BackgroundNon-invasive biomarkers offer potential to improve risk stratification and early diagnosis of lung cancer, complementing low-dose computed tomography (LDCT) screening. This study employed bibliometric analysis to identify global research trends, collaborative networks, and future directions in lung cancer biomarker research. Publications on lung cancer biomarkers for screening were retrieved from the Web of Science Core Collection (WoSCC). Data processing and visualisation were performed using Citespace, VOSviewer, KH Coder, Latent Dirichlet Allocation (LDA) topic modelling, and the online bibliometric analysis platform. Burst detection analysis was performed to predict emerging research trends.ResultsAnalysis of 3636 publications revealed exponential growth in research output since 2014. International collaboration demonstrated a dual-core structure centred on China and the United States, with Chinese institutions showing high publication volumes and American institutions demonstrating greater citation influence. Journal citation mapping revealed three evolutionary phases: basic mechanisms-clinical translation-intelligent integration. LDA topic modelling identified 22 topics grouped into five core research directions: imaging and pathological diagnostic techniques; molecular and omics marker research; liquid biopsy and new detection technologies; clinical and translational medicine research; and tumour biology and treatment mechanisms. Burst detection analysis predicted future four priority areas: epigenetic studies centred on DNA methylation for risk prediction; treatment resistance and invasion mechanisms; liquid biopsy technology development; and targeted therapy clinical trials.ConclusionsLung cancer biomarker research has evolved towards multimodal, intelligent screening approaches. Future research priorities include DNA methylation-based markers, circulating microRNA signatures, and artificial intelligence-assisted diagnostic platforms to improve early detection accuracy and complement LDCT screening.

BackgroundMalignant pleural and ascitic effusion (PAE) represents a prevalent complication of advanced cancer with significant diagnostic challenges. Current cytological examination lacks optimal sensitivity, necessitating novel diagnostic targets. Cell-in-cell (CIC) structures, characterized by one cell engulfing another, represent an emerging morphological biomarker with potential diagnostic and therapeutic implications. This study evaluates the diagnostic efficacy of CIC and its homotypic subtype (HoCIC) as independent morphological targets for malignant PAE detection.MethodsA total of 584 PAE samples were prepared as cell blocks from consecutive patients at a tertiary center (June 2020–May 2024). CIC structures were quantified in hematoxylin and eosin (H&E)-stained sections (per 10 high-power fields, 40× objective). Homotypic CIC (HoCIC) was identified using immunohistochemical (IHC) profiling (CK-pan, CD68) to distinguish tumor cell-tumor cell engulfment. Diagnostic performance was assessed by sensitivity, specificity, accuracy, and receiver operating characteristic (ROC) analysis with Youden’s index optimization.ResultsAmong 357 malignant and 227 benign PAE cases, CIC was detected in 87.39% (312/357) versus 8.37% (19/227) of benign cases (p < 0.001). HoCIC demonstrated higher specificity, present in 77.31% (276/357) malignant but only 1.32% (3/227) benign cases (p < 0.001). Diagnostic metrics for CIC: sensitivity 87.4%, specificity 91.6%, accuracy 89.0%, NPV 92.6%; for HoCIC: sensitivity 77.3%, specificity 98.7%, accuracy 85.6%, PPV 98.9%. Optimal cut-off values were 0.5/10 HPF or 1/20 HPF (Youden’s index 0.79 for CIC, 0.76 for HoCIC). Both markers showed significant independent discriminatory value.ConclusionCIC and HoCIC represent validated, readily implementable morphological biomarkers with complementary diagnostic utilities—CIC optimized for sensitive screening and HoCIC for specific confirmation. Integration of this tiered morpho-molecular approach into routine cytopathology workflows may enhance diagnostic precision and guide therapeutic decision-making in advanced malignancies.

