Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Objective:To evaluate the efficacy and safety of dupilumab in the treatment of prurigo nodularis (PN) in the real world.Methods:PN patients who were subcutaneously injected with dupilumab for over 12 weeks were collected from the China Type Ⅱ Inflammatory Skin Disease Clinical Research and Standardized Diagnosis and Treatment Project Database from June 2021 to October 2022. Their clinical data were retrospectively analyzed, which included demographic data, and changes in pruritus numeric rating scale (NRS), investigator global assessment for PN-Stage (IGA PN-S), dermatology life quality index (DLQI) and hospital anxiety and depression scale (HADS) scores before and after treatment. Differences in scores before and after treatment, as well as in efficacy between patients with and without a history of atopic diseases, were analyzed using Wilcoxon signed-rank test, paired t-test or chi-square test. Results:A total of 66 PN patients were collected, including 42 males and 24 females, and they were aged 8 to 89 (44.12 ± 24.17) years. Thirty-six patients had a history of atopic diseases, and 27 had a family history of atopic diseases. After 12-week treatment with dupilumab, the pruritus NRS, IGA PN-S and DLQI scores in the 66 patients significantly decreased from the baseline scores (7.00 [5.00, 8.00], 3.00 [3.00, 4.00], 12.00 [7.75, 20.25], respectively) to 3.00 [2.00, 4.25], 2.00 [2.00, 3.00], 5.00 [1.75, 8.25], respectively (all P < 0.001). Among the 66 patients, 39 continued the regular treatment with dupilumab after 12 weeks and were followed up to 16 weeks; their pruritus NRS and IGA PN-S scores at week 16 further decreased compared with those at week 12 (both P < 0.05). There were no significant differences in the proportion of patients showing an improvement of ≥ 4 points in the NRS score or the proportion of patients achieving IGA 0/1 at week 12 between the patients with history of atopic diseases and those without (both P > 0.05). Before treatment, 32 PN patients were accompanied by mild to severe anxiety and/or depression; after 12-week treatment, the HADS-A scores in the 28 patients with anxiety (HADS-A scores > 7 points) and the HADS-D scores in the 20 patients with depression (HADS-D scores > 7 points) significantly decreased compared with their baseline scores (both P < 0.001) ; 18 (56.52%) patients achieved remission in anxiety and depression (both HADS-A and HADS-D scores < 7 points). Among the 66 PN patients, there were 13 minor patients, including 7 males and 6 females, and they were aged 8 to 17 (13.77 ± 3.09) years; after 12-week treatment, their pruritus NRS, IGA PN-S, and DLQI scores significantly decreased compared with the corresponding baseline scores (all P < 0.05) ; 8 minor patients continued dupilumab treatment for 16 weeks, with a further decrease in the IGA PN-S score compared with that at week 12 ( P < 0.05), but without significant differences between the pruritus NRS and DLQI scores at week 16 and those at week 12 (both P > 0.05). Adverse reactions were observed in 7 adult patients, including eye pruritus, local injection reactions, and systemic erythema accompanied by pruritus on the day of injection. No adverse reactions were reported in minor patients. Conclusion:In the real world, dupilumab could markedly alleviate pruritus, skin lesions, anxiety and depression symptoms in PN, improve the quality of life, and exhibited a good safety profile.

Objective:To compare the clinical efficacy and safety of single microneedle radiofrequency versus photodynamic therapy in the treatment of inflammatory lesions of moderate and severe facial acne vulgaris.Methods:Sixty patients with moderate to severe facial acne vulgaris were retrospectively collected from Guangzhou Institute of Dermatology between December 2021 and July 2022, including 30 patients who had received single microneedle radiofrequency treatment, and 30 patients who had received photodynamic therapy. There were no significant differences in the age, gender distribution, and severity of acne between the two groups (all P > 0.05). The patients in the microneedle radiofrequency group were treated with single microneedle radiofrequency once every 4 weeks for 2 sessions; those in the photodynamic therapy group received aminolevulinic acid-based photodynamic therapy once every 2 weeks for 3 sessions; patients in both groups were still treated with oral doxycycline for 8 weeks. After 8-week treatment, the efficacy, pain severity and incidence of adverse reactions were compared between the two groups. Statistical analysis was carried out by using chi-square test, two independent samples t-test and Mann-Whitney U test. Results:After 8-week treatment, there was no significant difference in the response rate between the microneedle radiofrequency group (93.33%, 28/30) and photodynamic therapy group (86.67%, 25/30; χ2 = 0.74, P = 0.389). No significant difference was observed in the pain severity score between the microneedle radiofrequency group (4.80 ± 2.08) and photodynamic therapy group (4.13 ± 1.86, t = 1.32, P = 0.194), and there was also no significant difference in the pain degree between the two groups ( Z = -1.13, P = 0.260). In the microneedle radiofrequency group, burning sensation occurred in 3 cases (10.00%), swelling and pain in 4 (13.33%), erythema in 2 (6.67%), and dryness and desquamation in 2 (6.67%), and no reactive acne or hyperpigmentation was observed; in the photodynamic therapy group, burning sensation occurred in 10 cases (33.33%), swelling and pain in 9 (30.00%), erythema in 8 (26.67%), reactive acne in 11 (36.67%), hyperpigmentation in 2 (6.67%), and dryness and desquamation in 11 (36.67%). Compared with the photodynamic therapy group, the microneedle radiofrequency group showed significantly decreased incidence rates of burning sensation, erythema, reactive acne, and dryness and desquamation ( χ2 = 4.81, 4.32, 13.47, 7.95, respectively, all P < 0.05) ; there was no significant difference in the incidence rates of swelling and pain as well as hyperpigmentation between the two groups ( χ2 = 2.46, 2.07, respectively, both P > 0.05) . Conclusion:Single microneedle radiofrequency showed marked efficacy equivalent to that of photodynamic therapy in the treatment of moderate to severe facial acne vulgaris, but higher safety, providing more clinical treatment options for moderate to severe facial acne vulgaris.

