Single-cell transcriptome sequencing reveals that cell division cycle 5-like protein is essential for porcine oocyte maturation.

The brilliant cresyl blue (BCB) test is used in both basic biological research and assisted reproduction to identify oocytes likely to be developmentally competent. However, the underlying molecular mechanism targeted by the BCB test is still unclear. To explore this question, we first confirmed that BCB-positive porcine oocytes had higher rates of meiotic maturation, better rates of cleavage and development into blastocysts, and lower death rates. Subsequent single-cell transcriptome sequencing on porcine germinal vesicle (GV)-stage oocytes identified 155 genes that were significantly differentially expressed between BCB-negative and BCB-positive oocytes. These included genes such as cdc5l, ldha, spata22, rgs2, paip1, wee1b, and hsp27, which are enriched in functionally important signaling pathways including cell cycle regulation, oocyte meiosis, spliceosome formation, and nucleotide excision repair. In BCB-positive GV oocytes that additionally had a lower frequency of DNA double-strand breaks, the CDC5L protein was significantly more abundant. cdc5l/CDC5L inhibition by short interference (si)RNA or antibody microinjection significantly impaired porcine oocyte meiotic maturation and subsequent parthenote development. Taken together, our single-oocyte sequencing data point to a potential new role for CDC5L in porcine oocyte meiosis and early embryo development, and supports further analysis of this protein in the context of the BCB test.

Association of Dose and Frequency on the Survival of Patients on Maintenance of Hemodialysis in China: A Kaplan-Meier and Cox-Proportional Hazard Model Analysis.

BACKGROUND Dialysis frequency and dose are controversial prognostic factors of hemodialysis morbidity and mortality. The aim of this study was to find out the effect of frequency and dosage of dialysis on mortality and survival in a group of Chinese hemodialysis patients. MATERIAL AND METHODS In total, 183 patients seen from February 2008 to January 2018, who were on maintenance hemodialysis for at least 3 months, were included in the study cohort. An anonymized database of age, gender, diabetic status, comorbidities, date of initiation of dialysis, hematological characters, biochemical variables, and status of survived or died was established from DICOM (Digital Imaging and Communications in Medicine) files of patients. Kaplan-Meier and Cox-proportional hazard model was used for calculation of survival over time at 95% confidence level. RESULTS Overall, the 10-year survival rate was 27%. Kaplan-Meier analysis showed patient survival as 94% at one-year, 59% at 5-years, and 27% at 10-years. Hemoglobin, serum albumin, calcium, potassium, phosphorous, calcium-phosphorous-products, and hemodialysis frequency and the dose had a significant effect on survival. Cox regression proportional hazard model showed that patients with serum albumin level of >4 g/dL were better associated with survival. Patients who underwent twice-weekly hemodialysis had 4.26 times less chance of survival as compared to patients with thrice-weekly hemodialysis. A higher dialysis dose of >1.2 spKt/V offered better survival as compared to a lower dose of <1.2 spKt/V. CONCLUSIONS Hypoalbuminemia, hemodialysis time, and hemodialysis frequency were significantly associated with mortality.

Progesterone inhibited endoplasmic reticulum stress associated apoptosis induced by interleukin-1ß via the GRP78/PERK/CHOP pathway in BeWo cells.

