Effect of task-oriented training assisted by force feedback hand rehabilitation robot on finger grasping function in stroke patients with hemiplegia: a randomised controlled trial.

BACKGROUND: Over 80% of patients with stroke experience finger grasping dysfunction, affecting independence in activities of daily living and quality of life. In routine training, task-oriented training is usually used for functional hand training, which may improve finger grasping performance after stroke, while augmented therapy may lead to a better treatment outcome. As a new technology-supported training, the hand rehabilitation robot provides opportunities to improve the therapeutic effect by increasing the training intensity. However, most hand rehabilitation robots commonly applied in clinics are based on a passive training mode and lack the sensory feedback function of fingers, which is not conducive to patients completing more accurate grasping movements. A force feedback hand rehabilitation robot can compensate for these defects. However, its clinical efficacy in patients with stroke remains unknown. This study aimed to investigate the effectiveness and added value of a force feedback hand rehabilitation robot combined with task-oriented training in stroke patients with hemiplegia. METHODS: In this single-blinded randomised controlled trial, 44 stroke patients with hemiplegia were randomly divided into experimental (n = 22) and control (n = 22) groups. Both groups received 40 min/day of conventional upper limb rehabilitation training. The experimental group received 20 min/day of task-oriented training assisted by a force feedback rehabilitation robot, and the control group received 20 min/day of task-oriented training assisted by therapists. Training was provided for 4 weeks, 5 times/week. The Fugl-Meyer motor function assessment of the hand part (FMA-Hand), Action Research Arm Test (ARAT), grip strength, Modified Ashworth scale (MAS), range of motion (ROM), Brunnstrom recovery stages of the hand (BRS-H), and Barthel index (BI) were used to evaluate the effect of two groups before and after treatment. RESULTS: Intra-group comparison: In both groups, the FMA-Hand, ARAT, grip strength, AROM, BRS-H, and BI scores after 4 weeks of treatment were significantly higher than those before treatment (p < 0.05), whereas there was no significant difference in finger flexor MAS scores before and after treatment (p > 0.05). Inter-group comparison: After 4 weeks of treatment, the experimental group's FMA-Hand total score, ARAT, grip strength, and AROM were significantly better than those of the control group (p < 0.05). However, there were no statistically significant differences in the scores of each sub-item of the FMA-Hand after Bonferroni correction (p > 0.007). In addition, there were no statistically significant differences in MAS, BRS-H, and BI scores (p > 0.05). CONCLUSION: Hand performance improved in patients with stroke after 4 weeks of task-oriented training. The use of a force feedback hand rehabilitation robot to support task-oriented training showed additional value over conventional task-oriented training in stroke patients with hand dysfunction. CLINICAL TRIAL REGISTRATION INFORMATION: NCT05841108.

Amantadine hydrochloride monitoring by dried plasma spot technique: High-performance liquid chromatography-tandem mass spectrometry based clinical assay.

Amantadine plasma concentrations correlate well with desired therapeutic effects and adverse outcomes; information on amantadine exposure could be useful when multiple amantadine clearance pathways are impaired or non-compliance is suspected. Micro-sampling strategies, like dried plasma spot, would be particularly useful because ambulatory patients that do not attend a clinic can easily sample a few drops of blood by themselves at the required time of the dosing interval. We developed and validated a dried-plasma-spot-based high performance liquid chromatography-tandem mass spectrometry assay to quantify amantadine. This assay met relevant validation requirements within a hematocrit range of 20-50% and was linear from 100 to 2000 ng/mL. Amantadine was stable in dried plasma spots for up to 21 days at room temperature, regardless of whether the dried plasma spot was protected from light or not. The correlation between paired dried and wet plasma concentrations was assessed in 52 patients. Deming regression coefficients between wet plasma and simultaneously pipetted dried plasma spots were used to predict plasma concentrations. Bland-Altman plots revealed a strong agreement between dried and wet plasma concentrations, supporting the clinical usefulness of dried plasma spots for amantadine monitoring with a self-sampling strategy at a convenient time and place for the patient.

Dual-task training on gait, motor symptoms, and balance in patients with Parkinson's disease: a systematic review and meta-analysis.

