1.Application and progress of intelligent responsive hydrogels in articular cartilage injury repair.
Qingyu XU ; Baojian ZHANG ; Hongri LI ; Chengri LIU ; Shuhao BI ; Zhixiang YANG ; Yanqun LIU
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(2):250-256
OBJECTIVE:
To review clinical application and research progress of different types of intelligent responsive hydrogels in repairing articular cartilage injury.
METHODS:
The animal experiments and clinical studies of different types of intelligent responsive hydrogels for repairing articular cartilage injury were summarized by reviewing relevant literature at home and abroad.
RESULTS:
The intrinsic regenerative capacity of articular cartilage following injury is limited. Intelligent responsive hydrogels, including those that are temperature-sensitive, light-sensitive, enzyme-responsive, pH-sensitive, and other stimuli-responsive hydrogels, can undergo phase transitions in response to specific stimuli, thereby achieving optimal functionality. These hydrogels can fill the injured cartilage area, promote the proliferation and differentiation of chondrocytes, and expedite the repair of the damaged site. With advancements in cartilage tissue engineering materials research, intelligent responsive hydrogels offer a novel approach and promising potential for the treatment of cartilage injuries.
CONCLUSION
Intelligent responsive hydrogel is a kind of flexible, controllable, efficient, and stable polymer, which has similar structure and functional properties to articular cartilage, and has become one of the important biomaterials for cartilage repair. However, there is still a lack of unified treatment standards and simple and efficient preparation technology.
Hydrogels/therapeutic use*
;
Cartilage, Articular/injuries*
;
Tissue Engineering/methods*
;
Humans
;
Animals
;
Chondrocytes/cytology*
;
Biocompatible Materials/chemistry*
;
Tissue Scaffolds/chemistry*
2.Research progress on glycolipid metabolism of Sertoli cell in the development of spermatogenic cell.
Shuhao LI ; Liang KONG ; Jingyan LIANG ; Tan MA
Journal of Zhejiang University. Medical sciences 2025;54(2):257-265
Sertoli cells play an important role in the process of spermatogenesis, and the abnormalities in spermatogenesis are closely related to disruptions in glycolipid metabolism. The metabolic environment of Sertoli cells is hypoxic, with glycolysis and fatty acid β-oxidation being the primary metabolic pathways. In Sertoli cells, glycolysis produces lactate to provide energy for spermatogenic cells, while fatty acid β-oxidation generates ATP. Currently, the relationship between glycolipid metabolism in Sertoli cells and spermatogenic cell development, as well as the interplay between glucose and lipid metabolism remain unclear. Various hormones, including sex hormones, can affect glucose metabolism in Sertoli cells by endocrine regulation. The activation or inhibition of signaling pathways such as AMPK, mTOR, and Akt can alter the expression levels of glycolysis-related transporter genes and the synthesis of fatty acids, thereby affecting glycolipid metabolism in Sertoli cells. Some transcription factors such as PPARγ can regulate downstream fatty acid metabolism-related genes by directly binding to their response elements and promoting the oxidation of fatty acids in Sertoli cells. In this article we elaborate on the key factors influencing glycolipid metabolism in Sertoli cells and their interconnections, as well as their potential clinical implications, offering new insights for precisely targeted treatments of male infertility.
Sertoli Cells/cytology*
;
Male
;
Glycolipids/metabolism*
;
Spermatogenesis/physiology*
;
Humans
;
Lipid Metabolism
;
Animals
;
Fatty Acids/metabolism*
;
Signal Transduction
;
Glycolysis
3.Screen of FDA-approved drug library identifies vitamin K as anti-ferroptotic drug for osteoarthritis therapy through Gas6.
Yifeng SHI ; Sunlong LI ; Shuhao ZHANG ; Caiyu YU ; Jiansen MIAO ; Shu YANG ; Yan CHEN ; Yuxuan ZHU ; Xiaoxiao HUANG ; Chencheng ZHOU ; Hongwei OUYANG ; Xiaolei ZHANG ; Xiangyang WANG
Journal of Pharmaceutical Analysis 2025;15(5):101092-101092
Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.
