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Abstract Patients with diabetes are susceptible to acute kidney injury (AKI) as compared to counterparts without diabetes. However, data on the long-term clinical outcome of AKI specifically in people with diabetes are still scarce. We sought to study risk factors for and adverse cardio-renal outcomes of AKI in multi-ethnic Southeast Asian people with type 2 diabetes. 1684 participants with type 2 diabetes from a regional hospital were followed an average of 4.2 (SD 2.0) years. Risks for end stage kidney disease (ESKD), major adverse cardiovascular events (MACE) and all-cause death after AKI were assessed by survival analyses. 219 participants experienced at least one AKI episode. Age, cardiovascular disease history, minor ethnicity, diuretics usage, HbA1c, baseline eGFR and albuminuria independently predicted risk for AKI with good discrimination. Compared to those without AKI, participants with any AKI episode had a significantly high risk for ESKD, MACE and all-cause death after adjustment for multiple risk factors including baseline eGFR and albuminuria. Even AKI defined by a mild serum creatinine elevation (0.3 mg/dL) was independently associated with a significantly high risk for premature death. Therefore, individuals with diabetes and any episode of AKI deserve intensive surveillance for cardio-renal dysfunction.

Cardiovascular diseases (CVDs) are a major threat to public health globally. A large proportion of people with dyslipidaemia have poorly controlled lipid levels, emphasizing the need for alternative lipid-lowering treatments that are both effective and safe. Xuezhikang, a red yeast rice (RYR) extract, containing 13 kinds of monacolins and other bioactive components, emerges as one such promising option. Its discovery was built on a long history of RYR use as a functional food supplement and traditional Chinese medicine. Several randomized, controlled clinical trials have substantiated its lipid-lowering effects and its potential to protect against CVDs. Safety concerns with statins did not arise during decades of experience with Xuezhikang treatment in clinical practice. The approval of Xuezhikang in multiple regions of Asia marked a conceptual shift in CVD management, moving from single agents to polypills and from synthetic medicines to natural extracts. This review comprehensively addresses important topics related to this medicinal natural extract, including the ancient utilization of RYR, the development of Xuezhikang, its mechanisms of action, pleiotropic effects, clinical studies, challenges, and future perspectives to enhance our understanding regarding the role of Xuezhikang, a representative, domestic lipid-lowering drug of RYR, in prevention and treatment of CVD.

Background Endothelin-1 (ET-1) is an endogenous vasoconstrictor implicated in coronary artery disease (CAD) and diabetes. This study aimed to determine the prognostic value of ET-1 in the patients with stable CAD under different glucose metabolism states. Methods In this prospective, large-cohort study, we consecutively enrolled 7,947 participants with angiography-diagnosed stable CAD from April 2011 to April 2017. Patients were categorized by baseline glycemic status into three groups (normoglycemia, prediabetes, and diabetes) and further divided into nine groups by circulating ET-1 levels. Patients were followed for the occurrence of cardiovascular events (CVEs), including nonfatal myocardial infarction, stroke, and cardiovascular mortality. Results Of the 7,947 subjects, 3,352, 1,653, and 2,942 had normoglycemia, prediabetes, and diabetes, respectively. Over a median follow-up of 37.5 months, 381 (5.1%) CVEs occurred. The risk for CVEs was significantly higher in patients with elevated ET-1 levels after adjustment for potential confounders. When patients were categorized by both status of glucose metabolism and plasma ET-1 levels, the high ET-1 levels were associated with higher risk of CVEs in prediabetes (adjusted hazard ratio [HR], 2.089; 95% confidence interval [CI], 1.151 to 3.793) and diabetes (adjusted HR, 2.729; 95% CI, 1.623 to 4.588; both P

