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.

OBJECTIVE To analyze the characteristics of 57 acquired immune deficiency syndrome(AIDS)patients complicated with cryptococcal meningitis and observe the treatment outcomes.METHODS Totally 57 AIDS pa-tients with complicated cryptococcal meningitis who were treated in Guiyang Public Health Treatment Center from Jan.2019 to Jun.2023 were continuously assigned as the cryptococcal meningitis group,meanwhile,57 patients with simple AIDS were chosen as the simple AIDS group based on a 1∶1 ratio matching case-control study.Both groups received standardized therapies on basis of the criteria.The clinical characteristics,T lymphocyte subsets,biochemical indexes and treatment outcomes were observed and compared between the two groups.RESULTS There were no significant differences in gastrointestinal reactions,fever and eye discomfort between the two groups;the incidence of neurological symptoms of the cryptococcal meningitis group was higher than that of the simple AIDS group(P＜0.05).There was significant difference in the peripheral blood T lymphocyte subsets be-tween the cryptococcal meningitis group and the simple AIDS group(P＜0.05).The levels of whole blood CD4+,CD4+/CD8+and CD8+of the cryptococcal meningitis group were lower than those of the simple AIDS group;the serum glucose(GLU)level of the cryptococcal meningitis group was lower than that of the simple AIDS group;the serum adenosine deaminase(ADA)level of the cryptococcal meningitis group was higher than that of the sim-ple AIDS group;the serum immunoglobulin A(IgA)level of the cryptococcal meningitis group was higher than that of the simple AIDS group(P＜0.05).There were no significant differences in the immunological failure,vir-ological failure and immunological failure plus virological failure between the two groups after the treatment for 6 months.CONCLUSIONS The incidence of neurological symptoms is higher among the patients with AIDS com-plicated with cryptococcal meningitis than among the patients with simple AIDS.The patients have poor treatment outcomes and more severe damage of T lymphocyte subset functions,and the levels of biochemical indexes vary a-mong the patients,which may provide bases for diagnosis of diseases and assessment of curative effect and prog-nosis.

Objective To evaluate cardiac involvement in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) using echocardiography combined with electrocardiography. Methods A retrospective analysis was performed on the detailed medical records of AAV patients treated in Jining First People’s Hospital between January 2020 and December 2024. Eighty patients were enrolled in the AAV group, and the risk of heart disease was compared between the AAV group and a control group with 80 subjects matched for age, sex, and cardiovascular disease risk factors. Results Electrocardiographic abnormalities were observed in 78.75% of patients in the AAV group, while significant electrocardiographic abnormalities only occurred in symptomatic patients in the control group. There were no differences in left atrial enlargement or interventricular septal thickening between the AAV group and the control group. The overall left ventricular systolic function in the AAV group was lower than that in the control group (8.75% vs. 0). The incidence of reduced diastolic function in the AAV group was significantly higher than that in the control group (37.5% vs. 15%). The incidence rates of tricuspid regurgitation, mitral regurgitation, aortic regurgitation, and pericardial effusion in the AAV group were significantly higher than those in the control group. Pericardial thickening, aortic stenosis, pulmonary hypertension, and rare periaortic granulomas were found in the AAV group, but not in the control group. Conclusion Echocardiography and electrocardiography are important examination methods for evaluating cardiac involvement in AAV. These methods have key roles in disease screening, diagnosis and treatment, follow-up, and prognosis judgment.

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.

