1.Multiple applications of metal-organic framework materials in bone tissue engineering and orthopedic disease treatment
Yunxiang LIU ; Xiaoyu ZHANG ; Hao LI ; Rong ZHANG ; Liping LI ; Chongwei CHEN
Chinese Journal of Tissue Engineering Research 2025;29(10):2151-2161
BACKGROUND:Metal-organic frameworks exhibited great potential for bone tissue engineering and bone disease treatment because of its unique merits including tunable porosity,a large specific surface area,good biocompatibility,and easy structure modification. OBJECTIVE:To review the advancements,application,strengths,and weaknesses of metal-organic framework materials in bone repair,arthritis,bone infection,and bone tumors,offering guidance and strategies for future research. METHODS:Web of Science,PubMed,and CNKI databases were searched using Chinese and English keywords"metal-organic frameworks,MOFs,orthopedics,bone repair,bone regeneration,orthopaedic applications,bone tissue engineering,bone infection,arthritis,bone tumor,osteosarcoma"for related literature published from 2015 to 2023.Following initial screening based on inclusion and exclusion criteria,72 articles were finally included for review. RESULTS AND CONCLUSION:(1)During bone repair,metal ions of metal-organic frameworks can induce bone formation by activating specific signaling pathways,which include stimulating osteogenic gene expression,inhibiting osteoclasts,encouraging blood vessel formation,and speeding up bone mineralization.Hence,metal-organic frameworks with metals like calcium,strontium,cobalt,copper,and magnesium ions show significant potential in enhancing bone implant performance.(2)Metal-organic framework materials,especially zinc/cobalt-based metal-organic frameworks,exhibit enzyme-like activities and promote cartilage regeneration by scavenging reactive oxygen species.Compared with natural enzymes,it has the advantages of not easy inactivation and better stability.(3)Zinc-based metal-organic framework materials characterized with wide band gaps,efficient separation and migration of photogenerated carriers,and high stability,the enhancement of photocatalytic activity results from enhancing the excited electron-hole widely used for the eradication of bacteria and tumor cells.(4)Bimetallic metal-organic frameworks,the doping of additional metals,showed critical advantages in optimizing structural performance,such as zinc/magnesium-based metal-organic framework 74 offering increased stability for durable antibacterial activity,and the light absorption capacity and photocatalytic efficiency of tantalum/zirconium-based metal-organic framework greatly improved and thus enhancing the radiation therapy.(5)However,metal-organic framework materials still face challenges in clinical applications,such as the uncertainty of drug release,in vivo safety,and potential immune responses from long-term presence.
2.Efficacy of intelligent temperature-pressure-controlled flexible ureteroscopy combined with negative-pressure suction sheath lithotripsy in the treatment of ≤2.5 cm upper urinary tract stones
Xiaofu WANG ; Yunxiang ZHANG ; Xinyu SHI ; Yongli ZHAO ; Changbao XU ; Changwei LIU ; Haiyang WEI ; Xinghua ZHAO
Journal of Modern Urology 2025;30(4):311-314
Objective: To investigate the efficacy and safety of intelligent temperature-pressure-controlled flexible ureteroscopy combined with negative-pressure suction sheath lithotripsy in the treatment of upper urinary tract stones ≤2.5 cm. Methods: The clinical data of 225 patients with ≤2.5 cm upper urinary tract stones treated with this surgical method in our department during Aug. 2023 and Jul. 2024 were retrospectively analyzed. The patients were divided into the dual-control group (n=36) and conventional group (n=189) according to whether or not the intelligent temperature and pressure control device was used during operation. In the dual-control group,the intraoperative temperature and pressure in the renal pelvis were monitored and controlled in real time by the temperature and pressure sensors distributed at the end of the ureteral soft lens. The perioperative parameters,stone-removal rate,complication rate and renal function were compared between the two groups. Results: All operations were successfully completed in both groups. The postoperative procalcitonin (PCT) level [(22.75±5.85) ng/L vs. (29.08±6.60) ng/L,P=0.001],difference in the white blood cell (WBC) level [(0.24±2.12)×10
cells/L vs. (1.19±2.17)×10
cells/L,P=0.016],incidence of fever (2.8% vs. 16.9%,P=0.028) and overall complication rate (5.6% vs. 19.6%,P=0.042) were significantly lower in the dual-control group than in the conventional group,while the stone-clearance rate was slightly higher (88.9% vs. 82.5%,P=0.346),with no significant difference. Conclusion: For upper urinary tract stones ≤2.5 cm,intelligent temperature-pressure-controlled ureteroscopy combined with negative-pressure suction sheath lithotripsy has a satisfactory stone-removal rate and a low rate of complications,which is worthy of clinical promotion.
