OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

Objective:To validate and evaluate the performance of opened reagent warehouse of VITROS 5600 full automatic dry biochemical immunoassay analyzer,which carried domestic serum cystatin C(Cys C)kit of Lidman.Methods:The precision,correctness,linear range,the maximum dilution and biological reference interval of Cystatin C were validated according to evaluation criteria of the National Committee for Clinical Laboratory Standardization(NCCLS)for instrument,which also referred to,and others.Results:①Precision measurement results:the Sintra-assay of cystatin C were respectively 0.046 and 0.147,and the Sindoor were respectively 0.046 and 0.130,which were less than those of the Sintra-assay of the manufacturer's statement(0.083,0.178),and the requirement of industry standard for Sindoor(0.100,0.213)of imprecision.②Correctness:The absolute value|b|of bias of detecting standard substances of five concentration levels were respectively 0.032,0.014,0.062,0.013,and 0.200,all of which were less than the prescribed bias in the industry standards(0.04,0.08,0.16,0.32,0.64).③Linear range:The linear regression equation was y=1.011 2x+0.111,R2=0.997 4,showing a linear relationship.④The cystatin C:the measurement range was 0.51-7.66 mg/L,and the maximum acceptable dilution was 2-fold,and the clinically reportable range was 0.51～15.32 mg/L;⑤Biological reference interval validation:All the detection values of cystatin C of the health population(the age of 40 cases≤50 years old,and that of 20 cases>50 years old)were within the claimed reference intervals of manufactory.Conclusion:The precision,correctness,linear range and biological reference interval of the opened reagent warehouse of VITROS 5600 full automatic dry biochemical immunoassay analyzer,which carried Liedemann serum cystatin C kit,can meet the experimental requirements in clinical application,and can be used in detecting clinical routine specimen.

Objective To analyze the differences in the epidemiological characteristics,susceptible popula-tions,and laboratory index of patients with common acute upper respiratory tract infections(novel coronavir-us infection,influenza A and influenza B)between plateau and plain areas.Methods Clinical data of 408 008 patients with symptoms of fever or upper respiratory tract infection in the fever clinic of the Second Affiliated Hospital of Zhejiang University and General Hospital of Xizang Military Command from January 2023 to Au-gust 2024 were collected.The epidemic characteristics,susceptible populations,and peripheral blood test data were compared and analyzed.Results The total positive rate of novel coronavirus infection,influenza A virus and influenza B virus infection in plain group(17.86％)was higher than that in plateau group(14.49％),and the difference was statistically significant(P＜0.05).The positive rates(17.98％and 17.76％)of male and female upper respiratory tract infection pathogens(novel coronavirus,influenza A virus and influenza B virus)in plain group were higher than those in plateau group(13.94％and 16.00％),and the differences were statis-tically significant(P＜0.05).The total positive rates of three kinds of upper respiratory tract infection patho-gens were 16.21％,18.27％and 14.63％in the plain group,and 14.62％,14.06％and 21.26％in the plateau group,respectively.According to the results of pathogen analysis of susceptible populations,whether it was plateau or plain,the positive rate of influenza A virus was higher in the minor group,the positive rate of influ-enza B virus was highest in the adult group,and the positive rate of novel coronavirus was highest in the elder-ly group.In terms of epidemic season,plateau and plain areas were different,and the epidemic occurred earlier in the plain area.In terms of peripheral blood test indicators,there were statistically significant differences in lymphocyte count,monocyte count,neutrophil to lymphocyte ratio and other indicators between plateau group and plain group(P＜0.05),while there were no statistically significant differences in white blood cell count between plateau group and plain group(P＞0.05).Conclusion The epidemiological characteristics of acute upper respiratory tract infection in plateau area are obviously different from those in plain area,which may be related to the natural environment and human geography environment.

