Nonlinear relationship between viral load and TCT in single/multiple HPV52 infection.

PURPOSE: To determine the correlation between HPV (human papillomavirus) 52 viral load, multiple infections and ThinPrep cytology test (TCT), to inform clinical management of HPV52-positive women after cervical cancer screening. METHODS: A total of 1,882 female patients who had positive quantitative HPV tests at Yuebei People's Hospital from January 2020 to December 2022, of whom 533 tested positive for HPV52. We excluded patients who combined HPV16 and/or HPV 18 positivity and whom HPV52 viral load could not be calculated. The final enrollment was 488 patients, including 400 NILM, 48 ASC-US, 28 LSIL and 12 HSIL. The HPV test is a quantitative multiplexed fluorescent PCR assay that provides both HPV genotyping and viral load. RESULTS: In our study, there were differences in the median distribution of viral loads among various cytological class categories. The risk of TCT results (LSIL or worse) was increased with the increase of HPV52 viral load, for every LOG unit increase in HPV52 viral load, the risk increased by 26.6%. More importantly, we found a nonlinear relationship between HPV52 viral load and TCT results (LSIL or worse) in both single and multiple infections. When the viral load reaches a threshold, the risk of abnormal cytological results increases significantly. CONCLUSION: HPV52 viral load is an independent risk factor for TCT results (LSIL or worse). The relationship between HPV52 viral load and TCT results (LSIL or worse) is not linear. Viral load may be used as a triage indicator for HPV52-positive patients, thus improving the post-screening clinical management of HPV52-positive women.

Analysis of deafness susceptibility gene of neonates in northern Guangdong, China.

This study aimed to explore the molecular epidemiology characteristics of deafness susceptibility genes in neonates in northern Guangdong and provide a scientific basis for deafness prevention and control. A total of 10,183 neonates were recruited between January 2018 and December 2022 at Yuebei People's Hospital. Among these, a PCR hybridization screening group of 8276 neonates was tested for four deafness genes: GJB2, SLC26A4, mtDNA, and GJB3 by PCR hybridization. Another group used next-generation sequencing (NGS) to detect genetic susceptibility genes in 1907 neonates. In PCR hybridization screening group, 346 (4.18%) of 8276 neonates were found to be carriers of the deafness gene. Among these, 182 (2.2%) had GJB2 variants, 114 (1.38%) had SLC26A4 variants, 35 (0.42%) had mtDNA variants, and 15 (0.18%) had GJB3 variants. In NGS Screening Group, 195 out of 1907 neonates were found to be carriers of the deafness gene, with a positive rate of 10.22%. Among these, 137 (7.18%) had GJB2 variants, 41 (2.15%) had SLC26A4 variants, 11 (0.58%) had mtDNA variants, and 6 (0.31%) had GJB3 variants. The prevalence of deafness gene variants was high in Northern Guangdong Province. The most common gene for deafness was GJB2, followed by SLC26A4 and mtDNA. GJB3 variants are rare. Compared with PCR hybridization method, NGS technology can expand the screening scope and greatly improve the detection rate of deafness genes. The c.109G>A of GJB2 was found to occur at a high frequency, which should be considered. Therefore, it is important to conduct neonatal deafness gene screening to prevent and control hereditary deafness.

Neutralization Effect of Sera against Delta and Omicron in Patients Recovering from COVID-19 and Inactivated Vaccine Recipients.

