Anti-Ro52 antibodies are associated with the prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease.

OBJECTIVES: In the present study, we aimed to assess the prevalence and clinical significance of anti-Ro52 antibodies in a cohort of patients with idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) with different myositis-specific autoantibodies (MSAs). METHODS: A cohort of 267 IIM-ILD patients, including 62 patients with PM, 126 patients with DM and 79 patients with clinically amyopathic DM (CADM) were retrospectively analysed in this study. Clinical and laboratory findings, pulmonary function tests (PFTs), HRCT patterns and treatment information were compared between patients with and without anti-Ro52 antibodies. The association between prognosis and anti-Ro52 antibodies was also evaluated based on different MSA subgroups. RESULTS: Anti-Ro52 antibodies were more frequent in patients with anti-MDA5 (62.1%, P < 0.01) and anti-Jo1 (64.9%, P < 0.01) antibodies than in those with other MSAs. The proportion of patients with anti-Jo1 antibodies was higher in the anti-Ro52 antibody-positive group than in the anti-Ro52 antibody-negative group. Patients with anti-Ro52 antibodies were more likely to exhibit the Gottron sign than the anti-Ro52 antibody-negative group (P < 0.001). Furthermore, it was a predictive factor for rapid progression interstitial lung disease (RP-ILD) (P = 0.001) and was also associated with a higher mortality rate (log-rank test, P = 0.001). Furthermore, RP-ILD was more frequently exhibited in anti-MDA5- and anti-Ro52-positive patients. Moreover, anti-Ro52 antibody positivity was closely associated with a higher mortality rate in anti-MDA5-ILD patients (log-rank test, P < 0.05). CONCLUSIONS: Anti-Ro52 antibodies were highly prevalent in patients with anti-MDA5 and anti-Jo1 antibodies. Within all patients with IIM-ILD, those with anti-Ro52 autoantibodies had a higher frequency of RP-ILD and a poorer prognosis, especially in the anti-MDA5 antibody subgroup.

p75NTR Promotes Astrocyte Proliferation in Response to Cortical Stab Wound.

Astrogliosis after brain trauma can have a significant impact on functional recovery. However, little is known about the mechanisms underlying astrocyte proliferation and subsequent astrogliosis. In this study, we established a cortical stab wound injury mouse model and observed dramatic astrocyte activation and nerve growth factor receptor (p75NTR) upregulation near the lesion. We also found profound alterations in the cell cycle of astrocytes near the lesion, with a switch from a mitotically quiescent (G0) phase to the G2/M and S phases. However, no changes in the level of astrocyte apoptosis were observed. Cell cycle progression to the G2/M and S phases and CDK2 protein levels in response to cortical stab wound was inhibited after p75NTR knockdown in mouse astrocytes. Conversely, p75NTR overexpression in mouse astrocytes was sufficient in promoting cell cycle progression. In conclusion, our results suggested that p75NTR upregulation in astrocytes after brain injury induces cell cycle entry by promoting CDK2 expression and promoting astrocyte proliferation. Our findings provided a better understanding of astrocytic responses after cortical stab wound injury in mice.

Self-Assembly Bifunctional Tetranuclear Ln2Ni2 Clusters: Magnetic Behaviors and Highly Efficient Conversion of CO2 under Mild Conditions.

A series of heterometallic tetranuclear clusters, Ln2Ni2(NO3)4L4(µ3-OCH3)2·2(CH3CN) (Ln = Gd(1), Tb(2), Dy(3), Ho(4), Er(5); HL = methyl 3-methoxysalicylate), were synthesized solvothermally. The intramolecular synergistic effect of two metal centers of Ln(III) and Ni(II) and the exposed multimetallic sites serving as Lewis acid activators greatly increase the efficiency of the CO2 conversion, and the yield for cluster 3 can be achieved at 96% at atmospheric pressure and low temperature. In particular, the self-assembly multimetal center with polydentate ligand shows good generality and enhanced recyclability. The design of such 3d-4f heterometallic clusters provides an effective strategy for the conversion of CO2 under greener conditions. Meanwhile, magnetic investigations indicate that cluster 1 is a good candidate for magnetic refrigerant materials with a relatively large magnetocaloric effect (MCE) (-ΔSm = 28.5 J kg-1 K-1 at 3.0 K and 7.0 T), and cluster 3 shows single-molecular magnet behavior under zero dc field. Heterometallic clusters with special magnetic properties and good catalytic behavior for the conversion of CO2 are rare. Thus, they are potential bifunctional materials applied in practice.

