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Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
الموضوعات
Adult , Humans , Adolescent , Imatinib Mesylate/adverse effects , Incidence , Antineoplastic Agents/adverse effects , Retrospective Studies , Pyrimidines/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Treatment Outcome , Benzamides/adverse effects , Leukemia, Myeloid, Chronic-Phase/drug therapy , Aminopyridines/therapeutic use , Protein Kinase Inhibitors/therapeutic useالملخص
The presence of midline diastema is a common complaint of patients that may affect dentofacial esthetics. This article summarized the etiology of maxillary midline diastema, and introduced the clinical application of sectional feldspathic porcelain veneers in maxillary midline diastema closure, including indication selection as well as clinical procedure. It aimed to provide an alternative solution on clinical treatment of maxillary midline diastema.
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Objective: To investigate the characteristics, risk factors and outcomes of thalassemia major (TM) children with pericardial effusion (PE) after allo-geneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Clinical data of 446 TM children received allo-HSCT at Shenzhen Children's Hospital between January 2012 and December 2020 were analyzed retrospectively. Patients were divided into PE and non-PE group according to the occurrence of PE. Chi-square tests were used to investigate the risk factors that were associated with the development of PE. Kaplan-Meier method was used for survival analysis of the 2 groups. Results: Twenty-five out of 446 patients (5.6%) developed PE at a time of 75.0 (66.5, 112.5) days after allo-HSCT. Among these patients, 22 cases (88.0%) had PE within 6 months after allo-HSCT and 19 patients (76.0%) had PE within 100 days after allo-HSCT. The diagnoses of PE were confirmed using echocardiography. Pericardial tamponade was observed in only 1 patient, who later undergone emergency pericardiocentesis. The rest of patients received conservative managements alone. PE disappeared in all patients after treatment. Risk factors that were associated with the development of PE after allo-HSCT included the gender of patients, the type of transplantation, the number of mononuclear cells (MNC) infuse, pulmonary infection after HSCT and transplantation associated thrombotic microangiopathy (TA-TMA) (χ²=3.99, 10.20, 14.18, 36.24, 15.03, all P<0.05). In 239 patients that received haploidentical HSCT, the development of PE was associated with the gender of patients, pulmonary infection after HSCT and TA-TMA (χ²=4.48, 20.89, 12.70, all P<0.05). The overall survival rates of PE and non-PE groups were 96.0% (24/25) and 98.6% (415/421). The development of PE was not associated with the overall survival of TM children after allo-HSCT (χ²=1.73, P=0.188). Conclusions: PE mainly develop within 100 days after allo-HSCT in pediatric TM recipients. Haploidentical grafts, female gender, pulmonary infection after HSCT and TA-TMA are the main risk factors associated with PE development after transplant. However, the presence of PE don't have a significant impact on the outcomes of pediatric TM patients after allo-HSCT.
الموضوعات
Child , Female , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Pericardial Effusion/etiology , Retrospective Studies , Risk Factors , Thrombotic Microangiopathies/complications , beta-Thalassemia/therapyالملخص
Background/Aims@#Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic dysfunction. Among the multiple factors, genetic variation acts as important modifiers. Klotho, an enzyme encoded by the klotho (KL) gene in human, has been implicated in the pathogenesis of metabolic dysfunctions. However, the impact of variants in KL on NAFLD risk remains poorly understood. The aim of this study was to investigate the impact of KL rs495392 C>A polymorphism on the histological severity of NAFLD. @*Methods@#We evaluated the impact of the KL rs495392 polymorphism on liver histology in 531 Chinese with NAFLD and replicated that in the population-based Rotterdam Study cohort. The interactions between the rs495392, vitamin D, and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism were also analyzed. @*Results@#Carriage of the rs495392 A allele had a protective effect on steatosis severity (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42–0.89; P=0.010) in Chinese patients. After adjustment for potential confounders, the A allele remained significant with a protective effect (OR, 0.66; 95% CI, 0.45–0.98; P=0.040). The effect on hepatic steatosis was confirmed in the Rotterdam Study cohort. Additional analysis showed the association between serum vitamin D levels and NAFLD specifically in rs495392 A allele carriers, but not in non-carriers. Moreover, we found that the rs495392 A allele attenuated the detrimental impact of PNPLA3 rs738409 G allele on the risk of severe hepatic steatosis. @*Conclusions@#The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.
