Functional genetic variants of the disulfidptosis-related INF2 gene predict survival of hepatitis B virus-related hepatocellular carcinoma.

Disulfidptosis is a novel form of programmed cell death involved in migration and invasion of cancer cells, but few studies investigated the roles of genetic variants in disulfidptosis-related genes in survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We used Cox proportional hazards regression analyses, Kaplan-Meier curves and receiver operating characteristic curves to assess effects of genetic variants in 14 disulfidptosis-related genes on overall survival of 866 HBV-HCC patients. The Bayesian false discovery probability was used for multiple testing corrections. We also investigated biological mechanisms of the significant variants through expression quantitative trait loci analyses using the data from publicly available databases, luciferase reporter assays and differential expression analyses. As a result, we identified two independently functional single nucleotide polymorphisms (SNPs) (INF2 rs4072285 G > A and INF2 rs4444271 A > T) that predicted overall survival of HBV-HCC patients, with adjusted hazard ratios of 1.60 (95% CI = 1.22-2.11, P = 0.001) and 1.50 (95% CI = 1.80-1.90, P < 0.001), respectively, after multiple testing correction. Luciferase reporter assays indicated that both INF2 rs4072285 A and INF2 rs4444271 T alleles increased INF2 mRNA expression levels (P < 0.001) that were also higher in HCC tumor tissues than in adjacent normal tissues (P < 0.001); such elevated INF2 expression levels were associated with a poorer survival of HBV-HCC patients (P < 0.001) in the TCGA database. In summary, this study supported that INF2 rs4072285 and INF2 rs4444271 may be novel biomarkers for survival of HBV-HCC patients.

Adult type I Gaucher disease with splenectomy caused by a compound heterozygous GBA1 mutation in a Chinese patient: a case report.

Gaucher disease (GD) is an autosomal recessive ailment resulting from glucocerebrosidase deficiency caused by a mutation in the GBA1 gene, leading to multi-organ problems in the liver, spleen, and bone marrow. In China, GD is extremely uncommon and has a lower incidence rate than worldwide. In this study, we report the case of an adult male with an enlarged spleen for 13 years who presented with abdominal distension, severe loss of appetite and weight, reduction of the three-line due to hypersplenism, frequent nosebleeds, and bloody stools. Regrettably, the unexpected discovery of splenic pathology suggestive of splenic Gaucher disease was only made after a splenectomy due to a lack of knowledge about rare disorders. Our patient's delayed diagnosis may have been due to the department where he was originally treated, but it highlights the need for multidisciplinary consultation in splenomegaly of unknown etiology. We then investigated the patient's clinical phenotypes and gene mutation features using genetically phenotypical analysis. The analysis of the GBA1 gene sequence indicated that the patient carried a compound heterozygous mutation consisting of two potentially disease-causing mutations: c.907C > A (p. Leu303Ile) and c.1448 T > C (p. Leu483Pro). While previous research has linked the p. Leu483Pro mutation site to neurologic GD phenotypes (GD2 and GD3), the patients in this investigation were identified as having non-neuronopathic GD1. The other mutation, p. Leu303Ile, is a new GD-related mutation not indexed in PubMed that enriches the GBA1 gene mutation spectrum. Biosignature analysis has shown that both mutations alter the protein's three-dimensional structure, which may be a pathogenic mechanism for GD1 in this patient.

Pedigree Analysis of Nonclassical Cholesteryl Ester Storage Disease with Dominant Inheritance in a LIPA I378T Heterozygous Carrier.

BACKGROUND: Cholesterol ester storage disorder (CESD; OMIM: 278,000) was formerly assumed to be an autosomal recessive allelic genetic condition connected to diminished lysosomal acid lipase (LAL) activity due to LIPA gene abnormalities. CESD is characterized by abnormal liver function and lipid metabolism, and in severe cases, liver failure can occur leading to death. In this study, one Chinese nonclassical CESD pedigree with dominant inheritance was phenotyped and analyzed for the corresponding gene alterations. METHODS: Seven males and eight females from nonclassical CESD pedigree were recruited. Clinical features and LAL activities were documented. Whole genome Next-generation sequencing (NGS) was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations, and qPCR detected LIPA mRNA expression. RESULTS: Eight individuals of the pedigree were speculatively thought to have CESD. LAL activity was discovered to be lowered in four living members of the pedigree, but undetectable in the other four deceased members who died of probable hepatic failure. Three of the four living relatives had abnormal lipid metabolism and all four had liver dysfunctions. By liver biopsy, the proband exhibited diffuse vesicular fatty changes in noticeably enlarged hepatocytes and Kupffer cell hyperplasia. Surprisingly, only a newly discovered heterozygous mutation, c.1133T>C (p. Ile378Thr) on LIPA, was found by gene sequencing in the proband. All living family members who carried the p.I378T variant displayed reduced LAL activity. CONCLUSIONS: Phenotypic analyses indicate that this may be an autosomal dominant nonclassical CESD pedigree with a LIPA gene mutation.

