Enantioselective Nickel-Electrocatalyzed Reductive Propargylic Carboxylation with CO2.

The exploitation of carbon dioxide (CO2) as a sustainable, plentiful, and harmless C1 source for the catalytic synthesis of enantioenriched carboxylic acids has long been acknowledged as a pivotal task in synthetic chemistry. Herein, we present a current-driven nickel-catalyzed reductive carboxylation reaction with CO2 fixation, facilitating the formation of C(sp3)-C(sp2) bonds by circumventing the handling of moisture-sensitive organometallic reagents. This electroreductive protocol serves as a practical platform, paving the way for the synthesis of enantioenriched propargylic carboxylic acids (up to 98% enantiomeric excess) from racemic propargylic carbonates and CO2. The efficacy of this transformation is exemplified by its successful utilization in the asymmetric total synthesis of (S)-arundic acid, (R)-PIA, (S)-chizhine D, (S)-cochlearin G, and (S,S)-alexidine, thereby underscoring the potential of asymmetric electrosynthesis to achieve complex molecular architectures sustainably.

FcRn-Targeted Mucosal Vaccination against Influenza Virus Infection.

The respiratory tract is constantly exposed to various airborne pathogens. Most vaccines against respiratory infections are designed for the parenteral routes of administration; consequently, they provide relatively minimal protection in the respiratory tract. A vaccination strategy that aims to induce the protective mucosal immune responses in the airway is urgently needed. The FcRn mediates IgG Ab transport across the epithelial cells lining the respiratory tract. By mimicking this natural IgG transfer, we tested whether FcRn delivers vaccine Ags to induce a protective immunity to respiratory infections. In this study, we designed a monomeric IgG Fc fused to influenza virus hemagglutinin (HA) Ag with a trimerization domain. The soluble trimeric HA-Fc were characterized by their binding with conformation-dependent HA Abs or FcRn. In wild-type, but not FcRn knockout, mice, intranasal immunization with HA-Fc plus CpG adjuvant conferred significant protection against lethal intranasal challenge with influenza A/PR/8/34 virus. Further, mice immunized with a mutant HA-Fc lacking FcRn binding sites or HA alone succumbed to lethal infection. Protection was attributed to high levels of neutralizing Abs, robust and long-lasting B and T cell responses, the presence of lung-resident memory T cells and bone marrow plasma cells, and a remarkable reduction of virus-induced lung inflammation. Our results demonstrate for the first time, to our knowledge, that FcRn can effectively deliver a trimeric viral vaccine Ag in the respiratory tract and elicit potent protection against respiratory infection. This study further supports a view that FcRn-mediated mucosal immunization is a platform for vaccine delivery against common respiratory pathogens.

Efficacy and safety of over-the-scope clips (OTSC®) for closure of gastrointestinal fistulas less than 2 cm.

BACKGROUND AND AIM: Gastrointestinal (GI) fistula is a complication of surgery associated with potential morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of over-the-scope clips (OTSC®) for closing GI fistulas. METHODS: Patients with GI fistula who underwent endoscopic closure using OTSC® were enrolled. The clinical date, duration, location and diameter of the fistula, technical success of the OTSC®, complications, follow-up periods and clinical success were recorded. RESULTS: A total of 98 patients with GI fistula underwent OTSC® closure. Their median age was 50 years (range 16-88 years), and the median duration of the fistula was 185.5 days (range 12-3129 days). The mean diameter of fistula was 4.64 ± 1.16 mm. Technical success was achieved in 100% of the patients, and clinical success was achieved in 55.10% (54/98) of the patients after a median follow-up of 168.5 days (range 36-424 days). Based on the location of the fistula, the clinical success rate of treating a fistula in the esophagus and small intestine was 100%, followed by the rectum (70%, 7/10), anastomotic stoma (61.90%, 13/21), duodenum (53.33%, 8/15), colon (47.06%, 8/17), stomach (43.47%, 10/23) and appendix stump (33.33%, 2/6). The duration of the fistula (HR 3.609, 95% CI 1.387-9.387, P = 0.009) was a risk factor for clinical success by multivariate analysis. CONCLUSION: OTSC® is a safe and efficient treatment for GI fistula and is a potential alternative to the surgical approach. Before OTSC® placement, the duration of the fistula should be assessed since it is related to the successful closures with OTSC®.

