Background: This study will explore the therapeutic value of traditional Chinese medicine (TCM) in Hepatocellular Carcinoma (HCC) through meta-analysis, combined with network pharmacology analysis. Methods: The results of randomized controlled trials on TCM and HCC were retrieved and summarized from multiple databases. The effective active com-pounds and target genes of the high-frequency TCM were obtained using the TCMSP database, and disease targets of HCC were acquired through the public disease database. The network pharmacology analysis was used to get the core genes and investigate the potential oncogenic molecular mechanism. Results: A total of 14 meta-analysis studies with 1,831 patients suggested that therapy combined TCM is associated with better clinical efficacy and survival prognosis, as well as avoiding many adverse events. A total of 156 compounds, 247 herbal target genes and 36 core genes were identified. The function analysis suggested above genes may participate development in HCC through regulating some pathways, such as HIF-1 pathway and PD-L1 immune-related pathway. Conclusion: TCM, as a novel, safe, and effective multi-mechanism therapy, holds greater value in the treatment of HCC.

Extracellular vesicles or exosomes, often known as EVs, have acquired significant attention in the investigations of traumatic brain injury (TBI) and have a distinct advantage in actively researching the fundamental mechanisms underlying various clinical symptoms and diagnosing the wide range of traumatic brain injury cases. The mesenchymal stem cells (MSCs) can produce and release exosomes, which offer therapeutic benefits. Exosomes are tiny membranous vesicles produced by various cellular entities originating from endosomes. Several studies have reported that administering MSC-derived exosomes through intravenous infusions improves neurological recovery and promotes neuroplasticity in rats with traumatic brain damage. The therapeutic advantages of exosomes can be attributed to the microRNAs (miRNAs), which are small non-coding regulatory RNAs that significantly impact the regulation of posttranscriptional genes. Exosome-based therapies, which do not involve cells, have lately gained interest as a potential breakthrough in enhancing neuroplasticity and accelerating neurological recovery for various brain injuries and neurodegenerative diseases. This article explores the benefits and drawbacks of exosome treatment for traumatic brain injury while emphasizing the latest advancements in this field with clinical significance.

UNASSIGNED: The oncological relevance of proximal gastrectomy in advanced gastric cancer remains unclear. We aimed to examine the frequency of lymph node metastasis in advanced gastric cancer to determine the oncological validity of proximal gastrectomy selection.
UNASSIGNED: This study included consecutive 71 patients with locally advanced gastric cancer in the upper third of the stomach who underwent total gastrectomy at our institution between 2001 and 2017. Lymph node metastasis and its therapeutic value index were examined to identify candidates for proximal gastrectomy. Metastatic and 3-year overall survival rates of numbers 3a and 3b lymph nodes were examined from 2010 to 2019.
UNASSIGNED: The metastatic rate and therapeutic value index of numbers 4d, 5, 6, and 12a lymph nodes were zero or low. The number 3 lymph node had a metastatic rate and therapeutic value index of 36.6 % and 31.1, respectively. The metastatic and 3-year overall survival rates of the number 3a lymph node were 32.7 % and 89 %, respectively, whereas those of the number 3b lymph node were 3.8 % and 100 %, respectively. All patients with positive metastasis to the number 3b lymph node received adjuvant chemotherapy. Histopathological findings of positive metastasis to the number 3b lymph node were located in the lesser curvature, and the tumor diameter exceeded 40 mm.
UNASSIGNED: For advanced gastric cancer of the upper third of the stomach, the indications of localization to the lesser curvature and a tumor diameter of >40 mm should be considered cautiously.

OBJECTIVE: To examine whether there has been a change in the number of therapeutically important new medicines not being introduced into the Canadian market in light of the December 2017 announcement of regulatory changes to lower Canadian prices.
METHODS: A list was compiled of medicines approved by the Food and Drug Administration (FDA) between 2014-2021 but not submitted to Health Canada. The therapeutic value of these medicines was assessed based on evaluations by two independent sources. If no evaluation was available, potential therapeutic value was determined based on the presence of one or more of three medicine characteristics. Interrupted time series was used to determine if there were changes in overall new medicine introductions and therapeutically important new medicines.
RESULTS: The FDA approved 364 new medicines of which 116 (31.9%) were not submitted to Health Canada. There was a decrease in overall annual number of submissions but that was not related to the announcement at the end of 2017. There was no change in the introduction of therapeutically important new medicines as a percent of all medicines not marketed in Canada but there was a decrease in the absolute number.
CONCLUSIONS: The number of therapeutically important medicines not being introduced into Canada is increasing but that is not related to the proposed price reforms.

