1.Bacteroi des fragilis-derived succinic acid promotes the degradation of uric acid by inhibiting hepatic AMPD2: Insight into how plant-based berberine ameliorates hyperuricemia.
Libin PAN ; Ru FENG ; Jiachun HU ; Hang YU ; Qian TONG ; Xinyu YANG ; Jianye SONG ; Hui XU ; Mengliang YE ; Zhengwei ZHANG ; Jie FU ; Haojian ZHANG ; Jinyue LU ; Zhao ZHAI ; Jingyue WANG ; Yi ZHAO ; Hengtong ZUO ; Xiang HUI ; Jiandong JIANG ; Yan WANG
Acta Pharmaceutica Sinica B 2025;15(10):5244-5260
In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.
2.The comparison between endoscopic and surgical treatment of delayed iatrogenic bile duct injury by propensity score matching
Hengtong HAN ; Ping YUE ; Wenbo MENG ; Lei ZHANG ; Kexiang ZHU ; Xiaoliang ZHU ; Long MIAO ; Zhengfeng WANG ; Haiping WANG ; Xun LI
Chinese Journal of Surgery 2023;61(10):871-879
Objective:To compare the safety and clinical efficacy of endoscopic and surgical treatment of patients with delayed iatrogenic bile duct injury (DBDI) with severity (SG) grade 1 to 2.Methods:The clinical data of 129 patients with SG grade 1 to 2 DBDI who received endoscopic or surgical treatment in the First Hospital of Lanzhou University from November 2007 to November 2021 were retrospectively collected. There were 46 males and 83 females,aged ( M(IQR)) 54(22)years(range: 21 to 82 years). The baseline data of the two groups were matched 1∶1 by propensity score matching(caliper value was 0.2). Independent sample t test,rank sum test, χ2 test or Fisher exact probability test were used to analyze the data of the two matched groups. Results:There were 48 patients in each of the endoscopic treatment and surgical groups after matching,and there was no difference in general information between the two groups(both P>0.05). The bile duct injury-repair interval and intraoperative anesthesia complications were not statistically significant between the two groups after matching(all P>0.05). Compared with the surgical group, patients in the endoscopic treatment group had significantly shorter operative time(50 (30) minutes vs. 185 (100) minutes, Z=7.675, P<0.01) and postoperative hospital stay(5 (5) days vs. 12 (7) days, Z=5.848, P<0.01).For safety,there was no statistical difference in the incidence of immediate postoperative complications between the two groups with Clavien-Dindo classification of surgical complications<Ⅲ;the incidence of serious postoperative complications (Clavien-Dindo classification of surgical complications≥Ⅲ) was significantly higher in the surgical group than in the endoscopic treatment group( P=0.012). The incidence of long-term postoperative complications was not statistically different between the two groups(28.1% vs. 20.7%, P=0.562). In terms of efficacy,the postoperative liver function indexes of patients in both groups improved significantly compared with the preoperative period and returned to normal or near normal levels; the postoperative infection indexes of both groups showed an increasing trend,but were within the normal range. Of the 96 patients in both groups,61 obtained follow-up,and the follow-up time was (89.4±48.0)months(range: 3 to 165 months),and there was no statistical difference between the two groups( P=0.079). The probability of excellent long-term follow-up (78.1% vs. 86.2%) was not statistically different between the two groups( P=0.412).In patients with Strasberg-Bismuth type E1,the probability of excellent long-term follow-up was higher in the endoscopic treatment group compared with the surgical group(13/14 vs. 2/5, P=0.037). Conclusions:For DBDI patients with SG grade 1 to 2 and bile duct continuity,endoscopy can be used as the first deterministic treatment. The advantages of endoscopic therapy compared to surgery are the lower incidence of postoperative serious complications,and the shorter duration of surgery and postoperative hospital stay.
