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

AIM To investigate the therapeutic mechanism of tanshinone ⅡA in a mouse model of chronic colitis induced by trinitrobenzene sulfonic acid(TNBS).METHODS The BALB/c mice were randomly divided into the control group,the model group,and the low-dose and high-dose tanshinone ⅡA groups(10,20 mg/kg).Chronic inflammatory bowel disease(IBD)was induced in the model and tanshinone ⅡA groups by epicutaneous application of 3.75 mg TNBS(dissolved in 48％ethanol),followed by intrarectal administration of TNBS(0.75,1.5 and 2.25 mg in 40％ethanol)on days 7,14 and 21.Starting on day 7 post-modeling,the mice underwent their 14-day consecutive dosing of corresponding drugs by gavage.The mice had their disease activity index(DAI)assessed;their colon length and weight measured;and their levels of inflammatory factors IFN-γ and TNF-α in the colon mucosa detected by ELISA.The wild-type and PXR-/-mice were randomly divided into the control group,the model group,and the tanshinone ⅡA group(20 mg/kg).After modeling and drug administration using the aforementioned method,Masson staining was used to assess the intestinal fibrosis;immunohistochemistry was employed to detect the colon expression of ZO-1 and Occludin proteins;and immunofluorescence was used to detect the colon expression of NF-κB p65.RESULTS Tanshinone ⅡA(20 mg/kg)reduced DAI scores,colon weight/length ratio,and the colon levels of IFN-γ and TNF-α of the mouse models(P＜0.05,P＜0.01).Compared with the WT control group,the WT model group and PXR-/-control group exhibited increased colon histopathological scores and fibrosis areas(P＜0.01),decreased protein expressions of ZO-1 and Occludin(P＜0.01),and increased expression of p-NF-κB p65(P＜0.01).Compared with the WT model group,the WT tanshinone ⅡA group showed reduced colon weight/length ratio,histopathological scores,and fibrosis areas(P＜0.01);increased protein expressions of ZO-1 and Occludin(P＜0.05,P＜0.01);and decreased expression of p-NF-κB p65(P＜0.01).However,tanshinone ⅡA showed no significant therapeutic effect upon PXR-/-model mice(P＞0.05).CONCLUSION Tanshinone ⅡA(20 mg/kg)can effectively alleviate TNBS-induced chronic colitis in mice,and this protective effect may be exerted by the modulation of PXR/NF-κB signaling pathway.

This article aims to explore the effect and mechanism of Liujunzi Pills on the intestinal microbiota of rats with spleen Qi deficiency syndrome. The raw Rhei Radix et Rhizoma water extract(1 g·mL~(-1)) was used to prepare spleen Qi deficiency rat models. A total of 44 SD male rats were randomly divided into a control group, a model group, Liujunzi Pills groups at high(3.24 g·kg~(-1)), medium(1.62 g·kg~(-1)), low(0.81 g·kg~(-1)) doses, and Shenling Baizhu San(2.50 g·kg~(-1)) group. The drug effect was evaluated by observing the following aspects: spleen index, fecal water content, body weight, and intestinal propulsion index. Gut microbiota analysis and 16S rRNA gene sequencing were conducted on feces. Enzyme-linked immunosorbent assay(ELISA) and UV spectrophotometry were used to detect interleukin-1β(IL-1β) and adenosine triphosphate(ATP) levels in small intestine tissues. Hematoxylin-eosin staining and transmission electron microscopy were employed to observe changes in intestinal pathology and microstructure. The results show that, compared with the control group, fecal moisture content is significantly increased while spleen index, body weight, and intestinal propulsion index are significantly reduced in rats of the model group, indicating the successful establishment of the model. The above symptoms can be improved by both Shenling Baizhu San and Liujunzi Pills. Compared with the control group, in the model group, the gut microbiota abundance is changed with an unbalanced development: the abundance of beneficial bacteria within the Bacteroidetes phylum is reduced, accompanied by a significantly decreased Shannon index, and reduced signal levels of nicotinamide adenine dinucleotide phosphate(NADPH)-related enzymes relevant to mitochondria. However, Liujunzi Pills and Shenling Baizhu San can significantly improve the Bacteroidetes phylum abundance in gut microbiota, microbial diversity, and NADPH activity in the model group. Additionally, compared with the control group, the ATP level is decreased and the IL-1β level is increased in small intestinal tissues of the model group, with shorter small intestinal epithelial villi and decreased mitochondrial number. The above symptoms can be improved by Liujunzi Pills and Shenling Baizhu San. In conclusion, Liujunzi Pills can treat spleen Qi deficiency syndrome by enhancing mitochondrial function to regulate gut microbiota balance and diversity.
Animals ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Rats, Sprague-Dawley ; Rats ; Qi ; Spleen/metabolism* ; Splenic Diseases/metabolism* ; Humans ; Interleukin-1beta/genetics* ; Bacteria/drug effects* ; Feces/microbiology* ; Adenosine Triphosphate/metabolism*

