Long-term Efficacy of Fibroid Devascularization with Ultrasound-Guided High-Intensity Focused Ultrasound.

RATIONALE AND OBJECTIVES: High-intensity focused ultrasound (HIFU) has been increasingly used for treatment of uterine leiomyoma. The superiority of HIFU therapy targeting uterine leiomyoma blood vessels, however, still needs to be further explored. This study aims to evaluate the long-term efficacy of fibroid devascularization with ultrasound-guided HIFU (USgHIFU) and the effects of treatment on the ovarian reserve and endometrial injury. MATERIALS AND METHODS: Fibroid devascularization was assessed with the Adler grade obtained by color Doppler flow imaging and power Doppler imaging (PDI). The targeted vessels were covered and then sonicated by HIFU focal spots. The patients were followed up at 1 month, 3 months, 6 months, 1 year, 2 years and 3 years after treatment. Adverse effects and complications were recorded. The non-perfusion volume rate (NPVR), fibroid volume shrinkage rate (FVSR), Adler Grade, symptom severity score (SSS) and uterine fibroid symptom and quality of life (UFS-QOL) were evaluated. Adverse events (AEs) were recorded. In Center 1, the enrolled patients completed the anti-Müllerian hormone (AMH) test before and at 6 months after treatment. RESULTS: A total of 117 eligible patients were consecutively enrolled to receive interventions and follow-up evaluations of the three centers from January 2019 to May 2023. The 1-month and 6-month NPVRs were 66.60% ± 33.14% and 51.12% ± 39.84%, respectively. The mean FVSRs at 1 month and 6 months after treatment were 38.20% and 43.89%, respectively. No significant difference was observed in AMH levels before and after treatment (p > 0.05). No irreversible endometrial injury was observed in MR images after HIFU treatment. No significant difference was observed in both 1-month and 6-month FVSRs among Center 1, 2 and 3 (p > 0.05). No severe AEs occurred. For long-term outcomes, significant differences were observed in Adler grade, FV, FVSR, SSS, reduction in SSS and UFS-QOL before and after treatment (p < 0.001) whereas no significant difference was observed in Adler grade among 3 months, 1 year, 2 years and 3 years after treatment (p > 0.05). The SSSs were reduced by 33.42% at 1 year, 42.32% at 2 years and 52.46% at 3 years after treatment. CONCLUSION: For patients with uterine fibroids, USgHIFU-induced devascularization is a safe and effective treatment option. It has little effect on ovarian function and the endometrial injury is reversible, which could be attractive for patients who plan to become pregnant.

Application Values of 2D and 3D Radiomics Models Based on CT Plain Scan in Differentiating Benign from Malignant Ovarian Tumors.

BACKGROUND: Accurate identification of ovarian tumors as benign or malignant is highly crucial. Radiomics is a new branch of imaging that has emerged in recent years to replace the traditional naked eye qualitative diagnosis. OBJECTIVE: This study is aimed at exploring the difference in the application potential of two- (2D) and three-dimensional (3D) radiomics models based on CT plain scan in differentiating benign from malignant ovarian tumors. METHOD: A retrospective analysis was performed on 140 patients with ovarian tumors confirmed by surgery and pathology in our hospital from July 2017 to August 2020. These 140 patients were divided into benign group and malignant group according to the pathological results. The ITK-SNAP software was used to outline the regions-of-interest (ROI) of 2D or 3D tumors on the CT plain scan image of each patient; the texture features were extracted through analysis kit (AK), and the cases were randomly divided into training groups (n = 99) and validation group (n = 41) in a ratio of 7 : 3. The least absolute shrinkage and selection operator (LASSO) algorithm was used to perform dimensionality reduction, followed by the construction of the radiomics nomogram model using the logistic regression method. The receiver operating characteristic (ROC) curve was drawn, and the calibration curve and decision curve analysis (DCA) were used to evaluate and verify the results of the radiomics nomogram and compare the differences between 2D and 3D diagnostic performance. RESULTS: There were 396 quantitative radiomics feature parameters extracted from 2D group and the 3D group, respectively. The area under the curve (AUC) of the radiomics nomogram of the 2D training group and the validation group were 0.96 and 0.97, respectively. The accuracy, specificity, and sensitivity of the training set were 92.9%, 88.9%, and 96.3%, respectively, and those of the validation set were 90.2%, 82.6%, and 100.0%, respectively. The AUCs of the radiomics nomogram of the 3D training group and validation group were 0.96% and 0.99%, respectively. The accuracy, sensitivity, and specificity of the training set were 92.9%, 96.3%, and 88.9%, respectively, and those of the validation set were 97.6%, 95.7%, and 100.0%, respectively. DeLong's test indicated that there was no statistical significance between the two sets (P > 0.05). CONCLUSIONS: For the differential diagnosis of benign and malignant ovarian tumors, the 2D and 3D radiomics nomogram models exhibited comparable diagnostic performance. Considering that the 2D model was cost-effective and time-efficient, it was more recommended to use 2D features in future research.

