To investigate the effectiveness of a self-developed intelligent medical record writing assistant in enhancing the efficiency of discharge record writing and improving the quality of discharge records, and to assess physicians' satisfaction with the assistant.

OBJECTIVES: This study aimed to investigate the potential mediating role of plasma phosphorylated tau217 (p-tau217) in the association between periodontitis and mild cognitive impairment (MCI). METHODS: In this case-control study, patients diagnosed with MCI in the Neurology Department of the First Affiliated Hospital of Shandong Second Medical University from November 2023 to May 2024 were selected as the case group (MCI group). Cognitively normal (CN) volunteers, matched for age and education level and recruited from the physical examination center during the same period, served as the control group (CN group). The general demographic data of the study participants were collected. The Beijing versions of the Montreal Cognitive Assessment (MoCA), clinical dementia rating (CDR), and activities of daily living scale (ADL) were used to assess neuropsychological functions. Clinical periodontal examinations were conducted, the periodontal inflamed surface area (PISA) was calculated, and the periodontitis stage was determined in accordance with the 2018 classification. Fasting elbow venous blood samples were collected in the morning, and blood biochemical indicators were measured. Plasma p-tau217 levels were detected using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using t-test, Mann-Whitney U test, chi-square test, partial correlation analysis, multivariate Logistic regression analysis, multiple linear regression analysis, restricted cubic spline (RCS) regression analysis, and mediation effect analysis. RESULTS: Among the 192 participants, 96 belong to the MCI group and 96 to the CN group. The prevalence of periodontitis was 63.5% in the MCI group and 43.8% in the CN group, with a statistically significant difference (χ²=7.561, P=0.006). The plasma p-tau217 levels in the MCI group were significantly higher than those in the CN group [7.00 (4.27-9.65) ng/mL versus 2.02 (0.80-3.81) ng/mL, Z=-8.108, P<0.001]. Partial correlation analysis revealed that plasma p-tau217 levels were positively correlated with all the clinical periodontal indices (all P<0.001). After adjustments for baseline covariates, multivariate Logistic regression indicated that periodontitis was an independent risk factor for MCI. Patients with periodontitis had a 1.977-fold higher MCI risk than those without periodontitis (OR=1.977, 95%CI: 1.088-3.594, P=0.025). Moreover, the MCI risk for stage Ⅰ/Ⅱ periodontitis and stage Ⅲ/Ⅳ periodontitis was 1.878 times (OR=1.878, 95%CI: 1.029-3.425, P=0.040) and 2.625 times (OR=2.625, 95%CI: 1.073-6.246, P=0.035) higher than that for patients without periodontitis, respectively. Trend test showed that the MCI risk increased with periodontitis severity (P_trend=0.016). After adjustments for baseline covariates, multiple linear regression analysis showed that periodontitis was an independent risk factor for increased plasma p-tau217 levels (β=3.309, 95%CI: 2.363-4.254, P<0.001). Compared with patients without periodontitis, those with stage Ⅰ/Ⅱ periodontitis (β=1.838, 95%CI: 0.869-2.806, P<0.001) and stage Ⅲ/Ⅳ periodontitis (β=5.539, 95%CI: 4.442-6.636, P<0.001) had significantly higher plasma p-tau217 levels. In addition, trend test indicated that plasma p-tau217 levels increased with periodontitis severity (P_trend<0.001). After adjustments for baseline covariates, RCS regression analysis further revealed that PISA had a positive linear dose-response relationship with MCI risk (P_overall=0.002, P_nonlinear=0.344) and plasma p-tau217 levels (P_overall<0.001, P_nonlinear=0.140). After adjustments for baseline covariates, mediation analysis showed that plasma p-tau217 mediated the association between periodontitis and MCI, with a mediation proportion of 13.99% (95% Bootstrap CI: 0.38%-49.39%, P=0.038). CONCLUSIONS Periodontitis was independently positively associated with MCI risk, and plasma p-tau217 plays a mediating role in this association.
Humans ; Cognitive Dysfunction/complications* ; tau Proteins/blood* ; Periodontitis/complications* ; Case-Control Studies ; Male ; Female ; Phosphorylation ; Aged ; Middle Aged ; Activities of Daily Living