The photocatalytic conversion of soluble U(Ⅵ) to insoluble U(Ⅳ) is regarded as an effective method for the separation of solution uranium. During the photocatalytic reactions, the design of photocatalyst plays a role. As a metal free polymer semiconductor, carbon nitride(CN) has attracted increasing attentions in photo-catalytic reduction of U(Ⅵ) under visible light irradiation due to its low cost, easy preparation, excellent physicochemical stability and adjustable structure. However, the application of carbon nitride in photocatalytic U(Ⅵ) reduction is limited by its low photocatalytic reduction efficiency, which is caused by the poor reactive sites low separation rate of charge carriers, and slow transport efficiency of electrons. This study aimed to evaluate the transformation of U(Ⅵ) in aqueous solution over Y-doped CN(YCN). YCN photocatalysts with different amount of Y3+ were prepared by in situ doping to modify the energy band structure and physicochemical properties of carbon nitride. It was revealed that the presence of Y3+ changed the in-plane periodic topology and inter-layer stacking structure of the tri-s-triazine unit of carbon nitride, resulting in the incomplete polymerization of the tri-s-triazine unit. The doping of Y3+ lead to the formation of porous structure in YCN, which increases the specific surface area and the active sites. Comparing with pristine CN, YCN showes enhanced absorbance for light and increases separation rate of charge carriers. The average fluorescence life is subsequently increased under light irradiation, which is 1.8 times for YCN2 than the pristine CN. The EPR spectra demonstrates that, compared to CN, significantly more \begin{document}$ · {\mathrm{O}}_2^- $\end{document} radicals and less \begin{document}$· {\mathrm{OH}} $\end{document} radicals are generated on YCN2 under light irradiation. The free radical trapping experiments verifies that \begin{document}$ · {\mathrm{O}}_2^- $\end{document} radicals act as the dominant reactive species for the reduction of U(Ⅵ) and the small amount of other radicals do not bring obvious influence. The enhanced generation of \begin{document}$ · {\mathrm{O}}_2^- $\end{document} radicals on YCN2 therefore provides favorable conditions for the photocatalytic reduction of U(Ⅵ). When using methanol as a sacrificial agent, it can remove about 95% of U(Ⅵ) within 20 min for the YCN2-containing system under light. The rate of the photocatalytic reduction of U(Ⅵ) on YCN2(0.112 min−1) is 5.3 times higher than CN(0.021 min−1). Analysis of the products reveals that water-soluble U(Ⅵ) is reduced in the photocatalytic reaction, with approximately 80% U(Ⅳ) and 20% U(Ⅵ). The soluble U(Ⅵ) is mainly reduced to insoluble UO2+x deposited on the surface of YCN by \begin{document}$ { · {\mathrm{O}}_2^- } $\end{document} radicals. This study improves the photocatalytic performance of CN for the reduction of U(Ⅵ) by Y3+ doping.

Abstract Lipoprotein(a) [Lp(a)] is an emerging predictor for atherosclerotic cardiovascular disease (ASCVD) but the association from a perspective on current risk stratification was unknown. A cohort of 9944 Chinese patients with ASCVD was recruited and refined into very‐high‐risk (VHR) and non‐VHR subgroups according to current guideline. Lp(a) plasma levels were divided by its concentration (

Background : Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indices of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction. Methods : This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed. Results : Distribution of the TyAG and TyAG-BMI indices shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P

Abstract Background Diabetic kidney disease is an established risk factor for heart failure. However, the impact of incident heart failure on the subsequent risk of renal failure has not been systematically assessed in diabetic population. We sought to study the risk of progression to end stage kidney disease (ESKD) after incident heart failure in Asian patients with type 2 diabetes. Methods In this prospective cohort study, 1985 outpatients with type 2 diabetes from a regional hospital and a primary care facility in Singapore were followed for a median of 8.6 (interquartile range 6.2–9.6) years. ESKD was defined as a composite of progression to sustained eGFR below 15 ml/min/1.73m2, maintenance dialysis or renal death, whichever occurred first. Results 180 incident heart failure events and 181 incident ESKD events were identified during follow-up. Of 181 ESKD events, 38 (21%) occurred after incident heart failure. Compared to those did not progress to ESKD after incident heart failure (n = 142), participants who progressed to ESKD after heart failure occurrence were younger, had higher HbA1c and higher urine albumin-to-creatinine ratio at baseline. The excess risk of ESKD manifested immediately after heart failure occurrence, persisted for two years and was moderated thereafter. Cox regression suggested that, compared to counterparts with no heart failure event, participants with heart failure occurrence had 9.6 (95% CI 5.0- 18.3) fold increased risk for incident ESKD after adjustment for baseline cardio-renal risk factors including eGFR and albuminuria. It appeared that heart failure with preserved ejection fraction had a higher risk for ESKD as compared to those with reduced ejection fraction (adjusted HR 13.7 [6.3–29.5] versus 6.5 [2.3–18.6]). Conclusion Incident heart failure impinges a high risk for progression to ESKD in individuals with type 2 diabetes. Our data highlight the need for intensive surveillance of kidney function after incident heart failure, especially within the first two years after heart failure diagnosis.

Abstract In this study we aimed to investigate the prevalence of SARS-CoV-2 infection in psoriasis patients, and outcomes of SARS-CoV-2 infection and associated risk factors. A cross-sectional survey was conducted from February 2023 to March 2023. Information was obtained with online questionnaire about psoriasis patients on demographic characteristics, clinical characteristics, SARS-CoV-2 infection and outcomes, vaccination, and routine protection against COVID-19. Logistic regression analysis was used to explore risk factors with SARS-CoV-2 infection and exacerbation of psoriasis. A total of 613 participants were recruited. 516 (84.2%) were infected, and associated factors were sex, working status, routine protection against COVID-19, COVID-19 vaccination, impaired nail, infection exacerbate psoriasis, and severity of psoriasis. Among the patients infected with SARS-CoV-2, 30 (5.8%) required hospitalization, 122 (23.6%) had psoriasis exacerbation due to SARS-CoV-2 infection, and associated factors were subtype of psoriasis, discontinuation of psoriasis treatment during SARS-CoV-2 infection, response following COVID-19 vaccination, and severity of psoriasis. Booster dose vaccination contributed a low probability of COVID-19 sequelae. COVID-19 vaccine’s effectiveness was unsatisfactory, while booster dose vaccination reduced the occurrence of COVID-19 sequelae in psoriasis patients of Southwest China. Patients treated with psoriasis shown to be safe, without a higher incidence of SARS-CoV-2 infection or COVID-19hospitalization compared to untreated patients. Stopping treatment during SARS-CoV-2 infection led to psoriasis exacerbation, so psoriasis treatment could be continued except severe adverse reaction.

