Abstract Fluoroquinolones are an important class of antimicrobial agents to manage infectious diseases. However, knowledge about how host bile acids are modified by fluoroquinolones is limited. We investigated and compared the impact of fluoroquinolones on circulating bile acid profiles and gut microbiota from in vivo studies. We administered ciprofloxacin (100 mg/kg/day) or moxifloxacin (40 mg/kg/day) orally to male Wistar rats for seven days. Fifteen bile acids (BAs) from the serum and large intestine were quantified by HPLC-MS/MS. The diversity of gut microbiota after ciprofloxacin and moxifloxacin treatment was analyzed using high-throughput, next-generation sequencing technology. The two fluoroquinolone-treated groups had different BA profiles. Ciprofloxacin significantly reduced the hydrophobicity index of the BA pool, reduced secondary BAs, and increased taurine-conjugated primary BAs in both the serum and large intestine as compared with moxifloxacin. Besides, ciprofloxacin treatment altered intestinal microbiota with a remarkable increase in Firmicutes to Bacteroidetes ratio, while moxifloxacin exerted no effect. What we found suggests that different fluoroquinolones have a distinct effect on the host BAs metabolism and intestinal bacteria, and therefore provide guidance on the selection of fluoroquinolones to treat infectious diseases.

ABSTRACT Objectives To provide a meta-analysis of the clinical efficacy and safety of sodium glucose co-transporter 2 inhibitors (SGLT2-i), as a combination treatment with metformin in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with metformin alone. Materials and methods We have searched randomized controlled trials (RCTs) in the database: MEDLINE, Embase and Cochrane Collaborative database. We used mean differences (MD) to assess the efficacy of glycemic and other clinical parameters, and risk ratios (RR) to evaluate the adverse events for safety endpoints. The heterogeneity was evaluated by I2. Results Finally 9 studies were included. SGLT2-i plus metformin had higher reduction level in HbA1C [MD = -0.50, 95% CI (-0.62, -0.38), p < 0.00001], FPG [MD = -1.12, 95%CI (-1.38, -0.87), p < 0.00001], body weight [MD = -1.72, 95% CI (-2.05, -1.39), p < 0.00001], SBP [MD = -4.44, 95% CI (-5.45, -3.43), p < 0.00001] and DBP [MD = -1.74, 95% CI (-2.40, -1.07), p < 0.00001] compared with metformin monotherapy. However, SGLT2-i plus metformin group had higher risk of genital infection [RR = 3.98, 95% CI (2.38, 6.67), p < 0.00001]. No significant difference was found in the risk of hypoglycemia, urinary tract infection or volume related adverse events. Conclusions Although the risk of genital infection may increase, SGLT2-i plus metformin may provide an attractive treatment option to those T2DM patients who are unable to achieve glycemic control with metformin alone, based on its effects on glycemic control, reducing body weight and lowering blood pressure.

Abstract: Besides stimulating vasoconstriction, Angiotensin II is also well known in inducing reactive oxygen species and promoting inflammatory phenotype switch via its type 1 receptor. In clinic, Angiotensin II type 1 (AT1) receptor blocker like candesartan has been widely applied as an antihypertensive medication. We previous have demonstrated that a higher dose of candesartan plays a protective role after kidney injury. However, whether candesartan could exhibit anti-inflammatory effects remains unclear. Here, by stimulating isolated human embryonic kidney epithelial cells with tumor necrosis factor-α (TNF-α), we observed the anti-inflammation capacity of candesartan ex vivo. It was found that pre-treat with candesartan significantly suppressed transforming growth factor-β (TGF-β) and interleukin-6 (IL-6) expression after incubation with TNF-α. Surprisingly, silence of angiotensin II type 1 receptor has little effects on reducing TGF-β or IL-6 products. Furthermore, candesartan inhibited TNF-α-induced oxidative stress in the primary cultured tubular epithelial cells. Overall, our data indicates that candesartan suppresses TNF-α-induced inflammatory cytokine production by inhibiting oxidative stress, rather than block AT1 receptor activity.

