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 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.

AIM:To investigate the impact of mitochondrial carrier homologous protein 2(MTCH2)on the metastasis of oral squamous cell carcinoma and to elucidate its underlying mechanisms.METHODS:Human tongue squamous cell carcinoma CAL-27 cells were selected as the study model.An MTCH2 inhibition and overexpression model was established using small interfering RNA(siRNA)technology and overexpression plasmids.Based on the experimental design,cells were categorized into the following groups:siRNA negative control(siRNA-NC)group,MTCH2 siRNA(siRNA-MTCH2)group,empty vector(OE-NC)group,and MTCH2 overexpression(OE-MTCH2)group.Transwell as-says and wound healing assays were conducted to assess the invasion and migration capabilities of cells in each group.The morphological changes and distribution of actin microfilaments were examined using a red fluorescent probe.The mito-chondrial membrane potential was evaluated using a mitochondrial membrane potential detection kit.The levels of reactive oxygen species(ROS)were measured using a ROS detection kit.Adenosine triphosphate(ATP)production levels were assessed with an ATP detection kit.The protein expression levels of MTCH2 and matrix metalloproteinase 14(MMP14)were analyzed through cell fluorescence and Western blot techniques.RESULTS:The number of invasive cells in the siRNA-MTCH2 group was significantly reduced,and the cell migration rate was notably decreased.Conversely,the OE-MTCH2 group exhibited a significant increase in both the number of invasive cells and the cell migration rate(P<0.01).The fluorescence intensity of F-actin and MTCH2 in the siRNA-MTCH2 group was significantly diminished,while these in-tensities were markedly elevated in the OE-MTCH2 group(P<0.01).The ROS levels in the siRNA-MTCH2 group were significantly higher than those in the siRNA-NC group,whereas the levels of ATP and mitochondrial membrane potential were significantly lower.Conversely,the ROS levels in the OE-MTCH2 group were significantly lower than those in the OE-NC group,with corresponding increases in ATP levels and mitochondrial membrane potential(P<0.01).The expres-sion levels of MTCH2 and MMP14 proteins in the siRNA-MTCH2 group were significantly lower than those in the siRNA-NC group,while the OE-MTCH2 group showed significantly higher expression levels compared to the OE-NC group(P<0.01).CONCLUSION:The MTCH2 is associated with the development of oral squamous cell carcinoma and may facili-tate the metastasis of CAL-27 cells by regulating mitochondrial function and MMP14 protein expression.Therefore,MTCH2 may represent a novel therapeutic target for the treatment of oral cancer.

ObjectiveTo investigate the recurrence of ischemic stroke (IS) and to analyze the association between four indices of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) and the risk of IS recurrence by analyzing the follow-up data related to IS in the community-based natural population of Songjiang District, Shanghai, so as to provide a scientific basis for improving the prognosis of stroke patients in the community and controlling IS recurrence. MethodsA prospective follow-up study was conducted among the IS patients in the community-based cohort population, collecting data about patient’s age, gender, disease history, biochemical indicators, and etc. Cox regression model and restricted cubic spline model were used to analyze the relationship between different levels of plasma lipids and the recurrence of IS in these patients. ResultsA total of 1 368 patients with IS were included. The total follow-up duration was 7 171.46 person-years, with a median follow-up time of 6.24 years. There were 420 cases of IS recurrence, resulting in a cumulative recurrence rate of 30.70%. The results of multivariate Cox regression analysis showed that the recurrence risk of IS was reduced when the baseline TC and LDL-C levels of IS patients were in the ranges of 4.65‒5.67 mmol·L^-1 and 2.52‒3.46 mmol·L^-1, respectively. The results of restricted cubic spline analysis showed a U-shaped relationship between baseline TC and LDL-C levels and the recurrence risk in IS patients. ConclusionThe cumulative recurrence rate of patients with IS in the community of Songjiang District in Shanghai is high, and the levels of TC and LDL-C at baseline survey are correlated with the recurrence of IS in these patients. It is suggested to pay more attention to the levels of LDL-C and TC in patients with IS, so as to improve the prognosis.