Non-small cell lung cancer (NSCLC) is an aggressive malignant tumor characterized by early recurrence and poor prognosis. Homotypic cell-in-cell (HoCIC) are significantly associated with adverse outcomes in multiple tumors, serving as valuable indicators for patient outcome assessment. However, current HoCIC diagnosis methods rely primarily on manual microscopic observation and lack standardized detection biomarkers and methodologies, which may introduce bias into research findings. Therefore, this study aims to identify diagnostic markers for HoCIC in NSCLC, laying the foundation for further research into the biological roles and mechanisms of HoCIC. Kaplan‒Meier curves and log-rank tests were used to investigate the relationship between HoCIC and prognosis. Bioinformatics analysis of NSCLC gene expression data related to HoCIC from the Gene Expression Omnibus (GEO) dataset revealed differentially HoCIC expressed genes ( HoCICDEGs) between tumor tissues and normal tissues. We identified an overlapping HoCIC hub gene, BECN1, among the HoCICDEGs and autophagy-related genes (ARGs). The expression and biological functions of BECN1 were analysed via The Cancer Genome Atlas (TCGA) database. The Kaplan‒Meier, TIMER2.0, cBioPortal, and GSCA public databases were subsequently used to investigate the prognosis, immune infiltration, genetic alterations, and drug sensitivity associated with BECN1. Finally, clinical NSCLC samples were collected for immunohistochemical experiments to validate BECN1 expression and its diagnostic value for HoCIC. HoCIC was significantly correlated with poor overall survival (OS) and disease-free survival (DFS). We identified BECN1 as a core gene associated with HoCIC in NSCLC, which is highly expressed in tumor tissues and is correlated with unfavourable prognosis. BECN1 is correlated with the mitotic spindle, G2M checkpoint, and MYC pathways, suppresses immune cell infiltration, and is sensitive to most anticancer drugs. In our validated NSCLC cohort, BECN1 protein was highly expressed in tumor tissues and demonstrated a significant association with HoCIC, serving as an independent risk factor for HoCIC. The HoCIC prediction model constructed on the basis of BECN1 demonstrated favourable diagnostic capability, discriminatory power, and clinical benefit. In summary, this study identified BECN1 as a diagnostic biomarker associated with HoCIC in NSCLC, providing a strong foundation for improving diagnostic and research strategies related to this phenomenon.

Homotypic cell-in-cell structures (hoCICs) are associated with tumor proliferation, invasion, and metastasis and is considered a promising prognostic marker in various cancers. However, the role of hoCICs in non-small cell lung cancer (NSCLC) remains unclear. Tumor tissue sections were obtained from 411 NSCLC patients. We analyzed the relationship between clinicopathological variables and the number of hoCICs. LASSO and multivariate Cox regression analysis were employed to identify prognostic factors for NSCLC. The impact of hoCICs on overall survival (OS) and disease-free survival (DFS) was assessed using the Kaplan–Meier curves and log-rank test. Prognostic models for OS and DFS were developed and validated using the C-index, time-dependent area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curves and decision curve analysis (DCA). Among the cohort, 56% of patients had hoCICs while 44% did not. Notably, hoCICs were primarily found at the tumor invasion front. Male gender, smoking, squamous cell carcinoma, low differentiation, tumor size ≥ 3 cm, advanced TNM stage, lymph node metastasis, pleural invasion, vascular invasion, necrosis, P53 mutation, and high expression of Ki-67 were identified as relative risk factors for hoCICs. Furthermore, hoCICs was found to be a significant prognostic factor for both OS and DFS, with higher frequencies of hoCICs correlating with poorer outcomes. We constructed nomograms for predicting 1-, 3-, and 5-year OS and DFS based on hoCICs, and the calibration curves showed good agreement between the predicted and actual outcomes. The results of the C-index, time-dependent AUC, NRI, IDI, and DCA analyses demonstrated that incorporating hoCICs into the prognostic model significantly enhanced its predictive power and clinical applicability. HoCICs indicated independent perdictive value for OS and DFS in patients with NSCLC. Furthermore, the frequent localization of hoCICs at the tumor invasion front suggested a strong association between hoCICs and tumor invasion as well as metastasis.

The cell-in-cell (CIC) phenomenon has received increasing attention over recent years because of its wide existence in multiple cancer tissues. The mechanism of CIC formation is considerably complex as it involves interactions between two cells. Although the molecular mechanisms of CIC formation have been extensively investigated, the process of CIC formation remains ambiguous. Currently, CIC is classified into four subtypes based on different cell types and inducing factors, and the underlying mechanisms for each subtype are distinct. Here, we investigated the subtypes of CIC and their major mechanisms involved in cancer development. To determine the clinical significance of CIC, we reviewed several clinical studies on CIC and found that CIC could serve as a diagnostic and prognostic biomarker. The implications of CIC on the clinical management of cancers also remain largely unknown. To clarify this aspect, in the present review, we highlight the findings of recent investigations on the causal link between CIC and cancer treatment. We also indicate the existing issues that need to be resolved urgently to provide a potential direction for future research on CIC.

