Quanxin Feng

Astrocytic activation in thoracic spinal cord contributes to persistent pain in rat model of chronic pancreatitis

One of the most important symptoms in chronic pancreatitis (CP) is constant and recurrent abdominal pain. However, there is still no ideal explanation and treatment on it. Previous studies indicated that pain in CP shared many characteristics of neuropathic pain. As an important mechanism underlying neuropathic pain, astrocytic activation is probably involved in pain of CP. Based on the trinitrobenzene sulfonic acid (TNBS)-induce rat CP model, we performed pancreatic histology to assess the severity of CP with semiquantitative scores and tested the nociceptive behaviors following induction of CP. Glial fibrillary acidic protein (GFAP) expressions in the thoracic spinal cord were observed by immunohistochemistry and real-time reverse transcription polymerase chain reaction (RT-PCR). Meanwhile, we injected intrathecally astrocytic specific inhibitor l-alpha-aminoadipate (LAA) and observed its effect on nociception induced by CP. Compared to the naive and sham group, TNBS produced long lasting pancreatitis, and persistent mechanical hypersensitivity in the abdomen that was evident 1 week after TNBS infusion and persisted up to 5 weeks. Compared with naive or sham operated rats, GFAP staining was significantly increased 5 weeks after CP induction. Real-time RT-PCR indicated that GFAP expression was significantly increased in TNBS treated rats compared to the sham group. TNBS-induced astrocytic activation was significantly attenuated by LAA, compared with the saline control. Treatment with LAA significantly, even though not completely, attenuated the allodynia. Our results provide for the first time that astrocytes may play a critical role in pain of CP. Some actions could be taken to prevent astrocytic activation to treat pain in CP patients.

Overweight Is an Additional Prognostic Factor in Acute Pancreatitis: A Meta-Analysis

Background/Aims: It is generally accepted that there is a correlation between obesity and poor outcome in acute pancreatitis (AP); however, the relationship between overweight and the prognosis of AP is unknown. The aim of this study was to determine the correlation between overweight and the prognosis of AP. Methods: MEDLINE and PubMed were searched using the terms ‘acute pancreatitis’, ‘obesity’, ‘overweight’, and ‘body mass index’ (‘BMI’). All prospective clinical studies correlating BMI and AP were included. Obesity and overweight were defined as BMI ≧30 and from 25 to 30, respectively. A meta-analysis was performed with the endpoints severe AP (SAP), local complications, systemic complications, and mortality. Results: Eight studies including 939 patients were found. The incidence rates of SAP (OR 2.48, 95% CI 1.34–4.60), local complications (OR 2.58, 95% CI 1.20–5.57), and mortality (OR 3.81, 95% CI 1.22–11.83) were increased in overweight patients with AP. No difference was detected in the incidence of systemic complications between the normal-weight and overweight patients (OR 1.62, 95% CI 0.76–3.43). In addition, the correlation between obesity and poor prognosis was again confirmed. Conclusion: Overweight is an additional prognostic factor of severity, local complications, and mortality in AP.

Expression of NDRG2 in esophageal squamous cell carcinoma

N‐Myc downstream‐regulated gene 2 (NDRG2), a new member of the N‐Myc downstream‐regulated gene family, has been found to be a differentially expressed gene involved in a variety of cancers. The present study aimed to investigate the expression of NDRG2 in esophageal squamous cell carcinoma (ESCC). Immunohistochemistry was performed in 154 samples from patients with ESCC to detect the expression level of NDRG2 and C‐MYC. Results indicated that the expression level of NDRG2 in the cancer samples was significantly lower than that in normal tissues; the trend of C‐MYC was the reverse. The Wilcoxon–Mann–Whitney test showed significant difference in the expression of NDRG2 in patients with different T stage, TNM stage, and differentiation degree of cancers (P = 0.036, 0.031, 0.001, respectively). Patients in stages I and II were followed up for 5 consecutive years and Kaplan–Meier survival analysis demonstrated that the survival time of ESCC patients with high expression of NDRG2 was longer than those with low expression during the 5‐year follow‐up period (P = 0.0018). Cox regression analysis indicated that low expression of NDRG2, cancer stage of pT1, and distant organ metastasis (pM1) were the independent poor prognostic factors of ESCC (P = 0.004, 0.019, 0.0013, respectively). Furthermore, up‐regulation of NDRG2 was introduced to ESCC cell lines (EC9706 and EC109) by plasmid transfection. In vivo and in vitro studies indicated that overexpression of NDRG2 markedly reduced proliferation and promoted the apoptosis of EC9706 and EC109 cells. In summary, our results demonstrated that NDRG2 played an important role in the proliferation of ESCC cells and the expression of NDRG2 in ESCC was closely related with the prognosis.

