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.

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut-kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine-p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut-kidney axis.

The progression of hyperuricemia disease is often accompanied by damage to renal function. However, there are few studies on hyperuricemia nephropathy, especially its association with intestinal flora. This study combines metabolomics and gut microbiota diversity analysis to explore metabolic changes using a rat model as well as the changes in intestinal flora composition. The results showed that amino acid metabolism was disturbed with serine, glutamate and glutamine being downregulated whilst glycine, hydroxyproline and alanine being upregulated. The combined glycine, serine and glutamate could predict hyperuricemia nephropathy with an area under the curve of 1.00. Imbalanced intestinal flora was also observed. , , , , and other conditional pathogens increased significantly in the model group, while and , the short-chain fatty acid producing bacteria, declined greatly. At phylum, family and genus levels, disordered nitrogen circulation in gut microbiota was detected. In the model group, the uric acid decomposition pathway was enhanced with reinforced urea liver-intestine circulation. The results implied that the intestinal flora play a vital role in the pathogenesis of hyperuricemia nephropathy. Hence, modulation of gut microbiota or targeting at metabolic enzymes, , urease, could assist the treatment and prevention of this disease.

Objective To explore the perioperative outcomes and safety of enhanced recovery after surgery (ERAS) in laparoscopic radical cystectomy (LRC).Methods We retrospectively evaluated outcome of 10 LRC patients on ERAS protocol from May 2017 to October 2017,and 39 LRC patients on conventional recovery after surgery(CRAS) protocol from July 2015 to November 2016.There were (60.9 ±11.4) years and (63.7 ± 12.1) years in ERAS group and CRAS group respectively(P =0.514);(25.5 ±2.7) kg/m2 and (24.4 ± 3.6) kg/m2 with body mass index (P =0.375).Both of the median of charlson comorbidity index (P =0.931) and American Society of Anesthesiologists score (P =0.254) were 2 There was no statistical significance between the two groups for type of urinary diversion and preoperative laboratory studies (P ＞ 0.05).Patients' perioperative outcomes,early (30-day) complications and postoperative readmission rate were compared.Results The ERAS group had less intraoperative crystalloid infusion [(950.0 ± 474.3) ml vs.(1 797.4 ± 448.1) ml,P ＜ 0.001],faster removed gastric tube (0 d vs.4 d,P ＜0.001),and shorter passing flatus time [(1.6 ± 0.8) d vs.(2.9 ± 1.4) d,P =0.006] than the CRAS group;however,no difference was found in terms of intraoperative colliod infusion [(1 110.0 ± 331.5)ml vs.(1 117.9 ± 397.9) ml,P =0.954].No patients from either group required conversion to open surgery.There was no significant difference between the two groups for operative time (P =0.311),estimated blood loss (P =0.073),drain days (P =0.681),postoperative hospital stay (P =0.509),overall blood transfusion (P =1.000),intensive care unit stay (P =1.000) and tumor characteristics (pathological stage,histology,nodes removed,positive nodes,lymph node-positive patients,positive surgical margins).The 30-day postoperative complications were documented in 5 (50％)and 23 (59％)patients in groups ERAS and CRAS (P =0.878),respectively.And the most common complication were minor complications (Clavien-Dindo grade 1 and 2) in both groups (100.0％ vs.86.9％,P =0.729).The 30-day readmission rate was 20.0％ (2 patients) in ERAS group and 10.3％ (4 patients) in CRAS group with no statistical significance(P =0.588).Conclusions Our ERAS protocol expedited bowel function recovery after RC and urinary diversion without increasing in 30-day complications compared with CRAS.The key of implement ERAS pathway is to explore and develop their own protocol conformed to their medical treatment enviroment.

Radiotherapy is a treatment for cancer with undesired by-effects. In order to develop a new radiation protective agent that could reduce the by-effects, we tried to express and purify human cryptochrome 1 (hCRY1). The coding sequence of hCRY1 was inserted into prokaryotic expression plasmid pET28a(+), and this protein was purified from Escherichia coli BL21(DE3) after IPTG induction, ultrasonication, inclusion body dissolution, gradient dialysis, nickel column purification and ultrafiltration. The yield of hCRY1 in 1 L E. coli culture (LB medium) was about 10-15 mg. The radiation protective efficiency of hCRY1 was monitored by detecting X-ray-induced H2A.X foci in HaCaT cells. The results of immunofluorescence show that hCRY1 significantly reduces X-ray stimulated DNA damage response. The apoptosis of HaCaT cell was also detected, and the repression of H2A.X foci formation was not due to hCRY1's cytotoxity. All these data suggest a potential application of recombinant hCRY1 as a protective agent for radiotherapy.
Cryptochromes ; biosynthesis ; Escherichia coli ; Humans ; Plasmids ; Radiation-Protective Agents ; Recombinant Proteins ; biosynthesis

