This study investigated the effects and underlying mechanisms of the luteolin-naringenin combination(LN)on liver injury induced by acetaminophen(APAP).Forty-eight Kunming mice were randomly allocated into six groups:a normal control group,an APAP-induced liver injury model group,a positive drug treatment group,and three LN treatment groups with low,medium,and high doses.After the final drug administration,the mice were fasted for 12 hours prior to eu-thanasia for sample collection.Serum transaminase activity,oxidative stress indices,and hematoxy-lin-eosin(HE)staining were assessed to evaluate the effects of LN on APAP-induced hepatic inju-ry.Additionally,Western blot analysis was conducted to examine the expression levels of sphingo-sine kinase 1(SPHK1)and endoplasmic reticulum stress(ERS)-related proteins,thereby elucida-ting the potential mechanisms by which LN mitigates APAP-induced liver injury.The results dem-onstrated that varying concentrations of LN effectively ameliorated serum aminotransferase activi-ty and oxidative stress levels induced by APAP in a dose-dependent manner.Histopathological ex-amination via HE staining revealed significant improvement in APAP-induced liver tissue injury following treatment with different concentrations of LN.Furthermore,Western blot analysis indi-cated that the protein expressions of SPHK1,CHOP,p-IRE1α,ATF6,p-PERK,p-eIF2α,and ATF4 were markedly reduced after administration of various concentrations of LN.The results demonstrate that LN exhibits a significant protective effect against APAP-induced liver injury by inhibiting the SPHK1-mediated aberrant expression of ERS-related molecules.This study high-lights the importance of targeting SPHK1 in the treatment of APAP liver injury and provides a no-vel therapeutic approach through the multi-target and multi-pathway combination of monomers.

Objective:Bidirectional causal associations of 41 cytokines with atopic dermatitis(AD)were explored based on a Mendelian randomization(MR)approach.Methods:Pooled data from genome wide association study(GWAS)of 41 cytokines and AD were utilized for instrumental variable(IV)screening,and single nucleotide polymorphism(SNP)affecting the results of MR analyses was excluded by the MR-PRESSO outlier test as well as by the MR Steiger filtering method.Two-sample bidirectional MR analyses were performed using inverse variance weighting(IVW),MR-Egger regression,and weighted median methods(WM).MR-Egger intercept term test and Cochran's Q test were performed to test the pleiotropy and heterogeneity of IV,and MR results were visu-alized by scatterplots,funnel plots,and leave-one-out plots.Results:Forward MR analysis showed that MIG(IVW:OR=0.89;95%CI:0.81～0.97;P=0.006)reduced the risk of AD development.In contrast,IL-5(IVW:OR=1.17;95%CI:1.01～1.36;P=0.042)and IL-18(MR Egger:OR=1.17;95%CI:1.03～1.33;P=0.030)increased the risk of AD development.Inverse MR analysis showed a potential causal association between AD and increased MIG(IVW:Beta=0.10;95%CI:0.02～0.17;P=0.014).None of the sensitivity analyses indicated pleiotropy and heterogeneity of the included IV.Conclusion:MIG may be an important marker in the progression of AD with a potential bidirectional causal association with risk of morbidity.IL-5 and IL-18 have a potential positive causal association for AD.

Objective To analyze the characteristics of birth defects in seven hospitals in Suzhou from 2020 to 2022,and to provide a basis for the formulation of birth defect prevention strategies.Methods Information on 74,515 perinatal infants delivered in the participating hospitals was collected through birth defect monitoring,and the characteristics of birth defect incidence and changes in the ranking of occurrences were analyzed.Results From 2020 to 2022,the incidence of birth defects in perinatal infants was 173.12 per 10,000,with the incidence in male infants being 197.22 per 10,000 and in female infants 147.17 per 10,000,showing a statistically significant difference(χ2=27.383,P<0.05).The incidence of birth defects in male infants was significantly higher than in female infants,with a statistically significant difference(all P<0.05).In 2020 and 2021,the incidence of birth defects was higher in mothers under 20 years of age,with statistically significant differences(all P<0.05).From 2020 to 2022,the incidence of congenital heart disease in perinatal infants fluctuated between 49.49 and 75.35 per 10,000,ranking first each year.Conclusion Strengthening the management of high-risk populations,especially young pregnant women,and leveraging the multidisciplinary diagnosis and treatment capabilities of prenatal diagnosis centers and nationally recognized clinical key specialties are essential for the prevention and control of birth defects.

