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.

Background: Depressive symptoms (DS) can erode physical and mental health; social support (SS) is considered a buffer for DS and a promoter for improving coping and recovery abilities. However, there is almost no research on the mediating role of negative coping (NC) in SS and DS, especially among firefighters. Methods: A cross-sectional survey was conducted among firefighters in Chongqing, China, and the valid data of 407 firefighters were collected through questionnaires distributed on the WeChat platform in 2020. Statistical Product and Service Solutions (SPSS) 26.0 is used for descriptive statistics and correlation analysis. Structural equation modeling was adopted to analyze the association among SS, NC, and DS. The mediation effect is also evaluated. Results: Firefighters' detection rate of DS is 23.3%, and when they receive more SS were less likely to develop DS. NC was positively correlated with DS (β = 0.54, p < 0.001) after controlling for SS. Besides, the results of structural equation modeling showed that NC partially mediates the relationship between SS and DS (standard error = 0.039, indirect effects = 0.109, 95% confidence interval: 0.047–0.200 p < 0.001). Conclusion NC has a partial indirect effect between SS and DS among firefighters. SS could not only affect DS directly but also indirect work on it by affecting NC. This discovery will be a novel and meaningful part of the research on the firefighter population.

Objective:To determine the efficacy and safety of sacral neuromodulation (SNM) in incomplete spinal cord injured (SCI) subjects affected by neurogenic lower urinary tract symptoms.Methods:Clinical data of 36 patients with incomplete spinal cord injury who underwent SNM from February 2015 to April 2019 were retrospectively analyzed and were divided into group NUR (16 cases neurogenic urinary retention group) and group NOAB (20 cases of neurogenic bladder overactive group). If at least 50% clinical improvement occurred, the patient would undergo a permanent SNM procedure. The patients were evaluated by using bladder diary, postvoid residual volume measurement, frequency of clean catheterization and urodynamic parameters before and during the test, and after the permanent SNM.Results:Among the 36 patients, 21 cases (58.3%) were tested effectively and received permanent stimulator implantation, 7(19.4%) in NUR group and 14(38.9%) in NOAB group. The residual urine volume of bladder, the average number of catheterization and the average number of urination in NUR group were improved in different degrees. After operation, the symptoms of frequent urination, urgency of urination and incontinence in NOAB group were relieved to varying degrees. During the follow-up, 2 patients with urinary retention failed the treatment. After the Ⅰ phase of the contralateral S3, the curative effect was recovered. A patient were infected after operation, and the wound healed after removal of the infection.Conclusions:The SNM is safe and effective in the treatment of neurogenic lower urinary tract symptoms in some incomplete spinal cord injury patients, and is helpful to protect renal function in patients with spinal cord injury. SNM can not improve all symptoms at times, but the SNM can be considered in patients with ineffective or intolerant traditional treatment.

Santalene and santalol are the main components of valuable perfume sandalwood essential oil, and have good antibacterial, anti-oxidation and anti-tumor activities. Commercial sandalwood essential oil is mainly extracted from sandalwood tree that grows slowly and is difficult to cultivate. In addition, the extraction recovery of sandalwood essential oil from sandalwood tree is too low to meet the market demand. These factors make sandalwood essential oil expensive. An option is to use genetic engineering and molecular biological methods to heterologously express related synthase of santalene and santalol in microbial host. In this paper, the biosynthesis progress of santalene and santalol synthase, as well as the optimization of mevalonate metabolic pathways in the hosts are summarized. Furthermore, the strategies of applying protein engineering technology to carry out orthomutation of santalene synthase were also discussed, to provide reference for the optimal biosynthesis of santalene and santalol.

Objective To study the effect of electroencephalograph (EEG) bionic electrical stimulation at Wangu (GB12), Tianzhu (BL10), Neiguan (PC6) on cerebral blood flow and metabolism in patients with persistent vegetative state (PVS). Methods 60 patients with PVS were divided into observation group (n=30) and control group (n=30) according to the random number table. The control group received routine treatment, including basic management, hyperbaric oxygen therapy, awaking medicine, sensory stimulation, and so on; while the observation group received EEG bionic electrical stimulation at bilateral Tianzhu, Wangu (cheif electrodes) and Neiguan (auxiliary electrodes) in addition. They were treated for 30 days. They were assessed with the PVS score, and observed with transcranial Doppler ultrasound (TCD) and magnetic resonance spectroscopy (MRS) one day before and one day after treatment. Results The incidence of improvement was 86.67% in the observation group, more than 60.00% in the control group (P<0.05). The difference of blood flow velocity before and after treatment (ΔVm) of anterior-middle cerebral artery was more in the observation group than in the control group respectively (P< 0.001), as well as those of posterior cerebral-vertebral-basilar artery (P<0.01). The N-acetyl aspartic acid/creatine (NAA/Cr) increased more in the observation group than in the control group respectively (P<0.01), and the choline/creatine (Cho/Cr) decreased more (P<0.01), after treatment. Conclusion EEG bionic electrical stimulation can improve the cerebral circulation and metabolism in patients with PVS, which may associate with the wake promoting.