Objective:To investigate changes in skin microecological structures and functions between acute and remission phases in adult patients with severe atopic dermatitis (AD) .Methods:From October 2019 to November 2020, skin scale specimens were collected from 5 body sites (cheeks, cubital fossa, back of the hand, abdomen, lower limbs) of 4 adult patients with severe AD in the acute and remission phases, who visited the outpatient clinic of Guangzhou Institute of Dermatology. The next-generation high-throughput sequencing was performed for metagenomic sequencing to construct the microbial gene catalogue of these specimens, followed by gene annotation and bioinformatics analysis for each sample.Results:A total of 18 phyla, 37 classes, 73 orders, 142 families, 237 genera, and 331 species were identified in the skin specimens from the 4 patients with severe AD. The patients with AD in the remission phase showed significantly increased diversity of skin microbiota and markedly different relative abundance of skin microorganisms compared with those in the acute phase (both P < 0.05). At the microbial species level, Staphylococcus aureus showed the highest impact on the acute phase of AD, while Staphylococcus epidermidis, Moraxella osloensis, Francisella sp., Staphylococcus cohnii, Staphylococcus warneri, Malassezia globosa and Malassezia restricta were enriched in the remission phase of AD with the absolute value of the common logarithm of the linear discriminant analysis score > 2 (Kruksal-Wallis test, all P < 0.05). As KEGG pathway enrichment analysis showed, the differentially abundant genes were annotated into a total of 355 functional pathways, of which 38 pathways were significantly enriched (all P < 0.05), mainly involving Staphylococcus aureus infection, tryptophan metabolism, histidine metabolism, nitrogen metabolism, metabolism of arginine and proline, biosynthesis and degradation of valine, leucine and isoleucine, fatty acid degradation, peroxisome proliferator-activated receptor signaling pathway, etc. Conclusion:The skin microecological structure significantly differed between the acute and remission phases among the patients with severe AD, which may be related to multiple functional pathways, such as Staphylococcus aureus infection, tryptophan metabolism, histidine metabolism and nitrogen metabolism.

To establish mouse endometrial injury model by curettage or coagulation.Female ICR mice were randomly allocated into 2 groups: in curettage group, a blunt 20G needle was inserted in one uterine horn with 0.05 megapascals negative pressure; in coagulation group, one uterine horn was coagulated using a monopolar electric needle with 0.5 watts power. In both groups the contra-lateral uterine horn was used as control. The morphological changes and thickness of endometrium were evaluated 1 week after operation. The endometrial samples were taken on d4 of pregnancy, and the expressions of endometrial receptivity-related cytokines were examined. The number of implanted embryos on each side of uterus was calculated on d10 of pregnancy.There was no difference in operation time between 2 groups. In both groups, the endometrial glands and stroma were significantly reduced, and the endometrial thickness was also significantly decreased on injury side compared to contra-lateral horn. However, local injury was more severe in coagulation group, uterine obliteration and hydrops were developed in 2 mice of coagulation group, and none in curettage group. The expressions of leukemia inhibitory factor (LIF) and oncostatin M (OSM) were significantly reduced on injured side in both groups compared to opposite side; however, the expression of LIF and OSM in curettage group was higher than that in coagulation group. The numbers of implanted embryos were decreased in both groups on injured side compared to opposite side, and fetal death was only observed in coagulation group.Both curettage and coagulation can make injury on mouse endometrium, impair endometrial receptivity and reduce fertility. Curettage can cause moderate injury, and coagulation may lead to more severe injury.

OBJECTIVETo observe the clinical effects and the serous estradiol change of patients with menopause syndrome using Xianling Gubao capsules for treatment.

METHOD110 patients with manopause syndrome who were diagnosized by clinic index were recruited for the study. They were divided into two groups randomly. The treatment group were dealed with Xianling Gubao capsules and the control group with placebo of starch capsules for 8 weeks. The menopausal Kupperman index was used to assess change in menopausal symptoms before and after treatment. At the same time, serous estradiol and the thickness of uterine endometrium was evaluated.

RESULTThe Kupperman index were improved apparently in treatment group after treatment (P < 0.01). The serous estradiol level of treatment group was increased apparently after treatment (P < 0.05). However, There were no statistical deference in the thickness of uterine endometrium in the treatment and the control group before and after treatment.

CONCLUSIONThe treatment using Xianling Gubao capsules for patients with menopause syndrome could improve the clinic symptoms, increase the serous estradiol level, but do not increase the risk of endometrial hyperplasia.

Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Endometrium ; drug effects ; metabolism ; Female ; Humans ; Menopause ; drug effects ; metabolism ; Middle Aged ; Treatment Outcome