Analysis of carcinogenic signaling networks in endometrial cancer identifies RAB17 as a potential target.

Endometrial cancer is one of the most common malignancies in postmenopausal women. Several potential therapeutic targets have been investigated in current research, but few have been used clinically. Therefore, further investigating the potential pathogenesis of endometrial cancer and new effective therapeutic targets for endometrial malignancies is still necessary. Our study used a The Cancer Genome Atlas dataset and two Gene Expression Omnibus datasets for weighted gene coexpression network analysis to identify important genes associated with the histological grades of endometrial cancer. In addition, we performed gene set enrichment analysis on the three datasets and found that abnormally activated signaling pathways and metabolic pathways are the main biological behaviors of endometrial cancer. Moreover, we further used different algorithms and identified the RAB17 gene as a potential study object. To further illustrate the potential role of the genes we analyzed in clinical and cellular aspects, we performed a clinical correlation analysis. Finally, we demonstrated the important roles and mechanisms of the RAB17 gene in the cell cycle, proliferation, and metastasis of endometrial cancer. Using repeated database analysis and cell-level assays, we propose RAB17 as a potential target gene for endometrial cancer for further study.

Guiding-Strand-Controlled DNA Nucleases with Enhanced Specificity and Tunable Kinetics for DNA Mutation Detection.

Nucleases are powerful tools in various biomedical applications, such as genetic engineering, biosensing, and molecular diagnosis. However, the commonly used nucleases (endonuclease IV, apurinic/apyrimidinic endonuclease-1, and λ exonuclease) are prone to the nonspecific cleavage of single-stranded DNA, making the desired reactions extremely low-yield and unpredictable. Herein, we have developed guiding-strand-controlled nuclease systems and constructed theoretical kinetic models to explain their mechanisms of action. The models displayed excellent agreement with the experimental results, making the kinetics highly predictable and tunable. Our method inhibited the nonspecific cleavage of single-stranded probes while maintaining highly efficient cleavage of double-stranded DNA. We also demonstrated the clinical practicability of the method by detecting a low-frequency mutation in a genomic DNA sample extracted from the blood of a patient with cancer. The limit of detection could be 0.01% for PTEN rs121909219. We believe that our findings provide a powerful tool for the field and the established model provides us a deeper understanding of the enzymatic activities of DNA nucleases.

Cytokeratin 19 fragment is associated with severity and poor prognosis of interstitial lung disease in anti-MDA5 antibody-positive dermatomyositis.

OBJECTIVES: In the present study, we aimed to assess the clinical significance of cytokeratin 19 fragment (CYFRA21-1) in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM-interstitial lung disease (MDA5-DM-ILD). METHODS: A total of 73 MDA5-DM-ILD patients were retrospectively analysed in this work. Their clinical characteristics, including clinical manifestations, laboratory findings, peripheral blood lymphocyte subsets and lung function, were compared between patients with acute/subacute interstitial pneumonia (A/SIP) and chronic interstitial pneumonia (CIP). The level of serum CYFRA21-1 was also compared between the above-mentioned two groups of patients, and its association with the clinical features and mortality of MDA5-DM-ILD was also evaluated. RESULTS: Of the 73 MDA5-DM-ILD patients, 26 patients exhibited the A/SIP pattern. The level of serum CYFRA21-1 was higher in MDA5-DM patients with A/SIP compared with the CIP group (P = 0.009). Lower oxygenation index (OI), CD3+CD4+ T cell counts and percentage of CD3+CD4+ cells were also observed in MDA5-DM patients with A/SIP compared with the CIP group. Higher serum CYFRA21-1, lower OI, and lower zone consolidation were associated with a higher risk of A/SIP in MDA5-DM-ILD. In addition, 38 decedents with MDA5-DM-ILD exhibited a greater level of CYFRA21-1 compared with 35 survivors (P < 0.001). Furthermore, it was a prognostic factor and also associated with a higher mortality rate (log-rank test, P < 0.001). CONCLUSIONS: CYFRA21-1 could be a useful serum indicator associated with occurrence of A/SIP in MDA5-DM-ILD. Moreover, it was associated with a poor survival in MDA5-DM-ILD patients.