Human leukocyte antigen G is associated with esophageal squamous cell carcinoma progression and poor prognosis.

Human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule thought to play a key role in maternal-fetal tolerance and cancer immune evasion. This study aimed to investigate the HLA-G expression in lesion sections and plasma sHLA-G levels of primary esophageal squamous cell carcinoma (ESCC) patients and its clinical significance in diagnosis and prognosis of ESCC. 60 ESCC patients and 28 healthy controls were recruited, and the positive expression of HLA-G in ESCC lesions and adjacent normal tissues were 70% (42/60) and 8.6% (5/60) (P<0.05), respectively, while no expression was found in normal controls. HLA-G1 and HLA-G5 were determined to be dominating isoforms measured by RT-PCR. There was a significant difference in plasma sHLA-G levels between patients with ESCC (15.04 U/ml, range 4.33-250.00 U/ml) and healthy controls (6.81 U/ml, range 0-29.27 U/ml) (P<0.01). The plasma IL-10 level was higher in ESCC patients than the controls (23.86 pg/ml vs. 12.81 pg/ml, P<0.01). HLA-G expression in lesion tissues was correlated with cancer cell differentiation (P=0.033), lymph node metastasis (P=0.035) of ESCC. However, no obvious correlations were demonstrated between the plasma sHLA-G levels and the clinicopathological parameters. There was a significant correlation between sHLA-G and IL-10 expression (r=0.353, P=0.006) in patients with Esophageal squamous cell carcinoma. HLA-G positive expression showed poorer prognosis of ESCC. HLA-G positive expression might serve as a potential marker in the diagnosis or prediction of ESCC.

Red and processed meat consumption and colorectal cancer risk: a systematic review and meta-analysis

The associations between red and processed meat consumption and the risk of colorectal cancer types have not been conclusively defined. We performed a systematic review and meta-analysis to analyze these associations. We searched PubMed and EMBASE to identify studies published from inception through September 2016. Dose-response, subgroup and subtype analyses of colorectal cancer (colon cancer, proximal colon cancer, distal colon cancer and rectal cancer) were performed. We ultimately selected 60 eligible studies. Positive associations were observed for colorectal cancer in case-control studies (red meat, P<0.01; processed meat, P<0.01) and cohort studies (red meat, P<0.01; processed meat, P<0.01). However, subtype analyses yielded null results for distal colon cancer in case-control studies (P=0.41) and cohort studies (P=0.18) for red meat and null results for proximal colon cancer in case-control studies (P=0.13) and cohort studies (P=0.39) for processed meat. Additionally, although the results of case-control studies were positive (red meat, P<0.01; processed meat, P=0.04) for rectal cancer, there were no positive associations between red (P=0.34) and processed meat (P=0.06) consumption and the risk in cohort studies. In a systematic review and meta-analysis, we found consumption of red and processed meat was associated with the risk of overall colorectal cancer but not rectal cancer. Additionally, there were no associations between the consumption of red meat and distal colon cancer risk and between the consumption of processed meat and proximal colon cancer risk.

The ability of current scoring systems in differentiating transient and persistent organ failure in patients with acute pancreatitis

PURPOSE The purpose of this study is to investigate the accuracy of currently used scoring systems in differentiating transient and persistent organ failure in patients with acute pancreatitis (AP). MATERIALS AND METHODS In this retrospective study, 127 consecutive patients with AP and organ failure were included. Patients were divided into transient and persistent organ failure groups. The Acute Physiology and Chronic Health Examination II score, bedside index of severity in acute pancreatitis, harmless acute pancreatitis score, and modified Marshall scores within the first 24 hours of organ failure were collected, and their accuracy in predicting transient organ failure was assessed. RESULTS Transient organ failure occurred in 46 patients (36.2%). Fewer patients with transient organ failure initiated with multiple organ failure (13.0% vs 37.0%, P=.004) and renal failure (17.4% vs 44.4%, P=.002). In predicting transient organ failure, the area under the curves of the 4 scoring systems is from 0.66 to 0.71. The area under the curve of serum amylase was 0.78, which was slightly better than that of the modified Marshall and Acute Physiology and Chronic Health Examination II score and was significantly better than that of the bedside index of severity in acute pancreatitis and harmless acute pancreatitis score (P<.05). CONCLUSIONS Current scoring systems are not accurate enough in differentiating transient and persistent organ failure in patients with AP.

