Objective:To investigate the effects of learning flow experience on system thinking in medical students under the mixed mode.Methods:Medical students who completed Medical Statistics of the 2022-2023 academic year were enrolled.Then learning attitudes,learning flow experience,and system thinking were investigated using SATS-36 Scale,Adolescent Learning Flow Experience Questionnaire,and Systems Thinking Scale.Linear correlation analysis explored relationships among these variables.Multiple linear regression and restricted cubic spline(RCS)model analyzed linear/non-linear relationships between learning flow experience and system thinking after adjusting for gender,major,and learning attitude.Results:Among the 349 medical students surveyed,the mean score for learning attitudes was(4.31±0.59)and for learning flow experience was(3.33±0.65),both indicating a moderate to high level.The mean score for systems thinking was(59.01±13.57),indicating a moderate level.Positive correlations were found among learning flow experience,learning attitudes,and system thinking.Significant gender and major differences were observed in learning flow experience.After controlling for gender,major,and learning attitudes,multiple linear regression analysis revealed a significant linear trend between learning flow experience and system thinking(P＜0.01).RCS model analysis indicated a significant J-shaped nonlinear relationship between learning folw experience and system thinking(P for non-linearity＜0.01).Using the median score of 3.16 as the inflection point,when the learning flow experience score was＜3.16,it had no significant effect on medical students'system thinking(P=0.51).When the score was≥3.16,system thinking increased significantly with increasing learning flow experience(Beta per SD=0.56,95%CI:0.44-0.68,P＜0.01).Conclusions:The learning flow experience of medical students under the mixed mode can promote their system thinking.When the flow experience score is≥3.16,higher levels of learning flow experience are associated with increased systems thinking.Different dimensions of learning flow experience exhibit varying strengths of correlation with systems thinking.

Objective:To investigate the effects of learning flow experience on system thinking in medical students under the mixed mode.Methods:Medical students who completed Medical Statistics of the 2022-2023 academic year were enrolled.Then learning attitudes,learning flow experience,and system thinking were investigated using SATS-36 Scale,Adolescent Learning Flow Experience Questionnaire,and Systems Thinking Scale.Linear correlation analysis explored relationships among these variables.Multiple linear regression and restricted cubic spline(RCS)model analyzed linear/non-linear relationships between learning flow experience and system thinking after adjusting for gender,major,and learning attitude.Results:Among the 349 medical students surveyed,the mean score for learning attitudes was(4.31±0.59)and for learning flow experience was(3.33±0.65),both indicating a moderate to high level.The mean score for systems thinking was(59.01±13.57),indicating a moderate level.Positive correlations were found among learning flow experience,learning attitudes,and system thinking.Significant gender and major differences were observed in learning flow experience.After controlling for gender,major,and learning attitudes,multiple linear regression analysis revealed a significant linear trend between learning flow experience and system thinking(P＜0.01).RCS model analysis indicated a significant J-shaped nonlinear relationship between learning folw experience and system thinking(P for non-linearity＜0.01).Using the median score of 3.16 as the inflection point,when the learning flow experience score was＜3.16,it had no significant effect on medical students'system thinking(P=0.51).When the score was≥3.16,system thinking increased significantly with increasing learning flow experience(Beta per SD=0.56,95%CI:0.44-0.68,P＜0.01).Conclusions:The learning flow experience of medical students under the mixed mode can promote their system thinking.When the flow experience score is≥3.16,higher levels of learning flow experience are associated with increased systems thinking.Different dimensions of learning flow experience exhibit varying strengths of correlation with systems thinking.