Background Angle Kappa is the angle between the pupillary axis and visual axis,and it is a major consideration in corneal refractive surgery and strabismic surgery.Researches showed that age and refractive status affect angle Kappa value,and additionally,the measuring results of angle Kappa are associated with instruments.Objective This study was to investigate and weight the influences of axial length,anterior chamber depth and corneal curvature to angle Kappa.Methods A cross-sectional study was designed.Fifty health volunteers were included from Dec 2009 to Aug 2010,with the age of 18-38 years and average diopter of-1.0 D and best corrected visual acuity of 1.0.The horizontal and vertical angle Kappa was binocular measured with a testing machine designed by laboratory of School of Optometry & Ophthalmology Wenzhou Medical University.IOLMaster was employed to measure the ocular axial length,anterior chamber depth and corneal curvature radius.A multiple linear regression model was established to analyze the influences of axial length,anterior chamber depth and corneal curvature radius to angle Kappa.Results An efficacious regression equation was established as Y =15.554-0.587X1+0.724X2+ 0.232X3 with the independent variables as axial length(X1),anterior chamber depth (X2),corneal curvature (X3) and dependent variable as horizontal angle Kappa (Y) (R =0.788,R2 =0.621,P =0.000).Horizontal angle Kappa showed a negative correlation with axial length (b1 =-0.587,β1 =-1.002,P =0.000) and a positive correlation with anterior chamber depth (b2 =0.724,β32 =0.296,P =0.030).No significant correlation was found between corneal curvature radius and horizontal angle Kappa (b3 =-0.232,β3 =-0.068,P=0.338).A new regression equation was Y =14.235-0.622X1 + 0.824X2 after removed the corneal curvature variable (R =0.786,R2=0.618,P =0.000),with a negative correlation between horizontal angle Kappa and axial length (b1 =-0.622,β1 =-1.062,P＜0.05) or positive correlation between horizontal angle Kappa and the anterior chamber depth (b2 =0.824,β2 =0.337,P＜0.05).In addition,a multiple linear regression equation among 3 independent variables and dependent variable of vertical angle Kappa was Y =0.492-0.020X1 +0.038X2 +0.089X3 (R =0.436,R2 =0.191,P =0.000).However,no significant correlations were seen between vertical angle Kappa and axial length,anterior chamber depth or corneal curvature radius (all at P ＞ 0.05).Conclusions Ocular axial length and anterior chamber depth have an obvious influence to horizontal but not vertical angle Kappa.Axial length appears to have more influence to horizontal angle Kappa than anterior chamber depth.

Objective We conducted a survey on the awareness rate of stroke in Yangquan residents and analyzed factors affecting awareness to provide basic information for Yangquan residents to prevent and treat stroke in Shanxi.MethodsA questionnaire regarding awareness and basic knowledge of stroke was used in this study and applied to Yangquan residents.A cluster stratified sample of 7983 residents were questionnaired by cross-sectional method.Results7921 returned copies were valid.The awareness rate of stroke in 7921 selected Yangquan residents was 30.14％ (2387/7921). Upon the occurrence of stroke,the awareness rates of the way to see a doctor,the right department to look for medical care and test manners to diagnose the illness as stroke were relatively high in these investigated people,which were 74.03％ (5864/7921),78.17％ (6192/7921) and 84.04％ (6657/7921),respectively.However,the number of people who knew characteristic symptoms and complications of stoke,risk factors that cause stroke and how to treat stroke was 2021 (25.51％),841 ( 10.62％ ),and 902 ( 11.39％ ),respectively,which was relatively low. After multivariate analysis,the awareness rate of stroke in Yangquan residents was positively correlated with an education degree.ConclusionsYangquan residents know little about stroke.Therefore,it is necessary to increase the level of their knowledge regarding stroke by extended propaganda and encourage them to live a healthy life to be able to treat stoke in time and to reduce the possibility of stroke occurring.

Objective To investigate the prevalence of dyslipidemia in subjects with type 2 diabetes mellitus in Beijing urban communities.Methods Total 3316 subjects with type 2 diabetes (age 20-80 years) were recruited from 15 urban community health centers in Beijing using a multi-stage random sampling approach.Dyslipidemia was diagnosed according to Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults:2007 version.Results Among 3316 diabetic subjects (1329 malesand 1987 females),75.6％ (2506/3316) had dyslipidemia,the prevalence was 72.5％ (964/1329)in men and 77.6％ (1542/1987) in women.The prevalence of hypertriglyceridemia and hypercholesterolemia was 41.9％ (1388/3316) and 48.1％ (1595/3316),respectively.31.5％ (1043/3316) subjects had high levels of low-density lipoprotein cholesterol (LDL-C) and 21.2％ (703/3316) had low high-density lipoprotein cholesterol (HDL-C).Among all subjects with dyslipidemia only 22.9％ (575/2506) took hypolipid agents.The overall blood lipid control rates of triglyceride (TG),total cholesterol (TC),LDL-C and HDL-C in 1393 subjects with dyslipidemia history were 48.0％ (669/1393),17.4％ (242/1393),30.9％ (430/1393) and 75.8％ (1056/1393),respectively.Diabetics with dyslipidemia had higher body mass index,waist circumference,blood pressure,plasma glucose and hemoglobin A1c.The prevalence of dyslipidemia in the overweight and uncontrolled-glucose group were 79.0％ (1678/2125),78.9％ (1756/2227),respectively.Logistic regression analysis showed that gender,age,body mass index and hemoglobin A1c were associated with dyslipidemia.Conclusions The prevalence of dyslipidemia in diabetic subjects in Beijing urban communities is high and less than one quarter patients take hypolipid agents.Age,body mass index and hemoglobin A1c are the risk factors of dyslipidemia in type 2 diabetic patients.

