ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

This study aims to systematically characterize the targeted effects of Quanduzhong Capsules on cartilage lesions in knee osteoarthritis by integrating spatial transcriptomics data mining and animal experiments validation, thereby elucidating the related molecular mechanisms. A knee osteoarthritis model was established using Sprague-Dawley(SD) rats, via a modified Hulth method. Hematoxylin and eosin(HE) staining was employed to detect knee osteoarthritis-associated pathological changes in knee cartilage. Candidate targets of Quanduzhong Capsules were collected from the HIT 2.0 database, followed by bioinformatics analysis of spatial transcriptomics datasets(GSE254844) from cartilage tissues in clinical knee osteoarthritis patients to identify spatially specific disease genes. Furthermore, a "formula candidate targets-spatially specific genes in cartilage lesions" interaction network was constructed to explore the effects and major mechanisms of Quanduzhong Capsules in distinct cartilage regions. Experimental validation was conducted through immunohistochemistry using animal-derived biospecimens. The results indicated that Quanduzhong Capsules effectively inhibited the degenerative changes in the cartilage of affected joints in rats, which was associated with the regulation of Quanduzhong Capsules on the thioredoxin-interacting protein(TXNIP)-NOD-like receptor family pyrin domain containing 3(NLRP3)-bone morphogenetic protein receptor type 2(BMPR2)-fibronectin 1(FN1)-matrix metallopeptidase 2(MMP2) signal axis in the articular cartilage surface and superficial zones, subsequently inhibiting cartilage matrix degradation leading to oxidative stress and inflammatory diffusion. In summary, this study clarifies the spatially specific targeted effects and protective mechanisms of Quanduzhong Capsules within pathological cartilage regions in knee osteoarthritis, providing theoretical and experimental support for the clinical application of this drug in the targeted therapy on the inflamed cartilage.
Animals ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Male ; Humans ; Capsules ; Female ; Disease Models, Animal

This study aims to investigate the polarized microscopic mineral phase characteristics, inorganic element content, and potential health risks associated with the intake of raw and calcined fossil mineral Chinese medicinal material Draconis Os. Microscopy was employed to observe the mineralogical characteristics of Draconis Os and compare the microscopic features and phase composition of raw and calcined Draconis Os under monochromatic and orthogonal polarized light. Inductively coupled plasma mass spectrometry(ICP-MS) was employed to determine the content of 30 inorganic elements. Health risk assessment was conducted by calculating the single pollution index(P_i), average daily intake of elements for adults(ADI), target hazard quotient(THQ), non-carcinogenic assessment method-hazard quotient(HQ), and the carcinogenic risk of elements(CR). The results indicated that under monochromatic polarized light, the Draconis Os powder sections exhibited light gray-brown to gray-brown irregular fragments, some with undulating textures that were slightly curved. Under crossed polarized light, they appeared dark gray, grayish-white, and yellowish-white. Clear apatite was visible in the ground sections of Draconis Os under crossed polarized light. P_i results indicated that Draconis Os samples were free from contamination and were of good quality. According to the maximum allowable limits of heavy metals stipulated in ISO Traditional Chinese Medicine: Determination of heavy metals in herbal medicines used in Traditional Chinese Medicine, ADI, THQ, HQ, and CR were taken as assessment indicators. Only the THQ value for As(arsenic) in raw Draconis Os was greater than 1, while the THQ values for other heavy metal elements in the Draconis Os samples were all less than 1. The study demonstrates that the primary mineral phase of raw and calcined Draconis Os is apatite, with some samples co-existing with calcite, which can serve as one of the means for quality control of Draconis Os. The elemental analysis results from ICP-MS provide scientific evidence for the safety assessment of Draconis Os, indicating that Draconis Os is safe in clinical application.
Drugs, Chinese Herbal/analysis* ; Risk Assessment ; Minerals/chemistry* ; Fossils ; Humans ; Drug Contamination ; Mass Spectrometry

