Efficacy of Laparoscopic Surgery Combined With Leuprorelin in the Treatment of Endometriosis Associated With Infertility and Analysis of Influencing Factors for Recurrence.

Objective: To explore the curative effect of laparoscopic surgery combined with leuprorelin in the treatment of endometriosis with infertility and the related factors of recurrence after treatment. Methods: A total of 158 patients with endometriosis and infertility were selected in our hospital from January 2019 to June 2020. Patients were randomly divided into the control group and the observation group, with 79 patients in each group. Patients in the control group was treated by laparoscopy surgery combined with dydrogesterone, while those in the observation group was treated with laparoscopic surgery combined with leuprorelin. The hormone levels, recurrence rate, pregnancy rate and adverse reaction of the two groups were compared. Combined with clinical and pathological information, the related factors of postoperative recurrence were analyzed. Results: After treatment, the levels of luteinizing hormone, follicle-stimulating hormone and estradiol in the observation group were lower than those in the control group (P < 0.05). The recurrence rate at 12 months after operation in the observation group was lower than that in the control group, and the pregnancy rate was higher than that in the control group (P < 0.05). However, there was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Preoperative dysmenorrhea was an independent risk factor for postoperative recurrence in patients with endometriosis, and postoperative pregnancy was a protective factor for postoperative recurrence in patients with endometriosis (P < 0.05). Conclusion: Laparoscopy combined with leuprorelin in the treatment of endometriosis with infertility can improve hormone levels, increase the pregnancy rate and reduce the recurrence rate. Preoperative dysmenorrhea is an independent risk factor for postoperative recurrence, which should be quantified and included in the recurrence risk prediction model. Postoperative pregnancy can reduce the recurrence rate after operation, and patients with fertility requirements should be encouraged to make activ preparations for postoperative pregnancy.

ELK1-induced upregulation lncRNA LINC02381 accelerates the osteosarcoma tumorigenesis through targeting CDCA4 via sponging miR-503-5p.

Long noncoding RNAs (lncRNAs) have been identified as functional modulators in human tumors. The purpose of our study was to determine the expressing trend, clinical significance and functions of lncRNA LINC02381(LINC02381) in osteosarcoma. We observed that the expression of LINC02381 and cell division cycle-associated protein 4 (CDCA4) were distinctly increased in osteosarcoma specimens and cells, while miR-503-5p expression was decreased. Additionally, ETS transcription factor ELK1 (ELK1) could bind directly to the LINC02381 promoter region and activate its transcription. Clinical assays revealed that high LINC02381 was associated with advanced clinical progress and poor clinical outcome. Functionally, knockdown of LINC02381 suppressed the proliferation, migration and invasion of osteosarcoma cells. What's more, LINC02381 could down-regulate CDCA4 via sponging miR-503-5p, and there existed a negative correlation between LINC02381 expression and miR-503-5p expression in 92 osteosarcoma samples. Rescue experiments proved the carcinogenic role of LINC02381/miR-503-5p/CDCA4 axis in osteosarcoma progression. Overall, our data illustrated how LINC02381 played an oncogenic role in osteosarcoma and might offer a novel diagnostic and prognostic biomarker and potential therapeutic target for osteosarcoma.

C-reactive protein may rise after closed-suction drainage removal in patients undergoing revision arthroplasty: a retrospective study.

BACKGROUND: Serum C-reactive protein (CRP) has been one of the most commonly used markers to rule out early post-operative infection following total joint arthroplasty. The phenomenon that CRP values rise after prolonged drainage removal may occur in clinical settings. The purpose of this study is to investigate (i) the prevalence and risk factors of such a phenomenon and (ii) whether the raised CRP is associated with post-operative infection. METHODS: A retrospective review of 72 revision arthroplasties of the knee and hip with prolonged drainage from 2011 to 2016 was conducted. Perioperative CRP levels were obtained, and patients were divided into two groups according to whether CRP levels were elevated after drainage removal (raised CRP group and control group). Multivariate logistic regression analyses were performed to identify risk factors of raised CRP after drainage removal. The incidence of post-operative wound complications and infection was compared between groups. RESULTS: Overall, the prevalence of raised CRP after drainage removal was 29.17% (21/72). CRP level before drainage removal was associated with the occurrence of such a phenomenon (adjusted odds ratio per 10-mg/L increase 0.92, 95% confidence interval 0.87-0.97). The raised CRP levels decrease again within 3 days after drainage removal. There was no significant difference in the incidence of wound complications and infection between the raised CRP group and control group. CONCLUSION: Almost one in three patients have raised CRP values after prolonged drainage removal following revision arthroplasty. However, CRP values can decrease again within 3 days after drainage removal without specific management. Almost one in three patients have raised C-reactive protein values after prolonged drainage removal following revision arthroplasty. However, C-reactive protein values can decrease again within 3 days after drainage removal without specific management. Surgeons should remember that such a phenomenon may be not be a proxy for post-operative infection following revision arthroplasty.