Regulatory B10 cells play a protective role in severe acute pancreatitis

BackgroundB10 cells are specific B cell subsets with the capacity of producing IL-10 to inhibit immune responses. Several studies have demonstrated that B10 cells are correlated with some immune and inflammatory diseases, such as experimental autoimmune encephalomyelitis (EAE), collagen-induced arthritis (CA), colitis and contact hypersensitivity. However, its role in severe acute pancreatitis (SAP) has not been clearly demonstrated yet.PurposeIn this study, we show that B10 cells can inhibit inflammation of severe acute pancreatitis (SAP).Materials and methodsBlood from 17 patients with SAP and 22 age-matched healthy volunteers were collected to detect the proportion of B10 cells. CD19−/− mice were used as B10 cell-deficient mice. Amylase and lipase levels, pancreatic edema and HE staining were tested to assess the severity of SAP.ResultsCD19−/− mice, which lack B10 cells, suffered a more severe inflammation in pancreas compared with wild-type mice after caerulein injection. The frequency of B10 cells was decreased both in SAP patients and SAP animal models. Adoptive transfer of B10 cells ameliorates inflammatory injury of pancreatitis in CD19−/− mice.ConclusionThus, we identified B10 cells as a protective factor for SAP and provided a novel target for SAP treatment.

Is Continuous Venovenous Hemofiltration Effective Against Severe Acute Pancreatitis

Our aim was to investigate the efficacy of continuous venovenous hemofiltration (CVVH) in treating severe acute pancreatitis (SAP). A literature search was performed using PubMed (1992-present), and all studies investigating the efficacy of CVVH in treating SAP were included. Four comparative studies and seven case series comprising a total of 354 patients were included. The overall mortality rate of patients receiving CVVH was 20% (55/275). A decreased mortality rate and decreased serum cytokine levels were reported in the CVVH groups in only two studies. The starting time point, substitution fluid flow rate, filter membrane type, hemofilter change interval, anticoagulation, and sustaining times of CVVH varied among the studies, and the impact of these parameters on the efficacy of CVVH was poorly reported. High-volume CVVH, when started early, was demonstrated to be more effective in eliminating cytokines in only one study. After the application of CVVH, the patient conditions started to improve between the 6th and 72nd hours. In conclusion, no solid clinical evidence has proven the efficacy of CVVH in treating SAP. High-volume CVVH that is started early and sustained for at least 72 h may be adopted to investigate the efficacy of CVVH for treating SAP.

The day when infection is confirmed is a better time point for mortality prediction in patients with severe acute pancreatitis.

Objectives The objective of the study was to compare the accuracy of predictive methods for mortality in patients with severe acute pancreatitis (SAP) on admission and on the day when infection was confirmed. Methods Medical records of patients admitted for SAP in our hospital during January 2000 to November 2010 were retrospectively reviewed. Among those with infectious complications, time when infection was confirmed (TIC) and Acute Physiology and Chronic Health Evaluation II (APACHE II) score on admission and at the time when infection was confirmed (APACHE II OTIC) were studied. The correlations among the APACHE II score on admission, APACHE II OTIC score, and TIC were analyzed. The predictive accuracy was assessed by the area under the receiver operating characteristic curve. Results Time when infection was confirmed correlated negatively with the APACHE II score on admission and the APACHE II OTIC score (P < 0.05). The optimum cutoff value and the corresponding areas under the receiver operating characteristic curve for APACHE II score on admission, APACHE II OTIC score, and TIC were greater than 8, greater than 5, 12 days or less, and 0.67 (95% confidence interval [CI], 0.54–0.77), 0.84 (95% CI, 0.73–0.91), and 0.73 (95% CI, 0.61–0.82), respectively. Compared with the APACHE II score on admission, the APACHE II OTIC score was more accurate in predicting mortality (P = 0.029). Conclusions The time when infection is confirmed is a better time point for the reassessment of the outcome in patients with SAP.

RNA sequence analysis of rat acute experimental pancreatitis with and without fatty liver: a gene expression profiling comparative study

Fatty liver (FL) is one of the risk factors for acute pancreatitis and is also indicative of a worse prognosis as compared to acute pancreatitis without fatty liver (AP). The aim of the present study was to analyze, at the hepatic level, the differentially expressed genes (DEGs) between acute pancreatitis with fatty liver (APFL) rats and AP rats. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses of these DEGs indicated that PPARα signalling pathway and fatty acid degradation pathway may be involved in the pathological process of APFL, which indicated that fatty liver may aggravate pancreatitis through these pathways. Moreover, the excessive activation of JAK/STAT signaling pathway and toll-like receptor signaling pathway was also found in APFL group as shown in heat map. In conclusion, the inhibition of PPARα signaling pathway and the fatty acid degradation pathway may lead to the further disorder of lipid metabolism, which can aggravate pancreatitis.