Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.

ObjectiveTo analyze the adverse reactions associated with the clinical use of Banxia （Rhizoma Pinelliae）- Wutou （Aconitum） in the same formula， with the aim of providing a reference for the safety of their clinical application. MethodsLiterature on the clinical application of antagonistic herbs "Banxia-Wutou" used in the same formula， published from January 1st， 2014， to June 30th， 2023， was retrieved from databases including CNKI， VIP， Wanfang， SinoMed， PubMed， Cochrane Library， and Embase. A database was established， and information related to adverse reactions was extracted， including descriptions， classifications， specific manifestations， management and outcomes， patients' primary diseases （western medicine diseases and traditional Chinese medicine diagnoses and syndromes）， and medication information （dosage， ratio， administration routes， and dosage forms）. ResultsA total of 79 researches simultaneously used antagonistic herbs Banxia-Wutou in the same formula and reported associated advers reactions. Gastrointestinal adverse reactions were the most common， with 8 studies reporting management of adverse reactions and 3 studies reporting improvement with no intervention. Among the 11 researches， the adverse reaction relieved to extant， while other 69 researches didn't report the managment of adverse reaction and its prognosis. For the primary disease in western medicine system， chronic bronchitis and chronic obstructive pulmonary disease （COPD） were most common， while gastric pain was the most common symptom in traditional Chinese medicine with spleen and kidney deficiency and spleen stomach cold deficiency being the most frequent syndromes. The most common Banxia dosage was 10 g， while for the Wutou， Fuzi （Radix Aconiti Lateralis Praeparata） was predominant with the highest dose at 15 g. The most frequent herbal combination was Banxia-fuzi， with a 1∶1 ratio. The main administration route was oral， and the primary dosage form was decoction. ConclusionGastrointestinal adverse reactions are the most common in the clinical use of Banxia-Wutou antagonistic herb combinations. Research on the safety of "Banxia-Wutou" combinations should focus on respiratory system diseases and spleen-stomach related conditions.

Objective:To investigate the effects and possible mechanisms of targeted inhibition of Polo-like kinase 1 (PLK1) on the proliferation, mitosis and apoptosis of cervical cancer cells.Methods:Logarithmically growing human cervical cancer cell lines HeLa and C-33A were selected, and cells treated with 10 and 20 nmol/L PLK1 inhibitor GSK461364 were used as different concentrations of GSK461364 groups, while cells not treated with GSK461364 were used as the control group. CCK-8 method was used to detect cell proliferation ability (represented by absorbance values at wavelength 450 nm), flow cytometry was used to detect chromosome ploidy (propidium iodide staining), mitochondrial membrane potential detected by flow cytometry was used to evaluate cell apoptosis status (JC-1 fluorescent probe, the cells where the JC-1 monomers emitting green fluorescence were located were apoptotic cells), and Western blotting was used to detect the expression levels of cell cycle and apoptosis-related proteins.Results:The results of CCK-8 method showed that the proliferation ability of HeLa cells was lower than that of the control group after 24 hours of treatment with 10 and 20 nmol/L GSK461364 and continued culture for 24, 48 and 72 hours without GSK461364. The proliferation ability of C-33A cells was lower than that of the control group after 24 hours of treatment with 10 and 20 nmol/L GSK461364 and continued culture for 48 and 72 hours without GSK461364, and the differences were statistically significant (all P < 0.05). The results of flow cytometry analysis showed that after 24 hours of treatment with GSK461364 and continued culture for 72 hours without GSK461364, the proportions of polyploid cell subpopulations in HeLa cells of the 10 and 20 nmol/L GSK461364 groups and the control group were (13.89±3.73)%, (12.30±5.49)% and (9.86±1.15)%, respectively, with no statistically significant difference ( F = 0.82, P > 0.05); the proportions of polyploid cell subpopulations in C-33A cells of the 10 and 20 nmol/L GSK461364 groups and the control group were (8.45±2.20)%, (11.06±2.53)% and (5.42±1.36)%, respectively, with statistically significant difference ( F = 5.46, P = 0.045). Among them, the proportion of polyploid cell subpopulations in the 20 nmol/L GSK461364 group was higher than that in the control group, with statistically significant differences ( t = 3.40, P = 0.027). The results of flow cytometry detection of mitochondrial membrane potential showed that after 24 hours of treatment with GSK461364 and continued culture for 72 hours without GSK461364, the proportions of apoptotic cells in HeLa cells of the control group, 10 nmol/L GSK461364 group and 20 nmol/L GSK461364 group were (3.96±2.28)%, (24.38±4.89)%, and (46.24±4.38)%, respectively, and the difference was statistically significant ( F = 83.18, P < 0.000 1), the proportion of apoptotic cells in the 10 and 20 nmol/L GSK461364 groups was higher than that in the control group, and the difference was statistically significant (both P < 0.01), and the proportion of apoptotic cells in the 20 nmol/L group was higher than that in the 10 nmol/L group ( t = 5.76, P = 0.005); the proportions of apoptotic cells in C-33A cells of the control group, 10 nmol/L GSK461364 group and 20 nmol/L GSK461364 group were (1.81±1.59)%, (5.22±1.57)% and (15.87±5.81)%, respectively, with statistically significant differences ( F = 12.49, P = 0.007), and the proportion of apoptotic cells in the 20 nmol/L group was higher than that in the 10 nmol/L group and the control group (both P < 0.05). The results of Western blotting analysis showed that after 24 hours of treatment with GSK461364 and continued culture for 72 hours without GSK461364, the relative expression levels of cleaved Caspase-9 and cleaved polyadenosine diphosphate-ribose polymerase in HeLa and C-33A cells treated with 10 and 20 nmol/L GSK461364 were higher than those in the control group, and the relative expression levels of cdc25c and phosphorylated cdc25c (Ser216) were lower than those in the control group, and the differences were statistically significant (all P < 0.05). Conclusions:Targeted inhibition of PLK1 can inhibit the proliferation activity of cervical cancer cells in vitro, induce cell mitotic cycle arrest, and promote cell apoptosis; these may be achieved by regulating cell cycle and apoptosis-related proteins.

