Cleidocranial dysplasia, a rare genetic disorder primarily caused by Runt-related transcription factor 2 (RUNX2) heterozygous mutation, serves as a representative model for investigating regulatory mechanisms of RUNX2 in bone remodeling and tooth eruption. As a master transcription factor governing mineralized tissue development, RUNX2 orchestrates bone remodeling and tooth eruption through diverse regulatory networks. It drives alveolar bone formation via transcriptional activation, integration of multiple signaling cascades, and epigenetic modifications, thereby generating the biomechanical force for tooth eruption. Concurrently, RUNX2 promotes osteoblastic secretion of osteoclastogenic factors and directly regulates osteoclast precursor differentiation, facilitating bone resorption at the coronal aspect of dental follicles to estavlish the eruption pathway. Furthermore, RUNX2 modulates eruption progression by participating in stress-induced biological signal transduction within dental follicle cells (DFCs), remodeling the DFCs microenvironment, and regulating DFCs senescence. RUNX2 also influences root development via the NOTUM-Wnt axis, providing auxiliary biomechanical conditions conducive to eruption. This review systematically delineates the pivotal role of RUNX2 in coordinating bone remodeling and tooth eruption. Future studies should leverage organoid models and multi-omics technologies to further elucidate the spatiotemporal regulatory networks of RUNX2, potentially advancing precision diagnostics and therapeutics for rare skeletal-dental developmental disorders.

Cleidocranial dysplasia, a rare genetic disorder primarily caused by Runt-related transcription factor 2 (RUNX2) heterozygous mutation, serves as a representative model for investigating regulatory mechanisms of RUNX2 in bone remodeling and tooth eruption. As a master transcription factor governing mineralized tissue development, RUNX2 orchestrates bone remodeling and tooth eruption through diverse regulatory networks. It drives alveolar bone formation via transcriptional activation, integration of multiple signaling cascades, and epigenetic modifications, thereby generating the biomechanical force for tooth eruption. Concurrently, RUNX2 promotes osteoblastic secretion of osteoclastogenic factors and directly regulates osteoclast precursor differentiation, facilitating bone resorption at the coronal aspect of dental follicles to estavlish the eruption pathway. Furthermore, RUNX2 modulates eruption progression by participating in stress-induced biological signal transduction within dental follicle cells (DFCs), remodeling the DFCs microenvironment, and regulating DFCs senescence. RUNX2 also influences root development via the NOTUM-Wnt axis, providing auxiliary biomechanical conditions conducive to eruption. This review systematically delineates the pivotal role of RUNX2 in coordinating bone remodeling and tooth eruption. Future studies should leverage organoid models and multi-omics technologies to further elucidate the spatiotemporal regulatory networks of RUNX2, potentially advancing precision diagnostics and therapeutics for rare skeletal-dental developmental disorders.

【Objective】 To compare the MicroRNA (miRNA) expression profiles in the subchondral bone between patients with Kashin-Beck disease and knee osteoarthritis and to conduct target gene prediction and biological function and signal pathway analysis so as to construct the regulatory network of miRNAs and target genes. 【Methods】 The subchondral bone samples were collected from four pairs of patients with Kashin-Beck disease and osteoarthritis. The total RNA was extracted and the miRNA array profiling was performed using Affymetrix miRNA 4.0 Array. The target gene prediction was performed using six different prediction programs including miRWalk. Cytoscape software was used to construct the regulatory network of significantly different miRNAs and predicted target genes; GO biological function and KEGG pathway enrichment analysis were performed based on target genes. 【Results】 A total of 124 miRNAs were significantly downregulated in the subchondral bone of patients with Kashin-Beck disease than that in patients with osteoarthritis. Target genes were predicted for eight miRNAs with a fold change more than 5, and 542 target genes and 1094 miRNA-mRNA regulatory relationships were obtained. Enrichment analysis of target genes in the regulatory relationship showed that these target genes were mainly involved in protein digestion and absorption, focal adhesion, PI3K-Akt signaling pathway and ECM-receptor interaction, and other signaling pathways. 【Conclusion】 Differentially expressed miRNAs in the subchondral bone of patients with Kashin-Beck disease and osteoarthritis may be used as the differential diagnostic markers between the two diseases. In addition, we preliminarily explored the potential molecular mechanism of changes in the subchondral bone of Kashin-Beck disease by bioinformatics analysis.

