This study aimed to examine hTERC gene in different grades of cervical intraepithelial neoplasia (CIN) and cervical cancer, and the association between hTERC and high risk-human papillomavirus (HR-HPV) infection. Patients who underwent cervical cancer screening at the Second Affiliated Hospital of Kunming Medical University between October 2010 and December 2011 were enrolled. All patients underwent liquid-based cytology test and hybrid capture 2 (HC2) for HPV detection. hTERC was examined using fluorescence in situ hybridization (FISH). Cervical colposcopy biopsy was performed if any of the three results was positive. HC2, FISH, and pathology were compared. A total of 1200 women underwent screening, 150 patients underwent cervical biopsy: 32 in the normal group, 38 in the CIN1 group, 66 in the CIN2/3 group, and 14 in the invasive cervical cancer group. More patients had HR-HPV infection in the CIN2/3 group and ICC group compared with the CIN1 group. hTERC increased with increasing histological dysplasia. There was significant difference in hTERC positive rate between each of the three groups. More patients with hTERC gene amplification were observed in the positive HR-HPV group than in the HR-HPV negative group. In conclusion, hTERC is a potential marker for precancerous cervical cancer lesions. hTERC might be correlated with HR-HPV infection in cervical diseases.

Background Among recurrent implantation failure (RIF) patients, the rate of successful implantation remains relatively low due to the complex etiology of the condition, including maternal, embryo and immune factors. Effective treatments are urgently needed to improve the outcomes of embryo transfer for RIF patients. In recent years, many researchers have focused on immunotherapy using granulocyte colony-stimulating factor (G-CSF) to regulate the immune environment. However, the study of the G-CSF for RIF patients has reached conflicting conclusions. The aim of this systematic review and meta-analysis was performed to further explore the effects of G-CSF according to embryo transfer cycle (fresh or frozen) and administration route (subcutaneous injection or intrauterine infusion) among RIF patients. Method The PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for literature published from the initial to October 2020. The meta-analysis, random-effects model and heterogeneity of the studies with I2 index were analyzed. Stata 15 was used for statistical analysis. Results A total of 684 studies were obtained through the databases mentioned above. Nine RCTs included 976 RIF patients were enrolled in this meta-analysis. Subgroup analysis indicated that G-CSF improved the clinical pregnancy rate for both the fresh and frozen embryo transfer cycles (fresh RR: 1.74, 95% CI: 1.27–2.37, I2 = 0.0%, n = 410; frozen RR: 1.44, 95% CI: 1.14–1.81, I2 = 0.0.%, n = 366), and for both subcutaneous injection and intrauterine infusion (subcutaneous RR: 1.73, 95% CI: 1.33–2.23, I2 = 0.0%, n = 497; intrauterine RR: 1.39, 95% CI: 1.09–1.78, I2 = 0.0%, n = 479), but the biochemical pregnancy rate of the RIF group was also higher than that of the control group (RR: 1.85, 95% CI: 1.28–2.68; I2 = 20.1%, n = 469). There were no significant differences in the miscarriage rate (RR: 1.13, 95% CI: 0.25–5.21: I2 = 63.2%, n = 472) and live birth rate (RR: 1.43, 95% CI: 0.86–2.36; I2 = 52.5%; n = 372) when a random-effects model was employed. Conclusion The administration of G-CSF via either subcutaneous injection or intrauterine infusion and during both the fresh and frozen embryo transfer cycles for RIF patients can improve the clinical pregnancy rate. However, whether G-CSF is effective in improving livebirth rates of RIF patients is still uncertain, continued research on the utilization and effectiveness of G-CSF is recommended before G-CSF can be considered mainstream treatment for RIF patients.

