24-Hour Urinary Sodium Excretion Association with Cardiovascular Events:A Systematic Review and Dose-Response Meta-Analysis

Objective The relationship between sodium intake and cardiovascular(CV)events remains unconfirmed.Therefore,we carried out a systematic review and dose-response meta-analysis for evaluating the potential impact of 24-hour sodium excretion on CV risk.Besides,24-hour sodium excretion was used to replace daily sodium diet intake.Methods We searched ISI Web of Science,Embase,Pub Med,and the Cochrane Library.Our study included cohort studies reporting hazard ratio(HR).The random-effects model was used for summarizing the total relative risks(RRs)between the included studies.In addition,the generalized least-squares regression was employed to fit the study model.Results A total of 9 studies involving 645,006 participants were included in this study.A significant non-linear relationship was observed between sodium excretion and CV events(P^(non-linearity)<0.001).In studies collecting 24-h urine samples,the sodium excretion and CV events risk were associated linearly(RR:1.04;95%CI:1.01,1.07).Conclusion In a linear dose-response manner,every 1 g increase in sodium intake was associated with an increased risk of CV events up to 4%.Further studies are required to validate our conclusions further.

Association of a Tobacco-specific Nitrosamine Carcinogen with Urinary Cotinine,Urinary Sodium Excretion,and Total Energy Intake in Adolescents and Children

This study investigated the association of a tobacco-specific nitrosamine carcinogen,4-(methylnitrosamino)-1-(3-pyridy1)-I-butanol(NNAL)with urinary cotinine(uCot),urinary sodium(uNa)excretion,systolic blood pressure(sBP),and total energy intake in adolescents and children in relation to the subjects'age.A total of 790 subjects aged 6-19 years were evaluated.NNAL,uCot,corrected NNAL(cNNAL),the NNAL/uCot ratio,uNa,sBP,and nutrient intake were measured.A strong association between uCot and cNNAL was observed in children who were 11 years of age(r=0.881,P<0.001);however,no significant association was noted in adolescents who were 19 years of age.The uNa level was significantly higher(133.9 mmol/L vs.107.8 mmol/L,P<0.001)and sBP was significantly lower(105.3 mmHg vs.110.6 mmHg,P=0.012)in adolescents with elevated NNAL than in those without elevated NNAL.NNAL was significantly higher in subjects with increased uNa excretion than in those without increased uNa excretion.NNAL was positively correlated with uNa(r=0.183,P<0.001)and negatively correlated with sBP(r=0.142,P<0.001).Non-smokers with elevated NNAL/uCot ratios had significantly lower total energy intake than those without elevated NNAL/uCot ratios(1729.0 kcal/day vs.1911.0 kcal/day,P=0.008).The relationship between NNAL and uCot varied according to the subjects'age.NNAL seems to play a role in decreasing sBP by enhancing uNa excretion.Insufficient nutrient intake may contribute to endogenous formation of NNAL in non-smoking adolescents and children.

Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours

AIM: To study histidine decarboxylase(HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. METHODS: Control tissues from fundus(n = 3) and corpus(n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours(GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2(VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid(U-Me Im AA) was determined using highperformance liquid chromatography in 27 of the 64 patients.RESULTS: In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cellpopulation co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-Me Im AA excretion was detected, but only two of the patients exhibited related endocrine symptoms. CONCLUSION: Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Coexpression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.

Fractional excretion of sodium in hepatorenal syndrome:Clinical and pathological correlation

AIMTo determine the accuracy of fractional excretion of sodium (FeNa) in the diagnosis of hepatorenal syndrome (HRS). METHODSEighty-eight liver transplantation candidates with renal dysfunction and/or proteinuria were included in the study sample. The baseline characteristics of the patients were obtained. All the 88 patients underwent iothalamate glomerular filtration rate testing, 24-h urine collection for urinary sodium and protein excretions, random urine for sodium and creatinine testing, and percutaneous kidney biopsy. FeNa was calculated using the equation [(urine sodium &times; serum creatinine)/(serum sodium &times; urine creatinine)] &times; 100%. Diuretic use was recorded among the participants. Patients on renal replacement therapy were not included in the original sample. RESULTSSeventy-seven (87%) of the 88 patients had FeNa P = 0.4). FeNa P = 0.47). Calculated positive predictive value and negative predictive value for FeNa P = 0.41). CONCLUSIONFeNa 1%.