Genetic variants in m5C modification genes are associated with survival of patients with HBV-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high mortality rate. The 5-methylcytosine (m5C), a type of RNA modification, plays crucial regulatory roles in HCC carcinogenesis, metastasis, and prognosis. However, a few studies have investigated the effect of genetic variants in m5C modification genes on survival of patients with hepatitis B virus (HBV)-related HCC. In the present study, we evaluated associations between 144 SNPs in 15 m5C modification genes and overall survival (OS) in 866 patients with the HBV-related HCC. Expression quantitative trait loci (eQTL) analysis and differential expression analysis were conducted to investigate biological mechanisms. As a result, we identified that two SNPs (NSUN7 rs2437325 A > G and TRDMT1 rs34434809 G > C) were significantly associated with HBV-related HCC OS with adjusted allelic hazards ratios of 1.25 (95% confidence interval = 1.05-1.48 and P = 0.011) and 1.19 (1.02-1.38 and P = 0.027), respectively, with a trend of combined risk genotypes (Ptrend < 0.001). Moreover, the results of eQTL analyses showed that both NSUN7 rs2437325 G and TRDMT1 rs34434809 C alleles were associated with a reduced mRNA expression level in 208 normal liver tissues (P = 0.007 and P < 0.001, respectively). Taken together, genetic variants in the m5C modification genes may be potential prognostic biomarkers of HBV-related HCC after hepatectomy, likely through mediating the mRNA expression of corresponding genes.

Potentially functional genetic variants in RPS6KA4 and MAP2K5 in the MAPK signaling pathway predict HBV-related hepatocellular carcinoma survival.

Hepatocellular carcinoma (HCC) ranks the third leading cause of cancer deaths with a dismal 5-year survival rate. The mitogen-activated protein kinase (MAPK) signaling pathway is abnormally activated in HCC to promote growth and aggressive metastatic potential of cancer cells. Therefore, genetic variants in the MAPK signaling pathway may serve as potential predictors of Hepatitis B virus (HBV)-related HCC survival. In the present study, we performed a two-stage survival analysis to evaluate the associations between 10,912 single nucleotide polymorphisms (SNPs) in 79 MAPK signaling pathway genes and the overall survival (OS) of 866 HBV-related HCC patients, followed by functional annotation. In combined datasets, we identified two novel and potential functional SNPs (RPS6KA4 rs600377 T>G and MAP2K5 rs17300363 A>C) as prognostic factors for HBV-related HCC, with adjusted allelic hazards ratios of 1.24 (95% confidence interval [CI] = 1.05-1.46, p = 0.010) and 1.48 (1.15-1.91, p = 0.001), respectively. Furthermore, their combined risk genotypes also predicted a poor survival in a dose-response manner in the combined data set (Ptrend < 0.001). Additional functional analysis showed that RPS6KA4 rs600377 G and MAP2K5 rs17300363 C alleles were associated with elevated mRNA expression levels of the corresponding genes in normal tissues. These results provide new insights into the role of genetic variants in the MAPK signaling pathway genes in HBV-related HCC survival.

Genetic variants of SOS2, MAP2K1 and RASGRF2 in the RAS pathway genes predict survival of HBV-related hepatocellular carcinoma patients.

