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China is currently entering a stage of high-quality development, with urban development and governance facing systematic reconstruction of internal and external conditions, showing clear differences and the complex superposition of multi-stage development. The steady progress of urbanization has facilitated significant changes in the population structure of Chinese cities. It is expected that the population and industries will further converge to urban agglomerations and big cities, indicating basic multicenter and network patterns. Therefore, analyzing the negative population growth risks of urban agglomerations at different development stages is crucial. This study examined the cities of 19 urban agglomerations in China by adopting the data of the seventh population census, employing the optimized fuzzy logic method, building a complex network of population flow with ArcGIS and MATLAB platforms, and using the intensity of population flow and the registered population fertility rate to represent exogenous and endogenous growth, respectively. The negative population growth evaluation index system was constructed with five indicators: child ratio, aging rate, average family size, population density, and sex ratio. The risk index of negative population growth was measured using the fuzzy logic method, and the growth mechanism of negative population growth risk in urban agglomerations in China was analyzed using the spatial measurement method. (1) The negative population growth risk of growing urban agglomerations was influenced by both exogenous and endogenous growth, with exogenous growth having a greater impact. (2) The dynamic mechanism of negative population growth risk in large urban agglomerations is exogenous growth, whereas that of nurturing urban agglomerations is endogenous growth. (3) According to the risk of negative population growth in China's urban agglomerations and its influencing factors, negative population growth in 19 urban agglomerations can be divided into eight types. 1) The state of population growth of expanding urban agglomerations can be divided into two types, with the middle reaches of the Yangtze River and Chengdu-Chongqing urban agglomerations as one type; the capital city has a low risk of negative population growth, while other cities have a high risk of negative population growth. The Yangtze River Delta, Pearl River Delta, and Beijing-Tianjin-Hebei city clusters are the same, with the capital and other cities having a relatively low risk of negative population growth. 2) The status of large urban agglomerations can be divided into two types: Shandong Peninsula, Central Plains, Guanzhong Plain, and Beibu Gulf urban agglomerations. The capital city has a low risk of negative population growth, whereas other cities have a high risk of negative population growth. The risk of negative population growth in capital cities and other cities is relatively low. 3) The state of population growth of cultivated urban agglomerations can be divided into four types: the Harbin and Changsha urban agglomerations and the central and southern Liaoning urban agglomerations, which have a high risk of negative population growth. Meanwhile, the northern slope of the Tianshan Mountain City cluster and the Hubao Eyu City cluster have low risk of negative population growth. The risk of negative population growth is low in the provincial capital city and high in the other cities, while endogenous growth is positive in the provincial capital city and negative in the other cities. In the Jinzhong City, Central Guizhou City, and Central Yunnan City groups, the risk of negative population growth is low in provincial cities and high in other cities. Endogenous growth shows that the capital city and other cities have positive growth. In conclusion, this study posits that upgrading urban agglomerations should consider the spatial balance of population distribution, large urban agglomerations should fulfill their role in "blocking the flow" of big cities, and nurturing urban agglomerations should "consolidate human capital." This study presents a comprehensive and in-depth analysis of the negative population growth risk and its impact mechanisms in different development stages of urban agglomerations. This can provide a decision-making reference for the formulation of scientific and reasonable population and economic policies in various urban agglomerations and plays a significant role for maintaining a long-term stable population, economy, and social growth in the region.