Cosinor-rhythmometry for 24-h urinary sodium,potassium,creatinine excretion in the Chinese adult population

Background:The low accuracy of equations predicting 24-h urinary sodium excretion using a single spot urine sample contributed to the misclassification of individual sodium intake levels.The application of single spot urine sample is limited by a lack of representativity of urinary sodium excretion,possibly due to the circadian rhythm in urinary excretion.This study aimed to explore the circadian rhythm,characteristics,and parameters in a healthy young adult Chinese population as a theoretical foundation for developing new approaches.Methods:Eighty-five participants(mean age 32.4 years)completed the 24-h urine ollction by sccessively cllecing each of the single-voided specimens within 24 h.The concentrations of the urinary sodium,potassium,and creatinine for cach voided specimen were measured.Cosinor analysis was applied to explore the circadian rhythm of the urinary sodium,potassium,and creatinine excretion.The excretion per hour was computed for analyzing the change over time with repeated-measures analysis of variance and a cubic spline model.Results:The metabolism of urinary sodium,potassium,and creatinine showed different patterns of circadian rhythm,although the urinary sodiurm excretion showed non-significant parameters in the cosinor model.A significant circadian rhythm of urinary creatinine excretion was observed,while the circadian rhythm of sodium was less significant than that of potassium.The circadian rhythm of urinary sodium and creatinine excretion showed synchronization to some extent,which had a nocturnal peak and fell to the lowest around noon to afternoon.In contrast,the peak of potassium was observed in the morning and dropped to the lowest point in the evening.The hourly urinary excretion followed a similar circadian rhythm.Conclusion:It is necessary to consider the circadian rhythm of urinary sodium,potassium,and creatinine excretion in adults while exploring the estimation model for 24-h urinary sodium excretion using spot urine.

Urinary albumin excretion rate is correlated with severity of coronary artery disease in elderly type 2 diabetic patients

Background Coronary heart disease is the main complication of type 2 diabetes mellitus; its incidence is closely related to microalbuminuria. The aim of this study was to investigate the correlation between the urinary albumin excretion rate and the incidence and severity of coronary heart disease in elderly type 2 diabetes mellitus patients. Methods A total of 612 hospitalized type 2 diabetes mellitus patients aged 60 years or older, who were given coronary angiography for diagnosis of possible coronary heart disease, participated. Their urinary albumin excretion rate was measured, and the severity of coronary artery stenosis was quantified with the Gensini scoring system to analyze the incidence of coronary heart disease and the severity of coronary artery stenosis. The optimal urinary albumin excretion rate predictive value for coronary heart disease incidence in elderly type 2 diabetes mellitus patients was determined. Results The incidence of coronary heart disease, the number of patients with coronary vascular disease and the Gensini scores were significantly different between the microalbuminuria group and the normal atbuminuria group （P 〈0.05）. The urinary albumin excretion rate was independently correlated with the occurrence of coronary heart disease in elderly type 2 diabetes mellitus patients （odds ratio （OR） =1.058, P 〈0.0001,95% confidence interval （CI）： 1.036-1.080）. Urinary albumin excretion rate and the Gensini score were independently correlated in elderly type 2 diabetes mellitus patients （β=0.476, P 〈0.0001）. The best predictive value of urinary albumin excretion rate was 10.45 tJg/min for elderly type 2 diabetes mellitus patients. The area under the curve was 0.764, with a sensitivity and specificity of 70.0% and 72.2%, respectively. Conclusions The occurrence of coronary heart disease in elderly type 2 diabetes mellitus patients with microalbuminuria was higher than that in patients with normal albuminuria, and the severity of the disease also increased in patients with microalbuminuria. In elderly type 2 diabetes mellitus patients, urinary albumin excretion rate was positively correlated with the incidence and severity of coronary heart disease and was also an independent factor contributing to coronary heart disease.

