Hepatocellular carcinoma (HCC), the most common form of liver cancer, remains poorly understood in terms of its underlying mechanisms. The protein GNAI2 has been shown to regulate the transcription of multiple biomolecules and is thought to contribute to the onset and progression of several cancers. This study aimed to uncover how GNAI2 influences HCC development at the molecular level. To explore the expression patterns and prognostic significance of GNAI2, various resources including TIMER2.0, TCGA, GEO, and HPA were employed. The examination of clinical data from TCGA enabled the investigation of the relationships between GNAI2 levels and the clinical-pathological characteristics of HCC patients. The functional roles of GNAI2 in HCC were characterized using GO and KEGG analyses. Furthermore, the influence of GNAI2 expression on immune cell infiltration was evaluated utilizing the TISIDB and TIMER2.0 databases. Concurrently, single-cell RNA sequencing data sourced from the TISCH2 database offered valuable insights into the expression of GNAI2 within immune cells. Investigations into the role of GNAI2 in modulating drug responsiveness in HCC were also undertaken. Experimental validations were conducted to ascertain the biological roles and molecular mechanisms of GNAI2 in HCC. The findings indicate that GNAI2 is consistently upregulated in HCC tissues. Survival analysis pointed to a connection between higher GNAI2 levels and shorter overall survival in HCC patients, hinting at its possible use as a diagnostic indicator. GNAI2 expression was notably associated with T staging. Functional enrichment of GNAI2-related genes suggested that GNAI2 may drive HCC progression through the PI3K/AKT signaling pathway. Moreover, GNAI2 appeared to have a clear impact on immune infiltration within tumors, especially on M2 macrophages. Drug sensitivity analysis indicated a link between many of the tested drugs and PI3K/AKT inhibitors. Knocking down GNAI2 in HCCLM3 and MHCC97L cells led to reduced cell migration, proliferation, and invasion, increased apoptosis, and lower phosphorylation levels in the PI3K/AKT pathway. Taken together, these findings suggest that GNAI2 could serve as a useful biomarker for HCC diagnosis and prognosis. Silencing GNAI2 noticeably weakened the ability of HCC cells to grow, move, and invade, likely by modulating the PI3K/AKT signaling axis.

Ovarian cancer (OC) is a lethal malignancy with limited treatment options. While p53-associated cellular protein-testes derived (PACT) has been implicated in cellular stress responses, its role in OC progression and the regulation of ferroptosis remains unclear. The functional role of PACT was examined in A2780 and OVCAR-3 cells through siRNA-mediated knockdown and overexpression. The CCK-8 assay was used to evaluate cell proliferation, and the transwell assay was used to detect cell migration and invasion. Ferroptosis was assessed by measuring cell death, iron content, malondialdehyde (MDA), reactive oxygen species (ROS), and the expression of key proteins (SLC7A11, GPX4). Molecular mechanisms were investigated via co-immunoprecipitation (Co-IP), ubiquitination assays, and analysis of subcellular localization. In vivo validation was conducted using a xenograft model in BALB/c nude mice. The results showed that PACT knockdown significantly inhibited the proliferation, migration, and invasion of OC cells. It also promoted ferroptosis, as indicated by elevated iron accumulation, lipid peroxidation, and ROS levels, along with reduced SLC7A11 and GPX4 expression-effects that were reversed by ferrostatin-1. PACT was found to enhance TERT expression and telomerase activity via the Keap1-Nrf2 pathway by facilitating Keap1 ubiquitination and degradation, which promoted Nrf2 nuclear translocation. Importantly, Nrf2 knockdown abolished PACT-mediated TERT upregulation. In vivo, PACT silencing suppressed tumor growth and induced ferroptosis. In conclusion, PACT promotes OC progression by suppressing ferroptosis and enhancing malignant phenotypes through the Keap1-Nrf2-TERT axis. These findings suggest that targeting PACT may represent a promising therapeutic strategy for OC.