The RAS pathway participates in the cascade of proliferation and cell division process, and the activated RAS pathway can lead to tumorigenesis including hepatocellular carcinoma (HCC). However, few studies have explored the effects of genetic variants in the RAS pathway-related genes on the survival of patients with HBV-related HCC. In the present study, we assessed the associations between 11,658 single-nucleotide polymorphisms (SNPs) in 62 RAS pathway genes and the overall survival (OS) of 866 HBV-related HCC individuals, which were randomly split (1:1) into discovery and validation datasets. As a result, three potentially functional SNPs were identified, based on multivariable cox proportional hazards regression analyses, in SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2, rs4632055 A > G), Ras protein-specific guanine nucleotide releasing factor 2 (RASGRF2, rs26418A > G) and mitogen-activated protein kinase 1 (MAP2K1,rs57120695 C > T), which were significantly and independently associated with OS of HBV-related HCC patients [adjusted hazards ratios (HRs) of 1.42, 1.32 and 1.50, respectively; 95% confidence intervals (CI), 1.14 to 1.76, 1.15 to 1.53 and 1.15 to 1.97, respectively; P = 0.001, < 0.001 and 0.003, respectively]. Additionally, the joint effects as the unfavorable genotypes of these three SNPs showed a significant association with the poor survival of HCC (trend test P < 0.001). The expression quantitative trait loci (eQTL) analysis further revealed that the rs4632055 G allele and the rs26418 A allele were associated with lower mRNA expression levels of SOS2 and RASGRF2, respectively. Collectively, these potentially functional SNPs of RASGRF2, SOS2 and M2PAK1 may become potential prognostic biomarkers for HBV-related HCC after hepatectomy.

Liver-specific lncRNA FAM99A may be a tumor suppressor and promising prognostic biomarker in hepatocellular carcinoma.

BACKGROUND: Increasing evidence shows that liver-specific long non-coding RNAs (lncRNAs) play important roles in the development of hepatocellular carcinoma (HCC). We identified a novel liver-specific lncRNA, FAM99A, and examined its clinical significance and biological functions in HCC. METHODS: The expression level and clinical value of FAM99A in HCC were examined using The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases, and were further verified using quantitative real-time polymerase chain reaction (qRT-PCR) in our HCC cohort. Univariate and multivariate Cox proportional hazards regression models were also applied to identify independent prognostic indicators for HCC patients. Cell counting kit-8, colony formation, and Transwell assays were performed to evaluate the effects of FAM99A on the proliferation, migration, and invasion abilities of HCC cells in vitro. A subcutaneous xenograft tumor model was implemented to determine the effect of FAM99A on the tumor growth of HCC cells in vivo. RNA pull-down and mass spectrometry assays were performed to reveal the potential molecular mechanisms of FAM99A in HCC. RESULTS: The three public online databases and qRT-PCR data showed that FAM99A was frequently downregulated in HCC tissues and inversely correlated with microvascular invasion and advanced histological grade of HCC patients. Kaplan-Meier survival analysis indicated that decreased FAM99A was significantly associated with poor overall survival of HCC patients based on TCGA database (P = 0.040), ICGC data portal (P < 0.001), and our HCC cohort (P = 0.010). A multivariate Cox proportional hazards regression model based on our HCC cohort suggested that FAM99A was an independent prognostic factor of overall survival for HCC patients (hazard ratio: 0.425, P = 0.039). Upregulation of FAM99A suppressed the proliferation, colony formation, migration, and invasion capacities of HCC cells in vitro, and knockdown of FAM99A had the opposite effects. A subcutaneous xenograft tumor model demonstrated that overexpression of FAM99A significantly inhibited the tumor growth of HCC cells in vivo. Seven tumor-related proteins (PCBP1, SRSF5, SRSF6, YBX1, IGF2BP2, HNRNPK, and HNRNPL) were recognized as possible FAM99A-binding proteins by the RNA pull-down and mass spectrometry assays. CONCLUSION: Our results suggest that FAM99A exerts cancer-inhibiting effects on HCC progression, and it may be a promising prognostic indicator for HCC patients.

Clinical implications and biological features of a novel postoperative recurrent HCC classification: A multi-centre study.

