Metagenomic next-generation sequencing and proteomics analysis in pediatric viral encephalitis and meningitis.

Introduction: Early and accurate identification of pathogens is essential for improved outcomes in patients with viral encephalitis (VE) and/or viral meningitis (VM). Methods: In our research, Metagenomic next-generation sequencing (mNGS) which can identify viral pathogens unbiasedly was performed on RNA and DNA to identify potential pathogens in cerebrospinal fluid (CSF) samples from 50 pediatric patients with suspected VEs and/or VMs. Then we performed proteomics analysis on the 14 HEV-positive CSF samples and another 12 CSF samples from health controls (HCs). A supervised partial least squaresdiscriminant analysis (PLS-DA) and orthogonal PLS-DA (O-PLS-DA) model was performed using proteomics data. Results: Ten viruses in 48% patients were identified and the most common pathogen was human enterovirus (HEV) Echo18. 11 proteins overlapping between the top 20 DEPs in terms of P value and FC and the top 20 proteins in PLS-DA VIP lists were acquired. Discussion: Our result showed mNGS has certain advantages on pathogens identification in VE and VM and our research established a foundation to identify diagnosis biomarker candidates of HEV-positive meningitis based on MS-based proteomics analysis, which could also contribute toward investigating the HEV-specific host response patterns.

Self-supported spinel nanosphere as bifunctional electrocatalysts for energy-saving hydrogen production via urea-water electrolysis.

Electrochemical oxidation of urea is of great importance in the removal and energy exchange and storage of urea from wastewater as well as of potential applications in potable dialysis of end-stage renal disease. However, the lack of economical electrocatalysts hinders its widespread application. In this study, we successfully fabricated ZnCo2O4 nanospheres with bifunctional catalysis on nickel foam (NF). The catalytic system has high catalytic activity and durability for urea overall electrolysis. The urea oxidation and hydrogen evolution reactions required only 1.32 V and -80.91 mV to obtain ± 10 mA cm-2. Only 1.39 V was needed to obtain 10 mA cm-2 for 40 h without noticeably declining activity. The excellent performance could be attributed to the fact that the material can provide multiple redox couplings and a three-dimensional porous structure to facilitate the release of gases from the surface.

Genomic insights into secondary metabolites of pharmaceutical utility for Hyphococcus flavus MCCC 1K03223T, isolated from bathypelagic seawater.

During an attempt to screen secondary metabolites of pharmaceutical utility, we sequenced the complete genome of type strain of a novel marine bacterial genus, named genus Hyphococcus. The type strain, Hyphococcus flavus MCCC 1K03223T, was isolated from bathypelagic seawater of South China Sea at a depth of 2500 m. The complete genome of strain MCCC 1K03223T is composed of a circular chromosome of 3,472,649 bp with a mean G + C content of 54.8%. Functional genomic analysis showed that this genome encodes five biosynthetic gene clusters, which were annotated to synthesize medicinally important secondary metabolites. Secondary metabolites annotated include ectoine which acts cytoprotection, ravidomycin which is an antitumor antibiotic and three other different metabolites of terpene type. The secondary metabolic potentials of H. flavus revealed in this study provide more evidences on mining bioactive substances from marine bathypelagic microorganisms.

[Effect of Family Environment on Non-Suicidal Self-Injury Among Middle School Students During the COVID-19 Epidemic: The Mediating Role of Depression].

