1.Scientific basis for acupuncture combined with neural stem cells for repairing spinal cord injury
Xiaomeng HUANG ; Zhilan ZHANG ; Wenya SHANG ; Jing HUANG ; Huilin WEI ; Bing LI ; Yafeng REN
Chinese Journal of Tissue Engineering Research 2025;29(19):4111-4121
BACKGROUND:Spinal cord injury is a neurological disorder caused by traumatic or non-traumatic events,often leading to severe functional impairment below the injured segment.In recent years,neural stem cell transplantation has been considered to have significant therapeutic potential in regulating the inflammatory response after spinal cord injury,inhibiting excessive proliferation of glial scars,and promoting nerve regeneration. OBJECTIVE:To review and discuss the potential mechanism of action of acupuncture and neural stem cell transplantation therapy in inhibiting spinal cord injury-induced secondary injury,and to delve into the scientific basis for its treatment of spinal cord injury. METHODS:PubMed,Elsevier,WanFang,and CNKI databases were searched using"spinal cord injury,acupuncture,neural stem cells,SDF-1α/CXCR4 axis"as Chinese and English search terms.Totally 96 articles were finally included.The research findings of acupuncture combined with neural stem cells in the treatment of spinal cord injury were summarized and analyzed,and the mechanism of this combination therapy in the treatment of secondary injury after spinal cord injury was summarized. RESULTS AND CONCLUSION:(1)The stromal-derived factor 1α(SDF-1α)/chemokine receptor 4(CXCR4)axis plays a crucial role in neural stem cell transplantation for spinal cord injury.This signaling mechanism not only affects neural stem cell migration,proliferation,and differentiation,but is also a key factor in determining the efficiency of stem cell homing to the injury site.Therefore,the regulation of targeting this axis is of great significance in enhancing the therapeutic effect of spinal cord injury.(2)Acupuncture,as a traditional Chinese medicine therapy,shows unique advantages in the regulation of secondary injury in spinal cord injury.It can effectively reduce secondary injury after spinal cord injury by regulating inflammatory response,inhibiting apoptosis,improving microcirculation,reducing glial scar formation,and counteracting oxidative stress.(3)Acupuncture was also able to influence the expression and function of the SDF-1α/CXCR4 axis,thereby enhancing the homing and survival ability of neural stem cells and promoting nerve regeneration and functional recovery.(4)The therapy combining acupuncture and stem cell transplantation is an innovative treatment strategy for spinal cord injury and suitable for repairing neural circuits.It combines the wisdom of traditional Chinese medicine with the advantages of modern biotechnology,providing a new treatment option for spinal cord injury patients.However,this combination therapy is still in the research and exploration stage,and its long-term efficacy and safety need to be further verified.(5)Taken together,acupuncture and neural stem cell transplantation for the treatment of spinal cord injury has great potential for clinical application,but in-depth research and optimization of treatment options are still needed.In the future,we look forward to further revealing the efficacy mechanism and optimal indications of this therapy through more clinical trials and mechanism studies,so as to bring better hope of recovery and more efficient therapeutic effects to spinal cord injury patients.
