The UBP14-CDKB1;1-CDKG2 cascade controls endoreduplication and cell growth in Arabidopsis.

Endoreduplication, a process in which DNA replication occurs in the absence of mitosis, is found in all eukaryotic kingdoms, especially plants, where it is assumed to be important for cell growth and cell fate maintenance. However, a comprehensive understanding of the mechanism regulating endoreduplication is still lacking. We previously reported that UBIQUITIN-SPECIFIC PROTEASE14 (UBP14), encoded by DA3, acts upstream of CYCLIN-DEPENDENT KINASE B1;1 (CDKB1;1) to influence endoreduplication and cell growth in Arabidopsis thaliana. The da3-1 mutant possesses large cotyledons with enlarged cells due to high ploidy levels. Here, we identified a suppressor of da3-1 (SUPPRESSOR OF da3-1 6; SUD6), encoding CYCLIN-DEPENDENT KINASE G2 (CDKG2), which promotes endoreduplication and cell growth. CDKG2/SUD6 physically associates with CDKB1;1 in vivo and in vitro. CDKB1;1 directly phosphorylates SUD6 and modulates its stability. Genetic analysis indicated that SUD6 acts downstream of DA3 and CDKB1;1 to control ploidy level and cell growth. Thus, our study establishes a regulatory cascade for UBP14/DA3-CDKB1;1-CDKG2/SUD6-mediated control of endoreduplication and cell growth in Arabidopsis.

Factors associated with thermal injury of abdominal skin in focused ultrasound ablation of uterine fibroids.

OBJECTIVE: To investigate the factors which may cause thermal injury of abdominal skin in patients with uterine fibroids (UFs) who underwent ultrasound-guided focused ultrasound ablation surgery (FUAS). METHOD: A total of 123 patients were enrolled in the injury group. In contrast, 246 patients without thermal injury were assigned to the non-injury group. The relationship between patient and treatment parameters and injury were explored using univariate analysis and multiple logistic regression analyses. In addition, the factors influencing the degree of thermal injury were analyzed using Kruskal-Wallis H. RESULTS: (1) Abdominal scars (p = .007, OR = 2.187, 95% CI: 1.242-3.849), abdominal wall thickness (p < .001, OR = 1.042, 95% CI: 1.019-1.067), fundus fibroids (p = .038, OR = 1.790, 95% CI: 1.033-3.100), UFs with hyperintense/mixed T2-weighted imaging (T2WI) signals (p = .022, OR = 1.843, 95% CI: 1.091-3.115), average sonication power (AP) (p = .025, OR = 1.021, 95% CI: 1.003-1.039), and treatment time (TT) (p < .001, OR = 1.017, 95% CI: 1.011-1.023) were independent risk factors for thermal injury, while treatment volume (TV) (p = .002, OR = 0.775, 95% CI: 0.661-0.909) was a protective factor for injury. (2) Four groups were subdivided according to the degree of thermal injury(Group A: without skin injury. Group B: with changed T2WI signal in the abdominal wall, Group C: mild skin injury, Group D: severe skin injury), comparison of each with every other showed that the abdominal wall in Groups A and D was thinner than Groups B and C, with statistically significant differences (PAB<0.05, PAC<0.01, PDC<0.05, PDB<0.05); Group A was slightly thicker than D, however, without statistical difference. The ratio of sonication time (ST) to TV in Group A was the lowest of all (PAB, PAC, PAD all < 0.05). And as the level of thermal injury rose, the ratio gradually increased, however, without statistical difference. CONCLUSIONS: Based on our limited results, the following conclusion was made. (1) Abdominal scars, abdominal wall thickness, fundus fibroids, UFs with T2WI hyperintense/mixed signals, AP and TT were independent risk factor. (2) Neither too thick nor too thin abdominal walls would be recommended, as both might increase the risk of skin injury. (3) Noticeably, the risk of skin injury might increase considerably when the ST was longer and the sonication area was more fixed.

Long-term outcome and risk factors of reintervention after high intensity focused ultrasound ablation for uterine fibroids: a systematic review and meta-analysis.