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OBJECTIVE@#To investigate the effects of dasatinib on the maturation of monocyte-derived dendritic cells (moDCs) derived from healthy donors (HDs) and chronic myelogenous leukemia (CML) patients.@*METHODS@#Peripheral blood mononuclear cells (PBMCs) were isolated from HDs (n=10) and CML patients (n=10) who had got the remission of MR4.5 with imatinib treatment. The generation of moDCs from PBMCs was completed after 7 days of incubation in DC I culture medium, and another 3 days of incubation in DC II culture medium with or without 25 nmol/L dasatinib. On the 10th day, cells were harvested and expression of molecules of maturation related marker were assessed by flow cytometry. The CD80+CD86+ cell population in total cells was gated as DCs in the fluorescence-activated cell storting (FACS) analyzing system, then the expression of CD83, CD40 or HLA-DR in this population was analyzed respectively.@*RESULTS@#The proportion of CD80+CD86+ cells in total cells didn't show a statistical difference between HD group and patient group (89.46%±9.70% vs 87.39%±9.34%, P=0.690). Dasatinib significantly enhanced the expression of the surface marker CD40 (P=0.008) and HLA-DR (P=0.028) on moDCs derived from HDs compared with the control group, while the expression of CD83 on moDCs didn't show a significant difference between dasatinib group and the control group (P=0.428). Meanwhile, dasatinib significantly enhanced the expression of the surface marker CD40 (P=0.023), CD83 (P=0.038) and HLA-DR (P=0.001) on moDCs derived from patients compared with the control group.@*CONCLUSION@#For CML patients, the same high proportion of moDCs as HDs can be induced in vitro, which provides a basis for the application of DC-based immunotherapy strategy. Dasatinib at the concentration of 25 nmol/L can efficiently promote the maturation of moDCs derived from HDs and CML patients in vitro. Dasatinib shows potential as a DC adjuvant to be applied in DC-based immunotherapy strategies, such as DC vaccine and DC cell-therapy.
الموضوعات
Humans , Cell Differentiation , Cells, Cultured , Dasatinib/pharmacology , Dendritic Cells , HLA-DR Antigens/pharmacology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Leukocytes, Mononuclear , Monocytesالملخص
Objective To investigate the expression of dynein axonemal intermediate chain l(DNAI1) in lung adenocarcinoma (LUAD) and its influence on invasive ability of lung adenocarcinoma. Methods Microarray gene chip analysis was used to screen different expression genes in lung adenocarcinoma (3 samples) and adjacent normal tissues(3 samples); Heatmap and volcano plot were performed demonstrate the mRNA expression and distribution after screening; DAVID database used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes of Genomes (KEGG) analysis; STRING database and Cytoscape 3.6.1 software for protein-protein interaction (PPI) analysis and screening of Hub genes; Objective genes were selected based on the differential expression of each Hub gene in lung adenocarcinoma in DEGs and Ualcan database; Real-time PCR and Western blotting were used to detect the expression of DNAI1 in BEAS-2B, H1299 and A549; observe the morphological changes after DNAI1 overexpression; Transwell invasion assay was used to detect the change of invasion ability of A549 cells after DNAI1 overexpression. Results The microarray result showed that there were 86 up-regulated genes and 396 down-regulated genes; different genes were involved in the RNA polymerase II promoter positive regulation of transcription, apoptosis process of negative regulation, protein binding, and other functions, widely distributed within the cell, and associated with the metabolic pathway, cancer and other signal pathways were closely related ; DEGs database and Ualcan database showed that DNAI1 was the most downregulated among Hub genes in LUAD; the result of Real-time PCR and Western blotting showed that DNAI1 had lower expression in H1299 and A549 compared with BEAS-2B; after DNAI1 overexpression, A549 cells became round and a few shed off; invasion assay showed that the invasion ability of A549 cells was significantly reduced. Conclusion DNAI1 has a lower expression and inhibits the ability of invasion in LUAD, and this study can provide a potential molecular target and provide a theoretical basis for targeted therapy of LUAD.