Spatial learning and memory impaired after infection of non-neurotropic influenza virus in BALB/c male mice.

During the influenza pandemic or seasonal influenza outbreak, influenza infection can cause acute influenza-associated encephalopathy/encephalitis (IAE), even death. Patients with severe IAE will also have severe neurological sequelae. Neurologic disorders have been demonstrated in the mice treated with peripheral influenza viruses infection, whether neurotropic or non-neurotropic viruses. However, previous studies focused on the acute phase of infection, and rarely paid attention to a longer range of observations. Therefore, the long-term effect of non-neurotropic virus infection on the host is not very clear. In this study, adult mice were infected with influenza virus H1N1/PR8. Then, spontaneous behavior, body weight, expression of cytokines in brain, spatial learning ability and spatial memory ability were observed, until the complete recovery period. The results showed that cytokines in the brain were highly expressed in the convalescent phase (14 day post inoculation, dpi), especially BDNF, IBA1, CX3CL1 and CD200 were still highly expressed in the recovery phase (28 dpi). Otherwise the emotional and spatial memory ability of mice were impacted in the convalescent phase (14 dpi) and the recovery phase (28 dpi). In brief, BALB/c mice infected with non-neurotropic influenza virus H1N1, the weight and motor ability decreased in acute stage. During the recovery period, the body weight and activity ability were completely restored, whereas the emotion disordered, and the ability of spatial learning and memory were impacted in the infected mice. This long-term behavior impact may be the lag injury caused by non-neurotropic influenza infection.

Incidence and risk factors of surgical site infection following colorectal surgery in China: a national cross-sectional study.

PURPOSES: Surgical site infection (SSI) after colorectal surgery is a frequent complication associated with the increase in morbidity, medical expenses, and mortality. To date, there is no nationwide large-scale database of SSI after colorectal surgery in China. The aim of this study was to determine the incidence of SSI after colorectal surgery in China and to further evaluate the related risk factors. METHODS: Two multicenter, prospective, cross-sectional studies covering 55 hospitals in China and enrolling adult patients undergoing colorectal surgery were conducted from May 1 to June 30 of 2018 and the same time of 2019. The demographic and perioperative characteristics were collected, and the main outcome was SSI within postoperative 30 days. Multivariable logistic regressions were conducted to predict risk factors of SSI after colorectal surgery. RESULTS: In total, 1046 patients were enrolled and SSI occurred in 74 patients (7.1%). In the multivariate analysis with adjustments, significant factors associated with SSI were the prior diagnosis of hypertension (OR, 1.903; 95% confidence interval [CI], 1.088-3.327, P = 0.025), national nosocomial infection surveillance risk index score of 2 or 3 (OR, 3.840; 95% CI, 1.926-7.658, P < 0.001), laparoscopic or robotic surgery (OR, 0.363; 95% CI, 0.200-0.659, P < 0.001), and adhesive incise drapes (OR, 0.400; 95% CI, 0.187-0.855, P = 0.018). In addition, SSI group had remarkably increased length of postoperative stays (median, 15.0 d versus 9.0d, P < 0.001), medical expenses (median, 74,620 yuan versus 57,827 yuan, P < 0.001), and the mortality (4.1% versus 0.3%, P = 0.006), compared with those of non-SSI group. CONCLUSION: This study provides the newest data of SSI after colorectal surgery in China and finds some predictors of SSI. The data presented in our study can be a tool to develop optimal preventive measures and improve surgical quality in China.

Anaphase-promoting complex/cyclosome-Cdc-20 promotes Zwint-1 degradation.

