Claudin-6 enhances the malignant progression of gestational trophoblastic neoplasm by promoting proliferation and metastasis.

PURPOSE: Choriocarcinoma (CC) is a rare and highly malignant epithelial tumour. However, the mechanism underlying its occurrence and development remains unknown. We aimed to reveal the biological significance and prognostic value of Claudin-6 (CLDN6) in gestational trophoblastic disease (GTD). PATIENTS AND METHODS: We collected clinical GTD specimens from 2011 to 2019 and measured CLDN6 gene expression by immunohistochemistry (IHC). High-throughput mRNA sequencing (RNA-seq) revealed a GTD progression-associated gene. CCK-8, wound healing, and flow cytometry assays were used to assess the biological effects of CLDN6 overexpression and knockdown. The medical records of 118 GTD patients from 2011 to 2019 were retrospectively analysed to identify correlations between CLDN6 expression and GTD patient clinical-pathological parameters; these correlations were analysed using the chi-square test and one-way ANOVA. Univariate logistic regression was used to analyse various prognostic parameters of patients with post-molar GTN. RESULTS: CLDN6 had the second highest fold change in gene expression between GTN and normal samples. CLDN6 was highly expressed in GTN tissues and CC cell lines, and silencing CLDN6 inhibited the proliferation and migration and promoted the apoptosis of CC cells. CLDN6 overexpression was significantly correlated with uterine size (p = 0.01) and ovarian cysts > 6 cm (p = 0.027), CLDN6 expression was significantly higher in HR-GTNs than in low-risk GTNs (LR-GTNs) (p = 0.008), and logistic regression analysis showed that CLDN6 expression in hydatidiform moles (HMs) was related to a high risk of developing post-molar GTN (OR = 2.393, p = 0.03). CONCLUSION: We propose that CLDN6 participates in the development of GTD and may become a new therapeutic target for CC.

Evaluation of novel compound variants of CEP290 in prenatally suspected case of Meckel syndrome through whole exome sequencing.

BACKGROUND: Meckel syndrome (MKS) is a fatal disease characterized by multisystem fibrosis during the prenatal or perinatal period. It has an autosomal recessive genetic pattern and is characterized by meningo occipital encephalocele, polycystic kidney dysplasia, polydactyly, and hepatobiliary ductal plate malformation. Germline variations in CEP290 have been shown to cause MKS4. METHODS: In this study, a 23-year-old Chinese woman who was 18 weeks pregnant was examined. The pregnancy was terminated due to occipital meningocele and enlarged cystic dysplastic kidney revealed by ultrasonography. In addition, the patient had a history of adverse pregnancy whereby the fetus presented with double kidney enlargement. Karyotype analysis and chromosomal microarray examination (CMA) were carried out using amniotic fluid samples. Whole exome sequencing (WES) was performed using tissue specimens of the aborted fetus. RESULTS: Karyotype and CMA analyses showed normal results. However, compound heterozygous mutations of CEP290 c.3175dup and CEP290 c.1201dup were detected through WES. CEP290 c.1201dup is a novel heterozygous mutation of CEP290 that has not been reported previously. CONCLUSIONS: The findings of this study provide information on the correlation between MKS phenotype and genotype in CEP290. In addition, these findings indicate that WES is an effective method for detecting genetic causes of multiple structural defects especially those showing normal karyotype and CMA results.

Aging Immune System and Its Correlation With Liability to Severe Lung Complications.

Aging is considered to be a decline in physical and physiological events that extensively affect the body's immunity, and is linked with deterioration in both innate and adaptive immune responses. The immune system exhibits profound age-associated variations, known as immunosenescence, comprising a significantly low production of B and T lymphocytes in bone marrow and thymus, a decreased function of mature lymphocytes in secondary lymphoid tissues, a decrease in the synthesis of fresh naïve T cells, and reduced activation of T cells. Elderly individuals face a greater risk for many diseases particularly respiratory diseases due to their poor response to immune challenges as vigorously as the young. The current review explored the aging immune system, highlight the mortality rates of severe lung complications, such as pneumonia, COVID-19, asthma, COPD, lung cancer, IPF, and acute lung injury, and their correlation with aging immunity. This study can be helpful in better understanding the pathophysiology of aging, immune responses, and developing new approaches to improve the average age of the elderly population.

