There are more and more women with recurrent spontaneous abortion (RSA). The mechanism of RSA is still unclear. Immunological factors have been postulated to play a role in the etiology of RSA. Dendritic cells (DCs) are the most potent antigen-presenting cells in the immune system, and the decidual DCs may take part in the occurrence of RSA. The difference in maturity status of decidual DCs among women with RSA and women with normal pregnancies is worthy of studying for its application to prevention and therapy. The EnVision two-step immunohistochemical staining technique was used to detect the expression of CD83 and CD1a in the decidua of women with RSA (30 cases) and normal pregnancies (30 cases). The maturity status, distribution and quantity of DCs in the two groups were observed. Observation of the staining and cell counting were done using microscope within 30 randomly selected high-power fields (HPF, 40 × 10). All data analyses were conducted with SPSS 17.0 and the statistical significance was set at P <0.05. The decidua from the two groups contained DCs that stained with the anti-CD83 and anti-CD1a antibody. Most of the decidual CD83+DCs from two groups were located in the stroma. There were more CD83+DCs clustered with other DCs in the stroma from women with RSA than normal pregnancies. Most of the CD1a+DCs in the decidua from the two groups are located close to maternal glandular epithelium. No difference in the location of CD1a+DCs was found in the decidua between two groups. The number of decidual CD83+DCs was statistically significantly higher in RSA women than in normal early pregnant women (14.20 ± 13.34/30 HPF versus 4.77 ± 2.64/30 HPF; t = 3.800, P = 0.001). The number of CD1a+DCs in the decidua was statistically significantly lower in RSA women compared with normal early pregnant women (3.97 ± 3.75/30 HPF versus 7.60 ± 6.08/30 HPF; t = 2.786, P = 0.008). These findings suggest that the increase in the number of mature DCs and the decrease in the quantity of immature DCs in the decidua may be related to RSA. The maturation of decidual DCs may play an important role in the pathogenesis of RSA.

A comprehensive analysis of the molecular mechanism underlying colorectal tumor evaluated the development of colorectal cancer (CRC) and proposed targeting small molecular inhibitors. Nonetheless, the adoptive resistance of these therapies remains a challenge with respect to achieving an effective clinical response. Thus, identifying the molecular mechanisms guiding CRC growth is essential. The results of The Cancer Genome Atlas (TCGA) dataset analysis demonstrated a critical role of signal transducer and activator of transcription 3 (STAT3) pathway in tumor immune suppression via modulation of the recruitment of Treg cells and M2 type tumor-associated macrophages. The in vivo experiments elucidate that targeting STAT3 pathways markedly reduce the proportions of TAMs and Tregs by inhibiting tumor progression. These findings revealed crosstalk between Treg cells and M2 macrophages, proving a potential therapeutic strategy for CRC therapy. Combinatorial treatment with STAT3 inhibitor and programmed death 1 (PD-1) antibody therapy effectively prevents CRC tumor growth in a mouse model with high anti-tumor immunity. In summary, targeting STAT3 disrupts the interaction between Treg cells and M2 macrophages and improves the anti-tumor response in CRC, thereby offering a promising strategy to treat patients with CRC.

Mifepristone (RU486), a potent antagonist of progesterone and glucocorticoids, is involved in immune regulation. Our previous studies demonstrated that mifepristone directly augments the cytotoxicity of human uterine natural killer (uNK) cells. However, the mechanism responsible for this increase in cytotoxicity is not known. Here, we explored whether the increased cytotoxicity in uNK cells produced by mifepristone is due to either anti-progesterone or anti-glucocorticoid activity, and also investigated relevant changes in the mitogen-activated protein kinase (MAPK) pathway. Uterine NK cells were isolated from decidual samples and incubated with different concentrations of progesterone, cortisol, or mifepristone. The cytotoxicity and perforin expression of uNK cells were detected by mitochondrial lactate dehydrogenase-based MTS staining and flow cytometry assays, respectively. Phosphorylation of components of the MAPK signaling pathway was detected by Western blot. Cortisol attenuated uNK cell-mediated cytotoxicity in a concentration-dependent manner whereas progesterone had no effect. Mifepristone alone increased the cytotoxicity and perforin expression of uNK cells; these effects were blocked by cortisol. Furthermore, mifepristone increased the phosphorylation of ERK1/2 in a cortisol-reversible manner. Specific ERK1/2 inhibitor PD98059 or U0126 blocked cortisol- and mifepristone-induced responses in uNK cells. These results suggest that mifepristone acts as a glucocorticoid antagonist to augment uNK cell-mediated cytotoxicity via ERK activation, which may be caused by increased perforin expression. These observations may reveal an important mechanism by which mifepristone upregulates the cytotoxicity of uNK cells.

