BACKGROUND:Knee osteoarthritis(KOA)is a common chronic inflammatory disease that causes damage to joint cartilage and surrounding tissues.Immune cells play an important role in the immune-inflammatory response in knee osteoarthritis,but the specific mechanisms involved are still not fully understood. OBJECTIVE:To evaluate the potential causal relationship between 731 immune cell phenotypes and the risk of knee osteoarthritis using Mendelian randomization. METHODS:Summary statistics of genome-wide association studies(GWAS)for 731 immune cell phenotypes(from GCST0001391 to GCST0002121)obtained from the GWAS catalog and GWAS data for knee osteoarthritis from the IEUGWAS database(ebi-a-GCST007090)were used.Inverse variance-weighted method,MR-Egger regression,weighted median method,weighted mode method,and simple mode method were employed to investigate the causal relationship between immune cells and knee osteoarthritis.Sensitivity analyses were conducted to assess the reliability of the Mendelian randomization results.Reverse Mendelian randomization analysis was also performed using the same methods. RESULTS AND CONCLUSION:The forward MR analysis indicated significant causal relationships(FDR<0.20)between knee osteoarthritis and four immune cell phenotypes,namely CD27 on CD24+CD27+in B cells(OR=1.026,P=0.000 26,Pfdr=0.18),CD33 on CD33dim HLA DR-in myeloid cells(OR=1.014,P=0.000 50,Pfdr=0.18),and CD45RA+CD28-CD8br%CD8br in Treg cells(OR=1.001,P=0.000 78,Pfdr=0.18),and PDL-1 on monocytes in mononuclear cells(OR=0.952,P=0.000 98,Pfdr=0.18).These immune cell phenotypes showed direct positive or negative causal associations with the risk of knee osteoarthritis.Reverse Mendelian randomization analysis revealed no significant causal relationships(FDR<0.20)between knee osteoarthritis as exposure and any of the 731 immune cell phenotypes.The results of sensitivity analysis show that the P-values of the Cochran's Q test and the MR-Egger regression method for bidirectional Mendelian randomization were both greater than 0.05,indicating that there is no significant heterogeneity and pleiotropy in the causal effect analysis between immune cell phenotypes and knee osteoarthritis.To conclude,there may be four potential causal relationships between immune cell phenotypes,such as CD27 on CD24+CD27+cells,CD33 on CD33dim HLA DR-cells,CD45RA+CD28-CD8br%CD8br cells,and PDL-1 on monocytes,and knee osteoarthritis.These findings provide valuable clues for studying the biological mechanisms of knee osteoarthritis and exploring early prevention and treatment strategies.They also offer new directions for the development of intervention drugs.

The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

Objective To identify the reasons why the monitored personal doses of radiation worker A in an institution exceeded the investigation level in 2023 and 2024, and remind workers to wear personal dosimeters in a standardized manner in scenarios such as work and business trips to ensure the authenticity and reliability of the monitoring data. Methods A thermoluminescence measurement system was used to read the personal dosimeters worn by radiation workers. Investigations were carried out on personnel whose doses exceeded the investigation level described in the “Specifications for individual monitoring of occupational external exposure” (GBZ 128—2019). The reasons for doses exceeding the investigation level were analyzed using additional dosimeters and conducting on-site experiments. Results In 2023 and 2024, radiation worker A recorded a total of 5 personal dose equivalents exceeding the investigation level (1.23 mSv) over a total of 8 monitoring cycles (each lasting 90 days). Following one cycle where the dose exceeded the investigation level, two additional dosimeters (each for a 30-day cycle) were issued to worker A, revealing readings below the investigation level for the 30-day monitoring cycle (0.41 mSv). The reading for the dosimeter was 2-3 μSv per time when passing through an X-ray security scanner, and approximately 2.10 mSv per time when passing through a computed tomography security scanner. Conclusion Within a 90-day monitoring cycle, a single exposure of a personal dosimeter to a computed tomography security scanner can result in a dose exceeding the investigation level. Radiation workers should avoid placing dosimeters in backpacks or suitcases that pass through computed tomography security scanners during business trips, so as to reduce the impact of security scanner irradiation on personal dose monitoring.

