Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

Objective:Comprehensive characterization of B-cell phenotypes and spatial distribution in oral lichen planus (OLP) and related oral lichenoid lesions (OLL)(OLP/OLL), with an emphasis on transcriptomic profiling and functional analysis, to uncover the epigenetic mechanisms underlying B cell-mediated immune regulation within the oral mucosal microenvironment.Methods:Single-cell RNA sequencing raw data were sourced from the GSE211630 database, encompassing samples from 2 cases of erosive OLP (EOLP), 3 cases of non-erosive OLP (NEOLP) and 1 healthy control (NORMAL). Following stringent quality control, the data underwent normalization, selection of highly variable genes and batch effect correction. Subsequent analyses included dimensionality reduction and unsupervised clustering to identify distinct cell populations. This study collected pathological specimens from 3 OLP/OLL patients and 3 healthy controls who were treated at the Department of Oral Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2021 to December 2023. Using 10X Genomics Visium HD spatial transcriptomics technology, tissue sections were processed through dewaxing, staining and histological imaging, enabling the reconstruction of nucleic acid structures and the capture of gene expression profiles. Data analysis included quality assessment, gene quantification, normalization, dimensionality reduction and clustering. Furthermore, cell type deconvolution was performed using the robust cell type decomposition algorithm, integrating single-cell transcriptomic data to accurately predict and spatially resolve cell type distributions within the tissue microenvironment.Results:After integrating single-cell data from EOLP, NEOLP and NORMAL, cells were classified into seven major categories: B/plasma cells, endothelial cells, epithelial cells, fibroblasts, myeloid cells, smooth muscle cells and T/natural killer cells. The proportion of B/plasma cells varied significantly among the three groups, accounting for 10.7% (1 693/15 815), 3.8% (833/21 653) and 0.4% (47/11 556) of the total cells respectively. Further clustering analysis of B/plasma cells identified four distinct subpopulations: naive B cells, activated B cells, memory B cells and plasma cells. In the EOLP group, these subpopulations constituted 25.9% (348/1 344), 45.9% (617/1 344), 3.3% (45/1 344) and 24.9% (334/1 344) of the B/plasma cells respectively. In the NEOLP group, they represented 31.6% (195/617), 59.6% (368/617), 0.2% (1/617) and 8.6% (53/617). Howerer, only plasma cells were detected in the NORMAL group. Spatial analysis revealed that B cells were actively involved in the formation of tertiary lymphoid structures (TLS) at various stages in OLP/OLL samples, with a prominent structural organization observed in secondary follicle-like TLS. Within these structures, the expressions of T cells marker gene CD3E and B cells marker gene MS4A1 were significantly elevated. Additionally, in secondary follicle-like TLS, the gene encoding follicular dendritic cell secreted protein, germinal center marker gene B cell lymphoma 6 and the gene for activation induced cytidine deaminase also showed strong expression. In OLP/OLL samples, plasma cell marker gene CD38, immunoglobulin (IGH) G3, IGHG1, IGHM, IGHD, IGHE, imunoglobulin Kappa constant, immunoglobulin alpha 1, immunoglobulin Lambda constant 1 and complement gene C3 all exhibited high levels of expression.Conclusions:Compared to normal mucosa, extensive B-cell infiltration is observed in both OLP and OLL, accompanied by significant differences in B-cell phenotypes and proportions. B cells appear to play a central role in local immune responses, primarily through the formation of TLS. However, the precise functional mechanisms underlying their involvement require further investigation.

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections.Herein,we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering(SERS)and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease(MNase)in serum samples.The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine(TMB)molecules to SERS-enhanced oxidized TMB(oxTMB),accompanied by the color change from colorless to blue.In the presence of S.aureus,the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads(MBs)to release alkaline phosphatase(ALP),which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away.Using this"on-to-off"triggering strategy,the target S.aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode.Meanwhile,the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis(n=7)and healthy participants(n=3),as well as monitored the prog-nostic progression of the disease(n=2).Overall,benefiting from highly active and dense"hot spot"substrate,MNase-mediated cascade response strategy,and colorimetric/SERS dual-signal output,this methodology will offer a promising avenue for the early diagnosis of S.aureus infection.