2.Effect of Modified Chunzetang on Bladder Fibrosis and Detrusor Function in Rats with Neurogenic Bladder Urinary Retention Induced by Spinal Cord Injury via Regulating NF-κB/TGF-β1 Signaling Pathway
Zhenhua XU ; Yanjie LI ; Yafeng REN ; Haoyuan LIU ; Bochao ZHU ; Juan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):95-103
ObjectiveTo investigate the therapeutic effect and mechanism of modified Chunzetang on bladder fibrosis and detrusor function in rats with neurogenic bladder urinary retention induced by spinal cord injury. MethodsIn this study, an improved Hassan Shaker spinal cord transection method was used to establish a model of neurogenic bladder urinary retention induced by spinal cord injury, and rats with a spinal cord injury behavior score of 0 were selected for follow-up experiments. The selected rats were randomly divided into a model group (normal saline gavage), low-dose traditional Chinese medicine (TCM) group (gavage of 14.4 g·kg-1 modified Chunzetang), high-dose TCM group (gavage of 28.8 g·kg-1 modified Chunzetang), positive drug group [intraperitoneal injection of 0.05 g·kg-1 nuclear transcription factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC)], and combination group (intraperitoneal injection of 0.05 g·kg-1 PDTC + gavage of 28.8 g·kg-1 modified Chunzetang). The rats in these groups were administrated with corresponding drugs once a day for four weeks. The BL-420s biofunction acquisition system was used in the experiment to calculate the urodynamic indexes, and the isolated bladder was quickly weighed. The detrusor traction experiment was used to record the minimum bladder contraction tension and frequency in each group. The pathological morphology and tissue fibrosis of detrusor in each group observed by Hematoxycin-eosin (HE) staining and Masson staining were compared. The expression level of α-smooth muscle actin (α-SMA) was detected by immunohistochemistry. Western blot was used to detect the protein expression of NF-κB p65, nuclear transcription factor-κB suppressor protein α (IκBα), transforming growth factor-β1 (TGF-β1), type Ⅰ collagen (ColⅠ), and type Ⅲ collagen (ColⅢ) in bladder tissue of rats in each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the changes in serum levels of IL-6, IL-1β, and TNF-α. ResultsCompared with that in the sham operation group, the pressure at the urinary leakage point in the model group decreased (P<0.01), and the bladder mass, bladder contractile tension, maximum bladder capacity, and bladder compliance increased (P<0.05,P<0.01). HE staining showed that the arrangement of bladder epithelial cells was disordered, and the pathological manifestations such as mucosa and myometria neutrophil infiltration were obvious. The lamina propria structure was destroyed, and the muscle fiber arrangement was disordered. The interstitial widening and tissue edema were obvious. Masson staining showed that the bladder wall of the model group had more collagen fiber deposition, and the degree of detrusor fibrosis was more severe. The content of detrusor in the visual field was reduced. At the same time, the protein expressions of NF-κB p65, TGF-β1, IκBα, ColⅠ, and ColⅢ in bladder tissue of rats in the model group were significantly increased (P<0.01), and the serum levels of IL-6, IL-1β, and TNF-α were significantly increased (P<0.05). Compared with that in the model group, the pressure at the urinary leakage point in the modified Chunzetang and positive drug groups was increased (P<0.05), and the wet bladder weight, minimum bladder contractile tension, maximum bladder capacity, and bladder compliance were restored (P<0.05, P<0.01). HE and Masson showed that the bladder epithelial cells were relatively neatly arranged, and the structure of the bladder lamina propria was relatively stable. The detrusor bundles were arranged in an orderly manner, and the interstitium was narrow. The degree of tissue edema was relatively low, and the degree of bladder detrusor fibrosis in the modified Chunzetang and positive drug groups was reduced, while the degree of bladder detrusor fibrosis in the positive drug group and combination groups was not obvious. The results of Western blot showed that the expression of NF-κB p65, IκBα, TGF-β1, ColⅠ, and ColⅢ in bladder tissue, as well as the serum levels of IL-6, IL-1β, and TNF-α in modified Chunzetang and positive drug groups were significantly lower, and the expression of bladder tissue-related proteins and the serum levels of IL-6, IL-1β, and TNF-α in the TCM groups decreased significantly with the increase in dose (P<0.05). The results of immunohistochemistry suggested that modified Chunzetang could fully affect the expression of α-SMA in bladder tissue. ConclusionModified Chunzetang can inhibit collagen deposition in bladder tissue of rats with urinary retention induced by spinal cord injury, delay the occurrence and development of bladder fibrosis, and protect the normal contractile function of bladder detrusor, and its mechanism may be related to inhibiting the NF-κB/TGF-β1 signaling pathway, reducing the production of NF-κB p65, IκBα, TGF-β1, ColⅠ, ColⅢ, and other related proteins, and protecting the muscle strength of detrusor.