Objective:To detect key genes of local glucocorticoid therapy in oral lichen planus(OLP)through transcriptome sequencing.Methods:The study prospectively enrolled 28 symptomatic patients who visitied Department of Oral Mucosa,Peking University Hospital of Stomatology from November 2019 to March 2023.Topical inunction of 0.1 g/L of dexamethasone was applied for 1 min,3 times daily for 4 weeks.The patients'signs and pain symptoms were recorded and they were classified as effective group and ineffective group according to the treatment outcome.Their mucosa samples were collected before treatment.After isolating total RNA,transcriptome sequencing was performed.The gene expression data obtained by sequencing were analyzed differently using the DESeq2 package in R software,and the Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis was performed on the basis of the hypergeometric distribution algorithm to describe the biological function of differentially expressed genes(DEGs),accordingly detecting sensitivity related molecular affecting therapeutic effect of dexamethasone.Results:After 4 weeks treatment by topical dexamethasone,13 cases of the 28 OLP pa-tients responding well with the sign score reducing from 7.0(4.5,9.0)to 5.0(3.0,6.3),pain score decreasing from 5.0(2.0,5.5)to 2.0(0.0,3.5),oral health impact profile lessening from 5.0(3.5,9.0)to 1.0(0.0,5.0)significantly(P＜0.01)were classified as effective group and 15 cases with poor response to the drug were sorted as ineffective group.There were no significant differences of demographic and baseline levels of clinical features,especially disease severity between these two groups.A total of 499 DEGs including 274 upregulated and 225 downregulated genes were identified between ef-fective group and ineffective group.KEGG enrichment analysis showed that upregulated genes in effective group compared with ineffective group including CLDN8,CTNNA3,MYL2 and MYLPF were associated with leukocyte transendothelial migration,while downregulated genes were significantly enriched in tumor necrosis factor(TNF),interleukin-17(IL-17),nuclear factor kappa B(NF-κB)signaling pathways,and cortisol synthesis and secretory.Conclusion:High expressions of CLDN8,CTNNA3,MYL2 and MYLPF genes in patients with oral lichen planus have a good clinical response to topical dexamethasone,while patients with high expression genes of inflammation pathway such as TNF,IL-17,NF-κB and corti-sol synthesis and secretion received poor effect.

BACKGROUND:Rheumatoid arthritis is a chronic systemic autoimmune disease.It is important to study the immunological changes involved in it for diagnosis and treatment. OBJECTIVE:To identify immune-related biomarkers associated with rheumatoid arthritis utilizing bioinformatics techniques and examine alterations in immune cell infiltration as well as the relationship between immune cells and biomarkers. METHODS:Differential expression analysis was used to identify the immune-related genes that were up-regulated in rheumatoid arthritis based on the GEO and Immport databases.Kyoto encyclopedia of genes and genomes(KEGG)and gene ontology(GO)enrichment analyses were used to investigate the possible function of these elevated genes.The immunological characteristic genes associated with rheumatoid arthritis were screened using least absolute shrinkage and selection operator(Lasso)and support vector machine recursive feature elimination(SVM-RFE).Independent datasets were used for difference validation,and the diagnostic performance was evaluated by plotting receiver operating characteristic curves for feature genes.Immune cell infiltration was used to analyze the differential profile of immune cells in rheumatoid arthritis and the correlation between the characterized genes and immune cells.In order to ascertain the causal relationship between monocytes and rheumatoid arthritis in immune cells,Mendelian randomization analysis was ultimately employed. RESULTS AND CONCLUSION:There were 39 upregulated differentially expressed genes in rheumatoid arthritis.The genes were primarily enriched in chemotaxis,cytokine activity,and immune receptor activity,according to GO enrichment analysis,while kEGG enrichment analysis revealed that the genes were considerably enriched in the tumor necrosis factor signaling pathway and peripheral leukocyte migration.Lasso and SVM-RFE identified five feature genes:CXCL13,SDC1,IGLC1,PLXNC1,and SLC29A3.Independent dataset validation of the feature genes found them to be similarly highly expressed in rheumatoid arthritis samples,with area under the curve values greater than 0.8 for all five feature genes in both datasets.Immune cell infiltration indicated that most immune cells,including natural killer cells and monocytes,exhibited increased levels of infiltration in rheumatoid arthritis samples.The correlation analysis revealed a significant positive correlation between memory B cells and immature B cells and these five feature genes.Correlation analysis showed that the five feature genes were positively correlated with memory B cells and immature B cells.The inverse variance weighting method revealed that monocytes were associated with the risk of developing rheumatoid arthritis.