Objective: To investigate the clinical value of lymph node dissection (LND) in the radical resection of intrahepatic cholangiocarcinoma (ICC). Methods: The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 448 patients with ICC who were admitted to 12 medical centers from December 2011 to December 2017 were collected, including 279 in the Eastern Hepatobiliary Surgery Hospital of Navy Medical University, 32 in the Mengchao Hepatobiliary Hospital of Fujian Medical University, 21 in the First Hospital Affiliated to Army Medical University, 20 in the Cancer Hospital Chinese Academy of Medical Science and Peking Union Medical College, 19 in the West China Hospital of Sichuan University, 18 in the Second Hospital Affiliated to Zhejiang University School of Medicine, 18 in the Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 16 in the Beijing Friendship Hospital Affiliated to Capital Medical University, 10 in the Xuanwu Hospital Affiliated to Capital Medical University, 7 in the Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, 5 in the Beijing Tiantan Hospital Affiliated to Capital Medical University, and 3 in the Affiliated Hospital of North Sichuan Medical College. There were 281 males and 167 females, aged from 22 to 80 years, with a median age of 57 years. Of the 448 patients, 143 with routinely intraoperative LND were divided into LND group and 305 without routinely intraoperative LND were divided into control group, respectively. Observation indicators: (1) the propensity score matching conditions and comparison of general data between the two groups after matching; (2) intraoperative and postoperative situations; (3) follow-up; (4) survival analysis. Patients were followed up by outpatient examination, telephone interview and email to detect survival of patients and tumor recurrence up to October 31, 2018 or death. Follow-up was conducted once every 3 months within postoperative 1-2 years, once every 6 months within postoperative 2-5 years, and once a year after 5 years. The propensity score matching was realized using the nearest neighbor method with 1∶1 ratio. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Kaplan-Meier method was used to calculate survival rates and draw survival curve, and Log-rank test was used to perform survival analysis. Univariate analysis and multivaraiate analysis were conducted using the Log-rank test and COX regression model, respectively. Results: (1) The propensity score matching conditions and comparison of general data between the two groups after matching: 286 of 448 patients had successful matching, including 143 in each group. The number of males and females, cases with hepatitis, cases with grade A and B of Child-Pugh classification, cases with distance from margin to tumor <1 cm and ≥1 cm, cases with highly, moderately, and poorly differentiated tumor, cases with anatomical hepatectomy and nonanatomical hepatectomy before propensity score matching were 77, 66, 33, 96, 47, 70, 73, 105, 38, 79, 64 in the LND group, and 204, 101, 121, 165, 140, 207, 98, 251, 54, 124, 181 in the control group, respectively, showing significant differences in the above indices between the two groups (χ²=7.079, 11.885, 7.098, 14.763, 5.184, 8.362, P<0.05). After propensity score matching, the above indices were 77, 66, 33, 96, 47, 70, 73, 105, 38, 79, 64 in the LND group, and 79, 64, 29, 88, 55, 71, 72, 112, 31, 74, 69 in the control group, respectively, showing no significant difference in the above indices between the two groups (χ²=0.056, 0.329, 2.158, 0.014, 0.936, 1.400, P>0.05). (2) Intraoperative and postoperative situations: the operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion, cases with postoperative complications, and duration of postoperative hospital stay were 265 minutes (range, 160-371 minutes), 300 mL (range, 200-500 mL), 37, 46, 12 days (range, 9-17 days) for the LND group, and 59 minutes (range, 46-250 minutes), 200 mL (range, 100-400 mL), 24, 25, 9 days (range, 7-11 days) for the control group, respectively. There was no significant difference in the volume of intraoperative blood loss or cases with