AIM: Pre-eclampsia (PE) is a pregnancy complication characterized by new onset maternal hypertension and proteinuria. Its underlying mechanisms are unclear. This study investigated the relationship between progesterone and endoplasmic reticulum stress (ERS) associated apoptosis induced by interleukin (IL)-1ß via the glucose regulated protein 78 (GRP78)/protein kinase RNA-like endoplasmic reticulum kinase (PERK)/C/EBP-homologous protein (CHOP) pathway in BeWo cells. METHODS: Venous blood and placental tissues were collected from PE patients, normal pregnancy and preterm delivery cases, respectively. Progesterone serum levels were detected by enzyme-linked immunosorbent assay and ERS-related protein expression in placentas was examined by immunohistochemistry, reverse transcriptase-polymerase chain reaction and Western blot. BeWo cells were stimulated by IL-1ß to induce ERS associated apoptosis in vitro. The apoptotic rate was measured by flow cytometry. The mechanism of progesterone acting on IL-1ß induced ERS associated apoptosis was investigated by reverse transcriptase-polymerase chain reaction, Western blot and PERK small interfering RNA, with RU486 used as a receptor inhibitor. RESULTS: PE patients exhibited decreased serum levels of progesterone and activated ERS and increased ERS-related protein expression. IL-1ß could induce ERS and associated cell apoptosis by activating the GRP78/PERK/CHOP signal pathway, which could be inhibited by progesterone. PERK could be upregulated and phosphorylation activated in ERS. The protective effects of progesterone could be attenuated by RU486. CONCLUSION: IL-1ß could induce ERS associated cell apoptosis by activating the GRP78/PERK/CHOP signal pathway in BeWo cells and may play an important role in PE occurrence. Progesterone levels were decreased in patients with PE and seemed to have a protective effect by inhibiting ERS associated cell apoptosis.

miR-3156-3p is downregulated in HPV-positive cervical cancer and performs as a tumor-suppressive miRNA.

BACKGROUND: Cervical cancer (CC) is the second most common cancer in females in developing countries. The two viral oncoproteins E6 and E7 mediate the oncogenic activities of high-risk human papillomavirus (HR-HPV), and HR-HPV, especially HPV16 or/and HPV18 (HPV16/18) play critical roles in CC through different pathways. microRNAs (miRNAs) may be associated with CC pathogenesis. Researches have indicated that human papillomavirus (HPV) may regulate cellular miRNA expression through viral E6 and E7. Herein, the purposes of this study were to identify the relationship between HPV infection and aberrantly expressed miRNAs and to investigate their pathogenic roles in CC. METHODS: miRNA expression was assessed using a microRNAs microarray in HPV16 E6- and E7-integrated HPV-negative HT-3 cell lines and mock vector-transfected HT-3 cells. The microarray results were validated, and the expression of miR-3156-3p was identified in HPV-positive and -negative CC cell lines as well as primary CC and normal cervical epithelium tissues using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK8), flow cytometry, transwell analysis, tube formation, and Western blotting were used to identify the functional role of miR-3156-3p in CaSki, SiHa, and HeLa cell lines. RESULTS: Six underexpressed microRNAs (miR-3156-3p, 6779-3p, 4779-3p, 6841-3p, 454-5p and 656-5p) were consistently identified in HPV16 E6- and E7-integrated HT-3 cells. Further investigation confirmed a significant decrease of miR-3156-3p in HPV16/18 positive CC lesions. CCK8, flow cytometry, transwell analysis, tube formation assays, and Western blotting of the CC cell lines with miR-3156-3p over/under-expression in vitro showed that miR-3156-3p was involved in cell proliferation, apoptosis, migration, neovascularization, and SLC6A6 regulation. CONCLUSIONS: Our findings indicate that miR-3156-3p plays a suppressor-miRNA role in CC and that its expression is associated with HR-HPV infection.

Influence of hsa-miR-6727-5p on the proliferation, apoptosis, invasion and migration of Caski, Hela and SiHa cervical cancer cells.

