Clinical Phenotype and Gene Mutation Analysis of a Family with Early-Onset Familial Alzheimer′s Disease / 中山大学学报(医学科学版)

@#【Objective】A full exome sequencing of an early-onset family Alzheimer′s disease (EOFAD) was conduct? ed to identify the mutational sites which may cause diseases. The result of the current study may provide suggestion to genetic counseling and prenatal diagnosis.【Methods】Whole exome sequencing was performed on the family members and software PolyPhen-2 as well as SIFT was employed for hazard prediction (Prediction on functional effects of the missense mutation).【Results】The heterozygous mutation c.758A>G (p.Tyr253Cys) in exon 9 of TTC3 gene had been identified in proband whose mother had been proved with heterozygous mutation c.758A>G. According to the family separation and related bioinformatics analysis, the mutant gene was a possible pathogenic mutation. 【Conclusion】 A new mutation was found of c.758A>G in TTC3 gene within a Chinese EOFAD family and a new mutation to the spectrum of genetic mutation in EOFAD was expanded. The finding provides a significant groundwork for future exploration on the mechanisms underlying EOFAD.

Different doses of multislice spiral CT in screening pneumoconiosis / 中国职业医学

OBJECTIVE: To explore the effects of different doses of chest multislice spiral computed tomography( MSCT) in screening pneumoconiosis. METHODS: Forty workers exposed to coal dust and silica dust were selected by random sampling method,and scanned by conventional dose( 130 k V,25. 0-75. 0 m As) and low-dose of MSCT which included program 1( 110 k V,50. 0 m As),program 2( 110 k V,16. 0 m As) and program 3( 80 k V,16. 0 m As) respectively. Comparative analysis was given to the reconstructions of high-resolution 1. 5 mm thin-section,5. 0 mm of ordinary-section and the maximum intensity projection of 5. 0 mm coronary position respectively. RESULTS: Program 1 and program 2 exceeded program 3 in both image quality scores and low-dose MSCT image evaluation score( P < 0. 01). Both program 1 and 2 were able to show the p,q,s and t small shadows of 40 cases,and had no statistical significant difference in small shadow scores compared with those of conventional dose group( P > 0. 02),except the t small shadow scores of program 2;program 3 distinctly showed fewer images of the 4 kinds of small shadow and more false images,its images of p,q and t small shadow scores were lower than those of conventional dose group( P < 0. 01). We evaluated the radiation dose indexes including the CT dose index volume,CT dose index weighted,dose length product and the average effective dose,and all the results showed the following trend sequence from high to low: the conventional dose group > program 1 > program 2 >program 3 group( P < 0. 05). CONCLUSION: All low doses of MSCT schemes can meet the demands of pneumoconiosis screening. Using the program of 110 k V,16. 0 m As can not only achieve better quality image,but also effectively reduce the radiation doses that patients receive in screening.

Toxic epidermal necrolysis related to AP (pemetrexed plus cisplatin) and gefitinib combination therapy in a patient with metastatic non-small cell lung cancer / 癌症

Toxic epidermal necrolysis (TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related (80%-95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen (pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer (NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.

Therapy for brain metastasis from non-small cell lung cancer / 国际肿瘤学杂志

Therapeutic approaches to brain metastases from non-small cell lung cancer ( NSCLC ) include corticosteroids, anticonvulsants, surgery, radiotherapy and chemotherapy. In recent years, molecular targeted therapy such as the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) has become a new option. This article discussed the roles of surgery, brain radiation, chemotherapy, targeted therapy , and other new directions in the treatment of patients with brain metastases from NSCLC.

Establishment and evaluation of a prognostic prediction model for patients after complete resection of non-small cell lung cancer and multidisciplinary therapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>A bias may be produced when only TNM stage is used to predict the prognosis of non-small cell lung cancer (NSCLC) after complete resection and multidisciplinary treatment. The reason is that histological type, differentiation, and postoperative treatment which may also affect the survival are excluded in the prognosis prediction. The aim of this study is to establish and evaluate a prognostic prediction model for NSCLC patients based on pathological parameters after completely resection and postoperative treatment.</p><p><b>METHODS</b>According to the theory of Nottingham index model, a prognostic prediction model was established based on the pathological parameters and postoperative management of 899 NSCLC patients after complete resection and multidisplinary treatment in our hospital from Jan.1, 1997 to April, 2001, and its efficiency and feasibility were evaluated.</p><p><b>RESULTS</b>Univariate analysis and multivariate analysis showed that histological type (H), T stage (T), N stage (N), M stage (M), and postoperative mediastinal radiotherapy for positive lymph node (R) were independent factors affecting the survival of NSCLC after complete resection and multidisciplinary treatment. The prognostic prediction model based on these parameters is: S = 0.338H + 0.178T + 0.549N + 0.647M-0.361R. The high and low risks of prognostic index (PI) were 1.6695 and 1.1160, respectively. The 5-year survival rates of the patients in the low, middle and high risk groups stratified by this model were 70.1%, 54.5%, and 22.5%, respectively, with a significant difference among the groups (chi(2) = 132.091, P = 0.000).</p><p><b>CONCLUSION</b>A model based on the pathological parameters and postoperative management has been established, which may be helpful in predicting the prognosis for NSCLC after complete resection and multidisciplinary management.</p>

Nadaplatin or cisplatin combined with paclitaxol in treatment for non-small cell lung cancer: a randomized controlled study / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effect, long term survival and side effect on NSCLC patients treated with nadaplatin combined with paclitaxol and cisplatin combined with paclitaxol.</p><p><b>METHODS</b>NSCLC patients with stage IIIB or IV were randomized into two groups in this prospective clinical study. TN group: nadaplatin 30 mg/m2 dl-3, paclitaxol 175 mg/m2 dl, repeated every 4 weeks. TP group: DDP 30 mg/m2 dl-3, paclitaxol 175 mg/m2 dl, repeated every 4 weeks.</p><p><b>RESULTS</b>Sixty patients were enrolled and 57 were evaluable with 30 in TN group and 27 in TP group. The overall response rate were 43.3% vs. 48.1% (P = 0.716), and the disease control rate were 86.7% vs. 88.8% in TN and TP group (P = 0.799), respectively. The median survival time was 14.3 vs. 13.0 months, and the 1- and 2-year survival rate was 62.5% vs. 59.1%, 0% vs. 5.8% in TN and TP group (P = 0.839), respectively. The rates of neutropenia and thrombocytopenia were similar in TN and TP groups whereas more patients in TP group than in TN group suffered from anemia (38.5% vs. 17.5%, P = 0.001), nausea and vomiting (82.6% vs. 35.6%, P = 0.000), fatigue (35.9% vs. 14.1%, P = 0.000) and peripheral neurotoxicity (50.0% vs. 21.9%, calculated by case, P = 0.023).</p><p><b>CONCLUSION</b>Nadaplatin combined with paclitaxol is an effective treatment regimen for NSCLC patients. When compared with similar regimen with cisplatin, the response rate and survival were similar; however, nadaplatin regimen shows some superiority as regards some treatment side effect.</p>