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Cervical cancer is one of the most common malignancies in women with high morbidity and mortality. Human papillomavirus (HPV) infection is the primary cause of cervical cancer, of which HPV 16 is the predominant. Early detection and effective treatment of cervical precancerous lesions are the key to preventing cervical cancer. Vitamin D receptor (VDR) gene polymorphism is considered to be an important cause of cancer development. Here, we studied the association of VDR polymorphisms (FOKI, BsmI, ApaI, and TaqI) in HPV16-positive cervical intraepithelial neoplasia (CIN)2+ patients. HPV16-positive patients who visited the Colposcopy Clinic of Obstetrics and Gynecology, the Second Hospital of Shanxi Medical University for biopsy due to abnormal HPV and/or Thinprep cytologic test (TCT) from September 1, 2020 to October 1, 2021 were grouped by pathological results. The fasting blood samples were collected and VDR polymorphisms were detected using TaqMan fluorescent probes, and the three sites of BsmI-ApaI-TaqI were subjected to haplotype analysis. FOKI ff genotype (OR = 2.01 ; 95% CI = 1.12 − 3.59 ; p = 0.019) and f allele (OR = 1.48 ; 95% CI = 1.10 − 1.98 ; p = 0.009) were found to be associated with the risk of CIN2+. TaqI Tt genotype (OR = 2.03 ; 95% CI = 1.20 − 3.43 ; p = 0.008), tt genotype (OR = 2.09 ; 95% CI = 1.09 − 4.02 ; p = 0.028), and t allele (OR = 1.35 ; 95% CI = 1.01 − 1.80 ; p = 0.041) were associated with the risk of CIN2+. No haplotype was associated with CIN2+ risk. According to the results, FOKI and TaqI polymorphisms are associated with CIN2+ risk. [ABSTRACT FROM AUTHOR]

The objective of the current study was to look at the levels of blood micro ribonucleic acid- (miR-) 497, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 24-2, and hepatitis B surface antigen (HBsAg) in patients with colorectal cancer (CRC), as well as the clinical importance of these markers in CRC patients. The serum levels of miR-497, CEA, CA24-2, and HBsAg were compared between 60 patients with CRC (observation group) and another 60 patients with colorectal polyps (control group). The 4 indicators in patients with lymph node metastasis and liver metastasis were compared. The diagnostic effects of 4 detection methods and the combined detection were analyzed, and the influence of 4 indicators on the 5-year cumulative survival rate of patients was discussed. The results showed that the serum levels of miR-497 and HBsAg were lower, and the levels of CEA and CA24-2 were higher in the observation group (P < 0.05). The combined detection had the best diagnostic effect, and CEA alone had the best prediction effect. The serum level of miR-497 was significantly lower in patients with lymphatic metastasis, with the significantly higher levels of CEA and CA24-2 (P < 0.05). The HBsAg level of patients with liver metastases was greatly lower than that of patients without liver metastases (P < 0.05). The 5-year cumulative survival rate of patients with high levels of CEA and CA24-2 was significantly lower than that of patients with low level of CEA. The 5-year cumulative survival rate was lower in patients with low level of HBsAg, but the difference was small. The 5-year cumulative survival rate of patients with elevated serum miR-497 was observably lower. In conclusion, combined detection could diagnose CRC more accurately. Serum miR-497, CEA, and CA24-2 were important in the diagnosis of lymph node metastasis of CRC. HBsAg did a better job of predicting liver metastases in CRC patients. High level of CEA significantly reduced the cumulative survival rate of CRC patients and could predict the long-term survival rate of patients. Serum levels of miR-497, CEA, CA24-2, and HBsAg played a positive role in the diagnosis and evaluation of CRC and could identify lymph node and liver metastases, having a high clinical guidance value. [ABSTRACT FROM AUTHOR]

