Computer-aided diagnostic system with automated deep learning method based on the AutoGluon framework improved the diagnostic accuracy of early esophageal cancer.

Background: There have been studies on the application of computer-aided diagnosis (CAD) in the endoscopic diagnosis of early esophageal cancer (EEC), but there is still a significant gap from clinical application. We developed an endoscopic CAD system for EEC based on the AutoGluon framework, aiming to explore the feasibility of automatic deep learning (DL) in clinical application. Methods: The endoscopic pictures of normal esophagus, esophagitis, and EEC were collected from The First Affiliated Hospital of Soochow University (September 2015 to December 2021) and the Norwegian HyperKvasir database. All images of non-cancerous esophageal lesions and EEC in this study were pathologically examined. There were three tasks: task A was normal vs. lesion classification under non-magnifying endoscopy (n=932 vs. 1,092); task B was non-cancer lesion vs. EEC classification under non-magnifying endoscopy (n=594 vs. 429); and task C was non-cancer lesion vs. EEC classification under magnifying endoscopy (n=505 vs. 824). In all classification tasks, we took 100 pictures as the verification set, and the rest comprised as the training set. The CAD system was established based on the AutoGluon framework. Diagnostic performance of the model was compared with that of endoscopists grouped according to years of experience (senior >15 years; junior <5 years). Model evaluation indicators included accuracy, recall rate, precision, F1 value, interpretation time, and the area under the receiver operating characteristic (ROC) curve (AUC). Results: In tasks A and B, the accuracies of medium-performance CAD and high-performance CAD were lower than those of junior doctors and senior doctors. In task C, the medium-performance and high-performance CAD accuracies were close to those of junior doctors and senior doctors. The high-performance CAD model outperformed the junior doctors in both task A (0.850 vs. 0.830) and task C (0.840 vs. 0.830) in sensitivity comparison, but there was still a large gap between high-performance CAD models and doctors in sensitivity comparison. In task A, with the aid of CAD pre-interpretation, the accuracy of junior and senior physicians were significantly improved (from 0.880 to 0.915 and from 0.920 to 0.945, respectively); the time spent on film reading was significantly shortened (junior: from 11.3 to 8.7 s; senior: from 6.7 to 5.5 s). In task C, with the aid of CAD pre-interpretation, the accuracy of junior and senior physicians were significantly improved (from 0.850 to 0.865 and from 0.915 to 0.935, respectively); the reading time was significantly shortened (junior: from 9.5 to 7.7 s; senior: from 5.6 to 3.0 s). Conclusions: The CAD system based on the AutoGluon framework can assist doctors to improve the diagnostic accuracy and reading time of EEC under endoscopy. This study reveals that automatic DL methods are promising in clinical application.

Association of the fat mass index with hepatic steatosis and fibrosis: evidence from NHANES 2017-2018.

Limited population-based studies discuss the association between fat mass index (FMI) and the risk of liver diseases. This investigation utilized data from the National Health and Nutrition Examination Survey (NHANES) to examine the linkage between the FMI and liver conditions, specifically steatosis and fibrosis. The study leveraged data from NHANES's 2017-2018 cross-sectional study, employing an oversampling technique to deal with sample imbalance. Hepatic steatosis and fibrosis were identified by vibration-controlled transient elastography. Receiver operating curve was used to assess the relationship of anthropometric indicators, e.g., the FMI, body mass index (BMI), weight-adjusted-waist index (WWI), percentage of body fat (BF%), waist-to-hip ratio (WHR), and appendicular skeletal muscle index (ASMI), with hepatic steatosis and fibrosis. In this study, which included 2260 participants, multivariate logistic regression models, stratified analyses, restricted cubic spline (RCS), and sharp regression discontinuity analyses were utilized. The results indicated that the WHR and the FMI achieved the highest area under the curve for identifying hepatic steatosis and fibrosis, respectively (0.720 and 0.726). Notably, the FMI presented the highest adjusted odds ratio for both hepatic steatosis (6.40 [4.91-8.38], p = 2.34e-42) and fibrosis (6.06 [5.00, 7.37], p = 5.88e-74). Additionally, potential interaction effects were observed between the FMI and variables such as the family income-to-poverty ratio, smoking status, and hypertension, all of which correlated with the presence of liver fibrosis (p for interaction < 0.05). The RCS models further confirmed a significant positive correlation of the FMI with the controlled attenuation parameter and liver stiffness measurements. Overall, the findings underscore the strong link between the FMI and liver conditions, proposing the FMI as a potential straightforward marker for identifying liver diseases.