Objective: To study the current status of non-suicidal self-injury (NSSI) incidents among middle school students in Chengdu during the COVID-19 epidemic and to explore the mechanism of action of depression on the relationship between family environment and NSSI. Methods: Data were obtained from the Chengdu Positive Child Development (CDPD) cohort. In June and July 2020, after primary and secondary schools were reopened after the closure due to the COVID-19 epidemic, on-site questionnaire surveys were conducted with the Deliberate Self-Harm Inventory (DSHI), the Chinese Family Assessment Instrument (C-FAI), and Center for Epidemiologic Studies Depression Scale for Children (CES-DC), thereby obtaining the data of 3595 middle school students. Two-sample t-test and χ 2 test were used to compare the incidence of NSSI among middle school students of different grades and genders, and the Model 58 test of the SPSS PROCESS component was used to analyze the mediating effect of gender-mediated depression. Results: 1) The incidence of NSSI among middle school students in Chengdu during the COVID-19 epidemic was 49.67%. The incidence of NSSI among ninth-graders (80.70%) was significantly higher than those of the eighth graders (33.82%) and seventh graders (32.32%), and the incidence of NSSI among female middle school students (54.75%) was significantly higher than that of male students (44.52%). 2) Family environment ( r=0.34, P<0.001) and depression ( r=0.50, P<0.001) were positively correlated with NSSI. 3) Depression partially mediated the effect of family environment on NSSI, with the mediating effect accounting for 64.64% of the total effect. Compared with that of male students, the positive predictive effect between family environment and depression and that between depression and NSSI in female middle school students were more significant. Conclusion: During the COVID-19 pandemic, middle school students in Chengdu had a high incidence of NSSI, which indicates that the family environment should be improved, more attention should be given to gender differences, and early screening and intervention for depression should be strengthened to reduce the incidence of NSSI.

Reciprocal effect between non-suicidal self-injury and depressive symptoms in adolescence.

Background: Non-suicidal self-injury (NSSI) is a common psychological and behavioral problem among adolescents. The COVID-19 pandemic has had a significant impact on people's mental health. To date, few studies have documented the temporal changes in adolescents' psychological status during the pandemic, as well as the impact of large-scale public health intervention strategies. This study contributes to the existing evidence on the subject. Methods: Participants were 6,023 adolescents aged 10 years and older, with data from two waves of longitudinal surveys, including data for a 7-month interval before and during the pandemic. A cross-lagged model was used to test the bidirectional relationship between NSSI and depressive symptoms in adolescents; logistic regression analysis was used to explore the predictors of NSSI implementation in adolescents with depressive symptoms. Results: In this study, 32.69% participants reported depressive symptoms at baseline and 34.27% at follow-up; 44.34% participants with depressive symptoms reported NSSI at baseline and 53.44% at follow-up. The duration of the online class, depressed affect, and somatic and related activity were the risk factors for NSSI; sleep duration and positive mood were the protective factors. The lag effect of depression symptoms on NSSI is significant, and so is NSSI on depressive symptoms. Conclusion: During the COVID-19 pandemic, adolescents' mental health has worsened, resulting in an increase in the prevalence of NSSI among those with depressive symptoms compared to pre-pandemic levels. Early screening for depression is crucial in preventing or decreasing NSSI in adolescents.

Proteomic profiling of cerebrospinal fluid in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an autoimmune demyelinating disorder of the central nervous system. METHODS: Extracted proteins from 34 cerebrospinal fluid (CSF) samples [patients with MOGAD (MOG group, n = 12); healthy controls (HC group, n = 12); patients with MOG seronegative and metagenomics next-generation sequencing-negative inflammatory neurological diseases (IND group, n = 10)] were processed and subjected to label-free quantitative proteomics. Supervised partial least squares-discriminant analysis (PLS-DA) and orthogonal PLS-DA (O-PLS-DA) models were also performed based on proteomics data. Functional analysis of differentially expressed proteins (DEPs) was performed using Gene Ontology, InterPro, and Kyoto Encyclopedia Genes and Genomes. An enzyme-linked immunosorbent assay was used to determine the complement levels in serum from patients with MOGAD. RESULTS: Four hundred and twenty-nine DEPs (149 upregulated and 280 downregulated proteins) were identified in the MOG group compared to the HC group according to the P value and fold change (FC). Using the O-PLS-DA model, 872 differentially abundant proteins were identified with variable importance projection (VIP) scores > 1. Five proteins (gamma-glutamyl hydrolase, cathepsin F, interalpha-trypsin inhibitor heavy chain 5, latent transforming growth factor beta-binding protein 4 and leukocyte-associated immunoglobulin-like receptor 1) overlapping between the top 30 DEPs with top-ranked P value and FC and top 30 proteins in PLS-DA VIP lists were acquired. Functional analysis revealed that the dysregulated proteins in the MOG group were primarily involved in complement and coagulation cascades, cell adhesion, axon guidance, and glycosphingolipid biosynthesis compared to the HC group. CONCLUSION: The proteomic alterations in CSF samples from children with MOGAD identified in the current study might provide opportunities for developing novel biomarker candidates.

