α-ketoglutarate preconditioning extends the survival of engrafted adipose-derived mesenchymal stem cells to accelerate healing of burn wounds.

The application of adipose-derived stem cells (ADSCs) in treating hard-to-heal wounds has been widely accepted, while the short-term survival rate remains an obstacle in stem cell therapy. The aim of this study is to investigate the effect of preconditioning ADSCs with α-ketoglutarate (α-KG) on the healing of acid burn wounds and cell survival within wounds. Preconditioning of ADSCs was performed by treating cells at passage 3 with 3.5 mM DM-αKG for 24 h. Proliferation and migration of ADSCs was examined. An acid burn wound was created on the dorsal skin of mice. Cell suspension of ADSCs (2 × 106 cells/ml), either pre-treated with α-KG or not, was injected subcutaneously around the margin of wound. At 1,4,7,10,14 days after injection, the percentage of wound closure was evaluated. Expression of pro-angiogenic factors, matrix molecules and HIF1-α in pretreated ADSCs or in wounds was evaluated by qRT-PCR and immunohistochemistry staining, respectively. The survival rate of DiO-labelled ADSCs was determined with the in vivo bioluminescent imaging system. Treating with α-KG induced an enhancement in migration of ADSCs, while their proliferation was not affected. Expression of Vegf and Fgf-2 was significantly increased. With injection of pretreated ADSCs, healing of wounds was remarkably accelerated, along with increased ECM deposition and microvessel density. Moreover, pretreatment with α-KG resulted a prolonged survival of engrafted ADSCs was observed. Expression of HIF-1α was significantly increased in ADSCs treated with α-KG and in wounds injected with preconditioned ADSCs. Our results revealed that healing of acid burn wound was accelerated with administration of ADSCs pretreated with α-KG, which induced elevated expression of HIF-1α and prolonged survival of engrafted stem cells.

Exosome lncRNA IFNG-AS1 derived from mesenchymal stem cells of human adipose ameliorates neurogenesis and ASD-like behavior in BTBR mice.

BACKGROUND: The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear. RESULTS: The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis. CONCLUSION: We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD.

[Complete atrioventricular septal defect: a clinicopathologic study of 35 cases].

OBJECTIVE: To investigate the autopsy characteristics, pathologic type, malfomation and genetic characteristics of complete atrioventricular septal defect (CAVSD). METHODS: Thirty five cases of CAVSD were collected from Maternal and Child Hospital of Haidian District during Jan.2003 to Jan.2015. Autoptic material, clinical history and chromosome examination were reviewed. RESULTS: Among 35 cases of CAVSD between 18-38 gestational weeks, there were 26 cases with CAVSD A (74.3%, 26/35), 1 case with CAVSD B (2.8%, 1/35) and 8 cases with CAVSD C (22.8%, 8/35). Only CAVSD malformation was seen in 4 cases (11.4%, 4/35). Multiple malformations were seen in 31 cases (88.6%, 31/35). Combined malformations most frequently occurred in cardiovascular, respiratory and locomotor system. Among 15 cases with chromosome examination, chromosome aberrations was found in 13 cases (13/15) and trisomy-21 was found in 11 cases (11/15). CONCLUSIONS: CAVSD is a rare disease and CAVSD A is the most common type. CAVSD is usually combined with other malformations and chromosome aberrations.

[Early and late onset severe preeclampsia: a clinicopathologic study of 178 placentas].

