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Objective:To evaluate the long-term safety, tolerability and efficacy of Lacosamide add-on therapy in Chinese children with partial-onset seizures.Methods:SP848 was a global multicenter single-arm study involving 60 Chinese children with partial-onset seizures with the age of 4-17 years who were managed by Lacosamide add-on therapy at seven hospitals across China from April 2018 to May 2019.After treatment with at least two kinds of anti-seizure medications simultaneously or sequentially, partial seizures were still poorly controlled and Lacosamide oral solution (syrup) or tablets were added.The minimum initial oral dose was 2 mg/(kg·d), and the maximum allowable dose was 12 mg/(kg·d)or 600 mg/d during the study period.The dose was adjusted according to the tolerance and seizure control level of partial-onset seizures children.Seizure frequency and the median percentage change in partial-onset seizures per 28 days from baseline to the final visit were recorded, including 50% responder rate and 75% responder rate.Results:A total of 60 Chinese children with the mean age of 9.18 (4.00-15.40) years were included in this interim analysis, involving 39 males and 21 females.The mean course of epilepsy was 5.04 (0.50-15.20) years.A total of 43 patients (71.7%) still have been treated.One patient (1.7%) has completed the 6-12 months of follow-up, and 14 patients (23.3%) have completed the follow-up for less than 6 months.The median change in the frequency of partial seizures every 28 days from baseline to the last visit was -2.91, with its median percentage as -25.46%, and the proportions of ≥50%, while ≥75% responder rate were 40.0% and 28.3%, respectively.A total of 52 patients (86.7%) had 265 treatment emergent adverse events (TEAE), 11 patients (18.3%) had 19 serious TEAE, 37 patients (61.7%) had 127 drug-related TEAE, and 11 patients (18.3%) had 16 TEAE leading to the discontinuation of the trial.The most common TEAE were upper respiratory tract infections (20 cases, 33.3%), followed by drowsiness (16 cases, 26.7%), dizziness (15 cases, 25.0%) and vomiting (13 cases, 21.7%). There were no abnormal changes in the electrocardiographic findings during the treatment.Conclusions:For Chinese patients with partial seizures who are older than the age of 4 years and poorly controlled by other drugs, Lacosamide is effective and well tolerated as an add-on therapy drug.The safety characteristics are consistent with those reported in children and adults.No new safety concerns are identified.
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Objective:To investigate the development and influencing factors of frailty in elderly patients on maintenance hemodialysis.Methods:A cross-sectional survey involved 146 elderly patients on maintenance hemodialysis at the blood purification department of the First Affiliated Hospital of Xi'an Jiaotong University.A self-designed demographic questionnaire was used to collect general information of patients, the Simple Physical Performance Scale(SPPB)was used to assess physical function, the 5-item SARC-F was used as a tool for rapid screening of sarcopenia, and the Hospital Anxiety and Depression Scale(HADS)was used for screening of anxiety and depression.The FRAIL scale was used for frailty assessment and participants were divided into a no frailty group, a pre-frailty group and a frailty group according to different frailty scores.Relevant influencing factors of frailty were analyzed.Results:Among 146 hemodialysis patients, 33(22.6%)were in the non-frailty group, 86(58.9%)in the pre-frailty group, and 27(18.5%)in the frailty group.Univariate analysis showed that there were statistically significant differences in sex( χ2=6.220, P=0.045), age( F=5.197, P=0.007), body type( χ2=31.927, P<0.001), SARC-F score( χ2=24.283, P<0.001)and SPPB score( χ2=26.773, P<0.001)between different groups.There were 3 patients(9.4%)at high risk for sarcopenia in the no frailty group, 13 patients(40.6%)at high risk for sarcopenia in the pre-frailty group, and 16 patients(50%)at high risk for sarcopenia in the frailty group, and differences in the occurrence of sarcopenia between the different subgroups of frailty were statistically significant( χ2=27.496, P<0.001). Multifactorial Logistic regression analysis showed that age, ( OR=1.04, 95% CI: 0.99-1.08, P=0.049), sex( OR=0.39, 95% CI: 0.17-0.87, P=0.021), body size( OR=0.07, 95% CI: 0.01-0.50, P=0.008), SARC-F( OR=0.14, 95% CI: 0.05-0.38, P<0.001)were independent influencing factors of frailty in elderly maintenance hemodialysis patients( P<0.05). Conclusions:The incidence of frailty is high in elderly patients on maintenance hemodialysis, and the development of frailty is affected by age, body mass index and sarcopenia.
