ObjectiveTo investigate the mechanism by which Shenqi Yiliu prescription reverses cisplatin resistance in ovarian cancer cells by regulating the phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway-mediated glycolysis. MethodsThe human ovarian cancer A2780 cell line was intervened with progressively increasing doses of cisplatin （1 g·L^-1） to establish the cisplatin-resistant cell line A2780cisR， and the cell sensitivity to cisplatin was examined by the cell counting kit-8 （CCK-8） assay. High， medium， and low （39.9， 19.95， 9.98 g·kg^-1） doses of Shenqi Yiliu prescription-containing sera were used to treat A2780cisR cells for 48 h. Glucose consumption and lactate production were measured by the cuvette assay. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the activities of glucose transporter （GLUT）， phosphofructokinase （PFK）， and pyruvate kinase （PK）. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was used to detect apoptosis. Western blot was employed to quantify the protein levels of phosphorylated （p）-PI3K， p-Akt， p-mTOR， hexokinase 2 （HK2）， pyruvate kinase M2 （PKM2）， B-cell lymphoblastoma-2 （Bcl-2）， Bcl-2-associated X-protein （Bax）， and B-lymphoblastoma-2 gene-related promoter （Bad）. Real-time PCR was conducted to determine the mRNA levels of HK2， PKM2， Bax， Bcl-2， and Bad. ResultsThe median inhibitory concentration （IC₅₀） of cisplatin on A2780cisR cells was nearly 3 times that on A2780P cells. Compared with A2780P cells， A2780cisR cells showed increased glucose consumption， lactate production， GLUT， PFK， and PK activities， and mRNA and protein levels of p-PI3K， Akt， p-mTOR， HK2， PKM2， Bax （P<0.05）， and decreased apoptosis rate and Bcl-2 expression （P<0.05）. Compared with A2780cisR cells， medium- and high-dose Shenqi Yiliu prescription reduced the glucose consumption， lactate production， GLUT， PFK， and PK activities， and mRNA and protein levels of p-PI3K， Akt， p-mTOR， HK2， PKM2， Bax， and Bad （P<0.05）， while increasing the apoptosis rate and Bcl-2 expression （P<0.05）. ConclusionShenqi Yiliu prescription can inhibit glycolysis mediated by the PI3K/Akt/mTOR pathway to promote apoptosis， thereby reversing cisplatin resistance in ovarian cancer cells.

OBJECTIVE To compare the efficacy and safety of evolocumab and probucol in patients with ultra-high-risk atherosclerotic cardiovascular disease （ASCVD） following percutaneous coronary intervention （PCI）. METHODS A retrospective analysis was conducted on 156 ultra-high-risk ASCVD patients who underwent PCI in our institution between January 1， 2023 and December 31， 2024. According to the lipid-lowering regimen， the patients were categorized into evolocumab group （ n ＝86） and probucol group （ n ＝70）. Changes in lipid parameters [total cholesterol （TC）， low-density lipoprot ein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， triglycerides， lipoprotein （a）， and lipid goal achievement rate ] ， inflammatory markers [interleukin-6 （IL-6） and C-reactive protein （CRP） ] ， and cardiac function indices （left ventricular ejection fraction， left ventricular end-systolic diameter， left ventricular end-diastolic diameter， and N-terminal pro-B-type natriuretic peptide） were compared between two groups at baseline and after 6 months of treatment. The incidence of adverse clinical events during treatment， including acute myocardial infarction， in-stent restenosis， acute heart failure， cerebral hemorrhage， and stroke， was also evaluated. RESULTS No statistically significant differences were observed between the two groups at baseline （ P ＞0.05）. After 6 months of treatment， both groups demonstrated significant improvements in lipid profiles （except HDL-C） and inflammatory markers compared to those at baseline （ P ＜0.05）. The evolocumab group exhibited greater reductions in TC， LDL-C， IL-6， and CRP， along with a higher lipid target achievement rate， compared with the probucol group （ P ＜0.05）. There were no statistically significant differences in the cardiac function-related indicators before and after treatment between the two groups， nor in the incidence of adverse events during the treatment （ P ＞0.05）. CONCLUSIONS For ultra-high-risk ASCVD patients after PCI， both of the above treatment options are associated with improvements in blood lipid and inflammatory response， with good safety during short-term follow-up. Evolocumab shows superior efficacy in TC， LDL-C and inflammatory markers reduction and lipid target achievement， compared to probucol.

