Denervation often results in skeletal muscle atrophy.Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy.At the epigenetic level,mi RNAs are thought t...Denervation often results in skeletal muscle atrophy.Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy.At the epigenetic level,mi RNAs are thought to be highly involved in the pathophysiological progress of denervated muscles.We used mi RNA microarrays to determine mi RNA expression profiles from a typical slow muscle（soleus muscle） and a typical fast muscle（tibialis anterior muscle） at an early denervation stage in a rat model.Results showed that mi R-206,mi R-195,mi R-23 a,and mi R-30 e might be key factors in the transformation process from slow to fast muscle in denervated slow muscles.Additionally,certain mi RNA molecules（mi R-214,mi R-221,mi R-222,mi R-152,mi R-320,and Let-7e） could be key regulatory factors in the denervated atrophy process involved in fast muscle.Analysis of signaling pathway networks revealed the mi RNA molecules that were responsible for regulating certain signaling pathways,which were the final targets（e.g.,p38 MAPK pathway; Pax3/Pax7 regulates Utrophin and follistatin by HDAC4; IGF1/PI3K/Akt/m TOR pathway regulates atrogin-1 and Mu RF1 expression via Fox O phosphorylation）.Our results provide a better understanding of the mechanisms of denervated skeletal muscle pathophysiology.展开更多
The present study observed sciatic nerve and gastrocnemius muscle changes in denervated rats using morphology methods,and assessed expression of perlecan,an extracellular matrix component,which is located at the skele...The present study observed sciatic nerve and gastrocnemius muscle changes in denervated rats using morphology methods,and assessed expression of perlecan,an extracellular matrix component,which is located at the skeletal muscle cell surface as acetylcholine esterase,as well as synaptophysin,a synaptic marker.Results showed degeneration and inflammation following transection of the sciatic nerve.In addition,the sciatic nerve-dominated skeletal muscle degenerated with mild inflammation,indicating that skeletal muscle atrophy primarily contributed to denervation-induced nutritional disturbances.With prolonged injury time(1-4 weeks post-injury),perlecan expression gradually decreased and reached the lowest level at 4 weeks,but synaptophysin expression remained unchanged after denervation.Results suggested that perlecan expression was more sensitive to denervation and reflected regional extracellular matrix changes following denervation.展开更多
In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Gro...In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Group A served as controls without any treatment. Rats in groups B were injected intraperitoneally with 0.2 mL PBS and those in group C were injected intraperitoneally with 0.2 mL PBS+100 ymol/L, 0.2 mL N-[N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT, a gamma-secretase inhibitor that suppresses Notch signaling) respectively, on postoperative days 1, 3, 7, 10, and 14 in a model of denervation-induced skeletal muscle fibrosis by right sciatic nerve transection. Five rats from each group were euthanized on postoperative days 1, 7, 14, and 28 to collect the right gastrocnemii, and hematoxylin and eosin (HE) staining, immunohistochemistry test, real-time PCR, and Western blotting were performed to assess connective tissue hyperplasia and fibroblast density as well as expression of Notch 1, Jagged 1, and Notch downstream molecules Hes 1 and collagen I (COL I) on day 28. There was no significant difference in HE-stained fibroblast density between group B and C on postoperative day 1. However, fibroblast density was significantly higher in group B than in group C on postoperative days 7, 14, and 28. Notch 1, Jagged 1, Hes 1, and COL I proteins in the gastrocnemius were expressed at very low levels in group A but at high levels in group B. Expression levels of these proteins were significantly lower in group C than in group B (P<0.05), but they were higher in group C than in group A (P<0.05) on postoperative day 28. We are led to conclude that locking the Notch signaling pathway inhibits fibrosis progression of denervated skeletal muscle. Thus, it may be a new approach for treatment of fibrosis of denervated skeletal muscle.展开更多
Denervation-induced skeletal muscle atrophy can potentially cause the decline in the quality of life of patients and an increased risk of mortality.Complex pathophysiological mechanisms with dynamic alterations have b...Denervation-induced skeletal muscle atrophy can potentially cause the decline in the quality of life of patients and an increased risk of mortality.Complex pathophysiological mechanisms with dynamic alterations have been documented in skeletal muscle atrophy resulting from innervation loss.Hence,an in-depth comprehension of the key mechanisms and molecules governing skeletal muscle atrophy at varying stages,along with targeted treatment and protection,becomes essential for effective atrophy management.Our preliminary research categorizes the skeletal muscle atrophy process into four stages using microarray analysis.This review extensively discusses the pathways and molecules potentially implicated in regulating the four stages of denervation and muscle atrophy.Notably,drugs targeting the reactivare oxygen species stage and the inflammation stage assume critical roles.Timely intervention during the initial atrophy stages can expedite protection against skeletal muscle atrophy.Additionally,pharmaceutical intervention in the ubiquitin-proteasome pathway associated with atrophy and autophagy lysosomes can effectively slow down skeletal muscle atrophy.Key molecules within this stage encompass MuRF1,MAFbx,LC3II,p62/SQSTM1,etc.This review also compiles a profile of drugs with protective effects against skeletal muscle atrophy at distinct postdenervation stages,thereby augmenting the evidence base for denervation-induced skeletal muscle atrophy treatment.展开更多
Purpose: The objective of the present study was to determine whether a denervated muscle extract(DmEx) could stimulate satellite cell response in denervated muscle.Methods: Wistar rats were divided into 4 groups: norm...Purpose: The objective of the present study was to determine whether a denervated muscle extract(DmEx) could stimulate satellite cell response in denervated muscle.Methods: Wistar rats were divided into 4 groups: normal rats, normal rats treated with DmEx, denervated rats, and denervated rats treated with DmEx. The soleus muscles were examined using immunohistochemical techniques for proliferating cell nuclear antigen, desmin, and myogenic differentiation antigen(MyoD), and electron microscopy was used for analysis of the satellite cells.Results: The results indicate that while denervation causes activation of satellite cells, DmEx also induces myogenic differentiation of cells localized in the interstitial space and the formation of new muscle fibers. Although DmEx had a similar effect in nature on innervated and denervated muscles, this response was of greater magnitude in denervated vs. intact muscles.Conclusion: Our study shows that treatment of denervated rats with DmEx potentiates the myogenic response in atrophic denervated muscles.展开更多