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OBJECTIVES@#The excretion of urinary vitamin D-binding protein (uVDBP) is related to the occurrence and development of early-stage renal damage in patients with Type 2 diabetes (T2DM). This study aims to explore the significance of detecting uVDBP in T2DM patients and its relationship with renal tubules, and to provide a new direction for the early diagnosis of T2DM renal damage.@*METHODS@#A total of 105 patients with T2DM, who met the inclusion criteria, were included as a patient group, and recruited 30 individuals as a normal control group. The general information and blood and urine biochemical indicators of all subjects were collected; the levels of uVDBP, and a marker of tubular injury [urine kidney injury molecule 1 (uKIM-1), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine retinol-binding protein (uRBP)] were detected by enzyme-linked immunosorbent assay. The results were corrected by urinary creatinine (Cr) to uVDBP/Cr, uKIM-1/Cr, uNGAL/Cr and uRBP/Cr. The Pearson's and Spearman's correlation tests were used to analyze the correlation between uVDBP/Cr and urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) and markers of tubular injury, and multivariate linear regression and receiver operating characteristic curve were used to analyze the correlation between uVDBP/Cr and UACR or eGFR.@*RESULTS@#Compared with the normal control group, the uVDBP/Cr level in the patient group was increased (P<0.05), and which was positively correlated with UACR (r=0.774, P<0.01), and negatively correlated with eGFR (r=-0.397, P<0.01). There were differences in the levels of uKIM-1/Cr, uNGAL/Cr, and uRBP/Cr between the 2 groups (all P<0.01). The uVDBP/Cr was positively correlated with uKIM-1/Cr (r=0.752, P<0.01), uNGAL/Cr (r=0.644, P<0.01) and uRBP/Cr (r=0.812, P<0.01). The sensitivity was 90.0% and the specificity was 82.9% (UACR>30 mg/g) for evaluation of uVDBP/Cr on T2DM patients with early-stage renal damage, while the sensitivity was 75.0% and the specificity was 72.6% for evaluation of eGFR on T2DM patients with early-stage renal damage.@*CONCLUSIONS@#The uVDBP/Cr can be used as a biomarker in early-stage renal damage in T2DM patients.
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Humanos , Diabetes Mellitus Tipo 2/complicações , Creatinina , Proteína de Ligação a Vitamina D/urina , Lipocalina-2/urina , Rim/metabolismo , Taxa de Filtração Glomerular , BiomarcadoresRESUMO
Objective:To measure the anatomical parameters of the simulated low tibial tunnel of posterior cruciate ligament (PCL) based on knee CT images so as to provide clinical reference for accurate location of the tunnel.Methods:The CT images of 201 healthy knee joints collected at Department of Orthopedics, The Second Hospital of Lanzhou University from June 2016 to September 2021 were used for simulation of the PCL low tibial tunnel. The anatomical parameters of the tibial tunnel were measured using the RadiAnt DICOM Viewer. The primary measures included the angle between tibial plateau and tibial tunnel (ATPT) and the perpendicular distances from the tibial tunnel entrance and exit point to the tibial plateau (L1 and L2). The secondary measures included the angle between tibial plateau and posterior slope (PSA), the angle between tibial anatomical axis and central line of tibial tunnel (ATAA), the angle between posterior tibial slope line and the central line of tibial tunnel (APST), the anterior and posterior diameter of tibial plateau (APD), the length of posterior tibial slope (LPTS), and the length of tibial tunnel (LTT). The measurement results were analyzed according to the body height (divided into 3 groups: a 1.00 to 1.60 m group, a 1.61 to 1.70 m group, and a ≥1.71 m group) and gender using the software IBM SPSS 26.Results:The primary measures: ATPT was 37.0°±4.5°, and L1 and L2 were respectively (57.8±7.4) mm and (34.5±3.3) mm. The secondary measures: PSA 128.1°±5.4°, ATAA 52.7°±4.1°, APST 89.1°±5.9°, APD was (32.9±2.6) mm, LPTS (20.5±2.4) mm, and LTT (40.9±5.7) mm. After grouping by gender, there was no significant difference in PSA