Objective:Comprehensive characterization of B-cell phenotypes and spatial distribution in oral lichen planus (OLP) and related oral lichenoid lesions (OLL)(OLP/OLL), with an emphasis on transcriptomic profiling and functional analysis, to uncover the epigenetic mechanisms underlying B cell-mediated immune regulation within the oral mucosal microenvironment.Methods:Single-cell RNA sequencing raw data were sourced from the GSE211630 database, encompassing samples from 2 cases of erosive OLP (EOLP), 3 cases of non-erosive OLP (NEOLP) and 1 healthy control (NORMAL). Following stringent quality control, the data underwent normalization, selection of highly variable genes and batch effect correction. Subsequent analyses included dimensionality reduction and unsupervised clustering to identify distinct cell populations. This study collected pathological specimens from 3 OLP/OLL patients and 3 healthy controls who were treated at the Department of Oral Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2021 to December 2023. Using 10X Genomics Visium HD spatial transcriptomics technology, tissue sections were processed through dewaxing, staining and histological imaging, enabling the reconstruction of nucleic acid structures and the capture of gene expression profiles. Data analysis included quality assessment, gene quantification, normalization, dimensionality reduction and clustering. Furthermore, cell type deconvolution was performed using the robust cell type decomposition algorithm, integrating single-cell transcriptomic data to accurately predict and spatially resolve cell type distributions within the tissue microenvironment.Results:After integrating single-cell data from EOLP, NEOLP and NORMAL, cells were classified into seven major categories: B/plasma cells, endothelial cells, epithelial cells, fibroblasts, myeloid cells, smooth muscle cells and T/natural killer cells. The proportion of B/plasma cells varied significantly among the three groups, accounting for 10.7% (1 693/15 815), 3.8% (833/21 653) and 0.4% (47/11 556) of the total cells respectively. Further clustering analysis of B/plasma cells identified four distinct subpopulations: naive B cells, activated B cells, memory B cells and plasma cells. In the EOLP group, these subpopulations constituted 25.9% (348/1 344), 45.9% (617/1 344), 3.3% (45/1 344) and 24.9% (334/1 344) of the B/plasma cells respectively. In the NEOLP group, they represented 31.6% (195/617), 59.6% (368/617), 0.2% (1/617) and 8.6% (53/617). Howerer, only plasma cells were detected in the NORMAL group. Spatial analysis revealed that B cells were actively involved in the formation of tertiary lymphoid structures (TLS) at various stages in OLP/OLL samples, with a prominent structural organization observed in secondary follicle-like TLS. Within these structures, the expressions of T cells marker gene CD3E and B cells marker gene MS4A1 were significantly elevated. Additionally, in secondary follicle-like TLS, the gene encoding follicular dendritic cell secreted protein, germinal center marker gene B cell lymphoma 6 and the gene for activation induced cytidine deaminase also showed strong expression. In OLP/OLL samples, plasma cell marker gene CD38, immunoglobulin (IGH) G3, IGHG1, IGHM, IGHD, IGHE, imunoglobulin Kappa constant, immunoglobulin alpha 1, immunoglobulin Lambda constant 1 and complement gene C3 all exhibited high levels of expression.Conclusions:Compared to normal mucosa, extensive B-cell infiltration is observed in both OLP and OLL, accompanied by significant differences in B-cell phenotypes and proportions. B cells appear to play a central role in local immune responses, primarily through the formation of TLS. However, the precise functional mechanisms underlying their involvement require further investigation.

Total 732 subjects aged 30-60 years undergoing health check-up at Beijing Hospital Medical Examination Center in 2009,who had no history of non-alcoholic fatty liver disease (NAFLD) were recruited in the study.According to the quartile of hemoglobin (HGB) level,the subjects were divided into 4 groups:Q1:HGB ≤ 131 g/L (n =192),Q2:HGB ＞ 131 g/L and ≤ 140 g/L (n =178),Q3:HGB ＞ 140 g/L and ≤152 g/L (n =184),Q4:HGB ＞ 152 g/L (n =178).All participants were followed up for 4 years,the prevalence rates of NAFLD in groups Q1,Q2,Q3 and Q4 were 8.3％ (16/192),17.4％ (31/178),23.4％ (43/184) and 25.3％ (45/178),respectively (P ＜0.05).Logistic regression showed that the rates of NAFLD in groups Q2,Q3 and Q4 were 2.32 (1.22-4.41),3.36 (1.81-6.21) and 3.72(2.02-6.87) times higher as group Q1 (P ＜ 0.05).Multiple logistic regression analysis showed that the hemoglobin level,TG and BMI were the independent risk factors of NAFLD.