ZW10 interactor (Zwint-1) is an important component of the centromere and can recruit the dynamic protein kinase and dynein to promote chromosome movement and regulate the spindle assembly checkpoint (SAC). Zwint-1 activity is tightly regulated during the cell cycle. However, how the stability of Zwint-1 is regulated has not been clarified. Here, we show that the relative levels of Zwint-1 expression gradually decreased with the progression of cell cycling and decline sharply during mitotic exit. Treatment with cycloheximide reduced the levels of Zwint-1 while treatment with MG132 to inhibit endogenous ubiquitin-proteasome elevated the levels of Zwint-1 in HEK293T cells or Hela cells. Such data suggest that Zwint-1 may be degraded by endogenous ubiquitin-proteasome. Furthermore, induction of cell-division cycle protein 20 (Cdc20) overexpression decreased the levels of Zwint-1, which was abrogated by MG132 treatment. In contrast, Cdc20 silencing promoted the accumulation of Zwint-1. in vivo ubiquitination assay revealed that Cdc20 promoted the formation of Zwint-1 and ubiquitin-proteasome conjugates. Cotransfection with Cdc20 and wild-type Zwint-1, but not Zwint-1ΔD-box , reduced the levels of Zwint-1. Immunoprecipitation and western blot analyses showed that Cdc20 interacted with wild-type Zwint-1, but not Zwint-1ΔD-box although both Zwint-1 and Zwint-1ΔD-box overexpression did not induce mitotic arrest. Collectively, our data indicated that Zwint-1 was ubiquitinated by anaphase-promoting complex/cyclosome (APC/C)-Cdc20 in a D-box-dependent manner. Therefore, the APC/C-Cdc20 controls the stability of Zwint-1, ensuring accurate regulation of the spindle assembly during the cell cycling in HEK293T cells.

Current progress of source control in the management of intra-abdominal infections.

Intra-abdominal infection (IAI) is a deadly condition in which the outcome is associated with urgent diagnosis, assessment and management, including fluid resuscitation, antibiotic administration while obtaining further laboratory results, attaining precise measurements of hemodynamic status, and pursuing source control. This last item makes abdominal sepsis a unique treatment challenge. Delayed or inadequate source control is an independent predictor of poor outcomes and recognizing source control failure is often difficult or impossible. Further complicating issue in the debate is surrounding the timing, adequacy, and procedures of source control. This review evaluated and summarized the current approach and challenges in IAI management, which are the future research directions.

Surgical Site Infection After Gastrointestinal Surgery in China: A Multicenter Prospective Study.

BACKGROUND: There is no nationwide database of information on surgical site infection (SSI) after gastrointestinal surgery in China. This study aimed to determine the incidence of SSI after gastrointestinal surgery in China and evaluate the related risk factors. MATERIALS AND METHODS: The multicenter, prospective, observational study enrolled adult patients who underwent gastrointestinal surgery from May 1, 2018 to June 30, 2018 in 30 hospitals in China. The demographic and perioperative characteristics were collected, and the primary outcome was 30-d SSI. Predictors of SSI were determined by multivariable logistic regressions. Subgroup analysis was performed to determine the predictors of SSI in different surgeries. RESULTS: A total of 1290 patients were enrolled and SSI occurred in 68 patients (5.2%). Multivariate analysis with adjustments revealed that normal body mass index, normal blood glucose level, low national nosocomial infection surveillance risk index score, noncolon surgery, laparoscopic or robotic surgery, and use of mechanical bowel preparation were associated with reduced SSI in gastrointestinal surgery. Subgroup analysis revealed diverse predictors of SSI in diverse surgeries. National nosocomial infection surveillance risk index score of 2 and a high blood glucose level increased the incidence of SSI in colorectal and noncolorectal surgery, respectively. Besides, mechanical bowel preparation and laparoscopic or robotic surgery were protective factors for SSI in colorectal and noncolorectal surgery, respectively. CONCLUSIONS: This study provides the newest data of SSI after gastrointestinal surgery in China and revealed some predictors of SSI in diverse surgeries, which can be a tool to look for areas to target quality improvement initiatives.

