Macrophage polarization in cesarean scar diverticulum

Aims: To determine immunohistochemical features and correlations between M1/M2 polarization status with disease severity of post-cesarean scar diverticulum（CSD）. Methods: Histological and immunohistological staining were performed and inflammatory (CD16, CD163, and TNF-α), fibrosis (α-SMA), and angiogenic (CD31) markers were examined in uterine tissues collected from patients with uterine scar diverticula (CSD) (n=37) and cesarean section (CS) (n=3). Results: CSD tissues have higher expression of α-SMA, TNF-α, CD16, and CD31 and lower expression of CD163 than CS tissue (P <0.05). Compared with adjacent tissues, thick-walled blood vessels, glands, and fibrotic sites have higher expression of α-SMA, TNF-α, and CD16. Statistical correlation was observed between the expression of CD16 and TNF-α (R = 0.693, P <0.001), α-SMA (R = 0.404, P <0.05), and CD31 (R = 0.253, P <0.05) in CSD tissues, especially with the ratio of CD16/CD163 (R = 0.590, P <0.01). A more significant difference was observed between the expression of CD16/CD163 and α-SMA (R = 0.556, P <0.001), TNF-α (R = 0.633, P <0.0001) and CD31 (R = 0.336, P <0.05) Statistical correlation. Conclusion: In this study, TNF-α, α-SMA, CD16, and CD31 proteins were overexpressed in all CSD cases, and CD16/CD163 was positively correlated with tissue inflammation, fibrosis, and neovascularization. Abnormal mononuclear macrophage infiltration may be involved in the origin and progression of CSD.

Purpura fulminans, Toxic Epidermal Necrolysis, and disseminated herpes simplex. A rare combination.

A 52-year-old, previously healthy woman, developed SJS, potentially due to a reaction to CT contrast, although still unknown. This developed into Toxic epidermal necrolysis, later unexpected multiorgan failure and Purpura fulminans. Autopsy demonstrates herpes simplex virus in the bladder and lungs on immunohistological staining.

The Effects of NF-kB Inhibition with p65-TMD-Linked PTD on Inflammatory Responses at Peri-implantitis Sites

The objective of this study was to find out if suppression of NF-kB complex function by p65-TMD-linked PTD could reduce host inflammation and bone resorption at peri-implantitis sites in rats. Twenty-one male 5-week-old SD rats were divided into three groups: untreated control group (A), silk-induced peri-implantitis group (B), and nt (nucleus transducible)-p65-TMD-treated, silk-induced peri-implantitis group (C). Implant sulcus of a rat in group C were divided into two groups, namely group Cp and Cb. Palatal implant sulcus where nt-p65-TMD solution was applied with an insulin syringe were assigned to group Cp. Buccal implant sulcus without topical nt-p65-TMD application were assigned to group Cb. H&E staining, TRAP staining, and immunohistological staining were done. The crestal bone levels of group A were significantly higher than those of group B at p<0.01. The crestal bone levels of group Cp were significantly higher than those of group Cb at p<0.05. H-E staining showed increased apical migration of junctional epithelium and inflammatory cells in group Cb. TRAP staining revealed more multinucleated osteoclasts in group Cb. As for immunohistological staining, group Cb showed many IL-6-positive cells while group Cp had none. In this study, p65-TMD-linked PTD inhibited NF-kB functions and reduced inflammation and bone resorption at peri-implantitis sites in rats.

Effect of luminal surface structure of decellularized aorta on thrombus formation and cell behavior

Due to an increasing number of cardiovascular diseases, artificial heart valves and blood vessels have been developed. Although cardiovascular applications using decellularized tissue have been studied, the mechanisms of their functionality remain unknown. To determine the important factors for preparing decellularized cardiovascular prostheses that show good in vivo performance, the effects of the luminal surface structure of the decellularized aorta on thrombus formation and cell behavior were investigated. Various luminal surface structures of a decellularized aorta were prepared by heating, drying, and peeling. The luminal surface structure and collagen denaturation were evaluated by immunohistological staining, collagen hybridizing peptide (CHP) staining, and scanning electron microscopy (SEM) analysis. To evaluate the effects of luminal surface structure of decellularized aorta on thrombus formation and cell behavior, blood clotting tests and recellularization of endothelial cells and smooth muscle cells were performed. The results of the blood clotting test showed that the closer the luminal surface structure is to the native aorta, the higher the anti-coagulant property. The results of the cell seeding test suggest that vascular cells recognize the luminal surface structure and regulate adhesion, proliferation, and functional expression accordingly. These results provide important factors for preparing decellularized cardiovascular prostheses and will lead to future developments in decellularized cardiovascular applications.

Alveolar Echinococcosis of the Parotid Gland—An Ultra Rare Location Reported from Western Europe

(1) Background: Alveolar echinococcosis (AE) is restricted to the northern hemisphere with high endemic regions in Central Europe, North and Central Asia as well as Western China. The larval stage of Echinococcus multilocularis (E. multilocularis) causes AE with tumor-like growth. Humans are accidental hosts. This report is on the first case of AE becoming clinically manifested in the parotic gland. (2) Case presentation: A 52-year-old male patient presented with progressive and painful swelling of the right parotid gland persisting for one year. We performed a partial parotidectomy. The histological examination and immunohistological staining revealed larval stage of E. multilocularis. (3) Conclusion: E. multilocularis is known to infect animals and humans coincidentally, and leads to AE. It is one of the most life-threatening zoonoses in Europe. It typically manifests in the liver (50–77%), with further spreading to other organs being a rare phenomenon. Echinococcosis should be considered in the differential diagnosis of lesions of the parotid gland in endemic areas, but AE has not been described so far in the parotid gland as the sole manifestation and, therefore, impedes the correct diagnosis. A complete resection should be the aim, however, preservation of the facial nerve and adjuvant albendazole therapy is mandatory.

