[Relationship between serum brain-derived neurotrophic factor and clinical stage and dysmenorrhoea of enodmetriosis].

Objective: To explore the association between serum brain-derived neurotrophic factor and clinical stage and dysmenorrhoea of endometriosis. Methods: A total of 82 patients were studied with laparoscopically diagnosed endometriosis between June 2017 and June 2019, and 75 healthy women with reproductive age were selected as the control group during the same period. The endometriosis patients were scored by visual analogue scale(VAS)according to their preoperative dysmenorrhoea.And endometriosis was staged and scored according to the score of Revised American Fertility Society(r-AFS).Enzyme-linked immunosorbent assay (ELISA) was used to determine preoperative BDNF level in serum, and the correlation between BDNF level with clinical stage as well as dysmenorrhea of endometriosis were analysed. Results: The serum BDNF level in endometriosis patients was (1 082±43) ng/L, significantly higher than that in the normal control [(649±30) ng/L], there was statistical difference between the two groups(P<0.001). The BDNF expression in patients with r-AFS stage Ⅲ-Ⅳ was higher than that in patients with Ⅰ-Ⅱ stage [(1 164±389) ng/L vs (791±218)ng/L, P<0.001]. BDNF level in serum was closely correlated with the degree of dysmenorrhea (r=0.682), and the BDNF level in patients with moderate or severe dysmenorrhea was significantly higher than that in patients without dysmenorrhea and patients with mild dysmenorrhea [(1 292±43) ng/L vs(718±36) ng/L, P<0.001]. Conclusions: The serum BDNF level in endometriosis patients is positively correlated with clinical stage and dysmenorrhea.

Biological background of the genomic variations of cf-DNA in healthy individuals.

BACKGROUND: Cell-free DNA (cf-DNA)-based liquid biopsy is emerging as a revolutionary new method in individualized cancer treatment and prognosis monitoring, although detecting early-stage cancers using cf-DNA remains challenging, partially because of the undefined biological background of cf-DNA. MATERIALS AND METHODS: We investigated somatic mutations in the cf-DNA of 259 cancer-free individuals with a median age of 47 years using an endogenous barcoding duplex method with an ultralow base error rate (2 × 10-7) and compared the variant allele frequencies (VAFs) of these mutations between the cf-DNA and the corresponding blood cell DNA. RESULTS: Sixty percent (155/259) of the samples showed at least one nonsynonymous mutation on either of two similar target panels covering 508 and 559 cancer-related genes. For individuals older than 50 years of age, the positive rate increased to 76%. Most cf-DNA mutations were also present at similar VAFs in the paired blood cell DNA. The most frequently mutated genes were driver genes of hematologic malignancies, including DNMT3A, TET2, AXSL1, and JAK2. However, the other 58.4% (192/329) of the mutations were likely 'passenger mutations' of clonal hematopoiesis, including mutations in NOTCH2, FAT3, EXT2, ERBB4, and ARID2, which are driver genes of solid tumors. CONCLUSION: Hematopoietic clone-derived mutations, including 'driver mutations' and 'passenger mutations', are prevalent in the cf-DNA of both healthy individuals and cancer patients and may be a potential source of false positives in the liquid biopsy. Our results also suggest the ineffectiveness for distinguishing clonal hematopoietic mutations of low VAF (≤0.1%) from tumor-derived mutations using conventional next-generation sequencing of blood cell DNA. However, an error correction model with an ultralow error rate and high coverage depth is required for blood cell DNA sequencing, which is difficult and costly to achieve with current technologies.

[Clinical study of high intensity focused ultrasound ablation combined with GnRH-a and LNG-IUS for the treatment of adenomyosis].

Objective: To investigate the clinical effect of dysmenorrhea in patients with adenomyosis treated by high intensity focused ultrasound(HIFU)ablation combined with gonadotropin-releasing hormone agonist(GnRH-a)and levonorgestrel-releasing intrauterine system(LNG-IUS). Methods: From April 2012 to December 2015, 477 cases of adenomyosis patients with dysmenorrhea were treated by HIFU in the Third Xiangya Hospital. Among them, some patients were treated with HIFU alone, some of them were treated with HIFU combined with GnRH-a and(or)LNG-IUS, thus were classified as H group, H+G group, H+M group and H+G+M group. The improvements of clinical results were compared among the four groups and the influencing factors of HIFU treatment for adenomyosis were also analyzed. Results: During the follow-up period, the overall effective rates of the treatment decreased with time, 3 months 89.4%(345/386), 12 months 84.0%(221/263), 24 months 74.2%(98/132), and the overall recurrence rate was 12.9%(39/303). The significant difference in the curative at 3 months[H group 83.7%(170/203), H+M group 95.0%(95/100), H+G group 100.0%(43/43), H+G+M group 96.8%(30/31)], 12 months[H group 79.4%(123/155), H+M group 93.2%(69/74), H+G group 11/12, H+G+M group 15/17], and 24 months[H group 68.0%(51/75), H+M group 96.4%(27/28), H+G group 6/12, H+G+M group 15/15]after HIFU treatment and recurrence rate[H group 19.0%(29/153), H+M group 3.3%(3/90), H+G group 19.4%(6/31), H+G+M group 4.5%(1/22)]were observed among the four groups(P<0.05). Pairwise comparison further showed that, in 3 months after the treatment, the effect of H group was significantly lower than those of H+M group and H+G group(P= 0.003, P=0.005); in 12 months after the treatment, the effect of H group was significantly lower than that of H+M group(P=0.006); while in 24 months after treatment, the effect of H group was significantly lower than that of H+G+M group(P=0.005), and the effect of H+G group was lower than that of H+G+M group(P= 0.001); and the recurrence rate of H group was significantly higher than that of H+M group(P<0.008). In patients of group H, the effect of HIFU was related to uterine size, the effect of patients with large uterine volume was significantly higher than that of small volume of uterine of patients(P=0.017, OR=2.739, 95%CI: 1.200- 6.251); with increasing of age, the improvement of dysmenorrhea had a increasing trend(P<0.05). Conclusions: HIFU combined with GnRH-a and(or)LNG-IUS could improve the treatment effect in relief of dysmenorrhea. Based on our results, individual treatment protocol should be selected for different patients.