Clinical parameters and outcomes of necrotizing soft tissue infections secondary to gastrointestinal fistulas.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) is severe surgical infections which can occur following trauma or abdominal surgery. NSTIs secondary to gastrointestinal (GI) fistula is a rare but severe complication. METHODS: A retrospective cohort study was performed on all subjects presenting with GI fistulas associated NSTIs were included. Clinical characteristics, microbiological profile, operations performed, and outcomes of patients were analyzed. RESULTS: Between 2014 and 2017, 39 patients were finally enrolled. The mean age were 46.9 years and male were the dominant. For the etiology of fistula, 25 (64.1%) of the patients was due to trauma. Overall, in-hospital death occurred in 15 (38.5%) patients. Microbiologic findings were obtained from 31 patients and Klebsiella pneumoniae was the most common species (41.0%). Eight patients were treated with an open abdomen; negative pressure wound therapy was used in 33 patients and only 2 patients received hyperbaric oxygen therapy. Younger age and delayed abdominal wall reconstruction repair were more common in trauma than in non-trauma. Non-survivors had higher APACHE II score, less source control< 48 h and lower platelet count on admission than survivors. Multiple organ dysfunction syndrome, multidrug-resistant organisms and source control failure were the main cause of in-hospital mortality. CONCLUSIONS: Trauma is the main cause of GI fistulas associated NSTIs. Sepsis continues to be the most important factor related to mortality. Our data may assist providing enlightenment for quality improvement in these special populations.

Hybrid material for open abdomen: saving the wound from intestinal fistula.

Treatment of an open abdomen (OA) wound combined with an intestinal fistula is a challenge in the clinic. Here, inspired by the antibacterial activity of graphene (G) and its derivatives, we present a hybrid patch based on the ability of graphene and polycaprolactone (PCL) to kill bacteria and save the cells in a wound. Benefiting from the antibacterial ability of graphene oxide (GO), cells could survive in the presence of bacteria. With the increased ability to protect cells, this patch accelerated wound healing in an OA and intestinal fistula wound model. Additionally, the sub-acute toxicity score showed no extra damage to organs. In conclusion, the employment of the hybrid material for an OA and an intestinal fistula wound healing is encouraging. A hybrid patch based on graphene oxide and polycaprolactone electrospun was generated for open abdomen and fistula wound. The application of the hybrid patch could save the cells from bacteria which contribute to accelerating wound healing.

Chinese Trauma Surgeon Association for management guidelines of vacuum sealing drainage application in abdominal surgeries-Update and systematic review.

Vacuum sealing drainage (VSD) is frequently used in abdominal surgeries. However, relevant guidelines are rare. Chinese Trauma Surgeon Association organized a committee composed of 28 experts across China in July 2017, aiming to provide an evidence-based recommendation for the application of VSD in abdominal surgeries. Eleven questions regarding the use of VSD in abdominal surgeries were addressed: (1) which type of materials should be respectively chosen for the intraperitoneal cavity, retroperitoneal cavity and superficial incisions? (2) Can VSD be preventively used for a high-risk abdominal incision with primary suture? (3) Can VSD be used in severely contaminated/infected abdominal surgical sites? (4) Can VSD be used for temporary abdominal cavity closure under some special conditions such as severe abdominal trauma, infection, liver transplantation and intra-abdominal volume increment in abdominal compartment syndrome? (5) Can VSD be used in abdominal organ inflammation, injury, or postoperative drainage? (6) Can VSD be used in the treatment of intestinal fistula and pancreatic fistula? (7) Can VSD be used in the treatment of intra-abdominal and extra-peritoneal abscess? (8) Can VSD be used in the treatment of abdominal wall wounds, wound cavity, and defects? (9) Does VSD increase the risk of bleeding? (10) Does VSD increase the risk of intestinal wall injury? (11) Does VSD increase the risk of peritoneal adhesion? Focusing on these questions, evidence-based recommendations were given accordingly. VSD was strongly recommended regarding the questions 2-4. Weak recommendations were made regarding questions 1 and 5-11. Proper use of VSD in abdominal surgeries can lower the risk of infection in abdominal incisions with primary suture, treat severely contaminated/infected surgical sites and facilitate temporary abdominal cavity closure.

Risk factors and clinical outcomes of hypervirulent Klebsiella pneumoniae induced bloodstream infections.

