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.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.
3.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.
4.Clinical study on the treatment of diabetic foot ulcer of lateral tibia bone removal microvessel regeneration combined with hyperbaric oxygen
Zhongwei JIA ; Jianping YU ; Han YU ; Yunxing SU ; Jinbin YU ; Zhilan REN ; Jie WEI
Chinese journal of nautical medicine and hyperbaric medicine 2018;25(1):22-26
Objective To investigate clinical efficacy of lateral tibia bone removal micro vessel regeneration combined with hyperbaric oxygen (HBO) in the treatment of diabetic foot ulcer.Methods A retrospective analysis was made on the clinical practice of lateral tibia bone removal micro vessel regeneration combined with HBO in 21 patients (the treatment group)with diabetic foot ulcer who received treatment in the hospital from November 2015 to March 2017.The patients in the treatment group were compared with the 21 patients (the control group) with diabetic foot ulcer who were treated with HBO at the same period.For the patients in the treatment group,a bone window with an area of about 2 cm × 10 cm was performed at medial surface of the affected lateral tibia,and a special external fixation lateral traction frame was placed and debridement was performed on the affected foot at the same time.On the first day after surgery,the patients received HBO therapy with a pressure of 0.20 MPa,once a day,10 days a treatment course,with a total of 3 courses.On the fifty day after surgery,the bone window was slowly removed laterally (1 mm/day).For the patients in the control group,debridement of the affected foot was performed,and on the first day after surgery,HBO therapy was also implemented in the control group with the same treatment scheme as the treatment group.Before surgery and 3 months after surgery,corresponding dada of healing time,ankle brachial index (ABI) and Michigan neuropathy sensation instruments (MNSI) were closely observed in the patients of the 2 groups.Results The patients of the two groups all had medical followed-ups for an average of 9.3 months.In the control group,the wound of one patient with Wagner Ⅴ failed to heal and in the end had amputation,but the wound of the remaining patients all healed,with an average healing time of (39.52 ± 8.43) days.The wound of the treatment group all healed,with an average healing time of (31.74 ± 6.12) days.Three months after surgery,the ABI level of the treatment group increased from pre-surgical level 0.56 ± 0.18 to post-surgical level 0.94 ± O.16,and the MNSI level decreased from pre-surgical level 5.92 ± 1.13 to post-surgical level 4.11 ± 1.25.Three months after surgery,the ABI level of the control group increased from pre-surgical level 0.54 ±0.21 to post-surgical level 0.81 ±0.20,and the MNSI level decreased from pre-surgical level 5.74 ± 1.26 to post-surgical level 4.98 ± 1.34.Statistical significance could be noted in wound healing time when comparisons were made between the two groups.Three months after surgery,statistical significance could also be found in ABI and MNSI levels as compared with those detected before surgery.The treatment group was superior to the control group,also with statistical significance.Conclusions Lateral tibia bone removal micro vessel regeneration could be used to reconstruct vasoganglion below lower leg and promote surrounding vessel and nerve function recovery.Combined with HBO therapy,it could promote wound surface healing,with the advantages of simple surgery,accurate curative effect,high success rate of limb-salvage.For this reason,it was one of the ideal methods for the treatment of diabetic foot ulcer.