Objective:This study aims to explore the risk factors of Multi-center Investigator-Initiated Clinical Trials (MIITs), and provide a basis for developing study management strategies.Methods:The original draft of MIIT risk evaluation factors was determined through literature analysis and internal discussions of the research group. Thirty five experts were consulted using the Delphi method, and then the MIIT risk evaluation elements were finally determined. Analytic Hierarchy Process (AHP) was used to calculate the weights of each index.Results:The recovery rates of both rounds of expert consultation were 100%, and the degree of expert authority was 0.856. The study ultimately formed an MIIT risk evaluation framework consisting of three first-class indexes, twelve second-class indexes, and thirty-eight third-class indexes. The weight values of the first-class indexes (start-up period, implementation period, and summary period) were 0.209 8, 0.710 6, and 0.079 6, respectively. Meanwhile, the weight values of the second-class indexes and third-class indexes were determined.Conclusions:Exploring the risk evaluation factors of MIIT provides valuable insights into identifying critical risk points, which, in turn, contributes to enhancing MIIT management efficiency, research progress, and quality.

This paper systematically reviews the phased development history of spacesuit technology across various nations,analyzes its core technologies and breakthroughs,points out the limitations of current spacesuit technology,and explores future directions for spacesuit development in response to deep-space exploration and commercialization demands.It clarifies that spacesuits are transitioning from passive protective gear to intelligent operational platforms,requiring interdisciplinary innovations to overcome key challenges such as lightweight design,adaptive systems,high reliability,and efficient human-machine interaction.

When conducting extravehicular activities under low-gravity conditions like on the moon,the weight of the spacesuit is one of the loads that human body has to bear.The centroid position of the spacesuit will affect the motion control of the human-spacesuit system.In order to reveal the influence of the centroid position of the lunar spacesuit on human motion under lunar-gravity,a suspended 1/6 gravity simulation system was used for the experiment.When subjects were under different load centroids which include front and back on sagittal plane,left and right on coronal plane,up and down on cross-section plane,near to coordinate origin,the postures and plantar pressures of subjects during three typical movements:standing,single-knee standing and walking were captured.Inverse dynamics solution is adopted to analyze the joint torques of human body in above conditions.Combined with the subjective evaluation,the appropriate load centroid area was analyzed by comparative.The experiment shows that,human is non-sensitive to the up and down change of load centroid,the after is back change,the front and right load centroid are the mostly avoided.The results obtained by this study will provide a reference for the layout design of the lunar spacesuit.

