TLR4 Enhances Cerebral Ischemia/Reperfusion Injury via Regulating NLRP3 Inflammasome and Autophagy.

Ischemic stroke is a kind of central nervous disease characterized by high morbidity, high mortality, and high disability. Inflammation and autophagy play important roles in cerebral ischemia/reperfusion (CI/R) injury. The present study characterizes the effects of TLR4 activation on inflammation and autophagy in CI/R injury. An in vivo CI/R rat injury model and an in vitro hypoxia/reoxygenation (H/R) SH-SY5Y cell model were established. Brain infarction size, neurological function, cell apoptosis, inflammatory mediators' levels, and gene expression were measured. Infarction, neurological dysfunction, and neural cell apoptosis were induced in CI/R rats or in H/R-induced cells. The expression levels of NLRP3, TLR4, LC3, TNF-α, interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-18 (IL-18) clearly increased in I/R rats or in H/R-induced cells, while TLR4 knockdown significantly suppressed NLRP3, TLR4, LC3, TNF-α, and interleukin-1/6/18 (IL-1/6/18) in H/R-induced cells, as well as cell apoptosis. These data indicate that TLR4 upregulation induced CI/R injury via stimulating NLRP3 inflammasome and autophagy. Therefore, TLR4, is a potential therapeutic target to improve management of ischemic stroke.

lncRNA PINK1-AS Aggravates Cerebral Ischemia/Reperfusion Oxidative Stress Injury through Regulating ATF2 by Sponging miR-203.

Ischemic stroke is a common disease that led to high mortality and high disability. NADPH oxidase 2- (NOX2-) mediated oxidative stress and long noncoding RNA have important roles in cerebral ischemia/reperfusion (CI/R) injury, whereas whether there is interplay between them remains to be clarified. This study was performed to observe the role of lncRNA PINK1-antisense RNA (PINK1-AS) in NOX2 expression regulation. An in vivo rat model (MCAO) and an in vitro cell model (H/R: hypoxia/reoxygenation) were utilized for CI/R oxidative stress injury investigation. The expression levels of lncRNA PINK1-AS, activating transcription factor 2 (ATF2), NOX2, and caspase-3 and the production level of ROS and cell apoptosis were significantly increased in CI/R injury model rats or in H/R-induced SH-SY5Y cells, but miR-203 was significantly downregulated. There was positive correlation between PINK1-AS expression level and ROS production level. PINK1-AS and ATF2 were found to be putative targets of miR-203. Knockdown of lncRNA PINK1-AS or ATF2 or the overexpression of miR-203 significantly reduced oxidative stress injury via inhibition of NOX2. Overexpression of lncRNA PINK1 significantly led to oxidative stress injury in SH-SY5Y cells through downregulating miR-203 and upregulating ATF2 and NOX2. lncRNA PINK1-AS and ATF2 were the targets of miR-203, and the lncRNA PINK1-AS/miR-203/ATF2/NOX2 axis plays pivotal roles in CI/R injury. Therefore, lncRNA PINK1-AS is a possible target for CR/I injury therapy by sponging miR-203.

The mechanisms and roles of melatonin in gastrointestinal cancer.

Gastrointestinal (GI) cancer is a global health problem with wide lesions and numerous cases. The increased morbidity and mortality of GI cancer is a socio-economic challenge for decades to come. Melatonin, a nature indolamine, exerts a crucial role in molecular interactions involved in multiple functional and physiological processes. Increasing evidence indicates that melatonin can modulate GI tract, decrease the occurrence of GI cancer, and enhance the sensitivity to chemoradiotherapy. However, little is known about the exact role of melatonin in anti-carcinogenesis. In this review, we discuss the action of the beneficial effects of melatonin in GI carcinogenesis. Furthermore, we compile the understanding of the role of melatonin in GI cancer, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), colorectal cancer (CRC), and pancreatic cancer (PC). In addition, the potential therapeutic application and clinical evaluation of melatonin in GI cancer are also discussed.