Abstract Background Angiogenin, an enzyme belonging to the ribonucleases A superfamily, plays an important role in vascular biology. Here, we sought to study the association of plasma angiogenin and major adverse cardiovascular events (MACEs) in patients with type 2 diabetes (T2D). Methods This prospective study included 1083 T2D individuals recruited from a secondary hospital and a primary care facility. The primary outcome was a composite of four-point MACE (nonfatal myocardial infarction, stroke, unstable angina pectoris leading to hospitalization and cardiovascular death). Circulating angiogenin was measured by a proximity extension assay. Cox regression models were used to evaluate the association of baseline plasma angiogenin with the risk of MACE. Results During a median follow-up of 9.3 years, 109 (10%) MACE were identified. Plasma angiogenin was significantly higher in participants with MACE than in those without MACE (P

Abstract Background American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS, TR) 4 and 5 thyroid nodules (TNs) demonstrate much more complicated and overlapping risk characteristics than TR1-3 and have a rather wide range of malignancy possibilities (> 5%), which may cause overdiagnosis or misdiagnosis. This study was designed to establish and validate a dual-modal ultrasound (US) radiomics nomogram integrating B-mode ultrasound (BMUS) and contrast-enhanced ultrasound (CEUS) imaging to improve differential diagnostic accuracy and reduce unnecessary fine needle aspiration biopsy (FNAB) rates in TR 4–5 TNs. Methods A retrospective dataset of 312 pathologically confirmed TR4-5 TNs from 269 patients was collected for our study. Data were randomly divided into a training dataset of 219 TNs and a validation dataset of 93 TNs. Radiomics characteristics were derived from the BMUS and CEUS images. After feature reduction, the BMUS and CEUS radiomics scores (Rad-score) were built. A multivariate logistic regression analysis was conducted incorporating both Rad-scores and clinical/US data, and a radiomics nomogram was subsequently developed. The performance of the radiomics nomogram was evaluated using calibration, discrimination, and clinical usefulness, and the unnecessary FNAB rate was also calculated. Results BMUS Rad-score, CEUS Rad-score, age, shape, margin, and enhancement direction were significant independent predictors associated with malignant TR4-5 TNs. The radiomics nomogram involving the six variables exhibited excellent calibration and discrimination in the training and validation cohorts, with an AUC of 0.873 (95% CI, 0.821–0.925) and 0.851 (95% CI, 0.764–0.938), respectively. The marked improvements in the net reclassification index and integrated discriminatory improvement suggested that the BMUS and CEUS Rad-scores could be valuable indicators for distinguishing benign from malignant TR4-5 TNs. Decision curve analysis demonstrated that our developed radiomics nomogram was an instrumental tool for clinical decision-making. Using the radiomics nomogram, the unnecessary FNAB rate decreased from 35.3 to 14.5% in the training cohort and from 41.5 to 17.7% in the validation cohorts compared with ACR TI-RADS. Conclusion The dual-modal US radiomics nomogram revealed superior discrimination accuracy and considerably decreased unnecessary FNAB rates in benign and malignant TR4-5 TNs. It could guide further examination or treatment options.

Abstract Background Triple-negative breast cancer (TNBC) remains the most challenging subtype of breast cancer and lacks definite treatment targets. Aerobic glycolysis is a hallmark of metabolic reprogramming that contributes to cancer progression. PFKP is a rate-limiting enzyme involved in aerobic glycolysis, which is overexpressed in various types of cancers. However, the underlying mechanisms and roles of the posttranslational modification of PFKP in TNBC remain unknown. Methods To explore whether PFKP protein has a potential role in the progression of TNBC, protein levels of PFKP in TNBC and normal breast tissues were examined by CPTAC database analysis, immunohistochemistry staining (IHC), and western blotting assay. Further CCK-8 assay, colony formation assay, EDU incorporation assay, and tumor xenograft experiments were used to detect the effect of PFKP on TNBC progression. To clarify the role of the USP5-PFKP pathway in TNBC progression, ubiquitin assay, co-immunoprecipitation (Co-IP), mass spectrometry-based protein identification, western blotting assay, immunofluorescence microscopy, in vitro binding assay, and glycolysis assay were conducted. Results Herein, we showed that PFKP protein was highly expressed in TNBC, which was associated with TNBC progression and poor prognosis of patients. In addition, we demonstrated that PFKP depletion significantly inhibited the TNBC progression in vitro and in vivo. Importantly, we identified that PFKP was a bona fide target of deubiquitinase USP5, and the USP5-mediated deubiquitination and stabilization of PFKP were essential for cancer cell aerobic glycolysis and TNBC progression. Moreover, we found a strong positive correlation between the expression of USP5 and PFKP in TNBC samples. Notably, the high expression of USP5 and PFKP was significantly correlated with poor clinical outcomes. Conclusions Our study established the USP5-PFKP axis as an important regulatory mechanism of TNBC progression and provided a rationale for future therapeutic interventions in the treatment of TNBC.

