Multicentre, prospective, randomised controlled trial to evaluate hexaminolevulinate photodynamic therapy (Cevira) as a novel treatment in patients with high-grade squamous intraepithelial lesion: APRICITY phase 3 study protocol

INTRODUCTION: High-risk human papilloma virus (HPV)-associated cervical cancer is the fourth most common cancer in women worldwide. Current treatments of high-grade squamous intraepithelial lesion (HSIL) of the cervix are based on invasive surgical interventions, compromising cervical competence and functionality. APRICITY is a multicentre, prospective, double-blind, randomised controlled phase 3 study further evaluating the efficacy and safety of Cevira, an integrated drug-delivery and light-delivery device for hexaminolevulinate photodynamic therapy, which shows promise as a novel, non-invasive outpatient therapy for women with HSIL. METHODS AND ANALYSIS: Patients with biopsy-confirmed HSIL histology are invited to participate in the study planned to be conducted at 47 sites in China and 25 sites in Ukraine, Russia and the European Union. The aim is to include at least 384 patients, which will be randomised to either Cevira or placebo group (2:1). All patients will be assessed 3 months after first treatment and a second treatment will be administered in patients who are HPV positive or have at least low-grade squamous intraepithelial lesion. Primary endpoint is the proportion of the responders 6 months after first treatment. Secondary efficacy and safety endpoints will be assessed at 6 months, and data for secondary performance endpoints of the Cevira device will be collected at 3 months and 6 months, in case second treatment was administered. All patients in the Cevira group will be enrolled in an open, long-term extension study for 6 months to collect additional efficacy and safety data (study extension endpoints). ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the Peking Union Medical College Hospital and Hannover Medical University, Germany. Findings will be disseminated through peer review publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04484415; clinicaltrials.gov

Selective applications of excisional surgical treatments of cervical precancers

Cervical precancers encompass high-grade squamous intraepithelial lesion and adenocarcinoma in situ. Treatment of precancerous lesions can reduce cervical cancer mortality and prevent the development of invasive cervical cancer. The choice of treatment regimen needs to follow the principle of individualization and should be based on a combination of factors, including the patient's age, fertility requirements, pregnancy status, pathological type, type of colposcopic transformation zone, patient's follow-up conditions, and the experience of the treating provider. This article presents an opinion regarding the appropriate indications for excisional surgery and total hysterectomy in the management of precancerous lesions of the cervix, with the aim of establishing standardized therapeutic approaches for the treatment of precancerous lesions of the cervix

Distribution of human papilloma virus genotype prevalence in invasive cervical carcinomas and precancerous lesions in the Yangtze River Delta area, China

Abstract Background This study aimed to provide more information for cancer prevention strategies by determining the distribution of human papilloma virus (HPV) genotype prevalence in invasive cervical carcinoma (ICC) and precancerous lesion patients in the Yangtze River Delta area in China. Methods This multi-centre descriptive cross-sectional study involves four university hospitals in the Jiangzhehu area. Women with histologically confirmed cervical intraepithelial neoplasia (CIN) 1, CIN2, CIN3 or ICC who were diagnosed and treated in the four selected hospitals between February 2012 and April 2014 were eligible for recruitment. The average age of the patients was 40.93 ± 11.87 years old, among whom the youngest was 17 years old and the oldest was 76 years old.Those with immunodeficiency diseases or a previous history of cancer or CIN were excluded. HPV genotyping was performed by a central laboratory. The distribution and age and disease specificity of the HPV genotype prevalence were analysed. Results Of the 2181 collected samples, 251 were ICC and 1930 were CIN. The mean age of cervical cancer and CIN patients was 40.93 ± 11.8 years (range, 17–76 years). The five most commonly identified HPV types in each lesion class were as follows: CIN1: 52, 58, 16, 33, and CP; CIN2: 16, 58, 52, 33, and 31; CIN3: 16, 58, 33, 52, and 31; and ICC: 16, 58, 18, 52, and 33. CIN1 had an earlier age of onset (30–40 years) than CIN2, CIN3, and cervical cancer. The age of onset of cervical cancer exhibited two peaks at 40–44 and 50–54 years of age. In all infected patients, the frequency of HPV infection with a single type was 62.9%, and with multiple types, it was 38.1%. There was no difference in the frequencies of multiple types amongst the different cervical lesions. Conclusions The most prevalent genotypes in the investigated area (52, 58, 16 and 18) justify the necessity of anti-HPV vaccination in teenagers and young girls under 24 years old in the Yangtze River Delta area in China. Infection with multiple high-risk HPV types versus single infection does not increase the risk for ≥ CIN2 in ICC development

