OBJECTIVE To investigate the effects and potential mechanism of paeoniflorin on oxidative stress of ulcerative colitis （UC） mice based on adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor-erythroid 2-related factor 2 （Nrf2） pathway. METHODS Male BALB/c mice were randomly divided into control group， model group， inhibitor group （AMPK inhibitor Compound C 20 mg/kg）， paeoniflorin low-， medium- and high-dose groups （paeoniflorin 12.5， 25， 50 mg/kg）， high- dose of paeoniflorin+inhibitor group （paeoniflorin 50 mg/kg+Compound C 20 mg/kg）， with 8 mice in each group. Except for the control group， mice in all other groups were given 4% dextran sulfate sodium solution for 5 days to establish the UC model. Subsequently， mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally， once a day， for 7 consecutive days. The changes in body weight of mice were recorded during the experiment. Twenty-four hours after the last administration， colon length， malondialdehyde （MDA） content， and activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in colon tissues were measured； histopathological morphology of colon tissues， tight junctions between intestinal epithelial cells， and histopathological scoring were all observed and evaluated； the mRNA expressions of AMPK and Nrf2， as well as the protein expressions of heme oxygenase-1（HO-1）， occludin and claudin-1， were all determined in colon tissue. RESULTS Compared with model group， paeoniflorin groups exhibited recovery from pathological changes such as inflammatory cell infiltration and crypt damage in the colon tissue， as well as improved tight junction damage between intestinal epithelial cells. Additionally， significant increases or upregulations were observed in body weight， colon length， activities of SOD and GSH-Px， phosphorylation level of AMPK， and protein expression of Nrf2， HO-1， occludin， claudin-1， and mRNA expressions of AMPK and Nrf2； concurrently， MDA content and histopathological scores were significantly reduced （P＜ 0.05 or P＜0.01）. In contrast， the inhibitor group showed comparable （P＞0.05） or worse （P＜0.05 or P＜0.01） indicators compared to the model group. Conversely， the addition of AMPK inhibitor could significantly reverse the improvement of high- dose paconiflorin （P＜0.01）. CONCLUSIONS Paeoniflorin can repair intestinal epithelial cell damage in mice， improve tight junctions between epithelial cells， upregulate the expression of related proteins， and promote the expression and secretion of antioxidant-promoting molecules， thereby ameliorating UC； its mechanism may be associated with activating AMPK/Nrf2 antioxidant pathway.

Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.

Video-based intelligent action recognition remains challenging in the field of computer vision.The review analyzes the state-of-the-art methods of video-based intelligent action recognition,including machine learning methods with handcrafted features,deep learning methods with automatically extracted features,and multi-information fusion methods.In addition,the important medical applications and limitations of these technologies in the past decade are introduced,and the interdisciplinary views on the future application to improve human health are also shared.

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

ObjectiveTo explore the mechanism of Huanglian Jiedutang in inhibiting the pyroptosis mediated by NOD-like receptor protein 3 （NLRP3） inflammasomes and alleviating the acute liver injury （ALI） induced by lipopolysaccharide （LPS） in the mouse model of sepsis. MethodFifty-four male C57BL/6 mice were randomized into blank， model， low- （3.08 g·kg^-1）， medium- （6.15 g·kg^-1）， and high-dose （12.30 g·kg^-1） Huanglian Jiedutang， and positive control （dexamethasone） groups （n=9）. The mice were administrated with Huanglian Jiedutang at different doses by gavage for 7 days， and then LPS （15 mg·kg^-1） was injected intraperitoneally for the modeling of sepsis. In the positive control group， dexamethasone （0.05 g·kg^-1） was injected intraperitoneally 1.5 h after modeling， and the mouse sepsis score （MSS） was recorded 12 h after modeling. The mice were sacrificed for the collection of blood and liver tissue samples. The levels of alanine transaminase （ALT） and aspartate transaminase （AST） were measured by a biochemical analyzer. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， IL-1β， and IL-18 in the serum were measured by enzyme-linked immunosorbent assay kits. Hematoxylin-eosin staining was used to observe the pathological changes in the liver tissue. The content of NLRP3 was observed by the immunofluorescence assay. The expression of apoptosis-associated speck-like protein containing CARD （ASC） was detected by immunohistochemistry. The protein levels of NLRP3， ASC， Caspase-1， and gasdermin D （GSDMD） in the liver tissue were determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to determine the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18. ResultCompared with the blank group， the model group showed elevated levels of ALT and AST （P<0.01） and risen levels of inflammatory cytokines in the serum （P<0.01）. In addition， the modeling resulted in edema and necrosis in the liver， and up-regulated the protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.01） and the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the drug intervention groups showed reduced content of inflammatory cytokines （P<0.01）， alleviated pathological damage in the liver tissue， and down-regulated protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.05，P<0.01） and mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05，P<0.01） in the liver tissue. ConclusionHuanglian Jiedutang can inhibit pyroptosis and reduce inflammation by inhibiting the activation of NLRP3 inflammasomes， thus demonstrating a therapeutic effect on acute liver injury in the mouse model of sepsis induced by LPS.

