[Progressive massive fibrosis in pneumoconiosis is mimicking lung malignancy on (18)F-FDGPET-CT: two cases report].

Occupational pneumoconiosis is one of the main occupational diseases in China. Progressive massive fibrosis in pneumoconiosis should be distinguished from lung cancer for their similar imaging features which is often identified by (18)F-FDG PET-CT in clinic. Here we reported two cases of pneumoconiosis. Both of them were suspected of carrying malignant tumors by preoperative PET-CT exam, however, nodules in these two patients were all proved to be benign by intraoperative pathology which suggested that there is false-positive possibility in the distinguishment of pneumoconiosis nodules by (18)F-FDG PET-CT.

Genomic and transcriptional heterogeneity of multifocal hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) often presents with multiple nodules within the liver, with limited effective interventions. The high genetic heterogeneity of HCC might be the major cause of treatment failure. We aimed to characterize genomic heterogeneity, infer clonal evolution, investigate RNA expression pattern and explore tumour immune microenvironment profile of multifocal HCC. PATIENTS AND METHODS: Whole-exome sequencing and RNA sequencing were carried out in 34 tumours and 6 adjacent normal liver tissue samples from 6 multifocal HCC patients. Protein expression of Ki67, AFP, P53, Survivin and CD8 was detected by immunohistochemistry. Fluorescence in situ hybridization was carried out to validate the amplification status of sorafenib-targeted genes. RESULTS: We deciphered genomic and transcriptional heterogeneity among tumours in each multifocal HCC patient including mutational profiles, copy number alterations, tumour evolutionary trajectory and tumour immune microenvironment profiles. Of note, sorafenib-targeted alterations were identified in the trunk of phylogenetic tree in only one out of the six patients, which may explain the relative low treatment response rate to sorafenib in clinical practice. Moreover, we demonstrated RNA expression patterns and tumour immune microenvironment profiles of all nodules. We found that RNA expression pattern was associated with Edmondson-Steiner grading. Based on the differential expression of 66 reported immune markers, unsupervised hierarchical clustering analysis of 34 nodules identified immune subsets: one low expression cluster with seven nodules and one high expression cluster with 11 nodules. CD8+ T cells were more enriched in nodules of the high expression cluster. CONCLUSIONS: Our study provided a detailed view of genomic and transcriptional heterogeneity, clonal evolution and immune infiltration of multifocal HCC. The heterogeneity of druggable targets and immune landscape might help interpret the clinical responsiveness to targeted drugs and immunotherapy for multifocal HCC patients.

Synergism between arsenic trioxide and cyclopamine in the inhibition of PC3 cell survival via the Hedgehog signaling pathway.

Previous studies have shown that Hh signaling is overexpressed in the development and progression of prostate cancer (PCa), suggesting that Hh pathway inhibitors might be an effective strategy in the treatment of PCa. The combination of chemotherapeutic agents is one of the main approaches in cancer treatment, with the objective of improving efficacy. In the present study, we examined the effect of combing arsenic trioxide (ATO), a useful agent for Hedgehog-driven cancers, and cyclopamine (CYA), a classic Hh pathway inhibitor, on the suppression of PC3 cells (i.e., an androgen-independent PCa cell line). The combination of ATO and CYA more effectively inhibited the proliferation of PC3 cells than either single agent alone. In a xenograft mouse model, the combination of ATO and CYA significantly reduced tumor weight and volume in nude mice that were implanted with PC3 cells. The combination of ATO and CYA in PC3 cells resulted in a more distinct mode of Hh pathway inhibition and strengthened the S phase arrest. The present results indicate that a combination of ATO and CYA may be a rational strategy for treating PCa.

Assessment of genetic stability in tissue-cultured products and seedlings of Saussurea involucrata by RAPD and ISSR markers.

To control the genetic quality during the whole process of tissue culture of the traditional Chinese medicinal plant, Saussurea involucrate Kar. et Kir., DNA polymorphisms and genetic variations were investigated using randomly amplified polymorphic DNA (RAPD) and inter-simple sequence repeats (ISSR) markers. The genetic stability/variation in tissue-cultured products, including three calli, three adventitious shoots, regenerated plantlets and 2 year-old regenerated plantlets cultivated in the planting base in Tianshan Mountain, were assessed compared with 1 year-old and 2 year-old seedlings cultivated in the same planting base using aseptic seedlings as reference. Apparent genetic variation was detected in the 11 type of plant materials. The percentages of polymorphic bands in the RAPD and ISSR analysis were, respectively, 35% and 33%. Cluster analysis indicated that the genetic similarity values calculated on the basis of RAPD and ISSR data among the 11 type of plant materials were respectively ranged from 0.823 to 0.995 with a mean of 0.878 and 0.825 to 0.974 with a mean of 0.885, which classified the samples into three groups. The similarity coefficient also revealed that differences among three calli were not remarkable by both RAPD and ISSR analysis, and only chemical components and growth properties needed consideration in the screening of callus used for the next redifferentiation studies. But there are remarkable differences among three adventitious shoots analyzed by ISSR markers. Therefore, RAPD and ISSR markers are efficient tools in genetic variation assessment and quality control in plant tissue culture process.

