ABSTRACT
BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.
ABSTRACT
BACKGROUND: Femoral intertrochanteric fractures (ITF) occur frequently in the elderly, accounting for 45% of all hip fractures. Postoperative anemia after fracture tends to cause ischemia, hypoxia in cells, tissues and organs, increasing the rate of blood transfusion, risk of infection, disability and mortality. Meanwhile, traditional Chinese medicine is widely used in the treatment of anemia for activating blood circulation and removing blood stasis. METHODS: This study is a prospective, outcome assessor-, and data analyst-blinded randomized controlled clinical trial. The objective of this proposed study was to investigate whether Shengyu Decoction could improve the symptoms of anemia after proximal femoral nail antirotation in elderly ITF patients. After qualifying for screening, patients will be randomized into 2 groups with an allocation ratio of 1:1. Hemoglobin concentration, HBL, and HHS score are outcome measurements. The other outcomes also included time to get out of bed, discharge to home, 30-day readmission rates, and mortality. DISCUSSION: ITF is commonly occurring in senior citizens, and those who are senior in age generally suffer 1 or more basic diseases, whose nutritional status is already poor. Trauma and surgical stimulation not only aggravate the existing disease or induce corresponding cardiovascular complications, but also worsen the nutritional status, which can easily cause postoperative anemia in patients. Because of the limited clinical modalities available for the treatment of postoperative anemia after fracture surgery, and most of them have various side effects that are not easily tolerated by the elderly. Therefore, from a traditional Chinese medicine perspective, we proposed a protocol using mild Chinese herbal decoction to treat postoperative anemia in ITF.Registration number: OSF Registration number: DOI 10.17605/OSF.IO/JQ6ZF.