intraoperative blood transfusion between the two groups (Z=1.700, χ²=3.520, P>0.05). There were significant differences in the operation time, cases with postoperative complications, and duration of postoperative hospital stay (Z=6.520, χ²=8.260, Z=4.270, P<0.05). (3) Follow-up: 143 patients in the LND group was followed up for 18-26 months. The 1-, 3-, 5-year survival rates were 66.9%, 32.8%, 25.0%, and the median survival time was 22.0 months (range, 18.0-26.0 months). In the control group, 143 patients were followed up for 11-32 months. The 1-, 3-, 5-year survival rates were 71.7%, 38.0%, 31.0%, and the median survival time was 22.0 months (range, 11.0-32.0 months). There was no significant difference in the overall survival between the two groups (χ²=0.466, P>0.05). (4) Survival analysis: results of univariate analysis showed that distance from margin to tumor, tumor diameter, the number of tumors, microvascular tumor thrombus, and lymph node metastasis by pathological examination were related factors for prognosis of patients undergoing radical resection of ICC (χ²=10.662, 9.477, 16.944, 6.520, 11.633, P<0.05). Results of multivariate analysis showed that distance from margin to tumor<1 cm, tumor diameter>5 cm, multiple tumors, microvascular tumor thrombus, positive lymph node metastasis by pathological examination were independent risk factors for prognosis of patients undergoing radical resection of ICC (hazard ratio=0.600, 1.571, 1.601, 1.750, 1.723, 95% confidence interval: 0.430-0.837, 1.106-2.232, 1.115-2.299, 1.083-2.829, 1.207-2.460, P<0.05). Conclusion Lymph node metastasis is an independent risk factor affecting the prognosis of ICC patients, and it is necessary to perform LND in radical resection for patients with ICC and lymph node metastasis.

AIM: Sesamin (Ses) is one of the major lignans in sesame seeds with antihypertensive and antifibroticactivities, but its effect is weak. In this experiment, we combined vitamin E (VitE) and Ses to observe their effects on blood pressure and left ventricular fibrosis in spontaneously hypertensive rats (SHRs), and to explore its possible mechanism. METHODS: Male SHRs were randomly divided into SHRs+Ses+VitE group, SHRs+Ses group, SHRs+VitE group, and SHRs model group. Wistar-Kyoto (WKY) rats were setted as a normal control group. After 10 weeks of administration, systolic blood pressure (SBP) of rats was measured by tail cuff method, and the left ventricle was taken to calculate the organ index. Collagen deposition was observed by Masson staining, and cardiac collagen volume fraction (CVF) was analyzed. Expressions of collagen I, collagen III, transforming growth factor-β

Objective:To investigate the effect of RATEA16 scaffold on the proliferation of human umbilical vein endothelial cells (HUVEC) and the effect of new self-assembling peptide hydrogel (RATEA16) scaffold with vascular endothelial growth factor (VEGF) on promoting angiogenesis.Methods:RATEA16 hydrogel was prepared, then the injectability, microstructure, degradation, biocompatibility of RATEA16 hydrogel were determined. HUVEC were cultured with RATEA16 scaffold to detect cell morphology and proliferation. HUVEC were cultured on RATEA16 scaffold with VEGF for 24 h. The expression of VEGF-A, von Willebrand factor (vWF), matrix metalloproteinase-9 (MMP-9) and platelet endothelial cell adhesion molecule-1 (PECAM-1) were detected by using real-time PCR to evaluate the effects of the scaffold with VEGF system on HUVEC differentiation.Results:The sol-gel transition was completed under neutral condition (pH=7.4) adjusted by Tris-HCl solution. The hydrogel could be easily injected from a syringe. It presented a porous and interconnected internal structure and the porosity of the scaffold was (67.3±9.4)%. After 4 week degradation in vitro, the residual weight was still (82.354±0.006)%, which exhibited slow degradation. HUVEC grew well after being cultured in leach liquor of RATEA16 hydrogel for 24 h, and there was no significant difference in HUVEC cell viability compared with that of the control group ( P>0.05). HUVEC encapsulated in RATEA16 hydrogel appeared round