Background Prenatal exposure to fine particulate matter (PM_2.5) is closely associated with cortical damage and neuroinflammation in offspring. The cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway is a key regulator of inflammation and may be subject to epigenetic regulation. Objective To investigate the role of cGAS-STING pathway activation in PM_2.5-induced cortical damage in offspring mice during pregnancy and the underlying epigenetic regulatory mechanisms. Methods Open field tests were used to assess depressive-like behavior in offspring mice. Morphological analysis was conducted to evaluate cortical damage and microglial activation in offspring brains. Real-time fluorescent quantitative PCR (RT-qPCR) and Western blot (WB) were performed to detect changes in the expression of key molecules in the cGAS-STING pathway in cortical tissue. A PM_2.5-induced microglial cell injury model was established in BV2 cells. Microglial activation was observed, cell viability was measured using the Cell Counting Kit-8 (CCK-8), and the expression levels of inducible nitric oxide synthase (iNOS) and key molecules in the cGAS-STING pathway were detected by RT-qPCR and WB. Bioinformatics analysis was performed to explore the epigenetic regulatory association between the STING signaling pathway and lysine-specific demethylase 5A (KDM5A). Changes in KDM5A mRNA and protein expression, as well as the protein level of histone H3 lysine 4 trimethylation (H3K4me3), were detected in an in vitro PM_2.5 injury model. Using small interfering RNA (siRNA) technology, the KDM5A gene was silenced in BV2 cells exposed to PM_2.5. The protein expression of H3K4me3 was detected to evaluate improvements in microglial activation, changes in inflammatory markers such as iNOS and mannose receptor (CD206), and alterations in the cGAS-STING pathway. Results Compared with the control group, the total distance of offspring mice in the PM_2.5 group was significantly reduced, and both the distance traveled and the time spent in the central area of the open field were significantly decreased (P<0.01, P<0.001), indicating depressive-like behavior in the offspring mice. Compared with the control group, the offspring mice in the PM_2.5 group exhibited disorganized cortical structure and significantly activated microglia (P<0.01), with significantly increased mRNA and protein levels of cGAS and STING (P<0.05, P<0.01, or P<0.001). The in vitro experiments demonstrated that the PM_2.5 treatment induced BV2 cells to polarize toward the M1 phenotype, exhibiting a distinct amoeboid morphology, with upregulated expression of the pro-inflammatory factor iNOS (P<0.05, P<0.01, or P<0.001) and activation of the cGAS-STING pathway (P<0.05, P<0.01). The analysis of RNA-seq data from KDM5A knockout cells revealed significantly downregulated STING expression, suggesting that KDM5A may activate the STING signaling pathway. The in vitro experiments further confirmed that the PM_2.5-treated BV2 cells exhibited significantly elevated mRNA and protein levels of KDM5A (P<0.01), while the H3K4me3 protein levels were markedly reduced (P<0.05). After silencing KDM5A in BV2 cells exposed to PM_2.5, compared with the PM_2.5+siNC group, the PM_2.5+siKDM5A group showed no obvious microglial activation and polarized toward the M2 phenotype, with significantly decreased expression levels of iNOS, cluster of differentiation 16 (CD16), and interleukin-1β (P<0.05, P<0.01), and significantly increased expression levels of anti-inflammatory factors CD206, YM1, and interleukin-10 (P<0.01, P<0.001). Meanwhile, the expression levels of cGAS and STING were also reduced (P<0.05, P<0.01). Conclusion KDM5A activates microglia through the cGAS-STING pathway, thereby contributing to PM_2.5-induced cortical damage in offspring mice during pregnancy.

Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury. Clinical and experimental evidence demonstrates that liver injury involves complex inter-organ interactions among the brain, eye, liver, intestine, and kidney. Recent advances in basic and clinical research have illuminated the physiologic and molecular mechanisms underlying transporter alterations in liver injury, particularly those associated with bilirubin, reactive oxygen species, ammonia, bile acid, and inflammatory factors. Notably, the influence of these transporter modifications on drug pharmacokinetics in liver injury patients remains inadequately understood. Additional research is necessary to fully comprehend these effects and their therapeutic implications. The documented alterations of transporters in distant organs across various liver diseases indicate that dosage modifications may be required when administering transporter-substrate drugs, including both traditional Chinese and Western medicines, to patients with liver dysfunction. This strategy helps maintain drug concentrations within therapeutic ranges while reducing adverse reactions. Furthermore, when utilizing transporter inducers or inhibitors clinically, consideration of their long-term effects on transporters and subsequent therapeutic impact is essential. Careful attention must be paid to avoid compromising the elimination of toxic metabolites and proteins when inhibiting these transporters. Similarly, prudent use of inducers or inducer-type therapeutic drugs is necessary to prevent enhanced drug resistance. This review examines recent clinical and experimental findings regarding the inter-organ interaction of drug transporters in liver injury conditions and their clinical relevance.
Humans ; Liver/drug effects* ; Animals ; Chemical and Drug Induced Liver Injury/metabolism* ; Membrane Transport Proteins/metabolism* ; Biological Transport ; Liver Diseases/drug therapy* ; Pharmaceutical Preparations/metabolism*

Objective To investigate the effects of time in range(TIR)and microRNA-2245P(miR-2245P)interac-tions on the susceptibility and severity of diabetic retinopathy(DR)in the target range of glucose.Methods A prospec-tive study was conducted on 259 patients with DR(DR group)and 259 patients with type 2 diabetes mellitus(T2DM group)admitted to the Ophthalmology Department of Yantai Yeda Hospital from April 2022 to June 2024.TIR and miR-2245P were compared between the two groups,and the multivariate Logistic analysis was used to identify the factors associated with DR susceptibility.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of TIR,miR-2245 P,and their combination for DR.The interaction coefficient γ was used to analyze the effect of the interaction between TIR and miR-2245P on DR susceptibility.The Spearman correlation analysis was used to evaluate the correlation of TIR and miR-2245P with DR staging.Results The TIR and miR-2245P levels in the DR group were lower than those in the T2DM group(both P＜0.05).The multivariate logistic regression analysis showed that Logit(P)=0.083-0.470 × TIR-0.584 × miR-2245P,high levels of TIR and miR-2245P were independent protective factors of DR susceptibility(all P＜0.05).The areas under the ROC curve(AUC)of TIR,miR-2245P,and their combination for predicting DR were 0.76,0.79,and 0.91,respectively.The AUC of TIR combined with miR-2245P was greater than that of TIR and miR-2245P(both P＜0.05).The interaction analysis showed that the OR values of DR caused by low levels of TIR and miR-2245P alone were 2.05 and 1.92,respectively.The OR value of the interaction between TIR and miR-2245P was 10.69,greater than the prod-uct of OR values of TIR and miR-2245P alone.It indicates that the effect of the interaction of TIR and miR-2245P on suscep-tibility to DR is a super-multiplication model.The interaction coefficient was γ=3.31＞1,indicating a positive relationship of the interaction between the two factors with DR susceptibility.The Spearman correlation analysis showed that TIR and miR-2245P were negatively correlated with DR staging(both P＜0.001).Conclusion Both TIR and miR-2245P are asso-ciated with DR and its severity,and they have interactive effects on DR susceptibility.Combined detection can improve the predictive value of DR.This study provides a new idea and target for the prevention and treatment of DR.

Traditional Chinese medicine(TCM)serves as a treasure trove of ancient knowledge,holding a crucial position in the medical field.However,the exploration of TCM's extensive information has been hindered by challenges related to data standardization,completeness,and accuracy,primarily due to the decen-tralized distribution of TCM resources.To address these issues,we developed a platform for TCM knowledge discovery(TCMKD,https://cbcb.cdutcm.edu.cn/TCMKD/).Seven types of data,including syndromes,formulas,Chinese patent drugs(CPDs),Chinese medicinal materials(CMMs),ingredients,targets,and diseases,were manually proofread and consolidated within TCMKD.To strengthen the integration of TCM with modern medicine,TCMKD employs analytical methods such as TCM data mining,enrichment analysis,and network localization and separation.These tools help elucidate the molecular-level commonalities between TCM and contemporary scientific insights.In addition to its analytical capabilities,a quick question and answer(Q&A)system is also embedded within TCMKD to query the database efficiently,thereby improving the interactivity of the platform.The platform also provides a TCM text annotation tool,offering a simple and efficient method for TCM text mining.Overall,TCMKD not only has the potential to become a pivotal repository for TCM,delving into the pharmaco-logical foundations of TCM treatments,but its flexible embedded tools and algorithms can also be applied to the study of other traditional medical systems,extending beyond just TCM.