Repeated Sevoflurane Exposure in Neonatal Rats Enhances the Sensitivity to Pain and Traumatic Stress Later in Juvenile Life.

Purposeː: Sevoflurane exposure in the neonatal period of rodent animals was reported to be associated with neuroendocrine dysregulations later in life. We tested the hypothesis that repeated sevoflurane exposure in neonatal rats enhances the sensitivity to pain and acute traumatic stress response later in juvenile life and investigated whether the neonatal brain depolarizing γ-aminobutyric acid type A receptor (GABAAR) activity is involved in mediating these abnormalities. Methodsː: The postnatal 6 days (P6) Sprague-Dawley male rat pups pretreated with vehicle or the NKCC1 inhibitor, bumetanide, received sequential exposures to 2.1% sevoflurane exposure for 2 hours daily in 3 consecutive days. Resultsː: The results showed that repeated exposures to sevoflurane in neonatal rats significantly reduced the paw withdrawal thermal latency (PWTL) at P9, P45. Repeated exposures to sevoflurane in neonatal rats did not significantly affect the basal secretion of serum corticosterone at juvenile period P45, whereas the level of corticosterone for neonatal sevoflurane-exposed rats at P45 was significantly higher than the CON group after subject to conditioned fear traumatic stress (CFTS). The resulting NKCC1/KCC2 mRNA ratio was significantly increased immediately after the neonatal rats received the last sevoflurane exposure, which was alleviated by pretreated with the NKCC1 inhibitor bumetanide. Conclusionː: Repeated exposures to sevoflurane in neonatal rats enhanced the sensitivity to pain and acute traumatic stress response in juvenile life. The neonatal brain depolarizing GABAAR activity is involved in mediating these abnormalities.

Repeated Sevoflurane Exposures in Neonatal Rats Increased the Brain Vulnerability to Future Stress Exposure and Resulted in Fear Extinction Deficit.

Sevoflurane anesthesia during neonatal period was reported to sensitize the rodent animals to stress later in life. The authors tested the hypothesis that repeated sevoflurane exposures in neonatal rats increased the brain vulnerability to future stress exposure and resulted in fear extinction deficit and investigated whether the neonatal brain depolarizing γ-aminobutyric acid type A receptor (GABAAR) is involved in mediating these abnormalities. Neonatal Sprague-Dawley male rats, pretreated with vehicle or the NKCC1 inhibitor, bumetanide, received sequential exposures to 3% sevoflurane for 2 h on postnatal days (P) 5, P6, and P7 and then were exposed to electric foot shock stress in fear conditioning training at P14. Juvenile rats at different developmental brain stage receiving identical sevoflurane exposures on P25, P26, and P27 were also studied. The results showed repeated sevoflurane exposures in neonatal rats and increased the cation-chloride cotransporters NKCC1/KCC2 ratio in the PFC at P14. Repeated exposures to sevoflurane in neonatal rather than juvenile rats enhanced the stress response and exacerbated neuroapoptosis in the PFC after exposed to electric foot shock in fear conditioning training. Neonatal rather than juvenile sevoflurane-exposed rats exhibited deficits in fear extinction training and recall. Pretreatment of neonatal rats prior to sevoflurane exposures with bumetanide reduced the NKCC1/KCC2 ratio at P14 and ameliorated most of the subsequent adverse effects. Our study indicates that repeated sevoflurane exposures in neonatal rats might increase the brain vulnerability to future stress exposure and resulted in fear extinction deficit, which might be associated with the neonatal enhanced brain depolarizing GABAAR activity.

The efficacy and safety of ciprofol use for the induction of general anesthesia in patients undergoing gynecological surgery: a prospective randomized controlled study.

