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Objective:To observe any effect of exosomes derived from umbilical cord mesenchymal stem cells on pain, cartilage repair and the expression of transcriptional activator 3 (ATF-3) and growth related protein 43 (GAP-43) in the dorsal root ganglia (DRG), as well as to explore the mechanism of their relieving pain.Methods:Fifty-four male Sprague-Dawley rats were randomly divided into a sham-operation group, a monoiodoacetate group and an exosome group, each of 18. The knee cavities of the left hind limbs of all of the rats except those in the sham-operation group were injected with 50μl of monoiodoacetate to establish an arthritis pain model. The sham-operation group received only 50μl of saline solution as controls. Two weeks after the modelling, the knee joint cavities of the exosome group were injected with 50μl of exosomes, while the other two groups were injected with 50μl of normal saline. The rats′ mechanical and thermal pain thresholds were measured 1 day before the modeling, 7 and 14 days after the monoiodoacetate injection, as well as 7, 14 and 28 days after the exosome injection. Western blotting was used to detect the expression of ATF-3 and GAP-43 in the rats′ DRG, while hematoxylin and eosin staining was used to detect any cartilage repair.Results:Compared with the monoiodoacetate group, the latency of the mechanical and thermal pain thresholds had increased significantly in the exosome group 7 days after the exosome injection. The difference remained significant until the 28th day after the injection. The expression of ATF-3 protein decreased significantly and that of the GAP-43 protein increased significantly. Significant differences were observed in the average Osteoarthritis Research Society International (OARSI) knee cartilage score.Conclusions:Exosomes can alleviate the pain induced by monoiodoacetate adjuvant. The analgesic mechanism may be related to reducing nerve injury and promoting nerve and cartilage repair, with the nerve repair earlier than cartilage repair.
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Lateral epicondylitis is a common clinical disease with characteristics of lateral elbow pain, insidious onset and easy recurrence, which can cause forearm pain and decreased wrist strength, seriously affecting patients′ daily life and work. Although there are various treatment methods for lateral epicondylitis with different effects, standard treatments are still lacking nowadays. Platelet-rich plasma (PRP) has good effects on bone and tendon repair, and is now widely used in the treatment of lateral epicondylitis. However, there is a lack of a unified understanding of the technology and specifications of PRP in the treatment of lateral epicondylitis. Therefore, the Sports Medicine Branch of the Chinese Medical Association and Physical Medicine and Rehabilitation Branch of the Chinese Medical Association organized experts in the fields of sports medicine and rehabilitation medicine in China to formulate the "clinical expert consensus on platelet-rich plasma treatment for lateral epicondylitis (2022 version)", and proposed suggestions based on evidence-based medicine mainly from the concept, epidemiology and pathophysiology of lateral epicondylitis, symptoms, signs and imaging manifestations of lateral epicondylitis, PRP concept and application component requirements, quality control of PRP preparation technology, indications and contraindications of PRP in the treatment of lateral epicondylitis, PRP injection in the treatment of lateral epicondylitis, application of PRP in the operation of lateral epicondylitis, related problems after PRP treatment of lateral epicondylitis, evaluation of the results after PRP treatment of lateral epicondylitis, and health and economic evaluation of PRP treatment of lateral epicondylitis, so as to provide guidance for clinical diagnosis and treatment.