OBJECTIVE To analyze the characteristics of 57 acquired immune deficiency syndrome(AIDS)patients complicated with cryptococcal meningitis and observe the treatment outcomes.METHODS Totally 57 AIDS pa-tients with complicated cryptococcal meningitis who were treated in Guiyang Public Health Treatment Center from Jan.2019 to Jun.2023 were continuously assigned as the cryptococcal meningitis group,meanwhile,57 patients with simple AIDS were chosen as the simple AIDS group based on a 1∶1 ratio matching case-control study.Both groups received standardized therapies on basis of the criteria.The clinical characteristics,T lymphocyte subsets,biochemical indexes and treatment outcomes were observed and compared between the two groups.RESULTS There were no significant differences in gastrointestinal reactions,fever and eye discomfort between the two groups;the incidence of neurological symptoms of the cryptococcal meningitis group was higher than that of the simple AIDS group(P＜0.05).There was significant difference in the peripheral blood T lymphocyte subsets be-tween the cryptococcal meningitis group and the simple AIDS group(P＜0.05).The levels of whole blood CD4+,CD4+/CD8+and CD8+of the cryptococcal meningitis group were lower than those of the simple AIDS group;the serum glucose(GLU)level of the cryptococcal meningitis group was lower than that of the simple AIDS group;the serum adenosine deaminase(ADA)level of the cryptococcal meningitis group was higher than that of the sim-ple AIDS group;the serum immunoglobulin A(IgA)level of the cryptococcal meningitis group was higher than that of the simple AIDS group(P＜0.05).There were no significant differences in the immunological failure,vir-ological failure and immunological failure plus virological failure between the two groups after the treatment for 6 months.CONCLUSIONS The incidence of neurological symptoms is higher among the patients with AIDS com-plicated with cryptococcal meningitis than among the patients with simple AIDS.The patients have poor treatment outcomes and more severe damage of T lymphocyte subset functions,and the levels of biochemical indexes vary a-mong the patients,which may provide bases for diagnosis of diseases and assessment of curative effect and prog-nosis.

Objective:To analyze the blood differential metabolites of patients with intrahepatic cholestasis (IHC) by liquid chromatography-mass spectrometry metabolomics technology so as to find potential metabolic target.Method:Serum samples were collected from thirty patients with intrahepatic cholestasis and thirty healthy individuals after metabolomics analysis. The differential metabolites were initially screened based on the multiple differences and significance. KEGG enrichment analysis was performed on the differential metabolites to determine the candidate targets. The potential clinical application value of these characteristic metabolites was analyzed using the receiver operating characteristic curve.Result:A total of thirty patients with intrahepatic cholestasis and thirty healthy adults were included. The age difference between the two groups was not statistically significant ( P>0.05). The clinical condition was consistent with the statistically significant differences in liver biochemical indicators, blood routine, coagulation, and inflammatory indicators between the two groups ( P<0.05). Furthermore, a blood metabolomics screening analysis revealed 99 differentially expressed metabolites associated with intrahepatic cholestasis. Of these, 15 showed statistically significant differences. Glucose, lipid, and energy metabolisms were the various primary types of differential metabolites involved. The receiver operating characteristic curve>0.9 included the following twelve kinds of metabolites: 1H-indole-3-carboxaldehyde, 6-hydroxy-1H-indole-3-acetamide, phenylalanyl tryptophan, 1-methylguanosine, 2-ethoxy-5-methylpyrazine, p-hydroxybenzaldehyde, 5-(2-chlorophenyl)-3,4-dihydro-2H-pyrrole, methylthioadenosine, alanylisoleucine, anabsinthin, N-acetyl-DL-histidine monohydrate, N-methylnicotinamide, and others. The fifteen metabolites that were previously identified and calculated according to the differential quantitative value of the metabolite corresponding ratio exhibited fold-changes in the upregulated and downregulated potential biomarkers (phenylalanine tryptophan, phenylalanine, 5'-methylthioadenosine, anabsinthin, and N-methylnicotinamide) in combination with the area under the receiver operating characteristic curve>0.9. Conclusion:Phenylalanyl tryptophan, phenylalanylalanine, 5'-methylthioadenosine, anabsinthin, and N-methylnicotinamide may serve as potential metabolic markers to distinguish patients with cholestasis from healthy controls. N-methylnicotinamide, among them, is of great importance as a potential marker.

