BACKGROUND AND PURPOSE: Tafamidis functions to delay the loss of function in transthyretin familial amyloid polyneuropathy (TTR-FAP), which is a rare inherited amyloidosis with progressive sensorimotor and autonomic polyneuropathy. This systematic literature review and meta-analysis evaluated the efficacy and safety of tafamidis in TTR-FAP patients, with the aim of improving the evidence-based medical evidence of this treatment option for TTP-FAP. METHODS: A systematic search of the English-language literature in five databases was performed through to May 31, 2018 by two reviewers who independently extracted data and assessed the risk of bias. We extracted efficacy and safety outcomes and performed a meta-analysis. Statistical tests were performed to check for heterogeneity and publication bias. RESULTS: The meta-analysis identified six relevant studies. The tafamidis group showed smaller changes from baseline in the Neuropathy Impairment Score–Lower Limbs [mean difference (MD)=−3.01, 95% confidence interval (CI)=−3.26 to −2.75, p < 0.001] and the Norfolk Quality of Life-Diabetic Neuropathy total quality of life score (MD=−6.67, 95% CI=−9.70 to −3.64, p < 0.001), and a higher modified body mass index (MD=72.45, 95% CI=69.41 to 75.49, p < 0.001), with no significant difference in total adverse events [odds ratio (OR)=0.69, 95% CI=0.35 to 1.35, p=0.27]. The incidence of adverse events did not differ between tafamidis and placebo treatment except for fatigue (OR=0.13, 95% CI=0.02 to 0.72, p=0.02) and hypesthesia (OR=0.16, 95% CI=0.03 to 0.92, p=0.04). CONCLUSIONS: This systematic review and meta-analysis has demonstrated that tafamidis delays neurologic progression and preserves a better nutritional status and the quality of life. The rates of adverse events did not differ between the patients in the tafamidis and placebo groups. Tafamidis might be a safer noninvasive option for patients with TTR-FAP.
Amyloid Neuropathies ; Amyloid Neuropathies, Familial* ; Amyloidosis ; Bias (Epidemiology) ; Body Mass Index ; Extremities ; Fatigue ; Humans ; Hypesthesia ; Incidence ; Nutritional Status ; Polyneuropathies ; Population Characteristics ; Prealbumin* ; Publication Bias ; Quality of Life

Objective To investigate the changes of cognitive impairment with disease progression in patients with minor stroke/transient ischemic attack (TIA).Methods Consecutive patients with minor stroke/TIA were enrolled prospectively.Montreal Cognitive Assessment (MoCA) was used to conduct the cognitive function assessment within 7 d of the onset (baseline),at 1 and 3 months,respectively.Compared with the baseline,the total scores of MoCA in patients increased by ≥2 at 3 months were cognitive function improvement and increased <2 were no cognitive function improvement.Multivariate logistic regression analysis was applied to identify the independent risk factors for no cognitive improvement.ResultsA total of 112 patients with minor stroke/TIA were enrolled in the study,including 63 patients (56.2%) with TIA and 49 (43.8%) with minor stroke.At baseline,1 month,and 3 months,77 (68.8%),72 (64.3%) and 60 (53.6%) patients had cognitive impairment.At 3 months after the onset,the cognitive function of 25 patients (22.3%) were improved,in which 19 (76.0%) and 6 (24.0%) patients had TIA/minor stroke respectively;87 (77.7%) did not have any improvement.Compared with the improvement group,the level of education was significantly lower (3.29±3.48 years vs.5.63±4.26 years;t=2.814,P=0.006),the level of glycosylated hemoglobin was significantly higher (6.35%±1.26% vs.7.21%±1.26%;t=-3.088,P=0.003) in the no improvement group,and the proportions of patients with minor stroke (49.4% vs.24.0%;χ2=5.101,P=0.024),hypertension (52.9% vs.24.0%;χ2=6.509,P=0.011),hyperlipidemia (51.7% vs.24.0%;χ2=6.019,P=0.014),diabetes (41.4% vs.16.0%;χ2=5.448,P=0.020),and coronary heart disease (32.2% vs.8.0%;χ2=5.792,P=0.016) were significantly higher.Multivariate logistic regression analysis showed that the level of education (odds ratio [OR] 1.364,95% confidence interval [CI] 1.059-1.756;P=0.016),atrial fibrillation (OR 2.509,95% CI 1.020-6.167;P=0.045),and higher glycosylated hemoglobin level (OR 1.586,95% CI 1.021-2.034;P=0.030) were the independent risk factors for no cognitive function improvement at 3 months after the onset of minor stroke/TIA.As time went on,the MoCA score and visual spatial execution,memory,abstract and directional scores were increased significantly (P<0.001),while there were no significant differences in naming,attention,and language scores.Conclusion s About 2/3 patients with minor stroke/TIA had cognitive impairment,and as time went on,they were improved.The lower education level,atrial fibrillation and higher baseline glycated hemoglobin were the independent risk factors for affecting no cognitive impairment improvement after monor stroke/TIA.