4.Comparative study on protrusion and width of zygomatic bones between patients with maxillary retrusion and normal subjects
Shuhao LIU ; Zhe LI ; Kai TAO
Chinese Journal of Plastic Surgery 2025;41(5):473-479
Objective:To focus on the comparison of protrusion and width in zygomatic bones between the patients with the maxillary retrusion and normal subjects, in order to explore the relationship between maxillary retrusion and protrusion and width of zygomatic bones.Methods:DICOM data of spiral CT in craniomaxillofacial region were collected from the database of Department of Radiology, the Affiliated Hospital of Stomatology, China Medical University from January 2020 to July 2023. The study group included patients with maxillary retrusion and mandibular protrusion. The control group included the normal people with Angle’s Class Ⅰ occlusion. The three-dimensional(3D) images of craniofacial skeletons were built with ProPlan CMF 2.0 Software. The 3D-McNamara cephalometric analysis based on the coronal plane (CP) containing midpoint of the nasofrontal suture (N) were carried out for the anterior-posterior linear distances to the coronal plan of the maxillary alveolar base point (A-CP), the anterior-posterior linear distances of the landmark points of zygomatic bones (zygomatic protrusion), and for the width of the same landmark points on the left and right sides. The normal distribution measurement data were expressed as Mean±SD. The independent sample t-test was carried out between the same measurements of the two groups. In order to prove the relationship between the protrusion of maxilla and zygoma, the test of Pearson’s correlation analysis was carried out between the A-CP and the zygomatic landmarks of the orbital point of frontal-malar suture (Fmo-CP), the lowest point on the margin of the orbital (Or-CP), the most protrusive and front point of zygomatic bone (Mp-CP), and the lowest point of zygomatic-maxillary suture (Zm-CP). Results:A Total of 37 patients with maxillary retrusion were collected for study group (male 21, female 16, mean age of 21.1±3.2) and 33 normal subjects for control group (male 14, female 19, mean age of 21.1±2.5). The Mp-CP and the Zm-CP in the study group were significantly smaller than those in the control group ( P<0.05). Pearson’s correlation test showed that Mp-CP and Zm-CP were positively correlated with A-CP in the two groups ( r=0.38-0.49, P<0.05). But the horizontal width of zygomatic bones between the two groups did not show significant differences ( P>0.05). The ratio between the width of the lowest point of the zygomatic-temporal suture (Ztl) and the width of temporal points of frontal-malar suture (Fmt) was 1.21. Conclusion:The lower parts of zygomatic bones below the frontal-malar suture in patients with maxillary retrusion are affected by development of maxillary bones in sagittal direction and keep a positive relationship with the protrusion of maxillary bones. The zygomatic bone width of patients with maxillary retrusion is not affected by the sagittal development state of maxillary bones.
5.Application of a nomogram model based on cervical cancer radiomics and clinical features in the treatment of chronic radiation enteritis
Liyang ZHU ; Zhengting REN ; Shuhao PAN ; Ping LI ; Xiangxun CHEN ; Yin LYU
Chinese Journal of Radiological Medicine and Protection 2025;45(8):803-809
Objective:To predict the occurrence of chronic radiation enteritis (CRE) in cervical cancer patients by developing a prediction model based on the combination of radiomic features derived from magnetic resonance imaging (MRI) scans and clinical parameters, in order to provide a reference for clinicians to determine the prognosis of these patients and offer them individualized diagnosis and treatment.Methods:A retrospective analysis was conducted on 111 cervical cancer patients who received radical radiotherapy at the First Affiliated Hospital of Anhui Medical University. Radiological features were extracted from the T1-weighted MRI images of local lesions of cervical cancer obtained before the radiotherapy. Features were selected using the least absolute shrinkage and selection operator (LASSO) to obtain the radiomics score. The radiomics scores and clinical parameters were assessed using univariate and multivariate logistic regression analyses, followed by the establishment of nomograms. The ability of radiomics to achieve CRE prediction was assessed using the area under the curve (AUC) and the calibration and decision curves.Results:Multivariate logistic regression analysis result revealed that the independent risk factors for identifying CRE in patients included radiomics score ( HR: 17.457, 95% CI: 5.540-55.009, P<0.001), tumor volume ( HR: 3.617, 95% CI: 1.293-10.115, P=0.014), and pelvic lymph node metastasis ( HR: 3.559, 95% CI: 1.013-12.501, P=0.048). The model combining radiomics and clinical data demonstrated high performance, with its AUCs of the training and validation groups (0.888 and 0.870, respectively) higher than those of the radiomics model (0.842 and 0.804, respectively) and the clinical data model (0.721 and 0.704, respectively). The analyses of calibration and decision curves confirmed the application value of clinical radiomic nomograms. Conclusions:The model combining radiomics and clinical data allows for accurate CRE prediction. Therefore, radiomic features have the potential to serve as a promising imaging biomarker for CRE.
