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.Z-plasty combined with auricular cartilage grafting for the correction of cryptotia
Chenglong WANG ; Dejin GAO ; Rui GUO ; Jiaxin LIANG ; Qingguo ZHANG
Chinese Journal of Plastic Surgery 2024;40(11):1200-1205
Objective:To evaluate the effectiveness of Z-plasty combined with auricular cartilage grafting in the correction of cryptotia.Methods:A retrospective analysis was conducted on the clinical data of cryptotia patients who underwent Z-plasty combined with auricular cartilage grafting at the Department of Ear Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from January 2020 to December 2023. The surgery consisted of five steps: design of the Z-plasty flap, harvesting of auricular cartilage from the conchal cavity, dissection and reshaping of the auricular cartilage, transplantation of auricular cartilage, and skin coverage with flap transfer. Early and late complications were recorded according to postoperative follow-up, and the external ear morphology was evaluated by both plastic surgeons and the patients’ guardians using a Likert 4-point scale (the higher the score, the better the auricular morphology). Normally distributed data were presented as Mean±SD.Results:A total of 32 patients were included in the study, comprising 23 males and 9 females, aged 5 to 14 years, with an average age of 7.3 years. Two children were lost to follow-up, and 30 completed long-term follow-up, with follow-up periods ranging from 6 to 24 months, averaging 9.3 months. Early complications included hematoma in 2 cases [6.3%(2/32)] and flap vascular compromise in 1 case[3.1%(1/32)]. Late complications primarily involved hypertrophic scars in 2 cases[6.7%(2/30)], with no recurrence of deformity. After the operation, the cranioauricular sulcus on the upper pole of the auricle were significantly deepened, and the patients could wear masks and glasses. The average score for the external ear morphology was 3.5±0.5 by plastic surgeons and 3.5±0.5 by patients.Conclusion:Z-plasty combined with auricular cartilage grafting provides satisfactory result in the correction of cryptotia, with few postoperative complications and high patient satisfaction, making it suitable for the treatment of cryptotia.
3.Z-plasty combined with auricular cartilage grafting for the correction of cryptotia
Chenglong WANG ; Dejin GAO ; Rui GUO ; Jiaxin LIANG ; Qingguo ZHANG
Chinese Journal of Plastic Surgery 2024;40(11):1200-1205
Objective:To evaluate the effectiveness of Z-plasty combined with auricular cartilage grafting in the correction of cryptotia.Methods:A retrospective analysis was conducted on the clinical data of cryptotia patients who underwent Z-plasty combined with auricular cartilage grafting at the Department of Ear Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from January 2020 to December 2023. The surgery consisted of five steps: design of the Z-plasty flap, harvesting of auricular cartilage from the conchal cavity, dissection and reshaping of the auricular cartilage, transplantation of auricular cartilage, and skin coverage with flap transfer. Early and late complications were recorded according to postoperative follow-up, and the external ear morphology was evaluated by both plastic surgeons and the patients’ guardians using a Likert 4-point scale (the higher the score, the better the auricular morphology). Normally distributed data were presented as Mean±SD.Results:A total of 32 patients were included in the study, comprising 23 males and 9 females, aged 5 to 14 years, with an average age of 7.3 years. Two children were lost to follow-up, and 30 completed long-term follow-up, with follow-up periods ranging from 6 to 24 months, averaging 9.3 months. Early complications included hematoma in 2 cases [6.3%(2/32)] and flap vascular compromise in 1 case[3.1%(1/32)]. Late complications primarily involved hypertrophic scars in 2 cases[6.7%(2/30)], with no recurrence of deformity. After the operation, the cranioauricular sulcus on the upper pole of the auricle were significantly deepened, and the patients could wear masks and glasses. The average score for the external ear morphology was 3.5±0.5 by plastic surgeons and 3.5±0.5 by patients.Conclusion:Z-plasty combined with auricular cartilage grafting provides satisfactory result in the correction of cryptotia, with few postoperative complications and high patient satisfaction, making it suitable for the treatment of cryptotia.
4.Sequence analysis of whole genome of influenza A(H3N2) virus in Huai′an
Pengfei YANG ; Fang HE ; Wanli YIN ; Tong GAO ; Wang ZHANG ; Mingyue WEI ; Chenglong XIONG ; Wei HU
Chinese Journal of Experimental and Clinical Virology 2024;38(2):156-161
Objective:To study the biological traits and mutations of the influenza A (H3N2) virus in order to produce a vaccine and offer references for controlling and preventing influenza epidemics.Methods:Four strains of the influenza A(H3N2) virus were chosen from the Huai′an surveillance network laboratory. Nucleic acid extraction, library building, and sequencing (CridION x5 MKI Nanopore) were used to produce the whole-genome sequences. Using homologous alignments of whole-genome sequences, phylogenetic tree construction, and amino acid variant screening, bioinformatics analysis was carried out.Results:The nucleotide identity between 8 gene segments ranged from 97.1% to 100.0%. The gene that differed the most from the reference sequences was HA (97.1%-99.9%), and the gene that differed the least was MP (98.6%-99.9%). The HA gene (3.06%) and MP gene (1.43%) were the regions with the greatest and lowest frequencies of nucleotide site change, respectively. The rates of nucleotide change varied significantly between the genes ( χ2=14.293, P=0.046). Four influenza A(H3N2) virus strains′ whole-genome phylogenies from each of the eight gene segments maintained a roughly consistent topological structure. One strain was linked to the 3C.2a1b.1b clade, which was lost at the 142NWT, 149NGT(HA1), and 436NLS(NA). Three strains were linked to the 3C.2a1b.2a.1a clade lineage. Amantadine and NA inhibitors were effective against all Huai′an strains. Conclusions:The antigenicity of one strain of Huai'an strain changed and its matching with the vaccine strain of that year was low. It is suggested that the genetic surveillance of H3N2 influenza virus should be continuously strengthened to provide scientific basis for influenza prevention and control and influenza vaccine screening.
5.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.
6.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.
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.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)
9.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.
10.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.

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