Objectives:To evaluate the clinical values of cervical vertebral bone quality(CVBQ)score and cervical endplate bone quality(CEBQ)score in predicting the settlement of Zero Profile(Zero-P)cage after an-terior cervical discectomy and fusion(ACDF).Methods:A retrospective analysis was performed on 72 patients who underwent ACDF with Zero-P cage in the Second Affiliated Hospital of Soochow University.General pa-tient information(including sex,age,comorbidity),laboratory parameters(such as blood calcium and blood glu-cose),surgical details(surgical level and cage type),and imaging data(preoperative cervical MRI and anteropos-terior and lateral X-rays within one week and after more than three months)were collected.On the lateral X-rays taken within one week and＞3 months postoperatively,the heights of the upper and lower margins of vertebrae were measured,and the difference between was defined as the cage subsidence distance.Patients with a subsidence distance ≥ 2mm were assigned to the subsidence group,and those with＜2mm subsidence distance were divided to the non-subsidence group.On preoperative cervical sagittal T1-weighted MRI,plac-ing regions of interest(ROIs)in the medullary region of adjacent vertebral bodies,the subchondral bone region of the endplates,and the cerebrospinal fluid(CSF)in the cerebellomedullary cistern.CVBQ and CEBQ values were the ratios of the average signal intensity of the medullary region of the surgical adjacent vertebral bodies(for CVBQ)and the subchondral bone region of the endplates(for CEBQ)to the signal intensity of the cere-brospinal fluid in the cerebellomedullary cistern.A stratified analysis by gender was conducted to further clarify whether the predictive value of bone quality scores for subsidence is influenced by gender factors.The Pearson correlation coefficient was used to assess the relationship of CVBQ and CEBQ with cage subsidence distance.Receiver operating characteristic(ROC)curves were applied to evaluate the diagnostic efficacy of CVBQ and CEBQ for cage subsidence.Univariate logistic regression analysis was performed to screen for po-tential risk factors,after that age and diabetes,which showed statistical significance,along with CVBQ and CEBQ,were incorporated into the multivariate analysis to assess their independent effects.Results:Cage sub-sidence occurred in 14 patients(subsidence rate:19.4％).Compared with the non-subsidence group,the subsi-dence group of patients was older(male:61.4±16.5 years vs 51.1±10.8 years,P=0.049;female:62.6±13.1 years vs 51.2±7.8 years,P=0.005)and had a higher proportion of patients with diabetes(male:42.9％vs 3.4％,P=0.018;female:42.9％vs 6.9％,P=0.040).Both CVBQ and CEBQ were significantly higher in the subsidence group(CVBQ-male:2.75±0.73 vs 2.02±0.53,P=0.004;female:2.84±0.69 vs 2.00±0.40,P=0.005;CEBQ-male:2.82±0.688 vs 2.05±0.56,P=0.004;female:2.94±0.68 vs 2.05±0.42,P=0.002).Pearson correlation analysis re-vealed a moderate positive correlation between both CVBQ(r=0.58,P＜0.001)and CEBQ(r=0.59,P＜0.001)with subsidence distance.ROC curve analysis indicated that both CVBQ(AUC=0.83)and CEBQ(AUC=0.85)had good predictive values for subsidence,with CEBQ showing slightly better predictive performance.Univariate logistic regression analysis identified age,diabetes,CEBQ,and CVBQ as risk factors for subsidence(P＜0.05).Multivariate analysis showed that after adjusting for age and diabetes,both CEBQ(OR=11.466,P=0.004)and CVBQ(OR=8.804,P=0.005)remained independent risk factors for subsidence,while age and diabetes lost in-dependent significance.The strength of association with subsidence was greater in CEBQ than in CVBQ.Conclusions:Patients with higher CVBQ and CEBQ scores are more likely to experience fusion cage subsi-dence,and both CEBQ and CVBQ can be used to predict cage subsidence in patients after single-level ACDF,CEBQ has better predictive ability than CVBQ.