Conversion Therapy of Intrahepatic Cholangiocarcinoma Is Associated with Improved Prognosis and Verified by a Case of Patient-Derived Organoid

This study was performed to determine the efficacy of conversion therapy in intrahepatic cholangiocarcinoma (IHCC) and explore the feasibility of cancer organoid to direct the conversion therapy of IHCC. Patient data were retrospectively reviewed in this study and cancer organoids were established using tissues obtained from two patients. A total of 42 patients with IHCC received conversion therapy, 9 of whom were downstaged successfully, and another 157 patients were initially resectable. Kaplan–Meier curves showed that the successfully downstaged patients had a significantly improved overall survival compared to those in whom downstaging was unsuccessful (p = 0.017), and had a similar overall survival to that of initially resectable patients (p = 0.965). The IHCC organoid was successfully established from one of two obtained tissues. Routine hematoxylin and eosin staining and immunohistological staining found the organoid retained the histopathological characteristics of the original tissues. Whole exome sequencing results indicated the IHCC organoid retained appropriately 87% of the variants in the original tissue. Gemcitabine and paclitaxel exhibited the strongest inhibitory effects on the cancer organoid as determined using drug screening tests, consistent with the levels of efficacy observed in the patient from whom it was derived. This study indicates that conversion therapy could improve the survival of patients with IHCC despite its low success rate, and it may be directed by cancer organoids though this is merely a proof of feasibility.

Time-lapsed imaging of nanocomposite scaffolds reveals increased bone formation in dynamic compression bioreactors

Progress in bone scaffold development relies on cost-intensive and hardly scalable animal studies. In contrast to in vivo, in vitro studies are often conducted in the absence of dynamic compression. Here, we present an in vitro dynamic compression bioreactor approach to monitor bone formation in scaffolds under cyclic loading. A biopolymer was processed into mechanically competent bone scaffolds that incorporate a high-volume content of ultrasonically treated hydroxyapatite or a mixture with barium titanate nanoparticles. After seeding with human bone marrow stromal cells, time-lapsed imaging of scaffolds in bioreactors revealed increased bone formation in hydroxyapatite scaffolds under cyclic loading. This stimulatory effect was even more pronounced in scaffolds containing a mixture of barium titanate and hydroxyapatite and corroborated by immunohistological staining. Therefore, by combining mechanical loading and time-lapsed imaging, this in vitro bioreactor strategy may potentially accelerate development of engineered bone scaffolds and reduce the use of animals for experimentation.

Effect of luminal surface structure of decellularized aorta on thrombus formation and cell behavior

As the number of cardiovascular diseases increases, artificial heart valves and blood vessels have been developed. Although cardiovascular application using decellularized tissue have been studied, the mechanism of their functionality is still unknown. To find the important factor for preparing decellularized cardiovascular prothesis which shows good in vivo performance, the effect of luminal surface structure of decellularized aorta on thrombus formation and cell behavior was investigated. Various luminal surface structures of decellularized aorta were prepared by heating, drying and peeling. The luminal surface structure and collagen denaturation was evaluated by immunohistological staining, collagen hybridizing peptide (CHP) staining and scanning electron microscopy (SEM) analysis. To evaluate the effect of luminal surface structure of decellularized aorta on thrombus formation and cell behavior, blood clotting test and recellularization of endothelial cells and smooth muscular cells were performed. The results of blood clotting test showed that the closer the luminal surface structure is to native aorta, the higher the anti-coagulant property. From the result of cell seeding-test, it was suggested that vascular cells recognize the luminal surface structure and regulate adhesion, proliferation and functional expression. These results will provide important factor for preparing decellularized cardiovascular prothesis and lead to future development on decellularized cardiovascular applications.

Validation of the diagnostic criteria for IgG4-related kidney disease (IgG4-RKD) 2011, and proposal of a new 2020 version

Background In 2011, the IgG4-related kidney disease (IgG4-RKD) working group of the Japanese Society of Nephrology proposed diagnostic criteria for IgG4-RKD. The aim of the present study was to validate those criteria and develop a revised version. Methods Between April 2012 and May 2019, we retrospectively collected Japanese patients with kidney disease, for whom data on serum IgG4 values and/or immunohistological staining for IgG4 in renal biopsy samples were available. These patients were classified as IgG4-RKD or non-IgG4-RKD based on the diagnostic criteria for IgG4-RKD 2011, and the results were evaluated by expert opinion. Accordingly, we developed some revised versions of the criteria, and the version showing the best performance in the present cohort was proposed as the IgG4-RKD criteria for 2020. Results Of 105 included patients, the expert panel diagnosed 55 as having true IgG4-RKD and 50 as mimickers. The diagnostic criteria for IgG4-RKD 2011 had a sensitivity of 72.7% and a specificity of 90.0% in this cohort. Of the 15 patients with true IgG4-RKD who were classified as non-IgG4-RKD, all lacked biopsy-proven extra-renal lesions, although many had clinical findings highly suggestive of IgG4-RD. The revised version to which “bilateral lacrimal, submandibular or parotid swelling, imaging findings compatible with type 1 autoimmune pancreatitis or retroperitoneal fibrosis” was added as an item pertaining to extra-renal organ(s) improved the sensitivity to 90.9% while the specificity remained at 90.0%. Conclusion The revised version has considerably improved test performance after addition of the new extra-renal organ item (imaging and clinical findings).