Objective To investigate the effects and mechanisms of combined prescriptions of essential oils from five traditional Chinese medicinal herbs,namely peppermint,turmeric,ginger,Tibetan fennel,and cumin,on symptoms related to functional abdominal pain syndrome(FAPS).Methods Gas chromatography-mass spectrometry(GC-MS)was employed to analyze the chemical constituents of five essential oils,while network pharmacology was utilized to predict the key targets and signaling pathways associated with these essential oils in alleviating functional abdominal pain syndrome.A formula design methodology centered on these core targets and signaling pathways was developed for creating new prescriptions.Molecular docking technology was conducted to predict its the underlying mechanisms.Subsequently,animal experiments were performed to assess pharmacological activity,including hot plate tests and acetic acid-induced writhing assays to validate the analgesic effects of the newly formulated prescription,as well as xylene-induced ear swelling tests to evaluate its anti-inflammatory properties.The impact of the essential oil formulation on intestinal peristaltic function was examined through intestinal propulsion experiments.Additionally,enzyme-linked immunosorbent assay(ELISA)methods were employed to measure levels of serotonin(5-HT),prostaglandin E2(PGE2),and gamma-aminobutyric acid(GABA)in brain tissue.Western blot analysis was conducted to determine protein expression levels of TPH1 and SERT in the intestine,along with TPH2 and SERT in the brain.Results The main chemical components in five essential oils were identified and screened(peppermint:12,turmeric:8,ginger:14,cumin:2,fennel:6).Based on the network pharmacology analysis,four new essential oil prescriptions were successfully designed according to the complementary relationship between the five essential oils in improving functional abdominal pain syndrome at the target level,including 4 new prescription named Prescription A,B,C and D,these four prescriptions were all based on ginger and turmeric essential oils,with other essential oils serving as supplements or enhancements.The results of animal experiments showed that Prescription D could significantly reduce the writhe frequency of mice(P<0.05),all the four groups could significantly prolong the pain threshold of mice(P<0.05),and Prescription C had a significant effect on reducing the degree of ear swelling(P<0.05).The prescription of essential oil did not significantly affect the function of peristalsis and the speed of propulsion.The levels of 5-HT and PGE2 in the brain tissue were significantly inhibited(P<0.05),and the level of GABA was significantly increased(P<0.05).Prescription C could reduce the expression of TPH1 in the intestinal tissue(P<0.05),Prescription A,C and D could reduce the expression of TPH2,and all groups had a tendency to increase the expression of SERT in the brain tissue.Conclusion In summary,the therapeutic effects of the four novel prescriptions composed of the five essential oils demonstrated potential in improving symptoms related to FAPS,the mechanism might be through modulating abnormalities in the brain-gut axis system.

AIM:To investigate the role and mechanism of cell death-inducing DNA fragmentation factor al-pha(DFFA)-like effector B(Cideb)in promoting palmitic acid(PA)-induced lipid deposition in human hepatoblastoma HepG2 cells.METHODS:The HepG2 cells were divided into control group,model group,negative control silencing(siR-NC)group and Cideb silencing(siR-Cideb)group.The cells were treated with PA to establish a cellular model of lipid deposition.Specific siRNAs were used to silence the expression of Cideb,and the intracellular lipid content was mea-sured.Lipid deposition was observed by oil red O staining.RT-qPCR and Western blot were used to detect the expression levels of Cideb,sterol regulatory element-binding protein 1c(SREBP1c),acetyl-CoA carboxylase 1(ACC1),fatty acid synthase(FAS),stearoyl-CoA desaturase 1(SCD1)and AMP-activated protein kinase α(AMPKα)in the cells.The ef-fects of Cideb overexpression on HepG2 cells were observed by transfection with a Cideb eukaryotic expression plasmid.RESULTS:Compared with control group,the cells in PA model group presented lipid deposition,significantly increased triglyceride(TG)and total cholesterol(TC)content,elevated expression levels of Cideb,SREBP1c,ACC,FAS and SCD1,and decreased expression of AMPKα(P＜0.05).Compared with siR-NC group,the cells in siR-Cideb group pre-sented decreased lipid deposition,reduced intracellular TG and TC content,decreased SREBP1c,ACC,FAS and SCD1 expression levels,and increased AMPKα expression(P＜0.05).The overexpression of Cideb increased the lipid deposi-tion,TG and TC content,and the expression levels of SREBP1c,ACC,FAS and SCD1 in HepG2 cells,but decreased the expression of AMPKα(P＜0.05).CONCLUSION:Reduction of Cideb alleviates PA-induced lipid deposition in HepG2 cells by down-regulating the SREBP1c/ACC/FAS/SCD1 pathway and up-regulating the AMPKα pathway.