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Chronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain (especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses, but the underlying molecular mechanisms remain unclear. Here, we investigated how synaptic cell adhesion molecules (e.g., nectin3) are involved in the effects of adolescent chronic stress on mouse medial prefrontal cortex (mPFC). Male C57BL/6N mice were subjected to chronic social instability stress from postnatal days 29 to 77. One week later, the mice exposed to chronic stress exhibited impaired social recognition and spatial working memory, simplified dendritic structure, and reduced spine density in the mPFC. Membrane localization of nectin3 was also altered, and was significantly correlated with behavioral performance. Furthermore, knocking down mPFC nectin3 expression by adeno-associated virus in adolescent mice reproduced the stress-induced changes in behavior and mPFC morphology. These results support the hypothesis that nectin3 is a potential mediator of the effects of adolescent chronic stress on prefrontal structural and functional abnormalities.
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Synaptic cell adhesion molecules (CAMs) are a type of membrane surface glycoproteins that mediate the structural and functional interactions between pre- and post-synaptic sites. Synaptic CAMs dynamically regulate synaptic activity and plasticity, and their expression and function are modulated by environmental factors. Synaptic CAMs are also important effector molecules of stress response, and mediate the adverse impact of stress on cognition and emotion. In this review, we will summarize the recent progress on the role of synaptic CAMs in stress, and aim to provide insight into the molecular mechanisms and drug development of stress-related disorders.
الموضوعات
Humans , Cell Adhesion , Cell Adhesion Molecules , Physiology , Neuronal Plasticity , Stress, Physiological , Stress, Psychological , Synapsesالملخص
OBJECTIVE@#To investigate the clinical effects of dual mobility total hip prosthesis in treating femoral neck fracture patients with hemiplegia.@*METHODS@#A retrospective analysis was performed on 18 patients with femoral neck fracture combined with hemiplegia who underwent dual mobility total hip prosthesis replacement from March 2014 to December 2016. The follow up data of these patients was complete. There were 5 males and 13 females, aged 65 to 70 years old with an average of (66.50±1.38) years. The left side was involved in 12 cases, while the right side in 6 cases. There were 4 cases with Garden Ⅲ type and 14 cases with type Ⅳ. Limb muscle strength of hemiplegia were in grade Ⅳ. The posterior-lateral approach of hip joint was used in surgery for all patients. The implant position, dislocation and loosening of the prosthesis were evaluated by X-ray examination. Harris hip score and the Merle D'aubigne score were used to assess the hip function in the follow up.@*RESULTS@#The operation duration was for 70-90 (81.56±7.48) min and the blood loss during the operation was for 160-200 (170.32± 12.56) ml. No blood was transfused during the operation. Postoperative incisions were healed at the first stage. The follow-up time was for 28-60(36.0±3.5) months. Harris hip score increased from 16.94±0.73 preoperatively to 96.19±1.27 at the final follow-up(<0.05). Merle D 'Aubigne score increased from 3.96±0.06 preoperatively to 16.81±0.63 at the final follow-up(< 0.05). No fracture or nerve or vascular injury were found during the operation. The postoperative X-ray showed that the prosthesis was in good position. No complications such as joint dislocation, dislocation of prosthesis, loosening of prosthesis, fracture around the prosthesis, pain in the front of thethigh, fracture of the self tapping screw in the ilium, and delayed infection occurred in the patients after operation.@*CONCLUSION@#Dual mobility total hip prosthesis has the advantages of both good initial stability and low dislocation rate of the prosthesis, and the clinical application of total hip replacement in hemiplegic femoral neck fracture is satisfactory.