Abstract Introduction: Anti-HER2 antibody drug conjugates (ADCs) have demonstrated positive results in the treatment of breast cancer with HER2 low expression; however, traditional molecular typing does not evaluate HER2 low expression. Therefore, modified methods need to be designed to promote the use of ADCs for breast cancer treatment. This study propose a modified molecular typing approach for breast cancer based on immunohistochemical (IHC) staining of estrogen receptor (ER), progesterone receptor (PR), and HER2 to guide the application of ADCs for the treatment of breast cancer with low HER2 expression. Methods According to the classification criteria for the modified molecular typing based only on IHC staining of ER, PR, and HER2 status, 1448 breast cancer specimens were divided into luminal HER2 positive (LH+); luminal HER2 low positive (LH±); luminal HER2 negative (LH−); non-luminal HER2 positive (NLH+); non-luminal HER2 low positive (NLH±); and non luminal HER2 negative (NLH−). Results Among 1448 breast cancer specimens: 7.8% (113/1448) were LH+; 51.2% (741/1448) LH±; 16.5% (238/1448) were LH−; 10.4% (151/1448) were NLH+; 7.5% (109/1448) were NLH±; and 6.6% (96/1448) were NLH−. Significant differences were identified in the age at onset, lymphatic metastasis, TNM stage, and Ki67 index among the six molecular types of breast cancer according to the modified molecular typing approach. Conclusions Based only on IHC staining of ER, PR, and HER2 status, this study classifies breast tumors with low HER2 expression as an independent molecular subtype and proposes a modified molecular typing approach to divide breast cancer into six types, including luminal HER2+, luminal HER2 low positive, luminal HER2−, non-luminal HER2+, non-luminal HER2 low positive, and non-luminal HER2−. This molecular typing approach not only better distinguishes the molecular and biological characteristics of different molecular types of breast cancer, but it also guides the application of ADCs for breast cancer treatment.

Background Among the most aggressive and rapidly lethal types of lung cancer, lung adenocarcinoma is the most common type. Exosomes, as a hot area, play an influential role in cancer. By using proteomics analysis, we aimed to identify potential markers of lung adenocarcinoma in serum. Methods In our study, we used the ultracentrifugation method to isolate serum exosomes. The Liquid chromatography-mass spectrometry (LC–MS) and bioinformatics analysis were used to identify potential serum exosomal proteins with altered expression among patients with advanced lung adenocarcinoma, early lung adenocarcinoma, and healthy controls. A western blot (WB) was performed to confirm the above differential expression levels in a separate serum sample-isolated exosome, and immunohistochemistry (IHC) staining was conducted to detect expression levels of the above differential proteins of serum exosomes in lung adenocarcinoma tissues and adjacent tissues. Furthermore, we compared different expression models of the above differential proteins in serum and exosomes. Result According to the ITGAM (Integrin alpha M chain) and CLU (Clusterin) were differentially expressed in serum exosomes among different groups as well as tumor tissues and adjacent tissues. ITGAM was significantly and specifically enriched in exosomes. As compared to serum, CLU did not appear to be significantly enriched in exosomes. ITGAM and CLU were identified as serum exosomal protein markers of lung adenocarcinoma. Conclusions This study can provide novel ideas and a research basis for targeting lung adenocarcinoma treatment as a preliminary study.

目的 研究床旁检测活性氧(reactive oxygen species,ROS)和细胞游离亚铁原卟啉(cell free ferrous protoporphyrin,FH)在鉴别良恶性胸腹水中的临床意义.方法 收集胸腹水样本196例,所有样本由有资质的细胞病理学医生通过细胞蜡块和常规细胞涂片进行检查和细胞病理学诊断.同时,采用ROS和FH染色检测ROS和FH在上述样本中的阳性表达.最后,评估ROS和FH联合检测作为筛选良恶性胸腹水的分子靶标的敏感性、特异性、准确率、阳性预测值和阴性预测值.结果 细胞病理学检查发现,在196例胸腹水样本中,恶性肿瘤患者样本67例,非恶性肿瘤患者样本129例.ROS和FH联合染色发现在196例胸腹水样本中,ROS阳性者82例,FH阳性者171例,ROS和FH双阳性者82例.以ROS、FH和ROS+FH作为诊断指标,其敏感性分别为50.75％,89.55％和89.55％;特异性分别为62.79％,13.95％和12.40％;阳性预测值分别为41.46％,35.09％和34.68％;准确率分别为58.67％,39.80％和38.78％;阴性预测值分别为71.05％,72.00％和69.57％.结论 ROS和FH联合染色的阴性预测值比较高,可作为一种新的快速筛查方法用于良恶性胸腹水的鉴别.

