Long noncoding RNA H19 is repressed after birth, but can be induced by hypoxia. We aim to investigate the impact on and underlying mechanism of H19 induction after ischemic stroke.
Circulating H19 ...levels in stroke patients and mice subjected to middle cerebral artery occlusion were assessed using real-time polymerase chain reaction. H19 siRNA and histone deacetylase 1 (HDAC1) plasmid were used to knock down H19 and overexpress HDAC1, respectively. Microglial polarization and ischemic outcomes were assessed in middle cerebral artery occlusion mice and BV2 microglial cells subjected to oxygen-glucose deprivation.
Circulating H19 levels were significantly higher in stroke patients compared with healthy controls, indicating high diagnostic sensitivity and specificity. Moreover, plasma H19 levels showed a positive correlation with National Institute of Health Stroke Scale score and tumor necrosis factor-α levels. After middle cerebral artery occlusion in mice, H19 levels increased in plasma, white blood cells, and brain. Intracerebroventricular injection of H19 siRNA reduced infarct volume and brain edema, decreased tumor necrosis factor-α and interleukin-1β levels in brain tissue and plasma, and increased plasma interleukin-10 concentrations 24 hours poststroke. Additionally, H19 knockdown attenuated brain tissue loss and neurological deficits 14 days poststroke. BV2 cell-based experiments showed that H19 knockdown blocked oxygen-glucose deprivation-driven M1 microglial polarization, decreased production of tumor necrosis factor-α and CD11b, and increased the expression of Arg-1 and CD206. Furthermore, H19 knockdown reversed oxygen-glucose deprivation-induced upregulation of HDAC1 and downregulation of acetyl-histone H3 and acetyl-histone H4. In contrast, HDAC1 overexpression negated the effects of H19 knockdown.
Our findings indicate that H19 promotes neuroinflammation by driving HDAC1-dependent M1 microglial polarization, suggesting a novel H19-based diagnosis and therapy for ischemic stroke.
Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill ...patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.
Background Among patients with coronavirus disease 2019 (COVID-19), the cases of a significant proportion of patients are severe. A viral nucleic acid test is used for the diagnosis of COVID-19, and ...some hematological indicators have been used in the auxiliary diagnosis and identification of the severity of COVID-19. Regarding body fluid samples, except for being used for nucleic acid testing, the relationship between COVID-19 and routine body fluid parameters is not known. Our aim was to investigate the value of urine biochemical parameters in the prediction of the severity of COVID-19. Methods A total of 119 patients with COVID-19 were enrolled at Renmin Hospital of Wuhan University. According to the severity of COVID-19, the patients were divided into three groups (moderate 67, severe 42 and critical 10), and 45 healthy persons were enrolled in the same period as healthy controls. The relationship between the results of urine biochemical parameters and the severity of COVID-19 was analyzed. Results The positive rates of urine occult blood (BLOOD) and proteinuria (PRO) were higher in COVID-19 patients than in healthy controls (p < 0.05); the urine specific gravity (SG) value was lower in patients than in healthy controls (p < 0.05), and the urine potential of hydrogen (pH) value was higher in patients than in healthy controls (p < 0.01). The positive rates of urine glucose (GLU-U) and PRO in the severe and critical groups were higher than those in the moderate group (p < 0.01 and p < 0.05, respectively); other biochemical parameters of urine were not associated with the severity of COVID-19. Conclusions Some urine biochemical parameters are different between patients with severe acute respiratory syndrome (SARS)-CoV-2 and healthy controls, and GLU-U and PRO may be helpful for the differentiation of COVID-19 severity.
Recent climate and environment over the Tibetan Plateau (TP) have undergone significant changes, dominated by variations in the Westerlies and the Indian summer monsoon. However, long‐term shifts in ...atmospheric circulation during the transitional seasons are still lacking. Here we investigate the modern distribution of Tsuga pollen over the central‐western TP and confirm it as an indicator of variable atmospheric circulation in spring. By combining our Tsuga record from Taro Co with existing records in the Tsuga pollen source area, we suggest that a potential particle transport pathway from the southern slope of the Himalayas to the interior of the plateau appeared in the spring of the late Holocene. Our results show that the springtime atmospheric circulation over the southwestern TP during the early and late Holocene is closely related to the substantial remnants of ice sheets at northern high latitudes and the frequency of El Niño events, respectively.
