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.

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.

Objective:To analyze the impact and mechanism of grassroots Party building in public hospitals on departmental business, and to provide reference for promoting the integration and mutual promotion of Party building and business.Methods:In November 2023, a self-designed questionnaire was used to survey clinical medical staff in a tertiary hospital in Wuhan. A cluster random sampling method was employed to investigate the evaluation of grassroots Party building work by clinical medical staff and the role of grassroots Party building in departmental business. Descriptive quantitative analysis was conducted on the questionnaire data. From November to December 2023, typical sampling was used to select Party branch committee members from clinical and medical technology departments of the hospital for semi-structured interviews. The interview content included the status of grassroots Party building work, its role in departmental business development, and the underlying mechanisms. Grounded theory was used for three-level coding of the interview data, and role theory was applied to analyze the mechanism by which grassroots Party building promotes business development.Results:A total of 1 124 valid questionnaires were collected, covering personnel from various sequences, including medical, nursing, technical, and pharmacy staff. Over 95% of the respondents rated the Party branch work highly, and more than 94% believed that grassroots Party building had a positive impact on the department′s medical care, teaching, research, talent team building, management, and cultural construction. The analysis using grounded theory and role theory revealed that the promotion of departmental business by grassroots Party building mainly originated from three aspects of standardization and normalization construction of Party branches, participation of Party branches in departmental management, and the development of characteristic activities based on Party building carriers. These three aspects enhanced personal responsibility, discipline, and service awareness through five personal-level targets (correcting work attitudes, leading by example among Party members, strengthening integrity in professional practice, improving professional skills, and improving working methods). This, in turn, facilitated medical staff to better identify their role positioning, standardize role behavior, and enhance role learning. At the departmental level, seven targets (expanding channels for departmental transparency, emphasizing practical performance, Party branch involvement in important departmental matters, enhancing external communication, increasing emotional identification, improving internal communication, and strengthening integrity building) were identified to promote fairness and justice, democratic decision-making, external cooperation, unity, and a clean atmosphere within the department. This further improved role evaluation, created an atmosphere conducive to role learning, helped strengthen role identification, and guided role standardization.Conclusions:Grassroots Party building of public hospital has a positive impact on department business work and is widely recognized by clinical medical staff. Different Party building activities have different pathways of influence. It is recommended to conduct targeted Party building activities based on actual needs.

Objective:To investigate the feasibility and effectiveness of robot-assisted surgery in children with cholangiectasis under 3 months of age.Methods:This is a retrospective cohort study. The clinical data of 53 children with cholangiectasis under 3 months admitted to Department of General Surgery of Children′s Hospital Affiliated to Zhejiang University School of Medicine from April 2019 to December 2024 were included retrospectively. According to the surgical method, the patients were divided into robot-assisted surgery(RAS) group(5 males, 24 females, age ( M(IQR)) 49.0(36.0)days (range: 19.0 to 90.0 days), weight 5.00(1.65)kg (range: 3.40 to 7.50 kg)) and laparoscopic-assisted surgery(LAS) group (5 males, 19 females, age 55.5(27.3)days (range: 18.0 to 87.0 days), weight 4.90 (1.62)kg (range: 3.50 to 6.20 kg)). Nineteen cases in each group were prenatally diagnosed. Data were statistically analyzed using the Mann-Whitney U test and the Pearson χ 2 test, respectively. Results:No statistically significant differences were observed between the two groups in age, sex, weight, or preoperative biochemical indices(all P>0.05). All procedures were successfully completed without conversion to open surgery. Postoperative biochemical indices, fasting duration, cyst diameter, operative time, drainage tube retention time, and follow-up duration showed no significant differences between the groups(all P>0.05). Compared to the LAS group, the RAS group demonstrated significantly shorter postoperative hospital stays (9.0(5.0)days (range:7.0 to 18.0 days) vs. 11.5(5.5)days (range:7.0 to 38.0 days), U=236.5, P=0.044) and hepaticojejunostomy time (15.0(3.5)minutes (range:11.0 to 22.0 minutes) vs. 18.0(3.0)minutes (range:13.0 to 25.0 minutes), U=144.5, P=0.001). However, the RAS group incurred higher surgical costs (78 099.9(10 100.1)yuan (range: 72 148.7 to 112 898.6 yuan) vs. 30 158.6(15 283.1)yuan (range: 25 041.7 to 107 673.1 yuan), U=41.0, P<0.01). In the LAS group, 3 patients developed anastomotic leakage requiring reoperation, while the RAS group had 1 case of anastomotic stenosis 2 years postoperatively (received second hepaticojejunostomy) and 1 case of incision infection(received incision debridement and dressing of the abscess). Conclusion:Robot-assisted surgery can be used to treat children with cholangiectasis under 3 months of age and may achieve good results.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