Del Nido versus HTK cardioplegia for myocardial protection during adult complex valve surgery: a retrospective study.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) and del Nido (DN) cardioplegia are intracellular-type and extracellular-type solution respectively, both can provide a long period of myocardial protection with single-dose infusion, but studies comparing the two are rare for adult cardiac surgery. This study aims to evaluate whether DN is suitable for cardioplegia in complex and high-risk valve surgery with long-term cardiac ischemia when compared with HTK. METHODS: The perioperative records of adult patients infused with DN/HTK as a cardioplegic solution who underwent complex valve surgery with an expected myocardial ischaemic duration longer than 90 min between Oct 2018 and Oct 2019 were analysed retrospectively. RESULTS: Of the 160 patients who received DN/HTK and underwent complex valve surgery, we propensity matched 73 pairs. Both groups achieved satisfactory cardiac arrest effects, and no significant difference was found in their cTnI and CK-MB levels within 12 to 72 h postoperatively. The DN group had a higher rate of return to spontaneous rhythm (0.88 v 0.52, P < 0.001), a lower frequency of postoperative severe arrythmias (12% v 26%, P = 0.036), a higher postoperative stroke volume (65 v 59 ml, P = 0.011) and a higher cardiac output (6.0 v 4.9 L/min, P = 0.007) as evaluated by echocardiography, fewer transfusions and shorter ICU stays (both P < 0.05). The two groups had similar inotrope usage and similar incidences of low cardiac output, morbidities and mortality. Subgroup analysis showed that when the aortic clamping time was greater than 120 min, the advantages of DN were weakened. CONCLUSIONS: DN can be safely applied to complex valve surgery, and it has a similar myocardial protection effect as HTK. Further prospective studies are required to verify these retrospective findings. Trial registration retrospectively registered.

Preoperative autologous platelet pheresis reduces allogeneic platelet use and improves the postoperative PaO2/FiO2 ratio in complex aortic surgery: a retrospective analysis.

OBJECTIVES: An autologous platelet-rich plasma pheresis (aPP) strategy can harvest partial whole blood that is separated into erythrocytes, plasma and platelets, and can reduce blood loss and transfusion during cardiovascular surgery using cardiopulmonary bypass (CPB). However, the blood and organ conservation effects of this technique have not been confirmed in the context of complex aortic surgery. METHODS: Perioperative records of 147 adult patients who underwent complex aortic surgery were analysed retrospectively. RESULTS: All patients received regular blood conservation treatment, and 57 patients received aPP. Whether or not the participants were propensity matched, decreased platelet and cryoprecipitate transfusions were found in the aPP group (both P < 0.001), but there were non-significant differences in erythrocyte transfusion, Sequential Organ Failure Assessment scores and other outcomes when compared with the same parameters in the non-aPP group. The aPP group had a higher arterial oxygen partial pressure to inhaled oxygen concentration ratio on postoperative days 1, 2 and 7 than the non-aPP group (P < 0.001, P < 0.001 and P = 0.048, respectively). CONCLUSIONS: The utilization of aPP was associated with a reduction in allogeneic platelet and cryoprecipitate transfusions as well as minor lung-protective effects during complex aortic surgery using CPB.

Low expression of miR-199 in hepatocellular carcinoma contributes to tumor cell hyper-proliferation by negatively suppressing XBP1.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide, and microRNAs (miRs) are considered to serve important functions in the pathogenesis of HCC by regulating the expression of specific target genes. The present study was conducted to investigate the role of miR-199 and its putative target X-box binding protein 1 (XBP1) in HCC, as well as of the downstream gene cyclin D. The expression levels of miR-199, XBP1 and cyclin D were detected in clinical HCC specimens. The effect of miR-199 on the regulation of HCC cell proliferation and its underlying mechanism were examined in Hep3B2.1-7 cells, through expression assays and measurement of cell proliferation (via Cell Counting Kit-8, and 5-ethynyl-2'-deoxyuridine and DAPI double-staining assays) coupled with gain- and lose- of function experiments. The expression of XBP1 and cyclin D was significantly increased in HCC tissues when compared with adjacent non-HCC tissues, while the expression of miR-199 was decreased. Exogenous miR-199 significantly suppressed the expression of XBP1 and cyclin D in Hep3B2.1-7 cells. However, the expression of XBP1 and cyclin D significantly increased on treatment with miR-199 inhibitor. Consistently, Hep3B2.1-7 cells co-transfected with a wild type reporter plasmid [XBP1-3'untranslated region (UTR)-WT] and exogenous miR-199 exhibited lower relative luciferase enzyme activity than cells co-transfected with negative control miRNA and XBP1-3'UTR-WT, while cells co-transfected with mutated plasmid (XBP1-3'UTR-MU) and miR-199 exhibited no change. It was further observed that knockdown of XBP1 by small interfering RNA significantly decreased the expression of cyclin D in Hep3B2.1-7 cells. Additionally, exogenous miR-199 decreased the proliferation of Hep3B2.1-7 cells, which was contrary to the effect of miR-199 inhibitor. In conclusion, it was demonstrated that miR-199 negatively regulated the expression of XBP1 by directly binding to its 3'UTR and that XBP1 impacted cyclin D expression, which was associated with the cell cycle regulation in Hep3B2.1-7 cells. These findings suggested that a miR-199/XBP1/cyclin D axis may serve an important role in the pathogenesis of HCC.

