The renal tubular organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1) mediate the vectorial elimination of many drugs and toxins from the kidney, and endogenous biomarkers for vectorial transport (OCT2-MATE1) would allow more accurate drug dosing and help to characterize drug-drug interactions and toxicity. Human serum uptake in OCT2-overexpressing cells and metabolomics analysis were carried out. Potential biomarkers were verified in vitro and in vivo. The specificity of biomarkers was validated in renal transporter overexpressing cells and the sensitivity was investigated by Km. The results showed that the uptake of thiamine, histamine, and 5-hydroxytryptamine was significantly increased in OCT2-overexpressing cells. In vitro assays confirmed that thiamine, histamine, and 5-hydroxytryptamine were substrates of both OCT2 and MATE1. In vivo measurements indicated that the serum thiamine level was increased significantly in the presence of the rOCT2 inhibitor cimetidine, and the level in renal tissue was increased significantly by the rMATE1 inhibitor pyrimethamine. There were no significant changes in the uptake or efflux of thiamine in cell lines overexpressed OAT1, OAT2, OAT3, MRP4, organic anion transporting polypeptide 4C1, P-gp, peptide transporter 2, urate transporter 1, and OAT4. The Km for thiamine with OCT2 and MATE1 were 71.2 and 10.8 mu M, respectively. In addition, the cumulative excretion of thiamine at 2 and 4 h was strongly correlated with metformin excretion (R2 > 0.6). Thus, thiamine is preferentially secreted by the OCT2 and MATE1 in renal tubules and can provide a reference value for evaluating the function of the renal tubular OCT2-MATE1.

Renal tubular secretion mediated by organic anion transporters (OATs) and the multidrug resistance-associated protein 4 (MRP4) is an important means of drug and toxin excretion. Unfortunately, there are no biomarkers to evaluate their function. The aim of this study was to identify and characterize an endogenous biomarker of the renal tubular OATs-MRP4 channel. Twenty-six uremic toxins were selected as candidate compounds, of which kynurenic acid was identified as a potential biomarker by assessing the protein-binding ratio and the uptake in OAT1-, OAT3-, and MRP4-overexpressing cell lines. OAT1/3 and MRP4 mediated the transcellular vectorial transport of kynurenic acid in vitro. Serum kynurenic acid concentration was dramatically increased in rats treated with a rat OAT1/3 (rOAT1/3) inhibitor and in rOAT1/3 double knockout (rOAT1/3-/-) rats, and the renal concentrations were markedly elevated by the rat MRP4 (rMRP4) inhibitor. Kynurenic acid was not filtered at the glomerulus (99% of albumin binding), and was specifically secreted in renal tubules through the OAT1/3-MRP4 channel with an appropriate affinity (Km) (496.7 mM and 382.2 mM for OAT1 and OAT3, respectively) and renal clearance half-life (t1/2) in vivo (3.7 +/- 0.7 h). There is a strong correlation in area under the plasma drug concentration-time curve (AUC0-t) between cefmetazole and kynurenic acid, but not with creatinine, after inhibition of rOATs. In addition, the phase of increased kynurenic acid level is earlier than that of creatinine in acute kidney injury process. These results suggest that albumin-bound kynurenic acid is an appropriate endogenous biomarker for adjusting the dosage of drugs secreted by this channel or predicting kidney injury.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of Xi'an Jiaotong University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Aim: Although Cognitive behavioural therapy (CBT) potentially holds efficacy in addressing functional abdominal pain disorders (FAPDs) amongst children and adolescents, the persistent efficacy is uncertain.Methods: We searched three databases to identify related randomized controlled trials (RCTs). Meta-analysis was performed using RevMan and Stata. Subgroup analyses were mainly conducted based on follow-up time. The GRADE approach was used to evaluate the certainty of the evidence.Results: A total of 14 RCTs evaluating 858 patients were included. All RCTs were rated as having a high risk of bias. Compared with control groups, CBT was associated with improvement of general functional impairment (standardized mean difference (SMD) = -0.77, 95% CI [-1.12, -0.42], p < 0.05), higher treatment success (relative risk (RR) = 2.35, 95% CI [1.50, 3.69], p < 0.05), improvement of abdominal pain symptoms (SMD = -0.48, 95% CI [-0.73, -0.23], p < 0.05), QoL (SMD = 0.42, 95% CI [0.20, 0.64], p < 0.05), and psychological states (SMD = -0.95, 95% CI [-1.62, -0.27], p < 0.05).Conclusion: This meta-analysis provides low to moderate quality evidence that CBT could significantly improve clinical outcomes and QoL for children and adolescents with FAPDs with improvement persisting until short-term follow-up. However, there were discrepancies regarding CBT's effects at mid- and long-term follow-up across different outcomes. More high-quality and longer-duration studies are thus warranted to explore the effectiveness of CBT in the future.