Objective:To screen the differentially expressed miRNAs in umbilical cord tissue of children with nonsyndromic cleft lip and/or cleft palate( NSCL/P) using miRNA microarray and comprehensive bioinformatics analysis for the prediction of related the bio-logical process and signaling pathways. Methods:Umbilical cord tissues of 4 cases of healthy newborns' and 4 lip or palate tissues of 4 cases with NSCL/P without other disease aged younger than 2 years were collected. The differentially expressed miRNAs were screened by miRNA microarray. Targets of dysrugulated miRNAs were predicted by TARGETSCAN-VERT, MIRDB and RNA22-HSA. All the gene sets were analyzed by gene ontology and pathway enrichment. Results: MiRNA microarray demonstrated that 254 miRNAs were dysregulated(181 miRNAs were up-regulated and 73 downregulated,P <0. 05). The dysregulated miRNAs targets contained 5029 genes. The dysregulated miRNAs targets were enriched in anatomical structure development,cell adhesion,cell proliferation,cell motili-ty and other biological processes. The dysregulated miRNAs targets were enriched in Wnt, mTOR, cGMP-PKG, TGFβ, PI3K-Akt and other signaling pathways. Conclusion:The target genes set of miRNAs are enriched in multiple biological processes and signaling path-ways related to NSCL/P, which indicate that genetic and environmental factors may influence the development process of NSCL/P.

OBJECTIVE To investigate the effect of overexpression of vascular cell adhesion molecule-1(VCAM-1)on the migration in vitro of the murine mesenchymal stem cells(MSCs)and its possible mechanism. METHODS The migration ability of normal mouse MSC (C3) ,empty vector-transfected MSC(C3+N) and VCAM-1 transfected MSC(C3+VCAM-1)was assessed by Transwell culture system in vitro after incubation for 8 and 12 h,respectively. The fetal bovine serum (FBS) was used as the chemotactic agent to induce MSC migration. The transmigrated cells were detected with methylosaniliam chloride(crystal violet)as well as DAPI staining.Furthermore,the specific chemical inhibitors of mitogen-activation protein kinase (MAPK) pathway ( SB203580,PD98059 and JNK inhibitorⅡ)were added to the Transwell system for 12 h and the alteration of the MSC migration ability was evaluated. RESULTS After incubation with FBS for 8 and 12 h,the absolute migrated cell number(7467 ± 485 and 8795 ± 255)and migration rate〔(14.9 ± 1.0)% and(17.6 ± 0.5)%〕of MSC in C3+VCAM-1 group were significantly increased compared with C3 group〔2731±562 and 4779±224, (5.5 ± 1.1)%and(9.6 ± 0.4)%〕and C3+N group〔2539 ± 321 and 5645 ± 1080,(5.1 ± 0.6)%and(11.3 ± 1.1)%〕(P<0.05,P<0.01),but there was no significant difference between C3 and C3+N groups. Moreover,the MSC migration ability of C3+VCAM-1 group was partially suppressed by addition of JNK inhibitorⅡ. The transmigrated cell number(4843 ± 167)and migration rate〔(9.7 ± 0.3)%〕were decreased compared with those of C3+VCAM-1 group without JNK inhibitorⅡ(P<0.01). SB203580 and PD98059,as specific chemical inhibitors of MAPK pathway,had no effect on MSC migration. CONCLUSION VCAM-1 can enhance mouse MSC migration in vitro and th4e mechanism may be related to JNK/MAPK pathway activation.