Iodine-Rich Semiconducting Polymer Nanoparticles for CT/Fluorescence Dual-Modal Imaging-Guided Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) is a promising technique for cancer therapy, providing good therapeutic efficacy with minimized side effect. However, the lack of oxygen supply in the hypoxic tumor site obviously restricts the generation of singlet oxygen (1 O2 ), thus limiting the efficacy of PDT. So far, the strategies to improve PDT efficacy usually rely on complicated nanosystems, which require sophisticated design or complex synthetic procedure. Herein, iodine-rich semiconducting polymer nanoparticles (SPN-I) for enhanced PDT, using iodine-induced intermolecular heavy-atom effect to elevate the 1 O2 generation, are designed and prepared. The nanoparticles are composed of a near-infrared (NIR) absorbing semiconducting polymer (PCPDTBT) serving as the photosensitizer and source of fluorescence signal, and an iodine-grafted amphiphilic diblock copolymer (PEG-PHEMA-I) serving as the 1 O2 generation enhancer and nanocarrier. Compared with SPN composed of PEG-b-PPG-b-PEG and PCPDTBT (SPN-P), SPN-I can enhance the 1 O2 generation by 1.5-fold. In addition, SPN-I have high X-ray attenuation coefficient because of the high density of iodine in PEG-PHEMA-I, providing SPN-I the ability of use with computed tomography (CT) and fluorescence dual-modal imaging. The study thus provides a simple nanotheranostic platform composed of two components for efficient CT/fluorescence dual-modal imaging-guided enhanced PDT.

Surfactant protein D is associated with 3-month mortality of anti-MDA5 antibody-interstitial lung disease.

OBJECTIVES: To investigate the associations between serum levels of matrix metalloproteinase 7 (MMP7), surfactant protein D (SPD), interleukin 18 (IL-18) and chemokine ligand 18 (CCL18) with dermatomyositis and polymyositis-associated interstitial lung disease (DM/PM-ILD) and evaluate their prognostic values in the disease. METHODS: Seventy-eight patients with multiple disciplinary team diagnosis of DM/PM-ILD were enrolled and classified as anti-melanoma differentiation-associated protein 5 antibody (MDA5)-ILD, anti-synthetase antibodies (ARS)-ILD and other antibodies-ILD upon autoantibodies profiles. Clinical data were collected and serum levels of four biomarkers were analysed. The primary endpoint was 3-month mortality. The cut-off values of biomarkers for mortality were figured out by receiver operating characteristic (ROC) analysis. Cox regression was performed to evaluate predictive values. RESULTS: Serum levels of MMP7 (p=0.036), SPD (p<0.001), IL-18 (p<0.001) and CCL18 (p<0.001) in patients with DM/PM-ILD were significantly higher than healthy controls with levels of MMP7 (p=0.029) and SPD (p=0.029) in patients with MDA5-ILD significantly lower than patients with ARS-ILD. The 3-month mortality in MDA5-ILD was 54.5% (12/22). Multivariate analysis showed that age (p=0.001, HR 1.151, 95% CI 1.063-1.247) and an increased level of SPD (>75.90ng/ml, p=0.005, HR 16.411, 95% CI 2.369-113.711) were significant predictors for 3-month mortality in patients with MDA5-ILD. CONCLUSIONS: Elevated serum biomarkers were associated with DM/PM-ILD with differential levels between MDA5-ILD and ARS-ILD. Age and an increased SPD had prognostic values for predicting short-term mortality in patients with MDA5-ILD. Our study was important in providing a clue for understanding the classification and prognosis of DM/PM-ILD.

The Effects of miR-195-5p/MMP14 on Proliferation and Invasion of Cervical Carcinoma Cells Through TNF Signaling Pathway Based on Bioinformatics Analysis of Microarray Profiling.

