1.High expression of CDKN3 promotes migration and invasion of gastric cancer cells by regulating the p53/NF-κB signaling pathway and inhibiting cell apoptosis.
Yi ZHANG ; Yu SHEN ; Zhiqiang WAN ; Song TAO ; Yakui LIU ; Shuanhu WANG
Journal of Southern Medical University 2025;45(4):853-861
OBJECTIVES:
To investigate the expression of CDKN3 in gastric cancer and its impact on prognosis of gastric cancer patients.
METHODS:
We analyzed CDKN3 expression in clinical specimens from 114 gastric cancer patients and assessed its association with 5-year postoperative survival of the patients. GO and KEGG enrichment analyses were used to predict the biological function and possible mechanism of CDKN3. The effects of lentivirus-mediated CDKN3 knockdown on biological behaviors of gastric cancer cells were evaluated using Transwell assay, CCK-8 assay, TUNEL staining, flow cytometry, and Western blotting.
RESULTS:
CDKN3 expression was significantly higher in gastric cancer tissues than in the adjacent tissues with significant correlations with CEA level, CA19-9 level, and T and N staging (P<0.05). High CDKN3 expression was an independent risk factor affecting 5-year postoperative survival of the patients and predictive for long-term prognosis (P<0.01). Enrichment analyses suggested a probable association of CDKN3 with apoptosis. In MGC-803 cells, CDKN3 knockdown significantly lowered migration and invasion capacities of the cells, while CDKN3 overexpression produced the opposite effects. TUNEL staining revealed a significantly lower level of cell apoptosis in gastric cancer tissues than in adjacent tissues (P<0.01). CDKN3 knockdown obviously inhibited proliferation and increased apoptosis of MGC-803 cells. CDKN3 overexpression down-regulated the expressions of p53, p21 and Bax and up-regulated the expressions of p-p65 and Bcl-2.
CONCLUSIONS
CDKN3 is highly expressed in gastric cancer tissues and affects patient prognosis. CDKN3 overexpression promotes proliferation, invasion and migration and suppressed apoptosis of gastric cancer cells possibly through the p53/NF-κB signaling pathway.
Humans
;
Stomach Neoplasms/pathology*
;
Apoptosis
;
Signal Transduction
;
Tumor Suppressor Protein p53/metabolism*
;
Cell Movement
;
Cell Line, Tumor
;
NF-kappa B/metabolism*
;
Prognosis
;
Cyclin-Dependent Kinase Inhibitor Proteins/metabolism*
;
Cell Proliferation
;
Neoplasm Invasiveness
;
Male
;
Female
;
Dual-Specificity Phosphatases
2.Mechanism of PER1-mediated inhibition of proliferation and migration in head and neck squamous cell carcinoma via the NF-κB signaling pathway by regulating SPINK5
Wanchen LIU ; Hui SHEN ; Yakui MOU ; Hanrui WANG ; Yao WANG ; Ting YANG ; XiaoYu SONG ; Mingjun ZHANG ; Yuanchao CHENG ; Chao REN ; Xicheng SONG
Chinese Archives of Otolaryngology-Head and Neck Surgery 2025;32(8):512-517
OBJECTIVE To investigate the expression characteristics and regulatory mechanisms of the circadian clock gene period circadian regulator 1(PER1)and the tumor suppressor gene serine peptidase inhibitor Kazal type 5(SPINK5)in head and neck squamous cell carcinoma(HNSCC),and to elucidate the molecular mechanism by which PER1 regulates SPINK5 transcription via the NF-κB signaling pathway.METHODS Differentially expressed genes in HNSCC were screened using The Cancer Genome Atlas(TCGA)and GSE205155 datasets.The association between SPINK5 expression and patient prognosis was assessed via the GEPIA database.mRNA and protein expression levels of SPINK5 and PER1 in 60 clinical samples were detected by RT-qPCR,immunohistochemistry,and Western blot.PER1 knockdown(using siRNA)and overexpression(via plasmid transfection)were performed in the AMC-HN-8 cell line.Wound healing and colony formation assays were applied to evaluate the effects of PER1,SPINK5,and their interaction