PURPOSE: To study the influence of hsa-miR-6727-5p on the proliferation, apoptosis, invasion and migration of Caski, Hela and SiHa cervical cancer cells. METHODS: The CCK8 test, flow cytometry, Transwell and scratch healing experiments were used to measure the influence of hsa-miR-6727-5p on the proliferation, apoptosis, invasion and migration of Caski, Hela and SiHa cells. RESULTS: Compared with the negative control (empty vector) group, the hsa-miR-6727-5p expression in the cells transfected with hsa-miR-6727-5p mimics showed a significant increase (p<0.01). CCK8 results showed that the hsa-miR-6727-5p overexpression enhanced significantly the proliferation of cervical cancer cells. Annexin V FITC/PI staining cell results showed that hsa-miR-6727-5p overexpression strongly inhibited the cervical cancer cells apoptosis. Transwell invasion in vitro test showed that hsamiR-6727-5p overexpression significantly enhanced the invasion ability of cervical cancer cells. The scratch healing test suggested that, compared with the control group, the migration ability of cells transfected with hsa-miR-6727-5p mimics in the experimental group was stronger. CONCLUSION: We confirmed at the cellular level that hsa-miR-6727-5p promoted the proliferation, invasion and migration of cervical cancer cells and inhibited the apoptosis through the overexpression or inhibition of hsa-miR-6727-5p. These results indicated that hsamiR-6727-5p played a role in promoting the cervical cancer.

Serine/threonine kinases 31(STK31) may be a novel cellular target gene for the HPV16 oncogene E7 with potential as a DNA hypomethylation biomarker in cervical cancer.

BACKGROUND: Cervical cancer (CC) is a leading cause of mortality in females, especially in developing countries. The two viral oncoproteins E6 and E7 mediate the oncogenic activities of high-risk human papillomavirus (hrHPV), and hrHPV, especially HPV16 or/and HPV18 (HPV16/18) play critical roles in CC through different pathways. STK31 gene of which the expression has been proven to be regulated by the methylation status of its promoter, is one of the novel cancer/testis (CT) genes and plays important roles in human cancers. Reasearches have indicated that viral infection is correlated to the methylation statuses of some genes. Herein, we detected methylation status of the STK31 gene in cervical tumors and explored its interaction with HPV16 or/and HPV18 (HPV16/18) infection. METHODS: Bisulfite genomic sequencing PCR (BGS) combined with TA clone, methylation-specific PCR (MSP) were used to analyze methylation statuses of the STK31 gene promoter/exon 1 region in HPV16/18-positive, HPV-negative CC cell lines; ectopically expressed HPV16 E6, -E7, and -E6/E7 CC cells; normal cervical tissues and cervical tumor tissues of different stages. The mRNA and protein expressions of STK31 were detected by RT-PCR and western blotting. RESULTS: The STK31 gene promoter/exon 1 was hypomethylated in the HPV16/18-positive cell lines HeLa, SiHa and CaSki, and the mRNA and protein expression were detected. In contrast, the STK31 gene exhibited hypermethylation and silenced expression in the HPV-negative CC cells C33A and HT-3. Compared with the primary HPV-negative CC cell lines, the STK31 methylation was downregulated, and STK31 expression was induced in the HPV16E7/E67 transfected cells. The methylation statuses and expressions of STK31 were verified in the cervical tumor samples at different stages. Additionally, chemotherapy treatment may influence STK31 expression by regulating its methylation status. CONCLUSIONS: STK31 may be a novel cellular target gene for the HPV16 oncogeneE7. The HPV16 oncogene E7 may affect STK31 expression through a methylation-mediated mechanism. The aberrant methylation of the STK31 promoter/exon 1 region may be a precursor of human cervical carcinogenesis and a potential DNA aberrant methylation biomarker of conditions ranging from precancerous disease to invasive cancer.

Opportunities and challenges encountered in managing cervical cancer during the coronavirus disease 2019 pandemic.

OBJECTIVES: The COVID-19 pandemic, while putting pressure on the global healthcare system, has had a significant impact on the prevention, diagnosis, and treatment of cervical cancer. The aim of this study is to provide an overview of the challenges and opportunities presented to cervical cancer during the COVID-19 pandemic and to provide lessons for better coping with cervical cancer in future pandemics. METHODS: The search terms included the following: SARS-CoV-2 and/or COVID-19 with cervical cancer and HPV. The initial literature search began on June 1, 2022 and ended on March 1, 2023. OUTCOME: COVID-19 has hindered the cervical cancer screening, delayed the diagnosis and treatment of cervical cancer, increased the public's anxiety, and negatively affected the management of cervical cancer. However, the occurrence of COVID-19 pandemic has promoted the development of new human papillomavirus (HPV) tests and improved the rates of HPV self-sampling, offering a small window of opportunity to eliminate cervical cancer. CONCLUSIONS: In the next few years, the COVID-19 pandemic will come to an end, and the eradication of cervical cancer should always be carried out. We should draw lessons and experience from this global pandemic, and make efforts for the subsequent eradication of cervical cancer.