The study of histopathological phenotypes is vital for cancer research and medicine as it links molecular mechanisms to disease prognosis. It typically involves integration of heterogenous histopathological features in whole-slide images (WSI) to objectively characterize a histopathological phenotype. However, the large-scale implementation of phenotype characterization has been hindered by the fragmentation of histopathological features, resulting from the lack of a standardized format and a controlled vocabulary for structured and unambiguous representation of semantics in WSIs. To fill this gap, we propose the Histopathology Markup Language (HistoML), a representation language along with a controlled vocabulary (Histopathology Ontology) based on Semantic Web technologies. Multiscale features within a WSI, from single-cell features to mesoscopic features, could be represented using HistoML which is a crucial step towards the goal of making WSIs findable, accessible, interoperable and reusable (FAIR). We pilot HistoML in representing WSIs of kidney cancer as well as thyroid carcinoma and exemplify the uses of HistoML representations in semantic queries to demonstrate the potential of HistoML-powered applications for phenotype characterization.

Objective To investigate the effect of baicalein on polymicrobial sepsis-induced immune dysfunction and organ injury. Methods A sepsis model was induced in Sprague-Dawley rats via caecal ligation and puncture (CLP). Specific pathogen free rats were randomly divided into a sham group, CLP group and CLP + baicalein (Bai) group ( n =16 each). Rats in the CLP + Bai group were intravenously injected with baicalein (20 mg/kg) at 1 and 10 h after CLP. Survival rate, bacterial load, and organ damage were assessed. Then each group was evaluated at 6, 12, and 24 h to investigate the effect of baicalein on immune cells and inflammatory cytokines in septic rats. Results Baicalein treatment significantly improved the survival of septic rats, decreased the bacterial burden, and moderated tissue damage (spleen, liver, and lung), as observed by haematoxylin and eosin staining. Septic rats treated with baicalein had strikingly increased proportions of CD3 + CD4 + T cells and ratios of CD4 + /CD8 + T cells in the peripheral blood and spleen (all P <0.05). Moreover, baicalein treatment decreased the apoptotic rate of whole white blood cells and spleen cells at 24 h after surgery ( P <0.05). Baicalein significantly reduced the levels of tumor necrosis factor α and interleukin-6 (IL-6) and increased IL-10, and the expression levels of galectin 9 were also raised in the spleen ( P <0.01). Conclusion Baicalein may be an effective immunomodulator that attenuates overwhelming inflammatory responses in severe abdominal sepsis.

Objective:To explore a convenient method for dynamic monitoring of cytosolic calcium concentration of rat pancreatic acinar cells.Methods:The rat pancreas was collected aseptically and the fat and lymph tissues were removed. Then the rat pancreatic acinar cells were isolated by collagenase preheated at 37 ℃. The pancreatic acinar cells were incubated with Fluo-3/AM. The dynamic changes of calcium concentration were real-time monitored by flow cytometry.Results:The acinar cells of the control group were in a static status, there was no change in the cell fluorescence intensity over time. The calcium concentration in the acinar cells of the 8 rats in this experiment showed a consistent trend over time, with an average fluorescence intensity value of 307.75±36.45 ( n=8). The cell fluorescence intensity increased and reached the peak value in 27.76 seconds when adding the irritant sodium taurocholate to the cells compared with that before the stimulation. Conclusion:Flow cytometry provides another convenient method for the study of calcium cocentration and cell function of acinar cells and the subsequent study of the pathogenesis of acute pancreatitis.