Pancreatic β-cell dysfunction caused by obesity can be associated with alterations in the levels of miRNAs. However, the role of miRNAs in such processes remains elusive. Here, we show that pancreatic islet miR-27a-5p, which is markedly increased in obese mice and impairs insulin secretion, is mainly delivered by visceral adipocyte–derived extracellular vesicles (EVs). Depleting miR-27a-5p significantly improved insulin secretion and glucose intolerance in db / db mice. Supporting the function of EV miR-27a-5p as a key pathogenic factor, intravenous injection of miR-27a-5p–containing EVs showed their distribution in mouse pancreatic islets. Tracing the injected adeno-associated virus (AAV)-miR-27a-5p (AAV-miR-27a) or AAV-FABP4-miR-27a-5p (AAV-FABP4-miR-27a) in visceral fat resulted in upregulating miR-27a-5p in EVs and serum and elicited mouse pancreatic β-cell dysfunction. Mechanistically, miR-27a-5p directly targeted L-type Ca2+ channel subtype CaV1.2 (Cacna1c) and reduced insulin secretion in β-cells. Overexpressing mouse CaV1.2 largely abolished the insulin secretion injury induced by miR-27a-5p. These findings reveal a causative role of EV miR-27a-5p in visceral adipocyte–mediated pancreatic β-cell dysfunction in obesity-associated type 2 diabetes mellitus. Article Highlights: miR-27a-5p expression in the islets is increased in obesity-associated diabetes mouse models. miR-27a-5p overexpression in β-cells impairs β-cell function in vitro and in vivo. Visceral adipocyte–derived extracellular vesicles and their cargo miR-27a-5p lead to β-cell insulin secretion injury and glucose intolerance by targeting L-type Ca2+ channel subtype CaV1.2. Blockage of visceral adipocyte extracellular vesicle miR-27a-5p expression improves β-cell insulin secretion and glucose tolerance in db / db mice. [ABSTRACT FROM AUTHOR]

Aim: To assess the expression and function of miR‐483‐5p in diabetic β cells. Methods: The expression of miR‐483‐5p was evaluated in the pancreatic islets of obesity mouse models by quantitative reverse transcription polymerase chain reaction. Dual‐luciferase activity, and western blotting assays, were utilized for miR‐483‐5p target gene verification. Mice with β cell‐specific miR‐483‐5p downregulation were studied under metabolic stress (i.e. a high‐fat diet) condition. Lineage tracing was used to determine β‐cell fate. Results: miR‐483‐5p increased in the islets of obese mouse models. Expression levels of miR‐483‐5p were significantly upregulated with the treatment of high glucose and palmitate, in both MIN6 cells and mouse islets. Overexpression of miR‐483‐5p in β cells results in impaired insulin secretion and β‐cell identity. Cell lineage‐specific analyses revealed that miR‐483‐5p overexpression deactivated β‐cell identity genes (insulin, Pdx1 and MafA) and derepressed β‐cell dedifferentiation (Ngn3) genes. miR‐483‐5p downregulation in β cells of high‐fat diet‐fed mice alleviated diabetes and improved glucose intolerance by enhancing insulin secretory capacity. These detrimental effects of miR‐483‐5p relied on its seed sequence recognition and repressed expression of its target genes Pdx1 and MafA, two crucial markers of β‐cell maturation. Conclusions: These findings indicate that the miR‐483‐5p–mediated reduction of mRNAs specifies β‐cell identity as a contributor to β‐cell dysfunction via the loss of cellular differentiation. [ABSTRACT FROM AUTHOR]

Understanding the near-ground vertical and temporal photochemical O 3 formation mechanism is important to mitigate O 3 pollution. Here, we measured the vertical profiles of O 3 and its precursors at six different heights, ranging from 5 to 335 m, using a newly built vertical observation system in the Pearl River Delta (PRD) region of China. The net photochemical ozone production rate (P (O 3) net) and O 3 formation sensitivities at various heights were diagnosed using an observation-based model coupled with the Master Chemical Mechanism (MCM v3.3.1). Moreover, to assess model performance and identify the causative factors behind O 3 pollution episodes, the P (O 3) net was measured at 5 m above ground level with a custom-built detection system. In total, three O 3 pollution episodes and two non-episodes were captured. The identified O 3 pollution episodes were found to be jointly influenced by both photochemical production and physical transport, with local photochemical reactions playing a major role. The high index of agreement (IOA) calculated by comparing the modelled and measured P (O 3) net values indicated the rationality of investigating the vertical and temporal variability in O 3 formation mechanisms using model results. However, the measured P (O 3) net values were generally higher than the modelled P (O 3) net values, particularly under high-NO x conditions, which may indicate a potential underestimation of total RO 2 by the model. Throughout the measurement period, the contribution of different reaction pathways to O 3 production remained consistent across various heights, with HO 2 + NO as the major O 3 production pathway, followed by RO 2 + NO. We observed that P (O 3) net decreased with an increase in measurement height, which was primarily attributed to the reduction in O 3 precursors, such as oxygenated volatile organic compounds (OVOCs) and non-methane hydrocarbons (NMHCs). The O 3 formation regimes were similar at different heights during both episodes and non-episodes, either being located in the VOC-sensitive regime or in the transition regime that is more sensitive to VOCs. Diurnally, photochemical O 3 formation typically remained in the VOC-sensitive regime during the morning and noon, but it transitioned to the transition regime and was more sensitive to VOCs in the afternoon at around 16:00 LT (local time). Vertical and temporal photochemical O 3 formation is most sensitive to OVOCs, suggesting that targeting specific VOCs for control measures is more practical and feasible at the observation site. The vertical temporal analysis of O 3 formation mechanisms near the ground surface in this study provides critical foundational knowledge that can be used to formulate effective short-term emergency and long-term control strategies to combat O 3 pollution in the PRD region of China. [ABSTRACT FROM AUTHOR]

