Search

Objectives Mortality of dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 antibody (anti-MDA5-DM) is alarming, especially during the first several months. Infection is an important cause of early death. As there are no reports regarding the effect of prophylactic use of compounded sulfamethoxazole (coSMZ; each tablet contains 400 mg of sulfamethoxazole and 80 mg of trimethoprim) in anti-MDA5-DM patients, we conducted this study to evaluate the efficacy of coSMZ in reducing the incidence of Pneumocystis jirovecii pneumonia (PJP). Methods Consecutive patients with new-onset anti-MDA5-DM from June 2018 to October 2021 in our centre were retrospectively reviewed for >12 months. They were divided into two groups—coSMZ and non-coSMZ—based on the initial use of prophylactic coSMZ. Mortality and the incidence of severe infection within 12 months were compared between two groups. Results Compared with the non-coSMZ group (n  = 93), the coSMZ group (n  = 121) had lower mortality (18.8% vs 51.1%; P   <  0.001) and a lower incidence of PJP (6.8% vs 15.2%; P  = 0.040) and fatal infection (16.1% vs 3.3%; P  = 0.001) during the first 12 months from diagnosis. After adjusting for age, gender, disease duration, peripheral blood lymphocyte count, anti-MDA5 antibody titres, ground-glass opacity scores and treatments, an inverse association was revealed between the prophylactic use of coSMZ and incidence of PJP [adjusted odds ratio 0.299 (95% CI 0.102–0.878), P  = 0.028]. Conclusion Prophylactic use of coSMZ is an effective and safe way to improve the prognosis of anti-MDA5-DM patients by preventing the incidence of PJP. [ABSTRACT FROM AUTHOR]

Various millimetre-, centimetre- and metre-scale soft-sediment deformation structures (SSDS) have been identified in the Upper Ordovician and Lower-Middle Silurian from deep drilling cores in the Tarim Basin (NW China). These structures include liquefied-sand veins, liquefaction-induced breccias, boudinage-like structures, load and diapir- or flame-like structures, dish and mixed-layer structures, hydroplastic convolutions and seismic unconformities. The deformed layers are intercalated by undeformed layers of varying thicknesses that are petrologically and sedimentologically similar to the deformed layers.

The mechanism by which endometriosis, a common gynecological disease characterized by chronic pelvic pain and infertility, causes infertility remains elusive. Luteinized unruptured follicle syndrome, the most common type of ovulatory dysfunction, is a cause of endometriosis-associated infertility involving reduced numbers of retrieved and mature oocytes. Ovulation is controlled by luteinizing hormone and paracrine signals produced within the follicle microenvironment. Generally, interleukin (IL)-1β is elevated in endometriosis follicular fluid, whereby it amplifies ovulation signals by activating extracellular-regulated kinase 1/2 and CCAAT/enhancer binding protein β pathways. However, this amplification of ovulation by IL-1β does not occur in patients with endometriosis. To illuminate the mechanism of ovulatory dysfunction in endometriosis, we analyzed the effect of oxidative stress and IL-1β expression on endometriosis follicles. We found that oxidative stress decreased EZH2 expression and reduced H3K27Me3 levels in endometriosis ovarian granulosa cells (GCs). Selective Ezh2 depletion in mice ovarian GCs reduced fertility by disturbing cumulus-oocyte complex expansion and reducing epidermal growth factor-like factor expression. Gene expression and H3K27Me3 ChIP-sequencing (ChIP-Seq) of GCs revealed IL-1 receptor 2 (IL-1R2), a high-affinity IL-1β-receptor that suppresses IL-1β-mediated inflammatory cascades during ovulation, as a crucial target gene of the EZH2-H3K27Me3 axis. Moreover, IL-1β addition did not restore ovulation upon Ezh2 knockdown, indicating a vital function of IL-1R2 in endometriosis. Thus, our findings show that reducing EZH2 and H3K27Me3 in GCs suppressed ovulatory signals by increasing IL-1R2 expression, which may ultimately contribute to endometriosis-associated infertility. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the imaging potential of a novel near-infrared (NIR) probe conjugated to COC183B2 monoclonal antibodies (MAb) in ovarian cancer (OC)., Methods: The expression of OC183B2 antigen in OC was determined by immunohistochemical (IHC) staining using tissue microarrays with the H-score system and immunofluorescence (IF) staining of tumor cell lines. Imaging probes with the NIR fluorescent dye cyanine 7 (Cy7) conjugated to COC183B2 Mab were chemically engineered. OC183B2-positive human OC cells (SKOV3-Luc) were injected subcutaneously into BALB/c nude mice. Bioluminescent imaging (BLI) was performed to detect tumor location and growth. COC183B2-Cy7 at 1.1, 3.3, 10, or 30 μg were used for in vivo fluorescence imaging, and phosphate-buffered saline (PBS), free Cy7 dye and mouse isotype immunoglobulin G (IgG)-Cy7 (delivered at the same doses as COC183B2-Cy7) were used as controls., Results: The expression of OC183B2 with a high H-score was more prevalent in OC tissue than fallopian tube (FT) tissue. Among 417 OC patients, the expression of OC183B2 was significantly correlated with the histological subtype, histological grade, residual tumor size, relapse state and survival status. IF staining demonstrated that COC183B2 specifically expressed in SKOV3 cells but not HeLa cells. In vivo NIR fluorescence imaging indicated that COC183B2-Cy7 was mainly distributed in the xenograft and liver with optimal tumor-to-background (T/B) ratios in the xenograft at 30 μg dose. The highest fluorescent signals in the tumor were observed at 96 h post-injection (hpi). Ex vivo fluorescence imaging revealed the fluorescent signals mainly from the tumor and liver. IHC analysis confirmed that xenografts were OC183B2 positive., Conclusions: COC183B2 is a good candidate for NIR fluorescence imaging and imaging-guided surgery in OC., (Copyright © 2019 Chinese Journal of Cancer Research. All rights reserved.)

The diagnostic performance difference between digital breast tomosynthesis (DBT) and conventional full-field digital mammography (FFDM) for breast suspicious calcifications from various populations is unclear. The objective of this study is to determine whether DBT exhibits the diagnostic advantage for breast suspicious calcifications from various populations compared with FFDM. Three hundred and five patients were enrolled (of which seven patients with bilateral lesions) and 312 breasts images were retrospectively analyzed by three radiologists independently. The postoperative pathology of breast calcifications was the gold standard. Breast cancer was diagnosed utilizing DBT and FFDM with sensitivities of 92.9% and 88.8%, specificities of 87.9% and 75.2%, positive predictive values of 77.8% and 62.1%, negative predictive values of 96.4% and 93.6%, respectively. DBT exhibited significantly higher diagnostic accuracy for benign calcifications compared with FFDM (87.9% vs 75.2%), and no advantage in the diagnosis of malignant calcifications. DBT diagnostic accuracy was notably higher than FFDM in premenopausal (88.4% vs 78.8%), postmenopausal (90.2% vs 77.2%), and dense breast cases (89.4% vs 81.9%). There was no significant difference in non-dense breast cases. In our study, DBT exhibited a superior advantage in dense breasts and benign calcifications cases compared to FFDM, while no advantage was observed in non-dense breasts or malignant calcifications cases. Thus, in the breast cancer screening for young women with dense breasts, DBT may be recommended for accurate diagnosis. Our findings may assist the clinicians in applying the optimal techniques for different patients and provide a theoretical basis for the update of breast cancer screening guideline.