BACKGROUND/AIMS: This study is aimed at identification of miR-195-5p/MMP14 expression in cervical cancer (CC) and their roles on cell proliferation and invasion profile of CC cells through TNF signaling pathway in CC. METHODS: Microarray analysis, gene set enrichment analysis (GSEA) and DAVID were used to analyze differentially expressed miRNAs, mRNAs and signaling pathways. MiR-195-5p and MMP14 expression levels in CC cell were determined by qRT-PCR. Western blot was employed to measure MMP14 and TNF signaling pathway-relating protein level. Luciferase reporter system was used to confirm the targeting relationship between MMP14 and miR-195-5p. Cell proliferation and invasion was respectively deeded by CCK8, transwell. In vivo experiment was carried out to study the impact of MMP14 and miR-195-5p on CC development in mice. RESULTS: The microarray analysis and the results of qRT-PCR determined that miR-195-5p was under-expressed and MMP14 was over-expressed in CC cells. GSEA and DAVID analysis showed that TNF signaling pathway was regulated by miR-195-5p/MMP14 and activated in cervical carcinoma cells. The miR-195-5p and MMP14 have a negative regulation relation. In vivo experiment found that down-regulated MMP14 and up-regulated miR-195-5p suppressed the tumor development. CONCLUSION: Our results suggest that MMP14 is a direct target of miR-195-5p, and down-regulated MMP14 and up-regulated miR-195-5p suppressed proliferation and invasion of CC cells by inhibiting TNF signaling pathway.

Altered expression of hormone receptor, integrin ß3 and pinopode in the endometrium of luteal phase defect women.

OBJECTIVE: To invistigate estrogen receptor (ER), progesterone receptor (PR), integrin ß3, and pinopode expression in luteal phase deficiency (LPD) women. METHODS: There were 52 nulligravidas consecutive infertile patients undergoing a routine assistant reproduction consultation included in this study. An endometrial biopsy sample was randomly obtained between days 4 and 10 of the luteal phase. Endometrial morphology was examined with scanning electron microscopy. Expressions of ER, PR, integrin ß3 were determined in the endometrium of LPD patients with immunohistochemistry. RESULTS: The incidence of LPD was 15.3% (8/52) in this study. On day luteinizing hormone (LH) surge + 9∼LH + 10, noted regressing pinopodes resembling a day LH + 7∼LH + 8 in the endometrium of the control group. The expressions of ER and PR in glandular epithelium were significantly increased in endometrium of LPD than that in the control group (p < 0.05). In contrast, there was a statistically significant decrease expression of the integrin ß3 in women from the group of LPD (p < 0.05). CONCLUSION: The altered expression of ER and PR may be associated with the expression variation of integrin and pinopode formation in endometrium of LPD women. This alteration may imply the association of low rates of cycle fecundity and high rates of embryonic loss in LPD women.

Elevated growth differentiation factor 15 expression predicts poor prognosis in epithelial ovarian cancer patients.

The purpose of this study was to determine the expression of growth differentiation factor 15 (GDF15) and explore its clinical significance in epithelial ovarian cancer (EOC) patients. The expression of GDF15 in EOC tissues and serum samples was evaluated using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), respectively. The association of GDF15 expression with clinicopathologic parameters was analyzed. Survival time was assessed using the Kaplan-Meier technique and Cox regression model. Both in EOC tissues and serum, high GDF15 levels were obviously related with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, ascites, and chemoresistance. Kaplan-Meier analysis indicated that EOC patients with high GDF15 expression showed poorer progression-free survival (PFS) and overall survival (OS). Multivariate analysis demonstrated that GDF15 expression was an independent predictor of PFS in EOC patients. Our study shows that elevated GDF15 expression was associated with poor prognosis in EOC patients. We suggest that GDF15 is a novel biomarker for the early detection of EOC, prediction of the response to chemotherapy, and screening for recurrence in EOC patients.

Stromal cells of endometrial carcinoma promotes proliferation of epithelial cells through the HGF/c-Met/Akt signaling pathway.

Tumor microenvironment participates in the endometrial carcinoma pathogenesis. This study focuses on the interaction between endometrial cancer stromal cells and epithelial cells from normal endometrium tissue using in vitro transwell coculture system and in vivo xenograft model. We demonstrate that cancer interstitial (CI) cells stimulate normal epithelial (NE) cell proliferation. Tumor xenograft model confirmed the pro-proliferative effect of CI cells on epithelial cell growth. Tumor suppressor PTEN was reduced, and oncogene K-ras was increased in epithelial cells cocultured with CI cells. Moreover, we observed increased expression of hepatocyte growth factor (HGF) in CI cells and tumor xenografts derived from the coculturing system. Higher HGF secretion activated Akt signaling pathway, which was reversed by HGF receptor inhibitor (crizotinib). These results demonstrate that endometrial carcinoma stromal cells stimulate epithelial cell proliferation via the HGF/c-Met/Akt signaling pathway.

