Dachengqi Decoction

To explore the therapeutic effect and mechanism of Dachengqi decoction on patients with mild acute pancreatitis (MAP).

A parallel randomized controlled trial was conducted. Sixty-eight patients with acute pancreatitis (AP) admitted to Shanghai Traditional Chinese Medicine (TCM)-Integrated Hospital from March 2018 to February 2021 were enrolled. Referring to the condition on admission of the patients and whether they agreed to receive the Dachengqi decoction or not, they were divided into conventional treatment group and Dachengqi decoction group according to the principle of 1:1 equal randomness. Meanwhile, 20 healthy volunteers were recruited as controls. Both groups of patients were treated with octreotide, fasting, gastrointestinal decompression, antipyretic and analgesic, anti-inflammatory, inhibition of gastric acid and pancreatic juice secretion, maintenance of electrolyte balance and other western conventional medicine. The patients in the Dachengqi decoction group received Dachengqi decoction orally on the basis of routine treatment, 100 mL each time, twice a day, for seven consecutive days. The inflammation parameters [white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6)] before and after treatment and the recovery time of gastrointestinal function (first exhaust time, time to recover bowel sounds, first defecation time) of patients were recorded. 16S rRNA gene sequencing of stool samples was recorded, and normalized data were obtained after quality control and other related processing. The data were subjected to diversity analysis (Alpha diversity and Beta diversity) and linear discriminant analysis effect size analysis (LEfSe analysis) to observe changes in the gut microbiota of MAP patients. Spearman rank correlation coefficient was used to analyze the correlation between inflammatory indexes and microorganisms at the intestinal genus level. Blood, urine, stool samples, renal function, and electrocardiogram (ECG) during treatment of MAP patients were detected to assess the safety of the treatment.

Of the 68 patients with AP, 16 were excluded from moderate-severe AP, 4 were not collected or voluntarily abandoned treatment. Finally, 48 patients with MAP were enrolled, 24 in the conventional treatment group and 24 in the Dachengqi decoction group. The inflammation parameters levels at 7 days of treatment in both groups were significantly lower than those before treatment. CRP, PCT and IL-6 levels in the Dachengqi decoction group were significantly lower than those in the conventional treatment group [CRP (mg/L): 8.50 (3.50, 13.00) vs. 16.00 (9.25, 29.75), PCT (μg/L): 0.06 (0.03, 0.08) vs. 0.09 (0.05, 0.11), IL-6 (ng/L): 6.36 (3.96, 10.79) vs. 13.24 (6.69, 18.87), all P < 0.05]. The first exhaust time, time to recover bowel sounds and first defecation time in the Dachengqi decoction group were significantly shorter than those in the conventional treatment group [first exhaust time (days): 1.62±0.65 vs. 2.80±0.65, time to recover bowel sounds (days): 1.13±0.58 vs. 2.31±0.76, first defecation time (days): 3.12±0.75 vs. 4.39±0.76, all P < 0.05]. The analysis of intestinal microflora diversity showed that both the diversity and abundance of microbial communities were the highest in the healthy control group and the lowest in the conventional treatment group. In addition, the coincidence degree of microbial communities in healthy controls and MAP patients was small, while the coincidence degree of MAP patients among different treatment methods was relatively large. LEfSe analysis showed that Dachengqi decoction reduced the relative abundance of Escherichia coli-Shigella and Clostridium erysipelae, and increased the relative abundance of three beneficial bacteria, namely Lactobacillus, Rombutzia and Brutella. In the intestines of MAP patients, Lactobacillus mucilaginus and Lactobacillus conjunctus were significantly enriched. Correlation analysis showed that positive correlations between Escherichia coli-Shigella and the four inflammatory indicators including WBC, CRP, PCT, IL-6 were statistically significant (r value was 0.31, 0.41, 0.57, 0.43, respectively, all P < 0.05). There was no significant correlation between other bacteria and inflammatory indicators. During the treatment, there was no obvious abnormality in blood, urine and feces, renal function and ECG of MAP patients.

Dachengqi decoction could reduce inflammatory responses and promote recovery of intestinal microecological balance and gastrointestinal function in patients with MAP by regulating the composition of intestinal flora. No significant adverse effects were observed during the treatment period.

Intestinal dysfunction is not conducive to the recovery of patients after surgery. It is particularly important to restore the intestinal function as soon as possible. In recent years, ultrasonic drug penetration therapy as a new type of non-invasive therapy has been used to solve this problem, but its efficacy has not been confirmed.

Single-centre, parallel, randomized controlled clinical trial in China that included 184 patients undergoing laparoscopic gastrointestinal surgery. Ninety-one participants were randomly assigned to low-frequency ultrasound and electric pulses for transdermal drug delivery with Dachengqi Decoction (DCQD) (intervention group), and 90 were assigned to the control group after laparoscopic gastrointestinal surgery. The primary outcome was time to first flatus after surgery (by patient's subjective feeling). Secondary outcomes assessed the recovery time of bowel movement, time of the first defecation, postoperative gastrointestinal complications (e.g., nausea, vomit, and bloating), days of hospitalization and treatment costs.

Of 184 patients, 181 (98.4%) completed the trial. The sociodemographic characteristics and efficiency data were comparable in the two groups at baseline. The intervention group had a shorter mean time of bowel movement recovery than the control group [29.4 h (IQR, 22.0-35.0 h) vs. 33.7 h (IQR, 24.0-40.0 h; P=0.005)] and a shorter mean time to first flatus after surgery [35.8 h (IQR, 23.1-46.6 h) vs. 46.7 h (IQR, 25.9-61.3 h; P=0.012)]. Postoperative gastrointestinal reactions (e.g., nausea, vomit, and bloating) occurred in 28.6% in the intervention group and 43.3% in the control group (P=0.038). Two patients in the intervention group had electrical tingling sensations, and one patient had a skin rash during the treatment. There were no significant differences in the occurrence rates of AEs or SAE, days of hospitalization and treatment costs between the two groups.

Low-frequency ultrasound and electric pulses for transdermal drug delivery with DCQD can shorten the time of bowel movement recovery and accelerate first anal exhaust after laparoscopic gastrointestinal surgery.

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