A novel dilated contextual attention module for breast cancer mitosis cell detection.

Background and object: Mitotic count (MC) is a critical histological parameter for accurately assessing the degree of invasiveness in breast cancer, holding significant clinical value for cancer treatment and prognosis. However, accurately identifying mitotic cells poses a challenge due to their morphological and size diversity. Objective: We propose a novel end-to-end deep-learning method for identifying mitotic cells in breast cancer pathological images, with the aim of enhancing the performance of recognizing mitotic cells. Methods: We introduced the Dilated Cascading Network (DilCasNet) composed of detection and classification stages. To enhance the model's ability to capture distant feature dependencies in mitotic cells, we devised a novel Dilated Contextual Attention Module (DiCoA) that utilizes sparse global attention during the detection. For reclassifying mitotic cell areas localized in the detection stage, we integrate the EfficientNet-B7 and VGG16 pre-trained models (InPreMo) in the classification step. Results: Based on the canine mammary carcinoma (CMC) mitosis dataset, DilCasNet demonstrates superior overall performance compared to the benchmark model. The specific metrics of the model's performance are as follows: F1 score of 82.9%, Precision of 82.6%, and Recall of 83.2%. With the incorporation of the DiCoA attention module, the model exhibited an improvement of over 3.5% in the F1 during the detection stage. Conclusion: The DilCasNet achieved a favorable detection performance of mitotic cells in breast cancer and provides a solution for detecting mitotic cells in pathological images of other cancers.

Immunologic barriers in liver transplantation: a single-cell analysis of the role of mesenchymal stem cells.

Background: This study aimed to analyze the biomarkers that may reliably indicate rejection or tolerance and the mechanism that underlie the induction and maintenance of liver transplantation (LT) tolerance related to immunosuppressant or mesenchymal stem cells (MSCs). Methods: LT models of Lewis-Lewis and F344-Lewis rats were established. Lewis-Lewis rats model served as a control (Syn). F344-Lewis rats were treated with immunosuppressant alone (Allo+IS) or in combination with MSCs (Allo+IS+MSCs). Intrahepatic cell composition particularly immune cells was compared between the groups by single-cell sequencing. Analysis of subclusters, KEGG pathway analysis, and pseudotime trajectory analysis were performed to explore the potential immunoregulatory mechanisms of immunosuppressant alone or combined with MSCs. Results: Immunosuppressants alone or combined with MSCs increases the liver tolerance, to a certain extent. Single-cell sequencing identified intrahepatic cell composition signature, including cell subpopulations of B cells, cholangiocytes, endothelial cells, erythrocytes, hepatic stellate cells, hepatocytes, mononuclear phagocytes, neutrophils, T cells, and plasmacytoid dendritic cells. Immunosuppressant particularly its combination with MSCs altered the landscape of intrahepatic cells in transplanted livers, as well as gene expression patterns in immune cells. MSCs may be included in the differentiation of T cells, classical monocytes, and non-classical monocytes. Conclusion: These findings provided novel insights for better understanding the heterogeneity and biological functions of intrahepatic immune cells after LT treated by IS alone or in combination with MSCs. The identified markers of immune cells may serve as the immunotherapeutic targets for MSC treatment of liver transplant rejection.

Aerosol Inhalation of Chimpanzee Adenovirus Vectors (ChAd68) Expressing Ancestral or Omicron BA.1 Stabilized Pre-Fusion Spike Glycoproteins Protects Non-Human Primates against SARS-CoV-2 Infection.

Current COVID-19 vaccines are effective countermeasures to control the SARS-CoV-2 virus pandemic by inducing systemic immune responses through intramuscular injection. However, respiratory mucosal immunization will be needed to elicit local sterilizing immunity to prevent virus replication in the nasopharynx, shedding, and transmission. In this study, we first compared the immunoprotective ability of a chimpanzee replication-deficient adenovirus-vectored COVID-19 vaccine expressing a stabilized pre-fusion spike glycoprotein from the ancestral SARS-CoV-2 strain Wuhan-Hu-1 (BV-AdCoV-1) administered through either aerosol inhalation, intranasal spray, or intramuscular injection in cynomolgus monkeys and rhesus macaques. Compared with intranasal administration, aerosol inhalation of BV-AdCoV-1 elicited stronger humoral and mucosal immunity that conferred excellent protection against SARS-CoV-2 infection in rhesus macaques. Importantly, aerosol inhalation induced immunity comparable to that obtained by intramuscular injection, although at a significantly lower dose. Furthermore, to address the problem of immune escape variants, we evaluated the merits of heterologous boosting with an adenovirus-based Omicron BA.1 vaccine (C68-COA04). Boosting rhesus macaques vaccinated with two doses of BV-AdCoV-1 with either the homologous or the heterologous C68-COA04 vector resulted in cross-neutralizing immunity against WT, Delta, and Omicron subvariants, including BA.4/5 stronger than that obtained by administering a bivalent BV-AdCoV-1/C68-COA04 vaccine. These results demonstrate that the administration of BV-AdCoV-1 or C68-COA04 via aerosol inhalation is a promising approach to prevent SARS-CoV-2 infection and transmission and curtail the pandemic spread.