on HNSCC cell migration and proliferation.Western blot was utilized to examine the regulatory effect of NF-κB on SPINK5.RESULTS SPINK5 and PER1 were significantly downregulated in HNSCC tissues(all P<0.01),and their low expression was correlated with poor patient prognosis(for SPINK5,HR=0.69,P=0.006 7).A significant positive correlation was observed between PER1 and SPINK5 expression(R2=0.719 2,P=0.001 0).Knockdown and overexpression of PER1 respectively resulted in synchronous alterations in SPINK5 mRNA levels(all P<0.05).PER1 knockdown enhanced cell migration and proliferation(P<0.05),whereas SPINK5 overexpression suppressed these capabilities(P<0.01).Importantly,SPINK5 overexpression reversed the phenotypic changes induced by PER1 knockdown.Mechanistically,PER1 overexpression led to concomitant changes in NF-κB expression,activating the NF-κB pathway and thereby promoting SPINK5 transcription.CONCLUSION PER1 positively regulates SPINK5 transcription via the NF-κB pathway,inhibiting HNSCC cell proliferation and migration.These findings suggest that PER1 and SPINK5 may serve as potential therapeutic targets for HNSCC.
3.Adjuvant therapy by hyperbaric oxygen for high-energy lower limb fractures: a randomized controlled trial
Xiongfei WANG ; Yajuan LI ; Wenshuo DONG ; Liang LIU ; Yakui ZHANG ; Anhua LONG
Chinese Journal of Orthopaedic Trauma 2025;27(3):222-227
Objective:To explore the effects of adjuvant therapy by hyperbaric oxygen for high-energy lower limb fractures.Methods:This prospective case-control study enrolled the patients with high-energy lower extremity fracture who had been admitted to Department of Orthopaedics, Beijing Luhe Hospital, Capital Medical University from January 2021 to December 2022. Their fracture types included tibial plateau ones, pilon ones, ankle ones complicated with dislocation, and calcaneal ones. The patients were randomly divided into a control group receiving routine orthopedic treatment and a trial group receiving adjuvant therapy by hyperbaric oxygen in addition to routine orthopedic treatment using a random number table. The first adjuvant therapy by hyperbaric oxygen was conducted in the trial group within 48 h after injury before the timing for surgery was decided according to the soft tissue swelling at the affected limb. Follow-up was conducted until one year after surgery. The early and late wound complications, time from injury to surgery, and hospital stay were compared between the 2 groups.Results:A total of 160 patients with high-energy lower extremity fracture were enrolled in this study. Eventually, 7 patients were excluded, 72 patients [48 males and 24 females, with an age of (46.3±12.5) years] included in the trial group and 81 patients [61 males and 20 females, with an age of (47.8±13.4) years] in the control group. There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). The incidence of early wound complications in the trial group was 5.6% (4/72), significantly lower than that in the control group [18.5% (15/81)] ( P<0.05). The incidences of late wound complications in the trial and control groups were 12.5% (9/72) and 9.9% (8/81) respectively, showing no statistically significant difference ( P>0.05). The time from admission to surgery was respectively 4 (2, 8) days and 4 (2, 6) days, and the hospital stay respectively 10 (7, 14) days and 9 (6, 12) days for the trial and control groups, showing no statistically significant differences between the 2 groups ( P>0.05). Conclusion:In the treatment of high-energy lower extremity fractures, adjuvant therapy by hyperbaric oxygen can reduce the incidence of early wound complications without increasing the hospital stay, but it does not reduce the incidence of late wound complications or shorten the preoperative waiting time.