OBJECTIVES: To quantify the reintervention rate and analyze the risk factors for reintervention after high-intensity focused ultrasound (HIFU) ablation of uterine fibroids. METHODS: Eighteen studies were selected from the seven databases. A meta-analysis was applied to synthesize the reintervention rates for fibroids across various follow-up durations. Subgroup-analysis was conducted based on the year of surgery, sample size, guide methods, and non-perfusion volume ratio (NPVR). Signal intensity of T2-weighted imaging (T2WI) was independently evaluated for reintervention risk. RESULTS: The study enrolled 5216 patients with fibroids treated with HIFU. There were 3247, 1239, 1762, and 2535 women reaching reintervention rates of 1% (95% confidence interval (CI): 1-1), 7% (95% CI: 4-11), 19% (95% CI: 11-27), and 29% (95% CI: 14-44) at 12, 24, 36, and 60-month after HIFU. The reintervention rates of patients treated with US-guided HIFU (USgHIFU) were significantly lower than those of patients treated with MR-guided focused ultrasound surgery (MRgFUS). When the NPVR of fibroids was over 50%, the reintervention rates at 12, 36 and 60-month after HIFU were 1% (95% CI: 0.3-2), 5% (95% CI: 3-8), and 15% (95% CI: 9-20). The reintervention risk for hyper-intensity fibroids on T2WI was 3.45 times higher (95% CI: 2.7-4.39) for hypo-/iso-intensity fibroids. CONCLUSION: This meta-analysis showed that the overall reintervention rates after HIFU were acceptable and provided consultative suggestions regarding treatment alternatives for patients with fibroids. Subgroup-analysis revealed that USgHIFU, NPVR ≥ 50%, and hypo-/iso-intensity of fibroids on T2WI were significant factors in reducing reintervention. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023456094.

Temperature-Promoted Giant Unilamellar Vesicle (GUV) Aggregation: A Way of Multicellular Formation.

The evolution of unicellular to multicellular life is considered to be an important step in the origin of life, and it is crucial to study the influence of environmental factors on this process through cell models in the laboratory. In this paper, we used giant unilamellar vesicles (GUVs) as a cell model to investigate the relationship between environmental temperature changes and the evolution of unicellular to multicellular life. The zeta potential of GUVs and the conformation of the headgroup of phospholipid molecules at different temperatures were examined using phase analysis light scattering (PALS) and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), respectively. In addition, the effect of increasing temperature on the aggregation of GUVs was further investigated in ionic solutions, and the possible mechanisms involved were explored. The results showed that increasing temperature reduced the repulsive forces between cells models and promoted their aggregation. This study could effectively contribute to our understanding of the evolution of primitive unicellular to multicellular life.

Plant (di)terpenoid evolution: from pigments to hormones and beyond.

Covering: up to 2014-2022.Diterpenoid biosynthesis in plants builds on the necessary production of (E,E,E)-geranylgeranyl diphosphate (GGPP) for photosynthetic pigment production, with diterpenoid biosynthesis arising very early in land plant evolution, enabling stockpiling of the extensive arsenal of (di)terpenoid natural products currently observed in this kingdom. This review will build upon that previously published in the Annual Review of Plant Biology, with a stronger focus on enzyme structure-function relationships, as well as additional insights into the evolution of (di)terpenoid metabolism since generated.

Dauer larva-derived extracellular vesicles extend the life of Caenorhabditis elegans.

There is growing evidence that extracellular vesicles (EVs) play a functional role in tissue repair and anti-aging by transferring the contents of donor cells to recipient cells. We hypothesized that Dauer (C. elegans), known as "ageless" nematodes, can also secrete extracellular vesicles and influence the lifespan of C. elegans. Here, we isolated EVs of dauer larvae (dauer EVs). Dauer EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA), and Western blot analysis. Wild-type C. elegans were fed in the presence or absence of dauer EVs and tested for a range of phenotypes, including longevity, mobility and reproductive capacity. Results showed that dauer EVs increased the average lifespan of nematodes by 15.74%, improved mobility, slowed age-related pigmentation as well as body length, and reduced the accumulation of reactive oxygen species and lipids, while not impairing nematode reproductive capacity. These findings suggest that dauer EVs can extend the lifespan of C. elegans as well as the healthy lifespan by reducing ROS accumulation, with potential anti-aging capacity.

