OBJECTIVE To investigate the mechanism of isochlorogenic acid A against hepatocellular carcinoma based on the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway and multi-omics technology. METHODS The invasion rate and migration rate of human hepatocellular carcinoma HepG2 cells after 48 h of intervention with 0 （control group）， 0.25 and 0.5 mg/mL isochlorogenic acid A were examined； mRNA expression of DEP domain-containing mTOR-interacting protein （DEPTOR）， the protein expressions of mTOR， PI3K and phosphatase and tensin homologue deleted on chromosome ten （PTEN）， as well as the phosphorylation level of Akt protein were determined in the cells. Metabolomics analysis was performed using liquid chromatography-tandem mass spectrometry， and differential metabolites were screened and subjected to Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis； transcriptomics monitoring was conducted by RNA sequencing， and differentially expressed genes were screened and subjected to gene ontology （GO） and KEGG pathway enrichment analyses. RESULTS Compared with the control group， intervention with 0.25 and 0.5 mg/mL isochlorogenic acid A for 48 h significantly inhibited the invasion rate and migration rate of HepG2 cells， significantly up-regulated the mRNA expression of DEPTOR and the protein expression of PTEN， and significantly down-regulated the protein expression of PI3K and the phosphorylation level of Akt protein （except for 0.25 mg/mL isochlorogenic acid A） （ P ＜0.05）. A total of 304 differential metabolites and 212 differentially expressed genes were screened by multi-omics analysis. KEGG pathway enrichment analysis suggested that isochlorogenic acid A regulated key signaling of HepG2 cell growth mainly by inhibiting the PI3K/Akt signaling pathway， synergizing with metabolic reprogramming such as mTOR signaling pathway， ferroptosis， pentose phosphate pathway and purine/pyrimidine metabo lism. CONCLUSIONS The anti-hepatocellular carcinoma effect of isochlorogenic acid A is associated with the blockade of abnormal activation of the PI3K/Akt/mTOR signaling pathway. In addition， it may also be related to the inhibition of the pentose phosphate pathway and purine/pyrimidine metabolism， as well as the induction of ferroptosis，etc.

OBJECTIVE To construct a prevention and control index system suitable for stomatology outpatient de-partment of general hospital,so as to provide a theoretical basis for risk assessment of stomatology outpatient de-partment,and to provide an evidence-based basis for precise prevention and control.METHODS Based on the methods of literature research,literature quality evaluation and brainstorming,a draft index of the prevention and control of the general hospital's oral outpatient department was constructed,and the index system for the preven-tion and control in the stomatology outpatient department of a general hospital was finally established through re-search group discussion,content analysis and expert consultation.The three-level indicators in the index system were incorporated into the risk points of risk assessment,the failure mode and effects analysis were applied to con-duct the risk assessment,and the intervention measures and rectification cycles were formulated and implemented in clinical practice for the risk points with risk priority number(RPN)greater than 125.Based on the established index system and risk points with RPN＞125,the hospital infection prevention and control checklist for stoma-tology outpatient was developed and regularly checked in the clinic.After the rectification was completed,the risk points were evaluated again,and the RPN values were compared before and after the risk control.RESULTS The recovery rate of expert consultation questionnaire was 100.00％,and the average expert authority coefficient was 0.84.The consistency ratio(CR)for the first-level indicators was 0.0499,and the consistency ratio(CR)of the second-level indicators was 0.0000-0.0790,which was less than 0.1,and the consistency was acceptable.Final-ly,a hospital infection prevention and control index system was established,comprising 5 first-level indicators,7 second-level indicators and 23 third-level indicators.The improved key control risk points were evaluated again,and the RPN values before and after comparing the risk control were reduced and＜125,indicating that the im-provement measures were effective.CONCLUSION The evaluation system of prevention and control for the stoma-tology outpatient department of a general hospital established in this study is reliable,scientific and practical,and the improvement measures of risk assessment before and after the control of risk points are effective,which pro-vides evidence-based basis for risk assessment and precise prevention and control in the stomatology outpatient de-partment of general hospitals.

