Human papillomavirus infections among women with cervical lesions and cervical cancer in Yueyang, China: a cross-sectional study of 3674 women from 2019 to 2022.

PURPOSE: To investigate the distribution of the incidence and genotypes of human papillomavirus (HPV) among women with cervical cancer (CC) and precancerous cervical lesions in Yueyang City, China, to develop prevention and control strategies for CC. METHODS: A total of 3674 patients with cervical lesions and cervical cancer who attended 7 hospitals in Yueyang City between September 2019 and September 2022 were included. They included 1910 cervical intraepithelial neoplasia (CIN) I, 718 CIN II, 576 CIN II and 470 CC, respectively. The HPV genotyping of the above patients was detected by Real time-PCR in the laboratory department of each hospital. RESULTS: The total HPV prevalence was 74.69% (95% CI 73.28-76.09%) in 3674 patients. The incidence of high- and low-risk HPV was 73.46% and 7.21%, respectively. The prevalence of HPV in CIN I, CIN II, CIN III, and invasive CC (ICC) groups was 66.65% (1273/1910, 95% CI 64.53-68.77%), 80.78% (580/718, 95% CI 77.89-83.67%), 83.88% (483/576, 95% CI 80.84-86.87%), and 86.81% (408/470, 95% CI 83.74-89.88%), respectively. The top three HPV subtypes in ICC are HPV16, HPV52, and HPV58. The prevalence of HPV 16 increased with increasing disease severity, with this genotype being present in 12.57%, 20.89%, 36.98%, and 50.85% of CIN I, CIN II, CIN III, and ICC cases, respectively (p < 0.001). Single HPV infection was predominant in cervical lesions, with a prevalence of 48.50% (95% CI 46.89-50.12%). The HPV prevalence varied by age, being highest among women with ICC, CIN I, CIN II and CIN III aged ≥ 60 years, 50-59 years, 40-49 years, and 40-49 years, respectively. CONCLUSION: The prevalence of HPV in patients with cervical lesions in Yueyang City was very high, with HPV 16, 52, 58, 53, and 51 being the five most common HPV genotypes in patients with cervical lesions.

Cervical HPV infection in Yueyang, China: a cross-sectional study of 125,604 women from 2019 to 2022.

Objective: Human papillomavirus (HPV) infection is currently the main cause of cervical cancer and precancerous lesions in women. The aim of this study was to investigate the epidemiological characteristics of HPV genotypes among women in Yueyang city and to provide a basis for the prevention and treatment of cervical cancer in this city. Methods: A cross-sectional study was conducted on 125,604 women who had received treatment from eight hospitals in Yueyang city from September 2019 to September 2022. Analysis of the prevalence of HPV in patients. Results: The prevalence of HPV was 20.5% (95%CI: 20.2-20.7%), of which the high-risk type (HR-HPV) accounted for 17.5% (95%CI: 17.3-17.7%) and the low-risk type (LR-HPV) accounted for 5.0% (95%CI: 4.9-5.1%). Among the HR-HPV subtypes, the top five in prevalence, from the highest to the lowest, were HPV52 (5.1%), HPV16(2.7%), HPV58 (2.6%), HPV53 (2.4%), and HPV51 (1.7%). The main LR-HPV infection types were HPV81 (2,676 cases, OR = 2.1%; 95%CI, 2.0-2.1%). Among the infected patients, 19,203 cases (OR = 74.3%; 95%CI, 73.8-74.9%) had a single subtype, 4,673 cases (OR = 18.1%; 95%CI, 17.6-18.6%) had two subtypes, and 1957 cases (OR = 7.6%; 95%CI, 7.3-7.9%) had three or more subtypes. HPV prevalence is highest among women <25 years, 55-64 years and ≥ 65 years of age. Conclusion: The prevalence of HPV in women in Yueyang city was 20.5%, with HR-HPV being dominant. As women aged <25 years, 55-64 years, and ≥ 65 years are at a relatively higher risk, more attention should be paid to them for prevention and control of HPV infections.