Negative association of time in range and urinary albumin excretion rate in patients with type 2 diabetes mellitus:a retrospective study of inpatients

Background:Time in range(TIR)refers to the time an individual spends within their target glucose range,which now has been popularized as an important metric to classify glycemic management and also recognized as an important outcome of current diabetes therapies.This study aimed to investigate the association between TIR and the severity of the urinary albumin excretion rate(UAER)in patients with type 2 diabetes mellitus(T2DM).Methods:We retrospectively analyzed the data of 1014 inpatients with T2DM at the Department of Endocrinology and Metabolism of Peking University International Hospital,China.TIR was defined as the percentage of blood glucose within the target range of 3.90-10.00 mmol/L.Urine samples for assessment of UAER were collected for 3 consecutive days from the start of hospitalization.Results:The TIR values for patients with normal urine levels of albumin,microalbuminuria,and macroalbuminuria were 70%±20%,50%±20%,and 30%±20%,respectively(allP<0.001).The patients were stratified according to quartiles of TIR as follows:quartile(Q)1,<55%;Q2,55%-72%;Q3,73%-83%;and Q4,>83%.The incidences of microalbuminuria in Q1,Q2,Q3,and Q4 were 41.1%,21.6%,7.1%,and 5.5%(allP<0.001),respectively.The respective incidences of macroalbuminuria were 24.2%,1.1%,1.4%,and 0%(allP<0.001).In multinomial logistic regression analyses,TIR was significantly correlated with microalbuminuria(odds ratio[OR]0.58,95%confidence interval[CI]:0.52-0.65,P<0.001)and macroalbuminuria(OR 0.26,95%CI:0.18-0.38,P<0.001)after adjusting for age,sex,body mass index,diabetes duration,systolic blood pressure,and levels of triglycerides,glycosylated hemoglobin A1c,and creatinine.Conclusion:The proportion of blood glucose in TIR is closely related to the severity of UAER in patients with T2DM.

A Participant-assigned Interventional Research of Precesarean Internal Iliac Artery Balloon Catheterization for Managing Intraoperative Hemorrhage of Placenta Previa and Placenta Accreta Spectrum Disorders After Cesarean Section

Placenta accreta spectrum disorder (PASD) and placenta previa (PP) are two of the mosthideous obstetric complications which are usually associated with a history of cesarean section(CS). Moreover, women with PASD, PP and/or a cesarean scarred uterus are more likely to haveadverse pregnancy outcomes, including blood transfusion, hysterectomy, pelvic organs damage,postpartum hemorhage, disseminated intravascular coagulation, multi-organ dysfunction syndromeand even maternal or fetal death. This study aimed to investigate the efficacy of precesareaninternal iliac artery balloon catheterization (BC) for managing severe hemorhage caused by PASDand PP with a history of CS. This participant-assigned interventional study was conducted inTongji Hospital. We recruited 128 women with suspected PASD, PP and a history of CS. Womenin the BC group accepted precesarean BC of bilateral internal iliac arteries before the scheduledcesarean delivery. Women in the control group underwent a conventional cesarean delivery.Intraoperative hemorrhage, transfusion volume, radiation dose, exposure time, complicationsand neonatal outcomes were discussed. There were significant differences in calculated bloodloss (CBL) between BC group and control group (1015.0±144.9 vs. 1467.0±171.0 mL, P=0.04).Precesarean BC could reduce intraoperative red blood cell (RBC) transfusion as compared withcontrol group (799.5±136.1 vs. 1286.0±161.6 mL, P=0.02) and lessen the rate of using bloodproducts (57.1% vs. 76.4%, P=0.02). The incidence of hysterectomy was also lower in BC groupthan in control group. Postpartum outcomes showed no significant differences between the twogroups, except that postoperation hospitalization was longer in BC group than in control group(6.7±0.4 vs. 5.8±0.2 days, P=0.03). Precesarean BC of internal iliac artery is an effective methodfor managing severe hemorrhage caused by PASD and PP with a cesarean scarred uterus, as it couldreduce intraoperative blood loss, lessen intraoperative RBC transfusions and potentially decreasehysterectomies.

Practical insights into chronic management of hepatic Wilson’s disease

Wilson’s disease(WD)is a rare inherited disorder of human copper metabolism,with an estimated prevalence of 1:30000-1:50000 and a broad spectrum of hepatic and neuropsychiatric manifestations.In healthy individuals,the bile is the main route of elimination of copper.In WD patients,copper accumulates in the liver,it is released into the bloodstream,and is excreted in urine.Copper can also be accumulated in the brain,kidneys,heart,and osseous matter and causes damage due to direct toxicity or oxidative stress.Hepatic WD is commonly but not exclusively diagnosed in childhood or young adulthood.Adherent,non-cirrhotic WD patients seem to have a normal life expectancy.Nevertheless,chronic management of patients with Wilson’s disease is challenging,as available biochemical tests have many limitations and do not allow a clear identification of non-compliance,overtreatment,or treatment goals.To provide optimal care,clinicians should have a complete understanding of these limitations and counterbalance them with a thorough clinical assessment.The aim of this review is to provide clinicians with practical tools and suggestions which may answer doubts that can arise during chronic management of patients with hepatic WD.In particular,it summarises current knowledge on Wilson’s disease clinical and biochemical monitoring and treatment.It also analyses available evidence on pregnancy and the role of low-copper diet in WD.Future research should focus on trying to provide new copper metabolism tests which could help to guide treatment adjustments.