The chemical constituents from the n-butanol fraction of ethanol extract of safflower (Carthamus tinctorius L.) were isolated and purified using chromatographic process including MCI Gel CHP-20, ODS, Sephadex LH-20 column chromatography, and semi-preparative HPLC method, and one alkyne and two phenylpropanoid derivants were obtained. Their structures were identified as (5R,E)-tetradecane-12-ene-8,10-diyne-1,5,14-triol (1), (E)-8-O-β-D-glucopyranosyl n-butyl cinnamate (2), and (7S,8S)-7-(4-hydroxy-3-methoxybenzene)-7-butyl-8,9-diol (3) by modern spectroscopy methods (1D NMR, 2D NMR, UV, IR and MS). 1-3 are all new compounds. Compounds 1-3 were screened for their anti-renal fibrosis activities in vitro, and none of them showed obvious effect.

OBJECTIVES: To study the clinical characteristics of pediatric Behçet syndrome (BS). METHODS: A retrospective review was conducted on the medical records of children hospitalized in the Department of Pediatrics at the Second Hospital of Hebei Medical University between December 2014 and December 2024 who met diagnostic criteria for BS. RESULTS: Among 45 children with BS, 26 (58%) were male. Oral aphthous ulcers were the most common manifestation (43/45, 96%), followed by genital ulcers (23/45, 51%) and gastrointestinal involvement (18/45, 40%). Genital ulcers were more frequent in girls, whereas ocular involvement was more common in boys (P<0.05). The pathergy test was positive in 10 (22%), and HLA-B51 was positive in 13 (29%). Fecal calprotectin (FC) was elevated in 16 (36%); gastrointestinal involvement was more frequent in children with elevated FC than in those with normal FC (P<0.05). According to the respective criteria, 17 (38%) patients met the International Study Group criteria (1990), 33 (73%) met the International Criteria for Behçet Disease (2014), and 13 (29%) met the Pediatric Behçet Disease criteria (2015). CONCLUSIONS Pediatric BS shows marked clinical heterogeneity. HLA-B51 is associated with disease susceptibility.
Humans ; Behcet Syndrome/genetics* ; Male ; Female ; Child ; Retrospective Studies ; Adolescent ; Child, Preschool ; Leukocyte L1 Antigen Complex/analysis* ; HLA-B51 Antigen

Objective:To investigate the expression of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues and analyze their expression levels in relation to clinical features and prognosis. Methods:From January 1, 2019, to December 31, 2019, 69 cases of nasopharyngeal carcinoma tissues and adjacent non-cancerous tissues were collected from patients treated at Yunnan Cancer Hospital. Immunohistochemistry was employed to detect the expression of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues. The Kaplan-Meier method was used to predict survival time, and the clinicopathological features were evaluated using the log-Rank test. Results:The positive expression rates of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues were 87.0% and 84.5%, respectively. Compared to adjacent normal tissues, the expression levels of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues were significantly increased （P<0.05）. Furthermore, the expression of NFAT5 and IGF1R was positively correlated with T stage, N stage, skull base invasion, and cranial nerve palsy （P<0.05）. The overexpression of NFAT5 and IGF1R significantly affected the survival rate of patients with nasopharyngeal carcinoma and was negatively correlated with prognosis （P<0.05）. Conclusion:In nasopharyngeal carcinoma tissues, overexpression of NFAT5 and IGF1R is observed, which is closely linked to clinical features and patient outcomes. These markers may serve as valuable indicators for predicting the prognosis of nasopharyngeal carcinoma.
Humans ; Nasopharyngeal Carcinoma/pathology* ; Nasopharyngeal Neoplasms/metabolism* ; Prognosis ; Female ; Receptor, IGF Type 1/metabolism* ; Male ; Transcription Factors/metabolism* ; Middle Aged ; Survival Rate ; Adult ; Neoplasm Staging