OBJECTIVE: The aim of the present study was to systematically evaluate and quantify the effectiveness of dual-task training on gait parameters, motor symptoms and balance in individuals diagnosed with Parkinson's disease. DATA RESOURCES: A systematic review of published literature was conducted until May 2020, using PubMed, EMBASE, Cochrane Library, Web of Science, EBSCO and CNKI databases. METHODS: We included randomized controlled trials (RCTs) and non-RCTs to evaluate the effects of dual-task training compared with those of non-intervention or other forms of training. The measurements included gait parameters, motor symptoms and balance parameters. Methodological quality was assessed using the PEDro scale. Outcomes were pooled by calculating between-group mean differences using fixed- or random-effects models based on study heterogeneity. RESULTS: A total of 11 RCTs comprising 322 subjects were included in the present meta-analysis. Results showed that dual-task training significantly improved gait speed (standardized mean difference [SMD], -0.23; 95% confidence interval [CI], -0.38 to -0.08; P = 0.002), cadence (SMD, -0.25; 95% CI, -0.48 to -0.02; P = 0.03), motor symptoms (SMD, 0.56; 95% CI, 0.18 to 0.94; P = 0.004) and balance (SMD, -0.44; 95% CI, -0.84 to -0.05; P = 0.03). However, no significant changes were detected in step length or stride length. CONCLUSION: Dual-task training was effective in improving gait performance, motor symptoms and balance in patients with Parkinson's disease relative to other forms of training or non-intervention.

Anatomical distribution of lower-extremity deep venous thrombosis in patients with acute stroke.

OBJECTIVE: Post-stroke paralysis is a common contributor to deep vein thrombosis (DVT) of the lower extremities, but little is known about its epidemiology and anatomy. This prospective study aimed to investigate the clinical incidence and anatomical distribution of lower-extremity DVT in acute stroke. PATIENTS AND METHODS: A total of 679 patients diagnosed with acute stroke (ischemic stroke, n = 507; hemorrhagic stroke, n = 172) were enrolled. Lower-extremity DVT was evaluated using vascular ultrasonography, and classified into three subtypes: central type, peripheral type and mixed type. Then, the incidence and anatomical distribution of DVT were analyzed. RESULTS: For patients with ischemic stroke, a total of 107 patients (21.1%) were affected by DVT, and 119 extremities were found with DVT, which included 114 extremities with peripheral-type DVT and five extremities with mixed-type DVT. For patients with hemorrhagic stroke, a total of 49 patients (28.5%) were affected by DVT, and 55 extremities were found with DVT, which included 51 extremities with peripheral-type DVT and four extremities with mixed-type DVT. The incidence of DVT was significantly higher in patients with hemorrhagic stroke than in patients with ischemic stroke (P < 0.05). Intermuscular veins were the most commonly affected (96.6%), followed by peroneal veins (15.5%), posterior tibial veins (9.2%), popliteal veins (4.0%), and femoral veins (4.0%). There was no significant difference in the anatomical distribution of DVT between ischemic and hemorrhagic stroke (P > 0.05). CONCLUSION: DVT is a common complication of acute stroke, and hemorrhagic stroke is associated with a higher incidence of DVT. The anatomical distribution of DVT revealed no heterogeneity between ischemic and hemorrhagic stroke, and isolated DVT in intermuscular veins were the most common.

Therapeutic effect of gradual attention training on language function in patients with post-stroke aphasia: a pilot study.

OBJECTIVE: To investigate the effect of gradual attention training on language function with aphasia. DESIGN: Randomized controlled trial. PARTICIPANTS: A total of 40 patients (mean age: 53.47 years) with post-stroke aphasia came from the stroke rehabilitation unit of rehabilitation department in the First Hospital of Jilin University, of which 13 (32.5%) had intracerebral hemorrhage, 28 inpatients and 12 outpatients, 11 women and 29 men, 34 within three-month stroke and 6 within three months to one year. INTERVENTIONS: All participants were divided into control and experimental groups. Both groups received language treatment 20 minutes a day, six days/week, for five weeks, and the experimental group received gradual attention training 20 minutes a day, six days/week, for five weeks. MAIN MEASURES: Language function was assessed pre- and post-treatment by components of the Western Aphasia Battery (WAB) which included spontaneous speech, auditory comprehension, repetition, and naming and then calculated the aphasia quotient (AQ). RESULTS: The mean (SD) AQ of the experimental group and control group, respectively, was 25.71 (12.63) and 26.2 (12.31) at baseline. After treatment, the AQ mean (SD) was 43.08 (15.14) in the experimental group, which showed a significant improvement compared to 33.48 (14.04) in the control group (P = 0.02).All items of WAB were higher in experimental group than those in control group, especially in auditory comprehension and naming (P = 0.02, 0.01). CONCLUSION: Gradual attention training seemed to improve language function in post-stroke aphasia, specifically function of listening comprehension and naming.

