Respiratory syncytial virus (RSV) is a ubiquitous respiratory virus that affects individuals of all ages; however, there is a notable lack of targeted treatments. RSV infection is associated with a range of respiratory symptoms, including bronchiolitis and pneumonia. Baicalin (BA) exhibits significant therapeutic effects against RSV infection through mechanisms of viral inhibition and anti-inflammatory action. Nonetheless, the clinical application of BA is constrained by its low solubility and bioavailability. In this study, we prepared BA nanodrugs (BA NDs) with enhanced water solubility utilizing the supramolecular self-assembled strategy, and we further conducted a comparative analysis of this pharmacological activity between free drugs and NDs of BA. Both in vitro and in vivo results demonstrated that BA NDs significantly enhanced the dual effects of viral inhibition and inflammation relief compared to free BA, attributed to prolonged lung retention, improved cellular uptake, and increased targeting affinity. Our study confirms that the nanosizing strategy, a straightforward approach to enhance drug solubility, can also increase biological activity compared to free drugs with the same content, thereby providing a potential ND for RSV treatment. This correlation analysis between the existing forms of drugs and their biological activity offers a novel perspective for research on the active ingredients of traditional Chinese medicine.

ChuanWu (CW), the dried mother root of Aconitum carmichaelii Debx., is a well-known traditional Chinese medicine (TCM) recognized for its potent efficacy but inherent toxicity, primarily due to its alkaloid content. Traditional and modern detoxification methods for CW include proper processing, rational compatibility, and specialized decoction techniques, among which honey-boiled CW is particularly distinctive. However, research on the detoxification mechanism of honey-boiled CW remains limited. This study investigated this mechanism by analyzing alkaloid transformation and supramolecular aggregation. Honey-boiled and water-boiled CW preparations were compared. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to analyze CW alkaloids, specifically diester alkaloids (DDAs), monoester alkaloids (MDAs), and non-esterified diterpenoid alkaloids (NDAs). Transmission electron microscopy was employed to observe and identify supramolecular aggregates in the honey-boiled CW decoction. In vivo absorption of water-boiled, honey-boiled, and NADES-boiled CW was compared. Median lethal dose (LD₅₀) tests assessed toxicity, including hepatotoxicity and nephrotoxicity. In vitro experiments evaluated the safety, anti-inflammatory, and analgesic effects of CW-medicated serum on RAW264.7 cells, with in vivo validation in mice. Results showed that honey promoted the conversion of highly toxic DDAs to less toxic MDAs and prevented MDAs from hydrolyzing into NDAs. Honey-boiled CW formed approximately 250 nm supramolecular aggregates that encapsulated MDAs, inhibiting their conversion to NDAs. These encapsulated MDAs acted as a stable delivery system with higher bioavailability than free benzoylmesaconine. Subsequent mouse experiments confirmed that honey-boiled CW significantly increased the LD₅₀ of CW while reducing hepatotoxicity and nephrotoxicity. Additionally, honey-boiled CW significantly improved cell safety and enhanced anti-inflammatory and analgesic effects. Our findings reveal that honey-boiled CW exhibits a potent detoxification mechanism by influencing alkaloid transformation and facilitating the formation of supramolecular aggregates. This study lays the groundwork for developing detoxification or synergistic strategies within honey-boiled TCM.

Objective:To perform adenovirus detection and genetic evolutionary analysis on specimens from a fever outbreak in Kunming city.Methods:Pharyngeal swabs from typical febrile patients were collected and tested for nucleic acids of 30 common respiratory pathogens using TaqMan Array Card technology. The full-length sequences of three important genes of adenovirus, Penton base, Hexon and Fiber, were amplified, sequenced and typed using Nanopore high-throughput sequencing. A phylogenetic tree was constructed. Molecular variations and genetic evolution of the three genes were analyzed.Results:Five specimens were collected and all of them tested positive for adenovirus and Haemophilus influenzae. The sequences of the full-length coding regions of the Penton base, Hexon and Fiber genes were obtained by Nanopore sequencing. The homology of the three gene sequences in the five specimens was 100.0%, 99.9%-100.0% and 100.0% in nucleotide sequences, and 100.0% in amino acid sequences. The three genes in the specimens had the highest homology with those of the reference strain of human adenovirus type 3 (HAdV3, accession number: AY599834) in nucleotide sequences, which was 98.6%, 98.7% and 98.9%, respectively. Results of the phylogenetic analysis of the three genes were basically consistent. These Kunming strains were clustered into an independent clade with the reference HAdV3 strain and had a distant relationship with the strains isolated in foreign countries and Taiwan, China in the early years. They were closely related to the domestic and foreign strains in recent years and highly homologous to the 2019 Japanese strain (accession: LC703523) and the Guangzhou strain (accession: MZ540961). Compared with the reference strain, these Kunming strains had five amino acid variations in Penton base, 10 in Hexon and 11 in Fiber. Conclusions:All of the adenovirus strains isolated in this outbreak belong to P3H3F3 type based on the full-length sequences of Penton base, Hexon and Fiber genes. They share high homology with the domestic and foreign HAdV3 strains, including the reference strain. Compared with the reference strain, several amino acid mutations are identified in these Kunming strains, and most of them are in the high variability region or functional regions. M7L in the Hexon protein is an unique amino acid mutation site of Kunming strains.

