Time-restricted Feeding Changes as Inspiration for Drug Design.

Time-restricted feeding (TRF) is a special lifestyle intervention that improves glucose metabolism, regulates lipid metabolism, increases gut micro richness, and strengthens circadian rhythm. Diabetes is a remarkable component of metabolic syndrome, and individuals with diabetes can benefit from TRF. Melatonin and agomelatine can strengthen circadian rhythm, which is a crucial mechanism of TRF. New drug designs can be inspired by the related mechanisms and influences of TRF on glucose metabolism, and more researches are needed to clarify the specific diet-related mechanisms and apply this knowledge to further drug design.

Intermittent fasting and immunomodulatory effects: A systematic review.

Introduction: strategy of periodic food restriction and fixed eating windows, could beneficially modify individuals by losing body weight, regulating glucose or lipid metabolism, reducing blood pressure, and modulating the immune system. Specific effects of IF and its mechanisms have not yet been assessed collectively. Thus, this systematic review aims to summarize and compare clinical trials that explored the immunomodulatory effects of IF. Methods: After screening, 28 studies were included in this systematic review. Results: In addition to weight loss, IF could benefit health subjects by strengthening their circadian rhythms, migrating immune cells, lower inflammatory factors, and enriching microbials. In addition of the anti-inflammatory effect by regulating macrophages, protection against oxidative stress with hormone secretion and oxidative-related gene expression plays a key beneficial role for the influence of IF on obese subjects. Discussion: Physiological stress by surgery and pathophysiological disorders by endocrine diseases may be partly eased with IF. Moreover, IF might be used to treat anxiety and cognitive disorders with its cellular, metabolic and circadian mechanisms. Finally, the specific effects of IF and the mechanisms pertaining to immune system in these conditions require additional studies.

Antibiotic use at planned central line removal in reducing neonatal post-catheter removal sepsis: a systematic review and meta-analysis.

Background: Post-catheter removal sepsis (PCRS) is a notable complication of indwelling central venous catheters (CVCs) in neonates, which is postulated to be secondary to the disruption of biofilms formed along catheter tips up on CVCs removal. It remains controversial whether this could be prevented by antibiotic use upon CVCs removal. We aimed to evaluate the protective effect of antibiotic administration at the time of CVCs removal. Methods: We searched through PubMed, EMBASE, Cochrane databases and reference lists of review articles for studies comparing the use of antibiotics versus no use within 12 h of CVCs removal. Risk of bias was assessed using the modified Newcastle-Ottawa Scale and Cochrane risk-of-bias tool accordingly. Results of quantitative analyses were presented as mean differences (MD) or odds ratio (OR). Subgroup and univariate meta-regression analyses were performed to identify heterogeneity. Results: The review included 470 CVCs in the antibiotic group and 658 in the control group. Antibiotic use within 12 h of CVCs removal did not significantly reduce the incidence of PCRS (OR = 0.35, 95% CI: 0.08-1.53), but was associated with a lower incidence of post-catheter removal blood stream infection (OR = 0.31, 95% CI: 0.11-0.86). Dosage of vancomycin and world region were major sources of heterogeneity. Conclusion: Antibiotic administration upon CVCs removal does not significantly reduce the incidence of PCRS but offers less post-catheter removal blood stream infection. Whether this will be converted to better clinical outcomes lacks evidential support. Further randomized controlled studies with longer follow-up are needed. Summary: Results of our meta-analysis suggest that antibiotic use at planned central line removal removal does not significantly reduce the incidence of PCRS but offers less blood stream infection, which might contribute to future management of central lines in neonates. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO (CRD42022359677).

Robot-assisted vs. laparoscopic nephroureterectomy for upper urinary tract urothelial carcinoma: a systematic review and meta-analysis based on comparative studies.

