ObjectiveA middle cerebral artery occlusion (MCAO) mouse model is established by electrocoagulation of the middle cerebral artery. The study examines the mechanism by which exosomes (EXO) derived from human amniotic mesenchymal stem cells (hAMSCs) improve ischemic stroke and regulate neural ferroptosis-related injury. MethodsThirty-two SPF-grade male C57BL/6J mice aged 6 - 8 weeks were randomly divided into four groups (n=8 per group): sham group (Sham), model group (MCAO), MCAO plus normal saline group (MCAO+NaCl), and MCAO plus exosome group (MCAO+EXO). The mouse MCAO model was established by electrocoagulation of the middle cerebral artery. Mice in the Sham group underwent exposure of the middle cerebral artery without electrocoagulation. Twenty-four hours before MCAO induction, mice in the MCAO+EXO group received a tail vein injection of 100 μL of exosomes derived from the culture supernatant of hAMSCs at a concentration of 9.5×10¹¹ particles/mL. Mice in the MCAO+NaCl group were injected with an equal volume of normal saline via the tail vein. Twenty-four hours after model establishment, neurological deficits were evaluated using the Longa neurological deficit scoring system. Cerebral infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Hematoxylin and eosin (HE) staining was performed to evaluate morphological changes of neurons in the ischemic brain regions. The contents of ferrous iron (Fe²⁺), malondialdehyde (MDA), total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) in the infarct core and peri-infarct regions were determined using microcolorimetric assays to evaluate differences among groups. The mRNA expression levels of ferroptosis-related factors, including nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in the infarct core and peri-infarct regions were measured by real-time quantitative PCR. Protein expression levels of NRF2, SLC7A11, and GPX4 in the infarct and peri-infarct regions of each group were analyzed by Western blotting. ResultsCompared with the MCAO group, the Longa neurological deficit score was significantly reduced in the MCAO+EXO group (P<0.01). Prominent cerebral infarction was observed in the MCAO group, whereas the infarct volume ratio was markedly decreased in the MCAO+EXO group compared with the MCAO group (P<0.001). Histopathological analysis revealed that mice in the MCAO group exhibited obvious neuronal damage, including cytoplasmic vacuolar degeneration, nuclear pyknosis and fragmentation, unclear nuclear structure, and disorganized neuronal arrangement, compared with the Sham group. In contrast, neurons in the MCAO+EXO group showed relatively preserved morphology, with intact cellular structures and large, regular nuclei located centrally within the cells. Biochemical analysis demonstrated that Fe²⁺ and MDA levels in the infarct core and peri-infarct regions were significantly increased in the MCAO group compared with the Sham group (P<0.001). These levels were significantly reduced in the MCAO+EXO group compared with the MCAO group (P<0.01). In addition, total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) levels were markedly decreased in the MCAO group relative to the Sham group (P<0.01). Compared with the MCAO group, the MCAO+EXO group exhibited significantly increased levels of total GSH and GSH (P<0.001), while no significant change was observed in GSSG levels (P>0.05). Furthermore, both mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) were significantly downregulated in the MCAO group compared with the Sham group (P<0.01, P<0.001). In contrast, both mRNA and protein expression levels of NRF2, SLC7A11, and GPX4 were significantly upregulated in the MCAO+EXO group compared with the MCAO group (P<0.05). ConclusionIn the mouse MCAO model, tail vein injection of exosomes derived from hAMSCs can improve motor function, reduce infarct area, protect neuronal cell morphology, and reduce the degree of nerve injury. Exosomes may exert a protective effect by activating the NRF2/SLC7A11/GPX4 pathway and reducing ferroptosis in neuronal cells of MCAO model mice.