Traditional Chinese medicine (TCM) serves as a treasure trove of ancient knowledge, holding a crucial position in the medical field. However, the exploration of TCM's extensive information has been hindered by challenges related to data standardization, completeness, and accuracy, primarily due to the decentralized distribution of TCM resources. To address these issues, we developed a platform for TCM knowledge discovery (TCMKD, https://cbcb.cdutcm.edu.cn/TCMKD/). Seven types of data, including syndromes, formulas, Chinese patent drugs (CPDs), Chinese medicinal materials (CMMs), ingredients, targets, and diseases, were manually proofread and consolidated within TCMKD. To strengthen the integration of TCM with modern medicine, TCMKD employs analytical methods such as TCM data mining, enrichment analysis, and network localization and separation. These tools help elucidate the molecular-level commonalities between TCM and contemporary scientific insights. In addition to its analytical capabilities, a quick question and answer (Q&A) system is also embedded within TCMKD to query the database efficiently, thereby improving the interactivity of the platform. The platform also provides a TCM text annotation tool, offering a simple and efficient method for TCM text mining. Overall, TCMKD not only has the potential to become a pivotal repository for TCM, delving into the pharmacological foundations of TCM treatments, but its flexible embedded tools and algorithms can also be applied to the study of other traditional medical systems, extending beyond just TCM.

Objective To investigate the effects of three types of twin-block(TB)appliances on the stress and displacement of anterior teeth,periodontal ligaments,and alveolar bone.Methods A three-dimensional(3D)finite element model was constructed,including maxillofacial bones,articular discs,teeth,and periodontal ligaments.Three types of twin-block appliances were designed:classic twin-block(classic-TB),twin-block with acrylic capping(capping-TB),and clear twin-block aligner(CTBA).All appliances had an inclination angle of 70°,and a masticatory force of 200 N was applied to their inclined planes.The finite element method was used to analyze the stress distribution and displacement differences of anterior teeth.Results All three types of TB appliances induced lingual tilting of maxillary anterior teeth and labial tilting of mandibular anterior teeth.The CTBA group showed the greatest lingual displacement and stress of maxillary anterior teeth,with a maximum stress of 30.6 MPa,while the mandibular anterior teeth in this group exhibited the smallest labial displacement(approximately 0.02 mm)and stress.Additionally,the CTBA group had the lowest compressive stress in mandibular anterior teeth,periodontal ligaments,and alveolar bone,whereas the classic-TB group had the highest.Conclusions In the treatment of Angle Class Ⅱ malocclusion,classic-TB(with or without acrylic capping)causes labial inclination of mandibular anterior teeth.Compared with classic-TB,CTBA effectively reduces the compressive stress and displacement of mandibular anterior teeth,potentially minimizing adverse periodontal risks.However,attention should be paid to the lingual displacement of maxillary anterior teeth.

Objective To investigate the function of Ring finger protein 13(RNF13)in cerebral ischemia reperfusion injury(CIRI),and its mechanism.Methods The mouse middle cerebral artery embolization and primary neuron oxygen-glucose depri-vation and reoxygenation were used as disease models.The CRISPR/Cas9 gene knockout technique,immunohistochemical stai-ning,immunofluorescence staining,Western blot and lipid peroxidation detection were used to evaluate the regulatory effect and molecular mechanism of RNF13 on ferroptosis in CIRI.Student's t test was used for the comparison of two samples,and one-way analysis of variance was used for the comparison of multiple samples.Results The expression levels of RNF13 protein in mice and primary neurons were upregulated during CIRI.After knockout of RNF13,ferritin heavy chain 1(Fth1)and ferritin light chain(Ftl)were downregulated,and the content of free ferrous ions and the accumulation of lipid peroxides in mice brain tissues were promoted,leading to ferroptosis aggravation and neurological impairments.Overexpression of RNF13 protected a-gainst ferroptosis by reducing the production of free ferrous and lipid peroxides in neurons.Conclusion RNF13 alleviates fer-roptosis in neurons after CIRI,and the effect is induced by Fth1.