Background and objectives: Selenium deficiency is a primary risk factor of Kashin-Beck disease (KBD). This study aimed to investigate whether children in endemic areas could maintain sufficient selenium intake after termination of selenium supplement administration, and evaluate their comprehensive nutritional status and dietary structure. Methods: Duplicate portion sampling combined with a questionnaire was adopted to collect data on categories and quantity of all food ingested in three consecutive days. Occipital hair was also collected to detect selenium content by hydride generation atomic fluorescence spectrometry (HGAFS). CDGSS3.0 software and factor analysis were integrated to assess the children's comprehensive nutritional status and dietary structure. Results: This study included 240 sex-matched (1:1) children aged 7-12 years from KBD endemic (n = 120) and non-endemic (n = 120) areas. Overall, 720 solid food, 720 liquid, and 240 hair samples were collected for selenium determination. The mean selenium level in hair of children in endemic areas (0.38 +/- 0.16 mg/kg) was significantly lower than that in children in non-endemic areas (0.56 +/- 0.28 mg/kg, Z =-5.249, p < 0.001). The dietary selenium intake of children in endemic areas was 40.0% lower than that in children in non-endemic areas (Z =-9.374, p < 0.001). Children in endemic areas consumed significantly less diverse dietary items leading to significantly less intake of multiple nutrients compared to children in non-endemic areas. Conclusions: The dietary selenium intake of most children in endemic areas was less than the recommended amount. The dietary structure of children was undiversified, which limited the intake of multiple nutrients. Therefore, comprehensive nutrition rather than sole selenium intake should be the primary concern in the future.

Objective Adverse health effects of fine particles (particulate matter2.5) have been well documented by a series of studies. However, evidences on the impacts of black carbon (BC) or elemental carbon (EC) on health are limited. The objectives were (1) to explored the effects of BC and EC on cardiovascular and respiratory morbidity and mortality, and (2) to verified the reliability of the meta-analysis by drawing p value plots. Design The systematic review and meta-analysis using adapted Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and p value plots approach. Data sources PubMed, Embase and Web of Science were searched from inception to 19 July 2021. Eligibility criteria for selecting studies Time series, case cross-over and cohort studies that evaluated the associations between BC/EC on cardiovascular or respiratory morbidity or mortality were included. Data extraction and synthesis Two reviewers independently selected studies, extracted data and assessed risk of bias. Outcomes were analysed via a random effects model and reported as relative risk (RR) with 95% CI. The certainty of evidences was assessed by adapted GRADE. The reliabilities of meta-analyses were analysed by p value plots. Results Seventy studies met our inclusion criteria. (1) Short-term exposure to BC/EC was associated with 1.6% (95% CI 0.4% to 2.8%) increase in cardiovascular diseases per 1 µg/m3 in the elderly; (2) Long-term exposure to BC/EC was associated with 6.8% (95% CI 0.4% to 13.5%) increase in cardiovascular diseases and (3) The p value plot indicated that the association between BC/EC and respiratory diseases was consistent with randomness. Conclusions Both short-term and long-term exposures to BC/EC were related with cardiovascular diseases. However, the impact of BC/EC on respiratory diseases did not present consistent evidence and further investigations are required. PROSPERO registration number CRD42020186244.