OBJECTIVE: To explore the pathologic features and prognosis of early and late onset severe preeclampsia. METHODS: An observational study was conducted in 178 cases of severe preeclampsia collected during January 2010 to December 2014 from Haidian Maternal and Child Health Hospital.The cases were divided into two groups according to the onset of gestational age of the severe preeclampsia, with 54 cases of namely early onset (onset ≤ 34 weeks) and 124 cases of late onset (onset >34 weeks). Clinical characteristics of the patients, perinatal outcome and the pathologic characteristics of the placentas in each group were evaluated. RESULTS: Decidual vascular disease, placental infarction, abruptio placentae and placental villi dysplasia were seen in both groups. The incidence of placental villi dysplasia was the highest, followed by placental infarction. Incidence of severe decidual vascular disease of early and late onset severe decidual vascular disease were 16.7% (9/54) and 5.6% (7/124), respectively.Incidence of placental infarction of early and late onset severe preeclampsia were 48.1% (26/54) and 61.3% (76/124). Incidence of placental villi dysplasia of early and late onset severe preeclampsia were 79.6% (43/54) and 50.8% (63/124). Incidence of Severe decidual vascular disease, placental infarction and placental villi dysplasia were significantly different between early and late onset severe preeclampsia cases (P<0.05), while there was no difference in decidual vascular disease and placenta thrombi (P>0.05). Fetal survival rate of every group was 81.5% (44/54) and 93.5% (116/124). Incidence of fetal growth retardation was 55.6% (30/54) and 38.7% (48/124). The fetal survival rate and incidence of fetal growth retardation were different between two groups (P<0.05). CONCLUSIONS: The incidence of decidual vascular disease and placental villi dysplasia in early onset severe preeclampsia is higher than those in late onset severe preeclampsia. Neonatal outcome and prognosis in early onset severe preeclampsia are worse than those in late onset severe preeclampsia.

[Clinicopathologic study of 25 cases of placental chorioangioma].

OBJECTIVE: To investigate the clinicopathological characteristics, diagnostic criteria and differential diagnosis of placental chorioangioma. METHODS: Twenty-five cases of placental chorioangioma were analyzed for their clinical data, histomorphology and immumohisto chemical staining. Relevant literature was reviewed. RESULTS: The average age of the 25 patients was 29 years. Fourteen patients had full-term pregnancy, 10 had preterm labor, and 1 had intrauterine fetal death. Nineteen patients had pregnancy complications. The tumors presented as red or dusty pink nodules with clear borders. The tumor size ranged from 1 to 16 cm. Microscopically, the tumors possessed abundant capillaries or cavernous blood spaces lined by hyperplastic endothelial cells. These cells were positive for CD34 and Ki-67 index < 10%. CONCLUSIONS: Placental chorioangioma is a rare benign tumor of the placenta, and is associated with various pregnancy complications. Misdiagnosis of cell-rich type tumor should be avoided.

[Congenital pulmonary airway malformation of lung in fetus: a clinicopathological analysis].

OBJECTIVE: To study the etiology, pathogenesis, clinicopathologic characteristics, prognosis and treatment of congenital pulmonary airway malformation (CPAM). METHODS: Eighteen cases of CPAM were enrolled into the study. The clinical history, autopsy findings and immunohistochemical results were evaluated, with review of literature. The pathogenetic mechanism, pathologic features and differential diagnosis of CPAM were studied. RESULTS: Histologic examination showed that 2 cases were classified as Stocker type I, 12 cases as type II, and 4 cases as type III. The lesion was unilateral and involved single lobe in 13 cases. The remaining 5 cases had bilateral diseases. Of the 18 cases studied, 12 cases showed single organ involvement and 6 cases had malformations affecting multiple organs. The associated malformations included cardiac anomalies (4 cases), polycystic kidney with gastrointestinal atresia (1 case) and nuchal cystic hygroma with hydrothorax (1 case). CONCLUSIONS: CPAM is a rare pulmonary disorder. The etiology of this non-neoplastic condition is unknown. Imaging analysis is a valuable tool to suggest CPAM, while definite diagnosis requires pathologic examination. The overall prognosis is determined by the presence of associated malformations, fetal hydrops and pulmonary hypoplasia.

[Clinicopathologic features of fetal nuchal cystic hygroma: report of 40 cases].