Extracellular vesicles in atherosclerosis and vascular calcification: the versatile non-coding RNAs from endothelial cells and vascular smooth muscle cells.

Atherosclerosis (AS) is characterized by the accumulation of lipids, fibrous elements, and calcification in the innermost layers of arteries. Vascular calcification (VC), the deposition of calcium and phosphate within the arterial wall, is an important characteristic of AS natural history. However, medial arterial calcification (MAC) differs from intimal calcification and cannot simply be explained as the consequence of AS. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are directly involved in AS and VC processes. Understanding the communication between ECs and VSMCs is critical in revealing mechanisms underlying AS and VC. Extracellular vesicles (EVs) are found as intercellular messengers in kinds of physiological processes and pathological progression. Non-coding RNAs (ncRNAs) encapsulated in EVs are involved in AS and VC, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). The effects of ncRNAs have not been comprehensively understood, especially encapsulated in EVs. Some ncRNAs have demonstrated significant roles in AS and VC, but it remains unclear the functions of the majority ncRNAs detected in EVs. In this review, we summarize ncRNAs encapsulated in EC-EVs and VSMC-EVs, and the signaling pathways that are involved in AS and VC.

TLR9/FCRL3 regulates B cell viability, apoptosis, and antibody and IL-10 production through ERK1/2, p38, and STAT3 signaling pathways.

B cells play a role in the progression of multiple sclerosis (MS) and are closely related to Fc-receptor like-3 (FCRL3), but little is known about FCRL3 in B cells and MS. Activation of TLR9 in B cells with CpG found that CpG promoted FCRL3 expression in a dose- and time-dependent manner. CpG significantly activated ERK1/2, p38, and STAT3 pathways, and FCRL3 overexpression further promoted the activation of these pathways, while FCRL3 siRNA significantly inhibited the activation of these pathways by CpG. CpG stimulation significantly promoted the viability of B cells, inhibited cell apoptosis, and enhanced the production of antibodies and secretion of IL-10 by B cells. FCRL3 siRNA blocked most of the above regulatory effects of CpG, but promoted the further production of antibodies by B cells. FCRL3 overexpression enhanced the pro-survival, anti-apoptotic, and IL-10-inducing effects of CpG, but inhibited the effect of CpG on promoting antibody production. After adding inhibitors of ERK1/2, p38, and STAT3 pathways, respectively, the effects of CpG on promoting cell viability, antibody production, and IL-10 secretion were significantly reduced, but the anti-apoptotic effect of CpG was only affected by the blockade of STAT3 pathway. In addition, FCRL3 regulated B cell antibody and IL-10 secretion mainly through its ITIMs. These results indicate that TLR9 activation affects B cell proliferation, apoptosis, antibody production, and IL-10 secretion by upregulating FCRL3 expression, and is associated with ERK1/2, p38, and STAT3 pathways. Therefore, FCRL3 may be an important target for the diagnosis and treatment of B cell-related diseases.

FCRL3 promotes IL-10 expression in B cells through the SHP-1 and p38 MAPK signaling pathways.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that is caused by the interaction of genetic and environmental factors. Current studies have shown that Fc-receptor like-3 (FCRL3) is closely related to MS, but the specific role of FCRL3 in MS has not yet been clarified. This study further found that FCRL3 and interleukin 10 (IL-10) expression was downregulated in MS patients, but the expression of these proteins was higher in the remission phase than that in the acute phase. The C allele of rs7528684 was associated with MS, and the CC genotype could lead to the upregulation of FCRL3 expression and the increase in IL-10 secretion. Further in vitro experiments with B cells found that lipopolysaccharide (LPS) promoted FCRL3 expression in a dose- and time-dependent manner, thereby promoting IL-10 secretion. LPS regulated Src homology region 2 domain-containing phosphatase-1 (SHP-1) expression and p38 mitogen-activated protein kinase (MAPK) pathway activation through FCRL3, and FCRL3 upregulated the SHP-1 expression and p38 phosphorylation levels. When SHP-1 small interfering RNA or a p38 pathway inhibitor was added, the effect of FCRL3 on IL-10 secretion was significantly inhibited. In addition, FCRL3 inhibited the secretion of inflammatory factors (tumor necrosis factor-α, IL-1ß, IL-6, and IL-8); after inhibiting the expression of IL-10, the abovementioned effects of FCRL3 were blocked. These results suggest that FCRL3 can activate the SHP-1 and p38 MAPK pathways and then promote the secretion of IL-10 in B cells, thus inhibiting the secretion of inflammatory factors. Therefore, FCRL3 may play an immunoprotective role in MS, and it will be an effective target for the diagnosis and treatment of MS.