Critically ill with capillary leakage syndrome（CLS）presents with damaged vascular endothelial cells with glycocalyx degraded,which increases vascular permeability,and leads to the protein-rich fluid from the intravascular extravasate into the interstitial space.CLS can concomitant symptoms of hypovolemia and fluid overload.Fluid therapy is the most critical element in the treatment of CLS,but still lack of sufficient evidence to guide the choice of fluid management.Based on accurately hemodynamic monitoring,balanced salt or crystalloid + albumin or fresh frozen plasma may be input to ensure effective circulating blood volume.Albumin or fresh frozen plasma is particularly suitable for CLS patients failed to respond to crystalloids during the leakage period.In the later stage of leakage,conservative fluid management with “de-resuscitation”strategy was mainly used with diuretic and hemofiltration (renal replacement therapy/continuous renal replacement therapy) for attenuating fluid overload.Steroids and ulinastatin may be effective in CLS caused by sepsis.

OBJECTIVE To construct a prevention and control index system suitable for stomatology outpatient de-partment of general hospital,so as to provide a theoretical basis for risk assessment of stomatology outpatient de-partment,and to provide an evidence-based basis for precise prevention and control.METHODS Based on the methods of literature research,literature quality evaluation and brainstorming,a draft index of the prevention and control of the general hospital's oral outpatient department was constructed,and the index system for the preven-tion and control in the stomatology outpatient department of a general hospital was finally established through re-search group discussion,content analysis and expert consultation.The three-level indicators in the index system were incorporated into the risk points of risk assessment,the failure mode and effects analysis were applied to con-duct the risk assessment,and the intervention measures and rectification cycles were formulated and implemented in clinical practice for the risk points with risk priority number(RPN)greater than 125.Based on the established index system and risk points with RPN＞125,the hospital infection prevention and control checklist for stoma-tology outpatient was developed and regularly checked in the clinic.After the rectification was completed,the risk points were evaluated again,and the RPN values were compared before and after the risk control.RESULTS The recovery rate of expert consultation questionnaire was 100.00％,and the average expert authority coefficient was 0.84.The consistency ratio(CR)for the first-level indicators was 0.0499,and the consistency ratio(CR)of the second-level indicators was 0.0000-0.0790,which was less than 0.1,and the consistency was acceptable.Final-ly,a hospital infection prevention and control index system was established,comprising 5 first-level indicators,7 second-level indicators and 23 third-level indicators.The improved key control risk points were evaluated again,and the RPN values before and after comparing the risk control were reduced and＜125,indicating that the im-provement measures were effective.CONCLUSION The evaluation system of prevention and control for the stoma-tology outpatient department of a general hospital established in this study is reliable,scientific and practical,and the improvement measures of risk assessment before and after the control of risk points are effective,which pro-vides evidence-based basis for risk assessment and precise prevention and control in the stomatology outpatient de-partment of general hospitals.

Objective:To explore the application of the O-PIRTAS flipped classroom in teaching the course of "developmental psychology".Methods:This study involved second-year undergraduate students majoring in clinical psychology. The 26 undergraduate students enrolled in 2023 who participated in the late adulthood section of the course were selected as the experimental group (O-PIRTAS teaching), while the 25 undergraduate enrolled in 2022 in the same course were selected as the control group (traditional teaching). Assessments were conducted through closed-book tests and questionnaires. The student questionnaire evaluated their theoretical knowledge, class assessment, and class engagement. The teacher questionnaire assessed the completeness of the lecture, logical flow, and student engagement. SPSS 22.0 was used for t test. Results:In the theoretical examination, the experimental group showed significantly higher scores compared to the control group in knowledge application [(13.09±1.59) vs. (10.54±0.77)] and practical problem-solving ability [(8.27±0.57) vs. (6.95±0.32)]. In the questionnaire survey, 24 (92.00%) students in the experimental group expressed recognition of the flipped classroom mode. Teachers reported greater improvement in satisfaction with the classroom performance of the experimental group compared to the control group.Conclusions:O-PIRTAS flipped classroom improves the quality of teaching "developmental psychology", enhances student learning outcomes, and stimulates learning motivation.

