1.Causal relationship between 91 inflammatory proteins and cervical disc degeneration
Shuaiyi LIU ; Xiaoxuan ZHAO ; Qi LI ; Zheng XING ; Qingwen LI ; Xiaolei CHU
Chinese Journal of Tissue Engineering Research 2025;29(17):3732-3740
BACKGROUND:Cervical disc degeneration is a common degenerative disease,and inflammatory proteins play an important role in cervical disc degeneration,but the specific mechanisms involved remain to be thoroughly investigated.OBJECTIVE:Using the Mendelian randomization method to assess the potential causal relationship between 91 inflammatory proteins and cervical disc degeneration.METHODS:Genome-wide association analysis statistics for 91 inflammatory proteins(from GCST90274758 to GCST90274848)were obtained from the Genome-Wide Association Analysis Catalog of publicly available genome-wide association analysis data and genome-wide association analysis data for cervical disc degeneration from the Finngen database(finngen_R10_M13_CERVICDISCV).Inverse variance weighting,MR-Egger regression,weighted median,weighted modeling,and simple modeling were used to investigate the causal relationship between inflammatory proteins and cervical disc degeneration.Sensitivity analyses were performed to test whether the results of the Mendelian randomization analysis were reliable,and then the inverse Mendelian randomization analysis was performed in the same way.RESULTS AND CONCLUSION:The results of the forward analysis showed that a total of six inflammatory proteins were significantly and causally associated with cervical disc degeneration,of which glial cell lineage-derived neurotrophic factor(odds ratio(OR)=1.095,95%confidence interval(CI):1.012-1.184,P=0.023),interleukin 4(OR=1.094,95%CI:1.002-1.194,P=0.045)and monocyte chemotactic protein-1 levels(OR=1.062,95%CI:1.001-1.127,P=0.048)showed a direct positive causal association with the risk of cervical disc degeneration;interleukin 17C(OR=0.906,95%CI:0.839-0.979,P=0.013),interleukin 18(OR=0.924,95%CI:0.866-0.986,P=0.017)and interleukin 2 levels(OR=0.894,95%CI:0.821-0.973,P=0.010)showed a direct negative causal association with the risk of cervical disc degeneration.The results of the inverse analysis showed that when cervical disc degeneration was used as exposure data,there was no significant causal relationship with any of the 91 inflammatory proteins.The results of the sensitivity analysis showed that the Cochran's Q test for the two-way Mendelian randomization,the MR-Egger regression method,and the MR-PRESSO results had P values greater than 0.05,indicating that there was no significant heterogeneity or multiplicity in the analysis of the causal effect between inflammatory proteins and cervical disc degeneration.To conclude,there may be a relatively significant potential causal relationship between glial cell line-derived neurotrophic factor,interleukin 4,monocyte chemotactic protein-1,interleukin 17C levels,interleukin 18,and interleukin 2 levels and cervical disc degeneration,which provides valuable clues for research on the potential mechanisms of cervical disc degeneration as well as early prevention and drug treatment of cervical disc degeneration.
2.Different frequencies of electrical stimulation promote recovery from peripheral nerve injury
Minqi LIU ; Mingwei GAO ; Xiaolei CHU ; Zheng XING ; Shihao LI ; Ning DING ; Yajie LI ; Qi LI
Chinese Journal of Tissue Engineering Research 2025;29(14):3061-3069
BACKGROUND:Electrical stimulation is an effective treatment plan for peripheral nerve injuries,but different frequencies of electrical stimulation have different mechanisms and applications for promoting peripheral nerve recovery.OBJECTIVE:To systematically sort out and summarize the roles and applications of different frequencies of electrical stimulation in the treatment of peripheral nerve injuries,and to deeply analyze the advantages and disadvantages of various methods in order to find the most beneficial treatment strategy for patients'nerve recovery.METHODS:Computer-based searches were conducted in the China National Knowledge Infrastructure(CNKI)and PubMed databases from the inception of the databases to May 2024.The search terms included"peripheral nerve injury,electrical stimulation,low frequency electrical stimulation,medium frequency electrical stimulation,high frequency electrical stimulation,TENS,interfering electricity,short wave,ultrashort wave,frequency"in both English and Chinese.Ultimately,74 relevant documents were included for analysis.RESULTS AND CONCLUSION:Peripheral nerve injury,a common clinical disease,can cause sensory and motor dysfunction in patients.Low-frequency electrical stimulation can promote cell proliferation and accelerate the expression of nerve growth factor within the cell after electrical stimulation,promote macrophage recruitment and infiltration,accelerate the clearance of myelin debris,and promote myelin regeneration of damaged axons.Medium-frequency electrical stimulation can act on deeper tissues and is better for relieving neuropathic pain.High-frequency electrical stimulation can promote the proliferation of Schwann cells and macrophages,inhibit inflammatory factors,and rapidly recruit cells to the site of nerve injury,accelerating the speed of nerve repair.Different frequencies of electrical stimulation have their own advantages in promoting the recovery of peripheral nerve injuries,but there are still some issues,such as differences in the site of electrical stimulation and the treatment plans for various disease types.