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*

Objective:To analyze the impact and mechanism of grassroots Party building in public hospitals on departmental business, and to provide reference for promoting the integration and mutual promotion of Party building and business.Methods:In November 2023, a self-designed questionnaire was used to survey clinical medical staff in a tertiary hospital in Wuhan. A cluster random sampling method was employed to investigate the evaluation of grassroots Party building work by clinical medical staff and the role of grassroots Party building in departmental business. Descriptive quantitative analysis was conducted on the questionnaire data. From November to December 2023, typical sampling was used to select Party branch committee members from clinical and medical technology departments of the hospital for semi-structured interviews. The interview content included the status of grassroots Party building work, its role in departmental business development, and the underlying mechanisms. Grounded theory was used for three-level coding of the interview data, and role theory was applied to analyze the mechanism by which grassroots Party building promotes business development.Results:A total of 1 124 valid questionnaires were collected, covering personnel from various sequences, including medical, nursing, technical, and pharmacy staff. Over 95% of the respondents rated the Party branch work highly, and more than 94% believed that grassroots Party building had a positive impact on the department′s medical care, teaching, research, talent team building, management, and cultural construction. The analysis using grounded theory and role theory revealed that the promotion of departmental business by grassroots Party building mainly originated from three aspects of standardization and normalization construction of Party branches, participation of Party branches in departmental management, and the development of characteristic activities based on Party building carriers. These three aspects enhanced personal responsibility, discipline, and service awareness through five personal-level targets (correcting work attitudes, leading by example among Party members, strengthening integrity in professional practice, improving professional skills, and improving working methods). This, in turn, facilitated medical staff to better identify their role positioning, standardize role behavior, and enhance role learning. At the departmental level, seven targets (expanding channels for departmental transparency, emphasizing practical performance, Party branch involvement in important departmental matters, enhancing external communication, increasing emotional identification, improving internal communication, and strengthening integrity building) were identified to promote fairness and justice, democratic decision-making, external cooperation, unity, and a clean atmosphere within the department. This further improved role evaluation, created an atmosphere conducive to role learning, helped strengthen role identification, and guided role standardization.Conclusions:Grassroots Party building of public hospital has a positive impact on department business work and is widely recognized by clinical medical staff. Different Party building activities have different pathways of influence. It is recommended to conduct targeted Party building activities based on actual needs.

Objective:To investigate the feasibility and effectiveness of robot-assisted surgery in children with cholangiectasis under 3 months of age.Methods:This is a retrospective cohort study. The clinical data of 53 children with cholangiectasis under 3 months admitted to Department of General Surgery of Children′s Hospital Affiliated to Zhejiang University School of Medicine from April 2019 to December 2024 were included retrospectively. According to the surgical method, the patients were divided into robot-assisted surgery(RAS) group(5 males, 24 females, age ( M(IQR)) 49.0(36.0)days (range: 19.0 to 90.0 days), weight 5.00(1.65)kg (range: 3.40 to 7.50 kg)) and laparoscopic-assisted surgery(LAS) group (5 males, 19 females, age 55.5(27.3)days (range: 18.0 to 87.0 days), weight 4.90 (1.62)kg (range: 3.50 to 6.20 kg)). Nineteen cases in each group were prenatally diagnosed. Data were statistically analyzed using the Mann-Whitney U test and the Pearson χ 2 test, respectively. Results:No statistically significant differences were observed between the two groups in age, sex, weight, or preoperative biochemical indices(all P>0.05). All procedures were successfully completed without conversion to open surgery. Postoperative biochemical indices, fasting duration, cyst diameter, operative time, drainage tube retention time, and follow-up duration showed no significant differences between the groups(all P>0.05). Compared to the LAS group, the RAS group demonstrated significantly shorter postoperative hospital stays (9.0(5.0)days (range:7.0 to 18.0 days) vs. 11.5(5.5)days (range:7.0 to 38.0 days), U=236.5, P=0.044) and hepaticojejunostomy time (15.0(3.5)minutes (range:11.0 to 22.0 minutes) vs. 18.0(3.0)minutes (range:13.0 to 25.0 minutes), U=144.5, P=0.001). However, the RAS group incurred higher surgical costs (78 099.9(10 100.1)yuan (range: 72 148.7 to 112 898.6 yuan) vs. 30 158.6(15 283.1)yuan (range: 25 041.7 to 107 673.1 yuan), U=41.0, P<0.01). In the LAS group, 3 patients developed anastomotic leakage requiring reoperation, while the RAS group had 1 case of anastomotic stenosis 2 years postoperatively (received second hepaticojejunostomy) and 1 case of incision infection(received incision debridement and dressing of the abscess). Conclusion:Robot-assisted surgery can be used to treat children with cholangiectasis under 3 months of age and may achieve good results.

