PurposeTo analyze the clinical performance of p16/Ki-67 dual-stained cytology identifying high-grade cervical intraepithelial neoplasia (CIN2+) in Chinese women.Methods1079 women attending ongoing cervical cancer screening and 211 “enriched” women aged ≥30yrs with biopsy-confirmed CIN2+ from five Chinese hospitals were enrolled during year 2014-2015. Cervical specimens were collected for high-risk human papillomavirus (HR-HPV) DNA analysis, Liquid-based cytology (LBC) and p16/Ki-67 dual staining. Colposcopy and biopsy were performed on women with any abnormal result.Resultsp16/Ki-67 positivity increased with histologic severity. It was 18.4%(183/996) in normal histology, 54.0%(34/63) in CIN1, 81.0%(34/42) in CIN2, 93.3%(111/119) in CIN3, 71.4% (5/7) in adenocarcinoma and 95.2%(60/63) in squamous cell carcinoma. Compared with the HR-HPV negatives, p16/Ki-67 expression was significantly higher in the HPV16/18 positive (OR: 35.45(95%CI: 23.35-53.84)) and other 12 HR-HPV types positive group (OR: 8.01(95%CI: 5.81-11.05). The sensitivity and specificity of p16/Ki-67 to detect CIN2+ in the entire population were 90.9% and 79.5%, respectively. In women with ASC-US and LSIL, sensitivity and specificity for detection of CIN2+ were 87.5% and 66.4%, respectively, with a referral rate of 43.8%. In women who tested positive for HR-HPV, sensitivity and specificity of dual-staining for detection of CIN2+ were 92.7% and 52.7%, respectively, and the referral rate was 68.7%.Conclusionsp16/Ki-67 dual-stained cytology provided a high sensitivity and moderate specificity to detect underlying cervical precancer and cancers in various settings, and might be considered as an efficient screening tool in China.

The Rh(II)-catalyzed formal [3+2] and [3+3] cycloadditions of 1-tosyl 1,2,3-triazoles with 2H-azirines have been developed, which enable the efficient synthesis of polysubstituted 3-aminopyrroles and 1,2-dihydropyrazines, respectively. The reported [3+2] cycloaddition represents the first application of 1-sulfonyl 1,2,3-triazole as a [2C]-component in relevant cycloaddition reactions.

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PurposeTo evaluate the association of p16/Ki-67 co-expression and persistence of high-risk human papillomavirus (HR-HPV) infection as well as cervical abnormalities.MethodsWe performed a 3-year cohort study among which 2498 Chinese women aged 25 to 65 years were screened by different HPV tests in 2011. 690 women who were positive at any of the tests and a random sample of 164 women with all negative results received colposcopy, cervical specimens for cobas HPV test (Roche diagnostics) were collected before colposcopy; of this group, 737 cervical specimens were collected to perform cobas, Liquid-based cytology, HPV E6 test (Arbor Vita Corporation) and p16/Ki-67 dual staining (Roche diagnostics) in 2014. Colposcopy and biopsies was performed on women with any abnormal result.ResultsCompared to women without HR-HPV persistent infection, women in the HR-HPV persistence group had a higher risk of p16/Ki-67 positive, with an adjusted Odds Ratio(OR) and 95% confidence interval (CI) of 6.29 (4.07-9.72); moreover, adjusted odds ratio for women who had HPV16/18 persistent infection was nearly 4-folder higher than women with other 12 HR-HPV persistent infection (adjusted OR = 17.15, 95% CI: 7.11-41.33 vs adjusted OR = 4.68, 95% CI: 2.89-7.58). Additionally, p16/Ki-67 positivity rate significantly increased with the severity of the cytological and histological abnormalities, and resulted strongly associated with a CIN2+ diagnosis (OR = 16.03, 95% CI: 4.46-57.59).Conclusionsp16/Ki-67 co-expressions associated strongly with HR-HPV persistence, especially with HPV16/18, and the presence of a CIN2+ lesion. Therefore, p16/Ki-67 could be considered as a suitable biomarker for cervical cancer screening, particularly in HPV-based screening programs.

The first and collective total syntheses of periconiasins A-E, a group of naturally occurring cytochalasans, were achieved by a series of rationally designed or bioinspired transformations. Salient features of the syntheses include a tandem aldol condensation/Grob fragmentation to assemble the linear polyketide-amino acid hybrid precursor, a Diels-Alder macrocylization to construct the 9/6/5 tricyclic core of periconiasins A-C, and a transannular carbonyl-ene reaction to forge the polycyclic framework of periconiasins D and E.

The pathological development of lens epithelial cells (LECs) leads to posterior capsular opacification (PCO). This study was undertaken to investigate the effects of microRNA-486-5p (miR-486-5p) on TGF-β2-induced proliferation, invasion and epithelial-mesenchymal transition (EMT) in the lens epithelial cell line SRA01/04, and to explore the underlying molecular mechanisms. The expression of miR-486-5p in TGF-β2-induced SRA01/04 cells was down-regulated, and the expression of Smad2, p-Smad2 and p-Smad3 was up-regulated. A dual-luciferase reporter assay revealed that miR-486-5p directly targets the 30'-UTR of Smad2. MiR-486-5p mimic transfection markedly down-regulated the expression levels of Smad2, thus inhibiting the expression of p-Smad2 and p-Smad3. MiR-486-5p overexpression in SRA01/04 cells markedly suppressed TGF-β2-induced proliferation and invasion, inhibited protein expression of CDK2 and CDK4, down-regulated fibronectin, α-SMA and vimentin and up-regulated E-cadherin; these effects were partly reversed by Smad2 overexpression. In short, these data show that miR-486-5p overexpression can inhibit TGF-β2-induced proliferation, invasion and EMT in SRA01/04 cells by repressing Smad2/Smad3 signalling, implying that miR-486-5p may be an effective target to interfere in the progression of PCO.

A novel rhodium(II)-catalyzed formal [3 + 2] cycloaddition of N-sulfonyl-1,2,3-triazoles with isoxazoles has been achieved that provides an efficient method for the synthesis of polysubstituted 3-aminopyrrole derivatives. An operationally simple one-pot synthesis of the titled compounds from terminal alkynes, tosyl azide, and isoxazoles was also developed. The presented reaction affords an illustrative example of employing 1,2,3-triazoles as the [2C]-component in relevant cycloaddition reactions.

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