The use of light energy to drive asymmetric organic transformations to produce high-value-added organic compounds is attracting increasing interest as a sustainable strategy for solving environmental problems and addressing the energy crisis. Chiral covalent organic frameworks (COFs), as porous crystalline chiral materials, have become an important platform on which to explore new chiral photocatalytic materials due to their precise tunability, chiral structure, and function. This review highlights recent research progress on chiral COFs and their crystalline composites, evaluating their application as catalysts in asymmetric photocatalytic organic transformations in terms of their structure. Finally, the limitations and challenges of chiral COFs in asymmetric photocatalysis are discussed, with future opportunities for research being identified.

Circulating ceramide levels are dysregulated in kidney disease. However, their associations with rapid decline in kidney function (RDKF) and end-stage kidney disease (ESKD) in patients with type 2 diabetes (T2D) are unknown. In this prospective study of 1746 T2D participants, we examined the association of plasma ceramide Cer16:0, Cer18:0, Cer24:0, and Cer24:1 with RDKF, defined as an estimated glomerular filtration rate (eGFR) decline of 5 ml/min/1.73 m2 per year or greater, and ESKD defined as eGFR

Abstract The morphology and motion of auroras have been widely studied due to their indications on magnetospheric processes. Here, we report a new kind of “auroral curls,” which have wavelengths in the mesoscale (∼100 km) and propagate azimuthally. Utilizing data from the Chinese Antarctic Zhongshan Station (the all‐sky imager and the high‐frequency radar), the Active Magnetosphere and Planetary Electrodynamics Response Experiment and the Defense Meteorological Satellite Program, we analyze an event occurred on 23 April 2019. We find these curls are fine structures in the poleward boundary of multiple arcs. Corresponding field‐aligned currents manifest as a series of longitudinally arranged pairs, while ionospheric flow velocities nearby oscillate with periods in the Pc 5 band. Observational evidence suggests these curls are connected with ultra‐low frequency (ULF) waves, which opens the possibility of using auroras to globally image ULF waves.

This paper presents a new analytical solution to investigate the mechanism of transient confined-unconfined flow in a confined aquifer induced by pumping with a large rate during mine drainage. The study focuses on understanding the impact of non-Darcian effect on flow towards a fully penetrated pumping well. The nonlinear relationship between specific discharge and the hydraulic gradient is described using Izbash's equation. A novel approximate method is developed to linearize the mathematical model, and the solution is derived using the Boltzmann transform. The proposed solution is validated by comparing it with previous works. The findings indicate that increased non-Darcian index, quasi-hydraulic conductivity, and specific storage have negatively affect the development of the unconfined region and aquifer drawdown, as greater turbulence flow accelerates recharge to the pumping well. Drawdown is found to be sensitive to the non-Darcian index, quasi-hydraulic conductivity, while it is unaffected by specific yield and specific storage. The conclusions provide valuable insights for mine drainage and the application of geological and hydrological conditions.

Abstract A wide range of Cu(II)-catalyzed C–H activation reactions have been realized since 2006, however, whether a C–H metalation mechanism similar to Pd(II)-catalyzed C–H activation reaction is operating remains an open question. To address this question and ultimately develop ligand accelerated Cu(II)-catalyzed C–H activation reactions, realizing the enantioselective version and investigating the mechanism is critically important. With a modified chiral BINOL ligand, we report the first example of Cu-mediated enantioselective C–H activation reaction for the construction of planar chiral ferrocenes with high yields and stereoinduction. The key to the success of this reaction is the discovery of a ligand acceleration effect with the BINOL-based diol ligand in the directed Cu-catalyzed C–H alkynylation of ferrocene derivatives bearing an oxazoline-aniline directing group. This transformation is compatible with terminal aryl and alkyl alkynes, which are incompatible with Pd-catalyzed C–H activation reactions. This finding provides an invaluable mechanistic information in determining whether Cu(II) cleaves C–H bonds via CMD pathway in analogous manner to Pd(II) catalysts.

