High-dose vitamin C improves norepinephrine level in patients with septic shock: A single-center, prospective, randomized controlled trial.

BACKGROUND: The effects of vitamin C supplementation on patients with septic shock remain controversial. We aimed to evaluate the effects of different vitamin C dosages on norepinephrine (NE) synthesis in adult patients with septic shock. METHODS: A total of 58 patients with septic shock admitted to our intensive care unit (ICU) between July 2021 and December 2022 were included. Patients were randomly divided into 3 groups: high-dose vitamin C (150 mg/kg/d, group A), low-dose vitamin C (50 mg/kg/d, group B), and placebo (group C). NE synthesis-related indicators (dopamine-ß-hydroxylase [DßH], tyrosine hydroxylase [TH], tetrahydrobiopterin [BH4], and dopamine [DA]), plasma NE, and vitamin C levels were measured every 24 hours and analyzed. All-cause mortality within 28 days and other clinical outcomes (including Acute Physiology and Chronic Health Evaluation [APACHE], Sequential Organ Failure Assessment [SOFA], and Multiple-Organ Dysfunction Syndrome [MODS] scores) were compared. RESULTS: Changes in TH, BH4, and DßH levels at 96 hours in groups A and B were greater than those in group C. These differences became more pronounced over the course of the intravenous vitamin C administration. Significant differences between groups A and C were detected at 96-hours TH, 72-hours BH4, 96-hours BH4, 96-hours DA, and DßH levels every 24 hours. The 96-hours TH, 96-hours BH4, and 48-hours DßH in group B were significantly higher than those in group C. The NE levels every 24 hours in groups A and B were higher than those in group C, group A and group C had a statistically significant difference. The 96-hours exogenous NE dosage in groups A and B was significantly lower than that in group C. No significant reductions in APACHE, SOFA, or MODS scores were observed in the vitamin C group, including the duration of ICU stay and mechanical ventilation. The 28-days mortality was lower in groups A and B than in group C (0%, 10%, and 16.67%, P = .187), but the difference was not significant. CONCLUSION: For patients with septic shock, treatment with vitamin C significantly increased TH, BH4, and DßH levels and reduced the exogenous NE dosage, but did not significantly improve clinical outcomes.

Fucoxanthin inhibits gastric cancer lymphangiogenesis and metastasis by regulating Ran expression.

BACKGROUND: Lymph node metastasis is a key mechanism in gastric cancer (GC) metastasis and lymphangiogenesis is a vital step in the process of lymph node metastasis. Currently, there are no drugs which can treat lymph node metastasis in GC. Previous studies using the drug fucoxanthin have mainly focused on cell cycle arrest, induction of apoptosis, or inhibition of angiogenesis in GC. However, the effects of fucoxanthin on lymphangiogenesis and metastasis in GC have not been studied. METHODS: Cell counting kit 8 and transwell experiments were used to evaluate the inhibitory effect of fucoxanthin on cell proliferation, migration and invasion. HGC-27 and HLEC cells were co-cultured in a transwell chamber and the footpad metastasis model was established to evaluate lymphangiogenesis and lymph node metastasis. The possible regulatory targets of fucoxanthin in GC were analyzed using human tissue microarrays, bioinformatics analysis, and molecular docking. The regulatory pathway of fucoxanthin was verified using confocal laser microscopy, adenovirus transfection and western blotting. RESULTS: Tissue microarray and bioinformatics analyses showed that Ran was highly expressed in metastatic lymph nodes and has some predictive value for metastasis in GC. Molecular docking results revealed that fucoxanthin interacted with Met189 and Lys167 of Ran via hydrogen bonds. Mechanistically, fucoxanthin inhibits the nuclear transport of NF-κB by downregulating protein expression of Ran and importinß, thereby inhibiting VEGF-C secretion, and ultimately inhibiting tumor lymphangiogenesis and lymph node metastasis in vivo and in vitro. CONCLUSIONS: Fucoxanthin suppressed GC-induced lymphangiogenesis and metastasis in vitro and in vivo by regulating Ran expression via the importinß/NF-κB/VEGF-C nuclear transport signaling pathway. These novel findings provide the basis for the research and development of novel treatments using traditional Chinese medicine in treatment of lymph node metastasis, which has important theoretical significance and clinical value.

XueBiJing Injection Versus Placebo for Critically Ill Patients With Severe Community-Acquired Pneumonia: A Randomized Controlled Trial.

OBJECTIVES: To investigate whether XueBiJing injection improves clinical outcomes in critically ill patients with severe community-acquired pneumonia. DESIGN: Prospective, randomized, controlled study. SETTING: Thirty-three hospitals in China. PATIENTS: A total of 710 adults 18-75 years old with severe community-acquired pneumonia. INTERVENTIONS: Participants in the XueBiJing group received XueBiJing, 100 mL, q12 hours, and the control group received a visually indistinguishable placebo. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 8-day improvement in the pneumonia severity index risk rating. Secondary outcomes were 28-day mortality rate, duration of mechanical ventilation and total duration of ICU stay. Improvement in the pneumonia severity index risk rating, from a previously defined endpoint, occurred in 203 (60.78%) participants receiving XueBiJing and in 158 (46.33%) participants receiving placebo (between-group difference [95% CI], 14.4% [6.9-21.8%]; p < 0.001). Fifty-three (15.87%) XueBiJing recipients and 84 (24.63%) placebo recipients (8.8% [2.4-15.2%]; p = 0.006) died within 28 days. XueBiJing administration also decreased the mechanical ventilation time and the total ICU stay duration. The median mechanical ventilation time was 11.0 versus 16.5 days for the XueBiJing and placebo groups, respectively (p = 0.012). The total duration of ICU stay was 12 days for XueBiJing recipients versus 16 days for placebo recipients (p = 0.004). A total of 256 patients experienced adverse events (119 [35.63%] vs 137 [40.18%] in the XueBiJing and placebo groups, respectively [p = 0.235]). CONCLUSIONS: In critically ill patients with severe community-acquired pneumonia, XueBiJing injection led to a statistically significant improvement in the primary endpoint of the pneumonia severity index as well a significant improvement in the secondary clinical outcomes of mortality, duration of mechanical ventilation and duration of ICU stay.