الموضوعات
Aged , Female , Humans , Male , Arthroplasty, Replacement, Hip , Femoral Neck Fractures , General Surgery , Follow-Up Studies , Hemiplegia , Hip Prosthesis , Retrospective Studies , Treatment Outcomeالملخص
The main lysosomal protease cathepsin D (cathD) is essential for maintaining tissue homeostasis via its degradative function, and its loss leads to ceroid accumulation in the mammalian nervous system, which results in progressive neurodegeneration. Increasing evidence implies non-proteolytic roles of cathD in regulating various biological processes such as apoptosis, cell proliferation, and migration. Along these lines, we here showed that cathD is required for modulating dendritic architecture in the nervous system independent of its traditional degradative function. Upon cathD depletion, class I and class III arborization (da) neurons in Drosophila larvae exhibited aberrant dendritic morphology, including over-branching, aberrant turning, and elongation defects. Re-introduction of wild-type cathD or its proteolytically-inactive mutant dramatically abolished these morphological defects. Moreover, cathD knockdown also led to dendritic defects in the adult mushroom bodies, suggesting that cathD-mediated processes are required in both the peripheral and central nervous systems. Taken together, our results demonstrate a critical role of cathD in shaping dendritic architecture independent of its proteolytic function.
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Objective:To analyze the cardiopulmonary function of stable patients with pulmonary arterial hypertension (PAH), and to explore effects of the cardiopulmonary exercise testing (CPET)-based individualized moderate-intensity exercise prescription on cardiopulmonary functional reserve and exercise capacity in patients with PAH. Methods:From April, 2018 to July, 2019, 31 stable patients with PAH (PAH group) and 32 healthy counterparts (normal group) were enrolled. All subjects underwent CPET. PAH group was assessed with 6-Minute Walking Test (6MWT), and then was divided into exercise group (n = 16) and control group (n = 15). Both groups were treated with ordinary targeted drugs, while the exercise group was additionally provided with an individualized moderate-intensity exercise prescription of △50% power treadmill training, five days a week for eight weeks. CPET and 6MWT were conducted again after intervention. Results:Before intervention, body mass, body mass index (BMI), force vital capacity (FVC), forced expiratory volume in one second (FEV1), maximum voluntary ventilation (MVV), anaerobic threshold (AT), peak heart rate (HRpeak), peak systolic blood pressure (SBPpeak), peak load power (WRpeak), peak oxygen uptake (VO2peak), peak oxygen pulse (VO2/HRpeak), peak cardiac output (COpeak), peak minute ventilation (VEpeak), peak end-tidal carbon dioxide (PETCO2peak), peak pulse oxygen saturation (SpO2peak) and oxygen uptake efficiency plateau (OUEP) were significantly lower (t > 2.419, P < 0.05), and the rest heart rate (HRrest), peak dead space to tidal volume ratio (VD/VTpeak), minimum ventilatory equivalent for carbon dioxide (Lowest VE/VCO2) and slope of ventilatory equivalent for carbon dioxide (VE/VCO2 slope) were higher (|t| > 2.615, P < 0.05) in PAH group than in the normal group. After intervention, FEV1, MVV, VO2peak (ml/min/kg) and VO2/HRpeak decreased in the control group (t > 2.272, P < 0.05); FVC, FEV1, MVV, AT, SBPpeak, WRpeak, VO2peak, VO2/HRpeak, COpeak, VEpeak, PETCO2peak, SpO2peak and 6-Minute Walking Distance (6MWD) increased (|t| > 2.167, P < 0.05), while the average Lowest VE/VCO2 and VE/VCO2 slope decreased (t > 2.264, P < 0.05) in the exercise group. Compared with the control group, the FEV1/FVC, AT, WRpeak, VO2peak, VO2/HRpeak, COpeak and 6MWD increased in the exercise group (|t| > 2.168, P < 0.05). Conclusion:The holistic cardiopulmonary function of stable patients with PAH decreases. CPET-based individualized moderate-intensity exercise could enhance the cardiopulmonary functional reserve and exercise capacity of patients with PAH.
