2021年 · 第101卷第26期

Cervical cancer screening with high-risk human papillomavirus (hrHPV) testing is effective in reducing cervical cancer morbidity and mortality, but only clinically validated human papillomavirus (HPV) tests can be used for cervical cancer screening. In 2020, there were at least 254 different HPV tests worldwide, of which more than 90% lacked regulatory evaluation or were not clinically validated. Based on this, the study evaluated the current HPV detection methods with the second-generation hybrid capture method (HC2) recommended by the international validation standard (Meijer-2009) and the PCR-enzyme immunoassay (PCR-EIA) with GP5+ /6+ as the primer as the standard control, and updated the list of hrHPV detection methods that met the international validation standard (Meijer-2009) on the basis of the 2015 systematic review.

With advances in technology, more and more genes associated with non-syndromic deafness (hearing loss as the only obvious clinical manifestation) have been discovered. Among them, autosomal dominant genes account for about 20%. In this study, a whole exome sequencing (WES) approach was used to genetically analyze 863 unrelated Chinese to identify three possible novel variants in the MAP1B gene encoding highly conserved microtubule-associated proteins in three unrelated Chinese lineages (c.4198A>G, p.1400S>G; c.2768T>C, p.923I>T; c.5512T>C, p.1838F>L). Since the p.1400S>G, p.923I>T and p.1838F>L mutations are located at highly conserved MAP1B residues, they affect the extension of axons and other functions by acting on the microtubule system, especially Ser1400 in the MTA domain of MAP1B is located at a highly conserved phosphorylation site necessary for the function of embryonic cortical neurons. According to this, the authors hypothesize that the replacement of Ser1400 with glycine can lead to insufficient phosphorylation of MAP1B, which can lead to neuronal dysfunction. To elucidate the pathophysiological mechanism of the MAP1B mutation, the authors obtained induced pluripotent stem cells (iPSCs) from 1 member of a Chinese Han family bearing the MAP1B p.1400S>G mutation and a control group, and subsequently differentiated auricular sensory neuron-like (OSN-like) cells from these iPSCs. The effects of MAP1B p.1400S>G mutation on phosphorylation activity, morphology and electrophysiological characteristics of these cochlear neuron-like cells were evaluated. The results showed that the iPSCs of both mutant individuals and control group could be induced to differentiate into auditory nerve precursor cells, but the expression of MAP1B in the neurons of mutant individuals was significantly lower than that of control group. The axon length of OSN-like cells obtained by induced differentiation of mutant individual cells was 30% shorter than that of control cells. Further electrophysiological experiments demonstrated that MAP1B mutation affected the functional maturation of OSN-like cells. And CRISPR/Cas9 technology can repair the abnormal cells of mutant individuals to function normally. Finally, the authors used CRISPR/Cas9 technology to reproduce the abnormal morphology and dysfunction of Osn-like cells of patients and the hearing impairment phenotype of patients using MAP1B knockout mice. The experimental results showed that MAP1B knockout did not significantly affect the survival of hair cells in the inner ear of mice, but significantly affected the maturation of neurons and axon extension in the spiral ganglion of inner ear, which impaired the hearing of mice. In summary, this study skillfully and rigorously discovered a new deafness-related gene locus using a variety of techniques.

In order to actively respond to the major public health challenge of cervical cancer, the World Health Organization (WHO) released the Global Strategy for Accelerating the Elimination of Cervical Cancer in 2020 and proposed phased goals to be achieved by 2030. Human papillomavirus (HPV) vaccination coverage is an important key indicator. In order to understand the current status of HPV vaccine immunization program inclusion and vaccination coverage in various countries around the world, and to provide data support for the realization of the strategy of eliminating cervical cancer, WHO and the United Nations Children's Fund (UNICEF) used the immune system performance data reported by countries through the WHO/UNICEF joint report form from 2010 to 2019 to analyze the implementation effect of HPV vaccination programs and the vaccination coverage of the target population. As of June 2020, 55% (107/194) of WHO member countries included HPV vaccines in national or regional immunization programs, with the Americas (85%) and Europe (77%) being the regions with the highest proportion of countries with HPV vaccines included in immunization programs. In 2019, the number of countries that included HPV vaccines in their immunization programs reached a historical peak, with low-and middle-income countries (LMICs) accounting for 14/16. It is estimated that approximately 15% of girls completed the full course of HPV vaccination in 2019, with a first dose rate of 20%. In countries where the HPV vaccine has been included in the immunization programme, only 53% of girls aged 9 to 15 have completed the full course of vaccination. The current global HPV vaccination program has a first-dose coverage of 67% and a full-course coverage of 53%. Among them, the average first-dose vaccination rate of LMICs is higher than that of high-income countries (HICs), but its full-course vaccination rate is lower than that of HICs due to the high shedding rate. Of the 87 countries where HPV vaccine full-course vaccination data are available, only 5 countries have achieved the target of 90% full-course vaccination rate, and 22 countries have achieved full-course vaccination rates above 75%. The global HPV vaccination coverage of school-age girls is still far behind the phased target of eliminating cervical cancer by 2030. Therefore, we should continue to pay attention to the speed of HPV vaccine incorporation into national immunization programs, especially in countries with large populations, and further improve the implementation effect of current HPV vaccination programs.