Wider intraoperative glycemic fluctuation increases risk of acute kidney injury after pediatric cardiac surgery.

OBJECTIVE: The association between poor intraoperative glycemic control and postoperative acute kidney injury (AKI) in adult cardiac surgery has been observed, but data in the pediatrics remain unknown. We performed a hypothesis that intraoperative hyperglycemia and/or wider glycemic fluctuation were associated with the incidence of postoperative AKI in pediatric cardiac surgery. METHODS: A retrospective study was performed in pediatrics who underwent cardiac surgery from 2013 to 2016. Perioperative glycemic data up to 48 hours after surgery were collected and analyzed. Patients with AKI were matched 1:1 with patients without AKI by a propensity score. Variables of demographic data, preoperative renal function and glycemic level, perioperative cardiac condition were matched. RESULTS: The incidence of AKI was 11.5% (118/1026), with 53.4% (63/118), 30.5% (36/118), and 16.1% (19/118) categorized as AKIN stages I, II, and III, respectively. Children who experienced AKI were younger and cyanotic, underwent more complex surgeries, had higher peak intraoperative glucose levels, wider intraoperative glycemic fluctuation, greater inotropic scores and more transfusions, and poor outcomes (all p < .05). After matching, the AKI group had significantly wider intraoperative glycemic fluctuation (p < .05). Logistic regression showed intraoperative glycemic fluctuation was one of the risk factors for AKI (p = .033) and degree of AKI severity stage increased when the glycemic fluctuation increased (p < .01). CONCLUSIONS: Wider intraoperative glycemic fluctuation, but not hyperglycemia, was associated with an increased incidence of postoperative AKI after pediatric cardiac surgery.

Role of ALK5/SMAD2/3 signaling in the regulation of NOX expression in cerebral ischemia/reperfusion injury.

Nicotinamide adenine dinucleotide phosphate oxidase (NOX)-derived reactive oxygen species (ROS) serve an important role in cerebral ischemia/reperfusion (I/R) injury. However, the mechanism by which ROS generation is regulated has not yet been fully elucidated. The present study aimed to explore the role of transforming growth factor-ß signaling in ROS generation. Sprague Dawley rats were subjected to I/R injury and PC-12 cells were transfected with small interfering RNA against activin receptor-like kinase (ALK)5 or hypoxia/reoxygenation (H/R). The results indicated that I/R or H/R significantly increased ALK5 expression, SMAD2/3 phosphorylation and NOX2/4 expression and activity, concomitant with ROS generation and apoptosis. In addition, ALK5 knockdown significantly reversed changes induced by H/R treatment in PC-12 cells. These results suggest that ALK5/SMAD2/3 signaling serves a key role in oxidative stress. To the best of our knowledge, this is the first study to demonstrate that ALK5/SMAD2/3 activation is associated with the regulation of NOX2/4 expression and exacerbates I/R injury.

P2X7 receptor is involved in lung injuries induced by ischemia-reperfusion in pulmonary arterial hypertension rats.