Brain metastasis is a common and serious complication of breast cancer, which is commonly associated with poor survival and prognosis. In particular, the treatment of brain metastasis from triple-negative breast cancer (BM-TNBC) has to face the distinct therapeutic challenges from tumor heterogeneity, circulating tumor cells (CTCs), blood-brain barrier (BBB) and blood-tumor barrier (BTB), which is in unmet clinical needs. Herein, combining with the advantages of synthetic and natural targeting moieties, we develop a "Y-shaped" peptide pVAP-decorated platelet-hybrid liposome drug delivery system to address the all-stage targeted drug delivery for the whole progression of BM-TNBC. Inherited from the activated platelet, the hybrid liposomes still retain the native affinity toward CTCs. Further, the peptide-mediated targeting to breast cancer cells and transport across BBB/BTB are demonstrated in vitro and in vivo. The resultant delivery platform significantly improves the drug accumulation both in orthotopic breast tumors and brain metastatic lesions, and eventually exhibits an outperformance in the inhibition of BM-TNBC compared with the free drug. Overall, this work provides a promising prospect for the comprehensive treatment of BM-TNBC, which could be generalized to other cell types or used in imaging platforms in the future.

Aim To investigate the effect of Bigelovii A on HepG2 cell apoptosis and its possible mechanism. Methods MTT assay was used to determine the inhibitory effect of Bigelovii A on HepG2 cells. Flow cytometry was performed to detect apoptosis. Western blot was applied to detect the expression of proteins of STAT pathway. Results BA (20 μmol L

Objective:To explore how to optimize selection, acquisition, and matching for the use of an aged donor liver.Methods:A case of 81-year-old senior donor liver transplantation performed at our institution is reported, the donor was an 81-year-old female who was brain-dead and the recipient was a 21-year-old male who underwent liver transplantation because of chronic hepatitis B complicated with hepatocellular carcinoma. Combined with the literature, the preliminary experience of age-related marginal donor liver in clinical liver transplantation was discussed.Results:The recipient recovered smoothly. Aspartate aminotransferase(AST)and glutamate-pyruvate transaminase(ALT)were 1131 U/L and 846 U/L on the first postoperative day, and decreased gradually to normal until 2 weeks later.Total bilirubin(TBIL)56.4umol/L on the first day and decreased to 22.1umol/L on the third day after operation, however, it began to rise on postoperative day 5 to a maximum of 66.0 umol/L, which decreased to normal about 2 months after surgery. During the follow-up, AST, ALT, TBIL and other indexes were normal, and AFP decreased progressively.Conclusions:Using of elderly liver donors may achieve satisfactory results, asifthe elderly donors been evaluatedcarefullyandthe low-risk recipients been selected.

BACKGROUND: Lung cancer is the leading cause of cancer-related death, and small cell lung cancer (SCLC) has a poor prognosis in all types of lung cancer. This study evaluated the relationship between pretreatment serum apolipoprotein levels and prognosis in patients with SCLC, seeks a new index can guide diagnosis and treatment of SCLC. METHODS: This study retrospectively analyzed the clinical data of 122 patients with SCLC. The clinical results of patients with serum apolipoprotein levels within 2 weeks before treatment were collected, including apolipoprotein AI (ApoA-I), apolipoprotein B (ApoB), and the ratio of apolipoprotein B to apolipoprotein AI (ApoB/ApoA-I). Patients' progression-free survival (PFS) and overall survival (OS) are the main outcome indicators. The best critical to determine the index's value by X-tile tool. For survival analysis, Kaplan-Meier method was used for analysis, and Cox regression analysis method was used for single factor analysis and multifactor analysis. RESULTS: Compared with patients with low ApoA-I levels, patients with high ApoA-I levels (ApoA-I>1.12 g/L) had better OS (21.5 mon vs 12.3 mon, P=0.007) and PFS (7.3 mon vs 5.5 mon, P=0.017). In contrast, patients with higher ApoB/ApoA-I levels had worse median OS than patients with lower ApoB/ApoA-I levels (13.4 mon vs 20.7 mon, P=0.012). Multivariate Cox regression analysis showed that ApoA-I was an independent prognostic factor affecting PFS in SCLC patients (HR=0.67, 95%CI: 0.45-0.99, P=0.043). ApoB/ApoA-I is an independent risk factor for OS in patients with SCLC (HR=1.98, 95%CI: 1.21-3.23, P=0.007). CONCLUSIONS Serum ApoA-I level and ApoB/ApoA-I level before treatment can be important prognostic factors for SCLC, which is helpful to judge the prognosis of patients.

