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Background: Yigu decoction (YGD) is a traditional Chinese medicine prescription for the treatment of osteoporosis, although many clinical studies have confirmed its anti-OP effect, but the specific mechanism is still not completely clear.

Methods: In this study, through the methods of network pharmacology and molecular docking, the material basis and action target of YGD in preventing and treating OP were analyzed, and the potential target and mechanism of YGD in preventing and treating OP were clarified by TMT quantitative protein and experiment.

Results: Network pharmacology and molecular docking revealed that the active components of YGD were mainly stigmasterol and flavonoids. Molecular docking mainly studied the strong binding ability of stigmasterol to the target. Animal proteomics verified the related mechanism of YGD in preventing and treating OP. Based on the KEGG enrichment of network pharmacology and histology, our animal experiments in vivo verified that YGD may play a role in the treatment of OP by mediating hif1- α/vegf/glut1 signal pathway.

Conclusions: YGD prevention and treatment of OP may be achieved by interfering with multiple targets. This study confirmed that it may promote osteoblast proliferation and protect osteoblast function by up-regulating the expression of proteins related to HIF signal pathway.

Regulatory T cells (Tregs) contribute significantly to the immunosuppressive nature of the tumor microenvironment which is a main barrier for immunotherapies of solid cancers. Reducing Treg numbers enhances anti-tumor immune responses but current depletion strategies also impair effector T cells (Teffs), potentially leading to reduced anti-tumor immunity and/or autoimmune diseases. CD137 has been identified as the most differentially expressed gene between peripheral Tregs and intratumoral Tregs in virtually all solid cancers. Further, CD137 is expressed by malignant cells of certain cancers, making it a potential target for tumor immunotherapy. Here, we report the development of a fully human anti-human CD137 antibody of the IgG1 isotype, clone P1A1, that induces antibody-dependent cell-mediated cytotoxicity (ADCC) in CD137⁺ Tregs and cancer cells. P1A1 cross-reacts with murine CD137 which allowed testing murine chimeric P1A1 in syngeneic murine tumor models where P1A1 significantly reduced the number of CD137⁺ Tregs and inhibited tumor growth in a murine hepatocellular carcinoma (HCC) and a melanoma lung metastasis model. P1A1 can also be internalized thus enabling it as a carrier for drugs to target CD137⁺ Tregs and cancer cells. These anti-cancer properties suggest a translation of P1A1 to human immunotherapy.

Background: The body composition of National Collegiate Athletic Association (NCAA) athletes is well documented but no such data exist for university club sports athletes. Additionally, the majority of norms for NCAA athletes were created from individual methods requiring assumptions.

Objective: This study used a four-component (4C) model to measure the body composition of university club sports athletes.

Methods: Data were collected on club athletes participating in baseball, climbing, cycling, figure skating, gymnastics, ice hockey, lacrosse, pickleball, powerlifting, racquetball, rodeo, rugby, soccer, swimming, ultimate, and volleyball. The 4C model consisted of body volume, total body water, and bone mineral content measured by air displacement plethysmography, bioimpedance spectroscopy, and dual-energy x-ray absorptiometry, respectively. Percentile ranks were created for body fat percentage (%BF) and fat-free mass index (FFMI). Mean differences across teams were quantified with Cohen's d.

Results: In total, 225 athletes (137 men, 88 women) completed data collection. Athletes varied in competitive experience (1 to 22 y) and body mass index (16.9 to 36.4 kg·m^-2). The density of the FFM was significantly greater than the assumed value of 1.100 g·cm^-3 for both men (p = .043) and women (p = .011). The %BF ranged from 4.9% to 35.7% (14.3 ± 5.8% BF) for men and from 15.5% to 42.8% (25.2 ± 6.0% BF) for women. FFMI ranged from 15.6 kg·m^-2 to 26.8 kg·m^-2 (30.0 kg·m^-2 outlier removed) for men and from 14.1 kg·m^-2 to 22.6 kg·m^-2 for women. Differences across sports in %BF and FFMI were considered large-sized effects (d ≥ 0.80) for both men and women. Weight-sensitive sports (e.g. cycling and climbing) had the lightest athletes and were among the leanest, whereas power athletes (e.g. powerlifting and rugby) were among the heaviest athletes and had the highest FFMI.

Conclusions: Differences in %BF and FFMI are evident across sports. Due to the small sample size, use caution when interpreting the data as reference values for club sports athletes.