Objective:To investigate the effects of gut microbiota in patients with hepatitis B cirrhosis on function of intestinal mucosal barrier and progression of cirrhosis in mice.Methods:Fecal samples of 12 patients and 12 healthy individuals in the Second Affiliated Hospital of Xi′an Jiaotong University from September 2017 to June 2018 were collected. Gut microbiota structure was analyzed through 16S rDNA sequencing and bacterial suspension was prepared. Male C57BL/6 mice were randomly (random number) divided into four groups: healthy control group (HC group), cirrhosis model group (LC group), model group+ bacterial suspension of healthy individuals (FMT-HC group), model group+ bacterial suspension of patients (FMT-LC group). Cirrhosis model was established and mice were gavaged with bacterial suspension, lasting for 12 weeks. Colon pathological morphology was observed by hematoxylin-eosin staining, injury of intestinal mucosal barrier was detected using enzyme-linked immunosorbent assay and fluorescent probe, the expression of intestinal mucosal barrier and hepatic fibrosis related factors were detected by real-time quantitative polymerase chain reaction and immunofluorescence.Results:The expression levels of mucin-2 and claudins-2 in the colon of mice in FMT-LC group were significantly lower than those in FMT-HC group (0.36±0.21 vs. 1.00±0.36, t=4.659, P<0.01 and 0.61±0.42 vs. 1.00±0.17, t=2.596, P<0.05), and the concentrations of FITC-dextran and lipopolysaccharide in the peripheral blood were significantly higher than those in FMT-HC group [(9.32±2.24) μg/ml vs. (5.23±1.34) μg/ml, F=15.118, P<0.01 and (88.55±10.50) ng/ml vs. (76.48±10.13) ng/ml, F=5.473, P<0.05]. The expression levels of transforming growth factor-β1 (3.39±2.67 vs. 0.95±0.12, t=2.744, P<0.05) and other pro-fibrotic factors, as well as α-smooth muscle actin in the liver of mice in FMT-LC group were significantly higher than those in FMT-HC group, and the liver injury was aggravated. Conclusion:The gut microbiota of patients with hepatitis B cirrhosis can reduce the intestinal mucosal barrier function and promote cirrhosis development in mice.

Numerous reports have found that long non-coding (lnc) RNAs were associated with pancreatic cancer (PC) initiation and development. The lncRNA titin antisense RNA 1 (TTN-AS1) was identified as a tumor promoter in certain types of cancer; however, its role and mechanism in PC remain unclear. The aim of the present study was to investigate the role of TTN-AS1 in PC and elucidate the underlying mechanism. Reverse transcription-quantitative PCR analysis was performed to examine the mRNA expression level of TTN-AS1, microRNA(miR)-589-5p and forkhead box protein 1 (FOXP1). Knockdown experiments were performed to examine the effect of TTN-AS1 on PC cell proliferation, migration and invasion. Luciferase reporter assays validated the binding of miR-589-5p to TTN-AS1 and FOXP1. Chromatin immunoprecipitation and luciferase reporter assays confirmed the binding ability of FOXP1 to the TTN-AS1 promoter. As a result, TTN-AS1 and FOXP1 were found to be upregulated in PC cell lines and tissues, while miR-589-5p was expressed at low levels. Knockdown experiments indicated the suppressive effect of TTN-AS1 knockdown on cell proliferation, migration and invasion in PC cell lines. Further mechanistic research uncovered that TTN-AS1 functioned as a molecular sponge for miR-589-5p and its mRNA expression level in PC tissues was inversely associated with that of miR-589-5p. Furthermore, miR-589-5p was confirmed to target FOXP1. Of note, it was discovered that FOXP1 transcriptionally activated TTN-AS1 mRNA expression level. Taken together, the findings of the present study demonstrated that the new TTN-AS1/miR-589-5p/FOXP1 feedback loop may play an important role in PC.

目的 研究CD47在胃癌组织免疫微环境中的表达和浸润CD68+TAMs(CD68 positive tumor-associated macrophages)和CD163+TAMs(CD163 positive tumor-associated macrophages)的分布特征.方法 采用免疫组化法检测CD47、CD68、CD163在78例胃癌组织样本中的表达,观察CD47的表达,计算肿瘤微环境中浸润CD68+TAMs和CD163+TAMs的分级,采用配对卡方检验进行统计分析.结果 免疫组化染色显示CD47呈质膜型表达,在胃癌细胞和胃癌间质细胞中的表达明显强于其在癌旁胃黏膜腺体上皮细胞和间质细胞中的表达水平(P<0.05),且与淋巴结转移密切相关;同时,胃癌组织中浸润CD68+TAMs和CD163+TAMs的分级显著高于癌旁组织(P<0.01),但CD163/CD68比值在胃癌组织与癌旁组织中比较无差异.结论 胃癌组织中CD47的高表达和CD68+TAMs和CD163+TAMs的浸润是胃癌的共性免疫微环境特征.

