Risk assessment and triage strategy of cervical cancer primary screening on HPV integration status:5-year follow-up of a prospective cohort study

Objective:We investigated the relation between man papillomavirus(HPV)integration status and the immediate risk of cervical intraepithelial neoplasia(CIN),as well as the triage strategy based on HPV integration test.Methods:4086 women aged 20 to 65 years in China were enrolled in 2015 for a prospective,population-based,clinical observational study to evaluate the triage performance of HPV integration.Cervical exfoliated cells were collected for HPV testing and cytologic test.If high-risk HPV was positive,HPV integration test was performed at baseline,2-year and 5-year follow-up.Results:At baseline,HPV integration was positively correlated with the severity of cervical pathology,ranging from 5.0%(15/301)in normal diagnosis,6.9%(4/58)in CIN1,31.0%(9/29)in CIN2,70%(14/20)in CIN3,and 100%(2/2)in cervical cancer(P<0.001).Compared with cytology,HPV integration exhibits comparable sensitivity and negative predictive value for the diagnosis of CIN3+,higher specificity(92.8%[90.2%-95.4%]vs.75.5%[71.2%-79.8%],P<0.001)and higher positive predictive value(36.4%[22.1%-50.6%]vs.15.2%[8.5%-21.8%],P<0.001).HPV integration testing strategy yielded a significantly lower colposcopy referral rate than cytology strategy(10.7%[44/410]vs.27.3%[112/410],P<0.001).The HPV integration-negative group exhibited the lowest immediate risk for CIN3+(1.6%)and accounted for the largest proportion of the total population(89.3%),when compared with the normal cytology group(risk,1.7%;proportion,72.7%).Conclusion:As a key molecular basis for the development of cervical cancer,HPV integration might be a promising triage strategy for HPV-positive patients.

Research Progress of Anaerobic Digestion Pretreatment of Antibiotic Waste

Anaerobic digestion is one of the effective ways to dispose of antibiotic pharmaceutical waste. However,the inhibition of antibiotics on anaerobic fermentation microorganisms seriously hinders the normal physiological activities of anaerobic microorganisms and then affects the efficiency of anaerobic digestion. In order to solve this problem,related scholars have done a lot of research. It has been found that pretreatment of anaerobic microorganisms and antibiotic pharmaceutical waste can significantly improve the efficiency of anaerobic digestion. In this paper,the current feasible pretreatment methods were summarized,and the application of different pretreatment methods was analyzed to provide reference for improving pretreatment methods and improving anaerobic biological treatment ability of antibiotic waste.

RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B

Long non-coding RNAs(lncRNAs)play an indispensable role in the occurrence and development of ovarian cancer(OC).However,the potential involvement of lncRNAs in the progression of OC is largely unknown.To investigate the detailed roles and mechanisms of RAD51 homolog B-antisense 1(RAD51B-AS1),a novel lncRNA in OC,reverse transcription-quantitative polymerase chain reaction(RT-qPCR)was performed to verify the expression of RAD51B-AS1.Cellular proliferation,metastasis,and apoptosis were detected using the cell counting kit-8(CCK-8),colony-formation,transwell,and flow cytometry assays.Mouse xenograft models were established for the detection of tumorigenesis.The results revealed that RAD51B-AS1 was significantly upregulated in a highly metastatic human OC cell line and OC tissues.RAD51B-AS1 significantly increased the proliferation and metastasis of OC cells and enhanced their resistance to anoikis.Biogenetics prediction analysis revealed that the only target gene of RAD51B-AS1 was RAD51B.Subsequent gene function experiments revealed that RAD51B exerts the same biological effects as RAD51B-AS1.Rescue experiments demonstrated that the malignant biological behaviors promoted by RAD51B-AS1 overexpression were partially or completely reversed by RAD51B silencing in vitro and in vivo.Thus,RAD51B-AS1 promotes the malignant biological behaviors of OC and activates the protein kinase B(Akt)/B cell lymphoma protein-2(Bcl-2)signaling pathway,and these effects may be associated with the positive regulation of RAD51B expression.RAD51B-AS1 is expected to serve as a novel molecular biomarker for the diagnosis and prediction of poor prognosis in OC,and as a potential therapeutic target for disease management.

Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervical cancer:a randomized,non-inferiority,multicenter trial

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB–IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415–1.757;P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.