OBJECTIVE: To study the pathogenesis, pathologic features and prognosis of fetal nuchal cystic hygroma. METHODS: Forty autopsied cases of fetal nuchal cystic hygroma were collected during January 2003 to December 2012. The clinical history, pathologic changes and immunohistochemical (EnVision method) findings were reviewed, and the pathogenesis and pathologic characteristics were analyzed. RESULTS: Of the 40 cases, 16 (40.0%) showed single malformation and 24 (60.0%) were associated with multiple malformations in other organs and/or systems.Nineteen cases were septated and 21 were not. The associated malformations occurred in the respiratory system, skeletal system and urinary system.In the cases of combined malformations of umbilical cord, 3 were single umbilical artery malformations and 1 was torsion and stricture of umbilical cord.Four cases had chromosomal analysis, and all were trisomy-21. CONCLUSIONS: Fetal nuchal cystic hygroma is a rare disease. The etiology is unknown, but it is not neoplastic.Lymphangioma is divided into 3 types:capillary lymphangioma, cavernous lymphangioma and cystic hygroma according to their expansile growth pattern. The overall prognosis is determined by any co-existing chromosomal anomalies, associated malformations and the time of diagnosis of the cystic hygroma.

The topoisomerase inhibitor CPT-11 prevents the growth and metastasis of lung cancer cells in nude mice by inhibiting EGFR/MAPK signaling pathway.

Objective: The topoisomerase inhibitor CPT-11 has been applied in treatment of multiple cancer types. Here, we probed into the possible mechanism of CPT-11 in affecting growth and metastasis of lung cancer (LC) cells, with involvement of the EGFR/MAPK pathway. Methods: The target protein of CPT-11 was screened through bioinformatics analysis, and the LC-related microarray datasets GSE29249, GSE32863 and GSE44077 were obtained for differential analysis for identifying the target protein. A subcutaneous xenograft tumor model and a metastatic tumor model were constructed in nude mice for in vivo mechanism verification of the regulatory role of CPT-11 in LC through modulation of EGRF/MAPK pathway. Results: Bioinformatics analysis showed that EGFR was the target protein of CPT-11. In vivo animal experiments confirmed that CPT-11 enhanced LC cell growth and metastasis in nude mice. CPT-11 could inhibit activation of EGFR/MAPK pathway. EGFR promoted LC cell growth and metastasis in nude mice through activation of the MAPK pathway. Conclusion: The topoisomerase inhibitor CPT-11 may prevent LC growth and metastasis by inhibiting activation of EGFR/MAPK pathway.

Construction of prediction model of inflammation related genes in idiopathic pulmonary fibrosis and its correlation with immune microenvironment.

Background: The role of inflammation in the formation of idiopathic pulmonary fibrosis (IPF) has gained a lot of attention recently. However, the involvement of genes related to inflammation and immune exchange environment status in the prognosis of IPF remains to be further clarified. The objective of this research is to establish a new model for the prediction of the overall survival (OS) rate of inflammation-related IPF. Methods: Gene Expression Omnibus (GEO) was employed to obtain the three expression microarrays of IPF, including two from alveolar lavage fluid cells and one from peripheral blood mononuclear cells. To construct the risk assessment model of inflammation-linked genes, least absolute shrinkage and selection operator (lasso), univariate cox and multivariate stepwise regression, and random forest method were used. The proportion of immune cell infiltration was evaluated by single sample Gene Set Enrichment Analysis (ssGSEA) algorithm. Results: The value of genes linked with inflammation in the prognosis of IPF was analyzed, and a four-genes risk model was constructed, including tpbg, Myc, ffar2, and CCL2. It was highlighted by Kaplan Meier (K-M) survival analysis that patients with high-risk scores had worse overall survival time in all training and validation sets, and univariate and multivariate analysis highlighted that it has the potential to act as an independent risk indicator for poor prognosis. ROC analysis showed that the prediction efficiency of 1-, 3-, and 5-year OS time in the training set reached 0.784, 0.835, and 0.921, respectively. Immune infiltration analysis showed that Myeloid-Derived Suppressor Cells (MDSC), macrophages, regulatory T cells, cd4+ t cells, neutrophils, and dendritic cells were more infiltrated in the high-risk group than in the low-risk group. Conclusion: Inflammation-related genes can be well used to evaluate the IPF prognosis and impart a new idea for the treatment and follow-up management of IPF patients.

[An analysis on the clinicopathological characteristics of 79 cases atypical endometrial hyperplasia].