ABSTRACT Objectives: Previous studies have compared infectious outcomes on the basis of whether rectal preparation was performed; however, they failed to evaluate the quality of each rectal preparation, which may have led to confounding results. This study aimed to compare hospitalizations for urosepsis within 1 month after transrectal ultrasound-guided prostate biopsy between patients with adequate and traditional rectal preparations. Materials and Methods: Between January 2011 and December 2016, a total of 510 patients who underwent transrectal ultrasound - guided prostate biopsy at our institutions and were orally administered prophylactic antibiotics (levofloxacin) were included. Two rectal preparations were performed: (1) adequate rectal preparation confirmed by digital rectal examination and transrectal ultrasound (Group A, n = 310) and (2) traditional rectal preparation (Group B, n = 200). All patient characteristics were recorded. A logistic regression model was used to assess the effects of the two different rectal preparations on urosepsis, adjusted by patient characteristics. Results: There were a total of three and nine hospitalizations for urosepsis in Groups A and B, respectively. Differences in the demographic data between the two groups were insignificant. Logistic regression showed that adequate rectal preparation before biopsy significantly decreased the risk for urosepsis after biopsy (adjusted odds ratio: 0.2; 95% confidence interval: 0.05 – 0.78; P = 0.021). Conclusions: Adequate rectal preparation could significantly reduce hospitalizations for urosepsis within 1 month after transrectal ultrasound-guided prostate biopsy. The quality of rectal preparation should be evaluated before biopsy. If adequate rectal preparation is not achieved, postponing the biopsy and adjusting the rectal preparation regimen are suggested.

Background: Acute-on-chronic hepatitis B liver failure (ACHBLF) is an acute deteriorating liver disease and rapidly progresses to multiple organ failure. There is currently no adequate accurate predictive models of ACHBLF prognosis. Aims: To identify the methylation frequency of the estrogen receptor 1 (ESR1) promoter in ACHBLF and analyze the associated prognostic significance. Methods: Methylation-specific PCR (MSP) was used to determine the methylation frequency of the ESR1 promoter in peripheral blood mononuclear cells from a training and validation cohort of patients. The training cohort included 113 patients with ACHBLF, 73 with chronic hepatitis B (CHB) and 40 healthy controls (HCs). The validation cohort consisted of 37 patients with ACHBLF. Another 18 patients with pre-ACHBLF who progressed to ACHBLF were used to dynamically evaluate ESR1 promoter methylation changes associated with a severe clinical condition. Results: Death from ACHBLF was associated with hyperbilirubinemia, a higher score in the model for end-stage liver disease (MELD), a higher incidence of hepatic encephalopathy (HE) and an increased frequency of ESR1 promoter methylation during the 28 day follow-up. HE, MELD score and ESR1 promoter methylation were the independent risk factors associated with 28-day mortality from ACHBLF. The frequency of ESR1 promoter methylation was significantly higher than in patients with CHB and HCs. Albumin and the MELD score were significantly associated with ESR1 promoter methylation. Moreover, ESR1 promoter methylation frequency increased with ACHBLF progression. More importantly, ESR1 promoter methylation was an independent risk factor and had a high value to predict 28-day mortality from ACHBLF. Conclusions: Abnormal ESR1 methylation could be a prognostic biomarker for ACHBLF.

ABSTRACT With the acceleration of urbanization and industrialization, urban air pollution has become a serious threat to the health of urban residents. In this study, to investigate health hazards caused by air pollution for urban residents, concentrations of main air pollutants and annual coal consumption amounts during the period from 2000 to 2013 were analyzed. Our results showed that economic losses of Urumqi caused by air pollution amounted to 63.155 million yuan in 2013, accounting for 0.2 ‰ of its GDP and 5.7% of public utility expenditures for that year. The compensation mechanism analysis suggested that it is necessary to further improve the health care system and increase corporate environmental taxes. More environmental health protection taxes should be levied on key monitoredenterprises in Urumqi to achieve effective compensations for urban residents affected by air pollution-related health hazards.