Objective:Retrospective analysis of the correlation between clinicopathologic features and related indexes and prognosis in patients with recurrent nasopharyngeal carcinoma. Methods:One hundred and eight nasopharyngeal cancer（NPC） patients with post-treatment recurrence in Yunnan Cancer Hospital from January 2013 to January 2018 were collected, and the survival time was estimated by Kaplan-Meier method, and clinicopathological characteristics were analyzed by log-rank test; risk factors and prognosis were analyzed by Cox proportional risk model for single-factor and multifactorial analysis. A P-value <0.05 was considered statistically significant. Results:The median survival of all patients was 54 months, with a 3-year survival rate of 80.2% and a 5-year survival rate of 39.8%. The 5-year overall survival rate was 50.2% for patients >46 years old and 27.9% for patients ≤46 years old（P<0.05）, a statistically significant difference. Univariate analysis showed that overall survival was associated with age, chemotherapy regimen, EBV early antigen IgA, plasma D-dimer, glycan antigen-125, γ-interferon, α-tumor necrosis factor, IL-10, and IL-4（P<0.05）. Multifactorial analysis revealed that age, chemotherapy regimen, EBV early antigen IgA, plasma D-dimer, glycan antigen-125, and interleukin 10 were independent influences on the prognosis of recurrent nasopharyngeal carcinoma（P<0.05）. Conclusion:Differences in chemotherapy regimens affect the prognosis of recurrent nasopharyngeal carcinoma. Elevated plasma D-dimer, glycan antigen 125, and interleukin 10 levels affect the overall survival of recurrent nasopharyngeal carcinoma, which may be a valid independent prognostic factor, and are expected to provide new biomarkers for nasopharyngeal carcinoma in the clinic.
Humans ; Prognosis ; Nasopharyngeal Neoplasms/mortality* ; Nasopharyngeal Carcinoma ; Retrospective Studies ; Neoplasm Recurrence, Local ; Male ; Middle Aged ; Female ; Survival Rate ; Adult ; Risk Factors ; Interleukin-10/blood* ; Aged ; Proportional Hazards Models

As a novel form of cell death, ferroptosis is mainly regulated by the accumulation of soluble iron ions in the cytoplasm and the production of lipid peroxides and is closely associated with several diseases, including acute kidney injury, ischemic reperfusion injury, neurodegenerative diseases, and cancer. The term "immunosuppression" refers to various factors that can directly harm immune cells' structure and function and affect the synthesis, release, and biological activity of immune molecules, leading to the insufficient response of the immune system to antigen production, failure to successfully resist the invasion of foreign pathogens, and even organ damage and metabolic disorders. An immunosuppressive phase commonly occurs in the progression of many ferroptosis-related diseases, and ferroptosis can directly inhibit immune cell function. However, the relationship between ferroptosis and immunosuppression has not yet been published due to their complicated interactions in various diseases. Therefore, this review deeply discusses the contribution of ferroptosis to immunosuppression in specific cases. In addition to offering new therapeutic targets for ferroptosis-related diseases, the findings will help clarify the issues on how ferroptosis contributes to immunosuppression.
Ferroptosis/immunology* ; Humans ; Immune Tolerance/immunology* ; Animals ; Immunosuppression Therapy ; Iron/metabolism* ; Neoplasms/immunology*

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.