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Objective:To explore the effect of home-based rehabilitation on children with congenital muscular torticollis (CMT). Methods:From January, 2016 to January, 2018, 60 children with CMT were randomly divided in to control group (n = 30) and observation group (n = 30). Both groups received comprehensive physical therapy; the observation group received home-based rehabilitation in addition. Three months after treatment, the sternocleidomastoid thickness, severity classification of CMT, and clinic effect were compared. Results:After treatment, the sternocleidomastoid thickness decreased in both groups (t > 9.862, P < 0.001), and was better in the observation group than in the control group (t = 5.468, P < 0.001); the severity classification of CMT decreased in both groups (|Z| > 5.857, P < 0.001), and was better in the observation group than in the control group (Z = -2.226, P < 0.05), as well as the clinical effect (U = 2359, P = 0.018). Conclusion:Home-based rehabilitation combined with comprehensive physical therapy is superior to comprehensive physical therapy only.
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OBJECTIVE@#Systemic sclerosis (SSc) is a remarkably systemic heterogeneous connective tissue disease with many organs involved. The heart is one of the major organs involved, carrying the threat of sudden cardiac death, especially in diffuse cutaneous SSc. This review summarizes the pathophysiology, types, new diagnostic approaches, and imaging and novel therapies of primary cardiac complications while underlining the effects of recently developed non-contrast cardiovascular magnetic resonance (CMR) in early diagnosis.@*DATA SOURCES@#Medline and Embase were searched for articles published up to July 2019. A combination of Medical Subject Headings (MeSH) terms and keywords pertaining to SSc ("Scleroderma, Systemic" OR "Systemic sclerosis" OR' SSc"), AND cardiology ("cardiology" OR "heart" OR "cardiac") were applied to the search strategies.@*STUDY SELECTION@#Literature was mainly printed in English and Chinese about cardiac complications in systemic sclerosis. After selected simply on the title and abstract, the articles were included for the full text. Article type was not limited.@*RESULTS@#Relevant cardiac manifestations are complex, including arrhythmias, pericardial effusion, myocardial dysfunction, and valvular diseases. Even though the symptoms of cardiac complications are well known, unfortunately, they appear to be poor prognostic factors. As systemic sclerosis with cardiac complications has a high mortality rate and patients might have a poor quality of life, it is essential to promote early diagnosis and treatment. With the advent of non-invasive imaging techniques, such as CMR, early diagnosis of cardiac complications in SSc is becoming more effective.@*CONCLUSIONS@#Cardiac complications play an essential role in SSc and carry the threat of sudden cardiac death. More basic and clinical studies are warranted to develop better management of cardiac involvement in patients with SSc.
