Nucleus-targeting DNase I self-assembly delivery system guided by pirarubicin for programmed multi-drugs release and combined anticancer therapy.

The cell nucleus serves as the pivotal command center of living cells, and delivering therapeutic agents directly into the nucleus can result in highly efficient anti-tumor eradication of cancer cells. However, nucleus-targeting drug delivery is very difficult due to the presence of numerous biological barriers. Here, three antitumor drugs (DNase I, ICG: indocyanine green, and THP: pirarubicin) were sequentially triggered protein self-assembly to produce a nucleus-targeting and programmed responsive multi-drugs delivery system (DIT). DIT consisted of uniform spherical particles with a size of 282 ± 7.7 nm. The acidic microenvironment of tumors and near-infrared light could successively trigger DIT for the programmed release of three drugs, enabling targeted delivery to the tumor. THP served as a nucleus-guiding molecule and a chemotherapy drug. Through THP-guided DIT, DNase I was successfully delivered to the nucleus of tumor cells and killed them by degrading their DNA. Tumor acidic microenvironment had the ability to induce DIT, leading to the aggregation of sufficient ICG in the tumor tissues. This provided an opportunity for the photothermal therapy of ICG. Hence, three drugs were cleverly combined using a simple method to achieve multi-drugs targeted delivery and highly effective combined anticancer therapy.

Spontaneous rupture of an unscarred uterus during pregnancy: A rare but life-threatening emergency: Case series.

RATIONALE: In most cases, uterine rupture occurs during the third trimester of pregnancy or during labor. Even fewer reports have been published about the occurrence of this condition without a gynecologic history of any surgical procedure. Due to their scarcity and variable clinical presentation, early diagnosis of uterine rupture may be difficult, and if the diagnosis is not timely, the condition may be life-threatening. PATIENT CONCERNS: Herein, 3 cases of uterine rupture from a single institution are described. Three patients are at different gestational weeks and all have no history of uterine surgery. They came to the hospital due to acute abdominal pain, which is characterized by severe and persistent pain in the abdomen, with no apparent vaginal bleeding. DIAGNOSES: All 3 patients were diagnosed with uterine rupture during the operation. INTERVENTIONS: One patient underwent uterine repair surgery; while the other 2 underwent subtotal hysterectomy due to persistent bleeding and pathological examination after surgery confirmed placenta implantation. OUTCOMES: The patients recovered well after the operation, and no discomfort occurred in the follow-up. LESSONS: Acute abdominal pain during pregnancy can pose both diagnostic and therapeutic challenges. It is important to consider the possibility of uterine rupture, even in cases where there is no history of prior uterine surgery. The key to the treatment of uterine rupture is to shorten the diagnosis time as much as possible, this potential complication should be carefully monitored for and promptly addressed to ensure the best possible outcomes for both the mother and the developing fetus.

KLRB1 is a novel prognostic biomarker in endometrial cancer and is associated with immune infiltration.

Background: Endometrial cancer (EC) has the characteristics of high mortality and poor prognosis in the advanced stage, which seriously threatens women's health. Killer cell lectin-like receptor B1 (KLRB1) is a promising immune checkpoint of which the expression level can regulate the killing effect on tumor cells of the immune system, thereby affecting the survival and prognosis of tumor patients. However, it is still unclear whether KLRB1 is associated with survival and prognosis in patients with EC. Therefore, our study focused on the relationship between KLRB1 and immune cells to explore the role of KLRB1 on the immune microenvironment, and to further explore its feasibility as a prognostic marker in EC. Methods: In this study, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the messenger RNA (mRNA) expression level of KLRB1 in normal endometrial and EC tissues. The University of Alabama at Birmingham Cancer data analysis Portal (UALCAN) database was used to determine the correlation between KLRB1 mRNA expression and clinical features among the EC patients. KLRB1 expression levels were investigated in the Tumor IMmune Estimation Resource (TIMER) database to reveal its relationship with immune cell infiltration of EC. Finally, using the R package clusterProfiler, enrichment analysis was performed on KLRB1 to study its potential function. Results: The results suggested that KLRB1 expression varied in different tumor tissues, and the EC group had lower mRNA expression levels than did the control group. It was also found that patients with high expression of KLRB1 had a better prognosis. According to further enrichment and immune infiltration analyses, KLRB1 expression had a closed relationship with the level of infiltration of some immune cell types, such as B cells memory, eosinophils, and Tregs, among others. Conclusions: KLRB1 expression is associated with the infiltration of immune cells and can be used as a prognostic biomarker in EC.

[Expression of transient receptor potential vanilloid 3 ion channel protein in human odontoblasts].

OBJECTIVE: To investigate the expression of transient receptor potential vanilloid 3 (TRPV3) ion channel protein in human odontoblasts (OD). METHODS: Twenty intact and healthy third molars extracted for orthodontic purpose were included. The quality of dental tissue sections was determined through HE staining, and the OD layer was further determined by dentin sialophosphoproteins (DSPP) antibody staining, and finally the expression of TRPV3 ion channel protein in human dental pulp tissue was examined by TRPV3 ion channel protein-specific antibody. The expression of TRPV3 channel proteins in human OD at different part of dental pulp was compared using Image Pro Plus (IPP) and SPSS software. RESULTS: TRPV3 channel protein expressed on the cell body of OD in the coronal and root pulp, and the expression in the coronal pulp was significantly higher than that in the root pulp. The TRPV3 protein also expressed at the odontoblastic process, with the higher expression in the crown (IA = 2516 ± 162) than in the root (IA = 2224 ± 150) and external root (IA = 2121 ± 92) (P < 0.05), but the expression between the lateral root area and external root area was not significantly different (P > 0.05). CONCLUSIONS: Human odonoblasts expressed TRPV3 ion channel protein and the expression level was different at different part of dental pulp OD.