Liver cancer (LC) remains one of the most prevalent tumors globally. Despite considerable advancements in its clinical treatment in recent years, the global burden of this disease is projected to increase. According to World Health Organization statistics, the number of LC deaths worldwide in 2022 was 760,000, ranking third among all cancers. Therefore, there is an urgent need to delve deeper into the realms of LC diagnosis, prognosis, and treatment. Proteomics, as an emerging technology leveraging mass spectrometry (MS)-based protein identification, liquid chromatography separation, and bioinformatics-driven data integration, enables the systematic characterization of proteome dynamics to address critical challenges in LC research. These challenges include the discovery of diagnostic and prognostic biomarkers as well as therapeutic targets. By scrutinizing the expression of specific proteins in both normal and cancerous tissues through high-throughput protein microarrays, researchers can uncover novel biomarkers. The use of these biomarkers alone or in combination with established ones holds the potential to significantly advance the fields of LC diagnosis, prognosis, and treatment. In general, the application of proteomics has significantly promoted the development of LC research. In this review, we summarized the latest advancements in the application of proteomics in LC, with a particular focus on diagnosis, prognosis, and treatment. We also concluded selected protein markers, aiming to offer guidance for further applications and present additional therapeutic targets for LC.

The liver is one of the important metabolic organs in the body, and liver diseases are also one of the major public health issues globally. Currently, the lack of models that accurately simulating human physiology and pathology is the key challenge in liver disease research, and the emerging of organoid technology is an excellent solution to this challenge. Organoids are three-dimensional cellular structures cultured in vitro that can mimic the structure and function of real organs while maintaining genetic stability. The development of organoids has provided possibilities for personalized medicine and precision therapy and has become a key tool in the research and treatment of liver diseases. The authors focuse on the application and development of organoids in liver disease research, while also emphasizing their limitations and future prospects.

AIM:To compare the degree of disease simulation between the two mouse models of acute exacer-bation of chronic obstructive pulmonary disease(AECOPD)using intranasal instillation of lipopolysaccharide(LPS)and fine particulate matter(PM2.5)for 3 d based on exposure to cigarette smoke(CS)for 90 d.METHODS:Thirty-two male C57BL/6 mice were randomly divided into 4 groups:control group(n=8),CS group(n=8),CS+PM2.5 group(n=8)and CS+LPS group(n=8).The AECOPD models in CS+PM2.5 and CS+LPS groups were established by CS exposure combined with intranasal PM2.5 and LPS instillation.Lung function,lung pathology and airway goblet cell hyperplasia using histologi-cal staining were measured.To evaluate the degree of lung inflammation and mucus secretion in mice,the prorein levels of mucin 5AC(MUC5AC),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the bronchoalveolar lavage fluid(BALF)were detected by ELISA and total white blood cell(WBC)counts and the BALF differential cell counts(neutro-phils,macrophages,lymphocytes)were detected by Giemsa staining.RESULTS:In CS group,lung function decreased(P<0.05),and bronchial inflammation index increased(P<0.01),airway goblet cell hyperplasia and airway collagen de-position were significant(P<0.01),total WBC count and differential cell count in the BALF increased(P<0.05),MUC5AC and inflammatory factor IL-6 and TNF-α levels increased(P<0.05),compared with control group.Compared with CS group,lung function decreased(P<0.05),the bronchial inflammation index increased(P<0.01),airway goblet cell hyperplasia and airway collagen deposition were significant(P<0.01),total WBC count and differential cell count in the BALF increased(P<0.05),and MUC5AC and inflammatory factor IL-6 and TNF-α levels increased(P<0.05)in CS+PM2.5 and CS+LPS groups.Compared with CS+PM2.5 group,lung function decreased(P<0.05),the bronchial inflamma-tion index increased(P<0.01),airway goblet cell hyperplasia and airway collagen deposition were significant(P<0.01),total WBC count and differential cell count in the BALF increased(P<0.05),and MUC5AC and inflammatory factor IL-6 and TNF-α levels increased(P<0.05)in CS+LPS group.CONCLUSION:Exposure to CS combined with both intrana-sal PM2.5 and LPS instillation allowed for establishing AECOPD models in mice,and CS exposure combined with intrana-sal LPS instillation better simulated AECOPD characteristics.