3.Reviews and Recommendations in Comparative Studies on Quality of Wild and Cultivated Chinese Crude Drugs
Yapeng WANG ; Changsheng YUAN ; Jinxiu QIAN ; Yihan WANG ; Yanmeng LIU ; Yunxiang LIU ; Tiegui NAN ; Liping KANG ; Zhilai ZHAN ; Lanping GUO ; Luqi HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):1-20
By reviewing the research history on quality comparison between wild and cultivated Chinese crude drugs, this paper systematically combed the relevant research reports since the 1950s, and summarized and analyzed the results of existing comparative studies, and found that the existing comparative research on the quality of wild and cultivated Chinese crude drugs were mainly focused on several aspects, including characteristics, microstructures, chemical compositions, pharmacodynamic effects, and genetic diversity. Among these, comparative studies of chemical compositions have been the dominant approach, with a particular emphasis on comparing the contents of index components. However, research on pharmacodynamic effects remained relatively limited. Due to various factors such as sample quantity, sample origin, growth period and cultivation methods, the differences in quality between wild and cultivated Chinese crude drugs vary significantly. In general, most wild Chinese crude drugs exhibited higher quality than cultivated products, with significant differences in their characteristics. The contents and proportions of some chemical components underwent noticeable changes, particularly with a marked increase in the proportion of primary metabolites after cultivation. The quality of cultivated Chinese crude drugs is closely related to the cultivation practices employed. Chinese crude drugs produced through wild nurturing, simulated wild planting, ecological cultivation, and other similar methods demonstrate quality levels comparable to those of wild Chinese crude drugs. Based on the analysis results, it is recommended to explicitly specify the cultivation practices and cultivation period of cultivated Chinese crude drugs in comparative studies of the quality between wild and cultivated Chinese crude drugs. Multiple technical approaches, including characteristics, microscopy, non-targeted metabolomics combined with quantitative analysis of differential components, and bioefficacy evaluation, should be employed to comprehensively assess the quality disparities between wild and cultivated Chinese crude drugs. Moreover, research efforts should be intensified to investigate the changes in pharmacodynamic effects resulting from differences in plant cell wall composition, primary metabolites, and secondary metabolites, in order to guide the production of high-quality Chinese crude drugs.
4.Role of Ferroptosis in Bone Homeostasis and Traditional Chinese Medicine Intervention: A Review
Bo WEI ; Juan LI ; Yiwei JIANG ; Yuying ZHOU ; Chunhui LUO ; Zhongchao YU ; Pei LIU ; Yunxiang HAI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):249-257
Osteoporosis (OP) is a systemic metabolic bone disease characterized by bone microstructure degeneration and bone mass loss, which has a high prevalence and disability rate. Effective prevention and treatment of OP is a major difficulty in the medical community. The nature of OP is that multiple pathological factors lead to the imbalance of human bone homeostasis maintained by osteoblasts and osteoclasts. Ferroptosis is a non-apoptotic cell death pathway, and its fundamental cause is cell damage caused by iron accumulation and lipid peroxidation. Studies have shown that ferroptosis is involved in and affects the occurrence and development of OP, which leads to OP by mediating the imbalance of bone homeostasis. Ferroptosis is an adjustable form of programmed cell death. The intervention of ferroptosis can regulate the damage degree and death process of osteoblasts and osteoclasts, which is beneficial to maintain bone homeostasis, slow down the development process of OP, improve the clinical symptoms of patients, reduce the risk of disability, and improve their quality of life. However, there are few studies on ferroptosis in OP. Traditional Chinese medicine (TCM) is a medical treasure with unique characteristics and great application value in China. It has been widely used in China and has a long history. It has the multi-target and multi-pathway advantages in the treatment of OP, with high safety, few toxic and side effects, and low treatment cost, and has a significant effect in clinical application. The intervention of TCM in ferroptosis to regulate bone homeostasis may be a new direction for the prevention and treatment of OP in the future. This article summarized the regulatory mechanisms related to ferroptosis, discussed the role of ferroptosis in bone homeostasis, and reviewed the current status and progress of active ingredients in TCM compounds and monomers in the regulation of OP through ferroptosis, so as to provide a theoretical basis for the participation of TCM in the prevention and treatment of OP in the future.
