Low pretreatment PNI correlates with worse survival in patients with stage III/IV NSCLC who received chemotherapy.

The aim of this study was to investigate the prognostic value of the prognostic nutritional index (PNI) on the long-term survival of non-small cell lung cancer (NSCLC) patients who received platinum-based chemotherapy. Data on nutritional parameters and clinicopathological characteristics [e.g., albumin, total protein, body mass index (BMI), eastern cooperative oncology group (ECOG) performance status, stage, pathology, treatment strategy] were analyzed and retrospectively correlated with overall survival (OS). The PNI was calculated based on the concentration of albumin and lymphocyte count [10 × albumin, (g/dl) + 0.005 × lymphocyte (count/mm3)]. A receiver operating characteristic curve (ROC) analysis was used to find the optimal cut-off value of PNI. Univariate and multivariate analyses were used to evaluate the prognostic value of PNI. A total of 186 patients met the inclusion criteria. The optimal cut-off value for PNI was 50.45. Compared with the parameters of the low PNI group (n=76), high PNI was significantly associated with adenocarcinoma type, stage III, better ECOG and comprehensive treatment modality. The univariate analysis demonstrated that OS was superior when PNI ≥50.45, albumin ≥35 g/l, platelet-lymphocyte ratio (PLR) ≥163 and ECOG <2, and when the patient received a comprehensive treatment modality. In the multivariate analysis, PNI, TNM stage and treatment strategy were identified as independent predictors of survival in this study. This retrospective study demonstrated that a low PNI was related to worse overall survival in patients with stage III/IV NSCLC who received platinum-based chemotherapy. These data provided a conceptual basis for further research on the clinical application of the PNI index for patients receiving chemotherapy for intermediate- and advanced-stage NSCLC.

[Clinicopathological features and prognosis of 488 patients with neuroendocrine tumors].

Objective: To investigate the clinicopathological features and prognosis of patients with neuroendocrine tumors (NETs). Methods: The clinicopathologic data of enrolled patients with NETs between October 2012 and October 2017 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Results: Among the 488 NETs patients, the average age was (51.0±15.8) years, and the sex ratio (male/female) was 1∶1.1. Of the NETs, 370 were located in the digestive system (75.8%), 63 were pulmonary (12.9%), 14 were mediastinal (2.9%), 7 were of unknown primary origin (1.4%), and 34 were located in other sites (7.0%). Among the NETs, the pancreas, rectum and stomach were the most common sites. In the digestive system NETs, the most common tumor grade was G1 (190 cases, 51.4%), followed by G2 (143 cases, 38.6%) and NET-G3 (37 cases, 10.0%). In pulmonary NETs, typical and atypical carcinoid tumors was 47.6% and 52.4%, respectively. There were 310 patients at stage Ⅰ/Ⅱ, 53 at stage Ⅲ, 69 at stage Ⅳ and 56 at stage undiagnosed, respectively. The relationships among age, stage, grade, metastasis, treatment and prognosis were analyzed. All these factors could influence the survival rate of NET patients. Multivariate Cox analysis showed that age (>50 years old) (HR=2.831, 95%CI:1.414-7.029, P=0.025) and distant metastasis (HR=10.208, 95%CI:4.110-25.355, P<0.001) were independent risk factors. Conclusions: The most common primary sites of NETs are the pancreas, rectum, and stomach. Age and distant metastasis are independent risk factors for the prognosis of NETs.

[Functional lateralization of major Chinese language cortex for presurgical evaluation in neurosurgery].

Objective: To investigate the functional lateralization of major Chinese language cortex in patients with cerebral arteriovenous malformation (AVM) in dominant hemispheric via functional magnetic resonance imaging (fMRI). Methods: Nine right-handed normal volunteers and fourteen patients with cerebral AVM in dominant hemisphere diagnosed in Beijing Tiantan Hospital between December 2017 and June 2018 were included. Three language tasks (semantic judgment, word reading, and listening comprehension) were applied to activate language areas. Lateralization index (LI) was used to show the dominant hemisphere. Results: In the control group, right-sided lateralization of BOLD signal activations was observed in 0/27 (0%) of the language tasks. While in the AVM patients, right-sided lateralization of BOLD signal activations was observed in 8/42 (19%) language tasks. The difference was statistically significant (χ(2)=5.73, P=0.019). Conclusions: The dominant hemisphere of different language tasks may be different in patients with cerebral lesions. Compared with normal controls, patients with cerebral AVM in dominant hemispheric are more likely to have right-sided lateralization of language cortex.

