ObjectiveTo explore the mechanism of Yishen Qubi Tongluo Formula （益肾祛痹通络方， YQTF） in the treatment of rheumatoid arthritis（RA）. MethodsNetwork pharmacology was employed to retrieve and screen the active components and potential targets of YQTF as well as RA-related targets using databases including TCMSP， BATMAN， ETCM and GEO. The intersection of targets related to active components and RA-related targets was identified， and a protein-protein interaction （PPI） network was constructed. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed， and a drug-active component-common target network of YQTF in the treatment of RA was established. The core components of YQTF were molecularly docked with key targets. Human rheumatoid arthritis synovial fibroblast cell line MH7A was divided into blank group， model group， methotrexate group and YQTF group. The blank group was cultured with 10% fetal bovine serum， while the other three groups were stimulated with 10 μg/L of recombinant human tumor necrosis factor-α （TNF-α） for 24 h to establish the RA cell model. On this basis， the methotrexate group was treated with methotrexate suspension at a concentration of 20 μmol/L， and the YQTF group was treated with 10% YQTF-medicated serum. After 48 h of intervention， the levels of TNF-α and interleukin-17A（IL-17A）contents in cell supernatants were detected by enzyme-linked immunosorbent assay （ELISA）， and mRNA expressions of phosphatidylinositol 3-kinase（PI3K）， protein kinase B（AKT） and mammalian target of rapamycin（mTOR） were detected by real-time quantitative polymerase chain reaction （RT-qPCR）. ResultsNetwork pharmacological analysis identified 209 active components and 583 potential target genes of YQTF， as well as 818 RA-related targets. A total of 29 common targets were obtained from the intersection of drug-related targets and RA-related targets. Quercetin，β-sitosterol， kaempferol， stigmasterol and luteolin were the core active components of YQTF for the treatment of RA， while matrix metalloproteinase-9 （MMP9）， prostaglandin-endoperoxide synthase 2 （PTGS2）， Toll-like receptor 4 （TLR4）， tumor protein p53 （TP53） and transcription factor AP-1 subunit JUN were the key targets. The GO and KEGG pathway enrichment analysis showed that the involved biological processes and pathways were mainly associated with antioxidant responses， PI3K-AKT signaling pathway and Toll-like receptor （TLR） signaling pathway. Molecular docking results showed that MMP9 and PTGS2 exhibited high binding affinities with quercetin， β-sitosterol， kaempferol， stigmasterol and luteolin； TLR4 exhibited high binding activities with β-sitosterol， stigmasterol and luteolin； and TP53 showed high binding affinity with luteolin. The results of cell experiments showed that compared with the control group， the contents of TNF-α and IL-17A as well as the mRNA expressions of AKT and mTOR in the model group significantly increased （P＜0.05 or P＜0.01）. Compared with the model group， all the above indicators significantly decreased in the YQTF group， while the contents of TNF-α and the mRNA expression of AKT significantly decreased in the methotrexate group （P＜0.05 or P＜0.01）. ConclusionThe mechanism of YQTF in the treatment of RA may be associated with reducing inflammatory cytokine secretion and inhibiting the activation of the PI3K-AKT-mTOR signaling pathway.