Emerging evidence has demonstrated that microRNAs ( miRNAs/miRs) have various biological functions in the development of human epidermal growth factor receptor 2 (HER2) positive breast cancer. The aim of the present study is to reveal the mechanism of miR-193a-3p inhibiting the progress of HER2 positive breast cancer. The expression of miR-193a-3p was evaluated by quantitative polymerase chain reaction (PCR). The methylation status of miR-193a-3p was evaluated by PCR and pyrosequencing analysis. Overexpression of miR-193a-3p and growth factor receptor bound protein 7 (GRB7) combined with in vitro tumorigenic assays were conducted to determine the carcinostatic capacities of miR-193a-3p in HER2 positive breast cancer cells. The association between miR-193a-3p and GRB7 was determined by luciferase reporter assay. Protein level was evaluated using western blot analysis. miR-193a-3p was down-regulated in HER2 positive breast cancer cells and clinical tissues. Methylation-mediated silencing led to decreased expression of miR-193a-3p in HER2 positive breast cancer. Overexpression of miR-193a-3p could inhibit proliferation, migration and invasion of breast cancer cells. Overexpression of GRB7 could abolish this effect. miR-193a-3p could directly target the 3′ untranslated region of GRB7. miR-193a-3p could directly or indirectly target extracellular signal-regulated kinase 1/2 (ERK1/2) and forkhead box M1 (FOXM1) signaling. In conclusion, it was identified that silencing of miR-193a-3p through hypermethylation can promote HER2 positive breast cancer progress by targeting GRB7, ERK1/2 and FOXM1 signaling. The function of miR-193a-3p in HER2 positive breast cancer implicates its potential application in therapy.

Background The significance of HPV viral load in the detection of cervical lesions is still controversial. This study analyzed the correlation between the high-risk HPV viral load and different cervical lesion degrees. Methods This retrospective study included women positive for high-risk HPV DNA and screened for cervical lesions between 01/2015 and 06/2018. The high-risk HPV DNA load was measured by the second-generation Hybrid Capture technology and classified as low, moderate, and high. Colposcopy and biopsy were performed in all patients. The patients were grouped as normal, cervical intraepithelial neoplasia (CIN) grade 1, CIN grade 2, CIN grade 3, and cervical cancer. Multivariable logistic regression was performed to explore the association between high-risk HPV DNA load and cervical lesions. The odds ratios (ORs) represent the odds for increasing from low to high viral load. Results Finally, 265 patients were grouped as normal (n = 125), CIN 1 (n = 51), CIN 2 (n = 23), CIN 3 (n = 46), and cervical cancer (n = 20). Among them, 139 (52.5%) had a low viral load, 90 (34.0) had a moderate viral load, and 36 (13.4%) had a high viral load. Taking the normal control group as a reference, a high viral load was an independent factor for CIN 1 (OR = 3.568, 95% CI: 1.164–10.941, P = 0.026), CIN 2 (OR = 6.939, 95% CI: 1.793–26.852, P = 0.005), CIN 3 (OR = 7.052, 95% CI: 2.304–21.586, P = 0.001), and cervical cancer (OR = 8.266, 95% CI: 2.120–32.233, P = 0.002). Conclusions Among women who underwent cervical biopsy, higher high-risk HPV viral load in cervical lesions was associated with a higher risk of high-grade cervical lesions.

Recent studies have showed that IKBKE is overexpressed in several kinds of cancers and that IKBKE-knockdown inhibits tumor progression. In this article, we first verified that two glioblastoma cell lines, U87-MG and LN-229, were sensitive to CYT387 by measuring the half maximal inhibitory concentration (IC50) with a CCK-8 assay and then demonstrated that CYT387, as a potent IKBKE inhibitor, suppressed glioblastoma cell proliferation, migration and invasion. Additionally, CYT387 induced cell apoptosis and arrested the cell cycle at the G2/M checkpoint in vitro. Furthermore, we showed that CYT387 did not simply inhibit IKBKE activity but also decreased IKBKE expression at the protein level rather than at the mRNA level. We discovered that CYT387 restrained malignant tumor progression by activating the Hippo pathway in vitro. By coimmunoprecipitation (co-IP), we showed that IKBKE interacted with TEAD2 and YAP1, thus accelerating TEAD2 and YAP1 transport into the nucleus. In subsequent in vivo experiments, we found that CYT387 inhibited subcutaneous nude mouse tumor growth but had little impact on intracranial orthotopic xenografts, probably due to a limited ability to penetrate the blood–brain barrier (BBB). These results suggest that CYT387 has potential as a new antiglioblastoma drug, but an approach to allow passage through the blood–brain barrier (BBB) is needed.