BACKGROUND & AIMS: The multiplicity of hepatocellular carcinoma (HCC) recurrence patterns is the most important determinant of patients' postsurgical survival. A systematic HCC recurrence classification is needed to help prevent and treat postoperative HCC recurrence in the era of precision medicine. METHODS: A total of 1319 patients with recurrent HCC from four hospitals were enrolled and divided into a development cohort (n = 916), internal validation cohort (n = 225) and external validation cohort (n = 178). A comprehensive study of patients' clinicopathological factors and biological features was conducted. RESULTS: Four subtypes of recurrence were identified, which integrated recurrence features, survival, effects on systemic and liver function and potential therapeutics after recurrence: type I (solitary-intrahepatic oligorecurrence); type II (multi-intrahepatic oligorecurrence); type III (progression recurrence) and type IV (hyper-progression recurrence). Type III~IV recurrence indicated exceptionally poor prognosis. Subsequently, two nomogram models were established for type III~IV recurrence prediction, and both demonstrated excellent predictive performance and applicability of pre and postoperative strategy formulation. Multiple biological analyses revealed that HCC cases with type III~IV recurrence were characterized by enrichment in p53 mutations, CCND1 amplification, high proliferation/metastasis potential, inactive metabolism and immune exhaustion features. Over-expression of high mobility group protein 2 (HMGA2) enhanced the highly malignant behaviour of HCC through multiple molecular pathways, making it a potential prognostic predictor and therapeutic target. CONCLUSIONS: This 'recurrent HCC classification' has important potential value in identifying patients with surgical benefit, predicting postsurgical survival and guiding treatment strategies. Multidimensional biological insights also increased knowledge of factors associated with HCC recurrence.

Nodal downstaging to ypN0 after neoadjuvant chemotherapy positively impacts on survival of cT4N+ GC/GEJ patients.

BACKGROUND: The prognostic value of histomorphologic regression in primary gastric and gastroesophageal cancers (GC/GEJ) has been previously established, however, the impact of lymph node (LN) regression on survival still remains unclear. METHODS: A prospectively maintained database was reviewed to identify cT4N+ gastric and gastroesophageal cancers (GC/GEJ) after NAC (neoadjuvant chemotherapy). Patients were categorized into two groups based on LN status: cN+/ypN0 (downstaged N0) and cN+/ypN+ (persistent N+), long-term survival were analyzed using Kaplan-Meier survival estimates. RESULTS: In total, 125 patients with cT4N+ GC/GEJ underwent NAC followed by surgery were enrolled. A total of 39 patients (31.2%) had cN+/ypN0 (ypN0) disease, 86 patients (68.8%) had cN+/ypN+ (ypN+) disease. Prognosis in ypN+ patients was significantly worse than those in ypN0 group for 3- and 5-year overall survival (OS) (p < 0.05). The 3-year OS was 83%, 44% in ypN0 and ypN+ group, respectively. The 5-year OS was 75%, 35% in ypN0 and ypN+ group, respectively. Multivariable analysis suggested that multivisceral resection (hazard ratio [HR] = 0.33, 95% confidence interval [CI]: 0.14-0.76, p = 0.009), and ypN+ (HR = 3.42, 95% CI: 1.15-10.13, p =0.027) were independent prognostic factors for OS. CONCLUSION: Nodal downstaging is an important hallmark representing the effectiveness of NAC for GC/GEJ, and it positively impacts on survival of these patients.

Determination of the median effective dose of sufentanil for inhibiting the laryngeal mask insertion response in geriatric patients: a prospective, double-blinded, dose-response trial.

BACKGROUND: Laryngeal mask airway(LMA) have been widely used in clinical practice. Irritation to the patient during the insertion of a laryngeal mask can cause hemodynamic fluctuations, which is particularly unsafe for geriatric patients. We used probit regression analysis to determine the median effective dose of sufentanil to inhibit the response to LMA insertion in geriatric patients. METHODS: A total of 90 patients were selected for the study using the following inclusion criteria: age ≥ 65 years old, ASA grade I-III, and scheduled to undergo intravenous general anesthesia with LMA insertion. Each patient received a dose of sufentanil for anesthesia induction in one of six levels: 0.05, 0.1, 0.15, 0.2, 0.25, or 0.3 µg kg-1. LMA insertion was scored with a 3-point, 6-category scale, with scores ≥ 16 indicating effective LMA insertion, and < 16 indicating ineffective LMA insertion. Mean arterial blood pressure (MAP), heart rate (HR), and bispectral index (BIS) were recorded 1 min before induction (T1), 1 min after induction (T2), 1 min after LMA insertion (T3), and 5 min after LMA insertion (T4) in each group. In addition, the plasma norepinephrine (NE) levels and adverse reactions were measured at T2 and T3 in each dosage group. RESULTS: Probit regression analysis showed that the ED50 of sufentanil inhibiting the response to LMA insertion in geriatric patients was 0.18 µg kg-1 (95% CI: 0.16-0.21 µg kg-1), and the ED95 was 0.31 µg kg-1 (95% CI: 0.27-0.38 µg kg-1), and the probit(p) = -2.34 + 12.90 × ln(Dose)([Formula: see text] = 0.725, p = 0.948). Among all the patients, the number of effective LMA insertions was 57 (group A), and the number of ineffective LMA insertions was 33 (group B). The MAP, HR, and NE in group B were significantly higher than in group A at T3. CONCLUSIONS: Sufentanil can effectively inhibit the patient's response to LMA insertion, with stable hemodynamics and small stress response. The ED50 and ED95 were 0.18 µg kg-1 (95% CI: 0.16-0.21 µg kg-1) and 0.31 µg kg-1(95% CI: 0.27-0.38 µg kg-1), respectively. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2100051827 ) on October 6, 2021.

