Analysis on Efficacy of Hepatic Artery Infusion Chemotherapy with or without Lenvatinib for Unresectable Hepatocellular Carcinoma.

INTRODUCTION: For patients with advanced hepatocellular carcinoma (HCC), hepatic artery infusion chemotherapy (HAIC) is a common and mature treatment, but the safety and efficacy of HAIC combined with lenvatinib for advanced HCC patient treatment remains unclear. Therefore, this study compared the safety and efficacy of HAIC with or without lenvatinib in unresectable HCC patients. METHODS: We retrospectively analyzed 13 unresectable advanced HCC patients who received HAIC monotherapy or combination therapy of HAIC and lenvatinib. Overall survival (OS), disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), incidence of adverse events (AEs), and changes in liver function were compared between the two groups. We applied a Cox regression analysis to evaluate the independent risk factors affecting survival outcomes. RESULTS: The ORR in the HAIC+lenvatinib group was markedly increased compared to the HAIC group (p < 0.05), while the DCR in the HAIC group was higher (p > 0.05). No notable difference was found between the two groups in median OS and PFS (p > 0.05). Compared to the HAIC+lenvatinib group, more patients had improved liver function in the HAIC group after treatment, but the difference was not dramatical (p > 0.05). The AEs incidence was 100.00% in both groups, which was relieved with corresponding treatment. Besides, Cox regression analysis did not identify independent risk factors related to OS and PFS. CONCLUSION: Combination therapy of HAIC and lenvatinib notably performed better than the HAIC monotherapy in patients with unresectable HCC in terms of ORR and was well tolerated, which deserves further investigation with large-scale clinical trials.

Origami-Inspired Structure with Pneumatic-Induced Variable Stiffness for Multi-DOF Force-Sensing.

With the emerging need for human-machine interactions, multi-modal sensory interaction is gradually pursued rather than satisfying common perception forms (visual or auditory), so developing flexible, adaptive, and stiffness-variable force-sensing devices is the key to further promoting human-machine fusion. However, current sensor sensitivity is fixed and nonadjustable after fabrication, limiting further development. To solve this problem, we propose an origami-inspired structure to achieve multiple degrees of freedom (DoFs) motions with variable stiffness for force-sensing, which combines the ductility and flexibility of origami structures. In combination with the pneumatic actuation, the structure can achieve and adapt the compression, pitch, roll, diagonal, and array motions (five motion modes), which significantly increase the force adaptability and sensing diversity. To achieve closed-loop control and avoid excessive gas injection, the ultra-flexible microfiber sensor is designed and seamlessly embedded with an approximately linear sensitivity of ∼0.35 Ω/kPa at a relative pressure of 0-100 kPa, and an exponential sensitivity at a relative pressure of 100-350 kPa, which can render this device capable of working under various conditions. The final calibration experiment demonstrates that the pre-pressure value can affect the sensor's sensitivity. With the increasing pre-pressure of 65-95 kPa, the average sensitivity curve shifts rightwards around 9 N intervals, which highly increases the force-sensing capability towards the range of 0-2 N. When the pre-pressure is at the relatively extreme air pressure of 100 kPa, the force sensitivity value is around 11.6 Ω/N. Therefore, our proposed design (which has a low fabrication cost, high integration level, and a suitable sensing range) shows great potential for applications in flexible force-sensing development.

Effect of traditional Chinese medicine formula Sinisan on chronic restraint stress-induced nonalcoholic fatty liver disease: a rat study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) represents one of the most common forms of liver disease worldwide, and it is always regarded as a consequence of a sedentary, food-abundant lifestyle, sitting for an extended time, and a low physical activity level, which often coincide with chronic and long-lasting psychological stress. A Chinese medicine Sinisan (SNS) may be a potential formula for treating this kind of disease. METHODS: In this study, a long-term chronic restraint stress protocol was used to investigate the mechanism underlying stress-induced NALFD. To investigate the effect of SNS treatment on stress-induced NAFLD, we measured the liver and serum values of total cholesterol (TC), triglyceride (TG), liver free fatty acids (FFA), low-density lipoprotein, superoxide dismutase, tumor necrosis factor-α, malondialdehyde, interleukin (IL)-6, and serum values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase. Results are shown as a mean ± standard deviation. Significant differences between the groups were evaluated using the Student t-test. For multiple comparisons, one-way analysis of variance (ANOVA) was used. If the results of ANOVA indicated significant differences, post hoc analysis was performed with the Tukey test or Dunnett test, and p < 0.05 was considered statistically significant. RESULTS: Long-term chronic stress led to steatosis and non-alcoholic steatohepatitis. Additionally, SNS treatment significantly increased body weight gain (p < 0.01) and sucrose preference (p < 0.001), and it reduced the liver values of TC, TG, and FFA (p < 0.05). SNS also reduced the serum values of AST and ALT (p < 0.001), and the liver value of IL-6 (p < 0.01). CONCLUSIONS: This study's results demonstrate that psychological stress may be a significant risk factor of NAFLD. Furthermore, the traditional Chinese medicine formula SNS may have some beneficial effect in antagonizing psychological stress and stress-related NAFLD.

Erythropoietin Pathway: A Potential Target for the Treatment of Depression.

During the past decade, accumulating evidence from both clinical and experimental studies has indicated that erythropoietin may have antidepressant effects. In addition to the kidney and liver, many organs have been identified as secretory tissues for erythropoietin, including the brain. Its receptor is expressed in cerebral and spinal cord neurons, the hypothalamus, hippocampus, neocortex, dorsal root ganglia, nerve axons, and Schwann cells. These findings may highlight new functions for erythropoietin, which was originally considered to play a crucial role in the progress of erythroid differentiation. Erythropoietin and its receptor signaling through JAK2 activate multiple downstream signaling pathways including STAT5, PI3K/Akt, NF-κB, and MAPK. These factors may play an important role in inflammation and neuroprogression in the nervous system. This is particularly true for the hippocampus, which is possibly related to learning, memory, neurocognitive deficits and mood alterations. Thus, the influence of erythropoietin on the downstream pathways known to be involved in the treatment of depression makes the erythropoietin-related pathway an attractive target for the development of new therapeutic approaches. Focusing on erythropoietin may help us understand the pathogenic mechanisms of depression and the molecular basis of its treatment.