The ZBTB24-CDCA7 axis regulates HELLS enrichment at centromeric satellite repeats to facilitate DNA methylation

Dear Editor,Immunodeficiency,centromeric instability,and facial anomalies(ICF)syndrome is a rare autosomal recessive disorder characterized by antibody deficiency,facial dysmorphism,failure to thrive,and mental retardation.Patients with ICF syndrome suffer from recurrent and often fatal infections in early childhood.A hallmark of ICF syndrome is loss of DNA methylation in special genomic regions,most notably satellite repeats at centromeric regions,which leads to heterochromatin decondensation and chromosomal abnormalities in lymphocytes(Ehrlich et al.,2008).

Chemotherapy initiation with single-course methotrexate alone or combined with dactinomycin versus multi-course methotrexate for low-risk gestational trophoblastic neoplasia: a multi-centric randomized clinical trial

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia(GTN).In this trial (NCT01823315),276 patients were analyzed.Patients were allocated to three initiated regimens:single-course methotrexate(MTX),single-course MTX+dactinomycin(ACTD),and multi-course MTX(control arm).The primary endpoint was the complete remission(CR)rate by initial drug(s).The primary CR rate was 64.4%with multi-course MTX in the control arm.For the single-course MTX arm,the CR rate was 35.8%by one course;it increased to 59.3%after subsequent multi-course MTX,with non-inferiority to the control(difference-5.1%,95%confidence interval(CI)-19.4%to 9.2%,P=0.014).After further treatment with multi-course ACTD,the CR rate(93.3%)was similar to that of the control(95.2%,P=0.577).For the single-course MTX+ACTD arm,the CR rate was 46.7%by one course,which increased to 89.1%after subsequent multi-course,with non-inferiority(difference 24.7%,95%CI 12.8%-36.6%,P<0.001)to the control.It was similar to the CR rate by MTX and further ACTD in the control arm(89.1%vs.95.2%,P=0.135).Four patients experienced recurrence,with no death,during the 2-year follow-up.We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.

Background-free three-dimensional selective imaging of anisotropic plasmonic nanoparticles

There is an increasing demand for advanced optical imaging techniques that can detect and resolve nanosize objects at a spatial resolution below the optical diffraction limit, especially in three-dimensional （3D） cellular environments. In this study, using a polarization-activated localization scheme based on the orientation-dependent properties of anisotropic plasmonic metal nanoparticles （MNPs）, ＂photoswitchable＂ imaging of single gold nanorods （AuNRs） was accomplished not only in two dimensions but also in three dimensions. Moreover, the Rayleigh scattering background arising from the congested subcellular structures was efficiently suppressed. Thus, we obtained the 3D distributions of both the position and the orientation of the AuNRs inside the cells and investigated their intemalization kinetics. To our knowledge, this is the first demonstration of the confocal-like 3D imaging of non-fluorescence nanoparticles with a high resolution and almost zero background. This technique is easy to implement and should greatly facilitate MNP studies and applications in biomedicine and biology.

A ribosomal gene panel predicting a novel synthetic lethality in non-BRCAness tumors

Poly(ADP-ribose)polymerase(PARP)inhibitors are one of the most exciting classes of targeted therapy agents for cancers with homologous recombination(HR)deficiency.However,many patients without apparent HR defects also respond well to PARP inhibitors/cisplatin.The biomarker responsible for this mechanism remains unclear.Here,we identified a set of ribosomal genes that predict response to PARP inhibitors/cisplatin in HR-proficient patients.PARP inhibitor/cisplatin selectively eliminates cells with high expression of the eight genes in the identified panel via DNA damage(ATM)signaling-induced pro-apoptotic ribosomal stress,which along with ATM signaling-induced pro-survival HR repair constitutes a new model to balance the cell fate in response to DNA damage.Therefore,the combined examination of the gene panel along with HR status would allow for more precise predictions of clinical response to PARP inhibitor/cisplatin.The gene panel as an independent biomarker was validated by multiple published clinical datasets,as well as by an ovarian cancer organoids library we established.More importantly,its predictive value was further verified in a cohort of PARP inhibitor-treated ovarian cancer patients with both RNA-seq and WGS data.Furthermore,we identified several marketed drugs capable of upregulating the expression of the genes in the panel without causing HR deficiency in PARP inhibitor/cisplatin-resistant cell lines.These drugs enhance PARP inhibitor/cisplatin sensitivity in both intrinsically resistant organoids and cell lines with acquired resistance.Together,our study identifies a marker gene panel for HR-proficient patients and reveals a broader application of PARP inhibitor/cisplatin in cancer therapy.