Pelagibacterium flavum sp. nov., Isolated from Soil Sample.

A Gram-stain-negative, yellow, moist and circular, aerobic, motile, and rod-shaped bacterium, designated YIM 151497T, was isolated from soil sample collected from Blue-Bridge, Weizhou Island, Guangxi province, China. Classification using a polyphasic approach suggested that strain YIM 151497T belonged to the genus Pelagibacterium, and was closely relevant to Pelagibacterium nitratireducens JLT2005T (98.8%), Pelagibacterium halotolerans CGMCC 1.7692T (98.7%), Pelagibacterium lixinzhangensis H64T (98.1%), and Pelagibacterium luteolum CGMCC 1.10267T (97.1%). The growth ranges of temperature, pH, and NaCl were 4-40 â„ƒ, pH 4.0-10.0, and 0-7% NaCl, respectively. It was positive for catalase and oxidase. The primary respiratory quinone was Q-10. The elemental fatty acids were Summed Feature 8 (constituting C18:1ω7c and/or C18:1ω6c), C19:0 cyclo ω8c, C16:0, and C18:1ω7c 11-methyl. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol, and three unidentified glycolipids. The DNA G+C content based on the complete genome sequence was 60.7 mol%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) between strain YIM 151497T and species of Pelagibacterium were in the ranges of 73.9-86.3% and 19.7-31.3%, respectively. The Average Amino Acid Identity (AAI) between strain YIM 151497T and species of Pelagibacterium were in the ranges of 68.8-88.8%. On the basis of these data, strain YIM 151497T is considered to represent a novel species of the genus Pelagibacterium with the name of Pelagibacterium flavum sp. nov. Type strain is strain YIM 151497T (= KCTC 49826T = CGMCC 1.61521T = MCCC 1K08053T).

Investigating the Pharmacological Mechanisms of Total Flavonoids from Eucommia ulmoides Oliver Leaves for Ischemic Stroke Protection.

The aim of this study was to explore how the total flavonoids from Eucommia ulmoides leaves (EULs) regulate ischemia-induced nerve damage, as well as the protective effects mediated by oxidative stress. The cell survival rate was significantly improved compared to the ischemic group (p < 0.05) after treatment with the total flavonoids of EULs. The levels of reactive oxygen species (ROS), lactate dehydrogenase (LDH), and malondialdehyde (MDA) decreased, while catalase (CAT) and glutathione (GSH) increased, indicating that the total flavonoids of EULs can significantly alleviate neurological damage caused by ischemic stroke by inhibiting oxidative stress (p < 0.01). The mRNA expression level of VEGF increased (p < 0.01), which was consistent with the protein expression results. Meanwhile, the protein expression of ERK and CCND1 increased (p < 0.01), suggesting that the total flavonoids of EULs could protect PC12 cells from ischemic injury via VEGF-related pathways. MCAO rat models indicated that the total flavonoids of EULs could reduce brain ischemia-reperfusion injury. In conclusion, this study demonstrates the potential mechanisms of the total flavonoids of EULs in treating ischemic stroke and their potential therapeutic effects in reducing ischemic injury, which provides useful information for ischemic stroke drug discovery.

PPARγ inhibits small airway remodeling through mediating the polarization homeostasis of alveolar macrophages in COPD.

The role of Peroxisome Proliferator-Activated Receptor-γ (PPARγ) in alveolar macrophages(AMs) polarization homeostasis is closely associated with airway remodeling in COPD, but the definite mechanism remains unclear. In this study, elevated percentage of M1-type AMs and the expression of functionally cytokines were found in COPD patients and mice, which closely related to the disease severity. PPARγ was markedly up-regulated in M2-type AMs and down-regulated in M1-type AMs, and was associated with disease severity in COPD. Co-cultured with M1- or M2-type AMs promoted the epithelial-mesenchymal transition (EMT) of airway epithelial cells and the proliferation of airway smooth muscle cells. Moreover, airway remodeling and functional damage were observed in both IL4R-/- COPD mice with runaway M1-type AMs polarization and TLR4-/- COPD mice with runaway M2-type AMs polarization. Cigarette extract (CS) or lipopolysaccharide (LPS) stimulated PPARγ-/- AMs showed more serious polarization disorder towards M1, as well as CS induced PPARγ-/- COPD mice, which led to more severe airway inflammation, lung function damage, and airway remodeling. Treatment with PPARγ agonist significantly improved the polarization disorder and function activity in CS/LPS stimulated-AMs by inhibiting the JAK-STAT, MAPK and NF-κB pathways, and alleviated the airway inflammation, restored the lung function and suppressed airway remodeling in CS induced-COPD mice. Our research demonstrates that polarization homeostasis of AMs mediated by PPARγ has the protective effect in airway remodeling, and may be a novel therapeutic target for the intervention and treatment of airway remodeling in COPD.

Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most frequent and potentially life-threatening complications following pancreatic surgery. Fibrin sealants have been used in some centres to reduce POPF rate. However, the use of fibrin sealant during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2020. OBJECTIVES: To evaluate the benefits and harms of fibrin sealant use for the prevention of POPF (grade B or C) in people undergoing pancreatic surgery compared to no fibrin sealant use. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases, and five trials registers on 09 March 2023, together with reference checking, citation searching, and contacting study authors to identify additional studies. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared fibrin sealant (fibrin glue or fibrin sealant patch) versus control (no fibrin sealant or placebo) in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 14 RCTs, randomising 1989 participants, comparing fibrin sealant use versus no fibrin sealant use for different locations: stump closure reinforcement (eight trials), pancreatic anastomosis reinforcement (five trials), or main pancreatic duct occlusion (two trials). Six RCTs were carried out in single centres; two in dual centres; and six in multiple centres. One RCT was conducted in Australia; one in Austria; two in France; three in Italy; one in Japan; two in the Netherlands; two in South Korea; and two in the USA. The mean age of the participants ranged from 50.0 years to 66.5 years. All RCTs were at high risk of bias. Application of fibrin sealants to pancreatic stump closure reinforcement after distal pancreatectomy We included eight RCTs involving 1119 participants: 559 were randomised to the fibrin sealant group and 560 to the control group after distal pancreatectomy. Fibrin sealant use may result in little to no difference in the rate of POPF (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.73 to 1.21; 5 studies, 1002 participants; low-certainty evidence) and overall postoperative morbidity (RR 1.20, 95% CI 0.98 to 1.48; 4 studies, 893 participants; low-certainty evidence). After fibrin sealant use, approximately 199 people (155 to 256 people) out of 1000 developed POPF compared with 212 people out of 1000 when no fibrin sealant was used. The evidence is very uncertain about the effect of fibrin sealant use on postoperative mortality (Peto odds ratio (OR) 0.39, 95% CI 0.12 to 1.29; 7 studies, 1051 participants; very low-certainty evidence) and total length of hospital stay (mean difference (MD) 0.99 days, 95% CI -1.83 to 3.82; 2 studies, 371 participants; very low-certainty evidence). Fibrin sealant use may reduce the reoperation rate slightly (RR 0.40, 95% CI 0.18 to 0.90; 3 studies, 623 participants; low-certainty evidence). Serious adverse events were reported in five studies (732 participants), and there were no serious adverse events related to fibrin sealant use (low-certainty evidence). The studies did not report quality of life or cost-effectiveness. Application of fibrin sealants to pancreatic anastomosis reinforcement after pancreaticoduodenectomy We included five RCTs involving 519 participants: 248 were randomised to the fibrin sealant group and 271 to the control group after pancreaticoduodenectomy. The evidence is very uncertain about the effect of fibrin sealant use on the rate of POPF (RR 1.34, 95% CI 0.72 to 2.48; 3 studies, 323 participants; very low-certainty evidence), postoperative mortality (Peto OR 0.24, 95% CI 0.05 to 1.06; 5 studies, 517 participants; very low-certainty evidence), reoperation rate (RR 0.74, 95% CI 0.33 to 1.66; 3 studies, 323 participants; very low-certainty evidence), and total hospital cost (MD -1489.00 US dollars, 95% CI -3256.08 to 278.08; 1 study, 124 participants; very low-certainty evidence). After fibrin sealant use, approximately 130 people (70 to 240 people) out of 1000 developed POPF compared with 97 people out of 1000 when no fibrin sealant was used. Fibrin sealant use may result in little to no difference both in overall postoperative morbidity (RR 1.02, 95% CI 0.87 to 1.19; 4 studies, 447 participants; low-certainty evidence) and in total length of hospital stay (MD -0.33 days, 95% CI -2.30 to 1.63; 4 studies, 447 participants; low-certainty evidence). Serious adverse events were reported in two studies (194 participants), and there were no serious adverse events related to fibrin sealant use (very low-certainty evidence). The studies did not report quality of life. Application of fibrin sealants to pancreatic duct occlusion after pancreaticoduodenectomy We included two RCTs involving 351 participants: 188 were randomised to the fibrin sealant group and 163 to the control group after pancreaticoduodenectomy. The evidence is very uncertain about the effect of fibrin sealant use on postoperative mortality (Peto OR 1.41, 95% CI 0.63 to 3.13; 2 studies, 351 participants; very low-certainty evidence), overall postoperative morbidity (RR 1.16, 95% CI 0.67 to 2.02; 2 studies, 351 participants; very low-certainty evidence), and reoperation rate (RR 0.85, 95% CI 0.52 to 1.41; 2 studies, 351 participants; very low-certainty evidence). Fibrin sealant use may result in little to no difference in the total length of hospital stay (median 16 to 17 days versus 17 days; 2 studies, 351 participants; low-certainty evidence). Serious adverse events were reported in one study (169 participants; low-certainty evidence): more participants developed diabetes mellitus when fibrin sealants were applied to pancreatic duct occlusion, both at three months' follow-up (33.7% fibrin sealant group versus 10.8% control group; 29 participants versus 9 participants) and 12 months' follow-up (33.7% fibrin sealant group versus 14.5% control group; 29 participants versus 12 participants). The studies did not report POPF, quality of life, or cost-effectiveness. AUTHORS' CONCLUSIONS: Based on the current available evidence, fibrin sealant use may result in little to no difference in the rate of POPF in people undergoing distal pancreatectomy. The evidence is very uncertain about the effect of fibrin sealant use on the rate of POPF in people undergoing pancreaticoduodenectomy. The effect of fibrin sealant use on postoperative mortality is uncertain in people undergoing either distal pancreatectomy or pancreaticoduodenectomy.

Design, Synthesis and Biological Evaluation of Multi-Target Anti-Cancer Agent PYR26.

This study investigates the synthesis of a new compound, PYR26, and the multi-target mechanism of PYR26 inhibiting the proliferation of HepG2 human hepatocellular carcinoma cells. PYR26 significantly inhibits the growth of HepG2 cells (p < 0.0001) and this inhibition has a concentration effect. There was no significant change in ROS release from HepG2 cells after PYR26 treatment. The mRNA expressions of CDK4, c-Met and Bak genes in HepG2 cells were significantly inhibited (p < 0.05), while mRNA expression of pro-apoptotic factors such as caspase-3 and Cyt c was significantly increased (p < 0.01). The expression of PI3K, CDK4 and pERK proteins decreased. The expression level of caspase-3 protein was increased. PI3K is a kind of intracellular phosphatidylinositol kinase. PI3K signaling pathway is involved in signal transduction of a variety of growth factors, cytokines and extracellular matrix and plays an important role in preventing cell apoptosis, promoting cell survival and influencing cell glucose metabolism. CDK4 is a catalytic subunit of the protein kinase complex and is important for G1 phase progression of the cell cycle. PERK refers to phosphorylated activated ERK, which is translocated from cytoplasm to the nucleus after activation, and then participates in various biological reactions such as cell proliferation and differentiation, cell morphology maintenance, cytoskeleton construction, cell apoptosis and cell canceration. Compared with the model group and the positive control group, the tumor volume of the nude mice in the low-concentration PYR26 group, the medium-concentration group and the high-concentration group was smaller, and the organ volume was smaller than that in the model group and the positive control group. The tumor inhibition rates of low-concentration group PYR26, medium-concentration group and high-concentration group reached 50.46%, 80.66% and 74.59%, respectively. The results showed that PYR26 inhibited the proliferation of HepG2 cells and induced apoptosis of HepG2 cells by down-regulating c-Met, CDK4 and Bak, up-regulating the mRNA expression of caspase-3 and Cyt c genes, down-regulating PI3K, pERK and CDK4 proteins and up-regulating the protein level of caspase-3. In a certain range, with the increase in PYR26 concentration, the tumor growth was slower and the tumor volume was smaller. Preliminary results showed that PYR26 also had an inhibitory effect on the tumors of Hepa1-6 tumor-bearing mice. These results suggest that PYR26 has an inhibitory effect on the growth of liver cancer cells, therefore it has potential to be developed into a new anti-liver cancer drug.

CTLA4Ig/VISTAIg combination therapy selectively induces CD4+ T cell-mediated immune tolerance by targeting the SOCS1 signaling pathway in porcine islet xenotransplantation.

