OBJECTIVE: To investigate the therapeutic potential of octaarginine (R8)-modified essential oil from Fructus Alpiniae zerumbet (EOFAZ) lipid microspheres (EOFAZ@^R8LM) for cardiovascular therapy. METHODS: EOFAZ@^R8LM was developed by leveraging the volatilization of EOFAZ and integrating it with the oil phase of LM, followed by surface modification with cell-penetrating peptide R8 to target the site of vascular endothelial injury. The therapeutic effects of this formulation in alleviating lipopolysaccharide-induced vascular endothelial inflammation were evaluated by assessing mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels, as well as inflammatory factors interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels. RESULTS: EOFAZ@^R8LM effectively delivered EOFAZ to the site of injury and specifically targeted the mitochondria in vascular endothelial cells, thereby ameliorating mitochondrial dysfunction through regulation of MMP and reduction of intracellular ROS levels. Moreover, it attenuated the expression levels of IL-6 and IL-1β, exerting protective effects on the vascular endothelium. CONCLUSION Our findings highlight the significant therapeutic potential of EOFAZ@^R8LM in cardiovascular therapy, providing valuable insights for developing novel dosage forms utilizing EOFAZ for effective treatment against cardiovascular diseases.

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 analyze the distribution characteristics of 13 common respiratory pathogens in children in Zibo area from 2020 to 2022.Methods A total of 3091 hospitalized children with respiratory infections admitted to Zibo Maternal and Child Health Hospital from January 2020 to December 2022 were selected as the subjects.Throat swabs or bronchoalveolar lavage fluid samples were collected from the patients,and 13 common respiratory pathogens were tested to analyze the distribution differences among different genders,ages,and seasons.Results Among 3091 pediatric patients,1794 were found to be infected with pathogens.The top three pathogens were Mycoplasma pneumoniae,rhinovirus,and respiratory syncytial virus(RSV).The single infection rate was 47.75％,while the mixed infection rate was 10.28％,with the most common scenario being a mixed infection of two pathogens.There were statistically significant differences in the pathogen profiles across different age groups(P＜0.001):infants had the highest detection rate of RSV,young children were primarily infected with rhinovirus,preschool and school-age children were predominantly infected with Mycoplasma pneumoniae.Seasonal distribution showed that the highest positive rate was in autumn,while the lowest was in spring(P＜0.05).In spring,the main pathogens were rhinovirus and Mycoplasma pneumoniae;in summer,they were rhinovirus and parainfluenza virus;in autumn,they were Mycoplasma pneumoniae and RSV;and in winter,the detection rates of Mycoplasma pneumoniae and influenza B virus were higher.Conclusion From 2020 to 2022,Mycoplasma pneumoniae,rhinovirus and RSV were the main pathogens of children's respiratory tract infection in Zibo area,and there were significant differences in the distribution of pathogens among different ages and seasons.

Objective:To explore the effectiveness of digital health management in the management of community patients with essential hypertension comorbid with somatization symptom disorder.Methods:This was an intervention-controlled study. Patients with essential hypertension comorbid with somatization symptom disorder who visited the outpatient clinic of Jiangwan Town Community Health Service Center in Hongkou District, Shanghai from January to December 2022 were enrolled. Based on the time of initial diagnosis, patients were divided into a digital health management group (initial diagnosis from January to June 2022) and a control group (initial diagnosis from July to December 2022). Baseline clinical data were collected. The control group received conventional interventions, while the digital health management group utilized the Health Cloud APP 5.3.11 platform for online digital health management without altering the original medication regimen. The intervention lasted for 24 weeks. Before and after the intervention, the Somatization Symptom Scale (SSS), 9-item Patient Health Questionnaire (PHQ-9), and 7-item Generalized Anxiety Disorder Scale (GAD-7) were used to assess somatization symptoms, depression, and anxiety, respectively. The reduction rate in SSS scores was calculated, and blood pressure and heart rate were measured. The evaluation criteria for somatization symptom intervention effectiveness were as follows: at the endpoint of the intervention, SSS ≤29 or a reduction rate of SSS ≥ 75% was considered "cured"; a reduction rate of 50% to <75% was considered "markedly effective"; a reduction rate of 25% to <50% was considered "effective"; and a reduction rate of <25% was considered "ineffective".The overall effectiveness rate=(number of cured patients + number of markedly effective patients + number of effective patients)/total number of patients × 100%.Results:A total of 62 patients in the digital health management group and 65 patients in the control group were included in the final analysis. The mean age of the digital health management group was (50.5±3.5) years, with 30 males (48.4%), while the mean age of the control group was (50.2±3.2) years, with 31 males (47.7%). There were no statistically significant differences in the age or gender distribution between the two groups (both P>0.05). Before the intervention, there were no significant differences between the two groups in SSS sub-item scores, total SSS scores, PHQ-9 scores, GAD-7 scores, blood pressure, or heart rate (all P>0.05). After 24 weeks of intervention, all scores decreased in both groups, and did blood pressure and heart rate (all P<0.05). The differences in SSS sub-item scores, total SSS scores, PHQ-9 scores, GAD-7 scores, blood pressure, and heart rate before and after the intervention were greater in the digital health management group than in the control group (all P<0.05). The proportion of patients with effective intervention for somatization symptom was higher in the digital health management group than in the control group (57 cases (91.9%) vs. 38 cases (58.5%), P<0.001). Conclusion:Digital health management can improve somatization symptom disorder, blood pressure, and heart rate in patients with hypertension.