A miR-182 variant and risk of hepatocellular carcinoma in a southern Chinese population.

MicroRNAs (miRNAs) play important roles in the regulation of gene expression at the posttranscriptional level and are involved in human carcinogenesis. The aim of the current study was to investigate the associations between miR-182 single nucleotide polymorphisms and HCC risk in a southern Chinese population. In this case-control study of 863 HCC patients and 908 cancer-free controls, we performed genotyping of miR-182 rs4541843 and assessed its association with HCC risk. We found that individuals carrying the AG/AA genotypes of miR-182 rs4541843 were significantly associated with an increased risk of HCC compared with those carrying the GG genotype (adjusted odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.07-2.76, P = 0.026). In the stratified analysis, this increased risk was more pronounced in the subgroups of older individuals (adjusted OR = 1.98, 95% CI = 1.04-3.76, P = 0.037), males (adjusted OR = 1.81, 95% CI = 1.09-2.99, P = 0.021), and never drinkers (adjusted OR = 1.84, 95% CI = 1.03-3.30, P = 0.041). Our results suggested that miR-182 polymorphism rs4541843 may contribute to the susceptibility to HCC. Our findings require validation in further studies with larger sample sizes.

miR-136-3p targets PTEN to regulate vascularization and bone formation and ameliorates alcohol-induced osteopenia.

Alcohol consumption is regarded as one of the leading risk factors for secondary osteopenia. Coupled angiogenesis and osteogenesis via distinct type-H vessels orchestrates subtle biological processes of bone homeostasis. The dysfunction of angiogenesis and osteogenesis contributes to decreased bone mass during the development of osteopenia. Herein, we identified microRNA-136-3p was remarkedly downregulated in the mouse model of alcohol-induced osteopenia. Following the alcohol administration, downregulated microRNA-136-3p significantly suppressed vascularization and osteogenic differentiation in human umbilical vein endothelial cells (HUVECs) and bone mesenchymal stem cells (BMSCs), respectively. Furthermore, microRNA-136-3p could target phosphatase and tensin homolog deleted on chromosome ten (PTEN) in both HUVECs and BMSCs, thus substantially modulating the capacity of vessel formation and osteogenic differentiation. In the mouse model, microRNA-136-3p Agomir ameliorated alcohol-induced osteopenia, with the concomitant restoration of bone mass and type-H vessel formation. For the first time, this study demonstrated the pivotal role of microRNA-136-3p/PTEN axis in regulations of vascularization and bone formation, which might become the potential therapeutic target of alcohol-induced bone loss.

Calycosin modulates inflammation via suppressing TLR4/NF-κB pathway and promotes bone formation to ameliorate glucocorticoid-induced osteonecrosis of the femoral head in rat.

Glucocorticoid (GC) administration is one of the main causes of osteonecrosis of the femoral head (ONFH). Inflammation, especially the TLR4/NF-κB pathway, has been demonstrated to play a pivotal role in the pathogenesis of GC-induced ONFH. Calycosin, the main bioactive extract of Astragali Radix, could substantially regulate the TLR4/NF-κB pathway. Therefore, in this study, we hypothesized that calycosin could exert beneficial effects in GC-induced ONFH. In vitro, effects of calycosin on the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) were determined using Alizarin red staining, alkaline phosphatase activity examination, and osteogenic-related gene assay. Meanwhile, inflammatory cytokines were detected by enzyme-linked immunosorbent assay. In vivo, 60 male Sprague-Dawley rats were randomly separated into three groups: the control group, the methylprednisolone (MPS) group, and the MPS + calycosin group. The results showed that calycosin could significantly promote dynamic bone formation and retard TLR4/NF-κB pathway. in vivo investigations indicated that calycosin could decrease the morbidity of ONFH and alleviate pathological manifestations within the femoral head. Meanwhile, calycosin could protect osseous blood supply and facilitate dynamic bone formation. The findings collectively demonstrated that calycosin could ameliorate GC-induced ONFH in rat and might become a potential candidate for pharmaceutical prevention of this intractable disease.

