Background: High sodium intake is a crucial risk factor for the development and progression of chronic kidney disease (CKD). However, the latest global spatiotemporal patterns of CKD burden attributable to high sodium intake still remain unclear. We aimed to evaluate the level and trends of the CKD burden associated with high sodium intake according to sex, age, socio-demographic index (SDI), region, and country from 1990 to 2019.Methods: Data on CKD burden attributable to high sodium intake from 1990 to 2019 were extracted from the Global Burden of Disease (GBD) Study 2019. The CKD-related deaths, disability-adjusted life years (DALYs), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR) attributable to high sodium intake were estimated by age, sex, SDI, region, and country. The estimated annual percentage change (EAPC) was calculated to evaluate the secular trends of ASMR and ASDR of CKD attributable to high sodium intake from 1990 to 2019. We further explored the associations of SDI with the ASMR and ASDR of CKD attributable to high sodium intake.Results: Globally, the number of CKD-related deaths and DALYs attributable to high sodium intake were 45,530 (95% UI: 12,640 to 93,830) and 1.32 million (95% UI: 0.43 to 2.8) in 2019, both twice as many as those in 1990. However, the ASMR and ASDR slightly grew, with an EAPC of 0.22 (95% CI: 0.16 to 0.28) and 0.10 (95% CI: 0.04 to 0.16), respectively. The age-specific numbers and rates of deaths, as well as DALYs of CKD attributable to high sodium intake, rose with age and were greater in males than in females. The rates of deaths and DALYs peaked in the >95 age group for both females and males in 2019. From 1990 to 2019, the trends of both age-specific rates of mortality and DALYs of CKD attributable to high sodium intake were down in people under 60, while in people over 60, the trends were the opposite. The burden of CKD attributable to high sodium intake in 2019 and its temporal trends from 1990 to 2019 varied greatly by SDI quintile and geographic location. The ASMR or ASDR showed a non-linear negative correlation with SDI at the regional level. The EAPC in ASMR or ASDR showed a markedly negative correlation with ASMR or ASDR in 1990, with a coefficient of −0.40. Nevertheless, the EAPC in ASMR rather than ASDR was positively correlated with SDI in 2019, with a coefficient of 0.18.Conclusion: Our findings suggest that there are significant sexual and geographic variations in the burden of CKD attributable to high sodium intake and its temporal trends. Globally, the high sodium intake-caused CKD burden continues to elevate, posing a major challenge to public health. In response to this, strengthened and tailored approaches for CKD prevention and sodium intake management are needed, especially for elderly populations, males, and the population in the middle SDI regions.

Central post-stroke pain (CPSP) is an intractable neuropathic pain, which can be caused by primary lesion of central somatosensory system. It is also a common sequelae of the thalamic hemorrhagic stroke (THS). So far, the underlying mechanisms of CPSP remain largely unknown. Our previous studies have demonstrated that SDF1-CXCR4 signaling in the hemorrhagic region contributes to the maintenance of the THS pain hypersensitivity via mediation of the thalamic neuroinflammation. But whether the spinal dorsal horn, an initial point of spinothalamic tract (STT), suffers from retrograde axonal degeneration from the THS region is still unknown. In this study, neuronal degeneration and loss in the spinal dorsal horn were detected 7 days after the THS caused by intra-thalamic collagenase (ITC) injection by immunohistochemistry, TUNEL staining, electron microscopy, and extracellular multi-electrode array (MEA) recordings, suggesting the occurrence of secondary apoptosis and death of the STT projecting neuronal cell bodies following primary THS via retrograde axonal degeneration. This retrograde degeneration was accompanied by secondary neuroinflammation characterized by an activation of microglial and astrocytic cells and upregulation of SDF1-CXCR4 signaling in the spinal dorsal horn. As a consequence, central sensitization was detected by extracellular MEA recordings of the spinal dorsal horn neurons, characterized by hyperexcitability of both wide dynamic range and nociceptive specific neurons to suprathreshold mechanical stimuli. Finally, it was shown that suppression of spinal neuroinflammation by intrathecal administration of inhibitors of microglia (minocycline) and astrocytes (fluorocitrate) and antagonist of CXCR4 (AMD3100) could block the increase in expression levels of Iba-1, GFAP, SDF1, and CXCR4 proteins in the dorsal spinal cord and ameliorate the THS-induced bilateral mechanical pain hypersensitivity, implicating that, besides the primary damage at the thalamus, spinal secondary damage and neuroinflammation also play the important roles in maintaining the central post-THS pain hypersensitivity. In conclusion, secondary neuronal death and neuroinflammation in the spinal dorsal horn can be induced by primary thalamic neural damage via retrograde axonal degeneration process. SDF1-CXCR4 signaling is involved in the mediation of secondary spinal neuroinflammation and THS pain hypersensitivity. This finding would provide a new therapeutic target for treatment of CPSP at the spinal level.