Objective To conduct an in-depth analysis and feature extraction of the transcriptomics data of 10 types of cancers in order to realize the staging diagnosis of cancer samples.Methods The transcriptomics data of the top 10 cancers having the highest incidence were amassed from the UCSC Xena website,which comprised 4 938 samples and 59 428 genes.With the aid of variational autoencoder,we developed an incremental feature ranking and selection variational autoencoder(IFRSVAE)based on feature importance ranking and incorporating the masking algorithm and the Incremental Feature Selection(IFS).Subsequently,the performance efficiency of our IFRSVAE model was evaluated in conjunction with Random Forest(RF),Support Vector Machine(SVM),and eXtreme Gradient Boosting(XGboost),and it was also compared with other methods.Results Our research extracted 21 features for the ensuing classification.In comparison to the conventional variational autoencoder,recursive feature elimination,and Lasso regression models,the IFRSVAE model attained more favorable performance across all 3 classifiers(highest AUC value,and well performed other indicators).Notably,the IFRSVAE-RF exhibited the most outstanding performance,with an AUC value reaching 85.49%(95%CI:83.24%～87.74%).Moreover,Shapley additive explanations(SHAP)interpretable model illustrated well contributions of the features in our model.Conclusion Our developed IFRSVAE shows certain effectiveness in feature extraction.The constructed IFRSVAE-RF model demonstrates relatively good performance in the task of cancer staging diagnosis,which providing a new and referable idea for research orientation of deep-learning-based diagnostic methods for cancer staging.

Objective:To elucidate the mechanism by which Clostridium butyricum alleviates atopic dermatitis (AD) from three aspects: immune cells, gut microbiota, and the metabolites of gut microbiota, short-chain fatty acids (SCFAs), and provide a theoretical reference for clinical probiotic-assisted treatment of AD. Methods:A model of 2, 4-dinitrochlorobenzene (DNCB)-induced AD was established using BALB/c mice. Three groups including control group, AD group, and Clostridium butyricum intervention group were set up with 20 mice in each group. The dermatitis score, scratching score, pathological conditions and mast cell infiltration at the lesion site, and the levels of cytokines related to Th1/Th2 and Th17/Treg as well as IgE levels in serum samples were analyzed. Gut microbiota was detected by 16S rRNA gene sequencing. The contents of SCFAs in mouse fecal samples were detected by gas chromatography-mass spectrometry. Spearman correlation analysis was performed to investigate the correlation between the cytokines related to Th1/Th2 and Th17/Treg, gut microbiota, and SCFAs. Comparisons between groups were performed using one-way analysis of variance with Turkey post hoc test correction. Results:Clostridium butyricum intervention down-regulated various inflammatory indexes and alleviated pathological changes in AD mice, elevated the levels of IFN-γ ( P<0.05) and IL-10 ( P<0.01), reduced the levels of IL-4, IL-17 and IgE ( P<0.01), and maintained the balance of Th1/Th2 ( P<0.01) and Th17/Treg ( P<0.001). Besides, the intervention improved intestinal dysbiosis by decreasing the abundance of conditionally pathogenic bacteria such as Prevotellaceae_ UCG-001 ( P<0.01) and increasing the abundance of beneficial bacteria such as Lachnospiraceae_ NK4A136_ group and norank_ f_ Oscillospiraceae ( P<0.05), and enhanced the production of SCFAs ( P<0.05). Correlation analysis showed that allergy-associated immune cytokines were strongly correlated with the composition of gut microbiota and the content of SCFAs. Conclusions:Clostridium butyricum may regulate the microbiota-SCFAs signaling response by inhibiting the colonization of harmful bacteria and increasing the abundance of beneficial bacteria. This, in turn, increases the level of SCFAs, decreases the number of pro-inflammatory cytokines, and maintains the balance of Th1/Th2 and Th17/Treg in the body. Therefore, Clostridium butyricum may alleviate allergic diseases.

