Efficacy of botulinum toxin A combined with extracorporeal shockwave therapy in post-stroke spasticity: a systematic review.

Objectives: In recent years, there has been an increase in the number of randomized clinical trials of BTX-A combined with ESWT for the treatment of post-stroke spasticity. This has made it possible to observe the benefits of combination therapy in clinical practice. Therefore, this paper reviews the effectiveness of BTX-A in combination with ESWT for the treatment of post-stroke spasticity. Methods: By October 2023, a systematic review was conducted in the databases PubMed, Cochrane, Embase, Medline, Web of Science, China National Knowledge Infrastructure, Wan Fang Database, China Biology Medicine disc and China Science and Technology Journal Database were systematically searched. We included randomized controlled trials that reported outcome metrics such as MAS, FMA, and MBI score. Studies were excluded if MAS was not reported. The quality of the included studies was assessed by the Cochrane Collaboration's tool for assessing risk of bias, and the AMSTAR quality rating scale was selected for self-assessment. Results: A total of 70 articles were included in the initial search, and six were ultimately included. The results of the included studies showed that the combination therapy was effective in reducing MAS scores and improving FMA and MBI scores in patients with spasticity compared to the control group. Combination therapy has also been shown to improve joint mobility and reduce pain in spastic limbs. Conclusion: Cumulative evidence from clinical randomized controlled trial studies suggests that the combination therapy is effective in reducing lower limb spasticity and improving mobility after stroke. However, more clinical trials are still needed to corroborate the evidence regarding the efficacy of BTX-A combined with shockwave therapy. Systematic Review Registration: The system review can be searched in the PROSPERO database (CRD42023476654).

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.

Functional outcomes and adverse effects following three interventions for displaced midshaft clavicular fractures: A Bayesian network meta-analysis of randomized controlled trials.

INTRODUCTION: The efficacy of the most commonly used interventions for clavicle fractures remains controversial. These interventions are: open reduction and plate fixation (ORPF), non-surgical intervention (NSI), and use of an intramedullary nail (IMN). In adult patients with clavicle fractures, choosing which intervention might be best is challenging. MATERIALS AND METHODS: PubMed, Journals@Ovid Full Text, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, and Embase were performed to search English-language studies from the inception to February 2020. Randomized controlled trials (RCTs) comparing any of these three interventions were included. Patient and baseline characteristics, nonunion, major complications, Constant-Murley score (CMS), and Disabilities of the Arm, Shoulder and Hand score (DASH) were extracted. Then, we evaluated the functional outcomes and adverse effects after use of these three interventions for the management of displaced midshaft clavicle fractures in a Bayesian network meta-analysis. RESULTS: A Bayesian random-effects model was conducted, and nonunion and major complications were evaluated with: risk ratio (RR) and 95% confidential interval (CI); while CMS and DASH were evaluated with mean differences (MD) and the corresponding 95% confidential interval CI. The rank probability of each endpoint was assessed on the basis of the surface area under the cumulative ranking curve (SUCRA). DISCUSSION: ORPF is most likely to be successful in achieving objective functional outcomes as captured by the CMS, and IMN demonstrates significant efficacy for subjective functional outcomes, as captured by DASH scores. Compared with the other interventions examined, IMN was associated with decreased risk for adverse effects. LEVELS OF EVIDENCE: I; meta-analysis.

Up-regulation of DGAT1 in cancer tissues and tumor-infiltrating macrophages influenced survival of patients with gastric cancer.