This study aims to analyze the serum neutralization capacity against Delta and Omicron variants in three clusters of individuals, including those who had recovered from COVID-19 and those who had received two and three doses of inactivated vaccine. Pseudovirus neutralization tests were performed on serum samples. The neutralizing titers between different groups were compared using the Wilcoxon's signed-rank test. Among the two-dose vaccinees, the neutralization titers of the Omicron variant were reduced by approximately 3.1-fold compared to the wild-type virus (p < 0.05). Meanwhile, among the three-dose vaccinees, the neutralization titers for Delta and Omicron variants were 3.5-fold (p < 0.05) and 5.0-fold (p < 0.05) lower, respectively, as compared to the wild-type virus. In addition, among the recovering patients, the neutralization titers for Delta and Omicron variants were 3.9-fold (p < 0.05) and 29.1-fold (p < 0.05) lower, respectively, as compared to the wild-type virus. Overall, only 12.0% (11/92) of participants showed neutralizing titers against Omicron above the detection limit. The ability to neutralize wild-type pseudovirus was significantly boosted in three-dose vaccinees as compared to two-dose vaccinees. Sera from recovered patients showed greater neutralizing titers for the wild-type and Delta pseudoviruses than the two- and three-dose inactivated vaccine groups. The present study revealed a loss of neutralizing activity against the Omicron variant in almost all samples. Moreover, the immunization effect obtained through natural infection is more robust than that from the active immunization method of vaccination.

The prevalence of human papillomavirus among women in northern Guangdong Province of China.

Globally, cervical cancer, whose etiologic factor is Human papillomavirus (HPV), is the third most common cancer among women. In cervical cancer screening, HPV testing is important. However, the prevalence of HPV in northern Guangdong Province has not been conclusively determined. A total of 100,994 women attending Yuebei People's Hospital Affiliated to Shantou University Medical College between 2012 and 2020 were recruited. HPV was tested by a polymerase chain reaction (PCR)-based hybridization gene chip assay. The prevalence of HPV among these women was established to be19.04%. Peak prevalence was observed in women aged 40-49 (7.29%). Besides, the prevalence of single-type HPV infection (14.46%) was significantly high, compared to multiple-type infection (4.58%) (p < 0.01), while the prevalence of high-risk HPV infection (19.97%) was significantly higher than that of low-risk genotypes (5.48%) (p < 0.01). The most prevalent high-risk genotypes were HPV52 (4.16%), HPV16 (2.98%), HPV58 (2.15%), HPV53 (1.58%) and HPV68 (1.34%). HPV co-infection with up to 10 genotypes was reported for the first time. Our findings suggested a high burden of HPV infections among women in northern Guangdong. Establishing the prevalence and genotype distribution characteristics of HPV infections in the region can contribute to cervical cancer prevention through HPV vaccination.

Molecular epidemiological investigation of abnormal hemoglobin in Shaokwan region, southern China.

OBJECTIVES: Shaokwan is one of the inhabitant regions of Hakka population in Guangdong province of southern China. Previous survey has reported that a higher prevalence of abnormal hemoglobin (Hb) in this region. However, large-scale survey on the molecular characteristics of abnormal hemoglobin in this south-north junctional region has not been reported.In this study, we aim to investigate the molecular characteristics of abnormal hemoglobin in this area. METHODS: Blood samples from medical check-up center in one local hospital were selected for abnormal hemoglobin screening. Hemoglobin electrophoresis and routine blood tests were performed. Hemoglobin variants were further analyzed by PCR and DNA sequencing. RESULTS: Among the 9731 study subjects, 45 cases of hemoglobin variants were found by hemoglobin electrophoresis, which gave an incidence of 0.46% (45/9731) in Shaokwan region. 8 kinds of hemoglobin variants were identified by gene sequencing. Hb Q-Thailand (16/45) was the most common hemoglobin variants, followed by HbE (7/45), Hb NewYork (6/45) and Hb G-Chinese (6/45). DISCUSSION AND CONCLUSION: Hemoglobin variants had obviously genetic polymorphisms in Chinese. Our study of hemoglobin disorders in this special Hakka Chinese population will contribute considerably to our understanding of the historical, emigrational, and genetic relationships among different ethnic group in this region.

Human serum albumin variants in China: a molecular epidemiological investigation and literature review.