Objective To provide methodological examples for related research,the influencing factors of the evolution of Qi deficiency syndrome in chronic obstructive pulmonary disease(COPD)based on a nonlinear mixed effects model was explored.Methods A research questionnaire on the influencing factors of the evolution of Qi deficiency syndrome in chronic obstructive pulmonary disease was developed,and clinical data of 650 COPD patients on the 1st and 14th day of acute exacerbation,the 1st and 28th day of risk window,the first day of stable period,and the 90th day were dynamically collected from 10 tertiary hospitals across the country.8 baseline data including gender and age were collected through the PROC NLMIXED process by SAS 9.4 software.Coronary heart disease,diabetes and hypertension accounted for the highest proportion.Nine concurrent syndromes including wind cold syndrome and phlegm heat syndrome were used as fixed effects,and individual level was used as random effects to gradually fit the model and screen the influencing factors of Qi deficiency syndrome in the entire process of disease occurrence and development.Results A total of 637 eligible cases were included,and clinical datas were dynamically collected on the 1st and 14th day of acute exacerbation,the 1st and 28th day of the risk window,the 1st and 90th day of the stable period.It was found that the number of acute exacerbations,alcohol consumption,concomitant hypertension,coronary heart disease,blood stasis syndrome,yin deficiency syndrome,yang deficiency syndrome,6-minute walking distance,and the modified Medical Research Council Dyspnea Questionnaire(mMRC)had an impact on the evolution of Qi deficiency syndrome in the previous year(P<0.05).Conclusion The use of a nonlinear mixed effects model revealed the relevant factors affecting the evolution of Qi deficiency syndrome from complex multi temporal dynamic data,providing methodological references for other related studies.

Objective To provide methodological examples for related research,the influencing factors of the evolution of Qi deficiency syndrome in chronic obstructive pulmonary disease(COPD)based on a nonlinear mixed effects model was explored.Methods A research questionnaire on the influencing factors of the evolution of Qi deficiency syndrome in chronic obstructive pulmonary disease was developed,and clinical data of 650 COPD patients on the 1st and 14th day of acute exacerbation,the 1st and 28th day of risk window,the first day of stable period,and the 90th day were dynamically collected from 10 tertiary hospitals across the country.8 baseline data including gender and age were collected through the PROC NLMIXED process by SAS 9.4 software.Coronary heart disease,diabetes and hypertension accounted for the highest proportion.Nine concurrent syndromes including wind cold syndrome and phlegm heat syndrome were used as fixed effects,and individual level was used as random effects to gradually fit the model and screen the influencing factors of Qi deficiency syndrome in the entire process of disease occurrence and development.Results A total of 637 eligible cases were included,and clinical datas were dynamically collected on the 1st and 14th day of acute exacerbation,the 1st and 28th day of the risk window,the 1st and 90th day of the stable period.It was found that the number of acute exacerbations,alcohol consumption,concomitant hypertension,coronary heart disease,blood stasis syndrome,yin deficiency syndrome,yang deficiency syndrome,6-minute walking distance,and the modified Medical Research Council Dyspnea Questionnaire(mMRC)had an impact on the evolution of Qi deficiency syndrome in the previous year(P<0.05).Conclusion The use of a nonlinear mixed effects model revealed the relevant factors affecting the evolution of Qi deficiency syndrome from complex multi temporal dynamic data,providing methodological references for other related studies.