BACKGROUND: Diacylglycerol-acyltransferase 1 (DGAT1) plays an important role in the energy storage and is involved in cancer progression. A growing number of evidences showed that elevated expression of DGAT1 in cancer tissue indicated a poor outcome in cancer patients. However, the relationship between DGAT1 and gastric cancer is still unclear. Thus, Transcriptomic analysis and in vitro experiments were performed to investigate the role of DGAT1 in gastric cancer, as well as the potential therapy target in gastric cancer treatment. METHODS: We screened the public cancer datasets to identify the expression and function of DGAT1 in gastric cancer and tumor infiltrating lymphocytes. Then we testified the DGAT1 expression and function after sodium oleate treatment in AGS and MKN45 cell line. Finally, we analyzed ration of apoptosis, necrosis in gastric cancer cells by using flow cytometry after administration of DGAT1 inhibitor. RESULTS: Our results showed a highly expression of DGAT1 in gastric cancer tissues (n = 5, p = 0.0004), and tumor-infiltrating macrophages with elevated DGAT1 expression is associated with poor overall survival in gastric cancer patients. In addition, gastric cell lines AGS (n = 3, p < 0.05) and MKN45 (n = 3, p < 0.01) expressed higher level of DGAT1 than human gastric mucosal epithelial cell line GES-1. Administration of DGAT1 inhibitor effectively suppressed functional factors expression and induced cell death in MKN45. CONCLUSION: The findings of this research provide an in-depth insight into the potential role and influences involved in DGAT1 in the gastric cancer patients. And higher expression of DGAT1 leads to lower overall survival (OS) rate in patients with poorly differentiated gastric cancer. Our findings suggest a potential role for DGAT1 in the gastric cancer progression and inhibiting DGAT1 might be a promising strategy in gastric cancer treatment.

Pristimerin Suppresses Trophoblast Cell Epithelial-Mesenchymal Transition via miR-542-5p/EGFR Axis.

BACKGROUND: Ectopic pregnancy (EP) is an ectopic embryo implantation occurred outside the uterine cavity. Nowadays, more attention have garnered in fast and effective treatment with less side effects. Pristimerin is known as the clinical application for anti-cancer, and the effect on EP therapy is still unclear. MATERIALS AND METHODS: Trophoblast cell line HTR-8/SVneo was used; then, we performed cell counting kit-8 assay, wound healing assay, flow cytometry and real-time polymerase chain reaction analysis (RT-PCR) to detect the cell viability, migration ability, apoptosis and epithelial-mesenchymal transition (EMT) under pristimerin treatment. In addition, public bioinformatic database was used to discover the connection between molecular and genes. Finally, we used miRNA transfection and RT-PCR techniques to determine the underlying molecular mechanism. RESULTS: We revealed that pristimerin inhibited trophoblast cells proliferation, migration and EMT, while induced trophoblast cell apoptosis. Furthermore, expression of miR-542-5p, AGO2 and EGFR was suppressed in HTR-8/SVneo cells post pristimerin treatment, and miR-542-5p silence showed the same effect. Combing pristimerin treatment and miR-542-5p silence showed a synergistic action. CONCLUSION: Pristimerin could be an effective treatment to block embryo implantation by miR-542-5p and EGFR down-regulation.

Triphasic waves in electroencephalogram as a possible early marker of carcinomatous meningitis: a case report.

RATIONALE: Carcinomatous meningitis is a rare neurological complication. This condition is difficult to diagnose, and misdiagnosis is common because the clinical manifestations are variable. Cerebrospinal fluid (CSF) cytology is the gold standard for diagnosis. Repeated lumbar puncture is required because of the low positive rate. Our case showed triphasic waves (TWs) in an electroencephalogram (EEG) before cancer cells were detected in cytology. We report this case to demonstrate that TWs in EEG may be a prognostic marker in patients with carcinomatous meningitis. PATIENT CONCERNS: A 76-year-old Chinese male displayed incremental headache, nausea, emesis, and intermittent fever for 2 months. A routine scalp EEG showed mild slow background activity. The CSF analysis demonstrated a slight increase in protein, and the white blood cell count was in the normal range. Cytology did not show any atypical cells. Viral meningitis was considered for the first time. DIAGNOSIS: After admission, a long-term EEG was performed because of his fever and mild abnormalities in the routine EEG. The second EEG showed asymmetric TWs in the frontal brain regions. Lung adenocarcinoma was found after systemic investigation. Finally, the patient was diagnosed with carcinomatous meningitis based on repeated CSF cytology. INTERVENTIONS: The patient received systemic chemotherapy in the Department of Oncology. OUTCOMES: The patient was followed up monthly, and he was lost to follow-up in the sixth month after carcinomatous meningitis was diagnosed. LESSONS: It is difficult to make a diagnosis in the early stage of carcinomatous meningitis because the clinical manifestations lack specificity. Repeated lumbar puncture is time consuming and is painful for the patients. In our case, TWs in EEG were detected before cancer cells were found in cytology. EEG should be performed when carcinomatous meningitis is under consideration.