Objective:To analyze mortality risk factors in patients with severe pneumonia and investigate their varying influences across different time periods.Methods:A total of 134 patients with severe pneumonia admitted to the Emergency Department of Xiang’an Hospital, Xiamen University, between June 2019 and February 2020 were enrolled. All patients were treated in the EICU and followed up for four years. Based on outcomes, they were categorized into a death group ( n=77) and a survival group ( n=57). COX regression analysis was employed to identify mortality risk factors at different time points, while logistic regression analysis was used to assess risk factors influencing mortality during hospitalization, ICU stay, 1-month, and 1-year follow-up periods. Results:Mortality rates were 11.9% ( n=16) during ICU admission, 20.8% ( n=28) during hospitalization, 16.4% ( n=22) within 1 month, and 31.3% ( n=42) within 1 year. By the end of the follow-up, 57.4% ( n=77) of patients had died. Ten mortality risk factors were identified, with the number increasing over time. During ICU admission and hospitalization, significant risk factors included total bilirubin levels, APACHE-II score, invasive ventilation, ARDS, and vasopressor use in the ICU. One-month mortality risk additionally involved bacterial infection. One-year mortality risk further incorporated advanced age and chronic heart failure. By the end of follow-up, acute kidney injury (AKI) during ICU admission also emerged as a contributing factor, while higher body weight was identified as a protective factor. Conclusions:The number of mortality risk factors in severe pneumonia patients increases progressively over time. Early-stage factors during hospitalization and ICU admission exert a stronger impact on short-term mortality, whereas bacterial infection, advanced age, and chronic heart failure become increasingly significant in later stages. These findings highlight the dynamic nature of risk factors and underscore the importance of tailored monitoring and intervention strategies at different disease phases.

Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence on the biological effects of formulations.In this study,we reevaluated the delivery effect of CH using widely applied lipid microspheres(LM)as a model DDS.We conducted comprehensive in-vestigations into the impact of CH on the distribution,cell uptake,and protein corona(PC)of LM at sites of cardiovascular inflammatory injury.The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage.Then,the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy.Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma(PPAR-γ)expression in vascular endothelial cells and estrogen receptor alpha(ERα)protein levels in myocardial cells,thereby enhancing LM uptake at cardiovascular inflam-mation sites.Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V(Apoa5);this may be a major contributing factor to their prolonged circu-lation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites.It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations.The findings enhance the conceptualization of CH and LM delivery,providing novel strategies for investigating prescription factors' bioactivity.