Crosstalk between alternative splicing and inflammatory bowel disease: Basic mechanisms, biotechnological progresses and future perspectives.

BACKGROUND: Alternative splicing (AS) is an omnipresent regulatory mechanism of gene expression that enables the generation of diverse splice isoforms from a single gene. Recently, AS events have gained considerable momentum in the pathogenesis of inflammatory bowel disease (IBD). METHODS: Our review has summarized the complex process of RNA splicing, and firstly highlighted the potential involved molecules that target aberrant splicing events in IBD. The quantitative transcriptome analyses such as microarrays, next-generation sequencing (NGS) for AS events in IBD have been also discussed. RESULTS: Available evidence suggests that some abnormal splicing RNAs can lead to multiple intestinal disorders during the onset of IBD as well as the progression to colitis-associated cancer (CAC), including gut microbiota perturbations, intestinal barrier dysfunctions, innate/adaptive immune dysregulations, pro-fibrosis activation and some other risk factors. Moreover, current data show that the advanced technologies, including microarrays and NGS, have been pioneeringly employed to screen the AS candidates and elucidate the potential regulatory mechanisms of IBD. Besides, other biotechnological progresses such as the applications of third-generation sequencing (TGS), single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST), will be desired with great expectations. CONCLUSIONS: To our knowledge, the current review is the first one to evaluate the potential regulatory mechanisms of AS events in IBD. The expanding list of aberrantly spliced genes in IBD along with the developed technologies provide us new clues to how IBD develops, and how these important AS events can be explored for future treatment.

Non-coding RNAs and colitis-associated cancer: Mechanisms and clinical applications.

BACKGROUND: Colitis-associated cancer (CAC) is one of the most severe complications of inflammatory bowel disease (IBD), which has caused a worse survival rate in IBD patients. Although the exact aetiology and pathogenesis of CAC are not completely elucidated, evidence indicates that non-coding RNAs are closely involved and play a key role. METHODS: This review aims to summarise the major findings of non-coding RNAs in the development of CAC and present the potential mechanistic links between non-coding RNAs and CAC pathogenesis. The results show that non-coding RNAs can hinder DNA mismatch repair proteins and obstruct chromosome passenger complexes to increase microsatellite instability and accumulate chromosomal instability, respectively. The data also suggest that DNA promoter methylation or RNA methylation modifications of non-coding RNA are the main mechanisms to regulate oncogene or tumour suppressor expression during the CAC progression. Other factors, including gut microbiota perturbations, immune dysregulation and barrier dysfunction, are also regulated and influenced by non-coding RNAs. Besides, non-coding RNAs as molecular managers are associated with multiple critical signalling pathways governing the initiation, progression and metastasis of CAC, including the janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear factor-kappa B (NF-κB), extracellular signal-regulated kinase (ERK), Toll-like receptor 4 (TLR4), Wnt/ß-catenin and phosphatidylinositol 3-Kinase/Protein Kinase B (PI3K/AKT) pathways. In addition, non-coding RNAs can be detected in colon tissues or blood, and their aberrant expressions and diagnostic and prognostic roles are also discussed and confirmed in CAC patients. CONCLUSIONS: It is believed that a deepening understanding of non-coding RNAs in CAC pathogenesis may prevent the progression to carcinogenesis, and will offer new effective therapies for CAC patients.

Endoscopic full­thickness resection with clip­ and snare­assisted traction for gastric submucosal tumours in the fundus: A single­centre case series.