Objective:To study effect of matrine on TNF-α induced proliferation of human umbilical vein endothelial cells(HUVEC),as well as to explore whether its mechanism is related to regulation of miR-125b-5p and STAT3 expressions.Methods:HUVEC proliferation model was established by TNF-α stimulating.After matrine treatment,miR-125b-5p level was detected by real-time fluorescent quantitative PCR,proliferating cell nuclear antigen(PCNA),cell cycle protein D1(CyclinD1),matrix metallopro-teinase 2(MMP2),MMP9,STAT3 levels were detected by real-time fluorescent quantitative PCR and Western blot.Targeting rela-tionship between miR-125b-5p and STAT3 was verified by dual luciferase reporter gene assay.Results:Matrine inhibited TNF-α in-duced HUVEC proliferation(P<0.05),decreased PCNA,CyclinD1,MMP2,MMP9,STAT3 expressions(P<0.05),and increased miR-125b-5p expression(P<0.05).Overexpression of miR-125b-5p could reduce cell proliferation and PCNA,CyclinD1,MMP2,MMP9 expressions HUVEC induced by TNF-α(P<0.05).miR-125b-5p targeted STAT3 expression negatively in HUVEC,and inhi-biting miR-125b-5p expression could reverse effect of matrine on TNF-α induced cell proliferation and PCNA,CyclinD1,MMP2,MMP9 and STAT3 expressions.Conclusion:Matrine inhibits TNF-α induced proliferation of HUVEC,which is related to regulation of miR-125b-5p/STAT3 pathway.

Objective:To study effect of matrine on TNF-α induced proliferation of human umbilical vein endothelial cells(HUVEC),as well as to explore whether its mechanism is related to regulation of miR-125b-5p and STAT3 expressions.Methods:HUVEC proliferation model was established by TNF-α stimulating.After matrine treatment,miR-125b-5p level was detected by real-time fluorescent quantitative PCR,proliferating cell nuclear antigen(PCNA),cell cycle protein D1(CyclinD1),matrix metallopro-teinase 2(MMP2),MMP9,STAT3 levels were detected by real-time fluorescent quantitative PCR and Western blot.Targeting rela-tionship between miR-125b-5p and STAT3 was verified by dual luciferase reporter gene assay.Results:Matrine inhibited TNF-α in-duced HUVEC proliferation(P<0.05),decreased PCNA,CyclinD1,MMP2,MMP9,STAT3 expressions(P<0.05),and increased miR-125b-5p expression(P<0.05).Overexpression of miR-125b-5p could reduce cell proliferation and PCNA,CyclinD1,MMP2,MMP9 expressions HUVEC induced by TNF-α(P<0.05).miR-125b-5p targeted STAT3 expression negatively in HUVEC,and inhi-biting miR-125b-5p expression could reverse effect of matrine on TNF-α induced cell proliferation and PCNA,CyclinD1,MMP2,MMP9 and STAT3 expressions.Conclusion:Matrine inhibits TNF-α induced proliferation of HUVEC,which is related to regulation of miR-125b-5p/STAT3 pathway.

