The efficacy and safety of local 5-aminolevulinic acid-based photodynamic therapy in the treatment of cervical high-grade squamous intraepithelial lesion: a single center retrospective observational study.

Background: Typical treatments for cervical high-grade squamous intraepithelial lesion (HSIL) are invasive procedures. However, these procedures often come with several severe side effects, despite their positive effects on cervical HSIL. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive treatment that has been successfully used to treat cervical low-grade squamous intraepithelial lesion (LSIL). In this study, we aimed to further investigate the clinical efficacy and safety of ALA-PDT in the treatment of patients with cervical HSIL. Methods: A total of 40 patients aged 20 - 41 years with cervical HSIL and high-risk Human Papilloma Virus (HR-HPV) infections were enrolled in this retrospective study from January 2019 to December 2022. Patients were treated with six times of ALA-PDT at intervals of 7-14 days. Three months after the treatment, the efficacy was evaluated through HPV genotyping and cervical cytology examination. If the cytological result was worse than ASC -US, the patient underwent colposcopy-directed biopsy immediately. Otherwise, patients would receive rigorous follow-up observation. Results: Three months after receiving ALA-PDT treatment, 65% (26/40) of cervical HSIL patients at our center showed complete regression (cytological result: normal; HR-HPV: negative). This rate increased to 82.5% (33/40) at the 12-month follow-up. None of the patients experienced disease progression after ALA-PDT therapy. The risk of persistent HR-HPV infection was 32.5% (13/40) at the 3-month follow-up after ALA-PDT. Multivariate analyses identified cervical canal involvement as an independent risk factor for persistent HR-HPV infection at the 3-month follow-up after ALA-PDT treatment. During the treatment of the 40 patients with ALA-PDT, there were no reports of severe adverse reactions. Only a limited number of patients experienced slight discomfort symptoms. Conclusion: ALA-PDT is safe and effective noninvasive therapy for patients with cervical HSIL and HR-HPV infections. It is particularly suitable for young women, who have been confirmed with cervical HSIL and have demand for fertility protection. Three months after ALA-PDT treatment, if a patient still has either ASC-US cervical cytological result and/or HR-HPV infection, rigorous observation is considered safe for her. Cervical canal involvement is an independent risk factor for persistent HR-HPV infection at the 3-month follow-up after ALA-PDT treatment.

Sirt3 Protects Retinal Pigment Epithelial Cells From High Glucose-Induced Injury by Promoting Mitophagy Through the AMPK/mTOR/ULK1 Pathway.

Purpose: The regulation of mitophagy by Sirt3 has rarely been studied in ocular diseases. In the present study, we determined the effects of Sirt3 on AMPK/mTOR/ULK1 signaling pathway-mediated mitophagy in retinal pigment epithelial (RPE) cells in a high glucose environment. Methods: The mRNA expression levels of Sirt3, AMPK, mTOR, ULK1, and LC3B in RPE cells under varying glucose conditions were measured by real-time polymerase chain reaction (RT-PCR). The expressions of Sirt3, mitophagy protein, and AMPK/mTOR/ULK1 signaling pathway-related proteins were detected by Western blotting. Lentivirus (LV) transfection mediated the stable overexpression of Sirt3 in cell lines. The experimental groups were NG (5.5 mM glucose), hypertonic, HG (30 mM glucose), HG + LV-GFP, and HG + LV-Sirt3. Western blotting was performed to detect the expressions of mitophagy proteins and AMPK/mTOR/ULK1-related proteins in a high glucose environment during the overexpression of Sirt3. Reactive oxygen species (ROS) production in a high glucose environment was measured by DCFH-DA staining. Mitophagy was detected by labeling mitochondria and lysosomes with MitoTracker and LysoTracker probes, respectively. Apoptosis was detected by flow cytometry. Results: Sirt3 expression was reduced in the high glucose group, inhibiting the AMPK/mTOR/ULK1 pathway, with diminished mitophagy and increased intracellular ROS production. The overexpression of Sirt3, increased expression of p-AMPK/AMPK and p-ULK1/ULK1, and decreased expression of p-mTOR/mTOR inhibited cell apoptosis and enhanced mitophagy. Conclusions: Sirt3 protected RPE cells from high glucose-induced injury by activating the AMPK/mTOR/ULK1 signaling pathway. Translational Relevance: By identifying new targets of action, we aimed to establish effective therapeutic targets for diabetic retinopathy treatment.

Decreased expression of TNFRSF12A in thyroid gland cancer predicts poor prognosis: A study based on TCGA data.

Thyroid cancer (TC) is the most well-known endocrine neoplasia as well as a common malignant tumor in the head and neck. Our study was designed to assess the prognostic meaningful of TNFRSF12A expression in TC dependent on data acquired from TCGA and so as to increase further knowledge into the biological pathways involved in TC pathogenesis related TNFRSF12A.Information on gene expression and comparing clinical data were identified and downloaded from TCGA. Gene set enrichment analysis (GSEA) created an arranged list of all genes indicated by their connection with TNFRSF12A expression.Our study cohort included 370 (73.1%) female and 136 (26.9%) male patients. The scatter plot and paired plot showed the difference of TNFRSF12A expression between normal and tumor samples (P < .01). The univariate analysis suggested that TNFRSF12A-low associated essentially with age (HR: 1.15; 95%CI: 1.08-1.22; P < .01), stage (HR: 2.79; 95%CI: 1.43-5.46; I vs IV; P = .003) and tumor stage (HR: 2.39; 95%CI: 1.08-5.30; P = .031). The GSEA results show that type II diabetes mellitus, pantothenate and CoA biosynthesis, adipocytokine signaling pathway, PPAR signaling pathway, mTOR signaling pathway, insulin signaling pathway, are enriched in TNFRSF12A low expression phenotype.TNFRSF12A expression may be a potential useful prognostic molecular biomarker of bad survival in thyroid cancer, in addition, PPAR signaling pathway, insulin signaling pathway, mTOR signaling pathway may be the key pathway controlled by TNFRSF12A in thyroid cancer. Further experimental ought to be performed to demonstrate the biologic effect of TNFRSF12A.

Four-wave mixing signal enhancement and optical bistability of a hybrid metal nanoparticle-quantum dot molecule in a nanomechanical resonator.

We investigate theoretically four-wave mixing (FWM) response and optical bistability (OB) in a hybrid nanosystem composed of a metal nanoparticle (MNP) and a semiconductor quantum dot (SQD) coupled to a nanomechanical resonator (NR). It is shown that the FWM signal is enhanced by more than three orders of magnitude as compared to that of the system without exciton-phonon interaction, and the FWM signal can also be suppressed significantly and broadened due to the exciton-plasmon interaction. As the MNP couples strongly with the SQD, the bistable FWM response can be achieved by adjusting the SQD-MNP distance and the pumping intensity. For a given pumping constant and a fixed SQD-MNP distance, the enhanced exciton-phonon interaction can promote the occurrence of bistability. Our findings not only present a feasible way to detect the spacing between two nanoparticles, but also hold promise for developing quantum switches and nanoscale rulers.