Activated carbon filter is the main equipment used to remove pollutants in the ventilation system in a nuclear power plant. Its main function is to remove radioactive iodine to minimize radioactive hazards against workers in the ventilation area. Periodic evaluation is a key step for verifying its operation effectiveness, further to ensure the safety and long-term operation. In this paper, by changing the micropore structure and surface chemical properties of activated carbon, its physicochemical properties and adsorption performance against methyl iodide under the high humidity working environment are studied. The results show that the adsorption performance of activated carbon on organic compound decreases significantly under the high humidity conditions; however, the combination of potassium iodide, triethylene diamine and functional groups on the activated carbon surface form stable chemical bonds and a new surface structure, which enhances the adsorption performance and stability of activated carbon against pollutants and makes it difficult to remove pollutants. The adsorption capacity of nuclear activated carbon can be restored to 80.7% of the initial capacity, and the adsorption performance can be obviously improved.

Objective: To investigate the therapeutic effect and mechanism of sivelestat sodium on acute lung injury (AIL). Methods: A rat model for ALI/acute respiratory distress syndrome (ALI/ARDS) was established. Pathological examination of lung tissue was conducted to assess lung injury. Blood gas in the arteries was measured using a blood analyzer. Changes in PaO2, PaO2/FiO2, and lung wet/dry (W/D) weight ratio were carefully compared. ELISA assay was conducted to estimate cell adhesion and inflammation response. Finally, real-time reverse transcription polymerase chain reaction and western blotting assay was used to determine the activation of PI3K/AKT/mTOR pathway. Results: ARDS in vivo model was successfully constructed by LPS injection. Compared with the sham group, PaO2 and PaO2/FiO2 were significantly lower in the vehicle group, while the lung W/D ratio, the lung injury score, NE, VCAM-1, IL-8 andTNF-αwere significantly increased. After treatment with different doses of sivelestat sodium, we found PaO2, PaO2/FiO2 were prominently increased, while the lung W/D ratio, the lung injury score, NE, VCAM-1, IL-8, TNF-α levels were decreased in the dose-dependent manner. Meanwhile, compared with the vehicle group, the expression levels of Bax, PI3K, Akt and mTOR were significantly lower, and the expression of Bcl-2 was significantly higher after injection with sivelestat sodium. Conclusion: Sivelestat sodium has an interventional effect on ALI in sepsis by inhibiting the PI3K/AKT/mTOR signalling pathway. [ABSTRACT FROM AUTHOR]