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

Blood from a case of group B epidemic cerebrospinal meningitis identified in February 2024 in Ganzhou City,Jiangxi Province,and throat swabs from close contacts were collected for isolation and culture.The isolates were subjected to serogrouping,drug sensitivity testing,and whole genome sequencing and analysis,to provide a basis for epidemiological inves-tigation and clinical drug use.One strain of Neisseria meningitidis was isolated from the blood of the case and denoted group B.The MLST type was ST-7962,with no clonal group attribution.The phylogenetic tree showed that it was genetically close to the 1977 Shanghai carrier isolate(id-52231).Drug sensitivity results indicated that the strain was sensitive to 8 drugs:azithro-mycin,cefotaxime,minocycline,ceftriaxone,chloramphenicol,meropenem,rifampicin,and benzylpenicillin;resistant to cot-rimoxazole,levofloxacin,and ciprofloxacin;and showed an intermediate response to penicillin.This report describes the first case of ST-7962 group B meningoencephalitis found in Jiangxi Province.Monitoring of Neisseria meningitidis carriage,drug re-sistance,and molecular characteristics of strains in the healthy population in this region should be strengthened,to provide la-boratory support for the clinical use of medications,traceability,and control of the pathogen underlying meningoencephalitis infection.

Objective To collect and analyze outpatient prescription data for exogenous cough treatment from a hospital in Shenzhen,and to identify the characteristics and medication patterns of traditional Chinese medicine(TCM).Methods This study collected prescriptions from a hospital in Shenzhen for exogenous cough treatment in January 2024.R language for data mining were used to analyze the medication frequency,clustering patterns,and association rules in the treatment of exogenous cough by TCM and to explore the medication patterns and the usage of classic formulas in TCM for this condition.Results A total of 451 outpatient prescriptions for exogenous cough were include,the top ten most frequently used herbs were Licorice,Bitter almond,Bellflower,Ephedra,Tangerine peel,Stemonae radix,Tuckahoe,Pinellia ternata,Nepeta,Bulb of thunberg fritillary.Cluster analysis and association rules revealed that San'ao decoction,Kikyodon soup,and Zhisou powder were commonly prescribed,targeting lung function,dispersing wind,and resolving phlegm to effectively alleviate cough symptoms.Significant differences in medication usage were observed across different syndrome types.For the wind cold attacking lung pattern,the core herbs were warm in nature and focused on dispersing with acrid-warm properties.Conversely,the treatment of wind heat attacking the lung pattern typically involved cold-natured herbs,with a primary focus on clearing and draining lung heat.Stratification by age revealed that the pediatric group often used drugs with mild properties,such as Stemona and Shegan.The young adult group tended to be prescribed cold-natured drugs like Forsythia and Hogfonnel Root.The middle-aged and elderly group preferred warming and tonifying drugs such as Japanese Catnip and Perilla frutescens.Conclusion The TCM treatment of exogenous cough primarily focuses on releasing the exterior and dispersing the lung.Due to the region's subtropical monsoon climate and temperature fluctuations physicians flexibly modified classical formulas such as San'ao decoction and Zhisou powder according to individual constitutions and symptom patterns.This targeted,syndrome-based approach effectively disperses the lung qi,stops cough and transforms phlegm,and alleviates cough.

Objective To collect and analyze outpatient prescription data for exogenous cough treatment from a hospital in Shenzhen,and to identify the characteristics and medication patterns of traditional Chinese medicine(TCM).Methods This study collected prescriptions from a hospital in Shenzhen for exogenous cough treatment in January 2024.R language for data mining were used to analyze the medication frequency,clustering patterns,and association rules in the treatment of exogenous cough by TCM and to explore the medication patterns and the usage of classic formulas in TCM for this condition.Results A total of 451 outpatient prescriptions for exogenous cough were include,the top ten most frequently used herbs were Licorice,Bitter almond,Bellflower,Ephedra,Tangerine peel,Stemonae radix,Tuckahoe,Pinellia ternata,Nepeta,Bulb of thunberg fritillary.Cluster analysis and association rules revealed that San'ao decoction,Kikyodon soup,and Zhisou powder were commonly prescribed,targeting lung function,dispersing wind,and resolving phlegm to effectively alleviate cough symptoms.Significant differences in medication usage were observed across different syndrome types.For the wind cold attacking lung pattern,the core herbs were warm in nature and focused on dispersing with acrid-warm properties.Conversely,the treatment of wind heat attacking the lung pattern typically involved cold-natured herbs,with a primary focus on clearing and draining lung heat.Stratification by age revealed that the pediatric group often used drugs with mild properties,such as Stemona and Shegan.The young adult group tended to be prescribed cold-natured drugs like Forsythia and Hogfonnel Root.The middle-aged and elderly group preferred warming and tonifying drugs such as Japanese Catnip and Perilla frutescens.Conclusion The TCM treatment of exogenous cough primarily focuses on releasing the exterior and dispersing the lung.Due to the region's subtropical monsoon climate and temperature fluctuations physicians flexibly modified classical formulas such as San'ao decoction and Zhisou powder according to individual constitutions and symptom patterns.This targeted,syndrome-based approach effectively disperses the lung qi,stops cough and transforms phlegm,and alleviates cough.

