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.

To explore the application of sequential analysis in post-market safety dynamic surveillance of vaccines. Under the dynamic monitoring data of vaccines post-market approval, this research introduces the fundamental principles of maximizing sequential probability ratio test (MaxSPRT) and Bayesian sequential analysis, employing R software. Through an example of dynamic safety monitoring data of vaccines post-market approval, we analyze using the MaxSPRT and Bayesian sequential analysis. The MaxSPRT identified a safety signal in week 4 ( P<0.05), while Bayesian sequential analysis indicated that the 95% highest density interval for the RR value at week 4 is 1.13-3.27, suggesting the first appearance of a safety signal at week 4. The MaxSPRT and Bayesian sequential analysis effectively leverage continuously accumulating dynamic monitoring data, thereby serving as a valuable method for post-market safety surveillance of vaccines.

AIM:To evaluate the application effec-tiveness of a Bayesian mixture model based on the principal stratum strategy for estimating the com-plier average causal effect(CACE)in clinical trials with non-compliance.METHODS:Using a non-infe-riority randomized controlled trial investigating a novel drug for primary type 2 diabetes mellitus(non-inferiority margin:-0.4)as a case study,the primary analysis applied a Bayesian mixture model under the monotonicity assumption to estimate CACE of between-group differences in glycated he-moglobin(HbA1c)changes within the compliant stratum,followed by non-inferiority testing.Sensi-tivity analyses included a Bayesian mixture model relaxing the monotonicity assumption and compar-ing results with per-protocol set(PPS)analysis.RE-SULTS:In the primary analysis,the posterior mean of CACE for HbA1c change in the compliant stratum was 0.081％,with a one-sided 97.5％credible inter-val lower bound of-0.124,exceeding the non-infe-riority margin(-0.4％),supporting the non-inferiori-ty efficacy of the novel drug in the compliant stra-tum(P(H1|Data)=1).Consistent findings were ob-served in PPS analyses(estimated effect:0.136％;one-sided 97.5％credible interval lower bound:-0.069％),further validating methodological robust-ness.CONCLUSION:In clinical trials with noncom-pliance as an intercurrent event,the Bayesian mix-ture model under the principal stratum strategy ef-fectively adjusts for compliance-related bias and yields conservative,robust estimates of causal ef-fects,supporting its value in efficacy evaluation un-der complex compliance scenarios.

Objective: To analyze the occupational health literacy (OHL) level and its influencing factors among key populations in the tertiary industry in Lu'an City, Anhui Province, so as to provide a basis for developing targeted health interventions and improving regional occupational health policies. Methods: A stratified cluster random sampling method was employed to select five categories of key populations from the tertiary industry in Lu'an City as study subjects from August to September 2024. Data on gender, age, education level, and OHL were collected through the National OHL Monitoring Questionnaire for Key Populations. The OHL levels were analyzed, and influencing factors of OHL levels among key populations were analyzed using a multivariable logistic regression model. Results: A total of 1 243 individuals were surveyed, comprising 700 (56.32%) males and 543 (43.68%) females. The median age was 42.00 (interquartile range, 17.00) years. There were 609 individuals with OHL, and the OHL level was 48.99%. The OHL levels in fundamental knowledge of occupational health protection, healthy work styles and behaviors, knowledge of occupational health laws, and basic skills for occupational health protection were 84.71%, 60.34%, 43.93%, and 37.09%, respectively. Multivariable logistic regression analysis showed that educational level (primary school and below, OR=0.149, 95%CI: 0.064-0.344; junior high school, OR=0.340, 95%CI: 0.184-0.629; high school, OR=0.408, 95%CI: 0.230-0.723), average monthly personal income (3 000-<5 000 yuan, OR=1.655, 95%CI: 1.092-2.508; 5 000-<7 000 yuan, OR=2.195, 95%CI: 1.302-3.699; ≥7 000 yuan, OR=2.062, 95%CI: 1.016-4.183), employer nature (private enterprises, OR=2.992, 95%CI: 1.569-5.443), and industry category (education, OR=3.423, 95%CI: 1.407-8.327; courier / food delivery services, OR=0.459, 95%CI: 0.268-0.787; healthcare, OR=7.539, 95%CI: 3.255-17.461) were statistically associated with the OHL level among key population. Conclusion The OHL level among key population in the tertiary industry of Lu'an City can be further enhanced, with educational level, average monthly personal income, employer nature, and industry category identified as the primary influencing factors.

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.

To explore the application of sequential analysis in post-market safety dynamic surveillance of vaccines. Under the dynamic monitoring data of vaccines post-market approval, this research introduces the fundamental principles of maximizing sequential probability ratio test (MaxSPRT) and Bayesian sequential analysis, employing R software. Through an example of dynamic safety monitoring data of vaccines post-market approval, we analyze using the MaxSPRT and Bayesian sequential analysis. The MaxSPRT identified a safety signal in week 4 ( P<0.05), while Bayesian sequential analysis indicated that the 95% highest density interval for the RR value at week 4 is 1.13-3.27, suggesting the first appearance of a safety signal at week 4. The MaxSPRT and Bayesian sequential analysis effectively leverage continuously accumulating dynamic monitoring data, thereby serving as a valuable method for post-market safety surveillance of vaccines.

