METTL14 decreases FTH1 mRNA stability via m6A methylation to promote sorafenib-induced ferroptosis of cervical cancer.

Cervical cancer (CC) is a prevalent malignancy among women worldwide. This study was designed to investigate the role of METTL14 in sorafenib-induced ferroptosis in CC. METTL14 expression and m6A methylation were determined in CC tissues, followed by analyzes correlating these factors with clinical features. Subsequently, METTL14 was knocked down in CC cell lines, and the effects on cell proliferation, mitochondrial morphology and ferroptosis were assessed using CCK-8, microscopy, and markers associated with ferroptosis, respectively. The regulatory relationship between METTL14 and FTH1 was verified using qRT-PCR and luciferase reporter assays. The functional significance of this interaction was further investigated both in vitro and in vivo by co-transfecting cells with overexpression vectors or shRNAs targeting METTL14 and FTH1 after sorafenib treatment. METTL14 expression and m6A methylation were significantly reduced in CC tissues, and lower METTL14 expression levels were associated with a poorer CC patients' prognosis. Notably, METTL14 expression increased during sorafenib-induced ferroptosis, and METTL14 knockdown attenuated the ferroptotic response induced by sorafenib in CC cells. FTH1 was identified as a direct target of METTL14, with METTL14 overexpression leading to increased m6A methylation of FTH1 mRNA, resulting in reduced stability and expression of FTH1 in CC. Furthermore, FTH1 overexpression or treatment with LY294002 partially counteracted the promotion of sorafenib-induced ferroptosis by METTL14. In vivo xenograft experiments demonstrated that inhibiting METTL14 reduced the anticancer effects of sorafenib, whereas suppression of FTH1 significantly enhanced sorafenib-induced ferroptosis and increased its anticancer efficacy. METTL14 reduces FTH1 mRNA stability through m6A methylation, thereby enhancing sorafenib-induced ferroptosis, which contributes to suppressing CC progression via the PI3K/Akt signaling pathway.

High-grade cervical lesions diagnosed by JAM3/PAX1 methylation in high-risk human papillomavirus-infected patients. / é«˜å±åž‹äººä¹³å¤´ç˜¤ç— æ¯’æ„ŸæŸ“æ‚£è€ å®«é¢ˆè„±è½ç»†èƒžJAM3/PAX1é«˜ç”²åŸºåŒ–è¯Šæ–­å®«é¢ˆé«˜çº§åˆ«ç— å˜.

OBJECTIVES: Currently, traditional cervical cancer screening methods, such as high-risk human papillomavirus testing and liquid based cytology (LBC), still possess limitations. This study aims to identify new diagnostic biomarkers to achieve the goal of "precision screening" via exploring the clinical value of DNA methylation [ΔCtP: paired box gene 1 (PAX1)and ΔCtJ: junctional adhesion molecule 3 (JAM3)] detection in cervical exfoliated cells for the diagnosis of high-grade cervical lesions. METHODS: A total of 136 patients who underwent gynecological examinations in the vaginal room of the Department of Gynecology at the Third Xiangya Hospital of Central South University from June 2021 to June 2022 were retrospectively studied. Among them, 122 patients had non-high-grade cervical lesions, and 14 patients had high-grade cervical lesions. The variables included general information (age, body mass index, and menopause status), LBC, high-risk human papillomavirus, cervical tissue pathology, vaginal examination results, and the ΔCt values of JAM3 and PAX1 gene methylation. Logistic regression analysis was used to identify the factors affecting the diagnosis of high-grade cervical lesions, followed by correlation analysis and construction of a conditional inference tree model. RESULTS: Logistic regression analysis showed that the methylation ΔCt values of PAX1 and JAM3 genes and LBC detection results were statistically significant between the high-grade cervical lesions group and the non-high-grade cervical lesions group (all P<0.05). Correlation analysis revealed a negative correlation between cervical pathological changes and ΔCtP (r=-0.36, P<0.001), ΔCtJ (r=-0.448, P<0.001), LBC (r=-0.305, P<0.001), or bacterial diversity (r=-0.183, P=0.037). The conditional inference tree showed that when ΔCtJ>10.13, all of patients had non-high-grade cervical lesions, while ΔCtP>6.22, the number of non-high-grade lesions accounted for 97.5% (117/120), and high-grade lesions accounted for only 2.5% (3/120). When ΔCtJ>8.61 and LBC were atypical squamous cell of undetermined significance or negative for intraepithelial lesions or malignancy (NILM), 105 (99.1%) patients were non-high-grade cervical lesions, only 1 (0.9%) patient was high-grade lesion. When the results of LBC were high-grade lesions, only 9 patients' histopathological examination was the high-grade lesions and 3 non-high-grade lesions. When LBC indicated low-grade lesions, atypical squamous cell of undetermined significance, no intraepithelial lesions, and ΔCtP>6.22, 117 (97.5%) of patients' histopathological examination was the non-high-grade lesions. CONCLUSIONS: The JAM3/PAX1 gene methylation test can be used independently for the stratified diagnosis of high-grade/non-high-grade cervical lesions in women with high-risk human papillomavirus infection, independent of the cytological results of cervical excision. The JAM3/PAX1 gene methylation test can also be used in combination with LBC to make up for the shortcomings of low sensitivity of LBC. In addition, the application of methylation kit in large-scale cervical cancer screening in the future will be good to the detection of more patients with high-grade cervical lesions, and achieve early screening and early treatment for cervical lesions/cancer.

