The indication and treatment outcome predictors of mifepristone treating ectopic pregnancy.

OBJECTIVE: Ectopic pregnancy is a life-threatening disease and is an important cause of pregnancy-related mortality. MTX is the primary conservative treatment medicine of ectopic pregnancy, and mifepristone is also a promising medicine. Through studying the ectopic cases at the third affiliated hospital of Sun Yat-Sen University, the study aims to analyze the indication and treatment outcome predictors of mifepristone. METHODS: The data of 269 ectopic pregnancy cases treated with mifepristone during the year 2011-2019 were retrospectively collected. Logistic-regression analysis was used to analyze the factors affiliated with the treatment outcome of mifepristone. Then ROC curve was used to analyze the indication and predictors. RESULTS: Through logistic-regression analysis, HCG is the only factor related to the treatment outcome of mifepristone. The AUC of ROC curve predicting treatment outcome with pre-treatment HCG is 0.715, and the cutoff value of ROC curve is 372.66 (sensitivity 0.752, specificity 0.619). The AUC of 0/4 ratio predicting the treatment outcome is 0.886, and the cutoff value is 0.3283 (sensitivity 0.967, specificity 0.683). The AUC of 0/7 ratio is 0.947, and the cutoff value is 0.3609 (sensitivity 1, specificity 0.828). CONCLUSIONS: Mifepristone can be used to treat ectopic pregnancy. HCG is the only factor related to the treatment outcome of mifepristone. Patients with HCG less than 372.66 U/L can be treated by mifepristone. If HCG descends more than 67.18% on the 4th day or 63.91% on the 7th day, it is more likely to have a successful treatment outcome. It is more precise to retest on the 7th day.

An Acid Response IR780-Based Targeted Nanoparticle for Intraoperative Near-Infrared Fluorescence Imaging of Ovarian Cancer.

Introduction: Complete resection of all visible disease (R0 resection) is critical for the treatment of ovarian cancer patients, and accurate real-time guidance provided by intraoperative near-infrared (NIR) fluorescence images is beneficial for achieving complete resection of all visible disease. Methods: Based on the optical properties of IR780 and the characteristics of the acidic tumor microenvironment, we develop a new smart nanoparticle (eg, FA-IR780&PFOB-SNPs) by using the pH response nano framework (FA-PEG-PLGA-PEOz) and adjusting the amount of IR780. The FA-IR780&PFOB-SNPs was characterized for morphology, microstructure, particle size, pH-response, drug-loading efficiency and biological safety. The ultraclear fluorescence Navigation Endoscopy System was applied to evaluate the tumor recognition of FA-IR780&PFOB-SNPs in vivo. Results: The structure of FA-IR780&PFOB-SNPs was stable in a neutral environment, and the near-infrared (NIR) fluorescence was turned off, while the structure of FA-IR780&PFOB-SNPs was degraded in the acidic tumour microenvironment, and the NIR fluorescence was turned on. Through the ovarian subcutaneous xenograft tumour and ovarian intraperitoneal xenograft tumour models, it was confirmed that FA-IR780&PFOB-SNPs could clearly display the boundaries of abdominal micron-sized tumours through near-infrared fluorescence imaging, with a TBR greater than 5. Conclusion: The FA-IR780&PFOB-SNPs have the potential to provide to ovarian cancer intraoperative near infrared fluorescence navigation during precision tumour resection to achieve R0 and improve the prognosis of ovarian cancer patients.

OSI-906 restores the sensitivity of ovarian clear cell carcinoma to cisplatin by targeting the IGF1R/AKT pathway.

Among the various histologic subtypes of ovarian cancers (OCs), ovarian clear cell carcinoma (OCCC) represents a great challenge due to its disease aggressiveness and resistance to chemotherapy. IGF1 is overexpressed in epithelial ovarian cancer (EOC), and IGF1 pathway activation is related to the chemoresistance of various cancers. In this study, we found that the expression level of IGF1 was higher in OCCC than in the most common type of OC, high-grade serous adenocarcinoma (HGSC). Then, we investigated the role of IGF1 pathway activation in the progression of OCCC, observing that activation of the IGF1 pathway using IGF1 promoted the proliferation and migration of ES2 cells, while inactivation of the IGF1 pathway using the selective IGF1R inhibitor OSI-906 reversed the alteration mediated by IGF1. Based on the role of the IGF1 pathway in cancer chemoresistance, we proposed that OSI-906 may restore the sensitivity of OCCC to cisplatin. We first validated that IGF1 increased the IC50 value of cisplatin in ES2 cells, while OSI-906 decreased it. Then we confirmed that IGF1 decreased the apoptosis rate of ES2 cells induced by cisplatin, while OSI-906 increased it. Finally, we conducted animal experiments to investigate whether OSI-906 helps cisplatin control the growth of OCCC. As expected, OSI-906 increased the effect of cisplatin in attenuating the growth of OCCC in vivo. Therefore, we conclude that using OSI-906 may be an effective method to restore the sensitivity of OCCC to cisplatin by targeting the IGF1R/AKT pathway.