ObjectiveTo investigate the mechanism of Si Junzitang in treating liver injury in rats with spleen Qi deficiency syndrome based on transcriptomics and to experimentally verify its effects. MethodsSixty male SD rats were randomly divided into blank group， model group， low-dose Si Junzitang （6 g·kg^-1·d^-1）， medium-dose Si Junzitang group （12 g·kg^-1·d^-1）， high-dose Si Junzitang group （24 g·kg^-1·d^-1）， and natural recovery group， with 10 rats in each group. A composite multifactorial modeling method （forced swimming + intragastric administration of Xiao Chengqitang + irregular diet） was used to establish a spleen Qi deficiency model. After 30 days of continuous intervention， body weight and 3-hour food intake were measured， and macroscopic symptom scores for spleen Qi deficiency syndrome were evaluated. Serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） in each group were detected， and hematoxylin and eosin （HE） staining was used to observe histopathological changes in liver tissue. Transcriptome sequencing （RNA-Seq） was used to identify differentially expressed genes （DEGs） among the blank， model， and high-dose Si Junzitang groups. Gene ontology（GO） and Kyoto encyclopedia of genes and genome（KEGG） enrichment analyses were performed on the DEGs. Immunofluorescence （IF） and Western blot were used to detect NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein （ASC）， Caspase-1， and the N-terminal domain of gasdermin D （GSDMD-N）. Immunohistochemistry （IHC） was used to detect the expression of downstream inflammatory cytokines interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and interleukin-18 （IL-18）. ResultsCompared with the blank group， the model group showed significantly reduced body weight and 3-hour food intake， significantly increased macroscopic symptom scores， and elevated serum AST and ALT levels （P<0.01）， with mild inflammatory liver injury observed histologically. Compared with the model group， Si Junzitang at all doses significantly improved these parameters and alleviated liver injury in a dose-dependent manner （P<0.05，P<0.01）. RNA-Seq analysis revealed 1 254 DEGs between the blank and model groups， and 842 DEGs between the model and high-dose Si Junzitang groups. GO and KEGG enrichment analyses indicated that the NOD-like receptor signaling pathway was activated in liver injury associated with spleen Qi deficiency， suggesting that the NLRP3 inflammasome may be a key target. Results from IF， IHC， and Westernblot showed that compared with the blank group， the expression of NLRP3， ASC， Caspase-1， GSDMD-N， and the downstream inflammatory cytokines IL-1β， IL-6， and IL-18 were significantly increased in the model group （P<0.01）， while these levels were markedly decreased in the high-dose Si Junzitang group （P<0.01）. ConclusionSi Junzitang effectively improves mild inflammatory liver injury in rats with spleen Qi deficiency syndrome in a dose-dependent manner. Its mechanism may be associated with inhibition of the NLRP3/ASC/Caspase-1 signaling pathway， downregulation of the pyroptosis executioner protein GSDMD-N， and reduction of pyroptosis-related inflammatory cytokine release.

[This corrects the article DOI: 10.1016/j.apsb.2024.09.010.].

OBJECTIVES: To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice. METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining. RESULTS: After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups. CONCLUSIONS Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
Animals ; Periodontitis/microbiology* ; Mice ; Mice, Inbred C57BL ; Cognition ; Alveolar Bone Loss ; Hippocampus/pathology* ; Male ; Inflammation ; Maze Learning