BACKGROUND: Ciprofol is a recently developed, short-acting γ-aminobutyric acid receptor agonist sedative that is more potent than propofol, but there have been few clinical studies of this agent to date. Here, we sought to examine the safety and efficacy of ciprofol use for the induction of general anesthesia in individuals undergoing gynecological surgery. METHODS: Women between the ages of 18 and 60 years (ASA physical status 1 or 2) who were scheduled to undergo elective gynecological surgery under general anesthesia were randomly assigned to two equally sized groups in which anesthesia induction was performed using either ciprofol or propofol. General anesthesia induction success rates were the primary outcome for this study, while secondary outcomes included changes in BIS during the 10 min following the first administration of the study drug, the duration of successful induction, and adverse event incidence. RESULTS: A total of 120 women were included in the study. A 100% rate of successful induction was achieved in both the ciprofol and propofol groups, with no significant differences between these groups with respect to the duration of successful induction (34.8 ± 15.5 s vs 35.4 ± 9.5 s, P = 0.832), the time to the disappearance of the eyelash reflex (33.7 ± 10.6 s vs 34.0 ± 6.5 s, P = 0.860), or tracheal intubation (58.2 ± 31.1 s vs 53.9 ± 25.4 s, P = 0.448). Adverse event rates, including intubation responses, were significantly lower in the ciprofol group as compared to the propofol group(20% vs 48.33%, P = 0.0019). Ciprofol was associated with reduced injection pain relative to propofol (16.7% vs 58.3%, P < 0.001). CONCLUSIONS: Ciprofol exhibits comparable efficacy to that of propofol when used for the induction of general anesthesia in individuals undergoing gynecological surgery and is associated with fewer adverse events.

SAF-248, a novel PI3Kδ-selective inhibitor, potently suppresses the growth of diffuse large B-cell lymphoma.

PI3Kδ is expressed predominately in leukocytes and overexpressed in B-cell-related malignances. PI3Kδ has been validated as a promising target for cancer therapy, and specific PI3Kδ inhibitors were approved for clinical practice. However, the substantial toxicity and relatively low efficacy as a monotherapy in diffuse large B-cell lymphoma (DLBCL) limit their clinical use. In this study, we described a novel PI3Kδ inhibitor SAF-248, which exhibited high selectivity for PI3Kδ (IC50 = 30.6 nM) over other PI3K isoforms at both molecular and cellular levels, while sparing most of the other human protein kinases in the kinome profiling. SAF-248 exhibited superior antiproliferative activity against 27 human lymphoma and leukemia cell lines compared with the approved PI3Kδ inhibitor idelalisib. In particular, SAF-248 potently inhibited the proliferation of a panel of seven DLBCL cell lines (with GI50 values < 1 µM in 5 DLBCL cell lines). We demonstrated that SAF-248 concentration-dependently blocked PI3K signaling followed by inducing G1 phase arrest and apoptosis in DLBCL KARPAS-422, Pfeiffer and TMD8 cells. Its activity against the DLBCL cells was negatively correlated to the protein level of PI3Kα. Oral administration of SAF-248 dose-dependently inhibited the growth of xenografts derived from Pfeiffer and TMD8 cells. Activation of mTORC1, MYC and JAK/STAT signaling was observed upon prolonged treatment and co-targeting these pathways would potentiate the activity of SAF-248. Taken together, SAF-248 is a promising selective PI3Kδ inhibitor for the treatment of DLBCL and rational drug combination would further improve its efficacy.

The ß-1,3-glucan synthase gene GFGLS2 plays major roles in mycelial growth and polysaccharide synthesis in Grifola frondosa.