Fertility-sparing treatment for cervical mullerian adenosarcoma: A case report and literature review. / å­å®«é¢ˆè ºè‚‰ç˜¤ä¿ç•™ç”Ÿè‚²åŠŸèƒ½æ²»ç–—1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Currently, whole uterus and bilateral tubal resection and oophorectomy is the main treatment of cervical mullerian adenosarcoma. However, young patients generally wish to retain reproductive function. The clinical data of a patient with cervical mullerian adenosarcoma, who underwent fertility preservation surgery were collected. A 13-year-old girl with abnormal vaginal bleeding and a 1.0 cm flocculent echogenicity in the lower part of the uterine cavity to the cervical canal and a cervical mass of about 61 mm×37 mm was found in the pelvic MRI. After initial diagnosis of dysfunctional uterine bleeding in adolescence and cervical blood clot, the patient was treated with artificial cycle treatment, but her symptoms did not improve. Then she was transferred to the Third Xiangya Hospital of Central South University for uninjured virgin membrane hysteroscopy and cervical mass electrotomy, but a few pedicles remained after the operation, and the pathology suggested a cervical mullerian adenosarcoma. Because the patient was young and had not yet given birth, she was treated with primary IAP regimen of chemotherapy and subcutaneously injected with gonadotropin-releasing hormone analogue (GNRH-A) once every 28 days (6 times in total) to protect the ovarian function. After the chemotherapy, she was treated with uninjured virgin membrane hysteroscopy and pedicle electrotomy of cervical mullerian adenosarcoma. After the operation, she received chemotherapy with IAP regimen for 5 times. After discharge, she was treated with megestrol 200 mg per day for 3 years. During 5 years of regular follow-up, no abnormality was seen. Cervical mullerian adenosarcoma in non-sexual women is easily misdiagnosed as ovulation dysfunction abnormal uterine bleeding. The necessity of hysteroscopy should be emphasized, and for patients with low-grade early-stage lesions who wish to retain fertility, local resection could be chosen, but attention is paid to lifelong follow-up to exclude long-term recurrence.

LncRNA KCNQ1OT1 promotes the metastasis of ovarian cancer by increasing the methylation of EIF2B5 promoter.

BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as regulators of human malignancies, including ovarian cancer (OC). LncRNA KCNQ1OT1 could promote OC progression, and EIF2B5 was associated with development of several tumors. This project was aimed to explore the role of lncRNA KCNQ1OT1 in OC development, as well as the involving action mechanism. METHODS: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) or Western blotting was employed to determine the expression levels of KCNQ1OT1 and EIF2B5. OC cell proliferation was evaluated by MTT and colony formation assays, and wound healing and Transwell assays were implemented to monitor cell migration and invasion, respectively. The methylation status of EIF2B5 promoter was examined by MS-PCR, to clarify whether the expression of EIF2B5 was decreased. The binding activity of KCNQ1OT1 to methyltransferases DNMT1, DNMT3A and DNMT3B was determined by dual luciferase reporter assay or RIP assay, to explore the potential of KCNQ1OT1 alters the expression of its downstream gene. ChIP assay was carried out to verify the combination between EIF2B5 promoter and above three methyltransferases. RESULTS: Expression of lncRNA KCNQ1OT1 was increased in OC tissues and cells. EIF2B5 expression was downregulated in OC, which was inversely correlated with KCNQ1OT1. Knockdown of KCNQ1OT1 inhibited OC cell proliferation and metastasis. KCNQ1OT1 could downregulate EIF2B5 expression by recruiting DNA methyltransferases into EIF2B5 promoter. Furthermore, interference of EIF2B5 expression rescued KCNQ1OT1 depletion-induced inhibitory impact on OC cell proliferation and metastasis. CONCLUSION: Our findings evidenced that lncRNA KCNQ1OT1 aggravated ovarian cancer metastasis by decreasing EIF2B5 expression level, and provided a novel therapeutic strategy for OC.