Objective To explore the effectiveness of integrating virtual simulation technology with case-based learning(CBL)in the teaching of clinical blood transfusion testing technology.Methods From January to June 2024,99 undergraduate students majoring in medical laboratory science at our university were selected and divided into an observation group(50 students)and a control group(49 students)based on their classes.The control group followed a traditional theoretical teaching model,while the observation group employed virtual simulation technology combined with CBL.Results The study compared as-sessment scores for theory learning,practical skills,case analysis,and comprehensive quality,teaching effects such as coordina-tion and cooperation abilities,self-efficacy measured by the GSES scale,and teaching satisfaction between the two groups.The results indicated that the observation group had significantly higher scores in all assessment categories,teaching effect abilities,and total GSES scores compared to the control group(P＜0.05).The total teaching satisfaction rate in the observation group reached 100%,significantly higher than the 80% in the control group(P＜0.05).Conclusion The integration of virtual simu-lation technology with CBL innovates the teaching model for clinical blood transfusion testing courses,effectively enhancing students'professional skills and comprehensive quality,boosting self-efficacy,and achieving high student satisfaction,demon-strating significant potential for broader application.

Objective:To investigate protective effect and mechanism of Tim-3 on sepsis-induced acute lung injury(ALI)by pro-moting mitophagy of alveolar macrophages and inhibiting activation of NLRP3 inflammasome.Methods:LPS-stimulated mouse alveo-lar macrophage(MH-S)model and sepsis-induced ALI mouse model were constructed.Tim-3 siRNA interference technique was used to knock down Tim-3 expression in MH-S cells,and anti-Tim-3 antibody mice were injected intraperitoneally to block Tim-3 function.Western blot was used to detect protein expressions of NLRP3,ASC,cleaved-caspase-1 and mitophagy-related proteins(LC3B,P62,PINK1 and Parkin)in MH-S cells and lung tissue of mice with sepsis-induced ALI.Laser confocal fluorescence staining was used to measure ROS level and mitochondrial membrane potential of MH-S cells.Pathological examination of lung tissue was performed in mice with sepsis-induced ALI in each group,and degree of lung tissue injury was evaluated by Smith scoring system.Bronchoalveolar lavage fluid(BALF)and lung tissue were collected from mice with ALI induced by sepsis in each group.BCA protein quantification method was used to determine protein concentration in BALF.MPO activity in lung tissue was detected by colorimetry.MDA content in lung tissue was detected by TBA method.LC3B protein expression in lung tissue was detected by immunohistochemistry.Results:In mouse alveolar macrophages,Tim-3 knockdown could promote expressions of NLRP3,ASC,cleaved-caspase-1 and P62 proteins,increase ROS release,inhibit PINK1/Parkin pathway activation and LC3B protein expression,and reduce mitochondrial membrane potential.In mice with sepsis-induced ALI,Tim-3 functional blockade could promote expressions of NLRP3,ASC,cleaved-caspase-1 and P62 proteins in lung tissue,aggravate lung pathological injury and pulmonary edema,increase MPO activity and MDA content in lung tissue,and reduce positive rate of LC3B protein.Conclusion:Tim-3 plays a protective role in sepsis-induced ALI by promoting mitophagy in alveolar macrophages and inhibiting NLRP3 inflammasome activation via PINK1/Parkin.

Objective:To investigate the clinical efficacy of stereotactic body radiotherapy combined with chemotherapy in the treatment of patients with locally advanced pancreatic cancer.Methods:This study is a prospective randomized controlled study that included 80 patients with locally advanced pancreatic cancer admitted to Weinan Central Hospital from January 2020 to June 2022. Patients were randomly divided into two groups using a drawing lots method: the control group ( n = 40) received chemotherapy and conventional medication, while the observation group ( n = 40) received stereotactic body radiotherapy in addition to the treatments in the control group. Each patient was followed up for 1 year. The local control rate of pancreatic cancer, levels of serum carbohydrate antigen 19-9 and carcinoembryonic antigen, abdominal pain relief rate, jaundice resolution rate, incidence of adverse reactions, and 1-year survival rate were compared between the two groups. Results:The local control rate in the observation group reached 85.00% (34/40), which was significantly higher than that in the control group ( χ2 = 5.23, P < 0.05). After treatment, the levels of serum carbohydrate antigen 19-9 and carcinoembryonic antigen in the observation group were significantly lower than those in the control group ( χ2 = 2.60, 3.97, both P < 0.001). The 1-year survival rate in the observation group was 65.00% (26/40), which was significantly higher than that in the control group [42.50% (17/40), χ2 = 4.07, P < 0.05). However, there was no significant difference in incidence of adverse reactions between the two groups ( χ2 = 2.58, 0.05, 0.39, 2.05, all P > 0.05). Conclusions:Stereotactic body radiotherapy combined with chemotherapy has shown good therapeutic effects in patients with locally advanced pancreatic cancer, without significantly increasing the risk of adverse reactions. Therefore, this combination treatment regimen can be considered an effective option for the treatment of locally advanced pancreatic cancer.

