The crosstalk between NLRP3 inflammasome and gut microbiome in atherosclerosis.

Atherosclerosis (AS) is chronic pathological process based on the inflammatory reaction associated with factors including vascular endothelial dysfunction, inflammation, and autoimmunity. Inflammasomes are known to be at the core of the inflammatory response. As a pattern recognition receptor of innate immunity, the NLRP3 inflammasome mediates the secretion of inflammatory factors by activating the Caspase-1, which is important for maintaining the immune system and regulating the gut microbiome, and participates in the occurrence and development of AS. The intestinal microecology is composed of a large number of complex structures of gut microbiota and its metabolites, which play an important role in AS. The gut microbiota and its metabolites regulate the activation of the NLRP3 inflammasome. Targeting the NLRP3 inflammasome and regulating intestinal microecology represent a new direction for the treatment of AS. This paper systematically reviews the interaction between the NLRP3 inflammasome and gut microbiome in AS, strategies for targeting the NLRP3 inflammasome and gut microbiome for the treatment of AS, and provides new ideas for the research and development of drugs for the treatment of AS.

Xiao-Qing-Long Tang Prevents Cardiomyocyte Hypertrophy, Fibrosis, and the Development of Heart Failure with Preserved Ejection Faction in Rats by Modulating the Composition of the Gut Microbiota.

BACKGROUND: Changes in the gut microbiota are associated with cardiovascular disease progression. Xiao-Qing-Long Tang (XQLT), a traditional herbal formula, has an anti-inflammatory effect and regulates the steady state of the immune system, which is also associated with the progression of heart failure with preserved ejection faction (HFpEF). In this study, we investigated whether XQLT could contribute to prevent the development of HFpEF and whether the modulation of the gut microbiota by this herbal formula could be involved in such effect. METHODS: The gut microbiota, SCFAs, the histology/function of the heart, and systolic blood pressure were examined to evaluate the effect of XQLT on the gut microbiota and the progression of HFpEF after oral administration of XQLT to model rats. Furthermore, we evaluated, through fecal microbiota transplantation experiments, whether the favorable effects of XQLT could be mediated by the gut microbiota. RESULTS: Oral administration of XQLT contributed to the reduction of elevated blood pressure, inflammation, and compensatory hypertrophy, features that are associated with the progression of HFpEF. The gut microbiota composition, SCFA levels, and intestinal mucosal histology were improved after treatment with XQLT. Moreover, fecal transfer from XQLT-treated rats was sufficient to prevent the progression of HFpEF. CONCLUSIONS: These data suggested that XQLT prevented the development of HFpEF in model rats by regulating the composition of the gut microbiota.

Ultrasound-guided radiofrequency ablation of the segmental Glissonian pedicle: A new technique for anatomic liver resection.

BACKGROUND: Anatomic liver resection is widely accepted as the optimal surgical treatment for hepatocellular carcinoma (HCC); however, the complexity of conventional operative methods limits their use. To explore the possibility of using modern techniques to achieve a simpler approach, we have evaluated ultrasound-guided segmental radiofrequency ablation (RFA) of the Glissonian pedicle before liver resection in a porcine model and in HCC patients. METHODS: This study had 2 stages. First, we piloted anatomic liver resection using ultrasound-guided RFA of the segmental Glissonian pedicle in 6 Bama miniature pigs. Having found this technique safe and effective, we selected 21 HCC patients to treat with the same approach. RESULTS: The pigs had no postoperative mortality or morbidity. Demarcation areas were apparent in all targeted segments. The mean length of segmental portal, arterial, and biliary tract branches ablated was 1.7, 1.4, and 1.6 cm, respectively. Human HCC operations consisted of 8 subsegmentectomies, 8 segmentectomies, and 5 multisegmentectomies. The procedure was feasible in all patients, with no mortality, morbidity, or need for blood transfusions. A demarcation area was apparent in all patients within 157 seconds of RF application for each target feeding vessel. The mean number of target feeding vessels was 2 (range, 1-7). CONCLUSION: Our study demonstrates that ultrasound-guided RFA ablation of the segmental Glissonian pedicle is expedient, safe, and effective, and is suitable for resection of any hepatic segments or subsegments, from segments 2 to 8.

Risk scoring system and predictor for clinically relevant pancreatic fistula after pancreaticoduodenectomy.