Spinal cord injury(SCI)population with injury below T10 or injury to the cauda equina region is characterized by denervated muscles,extensive muscle atrophy,infiltration of intramuscular fat and formation of fibrous t...Spinal cord injury(SCI)population with injury below T10 or injury to the cauda equina region is characterized by denervated muscles,extensive muscle atrophy,infiltration of intramuscular fat and formation of fibrous tissue.These morphological changes may put individuals with SCI at higher risk for developing other diseases such as various cardiovascular diseases,diabetes,obesity and osteoporosis.Currently,there is no available rehabilitation intervention to rescue the muscles or restore muscle size in SCI individuals with lower motor neuron denervation.We,hereby,performed a review of the available evidence that supports the use of electrical stimulation in restoration of denervated muscle following SCI.Long pulse width stimulation(LPWS)technique is an upcoming method of stimulating denervated muscles.Our primary objective is to explore the best stimulation paradigms(stimulation parameters,stimulation technique and stimulation wave)to achieve restoration of the denervated muscle.Stimulation parameters,such as the pulse duration,need to be 100–1000 times longer than in innervated muscles to achieve desirable excitability and contraction.The use of electrical stimulation in animal and human models induces muscle hypertrophy.Findings in animal models indicate that electrical stimulation,with a combination of exercise and pharmacological interventions,have proven to be effective in improving various aspects like relative muscle weight,muscle cross sectional area,number of myelinated regenerated fibers,and restoring some level of muscle function.Human studies have shown similar outcomes,identifying the use of LPWS as an effective strategy in increasing muscle cross sectional area,the size of muscle fibers,and improving muscle function.Therefore,displaying promise is an effective future stimulation intervention.In summary,LPWS is a novel stimulation technique for denervated muscles in humans with SCI.Successful studies on LPWS of denervated muscles will help in translating this stimulation technique to the clinical level as a rehabilitation intervention after SCI.展开更多
In order to investigate the biological function of transforming growth factor-β1（TGF-β1） during fibrosis in denervated skeletal muscle,we recruited sciatic nerve injury model of SD rats in which denervated gastroc...In order to investigate the biological function of transforming growth factor-β1（TGF-β1） during fibrosis in denervated skeletal muscle,we recruited sciatic nerve injury model of SD rats in which denervated gastrocnemius was isolated for analysis.At different time points after operation,denervated muscle was examined by several methods.Masson trichrome staining showed morphological changes of denervated skeletal muscle.Quantitative RT-PCR detected the rapid increase of TGF-β1 expression at mRNA level after nerve injury.It was found that a peak of TGF-β1 mRNA expression appeared one week post-operation.The expression of collagen Ⅰ（COL Ⅰ） mRNA was up-regulated in the nerve injury model as well,and reached highest level two weeks post-injury.Immunoblot revealed similar expression pattern of TGF-β1 and COL Ⅰ in denervated muscles at protein level.In addition,we found that the area of the gastrocnemius muscle fiber was decreased gradually along with increased interstitital fibrosis.Interestingly,this pathological change could be prevented,at least partly,by local injection of TGF-β1 antibodies,which could be contributed to the reduced production of COL Ⅰ by inhibiting function of TGF-β1.Taken together,in this study,we demonstrated that the expression of TGF-β1 was increased significantly in denervated skeletal muscle,which might play a crucial role during muscle fibrosis after nerve transection.展开更多
The neuromuscular junction becomes progressively less receptive to regenerating axons if nerve repair is delayed for a long period of time. It is difficult to ascertain the denervated muscle＇s residual receptivity by...The neuromuscular junction becomes progressively less receptive to regenerating axons if nerve repair is delayed for a long period of time. It is difficult to ascertain the denervated muscle＇s residual receptivity by time alone. Other sensitive markers that closely correlate with the extent of denervation should be found. After a denervated muscle develops a fibrillation potential, muscle fiber conduction velocity, muscle fiber diameter, muscle wet weight, and maximal isometric force all decrease; remodeling increases neuromuscular junction fragmentation and plantar area, and expression of myogenesis-related genes is initially up-regulated and then down-regulated. All these changes correlate with both the time course and degree of denervation. The nature and time course of these denervation changes in muscle are reviewed from the literature to explore their roles in assessing both the degree of detrimental changes and the potential success of a nerve repair. Fibrillation potential amplitude, muscle fiber conduction velocity, muscle fiber diameter, mRNA expression levels of myogenic regulatory factors and nicotinic acetylcholine receptor could all reflect the severity and length of denervation and the receptiveness of denervated muscle to regenerating axons, which could possibly offer an important clue for surgical choices and predict the outcomes of delayed nerve repair.展开更多
Nerve injury commonly contributes to irreversible functional impairment, reconstruction of the function of muscle is big challenge. In denervated skeletal muscle, therapid expression of MyoD mRNA and protein also occu...Nerve injury commonly contributes to irreversible functional impairment, reconstruction of the function of muscle is big challenge. In denervated skeletal muscle, therapid expression of MyoD mRNA and protein also occurs during early postdenervation, which suggested that the function of denervation-induced MyoD may be to prevent denervation-induced skeletal muscle atrophy. However, the detail mechanism is not clear. Therefore, in this study, we established a stable-transfected MyoD L6 cell line. After the operation for cutting the rats’ tibial nerve, the MyoD-L6 cells were injected in the gastrocnemius, the function of the gastronemius was monitored. It was found that injected the MyoD-L6 cells could attenuate the muscle atrophy and dysfunction. Therefore, overexpression of MyoD could serve as a new therapy strategy to cure denervation-induced dysfunction of skeletal muscle.展开更多
This study investigated the protective effect of EGB761 on blood vessels of denervated gastrocnemius of rat and its possible mechanism. Fifteen male adult SD rats were randomly divided into three groups： normal contr...This study investigated the protective effect of EGB761 on blood vessels of denervated gastrocnemius of rat and its possible mechanism. Fifteen male adult SD rats were randomly divided into three groups： normal control group （n=3）, control group （n=6） and EGB761-treated group （n=6）. The rats in the control and EGB761-treated group underwent a neurotomy to bilateral sciatic nerves. Then, they were administered EGB761 [100 mg/（kg.d）] and isovolumic normal saline, respectively by gavage everyday. No treatment was given to the rats in the normal control group. Gastrocnemius was harvested at 1 and 3 week（s） postoperatively in each group. Immunohistochemical method was used to detect the ratio of capillary/fiber （CFR） of denervated gastrocnemius and the expression of VEGF, fetal liver kinase -l（Flk-1） receptor and HSP70 in the vascular wall. The results showed that in the normal control group, VEGF, Flk-1 and HSP70 were expressed in the vessel wall of gastrocnemius, with Flk-1 expressed only in the endothelial cell of vessels. CFR in the EGB761-treated group was significantly higher than that in the control group at 1 week and 3 week（s） after neurotomy. The expression of VEGF and Flk-1 in the vessel wall of both control and EGB761-treated group was much lower than that in the normal control group, and the expression of these proteins in the EGB761-treated group was decreased as compared with that in the control group. The expression of HSP70 in the vessel wall of both control and EGB761-treated groups was enhanced when compared with that in the normal control group, and it was substantially augmented in the EGB761-treated group in comparison to the control group. It was concluded that EGB761 has a protective effect on blood vessels of denervated gastrocnemius, which is related to the increased HSP70 expression but not the expression of VEGF and its receptor Flk-1.展开更多