Plain Language Summary
The spring climate over the Tibetan Plateau (TP) is undergoing significant changes that yield profound impacts on environmental changes such as variations in vegetation phenology and alpine treeline. Knowledge of long‐term variations in atmospheric circulation during spring can improve the understanding of current climatic and environmental change and the projection of future variability. In this paper, we use an exotic pollen grain, which can be transported long distances in the air, as an indicator to trace the variability of spring atmospheric circulation over the TP. The results indicate that the spring meridional atmospheric circulation from the southern slope of the TP to its interior has been enhanced in the last four thousand years, which is mainly influenced by the frequency of El Niño events.
Key Points
Spring atmospheric circulation change over the southwestern Tibetan Plateau (TP) during Holocene is reconstructed
Meridional atmospheric circulation in spring over the southwestern TP is strengthened in the late Holocene
High‐(low‐) latitude forcing mainly influence the variations in spring atmospheric circulation during the early (late) Holocene
Understanding the temporal trend of the disease burden of stroke and its attributable risk factors in China, especially at provincial levels, is important for effective prevention strategies and ...improvement. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is to investigate the disease burden of stroke and its risk factors at national and provincial levels in China from 1990 to 2019.
Following the methodology in the GBD 2019, the incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of stroke cases in the Chinese population were estimated by sex, age, year, stroke subtypes (ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage), and across 33 provincial administrative units in China from 1990 to 2019. Attributable mortality and DALYs of underlying risk factors were calculated by a comparative risk assessment.
In 2019, there were 3·94 million (95% uncertainty interval 3·43–4·58) new stroke cases in China. The incidence rate of stroke increased by 86·0% (73·2–99·0) from 1990, reaching 276·7 (241·3–322·0) per 100 000 population in 2019. The age-standardised incidence rate declined by 9·3% (3·3–15·5) from 1990 to 2019. Among 28·76 million (25·60–32·21) prevalent cases of stroke in 2019, 24·18 million (20·80–27·87) were ischaemic stroke, 4·36 million (3·69–5·05) were intracerebral haemorrhage, and 1·58 million (1·32–1·91) were subarachnoid haemorrhage. The prevalence rate increased by 106·0% (93·7–118·8) and age-standardised prevalence rate increased by 13·2% (7·7–19·1) from 1990 to 2019. In 2019, there were 2·19 million (1·89–2·51) deaths and 45·9 million (39·8–52·3) DALYs due to stroke. The mortality rate increased by 32·3% (8·6–59·0) from 1990 to 2019. Over the same period, the age-standardised mortality rate decreased by 39·8% (28·6–50·7) and the DALY rate decreased by 41·6% (30·7–50·9). High systolic blood pressure, ambient particulate matter pollution exposure, smoking, and diet high in sodium were four major risk factors for stroke burden in 2019. Moreover, we found marked differences of stroke burden and attributable risk factors across provinces in China from 1990 to 2019.
The disease burden of stroke is still severe in China, although the age-standardised incidence and mortality rates have decreased since 1990. The stroke burden in China might be reduced through blood pressure management, lifestyle interventions, and air pollution control. Moreover, because substantial heterogeneity of stroke burden existed in different provinces, improved health care is needed in provinces with heavy stroke burden.
National Key Research and Development Program of China and Taikang Yicai Public Health and Epidemic Control Fund.
Reconstructing vegetation and climate changes after the Last Glacial Maximum on the Tibetan Plateau (TP) is a key to understand past Indian Summer Monsoon (ISM) dynamics and the interplay between the ...ISM and Westerlies. In this study, a pollen record covering the last deglaciation and Holocene from Lake Tangra Yumco on the central TP is presented. A regional vegetation and climate history on the TP during the late glacial period is inferred, corresponding to long-term variations in the atmospheric circulation systems. Prior to 16,100 cal a BP, most areas of the TP are covered by treeless vegetation, mostly affected by the Westerlies. After that three major vegetation shifts to more humid-preferring vegetation types on the TP are detected during 16,100–14,600, 13,600–13,000, 12,400–10,400 cal a BP. These shifts should indicate three rapid intensifications in the ISM.
During the Holocene (11400–3000 cal a BP), alpine steppe persists in the Tangra Yumco basin. Moistest conditions with strongest ISM occur prior to 8600 cal a BP. After 8600 cal a BP, climate is probably drier with a weakened ISM. Moreover, drought events at 9600–9300, 8200–7400, 5500, 4700–3700, 3200 cal a BP indicate the weakening events of ISM. Vegetation and climate changes on the central TP are mainly insolation driven, but are also associated with the influence of Holocene abrupt cold events in the North Atlantic region.
•A new deglacial and Holocene pollen record from the central Tibetan Plateau is presented.•Three major vegetation shifts at 16100–14600, 13,600–13,000 and 12,400–10,400 cal a BP in the last deglaciation are detected.•Three abrupt increases corresponding to the major vegetation shifts in the Indian Summer Monsoon during the last deglaciation occurred.•Holocene drought phases correspond to Bond cold events.