Direct electrochemistry of glucose oxidase immobilized on a hexagonal mesoporous silica-MCM-41 matrix.

The direct electrochemistry of glucose oxidase (GOD) immobilized on a hexagonal mesoporous silica modified glassy carbon electrode was investigated. The adsorbed GOD displayed a pair of redox peaks with a formal potential of -417 mV in 0.1 M pH 6.1 phosphate buffer solution (PBS). The response showed a diffusion-controlled electrode process with a two-electron transfer coupled with a two-proton transfer reaction process. GOD immobilized on a hexagonal mesoporous silica retained its bioactivity and stability. In addition, the immobilized GOD could electrocatalyze the oxidation of glucose to gluconlactone by taking ferrocene monocarboxylic acid (FMCA) as a mediator in N(2) saturated solutions, indicating that the electrode may have the potential application in biosensors to analyze glucose. The sensor could exclude the interference of commonly coexisted uric acid, p-acetaminophenol and ascorbic acid and diagnose diabetes very fast and sensitively. This work demonstrated that the mesoporous silica provided a novel matrix for protein immobilization and the construction of biosensors.

[Application of directed acyclic graphs in control of confounding].

Observational study is a method most commonly used in the etiology study of epidemiology, but confounders, always distort the true causality between exposure and outcome when local inferencing. In order to eliminate these confounding, the determining of variables which need to be adjusted become a key issue. Directed acyclic graph(DAG)could visualize complex causality, provide a simple and intuitive way to identify the confounding, and convert it into the finding of the minimal sufficient adjustment for the control of confounding. On the one hand, directed acyclic graph can choose less variables, which increase statistical efficiency of the analysis. On the other hand, it could help avoiding variables that is not measured or with missing values. In a word, the directed acyclic graph could facilitate the reveal of the real causality effectively.

[The frequency distribution and establishment of fruit fly strain of segregation distorter in Drosophila melanogaster in China].

Segregation Distorter (SD) is a meiotic drive system of natural occurrence. Heterozygous SD/SD+ males transmit the SD chromosome in vast excess over the normal homolog. SD chromosomes have been recovered at low frequency (1%-5%) from almost every population that has been screened for them in many places of the world. To examine whether there is SD system in natural populations of Drosophila melanogaster in China, we surveyed a few populations of D. melanogaster in Beijing and Qingdao respectively. The results suggested that SD is also found in every population examined at frequency of 1%-5%. On the basis of learning distribution of SD in China, we established a fruit fly stoch of SD from wild population of D. melanogaster in Beianhe district of Beijing. Furthermore, instead of using traditional genetic hybridization, we used molecular approach, PCR, to examine the distribution of SD chromosomes, which has been proved a very effective, quick and convenient method.

[Mitochondrial DNA genetic polymorphism of Drosophila immigrans in China].

This article uses RFLP to analyze the mitochondrial DNA(mtDNA) variation in geographic populations of Drosophila immigrans from 6 regions of mainland of China. With the use of fourteen restriction endonucleases, we only discoveried a total of 11 mtDNA haplotypes among 46 isofemale lines. The mean value of I is 0.833, the mean value of J is 0.797, and the estimated Gst value is only 16.8%. We recognized that the genetic structures among the geographic populations of D. immigrans are highly uniform, and the genetic differentiation rate is low. The UPGMA analysis of nucleotide diversity of the 6 populations shows specific characteristics of mtDNA variation in population of Huayang, Qinling Mountains Regions. From the haplotypes special included in each population, the event that the population spread into the high altitute localities of Yunnan perhaps happened more recently. Referring other references, we inferred the population of D. immigrans distributed in mainland of China is more original than that in Chinese Taiwan and Japan.

[Computer simulation for infrared spectra of pollution clouds with FTIS remote detection].

A computer model of radiometric scene simulation for simulated spectra for pollution clouds in complicated environment is proposed. The model is used to introduce the effects of an actual hazardous pollution clouds, such as (CH3)2CHO(CH3)FPO or (CLCH2CH2)2S, into exiting measured background spectra by passive Fourier transform infrared spectrometer (FTIS). The simulated results agree well with the experimental results.

