ObjectiveTo explore the effects of different concentrations of oleic acid on human osteosarcoma cell lines 143B and HOS， as well as the impacts of the optimal concentration of oleic acid on cellular lipid droplet synthesis and cell functions. MethodsThe 143B and HOS cells were treated with varying concentrations of oleic acid （0， 25， 50， 100， and 200 µmol/L） for 48 hours. Following treatment， oil red O staining and BODIPY staining were performed to determine the optimal concentration. Subsequently， CCK-8 assays and colony formation experiments were conducted to assess the effect of this optimal concentration of oleic acid on the cell proliferation of both cell lines. Transwell migration assays were utilized to evaluate the influence of the optimal concentration on migratory capacity and Transwell invasion assays were utilized to evaluate the invasive ability. Additionally， Western blot analysis was employed to examine the expression levels of epithelial-mesenchymal transition （EMT） markers Epithelial cadherin （E-cadherin） and Neural cadherin （N-cadherin） in response to treatment with the optimal concentration of oleic acid. ResultsTreatment with oleic acid did not induce significant cell death in either 143B or HOS cells； however， an increase in intracellular lipid droplets was observed alongside enhanced proliferation， migration， invasion capabilities as well as EMT transformation potential （P<0.05）. ConclusionOleic acid induces lipid droplet synthesis in osteosarcoma cells which subsequently promotes their proliferation， migration and invasion abilities along with EMT transformation.

OBJECTIVE To prepare an intelligent responsive liposome-hydrogel nanopreparation co-loaded with gambogic acid （GA）， and characterize its antitumor activity in vitro . METHODS GA-ICG-Lip-gel was prepared by ethanol injection and cold dissolution， incorporating GA and the photosensitizer indocyanine green （ICG）. The appearance and microscopic morphology of GA-ICG-Lip-gel were observed， its encapsulation efficiency and drug loading capacity were measured， and its photothermal conversion performance， photothermal stability， and infrared imaging properties were investigated， along with the determination of its in vitro release profile. Human breast cancer MCF-7 cells were used as objects to investigate the effects of GA-ICG-Lip-gel （or with near-infrared light irradiation） on cell viability， migration ability， and the cellular uptake capacity of GA-ICG-Lip-gel. RESULTS GA-ICG-Lip-gel existed in a solution state at room temperature and transformed into a gel state at 37 ℃. Its microstructure was dense with small pores， and its encapsulation efficiency and drug loading were （96.07±0.86） % and （6.28±1.16） %， respectively. After exposure to near-infrared light， the temperature of GA-ICG-Lip-gel rose above 42 ℃， with no significant attenuation observed in the heating curve. The heating efficiency was dependent on both the irradiation time and drug concentration. Compared to media without gelatinase， the cumulative release rate of GA-ICG-Lip-gel increased in media containing gelatinase. In vitro studies showed that GA-ICG-Lip-gel could be efficiently taken up by MCF-7 cells； GA-ICG-Lip-gel significantly inhibited the viability and migration ability of MCF-7 cells （ P ＜0.05）， and this inhibitory effect was further enhanced under near-infrared light irradiation. CONCLUSIONS This study successfully prepares GA-ICG-Lip-gel， which exhibits favorable photothermal conversion properties and temperature/enzyme dual-responsive drug release characteristics， and demonstrates significant inhibitory effects on the proliferation and migration of breast cancer cells.

Objective:To study the changes in biliary fluid dynamics in patients with hepatolithiasis after cholecystectomy.Methods:The clinical data of 101 patients with hepatolithiasis who underwent percutaneous transhepatic scleroscopic choledochotomy for stone extraction at the First Hospital of Guangzhou Medical University from September 2021 to June 2024 were retrospectively analyzed, among which there were 47 males and 54 females with the age of (51.8±15.7) years. They were divided into two groups based on whether they had undergone previous cholecystectomy or not: cholecystectomy group ( n=53) and non-chole-cystectomy group ( n=48). The pressures in the left hepatic duct, right hepatic duct and lower end of the common bile duct were compared between the two groups, as well as the viscosity of bile at different rates of incision. Results:There were no significant differences in baseline characteristics such as gender, age, and liver function between the two groups (all P>0.05). Compared with the non-cholecystectomy group, the bile viscosity in the cholecystectomy group were significantly lower at shear rates of 1/s, 50/s, and 200/s [1/s: (8.96±1.15) mPa·s vs. (13.13±1.25) mPa·s; 50/s: (2.37±0.18) mPa·s vs. (3.59±0.34) mPa·s; 200/s: (1.82±0.13) mPa·s vs. (2.25±0.15) mPa·s], with statistically significant diffe-rences (all P<0.05). The biliary pressure in the left hepatic duct, right hepatic duct, and lower end of the common bile duct in the cholecystectomy group were significantly higher than that in the non-cholecystectomy group [left hepatic duct: (16.43±7.02) cmH 2O vs. (13.84±5.07) cmH 2O; right hepatic duct: (16.71±7.36) cmH 2O vs. (13.76±5.03) cmH 2O; lower end of the common bile duct: (14.60±6.73) cmH 2O vs. (10.58±4.84) cmH 2O] (1 cmH 2O=0.098 kPa), with statistically significant differences (all P<0.05). Conclusion:Bile viscosity decreases after cholecystectomy in patients with hepatolithiasis, whereas biliary pressure increases at the left and right hepatic ducts and at the lower end of the common bile duct, and these changes may be closely related to the mechanism of hepatolithiasis formation and recurrence.