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective:To discuss the ameliorative effect of total flavonoids from corn silk(TFCS)on kidney injury in the rats with urate nephropathy,and to clarify the possible mechanism.Methods:Sixty male Wistar rats were randomly divided into control group,model group,positive control group[benzbromarone(BZM)group,5 mg·kg-1·d-1],low dose of TFCS group(20 mg·kg-1·d-1),medium dose of TFCS group(40 mg·kg-1·d-1),and high dose of TFCS group(80 mg·kg-1·d-1),and there were 10 rats in each group.Except for control group,the rats in the other groups were administered potassium oxonate(350 mg·kg-1)and adenine(70 mg·kg-1)by gavage for 4 weeks to establish the hyperuricemic nephropthy models.The rats in different doses of TFCS groups were treated with TFCS for 2 weeks.Speckle blood flow imager was used to detect the renal blood perfusion of the rats in various groups and the kidney coefficients of the rats in various groups were caculated;HE staining and Masson staining were used to observe the pathomorphology and fibrosis degrees of kidney tissue of the rats in various groups and enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of uric acid(UA),creatinine(Cr),blood urea nitrogen(BUN),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in the serum and levels of β2-microglobulin(β2-MG)and microalbumin(ALB)in the urine of the rats in various groups;Western blotting method was used to detect the expression levels of urate transporter 1(URAT1),glucose transporter 9(GLUT9),and ATP-binding cassette transporter G2(ABCG2)proteins in kidney tissue of the rats in various groups.Results:Compared with control group,the renal blood perfusion volume of the rats in model group was significantly decreased(P<0.01).Compared with model group,the renal blood perfusion volumes of the rats in BZM group and low,medium,and high doses of TFCS groups were significantly increased(P<0.05 or P<0.01).Compared with control group,the kidney weight of the rats in model group was increased,with visible white granular spots on the surface,absence of blood color,and kidney volume was increased.Compared with model group,the kidney volumes of the rats in BZM group and medium and high doses of TFCS groups were decreased,with color tending toward that in control group,and the white granular spots on the surface were significantly reduced.Compared with model group,the kidney coefficients of the rats in BZM group and medium and high doses of TFCS groups were decreased(P<0.01).The HE staining results showed there were no abnormalities in kidney tissue structure in control group,while there were a small amount of brown-yellow urate crystal deposition and interstitial connective tissue hyperplasia in model group;compared with model group,the kidney tissue damage and inflammatory infiltration were alleviated to varying degrees in BZM group and different doses of TFCS groups.The Masson staining results revealed no obvious collagen fiber deposition in control group,whereas significant blue collagen fiber deposition in kidney tissue of the rats was found in model group,and the collagen volume fraction(CVF)was increased compared with control group(P<0.01);compared with model group,the CVFs of the rats in BZM group and different doses of TFCS groups were decreased(P<0.01).The ELISA results showed that compared with control group,the levels of UA,Cr,BUN,IL-6,and TNF-α in serum of the rats in model group were increased(P<0.01);compared with model group,the levels of UA,Cr,BUN,IL-6,and TNF-α in serum of the rats in BZM group and medium and high doses of TFCS groups were decreased(P<0.01).Compared with control group,the levels of β2-MG and ALB in urinary in model group were increased(P<0.01);compared with model group,the levels of β2-MG and ALB in urinary of the rats in different doses of TFCS groups were decreased(P<0.05 or P<0.01).The Western blotting results showed that compared with control group,the expression levels of URAT1 and GLUT9 proteins in kidney tissue of the rats in BZM group and model group were increased(P<0.01),while the expression level of ABCG2 protein was decreased(P<0.01).Compared with model group,the expression levels of URAT1 and GLUT9 proteins in kidney tissue of the rats in different doses of TFCS groups were decreased(P<0.05 or P<0.01),and the expression level of ABCG2 protein was increased(P<0.01).Conclusion:TFCS can significantly alleviate the kidney injury in the rats with urate nephropathy model,and its mechanism may be related to the downregulation of expression of URAT1 and GLUT9 proteins and upregulation of ABCG2 protein expression in kidney tissue.

Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔ_pMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.

