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.

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 explore the bidirectional relationship between adaptability and insomnia symptoms in college students.Methods:A longitudinal study was conducted across three phases over a span of two years,invol-ving a sample of 13 861 students from a comprehensive university in Shandong Province.The Adaptability Scale(APAS)and the Insomnia Symptoms Scale(ISI)were used to measure adaptability and insomnia symptoms,re-spectively.A latent variable structural equation model was applied to assess the cross-lagged associations between a-daptability and insomnia symptoms over time.Results:The Baseline APAS scores negatively predicted the ISI scores one year later(β=-0.05,P＜0.001),and the APAS scores at one year negatively predicted the ISI scores at the two-year mark(β=-0.04,P＜0.001).Similarly,the baseline ISI scores negatively predicted the APAS scores one year later(β=-0.06,P＜0.001),and the ISI scores at one year negatively predicted the APAS scores two years later(β=-0.03,P＜0.01).Conclusion:The study demonstrates that adaptability helps prevent insom-nia symptoms in students,while insomnia negatively impacts students'adaptability.

Objective:To explore the bidirectional relationship between adaptability and insomnia symptoms in college students.Methods:A longitudinal study was conducted across three phases over a span of two years,invol-ving a sample of 13 861 students from a comprehensive university in Shandong Province.The Adaptability Scale(APAS)and the Insomnia Symptoms Scale(ISI)were used to measure adaptability and insomnia symptoms,re-spectively.A latent variable structural equation model was applied to assess the cross-lagged associations between a-daptability and insomnia symptoms over time.Results:The Baseline APAS scores negatively predicted the ISI scores one year later(β=-0.05,P＜0.001),and the APAS scores at one year negatively predicted the ISI scores at the two-year mark(β=-0.04,P＜0.001).Similarly,the baseline ISI scores negatively predicted the APAS scores one year later(β=-0.06,P＜0.001),and the ISI scores at one year negatively predicted the APAS scores two years later(β=-0.03,P＜0.01).Conclusion:The study demonstrates that adaptability helps prevent insom-nia symptoms in students,while insomnia negatively impacts students'adaptability.

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.

AIM:To investigate the role and mechanism of histone demethylase lysine-specific demethylase 5A(KDM5A)in regulating the Notch signaling pathway in particulate matter 2.5(PM2.5)-induced cortical damage in off-spring mice.METHODS:A pregnancy PM2.5 exposure model was established using intratracheal nebulization.Pregnant mice were randomly divided into PBS control group and PM2.5 exposure group.The cortices of offspring mice were isolated 14 d after birth.Golgi staining,electron microscopy and other methods were used to detect damage to neurons and chroma-tin in the cortex.Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and protein ex-pression of KDM5A in the cortex,and the distribution of KDM5A co-localized with neural cells.A PM2.5-treated PC12 cell injury model was established to detect changes in cell viability and the expression of proteins related to cell proliferation and apoptosis.Further,Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and pro-tein expression of KDM5A,the distribution of KDM5A co-localized with neurons,and changes in the protein level of his-tone H3K4me3.Bioinformatics methods were used to predict the interaction between KDM5A and Notch1,which was fur-ther validated by transfection experiments.In both in vivo and in vitro PM2.5 exposure models,changes in key molecules of the Notch signaling pathway and the co-expression of Notch1 with neural cells in the cortices of 14-day-old offspring mice and PC12 cells were detected.RESULTS:Prenatal PM2.5 exposure during pregnant led to a reduction in the number of neurons and decreased dentritic complexity in the cerebral cortex of offspring at 14 d after birth.It also caused abnormal chromatin condensation within neuronal nuclei,decreased mRNA and protein expression of KDM5A protein in the cortex,increased H3K4me3 protein levels(P＜0.05),and a significant reduction in KDM5A/NeuN double-positive cells.Expo-sure to PM2.5 also resulted in decreased viability and proliferation,and increased apoptosis of PC12 cells,with reduced ex-pression of KDM5A mRNA and protein,increased H3K4me3 protein expression(P＜0.05),and a reduction in the num-ber of KDM5A/MAP-2 double-positive cells.Bioinformatics analysis and transfection experiments in PC12 cells revealed that Notch1 is a downstream target gene of KDM5A.Further in vivo and in vitro experiments found that PM2.5 exposure lead to decreased mRNA and protein expression of key Notch signaling molecules Notch1,Jagged1 and Hes1,and reduced numbers of Notch1/NeuN and Notch1/MAP-2 double-positive cells.CONCLUSION:Exposure to PM2.5 can lead to abnor-mal expression of KDM5A in the offspring's cerebral cortex,which may cause neuronal damage by down-regulating the Notch signaling pathway,a downstream target.This could be one of the significant factors contributing to the neurodevelop-mental disorders in offspring exposed to PM2.5 during pregnancy.