BACKGROUND: Bisalbuminemia is a hereditary and/or acquired abnormality characterized by a double albumin (ALB) band on serum protein electrophoresis. However, there have been no epidemiological investigations of ALB variants in Chinese populations. METHODS: This retrospective study examined 71,963 unrelated subjects from five provinces in southern China. ALB variants were screened by cellulose acetate electrophoresis at pH 8.6 and ALB mutations were confirmed by polymerase chain reaction-DNA sequencing. RESULTS: The average incidence of inherited bisalbuminemia in the southern Chinese population was 0.0264% (19/71,963). Thirteen cases showed slow and six showed fast genetic variants on cellulose acetate electrophoresis. Four kinds of ALB variants were identified: proalbumin Lille (p.Arg23His), ALB Castel di Sangro (p.Lys560Glu), ALB Fukuoka-1 (p.Asp587Asn), and a novel ALB Wuxi (p.Lys562Glu). The gene frequency of ALB variants in the Wuxi region (0.126%, 13/10,297) was significantly higher than in other regions in southern China, and 90.9% (10/11) of cases of proalbumin Lille were also found in the Wuxi region. CONCLUSIONS: This study provides the first report of the detailed prevalence and molecular characterization of ALB variants in southern China. Compared with other areas of China, Wuxi had a different pattern of ALB variants and a high prevalence of proalbumin Lille.

Molecular characterization of hemoglobinopathies and thalassemias in Northern Guangdong Province, China.

ABSTRACT: To detect the molecular characterization of hemoglobinopathies and thalassemias in Northern Guangdong Province of China.We recruited 10,285 subjects who were screened for hemoglobin (Hb) variants and thalassaemia genotypes in the outpatient department of Yuebei People's Hospital from January 2018 to December 2020. The subjects collected venous blood samples for blood cell parameter analysis and Hb electrophoresis analysis. When the average red blood cell volume is <82 fL, or the average red blood cell Hb is <27 pg, or HbA2 > 3.5%, or HbA2 < 2.5%, or HbF > 2.0%, the screening is positive if one of them is satisfied. All subjects who were screened positive were tested for the thalassaemia gene by gap-polymerase chain reaction, PCR-based reverse dot blot, and DNA sequencing.Among all subjects screened, the overall prevalence of hemoglobinopathies and thalassemias were 0.46% (47/10,285) and 21.02% (2162/10,285) in Northern Guangdong Province. We found that Hb Q-Thailand is the most common, and other types of hemoglobinopathies are followed by Hb E, Hb New York, Hb G-Chinese, Hb G-Coushatta, Hb J-Bangkok, Hb J-Broussais, Hb Ottawa, and Hb G-Taipei. We identified 1340 cases (13.03%) of α-thalassemia, mainly includes --SEA deletion (71.64%), -α3.7 deletion (12.01%), -α4.2 deletion (4.78%). And identified 652 cases (6.34%) of ß-thalassemia, the most prevalent being CD 41/42(-TTCT) (35.89%), IVS-II-654 (C > T) (33.44%), CD 17 (A > T) (10.28%) and -28(A > G) (9.66%). Furthermore, there are 170 cases (1.65%) of α combined ß thalassaemia. In addition, we found a rare case with -80 (T > A) of ß-thalassemia. The results of this study found a high prevalence of hemoglobinopathies and thalassemias in Northern Guangdong Province, China. There were some differences molecular characterizations of thalassemia in different areas of China.Our results enriched the related information of hemoglobinopathies and thalassemias in the region, which provided valuable references for the prevention and control of thalassemia.