Exposed endoscopic full-thickness resection (Eo-EFTR) has been recognized as a feasible therapy for gastrointestinal submucosal tumours (SMTs) originating deep in the muscularis propria layer; however, Eo-EFTR is difficult to perform in a retroflexed fashion in the gastric fundus. As a supportive technique, clip- and snare-assisted traction may help expose the surgical field and shorten the operation time in endoscopic resection of difficult regions. However, the application of clip- and snare-assisted traction in Eo-EFTR of SMTs in the gastric fundus is limited. Between April 2018 and December 2021, Eo-EFTR with clip- and snare-assisted traction was performed in 20 patients with SMTs in the gastric fundus at The First Affiliated Hospital of Soochow University. The relevant clinical data were collected retrospectively for all of the patients and analysed. All 20 patients underwent Eo-EFTR successfully without conversion to open surgery or severe adverse events. The en bloc resection rate and R0 resection rate were both 100%. Two patients had abdominal pain and fever after the operation, and five patients had fever, which recovered with medical therapy. No complications, such as delayed bleeding or delayed perforation, were observed. The postoperative pathology indicated that 19 cases were gastrointestinal stromal tumours and one case was leiomyoma. During the follow-up, no residual tumour, local recurrence or distant metastasis was detected by endoscopy or abdominal computed tomography. In conclusion, Eo-EFTR with clip- and snare-assisted traction appears to be a relatively safe and effective treatment for gastric SMTs in the fundus. However, prospective studies on a larger sample size are required to verify the effect of the clip- and snare-assisted traction in Eo-EFTR.

PRKAR2A-derived circular RNAs promote the malignant transformation of colitis and distinguish patients with colitis-associated colorectal cancer.

BACKGROUND: Emerging studies have proved that colonic inflammation caused by refractory inflammatory bowel disease (IBD) can initiate the colitis-associated cancer (CAC), but the transition from inflammation to carcinoma is still largely unknown. METHODS: In this study, mouse colitis and CAC models were established, and the RNA-seq by circRNA microarray was employed to identify the differentially expressed circRNAs and mRNAs in different comparisons (DSS vs. NC and AOM/DSS vs. DSS). The bioinformatics analyses were used to search the common characteristics in mouse colitis and CAC. RESULTS: The K-means clustering algorithm packaged these differential expressed circRNAs into subgroup analysis, and the data strongly implied that mmu_circ_0001109 closely correlated to the pro-inflammatory signals, while mmu_circ_0001845 was significantly associated with the Wnt signalling pathway. Our subsequent data in vivo and in vitro confirmed that mmu_circ_0001109 could exacerbate the colitis by up-regulating the Jak-STAT3 and NF-kappa B signalling pathways, and mmu_circ_0001845 promoted the CAC transformation through the Wnt signalling pathway. By RNA blasting between mice and humans, the human RTEL1- and PRKAR2A-derived circRNAs, which might be considered as homeotic circRNAs of mmu_circ_0001109 and mmu_circ_0001845, respectively, were identified. The clinical data revealed that RTEL1-derived circRNAs had no clinical significance in human IBD and CAC. However, three PRKAR2A-derived circRNAs, which had the high RNA similarities to mmu_circ_0001845, were remarkably up-regulated in CAC tissue samples and promoted the transition from colitis to CAC. CONCLUSIONS: Our results suggested that these human PRKAR2A-derived circRNAs could be novel candidates for distinguishing CAC patients and predicted the prognosis of CAC.

Circular RNA circCSPP1 promotes the occurrence and development of colon cancer by sponging miR-431 and regulating ROCK1 and ZEB1.