Understanding the near-ground vertical and temporal photochemical O3 formation mechanism is important to mitigate the O3 pollution. Here, we measured the vertical profiles of O3 and its precursors at six different heights from 5-335 m using a newly built vertical observation system in Pearl River Delta (PRD) region, China. The net photochemical ozone production rate (P (O3)net) and O3 formation sensitivities at various heights were diagnosed using an observation-based model coupled with the Master Chemical Mechanism (MCM v3.3.1). Moreover, for the assessment of model performance and the causative factors behind O3 pollution episodes, the net photochemical ozone production rate (P (O3)net) was measured at 5 m ground level utilizing a custom-built detection system. In total three O3 pollution episodes and two non-episodes were captured. The identified O3 pollution episodes were found to be jointly influenced by both photochemical production and physical transport, with local photochemical reactions play a dominate role. The high index of agreement (IOA) calculated from comparing the modelled and measured P (O3)net values indicated the rationality to investigate the vertical and temporal variability of O3 formation mechanism using modelling results. However, the measured P (O3)net values were generally higher than the modelled P (O3)net values, particularly under high NOx conditions, which may indicate a potential underestimation of total RO2 by the model. Throughout the measurement period, the contribution of different reaction pathways to O3 production remained consistent across various heights, with HO2+NO as the major O3 production pathway, followed by RO2+NO. We saw P (O3)net decreased with the increase of the measurement height, primarily attributed to the decreased O3 precursors anthropogenic organic compounds (AVOC) and oxygenated volatile organic compounds (OVOC). O3 formation regimes were similar at different heights during both episodes and non-episodes, which was located either in volatile organic compounds (VOCs) sensitive regime or in transition regime and more sensitive to VOCs. Diurnally, photochemical O3 formation typically remained in the VOCs sensitive regime during the morning and noon time, but in the transitional regime and more sensitive to VOCs in the afternoon at around 16:00 LT. The vertical and temporal O3 formation are most sensitive to AVOC and OVOC, which suggests that targeting VOCs, especially AVOC and OVOC, for control measures is more practical and feasible at the observation site. The vertical temporal analysis of O3 formation mechanisms near the ground surface in this study provides critical foundational knowledge for formulating effective short-term emergency and long-term strategies to combat O3 pollution in the PRD region of China. [ABSTRACT FROM AUTHOR]

Current process-based research mainly uses box models to evaluate photochemical ozone production and destruction rates, and it is unclear to what extent the photochemical reaction mechanisms are elucidated. Here, we modified and improved a net photochemical ozone production rate (NPOPR, P (O 3) net) detection system based on the current dual-channel reaction chamber technique, which makes the instrument applicable to different ambient environments, and its various operating indicators were characterized, i.e., "airtightness", light transmittance, wall losses of the reaction and reference chambers, conversion rate of O 3 to NO 2 , air residence time, and performance of the reaction and reference chambers. The limits of detection of the NPOPR detection system were determined to be 0.07, 1.4, and 2.3 ppbv h -1 at sampling flow rates of 1.3, 3, and 5 L min -1 , respectively. We further applied the NPOPR detection system to field observations at an urban site in the Pearl River Delta (China). During the observation period, the maximum value of P (O 3) net was 34.1 ppbv h -1 , which was ∼ 0 ppbv h -1 at night within the system detection error and peaked at approximately noon local time. The daytime (from 06:00–18:00 LT) average value of P (O 3) net was 12.8 (± 5.5) ppbv h -1. We investigated the detailed photochemical O 3 formation mechanism in the reaction and reference chambers of the NPOPR detection system using a zero-dimensional box model. We found that the photochemical reactions in the reaction chamber were very close to those in ambient air, but there was not zero chemistry in the reference chamber because the reaction related to the production and destruction of RO 2 (= HO 2 + RO 2) continued in the reference chamber, which led to a small amount of P (O 3) net. Therefore, the P (O 3) net measured here can be regarded as the lower limit of the real P (O 3) net in the atmosphere; however, the measured P (O 3) net was still ∼ 7.5 to 9.3 ppbv h -1 higher than the modeled P (O 3) net value depending on different modeling methods, which may be due to the inaccurate estimation of HO 2 / RO 2 radicals in the modeling study. Short-lived intermediate measurements coupled with direct P (O 3) net measurements are needed in the future to better understand O 3 photochemistry. Our results show that the NPOPR detection system can achieve high temporal resolution and continuous field observations, which helps us to better understand photochemical O 3 formation and provides a key scientific basis for continuous improvement of air quality in China. [ABSTRACT FROM AUTHOR]