CircAHNAK upregulates EIF2B5 expression to inhibit the progression of ovarian cancer by modulating the JAK2/STAT3 signaling pathway.

Recent studies highlighted non-coding RNAs as potential therapeutic targets in ovarian cancer. We aimed to investigate the roles of circAHNAK in ovarian cancer pathogenesis. Here, RNA immunoprecipitation, dual-luciferase reporter assay and RNA fluorescence in situ hybridization were adopted to determine circAHNAK, miR-28 or EIF2B5 interaction. CCK-8 assay was used to detect cell proliferation. Wound healing and Transwell assays were employed to assess cell migration and invasion, respectively. Flow cytometry was performed to measure cell apoptosis. The roles of circAHNAK on tumor growth in vivo were evaluated using subcutaneous xenograft model. The expression levels of circAHNAK, miR-28, EIF2B5, markers of EMT and JAK2/STAT3 pathway were measured by qRT-PCR, western blotting or immunohistochemistry staining. We reported that circAHNAK was decreased in ovarian cancer tissues. Forced expression of circAHNAK promoted apoptosis and inhibited cell proliferation, migration, invasion, EMT and JAK2/STAT3 signaling pathway. Mechanistically, circAHNAK acted as a miR-28 sponge. CircAHNAK deficiency resulted in the amassing of miR-28, which was elevated in ovarian cancer and promoted cancer cell malignancy. MiR-28 in turn inhibited EIF2B5 expression. Silence of EIF2B5 abolished the anticancer effects of miR-28 inhibitor. CircAHNAK overexpression retarded tumor growth in vivo, along with the decreased miR-28 and increased EIF2B, as well as EMT inhibition. In conclusion, circAHNAK targets miR-28 to upregulate EIF2B5 expression, thus inhibits progression of ovarian cancer by suppressing JAK2/STAT3 signaling pathway.

Correlative study of preoperative three-dimensional transvaginal ultrasound findings and ongoing pregnancy/live birth in patients with intrauterine adhesions following hysteroscopic adhesiolysis: a retrospective study.

Background: Three-dimensional transvaginal ultrasound (3D-TVUS) has recently been adopted in the gynecological sciences as it provides an accurate illustration of adhesions and the extent of cavity damage, and hence, can be used as an essential tool for the prognosis of intrauterine adhesions (IUA). This study aims to demonstrate whether preoperative 3D-TVUS features are relevant to ongoing pregnancy and live births in patients with IUA following hysteroscopic adhesiolysis (HA). Methods: From February 22, 2018, to October 31, 2018, a total of 401 patients with moderate to severe IUA and underwent HA were retrospectively enrolled. Preoperative 3D-TVUS diagnosed data and the patients' basic information were collected, and patients were followed up over 2 years after HA for reproductive outcomes. The correlation between each imaging variable and ongoing pregnancy or live birth was analyzed by binary logistic regression. Results: Among the 401 patients, 143 had live births, 41 patients had abortions, and 217 patients were infertile. Thick endometrium was found to be favorable for ongoing pregnancy (ongoing pregnancy group =5.4±1.95 mm, no-ongoing pregnancy group =4.7±2.24 mm, P=0.0095) and live birth (live birth group=5.6±1.92 mm, no-live birth group =4.7±2.20 mm, P=0.0029). Scar contraction was not conducive for pregnancy, while the lower segmentation was not a risk factor for ongoing pregnancy (P=0.0003). It also was a risk factor for ongoing pregnancy (P<0.0001) and live birth (P<0.0001) when the segmentation of the endometrial absence was mainly in the upper and middle segments of the uterine cavity. The area under the curves (AUCs) of the prediction model for ongoing pregnancy and live birth were 0.9116 and 0.8751, respectively, based on the meaningful variables above combined with other clinical characteristics. Conclusions: Preoperative 3D-TVUS features have a close correlation with ongoing pregnancy and live births in patients with IUA following HA, and can be applied for predicting ongoing pregnancy and live births in IUA patients post-HA.

High-intensity focused ultrasound therapy for pediatric and adolescent vulvar lichen sclerosus.