Extracellular vesicle-carried microRNA-27b derived from mesenchymal stem cells accelerates cutaneous wound healing via E3 ubiquitin ligase ITCH.

Mesenchymal stem cells (MSCs) have been highlighted as promising candidate cells in relation to cutaneous wound healing. The current study aimed to investigate whether MSC-derived extracellular vesicles (EVs) could transfer microRNA-27b (miR-27b) to influence cutaneous wound healing. The miR-27b expression was examined in the established cutaneous wound mouse model, and its correlation with the wound healing rate was evaluated by Pearson's correlation analysis. The identified human umbilical cord MSC-derived EVs were co-cultured with human immortal keratinocyte line HaCaT and human skin fibroblasts (HSFs). The mice with cutaneous wound received injections of MSC-derived EVs. The effects of EVs or miR-27b loaded on wound healing and cellular functions were analysed via gain- and loss-of-function approaches in the co-culture system. Dual-luciferase reporter gene assay was employed to verify the relationship between miR-27b and Itchy E3 ubiquitin protein ligase (ITCH). Rescue experiments were conducted to investigate the underlying mechanisms associated with the ITCH/JUNB/inositol-requiring enzyme 1α (IRE1α) axis. miR-27b was down-regulated in the mouse model, with its expression found to be positively correlated with the wound healing rate. Abundant miR-27b was detected in the MSC-derived EVs, while EV-transferred miR-27b improved cutaneous wound healing in mice and improved proliferation and migration of HaCaT cells and HSFs in vitro. As a target of miR-27b, ITCH was found to repress cell proliferation and migration. ITCH enhanced the JUNB ubiquitination and degradation, ultimately inhibiting JUNB and IRE1α expressions and restraining wound healing. Collectively, MSC-derived EVs transferring miR-27b can promote cutaneous wound healing via ITCH/JUNB/IRE1α signalling, providing insight with clinical implications.

Pristimerin Suppressed Breast Cancer Progression via miR-542-5p/DUB3 Axis.

BACKGROUND: Breast cancer is one of the most common and malignant tumors in the world. Nowadays more attention has been garnered in pristimerin anti-cancer effects. Here, we illustrate the function and regulatory mechanism of pristimerin in breast cancer therapy. MATERIALS AND METHODS: Breast cancer cell lines MCF-7, MDA-MB-231, and 4T1 were used. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate proliferation viability of breast cancer cells under pristimerin treatment. Wound healing assay was used to examine the migration ability, cell cycle, and cell apoptosis detection were tested by flow cytometry. Bioinformatic analysis was used to find the underlying molecular and gene connected with pristimerin and breast cancer survival. Finally, we used transfection and real-time polymerase chain reaction analysis to confirm the mechanism. RESULTS: We observed that pristimerin inhibited breast cancer cell viability, migration, and cell cycle, meanwhile induced cell apoptosis. In addition, under pristimerin treatment, miR-542-5p was up-regulated while DUB3 was down-regulated. Furthermore, bioinformatics analysis showed higher expression of DUB3 in breast cancer compared with normal tissue, also with poor prognosis. Overexpression miR-542-5p in breast cancer cells leads to a decrease in DUB3 level. The effect was obviously post pristimerin treatment and miR-542-5p overexpression. CONCLUSION: Pristimerin inhibited breast cancer progression through DUB3 expression via a canonical miRNA-mediated mechanism.

Tai chi chuan exercises improve functional outcomes and quality of life in patients with primary total knee arthroplasty due to knee osteoarthritis.