Objectives: To fabricate polysialic acid (PSA)-modified liposomes co-loaded with doxorubicin (DOX) and indocyanine green (ICG) for synergistic chemotherapy and photothermal therapy, and to enhance the anti-cervical cancer efficacy of liposomes via neutrophil targeting. Methods: PSA-DOX/ICG liposomes (PSA-DOX/ICG-Lip) were prepared by microfluidic technology. The physicochemical properties, including drug encapsulation efficiency (EE), loading capacity (LC), particle size, polydispersity index (PDI), zeta potential, and stability, were systematically characterized. The in vitro anti-tumor activity was evaluated using cellular uptake, apoptosis assays, reactive oxygen species (ROS) detection, and a cell scratch test in HeLa and C33a cells. The in vivo therapeutic efficacy was verified using a nude mouse xenograft model of cervical cancer combined with histopathological analysis. Results: Microfluidic preparation yielded PSA-DOX/ICG-Lip with favorable physicochemical properties: the EE and LC of DOX were 96.52 ± 0.43% and 8.70 ± 0.04%, respectively, while those of ICG were 90.72 ± 1.10% and 0.82 ± 0.02%. The average particle size was 92.68 ± 1.14 nm with a PDI of 0.04 and a zeta potential of −9.66 ± 0.46 mV. The liposomes maintained good stability in terms of EE, particle size, PDI, and zeta potential after 28 days of storage at 4 °C and room temperature, with PSA modification significantly reducing the drug leakage rate. In vitro drug release studies showed that 808 nm laser irradiation triggered a significant increase in drug release from the liposomes. ICG encapsulated in liposomes mediated localized photothermal heating, and PSA targeting precisely confined the therapeutic effect to the tumor site, minimizing damage to adjacent normal tissues. In vitro experiments demonstrated that PSA-DOX/ICG-Lip, combined with laser irradiation, significantly enhanced cellular uptake, elevated intracellular ROS levels, inhibited cancer cell migration, and induced apoptosis. In vivo studies confirmed that this formulation markedly suppressed tumor growth in nude mice, with a tumor inhibition rate of 81.5%, and exhibited good biocompatibility without obvious organ toxicity. Conclusions: The microfluidically prepared PSA-DOX/ICG-Lip possesses high drug encapsulation efficiency, uniform particle size, good stability and sustained drug release properties. It can efficiently convert light energy into thermal energy, target neutrophils to enhance the affinity for cervical cancer cells, and exert a synergistic anti-tumor effect via the combination of chemotherapy and photothermal therapy, which provides a promising nanoplatform for the precise treatment of cervical cancer.

Background: In China, the human papillomavirus (HPV) vaccine has not yet been included in the national immunization program (NIP). Nevertheless, several provinces and municipalities have launched pilot HPV vaccination programs targeting female adolescents in secondary schools since 2021. This study aimed to explore the roles of key stakeholders in the decision-making process regarding HPV vaccination and to provide recommendations for future promotional strategies. Methods: Semi-structured interviews were conducted with stakeholders from Shanghai, Jiangsu, Zhejiang, and Anhui, including public health professionals, school teachers, and parents of adolescent girls. The interview framework comprised both fixed-choice and open-ended questions. Key topics addressed included: (1) the support for prioritizing HPV vaccination within NIP, (2) the influence of stakeholders on vaccination decisions, and (3) suggestions for enhancing vaccination promotion. Results: Eighty-three people participated in the study. Only 30 % of respondents believed HPV vaccination should be prioritized in the NIP, citing concerns about public perception, cultural values, and financial feasibility. Health and class teachers were found to have a substantial impact on the vaccination choices of parents and their daughters. To boost vaccination uptake, a comprehensive approach that includes stakeholder collaboration, educational campaigns, digital technology, and improved access to immunization services was proposed. Conclusion: This research provides valuable insights into the decision-making processes surrounding HPV vaccination and advocacy efforts aimed at girls aged 9-14 years. The findings serve as important references for future initiatives aimed at promoting awareness and uptake of the vaccine.