BACKGROUND: Colon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors. The present study aims to investigate the role of a novel circular RNA (circCSPP1) in colon cancer and its underlying molecular mechanisms. METHODS: Bioinformatics analysis and reverse transcription-quantitative PCR were used to detect the expression levels of circCSPP1 in colon cancer tissues and cell lines. The effects of circCSPP1 on the behavior of colon cancer cells were investigated using CCK-8, transwell and clonogenic assays. Bioinformatics analysis along with luciferase, fluorescence in situ hybridization and RNA pull-down assays were used to reveal the interaction between circCSPP1, microRNA (miR)-431, Rho associated coiled-coil containing protein kinase 1 (ROCK1) and zinc finger E-box binding homeobox 1 (ZEB1). RESULTS: It was found that circCSPP1 expression was significantly upregulated in colon cancer tissues and cell lines. Overexpression of circCSPP1 significantly promoted the proliferation, migration and invasion of colon cancer cells, whereas silencing of circCSPP1 exerted opposite effects. Mechanistically, circCSPP1 was found to bind with miR-431. In addition, ROCK1 and ZEB1 were identified as the target genes of miR-431. Rescue experiments further confirmed the interaction between circCSPP1, miR-431, ROCK1 and ZEB1. Moreover, circCSPP1 promoted the expression level of ROCK1, cyclin D1, cyclin-dependent kinase 4, ZEB1 and Snail, and lowered the E-cadherin expression level. CONCLUSION: Taken together, the findings of the present study indicated that circCSPP1 may function as a competing endogenous RNA in the progression of colon cancer by regulating the miR-431/ROCK1 and miR-431/ZEB1 signaling axes.

The cross-talk between tumor cells and activated fibroblasts mediated by lactate/BDNF/TrkB signaling promotes acquired resistance to anlotinib in human gastric cancer.

Acquired resistance to tyrosine kinase inhibitors (TKIs) is the major obstacle to improve clinical efficacy in cancer patients. The epithelial-stromal interaction in tumor microenvironment influences cancer drug response to TKIs. Anlotinib is a novel oral multi-targeted TKI, and has recently been proven to be effective and safe for several tumors. However, if and how the epithelial-stromal interaction in tumor microenvironment affects anlotinib response in gastric cancer (GC) is not known. In this study, we found that anlotinib inhibited GC cells growth by inducing GC cells apoptosis and G2/M phase arrest in a dose- and time-dependent manner. Reactive oxygen species (ROS) mediated anlotinib-induced apoptosis in GC cells, while cancer-associated fibroblasts (CAFs) significantly suppressed anlotinib-induced apoptosis and ROS in GC cells. Increased BDNF that was derived from CAFs activated TrkB-Nrf2 signaling in GC cells, and reduced GC cells response to anlotinib. We identified secreted lactate from GC cells as the key molecule instructing CAFs to produce BDNF in a NF-κB-dependent manner. Additionally, functional targeting BDNF-TrkB pathway with neutralizing antibodies against BDNF and TrkB increased the sensitivity of GC cells towards anlotinib in human patient-derived organoid (PDO) model. Taken together, these results characterize a critical role of the epithelial-stroma interaction mediated by the lactate/BDNF/TrkB signaling in GC anlotinib resistance, and provide a novel option to overcome drug resistance.

Tumor suppressor lnc-CTSLP4 inhibits EMT and metastasis of gastric cancer by attenuating HNRNPAB-dependent Snail transcription.

Tumor metastasis is a crucial impediment to the treatment of gastric cancer (GC), and the epithelial-to-mesenchymal transition (EMT) program plays a critical role for the initiation of GC metastasis. Thus, the aim of this study is to investigate the regulation of lnc-CTSLP4 in the EMT process during GC progression. We found that lnc-CTSLP4 was significantly downregulated in GC tumor tissues compared with adjacent non-tumor tissues, and its levels in GC tumor tissues were closely correlated with tumor local invasion, TNM stage, lymph node metastasis, and prognosis of GC patients. Loss- and gain-of-function assays indicated that lnc-CTSLP4 inhibited GC cell migration, invasion, and EMT in vitro, as well as peritoneal dissemination in vivo. Mechanistic analysis demonstrated that lnc-CTSLP4 could bind with Hsp90α/heterogeneous nuclear ribonucleoprotein AB (HNRNPAB) complex and recruit E3-ubiquitin ligase ZFP91 to induce the degradation of HNRNPAB, thus suppressing the transcriptional activation of Snail and ultimately reversing EMT of GC cells. Taken together, our results suggest that lnc-CTSLP4 is significantly downregulated in GC tumor tissues and inhibits metastatic potential of GC cells by attenuating HNRNPAB-dependent Snail transcription via interacting with Hsp90α and recruiting E3 ubiquitin ligase ZFP91, which shows that lnc-CTSLP4 could serve as a prognostic biomarker and therapeutic target for metastatic GC.

