Cardiac Structural and Functional Features in Patients With Type 2 Diabetes Mellitus and Heart Failure With Preserved Ejection Fraction:A Study Based on Propensity Score Matching / 中国医学科学院学报

Objective To investigate the cardiac structural and functional characteristics in the patients with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM),and predict the factors influencing the characteristics. Methods A total of 783 HFpEF patients diagnosed in the Department of Geriatric Cardiology,the First Hospital of Lanzhou University from April 2009 to December 2020 were enrolled in this study.Echocardiography and tissue Doppler technique were employed to evaluate cardiac structure and function.According to the occurrence of T2DM,the patients were assigned into a HFpEF+T2DM group (n=332) and a HFpEF group (n=451).Propensity score matching (PSM)(in a 1∶1 ratio) was adopted to minimize confounding effect.According to urinary albumin excretion rate (UAER),the HFpEF+T2DM group was further divided into three subgroups with UAER<20 μg/min,of 20-200 μg/min,and>200 μg/min,respectively.The comorbidities,symptoms and signs,and cardiac structure and function were compared among the groups to clarify the features of diabetes related HFpEF.Multivariate linear regression was conducted to probe the relationship of systolic blood pressure,blood glucose,glycosylated hemoglobin,and UARE with cardiac structural and functional impairment. Results The HFpEF+T2DM group had higher prevalence of hypertension (P=0.001) and coronary heart disease (P=0.036),younger age (P=0.020),and larger body mass index (P=0.005) than the HFpEF group,with the median diabetic course of 10 (3,17) years.After PSM,the prevalence of hypertension and coronary heart disease,body mass index,and age had no significant differences between the two groups(all P>0.05).In addition,the HFpEF+T2DM group had higher interventricular septal thickness (P=0.015),left ventricular posterior wall thickness (P=0.040),and left ventricular mass (P=0.012) and lower early diastole velocity of mitral annular septum (P=0.030) and lateral wall (P=0.011) than the HFpEF group.Compared with the HFpEF group,the HFpEF+T2DM group showed increased ratio of early diastolic mitral filling velocity to early diastolic mitral annular velocity (E/e') (P=0.036).Glycosylated hemoglobin was correlated with left ventricular mass (P=0.011),and the natural logarithm of UAER with interventricular septal thickness (P=0.004),left ventricular posterior wall thickness (P=0.006),left ventricular mass (P<0.001),and E/e' ratio (P=0.049). Conclusion The patients with both T2DM and HFpEF have thicker left ventricular wall,larger left ventricular mass,more advanced left ventricular remodeling,severer impaired left ventricular diastolic function,and higher left ventricular filling pressure than the HFpEF patients without T2DM.Elevated blood glucose and diabetic microvascular diseases might play a role in the development of the detrimental structural and functional changes of the heart.

Use of organic acids to reduce Salmonella Typhimurium excretion in swine / Uso de ácidos orgânicos para reduzir a excreção de Salmonella Typhimurium em suínos

The use of antimicrobials as growth promoters and disease prevention is being constantly reduced in several animal production systems, including in the swine industry. Therefore, this study aimed to evaluate the effectiveness of using acidifiers to control Salmonella Typhimurium in 65-day-old pigs by detecting the pathogen in organs at euthanasia. For this, 24 piglets were divided into two experimental groups consisting of 12 piglets each. An untreated control group (G1) and a treatment group (G2) received a liquid organic acidifier in the drinking water for 10 days (D-5 to D5). Five days after the start of treatment (D0), all piglets were challenged with 106 CFU of Salmonella Typhimurium and assessed for 12 days (D12). Every three days (D3, D6, D9, and D12), three animals from each experimental group were euthanized and then submitted for necropsy. Samples from the intestines (ileum, cecum, mesenteric lymph nodes, and ileocolic lymph nodes), liver, spleen, and lungs were collected to isolate Salmonella. The results show that, numerically, Salmonella isolation in the organs of G2 was lower than in G1 and that the number of positive cecum samples in G1 (66.7%; 8/12) was statistically different from the number of positive models in G2 (16.7%; 2/12), with a reduction of 28.6% of the total cecum positive samples in the treated group compared to the control. Therefore, it was observed that the liquid organic acidifier product could reduce the colonization of organs by Salmonella Typhimurium. (AU)

Use of organic acids to reduce Salmonella Typhimurium excretion in swine / Uso de ácidos orgânicos para reduzir a excreção de Salmonella Typhimurium em suínos

The use of antimicrobials as growth promoters and disease prevention is being constantly reduced in several animal production systems, including in the swine industry. Therefore, this study aimed to evaluate the effectiveness of using acidifiers to control Salmonella Typhimurium in 65-day-old pigs by detecting the pathogen in organs at euthanasia. For this, 24 piglets were divided into two experimental groups consisting of 12 piglets each. An untreated control group (G1) and a treatment group (G2) received a liquid organic acidifier in the drinking water for 10 days (D-5 to D5). Five days after the start of treatment (D0), all piglets were challenged with 106 CFU of Salmonella Typhimurium and assessed for 12 days (D12). Every three days (D3, D6, D9, and D12), three animals from each experimental group were euthanized and then submitted for necropsy. Samples from the intestines (ileum, cecum, mesenteric lymph nodes, and ileocolic lymph nodes), liver, spleen, and lungs were collected to isolate Salmonella. The results show that, numerically, Salmonellaisolation in the organs of G2 was lower than in G1 and that the number of positive cecum samples in G1 (66.7%; 8/12) was statistically different from the number of positive models in G2 (16.7%; 2/12), with a reduction of 28.6% of the total cecum positive samples in the treated group compared to the control. Therefore, it was observed that the liquid organic acidifier product could reduce the colonization of organs by Salmonella Typhimurium.(AU)