Gastric cancer is a malignant tumor with high prevalence worldwide and limited therapeutic options.Chimeric antigen receptor T-cell(CAR-T)therapy has emerged as a promising approach for gastric cancer treatment;however,its application faces substantial challenges.This review provides comprehensive summary of the recent advances in CAR-T cell therapy for gastric cancer,systematic analysis of critical break throughs and core challenges from target discovery to clinical translation,and outlining of future perspectives.We describe the criter-ia for ideal target selection and highlight the current research landscape of major targets,including CLDN18.2 that demonstrated efficacy,and targets facing distinct challenges,including HER-2,CEA,EpCAM,and MUC1.This review also finely dissects three central barriers restrict-ing CAR-T cell efficacy,and discusses corresponding countermeasures:overcoming the immunosuppressive tumor microenvironment through strategies such as local delivery,armored CAR-T cells,and combination therapies;engineering approaches including affinity modula-tion and logic-gate designs to mitigate on-target/off-tumor toxicity;and optimization of manufacturing processes and reduction of costs via early leukapheresis,rapid production platforms,and universal CAR-T cell strategies.Future multidimensional,integrative,and innovative strategies are pivotal for achieving comprehensive break throughs in CAR-T cell therapy for solid tumors.

Objective:To investigate the clinical application of internal mammary perforator (IMP) as recipient vessels in immediate breast reconstruction using deep inferior epigastric perforator (DIEP) flap.Methods:The clinical data of 10 patients with early breast cancer who underwent DIEP for immediate breast reconstruction using IMP as the recipient vessels from January 2022 to December 2023 were analyzed. The number, position, and diameter of IMP, diameter of DIEP, the size of the flap, the operation time, surgical complications, cosmetic effect of breast, and patients' satisfaction were summarized and analyzed.Results:The number of IMPs was 2-3, and they were distributed in the second to the fourth ribs. The diameter of the IMP artery was (1.15±0.22) mm, and the diameter of the vein was (1.35±0.19) mm. The diameter of the DIEP was (1.55±0.28) mm, and that of its accompanying vein was (1.50±0.23) mm. The sizes of the flaps ranged from 10.0 cm×8.0 cm×3.0 cm to 12.0 cm×22.0 cm×4.0 cm, with an average of 20.5 cm×11.2 cm×2.8 cm. The weight of the flap was (389.1±51.5) g. The operation time was (574.8±68.1) min. All 10 cases of flaps survived. The reconstructed breasts were natural, soft, and symmetrical to the healthy side breasts. There was no obvious operative complication. The average BREAST-Q score of the patients was 93.5. No recurrence or metastasis was found during follow-up.Conclusions:Although technically difficult, using IMP as recipient vessels in DIEP flats for immediate breast reconstruction results in a low complication rate of the injuries in the internal mammary region. Under the premise of strictly adhering to the surgical indications, satisfactory results can be achieved, and it is safe and reliable.

Standardized research reporting is crucial for the translation of pharmacoepidemiology research findings,and visual reporting can significantly enhance the clarity,understandability,and transparency of research results.Based on the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition),this article systematically explains the key points for writing each component of a research report(including title,abstract,introduction,research methods,research results,discussion and conclusions,acknowledgments,conflict of interest statement,and references).This article also summarizes recognized international and domestic standards for pharmacoepidemiology research reporting,providing a reference for researchers.Furthermore,real-world cases will be used to demonstrate common forms of visualized reports and their interpretation methods.Finally,it further explores strategies for communicating research results.This study aims to provide pharmacoepidemiology researchers with detailed guidance on visually presenting research results and writing high-quality research reports,thereby enhancing the integrity and impact of their research.