BACKGROUND AND AIMS:Ketamine and morphine are among the most commonly abused drugs. Ketamine is classified as a new psychoactive substance, while morphine represents the opioid class. These two substances may exhibit synergistic or antagonistic effects in their pharmacological actions, and their combined abuse could lead to more severe health risks, such as respiratory depression. Therefore, simultaneous detection is crucial for comprehensive monitoring of drug abuse. This study developed a test strip capable of detecting both ketamine (KET) and morphine (MOP) in serum, utilizing Raman spectroscopy technology to meet the needs of various application scenarios. METHODS:A mixture of Raman microsphere-labelled KET and MOP antibodies was mixed with a mixed standard solution of KET and MOP and added dropwise to the sample pad of the prepared KET and MOP co-assay test strip, chromatographed for 10 min, and then the Raman spectra and Raman signals at the T-line were detected using a Raman spectrometer. RESULTS:The KET and MOP showed good correlation with the Raman signal response values in the concentration ranges of 0.0-100.0 ng/mL and 0.0-4.0 ng/mL, and the limits of detection (LODs) were 1.1986 ng/mL and 0.0113 ng/mL with the coefficients of variation (CV) of less than 10 %, the recoveries were in the ranges of 90 %-110 %, and interfering substances had no effect on the detection results. CONCLUSION:In this study, we developed a method for the quantitative detection of KET and MOP based on the spectroscopic properties of Raman microsphere (R-Sphere) and the principle of competitive immunity, which has the advantages of simple operation, rapidity, high sensitivity, and the possibility of combined detection, which makes the detection efficiency greatly improved.

In recent years, the SERS-LFIA platform has gained significant traction in in vitro diagnostics. However, a comprehensive review of its advancements and applications is still lacking. This review first employing a bibliometric approach to analyze research trends. It then outlines strategies to enhance sensitivity, focusing on Raman reporter molecules, SERS tags, coupling methods, detection instruments. Additionally, the review explores the use of SERS-LFIA for diagnosing multiple disease biomarkers, highlighting its potential to improve diagnostic accuracy. The review also synthesizes the application of multimodal SERS-LFIA technology, integrating signals such as colorimetric, magnetic, photothermal, fluorescent, and catalytic modalities. This approach enhances detection versatility and broadens diagnostic capabilities. Furthermore, it examines the current patent landscape, providing insights into the technology's commercial and technological progress. Lastly, the review discusses ongoing challenges, including stability and reproducibility and quantitative detection, while suggesting directions for future research. In summary, this review consolidates the latest advancements in SERS-LFIA technology for in vitro diagnostics over the past decade. Anticipated to furnish a robust scientific foundation and theoretical underpinning for the advancement of SERS-LFIA technology, this endeavor aims to enhance its efficacy in clinical diagnostics.

BACKGROUND:Papillary thyroid cancer (PTC) is among the most prevalent forms of endocrine malignancy with a rapid rise in incidence rates worldwide; however, the composition and characteristics of its immune microenvironment is poorly understand. Here, this work investigated the precise function of Dipeptidyl peptidase 4 (DPP4) in tumor-infiltrated T cells within PTC by investigating its role in cytokine-mediated signaling pathways. METHODS:TCGA and GEO data as well as human PTC specimens confirmed the expression of DPP4 in PTC. The CIBERSORT and TIMER tool were used to analyze the distribution of tumor-infiltrating immune cells in PTC. CD8+ T cells from PTC patient's peripheral blood were cultured and used in a three-dimensional model for direct co-culture with PTC tumors to investigate DPP4 function. RESULTS:Bioinformatic analyses has uncovered a significant upregulation of DPP4, which enhances the survival and migration of PTC cells in vitro. DPP4 upregulation significantly correlated with advanced grades, stages, and poor progression-free survival. DPP4 influences immune function and the exhaustion of CD8+ T cells through the IL13-IL13RA2 axis. The inhibition of DPP4 reduces CD8+ T cell exhaustion and IL13 secretion, while also blocking the IL13-IL13RA2 axis, thereby promoting the mesenchymal-to-epithelial transition of PTC cells. CONCLUSION:Blocking DPP4 leads to the conversion of exhausted CD8+ T cells with decreased IL13 level, resulting in downregulation of IL13RA2 to promote mesenchymal-to-epithelial transition of PTC cells. This highlights DPP4 as a potential therapeutic target, particularly between CD8+ T cells and PTC cells via IL13-IL13RA2 axis, and represents a novel avenue for combined immunotherapy in PTC.