6.Screen of FDA-approved drug library identifies vitamin K as anti-ferroptotic drug for osteoarthritis therapy through Gas6
Yifeng SHI ; Sunlong LI ; Shuhao ZHANG ; Caiyu YU ; Jiansen MIAO ; Shu YANG ; Yan CHEN ; Yuxuan ZHU ; Xiaoxiao HUANG ; Chencheng ZHOU ; Hongwei OUYANG ; Xiaolei ZHANG ; Xiangyang WANG
Journal of Pharmaceutical Analysis 2025;15(5):1033-1047
Ferroptosis of chondrocytes is a significant contributor to osteoarthritis(OA),for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis.Here,we screen for anti-ferroptotic drugs in Food and Drug Administration(FDA)-approved drug library via a high-throughput manner in chondrocytes.We identified a group of FDA-approved anti-ferroptotic drugs,among which vitamin K showed the most powerful protective effect.Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix(ECM)degradation in chondrocytes.Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus(DMM)mouse model.Mechanistically,transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6(Gas6).Furthermore,exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase(AXL)/phosphatidylinositol 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)axis.Together,we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis,indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.
7.Relationship between intervertebral disc degeneration and 473 gut microbiotas:what can be learned from big data information in the FinnGen database
Zikun WANG ; Shudong LI ; Shuang GAO ; Shuhao FAN ; Cheng LI ; Chunyang MENG
Chinese Journal of Tissue Engineering Research 2025;29(20):4369-4378
BACKGROUND:Some research has suggested that regulation of gut microbiota may influence the course of intervertebral disc degeneration.However,the causal relationship of gut microbiota on intervertebral disc degeneration is unknown.OBJECTIVE:To assess the potential causal relationship between gut microbiota and intervertebral disc degeneration using a Mendelian randomization method.METHODS:Genome-wide association analysis summary statistics for 473 gut microbiota and genome-wide association analysis summary data for intervertebral disc degeneration from the R11 of the FinnGen database(46 205 cases of intervertebral disc degeneration and 322 314 controls)from the most recent publicly available publication were applied.Inverse variance weighting,MR-Egger regression,weighted median,weighted modeling,and simple modeling were used to investigate the causal relationship between gut microbiota and intervertebral disc degeneration.Sensitivity analyses were used to test whether the results of Mendelian randomization analyses were reliable.Reverse Mendelian randomization was performed with all gut microbiota as the outcomes for effect analysis and sensitivity analysis.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method of the forward Mendelian randomization method showed that the order Trichosporonaceae,the family UBA-6960,the family Anaerobes thermophilus,the family Salmonellaceae,the genus Pseudomonas tufts,the species Gordonella and the species Euclidia showed a positive correlation with intervertebral disc degeneration.The order Spirochaetes,the order Pseudomonas,the family Spirochaetaceae,the genus CAG-776,the genus Helicobacter,the species CAG-448 sp003150135,the species CAG-776 sp000438195,the species Brautella-A sp000285855 and the species Hanson's Brautella showed a negative correlation with intervertebral disc degeneration.(2)The results of reverse Mendelian randomization showed that intervertebral disc degeneration was positively correlated with the genus Bartonella rosea,the genus Geobacillus C,the species Escherichia fumigatus,the species Propionibacterium fumigatus,the species UBA-1777 sp900319835,the species Pseudomonas aeruginosa and the species Bacillus subtilis,while negatively correlated with the species Streptomyces mingoldii,the species Prevotella sp000434975,the species Brault's A sp000285855,the species CAG-194 sp002441865 and the species CAG-590 sp000431135.(3)No heterogeneity or horizontal pleiotropy was found in the two-way sensitivity analysis.(4)The results described above indicate that the causal relationship between gut microbiota and intervertebral disc degeneration based on the Finnish database contributes to the exploration on new biomarkers for the early prediction and treatment of intervertebral disc degeneration in clinical practice.In addition,the establishment of a large database and the integration of medical data from multiple centers can be drawn upon in biomedical research in China to provide a solid foundation for studying the relationship between gut microbiota and intervertebral disc degeneration.We will strengthen communication and cooperation with research teams in other countries to jointly promote the research on the relationship between gut microbiota and diseases and contribute to the development of global medicine.