Objective·To construct a framework nucleic acid-based linear amplification platform for the sensitive and quantitative detection of bladder cancer-related microRNAs(miRNAs),facilitating early screening and accurate diagnosis of bladder cancer.Methods·This study combined a plasma fluorescence-enhanced chip with high-performance tetrahedral framework nucleic acid(tFNA)probes,targeting miRNAs as biomarkers,to construct a framework nucleic acid-based linear signal amplification platform for precise and high-throughput quantitative analysis of multiple targets.First,atomic force microscope(AFM)was used to verify the efficient synthesis of tFNA.The signal linear amplification capability of the reporter unit was verified by polyacrylamide gel electrophoresis(PAGE)and total internal reflection fluorescent microscope(TIRFM).The performance of the sensing interface substrates was compared,and the golden island chip with signal amplification was selected.The specificity of the detection system was verified by an interface specificity experiment.Five bladder cancer-related miRNAs were selected to construct standard curves for quantitative detection.Results·The efficient synthesis of tetrahedral monomer and dimer structures was verified by AFM.PAGE and TIRFM characterization verified the linear amplification of fluorescence signals from 1 to 6 valence fluorescence reporter units.In order to achieve further signal amplification,the plasma island chip and the traditional glass chip were compared.The results showed that the gold island chip exhibited a plasmonic effect,which significantly enhanced the near-infrared(NIR)fluorescence,with a signal amplification of up to 13.6 times compared to the glass chip.The specificity verification experiment showed that the signal-to-noise ratio of the system ranged from 7 to 10,demonstrating high specificity.Based on the high specificity of the system,along with the good interface regulation ability and linear amplification of the framework nucleic acid-based interface,dual-color parallel detection of the targets was finally realized.The working range was 100 fmol/L-10 nmol/L(R2≥0.991),and the detection limit was as low as 100 fmol/L.Conclusion·The establishment of this platform opens new avenues for highly sensitive quantitative analysis of biomarkers.Furthermore,the developed framework nucleic acid-based detection platform holds great potential for clinical diagnosis and prognosis of bladder cancer and other major diseases.Through early detection and precise subtype diagnosis,doctors can formulate more personalized treatment plans for patients,improving treatment efficacy and reducing unnecessary treatment plans and associated side effects.Therefore,this liquid biopsy technology not only provides new possibilities for early screening of bladder cancer but also serves as reference for research and clinical applications in other types of cancer.

Objective·To construct a framework nucleic acid-based linear amplification platform for the sensitive and quantitative detection of bladder cancer-related microRNAs(miRNAs),facilitating early screening and accurate diagnosis of bladder cancer.Methods·This study combined a plasma fluorescence-enhanced chip with high-performance tetrahedral framework nucleic acid(tFNA)probes,targeting miRNAs as biomarkers,to construct a framework nucleic acid-based linear signal amplification platform for precise and high-throughput quantitative analysis of multiple targets.First,atomic force microscope(AFM)was used to verify the efficient synthesis of tFNA.The signal linear amplification capability of the reporter unit was verified by polyacrylamide gel electrophoresis(PAGE)and total internal reflection fluorescent microscope(TIRFM).The performance of the sensing interface substrates was compared,and the golden island chip with signal amplification was selected.The specificity of the detection system was verified by an interface specificity experiment.Five bladder cancer-related miRNAs were selected to construct standard curves for quantitative detection.Results·The efficient synthesis of tetrahedral monomer and dimer structures was verified by AFM.PAGE and TIRFM characterization verified the linear amplification of fluorescence signals from 1 to 6 valence fluorescence reporter units.In order to achieve further signal amplification,the plasma island chip and the traditional glass chip were compared.The results showed that the gold island chip exhibited a plasmonic effect,which significantly enhanced the near-infrared(NIR)fluorescence,with a signal amplification of up to 13.6 times compared to the glass chip.The specificity verification experiment showed that the signal-to-noise ratio of the system ranged from 7 to 10,demonstrating high specificity.Based on the high specificity of the system,along with the good interface regulation ability and linear amplification of the framework nucleic acid-based interface,dual-color parallel detection of the targets was finally realized.The working range was 100 fmol/L-10 nmol/L(R2≥0.991),and the detection limit was as low as 100 fmol/L.Conclusion·The establishment of this platform opens new avenues for highly sensitive quantitative analysis of biomarkers.Furthermore,the developed framework nucleic acid-based detection platform holds great potential for clinical diagnosis and prognosis of bladder cancer and other major diseases.Through early detection and precise subtype diagnosis,doctors can formulate more personalized treatment plans for patients,improving treatment efficacy and reducing unnecessary treatment plans and associated side effects.Therefore,this liquid biopsy technology not only provides new possibilities for early screening of bladder cancer but also serves as reference for research and clinical applications in other types of cancer.