OBJECTIVE: To explore the clinicopathological characteristics in atypical endometrial hyperplasia patients. METHODS: A retrospective study was carried out on 79 cases with atypical endometrial hyperplasia patients admitted to Department of Gynecology, Peking University People's Hospital from Mar. 2007 to Jul. 2010. All patients were divided into two groups, hyperplasia group (merely atypical endometrial hyperplasia, 49 cases, 62%) and cancerization group (atypical endometrial hyperplasia accompanying endometrial carcinoma, 30 cases, 38%). RESULTS: The mean age of 79 cases were (50 ± 11) years old, while they were (50 ± 10) and (51 ± 11) years old for hyperplasia group and cancerization group, there were not difference (P = 0.994). The gravidity and delivery frequencies were also not differently between two groups. The rates of complicated other diseases were 47% (23/49) and 43% (13/30), which was not significantly different (P = 0.755). The body mass index (BMI) of cancerization group was higher than that of hyperplasia group [(27.9 ± 5.4) vs. (25.2 ± 2.9) kg/m², P = 0.024]. There were 50% (15/30) and 31% (15/49) menopause cases in two groups, respectively. Among them there were 13/15 and 8/15 cases showed vaginal bleeding. Among premenopausal patients, there were 12/15 and 68% (23/34) showed abnormal vaginal bleeding, but there were not significantly different between two groups (all P > 0.05). The uterine cavity mass found by ultrasonography in the cancerization group patients was more than that in hyperplasia group [73% (22/30) vs. 51% (25/49), P = 0.050]. There were 23 cases (29%), 44 cases (56%) and 12 cases (15%) were diagnosed by dilatation and curettage (D&G), hysteroscopy and hysterectomy, respectively. The rates of diagnosing atypical endometrial hyperplasia by D&G and hysteroscopy were 87% (21/23) and 93% (41/44), respectively. The rate of diagnosis of canceration were 6/12 and 12/16, respectively. While, the rate of missed diagnosis of canceration in the atypical endometrial hyperplasia patients by D&G and hysteroscopy were 6/13 and 19% (4/21), respectively. Which all did not shown significantly different (P > 0.05). CONCLUSION: Hysteroscopy or D&G should be chosen on those peri-menopausal patients with abnormal bleeding, while those atypical endometrial hyperplasia patients with high BMI and uterine cavity mass diagnosed with D&G and ultrasonography should consider the possibility of canceration.

[Immunohistochemistry of p57 and p53 protein in differential diagnosis of hydropic abortion, partial and complete hydatidiform mole].

OBJECTIVE: To investigate the role of p57 and p53 immunohistochemistry in the differential diagnosis of hydropic abortion, partial hydatidiform mole and complete hydatidiform mole. METHODS: Immunohistochemical stains (EnVision method) for p57 and p53 were performed in tissue samples of normal placenta chorionic villi (n=10), abortion chorionic villi (n=12), partial hydatidiform (n=23) and complete hydatidiform moles (n=20). RESULTS: The expression of p57 was predominantly localized in the nuclei of villous cytotrophoblasts and stromal cells. The positive rates of p57 in normal placenta, hydropic abortion and partial hydatidiform mole were 10/10, 12/12, and 100% (23/23), respectively, with no significant difference among the groups (P>0.05). However, none of the complete hydatidiform moles analyzed exhibited p57 positivity in cytotrophoblasts and stromal cells. There was a significant difference between partial and complete hydatidiform moles (P<0.05). The expression of p53 was observed in the nuclei of cytotrophoblastic cells and intermediate trophoblasts. No p53 expression was seen in normal placenta and only 1 of 12 hydropic abortion showed p53 positivity. The positive rates of p53 expression in partial and complete hydatidiform mole were 60.9% (14/23) and 85.0% (17/20) respectively. It was significantly higher in partial hydatidiform mole than that in hydropic abortion. A significant difference was also found between partial and complete hydatidiform moles (P<0.05). CONCLUSIONS: Our findings confirm that p57 immunohistochemistry assists the differential diagnosis of complete hydatidiform mole from partial hydatidiform mole. Expression of p53 may be helpful in distinguishing partial hydatidiform mole from hydropic abortion.