Long-term follow-up of photodynamic therapy of cervical intraepithelial neoplasia grade 2 (CIN2).

BACKGROUND: To determine the long-term efficacy and safety of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) for treating cervical intraepithelial neoplasia grade 2 (CIN2) as well as the suitability of ALA-PDT in treating of cervical lesions divided into cervical transformation zone type 3. METHODS: We included 81 patients diagnosed with CIN2 at the Department of Gynecology of the Affiliated Hospital of Qingdao University with data collected between January 2019 and January 2021 following ALA-PDT. Furthermore, we analyzed the superiority of ALA-PDT in fertility preservation among women of childbearing age based on follow-up data from 11 patients with fertility requirements. RESULTS: Our findings confirmed the long-term efficacy of ALA-PDT for CIN2 treatment, with an overall efficacy of 95.83 % (23/24) at follow-up of 25-36 months. Moreover, the cervical transformation zone type 3 improvement and human papillomavirus (HPV)-negative efficacy were 69.2 % (18/26) and 82.4 % (14/17), respectively. ALA-PDT is recommended for consenting patients with cervical transformation zone type 3. Additionally, women without primary infertility could experience natural pregnancy and full-term birth of more than one baby following ALA-PDT for CIN2 treatment, with a satisfaction rate of ≈100 %. CONCLUSIONS: ALA-PDT is recommendable for treating high-grade squamous intraepithelial lesions, especially in patients with fertility requirements.

Case report: A case of recurrent cervical cancer with bronchial and esophageal metastases presenting with hemoptysis and dysphagia.

Background: The treatment outcomes and prognosis for recurrent cervical cancer are generally poor, with a 5-year survival rate of only 10%-20%. Case presentation: In this case, the patient is a young woman who experienced a recurrence 5 years after the initial treatment of cervical cancer. Her primary symptoms were hemoptysis and dysphagia, indicative of hilar and mediastinal lymph node metastases, with further involvement of the bronchus and esophagus. Additionally, the patient also presented with tumor-associated dermatomyositis. Following combined treatment with albumin-bound paclitaxel, carboplatin, bevacizumab, and cadonilimab, the patient's tumor was effectively controlled.

Case report: A case of perineal prolapse of giant uterine fibroids complicated by multiple pulmonary embolisms and deep venous thrombosis.

A 43-year-old woman with a history of uterine fibroids, anemia, and deep vein thrombosis presented with a chief symptom of prolapse of tumor from the perineum, complicated by infection. The case was further complicated by bilateral pulmonary multiple embolism, deep vein thrombosis, acute cardiac insufficiency, acute renal insufficiency, and shock. The patient was treated with preoperative placement of an inferior vena cava filter, open hysterectomy, and perioperative anticoagulation with low-molecular-weight heparin. She smoothly navigated the perioperative period and recovered completely.

Polymorphisms of receptor for advanced glycation end products and risk of epithelial ovarian cancer in Chinese patients.

