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BACKGROUND: Previous observational evidence has indicated the potential involvement of the gut microbiota (GM) in the development of endometriosis. However, the causal relationship of the association remains to be investigated. METHOD: Genome-wide association study (GWAS) data of GM was obtained from the MiBioGen consortium, and GWAS for endometriosis data was from the FinnGen consortium. Initially, a two-sample Mendelian randomisation (MR) analysis was performed to identify specific bacteria associated with endometriosis. Inverse variance-weighted (IVW) was used as the main MR analysis to infer causal relationships. The other four popular MR methods including MR-Egger regression, weighted mode, weighted median, and simple mode were used for secondary confirmation. Subsequently, these selected bacteria were employed as exposure to investigate their causal effects on six sub-types of endometriosis. Furthermore, reverse MR analysis was implemented to evaluate the reverse causal effects. Cochran's Q statistics was used to test the heterogeneity of instrumental variables (IVs); MR-Egger regression was used to test horizontal pleiotropy; MR-PRESSO and leave-one-out sensitivity analysis were applied to find significant outliers. RESULT: A total of 1131 single nucleotide polymorphisms (SNPs) were collected as IVs for 196 GM taxa with endometriosis as the outcome. We identified 12 causal relationships between endometriosis and GM taxa including 1 phylum, 3 families, 2 orders, and 6 genera (Rikenellaceae RC9 gut group, Eubacterium ruminantium group, Faecalibacterium, Peptococcus, Clostridium sensu stricto 1, and Ruminococcaceae UCG005). Utilizing the Bonferroni method, we identified phylum Cyanobacteria as the strongest associated GM taxa. Subsequently, 6 significant causal effects were uncovered between the 12 selected specific GM and 6 sub-types of endometriosis. Meanwhile, no reverse causal relationship was found. Further, no horizontal pleiotropy and no significant outliers were detected in the sensitive analysis. CONCLUSIONS: This MR analysis revealed significant causal effects between GM and endometriosis and phylum Cyanobacteria had the strongest association.
The imbalance of gut microbiota (GM) is suggested to be involved in the development of endometriosis while the causal relationship between GM and endometriosis remains undetermined. This two-sample mendelian randomisation analysis firstly demonstrated the potential association between GM and the risk of endometriosis including 6 sub-types. We revealed 12 causal relationships between endometriosis and GM taxa including 1 phylum, 3 families, 2 orders, and 6 genera while Phylum Cyanobacteria was the strongest associated GM taxa by using Bonferroni method. Meanwhile, we identified 6 significant causal effects between 12 selected specific GM and 6 sub-types of endometriosis. Meanwhile, the result from reverse MR analysis showed that there was no causal effect of endometriosis on the identified specific GM taxa. Thus, we revealed the causal relationship between GM and endometriosis. It is necessary to further study its potential mechanism, which may contribute to the prevention and treatment of Endometriosis.
Subject(s)
Endometriosis , Gastrointestinal Microbiome , Genome-Wide Association Study , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Endometriosis/microbiology , Endometriosis/genetics , Humans , Female , Gastrointestinal Microbiome/genetics , CausalityABSTRACT
Because the pathogenesis of some hematologic malignancies (e.g., myeloproliferative disease, MPN; acute leukemia, AL;multiple myeloma, MM; and (hemophagocytic syndrome, HPS) involve abnormalities in the JAK/STAT pathway, a series of drugs that target the JAK/STAT pathway has been the subject of clinical trials. Ruxolitinib (also known as INCB018424), an inhibitor of the JAK1/2 pathway, was approved as the treatment choice for myelofibrosis (MF) and polycythemia vera (PV) by the U.S. Food and Drug Adminis-tration (FDA) in 2011. Moreover, some studies have shown that ruxolitinib can achieve exciting clinical results in the treatment of AL, MM, and HLH, making it a potential choice of treatment for those diseases. In this review, we summarize the advances in ruxolitinib therapy with regard to research and clinical results for the above-mentioned hematologic malignancies.