between men and women ( P>0.05) while there were significant differences in the other indexes between men and women ( P<0.05). After grouping by body height, there was no significant difference in ATPT, PSA, APST or ATAA between the 3 groups (1.00 to 1.60 m group, 1.61 to 1.70 m group and ≥1.71 m group) ( P>0.05) while there were significant differences in L1, L2, APD, LPTS and LTT between the 3 groups ( P<0.05). Conclusions:Based on the knee CT images, the primary measures of PCL low tibial tunnel are as follows: the angle between tibial plateau and tibial tunnel is 37.0°±4.5°, and the perpendicular distances from the tibial tunnel entrance and exit point to the tibial plateau are (57.8±7.4) mm and (34.5±3.3) mm, respectively. Gender and body height are the important factors influencing the above measurement outcomes.
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Objective To investigate whether elevated parathyroid hormone (PTH) levels could induce endothelial - to - mesenchymal transition (EndMT) and adipocyte transition in endothelial cells (ECs), and to determine the possible underlying mechanism. Methods (1) A rat model of secondary hyperparathyroidism and chronic kidney disease (CKD) was established. The adiposity in bone marrow was detected by oil red O staining. Immunofluorescence staining was performed to detect the expression and localization of cluster of differentiation 31 (CD31) and fibroblast-specific protein 1 (FSP1). (2) The human umbilical vein ECs were cultured in vitro. Western blotting was performed to detect protein expressions of EndMT-related markers CD31, FSP1 and α-smooth muscle actin (α-SMA) in interference groups with different PTH concentrations (0, 10-11, 10-9, 10-7 mol/L PTH for 48 h) and times (0, 12, 24, 48 h, 10-7 mol/L PTH), as well as the expression of β-catenin in interference groups with different PTH concentrations. The localizations of CD31, FSP1 and β - catenin were observed by cell immunofluorescence. Protein expressions of adipocytes markers peroxisome proliferator - activated receptor-γ (PPAR-γ) and CCAAT/enhancer binding protein-α (C/EBP-α) by Western blotting and the degree of adipogenesis by oil red O staining were detected after transformed ECs were cultured in adipogenic culture medium for one week. Small interfering RNA (siRNA) was performed to silenceβ - catenin expression. ECs were divided into control siRNA group, β - catenin siRNA group, PTH +control siRNA group and PTH+β-catenin siRNA group. Protein expressions of CD31, FSP1 and PPAR-γby Western blotting and the degree of adipogenesis by oil red O staining were determined. Results (1) In vivo, compared with the control, CKD rats had increased adipocytes in bone marrow (P<0.05), and the co-expression of CD31 and FSP1 in bone marrow ECs. (2) In vitro, PTH significantly inhibited the expression of endothelial marker CD31 and increased the expressions of mesenchymal markers FSP1 and α-SMA in concentration-and time-dependent manners. These indexes in 10-7 mol/L PTH group and 0 mol/L PTH group, in 48 h group and 0 h group showed statistical differences (all P<0.05). In PTH group ECs with 10-7 mol/L PTH for 48 h showed FSP1 accumulation in the cytoplasm and reduced expressions of CD31, and ECs had higher expressions of PPAR-γ and C/EBP-α as well as the degree of adipogenesis than those in control group (all P<0.05). Furthermore, PTH enhanced the nuclearβ-catenin protein levels in ECs in concentration-dependent. The expressions of β-catenin in 10-7 mol/L PTH group and 0 mol/L PTH group showed statistical differences (P<0.05). β - catenin expressed in the cytoplasm in control group, while it enter into the nucleus in PTH group. Compared with those in PTH+control siRNA group, the expressions of CD31 and PPAR-γ as well as the degree of adipogenesis decreased in PTH+β-catenin siRNA group (all P<0.05), while the expression of FSP1 increased (P<0.05). Conclusions PTH induces ECs - to - adipocytes transition by the canonical Wnt/β - catenin signaling pathway, which might account for bone loss in CKD. Silenced β - catenin expression can inhibit PTH-induced EndMT and adipogenesis.