OBJECTIVE:To discuss clinical efficacy and safety of alteplase combined with butylphthalide to the patients with acute ischemic stroke. METHODS:98 patients with acute ischemic stroke in our hospital were selected and divided into ob-servation group and control group according to random number table,with 49 patients in each group. Control group was addition-ally given Butylphthalide and sodium chloride injection 100 ml,ivgtt,bid,on the basis of routine treatment as controlling blood glucose,blood pressure,etc.;observation group additionally received Alteplase for injection 5 mg added into NS 10 ml,iv+Al-teplase for injection 45 mg added into NS 100 ml,ivgtt,qd,on the basis of control group. Both groups were treated for 2 weeks. Clinical efficacies of 2 groups were compared as well as cerebral infarction area,NIHSS score,ability score of daily liv-ing,the levels of IL-6,IL-8,IL-10,CRP,24 h urine protein,Scr and creatinine clearance rate before and after treatment. The occurrence of ADR was also recorded. RESULTS:1 patient of observation group and 2 patients of control group withdrew from the study due to severe hemorrhage. Total effective rate of observation group(95.83%)was significantly higher than that of con-trol group(80.85%),with statistical significance(P<0.05). Before treatment,there was no statistical significance in above in-dexes between 2 groups (P>0.05). The cerebral infarction area and NIHSS score were reduced significantly in observation group after treatment,ability score of daily living were increased significantly in observation group after treatment,and the im-provement of observation group was significantly better than control group,with statistical significance (P<0.05). 24 h urine protein and Scr of observation group was significantly lower than those of control group,with statistical significance(P<0.05). the level of IL-6 in observation group 1 week after treatment and the levels of IL-6,IL-8,IL-10 and CRP 2 weeks after treat-ment were significantly lower than in control group,with statistical significance(P<0.05). There was no statistical significance in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS:Alteplase combined with butylphthalide show signifi-cant therapeutic efficacy,can effectively reduce the level of serum inflammatory factors,control brain tissue ischemia and cere-bral infarction area,and improve neurologic function and pro-tect renal function in patients with acute ischemic stroke.

Objective To investigate the incidence,characteristics and risk factors of cognitive impairment in patients with transient ischemic attack(TI A) or minor stroke.Methods Montreal cognitive assessment(MoCA) was carried out in 279 patients with TIA or minor stroke and 150 healthy controls to assess their cognitive function.Results (1) Compared with the healthy controls,the TIA/minor stroke patients scored significantly lower on MoCA total score((23.98±2.55) vs (26.60±0.99),t=12.084,P＜0.01) and subtests including visuoexecutive function((3.68±0.94) vs (4.41±0.64),t=8.483,P＜0.01),digital span ((1.81±0.40) vs (1.95±0.23),t=3.771,P＜0.01),attention((0.84±0.37) vs (0.95±0.23),t=3.357,P＜ 0.01),repetition((1.59±0.62) vs (1.89±0.37),t=5.496,P＜0.01),verbal fluency((0.88±0.33) vs (0.95 ± ±0.23),t=2.286,P＜0.05),abstraction((1.55±0.64) vs (1.91±0.34),t=6.357,P＜0.01) and recall ((2.87±1.13) vs (3.18±0.41),t=3.281,P＜0.01) were significantly decreased.(2) Of 279 TIA/Minor stroke patients,213 (76.3％) suffered from cognitive impairment.The incidence of cognitive impairment was positively correlated with the gender,age,educational level,smoking,course,leukoaraiosis,comorbidities such as hypertension,diabetes mellitus(P＜0.05),and negatively correlated with hyperlipidemia(P＞0.05).Conclusion Extensive impairments of cognitive functions occur along with the incidence of TIA or minor stroke.It is thus suggested that cognitive assessment and interventions may be carried out at an early stage.

China ; Humans ; Thoracic Surgery ; trends ; Thoracic Surgical Procedures ; trends

OBJECTIVETo analyze the clinical characteristics and follow up record of patients with synchronous multiple lung cancers (SMLC).