Bifidobacterium-derived membrane vesicles inhibit triple-negative breast cancer growth by inducing tumor cell apoptosis.

BACKGROUND: Bacterial outer membrane vesicles have gained increasing attention for its antitumor effect and application in drug delivery. However, the bacterial membrane vesicles (MVs) that are secreted by Gram-positive bacteria are rarely mentioned. Bifidobacterium has a certain anti-tumor effect, but there is a certain risk when injected into human body. Here we investigated the potential of Bifidobacterium-derived membrane vesicles (B-MVs) as therapeutic agents to treat triple-negative breast cancer. METHODS AND RESULTS: Firstly, we discovered that Bifidobacterium can produce B-MVs and isolated them. In vivo, we found that B-MVs can inhibit tumor growth in mice and the mice were in good state. H&E staining displayed extensive apoptotic cells in tumor tissues. Western blotting and immunohistochemistry showed that B-MVs increased the expression of Bax, while decreased the expression of Bcl-2. These results suggested that B-MVs may induce apoptosis of tumor cells in vivo. Furthermore, to further confirm this phenomenon, we conducted experiments in vitro. Hoechst 33,258 staining assay, flow cytometry and western blotting also demonstrated B-MVs promoted cell apoptosis in vitro. CONCLUSIONS: We speculate B-MVs may inhibit tumor growth by inducing tumor cell apoptosis in triple-negative breast cancer, which provided a new direction in the treatment of TNBC.

Pregnancy outcomes of adenomyotic patients with primary infertility after high-intensity focused ultrasound treatment.

OBJECTIVE: To evaluate the therapeutic effect of high-intensity focused ultrasound (HIFU) treatment for adenomyotic patients with primary infertility and to explore the factors that affect the pregnancy outcomes. MATERIALS AND METHODS: Twenty-seven adenomyotic patients with primary infertility who underwent HIFU at HUNAN Provincial Maternal and Child Health Care Hospital, China, between July 2018 and December 2022 were retrospectively reviewed. We evaluated the pregnancy outcomes and analyzed the factors that may affect pregnancy outcomes including time to conception, pregnancy approach, gestational age, delivery mode, neonatal outcomes, and complications during pregnancy and delivery. RESULTS: Among the 27 adenomyotic patients with primary infertility, 10 patients had a total of 11 pregnancies after HIFU treatment. Of these, eight (72%) cases were natural pregnancies and three (23%) were in vitro fertilization (IVF) pregnancies. The median time to conception was 10 (range 4-25) months. There were eight (72%) successful deliveries. The rate of full-term deliveries was 90%. Of the eight live births, four (50%) were born vaginally and four (50%) by cesarean section. No severe complications occurred. The mean birth weight of newborns was 3.1 (range: 2.3-3.9) kg; all newborns developed well without complications during postpartum and breastfeeding. CONCLUSIONS: HIFU treatment for adenomyosis could improve fertility of patients with primary infertility. HIFU is a promising therapeutic approach for patients with adenomyosis and infertility who wish to achieve pregnancy and have live birth deliveries.

Comparison of menstruation recovery after ultrasound-guided suction curettage in patients with cesarean scar pregnancy pretreated using high-intensity focused ultrasound and uterine artery embolization.

OBJECTIVES: To investigate the menstruation recovery after two therapeutic regimens, high-intensity focused ultrasound (HIFU) or uterine artery embolization (UAE) combined with ultrasound-guided suction curettage, for premenopausal women with cesarean scar pregnancy (CSP). MATERIALS AND METHODS: Seventy patients with CSP treated with HIFU followed by ultrasound-guided suction curettage and 63 patients with CSP treated with UAE followed by ultrasound-guided suction curettage in our hospital were retrospectively reviewed. The treatment parameters and the menstrual blood loss (MBL) volume at 6 months after the two therapeutic regimens were compared between the two groups. RESULTS: There was no significant difference in treatment results between the two groups. With regard to postoperative MBL volume, 5 out of 70 patients in the HIFU group and 22 out of 63 patients in UAE group exhibited a reduction in MBL, respectively. Multivariate logistic regression revealed that hypomenorrhea was more likely to occur in the UAE group than in the HIFU group (UAE group vs. HIFU group; OR 11.328, 95% CI 3.158-55.871; p < 0.001). CONCLUSION: Compared to UAE, HIFU has less influence on postoperative MBL volume, which may be a fertility-sparing option for patients with CSP.