Associations Between Gut Microbiota and Asthma Endotypes: A Cross-Sectional Study in South China Based on Patients with Newly Diagnosed Asthma.

OBJECTIVE: This study aimed to investigate the gut microbiome profile in different inflammatory phenotypes of treatment-naive newly diagnosed asthmatic adults, to gain insight on the associations between intestinal microbiota and phenotypic features that characterize asthma heterogeneity to develop new treatments for asthma. METHODS: Fresh stool samples were obtained from 20 healthy subjects and 47 newly diagnosed asthmatic patients prior to any interventions. The asthmatics were divided into allergic and non-allergic cohorts. Intestinal microbiota was analyzed by 16S rRNA next-generation sequencing. Demographic and clinical parameters were collected. Alpha and beta diversity analysis were calculated to detect differences within sample phylotype richness and evenness between controls and asthmatic patients. Statistically significant differences between samples were analyzed for all used metrics, and features of gut bacterial community structure were evaluated in relation to extensive clinical characteristics of asthmatic patients. RESULTS: Gut microbial compositions were significantly different between asthmatic and healthy groups. Alpha-diversity of the gut microbiome was significantly lower in asthmatics than in controls. The microbiome between allergic and non-allergic asthmatic patients were also different, and 28 differential species were identified. PPAR signaling pathway, carotenoid biosynthesis, and flavonoid biosynthesis were significantly positively correlated with allergy-associated clinical index, including FENO value, blood eosinophil counts, and serum IgE and IL-4 levels. A combination of Ruminococcus bromii, Brevundimonas vesicularis, and Clostridium disporicum showed an AUC of 0.743 in the specific allergic/non-allergic cohort. When integrating C. disporicum, flavone, flavonol biosynthesis, and serum IL-4 values, the AUC achieved 0.929 to classify asthmatics. At the same time, C. colinum and its associated functional pathway exhibited an AUC of 0.78 to distinguish allergic asthmatics from those without allergies. CONCLUSION: We demonstrated a distinct taxonomic composition of gut microbiota in different asthmatic phenotypes, highlighting their significant relationships. Our study may support considerations of intestinal microbial signatures in delineating asthma phenotypes.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis Associated with Ovarian Teratoma in South China-Clinical Features, Treatment, Immunopathology, and Surgical Outcomes of 21 Cases.

OBJECTIVE: To study the clinical characteristics and surgical outcomes of anti-NMDAR encephalitis and the immunopathology of associated teratomas. METHODS: Twenty-one patients were enrolled in this retrospective study, who were diagnosed with anti-NMDAR encephalitis with ovarian teratoma and admitted to two tertiary hospitals in South China from July 2014 to December 2019. The clinical data of patients were reviewed. Comparisons were made between the patients with different outcomes after surgery. Immunohistochemical analyses of associated ovarian teratomas were performed. RESULTS: The mean age of the patients was 24.33 ± 5.12 years. The peak seasons of disease onset were autumn and winter (30.61% and 32.65%). The symptoms could be divided into 8 categories, including psychiatric abnormalities, seizures, movement dysfunction, consciousness disorders, autonomic dysregulation, speech disturbance, central hypoventilation, and memory deficits. All patients developed four or more categories of symptoms within the first four weeks. Twelve patients (57.1%) had a maximum mRS of 5, and 11 patients (52.4%) were admitted to ICU. Twenty patients received surgery, and only 3 patients were diagnosed pathologically with immature ovarian teratomas, while the other 17 patients had mature ovarian teratomas. After surgery, 17 patients (85.0%) got clinical improvement. The central hypoventilation symptom and mature ovarian teratomas were associated with surgical outcome. Immunohistochemical analysis revealed that there were NMDAR-positive neural tissues in all 8 teratomas and in which 3 cases also contained large numbers of NMDAR-positive sebaceous glands and squamous epithelial tissues. CONCLUSION: The disease is of high prevalence in autumn and winter. The central hypoventilation symptom and mature ovarian teratomas were associated with surgical outcome. NMDAR-positive neural tissue is not the only etiological factor of encephalitis. We speculate that encephalitis development in some patients may result from NMDAR expression in sebaceous glands and squamous epithelial tissues.