METHODSThe medical records of 1 868 lung cancer patients who underwent surgical treatments From January 2007 to December 2014 were reviewed, in which 103 patients were diagnosed SMLC by Martini and American College of Chest Physicians modified guideline. The average age was 60.5 years, including 34 male and 69 female patients. According to consolidation/tumor ratio (CTR) on thin-section computed tomography, 103 cases were classified into three groups: group A (multiple ground-glass opacities, CTR ≤ 50%), group B (with one solid dominant nodules, CTR > 50%), group C (with two solid dominant nodules). The surgical procedure was determined according to CT findings and respiratory function. The Kaplan-Meier method was used to analyze the duration of recurrence-free survival (RFS) and over-all survival (OS), and differences were assessed using the Log-rank test. Multivariate analysis using the Cox proportional hazards models was used to assess the potential independent effects on RFS or OS.

RESULTSThere were 38 patients in group A (36.9%), 40 patients in group B (38.8%) and 25 patients (24.3%) in group C. More female (73.7% vs. 48.0%, χ² = 4.291, P = 0.038), less smoker (21.1% vs. 44.0%, 2 = 3.770, P = 0.052), younger (56.2 years old vs. 65.9 years old, t = -4.172, P = 0.000) and less tumor size (1.24 cm vs. 2.31 cm, t = -4.573, P = 0.000) patients in group A than in group C. The 3, 5-year RFS were 80.3% and 64.9% for all patients, respectively. The 3, 5-year OS were 87.3% and 68.6% for all patients, respectively. The 3, 5-year RFS were 100% and 100% in group A, 77.7% and 51.8% in group B, 59.6% and 44.7% in group C (P = 0.029). No significance were found in OS between the three groups (P = 0.214). Multivariate Cox analysis demonstrated that size of dominant nodule larger than 2 cm (HR = 4.475, 95% CI: 1.138 to 17.604, P = 0.032) is associated with poor prognosis, whereas postoperative chemotherapy did not affect RFS.

CONCLUSIONSMultifocal ground-glass opacities and multiple solid lung cancers are different in nature. RFS of patients with SMLC is strongly affected tumor size. Surgical resection is effective and should be performed specifically to patients.

Female ; Humans ; Lung ; pathology ; surgery ; Lung Neoplasms ; diagnosis ; pathology ; surgery ; Male ; Middle Aged ; Multivariate Analysis ; Proportional Hazards Models ; Tomography, X-Ray Computed ; Treatment Outcome

Vascular cognitive impairment has been a research hotspot in the field of neurology in recent years.The Montreal Cognitive Assessment is a rapid screening tool for detecting mild cognitive impairment.Now it has been widely used in the evaluation of vascular cognitive impairment.This article reviews the content,features,application status,and development prospects of the Montreal Cognitive Assessment.

Objective Analyze the clinical feature of patients failed for diagnosis through endobronchial ultrasound transbronchial needle aspiration(EBUS-TBNA).Optimize the indication and increase diagnosis rate of EBUS-TBNA.Methods A total of 669 patients failed for diagnosis of EBUS-TBNA were included.Fifty-three of them(7.92％) were not exactly diagnosed.Perioperation clinical data and clinical feature were collected and evaluated based on specific disease,lesion location,size and operator' s experience.Results The undiagnosis rate was higher in lymphoma (77.78％),tuberculosis (23.08％) and sarcoidosis(9.09％) when analyzed from specific diseases.If the lesion location was taken into consideration,15.38％ upper paratracheal lymph nodes(R2) could not be diagnosed exactly by EBUS-TBNA,and the bilateral hilar lymph nodes(15.00％ for right,11.54 for left) were followed.Size of the lesion was not associated with the diagnosis rate.The operator's experience could also affect the results.The undiagnosis rate was highest in the first 10 cases among all operators.After at least 10 EBUS-TBNA processes,the undiagonsis rate stayed near 7.50％,which was close to the average.Conclusion It is necessary to select suitable indications for EBUS-TBNA based on the disease,lesion location and operatior experience,and cooperate with mediastinoscopy to rise diagnosis rate.