3.Application Progress of Virtual Reality Technology for the Treatment of Spinal Cord Injury
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):391-400
Spinal cord injury (SCI) is a prevalent neurological disorder that often results in motor, sensory, cognitive, balance, and walking impairments, and can even lead to pain, significantly affecting the physical and mental health and quality of life of patients. Conventional treatment methods, primarily conducted in hospital settings, tend to be monotonous and lack engagement, leading to low patients’ compliance, motivation and cooperation. In contrast, virtual reality (VR) technology can serve as an effective adjunctive therapeutic approach, immersing patients in simulated virtual environments for functional training in specific contexts and tasks, thereby providing a sense of real experience to achieve assessment and therapeutic outcomes. The interactive and engaging nature of VR technology markedly enhances patients’ interest and motivation in treatment, offering new possibilities for home-based rehabilitation and presenting patients with alternative treatment options. This review systematically introduces the application of VR technology in the treatment of patients with SCI, focusing on its roles in assessing functional impairments, improving motor function, enhancing balance and walking abilities, alleviating pain, and promoting recovery from cognitive and psychological disorders, as well as its impact on other functional impairments and its combined use with other technologies. Furthermore, this article delves into the current advantages and limitations of VR technology, aiming to deepen the understanding of VR among physicians and therapists, promote its widespread clinical application, advance the field of rehabilitation medicine, provide theoretical foundations and directions for future research, and offer new insights and references for clinical practice.
4.Predictive value of inflammatory cells and clinical features in prognosis for non-small cell lung cancer immunotherapy
Qingyue ZHENG ; Chunliang YAN ; Qishan XUE ; Yafeng LIU ; Liyun MA ; Xiyan REN
Chongqing Medicine 2024;53(16):2496-2502
Objective To investigate the predictive value of inflammatory cells and clinical features in the prognosis of immune checkpoint inhibitors (ICIs) treating non-small cell lung cancer (NSCLC).Methods The data of 163 cases of stage Ⅲ and Ⅳ NSCLC patients treated with the ICIs in this hospital from January 1,2017 to December 31,2022 were collected.The CT examination was conducted after 6-8 weeks treatment.The pa-tients were divided into the objective remission group[complete remission (CR)+partial remission (PR)]and non-objective remission group[stable disease (SD)+progressed disease (PD)],disease control group (CR+PR+SD) and non-disease control group (PD),persistent clinical benefit group (DCB) and non-DCB group.The differences in clinical features and inflammatory cells indicators were compared among the differ-ent groups.The receiver operating characteristic (ROC) curve was adopted to evaluate the predictive efficiency of the inflammatory cells indicators for DCB.The influencing factors analysis of progression free survival (PFS) time and overall survival (OS) time adopted the Cox regression analysis.Results The lymphocyte count (ALC) in the disease control group was higher than that in the non-disease control group.The neutro-phil to lymphocyte ratio (NLR),platelet-lymphocyte ratio (PLR) and mononuclear lymphocyte ratio (MLR) were lower than those in the non-disease control group.The proportions of squamous cell carcinoma,stage Ⅲ,ECOG score 0-1 point,adverse reactions in the DCB group were higher than those in the non-DCB group (P<0.05),the PLT count,NLR,PLR and MLR were lower than those in the non-DCB group (P<0.05). The ROC curve analysis results showed that PLT,NLR,PLR and MLR could serve as the indicators for pre-dicting DCB,the area under of ROC curve (AUC) was 0.633,0.602,0.635 and 0.604 respectively,the opti-mal cut off values were 187×109/L (P=0.004),5.0 (P=0.026),235 (P=0.003) and 0.35 (P=0.024) re-spectively.The multivariate Cox regression analysis showed that non-squamous carcinoma including adenocar-cinoma (HR=1.565,95%CI:1.057-2.316) and other pathologic types (HR=2.285,95%CI:1.326-3.936),ECOG score 2-3 points (HR=2.375,95%CI:1.652-3.415),AMC≥0.65×109/L (HR=1.847,95%CI:1.160-2.938) and PLR≥235 (HR=1.557,95%CI:1.016-2.386) were the independent risk factors for short PFS.The ECOG score 2-3 points (HR=4.615,95%CI:2.882-7.391),AMC≥0.65×109/L (HR=5.161,95%CI:2.984-8.925) and PLR ≥235 (HR=1.732,95%CI:1.059-2.833) were the independent risk fac-tors for short OS (P<0.05),and having adverse reactions (HR=0.472,95%CI:0.294-0.757) was the independ-ent protective factor for short OS (P<0.05).Conclusion Lower PLT,AMC,NLR,MLR and PLR,higher ALC,squamous cell carcinoma,TNM stage Ⅲ,ECOG score 0-1 point and immunotherapy related adverse reactions could prompt that the prognosis is good in ICIs treating advanced NSCLC.PLT,NLR,PLR and MLR could serve as the indicators for predicting DCB.