[Characterization and uncertainty evaluation of aqueous reference materials for cholesterol].

Objective: Characterization and evaluation of the uncertainty of the reference materials of cholesterol in aqueous solution. Methods: The certified reference material GBW09203b was weighed accurately and dissolved into methyl cyclodextrin aqueous solution to prepare six kinds of candidate reference materials of cholesterol according to the concentration. The materials were tested for homogeneity and stability using routine methods and were evaluated the uncertainty derived from the inhomogeneity and instability. The uncertainty due to measurement was derived from the purity of the raw material, the weighing and the density measurement. The certified values and expanded uncertainties were calculated according to the ISO Guide. The expanded uncertainty of the certified value was the combination of standard uncertainty of measurement, inhomogeneity and instability. The coverage factor, k, was determined from the Student's t-distribution corresponding to the calculated effective degrees of freedom and 95% level of confidence. Results: It showed that the six candidate reference materials were homogeneous and were tested to be stable for at least 1 year at -70 ℃ and -20 ℃ using the isochronous stability study. The relative uncertainties due to the inhomogeneity were 0.14%, 0.11%, 0.13%, 0.47%, 0.39% and 0.11%. The relative uncertainty due to the instability was 0.25% at -70 ℃. The uncertainties of measurement were 0.06%, 0.05%, 0.05%, 0.05%, 0.05% and 0.05%.The certified values (reference value ± expanded uncertainty, mmol/L) were as follows: (0.651±0.004), (1.310 ±0.007), (2.574±0.015), (5.210±0.055), (7.710±0.072), (10.242±0.056) mmol/L. Conclusions: Six kinds of certified reference materials for cholesterol in aqueous solution have been prepared, which were homogeneity, stable and reliable. It showed that the uncertainty of measurement was very small compared with the uncertainty due to inhomogeneity and instability.

Clinical efficacy of fiberoptic ductoscopy in combination with ultrasound-guided minimally invasive surgery in treatment of plasma cell mastitis.

OBJECTIVES: To analyze clinical efficacy between fiberoptic ductoscopy plus ultrasound-guided minimally invasive irrigation and lesion resection in treating plasma cell mastitis (PCM), aiming to provide clinical evidence for treating PCM. MATERIALS AND METHODS: 119 patients undergoing fiberoptic ductoscopy plus ultrasound-guided minimally invasive surgery in Ningxia People's Hospital were allocated into the breast duct irrigation group, and 95 counterparts receiving lesion resection in the Affiliated Hospital of Ningxia Medical University into the control group. Clinico-pathological characteristics and therapeutic effect were compared between two groups. RESULTS: The cure rate in the breast duct irrigation group was 98.31% (117/119), significantly higher than 90.53% in the control group (p < 0.05). In the breast duct irrigation group, overall treatment time was 20.13 days, significantly longer than 15.15 days in the control group (p < 0.05). During postoperative follow-up, no recurrence was observed, significantly lower compared with 48.8% (42/86) in the control group. The degree of satisfaction in the breast duct irrigation group was 95.79% (114/119), significantly higher compared with 74.74% (71/95) in the control group. CONCLUSIONS: Fiberoptic ductoscopy plus with ultrasound-guided minimally invasive drainage is a novel and effective treatment of PCM with high cure rate, low recurrence rate, slight pain, and effectively maintains breast integrity.

Members of the receptor for advanced glycation end products axis as potential therapeutic targets in patients with lupus nephritis.

The relationship of inflammation and the expression of full-length receptor for advanced glycation end products (flRAGE) on monocytes, plasma levels of RAGE ligand high mobility group box protein 1 (HMGB1), soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) was assessed to elucidate the effect of HMGB1/DNA/RAGE-mediated innate inflammatory responses in patients with lupus nephritis. Cell surface expression of flRAGE was elevated on the monocytes of lupus patients, correlated with plasma HMGB1 levels. Plasma sRAGE level negatively correlated with systemic lupus erythematosus (SLE) disease activity index. Plasma esRAGE level was significantly lower in SLE patients with flare while esRAGE/sRAGE ratio negatively correlated with complement C3 level. HMGB1 alone could moderately induce ex vivo IL-6 production from monocytes, resulting in activation of intracellular p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase and nuclear factor (NF)-κB. Moreover, toll-like receptor-9 ligand together with HMGB1 exhibited a synergistic effect on IL-6 and IL-12p70 secretions and the phosphorylation of p38 MAPK and NF-κB. Therefore, over-expression of flRAGE in lupus may lead to the amplification of RAGE ligands-mediated inflammatory responses through the activation of p38 MAPK and NF-κB. Plasma sRAGE may serve as a potential biomarker for disease activity and a future therapeutic target in SLE.

