A novel type of Brassica napus with higher stearic acid in seeds developed through genome editing of BnaSAD2 family.

KEY MESSAGE: Modifications of multiple copies of the BnaSAD2 gene family with genomic editing technology result in higher stearic acid content in the seed of polyploidy rapeseed. Solid fats from vegetable oils are widely used in food processing industry. Accumulating data showed that stearic acid is more favorite as the major composite among the saturate fatty acids in solid fats in considerations of its effects on human health. Rapeseed is the third largest oil crop worldwide, and has potential to be manipulated to produce higher saturated fatty acids as raw materials of solid fats. Toward that end, we identified four SAD2 gene family members in B. napus genome and established spatiotemporal expression pattern of the BnaSAD2 members. Genomic editing technology was applied to mutate all the copies of BnaSAD2 in this allopolyploid species and mutants at multiple alleles were generated and characterized to understand the effect of each BnaSAD2 member on blocking desaturation of stearic acid. Mutations occurred at BnaSAD2.A3 resulted in more dramatic changes of fatty acid profile than ones on BnaSAD2.C3, BnaSAD2.A5 and BnaSAD2.C4. The content of stearic acid in mutant seeds with single locus increased dramatically with a range of 3.1-8.2%. Furthermore, combination of different mutated alleles of BnaSAD2 resulted in more dramatic changes in fatty acid profiles and the double mutant at BnaSAD2.A3 and BnaSAD2.C3 showed the most dramatic phenotypic changes compared with its single mutants and other double mutants, leading to 11.1% of stearic acid in the seeds. Our results demonstrated that the members of BnaSAD2 have differentiated in their efficacy as a Δ9-Stearoyl-ACP-Desaturase and provided valuable rapeseed germplasm for breeding high stearic rapeseed oil.

Efficacy and Safety of Ceftazidime-Avibactam for the Treatment of Carbapenem-Resistant Enterobacterales Bloodstream Infection: a Systematic Review and Meta-Analysis.

Several clinicians use ceftazidime-avibactam (CAZ-AVI) to treat bloodstream infections (BSIs) due to carbapenem-resistant Enterobacterales (CRE), although no conclusive data support this practice. We aimed to assess the efficacy and safety of CAZ-AVI in the treatment of CRE bacteremia. PubMed, Embase, and Cochrane Library were systematically searched until 5 November 2021. Studies comparing the clinical outcome of CAZ-AVI with other regimens in CRE BSI were included if they reported data on mortality. Results were expressed as risk ratios (RRs) or mean differences with accompanying 95% confidence intervals (95% CIs). Eleven articles with 1,205 patients were included. CAZ-AVI groups showed a significantly lower 30-day mortality than control groups of other regimens (RR = 0.55, 95% CI of 0.45 to 0.68, P < 0.00001). The result is robust when a colistin-based regimen serves as the control group (RR = 0.48, 95% CI 0.33 of 0.69, P < 0.0001). In subgroup meta-analyses, the 30-day mortality was significantly lower in patients infected with CRE producing Klebsiella pneumoniae carbapenemase (RR = 0.59, 95% CI of 0.46 to 0.75, P < 0.0001). Additionally, patients in CAZ-AVI groups had a significantly higher clinical cure rate (RR = 1.75, 95% CI of 1.57 to 2.18, P < 0.00001) and lower nephrotoxicity rate (RR = 0.41, 95% CI of 0.20 to 0.84, P = 0.02). No significant differences of relapse rates were demonstrated in 2 groups (RR = 0.69, 95% CI of 0.29 to 1.66, P = 0.41). Although the current study is based on observational studies with a small sample of participants, the findings suggest that CAZ-AVI treatment is effective and safe compared with other antibiotics, including colistin, in CRE BSI. IMPORTANCE Ceftazidime-avibactam (CAZ-AVI) has been used as a frontline agent in the treatment of multidrug-resistant (MDR) Gram-negative bacterial infections. However, the efficacy and safety of CAZ-AVI on carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) remain unclear. Patients with CRE BSIs were often enrolled in small-sized clinical studies, together with other sites of infections, which reported pooled results. In this meta-analysis, the efficacy and safety were compared between CAZ-AVI and any other regimens used against CRE infections. The findings suggest that patients in the CAZ-AVI group had a significantly lower 30-day mortality than any other regimens and than colistin-based regimens. This paper provides a rationale for the use of CAZ-AVI in one of the most urgent antimicrobial-resistant infections of CRE bloodstream infections.