Drug-loaded liposomes incorporated in nanofibrous scaffolds is a promising approach as a multi-unit nanoscale system, which combines the merits of both liposomes and nanofibers (NFs), eliminating the drawback of liposomes' poor stability on the one hand and offering a higher potential of controlled drug release and enhanced therapeutic efficacy on the other hand. The current systematic review, which underwent a rigorous search process in PubMed, Web of Science, Scopus, Embase, and Central (Cochrane) employing (Liposome AND nanofib* AND electrosp*) as search keywords, aims to present the recent studies on using this synergic system for different therapeutic applications. The search was restricted to original, peer-reviewed studies published in English between 2014 and 2024. Of the 309 identified records, only 29 studies met the inclusion criteria. According to the literature, three different methods were identified to fabricate those nanofibrous liposomal scaffolds. The results consistently demonstrated the superiority of this dual system for numerous therapeutic applications in improving the therapy efficacy, enhancing both liposomes and drug stability, and releasing the encapsulated drug in a proper sustained release without significant initial burst release. Merging drug-loaded liposomes with NFs as liposomal nanofibrous scaffolds are a safe and efficient approach to deliver drug molecules and other substances for various pharmaceutical applications, particularly for wound dressing, tissue engineering, cancer therapy, and drug administration via the buccal and sublingual routes. However, further research is warranted to explore the potential of this system in other therapeutic applications.

Chronic Kidney Disease (CKD) is one of the most common conditions affecting felines, yet the metabolic alterations underlying its pathophysiology remain poorly understood, hindering progress in identifying biomarkers and therapeutic targets. This study aimed to provide a comprehensive view of metabolic changes in feline CKD across conserved biochemical pathways and evaluate their progression throughout the disease continuum. Using a multi-biomatrix high-throughput metabolomics approach, serum and urine samples from CKD-affected cats (n = 94) and healthy controls (n = 84) were analyzed with ultra-high-performance liquid chromatography-high-resolution mass spectrometry. Significant disruptions were detected in tryptophan (indole, kynurenine, serotonin), tyrosine, and carnitine metabolism, as well as in the urea cycle. Circulating gut-derived uremic toxins, including indoxyl-sulfate, p-cresyl-sulfate, and trimethylamine-N-oxide, were markedly increased, primarily due to impaired renal excretion. However, alternative mechanisms, such as enhanced bacterial formation from dietary precursors like tryptophan, tyrosine, carnitine, and betaine, could not be ruled out. Overall, the findings suggest that metabolic disturbances in feline CKD are largely driven by the accumulation of gut-derived uremic toxins derived from precursors highly abundant in the feline diet. These insights may link the strict carnivorous nature of felines to CKD pathophysiology and highlight potential avenues for studying preventive or therapeutic interventions.

Background: Vaccination is one of the best ways to control the SARS-CoV-2 outbreak. In Taiwan, healthcare workers were prioritized for vaccination, but the effectiveness of these vaccines for them remains unclear. Thus, it's essential to examine their neutralizing antibodies after prime-boost vaccinations.

Methods: In this prospective observational study, 514 healthcare workers from Chang Gung Memorial hospitals in Taiwan were included between 19 March 2021 and 21 August 2021. The two doses of COVID-19 vaccines were either a match or a mixing of AZD1222 and mRNA-1273, e.g. AZD1222 + AZD1222 (n = 406), mRNA-1273 + mRNA-1273 (n = 62), and AZD1222 + mRNA-1273 (n = 46). Blood specimens were drawn after two doses of vaccines, defined as post-vaccine days [median 34.00 days and interquartile range (IQR) 29.00-42.00 days], and examined for the neutralizing antibodies via SARS-CoV-2 neutralization kits. The results were analyzed as a percentage of inhibition based on the negative control.

Results: After 2 vaccination doses, subjects with AZD1222 + mRNA-1273 (median 97.15%, IQR 96.06-98.06%) and mRNA-1273 + mRNA-1273 (median 97.47%, IQR 96.75-97.89%) exhibited higher neutralizing antibodies than those receiving AZD1222 + AZD1222 vaccines (median 71.28%, IQR 49.39-89.70%) (the percentage was referred to inhibition of surrogate virus). The post-vaccination days negatively impacted the neutralizing antibodies, except for the mRNA-1273 + mRNA-1273 group. The presence of fever, headache, and myalgia after the second dosage was reflected in the higher neutralizing antibodies (median of no fever 76.00% vs. fever 97.00%, p < 0.0001; median of no headache 76.00% vs. headache 95.00%, p < 0.0001; median of no myalgia 75.50% vs. myalgia 96.00%, p < 0.0001). The subjects with underlying diseases, including hypertension and cancer showed lower neutralizing antibodies (median of no hypertension 81.00% vs. hypertension 56.00%, p = 0.0029; median of no cancer 81.00% vs. cancer 56.00%, p = 0.0143).

Conclusion: Heterologous prime-boost vaccines (AZD1222 + mRNA-1273) and two doses of mRNA vaccines are recommended. For future directions, we need to investigate the effectiveness of the vaccination against new SARS-CoV-2 variants.