OBJECTIVE: The study's objective was to retrospectively evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) for vulvar lichen sclerosus (VLS) in pediatric and adolescent patients. METHODS: Pediatric and adolescent patients presenting to our hospital from June 2007 to July 2021, with VLS were retrospectively evaluated. The participants' information, including age, symptoms and vulvar examination, were documented, and they were treated with HIFU. The effectiveness of HIFU and its complications were analyzed. RESULTS: A total of 36 patients with VLS undergoing HIFU for whom complete follow-up data were available participated in the study. The mean age of the patients at diagnosis was 13.3 ± 4.1 years. All patients successfully underwent HIFU therapy. The mean sonication time was 20.3 ± 8.6 min, and the median treatment energy was 3579.0 J. A few blisters developed in 8 (22.2%) patients and 2 (5.6%) had ulcers. The skin burns were treated medically without scar formation. On average, patients were followed up for 52.0 months after the procedure (a range of 6-175 months). At 6 months after therapy, the total response rate was 91.6%, and 86.6% at 12 months post HIFU. Overall, 16 patients were followed up for more than 5 years. The total response rate was 75%, and the recurrence rate was 12.5%. CONCLUSIONS: Based on our results, HIFU was demonstrated to be effective and relatively safe for the treatment of VLS in pediatric and adolescent patients, but it is necessary to pay attention to the possible skin burns.

Cdc25A inhibits autophagy-mediated ferroptosis by upregulating ErbB2 through PKM2 dephosphorylation in cervical cancer cells.

Cervical cancer is the leading cause of cancer-related deaths in women, and treatment for cervical cancer is very limited. Emerging evidence suggests that targeting ferroptosis is a promising way to treat cancer. Here, we investigated the role of ferroptosis in cervical cancer, with a focus on the Cdc25A/PKM2/ErbB2 axis. Cervical cancer cells were treated with sorafenib to induce ferroptosis. Cellular MDA/ROS/GSH/iron detection assays were used to measure ferroptosis. MTT assays were performed to assess cell viability. qRT-PCR, western blot, and immunostaining assays were performed to measure the levels of proteins. Autophagy was monitored by fluorescence microscopy. Nuclear and cytosolic fractions were isolated to examine the location of PKM2 modifications. Co-IP experiments were conducted to determine the Cdc25A/PKM2 interaction. ChIP assays were performed to measure the binding affinity between H3K9Ac and the ErbB3 promoter, and a dual luciferase assay was performed to examine the transcriptional activity of ErbB2. A nude mouse xenograft model was used to examine the effects of the Cdc25A/ErbB2 axis on tumour growth in vivo. Cdc25A was elevated in human cervical cancer tissues but was reduced during sorafenib-induced ferroptosis of cervical cancer cells. Overexpression of Cdc25A inhibited sorafenib-induced ferroptosis by dephosphorylating nuclear PKM2 and suppressing autophagy. Cdc25A regulated autophagy-induced ferroptosis by increasing ErbB2 levels via the PKM2-pH3T11-H3K9Ac pathway. Cdc25A increased the resistance of cervical cancer to sorafenib, while knockdown of ErbB2 blocked these effects. Cdc25A suppressed autophagy-dependent ferroptosis in cervical cancer cells by upregulating ErbB2 levels through the dephosphorylation of PKM2. These studies revealed that Cdc25A/PKM2/ErbB2 pathway-regulated ferroptosis could serve as a therapeutic target in cervical cancer.

Hsp90 up-regulates PD-L1 to promote HPV-positive cervical cancer via HER2/PI3K/AKT pathway.

BACKGROUND: HPV16 is the predominant cancer-causing strain that is responsible for over 50% of all cervical cancers. In this study, we aim to investigate the therapeutic effect of heat shock protein 90 (Hsp90) knockdown on HPV16+ cervical cancer progression and the underlying mechanism. METHODS: The transcript and protein expression of Hsp90 in normal cervical and HPV16+ cervical cancer tissues and cell lines were detected by qRT-PCR, immunohistochemistry staining and Western blot. Hsp90 knockdown clones were established using HPV16+ cervical cancer cell line Caski and SiHa cells. The effect of Hsp90 knockdown on HER2/PI3K/AKT pathway and PD-L1 expression was characterized using qRT-PCR and Western blot analysis. Cell proliferation and migration were determined using MTT and transwell assays. Using mouse xenograft tumor model, the impact of Hsp90 knockdown and PD-L1 overexpression on tumor progression was evaluated. RESULTS: Hsp90 expression was up-regulated in HPV16+ cervical cancer tissues and cells. Knockdown of Hsp90 inhibited proliferation and migration of Caski and SiHa cells. PD-L1 expression in cervical cancer tissues was positively correlated with Hsp90 expression, and Hsp90 regulated PD-L1 expression via HER2/PI3K/AKT signaling pathway. The results of mouse xenograft tumor model demonstrated Hsp90 knockdown suppressed tumor formation and overexpression of PD-L1 simultaneously eliminated the cancer-suppressive effect of Hsp90 knockdown. CONCLUSION: In this study, we demonstrated a promising tumor-suppressive effect of Hsp90 knockdown in HPV16+ cervical cancers, and investigated the underlying molecular pathway. Our results suggested that Hsp90 knockdown holds great therapeutic potential in treating HPV16+ cervical cancers.