BACKGROUND: Given the roles of receptor for advanced glycation end products (RAGE) in the pathogenesis of carcinogenesis, we propose that RAGE polymorphisms may be associated with risk of epithelial ovarian carcinoma (EOC). METHOD: This case-control study included 190 women over 40 years of age who were diagnosed with primary EOC and 210 healthy control subjects. RAGE gene polymorphisms, including 82G>S,-374T>A,-429C>T,and 1704G>T were determined. RESULTS: We found that only the frequencies of the 82G>S polymorphisms were significantly different between the EOC cases and controls. The 82SS genotype was significantly higher in EOC patients than in controls (37.89% vs. 23.33%,P<0.001). With the 82 GG genotype as reference, the OR for 82SS homozygous carriers reached to 2.65 (95% CI: 1.54-4.58; P =0.0004) after adjustment for age, smoking status, body mass index, family history, usage of contraceptives, tubal ligation history, use of menopausal hormones and menopausal status. The 82S allele carriage presented a higher risk for EOC (OR=1.71; 95% CI, 1.29-2.26; P=0.0002). The polymorphisms of 1704G>T,-374T>A and -429C>T did not affect the EOC risk. CONCLUSION: This result suggests that the 82G>S polymorphism of RAGE gene may be associated with the susceptibility of EOC.

Investigation of periodic characteristics of perturbed flow over a slender body.

The asymmetric flow over a slender body was particularly sensitive to the nose at a high angle of attack (AoA). Two patterns of separation occurred on the noses of the pointed-nosed slender body and blunt-nosed slender body as open- and close-type separation, respectively. The effects of the bluntness were investigated at high AoA (α = 50°) to clarify the evolution of the separated pattern from open-to close-type separation by the nose and by the periodic characteristics of perturbed flow. Wind tunnel experimental tests were conducted to investigate the periodic characteristics of asymmetric flow at a Reynolds number ReD = 1.54 × 105, based on incoming free-stream velocity (U∞) and the diameter (D) of the model. A particle was attached to the tip of the nose to induce the perturbed flow and attain a definite and predictable asymmetric flow in experimental tests. The pressure scanning and surface oil-flow visualization techniques were used to capture the pressure distributions and flow separations. The major findings were that axial flow increases with the increase of bluntness, resulting in open-type separation turning into close-type separation, and the perturbation moved from downstream to upstream of starting points of the separation line. The critical bluntness of separation pattern switching from open-type to close-type located between 1.5 and 3. Thus, the management of perturbation on asymmetric flow pattern switched from directly participating in separation to influencing separation through micro-flow. Therefore, the locations of perturbation and starting points of the separation line were closely related to asymmetric flow management by perturbation, then affecting the periodic characteristics of perturbed flow.

Role of extracellular vesicle in human papillomavirus-associated cervical cancer.

BACKGROUND: Cervical cancer is a gynecological malignant tumor and a serious threat to women's health. Although human papillomavirus (HPV) infection and the occurrence of cervical cancer are known to be closely related, the underlying carcinogenic mechanism of HPV is not fully understood. Extracellular vesicles (EVs) are found in a variety of body fluids and play an important role in both intercellular communication and cancer progression. Furthermore, the presence of EVs makes liquid biopsy of cervical cancer possible. The study of EVs in cervical cancer can provide clinical ideas for the diagnosis and treatment of the disease. OBJECTIVES: The purpose of this article is to summarizes the role of EV contents in HPV-associated cervical cancer and discusses the possible clinical application of EVs in cervical cancer treatment. METHODS: The search terms included the following: HPV with cervical cancer and extracellular vesicles. The initial literature search ended on March 1, 2023. CONCLUSIONS: In HPV-positive cervical cancer, EV contents are changed due to the presence of HPV. HPV-positive cervical cancer affects the cell microenvironment and other surrounding cells through the secretion of EVs.

Comparison of the clinical characteristics and prognosis between clear cell carcinomas and high-grade serous ovarian carcinomas.