4.Retrospective analysis of fully robot-navigated intramedullary nail fixation for elderly patients with intertrochanteric femoral fractures
Dacheng HAN ; Jialong WANG ; Qi YANG ; Zhiyong SI ; Yakui ZHANG ; Liang LIU ; Xuefei WANG
Journal of Capital Medical University 2025;46(5):799-804
Objective To investigate the clinical outcome differences between robotic-assisted intramedullary nailing and traditional manual surgery,and to analyze the advantages and feasibility of robotic-assisted intramedullary nail fixation in the treatment of intertrochanteric fractures in elderly patients.Methods From December 2023 to December 2024,elderly patients with intertrochanteric fractures who underwent surgery at Department of Trauma Orthopedics,Beijing Luhe Hospital,Capital Medical University were included.Patients were divided into two groups based on the surgical method.The robotic-assisted group underwent robotic-assisted intramedullary nail fixation,while the traditional group received manual intramedullary nail fixation.Baseline data and observation indicators were collected and compared between the two groups to assess any differences.Results There were no statistically significant differences in baseline data between the two groups(P>0.05).The intraoperative blood loss in the robotic-assisted group was(94.28±9.43)mL,compared to(143.00±11.11)mL in the traditional group(P<0.001).The operative time in the robotic-assisted group was(53.06±9.89)min,while in the traditional group,it was(66.74±10.18)min(P<0.001).The skin incision length for the main nail in the robotic-assisted group was(3.23±0.64)cm,whereas in the traditional group,it was(4.03±0.79)cm(P<0.01).Postoperative hemoglobin levels in the robotic-assisted group decreased by(12.63±4.27)g/L,compared to(17.29±4.32)g/L in the traditional group(P=0.018).At 6 months postoperatively,the Harris hip scores in the robotic-assisted group showed 30 cases of excellent,10 good,and 3 poor outcomes,while in the traditional group,there were 22 excellent,15 good,and 6 poor cases(P=0.198).Conclusion Robotic-assisted intramedullary nailing for intertrochanteric fractures offers advantages such as minimally invasive and precise procedures,shorter operative times,and reduced blood loss.Compared to traditional surgical methods,it demonstrates certain benefits in reducing postoperative complications in elderly patients.
5.A case-control study of minimally invasive internal fixation for pelvic fractures assisted by an orthopedic surgical robot
Anhua LONG ; Jiafan ZHANG ; Qi YANG ; Xiongfei WANG ; Yakui ZHANG ; Xuefei WANG ; Liang LIU
Journal of Capital Medical University 2025;46(5):791-798
Objective To explore the technical advantages and applicable scenarios of surgical robot-assisted versus conventional freehand minimally invasive surgery for pelvic fractures by comparing clinical indicators,thereby providing evidence for clinical decision-making.Methods A retrospective case-control study was conducted on 59 patients with pelvic fractures treated with minimally invasive internal fixation between January 2022 and December 2024.Patients were divided into a conventional group(26 cases)and a robot-assisted navigation group(33 cases)based on the surgical technique.Pre-and postoperative pelvic computed tomography(CT)scans were performed,and anteroposterior,outlet,and inlet view radiographs were obtained.The maximum residual displacement after pelvic reduction and screw placement accuracy were measured based on radiographic and CT imaging.Intraoperative fluoroscopy frequency,radiation dose,operative time,blood loss,number of implanted screws,maximum residual displacement after reduction,and screw accuracy were recorded.Results No significant differences were observed between the two groups in age,gender,injury mechanism,or fracture classification,indicating comparability.Blood loss and fracture reduction quality showed no significant differences.The operative time was 52.5(30.8,62.3)min in the conventional group and 60(50,82.5)min in the robot-assisted group.Intraoperative fluoroscopy frequency and radiation dose were(19.1±5.4)times and 33.1(27.5,43.9)mGy in the conventional group,compared to(12.1±4.9)times and 123.1(101.1,131.4)mGy in the robot-assisted group.The robot-assisted group demonstrated superior screw placement accuracy,increased utilization of anterior column screws,and shorter postoperative ambulation time.Conclusion Robot-assisted minimally invasive surgery for pelvic fractures significantly outperforms conventional freehand techniques in improving screw placement accuracy and reducing radiation exposure for surgeons.It represents a preferable option for treating unstable pelvic fractures.