Objective To explore the characteristics,potential challenges,and optimization paths of high-quality development policies for public hospitals in China,and to provide reference for policy formulation and implementation.Methods The 31 policy documents on high-quality development of public hospitals issued at the central and provincial levels between 2021 and 2024 were coded using Nvivo 11 software,and a three-dimensional analytical framework was constructed on the basis of the policy tools,stakeholders,and system dimensions,combining both quantitative and qualitative methods for content analysis.Results It found that the distribution of policy content in the three dimensions was characterized by stage imbalance:policy tools were mainly environmental,followed by supply,and demand;stakeholder attention was focused on public hospitals and healthcare administrations,and patient attention was low;The system dimension focused mainly on the macro level,with less distribution at the meso and micro levels.Although the unbalanced distribution of policy instruments is relevant at certain stages,the long-term structural imbalance may lead to insufficient systemic policies and weakened stakeholder synergies,and there is an urgent need to optimize the structure of instruments.Conclusions It is recommended to increase the proportion of demand-based policy instruments in policy design and dynamically adjust the synergistic application of the three types of instruments;to strengthen the attention to vulnerable stakeholders,such as patients;and to optimize the design of policies at the meso-levels and micro-levels in order to enhance the systemicity and sustainability of policy implementation.

Objective:To analyze the mediating effect of cardiovascular health status (CVH) on the association between educational level and cardiovascular disease (CVD).Methods:The participants were from Shanghai Suburban Adult Cohort and Biobank, and questionnaire survey, physical examination, blood biochemistry were conducted from 2016 to 2020 for baseline information collection, and follow up was conducted until March 31, 2024 based on the medical data, CVD incidence data and death surveillance data at different levels. The associations of educational level, CVH and time to CVD onset of the study population were analyzed using the accelerated failure time model to analyze the mediating effects of CVH, health behaviors, and health factors in the association of educational level and time to CVD onset. The mediating effects of educational level, gender, and age moderated associations were also analyzed.Results:A total of 57 312 participants were included, with 2 780 new cases of CVD during a median follow-up of 6.71 (6.71-6.72) years, and a mean incidence density of 7.77/1 000 person-years (95% CI: 7.48/1 000 person-years -8.06/1 000 person-years). In total, the less educational level and the lower CVH, the higher CVD incidence density ( P<0.05). The results of accelerated failure time models showed that the time ratio for CVD-free survival was 1.15 (95% CI: 1.06-1.24) and 1.33 (95% CI: 1.10-1.60) for moderate and high educational level, respectively. The results of the mediation effect analysis showed that the association between moderate and high educational level and time to CVD onset was 29.60% (20.50%-50.00%) and 36.10% (23.80%-59.00%), 9.97% (5.07%-20.00%) and 13.84% (6.84%-29.00%), 15.24% (9.64%-27.00%) and 17.55% (11.58%-33.00%) of mediators mediated by CVH, health behaviors, health factors, respectively. Among them, there was an exposure-mediated interaction of educational level and a positive moderating effect of age. Conclusion:CVH, health behaviors and health factors had a proportionate mediating effect in the association between educational level and risk of CVD development.

