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 investigate the clinical efficacy and safety of ultrasonic bone scalpel in nasal osteotomy.Methods:A retrospective analysis was conducted on clinical data from the patients who received ultrasonic bone scalpel-assisted nasal osteotomy in the Nasal Plastic & Reconstructive Surgery Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2023 and April 2024. All patients underwent open lateral approach osteotomy using an ultrasonic bone scalpel under direct vision, combined with augmentation rhinoplasty using autologous costal cartilage grafting. Intraoperatively, the nasal dorsum was fully exposed, and the lateral nasal cartilage was separated from the nasal septum, followed by precise bone tissue incision using the ultrasonic bone scalpel. Parameters recorded included operative time, and postoperative complications. Based on the standardized photographs taken before the operation and during the 6-month follow-up after the operation, the observer global aesthetic improvement scale (GAIS) was evaluated by a third-party doctor, with a score ranging from 1 to 5. The smaller the score, the more significant the improvement compared to before the operation. The satisfaction of patients with the surgical outcome was evaluated and classified into four levels: very satisfied, satisfied, dissatisfied, and very dissatisfied.Results:A total of 25 female patients were enrolled, aged 20 to 38 years, with an average age of 27.1 years. All procedures were completed successfully, with a mean operative time of (25.4±4.2) minutes. Postoperative localized swelling of varying degrees was observed. Follow-up ranged from 6 to 18 months, with nasal contour and curvature stabilizing by 6 months postoperatively. No complications, such as infection, nasolacrimal duct, lacrimal sac, medial canthal ligament, nerve injuries, or sensory disturbances, were reported. Two cases exhibited mild nasal bone widening at the 6-month follow-up, though no surgical revision was requested. Significant improvement in external nasal morphology was achieved in all patients, with high satisfaction rates. The patients satisfaction survey showed that 18 cases (72%) were very satisfied and 7 cases (28%) were satisfied with the surgical outcome. GAIS scores reflected positive evaluations [(1.24±0.51) points].Conclusion:The ultrasonic bone scalpel for nasal osteotomy offers the advantages of high-precision cutting and efficient hemostasis. It is highly effective in reshaping the nasal contour, with shorter osteotomy time, reduced intraoperative bleeding, and a lower postoperative complication rate. This study provides some insights into plastic surgeons in optimizing nasal bone modification strategies.

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.

Background and purpose:Internal mammary sentinel lymph node biopsy(IMSLNB)is a minimally invasive diagnostic technique for regional lymph nodes in breast cancer,which can provide accurate lymph staging and guide adjuvant treatment decision,but its clinical application has been controversial.The purpose of this study was to investigate the prognosis of IMSLNB in early breast cancer.Methods:In this study,a retrospective cohort of 7 949 patients with breast cancer from January 1,2016 to December 31,2021 was analyzed.After applying propensity score matching,the patients were divided into IMSLNB group and no-IMSLNB group,and the regional recurrence-free survival(RRFS),local recurrence-free survival(LRFS),distant metastasis-free survival(DMFS),disease-free survival(DFS)and overall survival(OS)of the two groups were compared.This study was approved by the Clinical Research Ethics Committee of the Affiliated Tumor Hospital of Shandong First Medical University(approval number:SDTHEC20130324).Results:A total of 990 patients were included in the final analysis(330 in the IMSLNB group and 660 in the no-IMSLNB group).IMSLN metastasis was found in 54 patients in the IMSLNB group,including 47 patients with axillary lymph node(ALN)metastasis and 7 patients with IMSLN metastasis only.The IMSLN transfer rate was 16.4%.The median follow-up of 41 months showed that the IMSLNB group demonstrated better 3-year DFS[98.4%vs 94.2%,hazard ratio(HR)=0.509;95%CI:0.312-0.828,P=0.007]and 5-year DFS(92.5%vs 87.3%,HR=0.214,95%CI:0.206-0.222,P=0.011)compared with no-IMSLNB group.However,no significant differences were observed in 3-year OS(99.1%vs 99.4%,HR=0.618,95%CI:0.231-1.655,P=0.338)or 5-year OS(98.5%vs 99.1%,HR=0.52,95%CI:0.51-0.53,P=0.392)between the two groups.The 3-year RRFS in the IMSLNB group was better compared with the no-IMSLNB group(99.09%vs 97.73%,HR=0.066;95%CI:0.061-0.071,P=0.048),while no significant differences were observed in 3-year LRFS(99.70%vs 98.19%,HR=0.209;95%CI:0.201-0.217,P=0.130)or DMFS(95.76%vs 96.06%,HR=0.865,95%CI:0.858-0.872,P=0.820)between the two groups.The exploratory subgroup analysis of DFS revealed that patients in the following subgroups could significantly benefit from IM-SLNB(P＜0.05):diagnosis age(≤50 years),premenopausal status,BMI(≤24),lymphovascular invasion(LVI,present),tumor location(lateral),molecular subtype[hormone receptor positive(HR+)/human epidermal growth factor receptor 2 negative(HER2-)],histological type(invasive ductal carcinoma),and axillary lymph node status(positive).Conclusion:IMSLNB can provide more accurate regional lymph node staging for early breast cancer,help optimize adjuvant radiotherapy strategies,and improve patients'DFS and RRFS.It can be promoted as a minimally invasive staging technique for regional lymph nodes.

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 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.

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.

Objective To investigate the current status of quality control of radiological diagnosis and treatment equipment in Shenzhen City, explore the problems in quality control testing of radiological diagnosis and treatment equipment, and provide control strategies. Methods According to the requirements of the Special Monitoring Work Plan for Radiation Health in Shenzhen, quality control tests were carried out on some radiological diagnosis and treatment equipment in Shenzhen according to the test items and methods of the currently valid national standards. Results From 2019 to 2023, a total of 72 medical institutions participated in radiological health monitoring program in Shenzhen, and 839 quality control tests were performed on radiological diagnosis and treatment equipment. The qualified rate was 91.8% in preliminary tests. The qualified rates of radiological diagnosis, radiotherapy, and nuclear medicine equipment were 91.9%, 96.3%, and 62.5%, respectively. The primary unqualified items were response uniformity, flatness of the X-ray irradiation field, and intrinsic spatial linearity. Conclusion The qualified rate in quality control of nuclear medical equipment is relatively low. Medical institutions should strengthen the routine maintenance of radiological diagnosis and treatment equipment. Radiological health technical service institutions should enhance the training of technical personnel to ensure the health and safety of patients and radiation workers.