O uso de antimicrobianos como promotores de crescimento e prevenção de doenças vem sendo constantemente reduzido em diversos sistemas de produção animal, inclusive na suinocultura. Portanto, o objetivo do presente estudo foi avaliar a eficácia do uso de acidificantes no controle de Salmonella Typhimurium em suínos de 65 dias de idade, detectando o patógeno em órgãos após a eutanásia. Para isso, 24 leitões foram divididos em dois grupos experimentais constituídos por 12 leitões cada. Um grupo controle não tratado (G1) e um grupo de tratamento (G2) que recebeu um acidificante orgânico líquido na água de beber por 10 dias (D-5 a D5). Cinco dias após o início do tratamento (D0), todos os animais foram inoculados oralmente com 106 UFC de Salmonella Typhimurium e avaliados por 12 dias (D12). A cada três dias (D3, D6, D9 e D12), três leitões de cada grupo experimental foram eutanasiados e posteriormente submetidos à necropsia. Amostras de intestino (íleo, ceco, linfonodos mesentéricos e linfonodos ileocólicos), fígado, baço e pulmões foram coletadas para o isolamento de Salmonella. Os resultados mostram que, numericamente, o isolamento de Salmonella nos órgãos do G2 foi inferior ao G1, e que o número de amostras positivas de ceco no G1 (66,7%; 8/12) foi estatisticamente diferente do número de amostras positivas no G2 (16,7%; 2/12), com redução de 28,6% do total de amostras positivas de ceco no grupo tratado em relação ao controle. Portanto, observou-se que o ácido orgânico líquido foi capaz de reduzir a colonização de órgãos por Salmonella Typhimurium.(AU)

Parotid duct anastomosis with an epidural catheter as a stent and evaluation of postoperative gland function / 口腔疾病防治

Objective @#To investigate the feasibility of epidural catheters in parotid gland duct anastomosis and the function of the affected side gland after parotid gland duct anastomosis. @* Methods@# Thirteen patients who were treated in the Department of Oral and Maxillofacial Surgery of Xuzhou Central Hospital using an epidural catheter as the scaffold for parotid gland catheter anastomosis were enrolled from Jan. 2019 to June 2021. The swelling, salivary fistula and catheter patency in the parotid gland area were evaluated two weeks after the operation. 99mTcO4- single photon emission computed tomography (SPECT) was used for quantitative detection of salivary gland secretion function@*Results@# Thirteen patients had no swelling or salivary fistula in the parotid gland area of the affected side two weeks after the operation, and the catheter secretion was unobstructed. There was no significant difference in the uptake rate between the parotid gland on the affected side and the parotid gland on the healthy side (t = -0.859, P = 0.399), and there was no significant difference in the excretion rate between the parotid gland on the affected side and the parotid gland on the healthy side (t = 0.693, P = 0.495). The parotid gland excretion function of the affected side was excellent three months after the operation.@*Conclusion @#Parotid duct anastomosis with an epidural catheter as the stent has good feasibility, and parotid gland secretion function recovers well after the operation, which is worthy of clinical application.

Comparison of in vivo plasma pharmacokinetics and urine excretion of main components in Xihuang Formula in rats with precancerous lesions of breast cancer / 中国中药杂志

The UPLC-MS/MS was established for the determination of acetyl-11-keto-beta-boswellic acid(AKBA) and β-boswellic acid(β-BA), the main active components of Olibanum and Myrrha extracts in Xihuang Formula, in rat plasma and urine. The effects of compatibility on the pharmacokinetic behaviors of AKBA and β-BA in rats were investigated, and the differences in pharmacokinetic behaviors between healthy rats and rats with precancerous lesions of breast cancer were compared. The results showed that compared with RM-NH and RM-SH groups, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05 or P<0.01), T_(max) decreased(P<0.05 or P<0.01), and C_(max) increased(P<0.01) after compatibility. The trends of AKBA and β-BA were the same. Compared with RM-SH group, the T_(max) decreased(P<0.05), C_(max) increased(P<0.01), and the absorption rate increased in the normal group of Xihuang Formula. The results of urinary excretion showed that there was a decreasing trend in the urinary excretion rate and total urinary excretion of β-BA and AKBA after compatibility, but there was no statistical difference. Compared with normal group of Xihuang Formula, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05), T_(max) increased(P<0.05), and the clearance rate decreased in the breast precancerous lesion group. AUC_(0-t) and AUC_(0-∞) of AKBA showed an increasing trend, the in vivo retention time was prolonged, and the clearance rate was reduced, but there was no significant difference compared with the normal group. The cumulative urinary excretion and urinary excretion rate of β-BA and AKBA decreased under pathological conditions, indicating that pathological conditions could affect the in vivo process of β-BA and AKBA, and reduce their excretion in the form of prototype drugs, showing different pharmacokine-tic characteristics from normal physiological conditions. In this study, UPLC-MS/MS analysis method was established, which was sui-table for in vivo pharmacokinetic analysis of β-BA and AKBA. This study laid a foundation for the development of new dosage forms of Xihuang Formula.