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OBJECTIVE@#To compare the immunomodulatory effects of the 2nd generation of tyrosine kinase inhibitors (TKIs)-dasatinib and nilotinib as well as the 1st generation of TKI-imatinib on chronic myeloid leukemia (CML) patients.@*METHOD@#To evaluate the T cell subtypes by flow cytometry on the CML patients of our center who received the treatment with dasatinib (n=10), nilotinib (n=26) or imatinib (n=44) for more than 3 months, and to analyze and correlate these data with the clinical remission situations and prognosis.@*RESULTS@#80.0% of the patients in dasatinib group, 16.6% of the patients in nilotinib group and 27.5% of the patients in imatinib group respectively had a Th1 proportion in the peripheral blood (Th1/CD4 T) above the upper limit of normal. More specifically, the Th1 proportion in dasatinib group (30.86%±9.75%) was significantly higher than that in nilotinib group(17.37%±9.35%) (P<0.001) and that in imatinib group (20.79%±9.01%) (P<0.001). Among the 3 groups, both the CD8 T cell proportion (CD8 T/Lymphocyte) and the Th2 proportion (Th2/CD4 T) in the peripheral blood did not show a statistically significant difference. The Treg proportion (Treg/CD4 T) in dasatinib group (1.31%±0.10%) was significantly lower than that in nilotinib group (2.65%±0.97%) (P<0.001) and that in imatinib group(2.99%±1.40%) (P<0.001).Among all the CML patients analyzed, for CML patients who had a Th1 proportion above the upper limit of normal(25.8%) (n=28), 84.62% of these patients obtained CCyR (complete cytogenetic response), 71.43% of these patients obtained MMR (major molecular response), 71.43% of these patients obtained MR4.5; for CML patients who had the Th1 proportion in the normal range(11.8%-25.8%) (n=45), 90.7% of these patients obtained CCyR, 75.56% of these patients obtained MMR, and 75.56% of these patients obtained MR4.5; for CML patients who had the Th1 proportion below the lower limit of normal (11.8%) (n=21), 57.14% of these patients obtained CCyR, 47.62% of these patients obtained MMR, and 47.62% of these patients obtained MR4.5. The above-mentioned data shows that the patients in high Th1 group and the normal Th1 group obtained the higher remission rate as well as the deeper remission level.@*CONCLUSION@#This study shows that during the CML treatment with TKIs, the increased or normal Th1 proportion indicates a bigger chance for CCyR, MMR, and MR4.5. Dasatinib may significantly increase the level of Th1 while decrease the level of Treg in the patients, as compared with nilotinib and imatinib.
الموضوعات
Humans , Dasatinib , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Protein Kinase Inhibitors , Protein-Tyrosine Kinases , T-Lymphocytes, Regulatory , Th1 Cells , Treatment Outcomeالملخص
BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) and bone marrow mononuclear cells(BMMNCs) have been both used to treat spastic cerebral palsy. However, the differences in their therapeutic effects remain unknown. OBJECTIVE: To compare the therapeutic effects of BMMSCs and BMMNCs in cerebral palsy children as well as on fine motor function. METHODS: 105 children with spastic cerebral palsy were enrolled and randomly assigned to three groups: BMMSCs group, BMMNCs group and control group. Patients in the two transplantation groups received four intrathecal cell injections, and those in the control group received Bobath therapy, twice a day, for consecutive 3 weeks. The Gross Motor Function Measure (GMFM) and Fine Motor Function Measure (FMFM) were used to evaluate the therapeutic efficacy at 3, 6 and 12 months after transplantation. RESULTS AND CONCLUSION: At 3 months after cell transplantation, scores in A dimension of GMFM and in A, C dimensions of FMFM in BMMSC group were all superior to those of BMMNC group and control group (P < 0.05). At 6 months after cell transplantation, scores in A, B dimensions of GMFM and in A, B, C, D and E dimensions of FMFM in BMMSC group were better than those of BMMNC group and control group (P< 0.05), and total scores of GMFM and FMFM were also better in the BMMSC group (P < 0.05). At 12 months after cell transplantation, scores in A, B and C dimensions of GMFM and A, B, C, D and E dimensions of FMFM scores in BMMSC group were all superior to those of BMMNC group and control group (P < 0.05) as well as the total GMFM and FMFM scores. There were six cases of low intracranial pressure headache in BMMNC group and six cases of low-grade fever in BMMSC group. In summary, both BMMSCs transplantation and BMMNCs transplantation are safe, effective and feasible for the treatment of spastic cerebral palsy in children, and moreover, BMMSCs transplantation is a better method than BMMNCs transplantation to improve gross and fine motor functions of spastic cerebral palsy children.