Objective:To explore the factors influencing the success rate of culturing patient-derived gastric and colorectal cancer organoids.Methods:From Feb 2022 to Oct 2023, 398 tumor tissue specimens from patients who underwent gastric cancer and colorectal cancer resection at the Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University, were used for organoid culture. The clinicopathological factors affecting the success rate of organoid culture were analyzed.Results:The overall success rate of organoid culture in this group was 75.1% (299/398), with the success rate of gastric cancer organoid culture being 79.8%(154/193) and that of colorectal cancer being 70.7% (145/205). Different clinicopathological T stage ( χ2=4.765, P<0.05),histological type ( χ2=11.248, P<0.05), and tumor regression grade (TRG) grade after neoadjuvant chemotherapy ( χ2=7.797, P<0.05) were related to the success rate of organoid culture . Multivariate analysis showed that the TRG grade was an independent influencing factor( P=0.040). For colorectal cancer, different pathological T stage ( χ2=5.108, P<0.05), histological type ( χ2=11.270, P<0.05), and TRG grade after neoadjuvant chemotherapy ( χ2=6.797, P<0.05) were related to the success rate of organoidculture . Different from gastric cancer, the results of multivariate analysis of colorectal cancer showed that the histological type was an independent influencing factor ( P=0.018). Conclusions:The pathologic T stage, histological type of tumors, and TRG of cancer patients all have a significant impact on the success rate of establishing tumor organoids. Among them, the TRG grade is an independent influencing factor for the culture of gastric cancer organoids, and the histological type is an independent influencing factor for colorectal cancer organoids.

Objective:Bidirectional causal associations of 41 cytokines with atopic dermatitis(AD)were explored based on a Mendelian randomization(MR)approach.Methods:Pooled data from genome wide association study(GWAS)of 41 cytokines and AD were utilized for instrumental variable(IV)screening,and single nucleotide polymorphism(SNP)affecting the results of MR analyses was excluded by the MR-PRESSO outlier test as well as by the MR Steiger filtering method.Two-sample bidirectional MR analyses were performed using inverse variance weighting(IVW),MR-Egger regression,and weighted median methods(WM).MR-Egger intercept term test and Cochran's Q test were performed to test the pleiotropy and heterogeneity of IV,and MR results were visu-alized by scatterplots,funnel plots,and leave-one-out plots.Results:Forward MR analysis showed that MIG(IVW:OR=0.89;95%CI:0.81～0.97;P=0.006)reduced the risk of AD development.In contrast,IL-5(IVW:OR=1.17;95%CI:1.01～1.36;P=0.042)and IL-18(MR Egger:OR=1.17;95%CI:1.03～1.33;P=0.030)increased the risk of AD development.Inverse MR analysis showed a potential causal association between AD and increased MIG(IVW:Beta=0.10;95%CI:0.02～0.17;P=0.014).None of the sensitivity analyses indicated pleiotropy and heterogeneity of the included IV.Conclusion:MIG may be an important marker in the progression of AD with a potential bidirectional causal association with risk of morbidity.IL-5 and IL-18 have a potential positive causal association for AD.