In treating patients with obstetric brachial plexus palsy,we noticed that denervated intrinsic muscles of the hand become irreversibly atrophic at a faster than denervated biceps.In a rat model of obstetric brachial p...In treating patients with obstetric brachial plexus palsy,we noticed that denervated intrinsic muscles of the hand become irreversibly atrophic at a faster than denervated biceps.In a rat model of obstetric brachial plexus palsy,denervated intrinsic musculature of the forepaw entered the irreversible atrophy far earlier than denervated biceps.In this study,isobaric tags for relative and absolute quantitation were examined in the intrinsic musculature of forepaw and biceps on denervated and normal sides at 3 and 5 weeks to identify dysregulated proteins.Enrichment of pathways mapped by those proteins was analyzed by Kyoto Encyclopedia of Genes and Genomes analysis.At 3 weeks,119 dysregulated proteins in denervated intrinsic musculature of the forepaw were mapped to nine pathways for muscle regulation,while 67 dysregulated proteins were mapped to three such pathways at 5 weeks.At 3 weeks,27 upregulated proteins were mapped to five pathways involving inflammation and apoptosis,while two upregulated proteins were mapped to one such pathway at 5 weeks.At 3 and 5 weeks,53 proteins from pathways involving regrowth and differentiation were downregulated.At 3 weeks,64 dysregulated proteins in denervated biceps were mapped to five pathways involving muscle regulation,while,five dysregulated proteins were mapped to three such pathways at 5 weeks.One protein mapped to inflammation and apoptotic pathways was upregulated from one pathway at 3 weeks,while three proteins were downregulated from two other pathways at 5 weeks.Four proteins mapped to regrowth and differentiation pathways were upregulated from three pathways at 3 weeks,while two proteins were downregulated in another pathway at 5 weeks.These results implicated inflammation and apoptosis as critical factors aggravating atrophy of denervated intrinsic muscles of the hand during obstetric brachial plexus palsy.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Fudan University,China(approval No.DF-325)in January 2015.展开更多
Background:Neurological injuries or diseases may cause ankle–foot deformities that seriously affect patients’quality of life.Objective:This study aimed to explore the feasibility of the Ilizarov technique for treati...Background:Neurological injuries or diseases may cause ankle–foot deformities that seriously affect patients’quality of life.Objective:This study aimed to explore the feasibility of the Ilizarov technique for treating complex ankle–foot deformity with neurotrophic disorders.Methods:In this retrospective study,10 patients,including 6 males and 4 females,with complex ankle–foot deformities with nerve injury were treated from January 2014 to May 2019.The age of the patients ranged from 13 to 57 years with an average of 27.9 years.The reasons of nerve injury were as follows:sequelae of spina bifida in five patients,post-traumatic injury of the common peroneal nerve and tibial nerve in four patients,and subacute degeneration of the spinal cord in one patient.Minimally invasive surgery was used for osteotomy,muscle strength balance,and external ring frame fixation,and various deformities were gradually corrected after the operation.The ankle–foot function was evaluated using the American Orthopedic Foot and Ankle Society(AOFAS)Ankle–Hindfoot Score before surgery and at long-term follow-up after surgery.Results:All 10 patients were followed up for 12 months to 3 years,with an average of 1.9 years.The deformities of all 10 patients were corrected;and of the 10 patients,three partially recovered their nerve function.A significant difference(p<0.001)between the AOFAS score(81.6±10.45)evaluated in the long-term follow-up and that evaluated preoperatively(31.1±14.69).The AOFAS comprehensive score was excellent in two patients,good in six patients,and fair in two patients.Conclusion:The Ilizarov technique combined with minimally invasive osteotomy and muscle strength balance could safely correct complex ankle–foot deformities with neurotrophic disorders.展开更多
OBJECTIVE: To observe the survival of embryonic motoneurons after they were transplanted into the denervated skeletal muscles and to find a new method to retard the atrophy of denervated muscles. METHODS: Dissociated ...OBJECTIVE: To observe the survival of embryonic motoneurons after they were transplanted into the denervated skeletal muscles and to find a new method to retard the atrophy of denervated muscles. METHODS: Dissociated embryonic motoneurons prelabled with 5-bromo-2'-deoxyuridine (Brdur) on the embryonic days 12 were injected into the denervated gastrocnemius muscles of adult rats. Then gastrocnemius muscles were processed with Nissl staining, acetylcholinesterase staining and Brdur immunocytochemical staining to show the implanted motoneurons at 9 and 22 weeks post-transplantation. Myofibrillar ATPase staining was used to show the morphology of muscle fibers. The rats in experimental group were implanted with embryonic motoneurons in the predenervation muscles, while the rats in control group were injected with just culture medium without motoneurons. RESULTS: Embryonic motoneurons survived, developed and extended long axons to form neuromuscular junctions with the denervated muscles. The differentiation of muscle fibers and fiber type grouping occurred among bigger fibers in experimental group. The transverse area was smaller and there was no apparent fiber type grouping in control group. CONCLUSIONS: Embryonic motoneurons can survive, develop and reinnervate denervated muscles after being transplanted into denervated muscles. It is worth further investigating on ameliorating the atrophy of denervated muscle.展开更多
Neuropathic pain is a chronic condition caused by damage or dysfunction in the nervous system.While the spleen may influence neuropathic pain,its role has been poorly understood.This study demonstrates that the spleen...Neuropathic pain is a chronic condition caused by damage or dysfunction in the nervous system.While the spleen may influence neuropathic pain,its role has been poorly understood.This study demonstrates that the spleen plays a crucial role in regulating neuropathic pain through the bed nucleus of the stria terminalis(BNST)-paraventricular nucleus of the hypothalamus(PVN)neural circuit in a chronic constriction injury(CCI)mouse model.Splenectomy,splenic denervation,or splenic sympathectomy significantly increased the mechanical withdrawal threshold(MWT)and reduced macrophage infiltration in the dorsal root ganglia(DRG)of CCI mice.Pseudorabies virus injections into the spleen revealed connections to the BNST and PVN in the brain.Chemogenetic inhibition of the BNST-PVN circuit increased macrophage infiltration in the DRG and decreased the MWT;these effects were reversed by splenectomy,splenic denervation,or sympathectomy.These findings underscore the critical role of the spleen,regulated by the BNST-PVN circuit,in neuropathic pain.展开更多
BACKGROUND Hypertension(HTN)is a prevalent chronic health condition that significantly increases the risk of cardiovascular diseases-associated mortalities.Despite the use of antihypertensive medications,numerous pati...BACKGROUND Hypertension(HTN)is a prevalent chronic health condition that significantly increases the risk of cardiovascular diseases-associated mortalities.Despite the use of antihypertensive medications,numerous patients fail to achieve guidelinerecommended blood pressure(BP)targets.AIM To evaluates the efficacy of catheter-based ultrasound renal denervation(uRDN)for the treatment of HTN.METHODS Relevant studies were identified through searches in PubMed,Embase,the Cochrane Library,Web of Science,and China National Knowledge Infrastructure,with a cut-off date at April 1,2024.A random-effects model was employed in this study to mitigate potential biases.The risk of bias for included studies was assessed using the Cochrane Risk of Bias assessment tool.Statistical analyses were conducted using Review Manager version 5.3.This meta-analysis incorporated four studies encompassing a total of 627 patients.The reporting bias of this study was deemed acceptable.RESULTS Compared to the Sham group,the uRDN group demonstrated a significant reduction in daytime ambulatory systolic BP(SBP)[mean difference(MD)-3.87 mmHg,95%confidence interval(CI):-7.02 to-0.73,P=0.02],office SBP(MD-4.13 mmHg,95%CI:-7.15 to-1.12,P=0.007),and home SBP(MD-5.51 mmHg,95%CI:-8.47 to-2.55,P<0.001).However,there was no statistically significant reduction observed in either 24-hour or nighttime ambulatory SBP levels.Subgroup analysis shows that uRDN can significantly reduce the SBP in patients with non-resistant HTN(MD-6.19 mmHg,MD-6.00 mmHg,MD-7.72 mmHg,MD-5.02 mmHg,MD-3.61 mmHg).CONCLUSION The current evidence suggests that uRDN may effectively reduce home,office,and daytime SBP in patients with HTN,particularly in those with non-resistant HTN.展开更多