Upper Limb Movement Decoding Scheme Based on Surface Electromyography Using Attention-Based Kalman Filter Scheme.

Convolutional neural network (CNN)-based models are widely used in human movement decoding based on surface electromyography. However, they capture only the spatial information of the surface electromyography and lack prior knowledge of the system, resulting in unsatisfactory decoding accuracy. To address these issues, we propose an attention-based Kalman filter scheme (AKFS), which uses an attention-based CNN model to better extract temporal information and a KF to add prior knowledge of the system. We further solve the problem of insufficient data due to the short training time of new subjects by using a transfer learning method based on a fine-tuning strategy. The proposed scheme was tested in four scenarios: intra-session, intra-session long-time use, inter-subject, and inter-subject with a fine-tuning strategy. The proposed attention-based CNN model outperformed the vanilla CNN model and a hybrid CNN-long short-term memory (LSTM) model in intra-session and intra-session long-time use. After fine-tuning with a small amount of data on a new subject, the attention-based CNN model achieved higher decoding accuracy than the vanilla CNN model and lower response time than CNN-LSTM model. Furthermore, the schemes with KF outperformed the schemes without KF in all scenarios. Our proposed scheme improves the decoding accuracy of the traditional CNN model for a single subject by better capturing the temporal information of the surface electromyography signal and increasing the prior knowledge of the system. Additionally, the proposed scheme can be easily transferred to a new subject using only a small amount of data.

Research progress in extracorporeal shock wave therapy for upper limb spasticity after stroke.

Spasticity is one of the most common complications after stroke. With the gradual intensification of spasticity, stroke patients will have a series of problems such as joint ankylosis and movement restriction, which affect the daily activities and increase the burden on patients' families, medical staff and society. There are many ways to treat post-stroke spasticity before, including physical therapy and exercise therapy, drug therapy, surgery and so on, but not satisfied because of a few shortcomings. In recent years, many researchers have applied extracorporeal shock wave therapy (ESWT) for the treatment of post-stroke spasm and achieved good clinical effect, because it is non-invasive, safe, easy to operate, low cost and other advantages compared with other treatment methods. This article reviews the research progress and existing problems of ESWT in the treatment of post-stroke spasticity.

Rehabilitation treatment of multiple sclerosis.

Multiple sclerosis is a slowly progressive disease, immunosuppressants and other drugs can delay the progression and progression of the disease, but the most patients will be left with varying degrees of neurological deficit symptoms, such as muscle weakness, muscle spasm, ataxia, sensory impairment, dysphagia, cognitive dysfunction, psychological disorders, etc. From the early stage of the disease to the stage of disease progression, professional rehabilitation treatment can reduce the functional dysfunction of multiple sclerosis patients, improve neurological function, and reduce family and social burdens. With the development of various new rehabilitation technologies such as transcranial magnetic stimulation, virtual reality technology, robot-assisted gait, telerehabilitation and transcranial direct current stimulation, the advantages of rehabilitation therapy in multiple sclerosis treatment have been further established, and more treatment means have also been provided for patients.

The effects and underlying mechanism of extracorporeal shockwave therapy on fracture healing.

The clinical efficacy of ESWT in treating bone non union has been widely recognized, but the biological mechanism of ESWT promoting bone non union healing is still unclear. ESWT can make old callus micro fracture through mechanical conduction, form subperiosteal hematoma, promote the release of bioactive factors, reactivate the fracture healing mechanism, rebalance the activities of osteoblasts and osteoclast, promote the angiogenesis of fracture site, and accelerate the healing of bone nonunion.Over recent years, great efforts have been made by both scientists and clinicians to explore the underlying mechanism behind the healing effect of ESWT on bone fractures. In this review, we introduced the growth factors during osteogenesis induced by ESWT hoping to provide new insights in the clinical use of ESWT.