Objective To establish dynamic nomogram models for postoperative recurrence and survival risk of patients with AFP-negative hepatocellular carcinoma(ANHC)based on multimodal clinical data,to identify ANHC-specific prognostic biomarker combinations by integrating tumor biological characteristics and treatment response parameters through machine learning,and to provide an individualized risk assessment tool for overcoming the limitations of traditional serum biomarkers.Methods A retrospective analysis was performed for 421 ANHC patients who underwent hepatectomy in Eastern Hepatobiliary Surgery Hospital from April 2012 to December 2018,and they were randomly divided into training group with 210 patients and validation group with 211 patients.The univariate and multivariate Cox proportional-hazards regression models were used to identify independent prognostic factors and establish a nomogram model,and the receiver operating characteristic(ROC)curve,the calibration curve,and the decision curve analysis were used to assess the performance of the model.Related indicators were measured,including prealbumin(PA),white blood cell count(WBC),tumor size,and microvascular invasion.The chi-square test or the Fisher's exact test was used for comparison of categorical variables between two groups,and the independent-samples t test or the Mann-Whitney U test was used for comparison of continuous variables between two groups.Results The multivariate analysis showed that multiple tumors(hazard ratio[HR]=3.30,P<0.001),WBC(HR=1.05,P=0.005),blood glucose(HR=1.15,P=0.026),CA19-9(HR=1.17,P=0.005),and tumor size(HR=1.17,P<0.001)were independent risk factors for disease-free survival(DFS),while PA(HR=0.99,P=0.022)was a protective factor.Incomplete tumor capsule(HR=0.60,P=0.009),age(HR=1.02,P=0.035),prothrombin time(PT)(HR=1.27,P=0.023),CA19-9(HR=1.01,P<0.001),and tumor size(HR=1.15,P<0.001)were independent risk factors for overall survival(OS).The DFS nomogram achieved an AUC of 0.74(95%confidence interval[CI]:0.64-0.84)in the training group and 0.67(95%CI:0.57-0.77)in the validation group,while the OS nomogram had an AUC of 0.76(95%CI:0.64-0.88)and 0.73(95%CI:0.60-0.87),respectively.The calibration curve and the decision curve analysis showed that the models had good predictive accuracy and clinical practicability.Conclusion Preoperative indicators,including tumor number,PA,WBC,and tumor size,can effectively predict postoperative recurrence in ANHC patients,while tumor capsule integrity,age,and PT are significantly associated with OS.The nomogram models established have good performance and can provide a basis for individualized prognostic assessment.

Objective To establish dynamic nomogram models for postoperative recurrence and survival risk of patients with AFP-negative hepatocellular carcinoma(ANHC)based on multimodal clinical data,to identify ANHC-specific prognostic biomarker combinations by integrating tumor biological characteristics and treatment response parameters through machine learning,and to provide an individualized risk assessment tool for overcoming the limitations of traditional serum biomarkers.Methods A retrospective analysis was performed for 421 ANHC patients who underwent hepatectomy in Eastern Hepatobiliary Surgery Hospital from April 2012 to December 2018,and they were randomly divided into training group with 210 patients and validation group with 211 patients.The univariate and multivariate Cox proportional-hazards regression models were used to identify independent prognostic factors and establish a nomogram model,and the receiver operating characteristic(ROC)curve,the calibration curve,and the decision curve analysis were used to assess the performance of the model.Related indicators were measured,including prealbumin(PA),white blood cell count(WBC),tumor size,and microvascular invasion.The chi-square test or the Fisher's exact test was used for comparison of categorical variables between two groups,and the independent-samples t test or the Mann-Whitney U test was used for comparison of continuous variables between two groups.Results The multivariate analysis showed that multiple tumors(hazard ratio[HR]=3.30,P<0.001),WBC(HR=1.05,P=0.005),blood glucose(HR=1.15,P=0.026),CA19-9(HR=1.17,P=0.005),and tumor size(HR=1.17,P<0.001)were independent risk factors for disease-free survival(DFS),while PA(HR=0.99,P=0.022)was a protective factor.Incomplete tumor capsule(HR=0.60,P=0.009),age(HR=1.02,P=0.035),prothrombin time(PT)(HR=1.27,P=0.023),CA19-9(HR=1.01,P<0.001),and tumor size(HR=1.15,P<0.001)were independent risk factors for overall survival(OS).The DFS nomogram achieved an AUC of 0.74(95%confidence interval[CI]:0.64-0.84)in the training group and 0.67(95%CI:0.57-0.77)in the validation group,while the OS nomogram had an AUC of 0.76(95%CI:0.64-0.88)and 0.73(95%CI:0.60-0.87),respectively.The calibration curve and the decision curve analysis showed that the models had good predictive accuracy and clinical practicability.Conclusion Preoperative indicators,including tumor number,PA,WBC,and tumor size,can effectively predict postoperative recurrence in ANHC patients,while tumor capsule integrity,age,and PT are significantly associated with OS.The nomogram models established have good performance and can provide a basis for individualized prognostic assessment.

The full-arch immediate implant restoration technique is one of the mainstream treatment options for edentulous patients.With the changes in disease patterns,health concepts,and the emphasis on the"patient-centered"philosophy,restoring function is no longer the sole goal of treatment for patients with tooth loss.Other factors such as patient expectations,improvements in quality of life,aesthetics,low economic burden,and convenience of maintenance are also important indicators for evaluating treatment outcomes.Pa-tient-reported outcomes provide a new perspective for assessing the effectiveness of full-arch immediate implant restoration.This study reviews the application and research progress of patient-reported outcomes in full-arch immediate implant restoration techniques,sys-tematically summarizing four evaluation indicators(oral health-related quality of life,quality of life,patient satisfaction,and health economic evaluation),in order to provide reference for clinical decision-making and humanistic care pathways in full-arch immediate implant restoration techniques.