Assessment of Chinese medicine for coronavirus-related pneumonia: A protocol for systematic review and meta-analysis.

BACKGROUND: The 2019 novel coronavirus disease has caused a global pandemic with substantial morbidity and mortality. Chinese medicine has been extensively employed in the coronavirus-related pandemic in China. We aim to assess the efficacy and safety of Chinese medicine in treatment of coronavirus-related pneumonia with the updated results of relevant clinical trials. METHODS: Six electronic databases including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Chongqing VIP, and SinoMed will be searched to identify randomized controlled trials up to May 2020. Patients diagnosed with coronavirus-related pneumonia including severe acute respiratory syndrome, Middle East respiratory syndrome, and 2019 novel coronavirus disease and administrated with Chinese medicine will be included. The primary outcome is the all cause mortality at the longest follow up available. The second outcomes include the length of stay in hospital and intensive care units, the duration of mechanical ventilation, and adverse events. The pooled effects will be analyzed and reported as risk ratios for dichotomous data using the Mantel-Haenszel method or mean differences for continuous data using the inverse-variance method. Sensitivity and subgroup analyses will be performed to test the robustness of the results and to explore the potential sources of heterogeneities. The Egger test and/or funnel plots will be used for the examination of publication bias. The grades of recommendation assessment, development, and evaluation methodology will be used to summarize the quality of evidence. The trial sequential analysis will be conducted to test whether the meta-analysis has a sufficient sample size after adjustment of the increased type I and II error risks. RESULTS: The evidence to date of Chinese medicine in treatment of coronavirus-related pneumonia will be systematically reviewed and meta-analyzed. CONCLUSION: The relevant studies will be summarized and further evidence will be provided.PROSPERO registration number: CRD42020178879.

Stress ulcer prophylaxis in intensive care unit patients receiving enteral nutrition: a systematic review and meta-analysis.

BACKGROUND: Pharmacologic stress ulcer prophylaxis (SUP) is recommended in critically ill patients with high risk of stress-related gastrointestinal (GI) bleeding. However, as to patients receiving enteral feeding, the preventive effect of SUP is not well-known. Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of pharmacologic SUP in enterally fed patients on stress-related GI bleeding and other clinical outcomes. METHODS: We searched PubMed, Embase, and the Cochrane database from inception through 30 Sep 2017. Eligible trials were RCTs comparing pharmacologic SUP to either placebo or no prophylaxis in enterally fed patients in the ICU. Results were expressed as risk ratio (RR) and mean difference (MD) with accompanying 95% confidence interval (CI). Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were explored. RESULTS: Seven studies (n = 889 patients) were included. There was no statistically significant difference in GI bleeding (RR 0.80; 95% CI, 0.49 to 1.31, p = 0.37) between groups. This finding was confirmed by further subgroup analyses and sensitivity analysis. In addition, SUP had no effect on overall mortality (RR 1.21; 95% CI, 0.94 to 1.56, p = 0.14), Clostridium difficile infection (RR 0.89; 95% CI, 0.25 to 3.19, p = 0.86), length of stay in the ICU (MD 0.04 days; 95% CI, -0.79 to 0.87, p = 0.92), duration of mechanical ventilation (MD -0.38 days; 95% CI, -1.48 to 0.72, p = 0.50), but was associated with an increased risk of hospital-acquired pneumonia (RR 1.53; 95% CI, 1.04 to 2.27; p = 0.03). CONCLUSIONS: Our results suggested that in patients receiving enteral feeding, pharmacologic SUP is not beneficial and combined interventions may even increase the risk of nosocomial pneumonia.