Sensitive silica-alumina modified capacitive non-Faradaic glucose sensor for gestational diabetes.

A highly sensitive silica-alumina (Si-Al)-modified capacitive non-Faradaic glucose biosensor was introduced to monitor gestational diabetes. Glucose oxidase (GOx) was attached to the Si-Al electrode surface as the probe through amine-modification followed by glutaraldehyde premixed GOx as aldehyde-amine chemistry. This Si-Al (∼50 nm) modified electrode surface has increased the current flow upon binding of GOx with glucose. Capacitance values were increased by increasing the glucose concentrations. A mean capacitance value was plotted and the detection limit was found as 0.03 mg/mL with the regression coefficient value, R² = 0.9782 [y = 0.8391x + 1.338] on the linear range between 0.03 and 1 mg/mL. Further, a biofouling experiment with fructose and galactose did not increase the capacitance, indicating the specific glucose detection. This Si-Al-modified capacitance sensor detects a lower level of glucose presence and helps in monitoring gestational diabetes.

Permanent neurological deficit caused by misdiagnosis of a giant intrapelvic sciatic schwannoma: A case report.

Sciatic schwannomas (SSs) are extremely rare, and most are benign. Herein, we report a case of giant SSs in a woman who presented with abdominal pain. Because of the pain pattern and auxiliary examination findings, the patient was initially diagnosed with an ovarian cystadenoma. Magnetic resonance imaging (MRI) revealed an intrapelvic tumor. Histopathological examination confirmed that the mass was a benign intrapelvic schwannoma. Two days after complete tumor resection, the patients experience impaired mobility of the right lower limb. The tumor was 7 × 5.5 × 5 cm3 in size and in contact with the sacrum. The patient was followed up for up to 2 years. No evidence of recurrence was observed in the MRI scan. Severe damages to the sciatic nerve during surgery resulted in permanent neurological deficits. Hence, we also discuss the diagnostic tools and treatments for intrapelvic SSs, as well as the importance of careful radiological examination and multidisciplinary collaboration.

A radiomics approach for automated diagnosis of ovarian neoplasm malignancy in computed tomography.

This paper develops a two-dimensional (2D) radiomics approach with computed tomography (CT) to differentiate between benign and malignant ovarian neoplasms. A retrospective study was conducted from July 2017 to June 2019 for 134 patients with surgically-verified benign or malignant ovarian tumors. The patients were randomly divided in a ratio of 7:3 into two sets, namely a training set (of n = 95) and a test set (of n = 39). The ITK-SNAP software was used to delineate the regions of interest (ROI) associated with lesions of the largest diameters in plain CT image slices. Texture features were extracted by the Analysis Kit (AK) software. The training set was used to select the best features according to the maximum-relevance minimum-redundancy (mRMR) criterion, in addition to the algorithm of the least absolute shrinkage and selection operator (LASSO). Then, we employed a radiomics model for classification via multivariate logistic regression. Finally, we evaluated the overall performance of our method using the receiver operating characteristics (ROC), the DeLong test. and tested in an external validation test sample of patients of ovarian neoplasm. We created a radiomics prediction model from 14 selected features. The radiomic signature was found to be highly discriminative according to the area under the ROC curve (AUC) for both the training set (AUC = 0.88), and the test set (AUC = 0.87). The radiomics nomogram also demonstrated good calibration and differentiation for both the training (AUC = 0.95) and test (AUC = 0.96) samples. External validation tests gave a good performance in radiomic signature (AUC = 0.83) and radiomics nomogram (AUC = 0.95). The decision curve explicitly indicated the clinical usefulness of our nomogram method in the sense that it can influence major clinical events such as the ordering or abortion of other tests, treatments or invasive procedures. Our radiomics model based on plain CT images has a high diagnostic efficiency, which is helpful for the identification and prediction of benign and malignant ovarian neoplasms.