Objective:To investigate the current status of,analyze its influencing factors and explore educational countermeasures,thus to provide evidence for establishing prevention model of medical students' soft addiction in medical colleges.Method:Using the self-designed questionnaire,a questionnaire survey related tosoft addiction was conduct among 780 medical students.The results were analyzed statistically.Results:At present,the proportion of soft addiction in medical students is relatively large.These students will affect their study and work because of the addiction to certain behaviors and have a negative impact on personal growth and self-development.Conclusion:University should pay attention to the prevention and treatment of medical students' soft addiction behavior.It should change the social concept of medical students,enhance interpersonal ability;improve their self-cultivation,stimulate the self-education;focus on time management,improve efficiency,overcome procrastination.

Objective To summary the pathological and genetic features in nine Chinese limb girdle muscular dystrophy 2I (LGMD2I) patients.Methods Nine LGMD2I patients were recruited from Peking University First Hospital between 2011 and 2016, who came from nine unrelated and non-consanguineous families.The mean age of onset was (8.2±5.2) years (2 to 19 years), and the mean disease duration was (10.4±6.1) years (1 to 24 years).There were six males and three females, present with weakness in limb girdle muscles, four of whom accompanied with calf hypertrophy and three with scapular winging.Serum creatine kinase was 964-23 131 U/L (normal 25-190 U/L).Five of them who conducted electromyogram showed myogenic pattern.Muscle biopsy and next generation sequencing were performed in these patients, then sanger sequencing was performed to determine whether the variants co-segregated with the phenotype in these families.Results Muscle biopsy revealed myopathy features in six patients, dystrophic change in one, and only mild changes in two.Major histocompatibility complex-Ⅰ was positive in six cases, and rimmed vacuoles were found in two.There were seven mutations in fukutin-related protein (FKRP) gene.A reported mutation of c.545A>G (p.Y182C) appeared in eight cases, including three homozygotes and five compound heterozygotes.The mutation of c.1067T>C (p.Ile356Thr) was reported too.And c.1263C>A (p.Tyr421X), c.534G>T(p.Thr178Cys), c.1027G>C (p.Glu343Gln), c.1027G>T(p.Glu343X), c.1448A>G (p.Tyr483Cys) were found to be novel mutations.Conclusions LGMD2I showed large variation in myopathology.The missense mutation A545G(Y182C) is a hot spot of FKRP gene in our series.

Background and objectivehTe high incidence of lung cancer in Xuanwei, China, has become an im-portant restricting factor for livelihood development, thus exerting local social and economic impacts. Coal is the main fuel of the local community and also the main source of indoor pollution. hTis study aims to explore the coal combustion inhalable ifne particulate matter (PM2.5) and its component output differences in different areas of Xuanwei, Yunnan. Moreover, the aim of this study is to investigate the relationship between inhalation of ifne particles and high incidence of local lung cancer.Meth-odsFor combustion test, coal mines designated as C1, K7 and M30 were collected from LaoLin Colliery of Laibing Town, Huchang Colliery of Baoshan Town, and Taiping Colliery of Wenxing Town in Xuanwei, respectively. PM2.5 of indoor air was weighed, analyzed for elemental composition, and morphologically compared. hTe pathological specimen of lung cancer pa-tients in Xuanwei who underwent operation was observed through electron microscope.Results hTe PM2.5 concentrations in indoor air were (8.244 ±1.460) mg/m3 (C1), (5.066±0.984) mg/m3 (K7), and (5.071±1.460) mg/m3 (M30). hTe differences among pairwise comparisons were statistically signiifcant (P=0.029). hTe iflter impurities of C1 coal seam primarily includeSi- and O-enriched compounds. Moreover, three membranes that comprised other elements, including C, S, and Si, were ob-served. hTese membranes were evident from the aggregation of silica and a Ca-Al membrane. Compared with that of other coal seams, C1 coal generated a mass of impurities, in which several particles have irregular shape. We found nanoscale ifne particles in some specimens of Xuanwei lung cancer patients.ConclusionhTe produced combustion of C1 coal was different from that of K7 and M30 coal. PM2.5 composition may be associated with the high local incidence of lung cancer.