Advances in the clinical application of orthotic devices for stroke and spinal cord injury since 2013.

Stroke and spinal cord injury are common neurological disorders that can cause various dysfunctions. Motor dysfunction is a common dysfunction that easily leads to complications such as joint stiffness and muscle contracture and markedly impairs the daily living activities and long-term prognosis of patients. Orthotic devices can prevent or compensate for motor dysfunctions. Using orthotic devices early can help prevent and correct deformities and treat muscle and joint problems. An orthotic device is also an effective rehabilitation tool for improving motor function and compensatory abilities. In this study, we reviewed the epidemiological characteristics of stroke and spinal cord injury, provided the therapeutic effect and recent advances in the application of conventional and new types of orthotic devices used in stroke and spinal cord injury in different joints of the upper and lower limbs, identified the shortcomings with these orthotics, and suggested directions for future research.

Observing the Structural Evolution of Quasi-Monolayer Pt Shell on Pd Core in the Electrocatalytic Oxygen-Reduction Reaction.

The use of a quasi-monolayer Pt shell (Ptqms) on a Pd core (Pdc) can reach cost and activity targets for the electrocatalytic oxygen-reduction reaction (ORR). The structure of PdcPtqms in the ORR will vary; however, direct observation of this issue is scarce. Here, during cyclic staircase voltammetry (ranging from 0.5 to 1.15 VRHE) in 0.1 M O2-saturated HClO4, the structure of PdcPtqms was monitored by in situ X-ray absorption spectroscopy. The qualitative and quantitative structural information clearly exhibits a complete picture that Ptqms will directly restructure to form Pt clusters and holes, while Pdc almost remains stable. These findings identify the initial structural evolution of PdcPtqms in the ORR, highlighting the importance of protecting Pdc in the development of high-performance PdcPtqms electrocatalysts.

Progress in the clinical application of constraint-induced therapy following stroke since 2014.

Stroke is a group of cerebrovascular diseases with high prevalence and mortality rate. Stroke can induce many impairments, including motor and cognitive dysfunction, aphasia/dysarthria, dysphagia, and mood disorders, which may reduce the quality of life among the patients. Constraint-induced therapy has been proven to be an effective treatment method for stroke rehabilitation. It has been widely used in the recovery of limb motor dysfunction, aphasia, and other impairment like unilateral neglect after stroke. In recent years, constraint-induced therapy can also combine with telehealth and home rehabilitation. In addition, constraint-induced therapy produces significant neuroplastic changes in the central nervous system. Functional magnetic resonance imaging, diffusion tensor imaging, and other imaging/electrophysiology methods have been used to clarify the mechanism and neuroplasticity. However, constraint-induced therapy has some limitations. It can only be used under certain conditions, and the treatment time and effectiveness are controversial. Further research is needed to clarify the mechanism and effectiveness of CI therapy.

Misdiagnosis of scalp angiosarcoma: A case report.

BACKGROUND: Angiosarcoma is a rare malignant tumor. Owing to the lack of specific clinical manifestations of this disease, it is difficult to achieve early diagnosis and start early treatment. CASE SUMMARY: A 78-year-old male patient was admitted to the hospital because of a bump on his head that did not heal for 4 mo. The patient was diagnosed with a refractory head wound. The patient underwent neoplasm resection and skin grafting surgery in the Plastic Surgery. The neoplasm was sent for pathological examination during the operation. The final pathological results were confirmed scalp angiosarcoma. CONCLUSION: Our research suggests that pathological examination should be performed for refractory ulcers of the scalp, and physical factor therapy should be used with caution before the diagnosis is clear.

Comparison of Wuqinxi Qigong with Stretching on Single- and Dual-Task Gait, Motor Symptoms and Quality of Life in Parkinson's Disease: A Preliminary Randomized Control Study.