6.Retrospective analysis of fully robot-navigated intramedullary nail fixation for elderly patients with intertrochanteric femoral fractures
Dacheng HAN ; Jialong WANG ; Qi YANG ; Zhiyong SI ; Yakui ZHANG ; Liang LIU ; Xuefei WANG
Journal of Capital Medical University 2025;46(5):799-804
Objective To investigate the clinical outcome differences between robotic-assisted intramedullary nailing and traditional manual surgery,and to analyze the advantages and feasibility of robotic-assisted intramedullary nail fixation in the treatment of intertrochanteric fractures in elderly patients.Methods From December 2023 to December 2024,elderly patients with intertrochanteric fractures who underwent surgery at Department of Trauma Orthopedics,Beijing Luhe Hospital,Capital Medical University were included.Patients were divided into two groups based on the surgical method.The robotic-assisted group underwent robotic-assisted intramedullary nail fixation,while the traditional group received manual intramedullary nail fixation.Baseline data and observation indicators were collected and compared between the two groups to assess any differences.Results There were no statistically significant differences in baseline data between the two groups(P>0.05).The intraoperative blood loss in the robotic-assisted group was(94.28±9.43)mL,compared to(143.00±11.11)mL in the traditional group(P<0.001).The operative time in the robotic-assisted group was(53.06±9.89)min,while in the traditional group,it was(66.74±10.18)min(P<0.001).The skin incision length for the main nail in the robotic-assisted group was(3.23±0.64)cm,whereas in the traditional group,it was(4.03±0.79)cm(P<0.01).Postoperative hemoglobin levels in the robotic-assisted group decreased by(12.63±4.27)g/L,compared to(17.29±4.32)g/L in the traditional group(P=0.018).At 6 months postoperatively,the Harris hip scores in the robotic-assisted group showed 30 cases of excellent,10 good,and 3 poor outcomes,while in the traditional group,there were 22 excellent,15 good,and 6 poor cases(P=0.198).Conclusion Robotic-assisted intramedullary nailing for intertrochanteric fractures offers advantages such as minimally invasive and precise procedures,shorter operative times,and reduced blood loss.Compared to traditional surgical methods,it demonstrates certain benefits in reducing postoperative complications in elderly patients.
7.A case-control study of minimally invasive internal fixation for pelvic fractures assisted by an orthopedic surgical robot
Anhua LONG ; Jiafan ZHANG ; Qi YANG ; Xiongfei WANG ; Yakui ZHANG ; Xuefei WANG ; Liang LIU
Journal of Capital Medical University 2025;46(5):791-798
Objective To explore the technical advantages and applicable scenarios of surgical robot-assisted versus conventional freehand minimally invasive surgery for pelvic fractures by comparing clinical indicators,thereby providing evidence for clinical decision-making.Methods A retrospective case-control study was conducted on 59 patients with pelvic fractures treated with minimally invasive internal fixation between January 2022 and December 2024.Patients were divided into a conventional group(26 cases)and a robot-assisted navigation group(33 cases)based on the surgical technique.Pre-and postoperative pelvic computed tomography(CT)scans were performed,and anteroposterior,outlet,and inlet view radiographs were obtained.The maximum residual displacement after pelvic reduction and screw placement accuracy were measured based on radiographic and CT imaging.Intraoperative fluoroscopy frequency,radiation dose,operative time,blood loss,number of implanted screws,maximum residual displacement after reduction,and screw accuracy were recorded.Results No significant differences were observed between the two groups in age,gender,injury mechanism,or fracture classification,indicating comparability.Blood loss and fracture reduction quality showed no significant differences.The operative time was 52.5(30.8,62.3)min in the conventional group and 60(50,82.5)min in the robot-assisted group.Intraoperative fluoroscopy frequency and radiation dose were(19.1±5.4)times and 33.1(27.5,43.9)mGy in the conventional group,compared to(12.1±4.9)times and 123.1(101.1,131.4)mGy in the robot-assisted group.The robot-assisted group demonstrated superior screw placement accuracy,increased utilization of anterior column screws,and shorter postoperative ambulation time.Conclusion Robot-assisted minimally invasive surgery for pelvic fractures significantly outperforms conventional freehand techniques in improving screw placement accuracy and reducing radiation exposure for surgeons.It represents a preferable option for treating unstable pelvic fractures.
