Biodegradable Thermosensitive Hydrogel for SAHA and DDP Delivery: Therapeutic Effects on Oral Squamous Cell Carcinoma Xenografts

Background: OSCC is one of the most common malignancies and numerous clinical agents currently applied in combinative chemotherapy. Here we reported a novel therapeutic strategy, SAHA and DDP-loaded PECE (SAHA-DDP/PECE), can improve the therapeutic effects of intratumorally chemotherapy on OSCC cell xenografts. Objective/Purpose: The objective of this study was to evaluate the therapeutic efficacy of the SAHA-DDP/PECE in situ controlled drug delivery system on OSCC cell xenografts. Methods: A biodegradable and thermosensitive hydrogel was successfully developed to load SAHA and DDP. Tumorbeared mice were intratumorally administered with SAHA-DDP/PECE at 50 mg/kg (SAHA) +2 mg/kg (DDP) in 100 ul PECE hydrogel every two weeks, SAHA-DDP at 50 mg/kg(SAHA) +2 mg/kg(DDP) in NS, 2 mg/kg DDP solution, 50 mg/kg SAHA solution, equal volume of PECE hydrogel, or equal volume of NS on the same schedule, respectively. The antineoplastic actions of SAHA and DDP alone and in combination were evaluated using the determination of tumor volume, immunohistochemistry, western blot, and TUNEL analysis. Results: The hydrogel system was a free-flowing sol at 10uC, become gel at body temperature, and could sustain more than 14 days in situ. SAHA-DDP/PECE was subsequently injected into tumor OSCC tumor-beared mice. The results demonstrated that such a strategy as this allows the carrier system to show a sustained release of SAHA and DDP in vivo, and coul

High-Accuracy Height-Independent 3D VLP Based on Received Signal Strength Ratio

Visible light positioning (VLP) has attracted intensive attention from both academic and industrial communities thanks to its high accuracy, immunity to electromagnetic interference, and low deployment cost. In general, the receiver in a VLP system determines its own position by exploring the received signal strength (RSS) from the transmitter according to a pre-built RSS attenuation model. In such model-based methods, the LED’s emission power and the receiver’s height are usually required known and constant parameters to obtain reasonable positioning accuracy. However, the LED’s emission power is normally time-varying due to the fact that the LED’s optical output power is prone to changing with the LED’s temperature, and the receiver’s height is random in a realistic application scenario. To this end, we propose a height-independent three-dimensional (3D) VLP scheme based on the RSS ratio (RSSR), rather than only using RSS. Unlike existing RSS-based VLP methods, our method is able to independently find the horizontal coordinate, i.e., two-dimensional (2D) position, without a priori height information of the receiver, and also avoids the negative effect caused by fluctuation of the LED’s emission power. Moreover, we can further infer the height of the receiver to achieve three-dimensional (3D) positioning by iterating the 2D results back into positioning equations. To quickly verify the proposed scheme, we conduct theoretical analysis with mathematical proof and experimental results with real data, which confirm that the proposed scheme can achieve high position accuracy without known information of the receiver’s height and LED’s emission power. We also implement a VLP prototype with five LED transmitters, and experimental results show that the proposed scheme can achieve very low average errors of 2.73 cm in 2D and 7.20 cm in 3D

The prognostic value and economic benefits of coronary angiography-derived fractional flow reserve-guided strategy in patients with coronary artery disease

Objective: This study aims to investigate the prognostic value and economic benefit of coronary angiography-derived fractional flow reserve (caFFR) guided percutaneous coronary intervention (PCI) in patients with coronary artery disease. Methods: All patients with coronary artery disease (CAD) who underwent coronary angiography in our center between April 2021 and November 2021 were retrospectively enrolled and divided into the caFFR guidance group (n = 160) and angiography guidance group (n = 211). A threshold of caFFR≤0.8 was used for revascularization. Otherwise, delayed PCI was preferred. The patients were prospectively followed up by telephone or outpatient service at six months for major adverse cardiovascular events (MACE) of all-cause death, myocardial infarction or target vessel revascularization, stent thrombosis, and stroke. All in-hospital expenses were recorded, including initial hospitalization and re-hospitalization related to MACE. Results: There was no significant difference in the baseline characteristics between the two groups. There were 2 (1.2%) patients in the caFFR guidance group and 5 (2.4%) patients in the angiography guidance group with MACE events during the following six months. Compared with angiography guidance, caFFR guidance reduced the revascularization rate (63.7% vs. 84.4%, p = 0.000), the average length of stents implanted (0.52 ± 0.88 vs. 1.1 ± 1.4, P < 0.001). The cost of consumables in the caFFR guidance group was significantly lower than that in the angiography guidance group (33257 ± 19595 CNY vs. 38341 ± 16485 CNY, P < 0.05). Conclusion: Compared with coronary angiography guidance, caFFR guidance is of great significance in reducing revascularization and cost, which has significant health and economic benefits

Figure 3

<p><b>Antitumor activity of SAHA-DDP/PECE in vivo.</b> In the mice model of oral squamous cell carcinoma xenografts, the female nude mice received 2 × 10⁶ HSC-3 cells via subcutaneously into the right flank regions. (A) The mice were then treated with NS, PECE, SAHA, DDP, SAHA-DDP and SAHA-DDP/PECE every two weeks for a total of two doses starting on day 7 (n = 6 mice per group). Tumor volumes of mice from different groups of HSC-3 tumor model. (B) Representative tumors of OSCC mice model from NS, PECE, SAHA, DDP and SAHA-DDP control group and SAHA-DDP/PECE treated mice. Data are representative of at least two separate experiments. Bars, means ± SD (*P<0.05).(C) When tumors were palpable, the mice were randomly assigned to two independent treatment groups( n = 12 mice per group): mice treated with 100 ml combine SAHA with DDP (SAHA-DDP), or treated with 100 ml SAHA and DDP in thermosensitive hydrogel (SAHA-DDP/PECE). At the date of 1, 3, 7, 14 and 21 three mice were sacrificed separately. The ribonucleoprotein of the tumor tissues was extracted and the expression of acetyl-Histone H3 and Histone H3 was detected by western blot.</p

Figure 6

<p><b>SAHA-DDP/PECE induced apoptosis in vivo.</b> (A) Induction of apoptosis was indicated by TUNEL assay. The TUNEL-positive cells display dark green nuclei and are observed under a fluorescence microgroup (×400 magnification). TUNEL-positive nuclei were significantly increased in SAHA-DDP/PECE treated tissues compared with those in the control groups (*P<0.05). (B) Detection of caspase-3, Caspase-8 and Caspase-9 by Western blots. GAPDH was used as equal loading control.</p

Figure 5

<p><b>SAHA-DDP/PECE inhibited cell proliferation and intratumoral angiogenesis in vivo.</b> (A) PCNA-positive cells were rich in NS and PECE groups. Whereas, the percentage of PCNA-positive cells in SAHA, DDP, SAHA-DDP and SAHA-DDP/PECE groups were significantly decreased in turn (*P<0.05). (magnification, × 200) (B) Angiogenesis within tumors was detected by CD34 staining of micro vessels. The average number of micro vessels per vascular hot spot was significantly decreased in SAHA-DDP/PECE treated tissues compared with those in the three control groups (*P<0.05).</p