The recombinant adeno-associated virus 8 (rAAV8) vector is a widely used tool in basic research and clinical trials. The cytomegalovirus immediate-early enhancer/chicken β-actin (CAG) promoter is a synthetic promoter used in adenoviral constructs with a wide spectrum and notable efficiency. The thyroxine binding globulin (TBG) promoter is a liver-specific promoter, which directs transgene expression in hepatocytes. However, the transduction efficiency of the rAAV vector is dependent on both the administration routes and the promoter elements. In the present study, the transduction efficiency in the liver following intraperitoneal (IP) and intravenous (IV) injections of rAAV8 with the CAG, TBG669 and TBG410 promoters was compared. Enhanced green fluorescent protein (EGFP) expression was used as the biomarker to indicate efficiency. Among the three different promoters, CAG exhibited the highest efficiency from both IV and IP injections. Following IV administration, EGFP expression, induced by the CAG promoter, was 67-fold higher compared with that in the TBG410 promoter group and 26-fold higher compared with that in the TBG669 promoter group. EGFP protein expression was higher with IV injection compared with that for IP injection for both the CAG and TBG669 promoters (P<0.05). With the CAG promoter, EGFP protein expression was 1.5-fold higher with the use of IV injection than with IP injection. With the TBG410 promoter, no differences were observed between the two administrations. In conclusion, these findings demonstrated that the CAG promoter was much more efficient at driving gene expression in the liver compared with that for the TBG promoters in rAAV8. In addition, IP administration produced comparable efficiency for gene delivery via the rAAV8 vector, particularly with the promoter TBG410. [ABSTRACT FROM AUTHOR]

Nitryl chloride (ClNO 2 ) is a key precursor of chlorine radicals, influencing atmospheric oxidation and secondary pollutants formation. Few studies have examined the ClNO 2 chemistry from the perspective of the planetary boundary layer. Here, we conducted a vertically resolved investigation of ClNO 2 at six heights (ranging from 5 to 335 m) on a 356 m tower in the Pearl River Delta, China, during winter 2021. Nocturnal ClNO 2 is notably lower at the surface than the upper layers, with the nocturnal median concentration at 220 m (51 parts per trillion by volume, pptv) being approximately three times higher than that recorded in the surface layer (16 pptv). Observation-constrained box model simulations show that the NO gradients primarily account for the vertical disparities. Compared to the hydroxyl radical (OH) production via the nitrous acid and ozone photolysis, ClNO 2 photolysis contributes to radical formation by 3.8% (1.8%) at 220 m (5 m) in the morning (07:00-08:00), indicates the enhanced significance of ClNO 2 chemistry aloft compared with the ground, and may cause the underestimation of ClNO 2 photolysis impacts if solely relying on surface measurements. We highlight that more field studies are needed to elucidate ClNO 2 chemistry across the boundary layer.

Background/aims: Dexamethasone (DEX) is a widely used exogenous therapeutic glucocorticoid in clinical settings. Its long-term use leads to many side effects. However, its effect on metabolic disorders in individuals on a high-fat diet (HFD) remains poorly understood., Methods: In this study, HFD-fed mice were intraperitoneally injected with DEX 2.5 mg/kg/day for 30 days. Lipid metabolism, adipocyte proliferation, and inflammation were assayed using typical approaches., Results: DEX increased the epididymal fat index and epididymal adipocyte size in HFD-fed mice. The number of epididymal adipocytes with diameters > 70 μm accounted for 0.5% of the cells in the control group, 30% of the cells in the DEX group, 19% of the cells in the HFD group, and 38% of all the cells in the D+H group. Adipocyte proliferation in the D+H group was inhibited by DEX treatment. Adipocyte enlargement in the D+H group was associated with increased the lipid accumulation but not the adipocyte proliferation. In contrast, the liver triglyceride and total cholesterol levels and their metabolism were downregulated by the same treatment, indicating the therapeutic potential of DEX for nonalcoholic fatty liver disease., Conclusion: DEX synergizes with HFD to promote lipid deposition in adipose tissues. A high risk of obesity development in patients receiving HFD and DEX treatment is suggested.