Relationship between urinary nephrin and urinary albumin changes in diabetic rats and effects of Yiqiyangyinhuayutongluo Recipe

OBJECTIVE:To investigate the dynamic changes of urinary nephrin,and the relationship between it and urinary albumin excretion rate(UAER) in a diabetic rat model,as well the effects of yiqiyangyinhuayutongluo recipe.METHODS:Diabetic model was induced by high fat diet combined with low-dose Streptozotocin(STZ) in rats.Normal group(NG),model group(MG),and yiqiyangyinhuayutongluo recipe treated group(YHTG) were set.Gastrointestinal Yiqiyangyinhuayutongluo recipe was administered once daily for 32 w.At the end of the 2nd w(2w),8w,16w,and 32w,fasting blood glucose(FBG),UAER and 24h urinary nephrin(U-nephrin) were detected.RESULTS:Compared with NG,FBG in MG increased notably(P<0.05).Compared with MG,FBG of YHTG reduced slowly,and the difference was significant(P<0.05) since 16w.U-nephrin and UAER in MG increased significantly from 2w,peaked at 16w,lessened in different degree at 32w,but were still higher than NG.The correlation analysis showed that there was a significant positive correlation between U-nephrin and UAER at different time,the correlation coefficient as r>0.9,and P<0.05.Compared with MG,U-nephrin and UAER in YHTG decreased markedly(P<0.05) except for U-nephrin at 8w.CONCLUSIONS:U-nephrin and UAER in diabetic rat model have a positive linear correlation.Yiqiyangyinhuayutongluo recipe can reduce UAER markedly,and preventing the lose of nephrin in urine maybe one of the mechanisms.

Design,synthesis and biological activity of cyclohexane-bearing C-glucoside derivatives as SGLT2 inhibitors

Seven cyclohexane-bearing C-glucoside derivatives（7,9,12,13 and 17-19） were designed and synthesized as SGLT2 inhibitors starting from a potent SGLT2 inhibitor we discovered in earlier work, （lS）-1-deoxy-l-[4-methoxy-3-（trans-n-propylcyclohexyl）methylphenyl]-D-glucose（1）.The in vitro and in vivo biological activities were evaluated by hSGLT2/hSGLTl inhibition and urinary glucose excretion （UGE）,respectively.Among the synthesized compounds 12,the 6-deoxy derivative of 1 was the most active and selective SGLT2 inhibitor（IC_（50）= 1.4nmol/L against hSGLT2;selectivity = 1576）.Compound 12 was a potent SGLT2 inhibitor,which could induce more urinary glucose than 1 and dapagliflozin in UGE.

Clinical Study on Treatment of Incipient Diabetic Nephropathy by Integrated Traditional Chinese and Western Medicine

Objective: To explore the curative effect of integrated traditional Chinese and western medicinal (TCM-WM) therapy on incipient diabetic nephropathy (DN).Methods: One hundred patients with incipient DN were randomly divided into two groups, the treated group (50 cases) was treated with TCM-WM therapy, which was carried out by using Jiangtang Jianshenling (JTJSL) capsule, a Chinese preparation for supplementing Qi and nourishing Yin, on the basis of effectively controlling blood glucose with western medicine. The 50 patients in the control group were treated with western medicine alone. The course of treatment was three months. Changes of symptoms, signs and related laboratory parameters were observed before and after treatment.Results: The total effective rate in the treated group was 90% while that in the control group 58%, the difference between the two groups was significant (P<0.05). The related parameters including 24 hrs urinary albumin excretion, blood sugar, microalbuminuria, blood and urine β2-microglobulin, blood lipids and hemorrheologic parameters were all improved after treatment in the treated group (P<0.05 or P<0.01).Conclusion: The curative effect of TCM-WM was better than that of western medicine alone in treating incipient DN.