Background: Robot-assisted nephroureterectomy (RANU) and laparoscopic nephroureterectomy (LNU) are two minimally invasive surgical management for upper urinary tract urothelial carcinomas (UTUC). Though more high-tech, it remains largely unclear whether RANU provides additional benefits over LNU. We aimed to quantitatively compare the perioperative and oncologic outcomes between RANU and LNU. Methods: The systematic review was performed based on a registered protocol (registration number CRD42022319086). We searched through PubMed, EMBASE and Cochrane databases, as well as conference proceedings and references of review articles (May 2022) for comparative studies reporting perioperative and oncologic outcomes independently in RANU and LNU groups. Selection of studies and data extraction were performed independently by two researchers. Risk of bias was assessed using the modified Newcastle-Ottawa Scale. Results of random-effects meta-analyses were presented as mean differences (MD) or Odds ratio (OR), as appropriate. Subgroup and univariate meta-regression analyses were performed to identify interstudy heterogeneities. Results: The review included 8470 patients undergoing RANU and 19872 patients undergoing LNU from 12 comparative original studies. RANU was associated with fewer overall complications (OR=0.71, 95%CI: 0.62 to 0.81), longer operative time (MD=27.70, 95%CI: 0.83 to 54.60) and shorter length of stay (MD=-0.53, 95%CI: -0.98 to -0.07) compared to LNU. In addition, patients receiving RANU were more likely to have lymph node dissected (OR=2.61, 95%CI: 1.86 to 3.65). Recurrence and survival outcomes did not differ between two surgical procedures. Sample size, types of LNU and world region were major sources of heterogeneity. Conclusion: For UTUC patients, RANU offers fewer complications and shorter hospitalization. However, RANU requires longer operative time and shares similar oncologic outcomes compared to LNU. Further randomized designed studies are warranted. Systematic Review Registration: www.crd.york.ac.uk/prospero/, identifier CRD42022319086.

Effects of time-restricted feeding with different feeding windows on metabolic health: A systematic review of human studies.

Time-restricted feeding (TRF), a feasible form of intermittent fasting, has been proven to benefit metabolic health in animal models and humans. TRF restricts the daily feeding window to 3 to 12 h for eating ad libitum, with fasting for the rest of the day. To our knowledge, specific guidance on the appropriate time period for eating during TRF has not yet been promoted. Therefore, the aim of the present review was to summarize the current literature on the effects of TRF with different eating windows in humans and compare their effects on metabolic health-related markers. Early TRF (which restricts food intake during the early period of the day) and delayed TRF (which restricts food intake during the later period of the day) studies have shown that both TRF regimens improve metabolic health in terms of reducing energy intake, decreasing body weight, improving insulin sensitivity, reducing blood pressure, and reducing oxidative stress. Differences between the consequences of early and delayed TRF were found, including differences in changes in blood lipid factors. These preliminary findings may help to provide guidance for choosing suitable eating windows during TRF. Future studies with rigorous designs and direct comparisons between the effects of TRF regimens with different eating windows on metabolic health markers are still needed.

Randomized controlled trial for time-restricted eating in healthy volunteers without obesity.

Time-restricted feeding (TRF) improves metabolic health. Both early TRF (eTRF, food intake restricted to the early part of the day) and mid-day TRF (mTRF, food intake restricted to the middle of the day) have been shown to have metabolic benefits. However, the two regimens have yet to be thoroughly compared. We conducted a five-week randomized trial to compare the effects of the two TRF regimens in healthy individuals without obesity (ChiCTR2000029797). The trial has completed. Ninety participants were randomized to eTRF (n=30), mTRF (n=30), or control groups (n=30) using a computer-based random-number generator. Eighty-two participants completed the entire five-week trial and were analyzed (28 in eTRF, 26 in mTRF, 28 in control groups). The primary outcome was the change in insulin resistance. Researchers who assessed the outcomes were blinded to group assignment, but participants and care givers were not. Here we show that eTRF was more effective than mTRF at improving insulin sensitivity. Furthermore, eTRF, but not mTRF, improved fasting glucose, reduced total body mass and adiposity, ameliorated inflammation, and increased gut microbial diversity. No serious adverse events were reported during the trial. In conclusion, eTRF showed greater benefits for insulin resistance and related metabolic parameters compared with mTRF. Clinical Trial Registration URL: http://www.chictr.org.cn/showproj.aspx?proj=49406 .