ObjectiveTo investigate the efficacy and safety of Shuganning injection in the treatment of liver injury by observing the clinical outcome of patients with liver injury after treatment with Shuganning injection and comparing it with reduced glutathione （GSH）. MethodsThis study was conducted among 175 patients with liver injury who attended 6 hospitals in China （Beijing YouAn Hospital， Capital Medical University； Nanyang First People’s Hospital； The Second Affiliated Hospital of Xi’an Jiaotong University； The Fifth Medical Center of Chinese PLA General Hospital； The Third Hospital of Hebei Medical University； The Affiliated Hospital of Guizhou Medical University） from April 25， 2019 to February 28， 2022. The patients were divided into experimental group （89 patients treated with Shuganning injection） and control group （86 patients treated with GSH）， and the course of treatment was 4 weeks for both groups. Related indicators were recorded before treatment， after treatment， and after drug withdrawal for 8 weeks， including liver function parameters， blood biochemical parameters， blood lipids， coagulation profiles， liver fibrosis markers， traditional Chinese medicine （TCM） syndrome score， and ultrasound findings， as well as adverse events during treatment. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The Wilcoxon signed-rank test was used for comparison of observation indicators before treatment， at week 4 of treatment， and after drug withdrawal for 8 weeks. When the efficacy evaluation of TCM syndromes was used as the outcome， a pooled analysis was performed for the effective cases and the markedly effective cases， and a Logistic regression model was used to calculate the odds ratio （OR） and its 95%CI. ResultsAfter 4 weeks of treatment with Shuganning injection， the patients showed significant reductions in TCM syndrome score （P<0.001） and the levels of aspartate aminotransferase， alanine aminotransferase， total bilirubin， and direct bilirubin （all P<0.001） and a significant increase in the level of albumin （P=0.002）， and these significant improvements persisted after drug withdrawal for 8 weeks. Furthermore， compared with the control group， the experimental group had a significantly higher proportion of patients assessed as effective or markedly effective cases （48.31% vs 32.56%， P=0.033）. Compared with the control group， the experimental group had a significantly greater change in TCM syndrome score at weeks 1-4 of treatment and after drug withdrawal for 8 weeks （P<0.05）. At week 4 of treatment， the experimental group had a significantly greater reduction in alanine aminotransferase than the control group （P<0.05）， and at week 8 after drug withdrawal， the experimental group had a significantly greater reduction in alanine aminotransferase and aspartate aminotransferase than the control group （all P<0.05）. One patient in the experimental group （1.12%） experienced an adverse event， which was determined to be associated with the progression of viral hepatitis. ConclusionShuganning injection can effectively improve liver injury， with good long-term efficacy and a low incidence rate of adverse reactions.

Objective:To evaluate the mechanical stability of the bone block after LeFort Ⅰ osteotomy with maxillary advancement using absorbable plates fixed with tenon-and-mortise structures.Methods:This study developed three finite element models: one for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with absorbable plates (Model 1); another for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with absorbable plates assisted by tenon-and-mortise structures (Model 2); and the last one for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with titanium plates and screws (Model 3). Simulated occlusal forces were applied on the anterior and posterior teeth in each model. The displacement changes of the nasal-palatine point (NP) and posterior nasal spine point (PNS) in the finite element coordinate system were compared and analyzed. The Mises equivalent stress distributions of the metal and absorbable plates were also examined to assess the mechanical stability of the three finite element models. Clinical data from 45 patients with dentofacial deformities treated from January 2017 to January 2023 at the Stomatology Hospital of China Medical University were collected. The age of the patients was 21±3 years. Among these, 15 patients had absorbable plates for fixation, 15 had absorbable plates assisted by tenon-and-mortise structures, and 15 had titanium plates and screws fixation after maxillary advancement. All patients underwent preoperative (T0), postoperative 3 days (T1), and 6 months (T2) spiral CT scans. The CT data in DICOM format were input into digital software, which was used to calculate the distances from the NP and PNS points to the horizontal plane (HP), right sagittal plane (FZSR), and coronal plane (CP) at T1 and T2. The distances at T1 and T2 were statistically analyzed using the Wilcoxon signed-rank test with SPSS 20.0, and a P value of<0.05 was considered statistically significant.Results:The finite element analysis showed that in the absorbable plate-only fixation group, the maximum displacement of the NP point (mm) under anterior and posterior tooth force conditions were 0.6 and 0.12, respectively, and for the PNS point, the maximum displacements were 0.5 and 0.11. In the tenon-and-mortise-assisted absorbable plate fixation group, the displacement of the NP point was 0.40 and 0.02 mm, and the displacement of the PNS point was 0.5 and 0.015 mm. In the titanium plate-screw fixation group, the NP point displacement was 0.33 and 0.055 mm, and the PNS point displacement was 0.16 and 0.1 mm. The Mises equivalent stress on the absorbable plates with tenon-and-mortise structure was significantly lower than that in the absorbable plate-only fixation group, while the titanium plate experienced the highest Mises equivalent stress. The clinical data analysis showed that in the horizontal direction, the postoperative stability of the three fixation methods was similar. However, in the vertical and anterior-posterior directions, the absorbable plate-only fixation group showed significant differences in the distances of PNS-HP, PNS-CP, and NP-CP between T1 and T2 ( P=0.018, P=0.009, P=0.017), suggesting significant postoperative bone displacement. In contrast, the tenon-and-mortise-assisted absorbable plate fixation group and the titanium plate-screw fixation group showed no significant differences in displacement during surgery and postoperatively(all P>0.05), demonstrating higher stability. Conclusions:The tenon-and-mortise-assisted absorbable plate fixation provides comparable stability to titanium plate fixation in clinical results, and it is more stable than absorbable plate-only fixation. In the mechanical study, when force was applied on the anterior teeth, the stability of the tenon-and-mortise-assisted absorbable plate fixation was slightly less than that of titanium plate fixation, but when posterior teeth were used, its stability exceeded both titanium plate fixation and absorbable plate-only fixation. The tenon-and-mortise-assisted absorbable plate fixation serves as an effective alternative to titanium plate fixation after LeFort Ⅰ osteotomy.