BACKGROUND:Colorectal Cancer (CRC) is a prevalent malignant tumor with a high incidence and mortality rate worldwide. Despite the availability of various treatment options, CRC remains a significant health challenge due to its complexity and heterogeneity. The objective of this study is to investigate the role of PIGK in CRC and to elucidate the underlying mechanisms that contribute to its impact on the disease. RESULTS:Our analysis of the TCGA database revealed that PIGK expression is significantly elevated in CRC tissues compared to normal tissues, with higher expression levels correlating with improved patient prognosis. In vitro experiments demonstrated that PIGK can suppress the proliferation of CRC cells by promoting autophagy. Further mechanistic exploration showed that PIGK upregulates the expression of ABHD5, influencing lipophagy. We also identified the pivotal role of the PIGK-ABHD5-PPARα signaling pathway in the regulation of lipophagy. Tumorigenesis experiments in nude mice confirmed PIGK's inhibitory effect on tumor growth and its role in modulating lipophagy through ABHD5. CONCLUSIONS:In summary, our findings not only highlight PIGK as a novel molecular target in CRC but also suggest that targeting the PIGK-ABHD5-PPARα signaling axis could offer a promising therapeutic strategy. By influencing lipophagy, PIGK presents a potential avenue for improving CRC treatment outcomes, which could have significant implications for patient management and the development of new treatment protocols.

Meropenem (MEM), a broad-spectrum carbapenem antibiotic, has a narrow therapeutic window and high interindividual variability. Existing detection methods are often limited by complex operations, long turnaround times, and inadequate sensitivity. To overcome these challenges, this study developed a novel lateral flow immunochromatographic assay (LFIA) platform with synchronous triple-signal output for rapid and accurate MEM detection. A fluorescent membrane sensor was fabricated by integrating Rhodamine 6G (R6G) as a fluorescence donor into a nitrocellulose membrane. Isoniazid (INH, code 064) was selected as the optimal Raman reporter, enabling the synthesis of Raman nanospheres (R-Sphere064) capable of delivering colorimetric, surface-enhanced Raman scattering (SERS), and background fluorescence-quenched immunochromatographic assay (bFQICA) signals simultaneously. Density functional theory (DFT) calculations indicated that the adsorption of INH on the nanosphere surface involves an electron injection effect that promotes charge transfer, with an adsorption energy of -0.19 eV and a charge transfer amount of 0.14 e. The characteristic SERS peak at 1006 cm⁻¹ was attributed to the breathing vibration of the pyridine ring in INH. With a 15 min detection time, the platform offers LODs of 0.8 ng mL− 1 (SERS) and 0.8 ng mL− 1 (bFQICA), a shared LoQ of 1 ng mL− 1, and a linear range of 1–10 ng mL− 1. It demonstrated high stability, reproducibility, and specificity. Validation using 22 clinical samples showed strong correlation with standard clinical methods. The platform can be easily adapted to monitor other therapeutic drugs by replacing the specific antibody, offering a universal solution for clinical therapeutic drug monitoring (TDM).

ObjectiveTo describe the prevalence of thyroid nodules (TNs), their ultrasonographic characteristics, and the cancer risk assessment using the Thyroid Imaging Reporting and Data System (TIRADS) in a natural population, while also exploring their association with multiple metabolic disorders. This study aims to provide insight into the disease burden of TNs in the coastal area of Southeast China.DesignA cross-sectional study.Setting and participantsA total of 6221 participants from the baseline survey of the Fuqing Cohort Study, an ongoing population-based study in a coastal city of Southeast China, were included.Primary and secondary outcome measuresTNs and its detailed ultrasonographic characteristics, risk grading in TIRADS, and metabolic factors.ResultsThe age- and sex-standardized prevalence of TNs was found to be 67.2%, with a higher prevalence observed in females and an increase with age. Additionally, multiple, solid, and < 10 mm TNs were common. Approximately 39.2% of participants were diagnosed with grade 3, while 2.3% were classified as grade ≥ 4a according to TIRADS. Metabolic syndrome was associated with TNs, but this association was significant only in females. The relationship between metabolic disorders and the characteristics and grade of TNs in TIRADS varied by sex.ConclusionThe prevalence of TNs in the coastal area of Southeast China is notable, with 2.3% of the population classified as grade ≥ 4a in TIRADS, indicating a high risk of cancer and necessitating further assessment for thyroid cancer. The association between TNs and metabolic disorders varies by sex and requires further confirmation.