Background:Although widely used,the rat model remains poorly transferable to humans for peripheral nerve regeneration studies.The rabbit is a much better choice from an anatomical perspective.However,it remains little...Background:Although widely used,the rat model remains poorly transferable to humans for peripheral nerve regeneration studies.The rabbit is a much better choice from an anatomical perspective.However,it remains little used due to the lack of available literature.The aim of this article is to demonstrate the feasibility and effectiveness of an electrophysiological protocol combined with a motor function assessment to analyze nerve repair.Methods:Ten white New Zealand rabbits underwent a 4 cm transection of the fibular nerve.Autograft regeneration over 36 weeks was compared to non-repaired controls.The compound muscle action potential(CMAP)was recorded in the tibialis anterior and the extensor digitorum brevis.An electromyogram(EMG)was obtained after needle insertion and resting muscle activity recording.The electrophysiological results were compared to the toe spread index(TSI),which assesses the motor functional recovery promoted by fibular nerve regeneration.Results:The autograft group regeneration starts between weeks 18 and 21 and normal EMG was observed around the 30th week.These electrophysiological results were compared to the well-defined toe spread reflex.This motor test showed a significant functional return of 59%at 36 weeks(p<0.05).Rabbits regain nearly 80%of their muscle mass.Conclusion:Nerve conduction allows detection of nerve regeneration of the muscle while electromyography indicates when muscle activity returns to normal.These studies are reliable and non-invasive techniques to evaluate fibular nerve regeneration in the rabbit's hindlimb.Nonetheless,it is necessary to have qualified personnel,since inter-manipulator variations have been observed.展开更多
Pancreatic cancer is a highly lethal malignancy characterized by rapid progression and increasing global incidence and mortality rates.Although surgery remains the only potentially curative treatment,most patients are...Pancreatic cancer is a highly lethal malignancy characterized by rapid progression and increasing global incidence and mortality rates.Although surgery remains the only potentially curative treatment,most patients are ineligible for surgical intervention at diagnosis.For those with unresectable pancreatic cancer,palliative therapies such as radiotherapy and systemic treatments are the primary options.In recent decades,interventional therapies have emerged as promising alternatives in the treatment landscape of pancreatic cancer,including transcatheter arterial infusion,ablation techniques,stent placement,and brachytherapy.Thesemethods are recognized for their effectiveness in improving both survival outcomes and patients'quality of life.This review explores the historical development,current applications,and future potential of interventional therapies for pancreatic cancer.展开更多
BACKGROUND Postoperative atrial fibrillation(POAF)is a complication after cardiac surgeries associated with increased morbidity and hospital stay.Surgical cardiac dener-vation,which reduces autonomic input to the hear...BACKGROUND Postoperative atrial fibrillation(POAF)is a complication after cardiac surgeries associated with increased morbidity and hospital stay.Surgical cardiac dener-vation,which reduces autonomic input to the heart,has been proposed as a good preventive against POAF.However,evidence on its effectiveness remains incon-sistent.AIM To evaluate the impact of surgical cardiac denervation on the incidence of POAF and related clinical outcomes.METHODS This meta-analysis adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.A literature search was conducted across PubMed,Cochrane,ScienceDirect,and EMBASE up to April 2025 using a preformed search strategy using Medical Subject Headings terms and free-text keywords.Risk of bias assessment was done via Risk of Bias 2.0 and Risk Of Bias In Non-randomized Studies-of Interventions tools.Study analysis was performed using Review Manager version 5.4,with heterogeneity assessed via I^(2) values and appropriate fixed-or randomeffects models applied.RESULTS Five studies(N=1266)were included,with 627 patients undergoing cardiac denervation and 639 serving as controls.Denervation did not significantly reduce overall POAF[odds ratio=0.71;95%confidence interval(CI):0.32-1.58;P=0.40;I^(2)=83%],but was associated with a significant reduction in persistent atrial fibrillation(odds ratio=0.19;95%CI:0.10-0.36;P<0.00001;I^(2)=0%).Among secondary outcomes,only postoperative serum magnesium levels significantly reduced the denervation group(mean difference:-0.07 mmol/L;95%CI:-0.08 to-0.06;P<0.00001).Other outcomes,such as reoperation for bleeding,stroke/transient ischemic attack,length of hospital stay,30-day mortality,and postoperative drainage,did not show any significant difference.CONCLUSION Surgical cardiac denervation does not significantly reduce overall POAF but does lower the incidence of persistent atrial fibrillation.It is also shown to decrease serum magnesium levels.Other outcomes,such as stroke,reoperation,and hospital stay,showed no significant differences.展开更多
Delay of axon regeneration after peripheral nerve injury usually leads to progressive muscle atrophy and poor functional recovery. The Wnt/β-catenin signaling pathway is considered to be one of the main molecular mec...Delay of axon regeneration after peripheral nerve injury usually leads to progressive muscle atrophy and poor functional recovery. The Wnt/β-catenin signaling pathway is considered to be one of the main molecular mechanisms that lead to skeletal muscle atrophy in the elderly. We hold the hypothesis that the innervation of target muscle can be promoted by accelerating axon regeneration and decelerating muscle cell degeneration so as to improve functional recovery of skeletal muscle following peripheral nerve injury. This process may be associated with the Wnt/β-catenin signaling pathway. Our study designed in vitro cell models to simulate myelin regeneration and muscle atrophy. We investigated the effects of SB216763, a glycogen synthase kinase 3 beta inhibitor, on the two major murine cell lines RSC96 and C2C12 derived from Schwann cells and muscle satellite cells. The results showed that SB216763 stimulated the Schwann cell migra- tion and myotube contraction. Quantitative polymerase chain reaction results demonstrated that myelin related genes, myelin associated glycoprotein and cyclin-D1, muscle related gene myogenin and endplate-associated gene nicotinic acetylcholine receptors levels were stimulated by SB216763. Immunocytochemical staining revealed that the expressions of ^-catenin in the RSC96 and C2C12 cytosolic and nuclear compartments were increased in the SB216763-treated cells. These findings confirm that the glycogen synthase kinase 3 beta in- hibitor, SB216763, promoted the myelination and myotube differentiation through the Wnt/β-catenin signaling pathway and contributed to nerve remyelination and reduced denervated muscle atrophy after peripheral nerve injury.展开更多
基金supported by the National Natural Science Foundation of China,No.81101365,81171722 and 81000805
文摘Denervation often results in skeletal muscle atrophy.Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy.At the epigenetic level,mi RNAs are thought to be highly involved in the pathophysiological progress of denervated muscles.We used mi RNA microarrays to determine mi RNA expression profiles from a typical slow muscle（soleus muscle） and a typical fast muscle（tibialis anterior muscle） at an early denervation stage in a rat model.Results showed that mi R-206,mi R-195,mi R-23 a,and mi R-30 e might be key factors in the transformation process from slow to fast muscle in denervated slow muscles.Additionally,certain mi RNA molecules（mi R-214,mi R-221,mi R-222,mi R-152,mi R-320,and Let-7e） could be key regulatory factors in the denervated atrophy process involved in fast muscle.Analysis of signaling pathway networks revealed the mi RNA molecules that were responsible for regulating certain signaling pathways,which were the final targets（e.g.,p38 MAPK pathway; Pax3/Pax7 regulates Utrophin and follistatin by HDAC4; IGF1/PI3K/Akt/m TOR pathway regulates atrogin-1 and Mu RF1 expression via Fox O phosphorylation）.Our results provide a better understanding of the mechanisms of denervated skeletal muscle pathophysiology.
