Objective To establish mouse models exposed to different doses of neodymium oxide via tracheal instillation,and to investigate the mechanisms underlying brain tissue damage induced by neodymium oxide exposure in mice.Methods Forty-eight male C57/BL6 mice were randomly assigned to four groups:the control group,the low-dose group,the medium-dose group,and the high-dose group.The low-dose,medium-dose,and high-dose groups received 62.5 mg/mL,125 mg/mL,and 250 mg/mL neodymium oxide,respectively,via non-exposed tracheal instillation.The control group received an equivalent volume of saline using the same administration method.After 35 days,the mice were euthanized,and brain tissues were collected.RT-PCR was used to assess the mRNA expression changes of Claudin-5 and Occludin.Western blot analysis was performed to evaluate the expression changes of Claudin-5 and Occludin tight junction proteins,as well as the expression changes of MMP-2 and MMP-9 in the brain tissues.Additionally,the expression of the RhoA/ROCK2 signaling pathway and downstream cofilin protein was examined.Changes in oxidative stress markers,including MDA,T-AOC,and NO,were measured using a kit method.Results The mRNA expression of Claudin-5 was significantly reduced in the middle-dose and high-dose groups compared to the control group(P<0.05).Similarly,the mRNA expression of Occludin was significantly lower in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).Additionally,the protein expression of Claudin-5,MMP-2,and Occludin was significantly decreased in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).The protein expression of MMP-9 and RhoA was also signifi-cantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05).Furthermore,the protein expression of ROCK2 and p-cofilin in the high-dose group was significantly lower than that in the control group(P<0.05).The content of MDA and T-AOC was significantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05),and the content of NO in the high-dose group was significantly lower than that in the control group(P<0.05).Conclusion Exposure to neodymium oxide results in increased permeability of the blood-brain barrier in mice,leading to oxidative stress,inflammatory responses,and activation of the RhoA/ROCK2 signaling pathway.

Purpose This study aims to analyze genetic mutations in patients with BCR ∷ABL negative myelopro-liferative neoplasms(MPN)and to explore their relationship with clinical features.Methods We retrospectively ana-lyzed the clinical data of 208 patients diagnosed with BCR ∷ABL negative MPN,which included 34 patients with poly-cythemia vera(PV),33 with essential thrombocytopenia(ET),and 141 with primary myelofibrosis(PMF).Mutations in driver genes were assessed in all patients.A total of 72 patients underwent next-generation sequencing(NGS)with 69-gene panel,and the relationship between gene mutations and clinical features were analyzed.Results Among the 208 MPN patients,at least one driver gene mutation(JAK2,CALR,MPL)was detected in 96.15％(200/208)of the patients.Only 0.48％(1/208)of the patients exhibited both JAK2 and CALR driver mutations.We analyzed the clinical data of 136 patients with only driver gene mutations to compare the relationship between the most common JAK2 mutations(identified in 110 patients)and clinical outcomes.The JAK2 mutation group demonstrated higher white blood cell(WBC)counts and lower platelet(PLT)counts compared to the group without JAK2 mutations.173 muta-tions in 40 genes were detected in 72 patients,per capita carried(2.40±1.40)mutations.TET2,ASXL1,and TP53 are the most prevalent non-driver gene mutations,with 44.4％(32/72)of patients exhibiting at least one mutation in these three genes.In comparison to patients without detected mutations in TET2,ASXL1,and TP53,those with muta-tions in these genes demonstrated lower hemoglobin(HGB)levels,a higher incidence of splenomegaly,and more se-vere bone marrow fibrosis.High-molecular risk category(HMR)mutations were detected in 22.22％(16/72)of the patients,and patients with HMR exhibited lower hemoglobin(HGB)levels,lower PLT counts,a higher likelihood of peripheral blood primitive cell percentage ≥ 1％,a greater incidence of splenomegaly,and more severe myelofibrosis.Mutations in the ASXL1 gene were exclusively observed in patients with PMF.Among the PMF patients with ASXL1 mutations(12 patients),there was a higher likelihood of having a peripheral blood primitive cell percentage of ≥1％,as well as a more severe degree of myelofibrosis.Conclusion Approximately 97％of patients with myeloproliferative neoplasms(MPN)exhibit positivity for driver genes,with a notably high mutation rate of the JAK2 gene.Each sub-group of MPN is characterized by distinct gene mutation patterns.Notably,ASXL1 mutations are exclusive to patients with primary myelofibrosis(PMF).Furthermore,PMF patients harboring ASXL1 mutations tend to demonstrate more pronounced bone marrow fibrosis and a greater proportion of blast cells in peripheral blood.