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Objective To evaluate the efficacy and quality of life of segmental bowel resection for bowel endometriosis. Methods Totally 62 symptomatic patients with bowel endometriosis undergoing segmental bowel resection were recruited. A visual analogue scale (VAS) and the 36-item short form health survey (SF-36) questionnaire were administered before and at least 1 year after surgery, respectively. Pregnancy rates were also recorded. Results Sixty-two patients in total underwent follow-up ranging from 12 to 74 months. All patients complained of obvious pain symptoms, including dysmenorrhea, dyspareunia, pain on defecation and chronic pelvic pain. The relief of dysmenorrhea (2.9 ± 2.2 versus 7.5 ± 2.9), dyspareunia (0.7 ± 0.5 versus 4.3 ± 2.2) and pain on defecation (1.6 ± 0.7 versus 7.3 ± 1.9) after surgery was statistically significant (all P<0.01). The scores for all 8 domains of the SF-36 questionnaire were significant improved after segmental bowel resection (all P<0.01). The complication rate was 45% (28/62), including 18 cases of urinary retention, 4 rectovaginal fistulas, 2 cases of vaginal dehiscence, and 1 case each of thrombogenesis, pelvic abscess and general peritonitis. All of the patients with complications recovered well throughout follow-up. The postoperative pregnancy rate of the previous infertile patients was 6/10. Among the 6 gestational cases, 2 had labour, 2 underwent caesarean sections, one had a spontaneous natural abortion, and one underwent uterine curettage. Conclusion Segmental bowel resection could significantly relieve pain and improve quality of life for patients with bowel endometriosis.
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Objective To investigate the long-term oncological outcomes of laparoscopic radical hysterectomy (LRH) plus lymph node dissection (LND) and abdominal radical hysterectomy (ARH) plus LND for patients with stage Ⅰ a2-Ⅱ a2 cervical cancer.Methods A retrospective review of stage Ⅰ a2-Ⅱ a2 cervical cancer patients who underwent LRH + LND (n=372) and ARH + LND (n=434) at the First Affiliated Hospital of Sun Yat-sen University from Jan.2005 to Aug.2013 was performed.Individual patient matching was performed by the risk factors for recurrence [tumor size,lymph vascular space invasion (LVSI),depth of cervical stromal invasion,lymph node metastasis,parametrialinvolvement,and resection margin involvement] between two groups.After matched,a total of 203 patient pairs (LRH-ARH) were enrolled.The survival data,surgery data,intraoperative and postoperative complications were compared between the two groups.To assess the prognosis factors,the univariate and multivariate Cox's proportional hazards modelanalysis were conducted.Stratified analysis was performed based on the independent prognosis factors to investigate the survival data between the two surgery groups.Results (1) Surgery data:The operating time [(239±44) vs (270±42) minutes],estimated blood loss [(210± 129) vs (428±320) ml],the duration of bowel motility return [(2.0±0.8) vs (3.0± 1.6) days] and hospital stay [(11 ±6) vs (13±6) days] in the LRH group were significantly shorter than those in ARH group (all P＜0.01).(2) Intraoperative and postoperative complications:The intraoperative complications rate was similar betweentwo groups [6.4％(13/203) vs 6.9％(14/203),P=1.000].The rate of postoperative complications (excluded bladder dysfunction) in the LRH group were significantly lower than those in the ARH group [9.4％ (19/203) vs 20.2％ (41/203),P=0.002].While there was no significant difference in the rates of bladder dysfunction between two groups [36.5％ (74/203) vs 37.4％ (76/203),P=0.910].(3) Recurrence and survival data:There was no significant difference in the recurrence rates between the LRH group and ARH groups [7.9％ (16/203) vs 9.4％ (19/203),P=0.850].There were similar 5-year recurrence-free survival (RFS;92.1％ vs 91.1％,P=0.790) and 5-year overall survival (OS;93.7％ vs 96.1％,P=0.900).(4) Prognosis factor:In univariate analysis,the results showed that tumor size,International Federation of Gynecology and Obstetrics (FIGO) stage,adjuvant therapy,LVSI,stromal invasion,parametrium invasion,pelvic lymph node metastasis,and para-aortic lymph node metastasis were significantly associated with poor prognosis (all P＜0.01).However,age,body mass index (BMI),surgery type,histological type,grade were not significantly associated with poor prognosis (all P＞0.05).The multivariate analysis results,showed that tumor size,pelvic lymph node metastasis,and para-aortic lymph node metastasis were significantly associated with poor prognosis (all P＜0.01).Stratified analysis showed that,even in patients with tumor size ＞4 cm,pelvic lymph node metastasis positive,and para-aortic lymph node metastasis positive in all subgroups,there were not significant difference for the estimated 5-year RFS and 5-year OS between LRH and ARH group (all P＞0.05).Conclusion For patients with stage Ⅰ a2-Ⅱ a2 cervical cancer,LRH plus lymph node dissection is an oncologically safe and surgical feasible alternative to ARH.