The objective of this study was to investigate the therapeutic effect of Wuqinxi Qigong vs. stretching on single- and dual-task gait, motor symptoms, and quality of life in people with mild and moderate Parkinson's disease (PD). This single-blind, randomized control trial included 40 participants with idiopathic PD who were randomized into the Wuqinxi Qigong (WQ) group or stretching group. Participants completed 12 weeks (two sessions/week) of intervention. The primary outcomes were gait parameters when performing single-task (comfortable pace) and dual-task (obstacle crossing, serial-3 subtraction and backward digit span) walking, including gait speed, stride length, and double support percentage. The secondary outcomes were ratings from the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), results of the timed-up-and-go test (TUGT), results of the Mini-Balance Evaluation Systems Test (MiniBESTest), and responses from the 39-item Parkinson's Disease Questionnaire (PDQ-39). All measures were assessed pre- and post-intervention. The WQ group demonstrated increased gait speed (p = 0.000) during the single task, and increased stride length (p = 0.001, p = 0.021) during the single-task and serial-3 subtraction task. Double support percentage significantly decreased (p = 0.004) in the WQ group during the obstacle crossing task, and also decreased (p = 0.045) in the stretching group during the single-task. TUGT (p = 0.005), MiniBESTest (p = 0.023) and PDQ-39 (p = 0.043) in the WQ group significantly improved, and both groups showed significant improvement in MDS-UPDRS after intervention. Wuqinxi Qigong is an effective method to improve single- and dual-task gait. While both exercises improve motor symptoms, Wuqinxi Qigong results in better mobility, balance and quality of life compared to stretching alone.

Heme oxygenase­1 improves the survival of ischemic skin flaps (Review).

Heat shock protein 32 (Hsp32), also known as heme oxygenase­1 (HO­1), is an enzyme that exists in microsomes. HO­1 can be induced by a variety of stimuli, including heavy metals, heat shock, inflammatory stimuli, heme and its derivatives, stress, hypoxia, and biological hormones. HO­1 is the rate­limiting enzyme of heme catabolism, which splits heme into biliverdin, carbon monoxide (CO) and iron. The metabolites of HO­1 have anti­inflammatory and anti­oxidant effects, and provide protection to the cardiovascular system and transplanted organs. This review summarizes the biological characteristics of HO­1 and the functional significance of its products, and specifically elaborates on its protective effect on skin flaps. HO­1 improves the survival rate of ischemic skin flaps through anti­inflammatory, anti­oxidant and vasodilatory effects of enzymatic reaction products. In particular, this review focuses on the role of carbon monoxide (CO), one of the primary metabolites of HO­1, in flap survival and discusses the feasibility and existing challenges of HO­1 in flap surgery.

Improvement of EMG Pattern Recognition Model Performance in Repeated Uses by Combining Feature Selection and Incremental Transfer Learning.

Electromyography (EMG) pattern recognition is one of the widely used methods to control the rehabilitation robots and prostheses. However, the changes in the distribution of EMG data due to electrodes shifting results in classification decline, which hinders its clinical application in repeated uses. Adaptive learning can solve this problem but takes additional time. To address this, an efficient scheme is developed by comparing the performance of 12 combinations of three feature selection methods [no feature selection (NFS), sequential forward search (SFS), and particle swarm optimization (PSO)] and four classification methods [non-adaptive support vector machine (N-SVM), incremental SVM (I-SVM), SVM based on TrAdaBoost (T-SVM), and I-SVM based on TrAdaBoost (TI-SVM)] in the classification of EMG data of 12 subjects for 5 consecutive days. Our results showed that TI-SVM achieved the highest classification accuracy among the classification methods (p < 0.05). The SFS method achieved the same classification accuracy as that of the scheme trained with the feature vectors selected by the NFS method (p = 0.999) while achieving a lower training time than that of TI-SVM combined with the NFS method (p = 0.043). Although the PSO method outperformed the NFS and SFS methods by achieving reduced training and response times (p < 0.05), the PSO method achieved a considerably lower classification accuracy than that of the scheme trained with the feature vectors selected by the NFS (p = 0.001) or SFS (p = 0.001) method. Furthermore, TI-SVM combined with the SFS method outperformed the CNN method with fine-tuning in classification accuracy on a small data set (p = 0.001). The results indicate that TI-SVM combined with the SFS method is suitable for improving the performance of EMG pattern recognition in repeated uses.

The Feasibility and Positive Effects of Wuqinxi Exercise on the Cognitive and Motor Functions of Patients with Parkinson's Disease: A Pilot Study.

