The examination of hematoxylin and eosin (H&E)-stained tissues on glass slides by conventional light microscopy is the foundation for histopathological diagnosis. However, this conventional method has some limitations in x-y axes due to its relatively narrow range of observation area and in z-axis due to its two-dimensionality. In this study, we applied a CUBIC pipeline, which is the most powerful tissue-clearing and three-dimensional (3D)-imaging technique, to clinical pathology. CUBIC was applicable to 3D imaging of both normal and abnormal patient-derived, human lung and lymph node tissues. Notably, the combination of deparaffinization and CUBIC enabled 3D imaging of specimens derived from paraffin-embedded tissue blocks, allowing quantitative evaluation of nuclear and structural atypia of an archival malignant lymphoma tissue. Furthermore, to examine whether CUBIC can be applied to practical use in pathological diagnosis, we performed a histopathological screening of a lymph node metastasis based on CUBIC, which successfully improved the sensitivity in detecting minor metastatic carcinoma nodules in lymph nodes. Collectively, our results indicate that CUBIC significantly contributes to retrospective and prospective clinicopathological diagnosis, which might lead to the establishment of a novel field of medical science based on 3D histopathology.

The incidence of inflammatory bowel disease (IBD) is increasing. Nucleic acid-based medicine has potential as a next-generation treatment, but it is rarely successful with IBD. The aim of this study was to establish a microRNA-based therapy in an IBD model. For this purpose, we used microRNA-29 (miR-29) and a supercarbonate apatite (sCA) nanoparticle as a drug delivery system. Injection of sCA-miR-29a-3p or sCA-miR-29b-3p into mouse tail veins markedly prevented and restored inflammation because of dextran sulfate sodium (DSS)-induced colitis. RNA sequencing analysis revealed that miR-29a and miR-29b could inhibit the interferon-associated inflammatory cascade. Subcutaneous injection of sCA-miR-29b also potently inhibited inflammation, and it efficiently targeted CD11c+ dendritic cells (DCs) among various types of immune cells in the inflamed mucosa. RT-PCR analysis indicated that the miR-29 RNAs in CD11c+ DCs suppressed the production of interleukin-6 (IL-6), transforming growth factor β (TGF-β), and IL-23 subunits in DSS-treated mice. This may inhibit Th17 differentiation and subsequent activation, which is critical in IBD pathogenesis. In vivo experiments using a non-natural artificial microRNA sequence revealed that targeting of DCs in the inflamed colon is an exceptional feature of sCA. This study suggests that sCA-miR-29s may open a new avenue in nucleic acid-based medicine for IBD treatment.

IntroductionTo confirm the safety and feasibility of single-incision laparoscopically assisted appendectomy (SILA) performed by resident doctors.Materials and methodsWe retrospectively analyzed 86 consecutive patients who underwent SILA between August 2010 and August 2016 at Kinki Central Hospital. During this period, 9 residents and 6 board-certified attending surgeons performed SILA. Data on the patients' characteristics and perioperative complications were collected from their medical records.ResultsResident doctors operated on 55% (47/86) of patients undergoing SILA. There were no significant differences between the groups with regard to patient characteristics. Mean operative time in the resident and staff surgeon groups was 74 min and 71 min, respectively (p = 0.5). Median blood loss in both the resident and staff surgeon groups was 0 mL (p = 0.3). The rate of conversion to a different operative procedure was 4% (2/47) in the resident group and 3% (1/39) in the staff surgeon group (p = 1). All three above-mentioned procedures, two (4%, 2/47) in the resident group and one (3%, 1/39) in the staff surgeon group, were converted to multi-port laparoscopic appendectomy. The mean postoperative hospital stay was 5 days for both the resident and staff surgeon groups (p = 0.7). Perioperative complications developed in 9% (4/47) of the patients in the resident group and 21% (8/39) of the patients in the staff surgeon group (p = 0.1).ConclusionsSILA performed by residents under the guidance of a staff surgeon is safe and feasible.

HighlightsActinomycosis is a chronic suppurative granulomatous disease caused by Actinomyces israelii.Actinomycosis is one of the differential diagnoses of an abdominal mass.The first choice of treatment for actinomycosis is surgical resection.

HighlightsMedullary carcinoma should be distinguished from other more aggressive, non-glandular tumors of the colon, because medullary carcinoma appears to have a better survival outcome than undifferentiated colon adenocarcinoma.Omental infarction should be considered in the differential diagnosis of acute abdomen after surgery.