m6A RNA Methylation Regulators Elicit Malignant Progression and Predict Clinical Outcome in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and N6-methyladenosine (m6A) is a predominant internal modification of RNA in various cancers. We obtained the expression profiles of m6A-related genes for HCC patients from the International Cancer Genome Consortium and The Cancer Genome Atlas datasets. Most of the m6A RNA methylation regulators were confirmed to be differentially expressed among groups stratified by clinical characteristics and tissues. The clinical factors (including stage, grade, and gender) were correlated with the two subgroups (cluster 1/2). We identified an m6A RNA methylation regulator-based signature (including METTL3, YTHDC2, and YTHDF2) that could effectively stratify a high-risk subset of these patients by univariate and LASSO Cox regression, and receiver operating characteristic (ROC) analysis indicated that the signature had a powerful predictive ability. Immune cell analysis revealed that the genes in the signature were correlated with B cell, CD4 T cell, CD8 T cell, dendritic cell, macrophage, and neutrophil. Functional enrichment analysis suggested that these three genes may be involved in genetic and epigenetic events with known links to HCC. Moreover, the nomogram was established based on the signature integrated with clinicopathological features. The calibration curve and the area under ROC also demonstrated the good performance of the nomogram in predicting 3- and 5-year OS in the ICGC and TCGA cohorts. In summary, we demonstrated the vital role of m6A RNA methylation regulators in the initial presentation and progression of HCC and constructed a nomogram which would predict the clinical outcome and provide a basis for individualized therapy.

Predicting Ovarian/Breast Cancer Pathogenic Risks of Human BRCA1 Gene Variants of Unknown Significance.

High-throughput sequencing is gaining popularity in clinical diagnoses, but more and more novel gene variants with unknown clinical significance are being found, giving difficulties to interpretations of people's genetic data, precise disease diagnoses, and the making of therapeutic strategies and decisions. In order to solve these issues, it is of critical importance to figure out ways to analyze and interpret such variants. In this work, BRCA1 gene variants with unknown clinical significance were identified from clinical sequencing data, and then, we developed machine learning models so as to predict the pathogenicity for variants with unknown clinical significance. Through performance benchmarking, we found that the optimized random forest model scored 0.85 in area under receiver operating characteristic curve, which outperformed other models. Finally, we applied the best random forest model to predict the pathogenicity of 6321 BRCA1 variants from both sequencing data and ClinVar database. As a result, we obtained the predictive pathogenic risks of BRCA1 variants of unknown significance.

Therapeutic effects of puerarin on polycystic ovary syndrome: A randomized trial in Chinese women.

BACKGROUND: This study aims to assess the therapeutic effects of a well-known component (puerarin) obtained from a Chinese herb root in patients with polycystic ovary syndrome (PCOS). METHODS: Women with premature ovarian failure (POF) were assigned to the obese group (body mass index [BMI] ≥24 kg/m2 and waist hip ratio [WHR] >0.85) or non-obese group (group 3, n = 21). Obese patients were further randomly assigned to the obese treatment group (group 1, n = 15) and obese control group (group 1, n = 15). All patients received standard treatment (Diane-35, 1 tablet/d, orally, plus metformin, 1.5 g/d, orally). In addition to the standard modality, patients in group 1 and group 3 also orally received 150 mg/d of puerarin tablets for 3 months. Venous blood was drawn before and after treatment. Then, the metabolic and antioxidant biomarkers were measured. The normality of distribution of the data was tested using the Kolmogorov-Smirnov method. The baseline characteristics were analyzed using one-factor analysis of variance (ANOVA), and post-hoc was performed using the least significance difference (LSD)-t test. RESULTS: Significantly improved blood levels of sex hormone binding globulin (SHBG) and superoxide dismutase (SOD) were observed in patients who received the additional treatment of puerarin, regardless of their lean or obese status, while these were not observed in patients who did not receive puerarin. Furthermore, obese patients with PCOS had significantly lower systolic blood pressure, total cholesterol, and testosterone blood levels, when compared with before treatment. CONCLUSION: The addition of puerarin to the present treatment protocol can be considered for the management of metabolic disorders and hyperandrogenism in PCOS patients.

Caregivers: the potential infection resources for the sustaining epidemic of hand, foot, and mouth disease/herpangina in Guangdong, China?