Objective:To discuss the protective effect of dexmedetomidine(DEX)on intestinal function in rats with enterogenous sepsis,and to clarify its potential mechanism based on E2F transcription factor 1(E2F1)/nuclear factor kappa B(NF-κB)signaling pathway.Methods:Sixty SD rats were selected,among which 50 rats were used to establish enterogenous sepsis models by cecal ligation and puncture(CLP),and the remaining 10 rats were used as sham operation group(only cecal separation without ligation or puncture).The 40 successfully modeled rats were randomly divided into model group,low dose of DEX group,medium,doses of DEX group,and high dose of DEX group,with 10 rats in each group.The rats in low,medium,and high dose of DEX groups were intraperitoneally injected with 20,40 and 60 μg·kg-1 DEX immediately after modeling,while the rats in sham operation group and model group were intraperitoneally injected with the same volume of saline.After 24 h of administration,the intestinal myoelectric activities of the rats in various groups were detected;the colony counts of Escherichia coli,Lactobacillus and Bifidobacterium in cecal contents of the rats in various groups were detected;the pathomorphology of small intestinal tissue of the rats was observed by HE staining;the levels of secretory immunoglobulin A(sIgA)in supernatant of small intestinal tissue homogenate and the levels of diamine oxidase(DAO)and D-lactic acid in serum of the rats in various groups were detected by kit;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the mRNA expression levels of macrophage polarization markers in small intestinal tissues of the rats in various groups;Western blotting method was used to detect the protein expression levels of macrophage polarization markers,E2F1,phosphorylated NF-κB p65(p-NF-κB p65),and NF-κB p65 in small intestinal tissue of the rats in various groups.Results:Compared with sham operation group,the slow wave frequency and amplitude of intestinal smooth muscle of the rats in model group were decreased(P<0.05);compared with model group,the slow wave amplitude of intestinal smooth muscle of the rats in low dose of DEX groups was increased(P<0.05),the slow wave frequency and amplitude of intestinal smooth muscle of the rats in medium and high doses of DEX groups were increased(P<0.05);compared with low dose of DEX group,the slow wave frequency and amplitude of the rats in medium and high doses of DEX groups were increased(P<0.05);compared with medium dose of DEX group,the slow wave frequency and amplitude of intestinal smooth muscle of the rats in high dose of DEX group were increased(P<0.05).Compared with sham operation group,the colony count of Escherichia coli in intestinal tract of the rats in model group was increased(P<0.05),while the colony counts of Bifidobacterium and Lactobacillus were decreased(P<0.05);compared with model group,the colony count of Bifidobacterium in intestinal tract of the rats in low dose of DEX group was decreased(P<0.05),the colony count of Escherichia coli in intestinal tract of the rats in medium,and high doses of DEX groups was decreased(P<0.05),while the colony counts of Bifidobacterium and Lactobacillus were increased(P<0.05);compared with low dose of DEX group,the colony count of Escherichia coli in intestinal tract of the rats in medium and high dose of DEX groups was decreased(P<0.05),while the colony counts of Bifidobacterium and Lactobacillus were increased(P<0.05);compared with medium dose of DEX group,the colony count of Escherichia coli in intestinal tract of the rats in high dose of DEX group was decreased(P<0.05),while the colony counts of Bifidobacterium and Lactobacillus were increased(P<0.05).The HE staining results showed that the small intestinal mucosal structure in sham operation group was normal and intact;the small intestinal mucosal epithelial cells in model group were necrotic,with damaged,collapsed and disordered villi;Compared with model groups,the pathological changes of small intestinal tissues in low,medium,and high doses of DEX groups were improved.Compared with sham operation group,the level of sIgA in supernatant of small intestinal tissue homogenate of the rats in model group was decreased(P<0.05),while the protein expression levels of DAO and D-lactic acid in serum were increased(P<0.05);compared with model group,the level of DAO in serum of the rats in low dose of DEX groups was decreased(P<0.05),the level of sIgA in supernatant of small intestinal tissue homogenate of the rats in medium and high doses of DEX groups was increased(P<0.05),while the protein expression levels of DAO and D-lactic acid in serum were decreased(P<0.05);compared with low dose of DEX group,the level of sIgA in supernatant of small intestinal tissue homogenate of the rats in medium and high doses of DEX groups was increased(P<0.05),while the protein expression levels of DAO and D-lactic acid in serum were decreased(P<0.05);compared with medium dose of DEX group,the level of sIgA in supernatant of small intestinal tissue homogenate of the rats in high dose of DEX group was significantly increased(P<0.05),while the protein expression levels of DAO and D-lactic acid in serum were decreased(P<0.05).The RT-qPCR results and Western blotting results showed that compared with sham operation group,the mRNA and protein expression levels of CD86,monocyte chemoattractant protein-1(MCP-1),and CD80 in small intestinal tissue of the rats in model group were increased(P<0.05),while the mRNA and protein expression levels of CD206,interleukin-4(IL-4)and,CD163 were decreased(P<0.05);compared with model group,the expression levels of CD80 mRNA,CD86 protein and MCP-1 protein in small intestinal tissue of the rats in low dose of DEX group were decreased(P<0.05),and the expression levels of IL-4 mRNA,CD163 mRNA,CD206 protein,and CD163 protein were decreased(P<0.05),the mRNA and protein expression levels of CD86,MCP-1,and CD80 in small intestinal tissue of the rats in medium and high doses of DEX groups were decreased(P<0.05),while the mRNA and protein expression levels of CD206,IL-4 and CD163 were increased(P<0.05);compared with low dose of DEX group,the mRNA and protein expression levels of CD86,MCP-1,and CD80 in small intestinal tissue of the rats in medium and high doses of DEX groups were decreased(P<0.05),while the mRNA and protein expression levels of CD206,IL-4,and CD163 were increased(P<0.05);compared with medium dose of DEX group,the mRNA and protein expression levels of CD86,MCP-1,and CD80 in small intestinal tissue of the rats in high dose of DEX group were decreased(P<0.05),while the mRNA and protein expression levels of CD206,IL-4,and CD163 were increased(P<0.05).The Western blotting results showed that compared with sham operation group,the protein expression level of E2F1 in small intestinal tissue of the rats in model group was decreased(P<0.05),while the ratio of p-NF-κB p65/NF-κB p65 was increased(P<0.05);compared with model group,the protein expression levels of E2F1 and ratio of p-NF-κB p65/NF-κB p65 in small intestinal tissue of the rats in low,medium and high doses of DEX groups were decreased(P<0.05);compared with low dose of DEX group,the protein expression level of E2F1 in small intestinal tissue of the rats in medium and high doses of DEX groups was increased(P<0.05),while the ratio of p-NF-κB p65/NF-κB p65 was decreased(P<0.05);compared with medium dose of DEX group,the protein expression level of E2F1 in small intestinal tissue of the rats in high dose of DEX group was increased(P<0.05),while the ratio of p-NF-κB p65/NF-κB p65 was decreased(P<0.05).Conclusion:DEX can improve the small intestinal mucosal injury in the rats with enterogenous sepsis and promote the polarization of macrophages to M2 type in small intestinal tissues,and its mechanism may be related to the regulation of E2F1/NF-κB signaling pathway by DEX.