Objective:To investigate the relationship between the level of prolyl 4-hydroxylase subunit alpha 2 (P4HA2) in peripheral blood and the adverse pregnancy outcome in patients with gestational diabetes mellitus (GDM).Methods:A retrospective collection of baseline data was conducted on 120 GDM patients who underwent regular prenatal check ups and deliveries in Wenzhou Central Hospital from March 2022 to March 2024, serving as the GDM group. Baseline data from 120 pregnant women with normal glucose tolerance (NGT) during the same period were collected as the NGT group. Baseline data of blood lipids, blood glucose, and peripheral blood P4HA2 between the two groups were compared, and Pearson correlation test was used to determine the correlation between P4HA2 and some clinical indicators. Statistical analysis was conducted on the pregnancy outcomes of GDM patients, divided into the adverse pregnancy group (32 cases) and the normal pregnancy group(88 cases). Baseline data on blood lipids, blood glucose, and peripheral blood P4HA2 were compared between the two groups. Univariate and multivariate Logistic regression analysis were used to screen for factors affecting adverse pregnancy outcomes in GDM patients. Receiver operating characteristic (ROC) curves were also plotted to analyze the predictive value of peripheral blood P4HA2 for adverse pregnancy outcomes in GDM patients.Results:Compared with the NGT group, the GDM group had higher levels of fasting glucose, 2-h glucose, 1-h glucose, glycosylated hemoglobin (HbA 1c), peripheral blood P4HA2, insulin resistance index, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC): (6.26 ± 0.24) mmol/L vs. (4.33 ± 0.15) mmol/L, (9.69 ± 0.18) mmol/L vs. (7.41 ± 0.19) mmol/L, (11.01 ± 0.29) mmol/L vs. (7.10 ± 0.27) mmol/L, (8.54 ± 0.43)% vs. (5.05 ± 0.61)%, (39.03 ± 3.33) μg/L vs. (35.55 ± 3.05) μg/L, 2.50 ± 0.34 vs. 1.95 ± 0.33, (2.56 ± 0.49) mmol/L vs. (2.08 ± 0.37) mmol/L, (3.85 ± 0.25) mmol/L vs. (3.26 ± 0.30) mmol/L, (6.92 ± 0.43) mmol/L vs. (6.25 ± 0.43) mmol/L, and significantly lower levels of high-density lipoprotein cholesterol (HDL)-C: (1.70 ± 0.11) mmol/L vs. (1.87 ± 0.22) mmol/L, there were statistical differences ( P<0.05). Pearson correlation analysis showed that peripheral blood P4HA2 was positively correlated with fasting blood glucose, 2-h blood glucose, 1-h blood glucose, HbA 1c, insulin resistance index, TG, LDL-C, and TC ( r>0, P<0.05); peripheral blood P4HA2 was negatively correlated with HDL-C ( r<0, P<0.05). The fasting blood glucose, 2-h blood glucose, 1-h blood glucose, insulin resistance index, peripheral blood P4HA2, and TC in the adverse pregnancy group were significantly higher than those in the normal pregnancy group:(6.35 ± 0.22) mmol/L vs. (6.23 ± 0.24) mmol/L, (9.78 ± 0.25) mmol/L vs. (9.66 ± 0.14) mmol/L, (11.12 ± 0.33) mmol/L vs. (10.97 ± 0.26) mmol/L, 2.61 ± 0.22 vs. 2.36 ± 0.37, (41.20 ± 3.62) μg/L vs. (38.24 ± 2.85) μg/L, (7.12 ± 0.55) mmol/L vs. (6.84 ± 0.35) mmol/L, there were statistical differences ( P<0.05). Logistic regression analysis showed that fasting blood glucose, 1-h blood glucose, 2-h blood glucose, TC, insulin resistance index, and peripheral blood P4HA2 were related factors affecting pregnancy outcomes in GDM patients ( P<0.05). The ROC curve showed that peripheral blood P4HA2 had good predictive value for adverse pregnancy outcomes in GDM patients, with an area under the curve of 0.729. Conclusions:The high expression of P4HA2 in peripheral blood of GDM patients is closely related to adverse pregnancy, which can provide some reference for clinical prediction of pregnancy outcomes in patients.