Comparison of efficacy and safety of high-intensity focused ultrasound at different powers for patients with vulvar lichen simplex chronicus.

OBJECTIVE: To compare the efficacy and safety of the treatment of vulvar lichen simplex chronicus (VLSC) using high-intensity focused ultrasound (HIFU) at different powers. METHODS: This retrospective study included 152 patients with VLSC. Among these patients, 70 were treated with HIFU at low power (level 2), and 82 were treated at normal power (level 3). The treatment responses, recurrence rates and intra- and postoperative complications were all compared. RESULTS: No statistically significant differences were found between the two groups in age, disease course, menopause status, lesion size and severity of symptoms. All patients received one session of HIFU therapy, and the treatment process was successful. No difference was found in the total response rate between the two groups at 1 (85.7% versus 87.8%, p = .35), 6 (80% versus 80.5%, p = .65) and 12 (80% versus 80.5%, p = .73) months after HIFU therapy. No significant difference was observed in the recurrence rate between the two groups at 6 (5.7% versus 9.8%, p = .36) and 12 (22.9% versus 26.8%, p = .57) months after HIFU treatment. Patients in the low-power group had a lower incidence of blisters (10% versus 23.3%, p = .04). CONCLUSION: Based on our results, low-power HIFU treatment can achieve a therapeutic effect similar to normal power HFU treatment for VLSC, but its incidence of side effects is lower.

Early versus late hysteroscopic resection after high-intensity focused ultrasound for retained placenta accreta.

Objective: To compare early and late hysteroscopic resection after high-intensity focused ultrasound (HIFU) for retained placenta accreta. Methods: This retrospective study included 63 women with retained placenta accreta who were treated with HIFU combined with hysteroscopic resection. They were divided into an early group (n = 40) and a late group (n = 23), depending on the time between the HIFU and the hysteroscopic resection. The number of sessions of hysteroscopy needed, adverse events, menstrual recovery, and reproductive outcomes were compared. Results: The mean largest diameter of the retained placenta accreta was 67.6 ± 14.0 mm and 71.6 ± 23.6 mm in each group (p = .47), respectively. In the early group, the first hysteroscopic procedure was done at a mean interval of 2.7 ± 1.4 days after HIFU ablation, while in the late group, the interval was 34.7 ± 15.0 days (p < .001). The rate of complete resection of placenta residue after one hysteroscopic procedure in the late group was 73.9% (17/23). This was significantly higher than in the early group, where the rate was 45% (p = .03). During the follow-up, there was no difference in menstrual recovery and pregnancy outcomes between the groups. Conclusion: This study was the first to compare the effects and safety of early and late hysteroscopic resection after HIFU for retained placenta accreta. Late hysteroscopic resection seems to increase the rate of complete resection of retained placenta accreta after one hysteroscopic procedure.

High-intensity focused ultrasound in the management of adenomyosis: long-term results from a single center.

OBJECTIVE: To investigate the long-term clinical outcomes of patients with adenomyosis treated by high-intensity focused ultrasound (HIFU). MATERIALS AND METHODS: From June 2012 to January 2020, 2311 patients with adenomyosis were treated with HIFU at our center, 1982 patients who have complete clinical data were retrospectively reviewed. Among the patients who completed the follow-up, 485 were treated with HIFU alone, 289 were treated with HIFU followed by GnRH-a, 255 were treated with HIFU combined with Mirena and 594 were treated with HIFU combined with GnRH-a and Mirena. The dysmenorrhea severity pain score and average menorrhagia severity score before and at 3 months, 6 months, 1 year, 2 years, 3 years and 5 years after HIFU were compared. The adverse effects were recorded. In addition, the efficacy between patients treated with GnRH-a and/or Mirena were compared. RESULTS: After HIFU ablation, the dysmenorrhea severity pain score and the menorrhagia severity score were significantly decreased at each follow-up time point. However, it was observed that as the follow-up time increased, the effective rate of HIFU treatment in improving dysmenorrhea and menorrhagia decreased. The 6 months and 3 years follow-up results showed that the efficacy of HIFU combined with Mirena and HIFU combined with GnRH-a and Mirena were significantly higher than HIFU alone and HIFU combined with GnRH-a (p < 0.05). The major complications were rare. CONCLUSION: HIFU is a safe and effective treatment for patients with adenomyosis. HIFU combined with Mirena or HIFU combined with GnRH-a and Mirena can significantly enhance the long-term treatment results.