Blood from a case of group B epidemic cerebrospinal meningitis identified in February 2024 in Ganzhou City,Jiangxi Province,and throat swabs from close contacts were collected for isolation and culture.The isolates were subjected to serogrouping,drug sensitivity testing,and whole genome sequencing and analysis,to provide a basis for epidemiological inves-tigation and clinical drug use.One strain of Neisseria meningitidis was isolated from the blood of the case and denoted group B.The MLST type was ST-7962,with no clonal group attribution.The phylogenetic tree showed that it was genetically close to the 1977 Shanghai carrier isolate(id-52231).Drug sensitivity results indicated that the strain was sensitive to 8 drugs:azithro-mycin,cefotaxime,minocycline,ceftriaxone,chloramphenicol,meropenem,rifampicin,and benzylpenicillin;resistant to cot-rimoxazole,levofloxacin,and ciprofloxacin;and showed an intermediate response to penicillin.This report describes the first case of ST-7962 group B meningoencephalitis found in Jiangxi Province.Monitoring of Neisseria meningitidis carriage,drug re-sistance,and molecular characteristics of strains in the healthy population in this region should be strengthened,to provide la-boratory support for the clinical use of medications,traceability,and control of the pathogen underlying meningoencephalitis infection.

Objective To investigate the effect of antinuclear antibodies(ANAs)on hormone response in patients with autoimmune hepatitis(AIH)-primary biliary cholangitis(PBC)overlap syndrome(AIH-PBC OS)and AIH-only within half a year.Methods A retrospective analysis of 77 patients with autoimmune liver disease(AILD)admitted to First Clinical Medical College of Lanzhou University from January 2018 to December 2021,all of whom were confirmed by liver biopsy and receiving glucocorticoid treatment.Among them,46 patients were in AIH-PBC OS group and 31 were in AIH-only group.The general clinical characteristics,liver puncture-related indexes,autoantibodies and immunoglobulin indexes of patients in each group at the time of diagnosis were collected and compared,and the biochemical and immunoglobulin indexes of patients at the time of hormone use and at the time of review within 6 months were also collected,and the hormone response within 6 months was evaluated according to the levels of glutamic transaminase(AST),glutamic alanine transaminase(ALT)and immunoglobulin G(IgG),and the effect of ANAs on hormone response outcomes in both groups over a six-month period was analyzed.Multifactorial ordered logistic analysis was performed to evaluate the effect of ANAs on hormone response between two groups.Results There was no statistically significant difference in the percentage of AIH-PBC OS and AIH-only patients among both ANAs-positive and-negative AILD patients(55.6%vs.44.4%and 65.6%vs.34.4%,P>0.05).Among 46 patients with AIH-PBC OS,there were 25 in ANAs-positive group and 21 in ANAs-negative group.The rate of complete hormone response within 6 months was lower than that of ANAs-negative group(44.0%vs.76.2%),while the rate of hormone non-response was higher than that of ANAs-negative group(20.0%vs.0),and the difference was statistically significant(P<0.05).There were 20 cases of ANAs-positive and 11 cases of ANAs-negative in the 31 AIH-only patients.There was no statistically significant difference in the results of hormone response within 6 months between the two groups(P>0.05).Multifactorial ordered logistic analysis showed that AIH-PBC OS patients were more likely to have a higher likelihood of 6-month hormone non-response rate in ANAs-positive patients,and the difference was statistically different(P<0.05).And there was no significant effect of ANAs type on hormone response outcome in AIH-only patients(P>0.05).Conclusion AIH-PBC OS ANAs-positive patients have a poor hormone response within half a year.In AIH-only patients,ANAs have no significant effect on hormone response results.