Objectives:To evaluate the clinical values of cervical vertebral bone quality(CVBQ)score and cervical endplate bone quality(CEBQ)score in predicting the settlement of Zero Profile(Zero-P)cage after an-terior cervical discectomy and fusion(ACDF).Methods:A retrospective analysis was performed on 72 patients who underwent ACDF with Zero-P cage in the Second Affiliated Hospital of Soochow University.General pa-tient information(including sex,age,comorbidity),laboratory parameters(such as blood calcium and blood glu-cose),surgical details(surgical level and cage type),and imaging data(preoperative cervical MRI and anteropos-terior and lateral X-rays within one week and after more than three months)were collected.On the lateral X-rays taken within one week and＞3 months postoperatively,the heights of the upper and lower margins of vertebrae were measured,and the difference between was defined as the cage subsidence distance.Patients with a subsidence distance ≥ 2mm were assigned to the subsidence group,and those with＜2mm subsidence distance were divided to the non-subsidence group.On preoperative cervical sagittal T1-weighted MRI,plac-ing regions of interest(ROIs)in the medullary region of adjacent vertebral bodies,the subchondral bone region of the endplates,and the cerebrospinal fluid(CSF)in the cerebellomedullary cistern.CVBQ and CEBQ values were the ratios of the average signal intensity of the medullary region of the surgical adjacent vertebral bodies(for CVBQ)and the subchondral bone region of the endplates(for CEBQ)to the signal intensity of the cere-brospinal fluid in the cerebellomedullary cistern.A stratified analysis by gender was conducted to further clarify whether the predictive value of bone quality scores for subsidence is influenced by gender factors.The Pearson correlation coefficient was used to assess the relationship of CVBQ and CEBQ with cage subsidence distance.Receiver operating characteristic(ROC)curves were applied to evaluate the diagnostic efficacy of CVBQ and CEBQ for cage subsidence.Univariate logistic regression analysis was performed to screen for po-tential risk factors,after that age and diabetes,which showed statistical significance,along with CVBQ and CEBQ,were incorporated into the multivariate analysis to assess their independent effects.Results:Cage sub-sidence occurred in 14 patients(subsidence rate:19.4％).Compared with the non-subsidence group,the subsi-dence group of patients was older(male:61.4±16.5 years vs 51.1±10.8 years,P=0.049;female:62.6±13.1 years vs 51.2±7.8 years,P=0.005)and had a higher proportion of patients with diabetes(male:42.9％vs 3.4％,P=0.018;female:42.9％vs 6.9％,P=0.040).Both CVBQ and CEBQ were significantly higher in the subsidence group(CVBQ-male:2.75±0.73 vs 2.02±0.53,P=0.004;female:2.84±0.69 vs 2.00±0.40,P=0.005;CEBQ-male:2.82±0.688 vs 2.05±0.56,P=0.004;female:2.94±0.68 vs 2.05±0.42,P=0.002).Pearson correlation analysis re-vealed a moderate positive correlation between both CVBQ(r=0.58,P＜0.001)and CEBQ(r=0.59,P＜0.001)with subsidence distance.ROC curve analysis indicated that both CVBQ(AUC=0.83)and CEBQ(AUC=0.85)had good predictive values for subsidence,with CEBQ showing slightly better predictive performance.Univariate logistic regression analysis identified age,diabetes,CEBQ,and CVBQ as risk factors for subsidence(P＜0.05).Multivariate analysis showed that after adjusting for age and diabetes,both CEBQ(OR=11.466,P=0.004)and CVBQ(OR=8.804,P=0.005)remained independent risk factors for subsidence,while age and diabetes lost in-dependent significance.The strength of association with subsidence was greater in CEBQ than in CVBQ.Conclusions:Patients with higher CVBQ and CEBQ scores are more likely to experience fusion cage subsi-dence,and both CEBQ and CVBQ can be used to predict cage subsidence in patients after single-level ACDF,CEBQ has better predictive ability than CVBQ.