Pregnancy outcomes following ultrasound-guided high-intensity focused ultrasound in submucous leiomyomas: a retrospective study.

OBJECTIVE: To investigate the impact of ultrasound-guided high-intensity focused ultrasound (USgHIFU) on pregnancy in submucous leiomyomas. MATERIALS AND METHODS: Between October 2015 and October 2021, a retrospective observational study was conducted at the Affiliated Hospital of North Sichuan Medical College, China, for 32 women with submucous leiomyomas who became pregnant after USgHIFU. Pregnancy outcomes, submucous leiomyomas characteristics, and USgHIFU parameters were analyzed. RESULTS: A total of 17 (53.1%) deliveries were successfully achieved, with full-term delivery in 16 (94.1%) patients and preterm delivery in 1 (5.9%). After USgHIFU, the effective volume in the uterus cavity and the volume of submucous leiomyomas shrank in all 32 patients. The median time to achieve pregnancy after USgHIFU was 11.0 months. Before pregnancy, myoma type was downgraded in 13 (40.6%) patients, stable in 10 (31.3%) and upgraded in 9 (28.1%). The vaginal expulsion rate of submucous leiomyomas was 28.1%, with complete expulsion in 3 (9.4%) patients and partial expulsion in 6 (18.8%). After USgHIFU, the size of submucous leiomyomas did not increase in each trimester (all p > 0.05). The high complications rate during pregnancy (7/17, 41.2%) was associated with advanced maternal age, with only one (5.9%) premature rupture of membranes possibly associated with submucous leiomyomas. There were 6 (35.5%) vaginal delivery and 11 (64.7%) cesarean sections. All 17 newborns developed well, with a mean birth weight of 3482 g. CONCLUSIONS: In patients with submucous leiomyomas, pregnancies and full-term deliveries can be successfully achieved following USgHIFU, with few related complications.

Comparison of high-intensity focused ultrasound for the treatment of internal and external adenomyosis based on magnetic resonance imaging classification.

OBJECTIVE: To compare the safety and efficacy of high-intensity focused ultrasound (HIFU) treatment for patients with internal or external adenomyosis based on magnetic resonance imaging (MRI) classification. MATERIALS AND METHODS: A total of 238 patients with internal adenomyosis and 167 patients with external adenomyosis who received HIFU treatment were enrolled. HIFU treatment results and adverse effects between patients with internal and external adenomyosis were compared. RESULTS: The treatment time and sonication time for patients with external adenomyosis were significantly longer than that for patients with internal adenomyosis. The total energy used and EEF for patients with external adenomyosis were higher than that for patients with internal adenomyosis (p < 0.05). The pre-HIFU median dysmenorrhea score in patients with internal or external adenomyosis was 5 or 8 points, the median score decreased to 1 or 3 points in these two groups at 18-month post-HIFU (p < 0.05). The relief rate of dysmenorrhea was 79.5% in patients with internal adenomyosis, and it was 80.8% in patients with external adenomyosis. The pre-HIFU median menorrhagia score in patients with internal or external adenomyosis was 4 or 3 points, the median score decreased to 1 point in both groups at 18-month post-HIFU with a relief rate of 86.2% and 77.1%, respectively (p = 0.030). No serious complication occurred in any of these patients. CONCLUSIONS: HIFU is a safe and effective treatment either for patients with internal adenomyosis or external adenomyosis. It seemed that internal adenomyosis is easier to be treated with HIFU and with a higher relief rate of menorrhagia than external adenomyosis.

An in vitro and in vivo study on extracorporeal transducer optimization for high-intensity focused ultrasound to improve the safety and efficacy of breast tumor ablation.

