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.

Objective To establish a high performance liquid chromatographic(HPLC)method for the determination of chidamide in human plasma.Methods The plasma sample was taken as 500 μL,and triamcinolone was used as the internal standard.After liquid-liquid extraction using methyl tert-butyl ether,the supernatant was centrifuged and blown dry under N2,then re-dissolved in 50 μL of water,and then centrifuged again,and then 10 μL of the supernatant was injected into the system.The separation was performed on a Shim-pack CLC-ODS(150 mm×60 mm,5 μm)at 35 ℃ using water-acetonitrile=(74∶26,v/v,adjusted to pH=3 by acetic acid)as mobile phase.The flow rate was 1.0 mL·min-1 and the wavelength was 260 nm.The specificity,standard curve,lower limit of quantitation,precision,recovery and stability of the method were investigated.In addition,the high performance liquid chromatography method described above was applied to determine the plasma drug concentration after oral administration of chidamide in one patient.Results The retention time of chidamide and internal standard was 8.00 and 9.40 min,respectively.The standard curve equation was y=10.28x-0.06(r=0.998).The intra-day and inter-day precision(RSD)of low,medium and high concentration quality control samples(0.02,0.15,0.75 μg·mL-)were 1.00％-4.87％(n=6),and the accuracy was-10.29％-3.37％.The average extraction recovery was 61.74％-69.85％.Conclusion The method was simple,sensitive and accurate,suitable for monitoring the concentrations of chidamide in human plasma.

Objective To establish a high performance liquid chromatographic(HPLC)method for the determination of chidamide in human plasma.Methods The plasma sample was taken as 500 μL,and triamcinolone was used as the internal standard.After liquid-liquid extraction using methyl tert-butyl ether,the supernatant was centrifuged and blown dry under N2,then re-dissolved in 50 μL of water,and then centrifuged again,and then 10 μL of the supernatant was injected into the system.The separation was performed on a Shim-pack CLC-ODS(150 mm×60 mm,5 μm)at 35 ℃ using water-acetonitrile=(74∶26,v/v,adjusted to pH=3 by acetic acid)as mobile phase.The flow rate was 1.0 mL·min-1 and the wavelength was 260 nm.The specificity,standard curve,lower limit of quantitation,precision,recovery and stability of the method were investigated.In addition,the high performance liquid chromatography method described above was applied to determine the plasma drug concentration after oral administration of chidamide in one patient.Results The retention time of chidamide and internal standard was 8.00 and 9.40 min,respectively.The standard curve equation was y=10.28x-0.06(r=0.998).The intra-day and inter-day precision(RSD)of low,medium and high concentration quality control samples(0.02,0.15,0.75 μg·mL-)were 1.00％-4.87％(n=6),and the accuracy was-10.29％-3.37％.The average extraction recovery was 61.74％-69.85％.Conclusion The method was simple,sensitive and accurate,suitable for monitoring the concentrations of chidamide in human plasma.

OBJECTIVE: To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability. METHODS: Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24⁺), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO₁₅), Gan (CO₁₂) and Shen (CO₁₀). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups. RESULTS: After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05). CONCLUSION Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.
Humans ; Depression ; Quarantine ; Serotonin ; Sleep Initiation and Maintenance Disorders ; COVID-19 ; Acupuncture Therapy ; Comorbidity

Child ; Humans ; Chromosomes, Human, Pair 16 ; Leukemia, Myeloid, Acute ; Neoplasms, Multiple Primary/genetics* ; Oncogene Proteins, Fusion/genetics* ; RNA-Binding Protein FUS/genetics* ; Sarcoma, Myeloid/genetics* ; Transcriptional Regulator ERG/genetics* ; Translocation, Genetic

In recent years, researchers, pharmaceutical companies, and political makers gradually using more real-world data (RWD) to produce real-world evidence (RWE) for policy-making. A research team of Harvard University launched the RCT DUPLICATE project in 2018, aiming to replicate 30 randomized controlled trials using the medical claims database in order to explore methods for quantifying the efficacy-effectiveness gap and explain its potential sources, to enhance the credibility of the RWE. This paper reviews the background of RCT DUPLICATE Initiative, highlights the research purposes, research design and implementation process of the RCT DUPLICATE Initiative, to help domestic scholars better understand the scope and application value of RWE.
Humans ; Randomized Controlled Trials as Topic ; Cognition ; Databases, Factual ; Research Personnel ; Universities