A high-dimensional omnibus test for set-based association analysis.

Set-based association analysis is a valuable tool in studying the etiology of complex diseases in genome-wide association studies, as it allows for the joint testing of variants in a region or group. Two common types of single nucleotide polymorphism (SNP)-disease functional models are recognized when evaluating the joint function of a set of SNP: the cumulative weak signal model, in which multiple functional variants with small effects contribute to disease risk, and the dominating strong signal model, in which a few functional variants with large effects contribute to disease risk. However, existing methods have two main limitations that reduce their power. Firstly, they typically only consider one disease-SNP association model, which can result in significant power loss if the model is misspecified. Secondly, they do not account for the high-dimensional nature of SNPs, leading to low power or high false positives. In this study, we propose a solution to these challenges by using a high-dimensional inference procedure that involves simultaneously fitting many SNPs in a regression model. We also propose an omnibus testing procedure that employs a robust and powerful P-value combination method to enhance the power of SNP-set association. Our results from extensive simulation studies and a real data analysis demonstrate that our set-based high-dimensional inference strategy is both flexible and computationally efficient and can substantially improve the power of SNP-set association analysis. Application to a real dataset further demonstrates the utility of the testing strategy.

Biological performance and membrane fouling of a microalgal-bacterial membrane photobioreactor for wastewater treatment without external aeration and carbonation.

Biological nutrient removal processes involving the use of activated sludge (AS) to treat municipal wastewater normally result in high aeration energy consumption and significant greenhouse gas (GHG) emissions. Therefore, developing cost-efficient and environmentally friendly processes for wastewater treatment is vital. In this work, a novel non-aerated microalgal-bacterial membrane photobioreactor (MB-MPBR) was proposed, and its feasibility for organic contaminant and nutrient removals was evaluated, for the first time. The effects of inoculation ratio (microalgae to bacteria (M/B)) on the biological performance and membrane fouling were systematically investigated. The results showed that 95.9% of the chemical oxygen demand (COD), 74.5% of total nitrogen (TN), 98.5% of NH4+-N and 42.0% of total phosphorus (TP) were removed at an inoculation M/B ratio of 3:2 at steady state, representing a significant improvement compared to the M/B inoculation ratio of 1:3. Additionally, the higher inoculation M/B ratio (3:2) significantly promoted the biomass production owing to the favorable mutual exchange of oxygen and carbon dioxide between microalgae and bacteria. Cake layer formation was the primary fouling mechanism owing to the absence of aeration scouring on the membrane surface. The membrane fouling rate was slightly higher at the higher inoculation ratio (M/B = 3:2) owing to the increased biomass and extracellular polymeric substances (EPS) productions, despite the larger particle size. These results demonstrated that the non-aerated MB-MPBR could achieve superior biological performance, of which the inoculation M/B ratio was of critical importance for the initiation and maintenance of microalgal-bacterial symbiotic system, yet possibly caused severer membrane fouling in the absence of external aeration and carbonation. This study provides a new perspective for further optimizing and applying non-aerated MB-MPBR to enhance municipal wastewater treatment.

17ß-Estradiol Mediates Staphylococcus aureus Adhesion in Vaginal Epithelial Cells via Estrogen Receptor α-Associated Signaling Pathway.

Staphylococcus aureus, a major opportunistic pathogen in aerobic vaginitis (AV), can potentially invade the host and occasionally cause infections. Estrogen is associated with an altered immune response of vaginal epithelial cells and prevention of certain vaginal infectious diseases. However, the molecular mechanisms involving estrogen and S. aureus adhesion to vaginal epithelial cells remain unclear. Thus, here, VK2/E6E7 vaginal epithelial cells were infected with S. aureus, and the role of the estrogen receptor α-associated signaling pathway (ERα/FAK/Src/iNOS axis) in S. aureus adhesion was evaluated. The estrogen-associated phosphorylation status of ERα, FAK, and Src and the protein level of iNOS were assessed by western blotting. We used a specific ERα inhibitor to validate the involvement of the ERα-associated signaling pathway. The results showed that with exposure to 1 nM estrogen for 24 h, transient ERα-associated pathway activation was observed, and the protein expression upregulation was accompanied by a dose-dependent increase in 17-ß-estradiol (E2) content and increased S. aureus adherence to vaginal epithelial cells. Estrogen-induced activation of the ERα/FAK/Src/iNOS axis was notably inhibited by the specific ERα inhibitor (ICI 182780). Simultaneously, a significant decrease in the number of adherent S. aureus was observed. However, this inhibitory effect diminished after inhibitor treatment for 24 h. Our findings suggested that the ERα-associated signaling pathway might be involved in S. aureus adherence to vaginal epithelial cells, which appeared to be linked to enhanced cell adhesion leading to AV.