Purpose: Whether a dilated intrahepatic bile duct (IHBD) has any effect on the prognosis of choledochal cyst (CC) remains controversial. We aimed to summarize the clinical characteristics and prognosis of CC with IHBD dilatation. Methods: One hundred ninety-two children diagnosed with CC were identified, including 127 without IHBD dilatation (group A) and 65 with IHBD dilatation (group B). A retrospective analysis was performed to explore the clinical characteristics and prognosis of CC with IHBD dilatation based on clinical indices, symptoms, and complications. Results: Compared with group A, incidences of jaundice and fever were higher in group B (P = 0.010 and P = 0.033). Preoperative total bilirubin, direct bilirubin, and indirect bilirubin were increased in group B compared to group A (P = 0.005, P < 0.001, and P = 0.014), as were preoperative ALT, AST, γ-GT, and total bile acid (P = 0.006, P = 0.025, P < 0.001, and P = 0.024). The risk of liver fibrosis or cirrhosis was significantly increased for group B compared with group A (P = 0.012) and also occurred earlier in group B (P = 0.006). In the dilated IHBDs, 95.4% (62 of 65) recovered to normal, and more than half of dilated IHBDs (37 of 65) recovered to normal in 1 week. Conclusion Most IHBDs can recover to normal postoperatively in a short time, and proactive treatment is recommended for CC patients with IHBD dilatation for significant abnormal liver functions.

Purpose To investigate the expression status of GNL3 in gastric cancer,and to explore the role of GNL3 in tumor proliferation,invasion and migration.Methods The ex-pression of GNL3 mRNA in gastric cancer tissues was analyzed by searching database.The expression of GNL3 protein in 51 gastric cancer tissues and 51 adjacent non-tumor tissues was de-tected by immunohistochemistry(IHC)SP method.The correla-tion between GNL3 protein expression and gastric cancer clinical pathological features was analyzed by x2 test.The expression of GNL3 in gastric cancer cells was silenced by transfection of sh-RNA,and the silencing efficiency was verified by Western blot.The effect of silencing GNL3 on the proliferation of gastric cancer cells was examined by CCK-8,colony formation and EdU stai-ning.In addition,wound-healing assay and Transwell assay were performed to detect the effect of GNL3 silencing on cell invasion and migration.Results SangerBox and UALCAN database re-trieval showed that the expression of GNL3 mRNA was signifi-cantly increased in gastric cancer tissues(P＜0.01).IHC stai-ning showed that the positive expression rate of GNL3 protein in gastric cancer tissues was 96.1％,and the high expression rate was 78.4％,which was significantly higher than that in adjacent non-tumor tissues(74.5％,51.0％,P＜0.01).Moreover,the high expression of GNL3 was significantly correlated with lymph node metastasis in gastric cancer patients(x2=4.933,P=0.026).CCK-8,colony formation and EdU staining showed that GNL3 silencing inhibited the proliferation of gastric cancer cell SGC-7901.The wound-healing and Transwell assay showed that GNL3 silencing inhibited the migration and invasion of gastric cancer cell.Conclusion The GNL3 protein is highly expressed in gastric cancer tissues,and closely related to the proliferation,migration and invasion of gastric cancer cells.