AIM: To establish a scoring system to predict clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). METHODS: The clinical records of 921 consecutive patients who underwent PD between 2008 and 2013 were reviewed retrospectively. Postoperative pancreatic fistula (POPF) was defined and classified by the international study group of pancreatic fistula (ISGPF). We used a logistic regression model to determine the independent risk factors of CR-POPF and developed a scoring system based on the regression coefficient of the logistic regression model. The optimal cut-off value to divide the risk strata was determined by the Youden index. The patients were divided into two groups (low risk and high risk). The independent sample t test was used to detect differences in the means of drain amylase on postoperative day (POD) 1, 2 and 3. The optimal cut-off level of the drain amylase to distinguish CR-POPF from non-clinical POPF in the two risk strata groups was determined using the receiver operating characteristic (ROC) curves. RESULTS: Grade A POPF occurred in 106 (11.5%) patients, grade B occurred in 57 (6.2%) patients, and grade C occurred in 32 (3.5%) patients. A predictive scoring system for CR-POPF (0-6 points) was constructed using the following four factors: 1 point for each body mass index ≥ 28 [odds ratio (OR) = 3.86; 95% confidence interval (CI): 1.92-7.75, P = 0.00], soft gland texture (OR = 4.50; 95%CI, 2.53-7.98, P = 0.00), and the difference between the blood loss and transfusion in operation ≥ 800 mL (OR = 3.45; 95%CI, 1.92-7.75, P = 0.00); and from 0 points for a 5 mm or greater duct diameter to 3 points for a less than 2 mm duct (OR = 8.97; 95%CI: 3.70-21.77, P = 0.00). The ROC curve showed that the area under the curve of this score was 0.812. A score of 3 points was suggested to be the best cut-off value (Youden index = 0.485). In the low risk group, a drain amylase level ≥ 3600 U/L on POD3 could distinguish CR-POPF from non-clinical POPF (the sensitivity and specificity were 75% and 85%, respectively). In the high risk group, the best cut-off was a drain amylase level of 1600 (the sensitivity and specificity were 77 and 63%, respectively). CONCLUSION: A 6-point scoring system accurately predicted the occurrence of CR-POPF. In addition, a drain amylase level on POD3 might be a predictor of this complication.

[Ablation of segmental glissonian pedicle by ultrasound-guided radiofrequency in precision liver resection in a porcine model].

OBJECTIVE: To demonstrate the ablation of segmental glissonian pedicle by ultrasound-guided radiofrequency in precision liver resection in porcine model. METHODS: The study was carried out on 6 Bama miniature pigs. Coagulative desiccation of the vessels feeding the segment to be resected was induced by introduction of a "cooled-tip" radiofrequency electrode under intraoperative ultrasound guidance at the level of the vessels. Then, an area of marked discoloration on the surface of the liver became obvious. Liver parenchymal transection followed without any form of hepatic inflow occlusion. Three segments (segment 3, 5, and 6) were resected on each pig. The criteria studied the local and general tolerance, the change of blood flow parameters of each segmental arterial and portal branches, and the microscopic appearance of the segmental arterial, portal and biliary tract branches. Using t test as the statistical methods. RESULTS: Postoperative mortality and morbidity were 0 and all serum parameters had normalized by 14 days. Demarcation area was obtained in 15 segments. The flow rate of the resected segmental portal branches was 0 cm/s after radiofrequency and the value of the arterial branches was (28 ± 18) cm/s which was significantly lower than pre-radiofrequency, which were (10.2 ± 3.0) cm/s and (60 ± 17) cm/s (t = 14.439, 5.502; P = 0.000). There was no significant difference in the flow rate of the remnant segmental arterial and portal branches among pre-radiofrequency, post-radiofrequency and 14 days after operation. On microscopic observation, the mean ablated length of segmental portal, arterial and biliary tract branches were (1.6 ± 0.4) cm, (1.2 ± 0.4) cm, and (1.7 ± 0.3) cm respectively. CONCLUSIONS: The ablation of the segmental glissonian pedicle by ultrasound-guided radiofrequency is quick, safe and effective. The probe needs to be away from vessels feeding segments 1.5 cm at least to avoid thermal injuries.

[Surgical management and outcome of solid-pseudopapillary tumor of pancreas: a series of 58 cases].

OBJECTIVE: To study the surgical management of solid-pseudopapillary tumor of the pancreas (SPTP) and its characteristics of outcome. METHODS: Fifty-eight patients with SPTP of the pancreas admitted from January 2001 to December 2010 were retrospectively analyzed. There were 7 male and 51 female patients, with an average age of 30 years (ranging 9 to 70 years). Most patients were symptomatic before admission; the most common symptom was abdominal pain. Of the 58 patients, 21 patients underwent pancreaticoduodenectomy, 30 patients underwent distal pancreatectomy, 6 patients underwent central pancreatectomy, 1 patient underwent simple tumor enucleation, and 1 patients underwent duodenum-preserving pancreatic head resection. RESULTS: The average length of stay in hospital was 23.8 days (ranging 12 to 64 days). Thirteen patients (22.4%) developed postoperative complications, including grade A postoperative pancreatic fistula of 8 cases, gastrointestinal tract bleeding of 1 case, pleural effusion of 2 cases, wound infection and fat liquefaction of 2 cases. Two patients underwent reoperation due to gastrointestinal tract bleeding or wound infection. There was no hospital death. Forty-four patients were followed-up for 7 to 136 months with an average of 41 months. All the 44 patients were alive, while 8 patients developed dyspepsia and 4 patients developed diabetes mellitus. There were no tumor recurrences or metastasis. CONCLUSIONS: SPTP is found primarily in young women. Excellent prognosis would be achieved with surgical resection.