Objective To investigate current status of use of oral hypoglycemic drugs and insulin among adult patients with type 2 diabetes mellitus (T2DM) in urban community of Beijing.Methods In total,3297 T2DM patients aged more than 20 years from 15 urban communities of Beijing were studied.Their body weight,height,fasting plasma glucose level and glycosylated hemoglobin Alc (HbAlc) were measured.A door-to-door questionnaire survey on use of oral hypoglycemic drugs and insulin was conducted for them.All the T2DM patients surveyed were divided into four groups based on their received intervention.Results ①Of 3279 T2DM patients,454 (13.8％) received lifestyle intervention,971 (29.5％) used only one oral hypoglycemic drug,1179 (35.7％) with combined oral hypoglycemic drugs,and 693(21.0％) with insulin.②There was significant difference in average HbAlc among the four groups of T2DM patients with lifestyle intervention,only one oral hypoglycemic drug,combined oral hypoglycemic drugs,and insulin,with HbAI c of (7.0 ± 1.9) ％,(7.1 ± 1.5) ％,(7.4 ± 1.5 ) ％,and (7.5 ± 1.5 ) ％for them,respectively ( F =15.1,P ＜ 0.01 ).Proportions of the T2DM patients with HbAlc equal to or higher than 7.0％ were 32.2％,39.4％,52.1％ and 59.5％ for the four groups,respectively ( x2 =117.7,P ＜ 0.01 ).③In the T2DM patients with lifestyle intervention,32.2％ (146/454) of them with HbA1 c equal to or higher than 7.0％ were untreated with any oral hypoglycemic drug.In those with only one oral hypoglycemic drug,39.4％ (383/971) of them with HbAlc equal to or higher than 7.0％ were not treated with combined oral hypoglycemic drugs and/or insulin.In those with combined oral hypoglycemic drugs,52.1％ (614/1079) of them with HbAlc equal to or higher than 7.0％ were not received combined insulin treatment.④ Fasting plasma glucose level,treatment strategies,postprandial 2-h blood glucose level and length of the illness were independent risk factors for HbAlc level equal to or higher than 7.0％,with odds ratio (OR) of 1.757,1.256,1.175 and 1.031,respectively.⑤ In 2843 T2DM patients with oral hypoglycemie drugs and/or insulin treatment,1494 (52.6％ ) received biguanides and 693 received (24.4％ )insulin,respectively.Conclusions More than half of adult patients with T2DM do not meet the target of glycemic control of HbAlc less than 7.0％ in urban communities of Beijing,due to not active use of oral hypoglycemic drugs,and not timely adoption of combined use of oral hypoglycemic drugs and insulin therapy.

Objective To study clinical characteristics of type 2 diabetic(T2D)patients with metabolic syndrome(MS)and its components in Beijing urban communities.Methods Totally,3295 T2D patients involved in a combined prospective diabetic management study from 15 urban communities in Beijing were classified as four groups, according to 2004 Chinese Diabetes Society's definition of MS, i. e, isolated T2D, T2D with one component of MS, T2D with two components of MS and T2D with three components of MS. Their clinical characteristics were analyzed. Results ( 1 ) Among 3295 T2D patients, 155 (4. 7% )were isolated T2D, 107 (32.6%) T2D with one component of MS, 1386 (42.1%) T2D with two components of MS and 679 (20.6%) T2D with three components of MS, with an overall 62.7% (2065/3295) of T2D patients complicated with MS. (2) In these T2D patients, the more components of MS they had, the higher body mass index (BMI), waist circumference, waist to hip circumference ratio (WHR),systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting serum levels of insulin and triglyceride (TG) and the lower level of high-density lipoprotein-cholesterol (HDL) were presented (P <0. 01 ). (3) Percentage of isolated T2D in women increased from 49. 0% (76/155) to 61.9% (420/679)of those with three components of MS ( P < 0 01 ), with increasing of components of MS. (4) Multiple logistic regression analysis showed that BMI, history of hypertension, decreased HDL, increased TG,increased blood pressure, all were risk factors for T2D patients complicated with MS. Conclusions Among T2D patients in urban communities of Beijing, 95.3% (3140/3295) of them complicated with one or more components of MS, and 61.9% (420/679) of them complicated with MS. So, community diabetic management must be implemented in an all-round way, including control of blood pressure, blood lipids,body weight and so on, in addition to control of blood sugar.