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

Purpose To explore the predictive value of fetal cardiothoracic ratio(CTR)and their Z-scores for homozygous α-thalassemia major in early pregnancy.Materials and Methods Retrospective analysis was conducted on fetuses at high risk of α-thalassemia major(at 11-13?? weeks of gestation)who received prenatal care at the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from June 2016 to December 2023.Ultrasound examinations were performed on these fetuses to measure the CTRs[including cardiothoracic diameter ratio(CTDR),cardiothoracic circumference ratio(CTCR)and cardiothoracic area ratio(CTAR)],which were simultaneously converted into Z-scores.The receiver operating characteristic curve was used to evaluate the predictive efficacy of each group of CTRs and their corresponding Z-scores for fetal α-thalassemia major.Results ①A total of 363 high-risk fetuses were included,including 91(25.1%)in the affected group and 272(74.9%)in the control group.②All the CTRs(including CTDR,CTCR and CTAR)and their corresponding Z-scores in the affected group were significantly higher than those in the control group(t=3.705-21.320,all P<0.001).③The area under the curve(AUC)analysis showed that the AUCs of cardiothoracic ratio Z-scores were higher than those of the corresponding cardiothoracic ratios.The AUCs were ranked from largest to smallest as CTDR Z-score,CTDR,CTAR Z-score,CTCR Z-score,CTAR,CTCR,and the CTDR Z-score had the highest predictive efficacy(when the optimal cut-off value was 1.10,AUC=0.959,with a sensitivity of 94.5%and a specificity of 90.4%).Conclusion The predictive efficacy of fetal CTR Z-scores is higher than that of the corresponding CTRs,which are new indicators for effectively predicting homozygous α-thalassemia major in early pregnancy.Among them,the CTDR Z-score has the highest predictive efficacy,which can improve the prenatal diagnosis rate of this disease and reduce some unnecessary invasive procedures.

Purpose To explore the predictive value of fetal cardiothoracic ratio(CTR)and their Z-scores for homozygous α-thalassemia major in early pregnancy.Materials and Methods Retrospective analysis was conducted on fetuses at high risk of α-thalassemia major(at 11-13?? weeks of gestation)who received prenatal care at the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from June 2016 to December 2023.Ultrasound examinations were performed on these fetuses to measure the CTRs[including cardiothoracic diameter ratio(CTDR),cardiothoracic circumference ratio(CTCR)and cardiothoracic area ratio(CTAR)],which were simultaneously converted into Z-scores.The receiver operating characteristic curve was used to evaluate the predictive efficacy of each group of CTRs and their corresponding Z-scores for fetal α-thalassemia major.Results ①A total of 363 high-risk fetuses were included,including 91(25.1%)in the affected group and 272(74.9%)in the control group.②All the CTRs(including CTDR,CTCR and CTAR)and their corresponding Z-scores in the affected group were significantly higher than those in the control group(t=3.705-21.320,all P<0.001).③The area under the curve(AUC)analysis showed that the AUCs of cardiothoracic ratio Z-scores were higher than those of the corresponding cardiothoracic ratios.The AUCs were ranked from largest to smallest as CTDR Z-score,CTDR,CTAR Z-score,CTCR Z-score,CTAR,CTCR,and the CTDR Z-score had the highest predictive efficacy(when the optimal cut-off value was 1.10,AUC=0.959,with a sensitivity of 94.5%and a specificity of 90.4%).Conclusion The predictive efficacy of fetal CTR Z-scores is higher than that of the corresponding CTRs,which are new indicators for effectively predicting homozygous α-thalassemia major in early pregnancy.Among them,the CTDR Z-score has the highest predictive efficacy,which can improve the prenatal diagnosis rate of this disease and reduce some unnecessary invasive procedures.