Um método in situ de microextração líquido-líquido dispersiva com líquidos iônicos (IL-DLLME) foi desenvolvido como uma nova abordagem para a detecção de quatro pesticidas piretróides em amostras de água do ambiente. O método é simples, rápido, preciso e ambientalmente amigável. O líquido iônico hidrofóbico, [C8MIM]-NTf2, formado pelo líquido iônico solúvel em água [C8MIM]Cl e o reagente de troca iônica LiNTf2 foi usado como solvente de extração. Os parâmetros experimentais que influenciam a eficiência de extração, incluindo a quantidade de líquido iônico (IL), a extração e tempos de centrifugação e a concentração de sal foram investigados e otimizados utilizando um design com matriz ortogonal (OAD). A razão molar adequada do LiNTf2 para [C8MIM]Cl nas recuperações de analitos foi determinada após otimização do OAD. O método mostrou uma boa resposta linear no intervalo de 0,5 a 500 µg L-1 com coeficientes de correlação (R²) acima de 0,9998. O desvio padrão relativo (RSD) variou de 0,6 a 1,9%. O fator de enriquecimento, o limite de detecção e recuperação variaram de 134 a 153, 0,02 a 0,18 µg L-1 e de 89,7 a 95,6%, respectivamente. Para as amostras de água, o RSD variou entre 0,02 e 2,34% e a recuperação variou de 91,4 a 99,9%.

An in situ ionic liquid dispersive liquid-liquid microextraction (IL-DLLME) method was developed as a new approach for the detection of four pyrethroid pesticides in environmental water samples. The method is fast, simple, accurate and environmentally friendly. The hydrophobic ionic liquid, [C8MIM]-NTf2, formed by the water-soluble ionic liquid [C8MIM]Cl and the ion exchange reagent LiNTf2 was used as the extraction solvent. The experimental parameters affecting the extraction efficiency, including the amount of the IL, the extraction and the centrifugation times and the salt concentration were investigated and optimized using an orthogonal array design (OAD). A suitable molar ratio of LiNTf2 to [C8MIM]Cl on the recoveries of analytes was determined after OAD optimization. The method showed a good linear response in the range of 0.5 to 500 µg L-1 with correlation coefficients (R²) above 0.9998. The relative standard deviation (RSD) varied from 0.6 to 1.9%. The enrichment factor, the limit of detection and recovery ranged from 134 to 153, 0.02 to 0.18 µg L-1 and 89.7 to 95.6%, respectively. For water samples, the RSD ranged from 0.02 to 2.34% and the recovery ranges from 91.4 to 99.9%.

OBJECTIVE: To estimate the occurrence and school-level clustering of drug involvement among school-attending adolescent youths in each of seven countries in Latin America, drawing upon evidence from the PACARDO research project, a multinational collaborative epidemiological research study. METHODS: During 1999-2000, anonymous self-administered questionnaires on drug involvement and related behaviors were administered to a cross-sectional, nationally representative sample that included a total of 12 797 students in the following seven countries: Costa Rica (n= 1 702), the Dominican Republic (n= 2 023), El Salvador (n= 1 628), Guatemala (n= 2 530), Honduras (n= 1 752), Nicaragua (n= 1 419), and Panama (n= 1 743). (The PACARDO name concatenates PA for Panamá,CA for Centroamérica,and RDO for República Dominicana). Estimates for exposure opportunity and actual use of alcohol, tobacco, inhalants, marijuana, cocaine (crack/coca paste), amphetamines and methamphetamines, tranquilizers, ecstasy, and heroin were assessed via responses about questions on age of first chance to try each drug, and first use. Logistic regression models accounting for the complex survey design were used to estimate the associations of interest. RESULTS: Cumulative occurrence estimates for alcohol, tobacco, inhalants, marijuana, and illegal drug use for the overall sample were, respectively: 52%, 29%, 5%, 4%, and 5%. In comparison to females, males were more likely to use alcohol, tobacco, inhalants, marijuana, and illegal drugs; the odds ratio estimates were 1.3, 2.1, 1.6, 4.1, and 3.2, respectively. School-level clustering was noted in all countries for alcohol and tobacco use; it was also noted in Costa Rica, El Salvador, Guatemala, and Panama for illegal drug use. CONCLUSIONS: This report sheds new light on adolescent drug experiences in Panama, the five Spanish-heritage countries of Central America, and the Dominican Republic, and presents the first estimates of school-level clustering of youthful drug involvement in these seven countries. Placed in relation to school survey findings from North America and Europe, these estimates indicate lower levels of drug involvement in these seven countries of the Americas. For example, in the United States of America 70% of surveyed youths had tried alcohol and 59% had smoked tobacco. By comparison, in these seven countries, only 51% have tried alcohol and only 29% have smoked tobacco. Future research will help to clarify explanations for the observed variations across different countries of the world. In the meantime, strengthening of school-based and other prevention efforts in the seven-country PACARDO area may help these countries slow the spread of youthful drug involvement, reduce school-level clustering, and avoid the periodic epidemics of illegal drug use that have been experienced in North America.

