Indoleamine 2,3-dioxygenase suppresses the cytotoxicity of 1 NK cells in response to ectopic endometrial stromal cells in endometriosis.

It has been reported that the impaired cytotoxicity of natural killer (NK) cells and abnormal cytokines that are changed by the interaction between ectopic endometrial cells and immune cells is indispensable for the initiation and development of endometriosis (EMS). However, the mechanism of NK cells dysfunction in EMS remains largely unclear. Here, we found that NK cells in peritoneal fluid from women with EMS highly expressed indoleamine 2,3-dioxygenase (IDO). Furthermore, IDO+NK cells possessed lower NKp46 and NKG2D but higher IL-10 than that of IDO-NK. Co-culture with endometrial stromal cells (nESCs) from healthy control or ectopic ESCs (eESCs) from women with EMS led to a significant increase in the IDO level in NK cells from peripheral blood, particularly eESCs, and an anti-TGF-ß neutralizing antibody suppressed these effects in vitro. NK cells co-cultured with ESC more preferentially inhibited the viability of nESCs than eESCs did, and pretreating with 1-methyl-tryptophan (1-MT), an IDO inhibitor, reversed the inhibitory effect of NK cells on eESC viability. These data suggest that ESCs induce IDO+NK cells differentiation partly by TGF-ß, and that IDO further restricts the cytotoxicity of NK cells in response to eESCs, which provides a potential therapeutic strategy for EMS patients, particularly those with a high number of impaired cytotoxic IDO+NK cells.

A potential link between polycystic ovary syndrome and non-alcoholic fatty liver disease: an update meta-analysis.

BACKGROUND: Epidemiological literature regarding the effect of polycystic ovary syndrome (PCOS) as a risk factor for non-alcoholic fatty liver disease (NAFLD) remains inconsistent. Furthermore, it remains debatable whether NAFLD is associated with PCOS as a consequence of shared risk factors or whether PCOS contributes to NAFLD in an independent fashion. Therefore, this meta-analysis was conducted. METHODS: This meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Relevant studies published before May 2017 were identified and retrieved from PubMed and Web of Science databases. The data were extracted, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: A total of 17 studies were included into the present analysis. Compared to the control group, the risk of NAFLD in the PCOS group was higher (OR = 2.25, 95% CI = 1.95-2.60). When stratified by BMI and geographic location, the results indicated that the frequency of NAFLD risk was significantly higher in obese subjects (OR = 3.01, 95% CI = 1.88-4.82), non-obese subjects (OR = 2.07, 95% CI = 1.12-3.85), subjects from Europe (OR = 2.00, 95% CI = 1.58-2.52), subjects from the Asia-Pacific Region, (OR = 2.32, 95% CI = 1.89-2.84) and subjects from America (OR = 2.96, 95% CI = 1.93-4.55). In addition, PCOS patients with hyperandrogenism (HA) had a significantly higher risk of NAFLD, compared with controls (OR = 3.31, 95% CI = 2.58-4.24). However, there was no association between PCOS patients without HA and higher risk of NAFLD (OR = 1.46; 95% CI =0.55-3.87). The results of this meta-analysis should be interpreted with caution due to the small number of observational studies and possible confounding factors. CONCLUSION: The meta-analysis results suggest that PCOS is significantly associated with high risk of NAFLD. Although this association was independent of obesity and geographic region, it might be correlated with HA.

IL15 promotes growth and invasion of endometrial stromal cells and inhibits killing activity of NK cells in endometriosis.

Endometriosis (EMS) is associated with an abnormal immune response to endometrial cells, which can facilitate the implantation and proliferation of ectopic endometrial tissues. It has been reported that human endometrial stromal cells (ESCs) express interleukin (IL)15. The aim of our study was to elucidate whether or not IL15 regulates the cross talk between ESCs and natural killer (NK) cells in the endometriotic milieu and, if so, how this regulation occurs. The ESC behaviors in vitro were verified by Cell Counting Kit-8 (CCK-8), Annexin/PI, and Matrigel invasion assays, respectively. To imitate the local immune microenvironment, the co-culture system between ESCs and NK cells was constructed. The effect of IL15 on NK cells in the co-culture unit was investigated by flow cytometry (FCM). In this study, we found that ectopic endometrium from patients with EMS highly expressed IL15. Rapamycin, an autophagy inducer, decreased the level of IL15 receptors (i.e. IL15Rα and IL2Rß). IL15 inhibits apoptosis and promotes the invasiveness, viability, and proliferation of ESCs. Meanwhile, a co-culture with ESCs led to a decrease in CD16 on NK cells. In the co-culture system, IL15 treatment downregulated the levels of Granzyme B and IFN-γ in CD16(+)NK cells, NKG2D in CD56(dim)CD16(-)NK cells, and NKP44 in CD56(bright)CD16(-)NK cells. On the one hand, these results indicated that IL15 derived from ESCs directly stimulates the growth and invasion of ESCs. On the other hand, IL15 may help the immune escape of ESCs by suppressing the cytotoxic activity of NK cells in the ectopic milieu, thereby facilitating the progression of EMS.