Objective To explore the relationship between serum S100 calcium-binding protein(S100)A4,S100A12 and the infection type and prognosis of neonatal infectious pneumonia(NIP).Methods A total of 300 children with NIP admitted to the Neijiang Second People's Hospital from January 2021 to March 2024 were selected and divided into the bacterial infection group(214 cases)and the non-bacterial infection group(86 cases)according to the types of pathogenic bacteria.Another 150 healthy newborns in the same hospital during the same period were selected as the control group.The levels of serum S100A4 and S100A12 were de-tected by enzyme-linked immunosorbent assay.Pearson correlation analysis was conducted to examine the cor-relations between serum S100A4,S100A12 and procalcitonin(PCT),white blood cell count(WBC),albumin(Alb),and platelet count(PLT).The receiver operating characteristic(ROC)curve was used to evaluate the differential value of serum S100A4,S100A12,PCT,WBC,Alb,and PLT alone and in combination for NIP bac-terial infection.According to the prognosis,children with NIP were divided into the poor prognosis group(63 cases)and the good prognosis group(237 cases).Multivariate Logistic regression model was used to analyze the influencing factors of poor prognosis in children with NIP,and ROC curve was used to analyze the value of each factor in predicting poor prognosis in children with NIP.Results The levels of serum S100A4,S100A12,PCT,WBC,and PLT in the bacterial infection group were higher than those in the non-bacterial infection group and the control group,while Alb was lower than that in the non-bacterial infection group and the control group,the differences were statistically significant(P<0.05).Pearson correlation analysis showed that serum S100A4 and S100A12 in children with NIP were positively correlated with PCT,WBC and PLT(P<0.05),and negatively correlated with Alb(P<0.05).The results of ROC curve analysis showed that the area under the curve(AUC)of serum S100A4 and S100A12 in differentiating NIP infection types was slightly lower than that of PCT,WBC,Alb,and PLT in differentiating NIP infection types.The results of multivariate Logistic re-gression analysis showed that elevated S100A4,elevated S100A12,elevated PCT,bacterial infection,and lung consolidation were independent risk factors for poor prognosis in children with NIP(P<0.05).The AUC of bacterial infection,lung consolidation,PCT,S100A4,and S100A12 for predicting the poor prognosis of chil-dren with NIP was 0.903.It was greater than the AUC predicted separately by bacterial infection,lung consol-idation,PCT,S100A4,and S100A12 levels(Z=9.989,9.460,5.514,4.084,4.376,P<0.001).Conclusion The combination of serum S100A4 and S100A12 with traditional markers has certain discrimina-tory value for the infection types of NIP,and the levels of serum S100A4 and S100A12 are related to the prog-nosis of NIP.

