increased risks for both MHO ( OR =8.50) and MUO ( OR =5.00) ( P <0.05). Conclusions The AA genotype of rs 35261542 ( CDKAL1 ) positively correlates with childhood obesity and metabolic abnormalities. The TT genotype of rs 3205718 ( FAIM 2) increases obesity risk but not metabolic phenotypes. The TT genotype of rs 2574704 ( VGLL 4) shows protective effects against metabolic dysfunction. Risk genotypes exhibit dosedependent cumulative effects on obesity and metabolic outcomes.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Objective:To evaluate the efficacy and safety of Luofuoshan-Baicao oil (LBO) and wind medicated oil for the treatment of Aedes albopictus bites. Methods:A paired self-controlled study was conducted. Thirty-six healthy volunteers were recruited from Guangdong Provincial Hospital of Traditional Chinese Medicine from February 2023 to March 2023. Each participant's forearms were subjected to Aedes albopictus bites, with 3 bites on each arm. For the first 18 participants, LBO was applied to the left arm, and wind medicated oil to the right arm; for the latter 18 participants, wind medicated oil was applied to the left arm, and LBO to the right arm. The observation period was 24 hours. Within the first 3 hours after the mosquito bites, the topical agents were applied once every other hour for a total of 3 sessions, with an applicator centered on the bite site at a dose of approximately 50 μl, covering a skin area of about 2 cm in diameter; after 3 hours, participants applied the topical agents themselves until symptoms subsided or the 24-hour observation period ended. All subjects were followed up at the occurrence of skin lesions after mosquito bites, 0 to 3 hours after the first treatment, as well as 24 hours after the first treatment. During the follow-up, the effects of both topical agents on pruritus, erythema, papules, or wheals were evaluated, differences in treatment frequency were analyzed, and treatment-related adverse events were recorded. The time to disappearance of pruritus after treatment was statistically analyzed using Kaplan-Meier survival analysis, and intergroup differences were analyzed using the log-rank (Mantel-Cox) test. Two independent samples t-test was used for comparisons of other measurement data, and Pearson's chi-square test or Fisher's exact test was used for comparisons of count data between groups. Results:Within 3 hours after the first treatment, the time to initial disappearance of pruritus was significantly shorter in the LBO group (20.71 ± 1.92 min) than in the wind medicated oil group (28.30 ± 2.20 min, P < 0.05). The cumulative pruritus rate (the proportion of participants with pruritus among all participants) over time showed an overall stable fluctuation, and the cumulative pruritus rates at all observation points were significantly lower in the LBO group than in the wind medicated oil group ( P<0.05). After 3 hours of treatment, the mean values of changes in erythema diameters were 25.83 mm in the LBO group and 26.24 mm in the wind medicated oil group, while the mean values of changes in papule or wheal diameters were 8.25 mm in the LBO group and 9.18 mm in the wind medicated oil group; within 24 hours after the first treatment, the average time to disappearance of papules or wheals was 71.85 minutes in the LBO group and 73.01 minutes in the wind medicated oil group, while the average time to disappearance of erythema was 82.27 minutes in the LBO group and 84.86 minutes in the wind medicated oil group; there were no significant differences in the above observational indices between the two groups (all P > 0.05). The number of pruritus episodes within 24 hours of treatment was 56 in both the LBO group and wind medicated oil group, and the treatment frequency was 107 in both two groups; there were also no significant differences in the frequencies of pruritus episodes or treatment (both P > 0.05). No adverse events or reactions occurred during the trial. Conclusion:LBO was more effective than wind medicated oil in reducing the time to disappearance of pruritus after Aedes albopictus bites, with a high safety profile.

