Therapeutic effects of focused ultrasound on vulvar squamous intraepithelial lesions in rat.

OBJECTIVE: In this study, we established a Sprague-Dawley rat model of vulvar squamous intraepithelial lesions and investigated the impact of focused ultrasound on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and mutant type p53 (mtp53) in the vulvar skin of rats with low-grade squamous intraepithelial lesions (LSIL). MATERIALS AND METHODS: The vulvar skin of 60 rats was treated with dimethylbenzanthracene (DMBA) and mechanical irritation three times a week for 14 weeks. Rats with LSIL were randomly allocated into the experimental group or the control group. The experimental group was treated with focused ultrasound, while the control group received sham treatment. RESULTS: After 14 weeks treatment of DMBA combined with mechanical irritation, LSIL were observed in 44 (73.33%) rats, and high-grade squamous intraepithelial lesions (HSIL) were observed in 14 (23.33%) rats. 90.91% (20/22) of rats showed normal pathology and 9.09% (2/22) of rats exhibited LSIL in the experimental group at four weeks after focused ultrasound treatment. 22.73% (5/22) of rats exhibited LSIL, 77.27% (17/22) of rats progressed to HSIL in the control group. Compared with the control-group rats, the levels of HIF-1α, VEGF and mtp53 were significantly decreased in experimental-group rats (p < 0.05). CONCLUSIONS: These results indicate that DMBA combined with mechanical irritation can induce vulvar squamous intraepithelial lesion in SD rats. Focused ultrasound can treat LSIL safely and effectively, prevent the progression of vulvar lesions, and improve the microenvironment of vulvar tissues by decreasing the localized expression of HIF-1α, VEGF, and mtp53 in rats.

Therapeutic Effects of Low-Intensity Pulsed Ultrasound on Premature Ovarian Insufficiency.

We explored the therapeutic effects of low-intensity pulsed ultrasound (LIPUS) on a rat model of ovarian damage induced by cyclophosphamide. A total of 44 female rats with premature ovarian insufficiency induced by cyclophosphamide were randomly divided into two groups (an ultrasound group and a control group); 22 normal rats without premature ovarian insufficiency were also included as a third group. The ultrasound group was treated with LIPUS, while the other two groups received the same treatment but without any power output. We monitored the estrous cycles of all rats. Seven days after treatment, 21 rats were selected to mate with male rats. We then recorded the pregnancy rate along with the number and weight of newborn rats per nest. We collected samples of blood, uterus and ovaries from the remaining 45 rats before they were sacrificed. Compared with the normal group, the control group exhibited disordered estrous cycles, more atretic follicles (p < 0.01), higher levels of serum follicle-stimulating hormone (p < 0.01), fewer other follicles (p < 0.01) and lower serum levels of E2 and anti-Müllerian hormone (p < 0.01). Compared with the control group, the ultrasound group had normal estrous cycles with fewer atretic follicles (p < 0.01), lower levels of serum follicle-stimulating hormone (p < 0.01), more other follicles (p < 0.01) and higher levels of serum E2 (p < 0.01). No significant difference in the levels of serum anti-Müllerian hormone was noted between the control group and the ultrasound group. No significant differences were observed between the three groups with respect to pregnancy rate or the number and weight of newborns per nest (p > 0.05). In conclusion, our data indicate that LIPUS could improve some ovarian functions of rats with premature ovarian insufficiency.

Effect of Toremifene on Endometrium and Neurocognitive Function in Patients with Breast Cancer Based on Resting-State Functional Magnetic Resonance Imaging.