5.Clinical study on the treatment of diabetic foot ulcer of lateral tibia bone removal microvessel regeneration combined with hyperbaric oxygen
Zhongwei JIA ; Jianping YU ; Han YU ; Yunxing SU ; Jinbin YU ; Zhilan REN ; Jie WEI
Chinese journal of nautical medicine and hyperbaric medicine 2018;25(1):22-26
Objective To investigate clinical efficacy of lateral tibia bone removal micro vessel regeneration combined with hyperbaric oxygen (HBO) in the treatment of diabetic foot ulcer.Methods A retrospective analysis was made on the clinical practice of lateral tibia bone removal micro vessel regeneration combined with HBO in 21 patients (the treatment group)with diabetic foot ulcer who received treatment in the hospital from November 2015 to March 2017.The patients in the treatment group were compared with the 21 patients (the control group) with diabetic foot ulcer who were treated with HBO at the same period.For the patients in the treatment group,a bone window with an area of about 2 cm × 10 cm was performed at medial surface of the affected lateral tibia,and a special external fixation lateral traction frame was placed and debridement was performed on the affected foot at the same time.On the first day after surgery,the patients received HBO therapy with a pressure of 0.20 MPa,once a day,10 days a treatment course,with a total of 3 courses.On the fifty day after surgery,the bone window was slowly removed laterally (1 mm/day).For the patients in the control group,debridement of the affected foot was performed,and on the first day after surgery,HBO therapy was also implemented in the control group with the same treatment scheme as the treatment group.Before surgery and 3 months after surgery,corresponding dada of healing time,ankle brachial index (ABI) and Michigan neuropathy sensation instruments (MNSI) were closely observed in the patients of the 2 groups.Results The patients of the two groups all had medical followed-ups for an average of 9.3 months.In the control group,the wound of one patient with Wagner Ⅴ failed to heal and in the end had amputation,but the wound of the remaining patients all healed,with an average healing time of (39.52 ± 8.43) days.The wound of the treatment group all healed,with an average healing time of (31.74 ± 6.12) days.Three months after surgery,the ABI level of the treatment group increased from pre-surgical level 0.56 ± 0.18 to post-surgical level 0.94 ± O.16,and the MNSI level decreased from pre-surgical level 5.92 ± 1.13 to post-surgical level 4.11 ± 1.25.Three months after surgery,the ABI level of the control group increased from pre-surgical level 0.54 ±0.21 to post-surgical level 0.81 ±0.20,and the MNSI level decreased from pre-surgical level 5.74 ± 1.26 to post-surgical level 4.98 ± 1.34.Statistical significance could be noted in wound healing time when comparisons were made between the two groups.Three months after surgery,statistical significance could also be found in ABI and MNSI levels as compared with those detected before surgery.The treatment group was superior to the control group,also with statistical significance.Conclusions Lateral tibia bone removal micro vessel regeneration could be used to reconstruct vasoganglion below lower leg and promote surrounding vessel and nerve function recovery.Combined with HBO therapy,it could promote wound surface healing,with the advantages of simple surgery,accurate curative effect,high success rate of limb-salvage.For this reason,it was one of the ideal methods for the treatment of diabetic foot ulcer.
6.A comparative study about the time of pregnancy and gestational age of SD rats by three methods
Zhilan HUANG ; Guihua YU ; Xing HUA ; Liuqi YANG ; Quanqing REN ; Yibulayin · ZAIMIRE ; Aierkeng · DILILUER ; Shataer · SAIMIRE ; Meiling ZHANG
Chinese Journal of Primary Medicine and Pharmacy 2017;24(21):3201-3204,后插1
Objective To explore more accurate method about the time of pregnancy and gestational age of SD rats.Methods 7 to 8-week-old SD rats (18 females,6 males) were selected,the ratios of male to female were 2:1,5:2,1:1 and 4:1.Through vaginal plug observation,vaginal smear method,weight comparison method to verify the exact date of pregnancy in the next morning.Results Vaginal observed at milky vaginal plug sperm could be observed as sickle rat sperm head.Body weight of pregnant rats changed obviously.Three detection methods were used to detect the pregnancy time for 18 females.The positive rate of vaginal plug observation was 5.6%.The positive rate of vaginal smear method was 44.4%.The false negative rate of vaginal smear method was 11.1%.The positive rate of body weight method was 11.1%.The false positive rate was 5.6%.Conclusion The accuracy of vaginal smear is higher than the vaginal plug method and weight comparison method,the vaginal plug method can be used as the premise of the other two methods.Comparison method can be used as supplementary that the other two methods missed.
