BackgroundOsteoarthritis (OA) is a serious health concern worldwide, and patients with OA are in urgent need of proper long-term disease management to prevent disability and improve the quality of life. Research has started to investigate the feasibility and effectiveness of telemedicine in providing disease management for patients with chronic diseases. Guangdong Online Hospital (GOH) is the first officially recognized web-based hospital that widely provides telemedicine services in southern China.ObjectivesThis study aimed to establish the feasibility and effectiveness of GOH in providing long-term disease management for patients with knee OA via a 6-month, randomised control trial (RCT).Methods40 patients with knee OA were randomly assigned to receive conventional therapy (CT) in the clinic or conventional therapy plus a brief GOH-based intervention (CT-GOHT). GOH-based intervention included educational lectures, medical suggestions and psychotherapy. The primary outcome was the drop-out rates and the secondary outcomes included the mean change of the self-reported total score of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Multidimensional Fatigue Inventory (MFI), the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI) from baseline to endpoint.Figure 1Flow chat of trial participationFigure 2A telemedicine intervention to patients with knee OAResultsThe baseline characteristics were comparable between the two groups. 3 patients in CT group and 1 patient in CT-GOHT group lost to follow-up during the study (P = 0.598). A statistically significant difference was observed in the mean change of WOMAC recommended index of joint pain (8.82 ± 5.02 vs. 13.90 ± 7.63, P = 0.026), morning stiffness (3.12 ± 1.50 vs. 4.42 ± 2.06, P = 0.039), functional limitation (27.65 ± 9.91 vs. 38.84 ± 17.28, P = 0.025), HADS-Anxiety (3.24 ± 2.41 vs. 5.32 ± 3.23, P = 0.037), and PSQI global score (2.35 ± 1.54 vs. 4.21 ± 3.34, P = 0.043) from baseline to endpoint when comparing the CT group to the CT-GOHT group. In addition, Guangdong Online Hospital was widely accepted by the including OA patients for their disease management.ConclusionDelivering a telemedicine intervention to patients with knee OA via GOH is a feasible and potentially effective method in long-term disease management, especially for patients living in remote areas. The results provide preliminary experiences and guidance for an upcoming full-scale RCT in disease management via telemedicine.Trial registrationChiCTR1800014465.Reference[1] Huang Z, et al. Implementation of telemedicine for knee osteoarthritis: study protocol for a randomized controlled trial. Trials, 2018, 19(1):232.Table 1Baseline characteristics of the two study groupsVariableCT group(n = 20)CT-GOH group(n = 20)Age72.25 ± 8.8467.25 ± 10.97Female, n1515Education, nPrimary schoolHigh school128146Han Chinese, n2020Income, n<¥2000¥2000 -¥5000>¥5000 81025132BMI, kg/m2 25.85 ± 3.8726.29 ± 2.96Distance to hospital, kilometre105.83 ± 100.35...
Patients with chromoblastomycosis (CBM) usually have a history of local skin damage related to outdoor activities, mainly manifested as chronic refractory proliferative pathologic changes. We report a case of a 56-year-old man with CBM, identified as Fonsecaea pedrosoi infection by fungal culture and gene sequencing. This patient was successfully treated with a regimen of oral itraconazole (ITZ) and terbinafine lasting 7 months. Through in vitro drug sensitivity tests, minimum inhibitory concentrations of amphotericin, ITZ, and terbinafine were 1 lg/ml, 0.25 lg/ml, and 1 lg/ml, respectively. In this case, terbinafine was found to be more effective than ITZ.
Objective: Long noncoding RNAs (lncRNAs) participate in cancer immunity. Herein, we characterized the clinical significance of immune-related lncRNA model and its associations with immune infiltrations and chemosensitivity in bladder cancer.Methods: Transcriptome data of bladder cancer specimens were employed from The Cancer Genome Atlas. Dysregulated immune-related lncRNAs were screened via Pearson correlation and differential expression analyses, followed by recognition of lncRNA pairs. Then, a LASSO regression model was constructed. Receiver operator characteristic curves of one-, three- and five-year survival were plotted. Akaike information criterion (AIC) value of one-year survival was determined as the cutoff of high- and low-risk subgroups. The differences in survival, clinical features, immune cell infiltrations and chemosensitivity were compared between subgroups.Results: Totally, 90 immune-related lncRNA pairs were selected, 15 of which were put into the prognostic model. The area under the curves of one-, three- and five-year survival were 0.806, 0.825 and 0.828, confirming the favorable predictive performance of this model. According to the AIC value, we clustered subjects into high- and low-risk subgroups. High-risk score indicated unfavorable outcomes. This risk model was in relation to survival status, age, stage and TNM. In comparison to conventional clinicopathological characteristics, the risk model displayed higher predictive efficacy and was an independent predictor. Also, it could well characterize immune cell infiltration landscape and predict immune checkpoint expression and sensitivity to cisplatin and methotrexate.Conclusion: This model conducted by paring immune-related lncRNAs regardless of expressions exhibited a favorable efficacy in predicting prognosis, immune landscape and chemotherapeutic response in bladder cancer.
Objective:To investigate the effects of serum from patients with pemphigus vulgaris (PV) on the transcription and protein expression level of calcium-transporting ATPase type 2C member 1 (ATP2C1) and plakophilin 3 (PKP3) in HaCaT cells.Methods:The HaCaT cells were divided into four groups: PV sera group, anti-Dsg3 monoclonal antibody group (AK23, positive control group), normal healthy serum group, and blank cell group. The groups were treated with corresponding different conditions for 24 hours. Quantitative polymerase chain reaction and Western blot were used to detect mRNA and protein levels of ATP2C1 and PKP3.Results:Compared with the blank group, the mRNA level of the ATP2C1 and PKP3 genes in PV sera group was significantly increased by 384% and 404%, respectively (both P < 0.001). The treatment of PV sera and anti-Dsg3 antibody increased PKP3 protein expression (P = 0.03 and P = 0.004) but decreased protein expression of ATP2C1 in HaCaT cells (both P < 0.001).Conclusions:Our study indicates that serum from patients with PV promotes both ATP2C1 and PKP3 transcription in HaCaT cells, implying that the two genes may be involved in the pathological process of PV.