In this study, the characteristics of hemodynamic changes with use of toremifene before and after neoadjuvant chemotherapy in breast cancer treatment were analyzed using resting-state functional magnetic resonance imaging. Also, the effect of toremifene on the quality of life of patients with advanced breast cancer was analyzed. The study population comprised 100 patients who received endocrine therapy after breast cancer surgery in our hospital from January 2016 to January 2019. Patients were randomly divided into an observation group and a control group, with 50 cases in each group. The observation group was treated with tamoxifen combined with toremifene treatment; the control group was treated with toremifene. Before and after chemotherapy, the same scheme was used to perform dynamic contrast-enhanced imaging of the breast using a 1.5T superconducting scanner with 3 mL/second bolus injection of adiphenine meglumine 0.2 mmol/kg. Semiquantitative blood flow measurement was completed on the workstation and before and after chemotherapy to compare results. The patient's quality of life, progesterone and estrogen levels, social function, physical function, mental function, and material function were analyzed. The mean values of the early enhancement parameters Efirst, Vfirst, Ee, and Ve before chemotherapy were greater than in the residual lesions after chemotherapy (P < 0.5). The semiquantitative study of resting brain function before and after breast cancer neoadjuvant chemotherapy showed that the hemodynamics of the residual lesions were significantly reduced, and the blood flow rate was significantly reduced. Compared with the clinical effect of tamoxifen in the treatment of breast cancer after surgery, tamoxifen combined with toremifene has more advantages in improving quality of life, improving progesterone levels, and reducing estrogen levels, and it has no detrimental effects on the endometrium.

Therapeutic Effects of Focused Ultrasound on Expression of Notch1, C-Fos and Transforming Growth Factor-ß3 in Vulvar Skin of SD Rats with Vulvar Lichen Simplex Chronicus.

The purpose of this study was to investigate the therapeutic effects of focused ultrasound on the expression of notch1, c-fos and transforming growth factor-ß3 (TGF-ß3) in genital skin of SD rats with vulvar lichen simplex chronicus (LSC). Fifty-six female SD rats with LSC were randomly divided into therapy and sham groups. The therapy group was exposed to focused ultrasound. The sham group received the same therapy with an instrument that had no power output. Four wk after a singly focused ultrasound therapy, histologic analyses revealed that recovered SD rats accounted for 75% of SD rats in the therapy group and 10.7% in the sham group. Total collagen fiber density in the superficial layer of dermis in the therapy group was significantly lower than that in the sham group. Notch1 and c-fos protein expression in the therapy group was significantly lower than that in the sham group, with the opposite effect present for TGF-ß3. Focused ultrasound therapy may inhibit superficial collagen fibrosis in the dermis by affecting expression of notch1, c-fos and TGF-ß3 in vulvar skin tissue and consequently reduce the recurrence rate of LSC.

Clinical efficacy and mechanism for focused ultrasound (FUS) in the management of cervical intraepithelial neoplasia 1 (CIN1).

Objective: This study was aimed at investigating the clinical efficacy and studying the possible mechanism of FUS applications to treat cervical intraepithelial neoplasia 1 (CIN1).Methods: This was a prospective clinical study, in which 30 patients with CIN1 (28/30 of the patients were HPV positive) were enrolled and treated with FUS therapy by gynecologist. All patients were followed up for 3 months after FUS therapy. Telephone interviews, PAP smear, colposcopic examinations, cervical biopsies and HPVDNA tests were performed to assess the safety and effectiveness of FUS therapy for HPV-positive CIN1. The expression of p16, Ki-67 and Fas in the cervical tissues were examined in order to account for the possible mechanism of FUS therapy for CIN1 with HPV infection.Results: FUS therapy was tolerated well, and no severe complications were observed in any patient. After FUS treatment, twenty-five patients were cured completely, and two cases were improved with the cervical smear results reversed to normal, and three cases remained the same status as before treatment. The total effectiveness rate was 90.00% (27/30). The expression of P16 and Ki-67 in the treated cervical tissues was significantly lower than that before treatment, and the expression of Fas was found up-regulated (all p < .05).Conclusion: FUS therapy appears to be a feasible and effective treatment for patients with HPV positive CIN1. FUS therapy may help to reduce the expression of p16 and Ki-67 and enhance the expression of Fas in the treated cervical tissues to regulate cell proliferation and increase apoptosis, and thus prevent the disease from evolving into high grade lesions.

[Focused ultrasound therapy for reducing recurrence of vulvar lichen simplex chronicus in rats: efficacy and mechanism].