BACKGROUND: Although several measures have been taken to control hand foot and mouth disease (HFMD) and herpangina (HA), these two diseases have been prevalent in China for 10 years with high incidence. We suspected that adults' inapparent infection might be the cause of the continued prevalence of HFMD/HA infection in mainland China. METHODS: To explore the role of adults (especially caregivers) in the transmission process of HFMD/HA among children, 330 HFMD/HA cases and 330 healthy children (controls) were selected for a case-control study. Then, data were analyzed by logistic regression. RESULTS: Single-variable analyses revealed that caregivers who tested positive for enterovirus was a significant risk factor of HFMD/HA transmission to children (adjusted odds ratio (OR) = 9.22; 95% CI, 1.16 to 73.23). In the final multivariable model, caregiver behavior, such as cooling children's food with mouth (OR = 1.85; 95% CI, 1.11 to 3.08) and feeding children with their own tableware (OR = 2.19; 95% CI, 1.07 to 4.45), significantly increased the risk of transmitting HFMD/HA to children. On the contrary, washing hands before feeding children reduced such risk. CONCLUSIONS: These results implied that the caregivers might be the infectious source or carriers of enterovirus. Therefore, preventing or treating the caregivers' enterovirus infection and improving their hygiene habits, especially when they are in contact with children, could provide a breakthrough for the effective control of HFMD/HA.

A Nomogram Based on a Three-Gene Signature Derived from AATF Coexpressed Genes Predicts Overall Survival of Hepatocellular Carcinoma Patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer with an extremely high mortality rate. Therefore, there is an urgent need in screening key biomarkers of HCC to predict the prognosis and develop more individual treatments. Recently, AATF is reported to be an important factor contributing to HCC. METHODS: We aimed to establish a gene signature to predict overall survival of HCC patients. Firstly, we examined the expression level of AATF in the Gene Expression Omnibus (GEO), the Cancer Genome Atlas (TCGA), and the International Union of Cancer Genome (ICGC) databases. Genes coexpressed with AATF were identified in the TCGA dataset by the Poisson correlation coefficient and used to establish a gene signature for survival prediction. The prognostic significance of this gene signature was then validated in the ICGC dataset and used to build a combined prognostic model for clinical practice. RESULTS: Gene expression data and clinical information of 2521 HCC patients were downloaded from three public databases. AATF expression in HCC tissue was higher than that in matched normal liver tissues. 644 genes coexpressed with AATF were identified by the Poisson correlation coefficient and used to establish a three-gene signature (KIF20A, UCK2, and SLC41A3) by the univariate and multivariate least absolute shrinkage and selection operator Cox regression analyses. This three-gene signature was then used to build a combined nomogram for clinical practice. CONCLUSION: This integrated nomogram based on the three-gene signature can predict overall survival for HCC patients well. The three-gene signature may be a potential therapeutic target in HCC.

Multi-omics Analysis of Microenvironment Characteristics and Immune Escape Mechanisms of Hepatocellular Carcinoma.

The immune environment in primary tumor has a profound impact on immunotherapy. However, the clinical relevance of immune environment in hepatocellular carcinoma (HCC) is largely unknown. Here, the immune profile and its clinical response in HCC were investigated. The gene expression profiles of 569 HCCs from three cohorts (The Cancer Genome Atlas, TCGA, n = 257; Gene Expression Omnibus, GEO, n = 170; International Cancer Genome Consortium, ICGC, n = 142) were used in the current study. Five gene expression subtypes (C1-C5) responsible for global immune genes were identified in HCCs at stage I/II. It was found that subtype C4 was associated with upregulation and subtype C5 was associated with downregulation of immune profiles in most metagenes. Immune-correlation analysis of the five subtypes demonstrated that C3 and C4 had higher immune score and better prognostic outcome, as compared with other subtypes. Moreover, the mutation frequencies of TP53, CTNNB1, and AXIN1 had significant difference in the five subgroups. Further, the expression of PDCD1, CD274, PDCD1LG2, CTLA4, CD86, and CD80 was higher in subtype C4 in comparison with the other subtypes. The WGCNA of immune-related genes in the five subtypes revealed that blue and turquoise modules were positively correlated with subtype C4 and were associated with 12 common pathways in the KEGG database. These results were validated in external cohorts from the NCI (National Cancer Institute) cohort (GSE14520) and the ICGC (International Cancer Genome Consortium) cohort. In summary, one immune-enhanced subtype and one immune-decreased subtype having different immune and clinical characteristics may provide guidance for developing novel treatment strategies for immune system malfunction-related cancer.

