Hemolysis is one of the main complications associated with the use of ventricular assist devices. The primary factors influencing hemolysis include the shear stress and exposure time experienced by red blood cells. In addition, factors such as local negative pressure and temperature may also impact hemolysis. The different combinations of hemolysis prediction models and their empirical constants lead to significant variations in prediction results; compared to the power-law model, the OPO model better accounts for the complexity of turbulence. In terms of improving hemolytic performance, research has primarily focused on optimizing blood pump structures, such as adjustments to pump gaps, impellers, and guide vanes. A small number of scholars have studied hemolytic performance through control modes of blood pump speed and the selection of blood-compatible materials. This paper reviews the main factors influencing hemolysis, prediction methods, and improvement strategies for rotary blood pumps, which are currently the most widely used. It also discusses the limitations in current hemolysis research and provides an outlook on future research directions.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

To determine the optimal cultivation duration and harvest period for cultivated Notopterygium incisum and promote its industrial development, this study established a characteristic chromatographic profile of cultivated N. incisum and employed chemometrics combined with entropy-weighted grey correlation analysis to assess differences in agronomic traits and quality indicators across different cultivation years and harvest periods. By comparing with reference substances, ten common peaks were identified, including chlorogenic acid, p-coumaric acid, ferulic acid, marmesinin, nodakenin, isochlorogenic acid B, notopterol, phenethyl ferulate, isoimperatorin, and falcarindiol. The similarity between the characteristic chromatographic profiles of N. incisum at different cultivation years and the reference profile was all above 0.932. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) revealed that the quality of 1-to 3-year-old cultivated N. incisum was highly dispersed and unstable, whereas the quality of 4-year-old cultivated N. incisum remained relatively stable across different harvest periods. This suggests that the accumulation of relevant compounds in the medicinal material had reached a plateau, confirming that the optimal cultivation period for N. incisum is four years. Entropy-weighted grey correlation analysis indicated that the quality of 4-year-old cultivated N. incisum across different harvest periods ranked from highest to lowest as follows: November, December, October, August, July, and September, demonstrating that November is the optimal harvest time. The findings of this study establish the suitable cultivation duration and optimal harvest period for N. incisum, providing a scientific basis for cultivation guidance and quality standardization.
Chromatography, High Pressure Liquid/methods* ; Apiaceae/chemistry* ; Entropy ; Chemometrics/methods* ; Drugs, Chinese Herbal/chemistry* ; Principal Component Analysis ; Quality Control

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery. In this study, by screening fungal extracts against coxsackievirus B3 (CVB3), three new aspochalasins, templichalasins A‒C (1‒3), along with six known aspochalasins (4‒9) were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045. Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system, while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons. Their structures were characterized through extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Additionally, we demonstrated that compound 4 can be readily converted into compounds 1‒3 under mild acidic conditions and proposed a plausible mechanism for this conversion. Bioactivity evaluation of compounds 1‒9 against CVB3 revealed the inhibitory effects of all compounds against the virus. Notably, compound 9 exhibited superior antiviral activity, surpassing the commercial drug ribavirin in selectivity index (SI) value.
Antiviral Agents/isolation & purification* ; Aspergillus/chemistry* ; Molecular Structure ; Enterovirus B, Human/drug effects* ; Endophytes/chemistry* ; Cytochalasins/isolation & purification* ; Drug Discovery ; Humans

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

Bio-mineralization has emerged as a promising strategy to enhance vaccine immunogenicity. This study optimized the calcium phosphate (CaP) mineralization process of foot-and-mouth disease virus-like particles (FMD VLPs) to achieve high mineralization efficiency and scalability. Key parameters, including concentrations of Ca²⁺, HPO₄^2-, NaCl, and VLPs, as well as stirring speed, were systematically optimized. Stability of the scaled-up reaction system and immunogenicity of the mineralized vaccine were evaluated. Optimal conditions [25.50 mmol/L Ca(NO₃)₂, 15 mmol/L Na₂HPO₄, 300 mmol/L NaCl, 0.75 mg/mL VLPs, and 1 500 r/min] yielded CaP-mineralized VLPs (VLPs-CaP) with high mineralization efficiency, uniform morphology, and a favorable particle size. Scaling up the reaction by 25 folds maintained consistent mineralization efficiency and particle characteristics. Immunization in mice demonstrated that VLPs-CaP induced higher titers of specific antibodies and neutralizing antibodies than unmineralized VLPs (P < 0.05). Higher IgG2a/IgG1 ratio and enhanced IFN-γ secretion (P < 0.05) further indicated robust cellular immune responses. We establish a stable and scalable protocol for VLPs-CaP, providing a theoretical and technical foundation for developing high-efficacy VLPs-CaP vaccines.
Vaccines, Virus-Like Particle/immunology* ; Immunogenicity, Vaccine ; Calcium Phosphates/chemistry* ; Foot-and-Mouth Disease Virus ; Biomineralization ; Particle Size ; Animals ; Mice ; Antibodies, Neutralizing/blood* ; Antibodies, Viral/blood* ; Immunity, Cellular