Predictive value of foramen ovale size on pain recurrence after percutaneous balloon compression. / 卵圆孔大小对经皮穿刺球囊压迫术后疼痛复发的预测价值.

OBJECTIVES: Primary trigeminal neuralgia (PTN) is a common cranial nerve disease in neurosurgery, which seriously endangers the physical and mental health of patients. Percutaneous balloon compression (PBC) has become an effective procedure for the treatment of PTN by blocking pain conduction through minimally invasive puncture. However, the recurrence of facial pain after PBC is still a major problem for PTN patients. Intraoperative balloon shape, pressure and compression time can affect the prognosis of patients with PBC after surgery. The foramen ovale size has an effect on the balloon pressure in Meckel's lumen. This study aims to analyse the predictive value of foramen ovale size for postoperative pain recurrence of PBC by exploring the relationship between foramen ovale size and postoperative pain recurrence of PBC. METHODS: A retrospectively analysis was conducted on the clinical data of 60 patients with PTN who were treated with PBC in Department of Neurosurgery, Affiliated Hospital of Chengde Medical College from November 2018 to December 2021. We followed-up and recorded the Barrow Neurological Institute (BNI) pain score at 1, 3, 6 and 12 months after operation. According to the BNI pain score at 12 months after surgery, the patients were divided into a cure group (BNI pain score I to Ⅱ) and a recurrence group (BNI pain score Ⅲ to Ⅴ). The long diameter, transverse diameter and area of foramen ovale on the affected side and the healthy side of the 2 groups were measured. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used for analysis the relationship between the recurrence of pain and the long diameter, transverse diameter, area of foramen ovale on the affected side, and aspect ratio, transverse diameter ratio, area ratio of foramen ovale on the affected side to healthy side in the 2 groups. RESULTS: At the end of 12 months of follow-up, 50 (83.3%) patients had pain relief (the cured group), 10 (16.7%) patients had different degrees of pain recurrence (the recurrence group), and the total effective rate was 83.3%. There were no significant differences in preoperative baseline data between the 2 groups (all P>0.05). The long diameter of foramen ovale on the affected side, the long diameter ratio and area ratio of foramen ovale on the affected/healthy side in the cured group were significantly higher than those in the recurrence group (all P<0.05), and there were no significant differences in the transverse diameter and area of foramen ovale on the affected side and the transverse diameter ratio of foramen ovale on the affected/healthy side between the 2 groups (all P>0.05). The ROC curve analysis showed that the AUC of the long diameter of foramen ovale on the affected side was 0.290 (95% CI 0.131 to 0.449, P=0.073), and the AUC of aspect ratio of foramen ovale on the affected side to healthy side was 0.792 (95% CI 0.628 to 0.956, P=0.004). The AUC of area ratio of foramen ovale on the affected side to healthy side was 0.766 (95% CI 0.591 to 0.941, P=0.008), indicating that aspect ratio and area ratio of foramen ovale on the affected side to healthy side had a good predictive effect on postoperative pain recurrence of PBC. When aspect ratio of foramen ovale on the affected side to healthy side was less than 0.886 3 or area ratio of foramen ovale on the affected side to healthy side was less than 0.869 4, postoperative pain recurrence was common. CONCLUSIONS: Accurate evaluation of the foramen ovale size of skull base before operation is of great significance in predicting pain recurrence after PBC.

Delayed Diagnosis of Acute Q Fever, China.

We report a patient in China with fever of unknown origin who visited 3 hospitals in 3 weeks and was finally given a diagnosis of acute Q fever, determined by metagenomics next-generation sequencing. Our results indicate that physicians are unfamiliar with Q fever and the disease is neglected in China.

A young patient with heart failure was diagnosed with extra-adrenal paraganglioma: a case report.