OBJECTIVES: To evaluate the short-term clinical efficacy of transcatheter edge-to-edge repair (TEER) in patients with moderate to severe mitral regurgitation. METHODS: Clinical data of patients with moderate to severe mitral regurgitation who underwent TEER in the Department of Cardiology, the First Affiliated Hospital of Xi'an Jiaotong University from April 2021 to May 2024, were retrospectively analyzed, including preoperative baseline clinical and echocardiography data, intraoperative data and 6-month postoperative follow-up data. RESULTS: A total of 67 patients' (47 males and 20 females) data were included, of whom 62 completed 6-month follow-up. The immediately postoperative success rate was 88.1% (59/67), and 83.9% (52/62) patients exhibited mitral regurgitation ≤2+ at 6 months postoperatively, showing significant improvement compared with preoperative (P<0.05). The proportion of patients with mitral regurgitation ≤2+ at 6 months was significantly higher in the degenerative mitral regurgitation (DMR) group than that in the functional mitral regurgitation (FMR) group (P<0.05). The mean mitral valve gradient (MVG) in DMR group was increased from (3.1±1.2) mmHg (1 mmHg=0.133 kPa) to (3.7±1.2) mmHg 6 months after operation (P<0.05), while there was no significant change in FMR group (P>0.05). Compared with those before operation, the N-terminal pro-B-type natriuretic peptide levels in both FMR and DMR groups were significantly lower at 6 months postoperatively (all P<0.05), and the left atrial volume index and left atrial anteroposterior diameter were also significantly lower (all P<0.05). The left ventricular end-diastolic diameter and left ventricular end-systolic diameter were significantly reduced 6 months after operation in the FMR group (all P<0.05), but no significant changes were observed in the DMR group (all P>0.05). The ejection fraction was not significantly changed before and after operation in both groups (all P>0.05). The mitral regurgitation, tricuspid regurgitant, and pulmonary artery pressure were significantly reduced in both groups at 6 months postoperatively (all P<0.05). CONCLUSIONS TEER is effective for moderate to severe mitral regurgitation. The improve-ments in left ventricular remodeling are more pronounced in patients with FMR while the degree of mitral regurgitation is more significant in DMR patients. However, MVG elevation is more common during the follow-up.
Humans ; Mitral Valve Insufficiency/surgery* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Treatment Outcome ; Mitral Valve/surgery* ; Cardiac Catheterization/methods* ; Heart Valve Prosthesis Implantation/methods* ; Adult ; Follow-Up Studies

Objective: To analyze the demographic characteristics of patients with red blood cell transfusion reactions, the usage of red blood cell preparations, and the differences in the composition ratio of adverse reactions based on multi-center data from the Haemovigilance Network, in order to reveal the clinical characteristics of red blood cell transfusion and its underlying issues. Methods: Clinical data of patients who experienced transfusion reactions after red blood cell transfusion in the Haemovigilance Network from 2018 to 2023 were collected. The demographic characteristics of patients who experienced transfusion reactions with different types of red blood cell preparations, the utilization of these preparations, and the differences of the composition ratios of transfusion reactions were analyzed. Count data were expressed as numbers (n) or percentages (%), and comparisons between groups were performed using the Chi-square test. Results: Red blood cell transfusion reactions were more common in females (53.56%), with the majority of patients aged 50-69 years (35.54%). The Han polulation accounted for the vast majority of patients (92.77%), and patients in the hematology and obstetrics/gynecology departments had a relatively high proportion of transfusion reactions (13.26% and 14.26%, respectively). Leukocyte-reduced red blood cells and suspended red blood cells were the most common types of transfusion reactions reported among red blood cell preparations. Allergic reactions and non-hemolytic febrile reactions were the most common transfusion reactions, and there were significant differences in the composition ratios of allergic reactions (χ =869.89, P<0.05) and non-hemolytic febrile reactions (χ =812.75, P<0.05) across various types of red blood cell preparations. Conclusion: There are differences in the demographic characteristics and composition ratio of transfusion reactions among different red blood cell preparations. The management of red blood cell transfusion reactions should be tailored to patient characteristics and conditions, and the selection and use of blood products should be optimized to reduce or avoid the occurrence of transfusion reactions, such as considering the use of washed red blood cells for patients with a history of transfusion allergies or those prone to allergies.

OBJECTIVE To explore the practice pathway and evaluate the effectiveness of the resident pharmacists stationed in the Drug Clinical Trial Institution Office （hereinafter referred to as the “GCP resident pharmacist”） in the management of dermatological drug clinical trials. METHODS The practical approach of GCP resident pharmacists participating in dermatological drug clinical trials at our hospital was introduced. A retrospective analysis was conducted on the data of dermatological drug clinical trials from 2021 to 2024， comparing efficiency and quality indicators between dermatological clinical trials and those of other specialties. RESULTS With the involvement of our hospital’s GCP resident pharmacists throughout, the process for dermatology drug clinical trials was constructed and optimized， a dedicated quality control system was established， and the acceleration strategy for subject enrollment was optimized. The number of dermatological drug clinical trials at our hospital showed a compound annual growth rate of 69.56% from 2021 to 2023. In terms of efficiency indicators， the approval waiting time for dermatological drug clinical trials was （12.31±4.99） days， which was significantly shorter than that of other specialties （[ 19.68±6.09） days， P＜0.05]. Regarding quality indicators， the enrollment rate for dermatological drug clinical trials was 75.71%（50.00%，114.48%）， which was significantly higher than that of other specialties [51.00%（25.00%，174.17%）， P＜0.05]. The numbers of first quality control issues （[ 8.31±3.25）items vs.（ 11.68±4.49）items] and protocol deviations [5.5（2.0，11.0）times vs. 11.0（5.5，17.5）times] were significantly lower than those of other specialties （P＜0.05）. CONCLUSIONS GCP resident pharmacists significantly enhance the overall efficiency of dermatological drug clinical trials， playing a crucial role in ensuring the reliability and authenticity of drug clinical trials， as well as safeguarding the rights and safety of trial subjects.