Objective: To analyze the prevalence and determinants of comorbid overweight/obesity and elevated blood pressure among primary and secondary school students in Yangzhou City, and to explore the association between sleep patterns, eating behavior and the comorbidity of overweight/obesity and elevated blood pressure, so as to provide reference for developing prevention strategies targeting common comorbidities in students. Methods: By using stratified cluster random sampling, a total of 8 735 primary and secondary school students were selected from 36 schools in six counties of Yangzhou from October to November 2023. Students underwent physical examinations and a questionnaire survey was conducted using the questionnaire on students health status and influencing factors. The Chi square test was used to compare the detection rate of comorbid overweight/obesity and elevated blood pressure in different groups of primary and secondary school students. The Logistic regression model was used to explore the association between sleep and dietary behaviors and their combined effects and coexistence. Results: The detection rate of comorbid overweight/obesity and elevated blood pressure among primary and secondary school students in Yangzhou was 9.85%, which was higher among boys (12.14%) than girls (7.59%)( χ 2=50.86, P <0.01). After controlling for gender, residence, educational stage, parental education, smoking, drinking, and moderate to vigorous exercise, multivariate Logistic regression analysis showed that irregular breakfast consumption and inadequate daily sleep were associated with a higher risk of comorbidities compared with regular breakfast consumption and adequate daily sleep among overall and primary school students (overall: OR =1.52, 95% CI =1.18- 1.96 , primary school students: OR =2.79, 95% CI =1.61-4.82)(both P <0.05). From the perspective of primary school students of different genders, the risk of comorbidities in girls who consumed breakfast irregularly and had inadequate daily sleep was 3.59 times higher than that in girls who consumed breakfast irregularly and had inadequate daily sleep (95% CI =1.65-7.82, P <0.01). Conclusion The sleep patterns and breakfast behaviors of primary and secondary school students are found to be associated with comorbid overweight/obesity and elevated blood pressure, especially in primary school girls.

Objective To understand the current situation of nutrition literacy of primary and secondary school students in Shijingshan District of Beijing, and analyze its influencing factors, and to put forward targeted suggestions for improving the students’ nutrition literacy and promoting their healthy growth. Methods A multi-stage stratified cluster sampling method was used to select 2480 primary and secondary school students and their parents from 5 primary schools, 3 middle schools and 1 high school in Shijingshan District. The multivariate logistic regression model was used to analyze the factors influencing the attainment rate of nutrition literacy. Results The median score of nutrition literacy of 2480 primary and secondary school students from grades 1 to 12 was 77.86 (in hundred-mark system), the quartile range (IQR) was 16.96, and the attainment rate of nutrition literacy was 42.46%. The cognitive level (45.12%) was higher than the skill level (41.20%) among students from grades 3 to 12. In terms of skills, the attainment rate of food preparation was the lowest, at 30.38%. The scores of nutrition literacy of girls were higher than those of boys, and the scores of primary school students were higher than those of secondary school students. Students with different levels of caregiver’s education, family income, and family food environment had different scores of nutrition literacy, and the differences were statistically significant (P<0.05). Multivariate logistic regression analysis showed that the attainment rate of nutrition literacy was closely related to student’s gender and study stage, caregiver’s education level, and family food environment. Conclusion The nutrition literacy of primary and secondary school students in Shijingshan District still needs to be improved, especially in the aspect of skills. Targeted nutrition education should be carried out.