The prevalence of hypervirulent Klebsiella pneumoniae (hvKP) is high in China, but clinical characteristics and outcomes of hvKP induced bloodstream infections (BSIs) are not clear. The purpose of the present study was to determine the risk factors and clinical outcomes of hvKP-BSIs in populations admitted in a teaching hospital of Nanjing, China. The genetic characteristics and antibiotic resistance patterns of the hvKP strains were further analyzed. A retrospective study was conducted in 143 patients with K. pneumoniae BSIs at Jinling Hospital in China from September 2015 to December 2016. A positive polymerase chain reaction (PCR) amplification of the plasmid-borne rmpA (p-rmpA) and aerobactin (iucA) was identified as hvKP. Overall, 24.5% (35/143) of K. pneumoniae isolates were hvKP. Multivariate analysis implicated diabetes mellitus (OR = 3.356) and community-acquired BSIs (OR = 4.898) as independent risk factors for hvKP-BSIs. The 30-day mortality rate of the hvKP-BSIs group was 37.1% (13/35) compared with 40.7% (44/108) in the cKP-BSIs control group (P = 0.706). The KPC-producing isolates (OR = 2.851), underlying disease with gastrointestinal fistula (OR = 3.054), APACHE II score ≥ 15 (OR = 6.694) and Pitt bacteremia score ≥ 2 (OR = 6.232) at infection onset were independent predictors for 30-day mortality of K. pneumoniae bacteremia patients. A high percentage (57.1%, 20/35) of KPC-producing isolates was observed among hvKP strains and ST11 was dominant in hvKP strains (17/35, 48.6%). KPC-producing hvKP is emerging, indicating the importance of epidemiologic surveillance and clinical awareness of this pathogen.

NS1 of H7N9 Influenza A Virus Induces NO-Mediated Cellular Senescence in Neuro2a Cells.

BACKGROUND/AIMS: The novel avian H7N9 influenza A virus has been detected in brain tissues and associated with central nervous system (CNS) symptoms in infected human and mice. Roles of its virulence factor, NS1 protein in influenza virus infected neuron has yet to be explored. METHODS: Nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression in H7N9/NS1-expressed Neuro2a cells were detected by Griess test and western blotting. Cell proliferation rate of H7N9/NS1-expressing cells was recorded by Cell Counting Kit-8. Effects of H7N9/NS1 on cellular senescence were investigated by senescence-associated ß-galactosidase (SA-ß-gal) staining, immunofluorescent staining of phosphorylated heterochromatin protein 1γ (pHP1γ) and qPCR analysis of IL-6 and IL-8. RESULTS: H7N9/NS1 in Neuro2a cells and primary cultured mouse cortical neurons increased the expression of iNOS and boosted NO release. Neuro2a cells constitutively expressing NS1 displayed a reduced proliferative ability, enhanced SA-ß-gal staining, increased level of IL-6 and IL-8 and a typical punctuate structure of pHP1γ in nuclei. In addition, p38 MAPK was elevated in NS1-expressing Neuro2a cells. Reduced iNOS expression and subdued cellular senescence effect was found in p38 MAPK inhibitor-treated NS1-expressing Neuro2a cells. CONCLUSION: Our results suggest that H7N9/NS1 protein increases the iNOS expression and NO release in Neuro2a cells, which can induce cell growth arrest and cellular senescence.

A Randomized Control Trial of Preoperative Oral Antibiotics as Adjunct Therapy to Systemic Antibiotics for Preventing Surgical Site Infection in Clean Contaminated, Contaminated, and Dirty Type of Colorectal Surgeries.

