Objective To investigate the diagnostic value of optic nerve damage in glaucoma patients caused by abnormal expression of(Klotho)and C-C chemokine receptor type 7(CXCR7).Methods A prospective study was conducted,totally 120 glaucoma patients treated in the hospital from January 2020 to December 2023 were selected as the study group,and 120 volunteers who underwent physical examination during the same period were selected as the control group.The expression levels of Klotho and CXCR7 in patients with glaucoma caused by abnormal expression of Klotho and CXCR7 were compared between the study group and the control group,the group with or without nerve function injury,and the patients with different degrees of nerve function injury,respectively,and the diagnostic value of optic nerve degree damage in glaucoma patients caused by abnormal expression of KlothO and CXCR7 was studied.Results Klotho and CXCR7 in study group were significantly higher than those in control group(t=93.175,33.855,both P＜0.001).Klotho and CXCR7 in patients with optic nerve damage was significantly higher than that in patients without optic nerve damage(t=5.619,6.507,both P＜0.001).There were statistically significant differences in the expression of Klotho and CXCR7 among patients with different degrees of optic nerve damage(F=12.332,11.209,both P＜0.001).The results of multivariate Logistic analysis showed that both Klotho(OR=3.353)and CXCR7(OR=3.102)were risk factors causing optic nerve damage in glaucoma patients(P＜0.05).According to re-ceiver operating characteristic(ROC)curve analysis,the combined detection of Klotho and CXCR7 showed significantly larger area under the curve for diagnosing glaucomatous optic nerve damage than that of single detection.Conclusion The abnormal expression of Klotho and CXCR7 could be used as an important diagnos-tic basis for the degree of optic nerve damage in glaucoma patients.

Objective To investigate the relationships of cerebrospinal fluid levels of collagen triple helix repeat containing-1(CTHRC1)and olfactomedin-3(OLFM3)with cognitive impairment and cere-brospinal fluid biomarker levels in patients with Alzheimer's disease(AD).Methods Ninety-six patients with AD were selected as study objects(AD group),and divided into mild group(n=34),moderate group(n=39)and severe group(n=33)according to Clinical Deentia Scale(CDR)score.Sixty patients without cognitive impairment who underwent lumbar puncture during the same period served as the control group.Enzyme-linked immunosorbent assays were used to measure cere-brospinal fluid levels of CTHRC1,OLFM3 and biomarkers[β-amyloid(Aβ)-40,Aβ-42,Aβ42/Aβ-40,total tau(T-tau)and phosphorylated tau(P-tau)].Cognitive impairment in AD patients was as-sessed using the Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA).The relationships of CSF CTHRC1 and OLFM3 levels with cognitive impairment and cerebrospinal flu-id biomarkers were analyzed.Results The AD group showed significantly higher cerebrospinal fluid levels of CTHRC1,T-tau and P-tau,and significantly lower levels of OLFM3,Aβ-42 and Aβ42/Aβ-40 compared to the control group(P＜0.05).The area under the curve(AUC)for diagnosing AD with cerebrospinal fluid CTHRC1 and OLFM3 was 0.839 and 0.822,respectively,and the com-bined AUC was 0.923.Cerebrospinal fluid CTHRC1 of mild group,moderate group and severe group were increased successively,and OLFM3 was decreased successively,the difference was sta-tistically significant(P＜0.05).Cerebrospinal fluid Aβ-42 and Aβ-42/Aβ-40 in mild,moderate and severe groups were decreased successively,while T-tau and P-tau were increased successively,with statistical significance(P＜0.05).The MMSE and MoCA scores of mild group,moderate group and severe group decreased successively,and the difference was statistically significant(P＜0.05).Cerebrospinal fluid CTHRC1 levels were positively correlated with disease severity,while OLFM3 levels were negatively correlated(P＜0.05).Cerebrospinal fluid CTHRC1 was negatively correlated with Aβ42,Aβ42/Aβ-40,MMSE scores and MoCA scores,and positively correlated with T-tau and P-tau(P＜0.05).Cerebrospinal fluid OLFM3 was positively correlated with Aβ-42,Aβ42/Aβ-40,MMSE scores and MoCA scores,and negatively correlated with T-tau and P-tau(P＜0.05).Conclusion In the cerebrospinal fluid of patients with AD,CTHRC1 is elevated while OLFM3 is decreased.Both CTHRC1 and OLFM3 are associated with the severity of AD,cog-nitive impairment and levels of cerebrospinal fluid biomarkers.