BACKGROUND: We present a case of pelvic paraganglioma that presented with heart failure as the primary symptom. CASE PRESENTATION: A 35-year-old man was admitted to hospital due to heart failure. Contrast-enhanced pelvic CT showed mass shadows in the posterior wall of the bladder and multiple enlarged lymph nodes in the retroperitoneal area. Ultrasound-guided puncture was performed, and the pathologic diagnosis was extra-adrenal paraganglioma. The patient refused any chemotherapy and died within six months of diagnosis. CONCLUSION: The possibility of neuroendocrine-related tumors, for example paragangliomas, should be considered in young patients with heart failure, especially those with concomitant hypertension and diabetes.

Abnormal fasting blood glucose enhances the risk of long-term exposure to air pollution on dyslipidemia: A cross-sectional study.

Both long-term exposure to air pollution and abnormal fasting blood glucose (FBG) are linked to dyslipidemia prevalence. However, the joint role of air pollution and FBG on dyslipidemia remains unknown clearly. In this study, we aimed to test whether abnormal FBG could enhance the risks of long-term exposure to air pollutants on dyslipidemia in general Chinese adult population. The present study recruited 8917 participants from 4 cities in Hebei province, China. Participants' individual exposure to air pollutants was evaluated by the Empirical Bayesian Kriging statistical model in ArcGIS10.2 geographic information system. Dyslipidemia was defined according to Guidelines for the Prevention and Treatment of Dyslipidemia in Chinese Adults. Subjects were grouped into normal, prediabetes, diabetes according to FBG level. Generalized linear models were applied to analyze the interaction of air pollutants and FBG on dyslipidemia prevalence. The prevalence of dyslipidemia was 43.83% in our investigation. After adjusting all covariates, we found the risk of four air pollutants (PM2.5, PM10, NO2, SO2) on dyslipidemia prevalence was stronger as higher FBG level, and the adjusted odd ratio of interaction (ORinter (95% CI)) between PM2.5, PM10, NO2, SO2 and FBG levels on dyslipidemia was 1.171 (1.162, 1.189), 1.119 (1.111, 1.127), 1.124 (1.115, 1.130), 1.107 (1.098, 1.115), respectively. Stratified analyses indicated the modifying effects of FBG on the association of air pollution with dyslipidemia were stronger among male, less than 65 years old, overweight/obesity (all Pinter<0.1). Our study concluded that high FBG levels strengthened the risk of long-term exposure to air pollution on dyslipidemia, especially more noticeable in male, less than 65 years old, overweight.

The Role of 17ß-Estrogen in Escherichia coli Adhesion on Human Vaginal Epithelial Cells via FAK Phosphorylation.

Estrogen, the predominant sex hormone, has been found to be related to the occurrence of vaginal infectious diseases. However, its role in the occurrence and development of bacterial vaginitis caused by Escherichia coli is still unclear. The objective of this study was to investigate the role of 17ß-estrogen in E. coli adhesion on human vaginal epithelial cells. The vaginal epithelial cell line VK2/E6E7 was used to study the molecular events induced by estrogen between E. coli and cells. An adhesion study was performed to evaluate the involvement of the estrogen-dependent focal adhesion kinase (FAK) activation with cell adhesion. The phosphorylation status of FAK and estrogen receptor α (ERα) upon estrogen challenge was assessed by Western blotting. Specific inhibitors for ERα were used to validate the involvement of ERα-FAK signaling cascade. The results showed that, following stimulation with 1,000 nM estrogen for 48 h, transient activation of ERα and FAK was observed, as was an increased average number of E. coli cells adhering to vaginal epithelial cells. In addition, estrogen-induced activation of ERα and FAK was inhibited by the specific inhibitor of ERα, especially when the inhibitor reached a 10 µM concentration and acted for 1 h, and a decrease in the number of adherent E. coli cells was observed simultaneously. However, this inhibitory effect diminished as the concentration of estrogen increased. In conclusion, FAK and ERα signaling cascades were associated with the increasing E. coli adherence to vaginal epithelial cells, which was promoted by a certain concentration of estrogen.

Associations of long-term exposure to traffic-related air pollution with risk of valvular heart disease based on a cross-sectional study.