Background/aim: Depression is associated with metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the interaction between them are still poorly known., Materials and Methods: In this study, mice on a choline deficiency, L-amino acid-defined, high-fat diet (CDAHFD) developing steatosis were challenged with chronic restraint stress (CRS), a protocol widely used to induce depression. The development of depression and steatosis was evaluated using histopathology analysis, ELISA, q-PCR and Western Blot., Results: The contribution of the activated HPA axis to hepatic steatosis progress was fully established, which was validated using a hepatocyte model. Histopathological and biochemical analysis indicated that steatosis was exacerbated by CRS challenge, and behavioral tests indicated that the mice developed depression. Among the screened endocrinal pathways, the hypothalamic-pituitary-adrenal (HPA) axis was significantly activated and the synergistic effect of CDAHFD and CRS in activating the HPA axis was observed. In the hypothalamus, expression of corticotropin-releasing hormone (CRH) was increased by 86% and the protein levels of hypothalamic CRH were upregulated by 25% to 33% by CRS treatment. Plasma CRH levels were elevated by 45-56% and plasma adrenocorticotropic hormone (ACTH) levels were elevated by 29-58% by CRS treatment. In the liver, target genes of the HPA axis were activated, accompanied by disruption of the lipid metabolism and progression of steatohepatitis. The lipid metabolism in the Hepa1-6 cell line treated with endogenous corticosterone (CORT) was in accordance with the aforementioned in vivo responses., Conclusion: Depression aggravated hepatic steatosis in CDAHFD-fed mice by activating the HPA axis. The risk of NAFLD development should be fully considered in depressive patients and improvement of psychotic disorders could be an etiological treatment strategy for them., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To analyze the clinical effect of high-flow nasal cannula (HFNC) oxygen therapy combined with naloxone on severe respiratory failure (SRF) in older adult patients., Methods: We enrolled 96 older adult patients with SRF who were admitted to Hai'an People's Hospital between February 2019 and March 2022. The patients were divided into two groups: the control group (treated with non-invasive positive pressure ventilation combined with naloxone) and the observation group (treated with HFNC oxygen therapy combined with naloxone). The blood gas measurement, respiratory rate (RR), St. George's Respiratory Questionnaire (SGRQ) score, Clara cell secreted protein (CC16) level, tumor necrosis factor-alpha (TNF-α) level, interleukin-1 (IL-1) level, length of intensive care unit (ICU) stay, tracheal intubation rate, and 28-day mortality rate were compared between the groups., Results: Blood gas measurement or RR did not differ significantly between the groups ( P >0.05). The observation group showed improved outcome, including reduced partial pressure of CO 2 , RR, and pH, and increased partial pressure of O 2 (PaO 2 ), PaO 2 /fraction of inspired O 2 ratio, and O 2 saturation after treatment ( P <0.05). Additionally, the observation group exhibited lower TNF-α level, IL-1 level, and SGRQ score, and higher CC16 level ( P <0.05). The length of ICU stay, tracheal intubation rate, and 28-day mortality rate were lower in the observation group ( P <0.05)., Conclusions: HFNC oxygen therapy combined with naloxone in older adult patients with SRF could improve blood gas results, disease duration, tracheal intubation rate, and 28-day mortality rate. This may occur through regulation of TNF-α, IL-1, and CC16 expression., Competing Interests: None., (AJTR Copyright © 2023.)