Optimal iodine supplementation during antithyroid drug therapy for Graves' disease is associated with lower recurrence rates than iodine restriction.

OBJECTIVE: A relationship between iodine intake and the effectiveness of antithyroid drug (ATD) therapy for Graves' disease (GD) has been suggested, and strict restriction of iodine intake has been tried in the treatment of GD in some studies. However, it is unclear whether dietary iodine supplementation improves the prognosis of ATD therapy for GD. This study aimed to clarify whether optimal iodine supplementation during antithyroid drug therapy for GD is associated with lower recurrence rates than iodine restriction. METHODS: This was a prospective randomized trial of newly diagnosed patients with GD. Patients with newly diagnosed GD were recruited. After ATD therapy and strict dietary iodine restriction for 1 month, patients (n = 459) were randomly assigned to iodine-supplemented and iodine-restricted groups. After exclusion, 405 patients finally completed the study. The iodine-supplemented group included 203 patients (61 males and 142 females) with an average age of 32.2 ± 10.5 years (17-65 years), and the iodine-restricted group included 202 patients (61 males and 141 females) with an average age of 31.9 ± 11.8 years (16-64 years). Patients in the iodine-supplemented group were given about 10 grams of iodized salt every day, while the iodine-restricted group received noniodized salt with low-iodine or noniodine diet. The dietary iodine intervention lasted for 24 months. Urinary iodine concentration (UIC), thyrotropin receptor antibody (TRAb), free T3 (FT3), free T4 (FT4) and thyrotropin (TSH) of 2 groups were measured every 3 months. The recurrence rates within 12 months after withdrawal of ATD were evaluated. RESULTS: UIC in the iodine-supplemented group was within the recommended range for optimal iodine intake (135-162 µg/L) and was significantly higher than that in iodine-restricted group (30-58 µg/L). Within 12 months of withdrawal of ATD, the total recurrence rate in the iodine-supplemented group was 35.5%, significantly lower than in the iodine-restricted group, which was 45.5%. CONCLUSION: Optimal dietary iodine supplementation during antithyroid drug therapy for GD is associated with lower recurrence rates than iodine restriction, and therefore, diet control with strict iodine restriction might be an adverse factor in the management of GD.

Associations of green tea and rock tea consumption with risk of impaired fasting glucose and impaired glucose tolerance in Chinese men and women.

OBJECTIVE: To explore the associations of green tea and rock tea consumption with risk of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). METHODS: A multistage, stratified, cluster, random-sampling method was used to select a representative sample from Fujian Province in China. In total, 4808 subjects without cardiovascular disease, hypertension, cancer, or pancreatic, liver, kidney, or gastrointestinal diseases were enrolled in the study. A standard questionnaire was used to gather data on tea (green, rock, and black) consumption and other relevant factors. The assessment of impaired glucose regulation (IGR) was using 75-g oral glucose tolerance test (OGTT), the diagnostic criteria of normal glucose tolerance was according to American Diabetes Association. RESULTS: Green tea consumption was associated with a lower risk of IFG, while rock tea consumption was associated with a lower risk of IGT. The adjusted odds ratios for IFG for green tea consumption of <1, 1-15, 16-30, and >30 cups per week were 1.0 (reference), 0.42 (95% confidence intervals (CI) 0.27-0.65), 0.23 (95% CI, 0.12-0.46), and 0.41 (95% CI, 0.17-0.93), respectively. The adjusted odds ratios for IGT for rock tea consumption of <1, 1-15, 16-30, and >30 cups per week were 1.0 (reference), 0.69 (95% CI, 0.48-0.98), 0.59 (95% CI, 0.39-0.90), and 0.64 (95% CI, 0.43-0.97), respectively. A U-shaped association was observed, subjects who consumed 16-30 cups of green or rock tea per week having the lowest odds ratios for IFG or IGT. CONCLUSIONS: Consumption of green or rock tea may protect against the development of type 2 diabetes mellitus in Chinese men and women, particularly in those who drink 16-30 cups per week.