Pulmonary arterial hypertension (PAH) is a progressive disease that ultimately leads to right heart failure and death. Current strategies are ineffective to prevent and cure PAH, especially in those who undergo cardiopulmonary bypass. P2 × 7 receptors (P2 × 7Rs) have been implied to participate in the pathogenesis of PAH and injuries induced by ischemia-reperfusion (IR). In the present study, we aimed to assess the potential therapeutic effects of anti-P2 × 7Rs on PAH and IR-induced lung injuries in rats and explore their underlying cellular and molecular mechanisms. In the present study, we have successfully established rat models with PAH and/or lung IR injuries. Immunohistochemical staining, western blot, and polymerase chain reaction were performed to detect the P2 × 7R expression in these models; P2 × 7R-specific inhibitor, Brilliant Blue G (BBG), was used to antagonize P2 × 7R, and enzyme-linked immunosorbent assay was used to help evaluate the P2 × 7R-mediated function in PAH with or without IR. Moreover, BBG, SB203580 (p38/MAPK inhibitor), and CD39 (adenosine triphosphate hydrolase) were applied to explore the inner signal pathway in vitro and in vivo. Our findings showed that P2 × 7R was involved in the development of PAH. By applying BBG, we have shown that the severity of PAH and IR was ameliorated through reducing the release of proinflammatory cytokines. Moreover, our results in vitro and in vivo indicated that P2 × 7R regulated the release of inflammatory mediators by the p38/MAPK signal pathway. Most important, CD39 showed the most dominant potential in improving inflammation in lung injuries caused by PAH and IR. In conclusion, the inhibition of P2 × 7R could effectively attenuate inflammation in lung injuries caused by PAH and IR in rats by reducing proinflammatory cytokines through regulating the p38/MAPK pathway.

[Association of hypoalbuminemia with acute kidney injury in children after cardiac surgery].

OBJECTIVE: To study whether hypoalbuminemia after pediatric cardiopulmonary bypass (CPB) for cardiac surgery is a risk factor for postoperative acute kidney injury (AKI). METHODS: A retrospective analysis was performed on the clinical data of 1 110 children who underwent CPB surgery between 2012 and 2016. According to the minimum serum albumin within 48 hours postoperatively, these patients were divided into hypoalbuminemia group (≤35 g/L) and normal albumin group (>35 g/L). The two groups were compared in terms of perioperative data and the incidence of AKI. Furthermore, the incidence of AKI was compared again after propensity score matching for the unbalanced factors during the perioperative period. The perioperative risk factors for postoperative AKI were analyzed by logistic regression. RESULTS: The overall incidence rate of postoperative AKI was 13.78% (153/1 110), and the mortality rate was 2.52% (28/1 110). The mortality rate of children with AKI was 13.1% (20/153). The patients with hypoalbuminemia after surgery (≤35 g/L) accounted for 44.50% (494/1 110). Before and after propensity score matching, the hypoalbuminemia group had a significantly higher incidence of AKI than the normal albumin group (P<0.05). The children with AKI had a significantly lower serum albumin level after surgery than those without AKI (P<0.05). The multivariate logistic regression analysis showed albumin ≤35 g/L was one of the independent risk factors for postoperative AKI. CONCLUSIONS: Albumin ≤35 g/L within 48 hours postoperatively is an independent risk factor for postoperative AKI in children after CPB surgery.

Upregulation of NOX2 and NOX4 Mediated by TGF-ß Signaling Pathway Exacerbates Cerebral Ischemia/Reperfusion Oxidative Stress Injury.