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BACKGROUND:Currently, there is no explicit evidence-based medicine evidence to prove the merits or demerits of absorbable materials in the treatment of fractures of the lateral humeral condyle in children. OBJECTIVE:To evaluate the clinical efficacies of open reduction with absorbable material versus open reduction with Kirschner wire fixation for lateral condylar fracture of the humerus in children.METHODS:WanFang, VIP, CNKI, CBMdisc, EMbase, PubMed were retrieved for controlled trials concerning open reduction with absorbable material versus open reduction with Kirschner wire fixation for treating lateral condylar fracture of the humerus in children. After data extraction and quality evaluations, RevMan 5.3 software was used for systematic review. Postoperative functional recovery of the elbow joint, average hospitalization expenses, adverse events, delayed union, postoperative infection, nerve injury and deformity of the elbow were compared in patients undergoing different treatments. RESULTS AND CONCLUSION:A total of seven articles, involving 449 children with lateral condylar fracture of the humerus, were included for this Meta-analysis. Children in test group received open reduction with absorbable material, while those in control group were subjected to open reduction with Kirschner wire fixation. For treating lateral condylar fracture of the humerus in children, no significant inter-group difference existed in the aspects of postoperative functional recovery of the elbow joint [odds ratio (OR)=0.72, 95% confidence interval (CI) (0.37, 1.41),P=0.34]; postoperative delayed union [OR=0.46, 95%CI(0.16, 1.30),P=0.14]; deformity of the elbow [OR=0.70, 95%CI (0.24, 2.10),P=0.53]. Less adverse events and postoperative infections were observed in the test group compared with the control group [OR=0.17, 95%CI (0.08, 0.38),P < 0.0001;OR=0.09, 95%CI (0.02, 0.38),P=0.001]. However, up to now, we knew of no comparable data concerning average hospitalization expenses and indicators for nerve injury between the two groups. To conclude, compared with Kirschner wire fixation, open reduction with absorbable material can achieve similar effects on lateral condylar fractures of the humerus, but has better effects to prevent adverse events and postoperative infection. Further investigation on large-scale, double-blind, high-quality randomized controlled trials is warranted for confirming our results.
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Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage (SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury (EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine (10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier (BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1β, IL-6, TNF-α, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.
الموضوعات
Animals , Male , Rats , Apoptosis , Blood-Brain Barrier , Brain Edema , Drug Therapy , Cytokines , Genetics , Metabolism , Disease Models, Animal , Fluoxetine , Pharmacology , Therapeutic Uses , In Situ Nick-End Labeling , Neuroprotective Agents , Pharmacology , Therapeutic Uses , Pain Measurement , Psychomotor Performance , RNA, Messenger , Metabolism , Rats, Sprague-Dawley , Subarachnoid Hemorrhage , Drug Therapy , Pathology , Time Factors , Vasospasm, Intracranial , Drug Therapyالملخص
Depression is a debilitating psychiatric disorder with a huge socioeconomic burden, and its treatment relies on antidepressants including selective serotonin reuptake inhibitors (SSRIs). Recently, the melatonergic system that is closely associated with the serotonergic system has been implicated in the pathophysiology and treatment of depression. However, it remains unknown whether combined treatment with SSRI and melatonin has synergistic antidepressant effects. In this study, we applied a sub-chronic restraint stress paradigm, and evaluated the potential antidepressant effects of combined fluoxetine and melatonin in adult male mice. Sub-chronic restraint stress (6 h/day for 10 days) induced depression-like behavior as shown by deteriorated fur state, increased latency to groom in the splash test, and increased immobility time in the forced-swim test. Repeated administration of either fluoxetine or melatonin at 10 mg/kg during stress exposure failed to prevent depression-like phenotypes. However, combined treatment with fluoxetine and melatonin at the selected dose attenuated stress-induced behavioral abnormalities. Moreover, we found that the antidepressant effects of combined treatment were associated with the normalization of brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling in the hippocampus, but not in the prefrontal cortex. Our findings suggest that combined fluoxetine and melatonin treatment exerts synergistic antidepressant effects possibly by restoring hippocampal BDNF-TrkB signaling.