Correction to: Total hip arthroplasty with modular stem for Crowe I and II developmental dysplasia of the hip.

In the original publication of this article [1], an sentence needs to be added in the end of the caption of Figure 1 and Figure 3: cited in our previous study [18].

Total hip arthroplasty with modular stem for Crowe I and II developmental dysplasia of the hip.

BACKGROUND: The variation of femoral anteversion is not completely consistent with the grade of developmental dysplasia of the hip (DDH), which poses challenges to hip replacement with the non-modular tapered stem. Currently, whether the modular stem should be used in Crowe I and II DDH is still controversial. The aim of this study is to compare the clinical efficacy of the modular stem and the non-modular tapered stem in Crowe I and II DDH patients. METHODS: We retrospective analyzed the clinical data of 196 patients with unilateral Crowe I and II DDH from January 2015 to January 2017. One hundred patients were operated by an experienced surgeon with the modular stems; the remaining 96 patient was operated by another equivalent surgeon with the non-modular tapered stems. The preoperative basic information, operating time, intraoperative and postoperative complications, postoperative leg length discrepancy (LLD) and offset, Harris hip score (HHS), and forgotten joint score (FJS) in postoperative 2 years were collected and analyzed. RESULTS: Postoperative LLD (P = 0.010) and FJS (P = 0.001) had significant difference between two groups. Concurrent acceptable LLD and offset were achieved in 87% of patients with the modular stem and in 68% of patients with the non-modular stem (P = 0.001). There was no significant difference in the operating time (P = 0.086), intraoperative complication (P = 0.096), postoperative dislocation rate (P = 0.056), postoperative offset difference (P = 0.108), and Harris score (P = 0.877) between two groups. CONCLUSIONS: Compared with the non-modular tapered stem, the modular stem was more likely to provide accurate reconstruction and forgotten artificial hip for Crowe I and II DDH patients. We recommend the modular stem as routine choice for these patients.

Chaperone-mediated autophagy substrate proteins in cancer.

All intracellular proteins undergo continuous synthesis and degradation. Chaperone-mediated autophagy (CMA) is necessary to maintain cellular homeostasis through turnover of cytosolic proteins (substrate proteins). This degradation involves a series of substrate proteins including both cancer promoters and suppressors. Since activating or inhibiting CMA pathway to treat cancer is still debated, targeting to the CMA substrate proteins provides a novel direction. We summarize the cancer-associated substrate proteins which are degraded by CMA. Consequently, CMA substrate proteins catalyze the glycolysis which contributes to the Warburg effect in cancer cells. The fact that the degradation of substrate proteins based on the CMA can be altered by posttranslational modifications such as phosphorylation or acetylation. In conclusion, targeting to CMA substrate proteins develops into a new anticancer therapeutic approach.

Myxoma viral serpin, Serp-1, inhibits human monocyte adhesion through regulation of actin-binding protein filamin B.

Serp-1 is a secreted myxoma viral serine protease inhibitor (serpin) with proven, highly effective, anti-inflammatory defensive activity during host cell infection, as well as potent immunomodulatory activity in a wide range of animal disease models. Serp-1 binds urokinase-type plasminogen activator (uPA) and the tissue-type PA, plasmin, and factor Xa, requiring uPA receptor (uPAR) for anti-inflammatory activity. To define Serp-1-mediated effects on inflammatory cell activation, we examined the association of Serp-1 with monocytes and T cells, effects on cellular migration, and the role of uPAR-linked integrins and actin-binding proteins in Serp-1 cellular responses. Our results show that Serp-1 associates directly with activated monocytes and T lymphocytes, in part through interaction with uPAR (P<0.001). Serp-1, but not mammalian serpin PA inhibitor-1 (PAI-1), attenuated cellular adhesion to the extracellular matrix. Serp-1 and PAI-1 reduced human monocyte and T cell adhesion (P<0.001) and migration across endothelial monolayers in vitro (P<0.001) and into mouse ascites in vivo (P<0.001). Serp-1 and an inactive Serp-1 mutant Serp-1(SAA) bound equally to human monocytes and T cells, but a highly proinflammatory mutant, Serp-1(Ala(6)), bound less well to monocytes. Serp-1 treatment of monocytes increased expression of filamin B actin-binding protein and reduced CD18 (beta-integrin) expression (P<0.001) in a uPAR-dependent response. Filamin colocalized and co-immunoprecipitated with uPAR, and short interference RNA knock-down of filamin blocked Serp-1 inhibition of monocyte adhesion. We report here that the highly potent, anti-inflammatory activity of Serp-1 is mediated through modification of uPAR-linked beta-integrin and filamin in monocytes, identifying this interaction as a central regulatory axis for inflammation.

Heparin alters viral serpin, serp-1, anti-thrombolytic activity to anti-thrombotic activity.