Adenomyosis and endometriosis are common causes of pelvic pain in women of reproductive age. Furthermore, adenomyosis is a major cause of menorrhagia. This study aimed to evaluate the effects of Etonogestrel implants on pelvic pain and menstrual flow in women requiring long-acting reversible contraception and suffering from adenomyosis or endometriosis. One hundred women with adenomyosis or endometriosis and asking for contraception with Etonogestrel implants were enrolled in this study and were followed-up for 24 months. Patients were interviewed on pelvic pain by visual analog scale (VAS) pain score, menstrual flow by the number of sanitary napkins, menstrual bleeding pattern, weight gain, breast pain, and any other treatment side effects. Seventy four patients who were treated with Etonogestrel implants completed the 24-month follow-up in which we found a significant decrease in pelvic pain VAS scores comparing baseline scores to 6, 12, and 24 months (baseline: 6.39 ± 2.35 to 24-month: 0.17 ± 0.69, P < 0.05). The menstrual volume decreased significantly compared with that at baseline ((40.69 ± 30.92) %, P < 0.05). However, vaginal bleeding, amenorrhea, weight gain, and acne occurred after treatment in some patients. Etonogestrel implants were effective in reducing pelvic pain and menstrual flow of adenomyosis or endometriosis.

Objective: To explore the effect of 4 mg/day, 6 mg/day, and 8 mg/day estradiol alone or in combination with an intrauterine device (IUD) in patients with moderate and severe intrauterine adhesion (IUA) after transcervical resection of adhesion (TCRA). Methods: Patients with moderate or severe IUA who reived 4 mg/day, 6 mg/day, and 8 mg/day estradiol alone or in combination with an intrauterine device (IUD) after TCRA in Women’s Hospital, Zhejiang University School of Medicine, from March 2014 to December 2014 were enrolled in this retrospective case–control study. In group A, 14 patients received estradiol 4 mg/day + IUD after the first operation; in group B, 29 patients (group B0) received estradiol 6 mg/day after the first operation, and 73 patients (group B1) received estradiol 6 mg/day + IUD; in group C, 14 patients received estradiol 8 mg/day + IUD after the first operation. Referring to ESGE's IUA diagnostic classification method, 72 patients had moderate adhesion, and 58 cases had severe adhesion. Outpatient follow-up was performed at 1 and 23 months and after 1 year. The postoperative menstrual improvement, uterine cavity recovery, drug side effects at two to three months, and pregnancy situation at one year were recorded. Results: There were no significant differences in age, BMI, and previous intrauterine operation times between the 3 groups (all p > 0.05). Compared with Group A, more patients in group C had severe IUA (p = 0.008). In addition, there were no differences in menstrual recovery, uterine cavity recovery, and pregnancy in one year between the 3 groups (p > 0.05) and between groups B₀ and B₁ (p > 0.05). In group B1, 51 (69.86%) patients had IUD incarceration. Conclusion: This data suggests that 4 mg/d doses of estrogen may have the same effect in improving the menstrual condition, uterine cavity morphology, and reproductive ability compared to a higher dosage (6 mg/day estrogen and 8 mg/day). In addition, the placement of IUD in the uterine cavity during TCRA may cause IUD incarceration, and the treatment results for the prevention of IUA are not better than without IUD.