INTRODUCTION: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are used in the diagnosis and prognostication of rheumatoid arthritis (RA). We wanted to determine the specific contributions of RF and ACPA to the biological nature of RA and whether they act synergistically. METHODS: We identified 731 patients from our prospective multi-ethnic RA cohort and categorised them into four groups: ACPA-positive, RF-positive, doubly positive and doubly negative. We compared the demographics, Disease Activity Score-28, Health Assessment Questionnaire score, quality of life using Short Form 36 and the use of prednisolone and disease-modifying antirheumatic drugs (DMARDs) of these patient groups. RESULTS: Four hundred and ninety-one patients (67.2%) were ACPA+RF+, 54 (7.4%) were ACPA+RF-, 82 (11.2%) were ACPA-RF+ and 104 (14.2%) were ACPA-RF-. Mean disease duration before the study entry was not different in the four groups. Patients with older age of onset were less likely to be positive for RF and ACPA. Fewer ACPA+RF+ patients were in remission compared to those in the other groups ( P < 0.05). Erythrocyte sedimentation rate (ESR) was higher at study entry in the ACPA+RF+ group (40.4 mm/h vs. 30.6-30.9 mm/h, P < 0.05). Prednisolone and number of DMARDs used were higher in the ACPA+RF+ group compared to the doubly negative group. There were no differences in the functional status and quality of life. CONCLUSIONS RA patients who were positive for both ACPA and RF had lower remission rate, higher baseline ESR and required more corticosteroid and DMARD treatment compared to those who were singly positive or doubly negative. Being doubly positive confers a worse outcome to RA patients.
Humans ; Arthritis, Rheumatoid/diagnosis* ; Male ; Female ; Middle Aged ; Rheumatoid Factor/blood* ; Anti-Citrullinated Protein Antibodies/blood* ; Adult ; Quality of Life ; Prospective Studies ; Antirheumatic Agents/therapeutic use* ; Aged ; Peptides, Cyclic/immunology* ; Prednisolone/therapeutic use* ; Surveys and Questionnaires ; Severity of Illness Index ; Prognosis

INTRODUCTION: Rheumatoid arthritis (RA) is associated with heightened cardiovascular disease and increased susceptibility to osteoporosis, with shared underlying mechanisms. This study aimed to investigate the association between vascular function and bone mineral density (BMD). METHODS: We conducted a cross-sectional study of 49 patients with RA at Tan Tock Seng Hospital, Singapore. Endothelial function was measured as reactive hyperaemia index (RHI)-endothelial peripheral arterial tonometry and aortic stiffness as carotid-femoral pulse wave velocity (cf-PWV) using SphygmoCor. Univariable and multivariable linear regression analyses were performed to evaluate the associations between BMD and vascular function. We used natural logarithm RHI (lnRHI) and cf-PWV as response variables, and each BMD as covariate, adjusting for body mass index, positive anti-cyclic citrullinated peptide, cumulative prednisolone dose, hydroxychloroquine use and Systematic COronary Risk Evaluation 2. RESULTS: We recruited 49 patients (mean age 61.08 ± 8.20 years), of whom 44 (89.80%) were women and 39 (81.25%) were Chinese. Significant associations were found between lnRHI and BMD at the lumbar spine (β = 0.4289, P = 0.037) and total hip (β = 0.7544, P = 0.014) in univariable analyses. Multivariable analyses confirmed these associations, showing that lower BMD at the lumbar spine (β = 0.7303, P = 0.001), femoral neck (β = 0.8694, P = 0.030) and total hip (β = 0.8909, P = 0.010) were significantly associated with worse lnRHI. No significant associations were found between BMD and cf-PWV. CONCLUSION Lower BMD is associated with endothelial dysfunction, but not aortic stiffness in patients with RA. Further longitudinal studies are needed to confirm these associations and understand the underlying mechanisms.
Humans ; Arthritis, Rheumatoid/complications* ; Female ; Male ; Bone Density ; Middle Aged ; Cross-Sectional Studies ; Vascular Stiffness ; Aged ; Singapore ; Pulse Wave Analysis ; Osteoporosis/complications* ; Endothelium, Vascular/physiopathology* ; Cardiovascular Diseases/complications* ; Carotid-Femoral Pulse Wave Velocity ; Hyperemia