Objective To compare different Nrf2 expressions in glioblastoma cell lines and glioma stem cells (GSCs) from xenografts and to study the concentration of Nrf2 in nuclear. Methods GSCs were analyzed by immunofluorescence and different expressions of Nrf2 in glioblastoma cell lines and GSCs from xenografts were detected with real-time RCR and Western. Results GSCs were successfully isolated from xenografts of U251 and U87 cell lines. The percentage of tumor stem cells in total cells was 1.24%, and that was 1.63% in xenografts. Immunofluorescence indicated that Nrf2 was overexpressed in GSCs as compared with that in glioblastoma cell lines. Conclusion Nrf2 may be a potential biomarker and rational therapeutic target for GSCs.

Objective To develop a LC-MS/MS method for the determination of inosine in human plasma and to apply it in the isoprinosine pharmacokinetic researches .Methods With adefovir as the internal standard ,methanol -10 mmol/L ammonium ace-tate(15 :85 ,v/v) was adopted as the mobile phase .The chromatographic column was the Agilent SB-C18 column(5 μm ,150 mm × 4 .6 mm I .D .) .Electrospray ionization(ESI) source was applied and the detection was conducted by the multiple-reaction monito-ring(MRM) mode .The ion reactions for the quantitative analysis were m/z 135 .0-267 .3(inosine) and m/z 134 .1-272 .0(adefo-vir) .Results The linear range of plasma inosine was 10-3 000 ng/mL .The lower detection limit was 10 ng/mL .The inter-and in-tra-day precisions(RSD) were less than 5% .The average recovery rate was above 90% without the matrix effect .Conclusion This method has the strong specificity ,convenience in treating the sample and high sensitivity ,and is suitable for the inosine pharmacokinetic re-searches .

Objective:To establish a method for the determination of asperosaponinⅥin Dieda Cuyu tablets by HPLC. Methods:A Hypersil C18(250 mm ×4.6 mm,5 μm)column was used. The mobile phase was acetonitrile-water(30∶70) with a flow rate of 1.0 ml·min-1 . The detection wavelength was 212 nm, the column temperature was room temperature,and the injection volume was 10μl. Results:AsperosaponinⅥ showed a good linear relationship within the range of 0. 04-0. 32 μg(r=0. 999 6). The average recovery was 97. 84%(RSD=1. 70%, n=6). Conclusion:The method is simple,accurate and reproducible, which can be used in the deter-mination of asperosaponinⅥ in Dieda Cuyu tablets.

Objective To combine grey relation analysis and partial least squares regression model to establish the forecasting model of per-patient hospitalization expenses .Methods Gray relational analysis was used to filter out the main factors affecting per-patient hospitalization expenses ,and then collinearity was examined between these factors .Partial least squares regression was used to establish prediction model of per-patient hospitalization expenses ,and the prediction accuracy was proved .Results After filtered by gray relational analysis ,the order of the importance of factors affecting per-patient hospitalization expenses was the west-ern medicine fee ,traditional Chinese medicine fees ,diagnosis and treat fees ,other fees ,inspection fees ,bed fees and operation fees . The established partial least squares regression model had a higher accuracy on fitting and prediction ,with low average relative er-ror ,respectively ,-0 .000 2% and 0 .349 3% .Conclusion The gray relational analysis and partial least squares regression are suit-able for the influencing factors and prediction analysis of hospitalization costs .It provides a reference for data with the small sample size and high collinearity between the variables .

OBJECTIVETo isolate and characterize endophytic fungi from seven Dendrobium species, and detect their antimicrobial activities.

METHODFungal endophytes were isolated by strictly sterile sample preparation and fungal identification methods were based on their ITS ribosomal DNA (ITS rDNA gene) sequences. The agar well diffusion method was then employed to evaluate the antimicrobial activity against six pathogenic organisms and the phylogenetic tree of active isolates was constructed by the MEGA.

RESULTNinety-eight endophytic fungi obtained from seven Dendrobium spp., and among them twenty-four isolates, representing 11 genera and 14 species, displayed anti-microbial activities. The phylogenetic assay based on ITS-rDNA showed that 24 active isolates were sorted to 7 taxonomic orders: Hypocreales, Sordariales, Capnodiales, Eurotiales, Botryosphaeriales, Xylariales and Mucorales. The results of antimicrobial activity assay revealed that 1.02%, 10.2%, 18.4%, 1.02%, 1.02% and 10.2% of fermentation broths of 98 isolates displayed significant antimicrobial activities against E. coli, B. subtilis, S. aureus, C. albicans, C. neoformans and A. fumigatus, respectively. Four strains DL-R-3, DL-S-6, DG-R-10 and DN-S-1 displayed strong and broad antimicrobial spectrum.

CONCLUSIONEndophytic fungi associated with Dendrobium species have fungal diversity, and possess diverse antimicrobial activity.

Anti-Infective Agents ; metabolism ; pharmacology ; Aspergillus fumigatus ; drug effects ; Bacillus subtilis ; drug effects ; Base Sequence ; Biodiversity ; Candida albicans ; drug effects ; China ; Cryptococcus neoformans ; drug effects ; DNA, Fungal ; chemistry ; isolation & purification ; DNA, Ribosomal Spacer ; chemistry ; genetics ; Dendrobium ; microbiology ; physiology ; Endophytes ; classification ; genetics ; isolation & purification ; physiology ; Escherichia coli ; drug effects ; Fungi ; classification ; genetics ; isolation & purification ; physiology ; Microbial Sensitivity Tests ; Molecular Sequence Data ; Phylogeny ; Plant Roots ; microbiology ; physiology ; Plant Stems ; microbiology ; physiology ; Sequence Alignment ; Sequence Analysis, DNA ; Staphylococcus aureus ; drug effects