ß-1,3-Glucans are well-known biological and health-promoting compounds in edible fungi. Our previous results characterized a glucan synthase gene (GFGLS) of Grifola frondosa for the first time to understand its role in mycelial growth and glucan biosynthesis. In the present study, we identified and functionally reannotated another glucan synthase gene, GFGLS2, based on our previous results. GFGLS2 had a full sequence of 5944 bp including 11 introns and 12 exons and a coding information for 1713 amino acids of a lower molecular weight (195.2 kDa) protein with different conserved domain sites than GFGLS (5927 bp with also 11 introns and a coding information for 1781 aa). Three dual-promoter RNA-silencing vectors, pAN7-iGFGLS-dual, pAN7-iGFGLS2-dual, and pAN7-CiGFGLS-dual, were constructed to downregulate GFGLS, GFGLS2, and GFGLS/GFGLS2 expression by targeting their unique exon sequence or conserved functional sequences. Silencing GFGLS2 resulted in higher downregulation efficiency than silencing GFGLS. Cosilencing GFGLS and GFGLS2 had a synergistic downregulation effect, with slower mycelial growth and glucan production by G. frondosa. These findings indicated that GFGLS2 plays major roles in mycelial growth and polysaccharide synthesis and provides a reference to understand the biosynthesis pathway of mushroom polysaccharides. KEY POINTS: • The 5944-bp glucan synthase gene GFGLS2 of G. frondosa was cloned and reannotated • GFGLS2 showed identity and significant differences with the previously identified GFGLS • GFGLS2 played a major role in fermentation and glucan biosynthesis.

The first mitochondrial genome of the genus Exhippolysmata (Decapoda: Caridea: Lysmatidae), with gene rearrangements and phylogenetic associations in Caridea.

The complete mitochondrial genome (mitogenome) of animals can provide useful information for evolutionary and phylogenetic analyses. The mitogenome of the genus Exhippolysmata (i.e., Exhippolysmata ensirostris) was sequenced and annotated for the first time, its phylogenetic relationship with selected members from the infraorder Caridea was investigated. The 16,350 bp mitogenome contains the entire set of 37 common genes. The mitogenome composition was highly A + T biased at 64.43% with positive AT skew (0.009) and negative GC skew (- 0.199). All tRNA genes in the E. ensirostris mitogenome had a typical cloverleaf secondary structure, except for trnS1 (AGN), which appeared to lack the dihydrouridine arm. The gene order in the E. ensirostris mitogenome was rearranged compared with those of ancestral decapod taxa, the gene order of trnL2-cox2 changed to cox2-trnL2. The tandem duplication-random loss model is the most likely mechanism for the observed gene rearrangement of E. ensirostris. The ML and BI phylogenetic analyses place all Caridea species into one group with strong bootstrap support. The family Lysmatidae is most closely related to Alpheidae and Palaemonidae. These results will help to better understand the gene rearrangements and evolutionary position of E. ensirostris and lay a foundation for further phylogenetic studies of Caridea.

The role of Rho1 gene in the cell wall integrity and polysaccharides biosynthesis of the edible mushroom Grifola frondosa.

Grifola frondosa polysaccharides, especially ß-glucans, showed the significant antitumor, hypoglycemic, and immune-stimulating activities. In the present study, a predominant regulatory subunit gfRho1p of ß-1,3-glucan synthase in G. frondosa was identified with a molecular weight of 20.79 kDa and coded by a putative 648-bp small GTPase gene gfRho1. By constructing mutants of RNA interference and over-expression gfRho1, the roles of gfRho1 in the growth, cell wall integrity and polysaccharide biosynthesis were well investigated. The results revealed that defects of gfRho1 slowed mycelial growth rate by 22% to 33%, reduced mycelial polysaccharide and exo-polysaccharide yields by 4% to 7%, increased sensitivity to cell wall stress, and down-regulated gene transcriptions related to PKC-MAPK signaling pathway in cell wall integrity. Over-expression of gfRho1 improved mycelial growth rate and polysaccharide production of G. frondosa. Our study supports that gfRho1 is an essential regulator for polysaccharide biosynthesis, cell growth, cell wall integrity and stress response in G. frondosa.

UDP-glucose pyrophosphorylase gene affects mycelia growth and polysaccharide synthesis of Grifola frondosa.