OBJECTIVE: To observe the characteristics of a new extracorporeal high intensity focused ultrasound transducer, titled Haifu system JCQ-B, and to compare its safety and efficacy for breast ablation with the standard Haifu system JC transducer. MATERIALS AND METHODS: Ox liver with pig skin and pork ribs were prepared in a semi-sphere shape, served as in vitro acoustic model. The udders of female goats were used as in vivo acoustic model. Both in vitro and in vivo models were ablated by either JCQ-B or JC transducer. The morphology of biological focal region (BFR), the coagulative necrosis volume, and the temperature increase were observed and compared. RESULTS: The BFR morphology of JCQ-B transducer was circular both in vitro and in vivo, with a length-width ratio close to one. Under the same sonication parameters (sonication power, time and depth in tissue), coagulation necrosis volume caused by JCQ-B transducer was larger than that caused by JC transducer both in vitro and in vivo. The increase in temperature in the near and far acoustic pathways with JCQ-B transducer was significantly lower than that of JC transducer in vitro. After receiving high sonication energy during in vivo experimentation, there were no complications observed after the ablation of JCQ-B transducer, while small skin damage was observed after the ablation of JC transducer. CONCLUSIONS: The JCQ-B transducer improved the safety and efficacy of treatment by optimizing BFR morphology and ablation efficiency, which could be applied in the treatment of breast tumor.

HIFU as an alternative modality for patients with uterine fibroids who require fertility-sparing treatment.

OBJECTIVES: To compare pregnancy outcomes after high-intensity focused ultrasound ablation (HIFU), myomectomy and uterine artery embolization (UAE) for fertility-sparing patients with uterine fibroids and to investigate the possible mechanism of improving pregnancy by HIFU. MATERIALS AND METHODS: A meta-analysis of 54 studies containing 12,367 patients was conducted to compare the pregnancy outcomes of three fertility-sparing therapies. And a retrospective self-control study of 26 patients with uterine fibroids from May 2019 to December 2020 was performed to assess the blood flow impedance of bilateral uterine arteries before and after HIFU. RESULTS: In the analysis by treatment option, the pregnancy rate after myomectomy was 0.43 (95% CI 0.36-0.49), which was higher than 0.18 (95% CI 0.10-0.26) after HIFU, the latter was significantly higher than that after UAE (ratio 0.08, 95% CI 0.06-0.10). The miscarriage rate after HIFU was 0.08 (95% CI 0.04-0.12), which was similar to 0.15 (95% CI 0.09-0.21) after myomectomy and also similar to 0.16 after UAE (95% CI 0.01-0.30). In the subgroup analysis, women who received ultrasound guided HIFU (USgHIFU) were more likely to have ideal pregnancy outcomes than that after magnetic resonance imaging-guided HIFU. The pulsatility index and resistance index on the right side were significantly higher 3 months after HIFU than before (1.637 ± 0.435 vs. 1.845 ± 0.469; p = 0.033; 0.729 ± 0.141 vs. 0.784 ± 0.081, p = 0.039). CONCLUSIONS: HIFU, especially USgHIFU, may be an alternative fertility-sparing modality for patients with uterine fibroids over 40 years old. HIFU may contribute to improving pregnancy rates by elevating uterine blood flow impedance.

Focused ultrasound: a novel therapy for improving vaginal microecology in patients with high-risk HPV infection.