Introduction: The spleen plays an important role in regulating the immune response to infectious pathogens. T-cells dysfunction and exhaustion have been reported in patients with hepatitis B/C virus (HBV/HCV) infection, which contributes to persistent virus infection. The aims of this study were to investigate spleen-related evidence of immunosuppression and immune tolerance in HCV cirrhotic patients with portal hypertension (PH). Methods: The expression of programmed cell death 1 (PD-1), T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) and its ligand PD-L1/2, and Galectin-9 in the spleens and livers of HCV cirrhotic patients ( n = 15) was analyzed using real-time PCR and immunohistochemistry. Flow cytometry was used to evaluate the expression of PD-1 and Tim-3 on splenic T-cells and the peripheral blood T-cells before and after splenectomy ( n = 8). Results: Spleens from patients with PH showed significantly increased mRNA levels of PD-L2, Tim-3, Galectin-9, CD80, and CD86, and decreased levels of CD28 compared to control spleens (spleens removed due to traumatic injury) (all p < 0.05). Additionally, protein expression of inhibitory signaling molecules was significantly increased in both the spleens and livers of cirrhotic patients compared with controls (all p < 0.05). Peripheral blood and splenic CD4+ and CD8+ T-cells also expressed higher protein levels of PD-1, Tim-3, and CTLA-4 in cirrhotic patients as compared with healthy controls (all p < 0.05). The proportion of PD-1+CD4+T lymphocytes (26.2% ± 7.12% vs. 21.0% ± 9.14%, p = 0.0293) and Tim-3+CD8+ T lymphocytes (9.4% ± 3.04% vs. 6.0% ± 2.24%, p = 0.0175) in peripheral blood decreased followed splenectomy. Conclusion: The CD4+ and CD8+ T-cells in spleen and peripheral blood highly expressed PD-1 and Tim-3 in HCV-infected and cirrhotic patients with portal hypertension. Highly expressed PD-1 and Tim-3 in peripheral blood T-lymphocytes can be partly reversed following splenectomy.

目的 探讨细胞吞食形成的Cell-in-Cell(CIC)样结构的形态特征及其在细胞病理学诊断中的价值.方法 收集2020年1月～2021年1月西安交通大学第二附属医院存档的细胞蜡块128例,其中恶性肿瘤98例,非恶性肿瘤30例,在显微镜下进行病理诊断,并观察CIC样结构的形态学特征和阳性检出率.结果 CIC样结构的形态学特征表现为宿主细胞体积膨大呈指环状,内见单核或多核,呈新月形偏于一侧;内部细胞呈圆形,可为单个或多个肿瘤或非肿瘤细胞,被宿主细胞膜完整包裹.在98例恶性肿瘤样本细胞蜡块中,CIC的检出率为26.5％(26/98),其中19例CIC阳性细胞占比1％～10％,5例CIC阳性细胞占比11％～20％,2例CIC阳性细胞占比>20％;30例非恶性肿瘤样本细胞蜡块中均未观察到CIC样结构.结论 CIC是晚期恶性肿瘤典型的细胞形态学特征,可用于体液样本的细胞病理学诊断.