Malignant obstructive jaundice is a severe pathophysiological disorder characterized primarily by hyperbilirubinemia secondary to biliary obstruction.To mitigate the adverse effects of hyperbilirubinemia and reduce postoperative complications,preoperative biliary drainage(PBD)has long been employed as a perioperative management strategy.Nevertheless,whether PBD confers definitive clinical benefits remains a subject of considerable debate.This review systematically summarizes the current literature,with particular emphasis on the indications,approaches,and clinical value of PBD in relation to obstruction at different anatomical sites,aiming to provide evidence-based guidance for surgical decision-making in patients with malignant obstructive jaundice.

Objective:To analyze the relationship among serum levels of fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D (25-OH-VD) and osteoporosis in children.Methods:Eighty children with osteoporosis admitted to Affiliated Hosptial of Jining Medieal University from Jun. 2019 to Jun. 2024 were included as the observation group, and 60 healthy children who underwent physical examination during the same period were included as the control group. Serum FGF23 and 25-OH-VD levels were compared between the two groups, and bone mineral density and bone metabolism indexes [CTX-1, osteocalcin (OC) and N-terminal propeptide of type I precollagen (PINP) ] were detected. Pearson correlation was used to analyze the correlation among serum FGF23, 25-OH-VD, bone metabolism indexes and bone mineral density. Logistic regression model was used to analyze the risk factors of osteoporosis in children.Results:Serum FGF23 and CTX-1 levels in the observation group were significantly higher than those in the control group ( t=15.77, 7.56, P < 0.05), while serum 25-OH-VD, OC, PINP and BMD levels were significantly lower ( t=14.09, 2.70, 13.25, 3.63, P < 0.05) ; Pearson correlation analysis showed that BMD was not correlated with age, BMI and OC ( r=-0.07, -0.02, 0.01, P > 0.05), BMD was negatively correlated with FGF23 and CTX-1, and positively correlated with 25-OH-VD and PINP ( r=-0.35, -0.34, 0.41, 0.40, P < 0.05). The stepwise regression model showed that FGF23 and 25-OH-VD were the main factors affecting BMD ( t=-2.40, 9.02, P<0.05). Multifactor Logistic regression model showed that FGF23 and 25-OH-VD were related factors of osteoporosis in children ( OR=3.01,1.16, P<0.05) . Conclusion:Serum FGF23 level is higher and 25-OH-VD level is lower in children with osteoporosis, which is significantly correlated with bone mineral density and is a related factor for osteoporosis in children.

Objective:To analyze the relationship among serum levels of fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D (25-OH-VD) and osteoporosis in children.Methods:Eighty children with osteoporosis admitted to Affiliated Hosptial of Jining Medieal University from Jun. 2019 to Jun. 2024 were included as the observation group, and 60 healthy children who underwent physical examination during the same period were included as the control group. Serum FGF23 and 25-OH-VD levels were compared between the two groups, and bone mineral density and bone metabolism indexes [CTX-1, osteocalcin (OC) and N-terminal propeptide of type I precollagen (PINP) ] were detected. Pearson correlation was used to analyze the correlation among serum FGF23, 25-OH-VD, bone metabolism indexes and bone mineral density. Logistic regression model was used to analyze the risk factors of osteoporosis in children.Results:Serum FGF23 and CTX-1 levels in the observation group were significantly higher than those in the control group ( t=15.77, 7.56, P < 0.05), while serum 25-OH-VD, OC, PINP and BMD levels were significantly lower ( t=14.09, 2.70, 13.25, 3.63, P < 0.05) ; Pearson correlation analysis showed that BMD was not correlated with age, BMI and OC ( r=-0.07, -0.02, 0.01, P > 0.05), BMD was negatively correlated with FGF23 and CTX-1, and positively correlated with 25-OH-VD and PINP ( r=-0.35, -0.34, 0.41, 0.40, P < 0.05). The stepwise regression model showed that FGF23 and 25-OH-VD were the main factors affecting BMD ( t=-2.40, 9.02, P<0.05). Multifactor Logistic regression model showed that FGF23 and 25-OH-VD were related factors of osteoporosis in children ( OR=3.01,1.16, P<0.05) . Conclusion:Serum FGF23 level is higher and 25-OH-VD level is lower in children with osteoporosis, which is significantly correlated with bone mineral density and is a related factor for osteoporosis in children.