This study investigated the effects and underlying mechanisms of the luteolin-naringenin combination(LN)on liver injury induced by acetaminophen(APAP).Forty-eight Kunming mice were randomly allocated into six groups:a normal control group,an APAP-induced liver injury model group,a positive drug treatment group,and three LN treatment groups with low,medium,and high doses.After the final drug administration,the mice were fasted for 12 hours prior to eu-thanasia for sample collection.Serum transaminase activity,oxidative stress indices,and hematoxy-lin-eosin(HE)staining were assessed to evaluate the effects of LN on APAP-induced hepatic inju-ry.Additionally,Western blot analysis was conducted to examine the expression levels of sphingo-sine kinase 1(SPHK1)and endoplasmic reticulum stress(ERS)-related proteins,thereby elucida-ting the potential mechanisms by which LN mitigates APAP-induced liver injury.The results dem-onstrated that varying concentrations of LN effectively ameliorated serum aminotransferase activi-ty and oxidative stress levels induced by APAP in a dose-dependent manner.Histopathological ex-amination via HE staining revealed significant improvement in APAP-induced liver tissue injury following treatment with different concentrations of LN.Furthermore,Western blot analysis indi-cated that the protein expressions of SPHK1,CHOP,p-IRE1α,ATF6,p-PERK,p-eIF2α,and ATF4 were markedly reduced after administration of various concentrations of LN.The results demonstrate that LN exhibits a significant protective effect against APAP-induced liver injury by inhibiting the SPHK1-mediated aberrant expression of ERS-related molecules.This study high-lights the importance of targeting SPHK1 in the treatment of APAP liver injury and provides a no-vel therapeutic approach through the multi-target and multi-pathway combination of monomers.

OBJECTIVE To provide standardized whole-process guidance on drug traceability codes for medical institutions in Sichuan province， ensuring medication safety and compliance with medical insurance supervision requirements. METHODS Based on evidence-based principles and expert consensus， Expert Consensus on Whole-process Management of Drug Traceability Codes in Medical Institutions of Sichuan Province （hereinafter referred to as the Consensus） was formulated through systematic literature review， field investigations， establishment of a multidisciplinary expert committee and multiple rounds of questionnare consultation via the modified Delphi method， and finalized through consensus meetings. RESULTS & CONCLUSIONS The Consensus clarifies key operating procedures for code verification， code assignment and code return， whole-process operational standards for drug warehouse acceptance and storage， drug warehouse outbound delivery and pharmacy acceptance check， drug distribution and dispensing in pharmacy and intravenous admixture center， medication administration in nursing units and examination departments， as well as drug return process. Key recommendations are proposed such as improving the core functions of the drug traceability system， unifying the hospital-wide traceability code database， strengthening the management of traceability codes for backup medications， establishing a management organization and institutional framework， and optimizing the architectural design and data governance requirements of the drug traceability system. The release of the Consensus will provide scientific， standardized and implementable practical guidelines for medical institutions of Sichuan province， helping to improve closed-loop management of the drug traceability system， strengthen medication safety and fulfil medical insurance fund supervision.

Objective:To study the effect of angiopoietin-1(Ang-1)and tyrosine kinase receptor 2(Tie2)inhibitor on glucose transportation in the human umbilical vein endothelial cells(HUVECs)cultured under high glucose conditions,and to clarify its mechanism.Methods:The HUVECs were cultured in high glucose(30 mmol·L?1)in vitro and treated with 0,200,500,1 000,and 2 000 μg·L?1 Ang-1 and 0,2 500,5 000,and 7 500 nmol·L?1 Tie2 inhibitor;cell counting kit-8(CCK-8)method was used to detect the cell activity to screen the optimal concentrations of Ang-1 and Tie2 inhibitor.Glucose kit was used to detect the glucose level in the supernatant of the HUVECs after Ang-1 intervention.The HUVECs were randomly divided into blank control group(NG group),high glucose group(HG group),HG+Tie2 inhibitor group(HG+In-Tie2 group),HG+Ang-1 