Opportunities and challenges of incretin-based hypoglycemic agents treating type 2 diabetes mellitus from the perspective of physiological disposition

The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus (T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1, and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM. Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug-drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug-drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired.

Metabolic study of trimetazidine using ultra-high performance liquid chromatography-tandem mass spectrometry

Abstract In the present study, the application of ultra-high performance liquid chromatography-tandem mass spectrometry allowed us to study of known-as well as hitherto unknown-trimetazidine (TMZ) metabolites in human urine and to propose their renal excretion profiles. Urine samples from a healthy volunteer were analyzed at baseline and at 0-4 h, 4-8 h, 8-12 h, and 12-24 h after a single dose of TMZ. A dilute-and-shoot procedure was used as sample treatment before separation. Full-scan spectra of possible metabolites were acquired. Additionally, product ion scan spectra of precursor ions of interest were also acquired at two collision energies. Intact TMZ was a major excretion product, with a maximum concentration at 4-8 h after administration. Moreover, five minor metabolites were observed, namely trimetazidine-N-oxide (M1), N-formyl trimetazidine (M2), desmethyl-trimetazidine O-sulfate (M3), desmethyl-trimetazidine O-glucuronide (M4), and desmethyl-trimetazidine-N-oxide-O-glucuronide (M5). Metabolite M5 has not previously been reported. Excretion curves were constructed based on the chromatographic peak areas of specific mass transitions (precursor ion > product ion) related to each of the detected metabolites

Evaluación de la técnica de conteo de grasas y ajuste de enzimas pancreáticas en un grupo de pacientes con insuficiencia pancreática secundaria a fibrosis quística con seguimiento en un hospital de alta complejidad / Evaluation of the fat counting technique and pancreatic enzyme adjustment in a group of patients with pancreatic insufficiency secondary to cystic fibrosis followed-up in a tertiary-level hospital

Objetivo: evaluar la efectividad de la técnica de conteo de grasas y ajuste de enzimas pancreáticas en un grupo de pacientes con insuficiencia pancreática secundaria a fibrosis quística (FQ). Materiales y métodos: En un grupo de pacientes con FQ, sin otra patología asociada, mayores de 1 año, con >10 000 UKD (unidades por kilo por día) de lipasa; se realizó educación y aplicación de técnica de conteo de grasas con ajuste enzimático, solicitando Van de Kamer y registro alimentario de 5 días durante la recolección de la muestra con un intervalo de 3 meses entre ambas determinaciones. Se evaluó la efectividad de la misma y las dosis de enzimas utilizadas mediante el porcentaje de excreción grasa (PEG), así como las variaciones en la cantidad de enzimas utilizadas y la ganancia de peso. Los datos se registraron en RED Cap (Research Electronic Data Capture) y se analizaron mediante Stata 12. Resultados: De un total de 21 pacientes, 16 completaron la intervención. El 50% presentó un índice de masa corporal (IMC) mayor del Plo 25 antes y después, un 87% alcanzó adecuación calórica mayor del 120% de la ingestas diarias recomendadas (RDA) al final, logrando un aumento promedio de z score de peso de 0,28 con una media inicial de 17 kg y final de 18,2 kg. En cuanto a la media del requerimiento enzimático fue de 14 800 UKD antes y 10 145 UKD después (z=0,002), asimismo el porcentaje de excreción grasa (PEG) tuvo una disminución del 38% (p=0,1705). Conclusiones: La implementación de la técnica de conteo de grasas y ajuste enzimático, podría ser una estrategia válida para aquellos pacientes con FQ que tienen dosis altas de enzimas e inadecuada ganancia de peso (AU)

Objective: To evaluate the effectiveness of the fat counting technique and pancreatic enzyme adjustment in a group of patients with pancreatic insufficiency secondary to cystic fibrosis (CF). Materials and methods: A group of patients with CF without other associated diseases, older than 1 year of age, lipase dose >10 000 UKD (units per kilo per day), received education on the fat counting technique with enzyme adjustment followed by its implementation of the intervention. Van de Kamer was requested and a 5-day food record was kept during the sample collection with an interval of 3 months between both measurements. The effectiveness of the technique and the enzyme doses used were evaluated based on the percentage of fat excretion (PFE), as well as the variations in the amount of enzymes used and weight gain. Data were recorded in RED Cap (Research Electronic Data Capture) and analyzed using Stata 12. Results: Of a total of 21 patients, 16 completed the intervention. Fifty percent had a body mass index (BMI) greater than Plo 25 before and after the intervention; 87% had achieved a caloric increase greater than 120% of the recommended daily intake (RDA) at the end of the study and an average increase in weight z score of 0.28 with an initial mean of 17 kg and a final mean of 18.2 kg. Mean enzyme requirement was 14 800 UKD before and 10 145 UKD after the intervention (z=0.002). PFE decreased by 38% (p=0.1705). Conclusions: The implementation of the technique of fat counting and enzyme adjustment may be a valid strategy for CF patients with high enzyme doses and inadequate weight gain. (AU)