Objective To investigate the role of STK4-AS1 in regulating the proliferation,invasion,and migration of esophageal squamous cell carcinoma(ESCC)cells through the MYG1/Notch signaling pathway.Methods Quantitative real-time PCR(qRT-PCR)was used to detect the expression of STK4-AS1 in ESCC cells.MTS assay,wound healing and Transwell assay were conducted to explore the proliferation,migration,and invasion abilities in each group in Eca109 and Kyse150 cells.mRNA sequencing(mRNA-seq)was used to detect the down-stream target genes of STK4-AS1.KEGG functional enrichment analyses were used to predict the possible biological processes and signaling pathways.qRT-PCR and western blot were performed to identify mRNA expression of MYG1 and the key downstream transcription factors HES1,HES5,and HEY1 of the Notch signaling pathway,as well as the protein expression of NICD1.Co-transfection plasmids(for over-expressing STK4-AS1 and MYG1)were used to detect the mRNA expression of HES1,HES5,and HEY1 and the protein expression of NICD1 which acted as the key downstream transcription factors in the Notch signaling pathway,as well as the effects on the proliferation,migration,and invasion abilities of ESCC cells.Results The expression of STK4-AS1 was decreased in ESCC cell lines(P<0.01).Over-expression of STK4-AS1 inhibited the proliferation,migration and invasion abilities in Eca109 and Kyse150 cells(P<0.05).STK4-AS1 negatively regulated the expression of MYG1(P<0.01),and the expression of MYG1 was increased in ESCC cell lines(P<0.01).Over-expression of MYG1 could partially reverse the effect of STK4-AS1 on the malignant biological behavior of Eca109 and Kyse150 cells(P<0.05),as well as the mRNA expressions of HES1,HES5,and HEY1 and the protein expression of NICD1(P<0.05).Conclusion STK4-AS1 affects the malignant biological behaviors of ESCC through the MYG1/Notch signaling pathway.

Objective:To elucidate the mechanism by which Clostridium butyricum alleviates atopic dermatitis (AD) from three aspects: immune cells, gut microbiota, and the metabolites of gut microbiota, short-chain fatty acids (SCFAs), and provide a theoretical reference for clinical probiotic-assisted treatment of AD. Methods:A model of 2, 4-dinitrochlorobenzene (DNCB)-induced AD was established using BALB/c mice. Three groups including control group, AD group, and Clostridium butyricum intervention group were set up with 20 mice in each group. The dermatitis score, scratching score, pathological conditions and mast cell infiltration at the lesion site, and the levels of cytokines related to Th1/Th2 and Th17/Treg as well as IgE levels in serum samples were analyzed. Gut microbiota was detected by 16S rRNA gene sequencing. The contents of SCFAs in mouse fecal samples were detected by gas chromatography-mass spectrometry. Spearman correlation analysis was performed to investigate the correlation between the cytokines related to Th1/Th2 and Th17/Treg, gut microbiota, and SCFAs. Comparisons between groups were performed using one-way analysis of variance with Turkey post hoc test correction. Results:Clostridium butyricum intervention down-regulated various inflammatory indexes and alleviated pathological changes in AD mice, elevated the levels of IFN-γ ( P<0.05) and IL-10 ( P<0.01), reduced the levels of IL-4, IL-17 and IgE ( P<0.01), and maintained the balance of Th1/Th2 ( P<0.01) and Th17/Treg ( P<0.001). Besides, the intervention improved intestinal dysbiosis by decreasing the abundance of conditionally pathogenic bacteria such as Prevotellaceae_ UCG-001 ( P<0.01) and increasing the abundance of beneficial bacteria such as Lachnospiraceae_ NK4A136_ group and norank_ f_ Oscillospiraceae ( P<0.05), and enhanced the production of SCFAs ( P<0.05). Correlation analysis showed that allergy-associated immune cytokines were strongly correlated with the composition of gut microbiota and the content of SCFAs. Conclusions:Clostridium butyricum may regulate the microbiota-SCFAs signaling response by inhibiting the colonization of harmful bacteria and increasing the abundance of beneficial bacteria. This, in turn, increases the level of SCFAs, decreases the number of pro-inflammatory cytokines, and maintains the balance of Th1/Th2 and Th17/Treg in the body. Therefore, Clostridium butyricum may alleviate allergic diseases.