UNASSIGNED: The combination of virtual reality (VR) with an omnidirectional walking platform (ODWP) may have potential in rehabilitation settings. However, its use, acceptance, safety, and effectiveness are unclear. This preliminary study aims to understand the feasibility, safety, and user experience (including investigating the onset of cybersickness) while walking on the ODWP with fully immersive VR.
UNASSIGNED: Participants engaged with eight immersive VR walking scenarios. The scenarios were created using 360-degree videos and were programmed to run with the ODWP. Safety modifications for the ODWP were made, with the addition of parallel bars. Quantitative feedback on the perceived safety and acceptance of using VR with an ODWP for rehabilitation was collected. Cybersickness was evaluated using the Simulation Symptoms Questionnaire (SSQ).
UNASSIGNED: Thirty-five participants (n = 8 physiotherapists, n = 27 healthy adults) were recruited for this study. The mean perceived safety score was 78.9/100 and acceptance was 64.5/100. Seventy-one percent of participants experienced mild to moderate symptoms of cybersickness as reported on the SSQ. The SSQ scores were not correlated to participant age or simulation exposure time.
UNASSIGNED: VR while using ODWP has the potential for rehabilitation, however, more consideration is needed to address acceptance and cybersickness.

Lipid metabolism is associated with lymphomagenesis and functions as a new therapeutic target in patients with lymphoma. Several serum lipids and lipoproteins have prognostic value in solid tumors; however, their value in diffuse large B-cell lymphoma (DLBCL) has been poorly described. We retrospectively analyzed and compared pre-treatment serum lipid and lipoprotein levels, including triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I (ApoA-I), and apolipoprotein B (ApoB) between 105 DLBCL and 105 controls (no DLBCL). The prognostic significance of serum lipid and lipoprotein levels was determined using univariate and multivariate Cox proportional hazards models. The primary outcomes, overall survival (OS) and progression-free survival (PFS), were assessed by the Kaplan-Meier method. We combined the International Prognostic Index (IPI) with ApoA-I to build a nomogram model (IPI-A) to predict the OS and PFS of DLBCL. Serum TG, LDL-C, HDL-C, ApoA-I, and ApoB levels were significantly lower in the DLBCL patients than in controls and significantly increased after chemotherapy. Multivariate analyses showed that the ApoA-I level was an independent predictor of OS and PFS. In addition, our findings indicated that the prognostic index IPI-A significantly improves risk prediction over the traditional IPI score system. ApoA-I is an independent prognostic factor associated with poor OS and PFS in DLBCL patients. Our findings suggested that IPI-A is a prognostic index accurately used for risk assessment in patients with DLBCL.

The present work aimed to biofabricate copper oxide nanoparticles (CuO NPs) using Tinospora cordifolia leaf extract. The biofabricated CuO NPs were treated against the malarial parasite of chloroquine-resistant Plasmodium falciparum (INDO) and the antilarval efficacy was evaluated against the malaria vector Anopheles stephensi and dengue vector Aedes aegypti. The prominence at 285 nm in the UV-visible spectrum helped to identify the produced CuO NPs. Based on the XRD patterns, the concentric rings correspond to reflections at 38.26° (111), 44.11° (200), 64.58° (220), and 77.34° (311). These separations are indicative of CuO\'s face-centered cubic (fcc) structure. The synthesized CuO NPs have FTIR spectra with band intensities of 3427, 2925, 1629, 1387, 1096, and 600 cm-1. The absorbance band at 3427 cm-1 is known to be associated with the stretching O-H due to the alcoholic group. FTIR proved that the presence of the -OH group is responsible for reducing and capping agents in the synthesis of nanoparticles (NPs). The synthesized CuO NPs were found to be polymorphic (oval, elongated, and roughly spherical) in form with a size range of 11-47 nm and an average size of 16 nm when the morphology was examined using FESEM and HRTEM. The highest antiplasmodial efficacy against the chloroquine-resistant strain of P. falciparum (INDO) was found in the synthesized CuO NPs, with LC50 values of 19.82 µg/mL, whilst HEK293 cells are the least toxic, with a CC50 value of 265.85 µg/mL, leading to a selectivity index of 13.41. However, the antiplasmodial activity of T. cordifolia leaf extract (TCLE) and copper sulfate (CS) solution showed moderate activity, with LC50 values of 52.24 and 63.88 µg/mL, respectively. The green synthesized NPs demonstrated extremely high antilarval efficacy against the larvae of An. stephensi and Ae. aegypti, with LC50 values of 4.06 and 3.69 mg/L, respectively.