Osthole stimulates bone formation, drives vascularization and retards adipogenesis to alleviate alcohol-induced osteonecrosis of the femoral head.

Characteristic pathological changes in osteonecrosis of the femoral head (ONFH) include reduced osteogenic differentiation of bone mesenchymal stem cells (BMSCs), impaired osseous circulation and increased intramedullary adipocytes deposition. Osthole is a bioactive derivative from coumarin with a wide range of pharmacotherapeutic effects. The aim of this study was to unveil the potential protective role of osthole in alcohol-induced ONFH. In vitro, ethanol (50 mmol/L) remarkably decreased the proliferation and osteogenic differentiation of BMSCs and impaired the proliferation and tube formation capacity of human umbilical vein endothelial cell (HUVECs), whereas it substantially promoted the adipogenic differentiation of BMSCs. However, osthole could reverse the effects of ethanol on osteogenesis via modulating Wnt/ß-catenin pathway, stimulate vasculogenesis and counteract adipogenesis. In vivo, the protective role of osthole was confirmed in the well-constructed rat model of ethanol-induced ONFH, demonstrated by a cascade of radiographical and pathological investigations including micro-CT scanning, haematoxylin-eosin staining, TdT-mediated dUTP nick end labelling, immunohistochemical staining and fluorochrome labelling. Taken together, for the first time, osthole was demonstrated to rescue the ethanol-induced ONFH via promoting bone formation, driving vascularization and retarding adipogenesis.

Thermodynamic Barrier for Nanoparticle Penetration into Nanotubes.

It is promising yet challenging to develop efficient methods to separate nanoparticles (NPs) with nanochannel devices. Herein, in order to guide and develop the separation method, the thermodynamic mechanism of NP penetration into solvent-filled nanotubes is investigated by using classical density functional theory. The potential of mean force (PMF) is calculated to evaluate the thermodynamic energy barrier for NP penetration into nanotubes. The accuracy of the theory is validated by comparing it with parallel molecular dynamics simulation. By examining the effects of nanotube size, solvent density, and substrate wettability on the PMF, we find that a large tube, a low bulk solvent density, and a solvophilic substrate can boost the NP penetration into nanotubes. In addition, it is found that an hourglass-shaped entrance can effectively improve the NP penetration efficiency compared with a square-shaped entrance. Furthermore, the minimum separation density of NPs in solution is identified, below which the NP penetration into nanotubes requires an additional driving force. Our findings provide fundamental insights into the thermodynamic barrier for NP penetration into nanotubes, which may provide theoretical guidance for separating two components using microfluidics.

Molecular Dynamics Simulation Insight into Interfacial Stability and Fluidity Properties of Microemulsions.

Although the interfacial properties of microemulsions have been extensively studied in both experimental and simulation research studies, the molecular mechanisms of stability and fluidity about microemulsion are still poorly understood. Herein, we report a molecular dynamics simulation study to elaborate the motion of an emulsion droplet involving dichain surfactant Aerosol OT (AOT) and its dynamics evolution at the oil-water interface. By varying the concentrations of AOT, we show that the interfacial thickness and emulsification rate display a piecewise change as the interfacial coverage increases and the W/O emulsion is more stable than the O/W one while O/W emulsion presents better fluidity. In addition, the dispersed system combined with water/AOT/n-heptane tends to form a W/O microemulsion instead of an O/W microemulsion due to the structural collapse of the latter. This work provides a molecular understanding of microemulsion interfacial stability and fluidity.

Is age and socioeconomic status associated with preference for birth mode in nulliparous women in China?