Serine protease inhibitors (serpins) regulate coagulation and inflammation. Heparin, a glycosaminoglycan, is an important cofactor for modulation of the inhibitory function of mammalian serpins. The secreted myxoma viral serpin, Serp-1 exerts profound anti-inflammatory activity in a wide range of animal models. Serp-1 anti-inflammatory and anti-atherogenic activity is dependent upon inhibition of the uPA / uPA receptor thrombolytic complex. We demonstrate here that heparin binds to Serp-1 and enhances Serp-1 inhibition of thrombin, a human pro-thrombotic serine protease, in vitro, altering inhibitory activity to a more predominant anti-thrombotic activity. Heparin also facilitates the simultaneous thrombin-mediated cleavage of Serp-1 and prevents formation of a serpin-typical SDS-resistant complex, implying mutual neutralization of Serp-1 and thrombin. In a cell-based assay, heparin facilitates Serp-1 reversal of cellular activation by stabilizing cellular membrane fluidity in thrombin-activated monocytes. In conclusion, heparin and other GAGs serve as cofactors enhancing Serp-1 regulation of local thrombotic and inflammatory pathways.

Viral serpin, Serp-1, inhibits endogenous angiogenesis in the chicken chorioallantoic membrane model.

BACKGROUND: Angiogenesis is a critical factor in the development of malignant tumors, in arthritic joints, and in cardiovascular disease. In cardiovascular disease, angiogenesis is recognised both as a potential therapy and as a complicating factor in atherosclerotic plaque rupture and thrombotic obstruction. Serine proteases regulate thrombosis, inflammation, and cell invasion, events that trigger various stages of angiogenesis and are in turn regulated by inhibitors, termed serpins. Serp-1 is a secreted anti-inflammatory viral serpin that profoundly inhibits early mononuclear cell invasion, and the development of atherosclerosis, transplant vasculopathy, and arthritis in a range of animal models. METHODS: The capacity of Serp-1 to alter angiogenesis was evaluated in the chicken chorioallantoic membrane (CAM) model using morphometric analysis of vascular changes and RT-PCR to explore alterations in gene expression. RESULTS: Serp-1 inhibited endogenous angiogenesis in a dose-dependent manner, with associated altered expression of laminin and vascular endothelial growth factor (VEGF). Serp-1 was ineffective in CAMs no longer in the rapid growth phase. Similar inhibition of angiogenesis was detected after inhibition of VEGF, but not after treatment with the inactivated reactive center loop mutant of Serp-1. CONCLUSIONS: The angiogenic process can be controlled using Serp-1, an anti-inflammatory agent that is effective at low concentrations with rapid reversibility, targets endothelial cells, and reduces the availability of VEGF. These properties may be especially important in cardiovascular disease, reducing plaque destabilization. It is likely that the anti-angiogenic activity of Serp-1 contributes to the observed anti-inflammatory and anti-atherogenic actions with potential importance in this therapeutic setting.

Correlation study showing no concordance between EPAS-1/HIF-2alpha mRNA and protein expression in transitional cellcancer of the bladder.

OBJECTIVES: Endothelial Per-ARNT-Sim (PAS) domain protein-1 (EPAS-1)/hypoxia-inducible factor (HIF)-2alpha is a recently identified, endothelial-specific, hypoxia-induced transcription factor and is reputed to have an important role in tumor angiogenesis and tumor progression. Only a few studies have reported on the clinical correlation with grade, stage, necrosis, and microvessel density in transitional cell carcinoma of the bladder. In vitro studies have reported no concordance of EPAS-1/HIF-2alpha mRNA and protein expression. We sought to elucidate these two issues. METHODS: Surgical specimens from 110 patients with transitional cell carcinoma comprised the study, including 51 from radical cystectomy and 59 from transurethral resection of bladder tumor. Immunohistochemistry and in situ hybridization were performed with antibodies against EPAS-1/HIF-2alpha, CD31, and a human EPAS-1/HIF-2alpha cDNA subclone probe. RESULTS: EPAS-1/HIF-2alpha protein expression was found almost exclusively in high-grade and high-stage tumors (P <0.0001). EPAS-1/HIF-2alpha mRNA expression was detectable only in high-grade (grade 3) and high-stage (pT3a or greater) cases with positive EPAS-1/HIF-2alpha protein expression (P = 0.0017). The presence of necrosis correlated with EPAS-1/HIF-2alpha expression, tumor grade, and tumor stage (P <0.0001). Microvessel density was much lower in invasive, larger tumor nodules in EPAS-1/HIF-2alpha-positive cases than in the negative cases (P <0.0001). CONCLUSIONS: EPAS-1/HIF-2alpha protein and mRNA levels correlate with higher grade and advanced bladder transitional cell carcinoma. In lower stage cases, no concordance was found between transcription and translation of EPAS-1/HIF-2alpha gene expression. Because EPAS-1/HIF-2alpha mRNA is only detectable in highly invasive cancer cases, it may serve as a therapeutic target (eg, by an antisense mRNA approach) for bladder cancer.