Abstract Background Although the adiponectin signalling exerts exercise‐mimicking effects, whether this pathway contributes to the anti‐ageing benefits of physical exercise has not been established yet. Methods Swim exercise training and wheel running were used to measure lifespan in the nematode Caenorhabditis elegans and skeletal muscle quality in mice, respectively. Muscle weight, muscle fibre cross‐sectional area (CSA) and myonuclei number were used to evaluate muscle mass. RNA sequencing (RNA‐Seq) analysis of skeletal muscle in exercised mice was used to study the underlying mechanisms. Western blot and immunofluorescence were performed to explore autophagy‐ and senescence‐related markers. Results The C. elegans adiponectin receptor PAQR‐1/AdipoR1, but not PAQR‐2/AdipoR2, was activated (3.55‐fold and 3.48‐fold increases in p‐AMPK on Days 1 and 6, respectively, P

Spinal cord injury (SCI) results in a large amount of tissue cell debris in the lesion site, which interacts with various cytokines, including inflammatory factors, and the intrinsic glial environment of the central nervous system (CNS) to form an inhibitory microenvironment that impedes nerve regeneration. The efficient clearance of tissue debris is crucial for the resolution of the inhibitory microenvironment after SCI. Macrophages are the main cells responsible for tissue debris removal after SCI. However, the high lipid content in tissue debris and the dysregulation of lipid metabolism within macrophages lead to their transformation into foamy macrophages during the phagocytic process. This phenotypic shift is associated with a further pro-inflammatory polarization that may aggravate neurological deterioration and hamper nerve repair. In this review, we summarize the phenotype and metabolism of macrophages under inflammatory conditions, as well as the mechanisms and consequences of foam cell formation after SCI. Moreover, we discuss two strategies for foam cell modulation and several potential therapeutic targets that may enhance the treatment of SCI.

BackgroundInflammation is a predictor of severe complications in patients with COVID-19 infection under a variety of clinical settings. A few studies suggested that COVID-19 infection was a trigger of hyperglycemic crises including diabetic ketoacidosis (DKA) and/or hyperglycemic hyperosmolar state (HHS). However, the association between inflammation and hyperglycemic crises in diabetic patients with COVID-19 infection is unclear.MethodsOne hundred and twenty-four patients with type 2 diabetes mellitus (T2DM) and COVID-19 infection from January 2023 to March 2023 were retrospectively analyzed. Demographic, clinical, and laboratory data, especially inflammatory markers including white blood cell (WBC), neutrophils, neutrophil-to-lymphocyte ratio (NLR), c-reactive protein (CRP) and procalcitonin (PCT) were collected and compared between patients with or without DKA and/or HHS. Multivariable logistic regression analysis was conducted to explore the association between inflammatory biomarkers and the prevalence of hyperglycemic crises. Patients were followed up 6 months for outcomes.ResultsAmong 124 diabetic patients with COVID-19, 9 were diagnosed with DKA or HHS. Comparing COVID-19 without acute diabetic complications (ADC), patients with DKA or HHS showed elevated levels of c-reactive protein (CRP, P=0.0312) and procalcitonin (PCT, P=0.0270). The power of CRP and PCT to discriminate DKA or HHS with the area under the receiver operating characteristics curve (AUROC) were 0.723 and 0.794, respectively. Multivariate logistic regression indicated 1.95-fold and 1.97-fold increased risk of DKA or HHS with 1-unit increment of CRP and PCT, respectively. However, neither CRP nor PCT could predict poor outcomes in diabetic patients with COVID-19.ConclusionIn this small sample size study, we firstly found that elevated serum CRP and PCT levels increased the risk of hyperglycemic crises in T2DM patients with COVID-19 infection. More study is needed to confirm our findings.

Diabetic cardiomyopathy (DCM), one of the common complications of diabetes, presents as a specific cardiomyopathy with anomalies in the structure and function of the heart. With the increasing prevalence of diabetes, DCM has a high morbidity and mortality worldwide. Recent studies have found that pyroptosis, as a programmed cell death accompanied by an inflammatory response, exacerbates the growth and genesis of DCM. These studies provide a theoretical basis for exploring the potential treatment of DCM. Therefore, this review aims to summarise the possible mechanisms by which pyroptosis promotes the development of DCM as well as the relevant studies targeting pyroptosis for the possible treatment of DCM, focusing on the molecular mechanisms of NLRP3 inflammasome-mediated pyroptosis, different cellular pyroptosis pathways associated with DCM, the effects of pyroptosis occurring in different cells on DCM, and the relevant drugs targeting NLRP3 inflammasome/pyroptosis for the treatment of DCM. This review might provide a fresh perspective and foundation for the development of therapeutic agents for DCM.