Abstract Objectives To investigate predictive biomarkers that could be used to identify patients’ response to treatment, plasma metabolomics and proteomics analyses were performed in Kashin-beck disease (KBD) patients treated with Fufang Duzhong Jiangu Granules (FDJG). Methods Plasma were collected from twelve KBD patients before treatment and one month after FDJG treatment. LC-MS was employed for plasma metabolomics profiling, while the olink inflammatory protein panel was used for obtaining inflammatory protein profiles. Patients were classified into responders and non-responders based on drug efficacy after one-month treatment. Enrichment analyses of differential metabolites and proteins of the responders at baseline and after treatment were conducted to study the mechanism of drug action. Differential metabolites and proteins between the two groups were screened as biomarkers to predict drug efficacy. ROC curve was used to evaluate the prediction accuracy of biomarkers. Results The changes of metabolites and inflammatory proteins in responders after treatment reflected the mechanism of FDJG treatment for KBD, which may act on glycerophospholipid metabolism, D-glutamine and D-glutamate metabolism, nitrogen metabolism, and NF-kappa B signaling pathway. We identified three metabolites as potential predictors: N-undecanoylglycine, beta-aminopropionitrile, and PC (18:3(6Z,9Z,12Z)/20:4(8Z,11Z,14Z,17Z)). For inflammatory protein, IL-8 was identified as predictive biomarkers to detect responders. Additionally, IL-8 persisted significant in comparison responders to non-responders after one month of therapy. Combined use of these four biomarkers had high predictive ability (AUC = 0.972). Conclusion Metabolomics and olink proteomics provide new insights for precision therapy. In our study, IL-8 may be a novel stable potential biomarker for predicting the efficacy of FDJG in KBD treatment.

Gastric cancer is a common malignant tumor with a high mortality rate. Abnormal APOBEC3B (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3B) expression increases tumor susceptibility. However, the exact molecular mechanism of APOBEC3B expression in the development of gastric cancer is still unknown. We investigated the effect of APOBEC3B on the malignant biological behavior of gastric cancer cells and discussed the role of APOBEC3B in the development and progression of gastric cancer. APOBEC3B protein levels were measured in 161 gastric cancer samples using western blotting and immunohistochemistry. Both in vitro and in vivo assays were performed, and molecules were analyzed using bioinformatics analysis and western blotting. APOBEC3B was overexpressed in gastric cancer. Moreover, APOBEC3B significantly enhanced cell proliferation in vitro and tumorigenicity in vivo. Regarding the underlying mechanism, APOBEC3B promoted the proliferation of gastric cancer cells by upregulating P53, MCM2 (minichromosome maintenance protein 2), and cyclin D1. Our results suggest that APOBEC3B is involved in cancer progression, providing a new theoretical basis for the prevention and treatment of gastric cancer.

To explore the distribution of γδT17/Th17/Tc17 cells in the peripheral blood of Uygur patients with chronic lymphoblastic leukemia (CLL) and clinical significance.

Background:The systematic comparison of cancer survival between China and the USA is rare. Here we aimed to assess the magnitude of survival disparities and disentangle the impact of the stage at diagnosis between a Chinese metropolitan city and the USA on cancer survival. Methods:We included 11,046 newly diagnosed cancer patients in Dalian Cancer Registry, China, 2015, with the follow-up data for vital status until December 2020. We estimated age-standardised 5-year relative survival and quantified the excess hazard ratio (EHR) of death using generalised linear models for all cancers and 20 individual cancers. We compared these estimates with 17 cancer registries' data from the USA, using the Surveillance, Epidemiology, and End Results database. We further estimated the stage-specific survival for five major cancers by region. Findings:Age-standardised 5-year relative survival for all patients in Dalian was lower than that in the USA (49.9% vs 67.9%). By cancer types, twelve cancers with poorer prognosis were observed in Dalian compared to the USA, with the largest gap seen in prostate cancer (Dalian: 55.8% vs USA: 96.0%). However, Dalian had a better survival for lung cancer, cervical cancer, and bladder cancer. Dalian patients had a lower percentage of stage Ⅰ colorectal cancer (Dalian: 17.9% vs USA: 24.2%) and female breast cancer (Dalian: 40.9% vs USA: 48.9%). However, we observed better stage-specific survival among stage Ⅰ-Ⅱ lung cancer patients in Dalian than in the USA. Interpretation:This study suggests that although the overall prognosis for patients was better in the USA than in Dalian, China, survival deficits existed in both countries. Improvement in cancer early detection and cancer care are needed in both countries. Funding:National Key R&D Program (2021YFC2501900, 2022YFC3600805), Major State Basic Innovation Program of the Chinese Academy of Medical Sciences (2021-I2M-1-010, 2021-I2M-1-046), and Talent Incentive Program of Cancer Hospital of Chinese Academy of Medical Sciences.