3.Electromyographic biofeedback therapy and motor function recovery after spinal cord injury
Jiajia LIANG ; Jiaojiao SUN ; Wenjie LIU ; Zheng XING ; Qi LI ; Qingwen LI ; Xiaolei CHU
Chinese Journal of Tissue Engineering Research 2025;29(14):3002-3010
BACKGROUND:Electromyographic biofeedback therapy has demonstrated unique advantages of non-invasive,real-time feedback,personalized treatment and promotion of neuroplasticity,and can promote the recovery of motor function in patients with spinal cord injury.OBJECTIVE:To review the current application status and therapeutic effects of electromyographic biofeedback combined with exercise therapy,robotic exoskeletons,and virtual reality technology in the recovery of motor function after spinal cord injury.METHODS:Relevant literature was retrieved from CNKI and PubMed databases up to May 2024.The search terms included"spinal cord injury,EMG biofeedback,physical therapy,robotic exoskeleton,VR,motor function,exercise"in both English and Chinese.Finally,71 articles were included for review.RESULTS AND CONCLUSION:Mechanisms by which electromyographic biofeedback therapy promotes spinal cord injury rehabilitation include promoting neural plasticity changes,strengthening neuromuscular connections and improving movement patterns.Electromyographic biofeedback,as an emerging tool for treating spinal cord injury,is often used in conjunction with other therapeutic methods,including exercise therapy,robotic exoskeletons,and VR,to promote the recovery of motor function after spinal cord injury.The effectiveness of combination therapy has been significantly improved.However,there are still some problems and challenges,such as the lack of detailed analysis of the mechanism,the lack of large-scale trials that provide strong evidence for combined efficacy,and the limited adaptability of the technology.Future research can focus on these aspects:to improve the personalization and accuracy of electromyographic biofeedback;to develop new rehabilitation equipment and expand the application areas of electromyographic biofeedback combined with more advanced technologies or engineering equipment;to apply electromyographic biofeedback to gait training systems,respiratory training systems,and limb-linkage rehabilitation systems,so as to improve the accuracy of the feedback and the effect of personalized treatment plans.At the same time,the ease of use and comfort of the equipment will be improved.
4.Exploratory study of fecal microbiota transplantation combined with immune checkpoint inhibitors in the treatment of end-stage malig-nant tumor patients
Yunqian CHU ; Ya XUE ; Hua JIANG ; Chunjian QI ; Hanjue DAI ; Qingying XIAN ; Wenyu ZHU
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(4):509-516
AIM:To explore the efficacy and safe-ty of fecal microbiota transplantation combined with immune checkpoint inhibitors(ICIs)for malig-nant tumor patients with failed multi line anti-tu-mor treatment and concomitant cachexia,and to explore the changes in blood immunity and intesti-nal microbial environment in patients.METHODS:Five patients with malignant tumors who failed multi line anti-tumor treatment were enrolled and treated with ICIs combined with fecal microbiota transplantation.The efficacy was evaluated every 2-3 cycles,and adverse reactions were observed.Fe-cal 16srRNA gene sequencing and serum immuno-logical indicators were dynamically detected.RE-SULTS:Except for one patient who died 2.5 months after transplantation due to excessive tumor bur-den at enrollment,the overall survival of the re-maining four patients were extended(7.4,8.3,28.5,52.3 months).One patient with multiple intra-cranial metastases of lung adenocarcinoma signifi-cantly reduced the intracranial metastasis after in-testinal microbiota transplantation and almost dis-appeared.The serum IL-2,IL-10,TGF-β and other indicators of patients increased rapidly and then slowly decreased with the increase of transplanta-tion time,and finally were higher than before trans-plantation,with statistical differences.16srRNA gene sequencing analysis revealed significant differ-ences in the overall distribution of gut microbiota in patients after transplantation,gradually ap-proaching healthy transplant donors.All patients did not experience grade 2 or above adverse reac-tions,and the safety was good.CONCLUSION:For patients with malignant tumors,the combination of fecal microbiota transplantation and immuno-therapy may improve their quality of life,serum im-mune environment,and intestinal microbiota com-position,have a positive impact on survival progno-sis,and are safe and controllable,opening up new treatment methods for end-stage patients.