Análisis comparativo de la actividad antimicrobiana de secreciones y excreciones larvarias de Calliphora vicina y Sarconesiopsis magellanica (Diptera: Calliphoridae) / A comparative analysis of Calliphora vicina and Sarconesiopsis magellanica (Diptera: Calliphoridae) larval secretions and excretions antimicrobial activity

Introducción. La creciente resistencia bacteriana a los antibióticos representa una amenaza mundial de salud pública. Las excreciones y secreciones larvarias derivadas de moscas necrófagas de la familia Calliphoridae podrían configurar una fuente promisoria para contrarrestar sus efectos. Objetivo. Comparar la actividad antimicrobiana de las excreciones y secreciones larvarias nativas, y de las mayores y menores de 10 kDa de Calliphora vicina y Sarconesiopsis magellanica (Diptera: Calliphoridae). Materiales y métodos. El bioensayo se hizo a partir de la técnica de turbidimetría y en el caso de las excreciones y secreciones menores de 10 kDa se determinó la concentración inhibitoria mínima (CIM). Resultados. Las excreciones y secreciones nativas y las menores de 10 kDa de C. vicina y S. magellanica, evidenciaron una potente actividad antibacteriana contra tres cepas de Staphylococcus aureus y cuatro bacterias Gram negativas, siendo las menores de 10 kDa más efectivas que las nativas en las dos especies de moscas evaluadas. Además, las menores de 10 kDa presentaron la misma efectividad, aunque en las pruebas de CIM se observó que las de S. magellanica fueron más potentes en todas las bacterias evaluadas, excepto contra la cepa de S. aureus ATCC 25923. Las mayores de 10 kDa no inhibieron el crecimiento bacteriano. Conclusión. Los resultados validaron, en general, que estas sustancias son fuente importante para el aislamiento y la caracterización de agentes antimicrobianos.

Introduction: The growing resistance to antibiotics worldwide represents a global threat to public health. The larval excretions and secretions derived from necrophagous flies from the Calliphoridae family could represent a promising source for counteracting their effects. Objective: To compare the antimicrobial activity of Calliphora vicina and Sarconesiopsis magellanica (Diptera: Calliphoridae) native excretions and secretions and those weighing more than 10 kDa and less. Materials and methods: We used the turbidimetry technique for the bioassay; we determined the minimum inhibitory concentration (MIC) for excretions and secretions weighing less than 10 kDa. Results: Calliphora vicina and S. magellanica native excretions and secretions and those weighing less than 10 kDa exhibited potent antibacterial activity against three Staphylococcus aureus strains and four Gram-negative bacteria; those weighing less than 10 kDa were more effective than the native ones in the two species of flies evaluated here. Furthermore, excretions and secretions weighing less than 10 kDa had the same effectiveness, except in the MIC trials where S. magellanica excretions and secretions weighing less than 10 kDa were more potent against all the bacteria evaluated, except for S. aureus ATCC 25923. Excretions and secretions weighing more than 10 kDa did not inhibit bacterial growth. Conclusions: These results potentially validate these substances as an important source for isolating and characterizing antimicrobial agents.

24 hour urinary sodium excretion in essential hypertension

Hypertension is a common medical condition; its prevalence increases with age. It is one of the most important risk factors for cardiovascular disease, which is the leading cause of mortality. High salt intake is associated with high blood pressure. The incidence of hypertension is higher in salt-sensitive individuals. Evidence shows that reduced sodium intake lowers blood pressure and can prevent hypertension. Urinary sodium excretion was used as measure of sodium intake, which equals urinary excretion under normal circumstances. The relationship between salt intake and renal ability to excrete sodium has suggested being a major importance for the long-term blood pressure treatment especially in essential hypertension. In the present study there was increased 24 hour sodium excretion in essential hypertensives indicating a high intake of sodium, which may be the cause for hypertension. Patients with high sodium excretion, who are salt sensitive hypertensives will respond to diuretics, when compared to others. The long term reduction in salt intake may significantly reduce the prevalence of hypertension and thereby decrease the associated morbidity and mortality.

Aspectos epidemiológicos de las infecciones de transmisión sexual en mujeres de la provincia de Santiago de Cuba / Epidemiologic aspects of sexually transmitted infections in women from the province of Santiago de Cuba