Objective:To validate and evaluate the performance of opened reagent warehouse of VITROS 5600 full automatic dry biochemical immunoassay analyzer,which carried domestic serum cystatin C(Cys C)kit of Lidman.Methods:The precision,correctness,linear range,the maximum dilution and biological reference interval of Cystatin C were validated according to evaluation criteria of the National Committee for Clinical Laboratory Standardization(NCCLS)for instrument,which also referred to,and others.Results:①Precision measurement results:the Sintra-assay of cystatin C were respectively 0.046 and 0.147,and the Sindoor were respectively 0.046 and 0.130,which were less than those of the Sintra-assay of the manufacturer's statement(0.083,0.178),and the requirement of industry standard for Sindoor(0.100,0.213)of imprecision.②Correctness:The absolute value|b|of bias of detecting standard substances of five concentration levels were respectively 0.032,0.014,0.062,0.013,and 0.200,all of which were less than the prescribed bias in the industry standards(0.04,0.08,0.16,0.32,0.64).③Linear range:The linear regression equation was y=1.011 2x+0.111,R2=0.997 4,showing a linear relationship.④The cystatin C:the measurement range was 0.51-7.66 mg/L,and the maximum acceptable dilution was 2-fold,and the clinically reportable range was 0.51～15.32 mg/L;⑤Biological reference interval validation:All the detection values of cystatin C of the health population(the age of 40 cases≤50 years old,and that of 20 cases>50 years old)were within the claimed reference intervals of manufactory.Conclusion:The precision,correctness,linear range and biological reference interval of the opened reagent warehouse of VITROS 5600 full automatic dry biochemical immunoassay analyzer,which carried Liedemann serum cystatin C kit,can meet the experimental requirements in clinical application,and can be used in detecting clinical routine specimen.

Objective To investigate the effect of chemokine CXC ligand 9(CXCL9)on cognitive function impairment in patients with breast cancer brain metastases undergoing whole-brain radiotherapy(WBRT)using bioinformatics methods.Methods The mRNA of breast cancer brain metastases datasets GSE43837 and GSE12276 and Alzheimer's disease(AD)dataset GSE161199 were screened and downloaded from GEO database.Limma method and Venn diagrams were used to identify common differentially expressed genes(DEGs),and protein-protein interaction and functional prediction through GeneMANIA website assays were performed.A total of 42 patients with breast cancer brain metastases who first visited the Department of Radiotherapy at the First Affiliated Hospital of Hebei North University from January 2021 to January 2023 were selected.Patients were divided into normal cognitive function group and cognitive function impairment group based on cognitive status.Enzyme-linked immunosorbent assay(ELISA)was employed to detect serum CXCL9 levels one week before and three months after radiotherapy.The mini-mental state examination(MMSE)was used to assess patients'cognitive function.Results The DEGs from datasets GSE43837 and GSE12276 included PKP1,POLDIP2,SPAG5,ALDOC,PTPRZ1,PKIA,TLCD1,CPE,PMP22 and CXCL9.The DEGs from GSE161199 included RPS16,CD79A,LYPD3,RPL28,HBG2,RPL23AP7,TRNR,CXCL9.Venn diagram showed that CXCL9 was a common DEG between breast cancer brain metastasis and AD.Functional enrichment analysis indicated that CXCL9 was involved in cellular responses to chemokines,negative regulation of immune system processes,negative regulation of vascular morphogenesis,Toll-like receptor signaling pathway,nucleotide oligomerization domain(NOD)-like receptor signaling pathway,and JAK-STAT signaling pathway.Before radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 61.9%and 38.1%,respectively,with a statistically significant difference in MMSE scores[(24.53±2.19)vs.(28.89±1.36),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had a significantly increased number of brain metastases and significantly lower Karnofsky performance status(KPS)scores and serum CXCL9 levels(P＜0.05).Three months after radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 47.6%and 52.4%,respectively,with a statistically significant difference in MMSE scores[(25.16±1.98)vs.(28.18±1.08),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had significantly lower CXCL9 levels(P=0.003).In patients with normal cognitive function,CXCL9 levels were remarkably lower after radiotherapy compared to those before radiotherapy(P=0.009).Conclusions Patients with cognitive function impairment had significantly lower CXCL9 levels than those with normal cognitive function,and whole-brain radiotherapy may be related to a certain degree of reduction in CXCL9 levels.