3.The comparison between endoscopic and surgical treatment of delayed iatrogenic bile duct injury by propensity score matching
Hengtong HAN ; Ping YUE ; Wenbo MENG ; Lei ZHANG ; Kexiang ZHU ; Xiaoliang ZHU ; Long MIAO ; Zhengfeng WANG ; Haiping WANG ; Xun LI
Chinese Journal of Surgery 2023;61(10):871-879
Objective:To compare the safety and clinical efficacy of endoscopic and surgical treatment of patients with delayed iatrogenic bile duct injury (DBDI) with severity (SG) grade 1 to 2.Methods:The clinical data of 129 patients with SG grade 1 to 2 DBDI who received endoscopic or surgical treatment in the First Hospital of Lanzhou University from November 2007 to November 2021 were retrospectively collected. There were 46 males and 83 females,aged ( M(IQR)) 54(22)years(range: 21 to 82 years). The baseline data of the two groups were matched 1∶1 by propensity score matching(caliper value was 0.2). Independent sample t test,rank sum test, χ2 test or Fisher exact probability test were used to analyze the data of the two matched groups. Results:There were 48 patients in each of the endoscopic treatment and surgical groups after matching,and there was no difference in general information between the two groups(both P>0.05). The bile duct injury-repair interval and intraoperative anesthesia complications were not statistically significant between the two groups after matching(all P>0.05). Compared with the surgical group, patients in the endoscopic treatment group had significantly shorter operative time(50 (30) minutes vs. 185 (100) minutes, Z=7.675, P<0.01) and postoperative hospital stay(5 (5) days vs. 12 (7) days, Z=5.848, P<0.01).For safety,there was no statistical difference in the incidence of immediate postoperative complications between the two groups with Clavien-Dindo classification of surgical complications<Ⅲ;the incidence of serious postoperative complications (Clavien-Dindo classification of surgical complications≥Ⅲ) was significantly higher in the surgical group than in the endoscopic treatment group( P=0.012). The incidence of long-term postoperative complications was not statistically different between the two groups(28.1% vs. 20.7%, P=0.562). In terms of efficacy,the postoperative liver function indexes of patients in both groups improved significantly compared with the preoperative period and returned to normal or near normal levels; the postoperative infection indexes of both groups showed an increasing trend,but were within the normal range. Of the 96 patients in both groups,61 obtained follow-up,and the follow-up time was (89.4±48.0)months(range: 3 to 165 months),and there was no statistical difference between the two groups( P=0.079). The probability of excellent long-term follow-up (78.1% vs. 86.2%) was not statistically different between the two groups( P=0.412).In patients with Strasberg-Bismuth type E1,the probability of excellent long-term follow-up was higher in the endoscopic treatment group compared with the surgical group(13/14 vs. 2/5, P=0.037). Conclusions:For DBDI patients with SG grade 1 to 2 and bile duct continuity,endoscopy can be used as the first deterministic treatment. The advantages of endoscopic therapy compared to surgery are the lower incidence of postoperative serious complications,and the shorter duration of surgery and postoperative hospital stay.
4.Serum diamine oxidase in gastrointestinal function and condition to evaluate the role of severe acute pancreatitis
Hengtong WANG ; Heping XIANG ; He LI ; Tianpeng WANG ; Changle ZHANG
Chinese Journal of Emergency Medicine 2014;23(12):1381-1384
Objective To study the change of serum diamine oxidase (DAO) level in patients with severely acute pancreatitis (SAP) in order to explore the role of DAO in assessing the severity of SAP and the magnitude of gastrointestinal dysfunction.Methods From January 2012 through December 2013,56 SAP patients with 33 male and 23 female and average age (45-± 14) years admitted within 3 days after onset were enrolled for this study.At admission,serum diamine oxidase (DAO) was detected,and APACHE Ⅱ score,computed tomography severity index (CTSI) score and Balthazar grading and gastrointestinal dysfunction score were calculated.And at the corresponding time,serum procalcitonin (PCT) was detected.The correlations between serum DAO level and 4 other markers were analyzed.Results The high level of serum DAO was found at admission in SAP patients correlating positively with serum PCT concentrations (r =0.516,P< 0.01),APACHE Ⅱ score (r =0.631,P< 0.01),CTIS score (r=0.640,P < 0.01),and the degree of gastrointestinal dysfunction (r =0.730,P < 0.01).Conclusions The role of serum DAO in assessing the severity of SAP and magnitude of gastrointestinal dysfunction in SAP patients is really valid.

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