Emerging evidence demonstrated that traffic-related air pollution induced adverse effects on cardiovascular system. We designed a population-based cross-sectional study to explore the association between residential proximity to major roadways, traffic density and the prevalence of valvular heart disease (VHD). A total of 34040 subjects from a Rural Health Project between 2013 and 2018 were collected. According to the inclusion and exclusion criteria, 4158 participants were enrolled in the final analysis. And we calculated the subjects' proximity to major roadways and collected the traffic density on the major roadways. Transthoracic echocardiography (TTE) was performed to diagnose the VHD, according to the current AHA/ACC (the American Heart Association and the American College of Cardiology) guidelines. Differences between groups were examined by the one-way ANOVAs for continuous variables and the chi-square tests for categorical variables. A logistic regression models were used to assess the associations. The stratified analysis by age and sex were conducted to further analyze the association. The restricted cubic spline analysis was performed to further evaluate the association between road way distance and VHD. Bonferroni test was used to adjust the significance level. The subjects closer to the major roads had the higher risk of tricuspid regurgitation (TR) (odds risk, OR = 1.519, 95% confidence intervals, 95%CI: 1.058-2.181), especially in female. The risk of VHD was positive (high traffic density VS low traffic density, OR = 1.799, 95%CI: 1.221-2.651), especially in female. In addition, the high traffic density was associated with the risk of mitral regurgitation (MR) (OR = 1.758, 95%CI: 1.085-2.848). The restricted cubic spline analysis found a threshold distance of about 300 m, where had the lowest risk of VHD, aortic regurgitation (AR), MR, TR. Our results found a positive association between traffic-related air pollution and VHD especially in female.

Antifungal Effect of Long Noncoding RNA 9708-1 in the Vulvovaginal Candidiasis Murine Model.

Vulvovaginal candidiasis (VVC) caused by Candida spp. affects 70-75% of women at least once during their lives. We aim to elucidate the potential mechanism of VVC and investigate the therapeutic effects of long noncoding RNA 9708-1. Female BALB/c mice were randomized to four treatment groups, including the blank control group, VVC control group, vehicle control group and lncRNA 9708-1-overexpressed group. Mice were euthanized on Day 4, Day 7 and Day 14 after treatment. Colony-forming unit (CFU) was measured, and the inflammation was detected by hematoxylin and eosin (H&E). Gene and protein expression levels of lncRNA 9708-1 and FAK were determined by real-time PCR, Western blot and immunohistochemistry. The overexpression of lncRNA 9708-1 significantly decreased the fungal load from Day 4 to 7. H&E staining indicated that the impaired histological profiles were improved in lncRNA 9708-1-overexpressed group. LncRNA 9708-1 led to a significant increase in FAK level of vagina tissue which is expressed mainly in epithelial basal layer. This study suggests that lncRNA 9708-1 played a protective role on murine experimental VVC by upregulating the expression levels of FAK.

Assembly of pigeon circovirus-like particles using baculovirus expression system.

Pigeon circovirus (PiCV) is able to infect racing and meat pigeons of all ages and is a key factor that triggers young pigeon disease syndrome (YPDS). PiCV vaccine research has been impeded because PiCV cannot be grown or propagated in cell cultures. Virus-like particles (VLPs), which can be generated by a wide range of expression systems, have been shown to have outstanding immunogenicity and constitute promising vaccines against a wide range of pathogens. Cap protein, which contains neutralizing antibody epitopes, is the only capsid protein of PiCV. In this study, the baculovirus expression system was utilized to express the PiCV Cap protein, which was self-assembled into VLPs with a spherical morphology and diameters of 15-18 nm. Specific antibodies against the Cap protein were induced after BALB/c mice immunized intramuscularly (i.m.) with VLPs combined with adjuvant. Based on these findings, PiCV VLPs may be a promising candidate vaccine against PiCV.

Fusion and hemagglutinin proteins of canine distemper virus promote osteoclast formation through NF-κB dependent and independent mechanisms.