T cell inhibitory receptors can regulate the proliferation or function of T cells by binding to their ligands and present a unique opportunity to manage destructive immune responses during porcine islet xenotransplantation. We applied ex vivo porcine islet xenotransplantation and in vitro mixed lymphocyte-islet reaction models to assess immune checkpoint receptor expression profiles in recipient T cells, investigated whether CTLA4 or VISTA immunoglobulin (Ig) combination therapy alone could suppress porcine islet xenograft rejection and further analyzed its potential immune tolerance mechanism. Recipient T cells expressed moderate to high levels of CTLA4, PD-1, TIGIT and VISTA, and the frequency of CTLA4+ CD4+ , TIGIT+ CD4+ , VISTA+ CD4+ and VISTA+ CD8+ T cells was positively correlated with porcine islet xenograft survival time in xenotransplant recipients. Combined treatment with CTLA4Ig and VISTAIg selectively inhibited recipient CD4+ T cell hyper-responsiveness and proinflammatory cytokine production and significantly delayed xenograft rejection. SOCS1 deficiency in CD4+ T cells stimulated by xenogeneic islets facilitated hyper-responsiveness and abolished the suppressive effect of combination therapy on recipient T cell-mediated porcine islet damage in vivo and in vitro. Further mechanistic studies revealed that combined treatment significantly induced SOCS1 expression and inhibited the Jak-STAT signalling pathway in wild-type recipient CD4+ T cells stimulated by xenogeneic islets, whereas SOCS1 deficiency resulted in Jak-STAT signalling pathway activation in recipient CD4+ T cells. We demonstrated a major role for CTLA4 and VISTA as key targets in CD4+ T cell hyper-responsiveness and porcine islet xenograft rejection. The selective inhibition of CD4+ T cell immunity by CTLA4Ig/VISTAIg is based on SOCS1-dependent signalling.

Acinetobacter faecalis Sp. Nov., Isolated from Elephant Faeces.

A Gram-negative coccobacillus, YIM 103518T, isolated from wild elephant feces in Xishuangbanna, Yunnan Province, West China, was characterized and identified using a polyphasic taxonomic approach. The strain was strictly aerobic, non-motile, catalase-positive and oxidase-negative, colonies were round, convex, smooth, and pale yellow. The strain growth at 4-40 ℃ (optimum, 28 ℃), pH 6.0-10.0 (optimum, pH 7.0) and 0-4% NaCl (optimum, 0%) in culture medium YIM 38. The major fatty acids of strain YIM 103518T were summed feature 3 (C16:1 ω6c/C16:1 ω7c), C16:0, and C18:1 ω9c. The predominant ubiquinone was Q-9. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and phospholipids. The 16S rRNA gene sequence showed moderate level of similarity with Acinetobacter portensis AC 877T (98.7%), Acinetobacter sichuanensis CCTCC AB 2018118T (97.1%), and Acinetobacter cumulans CCTCC AB 2018119T (97.1%). The G+C content of the genomic DNA was 36.5 mol%. Strain YIM 103518T showed an average nucleotide identity value of 86.6%, 77.3% and 78.5%, a digital DNA-DNA hybridizations value of 31.2%, 21.9% and 23.0% with the type strain of A. portensis, A. sichuanensis and A. cumulans based on draft genome sequences, respectively. The results of the phenotypic, chemotaxonomic and phylogenetic analyses, showed that strain YIM 103518T represents a novel species of the genus Acinetobacter, for which the name Acinetobacter faecalis sp. nov. is proposed. The type strain is YIM 103518T (=CCTCC AB 2019201T = NBRC 114057T).

Inhibition of syndecan-4 reduces cartilage degradation in murine models of osteoarthritis through the downregulation of HIF-2α by miR-96-5p.

The membranous receptor syndecan-4 (SDC-4) and the nuclear transcription factor hypoxia-induced factor-2α (HIF-2α) play critical roles in the pathogenesis of osteoarthritis (OA). The aim of this study was to determine whether SDC-4 inhibition downregulates HIF-2a expression by microRNA-96-5p (miR-96-5p) in murine chondrocyte and cartilage tissue. The OA model was induced surgically in mice, and SDC-4 polyclonal antibody, HIF-2α small interfering RNA (siRNA) and its control, miR-96-5p mimics and its scrambled controls or anti-miR-96-5p and its control were then injected into the knee joints. At 2 and 4 weeks after surgery, OA progression was evaluated microscopically, histologically, radiographically and immunohistochemically in these mice. Real-time polymerase chain reaction (RT-PCR) and western blotting were performed after treating with antibody and transfecting with miRNA mimic or siRNA to determine their effects on OA-related mediators. The potential miRNAs related to OA development were identified by using miRNA microarray analysis. Whether miRNAs play a pivotal role in OA development in vivo or in vitro was also investigated. MiR-96-5p expression was upregulated by SDC-4-specific antibodies in chondrocytes and cartilage tissue, and miR-96-5p directly targeted the 3'-UTR of HIF-2α to inhibit HIF-2α signaling in murine chondrocytes. Moreover, we demonstrated that anti-SDC-4-attenuated IL-1ß-induced chondrocyte hypertrophy and cartilage degradation by inhibiting HIF-2α signaling by a miR-96-5p-dependent mechanism. Our study revealed that the inhibition of SDC-4 exerts its effects on both cartilage homeostasis and the chondrocyte hypertrophy phenotype by inducing miR-96-5p expression, which results in targeting HIF-2α 3'-UTR sequences and inhibiting HIF-2α in murine cartilage tissue and chondrocytes.

Prophylactic abdominal drainage for pancreatic surgery.