BACKGROUND: Preoperative bowel preparation with or without oral antibiotics is controversial in terms of postoperative surgical site infections. OBJECTIVE: This study aimed to evaluate the efficacy of oral antibiotics as adjunct therapy to systemic antibiotics with mechanical bowel preparation for preventing surgical site infections in clean contaminated, contaminated, and dirty colorectal procedures. DESIGN: This was a single-center, prospective randomized study. SETTING: This study was conducted at the General Surgery Department at Jinling Hospital, Nanjing University, China, from July 15, 2014 to January 20, 2016. PATIENTS: Patients aged ≥18 years scheduled for abdominal surgery with clean-contaminated, contaminated, and dirty wounds were selected. INTERVENTIONS: Patients were randomly assigned to receive preoperative mechanical bowel preparation or mechanical bowel preparation with oral antibiotics. MAIN OUTCOMES: The primary outcome was the rate of surgical site infections. The secondary outcomes were extra-abdominal complications, duration of postoperative ileus, and readmission rate. RESULTS: Ninety-five patients were allocated to each group. Eight and 26 surgical site infections (8.42% vs 27.3 %, p = 0.004) occurred in the mechanical bowel preparation with oral antibiotics and mechanical bowel preparation groups. Thirteen extra-abdominal complications were reported: 6 in the mechanical bowel preparation with oral antibiotics group and 7 in the mechanical bowel preparation group (6.3% vs 7.3%, p = 0.77). Postoperative ileus duration did not differ between groups (p = 0.23). There were 4 readmissions in the mechanical bowel preparation group and none in the mechanical bowel preparation with oral antibiotics group (p = 0.04). On multivariable analysis, blood loss ≥500 mL (OR, 5.1; 95% CI, 1.27-20.4; p = 0.02), ASA score ≥3 (OR, 3.9; 95% CI, 1.2-12.5; p = 0.01), contaminated types (OR, 3.6; 95% CI, 1.5-8.6; p = 0.01), and administration of preoperative oral antibiotics (OR, 0.20; 95% CI, 0.06-0.60; p = 0.005) independently affected the incidence of surgical site infections. LIMITATIONS: This was a single-center study. CONCLUSION: Preoperative oral antibiotics, as adjunct therapy to systemic antibiotics and mechanical bowel preparation, significantly reduced surgical site infections and minimized the readmission rates in clean contaminated, contaminated, and dirty types of colorectal surgery. See Video Abstract at http://links.lww.com/DCR/A437.

Shifting trends in bacteriology and antimicrobial resistance among gastrointestinal fistula patients in China: an eight-year review in a tertiary-care hospital.

BACKGROUND: The purpose of this study was to determine the shifting trends in bacteriology and antimicrobial resistance of infectious specimens isolated from gastrointestinal (GI) fistula patients over eight years in China. METHODS: We retrospectively reviewed the microbial records of intra-abdominal specimens at a teaching hospital from 2008 to 2015. Study period was divided into the first half (2008-2011) and the second half (2012-2015). All isolates underwent antibiotic susceptibility testing by the micro dilution method. RESULTS: A total of 874 intra-abdominal isolates were consecutively collected from 502 GI fistula patients (mean age, 46.5 years, 71.1% male) during the study period. Patients in the second study period (2012-2015) were older (>65 years) and more likely to have experienced cancer. Over the entire study period, most infections were caused by E. coli (24.2%) and K. pneumonia (14.1%). There was a significant decrease in the proportion E. coli isolates that were extended- spectrum beta-lactamase (ESBL)-positive (P = 0.026). The proportion of E. coli resistant to imipenem increased from 14.3% in 2008-2011 to 25.9% in 2012-2015 (P = 0.037). Imipenem resistance prevalence was higher in ESBL-negative bacteria than ESBL-positive bacteria for both E. coli and K. pneumonia (P < 0.001). In Enterococcus, significant increase in resistance to ampicillin (P = 0.01) and moxifloxacin (P = 0.02) over time were observed. In Staphylococcus and fungi, rates of antibiotic resistance did not significantly change over the study period. CONCLUSIONS: Gram-negative bacteria predominated as causative agents of intra-abdominal infections in GI fistula patients, and there was an increase in levels of resistance to certain antibiotics, particularly carbapenems. Infection control and source control are important tools available to surgeons to prevent the emergence of antibiotic-resistant pathogens.

Risk factors of surgical site infections in patients with Crohn's disease complicated with gastrointestinal fistula.

