Immune checkpoint inhibitors (ICIs) are widely used in the treatment of malignant tumors, and their related immune-related adverse events (irAEs) have attracted increasing attention. This study reports the diagnosis and treatment process of a case of immune cystitis in a patient with hepatobiliary tract malignant tumor after treatment with pembrolizumab. The patient was admitted to the hospital due to frequent urination, urgency of urination and dysuria for 1 month. Previous repeated anti-infection treatments were ineffective. Combined with medical history, laboratory tests, imaging findings, cystoscopy and pathological results, the patient was clinically diagnosed with ICIs-associated immune cystitis (Pembrolizumab) ultimately. The patient's symptoms significantly improved after treatment with glucocorticoids. This case reindicates that clinicians need to improve awareness of ICI-related urinary system irAEs. Early identification and timely intervention can significantly improve patient prognosis.

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.

ObjectiveTo evaluate the safety and immunogenicity of two doses of live attenuated varicella vaccine in individuals aged 13 years and older, so as to provide a scientific basis for optimizing the varicella vaccination strategy for people aged 13 years and above.MethodsA total of 1 680 healthy adolescents and adults aged 13 to 50 years were selected from two sub-centers of the Hubei Provincial Center for Disease Control and Prevention, and were stratified by age between those aged 13 to 16 years and those aged 17 to 50 years. Subjects in each age group were randomly assigned in a 1∶1 ratio to receive two doses of the test vaccine according to the immunization schedules of 0, 4 or 0, 8 weeks, respectively. Adverse events were collected within 30 minutes and 0 to 14 days after each vaccine dose, as well as all adverse events within 28 days after each dose, and serious adverse events(SAEs) from the first dose to six months after full immunization. Serum varicella virus-specific antibodies were detected before immunization, before the second dose and 28 days after full immunization, and the antibody positive rates(titer ≥ 1∶8), seroconversion rates(antibody titer of susceptible individuals after immunization ≥ 1∶8 or antibody titer of non-susceptible individuals increased ≥ 4 times after immunization), geometric mean titers(GMTs) and geometric mean increases(GMIs) were calculated.ResultsAmong the 1 680 subjects,1 606 subjects completed the study,including 807 in the 13-16 age group and 799 in the 17-50 age group. There were 288 and 340 adverse events in the 13-16 and 17-50 age groups, respectively, mainly grade 1-2. A total of four grade 3 adverse events occurred(two cases of fever, one case of pruritus at the vaccination site, and one case of vaccination site swelling). Adverse events after vaccination mostly occurred within 0-14 days, and no vaccine-related SAE occurred within six months after full immunization. The antibody positive rates before the second dose and 28 days after full immunization were both 100. 00%(1 616/1 616). The seroconversion rates were 55. 32% and 80. 57%, respectively, and the latter was significantly higher than the former(χ~2= 235. 325, P < 0. 000 1).The GMTs were 310. 77 and 626. 63, respectively, and the latter was significantly higher than the former(t =-21. 383, P <0. 000 1). The GMIs were 3. 68 and 7. 42, respectively, and the latter was significantly higher than the former(t =-4. 387, P =0. 012). At 28 days after the full immunization, the seroconversion rates of the two immunization schedules at 0, 4 and 0, 8 weeks were 80. 52% and 80. 62%(χ~2= 0. 003 and 3. 811, P < 1. 000 and 0. 057, respectively), the GMTs were 628. 57 and624. 67(t =-2. 134 and 0. 232, P = 0. 102 and 0. 828, respectively), and the GMIs were 7. 49 and 7. 34(t =-0. 366, P =0. 733), respectively.ConclusionLive attenuated varicella vaccine demonstrates good safety and immunogenicity in individuals aged ≥13 years when administered according to a two-dose immunization schedule, with equivalent immune effects between the two immunization schedules of 0, 4 and 0, 8 weeks, and the vaccination interval can be flexibly selected according to the actual situation.

