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OBJECTIVE@#To detect pathological variant in two patients with Chediak-Higashi syndrome (CHS) from a consanguineous family and to explore its genotype-phenotype correlation.@*METHODS@#Clinical data was collected for this pedigree. Genomic DNA was prepared from probands' peripheral leukocytes and their relatives' fingernail. Whole exome sequencing and Sanger sequencing were carried out to detect potential variant of the LYST gene.@*RESULTS@#The proband presented with partial oculocutaneous albinism, immunodeficiency and acidophilic inclusion body in bone marrow and blood smears. A novel homozygous nonsense variant c.8782C>T (p.Gln2928*) was identified in exon 34 of the LYST gene in the sib pair. The same variant was found to be in heterozygous status in 6 unaffected individuals from the pedigree.@*CONCLUSION@#Above result enriched the mutational spectrum of CHS and provided a basis for genetic counseling and prenatal diagnosis for this pedigree.
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Humans , Chediak-Higashi Syndrome , Genetics , Exons , Heterozygote , Mutation , Pedigree , Sequence Analysis, DNA , Vesicular Transport Proteins , Genetics , Exome SequencingABSTRACT
Objective To investigate the effect of expression of Cullin 4B (CUL4B) on the prognosis of patients after liver transplantation for hepatocellular carcinoma (HCC).Methods The retrospective case-control study was conducted.The clinicopathological data of 79 patients who underwent liver transplantation for HCC in the First Affiliated Hospital of Sun Yat-sen University between January 1,2014 and June 30,2015 were collected.The specimens of HCC tissues were collected and embedded in paraffin,and then were detected by immunohistochemistry staining.Observation indicators:(1) expression of CUL4B in HCC tissues;(2) follow-up and survival;(3) prognostic factors analysis after liver transplantation;(4) association between expression of CUL4B and recurrence and metastasis of tumor after liver transplantation.Follow-up using outpatient examination and telephone interview was performed to detect tumor recurrence or metastasis and survival up to June 2018.Measurement data with normal distribution were represented as (x)±s.The comparison between groups of count data was done using the chi-square test.The survival curve drawn using the Kaplan-Meier method,and the survival analysis was done by Log-rank test.The univariate and multivariate analysis were respectively done using the COX regression model.The association analysis was done using the Pearson test.Results (1) Expression of CUL4B in HCC tissues:immunohistochemistry staining showed that CUL4B was mainly expressed in the cytoplasm,with a powerful brownish-yellow staining.The high expression and low expression of CUL4B in HCC tissues were detected in 64 and 15 patients,respectively.(2) Follow-up and survival:79 patients were followed up for 38-56 months,with an average time of 46 months.During the follow-up,37 patients had no tumor recurrence and 42 had tumor recurrence (32 with tumor extrahepatic metastasis and 10 with intrahepatic metastasis);36 had survival and 43 died;the 1-and 3-year overall survival rates were respectively 86.84％ and 63.25％,and 1-and 3-year tumorfree survival rates were respectively 62.31％ and 51.27％.