Objective To analyze the correlation between tongue image features and the risk levels of disease in patients with idiopathic membranous nephropathy(IMN).Methods Based on IMN clinical research electronic data acquisition system,a cross-sectional study method was used to analyze the clinical diagnosis and treatment data of 135 IMN patients from Guangdong Provincial Hospital of Chinese Medicine.The patients were grouped according to the risk levels of disease,and then the correlation between the risk levels of disease and tongue image features was analyzed.During the description of tongue image features,TB is for tongue body,TC is for tongue coating,L is for luminance,a is for red-green axis,G is for the value of green,B is for the value of blue,and AUT is for the value of autocorrelation.Results The comparison of tongue image feature indicators of patients with different risk levels of IMN showed that:(1)the higher the level of disease risk of IMN patients,the greater the values of TB-L,TB-G and TB-B(P<0.05 or P<0.01).The values of tongue image indicator TB-a and TC-a of the patients with different risk levels of IMN were shown in decreasing sequence:low-risk group>high-risk group>middle-risk group>extremely-high-risk group(P<0.05).(2)Linear regression analysis showed that TB-L,TB-G,and TB-B were significantly increased in the high-risk group compared with those in the middle-and low-risk groups(P<0.05 or P<0.01),whereas there were no significant differences between the middle-risk group and low-risk group(P>0.05).(3)The results of correlation analysis showed that there was a positive correlation among most of the tongue image feature indicators(including TB-L,TB-G,TB-B,TB-AUT,TC-L,TC-G,and TC-B,etc.)and the risk level of disease,while TB-a was negatively correlated with the risk level of disease,and the differences were all statistically significant(P<0.05 or P<0.01).(4)All patients were treated with Chinese medicine and/or Chinese patent medicine,and 46.7%of patients were given hormones and immunosuppressants,and there was no statistically significant difference in the the use of hormones and immunosuppressants among various groups(P=0.637).Conclusion There is a correlation between the tongue image features of IMN patients and the risk level of disease,and the results will provide an objective reference for the assessment of illness state and traditional Chinese medicine(TCM)syndrome differentiation of IMN patients.With reference to the changes in the tongue image features,the illness state can be precisely identified,which is more accurate than the inspection of four diagnostic methods of TCM.

Objective To investigate the diagnostic value of serum human β-defensin 2(HBD2)and soluble growth stimulating gene 2(sST2)levels in pediatric refractory Mycoplasma pneumonia.Methods A total of 145 children diagnosed with Mycoplasma pneumonia were recruited,and divided into refractory pneumonia group(n=53)and common pneumonia group(n=92)based on whether they had refractory or common pneumonia.General data were compared between the two groups.Ser-um HBD2 and sST2 levels were measured using enzyme-linked immunosorbent assay(ELISA).Multi-variate logistic regression analysis was used to identify influencing factors for the occurrence of refracto-ry Mycoplasma pneumonia.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the diagnostic value of serum HBD2 and sST2 levels in refractory Mycoplasma pneumonia.Results The proportion of lung consolidation and pleural effusion in refractory pneumonia group was significantly higher,and the fever time was significantly longer than that in common pneumonia group(P＜0.05).Serum HBD2 and sST2 levels in the refractory pneumonia group were signifi-cantly higher than those in the common pneumonia group(P＜0.05).Multivariate Logistic regres-sion analysis indicated that lung consolidation,pleural effusion,high serum HBD2 level and high serum sST2 level were risk factors for pediatric refractory Mycoplasma pneumonia(P＜0.05).The area under the curve and Youden's index for diagnosing pediatric refractory Mycoplasma pneumonia were 0.817 and 0.557 for serum HBD2 level,and 0.841 and 0.607 for serum sST2 level,respec-tively.Combined diagnosis using both markers resulted in an area under the curve of 0.916 and a Youden's index of 0.721.Conclusion The combined detection of serum HBD2 and sST2 levels holds significant diagnostic value for pediatric refractory Mycoplasma pneumonia.