Blueberry (Vaccinium spp.) is one of the five major healthy foods for humans and is recognized as the \"king of the world fruit\", which has attracted great interest in the phytogenic prebiotics market. Blueberry fruit is favored for its delicious taste and its various functional ingredients (organic acids, phenolics, minerals and vitamins) with multitherapeutic value (antioxidant, anti-inflammatory, anticancer, neuroprotective and vision improvement properties). However, fresh blueberries are highly perishable since they are vulnerable to mechanical damage and microbial decay, resulting in a short shelf life and inevitable subsequent economic losses. Due to the strong seasonal availability and limited storage period of blueberries, their derived bioactive products have emerged as functional foods. Novel food developments that are currently available include blueberry fruit juice, wine, vinegar, jam, dried fruit, pulp powder, colorant and flavoring additives used in cake, biscuit, bread, yogurt, and jelly. This review systematically describes the current status of blueberry fruit as bioactive ingredients and valuable food products with greater nutraceutical health potential of blueberries.

Calluna vulgaris, belonging to the Ericaceae family, is an invasive plant that has widely spread from Europe all across Asia, North America, Australia and New Zealand. Being able to survive in rigid soil and environmental conditions, it is nowadays considered to be of high nature-conservation value. Known for its nutritional and medicinal properties, C. vulgaris stands out for its varied physiochemical composition, spotlighting a wide range of biological activity. Among the most important bioactive compounds identified in C. vulgaris, the phenolic components found in different parts of this herbaceous plant are the main source of its diverse pro-health properties (antioxidant, anti-inflammatory, antimicrobial, chemoprotective, etc.). Nonetheless, this plant exhibits an excellent nectariferous potential for social insects such as honeybees; therefore, comparing the bioactive compounds observed in the plant and in the final product of the beehive, namely honey, will help us understand and find new insights into the health benefits provided by the consumption of C. vulgaris-related products. Thus, the main interest of this work is to review the nutritional profile, chemical composition and biological activities of the C. vulgaris plant and its related honey in order to encourage the future exploration and use of this health-promoting plant in novel foods, pharmacological products and apitherapy.

Objectives: Reimbursement decisions on new medicines require an assessment of their value. In Austria, when applying for reimbursement of new medicines, pharmaceutical companies are also obliged to submit forecasts of future sales. We systematically examined the accuracy of these pharmaceutical sales forecasts and hence the usefulness of these forecasts for reimbursement evaluations. Methods: We retrospectively analyzed reimbursement applications of 102 new drugs submitted between 2005 and 2014, which were accepted for reimbursement outside of hospitals, and for which actual reimbursed sales were available for at least 3 years. The main outcome variable was the accuracy ratio, defined as the ratio of forecasted sales submitted by pharmaceutical companies when applying for reimbursement to actual sales from reimbursement data. Results: The median accuracy ratio [95% confidence interval] was 1.33 [1.03; 1.74, range 0.15-37.5], corresponding to a median overestimation of actual sales by 33%. Forecasts of actual sales for 55.9% of all examined products either overestimated actual sales by more than 100% or underestimated them by more than 50%. The accuracy of sales forecasts did not show systematic change over the analyzed decade nor was it discernibly influenced by reimbursement status (restricted or unrestricted), the degree of therapeutic benefit, or the therapeutic area of the pharmaceutical product. Sales forecasts of drugs with a higher degree of innovation and those within a dynamic market tended to be slightly more accurate. Conclusions: The majority of sales forecasts provided by applicants for reimbursement evaluations in Austria were highly inaccurate and were on average too optimistic. This is in line with published results for other jurisdictions and highlights the need for caution when using such forecasts for reimbursement procedures.