Frequent KRAS mutations in oncocytic papillary renal neoplasm with inverted nuclei.

AIMS: Papillary renal neoplasm with reverse polarity (PRNRP) is a newly documented rare tumour type. Its molecular pathological features have thus far been very little studied. METHODS AND RESULTS: There were 13 PRNRP cases including 3 The Cancer Genome Atlas (TCGA) cases and our 10 cases in this study. The 3 TCGA cases were found by a combined analysis of GATA3 mRNA expression levels and digital slides from the TCGA papillary renal cell carcinoma project. KRAS codon 12 mutations were identified in the three PRNRPs from TCGA. Of our 10 PRNRP cases, the mutations were also discovered using Sanger sequencing in seven (77.8%) of nine cases with available DNA, where KRAS p.G12V (n = 3), p.G12D (n = 2), p.G12R (n = 1) and p.G12C (n = 1) alterations were found. PRNRP shared similar gene expression profiles with renal distal tubules via an interprofile correlation analysis. Gene set enrichment analysis revealed that genes involved in 'KEGG aldosterone regulated sodium reabsorption' or 'hallmark apical surface' were enriched in PRNRP. Moreover, polarised immunostaining patterns for L1CAM and EMA in the distal tubule were maintained in PRNRP. CONCLUSIONS: These results imply that the tumour potentially originates from the distal tubule, especially from the cortical collecting duct, and probably retains its cell polarity, except for nuclear inversion. We therefore propose that oncocytic papillary renal neoplasm with inverted nuclei (OPRNIN) is a better name for this tumour type. OPRNIN is a kidney site-specific KRAS mutation neoplasm different from conventional papillary renal cell carcinoma.

Combination of DNA ploidy analysis and miR-21 or miR-24 in screening malignant pleural effusion.

OBJECTIVES: The study aimed to assess the combination of DNA ploidy analysis (DPA) and the expression of microRNA-21 (miR-21) or microRNA-24 (miR-24) in the detection of malignant pleural effusion (MPE). METHODS: In this prospective research, a total of 40 samples (20 benign and 20 malignant effusions), flexural effusion exfoliated cells and cell-free miR-21 and miR-24 were collected. DPA and exfoliative cytology examinations were conducted to diagnose flexural effusion exfoliated cells. Quantitative reverse transcriptase polymerase chain reaction was carried out to measure the expressions of miR-21 and miR-24. Receiver operating characteristic curve and the area under the curve were applied to evaluate the accuracy rate of different diagnostic approaches on MPE. RESULTS: In the MPE group, DPA demonstrated a higher rate of accuracy in MPE diagnosis than exfoliative cytology. The expressions of miR-21 and miR-24 were significantly higher in MPE than in benign pleural effusion (P < 0.05). Furthermore, area under the curve, sensitivity and specificity were 0.942, 95% and 90% for the combination of miR-21 and DPA and 0.973, 100% and 80% for the union of miR-24 and DPA, respectively, representing a significant improvement in both accuracy and sensitivity. Therefore, the combination of DPA and miR-21 or miR-24 appears to be a better biomarker for discriminating MPE from benign pleural effusion. CONCLUSIONS: The combination of DPA and miR-21 or miR-24 may function as a promising diagnostic tool of MPE. Registration number: ChiCTR-TRC-14004719.