8.Adjuvant therapy by hyperbaric oxygen for high-energy lower limb fractures: a randomized controlled trial
Xiongfei WANG ; Yajuan LI ; Wenshuo DONG ; Liang LIU ; Yakui ZHANG ; Anhua LONG
Chinese Journal of Orthopaedic Trauma 2025;27(3):222-227
Objective:To explore the effects of adjuvant therapy by hyperbaric oxygen for high-energy lower limb fractures.Methods:This prospective case-control study enrolled the patients with high-energy lower extremity fracture who had been admitted to Department of Orthopaedics, Beijing Luhe Hospital, Capital Medical University from January 2021 to December 2022. Their fracture types included tibial plateau ones, pilon ones, ankle ones complicated with dislocation, and calcaneal ones. The patients were randomly divided into a control group receiving routine orthopedic treatment and a trial group receiving adjuvant therapy by hyperbaric oxygen in addition to routine orthopedic treatment using a random number table. The first adjuvant therapy by hyperbaric oxygen was conducted in the trial group within 48 h after injury before the timing for surgery was decided according to the soft tissue swelling at the affected limb. Follow-up was conducted until one year after surgery. The early and late wound complications, time from injury to surgery, and hospital stay were compared between the 2 groups.Results:A total of 160 patients with high-energy lower extremity fracture were enrolled in this study. Eventually, 7 patients were excluded, 72 patients [48 males and 24 females, with an age of (46.3±12.5) years] included in the trial group and 81 patients [61 males and 20 females, with an age of (47.8±13.4) years] in the control group. There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). The incidence of early wound complications in the trial group was 5.6% (4/72), significantly lower than that in the control group [18.5% (15/81)] ( P<0.05). The incidences of late wound complications in the trial and control groups were 12.5% (9/72) and 9.9% (8/81) respectively, showing no statistically significant difference ( P>0.05). The time from admission to surgery was respectively 4 (2, 8) days and 4 (2, 6) days, and the hospital stay respectively 10 (7, 14) days and 9 (6, 12) days for the trial and control groups, showing no statistically significant differences between the 2 groups ( P>0.05). Conclusion:In the treatment of high-energy lower extremity fractures, adjuvant therapy by hyperbaric oxygen can reduce the incidence of early wound complications without increasing the hospital stay, but it does not reduce the incidence of late wound complications or shorten the preoperative waiting time.
