[Early human papillomavirus testing predicts residual/recurrent disease after LEEP risk factors for predicting residual disease in high-grade squamous cervical intraepithelial neoplasia following LEEP conization].

OBJECTIVE: To explore the risk factors for residual/recurrent disease of cervical intraepithelial neoplasia (CIN) 2 or worse after loop electrosurgical excision procedure (LEEP) and the timing point for postoperative follow-up. METHODS: 428 patients with CIN 2 or CIN 3 who were treated with LEEP were retrospectively reviewed. Postoperative follow-up was performed by Pap smear and human papillomavirus (HPV) hybrid capture 2 (HC2) testing. The definition of persistent/recurrent disease was biopsy-proven CIN 2 or worse. RESULTS: 296 patients were CIN 2 and 132 were CIN 3 among 428 patients. The positive rate of HPV HC2 before LEEP was 86.7% (371/428). During follow-up, 26 patients (6.1%) had residual/recurrent disease, the positive LEEP margin, especially the cone top status, was a significant risk factor for persistent/recurrent disease. Other factors such as age, HPV viral load [> or =100 relative light units (RLU)], and HPV typing (type 16/18 vs. other types) did not predict recurrence. HPV HC2 test at 3 months after LEEP can find all the residual/recurrent disease, the sensitivity and negative predictive value of the HPV HC2 test for residual/recurrent disease were both 100% at 3 and 6 months. CONCLUSION: The positive margin of LEEP specimen especially the cone top status was a significant risk factor for residual/recurrent disease after LEEP. HPV test at 3 months during follow-up can offer timely information about residual/recurrent disease and help for the risk control in treatment selection.

[Relationship of Human Papillomavirus Subtypes and Multiple Infection with Different Cervical Precancerous Diseases in Sichuan Province].

OBJECTIVE: To investigate the relationship of human papillomavirus (HPV) subtypes and multiple infections with different cervical precancerous diseases. METHODS: Retrospective study was done to review 1 226 patients with different cervical lesions who were pathologically diagnosed and scanned for HPV 23 subtypes with positive results from June 2006 to May 2012. These patients were divided into the following groups, chronic cervicitis, cervical condyloma, cervical intraepithelium neoplasia grade I (CIN I), grade II (CIN II), grade III (CINIII). RESULTS: There were significant differences in the proportion of HPV low risk types and high risk types between cervicitis, condyloma, CIN I group and CIN II + III groups (P<0. 05). HPV low risk types in condyloma group were mainly 6 and 11 subtype, while the other four groups were 42 and 43 subtype. The four most prevalence high risk types were 58, 16, 52,18 subtype. The infection rates of HPV16 were significant different in cervicitis (11. 0%), CIN II (20. 3%), and CIN III (20. 2%)(P<0. 01), and the infection rates of HPV58 was quite different between cervicitis (15. 9%) and CIN II (21. 4%) (P<0. 05). HPV multiple infection rate in condyloma (68. 8%) was significant different from that of cervicitis (23. 1%), CINI (26. 1%), CIN II (27. 8%) and CIN III (27. 1%) (P<0. 01); while the rest four groups were not significantly different (P>0. 05). CONCLUSION: There is a unique epidemiologic characteristic of HPV infection in Sichuan Province. The HPV low risk types were mainly 42 and 43, and high risk types were mainly 58, 16, 52, 18. It seems that HPV multiple infection is not the leading cause of progression of cervical disease.

[Expression and clinical significances of c-myb and Bax proteins in endometrial carcinoma].

OBJECTIVE: To study the expressions of c-myb and Bax proteins and their relationships with clinic-pathological characteristics in endometrial carcinoma. METHODS: The expressions of c-myb and Bax protein were detected by immunohistochemistry in 42 normal endometrial tissues and 68 endometrial carcinoma tissues. Apoptosis index was detected by TUNEL technique. RESULTS: The positive expression rates of c-myb and Bax in endometrial carcinoma were significantly higher than those in normal endometrial tissues (P < 0.05). The expressions of c-myb and Bax in low differentiated endometrial carcinoma were higher than those in high and middle differentiated endometrial carcinoma (P < 0.05). The expressions of c-myb and Bax in stage III and stage IV endometrial carcinoma were higher than those in stage I and stge II endometrial carcinoma (P < 0.05). Apoptosis index in endometrial carcinoma was higher than that in normal endometrial carcinoma. The poorer the cellular differentiation was, the higher the apoptosis index was. There was positive correlation between the expression of Bax and apoptosis index (P < 0.05), but no correlation between the expression of c-myb and apoptosis index (P > 0.05). CONCLUSION: Endometrial carcinoma has high expression of c-myb and Bax, and the expression status of both c-myb and Bax may be related to the malignant degree and prognosis of endometrial carcinoma.

