Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be elucidated. Serum creatinine (SCr) and blood urea nitrogen (BUN) were detected through pathological evaluation after CTD (1.5 mg/kg) oral gavage in mice in 3 days. Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate lipids disorder after CTD exposure in mice. Then, spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to detect the kidney spatial distribution of lipids. Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro. The results showed that the levels of SCr and BUN were increased, and tubular necrosis was observed in mouse kidneys, resulting in acute tubular necrosis (ATN) in CTD-induced AKI. Then, lipidomics results revealed that after CTD exposure, 232 differential lipid metabolites and 11 pathways including glycerophospholipid (GP) and sphingolipid (SL) metabolism were disrupted. Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed. Subsequently, integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla, whereas SL metabolism was inhibited in the renal cortex. Up-regulated lysophosphatidylcholine (LysoPC) (18:2(9Z,12Z)), LysoPC (16:0/0:0), glycerophosphocholine, and down-regulated sphingomyelin (SM) (d18:0/16:0), SM (d18:1/24:0), and SM (d42:1) were key differential lipids. Among them, LysoPC (16:0/0:0) was increased in the CTD group at 1.1196 μg/mL, which aggravated CTD-induced ATN in human kidney-2 (HK-2) cells. LysoPC acyltransferase was inhibited and choline phosphotransferase 1 (CEPT1) was activated after CTD intervention in mice and in HK-2 cells. CTD induces ATN, resulting in AKI, by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla, LysoPC (16:0/0:0), LysoPC acyltransferase, and CEPT1 may be the therapeutic targets.

OBJECTIVE: To explore the toxicological mechanism of drug-induced liver injury(DILI) in rats induced by cantharidin(CTD). METHODS: SD rats were exposed to different doses of CTD(0.061 4, 0.092 1, 0.184 1 mg·kg−1) by oral gavage for 28 d. Liver index and serum liver function indictors were detected. HE staining was used to evaluate the pathological changes of liver. Then the proteins in endoplasmic reticulum stress(ERS), autophagy, and apoptosis-pathway were detected by Western blotting. RESULTS: The liver index was increased in CTD groups. The ALT, AST, LDH, ALP and T-Bil were increased by CTD with a dose-dependent manner. Disrupted hepatic architecture and dilatation of central vein were observed after CTD intervention. The protein expression levels of GRP78, CHOP, ATF4, Beclin-1, LC3, Caspase-3, Caspase-8, and Bax/Bcl-2 were increased after CTD intervention. Molecular docking results revealed that GRP78, ATF4, and Beclin-1 could directly interconnect with CTD. CONCLUSION CTD can activate ERS, autophagy and synergistically inducing downstream apoptosis in rat, providing a novel insight into the mechanism of CTD-induced DILI.

OBJECTIVETo predict the burden caused by fatal road traffic injuries from 2015 to 2030.

METHODSWe searched the websites of United Nations Population Division,United States Department of Agriculture, World Health Organization, China Energy Research Foundation and other agencies to obtain the predictive values of gross domestic product (GDP) per capita, urbanization, motorization and education from 2015 to 2030 in China. Predicted values were then applied to log-linear models to estimate the numbers and years of life lost due to road traffic injuries from 2015 to 2030.

RESULTSThe mortality rate caused by road traffic injury decreased slightly, from 13.7/100 000 in 2015 to 11.8/100 000 in 2030. 191, 189, 183, 169 thousand persons were estimated to die from road traffic crashes in 2015, 2020, 2025 and 2030, respectively, showing a declining trend. Years of Life Lost (YLLs) caused by road traffic deaths were predicted to be 6 918, 6 634, 6 189, 5 513 thousand years in 2015, 2020, 2025 and 2030, respectively, also showing a gradual downward trend. But the YLLs displayed an increase among people at 55 years of age or older, between 2015 and 2030. Results from the sensitivity analysis showed a stable forecasting result.

CONCLUSIONMortality, number of deaths and YLLs from road traffic crashes were predicted to decrease slightly, between 2015 and 2030 but the number of deaths and YLLs due to road traffic injuries will continue to increase from 2015 to 2030.

Accidents, Traffic ; mortality ; Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; epidemiology ; Cost of Illness ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Young Adult

Objective To predict the burden caused by fatal road traffic injuries from 2015 to 2030. Methods We searched the websites of United Nations Population Division,United States Department of Agriculture,World Health Organization,China Energy Research Foundation and other agencies to obtain the predictive values of gross domestic product(GDP)per capita,urbanization, motorization and education from 2015 to 2030 in China. Predicted values were then applied to log-linear models to estimate the numbers and years of life lost due to road traffic injuries from 2015 to 2030. Results The mortality rate caused by road traffic injury decreased slightly,from 13.7/100 000 in 2015 to 11.8/100 000 in 2030. 191,189,183,169 thousand persons were estimated to die from road traffic crashes in 2015,2020,2025 and 2030,respectively,showing a declining trend. Years of Life Lost(YLLs)caused by road traffic deaths were predicted to be 6 918,6 634,6 189,5 513 thousand years in 2015,2020,2025 and 2030,respectively,also showing a gradual downward trend. But the YLLs displayed an increase among people at 55 years of age or older,between 2015 and 2030. Results from the sensitivity analysis showed a stable forecasting result. Conclusion Mortality, number of deaths and YLLs from road traffic crashes were predicted to decrease slightly,between 2015 and 2030 but the number of deaths and YLLs due to road traffic injuries will continue to increase from 2015 to 2030.

OBJECTIVE: To determine the prevalence and incidence of illness of two-week duration, and the factors influencing these, among residents 15 years and older in four counties of Hunan Province. METHODS: Data were sampled from four counties of Hunan Province for the Fourth National Health Service Survey. Incidence and two-week prevalence of disease were used to assess the health service needs of residents. A non-conditional, stepwise logistic regression was employed to explore the influencing factors. RESULTS: The two-week prevalence and incidence were 11.5% and 3.9%, respectively, in four counties of Hunan. The three leading diseases of two-week prevalence were: respiratory diseases, digestive diseases, and musculoskeletal diseases. Non-conditional stepwise logistic regression showed that urban residents had 0.64 times the risk of two-week illness compared with the rural residents (P< 0.05); residents in the 45-59 year age group and the 60+ year age group had 1.69 and 2.62 times the risk of two-week illness compared with residents in the 15-44 year age group, respectively (P<0.05). The widowed had 1.91 times the risk of prevalence of two-week illness contrasted to singles (P<0.05); the students had 0.29 times the risk of two-week illness contrasted to the workers (P<0.05); urban residents had 0.63 times the risk of two-week illness compared with the rural (P<0.05); the widowed had 2.37 times the risk of incidence of two-week illness compared with singles (P<0.05). CONCLUSION The majority of health service needs of residents of four counties is generated by three diseases: respiratory diseases, digestive diseases, and musculoskeletal diseases. Relatively, rural residents, the elderly, employed persons and the widowed have higher health service needs than others and deserve specific attention.
Adolescent ; Adult ; Aged ; China ; epidemiology ; Community Health Services ; statistics & numerical data ; Digestive System Diseases ; epidemiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Musculoskeletal Diseases ; epidemiology ; Respiratory Tract Diseases ; epidemiology ; Sampling Studies ; Surveys and Questionnaires ; Young Adult