基金supported by the National Natural Science Foundation of China,No.30900300/C1002
文摘The present study observed sciatic nerve and gastrocnemius muscle changes in denervated rats using morphology methods,and assessed expression of perlecan,an extracellular matrix component,which is located at the skeletal muscle cell surface as acetylcholine esterase,as well as synaptophysin,a synaptic marker.Results showed degeneration and inflammation following transection of the sciatic nerve.In addition,the sciatic nerve-dominated skeletal muscle degenerated with mild inflammation,indicating that skeletal muscle atrophy primarily contributed to denervation-induced nutritional disturbances.With prolonged injury time(1-4 weeks post-injury),perlecan expression gradually decreased and reached the lowest level at 4 weeks,but synaptophysin expression remained unchanged after denervation.Results suggested that perlecan expression was more sensitive to denervation and reflected regional extracellular matrix changes following denervation.
文摘In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Group A served as controls without any treatment. Rats in groups B were injected intraperitoneally with 0.2 mL PBS and those in group C were injected intraperitoneally with 0.2 mL PBS+100 ymol/L, 0.2 mL N-[N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT, a gamma-secretase inhibitor that suppresses Notch signaling) respectively, on postoperative days 1, 3, 7, 10, and 14 in a model of denervation-induced skeletal muscle fibrosis by right sciatic nerve transection. Five rats from each group were euthanized on postoperative days 1, 7, 14, and 28 to collect the right gastrocnemii, and hematoxylin and eosin (HE) staining, immunohistochemistry test, real-time PCR, and Western blotting were performed to assess connective tissue hyperplasia and fibroblast density as well as expression of Notch 1, Jagged 1, and Notch downstream molecules Hes 1 and collagen I (COL I) on day 28. There was no significant difference in HE-stained fibroblast density between group B and C on postoperative day 1. However, fibroblast density was significantly higher in group B than in group C on postoperative days 7, 14, and 28. Notch 1, Jagged 1, Hes 1, and COL I proteins in the gastrocnemius were expressed at very low levels in group A but at high levels in group B. Expression levels of these proteins were significantly lower in group C than in group B (P<0.05), but they were higher in group C than in group A (P<0.05) on postoperative day 28. We are led to conclude that locking the Notch signaling pathway inhibits fibrosis progression of denervated skeletal muscle. Thus, it may be a new approach for treatment of fibrosis of denervated skeletal muscle.
基金supported by the National Natural Science Foundation of China(Grant No.32200940)Science and Technology Bureau of Nantong(Grant Nos.JC2020101,JC2021085)Municipal Health Commission of Nantong(Grant No.MA2020019).
文摘Denervation-induced skeletal muscle atrophy can potentially cause the decline in the quality of life of patients and an increased risk of mortality.Complex pathophysiological mechanisms with dynamic alterations have been documented in skeletal muscle atrophy resulting from innervation loss.Hence,an in-depth comprehension of the key mechanisms and molecules governing skeletal muscle atrophy at varying stages,along with targeted treatment and protection,becomes essential for effective atrophy management.Our preliminary research categorizes the skeletal muscle atrophy process into four stages using microarray analysis.This review extensively discusses the pathways and molecules potentially implicated in regulating the four stages of denervation and muscle atrophy.Notably,drugs targeting the reactivare oxygen species stage and the inflammation stage assume critical roles.Timely intervention during the initial atrophy stages can expedite protection against skeletal muscle atrophy.Additionally,pharmaceutical intervention in the ubiquitin-proteasome pathway associated with atrophy and autophagy lysosomes can effectively slow down skeletal muscle atrophy.Key molecules within this stage encompass MuRF1,MAFbx,LC3II,p62/SQSTM1,etc.This review also compiles a profile of drugs with protective effects against skeletal muscle atrophy at distinct postdenervation stages,thereby augmenting the evidence base for denervation-induced skeletal muscle atrophy treatment.
文摘Purpose: The objective of the present study was to determine whether a denervated muscle extract(DmEx) could stimulate satellite cell response in denervated muscle.Methods: Wistar rats were divided into 4 groups: normal rats, normal rats treated with DmEx, denervated rats, and denervated rats treated with DmEx. The soleus muscles were examined using immunohistochemical techniques for proliferating cell nuclear antigen, desmin, and myogenic differentiation antigen(MyoD), and electron microscopy was used for analysis of the satellite cells.Results: The results indicate that while denervation causes activation of satellite cells, DmEx also induces myogenic differentiation of cells localized in the interstitial space and the formation of new muscle fibers. Although DmEx had a similar effect in nature on innervated and denervated muscles, this response was of greater magnitude in denervated vs. intact muscles.Conclusion: Our study shows that treatment of denervated rats with DmEx potentiates the myogenic response in atrophic denervated muscles.