Aim. To explore the association between the serum C1q/tumor necrosis factor-related protein 9 (CTRP9) and the formation of coronary collateral circulation in obstructive coronary artery disease (CAD). Methods. A total of 206 patients who underwent coronary angiography at Beijing Anzhen Hospital and had epicardial arteries with at least 95% stenotic lesion were enrolled. Blood samples were taken after an overnight fasting before the coronary angiography. Serum CTRP9 level was measured using commercial enzyme linked immunosorbent assay (ELISA) kit. The development of coronary collateralization was determined according to the Rentrop classification system. Rentrop score 0-1 was graded as impaired or less-developed coronary collateralization (n = 54) while the Rentrop score 2-3 was defined as well-developed collateralization (n = 152). Results. Serum CTRP9 level was significantly higher in well-developed collateralization and diabetes groups (P < 0.001). To further explore the association between the CTRP9 level and coronary collateralization, the enrolled participants were divided into 3 tertiles according to the serum CTRP9 level. The prevalence of impaired coronary collateralization decreased stepwise with the increasing CTRP9 tertiles (P for trend <0.001). Multivariate regression analysis showed that the serum CTRP9 is independently associated with well-developed collateralization, with an OR (95% CI) of 4.49 (1.75-11.55) and 8.98 (2.75-29.35) in the tertiles 2 and 3, respectively. The following subgroup and receiver-operating characteristic (ROC) analysis also indicated that the diagnostic value of serum CTRP9 level for detecting the formation of collateralization persisted only in nondiabetic participants. Lastly, adding the serum CTRP9 into the baseline model could increase the diagnostic value of established model consisting of relevant factor for the discrimination of well-developed collateralization only in the nondiabetic group (P = 0.046). Conclusions. Serum CTRP9 reflects well-developed coronary collateralization in nondiabetic patients with obstructive CAD, and CTRP 9 level ≥ 1.217 indicated a greater chance to forming well-developed coronary collaterals. [ABSTRACT FROM AUTHOR]

Background. Age-related hearing impairment (ARHI) is considered an unpreventable disorder. We aimed to detect specific genetic variants that are potentially related to ARHI via genome-wide association study (GWAS). Methods. A sample of 131 dizygotic twins was genotyped for single-nucleotide polymorphism- (SNP-) based GWAS. Gene-based test was performed using VEGAS2. Pathway enrichment analysis was conducted by PASCAL. Results. The twins are with a median age of 49 years, of which 128 were females and 134 were males. rs6633657 was the only SNP that reached the genome-wide significance level for better ear hearing level (BEHL) at 2.0 kHz (P = 1.19 × 10 − 8 ). Totally, 9, 10, 42, 7, 17, and 5 SNPs were suggestive evidence level for (P < 1 × 10 − 5 ) BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and pure tone average (PTA), respectively. Several promising genetic regions in chromosomes (near the C20orf196, AQPEP, UBQLN3, OR51B5, OR51I2, OR52D1, GLTP, GIT2, and PARK2) nominally associated with ARHI were identified. Gene-based analysis revealed 165, 173, 77, 178, 170, and 145 genes nominally associated with BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and PTA, respectively (P < 0.05). For BEHLs at 0.5, 1.0, and 2.0 kHz, the main enriched pathways were phosphatidylinositol signaling system, regulation of ornithine decarboxylase, eukaryotic translation initiation factor (EIF) pathway, amine compound solute carrier (SLC) transporters, synthesis of phosphoinositides (PIPS) at the plasma membrane, and phosphatidylinositols (PI) metabolism. Conclusions. The genetic variations reported herein are significantly involved in functional genes and regulatory domains that mediate ARHI pathogenesis. These findings provide clues for the further unraveling of the molecular physiology of hearing functions and identifying novel diagnostic biomarkers and therapeutic targets of ARHI. [ABSTRACT FROM AUTHOR]

Objective. Multiple genes have been identified to cause dilated cardiomyopathy (DCM). Nevertheless, there is still a lack of comprehensive elucidation of the molecular characteristics for DCM. Herein, we aimed to uncover putative molecular features for DCM by multiomics analysis. Methods. Differentially expressed genes (DEGs) were obtained from different RNA sequencing (RNA-seq) datasets of left ventricle samples from healthy donors and DCM patients. Furthermore, protein-protein interaction (PPI) analysis was then presented. Differentially methylated genes (DMGs) were identified between DCM and control samples. Following integration of DEGs and DMGs, differentially expressed and methylated genes were acquired and their biological functions were analyzed by the clusterProfiler package. Whole exome sequencing of blood samples from 69 DCM patients was constructed in our cohort, which was analyzed the maftools package. The expression of key mutated genes was verified by three independent datasets. Results. 1407 common DEGs were identified for DCM after integration of the two RNA-seq datasets. A PPI network was constructed, composed of 171 up- and 136 downregulated genes. Four hub genes were identified for DCM, including C3 (degree = 24), GNB3 (degree = 23), QSOX1 (degree = 21), and APOB (degree = 17). Moreover, 285 hyper- and 321 hypomethylated genes were screened for DCM. After integration, 20 differentially expressed and methylated genes were identified, which were associated with cell differentiation and protein digestion and absorption. Among single-nucleotide variant (SNV), C>T was the most frequent mutation classification for DCM. MUC4 was the most frequent mutation gene which occupied 71% across 69 samples, followed by PHLDA1, AHNAK2, and MAML3. These mutated genes were confirmed to be differentially expressed between DCM and control samples. Conclusion. Our findings comprehensively analyzed molecular characteristics from the transcriptome, epigenome, and genome perspectives for DCM, which could provide practical implications for DCM. [ABSTRACT FROM AUTHOR]