OBJETIVO: Estimar el grado en que el consumo de drogas se produce y muestra una concentración en el nivel escolar entre adolescentes que asisten a la escuela en siete países de América Latina. Los datos presentados provienen del proyecto de investigación PACARDO, estudio epidemiológico conjunto multinacional. MÉTODOS: En el período de 19992000, se aplicaron cuestionarios anónimos autoadministrados sobre el consumo de drogas y conductas afines a una muestra transversal, representativa de la población nacional, que se compuso de un total de 12 797 estudiantes en los siguientes siete países: Costa Rica (n = 1 702), El Salvador (n = 1 628), Guatemala (n = 2 530), Honduras (n = 1 752), Nicaragua (n = 1 419), República Dominicana (n = 2 023) y Panamá (n = 1 743). (El nombre de PACARDO combina la PA de Panamá, la CA de Centroamérica y la RDO de República Dominicana). Se calcularon las oportunidades de exposición y el consumo de alcohol, tabaco, sustancias inhaladas, marijuana, cocaína (crack/pasta de cocaína), anfetaminas y metaanfetaminas, tranquilizantes, éxtasis y heroína sobre la base de las respuestas dadas a preguntas acerca de la edad en que se tuvo la oportunidad de probar cada una de las drogas, y en que se probó cada una de ellas, por primera vez. Para estimar las asociaciones de interés se aplicaron modelos de regresión logística con arreglo a la complejidad de la encuesta. RESULTADOS: Las siguientes fueron las frecuencias estimadas acumulativas del consumo de alcohol, tabaco, sustancias inhaladas, marijuana y drogas, respectivamente, en toda la muestra: 52%, 29%, 5%, 4% y 5%. Comparados con las mujeres, los varones fueron más propensos a consumir alcohol, tabaco, sustancias inhaladas, marijuana y drogas; las razones de posibilidades estimadas fueron, respectivamente, 1,3; 2,1; 1,6; 4,1 y 3,2. En todos los países se observó una concentración del consumo de alcohol y tabaco en el nivel escolar; el consumo ilegal de drogas también mostró una concentración escolar en Costa Rica, El Salvador, Guatemala y Panamá. CONCLUSIONES: Este informe arroja nueva luz sobre las experiencias de los adolescentes con la droga en Panamá, en los cinco países centroamericanos de tradición española, y en la República Dominicana. En él se presentan las primeras estimaciones del grado en que se concentra en las escuelas el consumo de drogas entre la juventud de estos siete países. Cuando se examinan a la luz de los resultados de encuestas escolares en América del Norte y en Europa, estas estimaciones apuntan a que el grado de consumo de drogas es más bajo en estos siete países americanos. Por ejemplo, en los Estados Unidos de América, 70% de los jóvenes encuestados habían consumido alcohol y 59% habían fumado tabaco. En cambio, en estos siete países, solamente 51% habían probado bebidas alcohólicas y solo 29% habían fumado tabaco. Futuras investigaciones ayudarán a explicar las variaciones observadas en los distintos países del mundo. En el entretiempo, el fortalecimiento de las iniciativas preventivas en las escuelas y otros ámbitos en el territorio de los siete países donde se lleva a cabo el proyecto PACARDO podría ayudar a estos países a frenar la diseminación del consumo de drogas entre la juventud, a reducir su concentración en las escuelas y a evitar las epidemias periódicas del consumo de drogas que se han producido en América del Norte.