5.Comparison of Wild and Cultivated Bupleurum chinense Based on Traditional Quality Evaluation
Yunxiang LIU ; Yapeng WANG ; Liping KANG ; Zhilai ZHAN ; Tiegui NAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):145-155
ObjectiveIn order to understand the quality differences between wild and cultivated Bupleurum chinense(BC), modern analytical techniques were used to systematically compare the quality of wild and cultivated BC in terms of appearance characteristics, primary and secondary metabolites. MethodSamples of wild and cultivated BC were collected from the main production areas of Shanxi, Shaanxi and Hebei, and images of BC were collected and their length and diameter were measured using vernier caliper to compare and analyze the characteristics of the two. Referring to the method under extract of CP in the 2020 edition of Chinese Pharmacopoeia, the extract contents of the two species were determined. The cellulose, hemicellulose and lignin compositions of both were determined using fiber analyzer. Quantitative determination of representative saikosaponins, flavonoids and saccharides in BC by ultra performance liquid chromatography(UPLC), headspace gas chromatography-mass spectrometry(HS-GC-MS) was used to determine the types and relative contents of volatile components, and UPLC-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) coupled with multivariate statistical analysis was used to screen and identify the differential compounds between wild and cultivated BC. ResultThere were significant differences in the appearance characteristics between wild and cultivated BC, the wild BC had a large root head, twisted and thick axial root, rough epidermis, and often had a stem base and lateral root with dark color and strong odor. However, the cultivated BC has long and straight taproots, delicate epidermis, few lateral roots, light root color and light smell. In terms of primary and secondary metabolites, the contents of alcohol-soluble extract and lignin of wild BC was significantly higher than those of cultivated BC, while the contents of water soluble extract and quercitrin was higher than those of cultivated BC, but the difference was not significant. The contents of cellulose, five saikosaponins, rutin, narcissoside and isorhamnetin-3-O-glucoside in cultivated BC were significantly higher than those of wild BC, and the total water-soluble polysaccharides, sucrose, hemicellulose and starch of cultivated BC were higher than those of wild BC, but the difference was not significant. The results of HS-GC-MS identification showed that a total of 67 volatile components were identified in wild and cultivated BC, 59 in wild BC and 51 in cultivated BC, with a total of 43 compounds in both, and the screening based on variable importance in the projection(VIP) value>1 revealed that the differential components were mainly concentrated in the aromatic and fatty acid compounds. The results of UPLC-Q-TOF-MS-based non-targeted metabolomics combined with multivariate statistical analysis showed that the two were significantly different in saikosaponins and the differential compounds had higher response values in cultivated BC. ConclusionThere are significant differences in the appearance, primary and secondary metabolite contents between wild and cultivated BC. At present, the quality evaluation system of cultivated BC is not perfect, and this study provides theoretical references for updating and revising the quality evaluation standard of cultivated BC and guiding the production of high-quality BC.
6.Angiopathic Mechanisms on Diabetic Delayed Healing Wounds:Impact and Advances in Therapeutic Agents
Yunxiang WANG ; Bin LI ; Xiaojuan MOU ; Jianjun LIU ; Qipeng HAN ; Taowen PAN ; Jing LIU ; Yunpeng DIAO
Herald of Medicine 2024;43(4):577-581
The prevalence of diabetes mellitus in China has recently been increasing year by year,and spontaneous skin ulcers in diabetic patients,as one of the most serious complications,often develop on the patient's extremities represented by foot ulcers.Due to the complexity and variety of its pathogenesis,it leads to poor clinical outcomes and difficulty in healing.Thus,pa-tients often face the risk of amputation and death.Therefore,the exploration of mechanisms of the vascular pathogenesis of diabetic delayed-healing wounds and targeted screening of therapeutic agents has become a current research hotspot.Herein,in this paper,we briefly review the role of impaired angiogenesis and vascular dysfunction in diabetic skin ulcers,and the research progress of classical hypoglycemic and natural compounds against vascular lesions is preliminarily summarized to provide a theoretical basis for effective clinical treatment.