Introducción: Las infecciones de transmisión sexual constituyen un relevante problema de salud a nivel mundial; particularmente afectan la salud sexual de las mujeres ocasionando dolencias y efectos muy negativos, como la infertilidad, los embarazos ectópicos y el cáncer cervicouterino. Objetivo: Describir las características epidemiológicas de las infecciones de transmisión sexual relevantes en mujeres de Santiago de Cuba. Métodos: Se realizó un estudio descriptivo y retrospectivo en la provincia de Santiago de Cuba de la población femenina que presentó infecciones de transmisión sexual durante el período 2007-2017, detallando cada afección según año, municipio, edad, entre otras variables de interés. Asimismo, se analizaron la frecuencia, las tasas de incidencia, las tendencias y las variaciones temporales. Resultados: Las entidades clínicas predominantes fueron el síndrome de dolor pélvico y la secreción vaginal, en tanto, las menos frecuentes resultaron ser el herpes genital y la blenorragia. En el análisis por cada tipo de infección se observó una mayor afectación en féminas de edades jóvenes. Conclusiones: Las infecciones de transmisión sexual constituyen un serio problema de salud en mujeres de la provincia de Santiago de Cuba, que deviene causa importante de embarazos ectópicos y esterilidad. Sin embargo, se debe mejorar la vigilancia epidemiológica de estas enfermedades, pues existe un marcado subregistro de algunas y, por ende, una inadecuada atención, sobre todo en el sexo femenino.

Introduction: Sexually transmitted infections constitute an outstanding health problem worldwide; they particularly affect the sexual health of women causing ailments and very negative effects as infertility, ectopic pregnancies and cervical uterine cancer. Objective: To describe the epidemiologic characteristics of the outstanding sexually transmitted infections in women from Santiago de Cuba. Methods: A descriptive and retrospective study was carried out in the province of Santiago de Cuba in the female population that presented sexually transmitted infections during 2007-2017, with details of each affection according to year, municipality, age, among other variables of interest. Also, frequency, rates of incidence, tendencies and temporary variations were analyzed. Results: The predominant clinical entities were the pelvic pain syndrome and vaginal secretion, as long as, the less frequent were genital herpes and blennorrhagia. In the analysis for each type of infection a higher affectation was observed in young females. Conclusions: Sexually transmitted infections constitute a serious health problem in women from the province of Santiago de Cuba that becomes important cause of ectopic pregnancies and sterility. However, the epidemiologic surveillance of these diseases should be improved, because there is a marked subrecord of some of them and, therefore, an inadequate care, mainly in the female sex.

Association of 24-hour urinary sodium excretion and 25-hydroxy vitamin D level with albuminuria in patients with type 2 diabetes / 中华内分泌代谢杂志

Objective:Using 24-hour urinary sodium excretion (24h-UNa) as the surrogate measure of sodium intake, to evaluate the joint association of 24h-UNa and serum 25-hydroxy vitamin D (25-OHD) levels with the risk of albuminuria in patients with type 2 diabetes mellitus (T2DM).Methods:This retrospective study included 670 hospitalized T2DM cases in the Department of Endocrinology and Metabolic Diseases, the First Affiliated Hospital of Zhengzhou University from January 2018 to October 2021. Patients were divided into the albuminuria-positive group or negative-group according to the level of 24-hour urinary albumin excretion (24h-UAE); They were also divided into the high-sodium group or low-sodium group according to the level of 24h-UNa; Patients were divided into the low-VD group or high-VD group according to the level of 25-OHD. Combining 24h-UNa and 25-OHD, the patients were further divided into four groups: high-VD low-sodium group ( n=85), high-VD high-sodium group ( n=122), low-VD low-sodium group ( n=248), and low-VD high-sodium group ( n=215). The effect of 24h-UNa and 25-OHD association on albuminuria was analyzed by binary regression. Results:There were significant differences in 24h-UAE level among the four groups ( P<0.01), the level of 24h-UAE in the low-VD high-sodium group was significantly higher than that in low-VD low-sodium group, high-VD low-sodium group, and high-VD high-sodium group [39.00(13.00, 319.00)mg/24 h vs 22.00(10.00, 99.00)mg/24 h, 22.00(9.00, 72.50)mg/24 h, 22.45(9.69, 72.75)mg/24 h; P=0.047, P=0.019, P=0.030]. Correlation analysis showed a positive correlation between 24h-UNa and 24h-UAE in the low-VD group ( P=0.017), but not in the high-VD group ( P=0.411). Binary regression analyses showed that both 24h-UNa ( P=0.017) and 25-OHD( P=0.023) were independent risk factors for positive albuminuria in patients with T2DM. The risk of positive albuminuria in the low-VD high-sodium group was 1.789 times higher than that in the high-VD low-sodium group ( P=0.037). Conclusion:24h-UAE in T2DM patients was affected by the combination of 24h-UNa and 25-OHD. A low level of 25-OHD increased the risk of albuminuria in high sodium intake T2DM patients.

Biological fate and interaction with cytochromes P450 of the nanocarrier material, d-α-tocopheryl polyethylene glycol 1000 succinate

d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS, also known as vitamin E-TPGS) is a biodegradable amphiphilic polymer prepared by esterification of vitamin E with polyethylene glycol (PEG) 1000. It is approved by the US Food and Drug Administration (FDA) and has found wide application in nanocarrier drug delivery systems (NDDS). Fully characterizing the in vivo fate and pharmacokinetic behavior of TPGS is important to promote the further development of TPGS-based NDDS. However, to date, a bioassay for the simultaneous quantitation of TPGS and its metabolite, PEG1000, has not been reported. In the present study, we developed such an innovative bioassay and used it to investigate the pharmacokinetics, tissue distribution and excretion of TPGS and PEG1000 in rat after oral and intravenous dosing. In addition, we evaluated the interaction of TPGS with cytochromes P450 (CYP450s) in human liver microsomes. The results show that TPGS is poorly absorbed after oral administration with very low bioavailability and that, after intravenous administration, TPGS and PEG1000 are mainly distributed to the spleen, liver, lung and kidney before both being slowly eliminated in urine and feces as PEG1000. In vitro studies show the inhibition of human CYP450 enzymes by TPGS is limited to a weak inhibition of CYP3A4. Overall, our results provide a clear picture of the in vivo fate of TPGS which will be useful in evaluating the safety of TPGS-based NDDS in clinical use and in promoting their further development.