Identification of key genes and long non-coding RNA associated ceRNA networks in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although multiple efforts have been made to understand the development of HCC, morbidity, and mortality rates remain high. In this study, we aimed to discover the mRNAs and long non-coding RNAs (lncRNAs) that contribute to the progression of HCC. We constructed a lncRNA-related competitive endogenous RNA (ceRNA) network to elucidate the molecular regulatory mechanism underlying HCC. METHODS: A microarray dataset (GSE54238) containing information about both mRNAs and lncRNAs was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and lncRNAs (DElncRNAs) in tumor tissues and non-cancerous tissues were identified using the limma package of the R software. The miRNAs that are targeted by DElncRNAs were predicted using miRcode, while the target mRNAs of miRNAs were retrieved from miRDB, miRTarBas, and TargetScan. Functional annotation and pathway enrichment of DEGs were performed using the EnrichNet website. We constructed a protein-protein interaction (PPI) network of DEGs using STRING, and identified the hub genes using Cytoscape. Survival analysis of the hub genes and DElncRNAs was performed using the gene expression profiling interactive analysis database. The expression of molecules with prognostic values was validated on the UALCAN database. The hepatic expression of hub genes was examined using the Human Protein Atlas. The hub genes and DElncRNAs with prognostic values as well as the predictive miRNAs were selected to construct the ceRNA networks. RESULTS: We found that 10 hub genes (KPNA2, MCM7, CKS2, KIF23, HMGB2, ZWINT, E2F1, MCM4, H2AFX, and EZH2) and four lncRNAs (FAM182B, SNHG6, SNHG1, and SNHG3) with prognostic values were overexpressed in the hepatic tumor samples. We also constructed a network containing 10 lncRNA-miRNA-mRNA pathways, which might be responsible for regulating the biological mechanisms underlying HCC. CONCLUSION: We found that the 10 significantly overexpressed hub genes and four lncRNAs were negatively correlated with the prognosis of HCC. Further, we suggest that lncRNA SNHG1 and the SNHG3-related ceRNAs can be potential research targets for exploring the molecular mechanisms of HCC.

Screening of potential biomarkers in hepatitis C virus-induced hepatocellular carcinoma using bioinformatic analysis.

Evidence suggests that hepatitis C virus (HCV) infection is among the main causes of hepatocellular carcinoma (HCC). In addition, HCV-induced HCC (HCV-HCC) exhibits adverse clinical outcomes and limited therapeutic treatments are available for this condition. To investigate key biomarkers in the occurrence and development of HCV-HCC, microarray datasets GSE62232, GSE69715 and GSE107170 were downloaded from the Gene Expression Omnibus database for analysis. The differentially expressed genes between HCV-HCC and normal tissue were identified using the GEO2R online tool. The function enrichment analyses including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were performed using the Database for Annotation, Visualization and Integrated Discovery online tool. A protein-protein interaction network was constructed using the Search Tool for the Retrieval of Interacting Genes database and visualized using Cytoscape. A total of 368 DEGs were identified, and the top 10 hub genes with a high degree of connectivity were selected for further analysis. Subsequently, overall survival and disease-free survival analysis revealed that there was a significant association between altered expression of HMMR, CCNB1 and KIF20A, and poor clinical outcome. In summary, these results indicate that HMMR, CCNB1 and KIF20A are potential targets for diagnosis and therapy of HCV-HCC.

An Integrated Model Based on a Six-Gene Signature Predicts Overall Survival in Patients With Hepatocellular Carcinoma.