Flow diverter (FD) can significantly improve the occlusion rate and reduce the recurrence rate of intracranial aneurysms, and has become an irreplaceable endovascular treatment option. Delayed aneurysm rupture (DAR) is one of the most serious complications after FD implantation, with a very high mortality rate. It is a major challenge to the safety of FD implantation. The mechanism of DAR is currently not fully understood and may be associated with the changes in hemodynamics after FD implantation, inflammation and mechanical stress within aneurysms, and changes in postoperative coagulation function. This article reviews the research progress on the occurrence mechanism of DAR and outlines future research directions, with the aim of reducing DAR occurrence and optimizing clinical decision-making.

Osteoporosis is a globally prevalent metabolic bone disease,with bone homeostasis imbalance being its key pathogenic mechanism.Over the years,studies on the relationship between ambient temperature and bone health have shown heterogeneous results due to different conditions.Epidemiological studies indicate that the incidence of osteoporotic fractures varies geographically and climatically.People in cold regions experience earlier bone loss,and high-latitude cold areas are high-risk zones for hip fractures.Osteoporosis is more prevalent in North China that in South China.Additionally,the early stage of the disease is insidious,highlighting the need for early prevention and treatment across the entire population.Mechanistically,low temperatures affect acral bone development,reduce bone blood circulation,cause degradation of bone microstructure,and increase osteocyte apoptosis,thereby promoting bone resorption and reducing bone mass.This review aims to provide data and new lines of thought for the early precise prevention and effective clinical treatment of osteoporosis in cold regions.

AIM: To analyze the abnormal refractive status of infants and young children aged 6 to 48 months, and to provide basis for the correction of ametropia and the early prevention and treatment of amblyopia.METHODS: Infants and young children aged 6 to 48 months were examined for refraction by Spot vision screener for natural optometry. Clinical data of infants and young children with refractive abnormalities were collected, Ciliary muscle paralysis agent was used for retinoscopy and optometry, and the results were statistically analyzed.RESULTS: A total of 168 cases(336 eyes)with abnormal Spot refractive outcomes were collected, with a high proportion of hyperopia and astigmatism abnormalities, 38.4% and 28.6%, respectively, while the proportion of myopia was low(12.2%). There were 90 cases of anisometropia(≥1.00 D), among which 41 cases(45.6%)were astigmatic anisometropia, 33 cases(36.7%)were hyperopic anisometropia, and 16 cases(17.8%)were myopic anisometropia, accounting for the least proportion. A total of 109 infants and young children with Spot refractive abnormalities completed ciliary muscle paralysis retinal optometry. The analysis of the difference and correlation between Spot diopter and post ciliary muscle paralysis optometry results showed that the difference in astigmatism was 0.34±0.64 D(P<0.001), the difference in hyperopia was -2.10±1.27 D(P<0.001), and the difference in myopia was -0.43±0.91 D(P=0.023). Although there was a statistical difference between the two results, astigmatism, hyperopia, and myopia were highly positively correlated, respectively(r=0.694, 0.762, 0.909).CONCLUSION: The main refractive abnormalities in infants and young children aged 6 to 48 months are astigmatism, hyperopia, and anisometropia, with fewer abnormalities in myopia. For screening abnormalities, further ciliary muscle paralysis agent retinoscopy and optometry should be performed, and glasses correction should be given to effectively prevent refractive amblyopia in infants and young children.