Objective To analyze the research status,hot directions and frontier trends of traditional Chinese medicine in the prevention and treatment of diseases by regulating Notch signaling pathway based on bibliometrics.Methods Based on Citespace and Vosviewer,the literature on the regulation of Notch signaling pathway by traditional Chinese medicine in CNKI and WoSCC was visually analyzed.Results 362 and 85 related literatures were published in Chinese and English respectively until January 2024.Since 2013,the number of literatures published in this field has shown a fluctuating increasing trend.China is the country with the most publications;Hunan University of Chinese Medicine were the institutions with the most publications in the Chinese database,and Beijing University of Chinese Medicine was the institution with the most publications in the English literature database.Combined with the research direction of each research team and keyword clustering and burst analysis,the research hotspots of traditional Chinese medicine regulating Notch signaling pathway are focused on cerebral ischemia,myelosuppression and hepatic fibrosis.Diseases such as Asthma,colorectal cancer have become emerging research directions in recent years.Electroacupuncture therapy to promote stem cell proliferation and treat neurological diseases is one of the frontier research trends in this field.Conclusion Recent years have seen a rapid development of traditional Chinese medicine's disease prevention and treatment that targets Notch signaling pathway.Various expert teams have obtained rich research results,and the research hotspots show a diversified trend.In-depth exploration of this can provide strong evidence for the molecular mechanism of traditional Chinese medicine in the treatment of various diseases.

Objective:To evaluate the mechanical stability of the bone block after LeFort Ⅰ osteotomy with maxillary advancement using absorbable plates fixed with tenon-and-mortise structures.Methods:This study developed three finite element models: one for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with absorbable plates (Model 1); another for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with absorbable plates assisted by tenon-and-mortise structures (Model 2); and the last one for the maxillary LeFort Ⅰ osteotomy with anterior advancement fixed with titanium plates and screws (Model 3). Simulated occlusal forces were applied on the anterior and posterior teeth in each model. The displacement changes of the nasal-palatine point (NP) and posterior nasal spine point (PNS) in the finite element coordinate system were compared and analyzed. The Mises equivalent stress distributions of the metal and absorbable plates were also examined to assess the mechanical stability of the three finite element models. Clinical data from 45 patients with dentofacial deformities treated from January 2017 to January 2023 at the Stomatology Hospital of China Medical University were collected. The age of the patients was 21±3 years. Among these, 15 patients had absorbable plates for fixation, 15 had absorbable plates assisted by tenon-and-mortise structures, and 15 had titanium plates and screws fixation after maxillary advancement. All patients underwent preoperative (T0), postoperative 3 days (T1), and 6 months (T2) spiral CT scans. The CT data in DICOM format were input into digital software, which was used to calculate the distances from the NP and PNS points to the horizontal plane (HP), right sagittal plane (FZSR), and coronal plane (CP) at T1 and T2. The distances at T1 and T2 were statistically analyzed using the Wilcoxon signed-rank test with SPSS 20.0, and a P value of<0.05 was considered statistically significant.Results:The finite element analysis showed that in the absorbable plate-only fixation group, the maximum displacement of the NP point (mm) under anterior and posterior tooth force conditions were 0.6 and 0.12, respectively, and for the PNS point, the maximum displacements were 0.5 and 0.11. In the tenon-and-mortise-assisted absorbable plate fixation group, the displacement of the NP point was 0.40 and 0.02 mm, and the displacement of the PNS point was 0.5 and 0.015 mm. In the titanium plate-screw fixation group, the NP point displacement was 0.33 and 0.055 mm, and the PNS point displacement was 0.16 and 0.1 mm. The Mises equivalent stress