Objective:To comprehensively evaluate the cost and cost-effectiveness of the colorectal cancer screening program for key populations in Zhejiang Province from 2020 to 2022, and provide reference for optimizing colorectal cancer screening strategies.Methods:Based on the colorectal cancer screening program for key populations in Zhejiang Province from 2020 to 2022, parameters such as initial screening positivity rates, colonoscopy compliance rates, and detection rates for colorectal-related lesions among residents aged 50-74 were obtained. Questionnaire surveys assessed program costs and direct medical costs associated with colorectal cancer-related lesions. From a health system perspective, the cost-effectiveness ratio was calculated using the Early Detection Cost Index (EDCI) and the cost per detected case, followed by sensitivity analysis.Results:A total of 5 881 364 screenings were completed from 2020 to 2022. The initial screening positive rate (positive for either questionnaire or fecal immunochemical testing ) was 16.83%, with a colonoscopy compliance rates of 33.96% ( n=336 150). Detection rates for non-advanced adenomas, advanced adenomas, and colorectal cancer were 24.83% ( n=83 453), 11.91% ( n=40 033), and 1.01% ( n=3 397), respectively. Initial screening positivity rates and detection rates increased with age, while colonoscopy compliance rates decreased with age. Cost analysis showed a total project investment of 378 730 457 yuan, with initial screening costing 146 633 103 yuan (38.72%) and diagnostic colonoscopy 232 097 354 yuan (61.28%). The average cost per initial screening and diagnostic colonoscopy was 24.93 and 690.46 yuan, respectively. Direct medical costs for non-advanced adenomas, advanced adenomas, and colorectal cancer at stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ were 4 921, 8 380, 42 547, 62 156, 66 720, and 72 334 yuan, respectively. Cost-effectiveness analysis indicated that screening needed to detect one case of colorectal cancer required 1 731 people and cost 111 490 yuan; the cost per detected advanced adenoma was 9 460 yuan, and the EDCI was 0.09. Costs decreased with increasing age per detected colorectal lesion. Sensitivity analysis showed that increasing colonoscopy compliance could reduce the cost-effectiveness ratio. Conclusions:The colorectal cancer screening program for key populations in Zhejiang Province demonstrates cost-effectiveness. Improving colonoscopy compliance can enhance overall screening effectiveness and economic benefits.

Objective: To investigate the efficacy of therapeutic plasma exchange and rituximab in the treatment of passenger lymphocyte syndrome (PLS) after ABO incompatible liver transplantation. Methods: PLS diagnosis was performed on the transplant patient using immunohematology testing techniques such as direct anti human globulin test (DAT), red blood cell elution test, and blood type antibody titer detection, combined with changes in hemolysis laboratory indicators; Severe immune hemolysis caused by PLS treated with red blood cell transfusion, therapeutic plasma exchange, and rituximab. Results: The patient was diagnosed with PLS 9 days after transplantation, and hemolysis caused by PLS continued until 20 days after transplantation; After three rounds of therapeutic plasma exchange and treatment with 100 mg rituximab, the titer of the patient's immune blood type antibody (IgG anti-B) decreased from 128 to 8 and was maintained until 27 days after transplantation. The patient's hemolytic symptoms improved and were discharged 32 days after transplantation. Conclusion: This case explores the application of therapeutic plasma exchange and rituximab in the treatment of severe hemolysis in PLS after transplantation, providing a reference for establishing standardized management of PLS after solid organ transplantation.