Zinc oxide nanoparticles synthesized from Aspergillus terreus induces oxidative stress-mediated apoptosis through modulating apoptotic proteins in human cervical cancer HeLa cells.

OBJECTIVES: This study was aimed to analyze the cytotoxicity of biogenic zinc oxide nanoparticles (ZnO NPs) in human cervical epithelial cancer HeLa. METHODS: The ZnO NPs was synthesized from the culture filtrated of Aspergillus terreus, and examined by UV-spectroscopy, X-ray diffraction (XRD), transmission electron microscope (TEM), energy-dispersive X-ray (EDX) and Fourier transform infrared (FTIR) analysis. The cytotoxicity of synthesized ZnO NPs was analyzed by the MTT assay, and the expression of apoptotic proteins was examined by Western blot analyses. KEY FINDINGS: The ZnO NPs exhibited concentration-dependent cytotoxicity on HeLa cells and induced the apoptosis as evidenced by reduced superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) levels, and increased reactive oxygen species (ROS) and diminished mitochondrial membrane potential (MMP) was noticed in ZnO NPs treated HeLa cells. Western blot analyses explored that the Bcl-2 expression was significantly downregulated, whereas, the expression of p53, Bax, Caspase-3, Caspase-9 and Cytochrome-c were significantly upregulated in ZnO NPs treated cells. CONCLUSION: Consequently, the mycosynthesized ZnO NPs induces apoptosis in HeLa cells by persuading oxidative damage and modulating the apoptotic proteins. Therefore, A. terreus synthesized ZnO NPs could be used as an effective chemotherapeutic agent for cervical cancer treatment.

Antitumor Effects of Baicalein and Its Mechanism via TGFß Pathway in Cervical Cancer HeLa Cells.

BACKGROUND: Due to dual-regulating carcinogenesis, the TGFß pathway is an ideal and alternative tumor target. Natural flavonoids possess the similar structures to estrogen and could exert an important benefit to cervical cancer. The present study aimed to screen the inhibitor of TGFß pathway from natural flavonoids and evaluate the function and mechanism of the TGFß pathway inhibitor on cervical cancer. MATERIALS AND METHODS: The cervical cancer HeLa cells were firstly treated with different flavonoids and probed by western blot for screening the inhibitor of TGFß pathway. And then, the effect of the identified inhibitor on cell proliferation was studied by CCK-8 and clone formation assay. Then, RT-PCR and western blot assay were performed to evaluate the effect of identified inhibitor on mTOR/p70S6K pathway, and the cell migration and EMT pathway were also examined using scratching analysis and western blot assay. Finally, the role of TGFß was assessed via the classic inhibitor of TGFß/SMAD pathway. RESULTS: Screening data by western blot assay showed that baicalein displayed the best inhibitor effect on TGFß expression. CCK-8 and clone formation assay showed that baicalein inhibited the cell proliferation and clone cell number. RT-PCR and western bolt for probing mTOR, p70S6K, and 4EBP1 revealed that baicalein could suppress their expression and phosphorylation. The scratching analysis and western blot assay displayed that baicalein inhibited the cell migration and EMT progression in HeLa. The use of SB431542, a TGFß inhibitor, revealed that TGFß was crucial to baicalein-regulating cell proliferation and migration in HeLa cells. CONCLUSION: Baicalein, a medicine agent screened from natural flavonoids targeting TGFß pathway, could suppress mTOR/p70S6K pathway-mediated cell proliferation and EMT pathway-related migration via TGFß pathway in cervical cancer HeLa cells.