in shape and exhibited effectively continuous proliferation. When HUVEC were cultured on RATEA16 hydrogel with VEGF for 24 h, the formation of vascular-like structures was observed. The expression of VEGF-A and MMP-9 was 1.5-2.0 times that of control group, and vWF was 10 times and PECAM-1 was 55 times compared with that of the control group ( P<0.05). Conclusions:The RATEA16 hydrogel used in this study could be prepared by simply adjusting pH to neutral. This hydrogel exhibited good biodegradability, slow degradation and injectability. HUVEC might attach and spread in RATEA16 scaffold. The RATEA16 scaffold with VEGF could promote angiogenic differentiation of HUVEC. The novel scaffold is expected to achieve the critical vascularization process in bone tissue regeneration.

Objective:To investigate the feasibility and safety of laparoscopic radical resection of hilar cholangiocarcinoma at multiple centers in China.Methods:Between December 2015 and August 2019, the clinical data of 143 patients who underwent LRHC in Affiliated Hospital of North Sichuan Medical College, Second Hospital of Hebei Medical University, Affiliated Hospital of Xuzhou Medical University, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Hunan Provincial People′s Hospital, the First Hospital Affiliated to Army Medical University, Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University, West China Hospital of Sichuan University, Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Chongqing Medical University were collected prospectively. There were 92 males and 51 females with age of (64±11) years (range: 53 to 72 years). Bismuth type: type I, 38 cases (26.6%), type Ⅱ, 19 cases (13.3%), type Ⅲa, 15 cases (10.5%), type Ⅲb, 28 cases (19.6%) and type Ⅳ, 43 cases (30.0%). The patients within the first 10 operation cases in each operation time (the first 10 patients in each operation team) were divided into group A (77 cases), and the patients after 10 cases in each operation time were classified as group B (66 cases); the cases with more than 10 cases in the center were further divided into group A 1 (116 cases), and the center with less than 10 cases was set as group A 2 (27 cases). T test or Wilcoxon test was used to compare the measurement data between groups, and the chi square test or Fisher exact probability method was used to compare the counting data between groups. Kaplan Meier curve was used for survival analysis. Results:All patients successfully completed laparoscopic procedure. The mean operation time was (421.3±153.4) minutes (range: 159 to 770 minutes), and the intraoperative blood loss was 100 to 1 500 ml (median was 300 ml) .Recent post-operative complications contained bile leakage, abdominal bleeding, abdominal infection, gastrointestinal bleeding, and delay gastric emptying, pulmonary infection, liver failure, et al.The post-operative hospital stay was (15.9±9.2) days. The operation time in group B was relatively reduced ( (429.5±190.7)minutes vs. (492.3±173.1)minutes, t=2.063, P=0.041) and the blood loss (465 ml vs. 200 ml) was also reduced ( Z=2.021, P=0.043) than that in group B. The incidence of postoperative biliary fistula and lung infection in patients in group A was significantly higher than that in group B (χ 2=4.341, 0.007; P=0.037, 0.047) .Compared with group A 2, the operation time in group A 1 was relatively reduced( (416.3±176.5)minutes vs. (498.1±190.4)minutes, t=2.136, P=0.034) , the incidence of bile leakage and abdominal cavity infection in group A 1 was lower than that in group A 2 (χ 2=7.537, 3.162; P=0.006, 0.046) . Kaplan Meier survival curve showed that the difference of short-term survival time between group A and group B was statistically significant ( P<0.05) . Conclusions:The completion of laparoscopic hilar cholangiocarcinoma radical surgery is based on improved surgical skills, and proficiency in standardized operation procedures.It is feasible for laparoscopic radical resection of hilar cholangiocarcinoma to well experienced surgeon with cases be strictly screened, but it is not recommended for widespread promotion at this exploratory stage.