INTRODUCTION: Parkinson's disease (PD) is a chronic degenerative disease of the central nervous system common in middle-aged and elderly people, which has a serious impact on patients' cognitive and motor functions. Exercise can improve the nonmotor symptoms of PD patients, but the optimal type of exercise for the cognitive function of patients is unclear. Therefore, the purpose of this study is the impact of 12 weeks of Wuqinxi exercise on the cognitive and motor function in PD patients. METHODS: Thirty PD patients participated in the study and were randomly assigned to two groups: Wuqinxi group (n = 15) or stretching group (n = 15). All the participants performed a 12-week exercise program twice a week, 90 min/session. The assessments were conducted before and after exercise intervention, included cognitive function (frontal assessment battery (FAB); Stroop test I and II), motor functions (Unified Parkinson's Disease Rating Scale Part III (UPDRS-III); timed up and go (TUG)). RESULTS: We found the FAB and Stroop I scores were significantly higher in the Wuqinxi group than in the stretching group. Participants in the Wuqinxi group significantly improved their UPDRS-III (17.73 ± 9.88) and TUG (10.50 ± 1.79) score after 12 weeks of training intervention. CONCLUSION: The results show that the use of Wuqinxi for rehabilitation therapy for cognition is feasible, widely accepted, and effective in patients with Parkinson's disease. This study provides preliminary evidence for further large-scale and controlled studies.

Translation, Cultural Adaptation, and Reliability and Validity Testing of a Chinese Version of the Freezing of Gait Questionnaire (FOGQ-CH).

Freezing of gait is a disabling symptom with a complex episodic nature that is frequently experienced by people with Parkinson's disease (PD). Although China has the largest population with PD in the world, no Chinese version of the freezing of gait questionnaire (FOGQ), the instrument that has been most widely used to assess FOG, has yet been developed. This study aimed to translate and adapt the original version of FOGQ to create a Chinese version, the FOGQ-CH, then assess its reliability, calculate the Minimal Detectable Change (MDC) and investigate its validity. The forward-backwards translation model was adopted, and cultural adaptation included expert review and pretesting. For the reliability study, 31 Chinese native speaking patients with PD were assessed two times in a 7-10 days interval. Internal consistency and test-retest reliability of the FOGQ-CH were measured by Cronbach's alpha (Cα) and the Intraclass Correlation Coefficient (ICC). For the validity study, 34 native speakers of Chinese with PD were included. To explore the convergent validity, relationships between the FOGQ-CH and the Unified Parkinson's Disease Rating Scale Part II (UPDRS II) and Part III (UPDRS III), Timed Up and Go Test (TUGT), Timed Up and Go Test in cognitive task (TUGT-Cog), walking speed (10 MWT speed), and step length (10 MWT step length) in a 10-m Walk Test were tested. To explore predictive validity, the number of falls followed up for 6 months were assessed. The area under the ROC curve (AUC) was employed to test the capacity of FOGQ-CH to discriminate those with falls. From the reliability study, Cα = 0.823, ICC = 0.786. The MDC0.90 = 4.538. From the validity study, the FOGQ-CH showed moderate correlations with UPDRS II (rho = 0.560, p = 0.001), UPDRS III (rho = 0.451, p = 0.007), TUGT (rho = 0.556, p = 0.007), TUGT-Cog (rho = 0.557, p = 0.001), 10MWT-speed (rho = -0.478, p = 0.004), 10MWT-step length (rho = -0.419, p = 0.014), and the number of falls followed up for 6 months (rho = 0.356, p = 0.045). The AUC = 0.777 (p = 0.036) for predicting whether the participants will have multiple falls (two or more) in the following 6 months. The FOGQ-CH showed good reliability and validity for assessing Chinese native speaking patients with PD. In addition, the FOGQ-CH showed good efficacy for predicting multiple falls in the following 6 months.

Toxicity reduction and water expelling effect preservation of Shizaotang after its toxic members processing with vinegar on rats with malignant pleural effusions.