Duplicated CCAAT/enhancer-binding protein ß (C/EBPß) gene: transcription and methylation changes in response to dietary betaine in Landes goose liver.

The CCAAT/enhancer-binding protein ß gene (C/EBPß) is one of the key regulating factors of lipid metabolic balance in the liver. To better understand how C/EBPß affects lipid accumulation in the Landes goose liver, its DNA was cloned. The goose C/EBPß DNA sequence (2,075 bp) contains a 984-bp open reading frame and part of the 5'-flanking region, and shares 96.66 and 62.07% similarity with the chicken and human sequences at the amino acid level, respectively. Tissue expression profiling showed that the relative expression level was high in the liver and adipose tissue. To understand the effect of betaine on C/EBPß in goose liver, the relative expression levels of C/EBPß were detected under different treatments. Compared with the control group, C/EBPß expression increased in the high-carbohydrate group (P < 0.01) and decreased in the betaine treatment group (P > 0.05). Using bisulfite sequencing PCR, the gene methylation status was analyzed among the different treatment groups. None of the 54 CpG sites in the promoter region or the 28 CpG sites in the structural domain of the coding region showed any significantly different methylation patterns among the groups. Taken together, the results showed that betaine decreased the goose C/EBPß gene expression, but did not directly regulate its methylation. The data may form the basis for further investigation of the mechanisms of the effect of C/EBPß on the regulation of lipometabolism in the goose liver and the effect of betaine on lipid metabolic genes at the molecular level.

Efficient and accurate replication in the presence of 7,8-dihydro-8-oxoguanine by DNA polymerase eta.

Oxidative damage to DNA has been proposed to have a role in cancer and ageing. Oxygen-free radicals formed during normal aerobic cellular metabolism attack bases in DNA, and 7, 8-dihydro-8-oxoguanine (8-oxoG) is one of the adducts formed. Eukaryotic replicative DNA polymerases replicate DNA containing 8-oxoG by inserting an adenine opposite the lesion; consequently, 8-oxoG is highly mutagenic and causes G:C to T:A transversions. Genetic studies in yeast have indicated a role for mismatch repair in minimizing the incidence of these mutations. In Saccharomyces cerevisiae, deletion of OGG1, encoding a DNA glycosylase that functions in the removal of 8-oxoG when paired with C, causes an increase in the rate of G:C to T:A transversions. The ogg1Delta msh2Delta double mutant displays a higher rate of CAN1S to can1r forward mutations than the ogg1Delta or msh2Delta single mutants, and this enhanced mutagenesis is primarily due to G:C to T:A transversions. The gene RAD30 of S. cerevisiae encodes a DNA polymerase, Poleta, that efficiently replicates DNA containing a cis-syn thymine-thymine (T-T) dimer by inserting two adenines across from the dimer. In humans, mutations in the yeast RAD30 counterpart, POLH, cause the variant form of xeroderma pigmentosum (XP-V), and XP-V individuals suffer from a high incidence of sunlight-induced skin cancers. Here we show that yeast and human POLeta replicate DNA containing 8-oxoG efficiently and accurately by inserting a cytosine across from the lesion and by proficiently extending from this base pair. Consistent with these biochemical studies, a synergistic increase in the rate of spontaneous mutations occurs in the absence of POLeta in the yeast ogg1Delta mutant. Our results suggest an additional role for Poleta in the prevention of internal cancers in humans that would otherwise result from the mutagenic replication of 8-oxoG in DNA.

Separation of oil/water emulsion using nano-particle (TiO(2)/Al(2)O(3)) modified PVDF ultrafiltration membranes and evaluation of fouling mechanism.

In the present study, nano-sized TiO(2)/Al(2)O(3) modified polyvinylidene fluoride (PVDF) membranes (MM) were fabricated and then utilized for oil/water emulsion separation. The results showed that, compared with PVDF membrane (OM), the contact angle of MM decreased and hydrophilicity increased. The ultrafiltration (UF) of oil in water emulsions with transmembrane pressure (TMP) increasing results in a sharp fall in relative flux with time. The cake filtration models did not always predict the performance over the complete range of filtration times very well. In the initial 30 min, all the four cake models can simulate this UF process to a certain extent, and the suitability was: cake filtration > intermediate pore blocking > standard pore blocking > complete pore blocking models. However, they were no longer adapted well with UF time extent to 60 min, but only cake filtration (R(2) = 0.9535) maintained a high adaptability. Surface and cross-sectional morphology of the membrane was investigated by SEM to make an advanced certificate of this UF mechanism.