文摘Spinal cord injury(SCI)population with injury below T10 or injury to the cauda equina region is characterized by denervated muscles,extensive muscle atrophy,infiltration of intramuscular fat and formation of fibrous tissue.These morphological changes may put individuals with SCI at higher risk for developing other diseases such as various cardiovascular diseases,diabetes,obesity and osteoporosis.Currently,there is no available rehabilitation intervention to rescue the muscles or restore muscle size in SCI individuals with lower motor neuron denervation.We,hereby,performed a review of the available evidence that supports the use of electrical stimulation in restoration of denervated muscle following SCI.Long pulse width stimulation(LPWS)technique is an upcoming method of stimulating denervated muscles.Our primary objective is to explore the best stimulation paradigms(stimulation parameters,stimulation technique and stimulation wave)to achieve restoration of the denervated muscle.Stimulation parameters,such as the pulse duration,need to be 100–1000 times longer than in innervated muscles to achieve desirable excitability and contraction.The use of electrical stimulation in animal and human models induces muscle hypertrophy.Findings in animal models indicate that electrical stimulation,with a combination of exercise and pharmacological interventions,have proven to be effective in improving various aspects like relative muscle weight,muscle cross sectional area,number of myelinated regenerated fibers,and restoring some level of muscle function.Human studies have shown similar outcomes,identifying the use of LPWS as an effective strategy in increasing muscle cross sectional area,the size of muscle fibers,and improving muscle function.Therefore,displaying promise is an effective future stimulation intervention.In summary,LPWS is a novel stimulation technique for denervated muscles in humans with SCI.Successful studies on LPWS of denervated muscles will help in translating this stimulation technique to the clinical level as a rehabilitation intervention after SCI.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30872627)
文摘In order to investigate the biological function of transforming growth factor-β1（TGF-β1） during fibrosis in denervated skeletal muscle,we recruited sciatic nerve injury model of SD rats in which denervated gastrocnemius was isolated for analysis.At different time points after operation,denervated muscle was examined by several methods.Masson trichrome staining showed morphological changes of denervated skeletal muscle.Quantitative RT-PCR detected the rapid increase of TGF-β1 expression at mRNA level after nerve injury.It was found that a peak of TGF-β1 mRNA expression appeared one week post-operation.The expression of collagen Ⅰ（COL Ⅰ） mRNA was up-regulated in the nerve injury model as well,and reached highest level two weeks post-injury.Immunoblot revealed similar expression pattern of TGF-β1 and COL Ⅰ in denervated muscles at protein level.In addition,we found that the area of the gastrocnemius muscle fiber was decreased gradually along with increased interstitital fibrosis.Interestingly,this pathological change could be prevented,at least partly,by local injection of TGF-β1 antibodies,which could be contributed to the reduced production of COL Ⅰ by inhibiting function of TGF-β1.Taken together,in this study,we demonstrated that the expression of TGF-β1 was increased significantly in denervated skeletal muscle,which might play a crucial role during muscle fibrosis after nerve transection.
基金sponsored by the Armed Forces Institute of Regenerative Medicine award number W81XWH-08-2-0034supported by the Sundt Fellowship fund,Department of Neurologic Surgery,Mayo Clinic,USA
文摘The neuromuscular junction becomes progressively less receptive to regenerating axons if nerve repair is delayed for a long period of time. It is difficult to ascertain the denervated muscle＇s residual receptivity by time alone. Other sensitive markers that closely correlate with the extent of denervation should be found. After a denervated muscle develops a fibrillation potential, muscle fiber conduction velocity, muscle fiber diameter, muscle wet weight, and maximal isometric force all decrease; remodeling increases neuromuscular junction fragmentation and plantar area, and expression of myogenesis-related genes is initially up-regulated and then down-regulated. All these changes correlate with both the time course and degree of denervation. The nature and time course of these denervation changes in muscle are reviewed from the literature to explore their roles in assessing both the degree of detrimental changes and the potential success of a nerve repair. Fibrillation potential amplitude, muscle fiber conduction velocity, muscle fiber diameter, mRNA expression levels of myogenic regulatory factors and nicotinic acetylcholine receptor could all reflect the severity and length of denervation and the receptiveness of denervated muscle to regenerating axons, which could possibly offer an important clue for surgical choices and predict the outcomes of delayed nerve repair.
文摘Nerve injury commonly contributes to irreversible functional impairment, reconstruction of the function of muscle is big challenge. In denervated skeletal muscle, therapid expression of MyoD mRNA and protein also occurs during early postdenervation, which suggested that the function of denervation-induced MyoD may be to prevent denervation-induced skeletal muscle atrophy. However, the detail mechanism is not clear. Therefore, in this study, we established a stable-transfected MyoD L6 cell line. After the operation for cutting the rats’ tibial nerve, the MyoD-L6 cells were injected in the gastrocnemius, the function of the gastronemius was monitored. It was found that injected the MyoD-L6 cells could attenuate the muscle atrophy and dysfunction. Therefore, overexpression of MyoD could serve as a new therapy strategy to cure denervation-induced dysfunction of skeletal muscle.
文摘This study investigated the protective effect of EGB761 on blood vessels of denervated gastrocnemius of rat and its possible mechanism. Fifteen male adult SD rats were randomly divided into three groups： normal control group （n=3）, control group （n=6） and EGB761-treated group （n=6）. The rats in the control and EGB761-treated group underwent a neurotomy to bilateral sciatic nerves. Then, they were administered EGB761 [100 mg/（kg.d）] and isovolumic normal saline, respectively by gavage everyday. No treatment was given to the rats in the normal control group. Gastrocnemius was harvested at 1 and 3 week（s） postoperatively in each group. Immunohistochemical method was used to detect the ratio of capillary/fiber （CFR） of denervated gastrocnemius and the expression of VEGF, fetal liver kinase -l（Flk-1） receptor and HSP70 in the vascular wall. The results showed that in the normal control group, VEGF, Flk-1 and HSP70 were expressed in the vessel wall of gastrocnemius, with Flk-1 expressed only in the endothelial cell of vessels. CFR in the EGB761-treated group was significantly higher than that in the control group at 1 week and 3 week（s） after neurotomy. The expression of VEGF and Flk-1 in the vessel wall of both control and EGB761-treated group was much lower than that in the normal control group, and the expression of these proteins in the EGB761-treated group was decreased as compared with that in the control group. The expression of HSP70 in the vessel wall of both control and EGB761-treated groups was enhanced when compared with that in the normal control group, and it was substantially augmented in the EGB761-treated group in comparison to the control group. It was concluded that EGB761 has a protective effect on blood vessels of denervated gastrocnemius, which is related to the increased HSP70 expression but not the expression of VEGF and its receptor Flk-1.