Objective:To compare the clinical efficacy of neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemo-immunotherapy (nCIT) for locally advanced esophageal squamous cell carcinoma (ESCC).Methods:Clinical data of patients who received nCRT or nCIT followed by esophagectomy for locally advanced ESCC between January 2010 and December 2022 were retrospectively collected from Zhejiang Cancer Hospital, with 155 patients in the nCRT group and 470 patients in the nCIT group. Propensity score matching (PSM) was performed in the two groups. After PSM, 120 patients were allocated to the nCRT group and 192 patients to the nCIT group. The pathological response and disease recurrence were compared between the two groups after PSM. Log rank test were used to compare the survival outcomes before and after PSM. Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors for locally advanced ESCC.Results:After PSM, the R0 resection rate in the nCRT group and the nCIT group was 93.3% (112/120) and 93.8% (180/192), respectively, with no statistical significance ( P=0.884). However, the pathological complete response rate in the nCRT group [36.7% (44/120)] was higher than that in the nCIT group [21.4% (41/192), P=0.003]. For patients with R0 resection, the major recurrence pattern was distant metastasis [18.8% (21/112)] in the nCRT group, while the pattern was locoregional recurrence [12.2% (22/180)] in the nCIT group. The 3-year disease-free survival rates were 52.7% and 66.1% ( P=0.022) and the 3-year overall survival rates were 59.2% and 75.5% ( P=0.002) in the nCRT and nCIT groups, respectively. Multivariate Cox regression analysis also revealed that the neoadjuvant therapy mode was an independent prognostic factor for patients with locally advanced ESCC. Compared with nCRT, nCIT could significantly prolong disease-free survival ( HR=0.58, 95% CI: 0.40-0.86) and overall survival ( HR=0.53, 95% CI: 0.35-0.79). Conclusion:These results suggest that nCIT could significantly improve disease-free survival rate and overall survival rate over nCRT in locally advanced ESCC, even with lower pathological complete response rate.

Objective:To compare the clinical efficacy of neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemo-immunotherapy (nCIT) for locally advanced esophageal squamous cell carcinoma (ESCC).Methods:Clinical data of patients who received nCRT or nCIT followed by esophagectomy for locally advanced ESCC between January 2010 and December 2022 were retrospectively collected from Zhejiang Cancer Hospital, with 155 patients in the nCRT group and 470 patients in the nCIT group. Propensity score matching (PSM) was performed in the two groups. After PSM, 120 patients were allocated to the nCRT group and 192 patients to the nCIT group. The pathological response and disease recurrence were compared between the two groups after PSM. Log rank test were used to compare the survival outcomes before and after PSM. Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors for locally advanced ESCC.Results:After PSM, the R0 resection rate in the nCRT group and the nCIT group was 93.3% (112/120) and 93.8% (180/192), respectively, with no statistical significance ( P=0.884). However, the pathological complete response rate in the nCRT group [36.7% (44/120)] was higher than that in the nCIT group [21.4% (41/192), P=0.003]. For patients with R0 resection, the major recurrence pattern was distant metastasis [18.8% (21/112)] in the nCRT group, while the pattern was locoregional recurrence [12.2% (22/180)] in the nCIT group. The 3-year disease-free survival rates were 52.7% and 66.1% ( P=0.022) and the 3-year overall survival rates were 59.2% and 75.5% ( P=0.002) in the nCRT and nCIT groups, respectively. Multivariate Cox regression analysis also revealed that the neoadjuvant therapy mode was an independent prognostic factor for patients with locally advanced ESCC. Compared with nCRT, nCIT could significantly prolong disease-free survival ( HR=0.58, 95% CI: 0.40-0.86) and overall survival ( HR=0.53, 95% CI: 0.35-0.79). Conclusion:These results suggest that nCIT could significantly improve disease-free survival rate and overall survival rate over nCRT in locally advanced ESCC, even with lower pathological complete response rate.

Objective UPLC-Q-TOF-MS integrated molecular network strategy was used to rapidly analyze and identify the chemical components of Yuye detoxification Particle. Methods The secondary mass spectrometry data of compounds were obtained using mass spectrometry scanning in both positive and negative ion mode. The similarity of MS/MS fragmentation patterns was calculated to create the global natural product social molecular networking (GNPS) platform. The major components in Yuye detoxification Particle were quickly identified according to the molecular clusters with similar structures in GNPS. Manual analysis and identification of other compounds were performed according to the mass fragment ion information of the primary and secondary mass spectrum data and related references by using the molecular feature extraction (MFE) function of Agilent Masshunter Qualitative Analysis workstation and traditional Chinese Medicine composition database (TCM-DATA). Results A total of 89 compounds in Yuye detoxification Particle were identified by LC-MS,including 22 phenoliacids,21 flavonoids and their glycosides,6 iridoid glycosides,28 triterpenoid saponins and 12 other types of ingredients. Conclusion UPLC-Q-TOF-MS/MS integrated molecular network technology can be used for rapid and systematic identification of chemical components of Yuye detoxification Particle,which provides theoretical basis for its quality control and clinical application. The established molecular network can provide reference for rapid qualitative analysis of components of traditional Chinese medicine compound.