Priority list of potential endocrine-disrupting chemicals in food chemical contaminants: a docking study and in vitro/epidemiological evidence integration.

Diet is an important exposure route of endocrine-disrupting chemicals (EDCs), but many unfiltered potential EDCs remain in food. The in silico prediction of EDCs is a popular method for preliminary screening. Potential EDCs in food were screened using Endocrine Disruptome, an open-source platform for inverse docking, to predict the binding probabilities of 587 food chemical contaminants with 18 human nuclear hormone receptor (NHR) conformations. In total, 25 contaminants were bound to multiple NHRs such as oestrogen receptor α/ß and androgen receptor. These 25 compounds mainly include pesticides and per- and polyfluoroalkyl substances (PFASs). The prediction results were validated with the in vitro data. The structural features and the crucial amino acid residues of the four NHRs were also validated based on previous literature. The findings indicate that the screening has good prediction efficiency. In addition, the epidemic evidence about endocrine interference of PFASs in food on children was further validated through this screening. This study provides preliminary screening results for EDCs in food and a priority list for in vitro and in vivo research.

RNA is favourable for analysing EGFR mutations in malignant pleural effusion of lung cancer.

Malignant pleural effusion (MPE) is a useful specimen allowing for the evaluation of EGFR status in nonsmall cell lung cancer (NSCLC). However, direct sequencing of genomic DNA from MPE samples was found not to be sensitive for EGFR mutation detection. To test whether EGFR analysis from RNA is less prone to interference from nontumour cells that have no or lower EGFR expression, we compared three methods (sequencing from cell-derived RNA versus sequencing and mass-spectrometric analysis from genomic DNA), in parallel, for EGFR mutation detection from MPE samples in 150 lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors (TKIs). Among these MPE samples, EGFR mutations were much more frequently identified by sequencing using RNA than by sequencing and mass-spectrometric analysis from genomic DNA (for all mutations, 67.3 versus 44.7 and 46.7%; for L858R or exon 19 deletions, 61.3 versus 41.3 and 46.7%, respectively). The better mutation detection yield of sequencing from RNA was coupled with the superior prediction of clinical efficacy of first-line TKIs. In patients with acquired resistance, EGFR sequencing from RNA provided satisfactory detection of T790M (54.2%). These results demonstrated that EGFR sequencing using RNA as template greatly improves sensitivity for EGFR mutation detection from samples of MPE, highlighting RNA as the favourable source for analysing EGFR mutations from heterogeneous MPE specimens in NSCLC.

Characterization of insertional variation of porcine endogenous retroviruses in six different pig breeds.

Pigs may need to be exploited as xenotransplantation donors due to the shortage of human organs, tissues and cells. Porcine endogenous retroviruses (PERVs) are a significant obstacle to xenotransplantation because they can infect human cells in vitro and have the potential for transmission of unexpected pathogens to humans. In this research, 101 pigs, including four commercial breeds (23 Berkshire, 13 Duroc, 22 Landrace and 14 Yorkshire pigs), one native breed (19 Korean native pigs) and one miniature breed (10 NIH miniature pigs) were used to investigate insertional variations for 11 PERV loci (three PERV-A, six PERV-B and two PERV-C). Over 60% of the pigs harbored one PERV-A (907F8) integration and five PERV-B (B3-3G, B3-7G, 742H1, 1155D9 and 465D1) integrations. However, two PERV-A loci (A1-6C and 1347C1) and one PERV-B locus (B3-7F) were absent in Duroc pigs. Moreover, two PERV-C loci (C2-6C and C4-2G) only existed in Korean native pigs and NIH miniature pigs. The results suggest that PERV insertional variations differ among pig breeds as well as among individuals within a breed. Also, the results presented here can be used for the selection of animals that do not have specific PERV integration for xenotransplantation research.

Molecular analysis of the coat protein gene of peanut stripe virus from China.

Peanut stripe virus (PStV) is one of the most common viruses infecting peanut that causes great economic losses every year. The 3ʹ-terminal 1082 bp of 74 PStV isolates collected from 12 districts of Shandong province, China were sequenced. Their coat protein (CP) genes were 864 bp in length and shared identities of 98.0%~100% and 98.3% ~100% at nt and aa levels. The identities between the CP genes of these isolates and other 36 isolates from the GenBank were 93.5%~100% and 92.0%~100% at nt and aa levels, respectively. PStV isolates can be clustered into two phylogenetic groups. The isolates from United States, mainland China, and Indonesia formed group I and those from Viet Nam, Thailand, and Taiwan formed group II. The PStV isolates in group I can be further classified to two subgroups. The gene flow of PStV populations within a country was frequent, but that between countries was infrequent.