OBJECTIVE: To explore the changes of collagen fibrosis in the vulva skin of SD rats with lichen simplex chronicus (LSC) after focused ultrasound therapy and explore the mechanism by which focused ultrasound reduces the recurrence of vulvar LSC. METHODS: Fifty female SD rat models of vulvar LSC were established and randomly divided into the treatment group and the control group (n=25) for treatment with focused ultrasound and sham treatment, respectively. Before and after the treatment, vulvar skin tissues were sampled to observe the pathological changes with HE staining and assess the density of collagen fibers using Masson staining. The ultrastructure of the collagen fibers in the superficial dermis was observed using transmission electron microscopy. The expressions of notch1 and c-fos in the vulvar tissue were detected by immunohistochemistry and Western blotting. RESULTS: After 4 weeks of focused ultrasound therapy, 16% (4/25) of the rats in the treatment group showed lesion progression to LSIL, 4% (1/25) still had LSC, and 80% (20/25) showed normal vulvar skin. In the control group, progression to LSIL occurred in 19 (76%) rats, 3 (12%) rats still showed LSC, and only 3 (12%) had normal vulvar skin. The difference in the cure rate differed significantly between the two groups (P < 0.05). The density of collagen fibers in the superficial dermis and the expressions of notch1 and c-fos in the vulvar skin were significantly lower in the treatment group than in the control group (P < 0.05). CONCLUSIONS: Focused ultrasound therapy can inhibit superficial collagen fibrosis of the dermis by lowering the expressions of notch1 and c-fos in the vulvar skin to reduce the recurrence of vulvar LSC in rats.

[Establishment of a rat model of dimethylbenzanthracene-induced vulvar squamous intraepithelial lesions].

OBJECTIVE: To establish a SD rat model of vulvar squamous intraepithelial lesions. METHODS: Seventy female SD rats were randomized into 4 groups, namely the blank control group (n=10), mechanical irritation group (n=10), acetone solution group (n=10), and mechanical irritation with DMBA acetone solution group (n=40, model group), and the corresponding treatments were administered 3 times a week for 14 weeks. The changes of the vulvar skin of the rats were observed regularly until the 18th week. The expression of mutant p53 (mtp53) and vascular endothelial growth factor (VEGF) proteins were detected using immunohistochemistry and Western blotting, and the expressions of mtp53 and VEGF mRNA were detected with qRT- PCR in the blank control group and model group. RESULTS: No significant differences were found in the morphological or histopathological changes of the skin among the blank control group, mechanical irritation group and acetone solution group. In the model group, low-grade squamous intraepithelial lesions (LSIL) occurred in 28 rats (70%) and high-grade squamous intraepithelial lesions (HSIL) in 11 rats (27.5%) at 14 weeks, with a success rate of 97.5% in inducing vulvar squamous intraepithelial lesions. Compared with the blank control group, the rats in the model group showed significantly increased expressions of mtp53 and VEGF at both the protein level (P < 0.05) and the mRNA level (P < 0.05). CONCLUSIONS: DMBA in acetone solution combined with mechanical irritation can induce vulvar squamous intraepithelial lesions in female SD rats.

[Low-intensity pulsed ultrasound promotes repair of cyclophosphamide?induced ovarian injury in rats].

OBJECTIVE: To study the effects of low?intensity pulsed ultrasound (LIPUS) in promoting repair of cyclophosphamide (CTX)?induced ovarian injury in female rats. METHODS: Fifty female SD rats were subjected to intraperitoneal injection of cyclophosphamide at 30 mg/kg for 5 consecutive days to induce premature ovarian failure. Successful modeling was achieved in 43 rats, which were then randomized into model group (21 rats) and treatment group (22 rats), with another 13 rats without any injections serving as the normal control group. The rats in the treatment group received low?intensity pulsed ultrasound treatment, and those in the other two groups received no interventions. The estrous cycle of the rats was monitored during the experiment, and all the rats were sacrificed 7 days after the treatment for analysis of serum estradiol (E2), follicle stimulating hormone (FSH), anti?Mullerian hormone (AMH), morphological changes of the ovary and the number of follicles. RESULTS: Compared with those in the normal control group, the rats in the model group showed disorders in the estrous cycle, reduced number of follicles at all levels, significantly decreased serum E2 and AMH, and increased serum FSH following CTX injection (P=0.01). Ultrasound treatment obviously promoted the recovery of estrous cycle, significantly increased the number of follicles and serum E2 (P=0.01), and decreased FSH (P=0.01) in the rats with CTX?induced ovarian injury, but AMH showed no significant changes after ultrasound treatment (P=0.50). CONCLUSION: Low?intensity pulsed ultrasound can promote the repair of the CTX?induced ovarian injury in SD rats.