[Expression of folate receptor alpha in ovarian epithelial tumors].

OBJECTIVE: to investigate the expression of folate receptor(FR)α in ovarian epithelial tumors and its clinopathological significance. METHODS: tissue microarrays (TMAs) were constructed from 86 epithelial ovarian cancers and 29 borderline ovarian tumors, followed by the FRα expression evaluation by immunohistochemistry. FRα mRNA expression was investigated by quantitative real-time PCR using fresh-frozen tissues from 40 cases of ovarian carcinoma and 14 cases of borderline tumor. FRα expression levels in ovarian tumors were also analyzed in correlation with tumor morphology, pathogenesis and FIGO stage. RESULTS: FRα expression was detected in 40 of 86 (46.5%) of ovarian cancers, with the highest rate of expression observed in serous carcinomas (62.7%, 32/51) compared with that of the other cancer types (P = 0.000). Depending on pathogenesis type, FRα expressions in type II ovarian carcinomas were significantly higher than those in type I ovarian carcinomas (P = 0.001). Ovarian carcinomas had a tendency to express higher FRα than the borderline tumors (46.5% vs 27.6%), although statistically not significant (P = 0.074). FRα expressions in ovarian carcinomas showed no correlation with the FIGO stage (P = 0.498). However, real-time PCR showed that FRα mRNA levels were significantly higher in ovarian carcinomas compared with that of the borderline tumors (P = 0.000) and also higher in serous ovarian borderline tumors compared with mucinous type (P = 0.007). CONCLUSION: higher level of FRα expression occurs frequently in ovarian epithelial tumors, especially in carcinomas and ovarian serous tumors.

miR-100 maintains phenotype of tumor-associated macrophages by targeting mTOR to promote tumor metastasis via Stat5a/IL-1ra pathway in mouse breast cancer.

Tumor-associated macrophages (TAMs), the main part of immune cells in tumor microenvironment (TME), play a potent role in promoting tumorigenesis through mechanisms such as stimulating angiogenesis, enhancing tumor migration and suppressing antitumor immunity. MicroRNAs (miRNAs) are considered as crucial regulators in multiple biological processes. The relationship between miRNAs and macrophages function has been extensively reported, but the roles that miRNAs play in regulating TAMs phenotype remain unclear. In this study, we screened highly expressed microRNAs in TAMs, and first identified that miR-100 represented a TAMs-high expression pattern and maintained TAMs phenotype by targeting mTOR signaling pathway. Moreover, miR-100 expression level in TAMs was positively related to IL-1ra secretion, a traditional immune-suppressive cytokine, which was determined to promote tumor cells stemness via stimulating Hedgehog pathway. Mechanism study suggested that mTOR/Stat5a pathway was involved in IL-1ra transcriptional regulation process mediated by miR-100. More importantly, tumor metastasis and invasion capacity were significantly decreased in a 4T1 mouse breast cancer model injected intratumorally with miR-100 antagomir, and combination therapy with cisplatin showed much better benefit. In this study, we confirm that highly expressed miR-100 maintains the phenotype of TAMs and promotes tumor metastasis via enhancing IL-1ra secretion. Interfering miR-100 expression of TAMs in mouse breast cancer model could inhibit TAMs pro-tumor function and reduce tumor metastasis, which suggests that miR-100 could serve as a potential therapy target to remodel tumor microenvironment in breast cancer.

ICAM3 mediates inflammatory signaling to promote cancer cell stemness.

