Prevalence and genotype distribution of HPV infection among women in Xiamen, China

ObjectiveThis study aimed to evaluate the prevalence of HPV and genotype distribution among female populations in Xiamen, Fujian Province, China, which can be conducive for local governments to formulate cervical cancer screening and HPV vaccine strategies.MethodsCervical swabs were collected from 47,926 participants aged 16–92 years at the Women and Children’s Hospital, Xiamen University, from November 2019 to June 2020. HPV DNA was extracted and detected using conventional PCR, followed by HPV subtype-specific hybridisation. HPV infection rates based on different groups were compared using the χ2 test. HPV prevalence and the corresponding 95% confidence intervals (95% CI) were calculated using SPSS 19.0.ResultsThe overall HPV prevalence among the 47,926 cervical swabs that were analysed was 15.13%, of which single, double, and multiple infections accounted for 76.83, 16.70 and 6.47%, respectively. The age-specific prevalence of HPV infection presented a “U” curve with a HPV prevalence peak observed in women aged <20 years. The gynaecology clinic group had significantly higher HPV positive rates than the health examination group (p < 0.001). The five most common HR-HPV subtypes in Xiamen were HPV52, 58, 16, 51, and 39 (2.69, 1.63, 1.23, 1.05, and 0.98%, respectively). The five most common LR-HPV subtypes were HPV54, 61, 81, 70, 34, and 84 (0.92, 0.86, 0.71, 0.45 and 0.35%, respectively).ConclusionOur findings demonstrate that the 9-valent HPV vaccine is recommended for regular immunisation in Xiamen. It is necessary for elderly women to participate in HPV screening to decrease the morbidity and mortality of cervical cancer

Atypical radio pulsations from magnetar SGR 1935+2154

Magnetars are neutron stars with extremely strong magnetic fields, frequently powering high-energy activity in X-rays. Pulsed radio emission following some X-ray outbursts have been detected, albeit its physical origin is unclear. It has long been speculated that the origin of magnetars' radio signals is different from those from canonical pulsars, although convincing evidence is still lacking. Five months after magnetar SGR 1935+2154's X-ray outburst and its associated Fast Radio Burst (FRB) 20200428, a radio pulsar phase was discovered. Here we report the discovery of X-ray spectral hardening associated with the emergence of periodic radio pulsations from SGR 1935+2154 and a detailed analysis of the properties of the radio pulses. The complex radio pulse morphology, which contains both narrow-band emission and frequency drifts, has not been seen before in other magnetars, but is similar to those of repeating FRBs - even though the luminosities are many orders of magnitude different. The observations suggest that radio emission originates from the outer magnetosphere of the magnetar, and the surface heating due to the bombardment of inward-going particles from the radio emission region is responsible for the observed X-ray spectral hardening.Comment: 47 pages, 11 figure

PRSS8 is Downregulated and Suppresses Tumour Growth and Metastases in Hepatocellular Carcinoma

Background: Protease serine 8 (PRSS8), a trypsin-like serine peptidase, has been shown to function as a tumour suppressor in various malignancies. The present study aimed to investigate the expression pattern, prognostic value and the biological role of PRSS8 in human hepatocellular carcinoma (HCC). Methods: PRSS8 expression in 106 HCC surgical specimens was examined by Real-time polymerase chain reaction (PCR) and immunohistochemistry, and its clinical significance was analysed. The role of PRSS8 in cell proliferation, apoptosis and invasion were examined in vitro and in vivo. Results: PRSS8 mRNA and protein expression were decreased in most HCC tumours from that in matched adjacent non-tumour tissues. Low intratumoral PRSS8 expression was significantly correlated with poor overall survival (OS) in patients with HCC (P = 0.001). PRSS8 expression was an independent prognostic factor for OS (hazard ratio [HR] = 1.704, P = 0.009). Furthermore, restoring PRSS8 expression in high metastatic HCCLM3 cells significantly inhibited cell proliferation and invasion. In contrast, silencing PRSS8 expression in non-metastatic HepG2 cells significantly enhanced cell growth and invasion. Moreover, our in vivo data revealed that attenuated PRSS8 expression in HepG2 cells greatly promoted tumour growth, while overexpression of PRSS8 remarkably inhibited tumour growth in an HCCLM3 xenograft model. Enhanced cell growth and invasion ability mediated by the loss of PRSS8 expression was associated with downregulation of PTEN, Bax and E-cadherin and an upregulation in Bcl-2, MMP9 and N-cadherin. Conclusions: Our data demonstrate that PRSS8 may serve as a tumour suppressor in HCC progression, and represent a valuable prognostic marker and potential therapeutic target for HCC

Salinomycin triggers endoplasmic reticulum stress through ATP2A3 upregulation in PC-3 cells

