Fusobacterium nucleatum induces colon anastomosis leak by activating epithelial cells to express MMP9

BackgroundDespite advances in anastomotic techniques and perioperative care, the incidence of anastomotic leak (AL) has not substantially decreased over time. Although it is known that AL etiology is multifactorial and the mechanisms involved remain unclear, there is accumulating evidence pointing at AL related to gut microbiota.MethodWe firstly performed a clinical study to analyze the gut microbiota between colorectal cancer patients who developed AL and those who did not (nAL) using 16S-rRNA sequencing and quantitative real-time PCR to identify AL risk bacterial taxa. Then we built a rat anastomosis model and performed a bacteria transplantation to ensure the cause-effect relationship. The anastomotic healing score was used to evaluate the healing of anastomosis. In addition, we assessed the adhesion ability of bacteria by staining with fluorescein isothiocyanate and attachment assay. The expression of matrix metalloproteinase 9 (MMP9) was detected by western blot, and the activity was detected by gelatin zymography.ResultsWe found that the abundance and positive rate of Fusobacterium nucleatum (Fn) were higher in the AL patients. Exposure of the rat’s colon anastomosis to Fn contributes to the loss of submucosa collagen I and III, leading to AL’s pathogenesis. Fn can attach to the gut epithelial cells and stimulate intestinal MMP9 expression in vitro and in vivo. We further confirmed that these effects of Fn depended on the E-cadherin/β-catenin signaling pathway.ConclusionThis work demonstrates that Fn attaches and then stimulates the expression of epithelial cells MMP9 by the E-cadherin/β-catenin signaling pathway. These effects contribute to collagen break down in the intestinal tissue, finally leading to AL

Spatial and temporal evolution of carbon stocks in Dongting Lake wetlands based on remote sensing data

Wetlands are one of the important carbon reservoirs on earth, assessing the spatial and temporal dynamics of wetland carbon stocks and their driving mechanisms is critical for stabilizing and enhancing the carbon sink function of wetlands. In this study, the carbon stocks of Dongting Lake wetland during 1995–2020 were estimated using the Integrate Valuation of Ecosystem Services and Tradeoffs Tool (InVEST) model and land use/cover data derived from remote sensing data. Subsequently, the geographically weighted regression (GWR) model was utilized to explore the driving mechanisms of the spatial and temporal dynamics of carbon stocks based on natural and socio-economic factors. Finally, evolution of land use status and carbon stocks was simulated based on patch-generating land use simulation (PLUS) model during 2030–2050 under different scenarios. The results showed that: 1) over the past 25 years, carbon stocks have been fluctuating in a ‘decrease–increase–decrease’ pattern, with an average decrease of 39.70 × 106 t per year; 2) compared with socio-economic factors, climate conditions have a greater influence on the change of carbon stocks distribution; 3) under the natural variation scenario, the carbon stocks in 2030 is 1345.36 × 106 t, which is increased compared with the year of 2020. However, the carbon stocks in 2040–2050 started to show a decreasing trend. Under the ecological conservation scenario, the increase in forest area leads to a significant increase in carbon stocks from 2030 to 2050, which showed a continuous growth trend and obviously enhanced the carbon sequestration capacity of the Ecological and Economic Circle around Dongting Lake. The results of this study are expected to provide a scientific basis for carbon balance, land use restructuring and wetland resource management planning in the ecological and economic circle around Dongting Lake. Highlights The carbon stocks of Dongting Lake wetland during 1995–2020 were estimated using the InVEST model. Over the past 25 years, carbon stocks of Dongting Lake wetlands have been fluctuating in a ‘decrease–increase–decrease’ pattern. Climate conditions have a greater influence on the change of carbon stocks distribution compared with socio-economic factors

The diffuse reduction in spleen density: an indicator of severe acute pancreatitis?