7.Triptolide ameliorates inflammation in AA rats by inhibiting pyroptosis through regulation of the lncRNA GAS5/miR-21/TLR4 signaling axis
A'min WANG ; Yunxiang CAO ; Jian LIU ; Nanfei ZHU ; Hui WANG
Immunological Journal 2024;40(5):418-424
The aim of this study is to investigate the mechanism by which triptolide(TP)ameliorates inflammation in adjuvant arthritis(AA)rats by inhibiting pyroptosis through the lncRNA GAS5/miR-21/TLR4 signaling axis.Rats were divided into 4 groups:normal control group(NC),model control group(MC),triptolide group(TP)and methotrexate group(MTX),with 6 rats in each group.The AA rat model was established,and the general state,right foot-plantar swelling and arthritis index were observed;HE staining was used to detect the histopathological morphology of synovial joints of rats in each group;ELISA was used to detect the levels of inflammatory factors IL-1β,IL-6,IL-18 and TNF-α;fluorescence quantitative PCR was used to detect the mRNA expression levels of Caspase-1,IL-1β,NLRP3,GSDMD,GAS5,TLR4,NF-κB and miR-21;and Western blot was used to detect the expression levels of Caspase-1,NLRP3,GSDMD,NF-κB,Caspase-4 and TLR4 proteins.Compared with the NC group,rats in the MC group showed significantly higher levels of swelling,arthritis index(P<0.05)and inflammatory cell infiltration;compared with the MC group,the levels of IL-1β,IL-6,IL-18 and TNF-α were decreased in the TP and MTX groups(P<0.05),and the levels of Caspase-1,IL-1β,NLRP3,GSDMD,TLR4,NF-κB,miR-21 mRNA expression decreased,GAS5 mRNA expression increased(P<0.05),and the protein levels of Caspase-1,NLRP3,GSDMD,NF-κB,Caspase-4 and TLR4 decreased(P<0.05);compared with the MTX group,the TP group showed lower levels of IL-1β,IL-6,IL-18,TNF-α(P<0.05),and lower expression levels of Caspase-1,IL-1β,NLRP3,GSDMD,TLR4,NF-κB and miR-21 mRNA(P<0.05).In conclusion,triptolide may inhibit the production of pro-inflammatory factors and inhibit pyroptosis through the lncRNA GAS5/miR-21/TLR4 signaling axis,thus ameliorate inflammation in AA rats.
8.Improving auto-segmentation accuracy for online magnetic resonance imaging-guided prostate radiotherapy by registration-based deep learning method
Yunxiang WANG ; Bining YANG ; Yuxiang LIU ; Ji ZHU ; Ning-Ning LU ; Jianrong DAI ; Kuo MEN
Chinese Journal of Medical Physics 2024;41(6):667-672
Objective To improve the performance of auto-segmentation of prostate target area and organs-at-risk in online magnetic resonance image and enhance the efficiency of magnetic resonance imaging-guided adaptive radiotherapy(MRIgART)for prostate cancer.Methods A retrospective study was conducted on 40 patients who underwent MRIgART for prostate cancer,including 25 in the training set,5 in the validation set,and 10 in the test set.The planning CT images and corresponding contours,along with online MR images,were registered and input into a deep learning network for online MR image auto-segmentation.The proposed method was compared with deformable image registration(DIR)method and single-MR-input deep learning(SIDL)method.Results The overall accuracy of the proposed method for auto-segmentation was superior to those of DIR and SIDL methods,with average Dice similarity coefficients of 0.896 for clinical target volume,0.941 for bladder,0.840 for rectum,0.943 for left femoral head and 0.940 for right femoral head,respectively.Conclusion The proposed method can effectively improve the accuracy and efficiency of auto-segmentation in MRIgART for prostate cancer.