Objective:To investigate the inhibitory effect of combined strategy of poly adenosine diphosphate ribose polymerase (PARP) inhibitor and interleukin-1β (IL-1β) inhibitor on homologous recombination deficiency (HRD)-proficient ovarian cancer cells.Methods:(1) HRD-proficient ovarian cancer cell lines OVCAR3 and CAOV3 were treated with PARP inhibitor olaparib. Screening by RNA sequencing analysis, the expression level of IL-1β was validated by enzyme-linked immunosorbent assay (ELISA) and western blot. (2) The dose-response curves of IL-1β inhibitor diacerein were evaluated by cell counting kit-8 (CCK-8) assays in OVCAR3 and CAOV3 cells. CCK-8 assays were further applied to determine the viabilities of OVCAR3 and CAOV3 cells. (3) To evaluate the synergistic effects of olaparib and IL-1β inhibitor in vivo, the transplanted ovarian cancer model was constructed. BALB/c-nude mice ( n=16) were injected intraperitoneally with 1×10 7 OVACR3 cells labelled with luciferase (OVCAR3-Luc). Immunohistochemistry (IHC) assay was performed to determine nuclear antigen associated with cell proliferation (Ki-67) expression. (4) Blood routine tests, kidney and liver function tests were performed to analyze the toxic reaction of different drug treatments. The potential drug-induced injuries of vital organs including heart, liver, spleen, lungs and kidneys of nude mice were determined by hematoxylin-eosin (HE) staining. Results:(1) The RNA sequencing results showed that the mRNA level of IL-1β was the most significantly increased among the 25 differentially expressed genes in OVCAR3 cells treated with olaparib, compared to the negative control group. Olaparib treatment significantly promoted the secretion and expression of IL-1β protein in both OVACR3 and CAOV3 cells by ELISA [(36.2±3.5) and (49.5±3.5) pg/ml, respectively; all P<0.001] and western bolt (2.87±0.37 and 2.05±0.08, respectively; all P<0.01). (2) The half maximal inhibitory concentration (IC 50) value of IL-1β inhibitor was determined as follows: 75 μmol/L for OVACR3 cells and 100 μmol/L for CAOV3 cells. The treatments were divided into four groups including control group, olaparib monotherapy group, IL-1β inhibitor monotherapy group and the combination therapy group. The cell viabilities of each group in OVCAR3 and CAOV3 were determined by CCK-8 assay. The data in each group were showed as follows for OVCAR3 and CAOV3 cells: (100.0±0.4)% and (100.0±3.5)% in control group; (63.1±6.2)% and (63.3±3.8)% in olaparib monotherapy group; (61.6±4.7)% and (63.8±3.5)% in IL-1β inhibitor monotherapy group; and (32.9±5.2)% and (30.0±1.3)% in the combination therapy group. The viability assay showed that the combined strategy exhibited a significant inhibition effect on OVACR3 and CAOV3 cells, compared to the monotherapy group and the control group (all P<0.01). (3) All mice with transplanted tumors of HRD-proficient ovarian cancer cells were randomly divided into four groups, and treated with four different treatments as mentioned above, respectively. After 4 weeks (on day 29), the vivo fluorescence imaging were determined. The results showed that the amount of fluorescence of transplanted tumors was mostly decreased in the combination therapy group [(0.5±0.4)×10 10 p/s], compared to the control group [(4.2±1.0)×10 10 p/s] or the groups treated with any single drug [(3.1±0.9)×10 10, (2.2±0.9)×10 10 p/s; all P<0.05]. Mice were then sacrificed under anesthesia, and all transplanted tumors detached and weighed for further investigation. The weight of transplanted tumors was significantly decreased in the combination therapy group [(0.09±0.03) g], compared to that in control group [(0.25±0.05) g] or groups treated with any single drug [(0.17±0.03), (0.19±0.04) g; all P<0.05]. The measurement of the expression of Ki-67 showed that it was significantly decreased in the combination therapy group (0.33±0.10), compared to that in the control group (1.00±0.20) or monotherapy groups (0.76±0.07, 0.77±0.12; all P<0.05). (4) There were no significant differences of body weights, blood routine test, renal and liver function tests among mice with different treatments (all P>0.05). Moreover, no significant injuries were observed in the vital organs among the four groups. Conclusions:The combination of olaparib and IL-1β inhibitor synergistically exhibits significant cytotoxicity in HRD-proficient ovarian cancer cells. Moreover, the blood routine and blood biochemistry results confirmed the biosafety of the combination of olaparib and IL-1β inhibitor.