5.Advances in the Mechanism of Action of Hydrogel in Repairing Spinal Cord Injury
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(5):785-796
Spinal cord injury(SCI)is a severe central nervous system disease with poor prognosis,and the resulting severe sensory,motor or autonomic dysfunction greatly reduces patients'quality of life.Although considerable progress has been made in the treatment and care of SCI,the clinical efficacy and prognosis of SCI are not satisfactory due to the inability of drugs to be delivered directly to the site of SCI through the blood-spinal cord barrier and the fact that the local microenvironment after SCI is not conducive to the survival,differentiation,and proliferation of implanted stem cells.Due to its excellent mechanical properties,plasticity,and good biocompatibility and biodegradability,hydrogel can be used as a delivery system for loading stem cells or drugs,providing a favorable environment and controlling their release,and as a biological scaffold to support and guide axonal regeneration,which can effectively improve the therapeutic effect of spinal cord injury.This paper mainly reviews the classification and functional properties of hydrogels,and further discusses the research progress of hydrogels in SCI repair to improve the inhibitory microenvironment of spinal cord injury,promote nerve regeneration,promote angiogenesis,and promote the repair of the blood-spinal cord barrier,with the aim of providing a theoretical basis for the clinical application of hydrogels in the treatment of SCI as well as for exploring and developing future spinal cord regeneration strategies.
6.Mechanism of Yiyuan moxibustion on improving urinary storage function in rats with neurogenic bladder after spinal cord injury through the AMPK-Cx43 pathway
Zhilan ZHANG ; Xiaomeng HUANG ; Huilin WEI ; Jing HUANG ; Wenya SHANG ; Bing LI ; Yafeng REN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(6):835-844
Objective To investigate the effect and mechanism of Yiyuan moxibustion on urinary storage function in rats with neurogenic bladder(NB)after suprasacral spinal cord injury(SCI)based on adenosine activated protein kinase(AMPK)-connexin 43(Cx43)pathway.Methods Twelve female Sprague-Dawley rats were selected as the sham operation group using the random number table method,and 68 rats were used to prepare the suprasacral SCI model according to the modified Hassan Shaker spinal cord transection method.After the SCI model was stable,the standard NB model after SCI was screened out.The rats with successful modeling were divided into the model group(n=14),the Yiyuan moxibustion group(n=14),the inhibitor group(n=14),and the Yiyuan moxibustion+inhibitor group(n=14)according to the random number table method.The rats in the Yiyuan moxibustion group were treated with Yiyuan moxibustion.The rats in the inhibitor group were injected with AMPK inhibitor dorsomorphin(0.2 mg/kg)by tail vein.The rats in the Yiyuan moxibustion+inhibitor group were treated with Yiyuan moxibustion combined with tail vein injection of dorsomorphin(0.2 mg/kg).The sham operation group and the model group did not receive any intervention for 14 days.After the intervention,the bladder function of rats was evaluated by urodynamics.HE staining was used to observe morphological changes of the bladder tissue;the content of adenosine triphosphate(ATP)in bladder tissue was detected by colorimetry.The positive expressions of phosphorylated AMPK(p-AMPK),Cx43 and tyrosine protein kinase receptor(C-kit)in bladder tissue were detected by immunohistochemistry.The protein expressions of AMPK,p-AMPK,Cx43 and C-kit in bladder tissue were detected by Western blotting.Results Compared with the model group,the maximum bladder capacity and bladder compliance of the rats in the