PURPOSE: Surgical site infection (SSI) is the most common complication following surgical procedures. This study aimed to determine risk factors associated with SSI in patients with Crohn's disease (CD) complicated with gastrointestinal fistula. METHODS: This was a retrospective review of patients who underwent surgical resection in gastrointestinal fistula patients with CD between January 2013 and January 2015, identified from a prospectively maintained gastrointestinal fistula database. Demographic information, preoperative medication, intraoperative findings, and postoperative outcome data were collected. Univariate and multivariate analysis was carried out to assess possible risk factors for SSI. RESULTS: A total of 118 patients were identified, of whom 75.4% were men, the average age of the patients was 34.1 years, and the average body mass index (BMI) was 18.8 kg/m2. The rate of SSI was 31.4%. On multivariate analysis, preoperative anemia (P = 0.001, OR 7.698, 95% CI 2.273-26.075), preoperative bacteria present in fistula tract (P = 0.029, OR 3.399, 95% CI 1.131-10.220), and preoperative enteral nutrition (EN) <3 months (P < 0.001, OR 11.531, 95% CI 3.086-43.079) were predictors of SSI. Notably, preoperative percutaneous abscess drainage was shown to exert protection against SSI in fistulizing CD (P = 0.037, OR 0.258, 95% CI 0.073-0.920). CONCLUSION: Preoperative anemia, bacteria present in fistula tract, and preoperative EN <3 months significantly increased the risk of postoperative SSI in gastrointestinal fistula complicated with CD. Preoperative identification of these risk factors may assist in risk assessment and then to optimize preoperative preparation and perioperative care.

Association Between Diabetes Mellitus and Outcomes of Patients with Sepsis: A Meta-Analysis.

BACKGROUND Diabetes mellitus (DM) is a critical medical problem that can make people more likely to develop infectious complications, even sepsis. However, the influence of DM on the outcomes of septic patients is still controversial. Thus, we conducted the present meta-analysis to investigate whether DM worsens outcomes of septic patients. MATERIAL AND METHODS We searched studies from PubMed, Embase, and Cochrane Library databases from 1966 to July 1, 2016. The primary outcome we chose was 28-day or 30-day mortality or in-hospital mortality. RESULTS Our meta-analysis of 10 enrolled studies performed between 2000 and 2016 shows that the mortality rate of septic patients with DM was slightly lower than that of non-diabetic patients (risk ratio [RR]=0.97, 95% confidence interval [CI]: 0.96 to 0.98, P<0.00001). On the other hand, septic patients with DM had a shorter hospital stay (weighted mean difference (WMD)=-2.27, 95% CI: -4.11 to -0.44, P=0.01), a higher incidence rate of AKI (RR=1.56, 95% CI: 1.25 to 1.95, P<0.001), and a similar incidence of respiratory dysfunction (RR=0.86, 95% CI: 0.71 to 1.04, P=0.11) compared with those without DM. CONCLUSIONS The results from the meta-analysis suggest that DM does not impair the outcome of patients with sepsis, and the incidence of acute kidney injury increases dramatically in septic patients with DM. Due to the limitations of the analysis, more well-designed trials are still necessary.

Delayed Diagnosis is Associated with Early and Emergency Need for First Crohn's Disease-Related Intestinal Surgery.

BACKGROUND Increasing evidence suggests that delayed diagnosis in Crohn's disease is associated with a complicated disease course. The aim of this study was to explore the association between delayed diagnosis and the timing of the first Crohn's disease-related intestinal surgery. MATERIAL AND METHODS A retrospective study included 215 Crohn's disease patients with previous surgical history in the Department of General Surgery of Jinling Hospital, China, between January 2013 and March 2016. Data were collected on demographics, clinical characteristics, medication history, and operation history. RESULTS The time from the first appearance of Crohn's disease-related symptoms to the first intestinal surgery in the delayed diagnosis group was obviously shorter than in the non-delayed diagnosis group (26.4±28.7 months vs. 42.6±58.4 months, respectively, p=0.032). Patients in the delayed diagnosis group tended to receive more ileal resections (47.8% vs. 26.4%, respectively, p=0.002) and less ileocecal resections (22.4% vs. 37.2%, respectively, p=0.032). More patients in the delayed diagnosis group received the first Crohn's disease-related intestinal surgery as an emergency one (20.9% vs. 4.7%, respectively, p=0.001). CONCLUSIONS Delayed diagnosis is associated with early and emergency need for the first Crohn's disease-related intestinal surgery.