In this study, we present a medium throughput siRNA screen platform to identify inflammation genes that regulate cancer cell stemness. We identified several novel candidates that decrease OCT4 expression and reduce the ALDH + subpopulation both of which are characteristic of stemness. Furthermore, one of the novel candidates ICAM3 up-regulates in the ALDH + subpopulation, the side population and the developed spheres. ICAM3 knockdown reduces the side population, sphere formation and chemo-resistance in MDA-MB-231 human breast cancer cells and A549 lung cancer cells. In addition, mice bearing MDA-MB-231-shICAM3 cells develop smaller tumors and fewer lung metastases versus control. Interestingly, ICAM3 recruits and binds to Src by the YLPL motif in its intracellular domain which further activates the PI3K-AKT phosphorylation cascades. The activated p-AKT enhances SOX2 and OCT4 activity and thereby maintains cancer cell stemness. Meanwhile, the p-AKT facilitated p50 nuclear translocation/activation enhances p50 feedback and thereby promotes ICAM3 expression by binding to the ICAM3 promoter region. On this basis, Src and PI3K inhibitors suppress ICAM3-mediated signaling pathways and reduce chemo-resistance which results in tumor growth suppression in vitro and in vivo. In summary, we identify a potential CSC regulator and suggest a novel mechanism by which ICAM3 governs cancer cell stemness and inflammation.

IKKß Enforces a LIN28B/TCF7L2 Positive Feedback Loop That Promotes Cancer Cell Stemness and Metastasis.

Considerable evidence suggests that proinflammatory pathways drive self-renewal of cancer stem-like cells (CSC), but the underlying mechanisms remain mainly undefined. Here we report that the let7 repressor LIN28B and its regulator IKBKB (IKKß) sustain cancer cell stemness by interacting with the Wnt/TCF7L2 (TCF4) signaling pathway to promote cancer progression. We found that LIN28B expression correlated with clinical progression and stemness marker expression in breast cancer patients. Functional studies demonstrated that the stemness properties of LIN28B-expressing human breast and lung cancer cells were enhanced by IKKß, whereas loss of LIN28B abolished stemness properties in these settings. These phenomena were driven through interactions with TCF7L2, which enhanced LIN28B expression by direct binding to intron 1 of the LIN28B gene, which in turn promoted TCF7L2 mRNA translation through a positive feedback loop. Notably, RNAi-mediated silencing of LIN28B or pharmacologic inhibition of IKKß was sufficient to suppress primary and metastatic tumor growth in vivo. Together, our results establish the LIN28B/TCF7L2 interaction loop as a central mediator of cancer stemness driven by proinflammatory processes during progression and metastasis, possibly offering a new therapeutic target for generalized interventions in advanced cancers.

[Value assessment of high-risk HPV test and TCT in the screening of cervical carcinoma].

OBJECTIVE: To estimate the status of coincidence of high-risk HPV (HR-HPV) test and thinprep cytology test(TCT) with biopsy histopathological diagnosis. And explore the diagnostic value in the cervical cancer and precancerous lesions by combination of these two methods. METHODS: Retrospective analysis cases with the positive cytological diagnosis. Acrodding to the principle of voluntariness and informed consent, 3197 cases were selected and further investigated by high-risk human papillomavirus testing and biopsy histopathological diagnosis. We had a comparative analysis to the coincidence of TCT, high-risk HPV-DNA test and biopsy histopathological diagnosis. RESULTS: Among 3197 cases, 58.6% cases with chronic inflammation, 26.1% cases with condyloma or CIN I, 14.1% cases with CIN II-III, and 1.2% cases with invasive cervical carcinoma. Compared with pathological biopsy, the coincident rate of the diagnosis of TCT cytology and histopathology were 21.2% (ASC-US), 28.6% (ASC-H), 39.6% (LSIL), 56.2% (HSIL) and 72.4% (cervical carcinoma), respectively. Among cases of positive TCT diagnosis, Compared HR-HPV test and histopathological diagnosis, infection rate of HR-HPV increases significantly with increasing pathological grade (chi2 = 292.354, P = 0.000 < 0.05). As the TCT diagnostic level increases, the positive rate of HR-HPV marked grows (chi2 = 144.113, P = 0.000 < 0.05). CONCLUSION: TCT can reduce the incidence of cancer effectively. But lower sensitivity in the low-grade cervical lesions may cause missed diagnosis. Combined TCT and HR-HPV test will improve the detection rate of cervical lesions; it is an ideal method to screening cervical cancer.