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*

Objective To establish mouse models exposed to different doses of neodymium oxide via tracheal instillation,and to investigate the mechanisms underlying brain tissue damage induced by neodymium oxide exposure in mice.Methods Forty-eight male C57/BL6 mice were randomly assigned to four groups:the control group,the low-dose group,the medium-dose group,and the high-dose group.The low-dose,medium-dose,and high-dose groups received 62.5 mg/mL,125 mg/mL,and 250 mg/mL neodymium oxide,respectively,via non-exposed tracheal instillation.The control group received an equivalent volume of saline using the same administration method.After 35 days,the mice were euthanized,and brain tissues were collected.RT-PCR was used to assess the mRNA expression changes of Claudin-5 and Occludin.Western blot analysis was performed to evaluate the expression changes of Claudin-5 and Occludin tight junction proteins,as well as the expression changes of MMP-2 and MMP-9 in the brain tissues.Additionally,the expression of the RhoA/ROCK2 signaling pathway and downstream cofilin protein was examined.Changes in oxidative stress markers,including MDA,T-AOC,and NO,were measured using a kit method.Results The mRNA expression of Claudin-5 was significantly reduced in the middle-dose and high-dose groups compared to the control group(P<0.05).Similarly,the mRNA expression of Occludin was significantly lower in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).Additionally,the protein expression of Claudin-5,MMP-2,and Occludin was significantly decreased in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).The protein expression of MMP-9 and RhoA was also signifi-cantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05).Furthermore,the protein expression of ROCK2 and p-cofilin in the high-dose group was significantly lower than that in the control group(P<0.05).The content of MDA and T-AOC was significantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05),and the content of NO in the high-dose group was significantly lower than that in the control group(P<0.05).Conclusion Exposure to neodymium oxide results in increased permeability of the blood-brain barrier in mice,leading to oxidative stress,inflammatory responses,and activation of the RhoA/ROCK2 signaling pathway.

Purpose This study aims to analyze genetic mutations in patients with BCR ∷ABL negative myelopro-liferative neoplasms(MPN)and to explore their relationship with clinical features.Methods We retrospectively ana-lyzed the clinical data of 208 patients diagnosed with BCR ∷ABL negative MPN,which included 34 patients with poly-cythemia vera(PV),33 with essential thrombocytopenia(ET),and 141 with primary myelofibrosis(PMF).Mutations in driver genes were assessed in all patients.A total of 72 patients underwent next-generation sequencing(NGS)with 69-gene panel,and the relationship between gene mutations and clinical features were analyzed.Results Among the 208 MPN patients,at least one driver gene mutation(JAK2,CALR,MPL)was detected in 96.15％(200/208)of the patients.Only 0.48％(1/208)of the patients exhibited both JAK2 and CALR driver mutations.We analyzed the clinical data of 136 patients with only driver gene mutations to compare the relationship between the most common JAK2 mutations(identified in 110 patients)and clinical outcomes.The JAK2 mutation group demonstrated higher white blood cell(WBC)counts and lower platelet(PLT)counts compared to the group without JAK2 mutations.173 muta-tions in 40 genes were detected in 72 patients,per capita carried(2.40±1.40)mutations.TET2,ASXL1,and TP53 are the most prevalent non-driver gene mutations,with 44.4％(32/72)of patients exhibiting at least one mutation in these three genes.In comparison to patients without detected mutations in TET2,ASXL1,and TP53,those with muta-tions in these genes demonstrated lower hemoglobin(HGB)levels,a higher incidence of splenomegaly,and more se-vere bone marrow fibrosis.High-molecular risk category(HMR)mutations were detected in 22.22％(16/72)of the patients,and patients with HMR exhibited lower hemoglobin(HGB)levels,lower PLT counts,a higher likelihood of peripheral blood primitive cell percentage ≥ 1％,a greater incidence of splenomegaly,and more severe myelofibrosis.Mutations in the ASXL1 gene were exclusively observed in patients with PMF.Among the PMF patients with ASXL1 mutations(12 patients),there was a higher likelihood of having a peripheral blood primitive cell percentage of ≥1％,as well as a more severe degree of myelofibrosis.Conclusion Approximately 97％of patients with myeloproliferative neoplasms(MPN)exhibit positivity for driver genes,with a notably high mutation rate of the JAK2 gene.Each sub-group of MPN is characterized by distinct gene mutation patterns.Notably,ASXL1 mutations are exclusive to patients with primary myelofibrosis(PMF).Furthermore,PMF patients harboring ASXL1 mutations tend to demonstrate more pronounced bone marrow fibrosis and a greater proportion of blast cells in peripheral blood.