Validation of the Toronto hepatocellular carcinoma risk index for patients with cirrhosis in China: a retrospective cohort study.

BACKGROUND: The Toronto hepatocellular carcinoma (HCC) risk index (THRI) was developed to predict HCC in patients with cirrhosis. This study aimed to validate the THRI in a 10-year Asian cohort. METHODS: A total of 2836 patients with cirrhosis at the First Affiliated Hospital of Soochow University between January 2008 and May 2018 were evaluated. Based on the THRI value at diagnosis, patients were divided into three groups (< 120, low-risk; 120-240, intermediate-risk; > 240, high-risk). Student's t test and Fisher's exact test were applied to compare parameters between the HCC group and the non-HCC group. The receiver operator characteristic (ROC) curve was drafted to identify the value of the THRI in predicting HCC. Logistic regression was utilized to assess the relationship between the development of HCC and THRI values. The incidence of HCC was calculated for the three groups using the Kaplan-Meier method, and curves were compared using the log-rank test. RESULTS: Of 520 patients enrolled in this study, 76 patients developed HCC. Patients who developed HCC had a higher THRI score than those who did not develop HCC (279.5 ± 57.1 vs. 232.3 ± 67.6, respectively, p < 0.001). The area under the ROC curve for the THRI to predict HCC was 0.707 ([95% CI 0.645-0.769], p < 0.001), with a sensitivity of 0.842 and a specificity of 0.486 when the cutoff THRI value was 226. Compared to the low-risk group, the high-risk group presented higher odds of developing HCC (adjusting odds ratio 1.026 [95% CI 1.002-1.051], p = 0.036). Differences existed in the cumulative incidence of HCC among the three risk groups (log-rank, p < 0.001). The 5-year cumulative HCC incidence of the low-risk group, intermediate-risk group, and high-risk group was 0%, 13%, and 34%, respectively. CONCLUSION: This study validated THRI values for predicting HCC in Asians with cirrhosis, which presented a fine sensitivity to identify the high-risk population of HCC for secondary prevention.

Epidemiological Trends in Gastrointestinal Cancers in China: An Ecological Study.

BACKGROUND: In recent decades, the patterns and trends of gastrointestinal (GI) cancer epidemics in Chinese population have been changing. AIMS: To present the epidemiological trends and geographic distributions of four major GI cancers (esophageal cancer, stomach cancer, liver cancer and colorectal cancer) in China from 2010 to 2014. METHODS: It used standardized data extracted from the National Central Cancer Registry database. RESULTS: The age-standardized incidence rates (ASIR) of esophageal cancer decreased from 16.7 to 12.2 per 100,000 and the age-standardized mortality rates (ASMR) decreased from 12.0 to 8.8 per 100,000. The ASIR and the ASMR of stomach cancer dropped from 23.7 to 19.5 per 100,000 and from 16.6 to 13.3 per 100,000. The ASIR of liver cancer fell from 21.4 to 17.8 per 100,000 and its ASMR fell from 18.4 per 100,000 to 15.3 per 100,000. The ASIR of colorectal cancer increased from 16.1 to 17.5 per 100,000, whereas the ASMR fluctuated between 7.6 and 7.9 per 100,000. Moreover, the incidence and mortality of each cancer differed between males and females, urban and rural residence, as well as various regions. CONCLUSION: From 2010 to 2014, esophageal cancer, stomach cancer and liver cancer showed downward trend, while the ASIR of colorectal cancer slightly rose and its ASMR presented stable.

miR-203a is involved in HBx-induced inflammation by targeting Rap1a.