Paget's disease (PD) features abnormal osteoclasts (OC) which sharply increase in number and size and then intensely induce bone resorption. The purpose of this study was to determine the direct effects of canine distemper virus (CDV) and its fusion protein and hemagglutinin protein (F + H) on receptor activator of nuclear factor kappa-B ligand (RANKL) induced OC formation in vitro. Immunofluorescence assay, OC morphological and functional detection, intracellular signaling pathway detection, Real-time PCR analysis and ELISA were applied in this study. Immunofluorescence assay provided the conclusive proof that CDV can infect and replicate in RAW264.7 mouse monocyte cell line, primary human peripheral blood mononuclear cells (PBMC) and their further fused OC. Both CDV and F + H significantly promoted OC formation and bone resorption ability induced by RANKL. Meanwhile, intracellular signaling transduction analysis revealed CDV and F + H specifically upregulated the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) induced by RANKL, respectively. Furthermore, without RANKL stimulation, both CDV and F + H slightly induced OC-like cells formation in RAW264.7 cell line even in the presence of NF-κB inhibitor. F + H upregulate OC differentiation and activity through modulation of NF-κB signaling pathway, and induce OC precursor cells merging dependent on the function of glycoproteins themselves. These results meant that F and H proteins play a pivotal role in CDV supporting OC formation. Moreover, this work further provide a new research direction that F and H proteins in CDV should be considered as a trigger during the pathogenesis of PD.

The Role of 17ß-Estrogen in Candida albicans Adhesion on Human Vaginal Epithelial Cells via FAK Phosphorylation.

PURPOSES: To investigate the role of 17ß-estrogen in Candida albicans (C. albicans) adhesion on human vaginal epithelial cells in vulvovaginal candidiasis (VVC). METHODS: The vaginal epithelial cell line, VK2/E6E7, was used to study the estrogen-induced molecular events between C. albicans and cells. An adhesion study was performed to evaluate the involvement of the estrogen-dependent focal adhesion kinase (FAK) activation in cell adhesion. The phosphorylation status of FAK and estrogen receptor α (ERα) upon estrogen challenge was assessed by western blotting. Specific inhibitors for ERα were used to validate the involvement of ERα-FAK signaling cascade. RESULTS: A transient activation of ERα and FAK was observed following the stimulation with 1000 nM estrogen for 48 h, as well as the increased average number of C. albicans adhering to each vaginal epithelial cell. Estrogen-induced activation of ERa and FAK was inhibited by the specific inhibitor of ERα, especially when the inhibitor reached a 10 µM concentration and allowed to act for 12 h. Simultaneously, a decrease in the number of adherent C. albicans was observed. However, this inhibitory effect diminished as the concentration of estrogen increased. CONCLUSION: FAK and ERα signaling cascades were involved in the early interaction between the vaginal epithelial cells and C. albicans, which appeared to be linked with the enhanced cell adhesion leading to VVC and promoted by a certain concentration of estrogen.

Antiviral efficacy of favipiravir against canine distemper virus infection in vitro.

BACKGROUND: Canine distemper (CD) is an acute infectious disease with high morbidity rates caused by a highly contagious pathogen (Canine Morbillivirus, also known as canine distemper virus, CDV). CDV can infect a broad range of carnivores resulting in complex clinical signs. Currently, there is no effective method to treat for CDV infections. Favipiravir (T-705), a pyrazine derivative, was shown to be an effective antiviral drug against RNA viruses, acting on RNA-dependent RNA polymerase (RdRp). However, whether the T-705 has antiviral effects following CDV infection is unclear. Here, we investigated the antiviral effect of T-705 against CDV-3 and CDV-11 strains in Vero and DH82 cell lines. RESULTS: Our data demonstrated that T-705 significantly inhibited the replication of CDV-3 and CDV-11 in both Vero and DH82 cells at different concentrations, ranging from 2.441 µg/ml to 1250 µg/ml. Additionally, T-705 exhibited efficacious antiviral effects when administered at different time points after virus infection. Cytotoxicity tests showed a slight decline in viability in Vero cells after T-705 treatment, and no apparent cytotoxicity was detected in T-705 treated DH82 cells. Comparison of anti-CDV polyclonal serum only inhibition of CDV in supernatant, T-705 directly inhibited viral replication in cells, and indirectly reduced the amount of virions in supernatant. The combination application of T-705 and anti-CDV polyclonal serum exhibited a rapid and robust inhibition against virions in supernatant and virus replication in cells. CONCLUSIONS: Our data strongly indicated that T-705 effectively inhibited viral replication following CDV infection in vitro, and could be a potential candidate for treatment for CD.