Measurement and analysis of 90Y radioactivity in urine of patients treated with 90Y resin microspheres / 中华放射医学与防护杂志

Objective:To evaluate 90Y activity concentration in renal excretions during the first 48 hours after being treated with 90Y resin microspheres seleceive internal radiation therapy(SIRI) and to provide advice on the management of patient excreta after surgery. Methods:After surgery, urine excreted from 3 patients during 0-24 h and 24-48 h was collected respectively, and the 90Y activity concentration in urine was tested and analyzed. Results:90Y radioctivity in the urine excreted from 3 patients after surgery was (1 266±258)kBq/GBq during 0-24 h and (140±106) kBq/GBq during 24-48 h, respectively, and 90Y activity concentration were (640±113) kBq/L during 0-24 h and (53±12) kBq/L during 24-48 h. Conclusions:90Y radioactivity in patient′s urine excreted at 1 d was about 10 times higher than that at 2 d. After surgery, patients can accelerate the reduction of free 90Y activity by increasing excretion. Urine excreted by the patients during hospitalization should be handled in accordance with the requirements of the national standard HJ 1188-2021 Radiation protection and safety requirements for nuclear medicine.

Magnesio e indicadores bioquímicos óseo-minerales según tasa de filtración glomerular en estudiantes sin enfermedad renal / Magnesium and osseous-mineral biochemical indicators according to glomerular filtration rate testing in students without kidney disease

Introducción: La variación del magnesio y de indicadores bioquímicos del metabolismo óseo-mineral según la tasa de filtración glomerular en jóvenes sin enfermedad renal es poco conocida por lo que es necesario considerarla para delimitar lo no atribuible a enfermedad renal crónica. El papel que desempeña el magnesio está en estudio. En la enfermedad renal crónica hay una alteración progresiva del metabolismo óseo-mineral que comienza tempranamente. Objetivos: Evaluar valores séricos de magnesio, calcio, fósforo, fosfatasa alcalina y parathormona, excreciones urinarias de 24 h y excreción fraccional de estos electrolitos según categoría G de tasa de filtración glomerular estimada por clearance de creatinina: G1 (normal a alta) y G2 (levemente disminuida) en estudiantes sin enfermedad renal crónica. Material y métodos: Estudio analítico y corte transversal con una muestra de 55 estudiantes voluntarios sin enfermedad renal en el periodo 2018 a 2019. Los analitos se determinaron en suero y algunos en orina de 24 h. Resultados: Solamente magnesio sérico y excreción fraccional de magnesio excreción fraccional de magnesio mostraron diferencias significativas según la categoría G (p < 0,05). Los valores de magnesio sérico magnesio sérico estuvieron dentro de los valores de referencia para el método. En G2, magnesio sérico, descendido respecto a G1 y excreción fraccional de magnesio aumentada, inversamente relacionados. El magnesio sérico disminuyó en promedio 0,26 mg/dL por unidad de aumento de excreción fraccional de magnesio (p = 0,0502). Conclusiones: Se observaron diferencias en magnesio sérico y excreción fraccional de magnesio al comparar los resultados en G1 y G2. Los demás indicadores bioquímicos estudiados no mostraron diferencias por categoría G. Diseños de corte longitudinal en muestras mayores pueden confirmar o no estos hallazgos. Tales estudios pueden aportar a la comprensión de cambios bioquímicos del metabolismo óseo-mineral en etapas iniciales de disminución de la tasa de filtración glomerular(AU)

Introduction: Not much is known about the variation in magnesium and biochemical indicators of the osseous-mineral metabolism according to glomerular filtration rate testing in young people without kidney disease. This variation should therefore be considered to delimit whatever is not attributable to chronic kidney disease. The role played by magnesium is currently under study. In chronic kidney disease a progressive alteration of the osseous-mineral metabolism starts early. Objectives: Evaluate serum values of magnesium, calcium, phosphorus, alkaline phosphatase and parathormone, 24-hour urinary excretion and fractional excretion of these electrolytes according to category G of the glomerular filtration rate estimated by creatinine clearance: G1 (normal to high) and G2 (slightly reduced) in students without chronic kidney disease. Methods: An analytical cross-sectional study was conducted of a sample of 55 student volunteers without kidney disease in the period 2018-2019. The analytes were determined in serum and some in 24-hour urine. Results: Only serum magnesium and magnesium fractional excretion displayed significant differences according to category G (p < 0.05). Serum magnesium values were within the reference values for the method. In G2, serum magnesium was lower than in G1, whereas magnesium fractional excretion was higher, i.e. an inverse relation is observed. Serum magnesium reduction averaged 0.26 mg/dl per unit of magnesium fractional excretion increase (p = 0.0502). Conclusions: Comparison of G1 and G2 results revealed differences in serum magnesium and magnesium fractional excretion. The remaining biochemical indicators studied did not show any differences in category G. Longitudinal studies with larger samples may or may not confirm these findings, thus contributing to a better understanding of the biochemical changes in osseous-mineral metabolism occurring in the initial stages of glomerular filtration rate reduction(AU)