9.Feasibility analysis of dose calculation for nasopharyngeal carcinoma radiotherapy planning using MRI-only simulation
Xuejie XIE ; Guoliang ZHANG ; Siqi YUAN ; Yuxiang LIU ; Yunxiang WANG ; Bining YANG ; Ji ZHU ; Xinyuan CHEN ; Kuo MEN ; Jianrong DAI
Chinese Journal of Radiation Oncology 2024;33(5):446-453
Objective:To evaluate the feasibility of using MRI-only simulation images for dose calculation of both photon and proton radiotherapy for nasopharyngeal carcinoma cases.Methods:T 1-weighted MRI images and CT images of 100 patients with nasopharyngeal carcinoma treated with radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2020 to December 2021 were retrospectively analyzed. MRI images were converted to generate pseudo-CT images by using deep learning network models. The training set, validation set and test set included 70 cases, 10 cases and 20 cases, respectively. Convolutional neural network (CNN) and cycle-consistent generative adversarial neural network (CycleGAN) were exploited. Quantitative assessment of image quality was conducted by using mean absolute error (MAE) and structural similarity (SSIM), etc. Dose assessment was performed by using 3D-gamma pass rate and dose-volume histogram (DVH). The quality of pseudo-CT images generated was statistically analyzed by Wilcoxon signed-rank test. Results:The MAE of the CNN and CycleGAN was (91.99±19.98) HU and (108.30±20.54) HU, and the SSIM was 0.97±0.01 and 0.96±0.01, respectively. In terms of dosimetry, the accuracy of pseudo-CT for photon dose calculation was higher than that of the proton plan. For CNN, the gamma pass rate (3 mm/3%) of the photon radiotherapy plan was 99.90%±0.13%. For CycleGAN, the value was 99.87%±0.34%. The gamma pass rates of proton radiotherapy plans were 98.65%±0.64% (CNN, 3 mm/3%) and 97.69%±0.86% (CycleGAN, 3 mm/3%). For DVH, the dose calculation accuracy in the photon plan of pseudo-CT was better than that of the proton plan.Conclusions:The deep learning-based model generated accurate pseudo-CT images from MR images. Most dosimetric differences were within clinically acceptable criteria for photon and proton radiotherapy, demonstrating the feasibility of an MRI-only workflow for radiotherapy of nasopharyngeal cancer. However, compared with the raw CT images, the error of the CT value in the nasal cavity of the pseudo-CT images was relatively large and special attention should be paid during clinical application.
10.The influence of the quantitative changes of γ-glutamyl transpeptidase on the prognosis of hepatocellular carcinoma patients undergoing hepatectomy
Kai QU ; Kun YANG ; Jia JIA ; Yuan LIU ; Xiaohua MA ; Yunxiang LONG ; Kunjin WU ; Kaibo YANG ; Xing ZHANG ; Chang LIU
Tumor 2024;44(2):146-157
Objective:To explore the assessment value of liver enzyme changes before and after hepatectomy on the prognosis of patients with primary hepatocellular carcinoma(HCC). Methods:A retrospective analysis was conducted on the clinical data of 421 patients with primary HCC who received at the First and Second Affiliated Hospitals of Xi'an Jiaotong University from January 2016 to December 2020.The univariate and multivariate COX regression analyses were used to screen the risk factors affecting the prognosis of patients with primary HCC,and the optimal cut-off value was selected to group the most valuable indicators among them,further analyzing the different factors among subgroups.The Kaplan-Meier method was used to assess the prognosis of the subgroups,and the survival curves were plotted and statistically tested. Results:Multivariate COX regression analysis revealed that Barcelona Clinic Liver Cancer(BCLC)stage,tumor number,alpha-fetoprotein(AFP),the quantitative change of γ-glutamyl transpeptidase(GGT)and total bilirubin(TBIL)before and after surgery were independent risk factors affecting the prognosis of patients with primary HCC(P<0.01),and there were differences in hepatitis B virus surface antigen(HBsAg),TNM stage,BCLC stage,tumor size,tumor number,tumor differentiation degree,AFP,surgery type,intraoperative bleeding volume,postoperative albumin-bilirubin(ALBI)and white blood cell count between the high and low GGT variation groups(P<0.05).Kaplan-Meier survival analysis showed that the prognosis of patients with primary HCC between the high and low GGT variation groups was significantly different,with a hazard ratio of 2.603 for mortality and 1.449 for recurrence(both P<0.01). Conclusion:The quantitative change of GGT before and after hepatectomy has an evaluation value for the prognosis of patients with primary HCC,and the quantitative change of GGT greater than 29.5 is an independent risk factor for the prognosis of patients with primary HCC.

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