Objective Adverse health effects of fine particles (particulate matter(2.5)) have been well documented by a series of studies. However, evidences on the impacts of black carbon (BC) or elemental carbon (EC) on health are limited. The objectives were (1) to explored the effects of BC and EC on cardiovascular and respiratory morbidity and mortality, and (2) to verified the reliability of the meta-analysis by drawing p value plots. Design The systematic review and meta-analysis using adapted Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and p value plots approach. Data sources PubMed, Embase and Web of Science were searched from inception to 19 July 2021. Eligibility criteria for selecting studies Time series, case cross-over and cohort studies that evaluated the associations between BC/EC on cardiovascular or respiratory morbidity or mortality were included. Data extraction and synthesis Two reviewers independently selected studies, extracted data and assessed risk of bias. Outcomes were analysed via a random effects model and reported as relative risk (RR) with 95% CI. The certainty of evidences was assessed by adapted GRADE. The reliabilities of meta-analyses were analysed by p value plots. Results Seventy studies met our inclusion criteria. (1) Short-term exposure to BC/EC was associated with 1.6% (95% CI 0.4% to 2.8%) increase in cardiovascular diseases per 1 mu g/m(3) in the elderly; (2) Long-term exposure to BC/EC was associated with 6.8% (95% CI 0.4% to 13.5%) increase in cardiovascular diseases and (3) The p value plot indicated that the association between BC/EC and respiratory diseases was consistent with randomness. Conclusions Both short-term and long-term exposures to BC/EC were related with cardiovascular diseases. However, the impact of BC/EC on respiratory diseases did not present consistent evidence and further investigations are required. PROSPERO registration number CRD42020186244.

The relationship between diabetes mellitus and short-term exposure to extreme temperatures remains controversial. A systematic review and meta-analysis were performed to assess the association between extreme temperatures and diabetes mellitus morbidity and mortality. PubMed, Embase, the Cochrane Library, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched since inception to January 1, 2019, and updated on November 17, 2020. The results were combined using random effects model and reported as relative risk (RR) with 95% confidence interval (CI). In total, 32 studies met the inclusion criteria. (1) Both heat and cold exposures have impact on diabetes. (2) For heat exposure, the subgroup analysis revealed that the effect on diabetes mortality (RR=1.139, 95% CI: 1.089–1.192) was higher than morbidity (RR=1.012, 95% CI: 1.004–1.019). (3) With the increase of definition threshold, the impact of heat exposure on diabetes rose. (4) A stronger association between heat exposure and diabetes was observed in the elderly (≥ 60 years old) (RR=1.040, 95% CI: 1.017–1.064). In conclusion, short-term exposure to both heat and cold temperatures has impact on diabetes. The elderly is the vulnerable population of diabetes exposure to heat temperature. Developing definitions of heatwaves at the regional level are suggested.

Research indicates that air pollution is a risk factor of an increased occurrence of diseases. However, evidence is limited on the effects of the pollution index on disease and whether temperature modifies the effects. The objectives were (i) to explore the effects of the Air Pollution Index (API) and specific indices for pollutants (PM 10 , NO 2 , and SO 2 ) on respiratory emergency department (ED) visits in Beijing and (ii) to investigate whether temperature modified the effects of main air pollutants on respiratory ED visits. A quasi-Poisson generalized additive model was employed to examine the association of API and indices for pollutants with respiratory disease. Bivariate response surface model and stratification model (cold days, moderately cold days, moderately hot days, and hot days) were used to analyze the modification effects of temperature on air pollution and respiratory disease. The results showed that (i) the effects of API on respiratory diseases were similar to the index for PM 10 in Beijing. (ii) API and PM 10 were associated with increased respiratory ED visits on cold days and moderately cold days. Furthermore, the effects of PM 10 on respiratory disease on moderately cold days [Relative risk (RR) = 1.006 per 10 μg/m 3 , 95% CI 1.002–1.009] were stronger than on cold days (RR = 1.004 per 10 μg/m 3 , 95% CI 1.000–1.008). (iii) PM 10 (API) had a greater impact on children aged 10 to 17 years and females on moderately cold days, while the elderly had an increased risk of respiratory disease to PM 10 (RR = 1.008 per 10 μg/m 3 , 95% CI 1.002–1.013) and API (RR = 1.013 per 10, 95% CI 1.004–1.022) on cold days. In conclusion, temperature can modify the association between API and respiratory morbidity. A stronger correlation existed between PM 10 and respiratory diseases on moderately cold days, while the effects of cold days were less than that attributable to moderately cold days.

With the World Bank Database's data of 217 countries from the year of 2000 to 2019, this paper conduct a dynamic panel model using the fixed effect estimation, random effect estimation and generalized moment estimation method to explore the relationship between technological progress and income gap. The results show that the technology can reduce the income gap. In addition, in order to get robust estimation, this paper also takes regional average level of technology as the instrumental variable to confirm this negative relationship. In order to narrow the income gap, this paper suggests that we should focus on promoting the development of social tertiary industry and high-tech industry and pay more attention to education expenditure in the distribution policy.