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Objective:To observe the effect of botulinum toxin A (BTX-A) on pain, the activation of microglia and the expression of tumor necrosis factor-α (TNF-α) in the spinal cord in arthritis, and to explore how BTX-A treatment relieves pain.Methods:Sixty clean, male Sprague-Dawley rats were randomly divided into a sham operated group, a Freund′s adjuvant group and a BTX-A group. The ankle cavities of the left hind limbs of all of the rats except those in the sham group were injected with 50μl of Freund′s adjuvant to establish an arthritis pain model. The sham operated group received 50μl of saline solution as controls. Afterward the sham operation group and the Freund′s adjuvant group were given another 20μl of normal saline, while the BTX-A group was injected with 20μl of botulinum toxin A, again into the ankle joint cavity of the left hind limb. The mechanical and thermal pain thresholds of the rats in each group were measured 1 day before the modeling and 1, 3, 7, 14 and 21 days afterward. Western blotting and immunofluorescence staining were used to detect the expression of IBA-1 and IBA-1-IR. In addition, the expression of TNF-α protein and TNF-α mRNA in the spinal cord was detected using ELISA and RT-PCR.Results:Compared with the Freund′s adjuvant group, the latency of the mechanical and thermal pain thresholds had increased significantly in the BTX-A group after 3 days. The differences remained significant until the 14th day after the injection. The expression of IBA-1 protein and the number of immunopositive cells in the spinal cord decreased significantly, as did the expression of TNF-α protein and mRNA.Conclusions:Botulinum toxin A can alleviate the pain induced by Freund′s adjuvant. The analgesic mechanism may be related to inhibiting the activation of spinal microglia and the release of TNF-α.
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Objective To observe the effects of mesenchymal stem cells (BMSCs) on the expression of Bcl2 and Bax in atrophied muscles.Methods Immature rats (80～ 100 g) were anesthetized to collect marrow from their femurs and tibias.BMSCs were isolated from the marrow,cultured and purified using the whole bone marrow adherence method.Their right hindlimbs were immobilized fiom the thigh to the paw with the knee in extension and the ankle in plantar flexion.After the modeling,24 of the male rats were divided into a sham-operation group,a BMSC group and a phosphate buffer solution (PBS) group,each of 8.The BMSC and PBS groups were injected with either approximately 106 BMSCs or an equal volume of PBS into the belly of the soleus muscle after they had been immobilized for 48 hours,while the control group did not undergo any treatment except for the injection of PBS.All of the rats were sacrificed for analysis after 14 days.Results The BMSCs were mainly spindle cells,showing radial colony arrangement.They grew vigorously and could passage in a continuous and stable manner over 10 passages.At the 4th passage the BMSCs were positive for CD44 (95.84％) and CD90 (96.00％),but negative for CD34 and CD45.Western blotting assay demonstrated that the expression of Bax protein as measured in grey-scale value (0.41±0.08)in the BMSC group was significantly lower than in the PBS group (0.63±0.10),but significantly higher than in the control group (0.14±0.11) on average.The expression of Bcl-2 (0.47±0.14) was also significantly higher in the BMSC group than in the PBS group (0.22-± 0.13),but significantly lower than in the control group (0.81 ± 0.06).Conclusion Bone marrow mesenchymal stem cells can upregulate the expression of anti-apoptotic Bcl-2 protein and downregulate that of the apoptotic Bax protein when injected early into the belly of a muscle in an immobilized limb.
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Objective To develop the preliminary version of a new scale on the severity of myasthenia gravis ( MG) suitable for Chinese patients .Methods The item pool was established based on the four widely used MG severity scales .Then the Delphi method was applied to collect the opinions from MG experts in China.Based on the consistency of expert opinions and previous evaluation of the items in source scales , the preliminary version of a new scale was developed .Results The item pool consists of 19 items from the above four scales .The enthusiasm coefficients of experts in two rounds of survey are 91.4%(32/35) and 96.9%(31/32).The authority coefficients are 0.79 and 0.80.The Kendall′s coefficients of concordance of expert opinions are 0.22 (χ2 =127.01, P<0.01) and 0.42 (χ2 =231.56, P<0.01), respectively.The preliminary version consists of 10 items, which cover six commonly involved muscle groups in MG, including the ocular, bulbar, facial, limb, axial and the respiratory muscles.Conclusion The preliminary version of the MG severity scale was established by combining Delphi method with the previous evaluation of items from source scales .