A comparative analysis of pregnancy outcomes of patients with uterine fibroids after high intensity focused ultrasound ablation and laparoscopic myomectomy: a retrospective study.

PURPOSE: The aim of this study was to retrospectively compare and analyze pregnancy outcomes of patients with uterine fibroids after high intensity focused ultrasound (HIFU) ablation and laparoscopic myomectomy (LM). MATERIALS AND METHODS: The study group consisted of 346 patients with uterine fibroids who wished to conceive, in which 152 patients received HIFU ablation treatment (HIFU group) and 194 patients received LM treatment (LM group). The parents' baseline characters were recorded and the pregnancy outcomes were evaluated in a median follow-up time of 42 months (range: 16 ∼ 81) after the treatment, and the differences of the two groups were compared. RESULTS: Patients with uterine fibroids in HIFU group had a significant shorter pregnancy interval than that in LM group (10 months VS. 13 months, p < .05). No significant differences were observed in pregnancy rate, miscarriage rate, live birth rate, natural pregnancy rate, cesarean section rate, and perinatal complications rate between the HIFU group and the LM group (p > .05). When stratified by age, infertility history, fibroid types, fibroid numbers, and fibroid sizes, there was no statistically significant difference in pregnancy rate between the HIFU group and the LM group (p > .05). CONCLUSIONS: Based on the results from this study, both HIFU and LM can be safely used to treat patients who wish to conceive. The pregnancy outcomes of post-HIFU are similar to that of post-LM.

Factors That Impact Fertility after Hysteroscopic Adhesiolysis for Intrauterine Adhesions and Amenorrhea: A Retrospective Cohort Study.

STUDY OBJECTIVE: To identify factors that affect reproductive outcomes after hysteroscopic adhesiolysis in patients with severe intrauterine adhesions (IUAs, scored between 9 and 12 according to the American Fertility Society classification) and amenorrhea. DESIGN: A retrospective cohort study. SETTING: A university-affiliated hospital. PATIENTS: One hundred fifty-one patients with severe IUAs and amenorrhea. INTERVENTION: Patients were diagnosed via hysteroscopy and underwent at least 1 hysteroscopic adhesiolysis between May 2012 and January 2016. MEASUREMENTS AND MAIN RESULTS: Of 151 patients, 12 were lost to follow-up, and 139 were included in the study with a follow-up period ranging from 2 to 6 years. Of the 139 evaluable patients, 107 (77%) recovered with a normal uterine cavity (free of IUAs), 28 (20.1%) had improved uterine cavity (fewer IUAs), and 4 (2.9%) showed no improvement. Moreover, 79 patients (56.8%) recovered with normal menstruation, 54 (38.9%) showed increased frequency of menstruation, and 6 (4.3%) had persistent amenorrhea. Seventy-seven (55.4%) became pregnant, of whom 13 had a spontaneous miscarriage, 11 birthed prematurely (at 31-36 gestational weeks), 44 experienced term delivery, and 9 were still pregnant at the end of the study. Age >32 years (p = .002, odds ratio [OR] = 3.442), >2 surgeries (p = .027, OR = 2.969), cervical canal adhesions (p = .047, OR = 2.112), and disease course >6 months (p = .037, OR = 2.335) were risk factors for infertility in patients with severe IUAs and amenorrhea. CONCLUSION: Younger age, earlier treatment within the disease course, fewer cervical canal adhesions, and fewer surgical procedures improve the reproductive outcome in patients with severe IUAs and amenorrhea.

[Effect of arterial flow on muscle atrophy].