Objective:To explore the feasibility and and clinical efficacy of lingual mucosa replacement ureteral stenosis repair and plasty for the treatment of long segment ureteral polyps.Methods:Clinical data of 3 patients (4 sides) with long-segment ureteral polyps admitted to the Second Hospital of Lanzhou University from October 2017 to October 2019 were retrospectively analyzed. Two cases were male and one case was female. The ages were22, 16, and 45 years old. Preoperative urologic ultrasound, CT urography and ureteroscopy were performed. The lesions were located on the left side in 3 cases and on the right side in 1 case; the stenosis was located in the middle and upper ureter; the length of the ureteral stenosis was 6, 7, 6, and 6 cm, respectively; and the preoperative blood creatinine was 72, 85, and 70 μmol/L, respectively. Three cases underwent ureteral stenosis repair and plasty with tongue mucosal substitution. During the operation, the ureter was fully exposed and longitudinally incised, polyps were removed, and 7.0-10.0 cm long and 1.5-2.0 cm wide lingual mucosa was harvested according to the length of the stenosis, and then the lingual mucosa was transplanted to the muscular layer and the inner surface of the sheath in the stenosed ureter, fixed with 6-0 thread until the muscular layer was rolled into shape and wrapped with a large omentum. All of them left one double-J tube in the ureter on the affected side. Perioperative results and complications were recorded. The patients' blood creatinine and anterior and posterior renal pelvic diameters were compared before and after treatment.Results:In our study, all three 4-sided surgeries were successfully completed without any serious intraoperative or postoperative complications (Clavien-Dindo score ≥ grade Ⅲ). Mean surgical. Time was (240.0±49.0) min, intraoperative bleeding was 50 ml, postoperative drain retention time was (6.3±2.5) d, and median postoperative hospitalization time was 6.5(3, 9)d. The double J-tube was removed at 3 months postoperatively, and renal function and imaging tests were reviewed. Because the postoperative follow-up results of patient 1 were missing, the mean value of blood creatinine in the other 2 patients was 73.0 μmol/L at 3 months postoperatively, which was significantly improved compared with the preoperative value of 58.2 μmol/L, and the difference was statistically significant ( P < 0.05). And the average value of anterior and posterior renal pelvic separation diameters of the other 2 patients after surgery was <5 mm, which was significantly improved compared with the preoperative value of 17.9 mm, but the difference was not statistically significant ( P>0.05).There was no restenosis in all 2 patients after surgery, and the intravenous urography showed that the ureter was patent after the surgery, and the degree of urinary obstruction did not aggravate. The group was followed up for 3 to 8 months (mean 4.7 months), and no recent complications have occurred so far. Conclusions:Lingual mucosa replacement ureteral stenosis repair and plasty for the treatment of ureteral polyps in the long segment has a high success rate and precise efficacy, and its operation is feasible.

Obesity represents a complex, heritable condition shaped by interactions among genetic, epigenetic, metagenomic, and environmental factors. Nevertheless, the mechanistic contributions of genetic variation and epigenetic regulation to obesity pathogenesis remain incompletely elucidated. Advances in molecular profiling technologies have enabled the identification of numerous biomarkers associated with childhood obesity phenotypes. These discoveries facilitate understanding of obesity etiology and its links to chronic diseases. This review synthesizes current research on genomic and epigenomic biomarkers influencing childhood obesity susceptibility, advances our comprehension of etiological heterogeneity and intervention strategies, and offers conceptual frameworks for precision prevention based on epigenetic mechanisms.

In order to explore the effects of lipopolysaccharide(LPS)on the repair of bovine endo-metrial stromal cells(BESCs)during inflammatory response,BESCs were treated by LPS in this study.Cell apoptosis rate was detected using flow cytometry,cell viability was measured using the CCK-8 assay,cell migration ability was observed using a scratch assay,and the expression of con-nective tissue growth factor(CTGF),transforming growth factor-beta 3(TGF-β3)and vascular endothelial growth factor(VEGF)mRNA was measured using qRT-PCR.Additionally,the expression of key proteins in the PI3K/AKT and Wnt/β-catenin signaling pathways was assessed using Western blot analysis.The results showed that cell viability of BESCs significantly decreased(P＜0.01),cell migration ability decreased(P＜0.05),apoptosis rate of BESCs increased(P＜0.01),CTGF and TGF-β3 mRNA expression levels decreased(P＜0.01),while VEGF mRNA ex-pression increased after treatment with LPS(P＜0.01).The phosphorylation levels of PI3K,AKT and GSK-3β proteins decreased(P＜0.05),as well as the expression levels of c-Myc and Cyclin-D1 proteins also decreased(P＜0.01).These results indicated that LPS can inhibit the proliferation of BESCs and promote cell apoptosis possibly through the inhibition of the PI3K/AKT and Wnt/β-catenin signaling pathways.