OBJECTIVES: To investigate changes in vaginal microecology in women with high-risk human papillomavirus (HR-HPV) infection after focused ultrasound (FU) treatment. MATERIALS AND METHODS: We collected vaginal secretions at the time of admission and 3 months after FU treatment from 169 women who received FU treatment for cervical HR-HPV infection between July 2020 and September 2022. Among them, there were 101 patients with cute vaginitis, we also collected their vaginal secretions after one week of drug treatment. These samples were evaluated for vaginal microecology and HPV-DNA examination. RESULTS: Of the 169 patients, 101 (59.7%) suffered from acute vaginitis at the time of admission. After one week of targeted antibiotics drug treatment, there were no pathogens or pus cells on the field of microscopic vision, but there was no significant difference(p > 0.05) in the diversity and density of vaginal flora, the proportion and function of Lactobacillus (H2O2 negative rate) between one week after treatment and at the time of admission. At the time of admission of the 169 patients, the normal flora rate was 40.3%, which increased to 93.5% three months after FU treatment. The differences in vaginal secretion parameters at the time of admission and 3 months after FU treatment were as follows: H2O2 negative rate (37.3% vs. 3.6%), leukocyte esterase positive rate (54.4% vs. 5.9%), sialidase positive rate (38.5% vs. 4.1%), bacterial vaginitis positive rate (55% vs. 4.7%), fungal vaginitis positive rate (44.4% vs. 5.9%), and trichomonal vaginitis positive rate (7.1% vs. 0). The difference was statistically significant (p < 0.01). The pH value and Nagent score at the time of admission were significantly higher than those three months after FU. Three months after FU, the positive rate of HPV was 5.8% in the group of patients with normal vaginal microecology at the time of admission and post-FU; it was 6.7% in the group of patients with abnormal vaginal microecology at the time of admission and normal vaginal microecology post-FU; and it was 100% in the group patients with abnormal vaginal microecology at the time of admission and post-FU. A significant difference was observed among the three groups (p < 0.01). CONCLUSION: FU is an effective treatment for patients with cervical HR-HPV infection. FU does not interfere with the vaginal microecology of HR-HPV positive patients with normal vaginal microecology.FU followed by antibiotic drug therapy for pathogens is beneficial to restore the function of Lactobacillus vaginalis in HR-HPV positive patients with acute vaginitis,so as to improve the vaginal microecology of HR-HPV positive patients with abnormal vaginal microecology.

Focused ultrasound ablation surgery for multiple breast fibroadenomas: pathological and follow-up results.

OBJECTIVE: To investigate the histopathological findings and follow-up outcome of focused ultrasound ablation surgery (FUAS) treatment of multiple fibroadenomas (FA). METHODS: A total of 20 patients with 101 multiple FAs were enrolled. After one session FUAS ablation, 21 lesions (≥15.0 mm) were surgically removed within one week for histopathological analysis, including 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, H&E staining, nicotinamide adenine dinucleotide (NADH) -flavretin enzyme staining, Transmission electron microscope (TEM) and scanning electron microscope (SEM). The remaining 80 lesions were followed up at 3, 6 and 12 months after treatment. RESULTS: All ablation procedures were performed successfully. Pathologic findings showed that irreversible damage of FA was confirmed. TTC, H&E and NADH staining and TEM/SEM demonstrated tumor cell death and tumor structural destruction at the gross, cellular, and subcellular levels, respectively. The median shrinkage rate at 12 months post-FUAS was 66.4 (43.6, 89.5) %. CONCLUSION: Histopathological analysis for FAs after FUAS treatment proved that FUAS could effectively induce irreversible coagulative necrosis of FA, and the tumor volume would gradually shrink in follow-up. FUAS was safe and effective to treat multiple FAs with good cosmesis.Key pointsThis study was the first study of detailed histopathological analysis for FAs after FUAS treatment.FUAS can effectively induce irreversible coagulative necrosis of fibroadenoma cells.FUAS ablation of multiple fibroadenomas is safe and effective.

Low intensity ultrasound-mediated drug-loaded nanoparticles intravaginal drug delivery: an effective synergistic therapy scheme for treatment of vulvovaginal candidiasis.