Prevalence of Human Papillomavirus and Genotype Distribution in Pregnant and Non-Pregnant Women in China.

PURPOSE: The status of human papillomavirus (HPV) infection in pregnant and non-pregnant women in China remains unclear. This study aimed to compare the prevalence and genotype distributions of HPV between pregnant and non-pregnant women in China. PATIENTS AND METHODS: A case-control study was conducted of pregnant women during the second trimester and age-matched non-pregnant women attending the Fujian Maternity and Child Health Hospital between January 1, 2017 and December 31, 2018. Participants underwent cervical cytology testing and HPV genotyping. The genotyping test was able to identify 14 high-risk HPV (HR-HPV), four possible HR-HPV, and five low-risk HPV (LR-HPV) types. Further colposcopy and a cervical biopsy were performed if indicated. The primary outcomes were HPV prevalence and genotype distribution. RESULTS: In total, 1077 pregnant and 1077 non-pregnant women were enrolled. Compared with non-pregnant women, pregnant women had a higher prevalence of HPV (24.2% vs 14.8%), HR-HPV (20.2% vs 11.7%), and LR-HPV (8% vs 4.5%) infection. In pregnant women, the most prevalent HPV genotypes were HPV-52 (6.0%), -16 (3.5%), -58 (2.6%), -53 (2.5%), and -51 (2.5%), while in non-pregnant women the most prevalent genotypes were HPV-52 (3.6%), -81 (1.9%), -51 (1.8%), -68 (1.4%), and -16 (1.3%). In women aged ≥35 years, HR-HPV (P=0.002) and LR-HPV (P=0.001) prevalence were significantly higher in pregnant women. However, in women aged <35 years, only HR-HPV prevalence was higher in pregnant women. Pregnant and non-pregnant women with HPV-16 and HPV-58 infection had a high prevalence of high-grade squamous intra-epithelial lesions (HSIL) (HPV-16: P<0.001 and P=0.005, HPV-58: P=0.043 and P=0.005); but with other HR-HPV genotypes, only non-pregnant women had an increased HSIL prevalence. CONCLUSION: In China, the HPV prevalence is higher in pregnant women than that in non-pregnant women and is also age- and genotype-dependent. HPV-infected pregnant women aged ≥35 years and those with HPV-16 should be closely monitored to enable rapid clinical intervention.

Current Status and Prospects of Spontaneous Peritonitis in Patients with Cirrhosis.

Spontaneous bacterial peritonitis (SBP) is a common cirrhotic ascites complication which exacerbates the patient's condition. SBP is caused by gram-negative bacilli and, to a lesser extent, gram-positive cocci. Hospital-acquired infections show higher levels of drug-resistant bacteria. Geographical location influences pathogenic bacteria distribution; therefore, different hospitals in the same country record different bacteria strains. Intestinal changes and a weak immune system in patients with liver cirrhosis lead to bacterial translocation thus causing SBP. Early diagnosis and timely treatment are important in SBP management. When the treatment effect is not effective, other rare pathogens should be explored.

[Progress in research on oocytes parthenogenetic activation].

Parthenogenetic activation is a procedure that an oocyte at meiosis II stage is activated into mitosis by some chemical or physical stimulation other than a sperm and the embryo is formed in the absence of any contribution from a male gamete. The activation of oocyte is the result of calcium ion oscillations and deactivation of some cytokines such as maturation promoting factor, mitogen-activated protein kinase and cytostatic factor. Parthenogenetic activation is artificially induced by various kinds of physical and/or chemical methods. The main activation method of human oocyte is chemical methods. The rates of activation and cleavage depend on the age, origin,and culture conditions of the oocyte.