The full-arch immediate implant restoration technique is one of the mainstream treatment options for edentulous patients.With the changes in disease patterns,health concepts,and the emphasis on the"patient-centered"philosophy,restoring function is no longer the sole goal of treatment for patients with tooth loss.Other factors such as patient expectations,improvements in quality of life,aesthetics,low economic burden,and convenience of maintenance are also important indicators for evaluating treatment outcomes.Pa-tient-reported outcomes provide a new perspective for assessing the effectiveness of full-arch immediate implant restoration.This study reviews the application and research progress of patient-reported outcomes in full-arch immediate implant restoration techniques,sys-tematically summarizing four evaluation indicators(oral health-related quality of life,quality of life,patient satisfaction,and health economic evaluation),in order to provide reference for clinical decision-making and humanistic care pathways in full-arch immediate implant restoration techniques.

Atherosclerosis(AS)is a chronic inflammatory disease involving disorders of lipid and iron metabolism.The establishment of suitable animal models is required to further the study of the etiology,pathogenesis,prevention,and therapeutic measures of AS.The main animal models of AS related to iron and lipid metabolism are mice and miniature piglets,especially male ApoE-/-mice.Single-factor high-fat diet-induced iron and lipid metabolism disorders are a common type of AS model,manifesting as elevated blood lipid levels,large plaques and iron deposition in the aorta,and significant increases in serum and liver iron levels.This review compares the effects of different intervention factors on iron and lipid metabolism in AS animal models,and summarizes the method of establishing AS animal models using dietary induction,chemical intervention,and gene modification,to provide references and inspiration for future research into AS and metabolic diseases and the development of new drugs.

Objective To investigate the effects and mechanisms of combined prescriptions of essential oils from five traditional Chinese medicinal herbs,namely peppermint,turmeric,ginger,Tibetan fennel,and cumin,on symptoms related to functional abdominal pain syndrome(FAPS).Methods Gas chromatography-mass spectrometry(GC-MS)was employed to analyze the chemical constituents of five essential oils,while network pharmacology was utilized to predict the key targets and signaling pathways associated with these essential oils in alleviating functional abdominal pain syndrome.A formula design methodology centered on these core targets and signaling pathways was developed for creating new prescriptions.Molecular docking technology was conducted to predict its the underlying mechanisms.Subsequently,animal experiments were performed to assess pharmacological activity,including hot plate tests and acetic acid-induced writhing assays to validate the analgesic effects of the newly formulated prescription,as well as xylene-induced ear swelling tests to evaluate its anti-inflammatory properties.The impact of the essential oil formulation on intestinal peristaltic function was examined through intestinal propulsion experiments.Additionally,enzyme-linked immunosorbent assay(ELISA)methods were employed to measure levels of serotonin(5-HT),prostaglandin E2(PGE2),and gamma-aminobutyric acid(GABA)in brain tissue.Western blot analysis was conducted to determine protein expression levels of TPH1 and SERT in the intestine,along with TPH2 and SERT in the brain.Results The main chemical components in five essential oils were identified and screened(peppermint:12,turmeric:8,ginger:14,cumin:2,fennel:6).Based on the network pharmacology analysis,four new essential oil prescriptions were successfully designed according to the complementary relationship between the five essential oils in improving functional abdominal pain syndrome at the target level,including 4 new prescription named Prescription A,B,C and D,these four prescriptions were all based on ginger and turmeric essential oils,with other essential oils serving as supplements or enhancements.The results of animal experiments showed that Prescription D could significantly reduce the writhe frequency of mice(P<0.05),all the four groups could significantly prolong the pain threshold of mice(P<0.05),and Prescription C had a significant effect on reducing the degree of ear swelling(P<0.05).The prescription of essential oil did not significantly affect the function of peristalsis and the speed of propulsion.The levels of 5-HT and PGE2 in the brain tissue were significantly inhibited(P<0.05),and the level of GABA was significantly increased(P<0.05).Prescription C could reduce the expression of TPH1 in the intestinal tissue(P<0.05),Prescription A,C and D could reduce the expression of TPH2,and all groups had a tendency to increase the expression of SERT in the brain tissue.Conclusion In summary,the therapeutic effects of the four novel prescriptions composed of the five essential oils demonstrated potential in improving symptoms related to FAPS,the mechanism might be through modulating abnormalities in the brain-gut axis system.