Hepatitis B virus (HBV) causes acute and chronic hepatitis, and is one of the major causes of cirrhosis and hepatocellular carcinoma. Accumulating evidence suggests that inflammation is the key factor for liver cirrhosis and hepatocellular carcinoma. MicroRNAs play important roles in many biological processes. Here, we aim to explore the function of microRNAs in the HBX-induced inflammation. First, microarray experiment showed that HBV+ liver samples expressed higher level of miR-203a compared to HBV- liver samples. To verify these alterations, HBx-coding plasmid was transfected into HepG2 cells to overexpress HBx protein. The real-time PCR results suggested that over-expression of HBx could induce up-regulation of miR-203a. To define how up-regulation of miR-203a can induce liver cells inflammation, we over-expressed miR-203a in HepG2 cells. Annexin V staining and BrdU staining suggested that overexpression of miR-203a significantly increased the cell apoptosis and proliferation, meanwhile, over-expression of miR-203a could lead to a decrease in G0/G1 phase cells and an increase in G2/M phase cells. Some cytokines production including IL-6 and IL-8 were significantly increased, but TGFß and IFNγ were decreased in miR-203a over-expressed HepG2 cells. Luciferase reporter assay experiments, protein mass-spectrum assay and real-time PCR all together demonstrated that Rap1a was the target gene of miR-203a. Further experiments showed that these alterations were modulated through PI3K/ERK/p38/NFκB pathways. These data suggested that HBV-infection could up-regulate the expression of miR-203a, thus down regulated the expression of Rap1a and affected the PI3K/ERK/p38/NFκB pathways, finally induced the hepatitis inflammation.

Anti-B7-H3 monoclonal antibody ameliorates the damage of acute experimental pancreatitis by attenuating the inflammatory response.

B7-H3, a recently discovered B7 family member, is documented as a regulator in the inflammatory response as well as T cell-mediated immune responses. In this paper, we find that patients with acute pancreatitis revealed overwhelming levels of serum soluble B7-H3 (sB7-H3) associated with the clinical outcomes. Furthermore, B7-H3 protein was marked increased in l-arginine-induced acute experimental pancreatitis. Anti-B7-H3 monoclonal antibody treatment attenuated the proinflammatory cytokine production, downregulated the activation of the NF-κB signaling pathway, and ameliorated the pancreas disruption in l-arginine-induced pancreatitis. In addition, although l-arginine alone failed to induce the production of proinflammatory cytokine and anti-B7-H3 mAb had no effect on the proinflammatory cytokine production of acinar cells, administration of anti-B7-H3 mAb in the coculture model of acinar cells and macrophages stimulated by l-arginine displayed the similar effects. On the whole, B7-H3 participates in the development of acute pancreatitis, and anti-B7-H3 monoclonal antibody ameliorates severity of acute experimental pancreatitis via attenuation of the inflammatory response.

[Diagnostic value of endoscopic ultrasonography for submucosal tumors of upper gastrointestinal tract].

OBJECTIVE: To evaluate the diagnostic value of endoscopic ultrasonography (EUS) for submucosal tumors (SMTs) of upper gastrointestinal tract. METHODS: A retrospective analysis was made based on clinical data of 206 upper gastrointestinal SMTs patients from January 2009 to July 2013 in The First Affiliated Hospital of Soochow University. Preoperative EUS findings were compared with postoperative pathological diagnosis, and the sensitivity, specificity and accuracy of EUS diagnosis in property and layer origin of SMTs were calculated. RESULTS: The sensitivity, specificity and accuracy of EUS diagnosis in SMTs property were 60.2%, 67.1% and 61.2%. The sensitivity, specificity and accuracy of EUS diagnosis in layer origin of SMTs were 98.0%, 98.2% and 98.1%. CONCLUSION: EUS has limited value in the diagnosis of property of SMT, and has high accuracy of identifying the origin layer, which is helpful to choose therapeutic schedule of SMT under endoscopy.

Melatonin is involved in the apoptosis and necrosis of pancreatic cancer cell line SW-1990 via modulating of Bcl-2/Bax balance.

Melatonin influences a number of physiological processes and is believed to play an antitumoral role in several types of cancers, but its impact on pancreatic cancer is not fully clarified. The growth inhibitory effect of melatonin on pancreatic cancer cell line SW-1990 was detected in vitro and in vivo. Annexin V/PI assay was applied to detect apoptosis and necrosis in SW-1990 cells. Changes of Bcl-2 and Bax expression were investigated by RT-PCR and Western blot. An obvious growth inhibition was found in SW-1990 after melatonin or combined treatment with melatonin and gemicitabine through both apoptosis and necrosis in vitro, and also found in transplanted tumors in nude mice. RT-PCR and Western blot showed that Bcl-2 expression was downregulated, while Bax expression was upregulated, after melatonin treatment. Melatonin may be a pro-apoptotic and pro-necrotic agent for pancreatic cancer cells via its modulation of Bcl-2/Bax balance.