Vaccination is a crucial strategy for the prevention and control of infectious diseases. Virus-like particles (VLPs), composed of structural proteins, have garnered significant attention as a novel type of vaccine due to their excellent safety and immunogenicity. However, similar to most vaccine antigens, VLPs exhibit insufficient thermal stability, which not only restricts the widespread application of vaccines but also increases the risk of vaccine inactivation. This study aims to enhance the stability and shelf life of VLPs derived from type A foot-and-mouth disease virus (FMDV) by employing vacuum freeze-drying technology. The optimal lyoprotectant formulation was determined through single-factor and combinatorial screening. Subsequently, the correlation between the immunogenicity of the freeze-dried vaccine and the content of FMDV VLPs was evaluated via a mouse model. The stability of FMDV VLPs before and after freeze-drying was further assessed by storing them at 4, 25, and 37 ℃ for varying time periods. Results indicated that the lyoprotectant formulation No.1, composed of 7.5% trehalose, 0.1% Tween 80, 50 mmol/L glycine, 1% sodium glutamate, and 3% polyvinylpyrrolidone (PVP), effectively preserved the content of FMDV VLPs during the vacuum freeze-drying process. The immunization trial in mice revealed that the levels of specific antibodies, immunoglobulin G1 (IgG1), interleukin-4 (IL-4), and neutralizing antibodies induced by freeze-dried FMDV VLPs were comparable to those induced by non-freeze-dried FMDV VLPs. The heat treatment results showed that the storage periods of freeze-dried FMDV VLPs at 4, 25, and 37 ℃ were significantly longer than those of non-freeze-dried FMDV VLPs. In conclusion, the selected lyoprotectant formulation effectively improved the stability of FMDV VLPs vaccines. This study provides valuable insights for enhancing the stability of novel subunit vaccines.
Freeze Drying/methods* ; Animals ; Foot-and-Mouth Disease Virus/immunology* ; Mice ; Vaccines, Virus-Like Particle/chemistry* ; Foot-and-Mouth Disease/immunology* ; Vacuum ; Drug Stability ; Mice, Inbred BALB C ; Viral Vaccines/immunology*

Background Currently,there has been a gradual increase in the incidence of mental diseases,becoming a problem that has attracted great concern of the general public.Zhuhai is a core city of the Guangdong-Hong Kong-Macao Greater Bay Area,and the local government have attached great importance to the mental health of residents.The systematic study on the mental health has focused largely on pregnant women and medical workers,yet few are on the adult residents.Objective To investigate the prevalence and its influencing factors of anxiety and depression among adult residents in Zhuhai,so as to provide references for formulating targeted psychological intervention strategies.Methods From September 1 to December 1,2021,a cohort of 5 600 permanent residents aged 18 years and above in Zhuhai were selected through multistage sampling.All participants were subjected to complete Patients' Health Questionnaire Depression Scale-9 item(PHQ-9),Generalized Anxiety Disorder Scale-7 item(GAD-7)and National Mental Health Literacy Questionnaire based on Wenjuanxing software.Then Logistic regression was employed to identify the factors associated with anxiety and depression among the residents.Results Among the 5 600 residents,depressive symptoms were detected in 842(15.04％)residents and anxiety symptoms in 579(10.34％)residents.Logistic regression analysis yielded that female gender(OR=1.488),living in Doumen district(OR=1.942),junior college/undergraduate level(OR=3.602),postgraduate and above(OR=5.904),irregular meal pattern(OR=3.320),comorbid chronic diseases(OR=3.244),disqualification of self-assessment(OR=3.414)and disqualification of mental health skill(OR=2.131)were risk factors for depression symptoms,whereas age≥25 years old(of all age groups OR<1),monthly per capita income>20 000 yuan(OR=0.438)and exercising≥3 times a week(OR=0.431)were protective factors for depression symptoms.Age of 25～34 years old(OR=2.051),living in Jinwan district(OR=1.729)or Doumen district(OR=1.901),junior college/undergraduate level(OR=2.955),postgraduate and above(OR=6.662),irregular meal pattern(OR=2.741),comorbid chronic diseases(OR=3.535),disqualification of self-assessment(OR=3.325)and disqualification of mental health skill(OR=1.838)were risk factors for anxiety symptoms,while monthly per capita income of 6 001～9 000 yuan(OR=0.665)and exercising≥3 times a week(OR=0.572)were protective factors for anxiety symptoms.Conclusion The mental health status of adult residents in Zhuhai is affected by various factors,including gender,age,region of residence,education level,meal pattern,exercise frequency and chronic diseases.

Objective To explore the effect of pristimerin combined with cisplatin on proliferation and apoptosis of nasopharyngeal carcinoma cells.Methods CCK-8 assay was used to examine the survival rate of HNE-1 and CNE-2Z cells following treatment for 24 h with different concentrations of pristimerin,cisplatin or their combination.The changes in colony formation ability,apoptosis,and intracellular reactive oxygen species(ROS)levels of the treated cells were analyzed using colony formation assay and flow cytometry.Western blotting was performed to detect the changes in protein expressions in the cells.The effects of pre-treatment with NAC on proliferation,apoptosis,and PI3K/AKT signaling pathway were observed in pristimerin-and/or cisplatin-treated cells.Results Both pristimerin and cisplatin significantly lowered the survival rate of HNE-1 and CNE-2Z cells(P<0.05).Compared with pristimerin or cisplatin alone,their combination more strongly inhibited survival and colony formation ability of the cells,increased cell apoptosis rate and intracellular ROS levels,upregulated the protein expressions of Bax,cleaved caspase-3,and cleaved PARP,and downregulated the protein expressions of Bcl-2,Mcl-1,PARP and p-PI3K and p-AKT(P<0.05).NAC pretreatment significantly attenuated proliferation inhibition and apoptosis-promoting effects of pristimerin combined with cisplatin,and partially restored the downregulated protein expressions of p-PI3K and p-AKT in HNE-1 and CNE-2Z cells with the combined treatment(P<0.05).Conclusion Pristimerin can enhance cisplatin-induced proliferation inhibition and apoptosis in nasopharyngeal carcinoma cells,the mechanism of which may involve ROS-mediated deactivation of the PI3K/AKT signaling pathway.