1.Restoration of osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide with psoralen
Chenglong WANG ; Zhilie YANG ; Junli CHANG ; Yongjian ZHAO ; Dongfeng ZHAO ; Weiwei DAI ; Hongjin WU ; Jie ZHANG ; Libo WANG ; Ying XIE ; Dezhi TANG ; Yongjun WANG ; Yanping YANG
Chinese Journal of Tissue Engineering Research 2025;29(1):16-23
BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.
2.Effective Ingredients of Chinese Medicine in Prevention and Treatment of Osteoarthritis by Regulating Oxidative Stress: A Review
Shuang ZHANG ; Yingyan BI ; Xiaoting LIU ; Yusuo GONG ; Xuerui LIU ; Baohua YUAN ; Chenglong LU ; Xufan CHEN ; Ying WANG ; Jiaru GUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):282-289
Osteoarthritis (OA) is a common degenerative joint disease with a rising incidence rate year by year. Treatment often relies on analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), which can lead to gastrointestinal damage with long-term use and the recurrence of symptoms. Chinese medicine has a long history of preventing and treating OA, with widespread application and fewer side effects. It offers unique advantages such as a broad treatment scope, multiple targets, and pathways. The effective components of Chinese medicine can reduce the content of reactive oxygen species (ROS), relieve oxidative stress (OS) damage, and increase the antioxidant capacity of the body by interfering with the expression of biomarkers of OS response such as malondialdehyde (MDA) and superoxide dismutase (SOD). Through the modulation of signaling pathways such as nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), NOD-like receptor protein 3 (NLRP3), and osteoprotegerin (OPG), they downregulated the expression of inflammatory factors such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), thereby effectively relieving local joint inflammation, protecting chondrocytes and bone tissue, inhibiting chondrocyte apoptosis, and further alleviating the progression of OA. Currently, there are still certain limitations in the medical research status and development trends of OA, necessitating the continued advancement of traditional Chinese medicine. This paper reviewed the literature on the regulation of OS response by effective components of Chinese medicine for the prevention and treatment of OA, providing new directions and ideas for future research.
3.Clinical efficacy of transcatheter arterial chemoembolization combined with lenvatinib and camrelizumab in the treatment of advanced hepatocellular carcinoma
Xuexian ZHANG ; Yuhan DING ; Wei LI ; Qingwei LI ; Jun ZHANG ; Dan DUAN ; Yongle LI ; Jian LONG ; Jidong YANG ; Chenglong ZHANG ; Peng WU ; Huijuan SUN ; Geng WU
Journal of Interventional Radiology 2024;33(1):57-62
Objective To evaluate the safety and efficacy of transcatheter arterial chemoembolization(TACE)combined with lenvatinib and camrelizumab in the treatment of advanced hepatocellular carcinoma(HCC).Methods The clinical data of a total of 63 patients with advanced HCC,who received TACE combined with lenvatinib and camrelizumab(triple therapy)or TACE combined with lenvatinib(dual therapy)at the Jingmen Municipal People's Hospital of China between April 2020 and December 2021,were retrospectively analyzed.Triple therapy group had 30 patients,and dual therapy group had 33 patients.The post-treatment tumor response,disease progression-free survival(PFS),overall survival(OS),and the incidence of adverse drug reactions were recorded.Results The median follow-up period of the two groups was 14 months(range of 4-26 months).Compared with the dual therapy group,in the triple therapy group the objective response rate(ORR)was remarkably higher(83.3%vs.57.6%,P=0.026),the disease control rate(DCR)was obviously higher(93.3%vs.69.7%,P=0.039),the median PFS was significantly longer(8.0 months vs.5.0 months,P<0.01),and the median OS was strikingly longer(24.0 months vs.12.0 months,P=0.004).No statistically significant difference in the incidence of adverse drug reactions existed between the two groups(P>0.05).Conclusion For the treatment of advanced HCC,TACE combined with lenvatinib and camrelizumab is clinically safe and effective.(J Intervent Radiol,2024,32:57-62)
4.The application of IVIM-DWI in evaluating the efficacy and prognosis of TACE using different embolization materials for hepatocellular carcinoma
Qinglong GUAN ; Haibo CHNE ; Chenglong LIU ; Gengfei CAO ; Haixiao ZHANG ; Chuanbao CUI
Journal of Interventional Radiology 2024;33(2):140-145
