Production of bilirubin by biotransformation of biliverdin using recombinant Escherichia coli cells.

Bilirubin, a natural intermediate in heme degradation, is a valuable Chinese medicine used in more than 50 traditional Chinese medicine (TCM) preparations. At present, bilirubin is mainly produced by extraction from pig bile, but a shortage of the raw material has increased the price, to about US$10,000/kg in the Chinese market. Biliverdin, the precursor of bilirubin, is more abundant and less expensive than bilirubin, but it is not used in TCM. Thus, the biotransformation of biliverdin by biliverdin reductase (BvdR) may be a practical way to produce bilirubin. In this study, the codon-optimized gene of biliverdin reductase (mbvdR) from the cyanobacterium Synechocystis was cloned into Escherichia coli BL21(DE3), and the conditions for BL21-mBvdR expressing BvdR were optimized. Resting BL21-mBvdR cells were employed as biocatalysts to biotransform biliverdin to bilirubin. At a concentration of biliverdin substrate of 450 mg/L in the reaction mixture, the bilirubin content in dry cells reached 20.8 ± 0.8 mg/g, with a conversion yield of 72.3%. Therefore, recombinant E. coli expressing BvdR can be applied to biotransform biliverdin to bilirubin, providing a potential alternative process for bilirubin production.

Estimated glomerular filtration rate and postoperative mortality in patients undergoing non-cardiac and non-neuron surgery: a single-center retrospective study.

BACKGROUND: There is limited evidence to clarify the specific relationship between preoperative estimated glomerular filtration rate (preop-eGFR) and postoperative 30-day mortality in Asian patients undergoing non-cardiac and non-neuron surgery. We aimed to investigate details of this relationship. METHODS: We reanalyzed a retrospective analysis of the clinical records of 90,785 surgical patients at the Singapore General Hospital from January 1, 2012 to October 31, 2016. The main outcome was postoperative 30-day mortality. RESULTS: The average age of these recruited patients was 53.96 ± 16.88 years, of which approximately 51.64% were female. The mean of preop-eGFR distribution was 84.45 ± 38.56 mL/min/1.73 m2. Multivariate logistic regression analysis indicated that preop-eGFR was independently associated with 30-day mortality (adjusted odds ratio: 0.992; 95% confidence interval [CI] 0.990-0.995; P < 0.001). A U-shaped relationship was detected between preop-eGFR and 30-day mortality with an inflection point of 98.688 (P for log likelihood ratio test < 0.001). The effect sizes and confidence intervals on the right and left sides of the inflection point were 1.013 (1.007 to 1.019) [P < 0.0001] and 0.984 (0.981 to 0.987) [P < 0.0001], respectively. Preoperative comorbidities such as congestive heart failure (CHF), type 1 diabetes, ischemic heart disease (IHD), and anemia were associated with the odds ratio of preop-eGFR to 30-day mortality (interaction P < 0.05). DISCUSSION: The relationship between preop-eGFR and 30-day mortality is U-shaped. The recommended preop-eGFR at which the rate of the 30-day mortality was lowest was 98.688 mL/min/1.73 m2.

Anemia and perioperative mortality in non-cardiac surgery patients: a secondary analysis based on a single-center retrospective study.

BACKGROUND: Evidence regarding the relationship between anemia and perioperative prognosis is controversial. The study was conducted to highlight the specific relationship between anemia and perioperative mortality in non-cardiac surgery patients over 18 years of age. METHODS: This study was a retrospective analysis of the electronic medical records of 90,784 patients at the Singapore General Hospital from January 1, 2012 to October 31, 2016. Multivariate regression, propensity score analysis, doubly robust estimation, and an inverse probability-weighting model was used to ensure the robustness of our findings. RESULTS: We identified 85,989 patients, of whom75, 163 had none or mild anemia (Hemoglobin>90g/L) and 10,826 had moderate or severe anemia (Hemoglobin≤90g/L). 8,857 patients in each study exposure group had similar propensity scores and were included in the analyses. In the doubly robust model, postoperative 30-day mortality rate was increased by 0.51% (n = 219) in moderate or severe anemia group (Odds Ratio, 1.510; 95% Confidence Interval (CI), 1.049 to 2.174) compared with none or mild anemia group (2.47% vs.1.22%, P<0.001). Moderate or severe anemia was also associated with increased postoperative blood transfusion rates (OR, 5.608; 95% CI, 4.026 to 7.811, P < 0.001). There was no statistical difference in Intensive Care Unit (ICU) admission rate among different anemia groups within 30 days after surgery (P=0.104). DISCUSSION: In patients undergoing non-cardiac surgery over 18 years old, moderate or severe preoperative anemia would increase the occurrence of postoperative blood transfusion and the risk of death, rather than ICU admission within 30 days after surgery.

The relationship between anesthetic technique and thirty-day mortality in patients undergoing noncardiac- and nonneurosurgery: A retrospective, propensity score-matched cohort study.

BACKGROUND: Currently, 310 million patients undergo surgery every year worldwide, and there is still controversy over which anesthetic technique to choose for a considerable of surgeries.This study evaluates the association of the anesthetic technique with thirty-day mortality after noncardiac- and nonneurosurgery. METHODS: Electronic medical records of 90,785 patients who underwent non-cardiac- and nonneurosurgery at the *** General Hospital from January 1, 2012 to October 31, 2016, were subject to secondary retrospective analysis. The principal exposure was regional versus general anesthesia. Outcome measures were death, intensive care unit (ICU) admission and blood transfusion requirement within 30 days after surgery. Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics. RESULTS: We identified 90,785 patients, of whom 76,442 received regional anesthesia and 14,343 received general anesthesia. A total of 11,351 patients in the general anesthesia group had propensity scores similar to those of patients who received regional anesthesia and were included in the analyses. In the propensity-score matched cohort, the postoperative 30-day mortality rate was 0.75% (n = 85) in the regional anesthesia group (Odds Ratio, 0.567; 95% CI, 0.434 to 0.741; P = 0.00003) compared with 1.31% (n = 149) in the general anesthesia group. Regional anesthesia was also associated with a reduced rate of ICU admission compared with that of patients who received general anesthesia (0.44% vs. 2.68%; OR, 0.161; 95% CI, 0.119 to 0.217, P < 0.00001). There was a nonsignificant relationship between the anesthetic technique and postoperative blood transfusion (P = 0.082). CONCLUSIONS: The results of this observational, propensity score-matched cohort study suggest a significant association between regional anesthesia and low thirty-day mortality and a worse postoperative prognosis in patients who underwent noncardiac- and nonneurosurgery, which provides information for anesthetic technique decision making in the clinical setting.