(3) Prognostic factors analysis after liver transplantation:① Results of univariate analysis showed that preoperative alpha-fetoprotein (AFP),Child-Pugh score,maximum tumour dimension,capsular invasion,intravascular tumor thrombus,Edmonson pathological grading and expression of CUL4B were related factors affecting the 3-year overall survival rate of patients after liver transplantation for HCC [Hazard Ratio (HR) =2.17,3.36,3.66,2.43,2.19,3.36,2.84,95％ confidence interval(CI):1.17-4.04,1.53-7.42,2.10-6.42,1.33-4.17,1.08-9.04,1.58-7.59,1.17-6.32,P＜ 0.05].The preoperative alpha-fetoprotein (AFP),Child-Pugh score,maximum tumour dimension,capsular invasion,intravascular tumor thrombus,Edmonson pathological grading and expression of CUL4B were related factors affecting the 3-year tumor-free survival rate of patients after liver transplantation for HCC (HR =2.06,3.72,3.16,2.36,2.83,3.21,1.69,95％CI:1.34-4.85,1.72-8.63,1.79-7.31,1.46-4.86,1.19-8.63,1.19-7.92,1.06-4.87,P＜0.05).② Results of multivariate analysis showed that maximum tumour dimension,intravascular tumor thrombus and expression of CUL4B were independent factors affecting the 3-year overall survival rate of patients after liver transplantation for HCC [Odds ratio(OR) =3.43,3.69,2.81,95％CI:1.16-6.02,1.96-9.38,1.04-9.63,P＜0.05].The maximum tumour dimension,intravascular tumor thrombus and expression of CUL4B were independent factors affecting the 3-year tumor-free survival rate of patients after liver transplantation for HCC (OR=2.25,4.72,2.74,95％C1:1.16-4.02,1.98-9.47,1.03-7.10,P＜ 0.05).The 3-year overall survival rate in patients with high-and low-expressions of CUL4B was respectively 66.7％ and 32.8％,with a statistically significant difference (x2 =5.69,P＜0.05).The 3-year tumor-free survival rate in patients with high-and low-expressions of CUL4B was respectively 73.3％ and 18.6％,with a statistically significant difference (x2 =4.63,P＜0.05).(4) Association between expression of CUL4B and recurrence and metastasis of tumor after liver transplantation:results of Pearson test showed that expression of CUL4B was significantly associated with HCC recurrence and metastasis after liver transplantation (r =0.62,P＜0.05).The further analysis showed that expression of CUL4B was significantly associated with extrahepatic metastasis after liver transplantation (r=0.84,P ＜ 0.05).Conclusion The expression of CUL4B is associated with HCC recurrence after liver transplantation,and it can be as a predictor for HCC recurrence and distant metastasis after liver transplantation.
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The concentrations and distributions of trace metals and rare earth elements (REE) in sediment and mussel samples collected from the India Ocean hydrothermal area were analyzed.The metal correlation between organisms and sediments was investigated, and the ecological and chemical characteristics of REE were also explored.The results showed that, the trace metals in sediments were mainly Fe (96.6 mg/kg), Mn (1.14 mg/kg) and Zn (322.6 μg/kg), and Fe had high ratio of 98.15% by normalized calculation, which indicated that the available sediments in this studying hydrothermal area mainly consisted of iron ore substances.Trace metals and REE distributions all had good correlation between deep-sea sediments and deep-sea mussels, and the correlation coefficients were 0.991 for trace metals and 0.996 for REE.The contents and distributions of metal elements in deep-sea mussels were different from those in offshore mussels.The REE distributions in sediments and mussels showed obvious fractionation phenomenon, and the enrichment of LREE in mussels was significant.Through the REE patterns, Eu and Gd in sediments and mussels all showed anomalies, and Eu had a significant abnormal phenomenon in deep-sea sediments and deep-sea mussels.Besides, δEu values were 9.50, 10.68 and 0.23 in deep-sea sediments, deep-sea mussels and offshore mussels, respectively, and δCe were 2.21, 2.71 and 4.38, which showed that the enrichment sources of REE in offshore mussels and deep-sea mussels were different, and the REE in sediments and mussels from the India Ocean were homologous.