OBJECTIVE To systematically evaluate the quality of the Heat-clearing and symptom-relieving formula and screen potential marker components that influence the quality of the formula. METHODS The contents of 11 components （calycosin-7- O - β -D-glucoside， ononin， hyperoside， isoquercitrin， baicalin， baicalein， cryptotanshinone， tanshinone Ⅱ A ， tanshinone Ⅰ， senkyunolide A， ferulic acid） in the Heat-clearing and symptom-relieving formula were determined by high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）. Using the contents of the aforementioned components as variables， cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were conducted using OriginPro 2024 software and SIMCA 14.1 software； marker components affecting the quality of the Heat-clearing and symptom-relieving formula were then screened based on the criteria of variable importance in the projection （VIP） value＞1 and P ＜0.05. The comprehensive evaluation of 20 batches of samples was carried out using the entropy weight-technique for order preference by similarity to ideal solution（TOPSIS） and grey correlation analysis （GCA） methods. RESULTS The contents of the above 11 components were 7.993-72.866， 4.542-31.228， 727.666-1 901.884， 496.846-1 293.279， 1 995.501-6 779.150， 54.500-241.280， 150.302-304.339， 79.698-189.206， 257.118-682.418， 5.498-21.687， 7.524-26.935 μg/g. CA， PCA and OPLS-DA results showed that 20 batches of samples were grouped into 2 categories. Q1， Q3， Q4， Q7-Q9， Q12， Q15， Q16 were grouped into one category， and the rest were grouped into another category； VIP values of ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin were all greater than 1 （ P ＜0.05）. Both the entropy weight-TOPSIS and GCA methods showed that the samples ranked in the top 11 according to the euclidean distance and relative correlation degree were Q2， Q5， Q6， Q10， Q11， Q13， Q14， Q17-Q20. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate and highly sens itive. Combined with chemical pattern recognition analysis， entropy weight-TOPSIS and GCA methods， this method can be used to evaluate the quality of the Heat-clearing and symptom-relieving formula. Ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin may be the marker components that affect the quality of this formula. The overall quality of 11 batches of the Heat-clearing and symptom-relieving formula， including Q17， is relatively superior.

Circular RNAs (circRNAs) represent a distinct group of RNA molecules produced through back-splicing of precursor mRNAs. Their covalently closed structure, which lacks both a 5′ cap and a poly(A) tail, renders them highly resistant to exonucleolytic degradation and contributes to their remarkable intracellular stability. Although circRNAs were historically viewed as noncoding transcripts, accumulating evidence indicates that certain circRNAs can undergo translation under appropriate molecular contexts. Two major modes of noncanonical translation have been described so far: initiation mediated by internal ribosome entry sites (IRESs) and translation triggered by N6-methyladenosine (m6A) modification. Recent studies have revealed that, beyond their canonical classification as non-coding RNAs, circRNAs can give rise to functional peptides through cap-independent translational mechanisms. Accumulating evidence indicates that circRNA-encoded peptides participate in key biological processes during tumor initiation and progression by modulating tumor-associated signaling pathways and protein-protein interaction networks. Functionally, these peptides may promote tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition, while others exert tumor-suppressive effects by inhibiting oncogenic signaling pathways or interfering with critical protein interactions. Their dual and context-dependent functions highlight the complexity of circRNA-mediated regulation and suggest that these translation products participate in multiple layers of tumor initiation and progression. In this review, we synthesize current knowledge regarding the molecular mechanisms that enable circRNAs to be translated, with particular attention to IRES-driven initiation, m6A-dependent regulation, ribosome accessibility, and the structural determinants required for translation competence. We further summarize well-characterized circRNA-encoded peptides and discuss how they influence tumor-associated signaling networks. In addition, we examine the potential translational applications of these peptides, including their value as diagnostic indicators, prognostic markers, or therapeutic entry points. Their inherent sequence stability, relative expression specificity, and detectability in clinical specimens make circRNA-derived peptides promising candidates for future biomarker and therapeutic development. Overall, circRNA translation research is reshaping our understanding of RNA function and offers new perspectives for studying tumor biology. We propose that expanding investigations into circRNA-encoded peptides will not only improve the mechanistic resolution of cancer research but may also pave the way for innovative strategies in precision oncology, including RNA-based therapeutics and peptide-targeting interventions.