Abstract Background and Aim The biological functions and clinical implications of lysophosphatidylcholine acyltransferase 1 (LPCAT1) remain unclarified in gastric cancer (GC). The aim of the current study was to explore the possible clinicopathological significance of LPCAT1 and its perspective mechanism in GC tissues. Materials and Methods The protein expression and mRNA levels of LPCAT1 were detected from in‐house immunohistochemistry and public high‐throughput RNA arrays and RNA sequencing. To have a comprehensive understanding of the clinical value of LPCAT1 in GC, all enrolled data were integrated to calculate the expression difference and standard mean difference (SMD). The biological mechanism of LPCAT1 in GC was confirmed by computational biology and in vitro experiments. Migration and invasion assays were also conducted to confirm the effect of LPCAT1 in GC. Results Both protein and mRNA expression levels of LPCAT1 in GC were remarkably higher than those in noncancerous controls. Comprehensively, the SMD of LPCAT1 mRNA was 1.11 (95% CI = 0.86–1.36) in GC, and the summarized AUC was 0.85 based on 15 datasets containing 1727 cases of GC and 940 cases of non‐GC controls. Moreover, LPCAT1 could accelerate the invasion and migration of GC by boosting the neutrophil degranulation pathway and disturbing the immune microenvironment. Conclusion An increased level of LPCAT1 may promote the progression of GC.

Abstract Background Familial hypercholesterolemia (FH) leads to high plasma low-density lipoprotein cholesterol (LDL-C) levels and early cardiovascular morbidity and mortality. We treated a pair of siblings with FH. The cardiovascular manifestations in the proband were more severe than those in his elder sister, although they had almost similar LDL-C levels, ages, and lifestyles. Herein, we report the cases of this family to explore the possible causes of clinical phenotypic differences within the same genetic background. Case presentation We treated a 27-year-old male patient and his 30-year-old sister, both with FH. The coronary angiogram in the male patient revealed 80, 70, and 100% stenosis of the initial, distal right coronary artery branch, and left anterior descending branch, respectively, whereas his sister had almost no coronary stenosis. We treated them accordingly and performed family screening. We found that the LDL-C/particle discordance of the proband is much greater than that of his elder sister. In addition, the average size of LDL-C particle in the proband was smaller than that in his sister. Conclusions Patients with FH have a much higher risk of premature atherosclerotic cardiovascular disease, but the clinical manifestations are heterogeneous. The smaller LDL particle size may be the underlying cause for different clinical outcomes in this pair of FH cases and be a potential novel indicator for predicting the prognosis of FH.

Background: For the patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) for at least 1 year is recommended in the guidelines to minimize the risk of stent thrombosis. Persistently uncovered stent strut means delayed neointima formation and extend the window of time in which the stent is prone to thrombosis. Previous studies showed that statins could improve post-stenting strut endothelial coverage for patients undergoing PCI. However, there are lack of evidences on whether early initiation of proprotein convertase subtilisin/Kexin type 9 monoclonal antibody (PCSK9mAb) after PCI in ACS patients can further improve the rate of stent strut coverage on the background of oral lipid-lowering therapy (LLT). Methods: This is a single-center, randomized trial to enroll 36 patients undergoing PCI with a clinical diagnosis of non-ST-segment elevation ACS. The baseline level of low-density lipoprotein cholesterol (LDL-C) of these patients are between 1.4 mmol/L and 3.4 mmol/L. Patients will be assigned to intensive lipid-lowering therapy (LLT) with PCSK9mAb group and conventional LLT without PCSK9mAb group for 12 weeks in a clinical follow-up setting according to 1: 1 randomization. the rate of stent strut endothelial coverage by optical coherence tomography (OCT) examination at 12 weeks after enrollment between the groups will be compared. Conclusion: This will be the first study to investigate changes in the rate of stent strut endothelial coverage under intensive LLT with PCSK9mAb by OCT examination in ACS patients undergoing PCI. The finding of this study will provide clinical evidence for future research about the hypothesis of a novel strategy of “intensive LLT (PCSK9mAb + statin ± ezetimibe) combined with shortened DAPT duration” for ACS patients undergoing PCI.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: ChiCTR2200063395.

Diabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mortality; however, few mechanistic biomarkers are available for high-risk patients, especially those without macroalbuminuria. Urine from participants with diabetes from the Chronic Renal Insufficiency Cohort (CRIC) study, the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D), and the American Indian Study determined whether urine adenine/creatinine ratio (UAdCR) could be a mechanistic biomarker for ESKD. ESKD and mortality were associated with the highest UAdCR tertile in the CRIC study and SMART2D. ESKD was associated with the highest UAdCR tertile in patients without macroalbuminuria in the CRIC study, SMART2D, and the American Indian study. Empagliflozin lowered UAdCR in nonmacroalbuminuric participants. Spatial metabolomics localized adenine to kidney pathology, and single-cell transcriptomics identified ribonucleoprotein biogenesis as a top pathway in proximal tubules of patients without macroalbuminuria, implicating mTOR. Adenine stimulated matrix in tubular cells via mTOR and stimulated mTOR in mouse kidneys. A specific inhibitor of adenine production was found to reduce kidney hypertrophy and kidney injury in diabetic mice. We propose that endogenous adenine may be a causative factor in DKD.