Objective To investigate the value of gemstone spectral CT multiparameter for risk assessment in acute pulmonary embolism(APE).Methods A total of 83 patients diagnosed with APE were categorized into three groups based on the European Society of Cardiology(ESC)guidelines:high-risk group(n=23),medium-high-risk group(n=29),and medium-low-risk group(n=31).The spectral CT multiparameters for each group were subsequently analyzed and compared.The predictive value of the region of interest perfusion defect iodine group value(ROI vPD),whole lung mean perfusion iodine group value(vMeanIP),and lung perfusion defect volume ratio(rPDvol)in high-risk APE patients were assessed using receiver operating characteristic(ROC)curves.Pearson correlation was employed to analyze the correlation of gemstone spectral CT multiparameter with pulmonary artery obstruction index(PAOI)and right ventricle/left ventricle diameter ratio(rRVD/LVD).Results Whole lung minimum perfusion iodine group value(vMinIP),whole lung maximum perfusion iodine group value(vMaxIP),vMeanIP,rPDvol and right ventricle/left ventricle volume ratio(rRVV/LVV)exhibited significant differences across all groups.The area under the curve(AUC)for ROI vPD,vMeanIP,and rPDvol in high-risk APE patients were 0.792,0.831,and 0.884,respectively.The sensitivity and specificity for ROI vPD(≤0.3),vMeanIP(≤1.1),and rPDvol(≥23.7％)were recorded at 95.7％and 60.0％,78.3％and 75.0％,as well as 91.3％and 75.0％,respectively.Simultaneously,the gemstone spectral CT multiparameter exhibited correlations with PAOI and rRVD/LVD.Conclusion The gemstone spectral CT multiparameter can be utilized to evaluate the severity and progression of patients with APE.

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To investigate the levels of gross α and gross β activities in different water types within a 40-kilometer radius around the Zhangzhou Nuclear Power Plant prior to its operation. Methods In 2018, drinking water samples were collected from the area surrounding the nuclear power plant during both the wet and dry seasons, including source water, treated water, tap water, and well water. The gross α and gross β activity concentrations were measured using a low-background α/β counter, followed by statistical analysis. Results A total of 80 water samples from different sources around the Zhangzhou Nuclear Power Plant were collected. The average gross α and gross β activity concentrations during the wet season were (0.110 ± 0.036) Bq/L and (0.643 ± 0.028) Bq/L, respectively, while those during the dry season were (0.124 ± 0.032) Bq/L and (0.624 ± 0.026) Bq/L, respectively. There were no significant differences in the gross α and gross β activity concentrations between the wet and dry seasons for the overall sample set (P > 0.05). However, there were statistically significant differences in the gross α and gross β activity concentrations between the wet and dry seasons for source water and well water (Z_wet = −2.005, −2.123; Z_dry = −1.943, −3.090; P < 0.05). Conclusion The radioactivity levels in different water types within various ranges around the Zhangzhou Nuclear Power Plant before its operation were determined. The measured activity concentrations were at the same level as those from previous investigations in other regions of Fujian Province.

Objective To analyze the risk factors for adverse drug reactions(ADRs)caused by montelukast sodium in the treatment of children with community-acquired pneumonia(CAP),and to construct and verify prediction model for ADRs.Methods The clinical data of CAP children who received montelukast sodium treatment in Suzhou Hospital Affiliated to Anhui Medical University from April 2023 to June 2024 were retrospectively collected.The patients were randomly divided into modeling group and verification group according to the 3∶2 ratio,and the modeling group were divided into the ADR subgroup and non-ADR subgroup based on the presence or absence of ADR.The modeling group data was used for model construction,and multivariate Logistic analysis were used to analyze the influencing factors of ADR and establish a predictive model.The verification group data was used for model validation.The model's predictive ability,calibration,and clinical net benefits were evaluated using the receiver operating characteristic(ROC)analysis,calibration curves,and decision curves.Results A total of 241 pediatric patients were included,including 144 in the modeling group and 97 in the validation group.A total of 50 children in the modeling group developed ADR,with an incidence rate of 34.72％.Multivariate Logistic regression results indicated that nebulized inhalation[OR=2.370,95％CI(1.099,5.111),P=0.028],use of methylprednisolone[OR=2.481,95％CI(1.057,5.824),P=0.037],and extrapulmonary complications[OR=7.411,95％CI(1.382,39.738),P=0.019]were independent risk factors for montelukast sodium related ADRs in children with CAP.The areas under the curve of the modeling group and validation group were 0.964 and 0.869,respectively.The calibration curve and decision curve showed good consistency between the predicted and actual values of the model,indicating good clinical net benefits.Conclusions Aerosol inhalation,methylprednisolone use,and extrapulmonary complications were independent risk factors for the occurrence of montelukast sodium-related adverse reactions in children with CAP.This model could help screen and identify ADR high-risk children.