Effects of Ovariectomy in an hSOD1-G93A Transgenic Mouse Model of Amyotrophic Lateral Sclerosis (ALS).

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by progressive muscular dystrophy and paralysis; most ALS patients die from respiratory failure within 3 to 5 years, and there is currently no effective treatment. Some studies have indicated sex differences in the incidence of ALS, and evidence suggests a neuroprotective role for estrogen. MATERIAL AND METHODS We used human Cu/Zn superoxide dismutase (hSOD1-G93A) transgenic mice to determine the effects of ovariotomy on the onset of disease and behavior; we also used Western blotting to measure the expression of aromatase and estrogen receptors, as well as the inflammatory cytokines and apoptosis markers, in the lumbar spinal cord to determine the mechanism of estrogen-mediated neuroprotection. RESULTS Ovariectomy advanced the onset of disease, down-regulated aromatase and estrogen receptor alpha (ER-a) expression, and inhibited expression of the anti-inflammatory factors arginase-1 and the anti-apoptotic factor B-cell lymphoma-2 (Bcl-2) in the lumbar spinal cord of hSOD1-G93A transgenic mice. CONCLUSIONS Ovariectomy resulted in earlier disease onset and attenuated the anti-inflammatory and anti-apoptotic actions of estrogen in hSOD1-G93A transgenic mice. Therefore, estrogen may play an important role in protecting spinal cord motor neurons.

Association between PNPLA3 gene polymorphisms and risk of hepatitis B virus-related hepatocellular carcinoma in Han population in China:a case-control study.

BACKGROUND AND AIM: Several recent studies showed that the genetic polymorphisms in the PNPLA3 region (rs738408, rs738409, rs2294918, rs2294919 and rs2281135) were with related to various kinds of liver diseases. We analyzed the five single-nucleotide polymorphisms (SNPs) for major HBV outcomes in Han Chinese. METHODS: A total of 2410 samples were involved and peripheral blood samples were collected in this study. The SNPs in the PNPLA3 region were genotyped by using Matrix-assisted laser desorption/ionization time of flight mass spectrometry. RESULTS: Our study indicated the clear relationship between the PNPLA3 rs2294918, rs2294919 and HBV-related HCC after control for the effects of sex, drinking and smoking. Health subjects with the PNPLA3 rs2294919 TC genotype would have a 0.605 (95% CI: 0.413, 0.886; p = .010) times lower odds of having HCC, and those with the rs2294918 AG genotype would have a 1.872 (95% CI: 1.256, 2.792; p = .002) times higher odds of having HCC, whereas the values of sex, age, drinking and smoking were fixed. In addition, CA haplotype of the haplotype block of rs738409 and rs2281135 was also associated with HBV-related HCC. CONCLUSIONS: Our study suggested that PNPLA3 loci (rs2294918, rs2294919) were associated with HBV-related HCC in Han Chinese.

PAX1 Methylation as a Potential Biomarker to Predict the Progression of Cervical Intraepithelial Neoplasia: A Meta-analysis of Related Studies.

OBJECTIVE: The methylation of paired box gene 1 (PAX1) has a great influence on the process of cervical lesion. However, available evidence for the association between PAX1 methylation and cervical intraepithelial neoplasia (CIN) are inconsistent. Here, we systematically reviewed and analyzed PAX1 methylation in progress of CIN. METHODS: Two investigators independently searched eligible studies of PAX1 methylation and CIN that were published in PubMed, Cochrane Library, EMBASE, and Web of Science databases until November 30, 2016. We extracted clinicopathologic features of CIN and cervical cancel relevant to PAX1 methylation. Odds ratios (ORs) with their 95% confidence intervals (CIs) were used to assess the association between PAX1 methylation and progression of patients with CIN. RESULTS: Seven studies composed of 1055 patients with various stages of CIN and cervical cancel were eventually included. The results revealed that PAX1 methylation was associated with transition of CIN I to CIN II/III (OR, 0.09; 95% CI, 0.04-0.19) and CIN II/III to cervical cancer (OR, 0.16; 95% CI, 0.05-0.46), and similar results were produced in sensitivity analysis. Also, we found that the OR value was associated with average age and number of patients, publication year, and study location of included articles. CONCLUSIONS: PAX1 gene methylation was associated with the transition of CIN I to CIN II/III and CIN II/III to cervical cancer, so that it could be an auxiliary biomarker to estimate the risk of CIN progress. Moreover, PAX1 may help to determine appropriate reexaminations and treatment for patients with various stages of CIN.