Abstract Background Salinomycin is a monocarboxylic polyether antibiotic and is a potential chemotherapy drug. Our previous studies showed that salinomycin inhibited cell growth and targeted CSCs in prostate cancer. However, the precise target of salinomycin action is unclear. Methods In this work, we analyzed and identified differentially expressed genes (DEGs) after treatment with or without salinomycin using a gene expression microarray in vitro (PC-3 cells) and in vivo (NOD/SCID mice xenograft model generated from implanted PC-3 cells). Western blotting and immunohistochemical staining were used to analyze the expression of ATP2A3 and endoplasmic reticulum (ER) stress biomarkers. Flow cytometry was used to analyze the cell cycle, apoptosis and intracellular Ca2+ concentration. Results A significantly upregulated gene, ATPase sarcoplasmatic/endoplasmatic reticulum Ca2+ transporting 3 (ATP2A3), was successfully identified. In subsequent studies, we found that ATP2A3 overexpression could trigger ER stress and exert anti-cancer effects in PC-3 and DU145 cells. ATP2A3 was slightly expressed, but the ER stress biomarkers showed strong staining in prostate cancer tissues. We also found that salinomycin could trigger ER stress, which might be related to ATP2A3-mediated Ca2+ release in PC-3 cells. Furthermore, we found that salinomycin-triggered ER stress could promote apoptosis and thus exert anti-cancer effects in prostate cancer cells. Conclusion This study demonstrates that ATP2A3 might be one of the potential targets for salinomycin, which can inhibit Ca2+ release and trigger ER stress to exert anti-cancer effects

DataSheet1_Evaluation of strategies for identification of infants with pathogenic glucose-6-phosphate dehydrogenase variants in China.docx

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which is caused by pathogenic variants of G6PD that result in decreased G6PD activity, is an X-linked inherited inborn error of metabolism that occurs worldwide. Individuals with G6PD deficiency and heterozygous females with normal G6PD activity (i.e., all individuals with pathogenic G6PD variants) are at risk of developing hemolytic anemia under increased oxidative challenge. However, this risk can be minimized by timely diagnosis. Currently, two assays are used to diagnose G6PD deficiency in China: evaluation of enzymatic activity and targeted genotyping. In terms of identification of all individuals with pathogenic G6PD variants, the performance and cost of different diagnostic strategies (isolated or combined evaluation of G6PD activity and G6PD genotyping) can vary, and these factors should be comprehensively evaluated. In this study, we examined 555 infants (437 males and 118 females) who were positive for the newborn screening of G6PD deficiency. We first evaluated the diagnostic performances of enzymatic testing and targeted genotyping. Both assays attained 100% specificities and positive predictive values for both male and female infants. In contrast, the sensitivities and negative predictive values (NPVs) of the diagnostic tests were different for male and female infants. For male infants, the sensitivities were 99.8 and 98.3%, and the NPVs were 94.1% and 69.6%, for enzymatic testing and targeted genotyping, respectively. For female infants, the sensitivities were 62.5% and 97.9%, and the NPVs were 37.9% and 91.7%, for enzymatic testing and targeted genotyping, respectively. We also evaluated the cost of the five different diagnostic strategies. The combination of G6PD activity testing of all infants, followed by genotyping of female infants with normal G6PD activity, attained high diagnostic sensitivity (99.8%) at a low cost (8.60 USD per diagnosed case). In the future, simultaneous examination of G6PD activity and whole-exon or whole-gene G6PD sequencing could become a standard clinical practice. Our data provide references for clinical practice on the standardization of current and future interventions for G6PD deficiency in China.</p

Single-component versus multicomponent dietary goals for the metabolic syndrome: a randomized trial

BACKGROUND: Few studies have compared diets to determine whether a program focused on 1 dietary change results in collateral effects on other untargeted healthy diet components. OBJECTIVE: To evaluate a diet focused on increased fiber consumption versus the multicomponent American Heart Association (AHA) dietary guidelines. DESIGN: Randomized, controlled trial from June 2009 to January 2014. (ClinicalTrials.gov: NCT00911885). SETTING: Worcester, Massachusetts. PARTICIPANTS: 240 adults with the metabolic syndrome. INTERVENTION: Participants engaged in individual and group sessions. MEASUREMENTS: Primary outcome was weight change at 12 months. RESULTS: At 12 months, mean change in weight was -2.1 kg (95% CI, -2.9 to -1.3 kg) in the high-fiber diet group versus -2.7 kg (CI, -3.5 to -2.0 kg) in the AHA diet group. The mean between-group difference was 0.6 kg (CI, -0.5 to 1.7 kg). During the trial, 12 (9.9%) and 15 (12.6%) participants dropped out of the high-fiber and AHA diet groups, respectively (P = 0.55). Eight participants developed diabetes (hemoglobin A1c level \u3e /=6.5%) during the trial: 7 in the high-fiber diet group and 1 in the AHA diet group (P = 0.066). LIMITATIONS: Generalizability is unknown. Maintenance of weight loss after cessation of group sessions at 12 months was not assessed. Definitive conclusions cannot be made about dietary equivalence because the study was powered for superiority. CONCLUSION: The more complex AHA diet may result in up to 1.7 kg more weight loss; however, a simplified approach to weight reduction emphasizing only increased fiber intake may be a reasonable alternative for persons with difficulty adhering to more complicated diet regimens. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute