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Vinblastine (VBL) is a major chemotherapeutic drug; however, in some cases, it may cause severe side effects in patients with cancer. Designing a novel VBL pharmaceutical formulation is a crucial and emerging concern among researchers for reducing the use of VBL. This study developed a stimuli-responsive controlled VBL drug release system from magnetically sensitive chitosan capsules. A magnetically responsive controlled drug release system was designed by embedding superparamagnetic iron oxide (SPIO) nanoparticles (NPs) in a chitosan matrix and an external magnet. In addition, droplet microfluidics, which is a novel technique for producing polymer spheres, was used for manufacturing monodispersed chitosan microparticles. The prepared VBL and SPIO NPs-loaded chitosan microparticles were characterized and analyzed using Fourier transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, a superconducting quantum interference device, and a biocompatibility test. The drug encapsulation efficiency was 67%–69%. The in vitro drug release test indicated that the VBL could be 100% released from chitosan composite particles in 80–130 min under magnetic stimulation. The pulsatile magnetically triggered tests showed individual and distinctive controlled release patterns. Thus, the timing and dose of VBL release was controllable by an external magnet. The results presume that using a magnetically responsive controlled drug release system offers a valuable opportunity for VBL drug delivery, where the delivery system is an active participant, rather than a passive vehicle, in the optimization of cancer treatment. The proposed actively targeted magnetic drug delivery system offers many advantages over conventional drug delivery systems by improving the precision and timing of drug release, easy operation, and higher compliance for pharmaceutical applications.

Background Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups. Methods We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan–Meier analysis. Results In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7–61.2], 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM. Conclusion The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.

Adiponectin and its receptors have been demonstrated to play important roles in regulating glucose and lipid metabolism in mice. Obesity, type II diabetes and cardiovascular disease are highly correlated with down-regulated adiponectin signaling. In this study, we generated mice overexpressing the porcine Adipor1 transgene (pAdipor1) to study its beneficial effects in metabolic syndromes as expressed in diet-induced obesity, hepatosteatosis and insulin resistance. Wild-type (WT) and pAdipor1 transgenic mice were fed ad libitum with a standard chow diet (Chow) or a high-fat/sucrose diet (HFSD) for 24 weeks, beginning at 6 to 7 weeks of age. There were 12 mice per genetic/diet/sex group. When challenged with HFSD to induce obesity, the pAdipor1 transgenic mice resisted development of weight gain, hepatosteatosis and insulin resistance. These mice had lowered plasma adiponectin, triglyceride and glycerol concentrations compared to WT mice. Moreover, we found that (indicated by mRNA levels) fatty acid oxidation was enhanced in skeletal muscle and adipose tissue, and liver lipogenesis was inhibited. The pAdipor1 transgene also restored HFSD-reduced phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose transporter 4 mRNA in the adipose tissues, implying that the increased Pck1 may promote glyceroneogenesis to reduce glucose intolerance and thus activate the flux of glyceride-glycerol to resist diet-induced weight gain in the adipose tissues. Taken together, we demonstrated that pAdipor1 can prevent diet-induced weight gain and insulin resistance. Our findings may provide potential therapeutic strategies for treating metabolic syndromes and obesity, such as treatment with an ADIPOR1 agonist or activation of Adipor1 downstream targets.

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Background The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages. Methods Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. Results In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0–96) months for the total cohort and was subdivided into 52 (8–96), 32 (1–96), 19 (0–84), and 12 (0–79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were (1) SR and cirrhosis; (2) SR, cirrhosis, and Child–Pugh (C–P) class; (3) SR, hepatitis B virus (HBV) infection, and C–P class; and (4) SR, HBV infection, and C–P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs. non-SR were 44.0% versus 28.7%, 72.2% versus 42.6%, 42.6% versus 36.2, 44.6% versus 23.5%, and 41.4% versus 15.3% (all P values < 0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages. Conclusions SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.

This paper introduces the relative-performance contract into a vertically differentiated product market and examines how the optimal trade policy and quality choice respond to the incentive mechanism. We find that the high quality firm makes better use of the delegation than the low quality firm in a cross-border decentralized model. The main difference between the present paper and the strategic trade theory literature is that in this paper the optimal policy is free trade, which does not depend on whether firms compete by prices or quantities, and on whether the goods are substitutes or full complements. JEL Classification: F12; F13; L13; L21.

Background Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). Methods We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. Results We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7 and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68–26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01–0.34), p = 0.004, and 0.07 (0.01–0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85–922), p = 0.008, and 17.9 (1.05–306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2 and 74.6% in high LC3 expression patients and 0 and 0% in those with low LC3 expression. Conclusion High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.