Yiyuan moxibustion group were increased,the leak point pressure was decreased,the cells in the Yiyuan moxibustion group were relatively regular and orderly,the vacuolar cells were reduced,and the tissue edema was reduced;the ATP content in the bladder tissue was decreased,the positive expression rate of p-AMPK was increased,the positive expression rate of Cx43 and C-kit were decreased,the protein expressions of p-AMPK protein was increased,the expression of Cx43 and C-kit were decreased,and the mRNA expression of Cx43 and C-kit were decreased(P<0.05).Compared with the Yiyuan moxibustion+inhibitor group,the maximum bladder capacity and bladder compliance of the rats in the Yiyuan moxibustion group increased,the leak point pressure decreased,the cells in the Yiyuan moxibustion group were arranged more closely and the tissue edema was reduced;the ATP content in the bladder tissue decreased,the positive expression rate of p-AMPK increased,the positive expression rates of Cx43 and C-kit decreased,the protein expression of p-AMPK increased,the protein expressions of Cx43 and C-kit decreased,and the mRNA expressions of Cx43 and C-kit decreased(P<0.05).Conclusion Yiyuan moxibustion can improve the urinary storage function of NB rats after suprasacral SCI,and its mechanism may be related to activating the AMPK-Cx43 pathway in bladder tissue,reducing the excitation transmission between bladder detrusor cells,thereby reducing the frequency of smooth muscle contraction.
7.Regulatory mechanisms and therapeutic strategies for pyroptosis after spinal cord injury
Wenya SHANG ; Yafeng REN ; Bing LI ; Huilin WEI ; Zhilan ZHANG ; Xiaomeng HUANG ; Jing HUANG
Chinese Journal of Tissue Engineering Research 2024;28(11):1772-1779
BACKGROUND:Cell death and neuroinflammation are two important targets in the treatment of spinal cord injury.Pyroptosis is a programmed cell death closely related to neuroinflammation and targeted inhibition of pyroptosis after spinal cord injury is a promising therapeutic strategy. OBJECTIVE:To summarize the molecular mechanism,positive and negative regulatory factors and therapeutic strategies of pyroptosis in spinal cord injury. METHODS:The search terms were"spinal cord injury,pyroptosis,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),Caspase,Gasdermin D(GSDMD),IL-1β,IL-18"and 93 English literatures included in PubMed and Web of Science were finally selected for review. RESULTS AND CONCLUSION:As a newly discovered programmed cell death,pyroptosis has been shown to play an important role in the secondary injury stage after spinal cord injury.Among the regulatory factors of pyroptosis after spinal cord injury,CD73,NRF2,GDF-11,dopamine,FANCC and miR-423-5P could inhibit pyroptosis,while TLR4 and Aopps could promote pyroptosis.In terms of treatment,the active ingredients of traditional Chinese medicine(paeonol,tripterine,betulinic acid,piperine,kaempferol,and camptothecin),exosomes of various cell origins,and some drugs(metformin,topotecan,lithium,zinc,and carbon monoxide-releasing molecule 3)can effectively inhibit pyroptosis and reduce secondary spinal cord injury,but the toxicity and specific dose of these drugs need to be further studied.The specific molecular mechanism by which pyroptosis aggravates spinal cord injury is still poorly understood.The role of non-classical pathways and other inflammasomes is worth further exploration.At present,the research on pyroptosis after spinal cord injury only stays at the animal experiment stage.There are no related clinical studies and no approved targeted therapeutic drugs.(6)The application of pyroptosis after spinal cord injury has great potential,and its specific regulatory mechanism should be further studied in the future to provide a new target for the treatment of spinal cord injury.