Objective To discuss the clinical application of intravoxel incoherent motion-diffusion weighted imaging(IVIM-DWI)in evaluating the efficacy and prognosis of transcatheter arterial chemoembolization(TACE)using different embolization materials for the treatment of hepatocellular carcinoma(HCC).Methods The clinical data of a total of 84 patients with inoperable HCC,who received TACE treatment at the Second Affiliated Hospital of Shandong First Medical University of China and the First Affiliated Hospital of Xinjiang Medical University of China between June 30,2019 and December 30,2022,were collected.According to the patient's condition,different embolization materials were used during TACE.IVIM-DWI check-up was performed before treatment as well as at one,6,12 months after treatment.Based on the fixed b-value set by IVIM-DWI sequence,the ADC value of the order index model for different embolization materials and the pure diffusion coefficient of double exponential model(D value),the pseudo-diffusion coefficient(D*value)and perfusion fraction(f value)were analyzed.According to modified Response Evaluation Criteria in Solid Tumors(mRECIST)and the embolization material used,the patients were divided into the stable group and progression group,and the changes in the ADC value,D value,D*value and f value were compared between the two groups.Multivariate Cox regression analysis was used to analyze the four clinical parameters(including age,Child-Pugh grade,AFP level and tumor size)and the eight functional quantitative indexes(including preoperative and postoperative ADC value,D value,D* value and f value)so as to determine the IVIM parameters with prognostic predictive value.Receiver operating characteristic(ROC)was adopted to analyze the diagnostic value and cut-off value of IVIM parameters with predictive value.Results After treatment,the ADC value of drug-loaded microspheres group(n=36)was significantly higher than that of iodized oil group(n=27),the D*value of drug-loaded microspheres group and iodized oil group was remarkably lower than that of PVA particle group(n=21),and the f value of drug-loaded microspheres group was strikingly lower than that of iodized oil group,the differences were statistically significant(all P<0.01).In the stable group,the efficacy of drug loaded microspheres group was obviously better than that of the iodized oil group and the PVA particle group.In the progression group,the iodized oil group was more likely to develop disease progression than the drug-loaded microspheres group and the PVA particle group.The preoperative f value in the stable group was prominently higher than that in the progression group(P=0.005),and the postoperative ADC value in the stable group was obviously higher than that in the progression group(P=0.029).ROC analysis showed that the median follow-up time in the drug-loaded microspheres group,iodized oil group,and PVA particle group was 30,19,and 26 months respectively,the overall average survival time was 25 months,and the difference was statistically significant(P<0.01).Multivariate Cox regression analysis showed that the preoperative D value(AUC=0.878),D*value(AUC=0.554)and postoperative D value(AUC=0.791),D*value(AUC=0.552),f value(AUC=0.467)were the independent factors affecting the short-term efficacy of TACE(all P<0.05).The preoperative and postoperative D value had higher diagnostic efficacy,while a preoperative D value of<0.505×10-3 mm2/s and a postoperative D value of<0.785×10-3 mm2/s predicted a poor prognosis.Conclusion The preoperative and postoperative D value is the optimal parameter for predicting the curative efficacy of TACE using different embolization materials for the treatment of HCC.
5.Progress in regulation of JAK/STAT signaling pathway by traditional Chinese medicine in treatment of osteoarthritis
Xiaoting LIU ; Jiaru GUANG ; Yusuo GONG ; Baohua YUAN ; Chenglong LU ; Xufan CHEN ; Bifeng ZHANG
Chinese Journal of Pathophysiology 2024;40(2):375-384
Osteoarthritis(OA)mainly lies in the lesions of articular cartilage and surrounding tissues,pro-ducing osteophytes and bone sclerosis,resulting in damage to the articular cartilage.The main pathological mechanism of OA rests with a large number of inflammatory cytokines and inflammatory mediators produced by joint synovial lesions as well as pathological vascular growth at the junction of the synovium and cartilage,which may be one of the key reasons for promoting synovitis and cartilage damage.The OA mainly occurs in the knees,hips,hands and the spine.It is mainly manifested by chronic joint pain,swelling and stiffness,and limitation of motion seriously affects the functional activities of patients.The treatment of OA mainly relies on oral administration or intraarticular injection of drugs to relieve symp-toms.When OA develops to the middle and late stages,the action and life of patients will be seriously affected.There-fore,surgical replacement of joints is considered to ensure the basic life demands of patients.Studies show that traditional Chinese medicine(TCM)treatment has attracted widespread attention and application due to its unique advantages in pre-vention and treatment of OA.Janus kinase(JAK)/signaling transduction and transcriptional activator(STAT)signaling pathway may be one of the important signaling pathways that regulate the chondrocyte proliferation,differentiation and apoptosis.Moreover,it is closely associated with intra-articular inflammatory response.The JAK/STAT signaling pathway regulates the expression of inflammatory factors and related proteins through TCM so as to reduce the inflammatory re-sponse and decrease the chondrocyte damage.It has an important reference value for OA treatment.In this paper,the roles and mechanisms of the TCM monomers and active ingredients and the Chinese herbal compounds in OA by regulating JAK/STAT signaling pathway and affecting related cytokine and protein expression levels have been reviewed,providing a new method and direction for TCM treatment of OA.