This study analyzed the inherent relation between arterial blood mass flow and muscle atrophy of residual limb to provide some necessary information and theoretical support for the clinical rehabilitation of lower limb amputees. Three-dimensional arterial model reconstruction was performed on both intact side and residual limb of a unilateral transfemoral amputee who is the subject. Then hemodynamic calculation was carried out to comparatively analyze the mass flow state at each arterial outlet of both lower extremities. The muscle atrophy ratio of residual limb was calculated by measuring the cross-sectional area of bilateral muscles. Based on the blood supply relationship, the correlation between arterial blood flow reduction ratio and muscle atrophy ratio was discussed. The results showed that the mass flow of superficial femoral arteries and lateral circumflex femoral arteries severely reduced. Meanwhile rectus femoris, vastus lateralis and vastus medialis which were fed by these arteries showed great atrophy too. On the contrary, the mass flow of deep femoral arteries and medial femoral circumflex arteries slightly reduced. Meanwhile gracilis, adductor longus, long head of biceps which were fed by these arteries showed mild atrophy too. These results indicated that there might be a positive and promotion correlation between the muscle atrophy ratio and the blood mass flow reduction ratio of residual limb during rehabilitation.

Analysis of the Reproductive Outcome of Patients with Cesarean Scar Pregnancy Treated by High-Intensity Focused Ultrasound and Uterine Artery Embolization: A Retrospective Cohort Study.

STUDY OBJECTIVE: To investigate risk factors for infertility and recurrent cesarean scar pregnancy (CSP) after previous CSP. DESIGN: A retrospective cohort study (Canadian Task Force classification II-1). SETTING: University hospital. PATIENTS: Between January 2007 and April 2016, a total of 650 patients were included, all diagnosed with CSP and treated by high-intensity focused ultrasound (HIFU) and uterine artery embolization (UAE), followed by suction curettage under hysteroscopic guidance. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Follow-up of the reproductive outcomes ended in June 2017. A total of 135 of the 650 patients with CSP were involved in the study, among whom 32 became infertile, 78 had an intrauterine pregnancy, and 25 had recurrent CSP after previous CSP. Age (≥35 years; odds ratio [OR], 4.252; p = .002), ß-human chorionic gonadotropin (≤5000 mIU/mL; OR, 3.778; p = .011), and longer duration of amenorrhea (>56 days; OR, 2.507; p = .05) were risk factors for infertility. Treatment with UAE (OR, 5.796; p = .003), more abortions (≥4; OR, 2.851; p = .022), and being asymptomatic (OR, 4.175; p = .039) were risk factors for recurrent CSP. There was no statistically significant difference in the subsequent outcomes of pregnant women in the HIFU and UAE groups (p >.05). CONCLUSION: More attention should be given to subsequent reproductive outcomes after CSP, not only for intrauterine pregnancy, but also for infertility and recurrent CSP. Early diagnosis and treatment of CSP could reduce the risk of infertility and recurrent CSP. HIFU seemed to be superior to UAE in reducing the risk of recurrent CSP. Patients with CSP should adhere to strict contraception if they do not desire more children.

MiR-34c/SOX9 axis regulates the chemoresistance of ovarian cancer cell to cisplatin-based chemotherapy.

Cisplatin (DDP)-based chemotherapy is a standard strategy for ovarian cancer (OC), while chemoresistance remains a major therapeutic challenge. Transcription factor SOX9 has been reported to be associated with tumor cell proliferation, metastasis, and chemoresistance. In the current study, we observed a higher SOX9 expression in OC cell lines; SOX9 overexpression might aggravate the chemoresistance of the OC cell to DDP, whereas its knockdown enhanced the chemoresistance. We screened for candidate microRNAs (miRNAs) which might target SOX9 using online tools and further verified the effect of miR-34c, one of the candidate miRNA that significantly inhibited SOX9 expression, in the regulation of OC cell proliferation and chemoresistance to DDP. Further, we verified the interaction between SOX9 and miR-34c, as well as the involvement of ß-catenin signaling in this process. Through the analysis of the correlation between miR-34c expression and the clinical features of patients with OC, we revealed that miR-34c might inhibit OC cell proliferation and chemoresistance to improve the prognosis of patients with OC. Further, the expression of SOX9, ß-catenin, and c-Myc in OC tissues was upregulated and inversely correlated with miR-34c expression, indicating that rescuing miR-34c expression, thus to inhibit SOX9, ß-catenin, and c-Myc expression presents a promising strategy of reducing the chemoresistance of the OC cell to DDP.

Inhibitory effects of telmisartan on culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes from Xinjiang Kazakh patients with hypertension.