Epigenetic variants carried by circulating tumor DNA can be used as biomarkers for early detection of hepatocellular carcinoma (HCC) by noninvasive liquid biopsy. However, traditional methylation analysis method, bisulfite sequencing, with disadvantages of severe DNA damage, is limited in application of low-amount cfDNA analysis. Through mild enzyme-mediated conversion, enzymatic methyl sequencing (EM-seq) is ideal for precise determination of cell-free DNA methylation and provides an opportunity for HCC early detection. EM-seq of methylation control DNA showed that enzymatic conversion of unmethylated C to U was more efficient than bisulfite conversion. Moreover, a relatively large proportion of incomplete converted EM-seq reads contains more than 3 unconverted CH site (CH = CC, CT or CA), which can be removed by filtering to improve accuracy of methylation detection by EM-seq. A cohort of 241 HCC, 76 liver disease, and 279 normal plasma samples were analyzed for methylation value on 1595 CpGs using EM-seq and targeted capture. Model training identified 283 CpGs with significant differences in methylation levels between HCC and non-HCC samples. A HCC screening model based on these markers can efficiently distinguish HCC sample from non-HCC samples, with area under the curve of 0.957 (sensitivity = 90%, specificity = 97%) in the test set, performing well in different stages as well as in serum α-fetoprotein/protein induced by vitamin K absence-II negative samples. Filtering of reads with ≥ 3 CHs derived from incomplete conversion can significantly reduce the noise of EM-seq detection. Based on targeted EM-seq analysis of plasma cell-free DNA, our HCC screening model can efficiently distinguish HCC patients from non-HCC individuals with high sensitivity and specificity.

Although single-drug chemotherapy regimens were used as second-line chemotherapy for advanced lung squamous cell carcinoma (LSCC) patients, there are still no standard guidelines for second-line chemotherapy. The purpose of this study was to compare the efficacy and safety of docetaxel combined with nedaplatin or carboplatin in the second-line treatment of advanced LSCC patients. One hundred and ninety-six LSCC patients receiving docetaxel plus nedaplatin (DN, n = 96) or carboplatin (DC, n = 100) were retrospectively collected until disease progression or unacceptable toxicity. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed in the two groups. The ORR was 18.8% versus 16.0%, and the DCR was 39.6% versus 34.0% in DN group and DC group ( P > .05 and P > .05), respectively. The PFS was 5.3 versus 3.8 months, and the OS was 8.5 and 6.7 months in DN group and DC group ( P = .013 and P = .404), respectively. The rate of digestive reaction and hepatotoxicity was similar in DN and DC groups, whereas more patients in DC group than in DN group suffered from leucopenia ( P < .05). Docetaxel combined with nedaplatin is an effective regimen for advanced LSCC patients. Compared with a similar regimen with carboplatin, the response rate was similar; however, nedaplatin regimen shows some superiority as regards survival and some treatment side effect.

Background:The diffuse large B-cell lymphoma (DLBCL) has the highest incidence of all lymphomas worldwide. To investigate the functions of lymphocyte activation gene 3 (LAG-3) and programmed cell death 1 (PD-1) in tissues and peripheral blood of patients with DLBCL, the expression of LAG-3 and PD-1 genes in DLBCL-TCGA were analyzed. Methods:LAG-3 and PD-1 mRNA levels in DLBCL were analyzed using data from The Cancer Genome Atlas (TCGA) database. Utilize the Genotype-Tissue Expression (GTEx) database for assessing the variance in the expression of LAG-3, PD-1, and other associated factors between the tissues of DLBCL patients and healthy individuals. Immunohistochemistry was applied to detect the expression of LAG-3 and PD-1 levels in 137 cases of DLBCL tissues and 20 cases of reactive lymphoid hyperplasia. The prognostic value of LAG-3 and PD-1 were assessed using the Kaplan-Meier curve. The Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) and ssGSEA algorithm were used to explore the immune microenvironment of DLBCL. Additionally, the expression and co-expression of LAG-3 and PD-1 were detected on CD4 and CD8 T cells in peripheral blood samples from 100 cases of DLBCL tissues and 30 cases of healthy individuals using flow cytometry. Results:According to TCGA database, LAG-3 and PD-1 gene expression levels were significantly up-regulated in DLBCL tissues. LAG-3 and PD-1 levels were also strongly positively correlated with those of most infiltrating immune cells. Overall survival of patients with high LAG-3 and PD-1 co-expression was significantly shorter than that of patients with low co-expression. In DLBCL patients, LAG-3 and PD-1 were highly expressed in peripheral blood CD8+ T cells. In addition, LAG-3 was highly expressed in CD4+ T cells, while the expression of PD-1 in CD4+ T cells of DLBCL patients showed no significant difference compared to healthy individuals. Additionally, CD8+ T cells and SU-DHL6/OCI-LY3 from patients with DLBCL were co-cultured in vitro; after addition of LAG-3 and/or PD-1 inhibitors alone, an increased perforin and granzyme B secretion levels by CD8+ T cells were detected, as well as an increase in the overall proportion of tumor cells undergoing apoptosis. Conclusion:High LAG-3 and PD-1 levels significantly inhibit CD8+ T cell function, resulting in weakened ability to kill tumor cells. Combined LAG-3 and PD-1 blockade can restore CD8+ T cell function and provides a potential avenue for development of personalized cellular immunotherapy for DLBCL.