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.

Objective:This study aims to construct an evaluation index system suitable for the core competency of Clinical Research Coordinators (CRCs) in Investigator-Initiated Trials (IITs) in China.Methods:This study developed a system framework through the Onion Model, literature research, and expert interviews, utilized the Delphi method to build the index system. and analyzed the weight of each indicator through the Analytic Hierarchy Process (AHP).Results:Four first-level indicators were basic knowledge (0.143), job skills (0.300 8), professional quality (0.483 9), and personality traits (0.072 3). Besides, 18 second-level indicators and 49 third-level indicators were developed through the Delphi method. According to the third round expert′s consultation, the average scores of all indexes were >3.50, the authoritative coefficient was 0.86, the coefficient of variation of each index was <0.30, and Kendall coefficients of concordance were 0.183~0.366 ( P<0.001). The consistency ratios of single-sort were<0.1, and the overall sort of all indexes was 0.043 7, which showed good logical reliability. Conclusions:This evaluation index system for Clinical Research Coordinators is of great scientific sense. It provides IIT-conducting investigators in institutions with a proficient assessment tool to help them find qualified and reliable CRCs.

Objective:To investigate the ultrasonographic features and risk factors of patients with papillary thyroid carcinoma（PTC）located in the isthmus of the thyroid gland combined with lymph node metastasis（LNM）.Methods:A retrospective analysis was performed on a cohort of 614 patients diagnosed with isthmic PTC through postoperative pathological confirmation at Zhejiang Cancer Hospital between January 2020 and June 2024. The patients were divided into the LNM group（ n=225）and non-LNM（ n=389）based on the pathological results. The baseline information and ultrasound characteristics of the nodules were compared between the two groups. The risk factors associated with the development of LNM in patients with isthmus PTC were explored using univariate and multivariate Logistic regression analysis. The predictive performance was analyzed using ROC curve. Results:Comparison of the baseline information revealed that the age，maximum diameter of the cancerous lesion，gender were statistically different between LNM group and non-LNM group（all P<0.05）. Comparison of thyroid nodule ultrasound characteristics showed that there were statistically significant differences in boundary，aspect ratio，calcification，and color Doppler blood flow imaging（CDFI）grades between the two groups（all P<0.05）. Univariate and multifactorial Logistic regression analyses showed that the maximum diameter of the cancer foci（ OR=1.180，95% CI=1.119-1.244），gender is female（ OR=1.798，95% CI=1.187-2.723），and microcalcification（ OR=1.509，95% CI=0.183-12.441）were the factors affecting LNM of the isthmus PTC. The AUC value of the model used to predict the occurrence of LNM in isthmus PTC was 0.756（95% CI=0.717 - 0.795），with a sensitivity of 75.8% and a specificity of 63.6%. Conclusions:The maximum diameter of the cancer foci，microcalcification and gender female were independent risk factors for the occurrence of LNM in patients with thyraid isthmus PTC. The model constructed based on the above characteristics has a better predictive performance for thyroid isthmus PTC with LNM，and patients with the above high-risk character istics should be more vigilant.

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.