Background: Pemphigus vulgaris (PV) is associated with autoantibodies against desmoglein (Dsg), including Dsg1 and Dsg3. However, the precise mechanism by which acantholysis occurs in response to PV-IgG and the effect of tacrolimus on PV remains unclear. Method: Human HaCaT keratinocytes were co-cultured with DMEM medium containing 5% PV-sera to establish a cell model of pemphigus in order to determine the effect of PV-sera and tacrolimus on Dsg mRNA transcription and protein expression in HaCaT cells. Dsg protein expression in HaCaT cells was evaluated by Western blotting and Dsg mRNA transcription by real-time PCR (RT-PCR ). The distribution of Dsg1 and Dsg3 in HaCaT cells was determined by indirect immunofluorescence (IIF). Results: The application of 5% PV serum resulted in an increase in Dsg1 and Dsg3 transcription and expression levels, whereas tacrolimus suppressed Dsg1 and Dsg3 expression. Tacrolimus inhibited PV serum-induced disruption of cell-cell contacts. Tacrolimus also down-regulated Dsg1 and Dsg3 expression compared with PV. IIF revealed that Dsg1 linear deposits on the surface of HaCaT cells in the PV-sera group disappeared and were replaced by granular and agglomerated fluorescent particles on the cell surface, whereas the Dsg3 linear deposits were still present, however this effect could be reversed by tacrolimus. Conclusion: The Dsg3 antibody disrupts desmosome junctions by inducing endocytosis, resulting in desmosomal dissociation. Tacrolimus can reverse PV serum-induced enhancement Dsg expression in HaCaT cells.
Background: Glucocorticoids are the first-line treatment for Pemphigus vulgaris (PV), but its serious side effects can be life-threatening for PV patients. Tacrolimus (FK506) has been reported to have an adjuvant treatment effect against PV. However, the mechanism underlying the inhibitory effect of FK506 on PV-IgG-induced acantholysis is unclear. Objective: The objective of this study was to explore the effect of FK506 on desmoglein (Dsg) expression and cell adhesion in an immortalized human keratinocyte cell line (HaCaT cells) stimulated with PV sera. Methods: A cell culture model of PV was established by stimulating HaCaT cells with 5% PV sera with or without FK506 and clobetasol propionate (CP) treatment. The effects of PV sera on intercellular junctions and protein levels of p38 mitogen-activated protein kinase (p38MAPK), heat shock protein 27 (HSP27), and Dsg were assayed using western blot analysis, immunofluorescence staining, and a keratinocyte dissociation assay. Results: PV sera-induced downregulation of Dsg3 was observed in HaCaT cells and was blocked by FK506 and/or CP. Immunofluorescence staining revealed that linear deposits of Dsg3 on the surface of HaCaT cells in the PV sera group disappeared and were replaced by granular and agglomerated fluorescent particles on the cell surface; however, this effect was reversed by FK506 and/or CP treatment. Furthermore, cell dissociation assays showed that FK506 alone or in combination with CP increased cell adhesion in HaCaT cells and ameliorated loss of cell adhesion induced by PV sera. Additionally, FK506 noticeably decreased the PV serum-induced phosphorylation of HSP 27, but had no effect on p38MAPK phosphorylation. Conclusion: FK506 reverses PV-IgG induced-Dsg depletion and desmosomal dissociation in HaCaT cells, and this effect may be obtained by inhibiting HSP27 phosphorylation.
Background: Glucocorticoids are the first-line treatment for Pemphigus vulgaris (PV), but its serious side effects can be life-threatening for PV patients. Tacrolimus (FK506) has been reported to have an adjuvant treatment effect against PV. However, the mechanism underlying the inhibitory effect of FK506 on PV-IgG-induced acantholysis is unclear. Objective: The objective of this study was to explore the effect of FK506 on desmoglein (Dsg) expression and cell adhesion in an immortalized human keratinocyte cell line (HaCaT cells) stimulated with PV sera. Methods: A cell culture model of PV was established by stimulating HaCaT cells with 5% PV sera with or without FK506 and clobetasol propionate (CP) treatment. The effects of PV sera on intercellular junctions and protein levels of p38 mitogen-activated protein kinase (p38MAPK), heat shock protein 27 (HSP27), and Dsg were assayed using western blot analysis, immunofluorescence staining, and a keratinocyte dissociation assay. Results: PV sera-induced downregulation of Dsg3 was observed in HaCaT cells and was blocked by FK506 and/or CP. Immunofluorescence staining revealed that linear deposits of Dsg3 on the surface of HaCaT cells in the PV sera group disappeared and were replaced by granular and agglomerated fluorescent particles on the cell surface; however, this effect was reversed by FK506 and/or CP treatment. Furthermore, cell dissociation assays showed that FK506 alone or in combination with CP increased cell adhesion in HaCaT cells and ameliorated loss of cell adhesion induced by PV sera. Additionally, FK506 noticeably decreased the PV serum-induced phosphorylation of HSP 27, but had no effect on p38MAPK phosphorylation. Conclusion: FK506 reverses PV-IgG induced-Dsg depletion and desmosomal dissociation in HaCaT cells, and this effect may be obtained by inhibiting HSP27 phosphorylation.
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