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Objective To develop the preliminary version of a new scale on the severity of myasthenia gravis ( MG) suitable for Chinese patients .Methods The item pool was established based on the four widely used MG severity scales .Then the Delphi method was applied to collect the opinions from MG experts in China.Based on the consistency of expert opinions and previous evaluation of the items in source scales , the preliminary version of a new scale was developed .Results The item pool consists of 19 items from the above four scales .The enthusiasm coefficients of experts in two rounds of survey are 91.4%(32/35) and 96.9%(31/32).The authority coefficients are 0.79 and 0.80.The Kendall′s coefficients of concordance of expert opinions are 0.22 (χ2 =127.01, P<0.01) and 0.42 (χ2 =231.56, P<0.01), respectively.The preliminary version consists of 10 items, which cover six commonly involved muscle groups in MG, including the ocular, bulbar, facial, limb, axial and the respiratory muscles.Conclusion The preliminary version of the MG severity scale was established by combining Delphi method with the previous evaluation of items from source scales .
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Objective To explore the analgesic effect of intra-articular botulinum neurotoxin type A (BoNTA) injection in rats with adjuvant-arthritis pain,to quantify the expression of calcitonin gene-related peptide (CGRP) in the dorsal root ganglia (DRG) associated with arthritis pain,and to investigate the retrograde axonal transport of BoNT-A into the DRG after peripheral injection.Methods Ninety Sprague-Dawley rats were randomly divided into groups A,B,C,D and E,each of 18.A murine model of adjuvant-arthritis pain was established by injecting 50 μL of complete Freund's adjuvant into the left ankle in all the mice except those in group A.The control group A was treated with intra-articular injection of 50 μL of saline solution.Three weeks later,groups A and B were treated with a 20 μL intra-articular saline injection,while groups C,D and E received an intra-articular injection of BoNT-A at 1 U/20 μL,3 U/20 μL or 10 U/20 μL respectively.Pain threshold and muscle strength were graded before and 1,5,15 and 21 days after the modelling,as well as at 1,3,5 and 14 days after the BoNT-A treatments.Protein expression and the CGRP-positive cell number were observed,as well as any BoNT-A-cleaved synaptosomal-associated 25 kDa protein (cl-SNAP-25) in the DRG using Western blotting and immunofluorescence.Results Compared with group A,there was a significant decrease in the average mechanical withdrawal threshold and muscle strength and a significant increase in the protein expression and the CGRP-positive cell number in the other 4 groups.Compared with group B,the mechanical withdrawal threshold had increased significantly more in groups D and E at 5 days after the BoNT-A injection and in group C at 14 days after the treatment.Compared with group B,the protein expression and the number of CGRP-positive cells were significantly lower in groups D and E at 3 days after the BoNT-A injection.The decrease in group C was significant after 14 days.No significant differences were found between groups D and E in any measurement at any time point.There was no significant difference among groups B,C and D in terms of muscle strength.Five days after the BoNT-A injection,significantly decreased muscle strength was observed in group E.In addition,BoNT-A cleaved-SNAP-25 was detected in the DRG.Conclusion BoNT-A can reduce arthritis pain through inhibiting the expression of CGRP in the DRG.Its analgesic effect has a dose response.A peripheral injection of BoNT-A can arrive at the DRG through retrograde axonal transport.
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Objective To verify the anti-inflammatory effects of intra-articular injection of botulinum toxin type A (BoNT/A) on adjuvant-induced arthritis using a rat model.Methods A murine model of chronic ankle arthritis was established in 90 Wistar rats by injection of 0.1 ml of complete Freund adjuvant (CFA) into the pads of their left paws.They were then randomly divided into a BoNT group (n =30) which received an intra-articular injection of 0.1 ml (20 IU) of BoNT/A,an NS group (n=30) which received intra-articular injection of0.1 ml of normal saline solution and a sham group (n =30) which were punctured without any injection.In addition,30 normal rats formed a control group.Infrared thermal imaging was performed and an index of arthritis was evaluated every three days.The infrared thermal imaging revealed the expression of interleukin-1β (IL-1β) through hematoxy-eosin (HE) staining.Results The arthritis index began to increase 3 days after the injection of CFA and it had increased significantly after 10 days,reaching a peak value of 18,24 days after the injection.The infrared thermal imaging showed that the temperature in the right paw increased greatly after the injection.Following the development of arthritis,the temperature declined gradually,arriving at a steady temperature of between 37.5 and 38.0 ℃ in both ankles 20 days after the injection.The average temperature in both paws of the BoNT group had decreased significantly more by 7 and 14 days after the injection than in the NS and sham groups.The expression of IL-1β in the synovium of the ankle joint also had decreased significantly more in the BoNT group after 7 and 14 days.HE scoring showed an obvious histopathologic change in the hypertrophic synovium,inflamnatory cell infiltration,cartilage destruction and exposure of subchondral bone after 7 and 14 days compared with right after the injection in all groups except the control group.Moreover,the average HE scores of the BoNT group rats after 7 and 14 days were significantly lower than those seen in the NS and sham groups at the same time points.Conclusion Intra-articular injection of botulinum toxin type A has an anti-inflammatory effect on arthritis induced by complete Freund adjuvant,at least in rats.