Endometrial cancer is one of the most common malignant tumors, lowering the quality of life among women worldwide. Autophagy plays dual roles in these malignancies. To search for prognostic markers for endometrial cancer, we mined The Cancer Genome Atlas and the Human Autophagy Database for information on endometrial cancer and autophagy-related genes and identified five autophagy-related long noncoding RNAs (lncRNAs) (LINC01871, SCARNA9, SOS1-IT1, AL161618.1, and FIRRE). Based on these autophagy-related lncRNAs, samples were divided into high-risk and low-risk groups. Survival analysis showed that the survival rate of the high-risk group was significantly lower than that of the low-risk group. Univariate and multivariate independent prognostic analyses showed that patients' age, pathological grade, and FIGO stage were all risk factors for poor prognosis. A clinical correlation analysis of the relationship between the five autophagy-related lncRNAs and patients' age, pathological grade, and FIGO stage was also per https://orcid.org/0000-0001-7090-1750 formed. Histopathological assessment of the tumor microenvironment showed that the ESTIMATE, immune, and stromal scores in the high-risk group were lower than those in the low-risk group. Principal component analysis and functional annotation were performed to confirm the correlations. To further evaluate the effect of the model constructed on prognosis, samples were divided into training (60%) and validation (40%) groups, regarding the risk status as an independent prognostic risk factor. A prognostic nomogram was constructed using patients' age, pathological grade, FIGO stage, and risk status to estimate the patients' survival rate. C-index and multi-index ROC curves were generated to verify the stability and accuracy of the nomogram. From this analysis, we concluded that the five lncRNAs identified in this study could affect the incidence and development of endometrial cancer by regulating the autophagy process. Therefore, these molecules may have the potential to serve as novel therapeutic targets and biomarkers. [ABSTRACT FROM AUTHOR]

Objective. To investigate the predictive factors associated with rapid progressive chronic kidney disease (CKD) in patients with primary glomerular disease (PGD). Methods. Baseline data, clinical biochemistry, laboratory data, and imaging data were collected from 112 PGD patients in CKD stages 3 and 4 who were hospitalized at the Third Xiangya Hospital. Patients were divided into rapid progression group (Group R) and no rapid progression group (NR) according to the definition of rapid progression of CKD. Results. The age, systolic blood pressure (SBP), serum β2-microglobulin (sβ2-MG), urinary α1-microglobulin (uα1-MG), and cardiothoracic ratio (CTR) of the R group were significantly higher than the NR group. However, the size of the kidney, high-dense lipoprotein (HDL), hemoglobin (Hb), and hematocrit of the R group were significantly lower than the NR group (P < 0.05). Binary logistic regression analysis showed that baseline CTR, SBP, size of the kidney, and HDL were independent risk factors for rapid progression of PGD. At the end of follow-up, CTR and SBP of group R were higher than the NR group, and the size of the kidney and HDL of group R were lower than the NR group. Conclusion. Increased baseline CTR and SBP and decreased baseline HDL and renal volume could be the predictors of rapid progression in patients of PGD at the CKD stages 3 and 4. [ABSTRACT FROM AUTHOR]

Purpose. Studies on genetic alterations of the heterogenous small cell lung cancer (SCLC) are rare. We carried out the present study to clarify the genomic alterations and TMB levels of Chinese SCLC patients by whole-exome sequencing. Materials and Methods. Whole-exome sequencing by next-generation sequencing technique was implemented on twenty SCLC samples. Significant somatic mutations and copy number variations were screened, followed by comparison with the data extracted from COSMIC. Besides, altered signaling pathways were examined in order to figure out actionable targets. Results. A total of 8,062 nonsynonymous mutations were defined. The number of mutations for each case ranged from 98 to 864. As for base substitutions, a total of 15,817 substitutions were detected with C > A conversion which was correlated to smoking occupying 25.57%. The TMB values ranged from 2.51/Mb to 22.1/Mb with a median value of 9.95/Mb. RB1 was the most frequently mutated gene altered in 18 (90%) cases, followed by TP53 altered in 17 (85%) cases. Other commonly changed genes were PTEN, and RBL1, with frequencies of 55% and 50%, respectively. SOX2 significantly amplified in 6 (30%) cases and MYCN amplified in 1 (5%) patient. Notch signaling pathway and PI3K/AKT/mTOR signaling pathway were universally and significantly changed. Major genomic alterations were in consistency with data from COSMIC, but frequencies of less common mutations were different. Conclusion. TP53 and RB1 inactivations were universally detected in SCLC. The Notch and PI3K/AKT/mTOR signaling pathways were both significantly altered, implying potential actionable targets. [ABSTRACT FROM AUTHOR]