Double-modified oncolytic adenovirus armed with a recombinant interferon-like gene enhanced abscopal effects against malignant glioma.

Background: The development of new therapies for malignant gliomas has been stagnant for decades. Through the promising outcomes in clinical trials of oncolytic virotherapy, there is now a glimmer of hope in addressing this situation. To further enhance the antitumor immune response of oncolytic viruses, we have equipped a modified oncolytic adenovirus (oAds) with a recombinant interferon-like gene (YSCH-01) and conducted a comprehensive evaluation of the safety and efficacy of this modification compared to existing treatments. Methods: To assess the safety of YSCH-01, we administered the oAds intracranially to Syrian hamsters, which are susceptible to adenovirus. The efficacy of YSCH-01 in targeting glioma was evaluated through in vitro and in vivo experiments utilizing various human glioma cell lines. Furthermore, we employed a patient-derived xenograft model of recurrent glioblastoma to test the effectiveness of YSCH-01 against temozolomide. Results: By modifying the E1A and adding survivin promoter, the oAds have demonstrated remarkable safety and an impressive ability to selectively target tumor cells. In animal models, YSCH-01 exhibited potent therapeutic efficacy, particularly in terms of its distant effects. Additionally, YSCH-01 remains effective in inhibiting the recurrent GBM patient-derived xenograft model. Conclusions: Our initial findings confirm that a double-modified oncolytic adenovirus armed with a recombinant interferon-like gene is both safe and effective in the treatment of malignant glioma. Furthermore, when utilized in combination with a targeted therapy gene strategy, these oAds exhibit a more profound effect in tumor therapy and an enhanced ability to inhibit tumor growth at remote sites.

Efficacy and Safety of Ultrasound-Guided Radiofrequency Ablation for Primary Hyperparathyroidism: A Prospective Study.

OBJECTIVE: To assess the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) in patients with primary hyperparathyroidism (PHPT). MATERIALS AND METHODS: This prospective study enrolled 39 participants (14 male, 25 female; mean age, 59.5 ± 15.3 [range, 18-87] years) between September 1, 2018, and January 31, 2021. All participants had parathyroid lesions causing PHPT, proven biochemically and through imaging. The imaging features of the PHPT nodules, including the shape, margin, size, composition, and location, were evaluated before treatment. Serum intact parathyroid hormone, calcium, and phosphorus levels; parathyroid nodule volume; and PHPT-related symptoms were recorded before and after treatment. We calculated the technical success, biochemical cure, and clinical cure rates for these patients. Complications were evaluated during and after the ablation. RESULTS: Complete ablation was achieved in 38 of the 39 nodules in the 39 enrolled participants. All the patients were treated in one session. The technical success rate was 97.4% (38/39). The mean follow-up duration was 13.2 ± 4.6 (range, 6.0-24.9) months. At 6 and 12 months post-RFA, the biochemical cure rates were 82.1% (32/39) and 84.4% (27/32), respectively, and the clinical cure rates were 100% (39/39) and 96.9% (31/32), respectively. Only 2.6% (1/39) of the patients had recurrent PHPT. At 1, 3, 6, and 12 months after technically successful RFA, 44.7% (17/38), 34.3% (12/35), 15.8% (6/38), and 12.5% (4/32) of participants, respectively, had elevated eucalcemic parathyroid hormone levels. Recurrent laryngeal nerve paralysis occurred in 5.1% (2/39) of the patients, who recovered spontaneously within 1-3 months. CONCLUSION: US-guided RFA was effective and safe for PHPT patients. RFA may be an alternative treatment tool for patients who cannot tolerate or refuse to undergo surgery.

Radiofrequency ablation for primary hyperparathyroidism and risk factors for postablative eucalcemic parathyroid hormone elevation.

OBJECTIVE: To investigate the efficacy of radiofrequency ablation (RFA) as a treatment option for primary hyperparathyroidism (pHPT) and risk factors for postablative eucalcemic parathyroid hormone elevation (ePTH). METHODS: This retrospective study included 51 patients with pHPT who underwent RFA. The patients were divided into the ePTH and normal PTH groups, based on the serum intact parathyroid hormone (iPTH) level one month after ablation. Serum iPTH, calcium, and phosphorus levels, and the volume reduction rates (VRR) of the parathyroid glands were compared between the groups at each follow-up point. Risk factors for ePTH at one month after ablation were examined. RESULTS: After RFA, one (2%) patient had persistent pHPT, and 50 (98%) patients were cured. The incidence rates of ePTH at 1, 3, 6, and 12 months were 48%, 30%, 20%, and 16%, respectively. Serum iPTH levels in the ePTH group were higher than those in the normal PTH group at each follow-up point (all p < 0.05), except 1 day after ablation (p > 0.05). Serum calcium and phosphorus levels, and the VRR of the glands were comparable in both groups at each follow-up point (all p > 0.05), except for calcium levels 3 days after RFA (p < 0.05). Baseline iPTH (odds ratio, 1.067; p = 0.045) and calcium (odds ratio, 3.923; p = 0.038) levels were independent risk factors for ePTH 1 month after RFA. CONCLUSIONS: RFA is safe and effective for the treatment of pHPT. Moreover, ePTH occurrence after RFA was associated with baseline iPTH and calcium levels and did not increase the risk of recurrent pHPT.

Microwave ablation versus radiofrequency ablation for primary hyperparathyroidism: a multicenter retrospective study.

OBJECTIVE: To compare the clinical outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA) in the treatment of primary hyperparathyroidism (pHPT). METHOD: This retrospective study included 104 pHPT patients treated by MWA or RFA between January 2015 and March 2020 in four centers. The clinical outcomes including effectiveness and complications were compared between the two groups. Ablation cure was defined as the reestablishment of normal values of serum calcium and intact parathyroid hormone (iPTH) at least more than 6 months. Clinical cure was defined as the reestablishment of normal values of serum calcium and iPTH throughout the entire follow-up period. RESULTS: A total of 77 patients underwent MWA (mean age, 55.5 ± 16.4 years) and 27 underwent RFA (mean age, 58.9 ± 15.6 years). During the follow-up (median, 18.7 months in the MWA group; 12 months in the RFA group), no difference was observed between ablation cure rates (88.3% vs. 88.9%, p = 1.000), clinical cure rates (87.0% vs. 82.3%, p = .880), recurrent pHPT (5.2% vs. 3.7%, p = .447), persistent pHPT (11.7% vs. 11.1%, p = 1.000) and complication rate (9.1% vs. 3.7%, p = .677). A maximum diameter less than 0.7 cm was an independent prognostic factor of uncured pHPT in ablation (hazard ratio, 0.1; 95% confidence interval: 0.02, 0.54; p = .007). Major complication - voice change encountered in five patients (6.5%) in the MWA group and in one patient (3.7%) in the RFA group. CONCLUSION: Both RFA and MWA are safe and effective techniques for patients with pHPT, with comparable clinical outcomes.

A smartphone-supported portable micro-spectroscopy/imaging system to characterize morphology and spectra of samples at the microscale.

A smartphone-based analysis system is favored for point-of-care testing applications. The present work proposes a novel micro-spectroscopy/imaging system comprising a portable spectrometer as an optical sensor and a compact homemade microscope to acquire the image and spectra of micron-scale regions. Protein concentration quantification based on the bicinchoninic acid method was demonstrated with the proposed micro-spectroscopy/imaging system to analyse the spectrometer signals. Morphologies of onion endothelial and human breast cancer cells, used as biological sample models, were characterized to demonstrate the microscopic imaging capacity of the device. The ability to simultaneously obtain morphological and spectral information using the proposed portable device was demonstrated by examining the 10 µm sub-pixels of a smartphone screen. These results highlight the potential for adopting a smartphone-based micro-spectroscopy/imaging system for point-of-care testing.

A Foldable Chip Array for the Continuous Investigation of Seed Germination and the Subsequent Root Development of Seedlings.

Seed germination and seedling root development are important indicators of plant development. This work designed and fabricated a foldable microfluidic chip array for conducting nondestructive and continuous evaluation of seed germination and subsequent seedling development in situ. Each plant chamber has two functional units: seed germination part and root-growth part. The root-growth parts are themselves connected to a single channel designed to provide a uniform culture medium for plant growth. The individual chips are connected into an array using elastic hinges that facilitate the folding and unfolding of the array to accommodate different viewing purposes. In the folded state, the seed germination chambers form a closely spaced array platform to facilitate the comparison of seed germination and plant development characteristics. Unfolding the array facilitates a clear examination of root development within the root-growth parts. The observation window of an individual chip facilitates either the direct examination of the developing seedling (e.g., stems and leaves) or the use of a microscope for examining microscale features (e.g., root tips and root hairs). The potential of the proposed foldable chip array as a new cultivation platform for botanic studies is demonstrated by examining the seed germination and seedling development of tobacco (Nicotiana tabacum) under different cultivation conditions.

The chemokine CXCL1 and its receptor CXCR2 contribute to chronic stress-induced depression in mice.

Depression is increasingly recognized as an inflammatory disease, with inflammatory crosstalk in the brain contributing its pathogenesis. Life stresses may up-regulate inflammatory processes and promote depression. Although cytokines are central to stress-related immune responses, their contribution to stress-induced depression remains unclear. Here, we used unpredictable chronic mild stress (UCMS) to induce depression-like behaviors in mice, as assessed through a suite of behavioral tests. C-X-C motif chemokine ligand 1 (CXCL1)-related molecular networks responsible for depression-like behaviors were assessed through intrahippocampal microinjection of lenti-CXCL1, the antidepressant fluoxetine, the C-X-C motif chemokine receptor 2 (CXCR2) inhibitor SB265610, and the glycogen synthase kinase-3ß (GSK3ß) inhibitor AR-A014418. Modulation of apoptosis-related pathways and neuronal plasticity were assessed via quantification of cleaved caspase-3, B-cell lymphoma 2-associated X protein, cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) protein expression. CXCL1/CXCL2 expression was correlated with depression-like behaviors in response to chronic stress or antidepressant treatment in the UCMS depression model. Intrahippocampal microinjection of lenti-CXCL1 increased depression-like behaviors, activated GSK3ß, increased apoptosis pathways, suppressed CREB activation, and decreased BDNF. Administration of the selective GSK3ß inhibitor AR-A014418 abolished the effects of lenti-CXCL1, and the CXCR2 inhibitor SB265610 prevented chronic stress-induced depression-like behaviors, inhibited GSK3ß activity, blocked apoptosis pathways, and restored BDNF expression. The CXCL1/CXCR2 axis appears to play a critical role in stress-induced depression, and CXCR2 is a potential novel therapeutic target for patients with depression.-Chai, H.-H., Fu, X.-C., Ma, L., Sun, H.-T., Chen, G.-Z., Song, M.-Y., Chen, W.-X., Chen, Y.-S., Tan, M.-X., Guo, Y.-W., Li, S.-P. The chemokine CXCL1 and its receptor CXCR2 contribute to chronic stress-induced depression in mice.