Characterization and anti-fouling performance of nano-Al2O3/PVDF membrane for Songhua river raw water filtration.

Polyvinylidene fluoride (PVDF) flat ultrafiltration membranes modified by nano-sized alumina (Al2O3) particles were prepared by phase inversion process and their properties and anti-fouling performances were examined. The influence of three types of natural organic matters on the modified membrane fouling was also studied. Raw water was taken from two different locations, i.e., Harbin and Zhaoyuan, of Songhua River. Dissolved organic compounds in the raw water were fractionated using XAD resins into three fractions, i.e., hydrophobic fraction, transphilic fraction, and hydrophilic fraction (HPI). The three adsorbed compounds were further eluted and dissolved into distilled water respectively to prepare the feed for the fouling tests. All solutions were adjusted to a concentration of 10.6 mg C/L, which equals to the total organic carbon (TOC) of the raw water. Results show that the addition of nano-Al2O3 particulars did not affect the inherent traits of the PVDF membranes, however, its surface hydrophilic properties were improved significantly with the addition of nanoparticles and anti-fouling performance was enhanced as well. The HPIs in the Songhua River were the main foulant, causing more fouling to membrane than hydrophobic and transphilic matters.

MicroRNA in lung cancer.

MicroRNAs (miRNAs) are small non-protein-coding RNAs that function as endogenous negative gene regulators. Dysfunctions of miRNAs are frequently found in malignancies, including lung cancer. In this review, we summarise the current understanding of miRNAs in lung cancer tumourigenesis, and highlight their potential in overcoming drug resistance, abetting histological sub-classification techniques, and serving as biomarkers for lung cancer risk stratification and outcome prediction.

[Seroprevalence of Toxoplasma gondii and Toxocara infections among pregnant women in Hangzhou City].

OBJECTIVE: To investigate the prevalence of Toxoplasma gondii and Toxocara infections among pregnant women in Hangzhou City, so as to provide baseline data for decreasing birth defects and improving the population quality. METHODS: A total of 235 pregnant women receiving prenatal diagnosis at the First People's Hospital of Yuhang District during the period between February 2018 through December 2019 were recruited as the observation group, and 235 age-matched, non-pregnant healthy women at the same hospital during the same period served as the control group. The subjects'medical records were captured from the hospital management information system. Blood samples were collected from the observation and control groups and detected for the presence of IgG antibodies against T. gondii and Toxocara using an enzyme-linked immunosorbent assay (ELISA). The seroprevalence of the IgG antibodies against T. gondii and Toxocara was compared between the observation and control groups. RESULTS: The subjects in the observation group had a mean age of 26.5 ± 4.3 years (range, 23 to 31 years), and gestational ages of 10 to 27 weeks, and the subjects in the control group had a mean age of 26.1 ± 5.7 years (range, 20 to 30 years). The seroprevalence rates of IgG antibodies against T. gondii (28.51% vs. 4.68%; χ2 = 34.85, P < 0.01) and Toxocara (24.26% vs. 5.11%; χ2 = 25.77, P < 0.01) were both significantly higher in the observation group than in the control group, and the seroprevalence of T. gondii and Toxocara co-infections was also significantly greater in the observation group than in the control group (13.19% vs. 2.13%; χ2 = 17.49, P < 0.01). CONCLUSIONS: The seroprevalence rates of T. gondii and Toxocara infections and their co-infections are all high among pregnant women in Hangzhou City. Screening of T. gondii and Toxocara infections is strongly recommended during pregnancy.

Requirement of yeast SGS1 and SRS2 genes for replication and transcription.

The SGS1 gene of the yeast Saccharomyces cerevisiae encodes a DNA helicase with homology to the human Bloom's syndrome gene BLM and the Werner's syndrome gene WRN. The SRS2 gene of yeast also encodes a DNA helicase. Simultaneous deletion of SGS1 and SRS2 is lethal in yeast. Here, using a conditional mutation of SGS1, it is shown that DNA replication and RNA polymerase I transcription are drastically inhibited in the srs2Delta sgs1-ts strain at the restrictive temperature. Thus, SGS1 and SRS2 function in DNA replication and RNA polymerase I transcription. These functions may contribute to the various defects observed in Werner's and Bloom's syndromes.