Background: Nowadays, clinical treatment outcomes of patients with hepatocellular carcinoma (HCC) have been improved. However, due to the complexity of the molecular mechanisms, the recurrence rate and mortality in HCC inpatients are still at a high level. Therefore, there is an urgent need in screening biomarkers of HCC to show therapeutic effects and improve the prognosis. Methods: In this study, we aim to establish a gene signature that can predict the prognosis of HCC patients by downloading and analyzing RNA sequencing data and clinical information from three independent public databases. Firstly, we applied the limma R package to analyze biomarkers by the genetic data and clinical information downloaded from the Gene Expression Omnibus database (GEO), and then used the least absolute shrinkage and selection operator (LASSO) Cox regression and survival analysis to establish a gene signature and a prediction model by data from the Cancer Genome Atlas (TCGA). Besides, messenger RNA (mRNA) and protein expressions of the six-gene signature were explored using Oncomine, Human Protein Atlas (HPA) and the International Cancer Genome Consortium (ICGC). Results: A total of 8,306 differentially expressed genes (DEGs) were obtained between HCC (n = 115) and normal tissues (n = 52). Top 5,000 significant genes were selected and subjected to the weighted correlation network analysis (WGCNA), which constructed nine gene co-expression modules that assign these genes to different modules by cluster dendrogram trees. By analyzing the most significant module (red module), six genes (SQSTM1, AHSA1, VNN2, SMG5, SRXN1, and GLS) were screened by univariate, LASSO, and multivariate Cox regression analysis. By a survival analysis with the HCC data in TCGA, we established a nomogram based on the six-gene signature and multiple clinicopathological features. The six-gene signature was then validated as an independent prognostic factor in independent HCC cohort from ICGC. Receiver operating characteristic (ROC) curve analysis confirmed the predictive capacity of the six-gene signature and nomogram. Besides, overexpression of the six genes at the mRNA and protein levels was validated using Oncomine and HPA, respectively. Conclusion: The predictive six-gene signature and nomograms established in this study can assist clinicians in selecting personalized treatment for patients with HCC.

Retraction Note: Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation.

This Article has been retracted.

A Case-control Study on Risk Factors for Severe Hand, Foot and Mouth Disease.

The objective of this study was to identify potential risk factors for severe hand, foot and mouth disease (HFMD). In this case-control study, 459 severe HFMD patients and 246 mild HFMD patients from Guangdong province and Henan province, China were included. Data comprising demographic characteristics, clinical symptoms and signs, laboratory findings and other factors were collected. Univariate analysis revealed 30 factors associated with severe cases. Further multivariate analysis indicated four independent risk factors: fatigue (p < 0.01, odd ratio [OR] = 204.7), the use of glucocorticoids (p = 0.03, OR = 10.44), the use of dehydrant drugs (p < 0.01, OR = 73.7) and maculopapular rash (p < 0.01, OR = 84.4); and one independent protective factor: herpes or ulcers in mouth (p = 0.01, OR = 0.02). However, more systematic research and validation are needed to understand the underlying risk factors for severe HFMD.

Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease.

Hand-Washing: The Main Strategy for Avoiding Hand, Foot and Mouth Disease.

Epidemics of hand, foot and mouth disease (HFMD) among children have caused concern in China since 2007. We have conducted a retrospective study to investigate risk factors associated with HFMD. In this non-matching case-control study, 99 HFMD patients and 126 control from Guangdong Province were enlisted as participants. Data comprising demographic, socio-economic, clinical and behavior factors were collected from children's parents through face-to-face interviews by trained interviewers using a standardized questionnaire. Results of the primary logistic regression analyses revealed that age, history of cold food consumption, hand-washing routines, and airing out bedding were significantly associated with HFMD cases. Results of further multivariate analysis indicated that older age (OR = 0.44, 95% CI: 0.34-0.56) and hand-washing before meals (OR = 0.3, 95% CI: 0.13-0.70) are protective factors, whereas airing out bedding more than thrice a month (OR = 4.55, 95% CI: 1.19-17.37) was associated with increased risk for HFMD. Therefore, hand-washing should be recommended to prevent HFMD, and the potential threat of airing out bedding should be carefully considered. However, further studies are needed to examine other possible risk factors.