Objective To investigate the relationship between serum uric acid and the risk of nonalcoholic fatty liver disease.Methods A cohort study was performed among individuals who had physical examination at Beijing Hospital medical examination center during 2009.A total of 732 subjects without nonalcoholic fatty liver disease,30-60 years old,were selected.Subjects were divided into 4 groups (Q1,Q2,Q3,Q4) according to serum uric acid level.Theincidence of NAFLD in each group in 2013 were observed.Serum alanine aminotransferase,aspartate aminotransferase,triglycerides,total cholesterol,high density lipoprotein-cholesterol,low density lipoprotein-cholesterol,fasting plasma glucose,and imaging examinations were determined.Cumulative incidence ofNAFLD was compared between each group and effect of baseline serum uric acid on new-onset NAFLI was assessed by logistic regression analysis.Results The cumulative incidence of NAFLD increased irconjunction with the increase of baseline serum uric acid in 4 groups (Q1 8.70％,Q2 13.04％,Q3 19.23％,Q4 32.97％,x2=37.865,P＜0.05).Logistic regression showed that the incidence of nonalcoholic fattyliver disease was increased along with elevated levels of serum uric acid.Subjects in the Q2,Q3,Q4 groups showed an increased risk of NAFLD,relative risks were 1.575 (0.807-3.074);2.580 (1.329-54.701);5.164 (2.838-9.397),compared to those in Q1 group.Moreover,after adjustment for baseline factors (e.g.Age,sex),risk of NAFLD remained higher,with odds ratio at 1.234,and the difference was statistically significant.Conclusions Serum uric acid was found to be correlated with the prevalence of nonalcoholic fatty liver disease.Serum uric acid appeared to be an independent risk factor for NAFLD.

Objective To assess the efficiency of an iontophoresis-based screening method (EZSCAN) in the detection of impaired glucose tolerance (IGT),diabetes mellitus (DM) and metabolic syndrome (MS).Methods A total of 166 subjects without medical history of dysglycaemia underwent fasting plasma glucose (FPG) and HbA1c measurement and oral glucose tolerance test (OGTT) by using traditional or EZSCAN method.Variance analysis (GLM),SNK analysis,logistic regression analysis,and ROC analysis were used to evaluate the diagnostic value of those screening techniques.Results DM,IGT,normal glucose tolerance (NGT) +MS,and NGT were found in 4,26,25 or 111 participants,respectively.For traditional test,FPG of 7.0 mmol/L showed a lower sensitivity to detect DM (0%).The sensitivity of EZSCAN to detect DM,IGT or MS was 50%,77% and 64%,respectively.Conclusions FPG may have lower sensitivity to detect DM,although EZSCAN could show higher sensitivity to detect IGT,DM,and MS.

Objective To investigate the association of body mass index (BMI),sex and age with blood pressure in non-physical labor population from Beijing area.Methods 14 237 subjects (67.06% male) ranged from 18.0-93.0 years (mean (SD):49.8(10.2)) wero recruited in the health examination in Beijing hospital. Statistical analysis wag performed using SPSS 12.0 software.Results The average BMI wag 22.30 ks/m~2 (SD: 3.08).Systolic blood pressure and diastolic blood pressure increaged with the increasing of BMI.The prevalence of hypertension in males <60.0 years wag considerably higher than that of female (24.28% and 13.77% for male and females, respectively, P=0.000).However,there were no significant statistical differences for the pmvalence between male and female older than 60.0 years (P=0.268).Multiple logistic regression showed that in males,using the group with BMI<18.0 kg/m~2 as reference group,in the groups of BMI 18.0-23.9,24.0-27.9,≥28.0 kg/m~2, OR wag 1.709 (95% CI:0.920-3.173),3.154(1.703-5.839),5.125 (95%CI:2.805-9.696),respeetively.In females.OR for hypertension in the groups of BMI 18.0-23.9,24.0-27.9,≥28.0 kg/m~2,OR was 1.988(95%CI:1.033-3.824),5.703(2.962-10.982),14.358(95%CI:7.334-28.106),respectively.Conclusions BMI is associated with hypertension.Prevention and eontrol of the risk factom of hypertension e.g.overweight and obesity is an important public health issue in China.

Objective To observe the therapeutic effect of manipulative reduction combined with small-splint fixation for the treatment of Barton's fracture.Methods The apposition state,time for swelling disappearance,time for pain relief,and the score evaluated with Gartland-Werley(GW) criteria modified by Sarmiento were observed for the evaluation of therapeutic effect on Barton's fracture patients.Results After manipulative reduction combined with small-splint fixation,the apposition state was good,and volar tilting angle and ulnar inclination were improved in the patients.Time for the disappearance of swelling on the back of hand ranged from 4 to 14 days,averaged 6.0?1.6 days.Time for pain relief ranged from 3 to 10 days,averaged 6.4?1.6 days.Time for the union of fracture ranged from 30 to 60 days,averaged 35.4?8.3 days.The mean modified GW score was 3.6?2.5,and the score was excellent in 29 patients and good in 41 patients.Conclusion Manipulative reduction combined with small-splint fixation is effective and practical for the treatment of Barton's fracture.