BACKGROUND AND PURPOSE: Postoperative rehabilitation plays an indispensable role for a successful total knee arthroplasty (TKA) and the optimal exercises programs are not known. A single-centre, single-blind, randomised controlled trial was designed to explore whether tai chi chuan (TCC) exercises can improve the functional outcomes and the quality of life (QOL) in patients with primary TKA due to knee osteoarthritis (OA). MATERIALS AND METHODS: One hundred seven participants with primary TKA for end-stage knee OA were enrolled from January 2014 to January 2017. Patients were treated for 12 weeks either with TCC exercises (intervention) or traditional physical exercises (control). Outcomes including western ontario and mcMaster universities arthritis index (WOMAC), 6-min walk test (6 MWT), knee range of motion (ROM), and short form (36) health survey (SF-36) were assessed. The adverse events related to TCC exercises or TKA were recorded. RESULTS: Before the intervention, the two groups were comparable after examining the general descriptions of patients. Compared with the control group (CG), the TCC group (TG) had significantly better scores in the WOMAC physical function score, 6 MWT, SF-36 physical component score (PCS), and the mental component score (MCS) (P < 0.05) after the 12-week intervention. Nevertheless, there were no significant differences in WOMAC pain score and knee ROM. There were no adverse events related to the TCC exercise program. In the CG, three patients reported one fall each, but those falls did not lead to a further problem. CONCLUSION: The TCC exercises improve the physical function and the QOL in patients with primary TKA without additional risks.

Therapeutic effects of sensory input training on motor function rehabilitation after stroke.

Motor dysfunction is a common and severe complication of stroke that affects the quality of life of these patients. Currently, motor function rehabilitation predominantly focuses on active movement training; nevertheless, the role of sensory input is usually overlooked. Sensory input is very important to motor function. Voluntary functional movement necessitates preparation, execution, and monitoring functions of the central nervous system, while the monitoring needs the participation of the sensory system. Sensory signals affect motor functions by inputting external environment information and intrinsic physiological status as well as by guiding initiation of the motor system. Recent studies focusing on sensory input-based rehabilitation training for post-stroke dyskinesia have demonstrated that sensory function has significant effects on voluntary functional movements. In conclusion, sensory input plays a crucial role in motor function rehabilitation, and the combined sensorimotor training modality is more effective than conventional motor-oriented approaches.

Marrubenol inhibits osteosarcoma cancer cell growth by inducing autophagic cell death and inhibiting cancer cell migration and invasion.

PURPOSE: The present study aimed at evaluating the anticancer activity of marrubenol against osteosarcoma cells along with evaluating its effects on autophagic cell death, reactive oxygen species (ROS) generation and cell migration and invasion tendency. METHODS: In this study the Saos-2 osteosarcoma cell line was used. Cell cytotoxicity effects were evaluated by MTT cell viability assay, while clonogenic assay assessed the effects on cancer cell colony formation. In vitro wound healing assay was used to evaluate the effects on cell migration. To confirm autophagy, we evaluated the expression of several autophagy-associated proteins Western blot assay along with transmission electron microscopy (TEM). RESULTS: The results indicated that the marrubenol exhibited an IC50 value of 45 µM and exerted its cytotoxic effects in a dose-dependent manner. Moreover, it was observed that the drug inhibited colony formation and induced autophagy dose-dependently. The underlying mechanism for the induction of autophagy was found to be ROS-mediated and significant inhibition of cell migration as well as cell invasion potential of osteosarcoma cells at the IC50 was observed. CONCLUSIONS: These results strongly indicate that marrubenol may be considered as a potent drug lead molecule for the treatment and management of osteosarcoma.

Synergistic effect of celecoxib in tumor necrosis factor­related apoptosis­inducing ligand treatment in osteosarcoma cells.

Tumor necrosis factor-related apoptosis­inducing ligand (TRAIL) is under clinical development as a cancer therapeutic as it has been shown to induce apoptosis in numerous types of cancer cells without significant toxicity towards normal cells. However, the majority of osteosarcoma (OS) tumors are resistant to TRAIL. Thus, the development of cancer therapeutics that overcome TRAIL resistance is required. In the present study, celecoxib (CXB), a non-steroidal anti­inflammatory drug, was administered in combination with TRAIL to induce cell apoptosis and the doses of the two drugs were simultaneously reduced. The effects of this combination treatment were examined in MG-63 human OS cancer cell lines in culture. Assays of proliferation, apoptosis and tumor growth were performed, along with analysis of the proteins involved. The results revealed that CXB sensitized TRAIL-resistant MG-63 OS cells to TRAIL­induced apoptosis through downregulation of cellular B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, caspase-8 and caspase-3. Furthermore, combination treatment reduced tumor growth in a nude rat model. In conclusion, the experimental results provided evidence that the combined administration of CXB and TRAIL is potentially a novel treatment method of OS tumors.