Neuroglobin - a potential biological marker of retinal damage induced by LED light.

Neuroglobin (NGB), a protein highly expressed in the retina, has been shown to be up-regulated to protect neurons from hypoxic and ischemic injuries. It exhibits neuroprotective functions and plays an important role in the survival of neurons. Recent studies show that light-emitting diode (LED) white light emitted significant amounts of blue light (short-wavelength), which may be harmful to retinal cells, but the studies about biomarkers for evaluating the damage from LED white light are still insufficient. In our study, we found that NGB levels in the retina showed a twofold increase and peaked at 1h after a 1-h exposure to blue light (453 nm) which did not cause damage to the retina. However, retinal damage was observed after 2h of blue-light irradiation, which induced an approximate sevenfold increase of NGB levels as confirmed by Western blot and RT-PCR analysis. Immunofluorescence study demonstrated that NGB was predominantly up-regulated in the ganglion cell layer (GCL), plexiform layer (PL) and photoreceptor layer (PRL). We also examined Ngb mRNA and protein expression in the damaged retina induced by light of other wavelengths given equal photon fluxes. The LED red light (625 nm), green light (527 nm) and blue light (453 nm) increased the expression of NGB and caused TdT-mediated dUTP nick-end labeling-positive cells, especially in the blue-light group. In addition, a negative correlation between NGB and rhodopsin was observed. These findings suggested that there was a correlation between NGB expression and the severity of the retinal damage, indicating NGB's potential function as a biological marker of retinal damage induced by LED light.

The availability of 16S rRNA for the identification of forensically important flies (Diptera: Muscidae) in China.

Many species of Muscidae are cosmopolitan synanthropic insects. It is frequently found on dead bodies after death, so an accurate identification of each species is necessary for the correct estimation of the postmortem interval (PMI). Identification species of Muscidae is traditionally performed through their morphological features. However, the morphological similarity of Muscidae in the level of species usually poses a challenge for forensic entomologists. Therefore a molecular method used 16S rRNA sequence on mitochondrial DNA was established for species identification. In this study, a 289 base pair region of mitochondrial DNA (mtDNA) coding for 16S rRNA was investigated for identification of the following forensically important species of Muscidae. The specimens were from four genera, including 18 Musca domestica (Linnaeus, 1758), 2 Ophyra spinigera (Stein, 1910), 2 Ophyra chalcogaster (Wiedemann, 1824), 1 Morellia hortorum (Fallén, 1817), and 1 Fannia canicularis (Linnaeus, 1761). 16S rDNA region allowed the identification of these species of Muscidae, indicating the possibility of separation congeneric species with molecular method.

[Olivopontocerebellar atrophy: clinical analysis of 100 cases].

The clinical features in 100 patients suffered from olivopontocerebellar atrophy (OPCA) and their genetic trait were studied. The diagnosis was verified in all cases with computed tomography, demonstrating the atrophy of cerebellum and brainstem, vascular, neoplastic, infectious and any other organic disorder suspected were excluded. 53 out of 100 cases were sporadic (SOPCA) and the remainder (47 cases) was familial (FOPCA). The age of onset in SOPCA group was 36.1 +/- 14.95 (M +/- SD) in average, while in FOPCA group was 28.9 +/- 11.8. It seems that the symptoms in FOPCA group develop earlier than that in SOPCA group (P less than 0.05). All 47 cases of FOPCA group belong to 36 families in which altogether 166 persons were involved. According to pedigree patterns, there were 26 families inherited as autosomal dominant trait and probably so in another 5 families. Autosomal recessive trait could be confirmed in 2 families, in which the parents of proband were consanguineous, and in 3 other families autosomal recessive trait of inheritance was highly suspected. Anticipation was demonstrated in 26 families with dominant inheritance. Generally, ataxia and weakness of legs develop as initial symptoms in 88% of cases, then followed by dysarthria, and ataxia of upper extremities. The rapid alternating test of hand was impaired in 95% of patients, however, tension tremor was revealed only in 53% of patients. A method for assessing the ataxia quantitatively was proposed, our data suggest that the quantitative alternating test in the upper extremity and the measurement of base-width in lower extremity seem to be valuable in identifying the intensity of ataxia.

van der Woude syndrome in two families in China.

We report on two unrelated families from the Beijing area in which the autosomal dominant gene for van der Woude syndrome (VWS) is segregating. The clinical features include paramedian lower lip pits (fistula labii inferioris congenita), cleft palate, and cleft lip with or without cleft palate. All three of the clinical features may occur together in an affected individual, or any two together, or any one as a single feature of an individual who carries the gene. The probands in each of our families also have ankyloglossia. This is the first report of VWS from China.