基金supported by the National Natural Science Foundation of China,No.816019591003263(to JXW)the National Basic Research Program of China(973 Program),No.2014CB542203(to LC)
文摘In treating patients with obstetric brachial plexus palsy,we noticed that denervated intrinsic muscles of the hand become irreversibly atrophic at a faster than denervated biceps.In a rat model of obstetric brachial plexus palsy,denervated intrinsic musculature of the forepaw entered the irreversible atrophy far earlier than denervated biceps.In this study,isobaric tags for relative and absolute quantitation were examined in the intrinsic musculature of forepaw and biceps on denervated and normal sides at 3 and 5 weeks to identify dysregulated proteins.Enrichment of pathways mapped by those proteins was analyzed by Kyoto Encyclopedia of Genes and Genomes analysis.At 3 weeks,119 dysregulated proteins in denervated intrinsic musculature of the forepaw were mapped to nine pathways for muscle regulation,while 67 dysregulated proteins were mapped to three such pathways at 5 weeks.At 3 weeks,27 upregulated proteins were mapped to five pathways involving inflammation and apoptosis,while two upregulated proteins were mapped to one such pathway at 5 weeks.At 3 and 5 weeks,53 proteins from pathways involving regrowth and differentiation were downregulated.At 3 weeks,64 dysregulated proteins in denervated biceps were mapped to five pathways involving muscle regulation,while,five dysregulated proteins were mapped to three such pathways at 5 weeks.One protein mapped to inflammation and apoptotic pathways was upregulated from one pathway at 3 weeks,while three proteins were downregulated from two other pathways at 5 weeks.Four proteins mapped to regrowth and differentiation pathways were upregulated from three pathways at 3 weeks,while two proteins were downregulated in another pathway at 5 weeks.These results implicated inflammation and apoptosis as critical factors aggravating atrophy of denervated intrinsic muscles of the hand during obstetric brachial plexus palsy.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Fudan University,China(approval No.DF-325)in January 2015.
基金the National Natural Science Foundation of China(Grant No.82172439).
文摘Background:Neurological injuries or diseases may cause ankle–foot deformities that seriously affect patients’quality of life.Objective:This study aimed to explore the feasibility of the Ilizarov technique for treating complex ankle–foot deformity with neurotrophic disorders.Methods:In this retrospective study,10 patients,including 6 males and 4 females,with complex ankle–foot deformities with nerve injury were treated from January 2014 to May 2019.The age of the patients ranged from 13 to 57 years with an average of 27.9 years.The reasons of nerve injury were as follows:sequelae of spina bifida in five patients,post-traumatic injury of the common peroneal nerve and tibial nerve in four patients,and subacute degeneration of the spinal cord in one patient.Minimally invasive surgery was used for osteotomy,muscle strength balance,and external ring frame fixation,and various deformities were gradually corrected after the operation.The ankle–foot function was evaluated using the American Orthopedic Foot and Ankle Society(AOFAS)Ankle–Hindfoot Score before surgery and at long-term follow-up after surgery.Results:All 10 patients were followed up for 12 months to 3 years,with an average of 1.9 years.The deformities of all 10 patients were corrected;and of the 10 patients,three partially recovered their nerve function.A significant difference(p<0.001)between the AOFAS score(81.6±10.45)evaluated in the long-term follow-up and that evaluated preoperatively(31.1±14.69).The AOFAS comprehensive score was excellent in two patients,good in six patients,and fair in two patients.Conclusion:The Ilizarov technique combined with minimally invasive osteotomy and muscle strength balance could safely correct complex ankle–foot deformities with neurotrophic disorders.
文摘OBJECTIVE: To observe the survival of embryonic motoneurons after they were transplanted into the denervated skeletal muscles and to find a new method to retard the atrophy of denervated muscles. METHODS: Dissociated embryonic motoneurons prelabled with 5-bromo-2'-deoxyuridine (Brdur) on the embryonic days 12 were injected into the denervated gastrocnemius muscles of adult rats. Then gastrocnemius muscles were processed with Nissl staining, acetylcholinesterase staining and Brdur immunocytochemical staining to show the implanted motoneurons at 9 and 22 weeks post-transplantation. Myofibrillar ATPase staining was used to show the morphology of muscle fibers. The rats in experimental group were implanted with embryonic motoneurons in the predenervation muscles, while the rats in control group were injected with just culture medium without motoneurons. RESULTS: Embryonic motoneurons survived, developed and extended long axons to form neuromuscular junctions with the denervated muscles. The differentiation of muscle fibers and fiber type grouping occurred among bigger fibers in experimental group. The transverse area was smaller and there was no apparent fiber type grouping in control group. CONCLUSIONS: Embryonic motoneurons can survive, develop and reinnervate denervated muscles after being transplanted into denervated muscles. It is worth further investigating on ameliorating the atrophy of denervated muscle.
基金supported by the National Natural Science Foundation of China(82201549)the Hubei Provincial Natural Science Foundation of China(220100579)the Guangdong Basic and Applied Basic Research Foundation(2021B1515120050 and 2023A1515110107).
文摘Neuropathic pain is a chronic condition caused by damage or dysfunction in the nervous system.While the spleen may influence neuropathic pain,its role has been poorly understood.This study demonstrates that the spleen plays a crucial role in regulating neuropathic pain through the bed nucleus of the stria terminalis(BNST)-paraventricular nucleus of the hypothalamus(PVN)neural circuit in a chronic constriction injury(CCI)mouse model.Splenectomy,splenic denervation,or splenic sympathectomy significantly increased the mechanical withdrawal threshold(MWT)and reduced macrophage infiltration in the dorsal root ganglia(DRG)of CCI mice.Pseudorabies virus injections into the spleen revealed connections to the BNST and PVN in the brain.Chemogenetic inhibition of the BNST-PVN circuit increased macrophage infiltration in the DRG and decreased the MWT;these effects were reversed by splenectomy,splenic denervation,or sympathectomy.These findings underscore the critical role of the spleen,regulated by the BNST-PVN circuit,in neuropathic pain.
基金Supported by Sichuan Provincial Medical Research Youth Innovation Project,No.Q22063Guang'an District People's Hospital Joint Development Research Project,No.2024 LHFZ04。
文摘BACKGROUND Hypertension(HTN)is a prevalent chronic health condition that significantly increases the risk of cardiovascular diseases-associated mortalities.Despite the use of antihypertensive medications,numerous patients fail to achieve guidelinerecommended blood pressure(BP)targets.AIM To evaluates the efficacy of catheter-based ultrasound renal denervation(uRDN)for the treatment of HTN.METHODS Relevant studies were identified through searches in PubMed,Embase,the Cochrane Library,Web of Science,and China National Knowledge Infrastructure,with a cut-off date at April 1,2024.A random-effects model was employed in this study to mitigate potential biases.The risk of bias for included studies was assessed using the Cochrane Risk of Bias assessment tool.Statistical analyses were conducted using Review Manager version 5.3.This meta-analysis incorporated four studies encompassing a total of 627 patients.The reporting bias of this study was deemed acceptable.RESULTS Compared to the Sham group,the uRDN group demonstrated a significant reduction in daytime ambulatory systolic BP(SBP)[mean difference(MD)-3.87 mmHg,95%confidence interval(CI):-7.02 to-0.73,P=0.02],office SBP(MD-4.13 mmHg,95%CI:-7.15 to-1.12,P=0.007),and home SBP(MD-5.51 mmHg,95%CI:-8.47 to-2.55,P<0.001).However,there was no statistically significant reduction observed in either 24-hour or nighttime ambulatory SBP levels.Subgroup analysis shows that uRDN can significantly reduce the SBP in patients with non-resistant HTN(MD-6.19 mmHg,MD-6.00 mmHg,MD-7.72 mmHg,MD-5.02 mmHg,MD-3.61 mmHg).CONCLUSION The current evidence suggests that uRDN may effectively reduce home,office,and daytime SBP in patients with HTN,particularly in those with non-resistant HTN.