PURPOSE: Vulvovaginal candidiasis (VVC) is a mucosal infection of the female lower genital tract for which treatment using conventional antifungal drugs shows limited effectiveness. Herein, amphotericin B-loaded poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (AmB-NPs) were fabricated and combined with low intensity ultrasound (US) to mediate AmB-NPs intravaginal drug delivery to achieve productive synergistic antifungal activity in a rabbit model of VVC. METHODS: Polymeric AmB-NPs were fabricated by a double emulsion method and the physical characteristics and biosafety of nanoparticles were analyzed. The distribution and tissue permeability of nanoparticles after intravaginal ultrasound irradiation (1.0 MHz, 1.0 W/cm2, 5 min, 50% duty ratio) were observed in the vagina. The synergistic therapeutic activity of US-mediated AmB-NPs treatment was evaluated using an experimental rabbit model of VVC. Vaginal C. albicans colony counts, the pathological structure of the vagina epithelium, and Th1/Th2/Th17-type cytokine and oxidative stress levels were analyzed to investigate the therapeutic effect in vivo. RESULTS: The prepared AmB-NPs showed an obvious shell and core structure with uniform size and good dispersion and displayed high biosafety and US-sensitive slow drug release. Ultrasound significantly enhanced nanoparticle transport through the mucus and promoted permeability in the vaginal tissue. US-mediated AmB-NPs treatment effectively increased drug sensitivity, even in the presence of the vaginal mucus barrier in vitro. On the seventh day after treatment in vivo, the combination treatment of AmB-NPs and US significantly reduced the fungal load in the vagina, achieving over 95% clearance rates, and also improved the pathological epithelium structural damage and glycogen secretion function. The expression of Th1 (IFN-γ, IL-2) and Th17 (IL-17) cytokines were significantly increased and Th2 (IL-6, IL-10) cytokines significantly decreased in the US + AmB-NP group. Furthermore, US-mediated AmB-NPs treatment effectively increased C. albicans intracellular reactive oxygen species (ROS) levels and promoted vaginal oxidation and antioxidants to normal levels. CONCLUSION: US-mediated drug-loaded nanoparticles with intravaginal drug delivery exhibited a productive synergistic antifungal effect, which may provide a new non-invasive, safe, and effective therapy for acute or recurrent fungal vaginitis.

Chronic endometritis increases the recurrence of endometrial polyps in premenopausal women after hysteroscopic polypectomy.

BACKGROUND: The reported recurrence rate of endometrial polyps (EPs) after hysteroscopic polypectomy varied widely, and the factors influencing the recurrence of EPs are still controversial. Furthermore, the known definite independent risk factors are almost unchangeable, such as the number of EPs and previous polypectomy history. The aim of this study was to evaluate the impact of chronic endometritis (CE) on the recurrence of EPs in premenopausal women who underwent hysteroscopic polypectomy. METHODS: A retrospective study was conducted at a university-affiliated hospital. Premenopausal women who underwent hysteroscopic polypectomy were enrolled, and those with definite confounding factors for polyp recurrence were excluded, including endometriosis and previous polypectomy history. A total of 233 women were enrolled in this study, including 64 (27.5%) cases with CE and 169 (72.5%) cases without CE. CE was diagnosed via immunohistochemical detection of CD138 on the endometrial specimen. Comparison of the recurrence rate of EPs was performed in women with or without CE at each monitoring stage (i.e., at 3, 6, 9 and 12 months) after hysteroscopic polypectomy. RESULTS: The recurrence rates of EPs at one year in patients with and without CE were 26.6% (95% confidence interval [CI] 15.8-37.4%) and 9.5% (95% CI 5.0-14.0%), respectively, with an overall recurrence rate of 14.2% (95% CI 9.7-18.7%). The hazard ratio (HR) for EPs recurrence in the EPs with CE cohort versus the EPs without CE cohort was 3.08 (95% CI 1.56-6.09) (P = 0.001). Similarly, the recurrence rate of EPs was significantly higher in women with CE than in those without CE at each monitoring stage (i.e., 3, 6 and 9 months). CE and multiple EPs were risk factors for EPs recurrence. The HR for EPs recurrence in the EPs with CE cohort compared with the EPs without CE cohort was 3.06, after adjustment for the number of EPs. CONCLUSIONS: CE was a harmful factor for the recurrence of EPs in premenopausal women after hysteroscopic polypectomy. Thus, routine screening for CE during hysteroscopic polypectomy was needed. Frequent monitoring was needed for multiple EPs as the number of EPs also contributed to polyp recurrence.

Recent Advances in Understanding Multi-scale Climate Variability of the Asian Monsoon.