Correspondence : Xuewei Bai ([email protected]) We observed that acute pancreatitis (AP) was associated with diffuse reduction in spleen density (DROSD) in some patients. Furthermore, the condition of these patients was more serious, and the potential relationship between DROSD and structural and functional injury of the spleen remained unclear. Therefore, we performed a preliminary exploration of these factors. We analysed pertinent clinical data for AP patients with normal spleen density (control group) and for those with DROSD (reduction group) at the First Affiliated Hospital of Harbin Medical University (June 2013-June 2015). We measured the immunoglobulin M (IgM) B-cells of the AP patients and examined pancreatic and splenic tissues from AP rats with optical microscopy and TEM. The reduction group had a higher acute physiology and chronic health evaluation II (APACHE II) score, a longer length of stay (LOS) and lower serum calcium than the control group. The levels of triglycerides (TG) and total cholesterol (TC) did not differ significantly between the two groups. The percentage of IgM memory B-cells was significantly lower in the DROSD group than in the control group. TEM revealed that the spleen T-lymphocytes were normal in AP rats, but pyroptotic and necrotic spleen B-cells were observed in the severe AP rats. In AP, DROSD was an independent indicator of more severe conditions. Furthermore, spleen B-lymphocytes showed obvious damage at the cellular level, and the immunological function of the spleen was down-regulated when AP was associated with DROSD

The effect of antibiotic prophylaxis on the incidence of surgical site infection after laparoscopic appendectomy for chronic appendicitis

Background: The guidelinesthat specify whether antibiotic prophylaxis should be administered before laparoscopic clean-contaminated wound to prevent postoperative surgical site infection (SSI) need to be improved. Studies have shown that elective laparoscopic cholecystectomy with clean-contaminated wound does not require antibiotic prophylaxis. However, there are no studies on the effect of antibiotic prophylaxis on SSI after laparoscopic appendectomy for chronic appendicitis (LCA), which is a clean-contaminated wound. Methods: We conducted a single-center, double-blind, randomized controlled clinical trial. A total of 106 effective patients were randomly divided into the antibiotic group and saline group. Cefuroxime or clindamycin was administered intravenously in the antibiotic group (n = 52). Saline (0.9%) was administered intravenously in the saline group (n = 54). Interventions were administered as a single dose 30 min before surgery. Results: Among the 106 effective patients (median age, 37 years old [IQR, 25–45]; females, 77 [72.6%]), there were 6 cases (5.70%) of SSI: 3 cases (5.56%) in the saline group and 3 cases (5.70%) in the antibiotic group (OR = 1.00, [95% CI (0.20–5.4)], P = 0.96). There were no significant differences in the clinical outcomes of anal exhaust time, postoperative complications, and the symptom of primary abdominal pain between the two groups. Conclusion: For patients with chronic appendicitis undergoing laparoscopic appendectomy, preoperative intravenous antibiotic prophylaxis did not reduce the risk of SSI within 30 days of the surgery compared to the saline group. Trial registration: Registration number of China Clinical Trials Registration Center: ChiCTR2100048336

Table_1_Fusobacterium nucleatum induces colon anastomosis leak by activating epithelial cells to express MMP9.docx

BackgroundDespite advances in anastomotic techniques and perioperative care, the incidence of anastomotic leak (AL) has not substantially decreased over time. Although it is known that AL etiology is multifactorial and the mechanisms involved remain unclear, there is accumulating evidence pointing at AL related to gut microbiota.MethodWe firstly performed a clinical study to analyze the gut microbiota between colorectal cancer patients who developed AL and those who did not (nAL) using 16S-rRNA sequencing and quantitative real-time PCR to identify AL risk bacterial taxa. Then we built a rat anastomosis model and performed a bacteria transplantation to ensure the cause-effect relationship. The anastomotic healing score was used to evaluate the healing of anastomosis. In addition, we assessed the adhesion ability of bacteria by staining with fluorescein isothiocyanate and attachment assay. The expression of matrix metalloproteinase 9 (MMP9) was detected by western blot, and the activity was detected by gelatin zymography.ResultsWe found that the abundance and positive rate of Fusobacterium nucleatum (Fn) were higher in the AL patients. Exposure of the rat’s colon anastomosis to Fn contributes to the loss of submucosa collagen I and III, leading to AL’s pathogenesis. Fn can attach to the gut epithelial cells and stimulate intestinal MMP9 expression in vitro and in vivo. We further confirmed that these effects of Fn depended on the E-cadherin/β-catenin signaling pathway.ConclusionThis work demonstrates that Fn attaches and then stimulates the expression of epithelial cells MMP9 by the E-cadherin/β-catenin signaling pathway. These effects contribute to collagen break down in the intestinal tissue, finally leading to AL.</p