BACKGROUND: The use of surgical drains is a very common practice after pancreatic surgery. The role of prophylactic abdominal drainage to reduce postoperative complications after pancreatic surgery is controversial. This is the third update of a previously published Cochrane Review to address the uncertain benifits of prophylactic abdominal drainage in pancreatic surgery. OBJECTIVES: To assess the benefits and harms of routine abdominal drainage after pancreatic surgery, compare the effects of different types of surgical drains, and evaluate the optimal time for drain removal. SEARCH METHODS: In this updated review, we re-searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, and the Chinese Biomedical Literature Database (CBM) on 08 February 2021. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared abdominal drainage versus no drainage in people undergoing pancreatic surgery. We also included RCTs that compared different types of drains and different schedules for drain removal in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the studies for inclusion, collected the data, and assessed the risk of bias. We conducted the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) or standardized mean difference (SMD) for continuous outcomes with 95% confidence intervals (CI). For all analyses, we used the random-effects model. We used GRADE to assess the certainty of the evidence for important outcomes. MAIN RESULTS: We identified a total of nine RCTs with 1892 participants. Drain use versus no drain use We included four RCTs with 1110 participants, randomised to the drainage group (N = 560) and the no drainage group (N = 550) after pancreatic surgery. Low-certainty evidence suggests that drain use may reduce 90-day mortality (RR 0.23, 95% CI 0.06 to 0.90; two studies, 478 participants). Compared with no drain use, low-certainty evidence suggests that drain use may result in little to no difference in 30-day mortality (RR 0.78, 95% CI 0.31 to 1.99; four studies, 1055 participants), wound infection rate (RR 0.98, 95% CI 0.68 to 1.41; four studies, 1055 participants), length of hospital stay (MD -0.14 days, 95% CI -0.79 to 0.51; three studies, 876 participants), the need for additional open procedures for postoperative complications (RR 1.33, 95% CI 0.79 to 2.23; four studies, 1055 participants), and quality of life (105 points versus 104 points; measured with the pancreas-specific quality of life questionnaire (scale 0 to 144, higher values indicating a better quality of life); one study, 399 participants). There was one drain-related complication in the drainage group (0.2%). Moderate-certainty evidence suggests that drain use probably resulted in little to no difference in morbidity (RR 1.03, 95% CI 0.94 to 1.13; four studies, 1055 participants). The evidence was very uncertain about the effect of drain use on intra-abdominal infection rate (RR 0.97, 95% CI 0.52 to 1.80; four studies, 1055 participants; very low-certainty evidence), and the need for additional radiological interventions for postoperative complications (RR 0.87, 95% CI 0.40 to 1.87; three studies, 660 participants; very low-certainty evidence). Active versus passive drain We included two RCTs involving 383 participants, randomised to the active drain group (N = 194) and the passive drain group (N = 189) after pancreatic surgery. Compared with a passive drain, the evidence was very uncertain about the effect of an active drain on 30-day mortality (RR 1.23, 95% CI 0.30 to 5.06; two studies, 382 participants; very low-certainty evidence), intra-abdominal infection rate (RR 0.87, 95% CI 0.21 to 3.66; two studies, 321 participants; very low-certainty evidence), wound infection rate (RR 0.92, 95% CI 0.44 to 1.90; two studies, 321 participants; very low-certainty evidence), morbidity (RR 0.97, 95% CI 0.53 to 1.77; two studies, 382 participants; very low-certainty evidence), length of hospital stay (MD -0.79 days, 95% CI -2.63 to 1.04; two studies, 321 participants; very low-certainty evidence), and the need for additional open procedures for postoperative complications (RR 0.44, 95% CI 0.11 to 1.83; two studies, 321 participants; very low-certainty evidence). There was no drain-related complication in either group. Early versus late drain removal We included three RCTs involving 399 participants with a low risk of postoperative pancreatic fistula, randomised to the early drain removal group (N = 200) and the late drain removal group (N = 199) after pancreatic surgery. Compared to late drain removal, the evidence was very uncertain about the effect of early drain removal on 30-day mortality (RR 0.99, 95% CI 0.06 to 15.45; three studies, 399 participants; very low-certainty evidence), wound infection rate (RR 1.32, 95% CI 0.45 to 3.85; two studies, 285 participants; very low-certainty evidence), hospital costs (SMD -0.22, 95% CI -0.59 to 0.14; two studies, 258 participants; very low-certainty evidence), the need for additional open procedures for postoperative complications (RR 0.77, 95% CI 0.28 to 2.10; three studies, 399 participants; very low-certainty evidence), and the need for additional radiological procedures for postoperative complications (RR 1.00, 95% CI 0.21 to 4.79; one study, 144 participants; very low-certainty evidence). We found that early drain removal may reduce intra-abdominal infection rate (RR 0.44, 95% CI 0.22 to 0.89; two studies, 285 participants; very low-certainty evidence), morbidity (RR 0.49, 95% CI 0.30 to 0.81; two studies, 258 participants; very low-certainty evidence), and length of hospital stay (MD -2.20 days, 95% CI -3.52 to -0.87; three studies, 399 participants; very low-certainty evidence), but the evidence was very uncertain. None of the studies reported on drain-related complications. AUTHORS' CONCLUSIONS: Compared with no drain use, it is unclear whether routine drain use has any effect on mortality at 30 days or postoperative complications after pancreatic surgery. Compared with no drain use, low-certainty evidence suggests that routine drain use may reduce mortality at 90 days. Compared with a passive drain, the evidence is very uncertain about the effect of an active drain on mortality at 30 days or postoperative complications. Compared with late drain removal, early drain removal may reduce intra-abdominal infection rate, morbidity, and length of hospital stay for people with low risk of postoperative pancreatic fistula, but the evidence is very uncertain.

LINC00963 targeting miR-128-3p promotes acute kidney injury process by activating JAK2/STAT1 pathway.

The role of long non-coding RNAs (lncRNAs) in kidney diseases has been gradually discovered in recent years. LINC00963, as an lncRNA, was found to be involved in chronic renal failure. However, the role and molecular mechanisms of LINC00963 engaged in acute kidney injury (AKI) were still unclear. In this study, we established rat AKI models by ischaemia and reperfusion (I/R) treatment. Urea and creatinine levels were determined, and histological features of kidney tissues were examined following HE staining. CCK8 assay was chosen to assess the viability of hypoxia-induced HK-2 cells. Dual-luciferase reporter gene assays were performed to verify the target relationship between LINC00963 and microRNA. The mRNA and protein levels were assayed by RT-qPCR and Western blot, respectively. Annexin V-FITC/PI and TUNEL staining were used to evaluate apoptosis. LINC00963 was highly expressed in the cell and rat models, and miR-128-3p was predicted and then verified as a target gene of LINC00963. Knockdown of LINC00963 reduced acute renal injury both in vitro and in vivo. LINC00963 activated the JAK2/STAT1 pathway to aggravate renal I/R injury. LINC00963 could target miR-128-3p to reduce G1 arrest and apoptosis through JAK2/STAT1 pathway to promote the progression of AKI.

Anti-inflammatory effects of adiponectin in cigarette smoke-activated alveolar macrophage through the COX-2/PGE2 and TLRs signaling pathway.

OBJECTIVES: Airway macrophages represents a central site for the mechanisms involved in the complex interactions between environmental triggers and airway inflammation. Based on anti-inflammatory activity of adiponectin, we hypothesize that adiponectin inhibits the proinflammatory cytokines production and the activation of alveolar macrophages expose to cigarette smoke. MATERIALS AND METHODS: To examine the effects of adiponectin on alveolar macrophages, we used the cigarette smoke-induced the alveolar inflammation model in C57BL/6 mice and the macrophages activation model in vitro, both in the presence or absence of adiponectin, to assess the accumulation of inflammatory cells and the concentration of inflammatory cytokines and chemokines in the bronchoalveolar lavage (BAL), and the proinflammatory cytokines production and M1/2 phenotype in alveolar macrophages. RESULTS: Our results showed that adiponectin improves cigarette smoke-induced airway inflammation in vivo and decreases proinflammatory cytokine production and alveolar macrophages polarization in vitro. Moreover, our study further demonstrates that anti-inflammatory activity of adiponectin depends on the suppression of the proinflammatory cytokine production through TLR2/4 signaling and the inhibition of macrophage polarization vit COX-2/PGE2 signaling. CONCLUSIONS: Our study suggests that the anti-inflammatory activity of adiponectin might contribute to its therapeutic potential in airway inflammation, such as COPD.

Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery.

BACKGROUND: Postoperative pancreatic fistula is one of the most frequent and potentially life-threatening complications following pancreatic resections. Fibrin sealants have been used in some centers to reduce postoperative pancreatic fistula. However, the use of fibrin sealants during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2018. OBJECTIVES: To assess the safety, effectiveness, and potential adverse effects of fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. SEARCH METHODS: We searched trial registers and the following biomedical databases: the Cochrane Library (2019, Issue 2), MEDLINE (1946 to 13 March2019), Embase (1980 to 11 March 2019), Science Citation Index Expanded (1900 to 13 March 2019), and Chinese Biomedical Literature Database (CBM) (1978 to 13 March 2019). SELECTION CRITERIA: We included all randomised controlled trials that compared fibrin sealant (fibrin glue or fibrin sealant patch) versus control (no fibrin sealant or placebo) in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes (or a Peto odds ratio (OR) for very rare outcomes), and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). MAIN RESULTS: We included 12 studies involving 1604 participants in the review. Application of fibrin sealants to pancreatic stump closure reinforcement after distal pancreatectomy We included seven studies involving 860 participants: 428 were randomised to the fibrin sealant group and 432 to the control group after distal pancreatectomy. Fibrin sealants may lead to little or no difference in postoperative pancreatic fistula (fibrin sealant 19.3%; control 20.1%; RR 0.96, 95% CI 0.68 to 1.35; 755 participants; four studies; low-quality evidence). Fibrin sealants may also lead to little or no difference in postoperative mortality (0.3% versus 0.5%; Peto OR 0.52, 95% CI 0.05 to 5.03; 804 participants; six studies; low-quality evidence), or overall postoperative morbidity (28.5% versus 23.2%; RR 1.23, 95% CI 0.97 to 1.58; 646 participants; three studies; low-quality evidence). We are uncertain whether fibrin sealants reduce reoperation rate (2.0% versus 3.8%; RR 0.51, 95% CI 0.15 to 1.71; 376 participants; two studies; very low-quality evidence) or length of hospital stay (MD 0.99 days, 95% CI -1.83 to 3.82; 371 participants; two studies; very low-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness. Application of fibrin sealants to pancreatic anastomosis reinforcement after pancreaticoduodenectomy We included four studies involving 393 participants: 186 were randomised to the fibrin sealant group and 207 to the control group after pancreaticoduodenectomy. We are uncertain whether fibrin sealants reduce postoperative pancreatic fistula (16.7% versus 11.7%; RR 1.14, 95% CI 0.28 to 4.69; 199 participants; two studies; very low-quality evidence). We are uncertain whether fibrin sealants reduce postoperative mortality (0.5% versus 2.4%; Peto OR 0.26, 95% CI 0.05 to 1.32; 393 participants; four studies; low-quality evidence) or length of hospital stay (MD 0.01 days, 95% CI -3.91 to 3.94; 323 participants; three studies; very low-quality evidence). There is probably little or no difference in overall postoperative morbidity (52.6% versus 50.3%; RR 1.04, 95% CI 0.87 to 1.24; 323 participants; three studies; moderate-quality evidence) between the groups. We are uncertain whether fibrin sealants reduce reoperation rate (5.2% versus 7.7%; RR 0.74, 95% CI 0.33 to 1.66; 323 participants; three studies, very low-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness. Application of fibrin sealants to pancreatic duct occlusion after pancreaticoduodenectomy We included two studies involving 351 participants: 188 were randomised to the fibrin sealant group and 163 to the control group after pancreaticoduodenectomy. Fibrin sealants may lead to little or no difference in postoperative mortality (8.4% versus 6.1%; Peto OR 1.41, 95% CI 0.63 to 3.13; 351 participants; two studies; low-quality evidence) or length of hospital stay (median 16 to 17 days versus 17 days; 351 participants; two studies; low-quality evidence). We are uncertain whether fibrin sealants reduce overall postoperative morbidity (32.0% versus 27.6%; RR 1.16, 95% CI 0.67 to 2.02; 351 participants; two studies; very low-quality evidence), or reoperation rate (13.6% versus 16.0%; RR 0.85, 95% CI 0.52 to 1.41; 351 participants; two studies; very low-quality evidence). Serious adverse events were reported in one study (169 participants; low-quality evidence): more participants developed diabetes mellitus when fibrin sealants were applied to pancreatic duct occlusion, both at three months' follow-up (33.7% fibrin sealant group versus 10.8% control group; 29 participants versus 9 participants) and 12 months' follow-up (33.7% fibrin sealant group versus 14.5% control group; 29 participants versus 12 participants). The studies did not report postoperative pancreatic fistula, quality of life, or cost effectiveness. AUTHORS' CONCLUSIONS: Based on the current available evidence, fibrin sealants may have little or no effect on postoperative pancreatic fistula in people undergoing distal pancreatectomy. The effects of fibrin sealants on the prevention of postoperative pancreatic fistula are uncertain in people undergoing pancreaticoduodenectomy.

MSCs promote the development and improve the function of neonatal porcine islet grafts.

Deficient insulin secretion caused by immaturity is the predominant disadvantage of neonatal porcine islets (NPIs) when they serve as a source for islet xenotransplantation. We hypothesize that the transplantation of NPIs with a combination of mesenchymal stem cells (MSCs) can accelerate NPI maturation and improve the engraftment and function of NPIs. After indirect coculturing with monkey MSCs over 21 d, insulin secretion and the expression of regulatory genes relevant to development were assessed in NPIs. NPIs alone or in combination with allogeneic MSCs were intraportally transplanted into diabetic monkeys. Glycemic control was monitored, and graft function was evaluated. Our results suggest that MSCs benefit both the development and proliferation of NPIs in the coexisting systems in vitro and in vivo. These effects are dependent on platelet-derived growth factor receptor-α and are relevant to the inhibition of downstream target Notch1 signaling and the activation of PI3K/protein kinase B signaling.-He, S., Wang, C., Du, X., Chen, Y., Zhao, J., Tian, B., Lu, H., Zhang, Y., Liu, J., Yang, G., Li, L., Li, H., Cheng, J., Lu, Y. MSCs promote the development and improve the function of neonatal porcine islet grafts.

Heparinized silk fibroin hydrogels loading FGF1 promote the wound healing in rats with full-thickness skin excision.