5.Research hotspots and trends in application of tissue engineering in peripheral nerve injury
Xiaoxuan ZHAO ; Shuaiyi LIU ; Zheng XING ; Qingwen LI ; Xiaolei CHU ; Qi LI
Chinese Journal of Tissue Engineering Research 2025;29(30):6591-6600
BACKGROUND:Peripheral nerve injuries can cause severe functional disabilities in patients,and long-segment nerve defects often fail to regenerate spontaneously.In recent years,tissue engineering techniques have gradually been applied to the repair of long-segment nerve injuries,yet research hotspots and development trends are unclear.OBJECTIVE:To analyze the research hotspots and trends in the field of peripheral nerve tissue engineering over the past 20 years using bibliometric software.METHODS:CiteSpace 6.2R6 software was employed to conduct highly cited analysis and keyword analysis on peripheral nerve tissue engineering literature published from 2004 to 2024 in the Web of Science and China National Knowledge Infrastructure(CNKI)databases.The keyword analysis encompasses keyword co-occurrence analysis,keyword clustering analysis,keyword timeline analysis,and keyword emergence analysis.RESULTS AND CONCLUSION:A total of 2 961 articles from the Web of Science database and 1171 articles from the CNKI database were included.The number of publications in the Web of Science database showed fluctuations but exhibited an overall increasing trend year by year,while the publication volume in the CNKI database remained relatively stable annually.Most of the top ten most cited articles in the Web of Science database were review articles.The results of the keyword analysis from Web of Science and CNKI databases indicated that the most studied nerve tissue engineering materials over the past 20 years include silk fibroin,collagen,chitosan,polycaprolactone,polylactic acid,and graphene.The biochemical cues investigated in these materials include olfactory ensheathing cells,Schwann cells,stem cells,and nerve growth factors.The most commonly employed external physical factor is electrical stimulation applied to the materials.Among various tissue engineering techniques,electrospinning technology and 3D printing technology have been the most extensively researched.
6.Exploratory study of fecal microbiota transplantation combined with immune checkpoint inhibitors in the treatment of end-stage malig-nant tumor patients
Yunqian CHU ; Ya XUE ; Hua JIANG ; Chunjian QI ; Hanjue DAI ; Qingying XIAN ; Wenyu ZHU
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(4):509-516
AIM:To explore the efficacy and safe-ty of fecal microbiota transplantation combined with immune checkpoint inhibitors(ICIs)for malig-nant tumor patients with failed multi line anti-tu-mor treatment and concomitant cachexia,and to explore the changes in blood immunity and intesti-nal microbial environment in patients.METHODS:Five patients with malignant tumors who failed multi line anti-tumor treatment were enrolled and treated with ICIs combined with fecal microbiota transplantation.The efficacy was evaluated every 2-3 cycles,and adverse reactions were observed.Fe-cal 16srRNA gene sequencing and serum immuno-logical indicators were dynamically detected.RE-SULTS:Except for one patient who died 2.5 months after transplantation due to excessive tumor bur-den at enrollment,the overall survival of the re-maining four patients were extended(7.4,8.3,28.5,52.3 months).One patient with multiple intra-cranial metastases of lung adenocarcinoma signifi-cantly reduced the intracranial metastasis after in-testinal microbiota transplantation and almost dis-appeared.The serum IL-2,IL-10,TGF-β and other indicators of patients increased rapidly and then slowly decreased with the increase of transplanta-tion time,and finally were higher than before trans-plantation,with statistical differences.16srRNA gene sequencing analysis revealed significant differ-ences in the overall distribution of gut microbiota in patients after transplantation,gradually ap-proaching healthy transplant donors.All patients did not experience grade 2 or above adverse reac-tions,and the safety was good.CONCLUSION:For patients with malignant tumors,the combination of fecal microbiota transplantation and immuno-therapy may improve their quality of life,serum im-mune environment,and intestinal microbiota com-position,have a positive impact on survival progno-sis,and are safe and controllable,opening up new treatment methods for end-stage patients.