6.AngioJet-assisted catheter-directed thrombolysis versus catheter-directed thrombolysis alone in the treatment of acute deep venous thrombosis of lower extremity: a mid-term controlled clinical study
Xinqing LI ; Aimin QIAN ; Chenglong LI ; Xiaobin YU ; Yeqing ZHANG ; Fengrui LEI ; Liwei ZHU ; Zhixin CAI ; Hongfei SANG
Chinese Journal of General Surgery 2024;39(2):110-114
Objective:To compare the mid-term clinical effects of AngioJet rheolytic thrombectomy assisted catheter-directed thrombolysis (ART+CDT) with catheter-directed thrombolysis (CDT) in the treatment of acute deep venous thrombosis of lower extremities.Methods:Ninety-one patients admitted to the Department from Jan 2016 to Dec 2017 were placed with inferior vena cava filters and divided into ART+CDT group (30 cases)and CDT group (61 cases). Total urokinase dosge, thrombolytic time, operative cost, length of hospital stay, detumescence rate, thrombus clearance rate, cumulative patency rate of lower limb veins, Villalta score at 2 years and 5 years, thrombosis recurrence rate and chronic venous insufficiency quality of life questionnaire were compared between the two groups.Results:The success rate of surgery was 100% in both groups, there was no mortality. There were significant differences in the short-term postoperative outcomes between the two groups in terms of total dosage of urokinase, thrombolysis time, total cost of surgery, length of hospital stay, detumescence rate, venous patency scores before and after treatment, and venous patency rate (all P<0.05). For the mid- and long-term postoperative outcomes of 2 and 5 years, there were no significant differences in the incidence of PTS, recurrence rate of thrombus, chronic venous function scale, and cumulative patency rate at 2 years (all P>0.05). Conclusions:ART+CDT has a significant advantage over CDT alone in terms of early efficacy and early reopening of blood flow in patients. Both ART+CDT and CDT have a low incidence of PTS and a low recurrence rate of thrombus in the mid-term follow-up, and both have satisfactory performance in the mid- and long-term efficacy of interventional treatment of deep venous thrombosis of lower limbs.
7.Traditional Chinese Medicine Intervention in Rheumatoid Arthritis-related Signaling Pathways: A Review
Zengpeng LU ; Haiyang YU ; Xiaogang ZHANG ; Hulin ZHANG ; Chenglong GUO ; Yuping ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):289-298
Rheumatoid arthritis (RA), as an autoimmune disease, is mainly characterized by persistent synovitis. It often involves multiple joints symmetrically and can lead to joint deformity, joint function loss, and even disability in severe cases. The pathogenesis of RA is complex, and the prevention and treatment are complicated. Therefore, it is difficult to cure the disease completely. Previous studies have validated important targets and mechanisms for the prevention and treatment of RA, including the nuclear factor-κB (NF-κB) signaling pathway that controls the inflammatory process, nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway that regulates oxidative stress, inhibits inflammation, and maintains cell homeostasis, Wnt/β-catenin signaling pathway that plays a key role in cell growth, differentiation, apoptosis, and inflammatory response, anti-inflammatory, anti-oxidation, and silent information regulator 1 (SIRT1) signaling pathway that regulates synovial cells, anti-inflammatory adenylate-activated protein kinase (AMPK) signaling pathway that regulates energy metabolism, and hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway related to angiogenesis in RA. At the same time, many studies have confirmed that traditional Chinese medicine prevents and treats RA by regulating the above signaling pathways and exerting their related effects, indicating the advantages of traditional Chinese medicine such as multiple regulatory pathways, long-term effects, and less adverse reactions. In this paper, by consulting many research reports, the role of the above-mentioned signaling pathways in RA was clarified, and the latest research results of traditional Chinese medicine intervention in the above-mentioned signaling pathways in the prevention and treatment of RA in recent years were summarized in detail. This paper aims to promote the in-depth study of the pathogenesis of RA and its treatment with traditional Chinese medicine, provide a scientific basis for the rational application of traditional Chinese medicine, and offer useful enlightenment for the development of new drugs and clinical practice for the treatment of RA in the future.