ETHNOPHARMACOLOGICAL RELEVANCE: Shizaotang (SZT), consisted of Euphorbia kansui S.L.Liou ex S.B.Ho (EK), Euphorbia pekinensis Rupr. (EP), Daphne genkwa Sieb. et Zucc. (DG，fried) and Ziziphus jujuba Mill. (ZJ), is usually used for treating malignant pleural effusions (MPE), but the toxicity of EK and EP limits its clinical safe application. It was reported that vinegar processing can reduce the toxicity of EK and EP. Whether EK and EP processing with vinegar can cause the reduced toxicity and retained pharmacological effects of SZT, it still remains unknown. AIM OF THE STUDY: We aimed to evaluate whether using vinegar processed EK and EP would reduce toxicity and preserve water expelling effect of SZT. MATERIALS AND METHODS: Network pharmacology and qualitative analysis of SZT/VSZT were used to construct compound-target-pathway network of their effects and toxicity. Pleural fluid weight, urine volume, uric electrolyte, pH, pro-inflammatory cytokines in pleural fluid, serum Renin-Angiotensin-Aldosterone System (RAAS), anti-diuretic hormone (ADH) and intestinal aquaporin 8 (AQP8) protein were used to evaluate the effect mechanisms involved in rats experiments. And liver damage, oxidative damage and HE staining (liver, stomach, and intestine) were used to determine the toxicity. RESULTS: Network pharmacology analysis reviewed inflammation-related pathways of the effect and toxicity of SZT/VSZT: VEGF-PI3K-AKT pathway inhibited MPE by changing the vasopermeability; PI3K-Akt/Mitogen-activated protein kinase (MAPK)/TNF-NF-κB signaling pathway inhibited MPE by up-regulating expression of AQP8 protein. In vivo experiments displayed that SZT/VSZT could reduce pleural fluid, increase urine volume, lower pro-inflammatory cytokines levels and up-regulate AQP8 protein expression significantly (P < 0.05, P < 0.01). In addition, disorders on electrolyte (Na+, K+ and Cl-) and pH were ameliorated (P < 0.05, P < 0.01). The levels of RAAS and ADH were significantly dose-dependently called back (P < 0.01). These findings were partly consistent with the results of network pharmacology analysis. Results of toxicity experiments demonstrated that SZT and VSZT exhibited certain toxicity on normal rats, and VSZT had lower toxicity than that of SZT. Interestingly, SZT and VSZT exerted alleviation effect to the liver damage and oxidative damage on model rats. CONCLUSION: SZT/VSZT improved MPE by regulating associated inflammation pathways. Besides, compared to SZT, VSZT showed lower toxicity and equivalent expelling MPE effect. This study may provide scientific basis for guiding the clinical application of SZT.

Constraint-Induced Movement Therapy Combined With Botulinum Toxin for Post-stroke Spasticity: A Systematic Review and Meta-Analysis.

Stroke is considered one of the main causes of adult disability and the second most serious cause of death worldwide. The combination of botulinum toxin type A (BTX) with rehabilitation techniques such as modified constraint-induced movement therapy (mCIMT) has emerged as a highly efficient intervention for stroke patients to start synchronized motor function along with spasticity reduction. The current systematic review and meta-analysis were conducted in order to evaluate the available literature about the safety and efficacy of constraint-induced movement therapy (CIMT) combined with BTX in stroke patients with upper limb spasticity. Searches were conducted on WoS (Web of Science), Ovid, EBSCO-ASC&BSC, and PubMed for identifying relevant literature published from 2000-2020. Randomized Controlled Trials (RCTs) and Quasi-experimental studies were considered for inclusion. Rayyan (systematic review tool) QCRI (Qatar Computing Research Institute) was used for independent screening of the studies by two reviewers. For risk of bias and study quality assessment, Cochrane risk of bias tool (RoB 2) and Physiotherapy Evidence Database (PEDro) scales were used. Cochrane review manager was used to carry out the meta-analyses of the included studies. The search resulted in a total of 13065 references, of which 4967 were duplicates. After the title, abstract and full-text screening, two RCTs were deemed eligible for inclusion. Both the RCTs scored 8 on PEDro and were level evidence. The studies were heterogeneous. The findings of this meta-analysis in all the three joints post-stroke spasticity assessed on modified Ashworth scale (MAS) at four weeks post-injection aren't statistically significant (elbow P-value 0.74, wrist P-value 0.57, fingers P-value 0.42), however, according to one of the included studies the therapeutic efficacy of the combination of BTX-mCIMT injection assessed at four weeks post-injection in wrist and finger flexors was promising.  The effectiveness of BTX-CIMT combination over conventional therapy (CT) for improving post-stroke spasticity still needs to be explored with long-term, multicenter rigorously designed RCTs having a good sample size. However, the BTX-CIMT combination is promising for enhancing motor function recovery and improving activities of daily living (ADLs).