Caprine arthritis-encephalitis virus (CAEV) is an under-studied virus infecting caprines and ovines worldwide. Over the last four decades, CAEV has spread in China, obtaining genomic data on CAEV strains circulating in China is of importance for developing diagnostic methods and eradicating associated diseases. However, there is limited information on the genome, including characterizations, and the probable origin. This work aimed to characterize Chinese CAEV genomes and population structures. Five CAEV strains isolated from infected dairy goats between 1989 and 1994 in Gansu, Guizhou, Shaanxi, Shandong and Sichuan provinces were cloned and sequenced. The Chinese CAEV had a 58–93% genome similarities to strains outside of China, and they belonged to subgenotype B1. The highest similarity levels (98.3–99.3%) were with two other Chinese strains, and they shared a 91.8–92.3% similarity with the strain Clements (GenBank accession no. NC_001463.1) from outside of China. The Chinese CAEV strains isolated from different provinces over five years were still highly homologous and contained unique ancestral population components, indicating that these Chinese strains had a common origin that differed from other known strains. Our results provide genomic data on circulating Chinese CAEV strains and will be useful for future epidemiological investigations and CAEV eradication programs.

The inability of damaged neurons to regenerate within the mature central nervous system (CNS) is a significant neuroscientific challenge. Astrocytes are an essential component of the CNS and participate in many physiological processes including blood-brain barrier formation, axon growth regulation, neuronal support, and higher cognitive functions such as memory. Recent reprogramming studies have confirmed that astrocytes in the mature CNS can be transformed into functional neurons. Building on in vitro work, many studies have demonstrated that astrocytes can be transformed into neurons in different disease models to replace damaged or lost cells. However, many findings in this field are controversial, as the source of new neurons has been questioned. This review summarizes progress in reprogramming astrocytes into neurons in vivo in animal models of spinal cord injury, brain injury, Huntington’s disease, Parkinson’s disease, Alzheimer’s disease, and other neurodegenerative conditions.

Spinal cord injury is a severe and devastating disease, and spasticity is a common and severe complication that is notoriously refractory to treatment. However, the pathophysiological mechanisms underlying spasticity and its development remain largely unknown. The goal of the present study was to find differences, if any, in metabolites of the left precentral gyrus and basal ganglia of patients who have spinal cord injury with or without spasticity, and to explore the relationship between the brain metabolite concentrations and clinical status. Thirty-six participants were recruited for magnetic resonance spectroscopic examination: 23 with spinal cord injury (12 with spasticity and 11 without spasticity) and 13 healthy controls. We acquired localized proton spectra from the precentral gyrus and basal ganglia via 10 mm3 voxels. Notably, univariate linear regression analysis demonstrated that the lower that the N-acetylaspartate concentration (a marker for neuronal loss) was in the precentral gyrus of the patients, the lower their ASIA (American Spinal Injury Association) light-touch scores, pinprick scores, and motor scores. Additionally, longer durations of injury were associated with higher N-acetylaspartate levels in the precentral gyrus. Compared with the healthy participants and patients without spasticity, N-acetylaspartate levels in the patients with spasticity were significantly lower in both the precentral gyrus and basal ganglia. Lower N-acetylaspartate levels also correlated with greater sensory and motor dysfunction in the patients who had spinal cord injury with spasticity.

This paper proposes a simplified analytical solution considering non-Darcian and wellbore storage effect to investigate the pumping flow in a confined aquifer with barrier and recharge boundaries. The mathematical modelling for the pumping-induced flow in aquifers with different boundaries is developed by employing image-well theory with the superposition principle, of which the non-Darcian effect is characterized by Izbash’s equation. The solutions are derived by Boltzmann and dimensionless transformations. Then, the non-Darcian effect and wellbore storage are especially investigated according to the proposed solution. The results show that the aquifer boundaries have non-negligible effects on pumping, and ignoring the wellbore storage can lead to an over-estimation of the drawdown in the first 10 minutes of pumping. The higher the degree of non-Darcian, the smaller the drawdown.

Stromal antigen 1 (STAG1), a component of cohesion, is overexpressed in various cancers, but it is unclear whether it has a role in the transcriptional regulation of hepatocellular carcinoma (HCC). To test this hypothesis, here, we screened global HCC datasets and performed multiscale embedded gene co‐expression network analysis to identify the potential functional modules of differentially expressed STAG1 co‐expressed genes. The putative transcriptional targets of STAG1 were identified using chromatin immunoprecipitation followed by high‐throughput DNA sequencing. The cohesin‐associated gene score (CAGS) was quantified using the The Cancer Genome Atlas HCC cohort and single‐sample gene set enrichment analysis. Distinct cohesin‐associated gene patterns were identified by calculating the euclidean distance of each patient. We assessed the potential ability of the CAGS in predicting immune checkpoint blockade (ICB) treatment response using IMvigor210 and GSE78220 cohorts. STAG1 was upregulated in 3313 HCC tissue samples compared with 2692 normal liver tissue samples (standard mean difference = 0.54). A total of three cohesin‐associated gene patterns were identified, where cluster 2 had a high TP53 mutated rate and a poor survival outcome. Low CAGS predicted a significant survival advantage but presaged poor immunotherapy response. Differentially expressed STAG1 co‐expression genes were enriched in the mitotic cell cycle, lymphocyte activation, and blood vessel development. PDS5A and PDGFRA were predicted as the downstream transcriptional targets of STAG1. In summary, STAG1 is significantly upregulated in global HCC tissue samples and may participate in blood vessel development and the mitotic cell cycle. A cohesin‐associated gene scoring system may have potential to predict the ICB response.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of Chinese guideline for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the “Guidelines for the prevention and treatment of dyslipidemia" were adapted into the “Chinese guideline for Lipid Management" (henceforth referred to as the new guidelines) by an Experts’ committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with cardiovascular disease (CVD) risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