A ternary composite based on graphene, hemin, and gold nanorods with high catalytic activity for the detection of cell-surface glycan expression.

A novel graphene-family ternary composite with high catalytic activity has been developed by using simple synthetic methods. The graphene-based ternary composite has abundant positively charged Au NRs, which greatly improved the catalytic properties of the graphene-family of peroxidase mimetics, because of the high electron-transfer rate of graphene and the synergistic interaction of three components. Sensitive detection of glycan expression on K562 cell surface can be achieved with a low detection limit of 10 cells. This finding constitutes a novel graphene-family hybrid nanomaterials-based peroxidase mimetic that is expected to be applied widely in the construction of simple, sensitive, and selective biosensors for nucleic acids and proteins both inside and outside of cells through catalytic reaction of H2 O2 .

Platinum sensitivity and CD133 expression as risk and prognostic predictors of central nervous system metastases in patients with epithelial ovarian cancer.

BACKGROUND: To characterize prognostic and risk factors of central nervous system (CNS) metastases in patients with epithelial ovarian cancer (EOC). METHODS: A retrospective analysis of Xijing Hospital electronic medical records was conducted to identify patients with pathologically confirmed EOC and CNS metastases. In addition to patient demographics, tumor pathology, treatment regimens, and clinical outcomes, we compared putative cancer stem cell marker CD133 expression patterns in primary and metastatic lesions as well as in recurrent EOC with and without CNS metastases. RESULTS: Among 1366 patients with EOC, metastatic CNS lesions were present in 29 (2.1%) cases. CD133 expression in primary tumor was the only independent risk factor for CNS metastases; whilst the extent of surgical resection of primary EOC and platinum resistance were two independent factors significantly associated with time to CNS metastases. Absence of CD133 expression in primary tumors was significantly associated with high platinum sensitivity in both patient groups with and without CNS metastases. Platinum resistance and CD133 cluster formation in CNS metastases were associated with decreased survival, while multimodal therapy including stereotactic radiosurgery (SRS) for CNS metastases was associated with increased survival following the diagnosis of CNS metastases. CONCLUSIONS: These data suggest that there exist a positive association between CD133 expression in primary EOC, platinum resistance and the increased risk of CNS metastases, as well as a less favorable prognosis of EOC. The absence of CD133 clusters and use of multimodal therapy including SRS could improve the outcome of metastatic lesions. Further investigation is warranted to elucidate the true nature of the association between platinum sensitivity, CD133 expression, and the risk and prognosis of CNS metastases from EOC.

Axonal injury mediated by neuronal p75NTR/TRAF6/JNK pathway contributes to cognitive impairment after repetitive mTBI.

Repetitive mild traumatic brain injury (rmTBI) is one of the leading causes of cognitive disorders. The impairment of axonal integrity induced by rmTBI is speculated to underlie the progression of cognitive dysfunction. However, few studies have uncovered the cellular mechanism regulating axonal impairment. In this study, we showed that after rmTBI, the activation of neuronal p75NTR signaling contributes to abnormal axonal morphology and impaired axonal transport, which further leads to cognitive dysfunction in mice. By neuron-specific knockdown of p75NTR or treatment with p75NTR inhibitor LM11A-31, we observed better recovery of axonal integrity and cognitive function after brain trauma. Further analysis revealed that p75NTR relies on its adaptor protein TRAF6 to activate downstream signaling via TAK1 and JNK. Overall, our results provide novel insight into the role of neuronal p75NTR in axonal injury and suggest that p75NTR may be a promising target for cognitive function recovery after rmTBI.

Factors influencing the accuracy and safety of preoperative computed tomography (CT)-guided soft hook-wire localization for pulmonary nodules: a comprehensive analysis.