Survival Impacts of Perineural Invasion on Patients Under Different Radical Hysterectomies Due to Early Cervical Cancer.

Objective: Cervical cancer is a common gynecological malignancy. In addition to the open radical hysterectomy (ORH) and laparoscopic radical hysterectomy (LRH), laparoscopic nerve-sparing radical hysterectomy (LNSRH) could be another treatment option since it could preserve urinary, colorectal, and sexual functions. However, LNSRH might result in early cancer metastasis and recurrence due to inadequate tumor resection. Additionally, whether LNSRH should be considered based on perineural invasion (PNI) status remains controversial. To assess different types of hysterectomy on the outcome of early cervical cancer with PIN. Methods: A retrospective study was performed in early cervical cancer patients who received ORH, LRH, or LNSRH between January 2012 and December 2019. Age, FIGO cancer stages, histopathological types, tumor size, histological grade, invasion depth, lymph node metastasis, lymphovascular space invasion, and PNI were documented. Disease-free survival (DFS) and overall survival (OS) were recorded. Results: A total of 174 patients were included, with 33, 69, and 72 patients received LRH, ORH, and LNSRH, respectively. Twenty-one patients (12.1%) had PNI. DFS (P = 0.000) and OS (P = 0.022) periods were shortened in positive PNI patients than in negative PNI patients (P = 0.000 and 0.022, respectively). In patients with positive PNI, lymph node metastasis, but not the surgery type, was an independent risk factor for DFS and OS (P = 0.000). Conclusion: Early cervical cancer patients with PNI had shorter postoperative DFS and OS periods. In these patients, lymph node metastasis, but not the type of hysterectomy, was independently associated with DFS and OS.

Can laparoscopic nerve-sparing ultra-radical hysterectomy play a role in locally advanced cervical cancer? A single-center retrospective study.

Background and objectives: The objective of this study is to investigate the outcomes of concurrent platinum-based chemoradiation therapy (CCRT), laparoscopic nerve-sparing ultra-radical hysterectomy (LNSURH), and open radical hysterectomy (ORH) on patients with locally advanced cervical carcinoma (LACC). Methods: A single-center retrospective study was conducted on LACC patients who received CCRT, ORH, or LNSURH from January 2011 to December 2019. Data on age, tumor size, overall survival (OS), disease-free survival (DFS), and early and late morbidities were collected. After 24 months of treatment, patients were asked a series of questions about their urinary, bowel, and sexual activities. Early morbidities were defined as those occurring during or within a month of treatment, whereas late morbidities and complications were defined as those occurring a month after treatment. The postoperative complications were classified with reference to the Clavien-Dindo classification (CD) system. Results: The Kaplan-Meier curves revealed no significant differences in OS and DFS among the three groups (P = 0.106 for DFS and P = 0.190 for OS). The rates of early complications in the CCRT group were comparable with those in the operated groups (P = 0.46). However, late complications were significantly lower in the ORH and LNSURH groups relative to those in the CCRT group. The scores of urinary and bowel functions were restored to the pretreatment state, although the sexual function scores were not satisfactory. Conclusions: The treatments of CCRT, ORH, and LNSURH can be considered options for patients with LACC, as their OS and DFS showed no significant difference. In addition, LNSURH exhibited a lower incidence of late complications and high sexual function scores.

A novel modification of conventional laparoscopic myomectomy using manual assistance for multiple uterine myomas.

OBJECTIVES: To evaluate the efficacy and feasibility of finger-assisted laparoscopic myomectomy for multiple myomas. STUDY DESIGN: A total of 565 patients with symptomatic myomas underwent finger-assisted laparoscopic myomectomy between January 2006 and March 2011 to remove multiple myomas at our center. Laparoscopic myomectomy technique was modified, and involved the insertion of two fingers into the vagina to elevate the uterus, while one or two fingers of the other hand were inserted into the abdomen through a suprapubic 15-mm trocar port for palpation of small myomas, which did not distort the uterine contour. RESULTS: The mean (SD; range) patient age was 38.26 years (5.84; 25-48 years). The diameter of the largest myoma in each case was 6.13 cm (1.21; 4-15 cm). The total number of myomas enucleated in the initial enucleation was 2228. There were 597 additional myomas enucleated with finger-assisted guidance. The mean diameter of the additionally enucleated myomas was 1.1 cm (range, 0.2-2.5 cm), which was significantly smaller than those of the initially enucleated myomas (p=0.002). The mean operative time was 97.1 min (30.2; 35-180 min). The decrease in postoperative hemoglobin concentration was 1.6g/dL (0.7; 0.4-3.2g/dL). During the operation, no patients required a blood transfusion. Six patients developed postoperative fever. There was no occurrence of bowel or urinary tract injury. The mean postoperative hospital stay was 3.2 days (0.9; 2-6 d). All procedures were successfully completed without the need for laparotomy. CONCLUSIONS: Finger-assisted laparoscopic myomectomy is a feasible and safe approach in the surgical treatment of multiple myomas.