Background:Hepatocellular carcinoma (HCC) is a highly malignant tumor with limited treatment options, suboptimal efficacy, and poor prognosis, resulting in an economic burden to countries worldwide. TOP2A is a mammalian protein that plays a vital role in DNA replication. Previous studies have shown that upregulation of TOP2A expression is associated with tumorigenesis and progression in various cancers, but the exact mechanism of upregulation remains unclear.Methods:We first conducted a pan-cancer analysis using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases to study the oncogenicity of TOP2A through the cBioPortal database. Next, using The Encyclopedia of RNA Interactomes (ENCORI) database, we identified microRNAs (miRNAs) that are associated with the downregulation of TOP2A and investigated potential long non-coding RNAs (lncRNAs) that may act as competing endogenous RNAs (ceRNAs) by binding to candidate miRNAs. We then analyzed immune cell infiltration and immune checkpoints using the TIMER database. Finally, we performed a multivariate regression analysis using lncRNAs and clinical pathological characteristics, constructed a nomogram to predict the prognosis of HCC based on the analysis results, and evaluated its diagnostic efficiency.Results:TOP2A was highly expressed in HCC and was associated with poor patient prognosis. TOP2A was subject to post-transcriptional regulation in HCC, with the ceRNA mechanism being a significant pathway. miR-139-5p was an important miRNA that suppressed the upregulation of TOP2A in HCC, and patients with low expression of miR-139-5p had worse overall survival (OS). After screening and analysis, three lncRNAs, AC078846.1, AC124798.1 and SNHG3, were found to inhibit the activity of miR-139-5p through the ceRNA mechanism, and patients with high expression of these three lncRNAs had worse prognosis. In addition, TOP2A was found to be closely related to tumor-infiltrating immune cells (TIICs) and immune checkpoints. A nomogram constructed using the three lncRNAs and selected clinicopathological features showed good predictive value for the prognosis of liver cancer.Conclusions:The TOP2A-miR-139-5p-AC078846.1/AC124798.1/SNHG3 axis plays a significant role in the progression of HCC and leads to poor patient outcomes. Additionally, TOP2A influences the development of HCC by affecting TIICs and immune checkpoints. A nomogram constructed using the three lncRNAs and clinicopathological features has good clinical utility.

BACKGROUNDDermatologists have been looking for ways to improve wound healing and postoperative scar appearance. The safety and efficacy of botulinum toxin type A (BTXA) in the prevention and treatment on pathological scars have become the current research hotspot since it was approved by the US FDA in medical cosmetology in 2002.PURPOSEThis article aims to provide an overview of the clinical research, limitations, and application prospects of BTXA in the prevention and treatment of traumatic or postoperative pathological scars, which can provide a reference and better understanding of relevant studies.METHODSThe current research progress was summarized and discussed, with new problems and research ideas being proposed ranging from the molecular mechanism of BTXA in preventing and treating pathological scars to its clinical application via investigation and reference research.RESULTSBTXA is effective in relieving itching and pain associated with pathological scars, limiting scar hyperplasia along with preventing scar contracture, but the specific mechanism is still not clear.CONCLUSIONMost of the clinicians have confirmed the clinical effectiveness of BTXA in the prevention and treatment of pathological scars, yet its mode of action and combination therapy need more research.