Objective: To analyze the clinical characteristics and risk factors of early acute liver injury in patients with heat stroke (HS), and to provide basis for early identification of HS-related liver injury and its pathogenesis in clinical practice., Methods: The clinical data of patients with HS admitted to the department of critical care medicine of Haian People's Hospital from June 2015 to August 2022 were retrospectively analyzed. The patients with HS were divided into early liver injury group and early non-liver injury group according to the occurrence of acute liver injury within 24 hours of admission. The differences of basic data, clinical data, laboratory indexes and clinical outcomes of the two groups were analyzed. Logistic regression was used to analyze the risk factors for early HS-related acute liver injury, and receiver operator characteristic (ROC) curves were drawn to evaluate their value in predicting the occurrence of early HS-related acute liver injury., Results: A total of 76 patients with HS were enrolled, and 46 patients with acute liver injury, accounting for 60.53%. In the early liver injury group, 14 patients (30.43%) had elevated aminotransferase alone, 9 patients (19.57%) had elevated total bilirubin (TBil) alone, and 23 patients (50.00%) had elevated both aminotransferase and TBil. Among the patients with elevated aminotransferases, 24 patients (64.87%) had mild elevation, 5 patients (13.51%) had moderate elevation, 8 patients (21.62%) had severe elevation. Compared with the early non-liver injury group, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), arterial blood lactate (Lac), interleukin-6 (IL-6), procalcitonin (PCT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), TBil, γ-gamma glutamyl transferase (γ-GGT), lactate dehydrogenase (LDH), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB), cardiac troponin I (cTnI), myoglobin (MYO), N-terminal B-type pro-brain natriuretic peptide (NT-proBNP), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer in the early liver injury group were significantly increased, while platelet count (PLT) were significantly decreased within 24 hours after admission, the 28-day mortality was significantly increased [28.26% (13/46) vs. 6.67% (2/30)], and the differences were statistically significant (all P < 0.05). Univariate Logistic regression analysis showed that APACHE II score, SOFA score, PLT, Lac, IL-6, PCT, γ-GGT, LDH, CK, CK-MB, cTnI, MYO, PT, APTT, D-dimer were risk factors of early HS-related acute liver injury (all P < 0.05). Multivariate Logistic regression analysis showed that PLT, IL-6, and LDH were independent risk factors of early HS-related acute liver injury [odds ratio (OR) and 95% confidence interval (95%CI) were 0.986 (0.974-0.998), 1.027 (1.012-1.041), and 1.002 (1.000-1.004), all P < 0.05]. The ROC curve analysis showed that the area under the ROC curve (AUC) of PLT, IL-6 and LDH for predicting the occurrence of early HS-related acute liver injury was 0.672 (95%CI was 0.548-0.797), 0.897 (95%CI was 0.824-0.971) and 0.833 (95%CI was 0.739-0.927), respectively. IL-6 had the highest predictive value for early HS-related liver injury. When the optimal diagnostic threshold of IL-6 was 48.25 ng/L, the sensitivity was 95.7%, the specificity was 73.3%, and the predictive value of PLT was the lowest., Conclusions: The early HS-related liver injury is mainly manifested as the simultaneous elevation of aminotransferase and TBil, and most of cases are mild liver injury. PLT, IL-6 and LDH are independent risk factors of early HS-related acute liver injury.

Platelet hyperreactivity and increased atherothrombotic risk are specifically associated with dyslipidemia. Peroxisome proliferator-activated receptor alpha (PPARα) is an important regulator of lipid metabolism. It has been suggested to affect both thrombosis and hemostasis, yet the underlying mechanisms are not well understood. In this study, the role and mechanism of PPARα in platelet activation and thrombosis related to dyslipidemia were examined. Employing mice with deletion of PPARα (Pparα-/-), we demonstrated that PPARa is required for platelet activation and thrombus formation. The effect of PPARα is critically dependent on platelet dense granule secretion, and is contributed by p38MAPK/Akt, fatty acid b-oxidation, and NAD(P)H oxidase pathways. Importantly, PPARα and the associated pathways mediated a prothrombotic state induced by a high-fat diet and platelet hyperactivity provoked by oxidized low density lipoproteins. Platelet reactivity was positively correlated with the levels of expression of PPARα, as revealed by data from wild-type, chimeric (Pparα+/-), and Pparα-/- mice. This positive correlation was recapitulated in platelets from hyperlipidemic patients. In a lipid-treated megakaryocytic cell line, the lipid-induced reactive oxygen species-NF-kB pathway was revealed to upregulate platelet PPARα in hyperlipidemia. These data suggest that platelet PPARα critically mediates platelet activation and contributes to the prothrombotic status under hyperlipidemia.