Genetic polymorphism of HLA-DQ confers susceptibility to hepatitis B virus-related hepatocellular carcinoma: a case-control study in Han population in China.

Several recent genome-wide studies showed that the genetic polymorphisms in the HLA-DQ region (rs9275572 and rs2856718) were related to chronic hepatitis B virus (HBV) infection and chronic hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC). We analyzed the two single-nucleotide polymorphisms for major HBV outcomes in Han Chinese. A total of 1291 samples were involved and peripheral blood samples were collected in this study. Matrix-assisted laser desorption/ionization time of flight mass spectrometry were used to genotype the single-nucleotide polymorphisms in the HLA-DQ region. Our study indicated the clear relationship between the HLA-DQ rs9275572 and HBV-related HCC after control for the effects of sex, drinking, and smoking. Health subjects with the HLA-DQ rs9275572 GA genotype would have a 0.641 (95 % CI 0.416, 0.985; P = 0.043) times lower odds of having HCC, and those with the AA genotype would have a 0.256 (95 % CI 0.106, 0.618; P = 0.002) times lower odds of having HCC, whereas the values of the other covariates were fixed. Whereas there was no significant difference found for the HLA-DQ rs2856718 AG and GG genotype. Our study suggested that HLA-DQ loci (rs9275572) were associated with HBV-related HCC as a protective factor in Han Chinese.

Correlation between polymorphisms in DNA mismatch repair genes and the risk of primary hepatocellular carcinoma for the Han population in northern China.

PURPOSE: This study investigated correlations between polymorphisms in DNA mismatch repair (MMR) genes and the risk of primary hepatocellular carcinoma (PHC). METHODS: Single nucleotide polymorphisms (SNPs) in the DNA MMR genes MLH3 (rs175080), PMS1 (rs5742933), PMS2 (rs1059060), MSH3 (rs26279), MSH5 (rs1150793, rs2075789) and MSH6 (rs1042821) were detected using the SNaPshot method in 250 PHC cases and in 308 patients without PHC in the Han population in northern China. RESULTS: The AA genotype in MLH3 (rs175080) increased the risk of PHC (odds ratio [OR] = 3.424; 95% confidence interval [CI]: 1.097-10.689). The AG and GG genotypes in MSH3 (rs26279) increased the risk of PHC (OR: 1.644 and 3.300; 95% CI: 1.112-2.428 and 1.765-6.168, respectively). The AA genotype in MSH5 (rs2075789) increased the risk of PHC (OR: 9.229; 95% CI: 1.174-72.535). The CT genotype in MSH6 (rs1042821) reduced the risk of PHC (OR: 0.629; 95% CI: 0.428-0.924). CONCLUSIONS: Our study suggests that polymorphisms in MLH3 (rs175080), MSH3 (rs26279), MSH5 (rs2075789) and MSH6 (rs1042821) may be independent risk factors for PHC.

The AC010247.2/miR-125b-5p axis triggers the malignant progression of acute myelocytic leukemia by IL-6R.

AML is a malignant tumor derived from the hematopoietic system, which has a poor prognosis and its incidence is increasing recent years. LncRNAs bind to miRNAs as competitive endogenous RNAs to regulate the occurrence and progression of AML， with IL-6R playing a crucial role in hematological malignancies. However, the mechanism by which noncoding RNAs regulate IL6R expression in AML remains unclear. This study found that the AC010247.2/miR-125b-5p axis promotes AML progression by regulating IL-6R expression. Specifically, knocking down or inhibiting AC010247.2 and miR-125b-5p affected IL6R and its downstream genes. Mechanistically, AC010247.2 acts as a ceRNA for miR-125b-5p, influencing IL-6R expression. Additionally, AC010247.2's regulation of AML progression partially depends on miR-125b-5p. Notably, the AC010247.2/miR-125b-5p/IL6R axis serves as a better polygenic diagnostic marker for AML. Our study identifies a key ceRNA regulatory axis that modulates IL6R expression in AML, providing a reliable multigene diagnostic method and potential therapeutic target.