Objective To analyze the characteristics of real-world adverse drug events(ADEs)of trabectedin based on the FDA Adverse Event Reporting System(FAERS)database in order to provide references for clinical drug safety management.Methods A total of 1 349 trabectedin-related reports were extracted from the FAERS database from Q1 2007 to Q4 2024.Using the MedDRA coding classification system for system organ class(SOC)and preferred term(PT),signal detection was performed through 4 proportional imbalance methods,including reporting odds ratio(ROR)and proportional reporting ratio(PRR).Subgroup analyses by gender,age,and temporal trends were also conducted.Results Hematological and lymphatic system disorders and hepatobiliary system disorders were the primary SOCs involved.High-frequency PTs included neutropenia(123 cases)and anemia(117 cases).Eight potential ADEs that have not been listed in the drug product instruction were identified.The median onset time of ADEs was 21 d,showing an early failure pattern,with differences observed by gender(females more prone to hematological toxicity)and age(elderly more susceptible to febrile neutropenia).Conclusion Trabectedin requires close attention to hematological toxicity,hepatotoxicity,and newly identified multi-system potential risks.Clinically,monitoring should be strengthened based on time windows and population characteristics to optimize drug regimens.Countermeasure It is recommended to strengthen the full cycle monitoring of anti-tumor drugs,standardize the reporting of adverse reactions,and establish a multi-departmental collaborative research platform.

Objective To investigate the therapeutic effects and underlying mechanisms of rutaecarpine on Helicobacter pylori(Hp)-induced chronic atrophic gastritis(CAG).Methods An Hp-induced CAG rat model was established.Successfully modeled rats were randomly divided into model group,low-dose rutaecarpine group,medium-dose rutaecarpine group,and high-dose rutaecarpine group,with 12 rats in each group.An additional 12 rats served as the normal control group.Body mass changes were recorded before and after treatment.Gastric mucosal histopathology was analyzed using hematoxylin-eosin(HE)staining.Levels of inflammatory cytokines(TNF-α,IL-6,IL-10)in gastric mucosal supernatants were measured by enzyme-linked immunosorbent assay(ELISA).mRNA expression levels of inducible nitric oxide synthase(iNOS),cluster of differentiation 86(CD86),arginase 1(Arg-1),and mannose receptor(CD206)in gastric mucosal tissues were detected by real-time quantitative polymerase chain reaction(RT-qPCR).Protein expression levels of nuclear factor κB(NF-κB)pathway-related proteins were determined by Western Blot.Results Compared with the normal group,the model group exhibited disorganized gastric mucosal epithelium,reduced glandular structures in the lamina propria,significant inflammatory cell infiltration,and elevated gastric mucosal histopathology scores.TNF-α,IL-6,and IL-10 levels in gastric mucosal supernatants,iNOS and CD86 mRNA expression,and phosphorylated NF-κB inhibitor α(p-IκBα)and phosphorylated NF-κB p65 subunit(p-p65)protein levels were significantly increased,while Arg-1 and CD206 mRNA expression were significantly decreased,the difference being statistically significant(P＜0.05).Compared with the model group,medium-and high-dose rutaecarpine treatment reduced inflammatory cell infiltration,restored cellular arrangement,increased glandular structures in the lamina propria,and significantly lowered gastric mucosal histopathology scores,TNF-α,IL-6,and IL-10 levels,iNOS and CD86 mRNA expression,and p-p65 and p-IκBα protein expression were significantly reduced,whereas Arg-1 and CD206 mRNA expression were significantly increased,the difference being statistically significant(P＜0.05),with dose-dependent effects.Conclusion Rutaecarpine ameliorates Hp-induced CAG by modulating macrophage polarization and attenuating inflammatory responses,likely through downregulation of p-p65 and p-IκBα expression and subsequent inhibition of NF-κB pathway activation.