Chlamydia trachomatis (CT) infection is an important factor for tubal pregnancy. However, whether Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) infections are also involved in tubal pregnancy remains unknown. This study is aimed to detect CT, UU, and MH in cervical secretions from patients with tubal pregnancy and control women in early pregnancy, to explore their prevalence rates and drug susceptibilities. Analysis was performed on patients with tubal pregnancy and those requiring termination of early pregnancy at <12 weeks from July 2013 to March 2014. Cervical secretions were tested for UU/MH with a UU/MH isolation and culture kit and for CT antigen by an immunochromatographic assay. Mycoplasma samples were tested for resistance to 12 antibiotics. There were no cases of CT infection detected. Mycoplasma infection rates (single or mixed) were similar in the tubal pregnancy and control groups, but the total rate of infection was higher for tubal pregnancy. All MH samples were sensitive to tetracyclines as well as josamycin and azithromycin. Josamycin and clarithromycin were effective against all UU cultures. Over 50% of the samples tested were resistant to ciprofloxacin.

This study investigated the repair effects of fat and fibrin graft interposition through a proximal tibia transphyseal injury model and assessed the effectiveness of treatment to physeal injury with the fibrin. In this study, a unilateral growth plate injury was created in the right proximal tibia of 28 rats without any graft interposition; all left tibias were left untouched. In the other group of 28 rats, a bilateral physeal injury was made with the left tibia filled with autogenously adipose tissue and the right tibia filled with fibrin. To compare the malformed extents induced by different interventions, the length and the metaphyseal-diaphyseal angle of the tibia of three injured groups were examined. Further studies on bone density analysis and histological change were used to compare the bony bridge formation under different interventions. Results showed that the deformity angle and medial length of the tibia were significantly different between the grafted groups and nongrafted group at 4, 16, and 24 weeks postoperative (P<0.01). Results also showed no significant difference between fibrin-graft and fat-graft groups (P>0.05). Furthermore, the bone mineralization density of bony bridge induced by injury was significantly different between the grafted group and nongrafted group at 4, 16, and 24 weeks postoperative (P<0.01). Histological findings showed that bony repair after physeal injury was inhibited by both fibrin and fat interventions. We concluded that fibrin could be a substitute of adipose tissue in preventing the deformities induced by epiphyseal injury. Similar to autogenous fat, fibrin was found to alleviate limb shortness and prevent angular malformation by forming a scar instead of a bony bridge. The use of fibrin can help us to develop effective and compound intervention grafts to prevent skeletal deformity and regenerate normal cartilage tissue in the future.

Background: The significance of HPV viral load in the detection of cervical lesions is still controversial. This study analyzed the correlation between the high-risk (HR)-HPV viral load and different cervical lesion degrees.Methods: This was a retrospective study of the patients who first visited the hospital between January 2015 and June 2018. Patients with positive HR-HPV were screening for cervical cancer. The HR-HPV DNA load was measured by the second generation hybrid capture (HC2) technology. The patients grouped as normal, CIN I, CIN II, CIN III, and cervical cancer. Multivariable logistic regression was performed to explore the association between HR-HPV DNA load and cervical lesions.Results: Finally, 265 patients were grouped as normal (n=125), CIN I (n=51), CIN II (n=23), CIN III (n=46), and cervical cancer (n=20). Among them, 139 (52.5%) had a low viral load, 90 (34.0) had a moderate viral load, and 36 (13.4%) had a high viral load. Taking the normal control group as a reference, a high viral load was an independent factor for CIN I (CIN I: OR=3.959, 95%CI: 1.300-12.059, P=0.015) CIN II (OR=6.211, 95%CI: 1.641-23.513, P=0.007), CIN III (OR=7.002, 95%CI: 2.308-21.244, P=0.001), and cervical cancer (OR=9.439, 95%CI: 2.394-37.22, P=0.001).Conclusion: Cervical lesions are closely related to HR-HPV infection. Higher HR-HPV viral load in cervical lesions was associated with a higher risk of high-grade cervical lesions.