A facile route for rapid synthesis of hollow mesoporous silica nanoparticles as pH-responsive delivery carrier.

In this paper, a facile and effective route has been developed for rapid synthesis of hollow mesoporous silica nanoparticles (HMSNs) by using tetradecyltrimethylammonium bromide (TTAB) as the porogen with the assistance of triethanolamine (TEA). The products were characterized by various techniques including TEM, SEM, BET, and FT-IR, etc. The HMSNs obtained possess spherical morphology, mesoporous channels and very high specific surface areas (1355m(2)g(-1)). According to the experimental results, a possible formation mechanism was discussed. Moreover, the ability of HMSNs as drug carrier was evaluated by selecting doxorubicin hydrochloride (DOX) as the model drug. The results indicated that HMSNs showed high loading capacity and controlled pH-responsive release behavior. Considering their unique nanostructures and porous properties, we expect the HMSNs prepared have more potential applications in various fields such as nanoreactors, cellular imaging, and biosensor.

Exploration of common bile duct for treating hepatic cystic echinococcosis.

OBJECTIVE: To compare the clinical efficacy of exploration of common bile duct through cystic duct or T type tube in CE patients. METHODS: One hundred and fifty six patients with chronic CE received decompression of biliary tract from January 2007 to December 2012 were included. Exploration of common bile duct was performed through cystic duct (n=102) or T type tube (n=54). Psychological reactions were monitored including inconvenient position alteration due to carrying of the drainage tube, anxiety of the folding and prolapse of drainage tube, folding of the drainage tube, and any pain during the body position change. RESULTS: No significant difference was noticed in the body position alteration discomfort in both groups (P>0.05). Statistical difference was noted in the anxiety of folding and prolapse of draining tube (P<0.05), and improvement of the clinical symptoms (P<0.05). CONCLUSIONS: A higher possibility of wound, enlarged tube-carrying duration, and lower sense of discomfort, were noticed in patients underwent exploration of common bile duct through T type tube. Higher sense of comfort was reported in patients received exploration of common bile duct through cystic duct tube.

[Secondary laryngeal tuberculosis at high altitudes of Tibet].

OBJECTIVE: To improve the diagnostic and therapeutic efficiency for secondary laryngeal tuberculosis through an analysis on the clinical features of patients with this disease. METHOD: A retrospective study was made among 49 cases with laryngeal tuberculosis treated in Tibetan General Hospital of Chinese PLA, and the clinical data were carefully analyzed to summarize the clinical experience of this disease. RESULT: Of 49 patients, 24 cases had 1 year history, 11 cases had 1 to 3 years, 9 cases had 3 to 5 years, 5 cases had 5 years or more. Thirty-eight patients had the history of tuberculosis and 11 had none. Thirty-four patients had taken anti-tuberculosis drugs but none had standard therapy as demanded. All cases had mild general symptoms (mild fever, night sweats, weight loss, et al) and atypical local symptoms (hoarseness, sore throat). Therefore, 42 cases were misdiagnosed as non-specific chronic laryngitis, of which 15 cases got worse after oral administration or inhaling of steroid hormones. Seven persons were misdiagnosed as laryngeal cancer. All patients were confirmed pulmonary tuberculosis by X ray exam or CT scanning. Twelve cases had strong positive PPD tests and 2 cases were detected positive by sputum smear. All patients was treated by standard systematic and local chemical therapy against tuberculosis (inhaling of antituberculosis drugs for 1 to 2 months). All were cured but one died in a road accident, and none had recurrence after 1- to 9- year follow-up. CONCLUSION: All of those the patients with long period hoarseness and sore throat should take chest CT scan or X-ray exam for the highest incidence of pulmonary tuberculosis at high altitudes. CT scanning is the prefer for its high resolution. Pathological biopsy and diagnostic therapy should be taken to make accurate diagnosis. Usually steroid hormones should not be recommended.