Background: Pre-operative risk scores are more valuable than post-procedure risk scores because of lacking effective treatment for contrast-induced acute kidney injury (CI-AKI). A number of pre-operative risk scores have been developed, but due to lack of effective external validation, most of them are also difficult to apply accurately in clinical practice. It is necessary to review and validate the published pre-operative risk scores for CI-AKI.Materials and methods: We systematically searched PubMed and EMBASE databases for studies of CI-AKI pre-operative risk scores and assessed their calibration and discriminatory in a cohort of 2669 patients undergoing coronary angiography or percutaneous coronary intervention (PCI) from September 2007 to July 2017. The definitions of CI-AKI may affect the validation results, so three definition were included in this study, CI-AKI broad1 was defined as an increase in serum creatinine (Scr) of 44.2 μmol/L or 25%; CI-AKI broad2, an increase in Scr of 44.2 μmol/L or 50%; and CI-AKI-narrow, an increase in Scr of 44.2 μmol/L. The calibration of the model was assessed with the Hosmer-Lemeshow test and the discriminatory capacity was identified by C-statistic.Results: Of the 8 pre-operative risk scores for CI-AKI identified, 7 were single-center study and only 1 was based on multi-center study. In addition, 7 of the scores were just validated internally and only Chen score was externally validated. In the validation cohort of 2669 patients, the incidence of CI-AKI ranged from 3.0%(Liu) to 16.4%(Chen) for these scores. Furthermore, the incidence of CI-AKI was 6.59% (178) for CI-AKI broad1, 1.44% (39) for CI-AKI broad2, and 0.67% (18) for CI-AKI-narrow. For CI-AKI broads, C-statistics varied from 0.44 to 0.57. For CI-AKI-narrow, the Maioli score had the best discrimination and calibration, what’s more, the C-statistics of Maioli, Chen, Liu and Ghani was ≥0.7.Conclusion: Most pre-operative risk scores were established based on single-center studies and most of them lacked external validation. For CI-AKI broads, the prediction accuracy of all risk scores was low. The Maioli score had the best discrimination and calibration, when using the CI-AKI-narrow definition.

High levels of low-density lipoprotein cholesterol (LDL-C) can lead to the occurrence and development of atherosclerosis, which is one of the important risk factors for ischemic stroke (IS). However, details regarding the evolution of the IS burden attributable to high LDL-C in China has not been available. The objective of this study was to examine the changes over time, from 1990 to 2019, in the burden of IS attributed to high levels of LDL-C in China and to estimate the individual impacts of age, period, and cohort on the burden of IS associated with high LDL-C. Detailed data on IS burden attributable to high LDL-C from 1990 to 2019 in China were extracted from the Global Burden of Disease (GBD) Study 2019. The numbers and age-standardized rates of IS-related mortality and disability-adjusted life years (DALYs) attributable to high LDL-C were assessed by age and sex. The annual percentage change (APC) and average annual percentage change (AAPC) in the burden of IS due to high LDL-C were analyzed using Joinpoint regression model. The age-period-cohort analysis was carried out to assess the individual impacts of age, period, and cohort on the trends over time of mortality and DALY rate. The number of IS-related deaths and DALYs due to high LDL-C in China were 182.7 thousand and 4.43 million in 2019, respectively, both more than double the corresponding numbers reported in 1990. However, despite these increased, the age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) remained unchanged. In 2019, men under 84 years of age had higher death and under 79 years of age had higher DALYs than women. However, above these ages, the gender disparities were reversed. Furthermore, age-specific rates of death, as well as DALY of IS attributable to high LDL-C in 2019 increased with age for both women and men, except for death in adults over 95 years old; and were greater in men than in women. From 1990 to 2019, males consistently had a higher ASMR and ASDR than females in China. During 1990–2019, the ASMR in women slightly decreased before 1997, sharply increased from 1997 to 2004, and then continuously decreased from 2004 to 2019, with an overall AAPC value of -0.4% (95% CI -0.8%, -0.0%). However, for the ASMR of men in China, the overall trend is upward and the AAPC is 0.5%(95% CI 0.1%, 0.8%). The ASDR in women and men had the similar trend as the ASMR over the time, with an AAPC of -0.4% (95% CI -0.7%, -0.1%) and 0.3% (95% CI 0.1%, 0.5%), respectively. The age-period-cohort analysis indicated a rise in period effects and a decline in cohort effects on mortality and DALY rate associated with IS caused by high LDL-C in both genders. Age effect on mortality rates from IS due to high LDL-C showed an exponential increased with age in all women and men except for the 60–69 age group and over 95 age group. The age relative risk of IS DALY rate due to high LDL-C increased with age in both genders except for 65–74 age group and over 95 age group. From 1990 to 2019, the burden of IS caused by high LDL-C in China significantly increased among both sexes combined and among men, while significantly decreased among women. Elderly have a substantial burden of IS attributable to high LDL-C. Therefore, effective and tailored strategies based on gender and age for IS primary prevention and management of IS and high LDL-C are urgently needed in China.