9.Evaluation of knee cartilage based on MRI artificial intelligence reconstruction model of knee joint
Hong GAO ; Binge XUE ; Sha WU ; Yakui WANG ; Pengfei FU ; Le SHEN ; Jiawang LOU ; Qi MA ; Pu LIU ; Xu CAI
Chinese Journal of Orthopaedics 2023;43(5):316-321
Objective:To explore the feasibility of the AI intelligent reconstruction model based on knee joint magnetic resonance data developed by Nuctech Company Limited for evaluating knee cartilage injury.Methods:Thirty-three patients (a total of forty-one knees) who were hospitalized with severe knee osteoarthritis in Beijing Tsinghua Changgung Hospital from May 2021 to April 2022 were selected. All of them were planned to be performed total knee arthroplasty (TKA) for the treatment of knee osteoarthritis. Fifteen males with an average age of 71±5 years old and twenty six females with an average age of 71±9 years old were included in this study. There were 19 cases of left knee and 22 cases of right knee. Thin layer MRI examination on the patients' knee joints was performed before the surgery, and artificial intelligence model based on the thin layer MRI data of the knee joint was reconstructed. The cartilage part of the model was selected and corrected by Principal Component Analysis (PCA) in order to realize model straightening. The tibial plateau cartilage of knee joint which intercepted during operation was classified according to the International Cartilage Repair Society (ICRS). Finally the results were compared with the ICRS classification results of knee artificial intelligence reconstruction model and artificial recognition of knee joint MRI images.Results:Compared with the grade of cartilage injury intercepted during our operation which was according to the ICRS classification, the sensitivity of artificial intelligence reconstruction model for the diagnosis of cartilage injury with ICRS classification grade four was 93.1%. The specificity of artificial intelligence reconstruction model was 91.4%. The positive predictive value (PPV) of artificial intelligence reconstruction model was 92.2%. And the negative predictive value (NPV) of artificial intelligence reconstruction model was 80.3%. The area under ROC curve (AUC) was 0.92. The ICRS classification consistency between artificial intelligence model and physical inspection results was good with kappa value 0.81 ( P<0.001) . In the aspect of artificial recognition of cartilage injury grading in MRI images, the sensitivity of artificial recognition was 92.10% compared with the manual identification of cartilage injury classification in MRI images. The specificity of artificial recognition was 91.60%. The positive predictive value (PPV) of artificial recognition was 97.20% and the negative predictive value (NPV) of artificial recognition was 78.8%. The kappa value of the cartilage injury classification in MRI images consistency between artificial recognition and manual identification was 0.79 ( P<0.001). Conclusion:Based on the evaluation of cartilage injury by AI reconstruction model of knee joint, the sensitivity and specificity of the diagnosis of ICRS grade IV cartilage injury can be acceptable, but still needs to be improved.
10.Evaluation of metal artifacts reduction with MAVRIC-SL after total knee arthroplasty
Yakui WANG ; Min WANG ; Zhuozhao ZHENG
Chinese Journal of Radiology 2021;55(9):929-933
Objective:To evaluate the metal artifacts reduction effect of multi-acquisition variable-resonance image combination (MAVRIC-SL) after total knee arthroplasty by comparing with two-dimensional fast spin-echo metal artifact reduction sequence (2D FSE MARS).Methods:A total of 78 patients (101 knees) who underwent total knee arthroplasty in Beijing Tsinghua Changgung Hospital from December 2018 to December 2020 were prospectively collected. All patients underwent 3.0 T MR examination within 2 weeks after surgery. The sequences included axial, sagittal, and coronal 2D FSE MARS and MAVRIC-SL. The ranges of prosthesis artifacts were measured, and the scores of the prosthesis clarity, anatomical structure clarity, and joint effusion diagnosis confidence were evaluated by Likert scale. Paired t test was used to compare the difference of artifact range between 2D FSE MARS and MAVRIC-SL. The Wilcoxon signed rank-sum test was used to compare image quality scores and joint effusion diagnosis confidence scores. Results:In 101 knees, the ranges of prosthesis artifacts in axial, sagittal, and coronal 2D FSE MARS were (63.3±8.5), (60.0±7.4) and (62.1±8.7) cm 2, while those of MAVRIC-SL were (49.5±5.8), (44.1±6.6) and (46.1±7.5) cm 2. The differences were statistically significant ( t=20.021, 21.834, 25.472, all P<0.001). The subjective scores of femoral prosthesis clarity, tibial prosthesis clarity, and anatomical structure clarity of MAVRIC-SL were significantly higher than those of 2D FSE MARS (all P<0.001). Confidence scores of 2D FSE MARS and MAVRIC-SL for diagnosing joint effusion were 2 (1, 3) and 3 (2, 3), respectively, and the difference was statistically significant ( Z=6.549, P<0.001). Conclusion:Compared with 2D FSE MARS, MAVRIC-SL can further reduce the metal artifacts in total knee arthroplasty and improve the diagnostic confidence of joint effusion.

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