Un modelo de estudio de la función tubular renal que no depende de la colección de orina de 24 horas / A model of study of renal tubular function that does not depend on the 24-hour urine collection

Introducción: El ensayo de muestras matutinas de orina pudiera mejorar el estudio de la función tubular en niños y adolescentes. Objetivo: Describir las tubulopatías diagnosticadas en niños y adolescentes después del ensayo de muestras matutinas de orina. Métodos: Se completó un estudio retrospectivo y analítico en el Laboratorio de Estudio de la Función Renal, Servicio de Laboratorio Clínico, Hospital Pediátrico Docente "Juan Manuel Márquez", con 70 informes de la función tubular hechos en muestras matutinas de orina de 56 probandos (varones: 50,0 por ciento; edad promedio: 4,3 ± 5,5 años; edades < 12 meses: 41,1 por ciento) atendidos entre 2015-2019 (ambos inclusive) que contenían los valores del filtrado glomerular, la excreción urinaria absoluta y fraccional de las sustancias de interés, la brecha aniónica, la presión parcial de los gases, y la acidez titulable, el pH, la densidad y la osmolaridad de los fluidos pertinentes. Los resultados obtenidos se integraron dentro de las construcciones de caso de varias tubulopatías. Resultados: La función tubular estaba conservada en el 41,1 por ciento de los probandos. La inmadurez tubular explicó los hallazgos en otros dos niños. La hipercalciuria idiopática (16,0 por ciento), la diabetes insípida de causa nefrogénica (8,9 por ciento) y la insuficiencia renal aguda (5,3 por ciento) fueron los hallazgos más frecuentes. En 14 de los probandos se diagnosticaron 10 tubulopatías que recorrieron el raquitismo carencial, la hipofosfatasia, la enfermedad de Leigh, el síndrome de Bartter, la enfermedad de Dent y la acidosis tubular I, II y IV. Conclusiones: El estudio tubular en muestras matutinas de orina permite el diagnóstico de importantes tubulopatías en las edades pediátricas(AU)

Introduction: The morning urine sample assay may improve the study of tubular function in children and adolescents. Objective: Describe the tubulopathies diagnosed in children and adolescents after the trial of morning urine samples. Methods: A retrospective and analytical study was completed at the Renal Function´s Study Laboratory, in the Clinical Laboratory Service at "Juan Manuel Marquez" Teaching Pediatric Hospital, with 70 reports of tubular function made in morning urine samples of 56 testees (males: 50.0 percent; average age: 4.3 ± to 5.5 years; ages< 12 months: 41.1 percent) attended from 2015 to 2019 (both inclusive) containing glomerular filtration values, absolute and fractional urinary excretion of substances of interest, anionic gap, partial gas pressure, and titrable acidity, pH, density and osmolarity of relevant fluids. The results obtained were integrated into the case constructions of various tubulopathies. Results: Tubular function was preserved in 41.1 percent of the testees. Tubular immaturity explained the findings in two other children. Idiopathic hypercalciuria (16.0 percent), nephrogenic diabetes insipidus (8.9 percent) and acute renal failure (5.3 percent) were the most frequent findings. In 14 of the testees, 10 tubulopathies were diagnosed were through deficiency rickets, hypophosphatasia, Leigh's disease, Bartter syndrome, Dent disease and tubular acidosis I, II and IV.. Conclusions: The tubular study with morning urine samples allows the diagnosis of important tubulopathies in the pediatric ages(AU)

Nitrogen balance of goat kids fed diets containing peach palm meal / [Balanço de nitrogênio em caprinos alimentados com dietas contendo farinha de pupunha]

O objetivo deste estudo foi avaliar o balanço de nitrogênio e a concentração de ureia no plasma em cabritos alimentados com dietas contendo farinha de pupunha em substituição ao milho (0, 10, 40, 60 e 85% MS). Trinta cabritos Boer × SRD, com 90 dias de idade e peso corporal inicial de 16,7 ± 3,5kg, foram distribuídos em um delineamento inteiramente ao acaso, com seis repetições. As dietas foram fornecidas diariamente ad libitum para permitir 10% das sobras. Três coletas foram realizadas a cada 28 dias. As dietas foram constituídas por milho, farelo de soja, farinha de pupunha, suplemento mineral e feno de Tifton-85, com a relação volumoso: concentrado de 30:70. O consumo de nitrogênio (N) diminuiu linearmente à medida que a farinha de pupunha substituiu o milho no concentrado. Com relação ao N digerido, os animais alimentados com níveis de farinha de pupunha apresentaram valores inferiores aos alimentados com o milho como única fonte de energia, com médias de 14,9 e 17,1g dia-1, respectivamente. A excreção urinária de N diminuiu à medida que a farinha de pupunha substituiu o milho no concentrado. O nível de 39% de farinha de pupunha reduziu a excreção urinária de ureia. Houve retenção máxima de N em 7,83g dia-1 para o nível de substituição de milho de 28,9% em farinha de pupunha.(AU)