OBJECTIVES: To compare the clinical characteristics and prognosis of women with clear cell versus high-grade serous ovarian carcinoma. MATERIAL AND METHODS: Retrospective analysis of the clinical data of 50 cases patients with ovarian clear cell carcinoma (OCCC) and 103 cases with high-grade serous ovarian carcinoma (HGSOC), who were initially treated and completed standardized therapy in Affiliated Hospital of Qingdao University from January 2013 to December 2017. RESULTS: There were significant differences in age, gravidity (G > 1), chief complaint, with ovarian endometriosis, tumor diameter, unilateral or bilateral, cystic and solid tumor, CA125, HE4, CA199, lactate dehydrogenase (LDH), and FIGO stage between the two groups. The differences in the prognosis between OCCC patients and HGSOC patients with early stage (FIGO I-II) were not statistically significant. The 5-year overall survival and progression-free survival of OCCC patients were significantly worse than those of HGSOC patients with advanced stage (FIGO III-IV) (p < 0.05). FIGO stage and non-R0 resection were independent risk factors affecting the prognosis of patients with ovarian clear cell carcinoma, screening by Cox regression analysis. FIGO stage, the lowest value of CA125, and non-R0 resection were independent risk factors affecting the prognosis of patients with high-grade serous ovarian cancer. CONCLUSIONS: The clinical characteristics and prognosis of OCCC are different from those of HGSOC. Ovarian clear cell carcinoma (OCCC) patients have a significantly worse prognosis than those with HGSOC in the advanced stage (FIGO Ⅲ-Ⅳ). Satisfactory tumor resection is an essential factor related to the prognosis of patients with OCCC and HGSOC.

Clinical outcome of photodynamic therapy for the treatment of cervical intraepithelial neoplasia grade 2.

Five-aminolaevulinic acid photodynamic therapy (ALA-PDT) was used to treat 79 cervical intraepithelial neoplasia 2 (CIN 2) patients who desired preservation of fertility ,between Oct 2018 and Dec 2020. Three months after treatment, among the 65 patients who returned for follow-up, full recovery and improvement rates were 43/65 and 16/65, respectively, resulting in a total response rate of 90.77%. This suggests that ALA-PDT is worthy of clinical application, even as monotherapy. The result of immune testing also indicated significant promotion of CD4+T expression during the recovery process, highlighting the importance of immune responses in different prognoses.

Identification of Distinct Immune Cell Subsets Associated With Asymptomatic Infection, Disease Severity, and Viral Persistence in COVID-19 Patients.

The cell-mediated protective and pathogenic immune responses to SARS-CoV-2 infection remain largely elusive. Here we identified 76 distinct cell subsets in the PBMC samples that were associated with various clinical presentations of COVID-19 using scRNA-seq technology coupled with a deep and comprehensive analysis of unique cell surface markers and differentially expressed genes. We revealed that (TRAV1-2+CD8+)MAIT cells and (NCAM1hiCD160+)NK cells significantly enriched in the asymptomatic subjects whereas (LAG3+CD160+CD8+)NKT cells increased in the symptomatic patients. We also observed that (CD68-CSF1R-IL1BhiCD14+)classical monocytes were positively correlated with the disease severity. Moreover, (CD33-HLA-DMA-CD14+)classical monocytes and (CLEC10A-S100A9lo)pDC were associated with the viral persistence. The GO and KEGG analyses identified enriched pathways related to immune responses, inflammation, and apoptosis. These findings may enhance our understanding of the immunopathogenesis of COVID-19 and help develop novel strategies against SARS-CoV-2 infection.

Distinct miRNAs associated with various clinical presentations of SARS-CoV-2 infection.

MicroRNAs (miRNAs) have been shown to play important roles in viral infections, but their associations with SARS-CoV-2 infection remain poorly understood. Here, we detected 85 differentially expressed miRNAs (DE-miRNAs) from 2,336 known and 361 novel miRNAs that were identified in 233 plasma samples from 61 healthy controls and 116 patients with COVID-19 using the high-throughput sequencing and computational analysis. These DE-miRNAs were associated with SASR-CoV-2 infection, disease severity, and viral persistence in the patients with COVID-19, respectively. Gene ontology and KEGG pathway analyses of the DE-miRNAs revealed their connections to viral infections, immune responses, and lung diseases. Finally, we established a machine learning model using the DE-miRNAs between various groups for classification of COVID-19 cases with different clinical presentations. Our findings may help understand the contribution of miRNAs to the pathogenesis of COVID-19 and identify potential biomarkers and molecular targets for diagnosis and treatment of SARS-CoV-2 infection.