BACKGROUND/AIMS: Ischemic stroke is still one of the leading debilitating diseases with high morbidity and mortality. NADPH oxidase (NOX)-derived reactive oxygen species (ROS) play an important role in cerebral ischemia/reperfusion (I/R) injury. However, the mechanism underlying the regulation of ROS generation is still not fully elucidated. This study aims to explore the role of transforming growth beta (TGF-ß) signals in ROS generation. METHODS: Sprague-Dawley rats were subjected to I/R injury, and PC-12 cells were challenged by hypoxia/reoxygenation (H/R) and/or treated with activin receptor-like kinase (ALK5) inhibitor Sb505124 or siRNA against ALK5. Brain damage was evaluated using neurological scoring, triphenyl tetrazolium chloride staining, hematoxylin and eosin staining, infarct volume measurement, TUNEL staining, and caspase-3 activity measurement. Expression of TGF-ß and oxidative stress-related genes was analyzed by real-time polymerase chain reaction and Western blot; NOX activity and ROS level were measured using spectrophotometry and fluorescence microscopy, respectively. RESULTS: I/R contributed to severe brain damage (impaired neurological function, brain infarction, tissue edema, apoptosis), TGF-ß signaling activation (upregulation of ALK5, phosphorylation of SMAD2/3) and oxidative stress (upregulation of NOX2/4, rapid release of ROS [oxidative burst]). However, Sb505124 significantly reversed these alterations and protected rats against I/R injury. As in the animal results, H/R also contributed to TGF-ß signaling activation and oxidative stress. Likewise, the inhibition of ALK5 or ALK5 knockdown significantly reversed these alterations in PC-12 cells. Other than ALK5 knockdown, ALK5 inhibition had no effect on the expression of ALK5 in PC-12 cells. CONCLUSIONS: Our studies demonstrated that TGF-ß signaling activation is involved in the regulation of NOX2/NOX4 expression and exacerbates cerebral I/R injury.

mir-193 targets ALDH2 and contributes to toxic aldehyde accumulation and tyrosine hydroxylase dysfunction in cerebral ischemia/reperfusion injury.

MicroRNAs (miRNAs, miR) play a fundamental role in cerebral ischemia/reperfusion (I/R) injury. However, the role of miRNAs in toxic aldehyde and tyrosine accumulation is not fully elucidated. We constructed a cerebral I/R rat model and found that overexpression of miR-193 was associated with the accumulation of 4-Hydroxynonenal (4-HNE), Malondialdehyde (MDA), and tyrosine, and with the decrease of aldehyde dehydrogenase (ALDH2), tyrosine hydroxylase (TH), and dopamine. To unveil the molecular mechanism of the miR-193-mediated phenotype in I/R injury as described above, we performed bioinformatic analysis and found that ALDH2 was a potential target of miR-193. Through in vitro experiments (such as miR-193 mimic/inhibitor transfection, luciferase reporter gene plasmid transfection, and 4-HNE exposure) and in vivo infusion of miR-193 agomir, we demonstrated that miR-193 directly suppressed the expression of ALDH2 and led to toxic aldehyde accumulation, resulting in dysfunction of tyrosine hydroxylase. The present study suggests that the overexpression of miR-193 in a rat model exacerbated brain injury due to the following sequential process: targeted suppression of ALDH2, aldehyde accumulation, and tyrosine hydroxylase dysfunction, leading to tyrosine accumulation and insufficiency of dopamine synthesis.

[Clinical characteristics and prognostic analysis of children with congenital heart disease complicated by postoperative acute kidney injury].

OBJECTIVE: To analyze the perioperative clinical data of children with congenital heart disease complicated by acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery, and to explore potential factors influencing the prognosis. METHODS: A retrospective analysis was performed among 118 children with congenital heart disease who developed AKI within 48 hours after CPB surgery. RESULTS: In the 118 patients, 18 died after 48 hours of surgery. Compared with the survivors, the dead children had significantly higher incidence of cyanotic disease and Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) scores before surgery; during surgery, the dead children had significantly longer CPB time and aortic cross-clamping time, a significantly higher proportion of patients receiving crystalloid solution for myocardial protection, and a significantly higher mean blood glucose level. Within 48 hours after surgery, the dead children had significantly higher positive inotropic drug scores, significantly higher creatinine values, a significantly higher incidence of stage 3 AKI, a significantly higher proportion of patients receiving renal replacement the, and significantly higher usage of blood products (P<0.05). The mortality rate of the patients increased with increased intraoperative blood glucose levels (P<0.05). Patients with intraoperative blood glucose levels >8.3 mmol/L had a significantly lower postoperative cumulative survival rate and a significantly shorter mean survival time than those with blood glucose levels ≤ 8.3 mmol/L (P<0.05). CONCLUSIONS: Intraoperative blood glucose levels are associated with the prognosis in children with congenital heart disease complicated by AKI after CPB surgery. Maintaining good intraoperative blood glucose control can improve the prognosis of the children.

Does magnesium-supplemented cardioplegia reduce cardiac injury? A meta-analysis of randomized controlled trials.