BACKGROUND:With the proven ability of traditional Chinese medicine such as icariin and berberine to promote bone regeneration by regulating various mechanisms and targets,researchers have combined active ingredients of traditional Chinese medicine with bone tissue engineering and found that they have unique advantages in treating bone defects. OBJECTIVE:Starting from the active ingredients of traditional Chinese medicines that promote bone formation,to screen cases of their effective combination with different drug-carrying scaffold materials,and summarize the active ingredients of traditional Chinese medicines that have the potential to be applied to bone tissue engineering. METHODS:CNKI,WanFang,PubMed,and Web of Science were searched for relevant literature published from 2000 to 2023,using the keywords of"bone tissue engineering,bone tissue-engineered scaffold materials,bone defect,bone repair,bone regeneration,traditional Chinese medicine"in Chinese and English.According to the inclusion and exclusion criteria,87 papers were finally included for review. RESULTS AND CONCLUSION:There are various kinds of active ingredients of traditional Chinese medicine to promote bone regeneration,mainly including flavonoids,non-flavonoid polyphenols,alkaloids,glycosides.These active ingredients have anti-inflammatory and analgesic effects,promote osteoblasts,inhibit osteoclasts and promote early angiogenesis.The combination of active ingredients of traditional Chinese medicine with bone tissue engineering is effective in anti-inflammation,accelerating collagen and bone formation,and promoting the expression of osteogenic genes,which provides a theoretical basis for the application of traditional Chinese medicine in bone tissue regeneration,and at the same time provides a new idea for the repair of bone defects.

Objective To use metabolomics method to study the metabolic profiles of amino acids and lysophosphatidylcholine(LPC)in the serum of rats with nonalcoholic fatty liver disease(NAFLD),to identify biomarkers for NAFLD,and to speculate on the possible mechanism responsible for its occurrence.Methods NAFLD rats were prepared by feeding a high-fat diet and intraperitoneal injection of carbon tetrachloride.Levels of 15 LPCs and 18 amino acids in the serum were determined in control and NAFLD rats by liquid chromatography-mass spectrometry.Changes in serum LPC and amino acid metabolic profiles in NAFLD rats were analyzed by principal component analysis and orthogonal partial least squares discriminant analysis.Correlations between biomarkers and NAFLD were analyzed by Pearson's correlation analysis.Results The metabolic profiles of serum LPC and amino acids differed significantly between the NAFLD group and the control group and were completely distinct.LPC(20∶1),arginine,and glutamic acid had significant contributions to NAFLD and were identified as biomarkers.Furthermore,LPC(20∶1)and arginine were significantly correlated with serum biochemical indicators such as aspartate transaminase,alanine transaminase,low-density lipoprotein,and total bilirubin.Conclusions The metabolic profiles of serum LPC and amino acids may be closely related to NALFD.

Objective In this study,we aimed to use network pharmacology techniques to predict the key targets of a prescription of Ziziphi spinosae semen formula(ZSSF)compound for depression,and to verify its mechanism of action using a zebrafish model of rifampicin-induced depression.Methods The drug targets of ZSSF were retrieved from the TCMSP database,and the target names were corrected using the UniProt database.Depression-related targets were identified using the GeneCards,OMIM,and NCBI databases.Protein-protein interaction information for the shared targets was predicted using the STRING database.The collected data were then analyzed using the Metascape database to determine GO and KEGG pathway enrichment,and the result were visualized using microbiotics.Behavioral experiments and reverse-transcription quantitative PCR experiments were conducted to verify the therapeutic effects of ZSSF on a zebrafish depression model induced by risperdal.Results 188 targets were screened to find the interactions between depression and ZSSF.The protein-protein interaction result showed that ZSSF primarily targeted TNF-α,IL-2,IL-6,IL-1β,and IL-10 to produce its antidepressant effect.KEGG pathway enrichment analysis revealed that ZSSF exerted its effects on depression through various signaling pathways,including the TNF,PI3K-Akt,and cGMP-PKG signaling pathways.The result of the animal experiments showed that the treatment groups given high,medium,and low doses of ZSSF exhibited significant improvements in movement distance under acoustic and light stimulation compared with the model group(P＜0.05).The speed of movement of the treatment groups was also significantly faster(P＜0.01).Additionally,the mRNA expression levels of TNF-α,IL-2,IL-6,IL-1β,and IL-10 were up-regulated in the brain tissues of zebrafish in the high-,medium-,and low-dosage groups of ZSSF compared those in the model group(P＜0.001).Conclusions ZSSF exerts its antidepressant effect through multiple components and targets,and its antidepressant effects may be associated with its inhibition of inflammatory factors.