on the absorbable plates with tenon-and-mortise structure was significantly lower than that in the absorbable plate-only fixation group, while the titanium plate experienced the highest Mises equivalent stress. The clinical data analysis showed that in the horizontal direction, the postoperative stability of the three fixation methods was similar. However, in the vertical and anterior-posterior directions, the absorbable plate-only fixation group showed significant differences in the distances of PNS-HP, PNS-CP, and NP-CP between T1 and T2 ( P=0.018, P=0.009, P=0.017), suggesting significant postoperative bone displacement. In contrast, the tenon-and-mortise-assisted absorbable plate fixation group and the titanium plate-screw fixation group showed no significant differences in displacement during surgery and postoperatively(all P>0.05), demonstrating higher stability. Conclusions:The tenon-and-mortise-assisted absorbable plate fixation provides comparable stability to titanium plate fixation in clinical results, and it is more stable than absorbable plate-only fixation. In the mechanical study, when force was applied on the anterior teeth, the stability of the tenon-and-mortise-assisted absorbable plate fixation was slightly less than that of titanium plate fixation, but when posterior teeth were used, its stability exceeded both titanium plate fixation and absorbable plate-only fixation. The tenon-and-mortise-assisted absorbable plate fixation serves as an effective alternative to titanium plate fixation after LeFort Ⅰ osteotomy.

Objective To investigate the role of circular RNAs(circRNA)in Alzheimer's disease(AD)and its potential mechanism.Methods Six-month-old APP/PS1 mouse model of AD and wild type(WT)mice were subjected and then randomly divided into WT group,WT+circ-Olfm1 knockout group,AD group(transgenic APP/PS1 mice),AD+circ-Olfm1 knockout group,AD+FOXO3a knockout group,with 3 mice in each group.① The total RNA of mouse brain was extracted,and the differential expression of circRNAs and mRNAs between the AD mice and WT mice was detected,and the obtained circRNAs and mRNAs were analyzed with gene ontology(GO)analysis.② RT-qPCR was used to detect the expression of the top 10 up-regulated and down-regulated circRNAs,as well as the expression of circ-Olfm1 and miR-330-5p.③ Lentiviral vectors were prepared and stereotaxically injected into the cortex or hippocampus of WT and AD mice to knock out circ-Olfm1 gene.Water maze test was used to evaluate the effect of circ-Olfm1 knockout on cognitive function,and immunofluorescence assay was employed to observe the deposition of amyloid β(Aβ)plaque in the brain.④ The interaction between circ-Olfm1 and miR-330-5p was verified by double luciferase reporter gene analysis.⑤ The protein levels of AMPK and FOXO3a were detected by Western blotting.⑥ Transmission electron microscopy was utilized to observe the mitochondria of the hippocampus.⑦ The levels of inflammatory factors IL-6,IL-1β and TNF-α were detected by ELISA.Results There were totally 52 differentially expressed circRNAs identified between the AD and WT mice,including 28 up-regulated and 24 down-regulated(fold change>1.5,P<0.05).These differentially expressed genes are mainly involved in signal transduction,learning and memory and other functions.circ-Olfm1 was identified as the most significantly differentially expressed circRNA,which is highly expressed in the neurons and up-regulated in the cerebral cortex and hippocampus of the AD mice.Knockout of circ-Olfm1 reduced the number of Aβ plaques in the cerebral cortex and hippocampus of AD mice(P<0.01).In starBase database,there are complementary sequences observed between circ-Olfm1 and miR-330-5p.Western blotting showed that the addition of Aβ42 significantly increased the expression of AMPK and FOXO3a in the neuronal cells(P<0.01).And silencing circ-Olfm1 led to decreased expression of AMPK and FOXO3a in neuronal cells+Aβ42(P<0.01).ELISA revealed that knockout of FOXO3a significantly increased the levels of inflammatory factors IL-6,IL-1β,and TNF-α(P<0.01).Transmission electron microscopy displayed that knocking FOXO3a out significantly aggravated mitochondrial damage(P<0.01).Conclusion circ-Olfm1 is up-regulated in the brain tissue and neurons+Aβ42 of AD rats,and the mechanism of cognitive impairment in AD rats may be through its regulating FOXO3a protein.