Pseudopleuronectes yokohamae is an important marine economic fish species in northern China and is vulnerable to various pathogens during the breeding process.To investigate the viru-lence of Edwardsiella tarda on Pseudopleuronectes yokohamae and elucidate the role of miRNAs in their interaction,we conducted pathological analyses on various tissues of Pseudopleuronectes yokohamae larvae pre-and post-infection with Edwardsiella tarda.Subsequently,Illumina high-throughput sequencing was employed to identify and functionally characterize differentially ex-pressed miRNAs in liver and kidney tissues.The results demonstrated that infection with Ed-wardsiella tarda led to ulceration,hemorrhaging,significant hepatomegaly,nephromegaly,and as-cites in the abdominal cavity.Histopathological examination revealed swollen hepatocytes with vac-uolization,minor blood cell infiltration,and enlarged renal corpuscles with signs of cellular lysis.miRNA sequencing analysis indicated that 24 miRNAs were significantly upregulated and 45 miR-NAs were significantly downregulated in the liver,while in the kidney,6 miRNAs were upregulat-ed and 58 were downregulated following infection.Functional enrichment analysis revealed signifi-cant enrichment of differentially expressed miRNAs in Toll and IMD signaling pathways,HIF-1 signaling pathway,Rap1 signaling pathway,MAPK signaling pathway,and Apelin signaling path-way.These findings suggest the involvement of these miRNAs in host metabolism,pathogen rec-ognition,and immune response in the interaction between Pseudopleuronectes yokohamae and Ed-wardsiella tarda.This research lays a foundation for elucidating the mechanisms underlying bacte-rial disease susceptibility and resistance in Pseudopleuronectes yokohamae.

Pseudopleuronectes yokohamae is an important marine economic fish species in northern China and is vulnerable to various pathogens during the breeding process.To investigate the viru-lence of Edwardsiella tarda on Pseudopleuronectes yokohamae and elucidate the role of miRNAs in their interaction,we conducted pathological analyses on various tissues of Pseudopleuronectes yokohamae larvae pre-and post-infection with Edwardsiella tarda.Subsequently,Illumina high-throughput sequencing was employed to identify and functionally characterize differentially ex-pressed miRNAs in liver and kidney tissues.The results demonstrated that infection with Ed-wardsiella tarda led to ulceration,hemorrhaging,significant hepatomegaly,nephromegaly,and as-cites in the abdominal cavity.Histopathological examination revealed swollen hepatocytes with vac-uolization,minor blood cell infiltration,and enlarged renal corpuscles with signs of cellular lysis.miRNA sequencing analysis indicated that 24 miRNAs were significantly upregulated and 45 miR-NAs were significantly downregulated in the liver,while in the kidney,6 miRNAs were upregulat-ed and 58 were downregulated following infection.Functional enrichment analysis revealed signifi-cant enrichment of differentially expressed miRNAs in Toll and IMD signaling pathways,HIF-1 signaling pathway,Rap1 signaling pathway,MAPK signaling pathway,and Apelin signaling path-way.These findings suggest the involvement of these miRNAs in host metabolism,pathogen rec-ognition,and immune response in the interaction between Pseudopleuronectes yokohamae and Ed-wardsiella tarda.This research lays a foundation for elucidating the mechanisms underlying bacte-rial disease susceptibility and resistance in Pseudopleuronectes yokohamae.

Critically ill with capillary leakage syndrome（CLS）presents with damaged vascular endothelial cells with glycocalyx degraded,which increases vascular permeability,and leads to the protein-rich fluid from the intravascular extravasate into the interstitial space.CLS can concomitant symptoms of hypovolemia and fluid overload.Fluid therapy is the most critical element in the treatment of CLS,but still lack of sufficient evidence to guide the choice of fluid management.Based on accurately hemodynamic monitoring,balanced salt or crystalloid + albumin or fresh frozen plasma may be input to ensure effective circulating blood volume.Albumin or fresh frozen plasma is particularly suitable for CLS patients failed to respond to crystalloids during the leakage period.In the later stage of leakage,conservative fluid management with “de-resuscitation”strategy was mainly used with diuretic and hemofiltration (renal replacement therapy/continuous renal replacement therapy) for attenuating fluid overload.Steroids and ulinastatin may be effective in CLS caused by sepsis.