8.Establishment and validation of the Sprague-Dawley rat model of osteoarthritis with kidney deficiency and blood stagnation
Cheng YANG ; Yusheng LI ; Hongzhuo JIAO ; Man SHANG ; Qi LIU ; Linzhen LI ; Fangyang FAN ; Chenglong ZHANG ; Xiaoyu ZHANG ; Juntao ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(27):4273-4280
BACKGROUND:Kidney deficiency and blood stasis syndrome are common traditional Chinese medicine syndromes observed in knee osteoarthritis,which serve as fundamental pathogenesis factors.There exists a significant connection between the two.Previous studies have demonstrated that kidney deficiency and blood stasis syndrome effectively contribute to knee joint cartilage degeneration and the progression of knee osteoarthritis.However,the mechanisms underlying the promotion of knee joint cartilage damage remain unclear and require further investigation. OBJECTIVE:To investigate the influence of kidney deficiency and blood stasis syndrome on the progression of knee osteoarthritis in Sprague-Dawley rats. METHODS:Sixteen Sprague-Dawley rats were randomly divided into two groups:a model observation group and a control group,with eight rats in each group.Animal models of kidney deficiency were induced by ovary removal in the model observation group,while the control group was given a sham procedure for ovarian removal.Two months after modeling,both groups underwent modified HULTH surgery to induce knee osteoarthritis.One week after modified HULTH surgery,the model observation group was subcutaneously given adrenaline hydrochloride to make blood stasis models,while the control group was subcutaneously given normal saline.At the 5th week after modified HULTH surgery,blood rheology,coagulation parameters,triiodothyronine,tetraiodothyronine,and estradiol levels were measured.Knee joint X-ray images were taken,and knee joint sections were stained with safranin O-fast green,hematoxylin-eosin,and immunohistochemistry. RESULTS AND CONCLUSION:Compared with the control group,the model observation group exhibited significant increases in whole blood viscosity at low,medium,and high shear rates,as well as increased plasma viscosity.Fibronectin levels in the coagulation parameters were significantly increased,while prothrombin time and activated partial thromboplastin time were significantly decreased.Triiodothyronine,tetraiodothyronine,and estradiol levels were all significantly decreased.Radiographic results showed that the model observation group exhibited more severe degree of knee joint space narrowing and surface roughness,with the appearance of high-density shadows.Hematoxylin-eosin and safranin O-fast green staining demonstrated more severe cartilage damage in the model observation group,with significantly higher OARSI and Mankin scores compared with the control group.Compared with the control group,immunohistochemistry results showed a significant reduction in the expression of extracellular matrix type II collagen and aggrecan protein in the cartilage of the model observation group rats.Moreover,there was a significant increase in the expression of matrix metalloproteinase 13 and aggrecanase 5,which are inflammatory factors.These results indicate that the Sprague-Dawley rat model of knee osteoarthritis with kidney deficiency and blood stasis was successfully established.Kidney deficiency and blood stasis syndrome further aggravate cartilage extracellular matrix degradation and cartilage degeneration by promoting the expression of inflammatory factors,thereby promoting the progression of knee osteoarthritis in rats.