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Background:Gastroesophageal reflux disease( GERD)that does not respond satisfactorily to standard proton pump inhibitor is defined as refractory gastroesophageal reflux disease( rGERD). Combined therapy is used to treat rGERD, however,the addition of baclofen is rarely studied. Aims:To investigate the efficacy of baclofen combined with esomeprazole and mosapride on rGERD. Methods:Seventy-two patients with rGERD from March 2013 to April 2014 at the First Hospital of Putian City were enrolled and randomly divided into group A and group B. Patients in group A were orally administrated with esomeprazole 20 mg bid + mosapride 5 mg tid + baclofen 5 mg tid. Patients in group B were treated with esomeprazole 20 mg bid + mosapride 5 mg tid. The treatment course was 8 weeks. The efficacy on symptoms, esophagitis under endoscopy and adverse effects were compared between the two groups. Results:After 8-week treatment, score of heartburn,regurgitation,retrosternal pain,dysphagia and overall symptom were significantly decreased in the two groups than before the treatment. The overall symptom alleviating rate was significantly higher in group A than in group B (90. 6% us. 70. 0%;χ2 =4. 585,P=0. 032). Esophagitis under endoscopy in the two groups was significantly improved, the effective rate was significantly higher in group A than in group B(93. 8% us. 75. 0%;χ2 =4. 500,P=0. 034). The main adverse effects of baclofen were somnolence,dizziness and fatigue,all the patients were well tolerated. Conclusions:Baclofen combined with esomeprazole and mosapride is an efficient option for rGERD.
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BACKGROUND:A number of in vitro experiments have confirmed that the tricalcium silicate not only can be closely integrated with the dentin through self-curing process, but also can induce dentin remineralization in the physiological environment, thereby effectively blocking the dentinal tubules. OBJECTIVE:To further verify the effects of tricalcium silicate solution on the occlusion of dentinal tubules. METHODS:Thirty-six dentinal discs were made of free first premolars from orthodontic patients, and divided into three pretreatment groups randomly. The teeth were soaked in pretreatment solution for 2 minutes, namely 0.29 mol/L ethylene diamine tetraacetie acid, 6%citric acid, and rinsed ultrasonical y with deionized water 20 minutes, respectively. Every above-mentioned group was randomly assigned into experimental group (tricalcium silicate), control group (sodium fluoride) and blank group, and corresponding materials in each group were used to coat the outer dentinal tubules (2 minutes/time). Then, the dentinal discs were saved in artificial saliva in a 37 observed using scanning electron microscope. Diameter and area of open dentinal tubules were calculated. RESULTS AND CONCLUSION:After pretreatment, the dentinal tubules were at open state;except for the blank control group to maintain the original state, acid etching and ethylene diamine tetraacetie acid pretreatment solutions had a stronger capacity of demineralization, which led to the dentinal tubules open. After the dentinal tubules were treated with sodium fluoride and tricalcium silicate, there were varying degrees of sediments, and open dentinal tubule area and average diameter in the sodium fluoride and tricalcium silicate groups were lower than those in the control group (P<0.05). The dentinal tubule treated with tricalcium silicate was almost entirely closed homogeneously, and occasional y, a single open dentinal tubule was seen. Open dentinal tubule area and average diameter in the tricalcium silicate group were significantly lower than those in the sodium fluoride group (P<0.05). The findings verify that dentin occlusion using tricalcium silicate is superior to that using sodium fluoride;and dentin tubule pretreatment with acid etching or ethylene diamine tetraacetie acid is beneficial to desensitization effects.