Objective:To systematically evaluate the effect of hepatitis B virus (HBV) infection on the risk of adverse pregnancy outcomes.Methods:We searched PubMed, Embase, Web of Science, and Cochrane databases. Two researchers independently screened the literature, extracted data, and evaluated the quality. Meta-analysis and cumulative meta-analysis were performed using R4.4.1 software. Fixed/random effects models were used to analyze heterogeneous and non-heterogeneous results. Heterogeneous modifiers were identified by subgroup analysis. Funnel plots and Peters' test were used to analyze potential publication bias.Results:A total of 48 studies involving 92 836 HBsAg-positive pregnant women and 7 123 292 HBsAg-negative pregnant women were included. In terms of adverse pregnancy outcomes, HBV infection was significantly correlated with the occurrence of gestational diabetes mellitus [odds ratio ( OR)=1.34, 95% confidence interval ( CI): 1.17-1.53] and intrahepatic cholestasis ( OR=2.48, 95% CI: 1.88-3.29), with statistically significant differences. In terms of adverse neonatal outcomes, HBV infection was significantly correlated with the occurrence of neonatal asphyxia ( OR=1.49, 95% CI: 1.20-1.86) and preterm birth ( OR=1.22, 95% CI: 1.12-1.33), with statistically significant differences. In addition, the cumulative meta-analysis demonstrated that the risk of gestational diabetes mellitus and preterm birth both tended to be stable in pregnant women with HBV infection following 2009 and 2010, respectively. The supplementary questions answered for repeated studies had limited significance. Conclusion:Intrahepatic cholestasis, gestational diabetes mellitus, neonatal asphyxia, and preterm birth occurrence risk can be raised with HBV infection in pregnant women.

Objective·To investigate the relation between urinary excretion of protein-bound uremic toxins(PBUTs)and upper urinary tract calculus.Methods·Residents aged 18?80 years in the community of Haitou,Danzhou city in Hainan Province were recruited.Basic information and diet for the last 3 d of the subjects were recorded.Their fasting sera and 24-hour urine samples were collected,and they also underwent ultrasound examination of kidneys and ureters.The subjects with upper urinary calculi detected by ultrasound or a clear history of upper urinary calculi were selected as the calculus group,and the others as the non-calculus group.The biochemical indicators related to the formation of calculus in blood and urine were detected,and the levels of PBUTs,including indoxyl sufate(IS),indole-3-acetic acid(IAA),and p-cresol sulfate(PCS)in blood and urine,as well as oxalic acid and citric acid in urine were detected by high-performance liquid chromatography.The related factors of upper urinary tract calculus formation were analyzed by multivariate Logistic regression.The correlations of urine PBUTs with urine uric acid,oxalic acid,and citric acid were analyzed by Spearman correlation test.Results·A total of 117 participants were screened out with 54 people in the calculus group and 63 people in the non-calculus group.There were no significant differences between the two groups in terms of gender,age,serum indicators,and prevalence of complications such as hypertension,diabetes,and hyperuricemia/gout.The 24-hour urine pH,calcium,uric acid,and chlorine in the calculus group were significantly higher than those in the non-calculus group(all P<0.05),while IS was significantly lower than that in the non-calculus group(P<0.05).Multivariate Logistic regression analysis showed that urinary IS(OR=0.929,95%CI 0.875?0.986,P=0.016)was related to the calculus formation independently,in addition to urinary calcium.The Spearman correlation analysis results showed that the levels of IAA(r=0.420,P=0.000)and PCS(r=0.307,P=0.001)in 24-hour urine were positively correlated with oxalic acid,PCS was positively correlated with uric acid(r=0.297,P=0.002),and IS was positively correlated with citric acid(r=0.289,P=0.002).Conclusion·In the population,a decrease in urinary excretion of IS may be an independent risk factor for the formation of upper urinary tract calculus,and PBUTs levels are correlated with levels of uric acid,oxalic acid,and citric acid.