Effect of Fluoxetine Hydrochloride on Routine Metabolism of Lambari (Deuterodon iguape, Eigenmann, 1907) and Phantom Shrimp (Palaemon pandaliformis, Stimpson, 1871)

HIGHLIGHTS Fluoxetine increases the metabolic rate and excretion of ammonia in both species. O:N ratio in fish showed higher values in the highest concentrations of fluoxetine. The LC50 - 96 hour values of Palaemon pandaliformis represented greater toxicity. Both species are a good biological model for fluoxetine exposure studies.

Abstract Fluoxetine is an emerging pollutant that acts as a selective serotonin reuptake inhibitor (SSRI) and being a hydrolytic molecule that is photolytically stable and accumulaties in biological tissues, its disposal in the aquatic environment can interfere with the physiology of fish and shrimp. Thus, the objective of this study was to analyze the effects of fluoxetine on routine metabolism (metabolic rate, specific ammonia excretion and O:N ratio) of Deuterodon iguape and Palaemon pandaliformis. For this, five groups of each species, were exposed to different concentrations of fluoxetine for 24 hours (D. iguape) and 2 hours (P. pandaliformis). The results demonstrated that in D. iguape exposure to fluoxetine significantly increased both the metabolic rate by 75%, 85%, 55% and 50% for concentrations of 0.05; 0.1; 0.5 and 1.0 mgL-1, respectively, and the specific ammonia excretion by 40%, 48% and 20% for concentrations of 0.05; 0.1 and 0.5 mgL-1, respectively, when compared with their control. The O:N ratio was statistically greater in concentrations of 0.5 and 1.0 mgL-1. Concerning P. pandaliformis, exposure to fluoxetine increased metabolic rate at concentrations 30.0 and 60.0 µgL-1, and also increased specific ammonia excretion at concentrations 10.0, 30.0 and 60.0 µgL-1, when compared with the control group. It was concluded that exposure to fluoxetine increases the routine metabolism of both species and that at the concentration 1.0 mgL-1, Deuterodon iguape required different energy substrates.

Preclinical efficacy against acute myeloid leukaemia of SH1573, a novel mutant IDH2 inhibitor approved for clinical trials in China

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults, with increasing incidence with age and a generally poor prognosis. Almost 20% of AML patients express mutant isocitrate dehydrogenase 2 (mIDH2), which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate (2-HG), resulting in poor prognosis. Thus, global institutions have been working to develop mIDH2 inhibitors. SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised. We have conducted a comprehensive study on its pharmacodynamics, pharmacokinetics and safety. First, SH1573 exhibited a strong selective inhibition of mIDH2 R140Q protein, which could effectively reduce the production of 2-HG in cell lines, serum and tumors of an animal model. It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models. Then, it was confirmed that SH1573 possessed characteristics of high bioavailability, good metabolic stability and wide tissue distribution. Finally, toxicological data showed that SH1573 had no effects on the respiratory system, cardiovascular system and nervous system, and was genetically safe. This research successfully promoted the approval of SH1573 for clinical trials (CTR20200247). All experiments demonstrated that, as a potential drug against mIDH2 R140Q acute myeloid leukaemia, SH1573 was effective and safe.

Herb-drug interaction in the protective effect of Alpinia officinarum against gastric injury induced by indomethacin based on pharmacokinetic,tissue distribution and excretion studies in rats / 药物分析学报

Alpinia officinarum Hance of the Chinese traditional herb for the treatment of emesis,abdominal pain and diarrhea has been used to counteract gastric disease induced by indomethacin in rats without obvious side effects.However,the role of herb-drug interaction between indomethacin and A.officinarum based on pharmacokinetic,tissue distribution and excretion still remains unknown.In this study,an ultra-fast liquid-tandem mass spectrometry(UFLC-MS/MS)method was developed for simultaneous determina-tion of indomethacin and its three metabolites,O-desmethylindomethacin(ODI),deschlor-obenzoylindomethacin(NDI)and indomethacin acyl-β-D-glucuronide(IDAβG)by oral administration of indomethacin solution with and without the ethanolic extract of A.officinarum and applied to comparative pharmacokinetic,tissue distribution and excretion studies.Our results clarified that oral administration of A.officinarum produced significant alterations in the pharmacokinetic parameters of indomethacin.And the pharmacokinetic interaction between indomethacin and A.officinarum reduced the systemic exposure of indomethacin and increased its elimination.Tissue distribution results demonstrated that co-administration of A.Officinarum could not reduce the accumulation of indo-methacin in the target tissue of the stomach,but could accelerate the excretions of indomethacin and its three metabolites including ODI,NDI and IDAβG in the bile and feces of rats in the excretion study.Therefore,A.Officinarum might have a gastrointestinal protective effect through the interaction role with indomethacin based on the pharmacokinetics and excretion in rats.