To elucidate potential roles of UDP-glucose pyrophosphorylase (UGP) in mycelial growth and polysaccharide synthesis of Grifola frondosa, a putative 2036-bp UDP-glucose pyrophosphorylase gene gfugp encoding a 53.17-kDa protein was cloned and re-annotated. Two dual promoter RNA silencing vectors of pAN7-iUGP-P-dual and pAN7-iUGP-C-dual were constructed to down-regulate gfugp expression by targeting its promoter or conserved functional sequences, respectively. Results showed that silence of gfugp promoter sequence had a higher down-regulating efficiency with slower mycelial growth and polysaccharide production than those of conserved sequence. The monosaccharide compositions/percentages of mycelial and exo-polysaccharides significantly changed with the increase of galactose and arabinose contents possibly due to block of UDP-glucose supply by gfugp silence and alteration of sugar metabolism via up-regulation of UDP-glucose-4-epimerase (gfuge) and UDP-xylose-4-epimerase (gfuxe) transcription. Our findings would provide a reference to know the biosynthesis pathway of mushroom polysaccharides and improve their production by metabolic regulation.

Insulin-Like Growth Factor-1 Down-Regulates the Phosphorylation of FXYD1 and Rescues Behavioral Deficits in a Mouse Model of Rett Syndrome.

Rett syndrome (RTT) is a neurodevelopmental disease in children that is mainly caused by mutations in the MeCP2 gene, which codes for a transcriptional regulator. The expression of insulin-like growth factor-1 (IGF-1) is reduced in RTT patients and animal models, and IGF-1 treatment is a promising therapeutic strategy for RTT. However, the mechanism underlying the effects of IGF-1 remains to be further explored. FXYD1 is an auxiliary subunit of Na, K-ATPase. Overexpression of FXYD1 is involved in the pathogenesis of RTT. However, whether IGF-1 exerts its effect through normalizing FXYD1 is completely unknown. To this end, we evaluated the effect of IGF-1 on FXYD1 expression and posttranslational modification in a mouse model of RTT (MeCP2308) using both in vitro and in vivo experiments. The results show that FXYD1 mRNA and phosphorylated protein (p-FXYD1) were significantly elevated in the frontal cortex in RTT mice, compared to wild type. In RTT mice, IGF-1 treatment significantly reduced levels of FXYD1 mRNA and p-FXYD1, in parallel with improvements in behavior, motor coordination, and cognitive function. For mechanistic insight into the effect of IGF-1 on p-FXYD1, we found the decreased phosphorylated forms of PI3K-AKT-mTOR signaling pathway components in the frontal cortex of RTT mice and the normalizing effect of IGF-1 on the phosphorylated forms of these components. Interestingly, blocking the PI3K/AKT pathway by PI3K inhibitor could abolish the effect of IGF-1 on p-FXYD1 level, in addition to the effect of IGF-1 on the phosphorylation of other components in the PI3K/AKT pathway. Thus, our study has provided new insights into the mechanism of IGF-1 treatment for RTT, which appears to involve FXYD1.

Multiple paternity assessed in the cuttlefish Sepiella japonica (Mollusca, Cephalopoda) using microsatellite markers.

Multiple paternity was demonstrated for seven clutches of eggs and 40 offspring sampled from these clutches in the cuttlefish Sepiella japonica from Fujian Shacheng Harbor Cultivation Base (Fujian Province, China), using four microsatellite DNA markers. It was observed that female cuttlefish copulated with different males. In this study, genotyping data suggest that at least three paternal allele genotypes were present in all seven clutches indicating that at least two males were responsible for each brood. Combined with behavioral observations, this study provides evidence for sperm competition and multiple paternity in S. japonica.

[Potential habitat and priority protection area of cranes with climate change in the Great Xing'an Mountains, China]. / æ°”å€™å˜åŒ–ä¸‹å¤§å ´å®‰å²­åœ°åŒºé¹¤ç±»æ½œåœ¨åˆ†å¸ƒåŠä¼˜å ˆä¿æŠ¤åŒº.