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The particles suspended in seawater have great influence on pollutant migration and transformation in marine environment, while the lipophilic algae toxins enriched by the particles suspended in seawater will lead more serious toxicity to marine filter feeders. In this study, a new method was developed for the simultaneous determination of eight lipophilic algae toxins in suspended particles by ultra performance liquid chromatography-tandem mass spectrometry ( UPLC-MS/MS ) . After extracted with methanol by ultrasonic-assisted extraction, the sample was separated on an Acquity UPLC BEH C18 column (50 mm×2. 1 mm, 1. 7 μm) using gradient elution of acetonitrile and water containing 5 mmol/L ammonium acetate as eluent modifiers. The qualitative and quantitative analyses were carried out by electrospray ionization ( ESI) tandem mass spectrometry in multiple reaction monitoring ( MRM) mode. Under the optimal conditions, satisfactory precision (relative standard deviations (RSD≤14. 1%), recoveries (83. 8%-110. 4%) and detection limits (2. 9-103 pg/g) of the method were achieved. Good linearity (R2≥0. 99) was also obtained for all studied analytes. Then, the method was applied to determine the amounts of the eight lipophilic marine toxins in authentic suspended particle samples collected from Qingdao near-shore area. Pectenotoxin 2 ( PTX2 ) was detected in the samples from Shilaoren beach and No. 3 bathing beach with concentration ranges of 717 and 790 pg/g, respectively.
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A total of 30 kunds of fush samples, 5 kunds of shellfush samples and 4 kunds of crustacean samples from the Nansha sea area of chuna were dugested by mucrowave dugestuon system wuth HNO3-H2 O2 as the dugestuon reagent. Then the contents ( ICP-MS determunatuon) and ecologucal chemucal characterustucs of rare earth elements ( REE) were studued. The results showed that the method of mucrowave dugestuon-ICP-MS for the determunatuon of rare earth elements was perfect, and the lunear relatuonshup for each element was good wuth r≥0 . 9997 . The detectuon lumut of the method could reach 1 . 0 ng/L wuth the relatuve standard devuatuon (RSD, n=3) of less than 5. 0%. The recoverues of rare earth elements were between 91. 50% and 106. 67%. The total amount of rare earth un fush samples, shellfush samples and crustacean samples were 5. 02-34. 8 μg/kg, 30. 4-1481 μg/kg and 103-863 μg/kg, respectuvely. The average enruchment contents of the rare earth un the 3 specues was crustacean > shellfush > fush. The contents of 14 rare earth elements un fush/shellfush/crustaceans showed sugnufucantly posutuve correlatuon ( r>0 . 80 ) . The contents of lught rare earth elements ( La-Eu) were hugher than that of heavy rare earth elements ( Gd-Lu) . The lught and heavy rare earth elements had obvuous fractuonatuon, and the REE dustrubutuon pattern was consustent un fush/shellfush/crustacean wuth Gd negatuve anomaly. The δEu values had negatuve anomalues, sumular to the δEu values un correspondung area sedument, and δCe values showed posutuve anomalues, whuch showed that Ce had dufferent process of oxudatuon and reductuon un the organusm and sedument deposutuon. At the same tume, the enruchment relatuonshup of rare earth elements un sedument and organusm was also studued. In thus study, the content and dustrubutuon of rare earth elements un the tropucal marune fush/shellfush/shellfush were analyzed, whuch could provude basuc data for the study of the level and mugratuon and accumulatuon of rare earth elements un the envuronment of the South Chuna Sea.
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Objective To explore the efficacy and safety of Linagliptin in combination with Metformin in newly diagnosed T2DM patients. Methods A total of 140 newly diagnosed T2DM patients were enrolled in this study. All the patients were admitted in the Endocrinology and Metabolism department of our hospital from January 2013 to October 2013. Random number table method was used in patients’ selection. All the patients were divided into two groups :Linagliptin plus Metformin group (Linagliptin group ,n=70) and Glipizide plus Metformin group (Glipizide group ,n=70) ,and followed up for 12 weeks. Efficacy and safety of treatment were compared between the two groups. Results The difference of FPG ,2 hPG and HbA1 c did not reach the statistical significance between the two groups at baseline treatment (P>0.05). FPG ,2 hPG and HbA1 c were significantly lower after treatment compared with baseline in both groups (P 0.05 ). All these indicators were improved after treatment in both groups (P< 0.05) ,and were significant better in Linagliptin group than in Glipizide group. Adverse events rate were significantly higher in Glipizide group than in Linagliptin group (18.57%vs 5.71% ,χ2 = 5.423 ,P= 0.020 ). Conclusion The efficacy of Linagliptin in combination with Metformin in newly diagnosed T2DM patients was similar with Glipizide plus Metformin. The β cell function improvement was better and APN level was higher after Linagliptin treatment.