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Objective To investigate the effects of lovastatin on inducing G1 phase synchromzation in HEC-1-A cells and examine the cell cycle progression after desynchronization.Methods The doubling time of HEC-1-A cells was detected by cell counting Kit-8 assay.To determine the best lovastatin concentration of G1 synchronization,HEC-1-A cells were treated with lovastatin at concentration of 10,20,30 and 40 μmol/L respectively for 1 × doubling time,and the cell cycle was detected by flow cytometry (FCM).To determine the best period of lovastatin treatment to achieve G1 synchronization,HEC-1-A cells were treated with lovastatin at the best concentration for 0.5 × to 2 × doubling time,and the cell cycle was detected every 4 h using FCM.Furthermore,the cell cycle progress of HEC-1-A cells after desynchronization was also observed.Results The doubling time of HEC-1-A cells was 24 h.Treated with lovastatin at concentration of 40 μmol/L for 28 h achieved maximum G1 arrest (87.87±0.70) ％ in HEC-1-A cells.Minimum G1 phase (58.42±0.54) ％ and maximum S phase (33.58±0.62) ％ were observed after desynchronizing for 20 h.Conclusion Maximum G1 synchronization of HEC-1-A cells is induced by lovastatin at concentration of 40 μmol/L for 28 h.The HEC-1-A cells show minimum G1 phase and maximum S phase after desynchronizing for 20 h.
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Objective To investigate the apoptotic and proliferation effects of signal transduction inhibitors on human endometrial carcinoma cells with different PTEN gene expression. Methods FTEN antisense oligonucleotide and pcDNA3.1/PTEN vector contained PTEN gene were transfected into endometrial carcinoma cells (HEC-1A and Ishikawa). The expression of PTEN protein was detected by confocal spectral microscopy. The endometrial carcinoma cells (HEC-1A, HEC-1A-PTEN-null, Ishikawa, Ishikawa-PTEN) were treated with signal transduction inhibitors, RG-14620, SB203580 (SB) and rapamycin, respectively. Cell apoptosis morphology, cell apoptosis and cell cycle were detected by Hoechst 33258 staining and flow cytometry. Cell viability was determined by methyl thiazolyl tetrazolium assay. Results The PTEN protein expression in two endometrial carcinoma cells (Ishikawa, HEC-1A) was exchanged by PTEN antisense oligonucleotide blocked and pcDNA3. 1/PTEN stable transfected. After treated with RG-14620, SB and rapamycin, marked morphological changes of apoptosis were observed in HEC-1A-PTEN-null and Ishikawa cells. The cell apoptosis of HEC-1A-PTEN-null and Ishikawa cells exposed to SB were significantly increase [(31.6±0.8)% and (37.8±0.8)%, respectively], the G1 phase cells were increased to (84.1±3.2)% and (87.5±1.9)%. While cell viability was significantly decreased in HEC-1A-PTEN-null and Ishikawa cells, the cell viability of HEC-1A-PTEN-null and Ishikawa cells exposed to SB were (54.0±2.1) % and (49.0±1.7) %. Conclusion Loss of PTEN in endometrial carcinoma cells may improve the G_1 phase cells and apoptotic effects, inhibit the cell proliferation, which due to the sensitivity of cells to related signal transduction inhibitors.
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Objective To explore the high-risk factors of the abdominal wound undesirable healing in gynecologic operations and its prevention and treatment.Methods A retrospective clinical study reviewed 58 cases in gynecologic operations.To investigate and analyze its frequent clinical risk factors.Results The risk factors in these wound healing defect such as the fat liquefied:3 cases(48.3%),the anaemia and/or hypoproteinemia:13 cases(22.4%);combined with diabetes:3 cases(5.2%),hypertension:6 cases(10.3%),wound infection:2 cases(3.5%)and wound hematoma:1 case(1.7%);two high risk factors coexisted:22 cases(37.9%),three or more risk factors coexisted:11 cases(19.0%).The complication of such wound healing defect such as effusion:26 cases(44.8%),flare and induration:28 cases(48.3%),low-grade fever:5 cases(8.6%).Conclusion The fat liquefaction is the important reason of the wound dehiscence in gynecology operations;the effusion,flare or induration is the precipitation of the wound healing defect.If we can treat these high-risk groups positively,we will improve the clinical prognosis.
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0.05). There were no adverse events or severe adverse events in all these 72 cases. Conclusion Ozone is effective and safe in the treatment of bacterial vaginosis.