Circular RNAs (circRNAs) represent a distinct group of RNA molecules produced through back-splicing of precursor mRNAs. Their covalently closed structure, which lacks both a 5′ cap and a poly(A) tail, renders them highly resistant to exonucleolytic degradation and contributes to their remarkable intracellular stability. Although circRNAs were historically viewed as noncoding transcripts, accumulating evidence indicates that certain circRNAs can undergo translation under appropriate molecular contexts. Two major modes of noncanonical translation have been described so far: initiation mediated by internal ribosome entry sites (IRESs) and translation triggered by N6-methyladenosine (m6A) modification. Recent studies have revealed that, beyond their canonical classification as non-coding RNAs, circRNAs can give rise to functional peptides through cap-independent translational mechanisms. Accumulating evidence indicates that circRNA-encoded peptides participate in key biological processes during tumor initiation and progression by modulating tumor-associated signaling pathways and protein-protein interaction networks. Functionally, these peptides may promote tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition, while others exert tumor-suppressive effects by inhibiting oncogenic signaling pathways or interfering with critical protein interactions. Their dual and context-dependent functions highlight the complexity of circRNA-mediated regulation and suggest that these translation products participate in multiple layers of tumor initiation and progression. In this review, we synthesize current knowledge regarding the molecular mechanisms that enable circRNAs to be translated, with particular attention to IRES-driven initiation, m6A-dependent regulation, ribosome accessibility, and the structural determinants required for translation competence. We further summarize well-characterized circRNA-encoded peptides and discuss how they influence tumor-associated signaling networks. In addition, we examine the potential translational applications of these peptides, including their value as diagnostic indicators, prognostic markers, or therapeutic entry points. Their inherent sequence stability, relative expression specificity, and detectability in clinical specimens make circRNA-derived peptides promising candidates for future biomarker and therapeutic development. Overall, circRNA translation research is reshaping our understanding of RNA function and offers new perspectives for studying tumor biology. We propose that expanding investigations into circRNA-encoded peptides will not only improve the mechanistic resolution of cancer research but may also pave the way for innovative strategies in precision oncology, including RNA-based therapeutics and peptide-targeting interventions.

AIM To investigate the tumor-suppressive mechanism of Guiqi Yiyuan Extract combined with cisplatin in Lewis lung cancer mice.METHODS Ten intact C57BL/6J mice were assigned to the blank group.Sixty additional mice were developed into Lewis lung cancer models bearing transplanted tumor and subsequently allocated into the model group,the cisplatin group(5 mg/kg),the high-dose Guiqi Yiyuan Extract group(6.6 g/kg),and the low-dose,medium-dose and high-dose Guiqi Yiyuan Extract combined with cisplatin group(1.6,3.3,6.6 g/kg+5 mg/kg),with 10 mice in each group.Mice in the blank and model groups received saline via daily gavage,while treatment groups were administered Guiqi Yiyuan Extract orally(once daily),and cisplatin injection intraperitoneally(once every other day).After 14 days of drug administration,mice were euthanized for endpoint analysis.The following assessments were conducted:general health status and body weight changes monitored throughout the study period;tumor excision and weighing for inhibition rate calculation;histopathological examination of tumors via hematoxylin-eosin(HE)staining;serum quantification of IL-1 β,IL-18 and HMGB1 by ELISA;ultrastructural analysis of tumor cell death using transmission electron microscopy(TEM);spatial localization of TXNIP and GSDMD-N in tumor sections via immunofluorescence(IF);and Western blot detection of TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD,GSDMD-N protein expressions in tumor tissues.RESULTS Compared to the model group,the cisplatin group and all combination therapy groups exhibited significant reduction in tumor weight(P＜0.05)and increased tumor suppression rate;enhanced tumor tissue necrosis with characteristic pyroptotic morphology;elevated serum levels of IL-1β,IL-18 and HMGB1(P＜0.05);and upregulated expressions of pyroptosis-associated proteins TXNIP,NLRP3,Caspase-1,cleaved Caspase-1,GSDMD and GSDMD-N(P＜0.05).The high dose combination group demonstrated optimal therapeutic efficacy(P＜0.05).CONCLUSION Guiqi Yiyuan Extract enhances cisplatin sensitivity,demonstrating synergistic anti-tumor effects in Lewis lung carcinoma-bearing mice.This combinatorial therapeutic effect likely involves modulation of the TXNIP/NLRP3/Caspase-1/GSDMD pathway.