الموضوعات
Animals , Male , Antidepressive Agents , Pharmacology , Behavior, Animal , Brain-Derived Neurotrophic Factor , Metabolism , Depression , Drug Synergism , Drug Therapy, Combination , Fluoxetine , Pharmacology , Hippocampus , Metabolism , Melatonin , Pharmacology , Membrane Glycoproteins , Metabolism , Mice, Inbred C57BL , Protein-Tyrosine Kinases , Metabolism , Restraint, Physical , Signal Transductionالملخص
OBJECTIVE@#To investigate the early clinical effects of transforaminal endoscopic spine system (TESSYS) for the treatment of bilateral lumbar disc herniation in single segment.@*METHODS@#The clinical data of 38 patients with single-segment bilateral lumbar disc herniation treated by TESSYS technique from February 2016 to February 2018 were retrospectively analyzed. There were 26 males and 12 females, aged from 30 to 55 years old with an average of(35.2±6.4) years, 6 cases of L₃,₄, 22 cases of L₄,₅, and 10 cases of L₅S₁1. Using the intervertebral foramen endoscope produced by Joimax GmbH, Germany, under local anesthesia, bilateral puncture to the outside of the intervertebral foramen of the diseased segment, four-stage dilatation catheter to complete the progressive enlargement of the intervertebral foramen, and the ring saw progressively enlarge the intervertebral foramen. The bilateral foramen was placed and the herniated nucleus was removed until the nerve root was completely released. Postoperatively, the patients were reviewed on regular outpatient visits and telephone follow-ups. Visual analogue scale (VAS) and Oswestry Disability Index (ODI) were compared before operation and after operation at 1, 3, 6, 12 months respectively. At the final follow-up, according to modified MacNab criteria to evaluate the clinical effect.@*RESULTS@#Thirty-six patients underwent successful surgery and were followed up for more than 12 months. The ODI score and VAS score of the lower extremities pain at 1, 3, 6, 12 months after operation were obviously improved (0.05). At the final follow-up, according to MacNab criteria, 14 cases got excellent results, 16 good, 4 fair, 2 poor.@*CONCLUSIONS@#Using TESSYS technique to remove the bilateral herniated nucleus from single segment can fully decompress for the nerve root, and can be effectively applied to patients with single-segment bilateral lumbar disc herniation.
الموضوعات
Adult , Female , Humans , Male , Middle Aged , Diskectomy, Percutaneous , Endoscopy , Intervertebral Disc Degeneration , Intervertebral Disc Displacement , Lumbar Vertebrae , Retrospective Studies , Treatment Outcomeالملخص
[Objective]To explore the adverse pregnancy outcomes(APO)and examine the predictive value of umbil-ical artery Doppler in systemic lupus erythematosus(SLE)pregnancies.[Methods]Data of 273 pregnancies from 2010 to 2016 were analyzed retrospectively. Pulsatility index(PI),resistance index(RI),and systolic/diastolic ratio(S/D)of the umbilical artery flow velocity data were monitored by Doppler ultrasound.[Results]One or more APO occurred in 61.9% of patients with SLE,among which pregnancy loss occurred in 60 cases;preterm birth in 56 cases;intrauterine growth retardation occurred in 20 cases;and fetal distress occurred in 21 cases.Twelve of pregnancies resulted in neona-tal Lupus. In total,118 patients underwent fetal umbilical artery Doppler during 28~34 gestational weeks. Doppler PI, RI,and S/D were significantly higher in the APO groups than in the patients without APO.[Conclusion]Pregnancies in lupus still had an increased risk of APO.Umbilical artery Doppler was useful in predicting APO in lupus pregnancies.