Beam-steering metasurfaces assisted coherent optical wireless multichannel communication system

The metasurface based beam-steering devices with the advantages of large steering angles, arbitrary channels and ultra-compactness have played an important role for data allocation and exchange in the optical wireless communication. However, the current metasurface based optical wireless communication systems are mainly on intensity modulation and direct detection (IM/DD), which shows a relative lower transmission capacity, lower received optical signal-to-noise ratio (OSNR) and complexity of system. In this study, a bidirectional multichannel optical wireless system enabled by a polarization independent metasurface with coherent modulation and reception is designed and experimentally demonstrated, which exhibits exclusive 100 Gbps coherent optical signals to multiusers with their own wavelengths, 2 m free space distance and field of view of 20° × 20°. In addition, the proposed system can support optical broadcasting system with capacity of 900 Gbps. The demonstrated metasurface assisted optical wireless communication system merges the optical coherent communication techniques and emerging concept of metasurface, which reduces the complexity and cost of the system while contributing a high transmission capacity, opening a new avenue for high performance optical wireless communications

Molecular Insights of Genetic Variation in <i>Erianthus arundinaceus</i> Populations Native to China

<div><p>Background</p><p><i>E. arundinaceus</i> (Retz.) Jeswiet is a warm-season, tall-growing perennial species native to much southern portion in China. The grass has been extensively used in sugarcane breeding and is recently targeted as a bioenergy feedstock crop. However, information on the genetic structure of the Chinese wild germplasm is limited. Knowledge of genetic variation within and among populations is essential for breeding new cultivars in the species. The major objective of this study was to quantify the magnitude of genetic variation among and within natural populations in China.</p><p>Methodology/Principal Findings</p><p>In this experiment, we analyzed genetic variation of 164 individuals of 18 populations collected from natural habitats in six Chinese provinces using 20 sequence-related amplified polymorphism (SRAP) primer pairs generating 277 polymorphic bands. Among and within the populations, the percentage of polymorphic bands (<i>PPB</i>) was 80.00% and 27.07%, genetic diversity (<i>H_E</i>) was 0.245 and 0.099, effective number of alleles (<i>N_E</i>) was 1.350 and 1.170, and Shannon's information index (<i>I</i>) was 0.340 and 0.147, respectively. The populations were clustered into six groups exhibiting a high level of genetic differentiation, which was highly associated with geographic origins of respective germplasm populations, but was not significantly associated with geographic distances between the populations.</p><p>Conclusions/Significance</p><p>This is the first report indicating that large genetic variation exists in the Chinese <i>E. arundinaceus</i> germplasm based on the SRAP molecular marker analysis of native populations. The genetic structure of populations in the species has been substantially affected by geographic landforms and environments. The diverse collection will be highly valuable in genetic improvement in the species per se and likely in sugarcane.</p></div

UPGMA phenogram illustrating genetic relationships among 18 populations of <i>E. arundinaceus</i>, based on Nei's (1978) genetic distances calculated from 294 polymorphic bands.

<p>Numbers on branches indicate bootstrap values with 1000 replicates.</p

Table 2. Twenty SRAP primer pair ID, sequences, amplified bands and percent polymorphic bands.

<p>Table 2. Twenty SRAP primer pair ID, sequences, amplified bands and percent polymorphic bands.</p

Genetic diversity indices for 18 <i>E. arundinaceus</i> populations collected in China.

<p><i>N</i>p  =  polymorphic loci; <i>PPB</i>  =  percentage of polymorphic loci; <i>N</i>_O  =  number of alleles per locus; <i>N</i>_E  =  effective number of alleles per locus; <i>I</i>  =  Shannon's information index; <i>H</i>_E  =  Nei's (1973) measure of gene diversity.</p

UPGMA cluster analysis based on Nei's (1978) genetic distances among individuals.

<p>Numbers on branches indicate bootstrap values from 1000 replicates. Symbols represent populations in the cluster tree as Pop1, ○ Pop2, * Pop3, △ Pop4, • Pop5, ▾ Pop6, ▪ Pop7, Pop8, ▴ Pop9, ☆ Pop10, ⊕ Pop11, ▽ Pop12, ⧫ Pop13, ◊Pop14, ★ Pop15, ⊙ Pop16, ¤ Pop17, Pop18.</p