Objective:To observe the clinical efficacy of acupuncture combined with Chinese medicine in the treatment of pediatric cough variant asthma(CVA)and the effects on clinical symptoms and inflammatory factor levels.Methods:A total of 136 children with CVA were randomly divided into a treatment group and a control group using the random number table method,with 68 cases in each group.Patients in the control group were treated with Chinese medicine,while patients in the treatment group were treated with Jiang Qi Ping Chuan(Qi-descending and asthma-relieving)acupuncture therapy in addition to the intervention of the control group.The clinical efficacy,cough severity,secondary symptom score,levels of inflammatory factors in induced sputum,and adverse reactions were observed after 4 weeks of treatment.Results:The total effective rate of the treatment group was higher than that of the control group,and the difference was statistically significant(P<0.05).The daytime cough score,nighttime cough score,and total cough score decreased significantly after treatment in both groups(P<0.05),and were notably lower in the treatment group than in the control group(P<0.05);the secondary symptom score and induced sputum inflammatory factor levels[interleukin(IL)-5,nerve growth factor(NGF),and substance P(SP)]decreased significantly after treatment in both groups(P<0.05),and were notably lower in the treatment group than in the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:The efficacy of acupuncture combined with Chinese medicine in the treatment of pediatric CVA is better than that of Chinese medicine alone;this combined method can rapidly relieve clinical symptoms and effectively inhibit inflammatory responses,with high safety.

Objective To investigate the mechanism of Astragali Complanati Semen in the prevention and treatment of hyperlipidemia;To provide theoretical basis for its clinical application.Methods The active components of Astragali Complanati Semen were retrieved and screened through TCMSP,TCMID and TDT databases to obtain the action targets of the active components.Hyperlipidemia targets were obtained through GeneCards,DisGeNET,and TTD databases,and the drug active component targets were intersected with hyperlipidemia targets.Cytoscape 3.9.1 software and STRING database were used to construct active component-target network and protein-protein interaction network,screening for major active components and core targets.GO and KEGG pathway enrichment analysis was performed using the DAVID database,and the CB-Dock platform was used for molecular docking.HepG2 cells were induced to construct a high-fat cell model using oleic acid and palmitic acid,and intervened with Astragali Complanati Semen freeze-dried powder solution.The mRNA expression of the core target was detected by RT-qPCR.Results A total of 10 active components of Astragali Complanati Semen and 67 potential action targets of hyperlipidemia were identified,involving signaling pathways such as AGE-RAGE,lipid metabolism,HIF-1,etc.Experimental results showed that intervention with Astragali Complanati Semen could reduce lipid accumulation in the high-lipid cell model,with an optimal intervention concentration of 500 μg/mL;RT-qPCR revealed significant down-regulation of TNFα,IL6,AKT1,PPARG,and other genes after intervention with Astragali Complanati Semen.Conclusion Astragali Complanati Semen exerts lipid-regulating effects through multiple targets and pathways,providing a basis for its application in the prevention and treatment of hyperlipidemia.

Objective:To develop a convolutional neural network model of whole slide imaging of cerebrospinal fluid cells for rapid and accurate identification and classification of tumor cells in cerebrospinal fluid.Methods:A total of 8 692 cerebrospinal fluid cytology smears from Huashan Hospital Affiliated to Fudan University from January 2nd, 2019, to December 27th, 2024. As randomly assigned, the training set included 4 941 benign and 1 745 malignant samples, while the validation set comprised of 1 368 benign and 638 malignant samples. Whole-slide digital images were acquired using a cytopathology scanner, cells (clusters) were annotated for classification, and a deep learning model was constructed via tiled image patches for cell detection and classification. Model performance was evaluated using accuracy, sensitivity, specificity, and other indicators. The classification efficiency of manual microscopy was compared.Results:The model achieved a mean precision of 96.75% for cerebrospinal fluid cell classification. For malignant tumor cells, the classification accuracy was 96.61% (mAP=98.36%, AUC=0.97). Subtype classification accuracies for epithelial/epithelioid tumors and small round cell tumors were 97.13% (AUC=0.98) and 95.58% (AUC=0.93), respectively. Compared with manual microscopy, which took (9.70±0.82) minutes for classifying 200 cells, (18.27±1.21) minutes for 500 cells, and often exceeded 60 minutes or infeasible for full slides, the AI model took (3.46±0.49) seconds for 200 cells, (6.76±0.82) seconds for 500 cells, and a median of 48.57 seconds for full slides ( P<0.001), representing an efficiency improvement of approximately 161-170 times, significantly enhancing diagnostic efficiency. Conclusion:This fully automated hierarchical deep learning model enables efficient and accurate tumor cell identification and classification in CSF, providing an effective auxiliary tool for the rapid diagnosis of meningeal carcinomatosis.