目的 探讨复方大黄素黄芩素组方的合理性,分析方中二组分对全方治疗重症急性胰腺炎(SAP)作用的影响.方法 SPF级雄性SD大鼠120只,采用5％ 牛磺胆酸钠逆行胰胆管注射法制备大鼠重症急性胰腺炎模型,根据拆方分析实验设计,设正常对照组、假手术组、单纯SAP组、阳性对照药单倍剂量大黄素组(A组,大黄素3.2 mg/kg)、阳性对照药2倍剂量大黄素组(2A组,大黄素6.4 mg/kg)、单倍剂量黄芩素组(B组,黄芩素7 mg/kg)、2倍剂量黄芩素组(2B组,黄芩素14 mg/kg)、复方低剂量组(1/2AB组,大黄素1.6 mg/kg+黄芩素3.5 mg/kg)、复方中剂量组(AB组,大黄素3.2 mg/kg+黄芩素7 mg/kg)、复方高剂量组(2AB组,大黄素6.4 mg/kg+黄芩素14 mg/kg)进行实验,各组均12只大鼠.各组干预药物均于模型复制后立即依次尾静脉注射不同剂量药物溶液(2 mL/kg),正常对照组、假手术组、单纯SAP组尾静脉注射等量生理盐水.各组大鼠分别于给药后12 h全部处死,收集胰腺组织、血清,分别进行胰腺组织病理学评分、血清ɑ-淀粉酶活性测定.结果 胰腺组织病理学评分和血清α-淀粉酶活性,各治疗组均明显低于单纯SAP组(P<0.05),AB组均明显低于2A和2B组(P<0.05).各复方组(1/2AB、AB、2AB组)随着剂量增加,胰腺组织病理学评分降低.结论 复方大黄素黄芩素的疗效好于2倍剂量大黄素,也好于2倍剂量黄芩素,组方中大黄素、黄芩素之间为协同作用,复方大黄素黄芩素组方合理.

[This retracts the article DOI: 10.2147/CMAR.S252635.].

Myeloid-derived suppressor cells (MDSCs) are classified into polymorphonuclear (PMN)-MDSCs and monocytic (M)-MDSCs. The predominant subtype of MDSCs in hepatocellular carcinoma (HCC) is still elusive. The spleen is the largest immune organ in the body and is the origin of many cells. It is still unknown whether the spleen is the origin of MDSCs. In this study, we investigated the expression, origin and mobilization of the predominant MDSC subtype in H22 orthotopic hepatoma mice. Compared with M-MDSCs, PMN-MDSCs were increased and dominant in the spleen, peripheral blood and tumor tissues. Splenectomy could decrease the percentages of PMN-MDSCs in the peripheral blood and tumor tissues, increase the frequencies of NK cells in the peripheral blood and CD3+CD4+T, CD3+CD8+T, NK and NKT cells in the tumor tissues, reduce the tumor weight and the amounts of ascites, and prolong survival time in hepatoma mice. The levels of chemokine (CC motif) ligand 9 (CCL9) and chemokine (CC motif) ligand 2 (CCL2) were elevated in the peripheral blood of tumor-bearing (TB) mice, and their receptors CCR1 and CCR2 were expressed on spleen PMN-MDSCs. Migration assay showed that CCL2 and CCL9 could attract spleen PMN-MDSCs in vitro. These results indicate that PMN-MDSCs were increased and dominant in orthotopic H22 hepatoma mice, the spleen contributed to the increase of PMN-MDSCs, and PMN-MDSCs could be mobilized from the spleen to the peripheral blood by CCL9 and CCL2, thus facilitated tumor growth.

The difference of splenic pathologic alterations and immune function changes in portal hypertension (PHT) with different etiology is unclear. We aimed to investigate the differences between the hypersplenic patients with hepatitis B virus (HBV)-related PHT and Budd-Chiari syndrome (B-CS). A total of 93 patients with hypersplenism due to Chinese primary B-CS (B-CS group), 105 patients with hypersplenism due to HBV-related cirrhosis (HBV/PHT group), and 31 healthy people (control group) were included in this study retrospectively. The peripheral bloods and paraffin sections of the spleen from part of patients were analyzed by flow cytometry and immunohistochemistry. Hypersplenism and PHT were more serious in HBV/PHT group than in B-CS group. In the peripheral blood, the percentages of regulatory T cell (15.1% vs. 8.1% vs. 2.2%, p = 0.0021) and myeloid-derived suppressive cells (2.8% vs. 0.8% vs. 0.9%, p = 0.009) were higher, but CD4+ T and CD8+ T cells were lower in HBV/PHT group compared with B-CS and control groups. In spleen, the percentages of CD4+ T and CD8+ T cells were lower, but CD68+ macrophages were higher in HBV/PHT group than in B-CS group. Moreover, CD86, inducible nitric oxide synthase, Toll-like receptor 4, and tumor necrosis factor-alpha expression in the spleen, as well as the plasma lipopolysaccharide (LPS) level (677.7 vs. 311.1 vs. 222.1 ng/mL, p = 0.0022), were significantly higher in HBV/PHT group than in B-CS and control groups. The HBV/PHT group showed more severe immunosuppression and immune dysfunction and more substantial hypersplenism and splenic phagocytosis than B-CS group.