Background: The necessity of localization of pulmonary nodules lies in ensuring the ability to locate the nodule quickly and accurately during surgery, thereby improving the success rate of the operation. The accuracy and risk of preoperative localization of pulmonary nodules need further exploration. Therefore, the purpose of this study was to investigate the factors of accuracy and safety of computed tomography (CT)-guided localization of pulmonary nodules using a flexible wire hook positioner. Methods: In this retrospective cross-sectional analysis, 281 patients with a single pulmonary nodule underwent video-assisted thoracoscopic surgery (VATS) following localization with a soft hook-wire guided by CT scan from January 2021 to July 2022 at Nanjing Drum Tower Hospital. The patients underwent VATS to remove pulmonary nodules within 24 hours after localization. The demographic, pulmonary nodule, and technical factors were analyzed retrospectively. Univariate and multivariate analysis were used to analyze the identified factors that influence pulmonary nodule localization accuracy and complications. Results: Localization was successfully performed in 280 patients, with only 1 patient being excluded due to a displaced positioner and the hook wire failing to enter the lung parenchyma as a result of pneumothorax. Out of the total cases, 191 (68.2%) were accurately positioned in group G0, whereas 89 cases (31.7%) were inaccurately positioned in group G1. Hemorrhage and self-limited hemoptysis were observed in 64 patients (22.8%), whereas pneumothorax was observed in 84 patients (29.9%). There were no serious complications such as air embolism or death. The accuracy of localization was found to be influenced by both the depth of pulmonary nodules [odds ratio (OR) =22.610, 95% confidence interval (CI): 10.351-49.391, P=0.001] and the depth of the needle used (OR =0.322, 95% CI: 0.136-0.765, P=0.010). Additionally, postoperative hemorrhage was found to be affected by several important factors, including the diameter (P=0.036) and depth of the nodule (P=0.011), as well as the thickness of the chest wall (P=0.043) and the depth of the needle used (P=0.005). Conclusions: The CT-guided flexible wire hook positioner has been found to be a safe and effective device for locating pulmonary nodules. The depth of pulmonary nodules and needle penetration are key factors affecting the accuracy of lung nodule localization under CT guidance and are important factors affecting postoperative bleeding.

Pretreatment mortality risk prediction model in patients with polymyositis/dermatomyositis-associated interstitial lung disease.

OBJECTIVES: Risk prediction for patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) is challenging due to heterogeneity in the disease course. We aimed to develop a mortality risk prediction model for PM/DM-ILD. METHODS: This prognostic study analysed patients with PM/DM-ILD admitted to Nanjing Drum Hospital from 2016 to 2021. The primary outcome was mortality within 1 year. We used a least absolute shrinkage and selection operator (LASSO) logistic regression model to identify predictive laboratory indicators. These indicators were used to create a laboratory risk score, and we developed a mortality risk prediction model by incorporating clinical factors. The evaluation of model performance encompassed discrimination, calibration, clinical utility and practical application for risk prediction and prognosis. RESULTS: Overall, 418 patients with PM/DM-ILD were enrolled and randomly divided into development (n=282) and validation (n=136) cohorts. LASSO logistic regression identified four optimal features in the development cohort, forming a laboratory risk score: C reactive protein, lactate dehydrogenase, CD3+CD4+ T cell counts and PO2/FiO2. The final prediction model integrated age, arthralgia, anti-melanoma differentiation-associated gene 5 antibody status, high-resolution CT pattern and the laboratory risk score. The prediction model exhibited robust discrimination (area under the receiver operating characteristic: 0.869, 95% CI 0.811 to 0.910), excellent calibration and valuable clinical utility. Patients were categorised into three risk groups with distinct mortality rates. The internal validation, sensitivity analyses and comparative assessments against previous models further confirmed the robustness of the prediction model. CONCLUSIONS: We developed and validated an evidence-based mortality risk prediction model with simple, readily accessible clinical variables in patients with PM/DM-ILD, which may inform clinical decision-making.

Quantitative assessment of the association between CYP1A1 A4889G polymorphism and endometrial cancer risk.

Cytochrome P450 1A1 (CYP1A1) A4889G polymorphism was supposed to be associated with endometrial cancer risk, but previous studies reported conflicting results. We therefore performed a meta-analysis of all relevant studies to get a comprehensive assessment of the association between CYP1A1 A4889G polymorphism and endometrial cancer risk. The pooled odds ratios (OR) with the corresponding 95% confidence interval (95% CI) was calculated to assess the association. Finally, ten studies with a total of 1,682 endometrial cancer cases and 2,510 controls were finally included into the meta-analysis. Meta-analysis of the total ten studies showed that CYP1A1 A4889G polymorphism was not associated with endometrial cancer risk (ORG versus A = 1.14, 95% CI 0.83-1.57, P OR = 0.417; ORGG versus AA = 1.23, 95% CI 0.70-2.18, P OR = 0.470; ORGG versus AA/AG = 1.03, 95% CI 0.59-1.81, P OR = 0.919; ORGG/AG versus AA = 1.22, 95% CI 0.82-1.81, P OR = 0.336). Subgroup analyses by ethnicity further showed that there was also no obvious association between CYP1A1 A4889G polymorphism and endometrial cancer risk in both Caucasians and Asians. Sensitivity analysis by excluding single study in turns showed that the pooled estimations were not stable. Therefore, evidence for currently available data suggests that CYP1A1 A4889G polymorphism is not associated with endometrial cancer risk. However, more studies with large number of participants are needed to further assess the association precisely.