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Objective To observe the effects of treadmill training at different intensities on the expression of p-AKT in rats' gastrocnemius muscles after focal cerebral ischemia,and to investigate whether intensive training is beneficial for the recovery of motor function.Methods Left middle cerebral artery occlusion (MCAO) was induced in 120 male Wistar rats using the intraluminal thread method,and they were divided into an MCAO group (no training),a normal training group (treadmill training once a day for 30 min) and an intensive training group (treadmill training twice a day for 60 min),each of 30 rats.There was also a sham control group with 30 members not given MCAO or training.The four groups were further divided into 3 day,7 day and 14 day subgroups.Five rats randomly selected from each subgroup were sacrificed for hematoxylin-eosin staining after 4％ paraformaldehyde treatment.Neurological function was evaluated using Zausinger scores,and the expression of p-Akt was detected by western blotting.Results No significant differences in Zausinger scores were observed between the intensive training group and the normal training group after 1,3 or 7 days of training.However the average Zausinger score in the intensive training group was significantly higher than in the normal training group after 14 d of treadmill training.After 7 d and 14 d of treadmill training the average cross-sectional area of the gastrocnemius muscles in the sham group was significantly higher than in the other three groups.The average area of the intensive training group was significantly larger than that of the normal training group.The expression of p-Akt in the gastrocnemius was significantly increased in the intensive training group compared with the normal training group in the 7 day and 14 day subgroups.Conclusion Treadmill training can improve the expression of p-Akt in atrophied gastrocnemius muscles caused by MCAO.Intensive training is more effective for the recovery of muscle function.
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Objective To observe the structural abnormalities of the painful shoulder in patients soon after stroke by M RI,and to identify the possible causes of post-stroke shoulder pain (PSSP).Methods Patients with hemiplegia following their first cerebrovascular accident were divided into 2 groups:PSSP group (32 patients) and post-stroke no shoulder pain (PSNSP) group (20 patients).Physical findings of affected shoulder and MRI findings of both affected and unaffected shoulders were evaluated.Results Shoulder subluxation was significantly more frequent in PSSP group than in PSNSP group (53％ vs 15％,P ＜0.05).In PSSP group,the incidence rate of rotator cuff injury,subacromial-subdeltoid bursa effusion,glenohumeral joint effusion,effusion of long head of biceps tendon was higher in affected side than that in unaffected side(63％ vs 13％,53％ vs 13％,75％ vs 31％,41％ vs 13％,respectively).In PSNSP group,the incidence rate of glenohumeral joint effusion was higher in affected side than that in unaffected side (70％ vs 17％).But compared with no pain hemiplegic shoulder,only rotator cuff injury and subacromial-subdeltoid bursa effusion were significantly higher in PSSP patients (63％ vs15％,53％ vs 25％,respectively),and there was significant difference between the two groups (P ＜0.05).Conclusion Rotator cuff injury was found to be a possible cause of PSSP.