7.Research hotspots and trends in application of tissue engineering in peripheral nerve injury
Xiaoxuan ZHAO ; Shuaiyi LIU ; Zheng XING ; Qingwen LI ; Xiaolei CHU ; Qi LI
Chinese Journal of Tissue Engineering Research 2025;29(30):6591-6600
BACKGROUND:Peripheral nerve injuries can cause severe functional disabilities in patients,and long-segment nerve defects often fail to regenerate spontaneously.In recent years,tissue engineering techniques have gradually been applied to the repair of long-segment nerve injuries,yet research hotspots and development trends are unclear.OBJECTIVE:To analyze the research hotspots and trends in the field of peripheral nerve tissue engineering over the past 20 years using bibliometric software.METHODS:CiteSpace 6.2R6 software was employed to conduct highly cited analysis and keyword analysis on peripheral nerve tissue engineering literature published from 2004 to 2024 in the Web of Science and China National Knowledge Infrastructure(CNKI)databases.The keyword analysis encompasses keyword co-occurrence analysis,keyword clustering analysis,keyword timeline analysis,and keyword emergence analysis.RESULTS AND CONCLUSION:A total of 2 961 articles from the Web of Science database and 1171 articles from the CNKI database were included.The number of publications in the Web of Science database showed fluctuations but exhibited an overall increasing trend year by year,while the publication volume in the CNKI database remained relatively stable annually.Most of the top ten most cited articles in the Web of Science database were review articles.The results of the keyword analysis from Web of Science and CNKI databases indicated that the most studied nerve tissue engineering materials over the past 20 years include silk fibroin,collagen,chitosan,polycaprolactone,polylactic acid,and graphene.The biochemical cues investigated in these materials include olfactory ensheathing cells,Schwann cells,stem cells,and nerve growth factors.The most commonly employed external physical factor is electrical stimulation applied to the materials.Among various tissue engineering techniques,electrospinning technology and 3D printing technology have been the most extensively researched.
8.ACOT11 Gene Knockout Aggravates Kidney Tissue Fibrosis in UUO Mice
Bo-liang KE ; Chu-jiang HE ; Qi-lin TANG ; Wei-ming MOU ; Yan ZHUANG ; Yi SHAO
Progress in Modern Biomedicine 2025;25(9):1441-1451
Objective:To explore the role and possible mechanism of ACOT11 in renal fibrosis model mice.Methods:A mouse model of renal fibrosis was established by unilateral ureteral obstruction(UUO)(Sham group and UUO7 group),and the expression of ACOT11 in the kidneys of UUO induced fibrosis mouse models was detected by protein immunoblotting and real-time fluorescence quantitative PCR(qRT-PCR).Subsequently,immunohistochemistry,Masson staining,H&E staining,PAS staining,and other experimental methods were used to detect the expression levels of fibrosis biomarkers fibronectin,α-SMA,and COL-1 in the kidneys of control and experimental group mice.In addition,by constructing ACOT11 gene knockout model mice and using the gene knockout model mice to construct a renal fibrosis model,the expression levels of fibrosis biomarkers such as fibronectin,α-SMA,COL-1,as well as fibrosis mechanism pathway related indicators TGF-β and Smad2 in the kidneys of each group of mice were further detected.Results:The results of WB and qRT-PCR experiments showed that the expression of ACOT11 in the kidney tissue of UUO model mice was significantly reduced compared to the Sham group.After knocking out the ACOT11 gene,H&E staining,PAS staining,and Masson staining showed that pathological inflammatory reactions such as abnormal glomerular and tubular structures,inflammatory cell infiltration and interstitial fibrous tissue proliferation in mice were significantly aggravated compared to the control group,and the expression of fibrosis markers Fibronectin,α-SMA,and COL-1 was significantly higher than that of the control group.Conclusion:ACOT11 plays a protective role in mice with unilateral ureteral obstruction model.After ACOT11 gene knockout,the fibrosis biomarkers of the mouse kidney increases and the degree of fibrosis worsens.