The significance of comprehensive staging surgery in malignant ovarian germ cell tumors.

OBJECTIVE: To evaluate the clinical significance of fertility-preserving comprehensive staging surgery (CSS) in the treatment of malignant ovarian germ cell tumors (MOGCTs). METHODS: A total of 92 cases of MOGCTs were retrospectively reviewed. RESULTS: Forty-six patients (50%) received CSS, which includes ipsilateral adnexectomy+omentectomy+retroperitoneal lymphadenectomy (appendectomy and multiple biopsies as required). Forty-six patients (50%) received USO, which includes ipsilateral adnexectomy+clinical intraoperative evaluation (including retroperitoneal lymph nodes, great omentum, peritoneal, and contralateral ovary), biopsy of suspicious sites, and excision of all visible lesions. The mean operation time (177.0 vs. 114.8 min; p<0.0001) and the mean intraoperative blood loss (499.1 ml vs. 112.9 ml; p=0.04) were significantly higher in the CSS group compared to those in the USO group. The complication rate (17.4% vs 0%, p=0.003), the relapse rate (10.9% vs 2.2%, p=0.102) and the mortality rate (4.3% vs 2.2%, p=0.500) were higher in the CSS group compared to those in the USO group. The difference in complication rate was statistically significant. The overall 5 year survival rates were 92% and 97% in the CSS and USO groups, respectively (p=0.575). Tumor-free survival rates at 5 years were 87% and 97% in the CSS and USO groups, respectively (p=0.115). CONCLUSIONS: The benefit of fertility-preserving CSS to MOGCT patients was not greater than that of USO. It is safer and more effective to perform ipsilateral adnexectomy+clinical intraoperative exploration surgery (including retroperitoneal lymph nodes, great omentum, peritoneal, and contralateral ovary), biopsy of suspicious sites, excision of all visible lesions, and adjuvant chemotherapy.

Apurinic/apyrimidinic endonuclease 1 polymorphisms are associated with ovarian cancer susceptibility in a Chinese population.

OBJECTIVE: Apurinic/apyrimidinic endonuclease 1 (APE1) plays an essential role in the base excision repair pathway. Recent studies have shown that APE1 polymorphisms are associated with an increased risk for many types of cancers. This study investigated the association between APE1 polymorphisms and the susceptibility of ovarian cancer. METHODS: A case-control study was performed on 124 patients with ovarian cancer and 141 controls. We genotyped the rs1760944 and rs1130409 polymorphisms and assessed their associations with the risk for ovarian cancer. RESULTS: The rs1130409 polymorphism was significantly associated with a risk for ovarian cancer. The TG/GG genotype and the G allele were associated with a decreased risk for ovarian cancer (adjusted odds ratio [aOR], 0.495; 95% confidence interval [CI], 0.267-0.920 for TG vs TT; aOR, 0.263; 95% CI, 0.132-0.521 for GG vs TT; aOR, 0.486; 95% CI, 0.344-0.0.688 for the G allele vs the T allele). In the stratified analyses, we found that when comparing the TG/GG genotype versus the TT genotype, the lower risk was more evident in subgroups of patients 50 years or older (aOR, 0.753; 95% CI, 0.604-0.938), patients with menarche age of 15 years or older (aOR, 0.722; 95% CI, 0.573-0.910), patients with gravidity of 3 or more times (aOR, 0.732; 95% CI, 0.587-0.912), and postmenopausal women (aOR, 0.763; 95% CI, 0.615-0.947). Meanwhile, the rs1760944 polymorphism was not found to be associated with a risk for ovarian cancer. However, by haplotype analysis, we found that the T-G and G-G haplotypes were associated with a decreased risk for ovarian cancer. CONCLUSIONS: Our results suggest that in a Han Chinese population, the APE1 rs1130409 polymorphism may correlate with ovarian cancer susceptibility.