[Chinese Herbs Combined Three-stage Sequential Therapy for Conservative Treatment of Ectopic Pregnancy].

Objective To observe the clinical efficacy and safety of three-stage sequential thera- py [(methotrexate + mifepristone + Gongwaiyun Recipe (GR)] for conservative treatment of ectopic pregnancy. Methods Recruited were 250 ectopic pregnancy patients, who received conservative treat- ment at Affiliated Ganzhou Hospital of Nanchang University and Ruijin Maternal & Child Health Care Hos- pital from January 2010 to December 2014. They were assigned to the observation group (153 cases) and the control group (97 cases) according to different treatment methods used. Patients in the control group were treated with Western medicine only (methotrexate + mifepristone). Those in the observation group were intramuscularly injected with methotrexate 50 mg/m² at day 1 . Then they took mifepristone 150 mg per day from day 2 to day 6, once per day for 5 successive days. Afterwards they took modified GR decoction from day 7, one dose per day. Clinical symptoms of all patients were observed. Blood levels of ß-hCG and progesterone were detected. Pelvic mass was examined in order to compare the curative effects between the two groups. Complications such as oral ulcer and gastrointestinal reactions were ob- served. Blood cells, hepatic and renal functions were monitored. The incidence of adverse reactions was compared between the two groups. Fallopian tube function was assessed by hysterosalpingography after healing. The fallopian tube patency rate was compared between the two groups. Results (1) The blood ß-hCG negative conversion time was (16. 70 ± 5. 88) days and the mass disappearance time was (4. 34 ±1. 15) weeks in the observation group, obviously shorter than those of the control group [ (22. 31 ±3. 35) days, (5. 80 ±0. 80 ) weeks , t = -7. 476, -9. 982; P <0. 01 ] in the control group. The cure rate was 98. 0% (150/153) in the observation group, and it was 73. 2% (71/97) in the control group, with statistical difference (x² =35. 730, P <0. 01). (2) The fallopian tube patency rate was 90. 7% (136/ 150) in the observation group and 78. 9% (56/97) in the control group, with statistical difference between the two groups (x² =5. 879, P <0. 05). (3) The incidence of adverse reactions: The incidence of gastro- intestinal reactions was 22. 0% (33/150) in the observation group and 22. 1% (15/71 ) in the control group. The incidence of mild gastrointestinal reactions was 9. 3% (14/150) in the observation group and 8. 5% (6/71) in the control group. The incidence of oral ulcer was 8. 0% (12/150) in the observation group and 7. 0% (5/71) in the control group. The incidence of leukopenia was 2. 0% (3/150) in the observation group and 2. 8% (2/71) in the control group. There was no statistical difference in these indices aforesaid between the two groups (x² =0. 022, 0. 046, 0. 062, 0. 145; P >0. 05). Conclusion Chinese herbs com- bined three-stage sequential therapy might be a safer and more effective treatment for ectopic pregnancy patients who had requirement for pregnancy.

N-Benzylcinnamide induces apoptosis in HPV16 and HPV18 cervical cancer cells via suppression of E6 and E7 protein expression.

Seventy percent of all cervical cancers are caused by human papillomavirus (HPV) infections. Natural products are being extensively explored for their potential ability to prevent and treat cervical cancers. N-benzylcinnamide (PT-3) is a natural product purified from Piper submultinerve. Whether or not PT-3 has an effect on cervical cancer cells is as yet unknown. Therefore, we set out to explore the mechanism of action behind PT-3 and how it affects cells that either contain or lack HPV DNA. Our results demonstrate that PT-3 slows the growth kinetics of CaSki (HPV-16 positive) and HeLa (HPV-18 positive) cells in a dose-dependent manner, but does not slows HPV-negative cells. Importantly, we also found that PT-3 induces apoptosis by suppressing expression of E6 and E7 viral oncogenes in HPV-infected cervical cancer CaSki and HeLa cells. Moreover, we found that suppression of E6 and E7 expression leads to modulations in p53 and protein retinoblastomas, which are not changed in HPV-negative cervical cancer C33A cells. These findings demonstrate that PT-3 can effectively promote apoptosis by downregulating expression of E6 and E7.