Objective To analyze the research status,hot directions and frontier trends of traditional Chinese medicine in the prevention and treatment of diseases by regulating Notch signaling pathway based on bibliometrics.Methods Based on Citespace and Vosviewer,the literature on the regulation of Notch signaling pathway by traditional Chinese medicine in CNKI and WoSCC was visually analyzed.Results 362 and 85 related literatures were published in Chinese and English respectively until January 2024.Since 2013,the number of literatures published in this field has shown a fluctuating increasing trend.China is the country with the most publications;Hunan University of Chinese Medicine were the institutions with the most publications in the Chinese database,and Beijing University of Chinese Medicine was the institution with the most publications in the English literature database.Combined with the research direction of each research team and keyword clustering and burst analysis,the research hotspots of traditional Chinese medicine regulating Notch signaling pathway are focused on cerebral ischemia,myelosuppression and hepatic fibrosis.Diseases such as Asthma,colorectal cancer have become emerging research directions in recent years.Electroacupuncture therapy to promote stem cell proliferation and treat neurological diseases is one of the frontier research trends in this field.Conclusion Recent years have seen a rapid development of traditional Chinese medicine's disease prevention and treatment that targets Notch signaling pathway.Various expert teams have obtained rich research results,and the research hotspots show a diversified trend.In-depth exploration of this can provide strong evidence for the molecular mechanism of traditional Chinese medicine in the treatment of various diseases.

Objective To investigate the effects of eicosanoic acid(C20DC)on the proliferation and migration of human retinal endothelial cells(HRECs)and its mechanism.Methods The optimal working concentration of C20DC in human retinal pigment epithelium 19(ARPE-19)cells and HRECs was determined as 30 mg·L-1 and 25 mg·L-1,respec-tively.HRECs were divided into the C20DC treatment group(HRECs treated with C20DC)and the control group[HRECs treated with dimethyl sulfoxide(DMSO)].The effects of C20DC on the migration and proliferation of HRECs were detec-ted by cell proliferation and migration experiments.The molecular docking method was used to simulate the binding ability of C20DC to peroxisome proliferator-activated receptor δ(PPARδ).ARPE-19 cells were divided into the C20DC+ARPE-19 group(ARPE-19 cells treated with C20DC)and the DMSO+ARPE-19 group(ARPE-19 cells treated with DMSO).The ex-pression levels of PPARδ and angiopoietin-like protein 4(ANGPTL4)in ARPE-19 cells and ANGPTL4 protein in HRECs were detected using Western blot.The ANGPTL4 protein expression levels in ARPE-19 cells and HRECs were quantitatively analyzed using enzyme-linked immunosorbent assay(ELISA).Results Compared with the control group,the prolifera-tion and migration of cells in the C20DC treatment group significantly increased(both P＜0.05),and C20DC could stably bind to PPAR8(binding energy:-7.20 kcal·mol-1).Western blot showed that the expression level of ANGPTL4 protein in the C20DC+ARPE-19 group was higher than that in the DMSO+ARPE-19 group,and the difference was statistically sig-nificant(P＜0.05);there was no statistically significant difference in the expression level of PPARδ receptor protein be-tween the two groups(P＞0.05).The expression level of ANGPTL4 protein in the C20DC treatment group was higher than that in the control group,and the difference was statistically significant(P＜0.05).ELISA quantitative analysis showed that the expression level of ANGPTL4 in the C20DC+ARPE-19 group was higher than that in the DMSO+ARPE-19 group(P＜0.001);the expression level of ANGPTL4 in the C20DC treatment group was higher than that in the control group,and the difference was statistically significant(P＜0.05).Conclusion C20DC can promote the expression of ANGPTL4 pro-tein by binding to PPARδ and thus increase the proliferation and migration of retinal related cells(HRECs and ARPE-19 cells).Its mechanism may be related to the increased angiogenesis in retinopathy of prematurity.