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.

AIM:To investigate the impact of mitochondrial carrier homologous protein 2(MTCH2)on the metastasis of oral squamous cell carcinoma and to elucidate its underlying mechanisms.METHODS:Human tongue squamous cell carcinoma CAL-27 cells were selected as the study model.An MTCH2 inhibition and overexpression model was established using small interfering RNA(siRNA)technology and overexpression plasmids.Based on the experimental design,cells were categorized into the following groups:siRNA negative control(siRNA-NC)group,MTCH2 siRNA(siRNA-MTCH2)group,empty vector(OE-NC)group,and MTCH2 overexpression(OE-MTCH2)group.Transwell as-says and wound healing assays were conducted to assess the invasion and migration capabilities of cells in each group.The morphological changes and distribution of actin microfilaments were examined using a red fluorescent probe.The mito-chondrial membrane potential was evaluated using a mitochondrial membrane potential detection kit.The levels of reactive oxygen species(ROS)were measured using a ROS detection kit.Adenosine triphosphate(ATP)production levels were assessed with an ATP detection kit.The protein expression levels of MTCH2 and matrix metalloproteinase 14(MMP14)were analyzed through cell fluorescence and Western blot techniques.RESULTS:The number of invasive cells in the siRNA-MTCH2 group was significantly reduced,and the cell migration rate was notably decreased.Conversely,the OE-MTCH2 group exhibited a significant increase in both the number of invasive cells and the cell migration rate(P<0.01).The fluorescence intensity of F-actin and MTCH2 in the siRNA-MTCH2 group was significantly diminished,while these in-tensities were markedly elevated in the OE-MTCH2 group(P<0.01).The ROS levels in the siRNA-MTCH2 group were significantly higher than those in the siRNA-NC group,whereas the levels of ATP and mitochondrial membrane potential were significantly lower.Conversely,the ROS levels in the OE-MTCH2 group were significantly lower than those in the OE-NC group,with corresponding increases in ATP levels and mitochondrial membrane potential(P<0.01).The expres-sion levels of MTCH2 and MMP14 proteins in the siRNA-MTCH2 group were significantly lower than those in the siRNA-NC group,while the OE-MTCH2 group showed significantly higher expression levels compared to the OE-NC group(P<0.01).CONCLUSION:The MTCH2 is associated with the development of oral squamous cell carcinoma and may facili-tate the metastasis of CAL-27 cells by regulating mitochondrial function and MMP14 protein expression.Therefore,MTCH2 may represent a novel therapeutic target for the treatment of oral cancer.

Objective To explore the effectiveness of integrating virtual simulation technology with case-based learning(CBL)in the teaching of clinical blood transfusion testing technology.Methods From January to June 2024,99 undergraduate students majoring in medical laboratory science at our university were selected and divided into an observation group(50 students)and a control group(49 students)based on their classes.The control group followed a traditional theoretical teaching model,while the observation group employed virtual simulation technology combined with CBL.Results The study compared as-sessment scores for theory learning,practical skills,case analysis,and comprehensive quality,teaching effects such as coordina-tion and cooperation abilities,self-efficacy measured by the GSES scale,and teaching satisfaction between the two groups.The results indicated that the observation group had significantly higher scores in all assessment categories,teaching effect abilities,and total GSES scores compared to the control group(P＜0.05).The total teaching satisfaction rate in the observation group reached 100%,significantly higher than the 80% in the control group(P＜0.05).Conclusion The integration of virtual simu-lation technology with CBL innovates the teaching model for clinical blood transfusion testing courses,effectively enhancing students'professional skills and comprehensive quality,boosting self-efficacy,and achieving high student satisfaction,demon-strating significant potential for broader application.