OBJECTIVE: To explore the clinical characteristics and prognosis of children with SIL-TAL1-positive T-cell acute lymphoblastic leukemia ( SIL-TAL1⁺ T-ALL). METHODS: The clinical data of 110 children with newly diagnosed T-ALL admitted to the pediatric department of our hospital from January 2010 to December 2018 were reviewed to compare the clinical characteristics, treatment response and prognosis between SIL-TAL1⁺ group and SIL-TAL1^-group. RESULTS: Among the 110 children with T-ALL, 25 cases (22.7%) were in the SIL-TAL1⁺ group and 85 cases (77.3%) in the SIL-TAL1^- group. The white blood cell (WBC) count in the SIL-TAL1⁺ group was significantly higher than that in the SIL-TAL1^- group (P < 0.05), while the other clinical characteristics and treatment response were not significantly different between the two groups. The 5-year overall survival (OS) rates of SIL-TAL1⁺ group and SIL-TAL1^- group were 80.0% and 75.5%, and 5-year disease-free survival (DFS) rates were 76.0% and 72.9%, respectively. There were no significant differences in OS rate and DFS rate between the two groups ( P >0.05). In children aged < 10 years, the 5-year OS rate of SIL-TAL1⁺ group and SIL-TAL1^- group was 100% and 75.1%, respectively, and the difference between the two groups was statistically significant (P < 0.05). CONCLUSION Although the WBC level is significantly higher in children with SIL-TAL1⁺ T-ALL than that in those with SIL-TAL1^- T-ALL, the treatment efficacy is similar between the two groups. In children aged < 10 years, the longterm survival rate is superior in the SIL-TAL1⁺ group.
Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Prognosis ; Child ; Male ; Female ; Survival Rate ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Child, Preschool ; Oncogene Proteins, Fusion ; Leukocyte Count

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

This study assessed the role and mechanism of the recombinant Bacillus Calmette-Gue?rin vaccine(rBCG)with c-di-AMP adjuvant in regulating metabolism and immunity in epididymal white adipose(eWAT)in mice.Male C57BL/6 mice were intravenously immunized with BCG and rBCG,and their body weights were monitored.eWAT was isolated from the mice,and the stromal vascular fractions(SVFs)cell number was counted with a hemocytometer.Sections of mouse adipose tissue were prepared,and the size,number,and morphology of eWAT adipocytes and crown-like structure(CLS)formation were compared under a microscope after HE staining.The transcription levels of lipid metabolism-associated factors,cytokines and aging-associated genes in each group were determined with qRT-PCR.The body weights of mice gradually increased after immunization with BCG and rBCG.The proportions of eWAT increased,and the SVFs cell number decreased,in rBCG immunized mice.HE staining indicated that BCG immunization promoted hyperplasia,whereas rBCG immunization promoted hypertrophy of eWAT adipocytes;moreover,both BCG and rBCG immunization induced CLS formation in eWAT.The qRT-PCR results indicated that rBCG immunization inhibited the expression of genes associated with lipolysis and energy expenditure in eWAT.BCG immunization had little effect on cytokine transcription,whereas rBCG significantly induced the transcription of IFN-γ and IL-1Ra,and inhibited that of IL-15 and IL-2,but did not induce the expression of aging-associated genes.Thus,rBCG immunization induced eWAT adipocyte hypertrophy,which was associated with the inhibition of eWAT lipolysis and the regulation of cytokine expression.

This study was aimed at developing an in vitro fluorescent substrate assay for the activity of leucyl aminopeptid-ase(LAP)from Echinococcus multilocularis and comparing it with the chemical chromogenic substrate enzyme activity assay.Through the establishment of reaction conditions for the fluorescent substrate-based in vitro enzyme activity assay,we com-pared the differences between the fluorescent substrate L-Leucine-7-amido-4-methylocoumarin(Leu-AMC)and the chemical chromogenic substrate L-Leucine-4-nitroanilide(Leu-pNA)through molecular docking,inhibition rates,and precision measures.Molecular docking revealed that the fluorescent substrate Leu-AMC had higher affinity for the protein than the chemical chromogenic substrate Leu-pNA.Through analysis of the effects of varying reaction conditions on fluorescence intensi-ty,we optimized the fluorescent substrate enzyme activity assay to demonstrate favorable performance at a reaction temperature of 37℃,a pH of 9.0,a protein concentration of 800 nmol/L,and a reaction duration of 60 minutes.Leu-AMC exhibited significant and distinct responses at a 5 μmol/L substrate concentration,under varying substrate conditions.The fluo-rescent substrate assay demonstrated more significant intergroup differences than the chemical chromogenic substrate assay when various inhibitors were added.This study established a fluorescence-based enzyme activity assay for leucyl aminopeptidase from Echinococcus multilocularis by using Leu-AMC as the substrate;this method demonstrated a more significant intergroup difference and sensitivity than the chemical chromogenic substrate assay.