Objective To explore the clinical significance of human papillomavirus L1 capsid protein detection in cervical exfoliated cells in high-risk HPV positive women. Methods From November 2012 to June 2013,386 high-risk HPV positive (detected by hybrid capture Ⅱ) cases were enrolled as eligible women from Huzhou Maternity&Child Care Hospital and Women′s Hospital,School of Medicine, Zhejiang University. All eligible women underwent liquid-based cytology (ThinPrep) followed by colposcopy. Biopsies were taken if indicated. Cervical exfoliated cells were collected for HPV L1 capsid protein detection by immunocytochemistry. Expression of HPV L1 capsid protein in groups with different histological diagnosis were compared, and the role of HPV L1 capsid protein detection in cervical exfoliated cells in cervical lesions screening was accessed. Results Total 386 enrolled eligible women were finally diagnosed histologically as follwed:162 normal cervix, 94 low-grade squamous intraepithelial lesion (LSIL), 128 high-grade squamous intraepithelial lesion (HSIL) and 2 squamous cervical cancer (SCC). The positive expression rate of HPV L1 in HSIL+(HSIL or worse) group was significantly lower than that in LSIL-(LSIL or better) group (19.2% vs 66.4%,P=0.000). While identifying HSIL+ in HPV positive cases and compared with cytology, HPV L1 detection resulted in significant higher sensitivity (80.77%vs 50.77%,P=0.000) and negative predictive value (NPV;87.18% vs 76.47%,P=0.004), significant lower specificity (66.41% vs 81.25%,P=0.000),and comparable positive predictive value (PPV;54.97% vs 57.89%, P=0.619). To identify HSIL+in HPV-positive/cytology-negative women, the sensitivity, specificity, PPV, and NPV of HPV L1 detection were 87.50%, 61.54%, 41.18%, and 94.12%respectively, while 80.00%, 86.36%, 80.00%and 86.36%respectively in HPV-positive/atypical squamous cell of undetermined significance(ASCUS)women. Conclusions HPV L1 capsid detection in cervical exfoliated cells have a role in cervical lesions screening in high-risk HPV positive women, and may be a promising triage for high-risk HPV-positive/cytology-negative or ASCUS women.

Yunüjian （Jing Yue's Collected Works）， composed of Gypsum Fibrosum， Rehmanniae Radix Praeparata， Anemarrhenae Rhizoma， Ophiopogonis Radix， and Achyranthis Bidentatae Radix， is used for the treatment of "headache， toothache， consumptive thirst， and other diseases caused by heat and Yin deficiency in the stomach". In modern clinical settings， it has definite hypoglycemic efficacy， as it improves insulin resistance， inhibits oxidative stress and inflammatory response， and down-regulates estrogen level. It is often directly used， modified before use， combined with other formulae （Liuwei Dihuangtang， Shashen Maidongtang， Shenqi Sanjingtang， Huangqi Guizhi Wuwutang， Zengyetang， Zengye Baihutang， etc.）， or used together with western medicine （insulin， metformin， pioglitazone， glurenorm， etc.）. Modified Yunüjian can be applied for the treatment of type 2 diabetes mellitus， gestational diabetes， polycystic ovary syndrome with insulin resistance， pruritus induced by diabetes mellitus， diabetic peripheral neuropathy， diabetic nephropathy， diabetic ketoacidosis， diabetic retinopathy， and diabetic periodontitis. According to previous experiment， the protection for pancreatic islet β-cells is an important way of Yunüjian to improve diabetes mellitus. The formula can remove damaged proteins and organelles by increasing the expression of autophagy-related 2B （Atg2B）， ubiquitin-like-conjugating enzyme （Atg3）， γ-aminobutyric acid type A receptor-associated protein （GABARAP）， selective autophagy receptor （p62/SQSTM1）， etc. Moreover， it plays an active role in islet cell proliferation and apoptosis by regulating the expression of mammalian target of rapamycin （mTOR） and reducing the expression of islet β-cell autophagy gene （Beclin）. These are pivotal for maintaining the quantitative structure and functions of islet cells. The modulatory effect of Yunüjian on growth hormone-releasing peptide （ghrelin）， gastrin， and growth hormone secretagogue receptor （GHSR） mRNA expression is also the underlying mechanism for the formula to protect pancreatic β-cells. In this study， we summarized the clinical and experimental studies on the therapeutic effect of this formula on diabetes mellitus， discussed the mechanisms， and proposed suggestions on the problems， hoping to provide a reference for the clinical application and further development of Yunüjian. This study is of practical significance for the scientific interpretation of the modern connotation of Yunüjian and the expansion of its clinical application.