Association between the -159C/T polymorphism in the promoter region of the CD14 gene and sepsis: a meta-analysis.

BACKGROUND: The association between CD14-159C/T polymorphism and sepsis has been assessed but results of current studies appeared conflicting and inconstant. This analysis was aimed to determine whether the CD14-159C/T polymorphism confers susceptibility to sepsis or is associated with increased risk of death from sepsis. METHOD: The authors conducted a comprehensive search of PubMed, EMBASE, ISI Web of Science, Cochrane library, ScienceDirect, Wiley Online Library and CNKI databases according to a prespecified protocol. Language limits were restricted to English and Chinese. Two reviewers independently selected the articles and extracted relevant data onto standardized forms. Disagreements were settled by discussion and suggestions from senior consultants. The strength of association were evaluated by odds ratio (OR) and 95% confidence interval (CI). Studies failed to fit the Hardy-Weinberg-Equilibrium were excluded. RESULTS: The research identified a total of 2317 full-text articles of which 14 articles met the predefined inclusion criteria. Meta-analysis was performed for allele frequency of C versus T, as well as genotypes CC + CT versus TT (dominant model), CC versus TT + CT (recessive model), CT versus TT and CC versus TT (additive model). All control samples were in Hardy-Weinberg proportion. No significant association between CD14-159C/T polymorphism and sepsis susceptibility or mortality were detected in the overall population. Nonetheless, subgroup analysis of Asian ethnicity revealed significant association between the CD14-159C/T polymorphism and susceptibility to sepsis in additive model (CC versus TT: OR = 0.52, 95% CI 0.29-0.92, p = 0.03) and recessive model (CC versus CT + TT: OR = 0.50, 95% CI 0.30-0.84, p = 0.009). Of note, three out of the five papers included in the subgroup focused exclusively on burn ICU patients. CONCLUSIONS: This meta-analysis demonstrated that CD14-159C/T polymorphism is likely to be associated with susceptibility to sepsis in Asian population, especially for the TT genotype. However, bias may rise for etiologic reasons because the majority of subjects in the subgroup came from burn ICU. CD14-159C/T polymorphism is not relevant to sepsis mortality in any genetic models, regardless of the ethnicities. Due to the exploratory nature of the study, no adjustment for multiple testing was adopted, and therefore the results should be interpreted with precaution. Well-designed studies with larger sample size and more ethnic groups are required to further validate the results.

Emodin Inhibition of Influenza A Virus Replication and Influenza Viral Pneumonia via the Nrf2, TLR4, p38/JNK and NF-kappaB Pathways.

Lasting activations of toll-like receptors (TLRs), MAPK and NF-κB pathways can support influenza A virus (IAV) infection and promote pneumonia. In this study, we have investigated the effect and mechanism of action of emodin on IAV infection using qRT-PCR, western blotting, ELISA, Nrf2 luciferase reporter, siRNA and plaque inhibition assays. The results showed that emodin could significantly inhibit IAV (ST169, H1N1) replication, reduce IAV-induced expressions of TLR2/3/4/7, MyD88 and TRAF6, decrease IAV-induced phosphorylations of p38/JNK MAPK and nuclear translocation of NF-κB p65. Emodin also activated the Nrf2 pathway, decreased ROS levels, increased GSH levelss and GSH/GSSG ratio, and upregulated the activities of SOD, GR, CAT and GSH-Px after IAV infection. Suppression of Nrf2 via siRNA markedly blocked the inhibitory effects of emodin on IAV-induced activations of TLR4, p38/JNK, and NF-κB pathways and on IAV-induced production of IL-1ß, IL-6 and expression of IAV M2 protein. Emodin also dramatically increased the survival rate of mice, reduced lung edema, pulmonary viral titer and inflammatory cytokines, and improved lung histopathological changes. In conclusion, emodin can inhibit IAV replication and influenza viral pneumonia, at least in part, by activating Nrf2 signaling and inhibiting IAV-induced activations of the TLR4, p38/JNK MAPK and NF-κB pathways.