Objective To explore the diagnostic value of serum Irisin,fibroblast growth factor 23(FGF23)and N-mid osteocalcin(N-MID)in the elderly patients with type 2 diabetes mellitus(T2DM)with osteoporo-sis(OP).Methods A total of 120 patients with T2DM combined with OP who were treated in the hospital from January 2021 to June 2023 were selected as the T2DM+OP group,and 120 patients with pure T2DM who were treated in the hospital during the same period were selected as the T2DM group.The levels of serum Irisin,FGF-23 and N-MID were compared between two groups.Multivariate Logistic regression was applied to analyze the influencing factors of OP in T2DM patients.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum Irisin,FGF-23 and N-MID levels for the occurrence of OP in T2DM patients.Results FGF-23,N-MID,fasting plasma glucose(FPG),fasting insulin(FINS),high-density lipoprotein cholesterol(HDL-C)in T2DM+OP group were obviously higher than those in T2DM group(P＜0.05),course of diabetes was longer than that in T2DM group(P＜0.05),and bone mineral density and ser-um Irisin level were lower than those in T2DM group(P＜0.05).Multivariate Logistic regression analysis showed that FGF-23,N-MID,diabetes course,FPG and FINS were independent risk factors for OP in T2DM patients(P＜0.05),while Irisin and bone mineral density were protective factors for OP in T2DM patients(P＜0.05).The area under the curve(AUC)of the combined diagnosis of serum Irisin,FGF-23 and N-MID in T2DM patients with OP was 0.886,with sensitivity of 90.00％and specificity of 74.17％.The AUC of the combination of the three for diagnosing OP in T2DM patients was larger than that of serum Irisin,FGF-23 and N-MID alone(Zcombination-Irisin=3.945,Zcombination-FGF23=5.119,Zcombination-N-MID=3.778,all P＜0.001).Conclusion The serum levels of FGF-23 and N-MID in patients with T2DM combined with OP increase,while the level of Iri-sin decreases.The combination of the three has high diagnostic value for the occurrence of OP in elderly T2DM patients.