9.Causal relationship between 91 inflammatory proteins and cervical disc degeneration
Shuaiyi LIU ; Xiaoxuan ZHAO ; Qi LI ; Zheng XING ; Qingwen LI ; Xiaolei CHU
Chinese Journal of Tissue Engineering Research 2025;29(17):3732-3740
BACKGROUND:Cervical disc degeneration is a common degenerative disease,and inflammatory proteins play an important role in cervical disc degeneration,but the specific mechanisms involved remain to be thoroughly investigated.OBJECTIVE:Using the Mendelian randomization method to assess the potential causal relationship between 91 inflammatory proteins and cervical disc degeneration.METHODS:Genome-wide association analysis statistics for 91 inflammatory proteins(from GCST90274758 to GCST90274848)were obtained from the Genome-Wide Association Analysis Catalog of publicly available genome-wide association analysis data and genome-wide association analysis data for cervical disc degeneration from the Finngen database(finngen_R10_M13_CERVICDISCV).Inverse variance weighting,MR-Egger regression,weighted median,weighted modeling,and simple modeling were used to investigate the causal relationship between inflammatory proteins and cervical disc degeneration.Sensitivity analyses were performed to test whether the results of the Mendelian randomization analysis were reliable,and then the inverse Mendelian randomization analysis was performed in the same way.RESULTS AND CONCLUSION:The results of the forward analysis showed that a total of six inflammatory proteins were significantly and causally associated with cervical disc degeneration,of which glial cell lineage-derived neurotrophic factor(odds ratio(OR)=1.095,95%confidence interval(CI):1.012-1.184,P=0.023),interleukin 4(OR=1.094,95%CI:1.002-1.194,P=0.045)and monocyte chemotactic protein-1 levels(OR=1.062,95%CI:1.001-1.127,P=0.048)showed a direct positive causal association with the risk of cervical disc degeneration;interleukin 17C(OR=0.906,95%CI:0.839-0.979,P=0.013),interleukin 18(OR=0.924,95%CI:0.866-0.986,P=0.017)and interleukin 2 levels(OR=0.894,95%CI:0.821-0.973,P=0.010)showed a direct negative causal association with the risk of cervical disc degeneration.The results of the inverse analysis showed that when cervical disc degeneration was used as exposure data,there was no significant causal relationship with any of the 91 inflammatory proteins.The results of the sensitivity analysis showed that the Cochran's Q test for the two-way Mendelian randomization,the MR-Egger regression method,and the MR-PRESSO results had P values greater than 0.05,indicating that there was no significant heterogeneity or multiplicity in the analysis of the causal effect between inflammatory proteins and cervical disc degeneration.To conclude,there may be a relatively significant potential causal relationship between glial cell line-derived neurotrophic factor,interleukin 4,monocyte chemotactic protein-1,interleukin 17C levels,interleukin 18,and interleukin 2 levels and cervical disc degeneration,which provides valuable clues for research on the potential mechanisms of cervical disc degeneration as well as early prevention and drug treatment of cervical disc degeneration.
10.Different frequencies of electrical stimulation promote recovery from peripheral nerve injury
Minqi LIU ; Mingwei GAO ; Xiaolei CHU ; Zheng XING ; Shihao LI ; Ning DING ; Yajie LI ; Qi LI
Chinese Journal of Tissue Engineering Research 2025;29(14):3061-3069
BACKGROUND:Electrical stimulation is an effective treatment plan for peripheral nerve injuries,but different frequencies of electrical stimulation have different mechanisms and applications for promoting peripheral nerve recovery.OBJECTIVE:To systematically sort out and summarize the roles and applications of different frequencies of electrical stimulation in the treatment of peripheral nerve injuries,and to deeply analyze the advantages and disadvantages of various methods in order to find the most beneficial treatment strategy for patients'nerve recovery.METHODS:Computer-based searches were conducted in the China National Knowledge Infrastructure(CNKI)and PubMed databases from the inception of the databases to May 2024.The search terms included"peripheral nerve injury,electrical stimulation,low frequency electrical stimulation,medium frequency electrical stimulation,high frequency electrical stimulation,TENS,interfering electricity,short wave,ultrashort wave,frequency"in both English and Chinese.Ultimately,74 relevant documents were included for analysis.RESULTS AND CONCLUSION:Peripheral nerve injury,a common clinical disease,can cause sensory and motor dysfunction in patients.Low-frequency electrical stimulation can promote cell proliferation and accelerate the expression of nerve growth factor within the cell after electrical stimulation,promote macrophage recruitment and infiltration,accelerate the clearance of myelin debris,and promote myelin regeneration of damaged axons.Medium-frequency electrical stimulation can act on deeper tissues and is better for relieving neuropathic pain.High-frequency electrical stimulation can promote the proliferation of Schwann cells and macrophages,inhibit inflammatory factors,and rapidly recruit cells to the site of nerve injury,accelerating the speed of nerve repair.Different frequencies of electrical stimulation have their own advantages in promoting the recovery of peripheral nerve injuries,but there are still some issues,such as differences in the site of electrical stimulation and the treatment plans for various disease types.

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