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Objective To investigate the influence of aerobic exercise on the vulnerability of atherosclerotic plaques and to observe the concentration of matrix metalloproteinase-9 ( MMP-9 ) and matrix metalloproteinase-14(MMP-14) in carotid atherosclerotic plaques in apolipoprotein E (APoE) gene deficient mice.Methods Eighty male, APoE gene deficient mice were divided into two equal groups: an aerobic exercise group and a limited action control group. Carotid atherosclerotic lesions were induced by perivascular constrictive collars placed on the right common carotid artery. Blood lipid levels in the exercise group were measured after 8 weeks of treadmill running and also in the control group. The morphological characteristics of carotid atherosclerotic plaques were observed in the two groups. Plaque area and fibrous cap thickness were measured. Lipid and collagen positive areas were quantified and the ratios correlated with the entimal areas were calculated. Plaque rupture rate and vulnerable index were calculated.Immunostaining was used to detect MMP-9 and MMP-14 expression in the atherosclerotic plaques. The mRNA levels of MMP-9 and MMP-14 mRNA in the fresh carotid plaques were quantified using a real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Western blotting was performed for examining MMP-9 and MMP-14 protein expression in the fresh carotid plaques.Results No significant difference in serum lipid profiles or plaque area was found between the exercise and control groups. Compared with the control group, mean fibrous cap thickness, cap/core ratio and collagen content were all significantly higher in the exercise group, and lipid content was significantly lower. Plaque rupture rate and the vulnerable index were both significantly lower in the exercise group. Immunostaining showed that MMP-9 and MMP-14 expression were lower in the exercise group compared with the control group.The mRNA expression of MMP-9 and MMP-14 was also significantly lower.Conclusions Aerobic exercise can decrease the expression of MMP-9 and MMP-14 in carotid atherosclerotic plaques in ApoE gene deficient mice. Aerobic exercise may play a role in forestalling atherosclerosis by increasing the stability of plaque and decreasing plaque vulnerability.
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Objective To explore the effects of three- stage swallowing rehabilitation on the swallowing a-bility of stroke patients with dysphagia. Methods 60 stroke patients were divided into primary cerebral infarction and primary cerebral hemorrhage groups, then further divided into treated and control groups randomly. All groups were given the same routine internal medicine treatment. Patients in the treated group were given three stage swallo-wing rehabilitation training additionally. All patients were assessed using Caiteng's Grading Method at the outset and at the end of the 2nd week, the Ist month and the 2nd month. Results Swallowing function scores in the treated groups were higher than those in the control groups at every stage (P≤0.05). The treated groups' scores also im-proved more quickly than those in the control groups. Conclusion Three stage swallowing rehabilitation can signifi-cantly improve stroke patients' swallowing function.
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Objective To explore the efficacy of a new elastic suspension strap orthosis, designed by the authors, in improving the motor function and walking ability of stroke patients. Methods Thirty-nine stroke pa-tients less than 1 month after stroke were recruited and divided randomly into a treatment group and a control group. The patients in the treatment group accepted walking training with the assistance of an elastic suspension strap orthosis, 5 times a week for 8 weeks, while the control group accepted the same training without the assistance of the elastic suspension strap orthosis. Results The treatment group improved significantly more than the control group with regard to its average Fugl-Meyer score, the functional ambulation categories of its members, and their walking speeds. Conclusions The elastic suspension strap orthosis could help correct abnormal gait patterns, improve walking speed, and enhance the recovery of walking ability in stroke patients.
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0.05). Conclusion The lesions of left and right hemisphere can both cause cognitive impairment, which is significantly correlated with the severity of motor dysfunction in acute stroke patients with subcortical lesion.Great attention should be paid to the evaluation and treatment of cognitive dysfunction in patients with serious hemiplegia.
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Objective To observe the efficacy of continuous ultrasonic wave therapy on post-stroke gastrocnemius spasticity. Methods 26 patients with gastrocnemius spasticity after stroke were randomly divided into ultrasonic group and control group. The stretch therapy was used in the two groups,and the continuous ultrasonic wave therapy was added on ultrasonic group for 4 weeks. The scores of modefied Ashworth scale (mAS),the ratio of Hmax and Mmax,and the fascicle length of gastrocnemius pre and post treatment were observed and compared respectively in the two groups.Results Compared with pre treatment,the score of mAS and the value of Hmax/Mmax in ultrasonic group wrer significantly reduced post treatment(all P