To explore screening tools for children with autism spectrum disorder (ASD), which are convenient for primary hospitals, it can provide basic data for formulating ASD prevention policies. This was a cross-sectional study by cluster sampling. Huyi District and Xincheng District were extracted for investigation in Xi′an City. From July 2021 to September 2022, all children aged from 3 months to 36 months who live in the two districts were subjected to primary screening. The child care physician used the routine screening tool "warning signs checklist for screening psychological, behavioral and developmental problems of children" and cartoon pictures of "early high-risk warning signs of autism", the children who were positive in the initial screening were referred to the district level maternal and child health hospital for re-screening, and those who were positive in the re-screening were referred to Xi ′an Children′s Hospital for diagnosis. The results showed that a total of 17 905 children aged from 3 months to 36 months were initially screened in the two districts, including 10 588 children aged from 18 months to 36 months, 50 children who were positive in the initial screening and 50 children who were re-screened. 23 children (18 boys and 5 girls) were diagnosed with ASD. The prevalence rate of ASD in children was 2.17‰ (95% confidence interval:1.29‰-3.06‰). 42 children were positive for "warning signs checklist" at the preliminary screening, and 19 were confirmed as ASD. 27 children were positive for "cartoon pictures" in the preliminary screening, and 23 were confirmed with ASD. The "cartoon pictures" in the preliminary screening and diagnosis of consistent rate was higher than the "warning signs checklist", two kinds of screening methods comparison were statistically significant difference in the odds of consistent (χ 2=11.01, P=0.001). In conclusion, relying on the three-level network of maternal and child health care, it is conducive to the whole process management of screening and diagnosis of children with ASD, and to guide the formulation of prevention policies. The cartoon pictures of "early high-risk warning signs of autism" can assist the identification of children with ASD based on the "warning signs checklist", which is simple, effective and suitable for promotion in the community health care.

Objective To investigate the correlations of serum levels of NOD-like receptor family CARD domain containing 3 (NLRC3) and extracellular matrix protein 1 (ECM1) with the development of acute respiratory distress syndrome (ARDS) in patients with sepsis. Methods A total of 133 patients with sepsis were enrolled in sepsis group, and 80 healthy individuals during the same period were included in control group. The sepsis group was further divided into ARDS group (52 cases) and non-ARDS group (81 cases) based on the presence or absence of ARDS. Serum levels of NLRC3 and ECM1 expression were measured using enzyme-linked immunosorbent assays (ELISA). Multivariate Logistic regression analysis was used to identify factors associated with the development of ARDS in sepsis patients. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of serum NLRC3 and ECM1 levels for ARDS in sepsis patients. Results Compared with the control group, the sepsis group had significantly lower serum NLRC3 level and higher ECM1 level (P < 0.05). The incidence of ARDS in the 133 sepsis patients was 39.10% (52/133). Compared with the non-ARDS group, the ARDS group had significantly lower serum NLRC3 level and higher ECM1 level (P < 0.05). Independent risk factors for the development of ARDS in sepsis patients were increased Sequential Organ Failure Assessment (SOFA) score, elevated blood lactate level and increased ECM1 level, while increased NLRC3 level was an independent protective factor (P < 0.05). The area under the curve for the combined prediction of serum NLRC3 and ECM1 expression in sepsis patients with ARDS was 0.887, which was greater than 0.811 and 0.792 predicted by serum NLRC3 and ECM1 expression alone (P < 0.05). Conclusion Decreased serum NLRC3 level and increased ECM1 level are closely associated with the development of ARDS in sepsis patients. The combined assessment of serum NLRC3 and ECM1 level has a high predictive value for ARDS in sepsis patients.