Thoracic anesthesia with spontaneous respiration represents a form of precision anesthesia meticulously customized to individual patients.Considering the more stringent requirements this anesthesia approach imposes on the regulation of respiratory function,the writing group of the"Consensus of Experts on the Management of Thoracic Anesthesia with Spontaneous Respiration"has formulated elaborate guidelines regarding indications and contraindications,preoperative evaluation,anesthesia implementation,common complications,and treatment strategies.This was accomplished by referencing relevant domestic and international literature and integrating it with actual clinical requirements.The objective is to standardize the rational application of this anesthesia method.

AIM:To evaluate the application effec-tiveness of a Bayesian mixture model based on the principal stratum strategy for estimating the com-plier average causal effect(CACE)in clinical trials with non-compliance.METHODS:Using a non-infe-riority randomized controlled trial investigating a novel drug for primary type 2 diabetes mellitus(non-inferiority margin:-0.4)as a case study,the primary analysis applied a Bayesian mixture model under the monotonicity assumption to estimate CACE of between-group differences in glycated he-moglobin(HbA1c)changes within the compliant stratum,followed by non-inferiority testing.Sensi-tivity analyses included a Bayesian mixture model relaxing the monotonicity assumption and compar-ing results with per-protocol set(PPS)analysis.RE-SULTS:In the primary analysis,the posterior mean of CACE for HbA1c change in the compliant stratum was 0.081％,with a one-sided 97.5％credible inter-val lower bound of-0.124,exceeding the non-infe-riority margin(-0.4％),supporting the non-inferiori-ty efficacy of the novel drug in the compliant stra-tum(P(H1|Data)=1).Consistent findings were ob-served in PPS analyses(estimated effect:0.136％;one-sided 97.5％credible interval lower bound:-0.069％),further validating methodological robust-ness.CONCLUSION:In clinical trials with noncom-pliance as an intercurrent event,the Bayesian mix-ture model under the principal stratum strategy ef-fectively adjusts for compliance-related bias and yields conservative,robust estimates of causal ef-fects,supporting its value in efficacy evaluation un-der complex compliance scenarios.

Thoracic anesthesia with spontaneous respiration represents a form of precision anesthesia meticulously customized to individual patients.Considering the more stringent requirements this anesthesia approach imposes on the regulation of respiratory function,the writing group of the"Consensus of Experts on the Management of Thoracic Anesthesia with Spontaneous Respiration"has formulated elaborate guidelines regarding indications and contraindications,preoperative evaluation,anesthesia implementation,common complications,and treatment strategies.This was accomplished by referencing relevant domestic and international literature and integrating it with actual clinical requirements.The objective is to standardize the rational application of this anesthesia method.

Objective To observe the effects of Yiqi Huoxue Tuodu Prescription on Keap1Nrf2/HO-1 signaling pathway in rats with chronic nonbacterial prostatitis(CNP);To explore its mechanism for the treatment of CNP.Methods CNP rat model was prepared using castration combined with estrogen induction method.Totally 48 SD rats were divided into blank group,model group,celecoxib group and Yiqi Huoxue Tuodu Prescription group according to the random number table method,with 12 rats in each group.In the celecoxib group,celecoxib suspension was instilled 0.035 g/kg,and in the Yiqi Huoxue Tuodu Prescription group,Yiqi Huoxue Tuodu Prescription water decoction was instilled 8.64 g/kg,and the blank group and the model group were instilled with equal volume of normal saline for 28 days.Mechanical pain threshold in rats was measured using Von Frey fiber optic pain gauge,HE staining was used to observe pathological changes in prostate tissue and pathological scoring,the content of reactive oxygen species(ROS)in prostate tissue were detected by chemical fluorescence method and the glutathione peroxidase(GSH-Px)activity and malondialdehyde(MDA)content in prostate tissue were detected by colorimetric method,Western blot was used to detect the expressions of Kelch like ECH related protein 1(Keap1),nuclear factor E2 related factor 2(Nrf2),and heme oxygenase-1(HO-1)protein in prostate tissue.Results Compared with the blank group,rats in the model group had significantly lower mechanical pain threshold and significantly decreased prostate index(P<0.01);the size of the glandular cavity in prostate tissue varied,with the disappearance of secretions in the cavity,interstitial looseness and edema,a large amount of fibrous tissue hyperplasia and inflammatory cell infiltration,and a significant increase in pathological scores(P<0.01);the contents of ROS and MDA in prostate tissue significantly increased,the activity of GSH-Px significantly decreased(P<0.01),the expression of Keap1 and Nrf2 proteins significantly decreased,and the expression of HO-1 protein significantly increased(P<0.01,P<0.05).Compared with the model group,the mechanical pain threshold of the rats in the Yiqi Huoxue Tuodu Prescription group was significantly higher(P<0.01);there was mild damage to prostate tissue,with a small amount of fibrous hyperplasia and inflammatory cell infiltration,and a significant decrease in pathological scores(P<0.01,P<0.05);the contents of ROS and MDA in prostate tissue significantly decreased,and the GSH-Px activity significantly increased(P<0.01),the Keap1 and Nrf2 protein expressions significantly increased and HO-1 protein expression significantly decreased in prostate tissue(P<0.01,P<0.05).Conclusion Yiqi Huoxue Tuodu Prescription can effectively improve the histopathological morphology and increase the pain threshold of the prostate gland in CNP rats,and its mechanism of action may be related to the regulation of Keap1/Nrf2/HO-1 signaling pathway and reduction of oxidative stress damage in prostate tissue of rats.