BACKGROUND: Magnesium is often used to supplement cardioplegic solutions during cardiopulmonary bypass due to its cardioprotective effect during ischemia and reperfusion. The aim of this meta-analysis was to evaluate the effects of magnesium-supplemented cardioplegia versus an inactive (placebo) control cardioplegia on reducing cardiac injury after cardiac arrest surgery, as found by randomized, controlled trials. METHODS: The Medline, Cochrane Library, and Chinese literature databases (CJFD, CBM, CSJD, Wanfang) were comprehensively searched for reports of randomized, controlled trials (RCTs) evaluating magnesium-supplemented cardioplegic solutions. The clinical parameters and outcomes of interest were the incidence of postoperative low cardiac output, auto-rebeating rate, ICU stay length, new onset postoperative atrial fibrillation, peak value of CK-MB (and/or cTnI), incidence of myocardial infarction, and in-hospital mortality. RESULTS: Ten trials, with a total of 1214 patients, were included. The frequency of low cardiac output, inotropic utilization, and myocardial infarction, as well as auto-rebeating rate, length of ICU stay and in-hospital mortality, were similar between the two groups. There was a marginal reduction in the incidence of new-onset postoperative atrial fibrillation in the magnesium-supplemented cardioplegia group. CONCLUSIONS: The advantage of magnesium-supplemented cardioplegia, compared with cardioplegia without magnesium, remains unconvincing based on the current evidence. The decision to add magnesium to the cardioplegic solution to a patient undergoing cardiac arrest surgery should be carefully considered.

GPC-1 may serve as a predictor of perineural invasion and a prognosticator of survival in pancreatic cancer.

OBJECTIVE: The purpose of this study was to investigate the expression of glial cell derived neurotrophic factor (GDNF), glypican-1 (GPC-1), and matrix metalloproteinase-9 (MMP-9), and their association with clinicopathologic characteristics as well as prognostic significance in pancreatic cancer. METHODS: Immunohistochemical assessment of GDNF, GPC-1, and MMP-9 was performed in 62 cases of surgically resected pancreatic cancer. Perineural invasion in pancreatic cancer was observed by marking nerve fiber with S-100, while 16 normal pancreatic tissues were used as normal control. Correlations of GDNF, GPC-1 and MMP-9 expressions with clinicopathologic parameters were analyzed. A survival analysis was performed to find the prognostic significance. RESULTS: The expressions of GDNF, GPC-1 and MMP-9 in pancreatic cancer tissue were significantly higher than of those in normal pancreatic tissues (41/62 vs. 5/16 for GDNF, 35/62 vs. 2/16 for GPC-1, and 37/62 vs. 3/16 for MMP-9; p<0.01, respectively). The overexpression of GDNF, GPC-1, and MMP-9 in pancreatic cancer tissue was significantly related to the perineural invasion (p<0.05). Although the overexpression of these genes was related to poor survival, GPC-1 had an independent prognostic effect on overall survival. CONCLUSION: GPC-1 is significantly related to the perineural invasion of pancreatic cancer, holding some prognostic significance in patients with pancreatic cancer.

[Expression and significance of Ezrin gene in pancreatic carcinoma tissues].

BACKGROUND & OBJECTIVE: Ezrin protein is a membrane cytoskeletal crosslinker between the cell membrane and cytoskeleton. Increasing evidence has shown that Ezrin may be associated with tumor invasion and progression. This study was to explore the correlation of Ezrin to metastasis of pancreatic carcinoma. METHODS: The expression of Ezrin mRNA in fresh specimens of 32 pancreatic carcinoma, 19 metastatic lesions and 10 non-cancerous pancreatic tissues were assessed by reverse transcription-polymerase chain (RT-PCR). RESULTS: The mRNA expression of Ezrin was significantly higher in pancreatic carcinoma tissues (1.9+/-1.1) than in non-cancerous tissues (0.9+/-0.5)(P<0.05), significantly higher in metastatic lesions (2.6+/-0.8) than in the primary tumor focus (1.9+/-1.1) (P<0.05), and significantly higher in pancreatic carcinoma lesions with metastasis (2.1+/-1.2) than in those without (1.4+/-0.7) ( P<0.05). Ezrin mRNA was differently expressed in tumors with different clinical pathologic characters. It was highly expressed in poorly differentiated or distantly metastatic carcinomas. CONCLUSIONS: Ezrin gene is closely related to invasion and metastasis of pancreatic carcinoma, which might be used as a marker in predicting the metastasis of pancreatic carcinoma.