Objective:To investigate the feasibility and safety of laparoscopic radical resection of hilar cholangiocarcinoma at multiple centers in China.Methods:Between December 2015 and August 2019, the clinical data of 143 patients who underwent LRHC in Affiliated Hospital of North Sichuan Medical College, Second Hospital of Hebei Medical University, Affiliated Hospital of Xuzhou Medical University, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Hunan Provincial People′s Hospital, the First Hospital Affiliated to Army Medical University, Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University, West China Hospital of Sichuan University, Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Chongqing Medical University were collected prospectively. There were 92 males and 51 females with age of (64±11) years (range: 53 to 72 years). Bismuth type: type I, 38 cases (26.6%), type Ⅱ, 19 cases (13.3%), type Ⅲa, 15 cases (10.5%), type Ⅲb, 28 cases (19.6%) and type Ⅳ, 43 cases (30.0%). The patients within the first 10 operation cases in each operation time (the first 10 patients in each operation team) were divided into group A (77 cases), and the patients after 10 cases in each operation time were classified as group B (66 cases); the cases with more than 10 cases in the center were further divided into group A 1 (116 cases), and the center with less than 10 cases was set as group A 2 (27 cases). T test or Wilcoxon test was used to compare the measurement data between groups, and the chi square test or Fisher exact probability method was used to compare the counting data between groups. Kaplan Meier curve was used for survival analysis. Results:All patients successfully completed laparoscopic procedure. The mean operation time was (421.3±153.4) minutes (range: 159 to 770 minutes), and the intraoperative blood loss was 100 to 1 500 ml (median was 300 ml) .Recent post-operative complications contained bile leakage, abdominal bleeding, abdominal infection, gastrointestinal bleeding, and delay gastric emptying, pulmonary infection, liver failure, et al.The post-operative hospital stay was (15.9±9.2) days. The operation time in group B was relatively reduced ( (429.5±190.7)minutes vs. (492.3±173.1)minutes, t=2.063, P=0.041) and the blood loss (465 ml vs. 200 ml) was also reduced ( Z=2.021, P=0.043) than that in group B. The incidence of postoperative biliary fistula and lung infection in patients in group A was significantly higher than that in group B (χ 2=4.341, 0.007; P=0.037, 0.047) .Compared with group A 2, the operation time in group A 1 was relatively reduced( (416.3±176.5)minutes vs. (498.1±190.4)minutes, t=2.136, P=0.034) , the incidence of bile leakage and abdominal cavity infection in group A 1 was lower than that in group A 2 (χ 2=7.537, 3.162; P=0.006, 0.046) . Kaplan Meier survival curve showed that the difference of short-term survival time between group A and group B was statistically significant ( P<0.05) . Conclusions:The completion of laparoscopic hilar cholangiocarcinoma radical surgery is based on improved surgical skills, and proficiency in standardized operation procedures.It is feasible for laparoscopic radical resection of hilar cholangiocarcinoma to well experienced surgeon with cases be strictly screened, but it is not recommended for widespread promotion at this exploratory stage.

A 54 years old male patient with chronic leg ulcers was admitted in our hospital in November 2017. He was diagnosed as pyoderma gangrenosum by the pathological examination. Then the wound was treated with simple vacuum sealing drainage combined with irrigation of oxygen loaded fluid. This therapy overcame the shortage of hypoxia in the Tibetan Plateau on wound healing, resulting in a better wound healing. The patient was eventually cured and discharged from hospital.