Objective:To study the effects of broad-spectrum antibiotics and induced antibiotic-resistant bacteria on the efficacy of 5-fluorouracil (5-FU) chemotherapy for mice with colon cancer and to investigate the underlying mechanisms associated with anti-tumor immune responses.Methods:BALB/c mice were subcutaneously injected with CT26 colon cancer cells and randomized into four groups: tumor-bearing control group, antibiotic group treated with ampicillin, streptomycin and colistin, 5-FU group and anitibiotic+ 5-FU group. Tumor volumes and body weights were measured and recorded. Seven days after the last 5-FU treatment, the percentages of splenic immune cell subpopulations and proliferated CD8 + T cells after co-culturing with CT26 were analyzed by flow cytometry. Gut microbiota composition was detected by 16S rRNA sequencing and the bacteria in mesenteric lymph nodes (mLN) were isolated and cultured. Bone marrow-derive macrophages were stimulated with identified bacteria and the expression of M1 and M2 polarization markers were assessed by quantitative PCR. The proliferation of CD8 + T cells co-cultured with bacteria-treated macrophages was analyzed by flow cytometry. In addition, tumor-bearing mice were treated with 5-FU and oral gavage of bacteria isolated from antibiotic+ 5-FU group or PBS. Tumor volumes, gut microbiota composition and the percentages of proliferated CD8 + T cells co-cultured with CT26 were assessed. Results:Tumor volumes were larger and body weights were lower in the antibiotic+ 5-FU group than in the 5-FU group. The percentages of CD4 + T cells, CD8 + T cells and neutrophils did not varied significantly after using antibiotics, however, the percentage of monocytes was increased in the antibiotic group. The percentage of proliferated tumor-specific CD8 + T cells in the antibiotic+ 5-FU group was decreased compared with that in the 5-FU group. Compared with the control group and 5-FU group, antibiotic usage was associated with the changes in gut microbiota composition with decreased α diversity indexes. Escherichia coli, Klebsiella pneumonia, and Proteus mirabilis were isolated from mLNs of the antibiotic group, 5-FU group and antibiotic+ 5-FU group, respectively. Bone marrow-derived macrophages stimulated with Proteus mirabilis expressed arginase at a high level, which was a M2 polarization marker of macrophage, and associated with the decreased percentage of proliferated CD8 + T cells after co-culturing. Bacteria of the genus Proteus were enriched in the gut microbiota of 5-FU-treated tumor-bearing mice with the oral gavage of Proteus mirabilis. Although no significant inhibitory effect on tumor growth was observed, the oral gavage of Proteus mirabilis was associated with the decreased percentage of proliferated tumor-specific CD8 + T cells in vitro. Conclusions:Broad-spectrum antibiotics inhibited the efficacy of chemotherapy and the proliferation of tumor-specific CD8 + T cells, in which antibiotic-resistant bacteria might be involved.

Objective:To investigate the relationship of eosinophil cationic protein (ECP) levels in sera and blister fluids with bullous pemphigoid (BP) .Methods:From January 2012 to October 2019, 40 patients with newly diagnosed BP and 40 healthy individuals were enrolled from Department of Dermatology, Peking Union Medical College Hospital, and serum ECP levels were detected by enzyme-linked immunosorbent assay. Meanwhile, another 33 patients with newly diagnosed BP and 41 patients with non-autoimmune bullous diseases were enrolled, and the ECP level was detected in blister fluids by enzyme-linked immunosorbent assay. Pathological sections of skin lesions of 1 patient with BP and 1 with contact dermatitis were subjected to immunohistochemical staining for ECP. Normally distributed data were compared between 2 groups by using t test or t′ test, while enumeration data were compared by using chi-square test. Pearson′s correlation coefficient was used to analyze the relationship between serum levels of ECP and proportions of peripheral blood eosinophils in patients with BP. Results:The serum level of ECP was significantly higher in the BP group (116.9 ± 19.3 ng/L) than in the healthy control group (93.3 ± 15.9 ng/L, t = 5.96, P<0.001) , and the blister fluid level of ECP was also significantly higher in the BP group (665.8 ± 189.0 ng/L) than in the non-autoimmune bullous disease group (547.5 ± 240.6 ng/L, t = 2.31, P = 0.02) . Immunohistochemical study showed more brown-yellow particles in the cytoplasm of ECP-positive cells in the BP group than in the contact dermatitis group. There was no significant correlation between the serum level of ECP and proportion of peripheral blood eosinophils in the BP patients ( r = -0.15, P = 0.35) . Conclusion:The levels of ECP in the sera and blister fluids markedly increased in the patients with BP, and blister fluid levels of ECP were much higher than serum levels of ECP, suggesting that ECP may be involved in the occurrence of BP.

Objective To investigate the effect and possible mechanism of high mobility group box (HMGB) 1 in the development and progress of rheumatoid arthritis.Methods PBMC and serum samples were obtained from 74 RA patients (38 in active stage and 36 in stable stage) and 26 healthy controls.The expression of HMGB1 mRNA and protein was detected by RT-PCR and ELISA.Flow cytometry analysis ( FCM ) was used to detect the expression of Toll-like receptor 4 on PBMC.Results ①The expression of HMGBI mRNA and protein in active RA patients was significantly higher than that in healthy controls and inactive RA patients [2.63 vs 0.71，0.93 and (10.2±1.2) vs (7.5±1.8)，(8.3±1.8) ng/ml，respectively](P＜0.01 ).② The relative expression of TLR4 protein on CD14+ monocytes and CD3+ lymphocytes in active RA patients was increased than that in inactive RA and healthy controls (P＜0.05 or P＜0.01 ).It was also higher in inactive RA than in healthy controls (P＜0.05 or P＜0.01 ).③ Level of HMGB1 protein in serum of RA patients was positively correlated with ESR，CRP，RF，the numbers of tender joints and swollen joints as well as radiographic changes.Conclusion HMGB1 can be synthesized and released by PBMC of active RA patients，and then bind to TLR4 of PBMC to promote inflammatory responses and bone erosion.