基金The Quebec Cell,Tissue and Gene Therapy Network–ThéCell,a thematic network supported by the FRQCanadian Institutes of Health Research,Grant/Award Number:PJT-175015+1 种基金the Fonds de recherche du Québec(FRQ)through the research centre grant for the CHU de Québec-UniversitéLaval Research Center,Grant/Award Number:30641the FRQ,the Fondation du CHU de Québec-UniversitéLaval and from Neuro Québec。
文摘Background:Although widely used,the rat model remains poorly transferable to humans for peripheral nerve regeneration studies.The rabbit is a much better choice from an anatomical perspective.However,it remains little used due to the lack of available literature.The aim of this article is to demonstrate the feasibility and effectiveness of an electrophysiological protocol combined with a motor function assessment to analyze nerve repair.Methods:Ten white New Zealand rabbits underwent a 4 cm transection of the fibular nerve.Autograft regeneration over 36 weeks was compared to non-repaired controls.The compound muscle action potential(CMAP)was recorded in the tibialis anterior and the extensor digitorum brevis.An electromyogram(EMG)was obtained after needle insertion and resting muscle activity recording.The electrophysiological results were compared to the toe spread index(TSI),which assesses the motor functional recovery promoted by fibular nerve regeneration.Results:The autograft group regeneration starts between weeks 18 and 21 and normal EMG was observed around the 30th week.These electrophysiological results were compared to the well-defined toe spread reflex.This motor test showed a significant functional return of 59%at 36 weeks(p<0.05).Rabbits regain nearly 80%of their muscle mass.Conclusion:Nerve conduction allows detection of nerve regeneration of the muscle while electromyography indicates when muscle activity returns to normal.These studies are reliable and non-invasive techniques to evaluate fibular nerve regeneration in the rabbit's hindlimb.Nonetheless,it is necessary to have qualified personnel,since inter-manipulator variations have been observed.
基金supported by National Natural Science Foundation of China(No.82130060)Jiangsu Provincial Basic Research Program Natural Science Foundation-Frontier Leading Technology Basic Research Project(No.BK20232008)Jiangsu Provincial Special ProgramofMedical Science(No.BE2022855).
文摘Pancreatic cancer is a highly lethal malignancy characterized by rapid progression and increasing global incidence and mortality rates.Although surgery remains the only potentially curative treatment,most patients are ineligible for surgical intervention at diagnosis.For those with unresectable pancreatic cancer,palliative therapies such as radiotherapy and systemic treatments are the primary options.In recent decades,interventional therapies have emerged as promising alternatives in the treatment landscape of pancreatic cancer,including transcatheter arterial infusion,ablation techniques,stent placement,and brachytherapy.Thesemethods are recognized for their effectiveness in improving both survival outcomes and patients'quality of life.This review explores the historical development,current applications,and future potential of interventional therapies for pancreatic cancer.
文摘BACKGROUND Postoperative atrial fibrillation(POAF)is a complication after cardiac surgeries associated with increased morbidity and hospital stay.Surgical cardiac dener-vation,which reduces autonomic input to the heart,has been proposed as a good preventive against POAF.However,evidence on its effectiveness remains incon-sistent.AIM To evaluate the impact of surgical cardiac denervation on the incidence of POAF and related clinical outcomes.METHODS This meta-analysis adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.A literature search was conducted across PubMed,Cochrane,ScienceDirect,and EMBASE up to April 2025 using a preformed search strategy using Medical Subject Headings terms and free-text keywords.Risk of bias assessment was done via Risk of Bias 2.0 and Risk Of Bias In Non-randomized Studies-of Interventions tools.Study analysis was performed using Review Manager version 5.4,with heterogeneity assessed via I^(2) values and appropriate fixed-or randomeffects models applied.RESULTS Five studies(N=1266)were included,with 627 patients undergoing cardiac denervation and 639 serving as controls.Denervation did not significantly reduce overall POAF[odds ratio=0.71;95%confidence interval(CI):0.32-1.58;P=0.40;I^(2)=83%],but was associated with a significant reduction in persistent atrial fibrillation(odds ratio=0.19;95%CI:0.10-0.36;P<0.00001;I^(2)=0%).Among secondary outcomes,only postoperative serum magnesium levels significantly reduced the denervation group(mean difference:-0.07 mmol/L;95%CI:-0.08 to-0.06;P<0.00001).Other outcomes,such as reoperation for bleeding,stroke/transient ischemic attack,length of hospital stay,30-day mortality,and postoperative drainage,did not show any significant difference.CONCLUSION Surgical cardiac denervation does not significantly reduce overall POAF but does lower the incidence of persistent atrial fibrillation.It is also shown to decrease serum magnesium levels.Other outcomes,such as stroke,reoperation,and hospital stay,showed no significant differences.
基金funded by the National Basic Research Program of China(973 Program),No.2014CB542201the National High Technology Research and Development Program of China(863 Program),No.SS2015AA020501the National Natural Science Foundation of China(General Program),No.31571235,31771322,31671248,31571236,31271284,31171150,81171146,31471144,30971526,31100860,31040043,31371210,and 81372044
文摘Delay of axon regeneration after peripheral nerve injury usually leads to progressive muscle atrophy and poor functional recovery. The Wnt/β-catenin signaling pathway is considered to be one of the main molecular mechanisms that lead to skeletal muscle atrophy in the elderly. We hold the hypothesis that the innervation of target muscle can be promoted by accelerating axon regeneration and decelerating muscle cell degeneration so as to improve functional recovery of skeletal muscle following peripheral nerve injury. This process may be associated with the Wnt/β-catenin signaling pathway. Our study designed in vitro cell models to simulate myelin regeneration and muscle atrophy. We investigated the effects of SB216763, a glycogen synthase kinase 3 beta inhibitor, on the two major murine cell lines RSC96 and C2C12 derived from Schwann cells and muscle satellite cells. The results showed that SB216763 stimulated the Schwann cell migra- tion and myotube contraction. Quantitative polymerase chain reaction results demonstrated that myelin related genes, myelin associated glycoprotein and cyclin-D1, muscle related gene myogenin and endplate-associated gene nicotinic acetylcholine receptors levels were stimulated by SB216763. Immunocytochemical staining revealed that the expressions of ^-catenin in the RSC96 and C2C12 cytosolic and nuclear compartments were increased in the SB216763-treated cells. These findings confirm that the glycogen synthase kinase 3 beta in- hibitor, SB216763, promoted the myelination and myotube differentiation through the Wnt/β-catenin signaling pathway and contributed to nerve remyelination and reduced denervated muscle atrophy after peripheral nerve injury.
