Cervical metastasis of breast cancer: A case report and literature review.

RATIONALE: Cervical metastasis of breast cancer is rare and its clinical manifestations are similar to those of primary cervical cancer. It is thus easy to misdiagnose, with diagnosis mainly depending on pathology and immunohistochemistry. There have been few studies on its treatment and there is thus no standard treatment plan. PATIENT CONCERNS: This is a 64-year-old female patient presented with a 2-month history of abnormal postmenopausal vaginal discharge, who had previous history of breast cancer. DIAGNOSES: Based on the gynecological examination, imaging results, pathology, and immunohistochemical results, a diagnosis of metastatic carcinoma of the cervix and breast cancer was confirmed. INTERVENTIONS: She received computed tomography-guided 3-dimensional high-dose-rate brachytherapy in combination with chemotherapy. OUTCOMES: She achieved complete response locally. This case provides a new local treatment option for patients with inoperable localized cervical metastases. LESSONS: We hope that this report and the accompanying review help to enrich the literature pertaining to the treatment of rare cervical metastases, providing a foundation for the improved survival of affected patients.

Paleoenvironment Evolutionary Characteristics of Niutitang Shale in Western Hubei, Middle Yangtze, China.

The black shale developed in the first section of the Niutitang formation (ϵ1 n 1) is one of the most important shale gas reservoirs in western Hubei, and its geological characteristics have been sufficiently studied by many predecessors. However, there are still three aspects that need further research: the origin of silicon, the discrimination of the euxinic sulfuretted and the anoxic ferruginous conditions, and the main controlling factors of organic matter enrichment. Based on geochemical data from well ZD1 located in the city of Yichang in western Hubei, first, the geochemical characteristics of ϵ1 n 1 are analyzed, then the provenance, depositional site, and paleoenvironment evolution are discussed, and finally, the main controlling factor of organic matter enrichment is revealed. The results show that ϵ1 n 1 can be divided into two units, organic-rich shales (ORS) and organic-lean shales (OLS), which have average total organic carbon contents of 4.21 and 0.84%, respectively. Additionally, the ORS is characterized by high contents of SiO2, U, V, Ni, Zn, and Cu and left-inclining types of rare earth element distribution curves. ϵ1 n 1 is located in a passive continental margin with a material source mainly from mixed felsic and mafic rocks. Compared with the OLS, the content of biological quartz is much greater, and the terrigenous input is less in the ORS. The paleoclimate is cold and humid with low salinity in the ORS, whereas it is hot and dry with high salinity in the OLS. ϵ1 n 1 is deposited in a semistagnant basin, and the ORS shows a relatively lower stagnant degree with euxinic to anoxic conditions and moderate to high paleoproductivity, while the OLS shows a high stagnant degree with suboxic to oxic conditions and lower paleoproductivity. The redox conditions are the main controlling factors affecting organic matter enrichment. The environmental evolution model with three stages shows that there is a good causal relationship between redox conditions, paleoproductivity, and sea level fluctuation. The black carbonaceous siliceous in the lower part of the ORS with a thickness of approximately 40 m is the most favorable layer, which will provide a theoretical basis for further shale gas exploration of ϵ1 n 1 in the western Hubei.

Effect of e-health intervention on disease management in patients with chronic heart failure: A meta-analysis.

Objective: The aim of this meta-analysis was to assess the impact of e-health interventions on disease management in patients with CHF. Methods: Six databases including Embase, Web of Science, Scopus, PubMed, Cochrane, and EBSCO were searched by computer. The search time is before May 1, 2022. Odds ratios (OR) were used for binary categorical data and weighted mean differences (WMD) for continuous variables. The 95% confidence intervals (CI) were used to express the effect sizes for both count and measurement data. RevMan 5.4 and Stata 16.0 were employed to complete this meta-analysis. Results: The study included 22 research studies and 5,149 patients. e-health intervention can effectively reduce all-cause mortality [OR = 0.801, 95%CI: (0.650, 0.987), P < 0.05], all-cause hospitalization rate [OR = 0.66, 95%CI: (0.46, 0.95), P < 0.05] and heart failure related hospitalization rate [OR = 0.750, 95%CI: (0.632, 0.891), P < 0.05]. e-health intervention is also effective in improving the quality of life [WMD = 2.97, 95%CI: (1.54, 4.40), P < 0.05] and the self-management ability of patients [WMD = -2.76, 95%CI: (-5.52, -0.11), P < 0.05]. Conclusion: e-health interventions can reduce all-cause mortality, all-cause hospitalization, and heart failure-related hospitalization in patients with CHF. Furthermore, it can improve the health-related quality of life of patients.

Multi-omics profiling of primary small cell carcinoma of the esophagus reveals RB1 disruption and additional molecular subtypes.

Primary small cell carcinoma of the esophagus (PSCCE) is a lethal neuroendocrine carcinoma. Previous studies proposed a genetic similarity between PSCCE and esophageal squamous cell carcinoma (ESCC) but provided little evidence for differences in clinical course and neuroendocrine differentiation. We perform whole-exome sequencing, RNA sequencing and immunohistochemistry profiling on 46 PSCCE cases. Integrated analyses enable the discovery of multiple mechanisms of RB1 disruption in 98% (45/46) of cases. The transcriptomic landscape of PSCCE closely resembles small cell lung cancer (SCLC) but differs from ESCC or esophageal adenocarcinoma (EAC). Distinct gene expression patterns regulated by ASCL1 and NEUROD1 define two molecular subtypes, PSCCE-A and PSCCE-N, which are highly similar to SCLC subtypes. A T cell excluded phenotype is widely observed in PSCCE. In conclusion, PSCCE has genomic alterations, transcriptome features and molecular subtyping highly similar to SCLC but distinct from ESCC or EAC. These observations are relevant to oncogenesis mechanisms and therapeutic vulnerability.

Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease.

Impaired amyloid-ß clearance from the brain is a core pathological event in Alzheimer's disease. The therapeutic effect of current pharmacotherapies is unsatisfactory, and some treatments cause severe side effects. The meningeal lymphatic vessels might be a new route for amyloid-ß clearance. This study investigated whether promoting dural lymphangiogenesis facilitated the clearance of amyloid-ß from the brain. First, human lymphatic endothelial cells were treated with 100 ng/mL recombinant human vascular endothelial growth factor-C (rhVEGF-C) protein. Light microscopy verified that rhVEGF-C, a specific ligand for vascular endothelial growth factor receptor-3 (VEGFR-3), significantly promoted tube formation of human lymphatic endothelial cells in vitro. In an in vivo study, 200 µg/mL rhVEGF-C was injected into the cisterna magna of APP/PS1 transgenic mice, once every 2 days, four times in total. Immunofluorescence staining demonstrated high levels of dural lymphangiogenesis in Alzheimer's disease mice. One week after rhVEGF-C administration, enzyme-linked immunosorbent assay results showed that levels of soluble amyloid-ß were decreased in cerebrospinal fluid and brain. The Morris water maze test demonstrated that spatial cognition was restored. These results indicate that the upregulation of dural lymphangiogenesis facilities amyloid-ß clearance from the brain of APP/PS1 mice, suggesting the potential of the VEGF-C/VEGFR-3 signaling pathway as a therapeutic target for Alzheimer's disease.

IL-4 mediates the delayed neurobehavioral impairments induced by neonatal hepatitis B vaccination that involves the down-regulation of the IL-4 receptor in the hippocampus.

We have previously verified that neonatal hepatitis B vaccination induced hippocampal neuroinflammation and behavior impairments in mice. However, the exact mechanism of these effects remain unclear. In this study, we observed that neonatal hepatitis B vaccination induced an anti-inflammatory cytokine response lasting for 4-5 weeks in both the serum and the hippocampus, primarily indicated by elevated IL-4 levels. Three weeks after the vaccination schedule, however, hepatitis B vaccine (HBV)-mice showed delayed hippocampal neuroinflammation. In periphery, IL-4 is the major cytokine induced by this vaccine. Correlation analyses showed a positive relationship in the IL-4 levels between serum and hippocampus in HBV-mice. Thus, we investigated whether neonatal over-exposure to systemic IL-4 influences brain and behavior. We observed that mice injected intraperitoneally with recombinant mouse IL-4 (mIL-4) during early life had similar neuroinflammation and cognition impairment similar to those induced by neonatal hepatitis B vaccination. Next, the mechanism underlying the effects of IL-4 on brain in mice was explored using a series of experiments. In brief, these experiments showed that IL-4 mediates the delayed neurobehavioral impairments induced by neonatal hepatitis B vaccination, which involves the permeability of neonatal blood-brain barrier and the down-regulation of IL-4 receptor. This finding suggests that clinical events concerning neonatal IL-4 over-exposure, including neonatal hepatitis B vaccination and allergic asthma in human infants, may have adverse implications for brain development and cognition.

Immunization with Bacillus Calmette-Guérin (BCG) alleviates neuroinflammation and cognitive deficits in APP/PS1 mice via the recruitment of inflammation-resolving monocytes to the brain.

The immune system plays a crucial role in the progression of Alzheimer's disease (AD). Recently, immune-dependent cascade induced by systemic immune activation has been verified to play a beneficial role in AD mouse models. Here, we tested whether Bacillus Calmette-Guérin (BCG) immunization alters AD pathology and cognitive dysfunction in APP/PS1 AD mouse model, and with 4Aß1-15 vaccination as positive control. It was found that BCG treatment reversed the cognitive decline to the extent observed in 4Aß1-15 group, but did not reduce the ß-amyloid (Aß) burden in the brain. Then, we demonstrated the enhanced recruitment of inflammation-resolving monocytes across the choroid plexus and perivascular spaces to cerebral sites of plaque pathology in APP/PS1 mice immunized with BCG. Furthermore, elevated splenocyte Foxp3+ regulatory T cell levels in the control APP/PS1 mice were down-regulated back to the wild-type (WT) levels by BCG treatment but not 4Aß1-15 vaccination. In addition, BCG treatment induced the production of more circulating interferon (IFN)-γ than the controls and 4Aß1-15 vaccination. Though the similar reductions in brain levels of pro-inflammatory cytokines were observed in the BCG and 4Aß1-15 groups compared to the controls, only BCG had the great effect in upregulating cerebral anti-inflammatory cytokine levels as well as elevating the expression of neurotrophic factors in the brain of APP/PS1 mice. Thus, it is suggested that BCG exerts a beneficial immunomodulatory effect in APP/PS1 mice through mitigation of systemic immune suppression, induction of IFN-γ response and alleviation of the neuroinflammatory response.