8.Application of a nomogram model based on cervical cancer radiomics and clinical features in the treatment of chronic radiation enteritis
Liyang ZHU ; Zhengting REN ; Shuhao PAN ; Ping LI ; Xiangxun CHEN ; Yin LYU
Chinese Journal of Radiological Medicine and Protection 2025;45(8):803-809
Objective:To predict the occurrence of chronic radiation enteritis (CRE) in cervical cancer patients by developing a prediction model based on the combination of radiomic features derived from magnetic resonance imaging (MRI) scans and clinical parameters, in order to provide a reference for clinicians to determine the prognosis of these patients and offer them individualized diagnosis and treatment.Methods:A retrospective analysis was conducted on 111 cervical cancer patients who received radical radiotherapy at the First Affiliated Hospital of Anhui Medical University. Radiological features were extracted from the T1-weighted MRI images of local lesions of cervical cancer obtained before the radiotherapy. Features were selected using the least absolute shrinkage and selection operator (LASSO) to obtain the radiomics score. The radiomics scores and clinical parameters were assessed using univariate and multivariate logistic regression analyses, followed by the establishment of nomograms. The ability of radiomics to achieve CRE prediction was assessed using the area under the curve (AUC) and the calibration and decision curves.Results:Multivariate logistic regression analysis result revealed that the independent risk factors for identifying CRE in patients included radiomics score ( HR: 17.457, 95% CI: 5.540-55.009, P<0.001), tumor volume ( HR: 3.617, 95% CI: 1.293-10.115, P=0.014), and pelvic lymph node metastasis ( HR: 3.559, 95% CI: 1.013-12.501, P=0.048). The model combining radiomics and clinical data demonstrated high performance, with its AUCs of the training and validation groups (0.888 and 0.870, respectively) higher than those of the radiomics model (0.842 and 0.804, respectively) and the clinical data model (0.721 and 0.704, respectively). The analyses of calibration and decision curves confirmed the application value of clinical radiomic nomograms. Conclusions:The model combining radiomics and clinical data allows for accurate CRE prediction. Therefore, radiomic features have the potential to serve as a promising imaging biomarker for CRE.
9.Comparative study on protrusion and width of zygomatic bones between patients with maxillary retrusion and normal subjects
Shuhao LIU ; Zhe LI ; Kai TAO
Chinese Journal of Plastic Surgery 2025;41(5):473-479
Objective:To focus on the comparison of protrusion and width in zygomatic bones between the patients with the maxillary retrusion and normal subjects, in order to explore the relationship between maxillary retrusion and protrusion and width of zygomatic bones.Methods:DICOM data of spiral CT in craniomaxillofacial region were collected from the database of Department of Radiology, the Affiliated Hospital of Stomatology, China Medical University from January 2020 to July 2023. The study group included patients with maxillary retrusion and mandibular protrusion. The control group included the normal people with Angle’s Class Ⅰ occlusion. The three-dimensional(3D) images of craniofacial skeletons were built with ProPlan CMF 2.0 Software. The 3D-McNamara cephalometric analysis based on the coronal plane (CP) containing midpoint of the nasofrontal suture (N) were carried out for the anterior-posterior linear distances to the coronal plan of the maxillary alveolar base point (A-CP), the anterior-posterior linear distances of the landmark points of zygomatic bones (zygomatic protrusion), and for the width of the same landmark points on the left and right sides. The normal distribution measurement data were expressed as Mean±SD. The independent sample t-test was carried out between the same measurements of the two groups. In order to prove the relationship between the protrusion of maxilla and zygoma, the test of Pearson’s correlation analysis was carried out between the A-CP and the zygomatic landmarks of the orbital point of frontal-malar suture (Fmo-CP), the lowest point on the margin of the orbital (Or-CP), the most protrusive and front point of zygomatic bone (Mp-CP), and the lowest point of zygomatic-maxillary suture (Zm-CP). Results:A Total of 37 patients with maxillary retrusion were collected for study group (male 21, female 16, mean age of 21.1±3.2) and 33 normal subjects for control group (male 14, female 19, mean age of 21.1±2.5). The Mp-CP and the Zm-CP in the study group were significantly smaller than those in the control group ( P<0.05). Pearson’s correlation test showed that Mp-CP and Zm-CP were positively correlated with A-CP in the two groups ( r=0.38-0.49, P<0.05). But the horizontal width of zygomatic bones between the two groups did not show significant differences ( P>0.05). The ratio between the width of the lowest point of the zygomatic-temporal suture (Ztl) and the width of temporal points of frontal-malar suture (Fmt) was 1.21. Conclusion:The lower parts of zygomatic bones below the frontal-malar suture in patients with maxillary retrusion are affected by development of maxillary bones in sagittal direction and keep a positive relationship with the protrusion of maxillary bones. The zygomatic bone width of patients with maxillary retrusion is not affected by the sagittal development state of maxillary bones.