[Debridement and drainage of infected necrosis for severe acute pancreatitis via lumbo-retroperitoneal route].

OBJECTIVE: To determine the route and ways of debridement and drainage of infected necrosis for severe acute pancreatitis (SAP) combined with pancreatic infection. METHODS: Clinical data of 28 patients with SAP accompanied with secondary pancreatic infection, who underwent lumbo-retroperitoneal debridement, drainage and lavage after the operation were retrospectively investigated. RESULTS: Four patients underwent one operation, 21 underwent 2 operations, and 3 underwent 3 operations. All patients recovered or improved and were discharged by postoperative lavage. Four patients had complications, including 1 gastrointestinal bleeding,1 intestinal fistula and 2 pancreatic fistula. CONCLUSION: Debridement and drainage of infected necrosis for SAP combined with pancreatic infection via lumbo-retroperitoneal route is direct, safe and effective.

[Surgical treatment of 2465 primary hepatolithiasis cases].

OBJECTIVE: To summarize the experience of surgical treatment of primary hepatolithiasis. METHODS: To analyze the clinical data, operation choice, postoperative complications of 2465 cases of primary hepatolithiasis retrospectively. RESULTS: Of the patients, 2034 received external drainage (82.5%) and 431 received internal drainage (17.5%) and 586 were performed adjunctive partial hepatectomy (23.8%). The postoperative complications were found in 211 cases (8.6%) and 17 cases (0.7%) died after the operation. One thousand seven hundred and sixty-seven cases (71.7%) have been followed up for 2 to 25 years, among them therapeutic effect of 1518 cases (85.9%) was excellent or good, 315 cases (17.8%) had residual stone and 115 cases (6.5%) recurred. CONCLUSIONS: It could decrease the incidence rate of complications, residual stone and recurrence in the patients with hepatolithiasis after surgical therapy to pinpoint the situs of the lithiasis and biliary stricture and managed properly before the surgery.

Effect of normothermic liver ischemic preconditioning on the expression of apoptosis-regulating genes C-jun and Bcl-XL in rats.

AIM: To explore the expression of apoptosis-regulating genes C-jun and Bcl-XL after normothermic liver ischemic preconditioning and its protective effect on hepatocytes in the rat. METHODS: Wistar rats are randomly divided into sham operation group (S group, n = 10), ischemic reperfusion group (IR group, n = 10) and ischemic preconditioning group (IP group, n = 10). After dissection of the hepatoduodenal ligament in S group, and after 30-min reperfusion in IR group and in IP group, the samples of liver tissue were taken for studying the hepatocellular apoptosis, the expressions of C-jun mRNA, Bcl-XL mRNA and their proteins, and morphologic changes at 0, 3, 6, 20 h. Meanwhile the venous blood samples were drawn at 3, 6 and 20 h for testing ALT, AST and LDH. RESULTS: The levels of ALT, AST and LDH in IR group and IP group were significantly higher than those in S group. Hepatocellular apoptosis was significantly increased in both IR group and IP group, especially in IR group. Expressions of C-jun mRNA and protein were significantly increased in IR group compared with those in both IP group and S group, but no significant difference between IP group and S group (P>0.05). Expressions of Bcl-XL mRNA and protein in IR group and S group were not significant (P>0.05), but were significantly increased in IP group compared with those in both S group and IR group. Patch necrosis of hepatocytes because of severe injury could be seen in IR group microscopically, and the ultrastructural changes were irreversible. Meanwhile in IP group, no hepatocellular necrosis occurred, and the ultrastructural changes were reversible because of mild injury. CONCLUSION: (1) IP can protect the rat liver from normothermic IR injury by modulation of the expression of apoptosis-regulating genes C-jun and Bcl-XL; (2) IR injury may activate the apoptosis of hepatocytes by increasing the expression of apoptosis-inducing gene C-jun; (3) IP may prohibit the apoptosis of hepatocytes by increasing the expression of apoptosis-inhibitory gene Bcl-XL.