Objective To analyze the distribution and drug resistance patterns of pathogenic bacteria in bile and blood cultures obtained from patients with biliary stones accompanied by acute biliary tract infection,to evaluate the clinical appropriate-ness of antibiotic use based on drug sensitivity results,and to provide evidence for empirical antibiotic treatment in such patients.Methods The clinical data of 161 patients with biliary calculi complicated by acute biliary tract infection who were admitted to the First People's Hospital of Neijiang from 2017 to 2023 were retrospectively analyzed.The results of microbial culture,drug sensitivity analysis,and patient characteristics were assessed to evaluate the appropriateness of clinical antimicrobial therapy.Results Among the 161 patients with positive cultures,212 strains of pathogenic bacteria were detected.The predominant patho-gens were Escherichia coli,Klebsiella pneumoniae subspecies,and Enterococcus faecium.Age and underlying diseases significantly affected the distribution of Escherichia coli and Klebsiella pneumoniae subspecies.Within the gram-negative bacterial group,Esche-richia coli and Klebsiella pneumoniae subspecies exhibited higher drug resistance to commonly used broad-spectrum penicillin,third-generation cephalosporin and quinolones but lower resistance rates to piperacillin and tazobactam;furthermore,elderly indi-viduals aged ≥65 years showed higher resistance rates to ceftriaxone than those under age 65 while people with drug exposure history had higher ceftazidime resistance rates that were statistically significant.In contrast to Enterococcus faecalis which displayed low antimicrobial resistance rates for most drugs tested in this study,Enterococcus faecium demonstrated high levels of antibiotic resistance;however,both Enterococcus faecalis and Enterococcus faecium exhibited zero-resistance rates against vancomycin and tigecycline although this may be attributed to their small sample size in our study cohort.Finally,we found that empirical anti-in-fective drugs,as well as target anti-infective drugs,were not prescribed rationally among these patients due mainly to inappropriate combinations of antibiotics or incorrect dosages.Conclusions The predominant pathogens in patients with acute biliary tract infection are gram-negative bacteria,Gram-positive bacteria,and fungi;however,the potential involvement of anaerobic bacteria should not be overlooked.Vancomycin exhibits sensitivity against gram-positive bacteria,yet the overall rationality of antibiotic usage remains suboptimal.Enhanced clinical testing for pathogenic microorganisms is imperative in the management of biliary stones accompanied by acute biliary tract infection.In contrast,clinical pharmacists should provide comprehensive training on anti-infective drugs to clinicians to facilitate their judicious selection of antibiotics based on drug sensitivity results and prevent the e-mergence of multidrug-resistant bacteria.

Background and Aims:Acute inferior vena cava thrombosis(IVCT)commonly occurs secondary to inferior vena cava filter(VCF)implantation.If not promptly treated,it may lead to serious complications such as bilateral lower limb swelling and pulmonary embolism and can also reduce the likelihood of successful filter retrieval.Percutaneous mechanical thrombectomy(PMT)and catheter-directed thrombolysis(CDT)are currently the main interventional treatments for IVCT,but comparative studies evaluating their efficacy and safety remain limited.This study was to conduct a prospective randomized controlled trial to compare the clinical efficacy and safety of AngioJet mechanical thrombectomy versus conventional CDT in the treatment of acute IVCT and to explore factors influencing filter retrieval rates,thereby providing evidence-based guidance for clinical decision-making.Methods:From January 2022 to December 2024,patients diagnosed with acute IVCT following VCF implantation were prospectively enrolled at the Department of Vascular Surgery,Beijing Jishuitan Hospital,Capital Medical University.Patients were randomly assigned to either the CDT group(n=46)or the PMT group(n=48)according to the interventional procedure used.The two groups were compared in terms of filter retrieval rates,thrombus clearance outcomes,operative time,thrombolytic drug dosage,and incidence of complications.Logistic regression analysis was used to identify factors associated with primary filter retrieval.Results:A total of 94 patients were enrolled,with 46 in the CDT group and 48 in the PMT group.Compared to the CDT group,the PMT group demonstrated a significantly higher primary filter retrieval rate(77.1%vs.43.5%),grade Ⅲ thrombus clearance rate(70.8%vs.37.0%),and better postoperative thrombus scores.Additionally,the PMT group required lower urokinase doses and shorter thrombolysis duration(all P<0.05).The overall filter retrieval rate and 3-month IVC patency were similar between groups,both exceeding 93%.Regarding safety,the CDT group had a higher incidence of catheter-related infections and medical adhesive-related skin injury,while vagal reflex symptoms were more frequent in the PMT group.Logistic regression analysis identified thrombus clearance rate as an independent factor significantly associated with primary filter retrieval in the PMT group(OR=190.773,P<0.05).Conclusion:Compared to CDT,AngioJet mechanical thrombectomy combined with manual aspiration achieves higher thrombus clearance and primary filter retrieval rates in the treatment of acute IVCT while also reducing thrombolysis duration and drug dosage.However,attention should be paid to the increased risk of vagal reflex symptoms.There was no significant difference between the two groups in secondary filter retrieval rates or long-term IVC patency.The choice of intervention should be based on the patient's condition,timing of filter retrieval,and individualized clinical considerations.