8.Establishment and evaluation of a textbook outcome prediction model of laparoscopic radical surgery for patients with pancreatic body and tail tumor
Senmao MU ; Bingyao LI ; Changqian TANG ; Yongnian REN ; Xingbo WEI ; Yuqi GUO ; Shipeng LI ; Yafeng WANG ; Liancai WANG ; Deyu LI
Chinese Journal of Hepatobiliary Surgery 2024;30(7):509-515
Objective:To analyze the influencing factors of not achieving textbook outcome (TO) after laparoscopic radical surgery in patients with malignant pancreatic body and tail tumor, and to establish and evaluate a nomogram for predicting the failure to achieve TO.Methods:The clinical data of 111 patients with malignant pancreatic body and tail tumors undergoing laparoscopic radical surgery in the Department of Hepatobiliary and Pancreatic Surgery in Henan Provincial People's Hospital from January 2020 to December 2022 were retrospectively analyzed, including 44 males and 67 females, aged (53.8±14.7) years. All patients were staged TNM I to II, including pancreatic ductal adenocarcinoma ( n=102, 91.9%), pancreatic neuroendocrine tumor ( n=5, 4.5%), and pancreatic intraductal papillary mucinous tumors ( n=4, 3.6%). The patients were randomly divided into a training set ( n=78) and a test set ( n=33) at a ratio of 7∶3. The 78 patients in the training set were further divided into TO group ( n=28) and control group ( n=50, not achieving TO). Based on the univariate and multivariate logistic regression analysis of training set, the influencing factors of failure to achieve TO after laparoscopic radical surgery in patients with pancreatic body and tail tumor were analyzed. A nomogram based on the multi-factors were established to predict the failure to achieve TO. Receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) were utilized to evaluate the nomogram. Results:There were significant differences in tumor diameter, positive lymph nodes, operation time and CT value of pancreas between the TO and control groups (all P<0.05). Multivariate logistic regression analysis showed that tumor diameter >4 cm ( OR=9.673, 95% CI: 2.198-42.579), positive lymph node ( OR=5.385, 95% CI: 1.514-19.154), pancreatic CT value ( OR=0.594, 95% CI: 0.392-0.902) were the influencing factors for patients who did not achieve TO (all P<0.05). Based on the results of multiple factors, a nomogram was established to predict the failure to achieve TO after laparoscopic radical surgery. The area under the ROC curve of the nomogram was 0.849 (95% CI: 0.757-0.940) and 0.873 (95% CI: 0.730-1.000) in the training and test sets, respectively. The calibration curve was close to the ideal curve and the predicted results of the nomogram matched well with the actual results. The DCA showed that the nomogram has obvious positive net benefit. Conclusion:The nomogram constructed with tumor diameter > 4 cm, positive lymph nodes and CT value of pancreas for prediction of the patients with pancreatic body and tail malignant tumor after laparoscopic radical surgery did not achieve TO has good performance.
9.Research progress of tumor microenvironment in the treatment of basal cell carcinoma
Yuchen ZHAO ; Yafeng LI ; Haihua REN ; Xiaobing WANG
Chinese Journal of Plastic Surgery 2023;39(8):921-926
Basal cell carcinoma has a low mortality rate, but its multiple occurrence, recurrence and metastasis have caused problems for patients and clinical work. In recent years, with the in-depth study of the tumor microenvironment in basal cell carcinoma, previous understanding and treatment concepts for basal cell carcinoma have been changed. This article focuses on the role of tumor microenvironment in the occurrence and development of basal cell carcinoma, and reviews the treatment method based on this.
10.Research progress of tumor microenvironment in the treatment of basal cell carcinoma
Yuchen ZHAO ; Yafeng LI ; Haihua REN ; Xiaobing WANG
Chinese Journal of Plastic Surgery 2023;39(8):921-926
Basal cell carcinoma has a low mortality rate, but its multiple occurrence, recurrence and metastasis have caused problems for patients and clinical work. In recent years, with the in-depth study of the tumor microenvironment in basal cell carcinoma, previous understanding and treatment concepts for basal cell carcinoma have been changed. This article focuses on the role of tumor microenvironment in the occurrence and development of basal cell carcinoma, and reviews the treatment method based on this.

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