[Effects of N-acetylcysteine on mRNA expression of monocyte chemotactic protein and macrophage inflammatory protein 2 in acute necrotizing pancreatitis: experiment with rats].

OBJECTIVE: To explore the potential role of monocyte chemotactic protein 1 (MCP-1) and macrophage inflammatory protein 2 (MIP-2) in the pathogenesis of acute necrotizing pancreatitis (ANP), and to study the effect of N-acetylcysteine (NAC) on the mRNA expression of MCP-1 and MIP-2. METHODS: Thirty-five SD rats were randomly divided into 3 groups: sham-operation (SO) group (n = 5), acute necrotizing pancreatitis (ANP) group (n = 15), and NAC-pretreated group (n = 15), ANP were induced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct. The NAC- groups underwent intraperitoneal injection of NAC 500 mg/kg 30 minutes before the induction of sodium taurocholate. The ANP and NAC groups were re-divided into 3 equal subgroups respectively: 3 h, 6 h, and 12 h subgroups. 3, 6, and 12 hours after the establishment of models heart blood samples were collected from 5 rats from each model group to detect the serum amylase. Then the rats were killed by blood letting with their pancreases taken out. HE staining and microscopy were used to observe the pathological changes of the pancreas. The wet/dry ratio of pancreas was determined. Enzyme histochemical method was used to detect the activity of myeloperoxidase (MPO) in the pancreas. RT-PCR was used to examine the mRNA expression of MCP-1 and MIP-2. RESULTS: The levels of serum amylase, wet/dry ratio of pancreas, pancreatic MPO activity, and histological score of pancreas of the ANP group increased time-dependently, all the levels at different time-points were significantly higher than those of the SO group (all P < 0.01). The expression levels of MCP-1 mRNA at the time points 3, 6, and 12 h of the ANP group were 0.3653 +/- 0.0213, 0.5890 +/- 0.0225, and 0.7164 +/- 0.0275 respectively, all significantly higher than that of the SO group (0.1492 +/- 0.0036, all P < 0.01). The expression levels of MIP-2 mRNA at different time points of the ANP group were 0.3871 +/- 0.0286, 0.6040 +/- 0.0448, and 0.7692 +/- 0.0620 respectively, all significantly higher than that of the SO group (0.1593 +/- 0.0117, all P < 0.01). The intrapancreatic MPO levels at the time points 3 h, 6 h, and 12 h of the NAC group were 0.63 +/- 0.03, 0.88 +/- 0.05, and 1.31 +/- 0.09 respectively, all significantly lower than those of the ANP groups (0.89 +/- 0.03, 1.42 +/- 0.14, and 1.94 +/- 0.07, all P < 0.05). The MCP-1 mRNA expression levels at different time points the NAC group were 0.2497 +/- 0.0168, 0.4457 +/- 0.0097, and 0.6306 +/- 0.0423 respectively, and the MIP-2 mRNA expression levels at the time points 3 h, 6 h, and 12 h of the NAC group were 0.2436 +/- 0.0099, 0.4312 +/- 0.0221, and 0.6302 +/- 0.0288 respectively, all significantly lower than those of the ANP group (all P < 0.05). The pancreatic histological scores at different time points of the NAC group were 3.50 +/- 0.61, 5.60 +/- 0.65, and 7.50 +/- 0.79, all significantly lower than those of the ANP group (5.10 +/- 0.42, 7.50 +/- 0.50, and 9.90 +/- 0.96, all P < 0.05). The MCP-1 mRNA expression and MIP-2 mRNA expression were both correlated with the severity of pancreatic injury (r = 0.76 and 0.82, both P < 0.05). CONCLUSION: The chemokines of MCP-1 and MIP-2 are overexpressed at the early stage of acute pancreatitis. Both of them may play an important role in the pathogenesis of AP. NAC may have beneficial effects on AP through downregulation of the expression of MCP-1 and MIP-2.