To clarify the impacts of climate change on the potential distribution of six crane species in the Great Xing'an Mountains region, and promote the effective protection of these species, we selected key environmental variables such as climate, topography, and vegetation type based on Pearson correlation and Jackknife analysis, and modeled the potential distribution of six crane species in the Great Xing'an Mountains using MaxEnt with the current and the future climate change scenarios (RCP4.5 and RCP8.5). We identified the priority protection areas (PPAs) and the target PPAs by zonation and ArcGIS. The results showed that with the current climate condition, the sui-table habitats of these species were mainly distributed in the central and the northwest part of the Great Xing'an Mountains. With RCP4.5 and RCP8.5 scenarios, the suitable habitats of Grus monacha, Grus japonensis, Grus vipio, Grus grus and Anthropoides virgo would decrease, while that of Grus leucogeranus would expand by 5.4%-6.3%. With current and the future climate change scenarios, the PPAs of these species were mainly distributed in the northwest, southeast and west-central parts of the Great Xing'an Mountains. The protect rate could reach about 20.1%-23.8% of the target PPAs conserved by protected areas (PAs). The protection gaps were mainly distributed in the west of Mohe County, the north-central of Ergun, the central and east of Genhe, the northeast of Yakeshi, and the south of Oroqen Autonomous Banner. We proposed to expand PAs to provide a strong guarantee for the effective protection of cranes species.

Expression and prognostic value of HER-2/neu, STAT3 and SOCS3 in hepatocellular carcinoma.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with several genomic alterations, while the viral-chemical etiology along with molecular mechanisms of HCC pathogenesis remains largely unknown. This study aimed to determine expression profile and prognostic value of HER-2/neu, STAT3 and SOCS3 in HCC. METHODS: Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to evaluate the expression of HER-2/neu, STAT3 and SOCS3 in HCC tissues and adjacent normal tissues collected from 176 HCC patients. RESULTS: HER-2/neu and STAT3 levels were higher and SOCS3 expression was lower in HCC tissues than in adjacent normal tissues. HER-2/neu, STAT3 and SOCS3 levels were associated with histological grade, tumor diameter, TNM stage, vascular invasion, lymph node metastasis and distant metastasis in HCC. SOCS3 expression was negatively associated with HER-2/neu and STAT3 expression. HCC patients with higher HER-2/neu and STAT3 levels had shorter overall, disease-free and disease-specific survival, whereas the opposite was found in patients with higher SOCS3 expression. In Cox regression analysis, tumor size, TNM stage, and STAT3 expression were identified as independent prognostic factors of HCC. CONCLUSION: Taken together, these observations suggest that HER-2/neu, STAT3 and, SOCS3 are related to the aggressive tumor behavior and STAT3 has potential value as a prognostic factor for HCC.

Nonspecific benign pathological results on computed tomography-guided lung biopsy: A predictive model of true negatives.

OBJECTIVE: The aim of this study is to develop a predictive model for identifying true negatives among nonspecific benign results on computed tomography-guided lung biopsy. MATERIALS AND METHODS: This was a single-center retrospective study. Between December 2013 and May 2016, a total of 126 patients with nonspecific benign biopsy results were used as the training group to create a predictive model of true-negative findings. Between June 2016 and June 2017, additional 56 patients were used as the validation group to test the constructed model. RESULTS: In the training group, a total of 126 lesions from 126 patients were biopsied. Biopsies from 106 patients were true negatives and 20 were false-negatives. Univariate and multivariate logistic regression analyses were identified a biopsy result of "chronic inflammation with fibroplasia" as a predictor of true-negative results (P = 0.013). Abnormal neuron-specific enolase (NSE) level (P = 0.012) and pneumothorax during the lung biopsy (P = 0.021) were identified as predictors of false-negative results. A predictive model was developed as follows: Risk score = -0.437 + 2.637 × NSE level + 1.687 × pneumothorax - 1.82 × biopsy result of "chronic inflammation with fibroplasia." The area under the receiver operator characteristic (ROC) curve was 0.78 (P < 0.001). To maximize sensitivity and specificity, we selected a cutoff risk score of -0.029. When the model was used on the validation group, the area under the ROC curve was 0.766 (P = 0.005). CONCLUSIONS: Our predictive model showed good predictive ability for identifying true negatives among nonspecific benign lung biopsy results.