INTRODUCTION: Activation of T lymphocytes, for which potassium channels are essential, is involved in the development of hypertension. In this study, we explored the inhibitory effects of telmisartan on the culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes derived from Xinjiang Kazakh patients with hypertension. METHODS: CD4+ T-cell samples from hypertensive Kazakh patients and healthy Kazakh people were divided into healthy control, case control, telmisartan, and 4-aminopytidine groups. Changes in the expression levels of interleukin (IL)-6 and IL-17 in the blood of the healthy control and case control subjects were detected by enzyme-linked immunosorbent assay. Peripheral blood CD4+ T lymphocytes were first activated and proliferated in vitro and then incubated for 0, 24, and 48 h under various treatment conditions. Thereafter, changes in CD4+ T-lymphocytic proliferation were determined using Cell Counting Kit-8 and microscope photography. Changes in messenger RNA (mRNA) and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes were detected using real-time quantitative polymerase chain reaction and Western blots, respectively. RESULTS: The IL-6 and IL-17 expression levels were significantly higher in the blood of the hypertensive Kazakh patients than in the healthy Kazakh people. Telmisartan inhibited T-lymphocytic proliferation, as well as the mRNA and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes, and the inhibitory effects were time-dependent, with the strongest inhibition observed after 48 h and significantly weaker inhibition observed after 24 h of treatment. CONCLUSIONS: Telmisartan may potentially regulate hypertensive inflammatory responses by inhibiting T-lymphocytic proliferation and Kv1.3 potassium channel expression in CD4+ T lymphocytes.

The effects of telmisartan on the nuclear factor of activated T lymphocytes signalling pathway in hypertensive patients.

HYPOTHESIS: Previous studies provide links between the nuclear factor of activated T lymphocytes (NFAT) signalling pathway and the development of hypertension. Our preliminary studies indicate that telmisartan can block Kv1.3 potassium channels and effectively inhibit potassium current densities, along with Kv1.3 mRNA and protein expression levels. This paper aims to investigate whether telmisartan has an inhibitory effect on the NFAT signalling pathway after activation and proliferation of peripheral blood T lymphocytes in Kazakh patients with essential hypertension (EH) from Xinjiang, China. MATERIALS AND METHODS: T lymphocytes were isolated using the immunomagnetic cell sorting method (MACS). The mRNA expression of NFATc1, IL-6 and TNF-α was measured by quantitative polymerase chain reaction (qRT-PCR) and relative protein levels were evaluated by Western blot. T cell samples from 50 hypertensive Kazakh patients from Xinjiang were randomly divided into control, telmisartan, cyclosporin A (CsA), VIVIT, and 4-aminopytidine (4-AP) groups. Peripheral blood T lymphocytes were first activated and proliferated in vitro, then incubated for 48 h under different treatment conditions before determination of protein and mRNA expression of NFATc1, IL-6, and TNF-α by Western blot and qRT-PCR analyses, respectively. RESULTS: There were no significant differences in cardiovascular risk factors among the patients with samples assigned to the five groups (p > 0.05). Expression of NFATc1, IL-6, and TNF-α mRNA and protein was significantly reduced in T lymphocytes in all treatment groups (telmisartan, CsA, VIVIT, and 4-AP) compared with controls. CONCLUSIONS: Antihypertensive function and inhibitory effects of telmisartan on the T lymphocyte NFAT signalling pathway are unlikely to affect the normal immune function of hypertensive patients. Telmisartan may exert anti-inflammatory effects by inhibition of the NFAT signalling pathway in the T lymphocytes of hypertensive patients.

[Analysis of human papillomavirus infection in 16 320 patients from gynecologic clinic].

OBJECTIVE: To evaluate the genital human papillomavirus (HPV) infection in patients from gynecology clinic, and to investigate the association of persistent HPV infection with cervical lesions. METHODS: From January, 2009 to December, 2013, clinical data of 16 320 patients in Third Xiangya Hospital were collected. A retrospective analysis was carried out to evaluate the overall prevalence of HPV infection. The prevalence of HPV infection in different ages and subtypes were compared. The prevalence of persistent HPV infection and results of cervical cytology were analyzed. RESULTS: The overall HPV prevalence was 26.54%. The lowest overall and high-risk HPV prevalence were found in women at the age of 30-39 years old (P<0.05); the highest ones were found at the age of over 60 years old, with significant difference among the aged groups (P<0.05). There was no significant difference in low-risk HPV prevalence among the aged groups (P=0.693). The clearance rate of HPV was 87.65% one year later. There was no significant difference in high-risk and low-risk HPV infection between the non-persistent positive group and the persistent positive group (P=0.545), but the difference in single and multiple subtypes infection between these 2 groups was significant (P<0.05). In the persistent positive group, the most common genotypes were HPV 16, 52, 58, CP8304, and 33. The incidence of ASC-US, HSIL or SCC was significantly increased in the persistent positive group. CONCLUSION: Persistent HPV infection mainly consists of multiple and high-risk HPV infection. It is necessary to focus on the prevention of HPV 16, 52 and 58 persistent infection in our region.