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.

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.

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.

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 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.

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.

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.