Objective:To study the reproductive toxicity of lithium chloride (LiCl) in male mice and to explore the molecular mechanism of the protective effect of quercetin on testosterone production dysfunction.Methods:Twenty-five male C57BL/6 mice aged 4-5 weeks were randomly divided into five groups according to the random number table method: control group, LiCl infected group [38.4 mg/(kg·d) LiCl+corn oil, noted as LiCl group], quercetin control group [50 mg/(kg·d) quercetin, noted as High-Quer group], low-dose quercetin combined with LiCl infection group [38.4 mg/(kg·d) LiCl+10 mg/(kg·d) quercetin, noted as Low-Quer+LiCl group] and high dose quercetin combined with LiCl infected group [38.4 mg/(kg·d) LiCl+50 mg/(kg·d) quercetin, noted as High-Quer+LiCl group]. The structure of testicular tissue, semen parameters, and the ultrastructure of Leydig cells in mice were detected by HE staining, computer-aided sperm analysis system (CASA), and transmission electron microscopy, respectively. TM3 mouse Leydig cells were treated with 0 mmol/L, 5 mmol/L, 10 mmol/L, 20 mmol/L LiCl for 24 h. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), mitochondrial membrane potential (MMP), lipid peroxidation levels, and expression levels of testosterone-related protein were measured by SOD and GSH-Px kits, TMRE probe, Image-iT TM lipid peroxidation probe, and Western blotting, respectively. Intracellular Fe 2+ concentration was detected by Fe 2+ detection kit and FerroOrange probe. The levels of testosterone, progesterone, and estradiol were measured using enzyme-linked immunosorbent assay kits. Results:In the LiCl group, the total sperm count [(36.78±1.81)×10 6], sperm concentration [(18.39±0.90)×10 6/mL], sperm motility [(25.70±3.32)%] and serum testosterone level [(7.26±0.29) μg/L] were lower than those of control group [(51.60±4.96)×10 6, P=0.002; (25.80±2.48)×10 6/mL, P=0.002; (41.47±2.83)%, P=0.001; (7.87±0.29) μg/L, P=0.013], the expression levels of Cyp11a1, StAR and Cyp17a1, Leydig cell biomarkers (3β-HSD1, 17β-HSD3) and ferroptosis regulatory proteins (GPX4, SLC7A11 and Nrf2) in testis were significantly down-regulated compared with control group (all P<0.001). LiCl also induced mitochondrial vacuoles and swelling of Leydig cells. However, low-dose quercetin intervention could significantly ameliorate the above LiCl-induced damage (total sperm count: P<0.001, sperm concentration: P<0.001, sperm motility: P=0.015, serum testosterone level: P=0.026, Cyp11a1, StAR, Cyp17a1, 3β-HSD1, 17β-HSD3, GPX4, SLC7A11, and Nrf2: all P<0.001). In 20 mmol/L LiCl group, the testosterone level [(7.28±0.24) μg/L] in TM3 cells was lower than that of 0 mmol/L LiCl group [(12.50±0.38) μg/L, P<0.001], the protein levels of Cyp11a1, StAR and Cyp17a1 were significantly down-regulated compared with 0 mmol/L LiCl group (all P<0.001), the activities of SOD [(2.42±0.11) U/mg], GSH-Px [(1.29±0.03) mU/mg] and MMP [(57.24±1.69)%] were lower than those of 0 mmol/L LiCl group [(3.11±0.09) U/mg, (1.54±0.01) mU/mg, (100.00±0)%, all P<0.001], the level of lipid peroxidation [(211.18±3.60)%] and the concentration of Fe 2+ [(26.44±0.94) μmol/L] were higher than those of 0 mmol/L LiCl group [(100.00±0)%, (7.12±0.29) μmol/L, all P<0.001], and the expression of ferroptosis regulatory proteins was significantly down-regulated compared with 0 mmol/L LiCl group (all P<0.001). Compared with 20 mmol/L LiCl group cells [lipid peroxidation: (194.46±3.16)%, (194.70±3.93)%; MMP: (78.74±0.52)%, (75.32±1.29)%], ferroptosis inhibitors Fer-1 and quercetin significantly decreased the level of lipid peroxidation [(181.71±3.80)%, P=0.004; (166.88±3.22)%, P<0.001], increased the level of MMP [(86.26±0.79)%, P=0.040; (81.09±1.32)%, P=0.001], and significantly up-regulated the expression of key enzymes in testosterone synthesis and ferroptosis regulatory proteins (all P<0.05). Conclusion:Quercetin may protect LiCl-induced Leydig cells injury and testosterone production dysfunction by inhibiting cell ferroptosis.

Objective To evaluate the application value of the three-point localization method in improving the quality and efficiency of four-chamber view acquisition in cardiac magnetic resonance(CMR)imaging.Methods A total of 215 patients who underwent four-chamber view in CMR imaging from January 2022 to October 2023 were retrospectively enrolled and divided into two groups.The control group(n=109)received traditional localization method while the study group(n=106)received three-point localization method.The image quality of mitral valve,tricuspid valve and cruciform structure in four-chamber view images were assessed by two radiologists using a Likert 4-piont scale.The time-consumption from scout imaging to the finish of four-chamber view imaging was recorded.Constituent data and numeral data were compared by Chi-square test and two-sample t test,respectively.Kappa test was used to analyze the inter-observer consistency.Results There were no significant inter-group differences in gender,age,disease profile,or the radiographers'experience.The mean quality scores of the mitral valve,tricuspid valve and cruciform structure in the control group and the study group were 3.44±0.64 and 3.63±0.49(P=0.023),3.43±0.67 and 3.53±0.60(P=0.202),3.71±0.49 and 3.83±0.35(P=0.047),respectively.The image quality score was higher in the study group than in the control group,with the differences in mitral valve and cruciform structure reaching statistical significance.The time-consumption for obtaining four-chamber view for the control group and the study group was 11.67±3.49 minutes and 7.212±1.83 minutes,respectively,with statistically significant differences(P＜0.001).Conclusion Compared with the traditional localization method,the three-point localization method provides better image quality in four-chamber view imaging with shortened imaging time.