An efficient conservative treatment modality for cervical pregnancy: angiographic uterine artery embolization followed by immediate curettage.

OBJECTIVE: We sought to evaluate a conservative treatment modality, angiographic uterine artery embolization (UAE) followed by immediate curettage, in the treatment of cervical pregnancy. STUDY DESIGN: Sixteen patients with cervical pregnancy were first treated by UAE to control or prevent vaginal bleeding. Curettage of cervical canal was performed immediately after UAE to remove gestational tissue from the cervix. Clinical outcome assessments include vaginal bleeding, serum ß-human chorionic gonadotropin level, cervical mass, menstruation, fertility, and hospitalization time. RESULTS: Fifteen patients were successfully treated by UAE followed by immediate curettage. One patient at very early gestational age underwent UAE only. Quick regression of serum human chorionic gonadotropin level and cervical mass, fertility preservation, and a short hospital stay were observed. CONCLUSION: UAE followed by immediate curettage is an efficient conservative treatment for cervical pregnancy. This procedure may become a useful alternative to other conservative approaches.

T-box transcription factor TBX1, targeted by microRNA-6727-5p, inhibits cell growth and enhances cisplatin chemosensitivity of cervical cancer cells through AKT and MAPK pathways.

Cervical cancer (CC) is the fourth most common cancers among women worldwide. T-box transcription factor 1 (TBX1), a member of the T-box family, has anti-tumor effects in some types of cancer, but its role in CC is yet unknown. The aim of this study is to investigate the functions and underlying mechanisms of TBX1 in CC. Online database UALCAN showed that TBX1 was down-regulated in CC tissues compared with normal tissues and patients with lower TBX1 expression level had a poor prognosis. TBX1 overexpression significantly decreased the proliferation, migration, and invasion of Hela and SiHa cells. Conversely, cell apoptosis and chemosensitivity to cisplatin were promoted in TBX1-overexpressing CC cells. Moreover, up-regulation of TBX1 inhibited both AKT and MAPK signaling pathways. Furthermore, dual luciferase report assay indicated that TBX1 could directly bind to miR-6727-5p. In addition, TBX1 expression was inhibited by miR-6727-5p mimic and up-regulated by miR-6727-5p inhibitor. Knockdown of TBX1 reversed the inhibitory effect of the miR-6727-5p inhibitor on CC cells. This study demonstrates that TBX1, a target gene of miR-6727-5p, acts as a tumor suppressor in CC, indicating that TBX1 may be a new target for CC therapy.

Loop electrosurgical excision procedure followed by 5-aminolevulinic acid photodynamic therapy for cervical intraepithelial neoplasia, a report of six cases.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) may progress to cervical cancer if left untreated. The loop electrosurgical excision procedure (LEEP) of the transitional zone of the cervix is a standard form of treatment. However, human papillomavirus (HPV)-induced CIN may recur after LEEP. The purpose of this case report is to describe the successful use of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) as an adjunct to LEEP, in preventing the recurrence of CIN. METHODS: The effectiveness of this combined treatment was evaluated in six women. The diagnosis of HPV-induced CIN was determined using HPV DNA tests and liquid-based cervical cytology. Lesion removal was performed 3 h after application of ALA using a 635 nm light density of 80 mw/cm2. RESULTS: We treated 6 women aged 31-62 years who had persistent CIN following LEEP, with ALA-PDT (range, 4-7 treatments). Five of the 6 women were HPV negative on retesting 6-7 months after ALA-PDT. Most patients showed no signs of recurrence during the follow-up period. CONCLUSIONS: Use of ALA-PDT following LEEP may prevent the recurrence of CIN. Monitoring HPV status by means of DNA testing and liquid-based cytology may be used as a standard for clinical diagnosis and treatment. Post-treatment care should be carefully considered because improper post-treatment care might directly lead to relapse.