BACKGROUND: Silk fibroin hydrogel, derived from Bombyx mori cocoons, has been shown to have potential effects on wound healing due to its excellent biocompatibility and less immunogenic and biodegradable properties. Many studies suggest silk fibroin as a promising material of wound dressing and it can support the adhesion and proliferation of a variety of human cells in vitro. However, lack of translational evidence has hampered its clinical applications for skin repair. Herein, a heparin-immobilized fibroin hydrogel was fabricated to deliver FGF1 (human acidic fibroblast growth factor 1) on top of wound in rats with full-thickness skin excision by performing comprehensive preclinical studies to fully evaluate its safety and effectiveness. The wound-healing efficiency of developed fibroin hydrogels was evaluated in full-thickness wound model of rats, compared with the chitosan used clinically. RESULTS: The water absorption, swelling ratio, accumulative FGF1 releasing rate and biodegradation ratio of fabricated hydrogels were measured. The regenerated fibroin hydrogels with good water uptake properties rapidly swelled to a 17.3-fold maximum swelling behavior over 12 h and a total amount of 40.48 ± 1.28% hydrogels was lost within 15 days. Furthermore, accumulative releasing data suggested that heparinized hydrogels possessed effective release behavior of FGF1. Then full-thickness skin excision was created in rats and left untreated or covered with heparinized fibroin hydrogels-immobilized recombinant human FGF1. The histological evaluation using hematoxylin and eosin (HE) and Masson's trichrome (MT) staining was performed to observe the dermic formation and collagen deposition on the wound-healing site. To evaluate the wound-healing mechanisms induced by fibroin hydrogel treatment, wound-healing scratch and cell proliferation assay were performed. it was found that both fibroin hydrogels and FGF1 can facilitate the migration of fibroblast L929 cells proliferation and migration. CONCLUSION: This study provides systematic preclinical evidence that the silk fibroin promotes wound healing as a wound-healing dressing, thereby establishing a foundation toward its further application for new treatment options of wound repair and regeneration.

Continuous veno-venous hemofiltration for severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis is associated with high rates of mortality and life-threatening complications. Continuous veno-venous hemofiltration (CVVH) has been used in some centers to reduce mortality and avoid local or systemic complications, however its efficiency and safety is uncertain. OBJECTIVES: To assess the benefits and harms of CVVH in patients suffering from severe acute pancreatitis; to compare the effects of different CVVH techniques; and to evaluate the optimal time for delivery of CVVH. SEARCH METHODS: We searched the Cochrane Library (2019, Issue 8), MEDLINE (1946 to 13 September 2019), Embase (1974 to 13 September 2019), and Science Citation Index Expanded (1982 to 13 September 2019). SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that compared CVVH versus no CVVH in participants with severe acute pancreatitis. We also included RCTs that compared different types of CVVH and different schedules for CVVH in participants with severe acute pancreatitis. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes, and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). MAIN RESULTS: We included two studies, involving a total of 94 participants, in the review.Continuous veno-venous hemofiltration versus no interventionWe included one study in which 64 participants with severe acute pancreatitis were randomized to undergo CVVH (32 participants) or no intervention (32 participants). There were no deaths in either group (very low-quality evidence). Adverse events, length of stay in the intensive care unit (ICU), length of hospital stay, total hospital cost, and quality of life were not reported in the study.One type of continuous veno-venous hemofiltration versus a different type of continuous veno-venous hemofiltrationWe included one study in which 30 participants with severe acute pancreatitis were randomized to undergo high-volume CVVH (15 participants) or standard CVVH (15 participants). High-volume CVVH may lead to little or no difference in in-hospital mortality rates (20.0% in the high-volume CVVH group versus 33.3% in the standard CVVH group; risk ratio (RR) 0.60, 95% confidence interval (CI) 0.17 to 2.07; 30 participants; 1 study; low-quality evidence). We are uncertain whether high-volume hemofiltration reduces rates of adverse events (13.3% in both groups; RR 1.00, 95% CI 0.16 to 6.20; 30 participants; 1 study; very low-quality evidence). Length of ICU stay, length of hospital stay, total hospital cost, and quality of life were not reported in the study. AUTHORS' CONCLUSIONS: The quality of the current evidence is very low or low. For both comparisons addressed in this review, data are sparse. It is unclear whether CVVH has any effect on mortality or complications in patients with severe acute pancreatitis. It is also unclear whether high-volume CVVH is superior, equivalent or inferior to standard CVVH in patients with severe acute pancreatitis.

MiR-27-3p regulates TLR2/4-dependent mouse alveolar macrophage activation by targetting PPARγ.

Activation of alveolar macrophages (AMs) and the release of cytokines play critical roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, little is known about the mechanisms of AM activation. miRNAs have recently emerged as key regulators of inflammation and as mediators of macrophage activation and polarization. We identified potential miRNAs related to AM activation using miRNA microarray analysis, which showed that miR-27-3p expression was up-regulated in AMs and the lung tissues of mice exposed to cigarette smoke (CS)/lipopolysaccharide (LPS), and found that miR-27-3p regulated proinflammatory cytokine production and AM polarization depending on TLR2/4 intracellular signaling in AMs. We also found that miR-27-3p controlled TLR2/4 signaling in AMs via targetting the 3'-UTR sequences of peroxisome proliferator-activated receptor γ (PPARγ) and inhibiting PPARγ activation. Moreover, we found that PPARγ activation not only inhibited CS/LPS-induced TLR2/4 expression and miR-27-3p-mediated TLR2/4 signaling cascades involving the nuclear factor-κB (NF-κB), c-Jun NH2-terminal kinase (JNK)/p38, and Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathways in AMs but also ameliorated CS/LPS-induced AM activation and pulmonary inflammation. Our study revealed that miR-27-3p mediated AM activation by the inhibition of PPARγ activation and sensitization of TLR signaling.

Deregulated expression of miR-107 inhibits metastasis of PDAC through inhibition PI3K/Akt signaling via caveolin-1 and PTEN.

Pancreatic ductal adenocarcinoma (PDAC) displays a highly aggressive malignancy and is considered to be an incurable and rapidly lethal disease. MicroRNAs (miRNAs) are small non-coding RNAs of approximately nucleotides that regulate several aspects of tumors pathogenesis, including migration, invasion, metastasis and epithelial-mesenchymal transition. We have found that miR-107 was significantly high expression in PDAC tissues and cells. High miR-107 expression is associated with poor clinicopathological parameters and prognosis in PDAC patients. Deregulated expression of miR-107 in PDAC cells (AsPC-1 and Panc-1) is sufficient to reduce cell migration and invasion, and to induce upregulation of epithelial markers (ß-catenin, ZO-1 and E-cadherin) and a decrease of mesenchymal marker expression (ZEB-1 and vimentin). We also found that the caveolin-1, PTEN and p-Akt expression are modulated by miR-107 in PDAC cells. Moreover, our study clearly demonstrated that deregulated expression of miR-107 inhibited cell migration and invasion and EMT by up-regulation of caveolin-1 and PTEN, and inhibition of PI3K/Akt signaling in PDAC cells. Our study suggested that miR­107 expression might both be a useful indicator of the metastatic potential and provided a new potential therapeutic target in PDAC.

Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery.

BACKGROUND: Postoperative pancreatic fistula is one of the most frequent and potentially life-threatening complications following pancreatic resections. Fibrin sealants are introduced to reduce postoperative pancreatic fistula by some surgeons. However, the use of fibrin sealants during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2016. OBJECTIVES: To assess the safety, effectiveness, and potential adverse effects of fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. SEARCH METHODS: We searched trial registers and the following biomedical databases: the Cochrane Library (2018, Issue 4), MEDLINE (1946 to 12 April 2018), Embase (1980 to 12 April 2018), Science Citation Index Expanded (1900 to 12 April 2018), and Chinese Biomedical Literature Database (CBM) (1978 to 12 April 2018). SELECTION CRITERIA: We included all randomized controlled trials that compared fibrin sealant (fibrin glue or fibrin sealant patch) versus control (no fibrin sealant or placebo) in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes (or a Peto odds ratio (OR) for very rare outcomes), and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). MAIN RESULTS: We included 11 studies involving 1462 participants in the review.Application of fibrin sealants to pancreatic stump closure reinforcement after distal pancreatectomyWe included seven studies involving 860 participants: 428 were randomized to the fibrin sealant group and 432 to the control group after distal pancreatectomy. Fibrin sealants may lead to little or no difference in postoperative pancreatic fistula (fibrin sealant 19.3%; control 20.1%; RR 0.96, 95% CI 0.68 to 1.35; 755 participants; four studies; low-quality evidence). Fibrin sealants may also lead to little or no difference in postoperative mortality (0.3% versus 0.5%; Peto OR 0.52, 95% CI 0.05 to 5.03; 804 participants; six studies; low-quality evidence), or overall postoperative morbidity (28.5% versus 23.2%; RR 1.23, 95% CI 0.97 to 1.58; 646 participants; three studies; low-quality evidence). We are uncertain whether fibrin sealants reduce reoperation rate (2.0% versus 3.8%; RR 0.51, 95% CI 0.15 to 1.71; 376 participants; two studies; very low-quality evidence). There is probably little or no difference in length of hospital stay between the groups (12.1 days versus 11.4 days; MD 0.32 days, 95% CI -1.06 to 1.70; 755 participants; four studies; moderate-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness.Application of fibrin sealants to pancreatic anastomosis reinforcement after pancreaticoduodenectomyWe included three studies involving 251 participants: 115 were randomized to the fibrin sealant group and 136 to the control group after pancreaticoduodenectomy. We are uncertain whether fibrin sealants reduce postoperative pancreatic fistula (1.6% versus 6.2%; RR 0.25, 95% CI 0.01 to 5.06; 57 participants; one study; very low-quality evidence). Fibrin sealants may lead to little or no difference in postoperative mortality (0.1% versus 0.7%; Peto OR 0.15, 95% CI 0.00 to 7.76; 251 participants; three studies; low-quality evidence) or length of hospital stay (12.8 days versus 14.8 days; MD -1.58 days, 95% CI -3.96 to 0.81; 181 participants; two studies; low-quality evidence). We are uncertain whether fibrin sealants reduce overall postoperative morbidity (33.7% versus 34.7%; RR 0.97, 95% CI 0.65 to 1.45; 181 participants; two studies; very low-quality evidence), or reoperation rate (7.6% versus 9.2%; RR 0.83, 95% CI 0.33 to 2.11; 181 participants; two studies, very low-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness.Application of fibrin sealants to pancreatic duct occlusion after pancreaticoduodenectomyWe included two studies involving 351 participants: 188 were randomized to the fibrin sealant group and 163 to the control group after pancreaticoduodenectomy. Fibrin sealants may lead to little or no difference in postoperative mortality (8.4% versus 6.1%; Peto OR 1.41, 95% CI 0.63 to 3.13; 351 participants; two studies; low-quality evidence) or length of hospital stay (17.0 days versus 16.5 days; MD 0.58 days, 95% CI -5.74 to 6.89; 351 participants; two studies; low-quality evidence). We are uncertain whether fibrin sealants reduce overall postoperative morbidity (32.0% versus 27.6%; RR 1.16, 95% CI 0.67 to 2.02; 351 participants; two studies; very low-quality evidence), or reoperation rate (13.6% versus 16.0%; RR 0.85, 95% CI 0.52 to 1.41; 351 participants; two studies; very low-quality evidence). Serious adverse events were reported in one study: more participants developed diabetes mellitus when fibrin sealants were applied to pancreatic duct occlusion, both at three months' follow-up (33.7% fibrin sealant group versus 10.8% control group; 29 participants versus 9 participants) and 12 months' follow-up (33.7% fibrin sealant group versus 14.5% control group; 29 participants versus 12 participants). The studies did not report postoperative pancreatic fistula, quality of life, or cost effectiveness. AUTHORS' CONCLUSIONS: Based on the current available evidence, fibrin sealants may have little or no effect on postoperative pancreatic fistula in people undergoing distal pancreatectomy. The effects of fibrin sealants on the prevention of postoperative pancreatic fistula are uncertain in people undergoing pancreaticoduodenectomy.

Prophylactic abdominal drainage for pancreatic surgery.