Ghrelin promotes neural differentiation of adipose tissue-derived mesenchymal stem cell via AKT/mTOR and ß-catenin signaling pathways.

Adipose tissue-derived mesenchymal stem cells (ADSCs) are multipotent cells that can differentiate into various cell types. This study aimed to investigate the effect of ghrelin on the neural differentiation of rat ADSCs and underlying molecular mechanisms. Rat ADSCs were isolated and third-passage ADSCs were used in this study. The isolated ADSCs were characterized by flow cytometry analysis for MSCs' surface expression markers as evidenced by positive for CD90, CD44, and CD29 and negative for CD34, CD45, and CD11b/2f/c. The multilineage differentiation of ADSCs was confirmed by adipogenic, osteogenic, and neural differentiation. After induction of neurogenesis, the differentiated cells were identified by development of neuron-like morphology and expression of neural markers including glial fibrillary acidic protein, Nestin, MAP2, and ß-Tubulin III using immunofluorescence and western blot. Ghrelin concentration dependently elevated the proportion of neural-like cells and branching dendrites, as well as upregulated the expression of neural markers. Further, the expression of nuclear ß-catenin, p-GSK-3ß, p-AKT, and p-mTOR was increased by ghrelin, indicating an activation of ß-catenin and AKT/mTOR signaling after the ghrelin treatment. Importantly, inhibition of ß-catenin or AKT/mTOR signaling suppressed ghrelin-induced neurogenesis. Therefore, we demonstrate that ghrelin promotes neural differentiation of ADSCs through the activation of ß-catenin and AKT/mTOR signaling pathways.

Caveolin-1 plays a key role in the oleanolic acid-induced apoptosis of HL-60 cells.

Our previous study found that caveolin-1 (CAV-1) protein expression is upregulated during oleanolic acid (OA)-induced inhibition of proliferation and promotion of apoptosis in HL-60 cells. CAV-1 is the main structural protein component of caveolae, playing important roles in tumorigenesis and tumor development. It has been shown that cav-1 expression is lower in leukemia cancer cell lines SUP-B15, HL-60, THP-1 and K562 and in chronic lymphocytic leukemia primary (CLP) cells when compared with normal white blood cells, with the lowest cav-1 expression level found in HL-60 cells. To study the effects of cav-1 in HL-60 cells and the effects of cav-1 overexpression on OA drug efficacy, cav-1 was overexpressed in HL-60 cells using lentiviral-mediated transfection combined with OA treatment. The results showed that cav-1 overexpression inhibited HL-60 cell proliferation, promoted apoptosis, arrested the cell cycle in the G1 phase and inhibited activation of the PI3K/AKT/mTOR signaling pathway. Overexpression of CAV-1 also increased HL-60 cell sensitivity to OA. To further verify whether OA affects HL-60 cells via the activation of downstream signaling pathways by CAV-1, cav-1 gene expression was silenced using RNAi, and the cells were treated with OA to examine its efficacy. The results showed that after cav-1 silencing, OA had little effect on cell activity, apoptosis, the cell cycle and phosphorylation of HL-60 cells. This study is the first to show that CAV-1 plays a crucial role in the effects of OA on HL-60 cells.

Adipose-derived stem cells promote peripheral nerve repair.

INTRODUCTION: Recent evidence suggests that the implantation of bone marrow-derived mesenchymal stem cells improves peripheral nerve regeneration. In this study we aimed to investigate whether adipose-derived stem cells (ADSCs) can be used for peripheral nerve repair. MATERIAL AND METHODS: In a rat model, nerve regeneration was evaluated across a 15 mm lesion in the sciatic nerve by using an acellular nerve injected with allogenic ADSCs. The walking behaviour of rats was measured by footprint analysis, and electrophysiological analysis and histological examination were performed to evaluate the efficacy of nerve regeneration. RESULTS: Cultured ADSCs became morphologically homogeneous with a bipolar, spindle-like shape after ex vivo expansion. Implantation of ADSCs into the rat models led to (i) improved walking behaviour as measured by footprint analysis, (ii) increased conservation of muscle-mass ratio of gastrocnemius and soleus muscles, (iii) increased nerve conduction velocity, and (iv) increased number of myelinated fibres within the graft. CONCLUSIONS: Adipose-derived stem cells could promote peripheral nerve repair in a rat model. Although the detailed mechanism by which ADSCs promote peripheral nerve regeneration is being investigated in our lab, our results suggest that ADSCs transplantation represents a powerful therapeutic approach for peripheral nerve injury.