Conditional guide RNA through two intermediate hairpins for programmable CRISPR/Cas9 function: building regulatory connections between endogenous RNA expressions.

A variety of nanodevices developed for nucleic acid computation provide great opportunities to construct versatile synthetic circuits for manipulation of gene expressions. In our study, by employing a two-hairpin mediated nucleic acid strand displacement as a processing joint for conditional guide RNA, we aim to build artificial connections between naturally occurring RNA expressions through programmable CRISPR/Cas9 function. This two-hairpin joint possesses a sequence-switching machinery, in which a random trigger strand can be processed to release an unconstrained sequence-independent strand and consequently activate the self-inhibitory guide RNA for conditional gene regulation. This intermediate processor was characterized by the fluorescence reporter system and applied for regulation of the CRISPR/Cas9 binding activity. Using plasmids to generate this sequence-switching machinery in situ, we achieved the autonomous genetic regulation of endogenous RNA expressions controlled by other unrelated endogenous RNAs in both E. coli and human cells. Unlike previously reported strand-displacement genetic circuits, this advanced nucleic acid nanomachine provides a novel approach that can establish regulatory connections between naturally occurring endogenous RNAs. In addition to CRISPR systems, we anticipate this two-hairpin machine can serve as a general processing joint for wide applications in the development of other RNA-based genetic circuits.

Comprehensive Analysis of Prognostic Alternative Splicing Signatures in Endometrial Cancer.

BACKGROUND: Alternative splicing (AS) is one of the critical post-transcriptional regulatory mechanisms of various cancers and also plays a crucial role in the development of cancers, including endometrial cancer (EC). METHODS: The splicing data and gene expression profiles of EC were obtained from The Cancer Genome Atlas. The corresponding clinical data were extracted from TCGA-CDR. With univariate Cox regression analysis, least absolute shrinkage and selection operator model, and multivariate Cox regression analysis, the survival-related AS events were selected. Functional enrichment analysis was also performed to investigate the functions of these AS events. Splicing factors and AS regulation network were constructed to understand the correlation among these AS events. RESULT: A total of 1826 AS events were identified as survival-related events. Functional enrichment analysis showed that these AS events were associated with several immune system-related processes. Then, the prognostic signatures were developed based on these survival-related events and acted as an independent prognostic factor for EC. Splicing factors and AS regulation network were also constructed to understand the regulatory mechanisms of AS events in EC. CONCLUSION: This study systematically analyzed the role of AS events in EC and developed the prognostic model for EC.

[Value of hysteroscopy and dilatation and curettage in diagnosis of endometrial cancer].

OBJECTIVE: To evaluated the value of hysteroscopy and dilatation and curettage (DC) in diagnosis of endometrial cancer. METHODS: This retrospective analysis included clinical pathologic data of 3 676 patients with endometrial cancer from Jan. 1, 2000 to Dec. 31, 2010 in hospitals of endometrial cancer prevention projects in Guangdong Province. RESULTS: A total of 3 676 patients with endometrial cancer were divided into DC group (3 211 patients) and hysteroscopy group (465 patients). Compared to the results of pathological diagnosis, the accuracy rate between DC group and in hysteroscopy group were no statistically difference was 91.00% (2 922/3 211) vs 90.75% (422/465; χ² = 0.030, P = 0.862). The accuracy rate, sensitivity, specificity, positive predictive value and negative predictive value of cervical involvement between DC group and hysteroscopy group were 81.28% vs 86.45% (P < 0.01), 24.78% vs 23.68% (P > 0.05), 93.76% vs 98.71% (P < 0.01), 46.75% vs 78.26% (P < 0.01) and 84.95% vs 86.88% (P > 0.05), respectively. Rate of positive peritoneal cytology in DC group was 4.76% (153/3 211), and the rate was 3.23% (15/465) in hysteroscopy group, which were no statistically difference (χ² = 2.206, P = 0.137). There were no statistically difference in 5-year overall survival (91.02% vs 92.03%; χ² = 0.033, P = 0.856) and 5-year progression-free survival (89.81% vs 91.83%; χ² = 1.508, P = 0.219) between DC group and hysteroscopy group. CONCLUSIONS: Hysteroscopy and dilatation and curettage is an effective method in diagnosis of endometrial cancer, especially hysteroscopy is better in diagnosis of cervical involvement. Hysteroscopy don't improve risks of positive peritoneal cytology and don't affect the prognosis of patients with endometrial cancer.