9.Therapeutic Effects of Xiao Xumingtang Combined with Electroacupuncture on Cerebral Ischemia/Reperfusion Injury via NLRP3/GSDMD/Caspase-1 Pathway
Wei MAO ; Haiyang WU ; Ying WANG ; Haitao WANG ; Haisheng JI ; Junyu ZHANG ; Chenglong LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):39-47
ObjectiveTo comprehensively elucidate the potential mechanisms of Xiao Xumingtang (XXMT) combined with electroacupuncture (EA) collaboratively in alleviating cerebral ischemia/reperfusion (I/R) injury. MethodThe rat model of cerebral I/R injury was established using the modified suture-occluded method. Seven days after modeling, rats in the XXMT+EA groups were administered XXMT at low (15 g·kg-1), medium (30 g·kg-1), and high (60 g·kg-1) doses, alongside daily 20-min EA treatment (stimulating acupoints GV14 and GV20). Cerebral infarction and neuronal damage were evaluated using the Zea Longa test score, TTC staining, and TUNEL staining. Real-time fluorescence quantitative PCR and Western blot were used to detect the expression of NOD-like receptor hot protein domain related protein 3 (NLRP3), Gasdermin D (GSDMD), cysteinyl aspartate specific proteinase-1 (Caspase-1), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in the ischemic area of the cerebral cortex. ResultCompared with the sham group, the I/R group showed a significant increase in neurological deficit scores and infarct volume (P<0.01), along with a higher apoptosis rate of cortical neurons and elevated mRNA and protein expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, and IL-18 (P<0.05). In contrast, the medium- and high-dose XXMT combined with EA treatment significantly reduced neurological deficit scores and infarct volume (P<0.01), and decreased the apoptosis rate of cortical neurons as well as the mRNA and protein expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, and IL-18 (P<0.05). The improvement showed a dose-dependent relationship with XXMT. ConclusionThe combined use of XXMT and EA can exert neuroprotective effects by modulating the NLRP3/GSDMD/Caspase-1 signaling pathway, thereby reducing neurological deficits, minimizing brain infarct size, and improving cortical neuronal damage.
10.Survival analysis and compliance nomogram model construction of patients with non-small cell lung cancer over 65 years old after chemotherapy
Man ZHANG ; Peng SHEN ; Chenglong LI ; Yan LIU
Shanghai Journal of Preventive Medicine 2024;36(5):475-481
ObjectiveTo explore the risk factors and survival analysis of chemotherapy compliance in ≥65 years old patients with non-small cell lung cancer. MethodsFrom December 2018 to August 2020, 110 patients with non-small cell lung cancer ≥65 years old in our hospital were selected for study. According to their chemotherapy compliance, the patients were divided into untreated (25 cases), partial chemotherapy (30 cases) and full chemotherapy (55 cases). Multivariate Cox regression was used to analyze the independent risk factors affecting the compliance of chemotherapy among the three groups, and constructed a column chart prediction model and evaluated the diagnostic effectiveness of the model using receiver operating characteristic (ROC) curves, calibration curves, and clinical decision curves. The patients were followed up until August 2023. Kaplan-Meyer survival curve and Log-rank test were used to compare the differences in survival time between the groups. ResultsThere were significant differences among the three groups in gender, long-term smoking history, education level, Charlson complication index, toxic and side effects of chemotherapy drugs and dosage, pathological type, operation mode, place of residence, payment mode, chemotherapy stage, white blood cell count and neutrophils (P<0.05). Multivariate Cox analysis showed that patients' education level, pathological TNM stage, toxic and side effects of chemotherapy drugs and dosage, operation mode, residence, payment mode and chemotherapy stage were independent risk factors affecting chemotherapy compliance of patients with non-small cell lung cancer (all P<0.05). There were significant differences in the survival rates between the non-chemotherapy group and the full chemotherapy group, and between the partial chemotherapy group and the full chemotherapy group (P<0.05), but there was no significant difference between the non-chemotherapy group and the partial chemotherapy group (P>0.05). And based on this, a prediction model was constructed, and the ROC curve was drawn to show that the AUC of the model was 0.758 (95%CI: 0.743‒0.855), the sensitivity was 0.788, and the specificity was 0.853, indicating that the model had high discrimination, the calibration curve indicated that the prediction model had good accuracy, the clinical decision curve indicated that the predictive model had strong clinical practicality. ConclusionNSCLC tends to occur in the elderly. We should focus on the patients with low educational level, late pathological TNM stage, severe toxicity and side effects, high dose of chemotherapy drugs, having undergone open chest surgery, living in rural areas, without medical insurance, and in the period of chemotherapy consolidation and refractory relapse, so as to improve their compliance with chemotherapy.

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