Background: The global seasonal influenza activity has decreased during the coronavirus disease 2019 (COVID-19) pandemic. Non-pharmaceutical interventions (NPIs), such as reducing gatherings and wearing masks, can have varying impacts on the spread of influenza. We aim to analyse the basic characteristics, epidemiology and space-time clustering of influenza in Quzhou city before and after the COVID-19 pandemic based on five years of surveillance data.

Methods: Influenza case incidence data from 2018-2023 were collected and organized in Quzhou City to analyse the space-time aggregation of influenza incidence before and after COVID-19 pandemic through global spatial autocorrelation analysis and space-time scan analysis methods.

Results: The annual average fluctuation of influenza in Quzhou City from 2018-2023 was large, with gradual decreases in 2019-2020, 2020-2021 and 2021-2022, all of which showed obvious winter and spring peaks; The highest incidence rate in 2022-2023, with a bimodal distribution. The majority of the population is under 15 years of age, accounting for more than 70% of the population. The population classification is dominated by students, nursery children and children in the diaspora. In 2020-2021, the cases in the student group of the 5-14 years old population declined. Global spatial autocorrelation analysis of influenza incidence rate in Quzhou City in each year of 2019-2023Moran's I > 0 and p < 0.05. Space-time scan analysis of the aggregation area is located in Longyou County and the township streets on the border of urban counties, and the number of aggregation areas decreased significantly in 2020-2021 and 2021-2022.

Conclusion: The COVID-19 pandemic has an important impact on changes in influenza incidence levels and spatial and temporal epidemiologic aggregation patterns. Influenza incidence in Quzhou City fluctuates widely, with large changes in the age and occupational composition ratios of the incidence population, and influenza incidence presents a more pronounced spatial correlation and aggregation.

Background: Malnutrition is prevalent in patients with inflammatory bowel disease (IBD); however, its ability to predict the disease activity in IBD remains unexplored. Therefore, this study aimed to explore the association between malnutrition and disease activity in IBD.

Methods: In this retrospective study, we enrolled 1006 patients diagnosed with IBD from the First Affiliated Hospital of Wenzhou Medical University from 2011 to 2022. Malnutrition was assessed based on the prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and controlling nutritional status (CONUT) scores. Logistic regression analyses were performed to identify predictors for disease activity. Restricted cubic spline analysis was performed to evaluate the possible nonlinear relations, and subgroup analysis was performed to explore potential interactions. Additionally, prediction performances were compared through receiver operating characteristic curves, net reclassification improvement, and integrated discrimination improvement.

Results: The prevalence of malnutrition calculated by the PNI, GNRI, and CONUT scores in IBD was 16.9%, 72.1%, and 75.6%, respectively and significant correlations were observed among them. Multivariate logistic regression analysis showed that PNI, GNRI, and CONUT were independent risk factors for disease activity, and no significant nonlinear relationship was observed between disease activity and all three indexes. No statistically significant interactive effect was found in nearly all the subgroups. GNRI showed the highest predictive value compared with PNI and CONUT. Additionally, combining any of the three indexes improved the ability of C-reactive protein to predict IBD activity.

Conclusions: All three nutritional indexes evaluated malnutrition to be an independent risk factor for IBD activity.

Purpose: Neoadjuvant chemotherapy (NAC) has proven valuable in treating locally advanced colon cancer (LACC) and is included as a treatment option for patients with clinical T4b colon cancer by the National Comprehensive Cancer Network. However, the long-term survival benefit of NAC in LACC remains debated, due to a lack of conclusive clinical trial results identifying the patients who would benefit most from NAC. This study aimed to assess the efficacy of NAC in patients with LACC based on histological subtype.

Patients and methods: This retrospective study analyzed 3,709 patients with LACC who underwent curative resection at Harbin Medical University Cancer Hospital between 2014 and 2018. Patients were grouped into two groups: neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) groups. Propensity score matching (PSM) was used to adjust for confounders, and survival outcomes of the two groups across different histological subtypes were evaluated using Kaplan-Meier (K-M) curves and log-rank tests.

Results: Patients with non-mucinous adenocarcinoma (NMAC) treated with NAC had a significantly improved 5-year OS rate (76.3% vs. 69.2%, p = .039) and DFS rate (67.2% vs. 60.1%, p = .041) compared with patients treated with AC. However, there was no significant difference in OS and DFS between the two treatment groups among patients with mucinous adenocarcinoma (MAC) and signet ring cell carcinoma (SRCC).

Conclusion: In patients with LACC, the prognostic value of NAC varied by histology. NMAC may serve as a predictor of improved long-term survival benefit from NAC in these patients.