Prognostic significance of mast cell count following curative resection for pancreatic ductal adenocarcinoma.

BACKGROUND: Recently, there is evidence that the number of mast cells in various solid cancers increases with tumor progression. The role of mast cells in promoting tumor progression, however, has not been well studied in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the prognostic value of mast cell counts in different zones of the neoplasm in patients with PDAC after curative resection. METHODS: Numbers of mast cells and microvessels were assessed by immunohistochemistry in tissues from 103 patients with PDAC and 10 patients with normal pancreas. All patients with PDAC underwent partial pancreatic resection. The investigators paid particular attention to the distribution of mast cells in each specimen. RESULTS: High mast cell counts in the intratumoral border zone correlated with the presence of lymphatic and microvascular invasion, lymph node metastasis, and TNM stage, and were an independent prognostic factor for overall survival (P < .001). In contrast, neither in the intratumoral center zone nor in the peritumoral zones was mast cell count associated with OS. Mast cell counts in the intratumoral border zone, but not in the peritumoral or in the intratumoral center zone, were correlated with microvessel counts. CONCLUSION: The present study shows a zone-specific distribution of mast cells in PDAC and highlights the importance of invasive front in the prognosis of patients with PDAC after curative resection. Zone-specific evaluation of mast cell and microvessel counts may be helpful for prognostic assessment and therapeutic decision making in PDAC.

Improvement of spinosad production by overexpression of gtt and gdh controlled by promoter PermE* in Saccharopolyspora spinosa SIPI-A2090.

Spinosyns A and D are novel macrolide secondary metabolites containing two deoxysugars. Each of the sugars is derived from a common intermediate, which is biosynthesized sequentially by NDP-glucose synthase and glucose dehydratase. Systematical duplication of gtt and gdh was carried out by genetic engineering in Saccharopolyspora spinosa. Introduction of additional gtt and gdh genes under the control of PermE* promoter showed significant increase on their transcript levels. The production of spinosad was increased by over threefold to reach 800 µg/ml in the recombinant strain SIPI-M2093.

Overexpression of aveBIV leading to the improvement of 4'-epidaunorubicin production in Streptomyces coeruleorubidus strain SIPI-A0707.

The 4'-epidaunorubicin is the semisynthesis precursor of epirubicin which is a clinically useful antitumor drug thought to have slightly less cardiotoxicity than doxorubin. The 4'-epidaunorubicin was formed by overexpression of heterologous Streptomyces avermitilis aveBIV in Streptomyces coeruleorubidus SIPI-A0707 dnmV mutant blocked in the biosynthesis of daunosamine, the deoxysugar component of daunorubicin. But there was a low-yield production of 4'-epidaunorubicin. In our study, product yields were enhanced considerably by increasing aveBIV gene copy number or changing means of aveBIV integration. The 4'-epidaunorubicin titer was improved by around threefold in the recombinant strain DYG1006 with the aveBIV increased threefold copy numbers. The transcript levels of aveBIV gene meet the expectation of fermentation levels of 4'-epidaunorubicin. The method described here provides the means to produce 4'-epidaunorubicin efficiently on an industrial scale.

[Determinants of long-term survival after pancreaticoduodenectomy for ampulla of Vater carcinoma].

OBJECTIVE: To investigate the determinants of long-term survival for ampulla of Vater carcinoma treated by pancreaticoduodenectomy. METHODS: A total of 77 patients with ampulla of Vater carcinoma undergoing pancreaticoduodenectomy were reviewed. Kaplan-Meier method was used to analyze the survival rate. Independent t test was used for statistical comparison and COX regression model for multivariate analysis. RESULTS: No patient died as a result of surgery. The overall 5-year survival was 40.7%. Univariate analysis showed that perioperative serum carcinoembryonic antigen (CEA) level (P = 0.012), tumor invasion depth (P = 0.000), UICC stage (P = 0.000) and tumor size (P = 0.001) were significant prognostic factors of ampulla of Vater carcinoma; in multivariate analysis, only the tumor size (P = 0.000) was an independent prognostic factor of ampulla of Vater carcinoma. CONCLUSION: Pancreaticoduodenectomy is associated with significant survival. Tumor size is the most important influencing factor of outcome after pancreaticoduodenectomy; in addition, perioperative serum CEA level, tumor invasion depth and UICC stage may also influence the survival rate, there exists a need for further follow-up studies.