PURPOSE: To examine the association between sociodemographic factors and preference for birth mode in nulliparous women in China. METHODS: A total of 4606 women before or in early pregnancy were recruited from 2013 to 2016 in the Shanghai Birth Cohort Study. Generalized linear regression was used to examine the association of sociodemographic characteristics with preferred birth mode and actual cesarean section (CS) without clinical indications in 2713 nulliparous women, and the changes from preference of vaginal birth to actual CS without clinical indications in 2369 nulliparous women. RESULTS: After controlling for potential confounders, preference for CS was associated with older maternal age [31-34 years: adjusted risk ratio (ARR) 2.73, 95% confidence interval (CI) 1.56-4.78; ≥ 35 years: 6.27, 3.28-12.01, p for trend < 0.0001] and lower level of education (below junior college vs college or above: 1.51, 1.10-2.09). Older maternal age (≥ 35 years: 3.37, 1.74-6.50), born in city or township (city vs countryside: 3.18, 1.93-5.24; township vs countryside: 1.97, 1.06-3.66), and lower level of education (below junior college vs college or above: 1.38, 1.01-1.88) were significantly associated with a CS without clinical indications. Women who preferred vaginal birth but had an actual CS without clinical indications were more likely to be older (≥ 35 years: 4.30, 1.44-12.83) and born in city (city vs countryside: 2.89, 1.33-6.30). CONCLUSIONS: Older age, lower education level, and being born in city or township were risk factors for CS without clinical indication in China.

Associations between single nucleotide polymorphisms in RYBP and the prognosis of hepatocellular carcinoma in a Chinese population.

Down-regulated RINGl and YYl binding protein (RYBP) is reported to be an independent predictor of a poor prognosis in patients with hepatocellular carcinoma (HCC). However, the genetic association of RYBP polymorphisms with HCC risk and prognosis has not been investigated now. In this study, five RYBP SNPs, rs12956, rs2118593, rs17009699, rs4676875 and rs4532099, were studied from a hospital-based case-control study including 1100 cases (HCC patients) and 1100 controls (non-HCC patients) in Guangxi, China. All these SNPs interacted with environmental risk factors, such as HBV infection, alcohol intake and smoking in the pathogenesis of HCC. Compared to the CC genotype, patients with TT genotype of rs12956 had a decreased risk of HCC (OR = 0.587, 95% CI = 0.403~0.923) and an increased survival time (Co-dominant, HR = 0.745, 95% CI = 0.594~0.934), while those with TT genotype of rs2118593 had an increased risk of HCC (OR = 1.538, 95% CI = 1.093~2.735) and a decreased survival time (Co-dominant, HR = 1.447, 95% CI = 1.174~1.782). No significant difference was found between the other three RYBP polymorphisms with HCC risk and prognosis. Furthermore, we found that tumor number, tumor staging, metastasis and rs2118593 were associated with the overall survival of HCC patients by multivariate COX regression analysis. Our study suggests RYBP SNP, rs2118593 as a new predictor for poor prognosis of HCC patients.

Overexpression of Yes-associated protein and its association with clinicopathological features of hepatocellular carcinoma: A meta-analysis.

BACKGROUND: Yes-associated protein (YAP) overexpression is reported to be associated with risk of hepatocellular carcinoma (HCC) but current studies have not explored the relationship between YAP expression with HCC clinicopathological features. METHODS: To assess these associations, a meta-analysis was performed which included four eligible studies including 391 HCC cases and 334 controls. There were eight eligible studies to investigate the association between YAP expression in HCC and clinicopathological features of liver cancer patients. Literature was obtained from PubMed, Embase, Wangfang and China National Knowledge Infrastructure. RESULTS: Analysis indicated that YAP expression in HCC was greater than in adjacent non-tumour tissue (odds ratio [OR], 15.80, 95% confidence interval [CI], 10.53-23.70, P<.00001; heterogeneity=.30). YAP overexpression in HCC was significantly associated with vascular invasion (OR, 2.21, 95% CI, 11.64-2.97, P<.00001, heterogeneity=.10), less cellular differentiation (OR, 2.38, 95% CI, 1.61-3.51, P<.00001, heterogeneity=.333), tumours larger than 5 cm (OR, 2.52, 95% CI, 1.75-3.62, P<.00001; heterogeneity=.17) and TNM tumour stage I + II (OR, 0.44, 95% CI, 0.28-0.75, P=.00003, heterogeneity=.12). CONCLUSIONS: Overexpression of YAP contributes to HCC formation, and its overexpression is associated with vascular invasion, low cellular differentiation tumours larger than 5 cm and TNM tumour stage III + IV.