Genetic variations in cytotoxic T-lymphocyte antigen-4 and susceptibility to cervical cancer.

Cytotoxic T-lymphocyte antigen-4 (CTLA-4), a molecule expressed predominantly on activated T cells, plays an important role in the down-regulation of T-cell activation. To evaluate the potential effects of CTLA-4 gene polymorphisms on susceptibility to cervical cancer, we genotyped polymorphisms in CTLA-4 (- 318 T/C, CT60 G/A,+49 G/A, - 658 T/C, and - 1661 G/A) and calculated odds ratios for the genotype and allele distributions between patients and controls. We then examined the functional relevance of the polymorphisms using enzyme-linked immunosorbent assays (ELISAs), in vitro lymphocyte proliferation assay, and cytotoxic assay. The CTLA-4 - 318 CC, CT60 AA, and+49 GG genotype frequencies were lower in patients than in controls (p <0.05). The frequencies of CTLA-4 - 318 T allele and CT60G allele carriers were significantly higher in patients than in controls (p <0.05). Upon stimulation, peripheral blood mononuclear cells (PBMCs) carrying the - 318TT and CT60GG genotypes exhibited significantly lower proliferation, IL-2, and IL-4 levels; fewer cytolytic activities; and higher TGF-ß levels compared with PBMCs carrying the - 318 CC/CT or CT60 AA/AG genotypes. We also found that CTLA-4 - 318 T/C and CT60 G/A single nucleotide polymorphisms were associated with the severity of cervical cancer. These results indicate that CTLA-4 - 318 T/C and CT60 G/A can affect cervical cancer susceptibility by altering the immune status of an individual.

Effects of estrogen on CD4(+) CD25(+) regulatory T cell in peripheral blood during pregnancy.

OBJECTIVE: To investigate the effects of estrogen (E2) level on regulatory T cells (Treg) in peripheral blood during pregnancy. METHODS: A total of 30 healthy non-pregnant women were selected as control group, 90 pregnant women of early, middle and late pregnancy and 30 postpartum women at 1 month after parturition were selected as experimental groups including early pregnancy group, middle pregnancy group and late pregnancy group; the proportions of CD4(+)CD25(+) Treg and CD4(+)CD25(+)CD127(-) Treg among CD4(+)T cells were detected by flow cytometry; the serum estrogen content in peripheral blood was detected by electrochemical immune luminescence method. RESULTS: E2 level was coincident with the change of Tregs number during pregnancy. The estrogen content in peripheral blood increased gradually from early pregnancy to late pregnancy, then decreased significantly after parturition, and the level at 1 month after parturition down to the level in non- pregnancy group (P>0.05); the level of E2 in pregnancy groups were significantly higher than those in non- pregnancy group (P<0.01); and there were significant differences among early pregnancy group, middle pregnancy group and late pregnancy group (P<0.05). The proportions of CD4(+) CD25(+) Treg and CD4(+) CD25(+) CD127(-) Treg in pregnancy groups were significantly higher than those in non- pregnancy group (P<0.05), but decreased significantly after parturition, and there was no significant difference between non- pregnancy group and postpartum women group (P>0.05); the proportions in middle and late pregnancy groups were significantly higher than those in early pregnancy group (P<0.05), but decreased slightly in late pregnancy group, there was no significant difference between late pregnancy group and middle pregnancy group (P>0.05). There was correlation between Tregs number with estrogen level during pregnancy. The proportion of CD4(+) CD25(+) Treg and CD4(+) CD25(+) CD127(-) Treg were positively correlated with estrogen level. CONCLUSIONS: High proportion of CD4(+) CD25(+) Treg and CD4(+)CD25(+)CD127(-) Treg is closely related to the high level of E2 during pregnancy. It suggested that high level of estrogen may induce an increase of CD4(+) CD25(+) Treg in peripheral blood, and then influence the immune function of pregnant women. The results of this experiment might play an important role of estrogen in immune-modulation during pregnancy.