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A novel method for the simultaneous quantification of seven metabolites of polycyclic aromatic hydrocarbon in human urine was developed using online solid phase extraction-HPLC with double ternary liquid chromatography system combined with fluorescence detector. The target compounds were online concentrated on the Turboflow Cyclone solid phase extraction column at first, then transferred by the six-way valve to the Hypersil Green PAH column for separation with acetonitrile and water as mobile phase at a flow rate of 1. 0 mL/min and at 35 ℃. A single sample analysis cycle took only 20 min. Under the optimized chromatographic conditions, the method showed good linear relationship ( r≥0. 999 ) in the range of 5-2000 ng/L or 50-20000 ng/L. The LODs were 0. 5-15 ng/L, and the recoveries were 80. 7%-110. 7%. The proposed method was successfully applied in the detection of metabolites of polycyclic aromatic hydrocarbons in urine from several smokers and non-smokers. The concentrations of 2-hydroxynaphthalene, 1-hydroxynaphthalene, 2-hydroxyfluorene, 2-hydroxyphenanthrene, 4-hydroxyphenanthrene and 6-hydroxychrysene in the smokers urine were much higher than that in non-smokers.
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<p><b>BACKGROUND</b>To investigate the clinical characteristics of thoracic lymph node metastasis in lung cancer.</p><p><b>METHODS</b>Three hundred and eighteen patients with lung cancer underwent pneumonectomy or lobectomy and lymphadenectomy from Jan 2000 to Jan 2002.</p><p><b>RESULTS</b>A total of 1534 groups of lymph nodes were removed. Metastatic frequency of thoracic lymph nodes was 58.5% (186/318), in which N1 was 27.0% (86/318), N2 was 31.4% (100/318). There were higher frequencies of lymph node metastasis in 4, 7, 10, 11 regions around the root of lung. Among the skipping N2 metastasis (14.5%, 46/318), upper lobe cancer led to only upper mediastinal lymph node metastasis, however, lower or right middle lobe cancer caused both upper and lower mediastinal lymph node metastasis. Of the patients with swelling hilar and mediastinal lymph nodes reported by preoperative CT scan, only 48.2% were confirmed with lymph node metastasis by postoperative histopathology; while 22.4% of the patients with normal size lymph nodes had lymph node metastasis.</p><p><b>CONCLUSIONS</b>If there is no hilar and inferior carinal metastatic lymph node in patients with upper lobe cancer, the lower mediastinal lymph node dissection might not be necessary. But systematic mediastinal lymph node dissection should be performed in patients with lower lobe or right middle lobe cancer whether there is hilar or inferior carinal metastatic lymph node or not. The extent of lymph node dissection should not depend on the results of preoperative chest CT scan.</p>
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Objective To study endocrine disruptor chemicals causing malformed frogs in an irrigation canal in T city and a pool in CH city. Methods Water samples collected from an irrigation canal in T city and a pool in CH city where malformed frogs were found were concentrated through H103 resin. The concentrated samples were purified and derivated. The endocrine disruptor chemicals in the derivatives were determined by GC/MS and the estrogenic activities in concentrated water samples were assessed by the recombinant yeast estrogen system (RYES). Results Endocrine disruptor chemicals bisphenol_A (5.6?10-3～1.52 ?g/L) and nonylphenol (0.46～0.58 ?g/L) were found in the concentrated water samples of the irrigation canal in T city and the pool in CH city. RYES showed that the estrogenic activities were positive and this result accorded with the data given by GC/MS. Conclusion The results indicated that the cause resulted in malformation of frogs in the irrigation canal in T city and the pool in CH city might be related to endocrine disruptor chemicals.