Glycerol dialkyl glycerol tetraethers (GDGTs) are powerful molecular tools that are suitable for paleoenvironmental reconstruction. The widely distributed lakes on the Tibetan Plateau (TP) are ...important terrestrial paleoenvironmental archives. However, studies on the distributions and environmental responses of branched GDGTs (brGDGTs; analyzed by a new method) are scarce, which makes their environmental response uncertain, further hindering the development of paleoclimate research and the reliability of reconstruction results for the TP region. Herein, we report the distribution of brGDGTs and archaeols in surface sediments from 83 lakes and 22 surrounding soils across the TP. The potential source, environmental response of sedimentary brGDGTs, and the implications for the application of GDGT-based indicators are further discussed. Our results indicate that the sedimentary brGDGTs in the TP lakes were mainly produced in-situ. Lake salinity had a noticeable effect on the brGDGT-based temperature indicators. Coupled with the global lake dataset, we found that the methylation index of 5-methyl brGDGTs (MBT'5ME) responded to temperature in freshwater lakes, while that of 6-methyl brGDGTs (MBT'6ME) showed a better correlation with temperature in saline lakes. However, both indices showed a poor correlation in brackish lakes. These varied responses implied that biological communities producing 5- and 6-methyl brGDGTs were likely to be different, and that 6-methyl brGDGTs might be predominantly synthesized in high-salinity environments. Furthermore, these responses will affect the reliability of paleotemperature records reconstructed by MBT'5ME or MBT'6ME paleothermometers. Therefore, it is essential to evaluate the applicability of these two proxies before using them for paleotemperature reconstruction. In addition, the applicability of GDGT-based salinity indicators on the TP was assessed. Both the archaeol and caldarchaeol ecometric (ACE) and its alternative approach ACE' showed good correlation with lake salinity on the TP, and their high response thresholds to salinity were also noted. It is therefore that these salinity proxies may only be applicable to large paleo-hydrological/salinity fluctuations. In contrast, the isomer ratio of 6- and 7-methyl brGDGTs (IR6 + 7ME and its revised form IR'6 + 7ME) was sensitive to salinity and covered different salinity ranges, which may represent novel salinity proxies. The integration of ACE and IR'6 + 7ME indicators could provide a basis for producing relatively reliable records of paleosalinity and palaeohydrological fluctuations. In conclusion, our work highlights the influence of salinity on GDGT-based indicators and can serve as a reference for paleotemperature and paleosalinity reconstructions in lakes.
•A new brGDGTs dataset of lake sediments from the Tibetan Plateau is presented.•Different responses of MBT'5ME and MBT'6ME to temperature in different salinity ranges were identified.•Two salinity indicators, ACE and IR'6 + 7ME, were evaluated from 83 lakes on the Tibetan Plateau.
Climate change characteristics in the Qinghai-Tibetan Plateau (QTP) exhibit spatial differences. These differences are due to different large circulation systems, comprising Asian summer monsoons and ...mid-latitude Westerlies. However, the paleoclimate pattern at the transition zone between the two systems existing since the Late Glacial remains unclear. We present a 13,000-year high-resolution record of climate change and monsoon effects in the source region of the Yangtze River at the modern limit of the Indian Summer Monsoon (ISM) influence, which lies in the interaction zone with the Westerlies. Multi-proxy records—such as grain size (GS), total inorganic carbon (TIC) and element geochemistry—suggest four stages of paleoclimate change since the Late Glacial: 1) relatively cold in the Late Glacial, 2) warm-wet conditions in the early Holocene, 3) cool-dry conditions in the mid- and late Holocene and 4) a warming and wetting trend over the last 2000 years. Correspondingly, the lake experienced a shallow-water phase in the Late Glacial and a deep-lake phase during the Holocene. The cold Younger Dryas (YD) event occurred from 12.7 to 11.0 cal. kyr BP in the core, with extremely low total organic carbon (TOC) and coarse GS. In contrast, the Holocene Megathermal occurred between 10.0 and 9.1 cal. kyr BP, as recorded by the TOC maxima, which had a finer grain size. In this study, the TIC (plus the XRF-Ca and Ca/Si ratio) reflected the combined effects of biochemical processes (e.g., algal photosynthesis) and hydrological changes (e.g., precipitation, evaporation and runoff). Comparisons between regional records and reconstructed paleoclimate indexes suggested that the studied area's effective moisture pattern mostly followed fluctuations in the ISM-dominated region. The monsoonal circulation drove the paleoclimate variations on the central QTP since the Late Glacial, mainly controlled by enhanced summer insolation until the mid-Holocene. Further, the effective moisture variation was influenced by the August insolation (increased evaporation), on which the Westerlies effect (related to intensely cold air) and the meltwater runoff were later superimposed. Recently, the hydro-climatic conditions have acquired a temperate-humid status in the study area, which likely approaches that in the early Holocene's late phase. Therefore, the paleoclimate pattern of the source region of the Yangtze River exhibits a transitional nature (phase) between two circulation regions during the Holocene.