BACKGROUND: The use of surgical drains has been considered mandatory after pancreatic surgery. The role of prophylactic abdominal drainage to reduce postoperative complications after pancreatic surgery is controversial. OBJECTIVES: To assess the benefits and harms of routine abdominal drainage after pancreatic surgery, compare the effects of different types of surgical drains, and evaluate the optimal time for drain removal. SEARCH METHODS: For the last version of this review, we searched CENTRAL (2016, Issue 8), and MEDLINE, Embase, Science Citation Index Expanded, and Chinese Biomedical Literature Database (CBM) to 28 August 2016). For this updated review, we searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, and CBM from 2016 to 15 November 2017. SELECTION CRITERIA: We included all randomized controlled trials that compared abdominal drainage versus no drainage in people undergoing pancreatic surgery. We also included randomized controlled studies that compared different types of drains and different schedules for drain removal in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: We identified six studies (1384 participants). Two review authors independently identified the studies for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). For all analyses, we used the random-effects model. MAIN RESULTS: Drain use versus no drain useWe included four studies with 1110 participants, who were randomized to the drainage group (N = 560) and the no drainage group (N = 550) after pancreatic surgery. There was little or no difference in mortality at 30 days between groups (1.5% with drains versus 2.3% with no drains; RR 0.78, 95% CI 0.31 to 1.99; four studies, 1055 participants; moderate-quality evidence). Drain use probably slightly reduced mortality at 90 days (0.8% versus 4.2%; RR 0.23, 95% CI 0.06 to 0.90; two studies, 478 participants; moderate-quality evidence). We were uncertain whether drain use reduced intra-abdominal infection (7.9% versus 8.2%; RR 0.97, 95% CI 0.52 to 1.80; four studies, 1055 participants; very low-quality evidence), or additional radiological interventions for postoperative complications (10.9% versus 12.1%; RR 0.87, 95% CI 0.79 to 2.23; three studies, 660 participants; very low-quality evidence). Drain use may lead to similar amount of wound infection (9.8% versus 9.9%; RR 0.98 , 95% CI 0.68 to 1.41; four studies, 1055 participants; low-quality evidence), and additional open procedures for postoperative complications (9.4% versus 7.1%; RR 1.33, 95% CI 0.79 to 2.23; four studies, 1055 participants; low-quality evidence) when compared with no drain use. There was little or no difference in morbidity (61.7% versus 59.7%; RR 1.03, 95% CI 0.94 to 1.13; four studies, 1055 participants; moderate-quality evidence), or length of hospital stay (MD -0.66 days, 95% CI -1.60 to 0.29; three studies, 711 participants; moderate-quality evidence) between groups. There was one drain-related complication in the drainage group (0.2%). Health-related quality of life was measured with the pancreas-specific quality-of-life questionnaire (FACT-PA; a scale of 0 to 144 with higher values indicating a better quality of life). Drain use may lead to similar quality of life scores, measured at 30 days after pancreatic surgery, when compared with no drain use (105 points versus 104 points; one study, 399 participants; low-quality evidence). Hospital costs and pain were not reported in any of the studies.Type of drainWe included one trial involving 160 participants, who were randomized to the active drain group (N = 82) and the passive drain group (N = 78) after pancreatic surgery. An active drain may lead to similar mortality at 30 days (1.2% with active drain versus 0% with passive drain; low-quality evidence), and morbidity (22.0% versus 32.1%; RR 0.68, 95% CI 0.41 to 1.15; low-quality evidence) when compared with a passive drain. We were uncertain whether an active drain decreased intra-abdominal infection (0% versus 2.6%; very low-quality evidence), wound infection (6.1% versus 9.0%; RR 0.68, 95% CI 0.23 to 2.05; very low-quality evidence), or the number of additional open procedures for postoperative complications (1.2% versus 7.7%; RR 0.16, 95% CI 0.02 to 1.29; very low-quality evidence). Active drain may reduce length of hospital stay slightly (MD -1.90 days, 95% CI -3.67 to -0.13; one study; low-quality evidence; 14.1% decrease of an 'average' length of hospital stay). Additional radiological interventions, pain, and quality of life were not reported in the study.Early versus late drain removalWe included one trial involving 114 participants with a low risk of postoperative pancreatic fistula, who were randomized to the early drain removal group (N = 57) and the late drain removal group (N = 57) after pancreatic surgery. There was no mortality in either group. Early drain removal may slightly reduce morbidity (38.6% with early drain removal versus 61.4% with late drain removal; RR 0.63, 95% CI 0.43 to 0.93; low-quality evidence), length of hospital stay (MD -2.10 days, 95% CI -4.17 to -0.03; low-quality evidence; 21.5% decrease of an 'average' length of hospital stay), and hospital costs (MD -EUR 2069.00, 95% CI -3872.26 to -265.74; low-quality evidence; 17.0% decrease of 'average' hospital costs). We were uncertain whether early drain removal reduced additional open procedures for postoperative complications (0% versus 1.8%; RR 0.33, 95% CI 0.01 to 8.01; one study; very low-quality evidence). Intra-abdominal infection, wound infection, additional radiological interventions, pain, and quality of life were not reported in the study. AUTHORS' CONCLUSIONS: It was unclear whether routine abdominal drainage had any effect on the reduction of mortality at 30 days, or postoperative complications after pancreatic surgery. Moderate-quality evidence suggested that routine abdominal drainage probably slightly reduced mortality at 90 days. Low-quality evidence suggested that use of an active drain compared to the use of a passive drain may slightly reduce the length of hospital stay after pancreatic surgery, and early removal may be superior to late removal for people with low risk of postoperative pancreatic fistula.

Hypoxia/reoxygenation-induced HMGB1 translocation and release promotes islet proinflammatory cytokine production and early islet graft failure through TLRs signaling.

High-mobility group box 1 (HMGB1) translocation and release, which is involved in several tissue types of ischemia-reperfusion injuries, activate innate immunity by inducing proinflammatory cytokine production through its interaction with toll-like receptors (TLRs). Our objective was to determine the role of HMGB1 and the degree of activation of TLR-related signal transduction pathways in hypoxia/reoxygenation (H/R)-induced proinflammatory cytokine production and intra-islet graft inflammation. After islets are exposed to hypoxia-reoxygenation for 24h, TLR2/4 expression and TLR-mediated signaling was up-regulated in islets, and HMGB1 was translocated from the nucleus to the cytoplasm and released to the extracellular space. With H/R exposure, proinflammatory cytokine production (IL-1ß and TNF-α) and islet injury were significantly increased, and these effects depend on TLR2/4 signaling pathways. Exogenous HMGB1 also induces islet inflammation and increases the phosphorylation of STAT3, p38 and IκBα in wild-type islets. TLR2 deficiency in TLR2-KO islets resulted in the inhibition of IL-1ß production and STAT3/p38 phosphorylation after HMGB1 exposure. TLR4 deficiency in TLR4-KO islets resulted in the inhibition of TNF-α production and IκBα phosphorylation after HMGB1 exposure. Pre-incubation of the STAT3, p38, or NF-κB inhibitors significantly inhibited HMGB1-induced IL-1ß or TNF-α production in islets, but the effect of HMGB1 or H/R-induced islet injury was not counteracted by a separate treatment of the STAT3 inhibitor, p38 inhibitor, or NF-κB inhibitors. HMGB1 inhibition by ethyl pyruvate or blockade by neutralizing antibodies significantly decreased the phosphorylation of STAT3, p38 and IκBα, the production of IL-1ß and TNF-α, and the islet injury in wild-type islets after exposure to H/R and significantly improved early islet graft failure. Thus, our results suggest that HMGB1 released from H/R induced islets works in an autocrine manner to up-regulate STAT or p38 and augment IL-1ß production via TLR2, and up-regulate NF-κB and augment TNF-α production via TLR4 in intra-islet, which are associated with H/R-induced islet injury and early graft failure.