Objective To examine the hypoglycemic effect of Chinese yam polysaccharide on the 3T3-L1 insulin resistance cell model.Methods IR-3T3-L1 adipocytes were randomly divided into control group(Con),model group(DEX),metformin group(Met,positive drug group)and CYPS group(0.05,0.15,0.45 mg/mL).After the creation of the IR-3T3-L1 cell model by dexamethasone(DEX)(1 μmol/L)stimulation,Chinese yam polysaccharide treatment was applied.Glucose intake and the levels of TC,TG,LDL-C,HDL-C,GSH-Px,MDA,HK,and PK were then measured.AMPK-PI3K/Akt signaling pathway-associated gene expression was identified using qRT-PCR.Results The glucose consumption of IR-3T3-L1 cells was considerably decreased after 48 hours of treatment with 1 μmol/L DEX compared to that of the Con group(P＜0.01),and the reduction persisted for 60 hours.0.05,0.15,0.45 mg/mL CYPS treatment significantly increased glucose consumption(P＜0.01),HK,PK,GSH-Px enzyme activities(P＜0.01),HDL-C content(P＜0.01),and decreased MDA enzyme activity(P＜0.01),T-CHO,TG,LDL-C content(P＜0.01)in IR-3T3-L1 cells.01).Additionally,CYPS administration dramatically decreased PI3K,Akt,GLUT-4,AMPK,IRS-2,PPARa,and adiponectin mRNA expression levels(P＜0.05)and reduced IRS-1,GSK-3β,ACC,and FAS mRNA expression levels(P＜0.01).Conclusions In IR-3T3-L1 cells,CYPS can reduce oxidative stress,control lipid metabolism disorders,and enhance DEX-induced glucose intake.AMPK-PI3K/Akt signaling pathway-associated genes may be connected to the process.

Objective To investigate the prenatal diagnosis and perinatal outcomes between anterior pla-centa accreta and non-anterior placenta.Methods A retrospective analysis was done for 560 pregnant women who were diagnosed with placenta accreta and delivered in the Third Affiliated Hospital of Guangzhou Medical Uni-versity.According to the location of the placenta,the group was dividing into anterior placenta accreta group(319 cases)and non-anterior placenta accreta group(241 cases).The general characteristics,maternal and infant out-comes of the two groups were analyzed.The non-anterior placenta accrete group(241 cases)then were dividing into two groups according to the time of clear diagnosis.Those who were firstly diagnosed with placenta accrete dur-ing or after the operation was the intrapartum diagnosis group(missed diagnosis)(70 cases),and those who were diagnosed with clear placenta accreta before the delivery was prenatal diagnosis group(171 cases).The general characteristics,maternal and infant outcomes of the two groups were also analyzed.Results There were statisti-cally significant differences in the parity,history of cesarean section,delivery mode,degree of placenta accreta,missed diagnosis rate,neonatal birth weight,and hysterectomy rate between the non-anterior placenta accrete group and the anterior placenta accreta group.In the case of prenatal diagnosis of different degrees of placenta accreta,the prenatal diagnosis rate of placental adhesion in the non-anterior placenta accreta group was lower than that of the anterior placenta accreta group,which was statistically significant.In the non-anterior placenta accrete group,there were statistically significant differences in the age,cesarean section history,placenta previa status,mode of delivery,degree of implantation,24-hour bleeding volume,blood transfusions,NICU transfer rate,uterine loss rate between the intrapartum diagnosis group(missed diagnosis)and the prenatal diagnosis group.Conclusions The high-risk factors of patients with non-anterior placenta accreta are different from those of patients with anterior placenta accreta.Multiple births and a history of cesarean section are high-risk factors for anterior placenta accreta patients.Non-anterior placenta accreta are more likely to be missed diagnosed,especially the placental adhesion.For pregnant women with non-anterior placenta accreta missed diagnosis,there is a high rate of adverse birth out-comes,especially in the rate of neonatal transfer to the NICU.