AIM:To investigate the role and mechanism of histone demethylase lysine-specific demethylase 5A(KDM5A)in regulating the Notch signaling pathway in particulate matter 2.5(PM2.5)-induced cortical damage in off-spring mice.METHODS:A pregnancy PM2.5 exposure model was established using intratracheal nebulization.Pregnant mice were randomly divided into PBS control group and PM2.5 exposure group.The cortices of offspring mice were isolated 14 d after birth.Golgi staining,electron microscopy and other methods were used to detect damage to neurons and chroma-tin in the cortex.Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and protein ex-pression of KDM5A in the cortex,and the distribution of KDM5A co-localized with neural cells.A PM2.5-treated PC12 cell injury model was established to detect changes in cell viability and the expression of proteins related to cell proliferation and apoptosis.Further,Western blot,RT-qPCR and immunofluorescence staining were used to detect the mRNA and pro-tein expression of KDM5A,the distribution of KDM5A co-localized with neurons,and changes in the protein level of his-tone H3K4me3.Bioinformatics methods were used to predict the interaction between KDM5A and Notch1,which was fur-ther validated by transfection experiments.In both in vivo and in vitro PM2.5 exposure models,changes in key molecules of the Notch signaling pathway and the co-expression of Notch1 with neural cells in the cortices of 14-day-old offspring mice and PC12 cells were detected.RESULTS:Prenatal PM2.5 exposure during pregnant led to a reduction in the number of neurons and decreased dentritic complexity in the cerebral cortex of offspring at 14 d after birth.It also caused abnormal chromatin condensation within neuronal nuclei,decreased mRNA and protein expression of KDM5A protein in the cortex,increased H3K4me3 protein levels(P＜0.05),and a significant reduction in KDM5A/NeuN double-positive cells.Expo-sure to PM2.5 also resulted in decreased viability and proliferation,and increased apoptosis of PC12 cells,with reduced ex-pression of KDM5A mRNA and protein,increased H3K4me3 protein expression(P＜0.05),and a reduction in the num-ber of KDM5A/MAP-2 double-positive cells.Bioinformatics analysis and transfection experiments in PC12 cells revealed that Notch1 is a downstream target gene of KDM5A.Further in vivo and in vitro experiments found that PM2.5 exposure lead to decreased mRNA and protein expression of key Notch signaling molecules Notch1,Jagged1 and Hes1,and reduced numbers of Notch1/NeuN and Notch1/MAP-2 double-positive cells.CONCLUSION:Exposure to PM2.5 can lead to abnor-mal expression of KDM5A in the offspring's cerebral cortex,which may cause neuronal damage by down-regulating the Notch signaling pathway,a downstream target.This could be one of the significant factors contributing to the neurodevelop-mental disorders in offspring exposed to PM2.5 during pregnancy.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

The standardization of pediatric Tuina is beneficial to pediatric Tuina practitioners in a norm practices. The paper collects the content from teaching textbooks, TCM ancient books and database literature, and tries to develop the technical specifications of pediatric Tuina by four rounds Delphi surveys and expert consensus. This specification covers the manipulation of pediatric Tuina, the position of acupoints, the effects of acupoints and the diagnosis and treatment of pediatric Tuina, including indications, contraindications, cautious use, operation steps and methods.

Objective To construct and identify the efficacy of a lentiviral vector harboring RNAi sequence targe-ting NSBP1 gene. Methods Three siRNA targeting the NSBP1 mRNA were designed, the pGCSIL-GFP-NSBP1 lentivirus vectors were constructed and confirmed by DNA sequencing. A total of 293T cells were co-transfected with pGCSIL-GFP-NSBP1, pHelper1.0 and pHelper2.0 for the virus stocks produced, the titer of the virus was test-ed. After lentivirus transfecting into DU145 ceils, Western-blot and MTT methods were used to determine the ex-pression and biological activity of NSBP1 gene, the cells were transplanted into nude mice, then inhibitive effect was observed. Results PCR analysis and DNA sequencing demonstrated that the RNAi sequence targeting the hu-man NSBP1 gene was successfully inserted into the lentiviral vector. The titer of the recombinant]entiviral vector was 2 × 10~8TU/mL. NSBP1 protein expression level in transfected cells was significantly decreased and growth rate of cells transfected with lentivirus was decreased by MTT assay, the downregulation of NSBP1 reduced growth rate of transplantated tumor, whereas tumorgenicity was not influenced. Conclusion The construction of the]entiviral vector of NSBP1 has been successfully prepared and NSBP1 plays an important regulatory role in androgen-inde-pendent prostate cancer cell proliferation.