Studies of the multi-scale climate variability of the Asian monsoon are essential to an advanced understanding of the physical processes of the global climate system. In this paper, the progress achieved in this field is systematically reviewed, with a focus on the past several years. The achievements are summarized into the following topics: (1) the onset of the South China Sea summer monsoon; (2) the East Asian summer monsoon; (3) the East Asian winter monsoon; and (4) the Indian summer monsoon. Specifically, new results are highlighted, including the advanced or delayed local monsoon onset tending to be synchronized over the Arabian Sea, Bay of Bengal, Indochina Peninsula, and South China Sea; the basic features of the record-breaking mei-yu in 2020, which have been extensively investigated with an emphasis on the role of multi-scale processes; the recovery of the East Asian winter monsoon intensity after the early 2000s in the presence of continuing greenhouse gas emissions, which is believed to have been dominated by internal climate variability (mostly the Arctic Oscillation); and the accelerated warming over South Asia, which exceeded the tropical Indian Ocean warming, is considered to be the main driver of the Indian summer monsoon rainfall recovery since 1999. A brief summary is provided in the final section along with some further discussion on future research directions regarding our understanding of the Asian monsoon variability.

Evaluation of high intensity focused ultrasound treatment for different types of adenomyosis based on magnetic resonance imaging classification.

OBJECTIVE: To evaluate the mid-term symptom improvement of patients with different types of adenomyosis based on magnetic resonance imaging (MRI) classification after ultrasound-guided high intensity focused ultrasound (USgHIFU) treatment. MATERIALS AND METHODS: A total of 321 patients with adenomyosis who underwent HIFU and completed 18-month follow-up were retrospectively reviewed. Based on the relationship between the adenomyotic lesion and the uterine structural components on T2-weighted imaging (T2WI), adenomyotic lesions were classified as internal, external, full thickness and intramural adenomyosis. Based on the extent of the myometrial involvement, these lesions were further subclassified as asymmetric and symmetric adenomyosis. RESULTS: All patients completed HIFU ablation in one session. The range of median menstrual pain score in patients with asymmetric internal, symmetric internal, asymmetric external, asymmetric full thickness, symmetric full thickness, and intramural adenomyosis was between 6 and 8 points before HIFU, the median menstrual pain score decreased to 2-4 points 18-month post-HIFU (p < .005). The menstrual pain relief rate was 68.3%, 62.1%, 54.7%, 64.1%, 60%, and 100%, respectively. The median menstrual blood volume score range was between 2 and 4 points in the different groups of patients before HIFU, it decreased to 1-3 points 18-month after HIFU with a relief rate of 68.3%, 51.6%, 51.0%, 55.5%, 57.2%, and 100%, respectively. No serious complication occurred in any of these patients. CONCLUSIONS: Based on our results, USgHIFU is safe and effective in the treatment of patients with different subtypes of adenomyosis with mid-term sustained improvement in symptoms of menstrual pain and menstrual blood volume.

Dosimetric analysis of ultrasound-guided high intensity focused ultrasound ablation for breast fibroadenomas: a retrospective study.

OBJECTIVE: To investigate the factors influencing the sonication dosage and efficiency of ultrasound-guided high intensity focused ultrasound (USgHIFU) for breast fibroadenomas. MATERIALS AND METHODS: Forty-nine patients with 78 breast fibroadenomas who underwent USgHIFU were retrospectively analyzed. The energy efficiency factor (EEF) was set as dependent variable, and the factors possibly influencing the sonication dosage, including age, body mass index (BMI), fibroadenoma size, distance from the shallow margin of the fibroadenoma to skin, distance from the deep margin of the fibroadenoma to pectoralis major, types of near field acoustic pathway, and Adler blood flow classification of ultrasound, were set as independent variables. The correlation between EEF and these independent variables were analyzed, and an optimal scaling regression model was established. RESULTS: Fibroadenoma size, distance from the shallow margin of the fibroadenoma to skin and type of near field acoustic pathway had significant correlation with EEF (p < 0.05). An EEF (y) dosimetry model of y= -0.496X1 + 0.287X2 + 0.203X3 was established, in which X1 stands for size of fibroadenoma, X2 stands for the distance from shallow margin of the fibroadenoma to skin, and X3 stands for type of near field acoustic pathway. The predicted EEF value was significantly related to actual EEF (R = 0.698, p = 0.000). CONCLUSIONS: Fibroadenoma size, distance from the shallow margin of the fibroadenoma to skin and type of near field acoustic pathway could be used as predictors to evaluate the dosage delivery of USgHIFU treatment for breast fibroadenomas.