•We distinguished four stages of paleoclimate changes over the past 13,000 years.•We developed two paleoclimate change indexes for the studied area.•Paleoclimate changes were forced by solar insolation with superimposed Westerlies effect and meltwater.
Aim: Mechanical thrombectomy (MT) has become the gold standard for the treatment of large vessel occlusion (LVO) in acute ischemic stroke. However, it remains controversial whether emergency ...angioplasty or stenting in patients with intracranial atherosclerotic stenosis (ICAS) should be adopted. Thus, we performed a retrospective analysis of clinical data to determine whether emergency angioplasty or stenting is necessary. Methods: We retrospectively analyzed data from patients undergoing MT with ICAS-related LVO of the acute anterior circulation between 2017 and 2019. Eligible patients were divided into two treatment groups: those who received rescue angioplasty or stenting Patients treated with rescue angioplasty or stenting (PTAS) group and those who received thrombectomy alone (non-PTAS group). The primary outcomes were good prognosis at 90 days (mRS: 0–2). Mortality, symptomatic intracranial hemorrhage, and reocclusion rate were evaluated as secondary outcomes. Results: A total of 184 patients with severe stenosis after MT were enrolled, including 64 patients receiving rescue angioplasty or stenting and 120 patients without rescue angioplasty or stenting. Compared with the non-PTAS group, a better functional outcome (mRS0-2) (51.6% vs. 35.0%, adjusted odds ratio: 2.11, 95% confidence interval CI: 1.22–4.29; P=0.02), lower 7-day National Institutes of Health Stroke Scale 6 (3–12.75) vs. 10 (4–16); P=0.04, lower 24-h neurological deterioration rate (7.8% vs. 21.7%, P=0.02), and lower 24-h reocclusion rate were observed in the PTAS group (6.3% vs. 17.5%, P=0.03). There were no significant differences in mortality or incidence of symptomatic intracerebral hemorrhage. Conclusion: Emergency angioplasty or stenting could be a safe and feasible therapeutic option with better outcomes for stroke patients with ICAS-related LVO.
Selin Co, the largest lake situated on the central Tibetan Plateau (TP) and lying in the transitional zone between the Indian Summer Monsoon and the Westerlies, is an ideal site to investigate the ...region's paleoclimatic evolution since the Late Pleistocene. In this study, we present a high-resolution geochemical and mineralogical record retrieved from a 585-cm core in Selin Co covering the last 13 cal kyr BP based on a robust AMS 14C-determined chronology with a reservoir effect calibration. Various proxies, such as the mean grain size, Ti, Ca, Rb/Sr, total inorganic carbon (TIC) and total organic carbon (TOC), showed that the period from 12.9 to 11 cal kyr BP was characterized by stronger runoff, lower salinity and a higher lake level, indicating a cold and wet period. A Younger Dryas event likely occurred during the period 12.8–12.5 cal kyr BP, and all proxies exhibited a sharp change from 11.2 to 10.8 cal kyr BP that showed the termination of the cold/wet period followed by the onset of the Holocene. From 11 to 8 cal kyr BP, a transition from a drier to a relatively wet period occurred. An abrupt decrease in the TOC record in Selin Co at ~9.2 cal kyr BP suggested a cold event. During the period 8 to 4 cal kyr BP, a relatively warm and dry climate was observed. At ~4 cal kyr BP, all proxies indicated a low lake level and hence a dry event in Selin Co. A stable low lake level after 4 cal kyr BP was observed until an increase beginning at 800 cal yr BP. A significant lake level rise has coincided with the strengthening Westerlies during recent decades. These climatic variabilities in the Selin Co area since the Late Glacial have primarily been driven by temperature-induced evaporation in addition to precipitation via monsoonal circulation and/or westerly jets.
•We present a high-resolution paleo-climatic record from Selin Co since 13 cal kyr BP.•Four stages with distinct climate and lake level variability were identified.•Younger Dryas and onset of Holocene were observed at 12.8–12.5 and 11 cal kyr BP.•Both Indian summer monsoon and the Westerly show impact on the climate.
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