7.The clinical value of early mechanical ventilation in treatment of patients with severe acute pancreatitis
Cong ZHANG ; Yingli CAI ; Zhilan LIU ; Shuiqun XIE ; Yanhua REN
Chinese Journal of Primary Medicine and Pharmacy 2016;23(11):1695-1699
Objective To study the effect of early mechanical ventilation in treatment of patients with severe acute pancreatitis(SAP).Methods Fifty-two patients with SAP admitted in the First People's Hospital of Zhaoqing from January 2010 to January 2015 were randomly allocated into two groups (n =26),early mechanical ventilation group(observation group) and conventional mechanical ventilation group(control group).Patients in the observation group treated with early lung protective ventilation when PaO2 < 13.3kPa.Patients in the control group treated without mechanical ventilation untill PaO2 < 8kPa.The symptoms,the extent of inflammatory reaction,the severity of lung lesions and the mortality of two groups were compared through monitoring vital signs,abdominal circumference,APACHE Ⅱ score,bladder pressure,oxygenation index (PaO2/FiO2),C reactive protein (CRP),procalcitonin (PCT),hospital stay and mortality.Results No statistically significant differences in the APACHE Ⅱ score,bladder pressure,oxygenation index,CRP and PCT in two groups before treatment were observed(P > 0.05).The APACHE Ⅱ score (12.8 ± 7.6) points,bladder pressure (14.9± 7.9) cmH2O,CRP (48.8 ± 30.1) rmg/L,PCT (1.25 ± 0.55) μg/L,mortality (3.84%) of the observation group after treatment were significantly lower than those of the control group (t =2.057,2.091,3.252,2.697,x2 =4.305,all P < 0.05),while the oxygenation index in the observation group [(300.0 ± 34.9) mmHg] was significantly higher than that in the control group [(278.1 ± 32.8) mmHg],the difference of the two groups was statistically significant (t =3.322,P < 0.05).Conclusion Early lung protective ventilation is safe and effective for treatment of the patients with SAP.
8.Clinicopathologic features of 234 cases with borderline ovarian tumors
Fie REN ; Jiangyan LOU ; Hui LIU ; Ping WANG ; Jiawen ZHANG ; Kaixuan YANG ; Hongjing WANG ; Mingrong QIE ; Zhilan PENG
Chinese Journal of Obstetrics and Gynecology 2009;44(2):116-120
Objective To determine the clinicopathologic characteristics and prognostic factors that may be used to predict the poor outcome of patients with borderline ovarian tumors. Methods All cases with borderline ovarian tumors treated in the West China Second University Hospital from January 2001 to June 2007 were analyzed retrospectively for elinicopathologic features, treatment parameters and outcome of treatment. Univariate and multivariate analyses were used to assess independent prognostic factors using the logistic regression model. Results The median age of 234 patients was 40. 1 years with a range of 14 to 80 years. There were 101 (43.2%), 94 (40.2% ) , 19 (8.1% ), 12 (5.1%) , 8 (3.4%) cases of serous, mutinous, mixed, endometrioid and clear cell tumors, respectively. Out of 234 cases, 182 (77.8%) underwent laparotomy and 45 ( 19.2% ) underwent laparoscopy. Seven women underwent laparoconversion. Fertility sparing surgery was performed on 119 cases (50.9% ) and radical surgery was performed on 115 cases (49.1% ). Totally 161 (68.8% ) patients had stage Ⅰ , 19 ( 8.1% ) had stage Ⅱ, 54 ( 23.1% ) had stage Ⅲ, and none had stage Ⅳ disease. Sixty-four women received postoperative chemotherapy. The median follow-up was 40 months with a range of 8 to 78 months. Recurrence was found in 26 cases (11.1%) during follow-up, and no tumor-related death was reported. The logistic regression model showed that surgery procedure ( OR=2.304, P=0.024), cyst rupture ( OR=2.213, P=0.038 ), stage ( OR= 4.114, P<0.01 ), microinvasion ( OR=2.291, P=0.046) and peritoneal implants ( OR=2.101, P = 0.016) were the five independent prognostic factors affecting recurrence. Conclusions Although patients with borderline ovarian tumors have an excellent prognosis, the risk of recurrence remains in some patients. Emphasis should be put on these patients with high risk factors and preventive strategies should be taken to prevent their progression.

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