10.Relationship between intervertebral disc degeneration and 473 gut microbiotas:what can be learned from big data information in the FinnGen database
Zikun WANG ; Shudong LI ; Shuang GAO ; Shuhao FAN ; Cheng LI ; Chunyang MENG
Chinese Journal of Tissue Engineering Research 2025;29(20):4369-4378
BACKGROUND:Some research has suggested that regulation of gut microbiota may influence the course of intervertebral disc degeneration.However,the causal relationship of gut microbiota on intervertebral disc degeneration is unknown.OBJECTIVE:To assess the potential causal relationship between gut microbiota and intervertebral disc degeneration using a Mendelian randomization method.METHODS:Genome-wide association analysis summary statistics for 473 gut microbiota and genome-wide association analysis summary data for intervertebral disc degeneration from the R11 of the FinnGen database(46 205 cases of intervertebral disc degeneration and 322 314 controls)from the most recent publicly available publication were applied.Inverse variance weighting,MR-Egger regression,weighted median,weighted modeling,and simple modeling were used to investigate the causal relationship between gut microbiota and intervertebral disc degeneration.Sensitivity analyses were used to test whether the results of Mendelian randomization analyses were reliable.Reverse Mendelian randomization was performed with all gut microbiota as the outcomes for effect analysis and sensitivity analysis.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method of the forward Mendelian randomization method showed that the order Trichosporonaceae,the family UBA-6960,the family Anaerobes thermophilus,the family Salmonellaceae,the genus Pseudomonas tufts,the species Gordonella and the species Euclidia showed a positive correlation with intervertebral disc degeneration.The order Spirochaetes,the order Pseudomonas,the family Spirochaetaceae,the genus CAG-776,the genus Helicobacter,the species CAG-448 sp003150135,the species CAG-776 sp000438195,the species Brautella-A sp000285855 and the species Hanson's Brautella showed a negative correlation with intervertebral disc degeneration.(2)The results of reverse Mendelian randomization showed that intervertebral disc degeneration was positively correlated with the genus Bartonella rosea,the genus Geobacillus C,the species Escherichia fumigatus,the species Propionibacterium fumigatus,the species UBA-1777 sp900319835,the species Pseudomonas aeruginosa and the species Bacillus subtilis,while negatively correlated with the species Streptomyces mingoldii,the species Prevotella sp000434975,the species Brault's A sp000285855,the species CAG-194 sp002441865 and the species CAG-590 sp000431135.(3)No heterogeneity or horizontal pleiotropy was found in the two-way sensitivity analysis.(4)The results described above indicate that the causal relationship between gut microbiota and intervertebral disc degeneration based on the Finnish database contributes to the exploration on new biomarkers for the early prediction and treatment of intervertebral disc degeneration in clinical practice.In addition,the establishment of a large database and the integration of medical data from multiple centers can be drawn upon in biomedical research in China to provide a solid foundation for studying the relationship between gut microbiota and intervertebral disc degeneration.We will strengthen communication and cooperation with research teams in other countries to jointly promote the research on the relationship between gut microbiota and diseases and contribute to the development of global medicine.

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