group,HG+Ang-1+Tie2 inhibitor group(HG+Ang-1+In-Tie2 group),and HG+Ang-1+phosphatidylinositol 3-kinase(PI3K)inhibitor group(HG+Ang-1+LY294002 group).5-Ethynyl-2'-deoxyuridine(EdU)method was used to detect the proliferation activities of the cells in various groups;YO-PRO-1/PI method was used to detect the apoptotic rates of the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Ang-1 mRNA and Tie2 mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Tie2,glucose transporter 1(GLUT1),and glucose transporter 4(GLUT4)proteins and the ratios of phosphorylated PI3K(p-PI3K)/PI3K and phosphorylated protein kinase B(p-AKT)/AKT in the cells in various groups.Results:The CCK-8 assay results showed that compared with 0 μg·L?1 Ang-1 group,the activity of the HUVECs was significantly increased after treated with 200 μg·L?1 Ang-1 for 48 h(P<0.01);compared with 0 nmol·L?1 Tie2 inhibitor group,the activity of the HUVECs was significantly decreased after treated with 2 500、5 000 and 7 500 nmol·L?1 Tie2 inhibitor(P<0.01);the optimal concentrations of Ang-1 and Tie2 inhibitor were 200 μg·L?1 and 2 500 nmol·L?1,respectively.Compared with NG group,the glucose level in the supernatant of the HUVECs in HG group was significantly increased(P<0.01);compared with HG group,the glucose level in the supernatant of the HUVECs in Ang-1 group was significantly decreased(P<0.01).The EdU assay results showed that compared with NG group,the proliferation activity of the HUVECs in HG group was significantly decreased(P<0.01);compared with HG group,the proliferation activity of the HUVECs in HG+In-Tie2 group was significantly decreased(P<0.01),and the proliferation activity of the HUVECs in HG+Ang-1 group was significantly increased(P<0.01);compared with HG+Ang-1 group,the proliferation activities of the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.01).The YO-PRO-1/PI assay results showed that compared with NG group,the apoptotic rate of the HUVECs in HG group was significantly increased(P<0.01);compared with HG group,the apoptotic rate of the HUVECs in HG+In-Tie2 group was significantly increased(P<0.01),and the apoptotic rate of the HUVECs in HG+Ang-1 group was significantly decreased(P<0.01);compared with HG+Ang-1 group,the apoptotic rates of the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly increased(P<0.01).The RT-qPCR results showed that compared with NG group,the expression levels of Ang-1 mRNA and Tie2 mRNA in the HUVECs in HG group and HG+In-Tie2 group were significantly decreased(P<0.01);compared with HG group,the expression levels of Ang-1 mRNA and Tie2 mRNA in HG+In-Tie2 group were significantly decreased(P<0.01),and the expression levels of Ang-1 mRNA and Tie2 mRNA in the HUVECs in HG+Ang-1 group were significantly increased(P<0.05);compared with HG+Ang-1 group,the expression levels of Ang-1 mRNA and Tie2 mRNA in the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.05 or P<0.01).The Western blotting results showed that compared with NG group,the expression level of Tie2 protein in the HUVECs in HG group was significantly decreased(P<0.01),and the expression levels of GLUT1 and GLUT4 proteins were significantly increased(P<0.01);compared with HG group,the expression levels of Tie2,GLUT1,and GLUT4 proteins in the HUVECs in HG+In-Tie2 group were significantly decreased(P<0.01),the expression level of Tie2 protein in the HUVECs in HG+Ang-1 group was significantly increased(P<0.01),and the expression levels of GLUT1 and GLUT4 proteins were significantly decreased(P<0.01);compared with HG+Ang-1 group,the expression levels of Tie2,GLUT1,and GLUT4 proteins in the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.01).Compared with NG group,the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG group were significantly increased(P<0.01);compared with HG group,the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG+In-Tie2 group were significantly decreased(P<0.01),and the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG+Ang-1 group were significantly decreased(P<0.01);compared with HG+Ang-1 group,the p-PI3K/PI3K and p-AKT/AKT ratios in the HUVECs in HG+Ang-1+In-Tie2 group and HG+Ang-1+LY294002 group were significantly decreased(P<0.01).Conclusion:Ang-1 down-regulates the expressions of GLUT1 and GLUT4 in the HUVECs cultured under high glucose conditions;the binding of Ang-1 to Tie2 may down-regulate GLUT1 and GLUT4 via the PI3K/AKT signaling pathway to participate in the glucose transportation in the HUVECs cultured under high glucose conditions.