Objective:To develop a risk prediction model for the recurrence of diabetic foot ulcer (DFU) in diabetic patients and primarily validate its predictive value.Methods:Meta-analysis combined with retrospective cohort study was conducted. The Chinese and English papers on risk factors related to DFU recurrence publicly published in China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and PubMed, Embase, Cochrane Library, and Web of Science, and the search time was from the establishment date of each database until March 31 st, 2022. The papers were screened and evaluated, the data were extracted, a meta-analysis was performed using RevMan 5.4.1 statistical software to screen risk factors for DFU recurrence, and Egger's linear regression was used to assess the publication bias of the study results. Risk factors for DFU recurrence mentioned in ≥3 studies and with statistically significant differences in the meta-analysis were selected as the independent variables to develop a logistic regression model for risk prediction of DFU recurrence. The medical records of 101 patients with DFU who met the inclusion criteria and were admitted to Affiliated Hospital of Guizhou Medical University from January 2019 to June 2022 were collected. There were 69 males and 32 females, aged (63±14) years. The receiver operating characteristic (ROC) curve of the predictive performance of the above constructed predictive model for DFU recurrence was drawn, and the area under the ROC curve, maximum Youden index, and sensitivity and specificity at the point were calculated. Dataset including data of 8 risk factors for DFU recurrence and the DFU recurrence rates of 10 000 cases was simulated using RStudio software and a scatter plot was drawn to determine two probabilities for risk division of DFU recurrence. Using the β coefficients corresponding to 8 DFU recurrence risk factors ×10 and taking the integer as the score of coefficient weight of each risk factor, the total score was obtained by summing up, and the cutoff scores for risk level division were calculated based on the total score × two probabilities for risk division of DFU recurrence. Results:Finally, 20 papers were included, including 3 case-control studies and 17 cohort studies, with a total of 4 238 cases and DFU recurrence rate of 22.7% to 71.2%. Meta-analysis showed that glycosylated hemoglobin >7.5% and with plantar ulcer, diabetic peripheral neuropathy, diabetic peripheral vascular disease, smoking, osteomyelitis, history of amputation/toe amputation, and multidrug-resistant bacterial infection were risk factors for the recurrence of DFU (with odds ratios of 3.27, 3.66, 4.05, 3.94, 1.98, 7.17, 11.96, 3.61, 95% confidence intervals of 2.79-3.84, 2.06-6.50, 2.50-6.58, 2.65-5.84, 1.65-2.38, 2.29-22.47, 4.60-31.14, 3.13-4.17, respectively, P<0.05). There were no statistically significant differences in publication biases of diabetic peripheral neuropathy, diabetic peripheral vascular disease, glycosylated hemoglobin >7.5%, plantar ulcer, smoking, multidrug-resistant bacterial infection, or osteomyelitis ( P>0.05), but there was a statistically significant difference in the publication bias of amputation/toe amputation ( t=-30.39, P<0.05). The area under the ROC curve of the predictive model was 0.81 (with 95% confidence interval of 0.71-0.91) and the maximum Youden index was 0.59, at which the sensitivity was 72% and the specificity was 86%. Ultimately, 29.0% and 44.8% were identified respectively as the cutoff for dividing the probability of low risk and medium risk, and medium risk and high risk for DFU recurrence, while the corresponding total scores of low, medium, and high risks of DFU recurrence were <37, 37-57, and 58-118, respectively. Conclusions:Eight risk factors for DFU recurrence are screened through meta-analysis and the risk prediction model for DFU recurrence is developed, which has moderate predictive accuracy and can provide guidance for healthcare workers to take interventions for patient with DFU recurrence risk.

Objective:To construct the Patient Version of Guideline for Ketogenic Diet Therapy in Children with Refractory Epilepsy. Methods:This guideline was based on the theoretical framework of A Guideline Adaptation and Implementation Planning Resource (CAN-IMPLEMENT) and patient-oriented knowledge tools, forming the research roadmap. The Patient Version of Guideline for Ketogenic Diet Therapy in Children with Refractory Epilepsy was constructed by clarifying research questions, evidence integration, guideline formation and other normative steps. Results:A total of 17 research questions on ketogenic diet therapy in children with refractory epilepsy were formed. A total of 11 papers were included, including 4 guidelines and 7 consensuses. The final patient version of guideline included 4 themes, involving assessment, pre-implementation preparation, implementation and monitoring, follow-up, evaluation and termination, and 29 recommended items.Conclusions:The patient version of guideline constructed in this study is based on a scientific construction framework and method, and fully considers the needs of patients, which can provide a reference for the management of ketogenic diet therapy in children with refractory epilepsy.