Abstract Background Tuberculosis (TB) poses a severe public health challenge in China and worldwide. This study evaluated the effects of age, period, and birth cohort on reported incidence trends of TB based on population and refined the characteristics of high-risk groups. Methods Aggregate data that reported pulmonary tuberculosis (PTB) cases from China Tuberculosis Management Information System (TBIMS) from 2006 to 2020 were used to analyze effect coefficients through the age–period–cohort (APC) model based on intrinsic estimator (IE) method, and converted them into relative risk (RR) to estimate trends. Results A total of 14.82 million cases of PTB were reported in China from 2006 to 2020, showing a continuous downward trend. The reporting rate increased with age by age group, with 70–74 years old being 2–3 times higher than that in 20–24 years old. APC analysis model showed that age effects were bimodal in 20–24 years old [RR = 2.29, 95% confidence interval (CI): 1.73–3.03] and 70–74 years old (RR = 1.95, 95% CI: 1.67–2.27), and lower than the overall average in the groups under 15 years old. Stratified results showed that the risk was higher for women under age 40 than men and higher for men over 40. The risk was higher in urban than in rural areas under 30 years old and slightly higher in rural than in urban between 30 and 64 years old. The risk for 15–34 years old was significantly higher in the east than in other regions. The period effects showed a decreasing trend, and the risk was higher in rural in recent years. Except for cohorts born in 1961–1965 and 2001–2005, where the RR increased, the later the cohort was born, the lower the risk. The cohort 1926–1930 in eastern had the highest risk (RR = 3.49, 95% CI: 2.44–4.98). Conclusions The reported incidence of PTB continued to decline in China from 2006 to 2020. The young (20–24 years old) and the elderly (70–74 years old) were equally at high risk. There were differences in the age, period and cohort effects on PTB incidence among gender, urban–rural and regions. Our findings better reflected the characteristics of high-risk populations, thus contributing to the development of timely and effective intervention strategies, and providing clues for etiological research. Graphical abstract

Glycans are an important group of natural biopolymers, which not only play the role of a major biological energy resource but also as signaling molecules. As a result, structural characterization or sequencing of glycans, as well as targeted synthesis of glycans, is of great interest for understanding their structure–function relationship. However, this generally involves tedious manual operations and high reagent consumptions, which are the main technical bottlenecks retarding the advances of both automatic glycan sequencing and synthesis. Until now, automated enzymatic glycan sequencers or synthesizers are still not available on the market. In this study, to promote the development of automation in glycan sequencing or synthesis, first, programmed degradation and synthesis of glycans catalyzed by enzymes were successfully conducted on a digital microfluidic (DMF) device by using microdroplets as microreactors. In order to develop automatic glycan synthesizers and sequencers, a strategy integrating enzymatic oligosaccharide degradation or synthesis and magnetic manipulation to realize the separation and purification process after enzymatic reactions was designed and performed on DMF. An automatic process for enzymatic degradation of tetra-N-acetyl chitotetraose was achieved. Furthermore, the two-step enzymatic synthesis of lacto-N-tetraose was successfully and efficiently completed on the DMF platform. This work demonstrated here would open the door to further develop automatic enzymatic glycan synthesizers or sequencers based on DMF.

BackgroundSpontaneous hemorrhage of gastro-omental hemangioma is a rare disease. The treatment strategy for this disease changes as it develops. In the acute stage, surgery is the first priority, among which laparoscopic treatment should be the most frequently considered option in large general hospitals. Due to the rarity of this disease, such cases have rarely been reported.Case descriptionWe present the first report of two eldely cases with gastro-omental hemangioma with hemorrhage by laparoscopic treatment. Both cases were initially admitted with upper abdominal pain, and abdominal computed tomography (CT) scan revealed masses alongside the greater curvature of the stomach. Laparoscopic surgery was conducted immediately in both patients. The two cases recovered well after surgery, and no obvious abnormalities were observed in the follow-up period.ConclusionGastro-omental hemangioma rupture remains an uncommon cause of intraperitoneal hemorrhage. Timely diagnosis and surgery are paramount for treatment. Medical institutions with the correct technology and equipment should perform laparoscopic treatment to minimize surgical trauma and promote rapid recovery of patients with abdominal apoplexy.

Abstract Throat auroras and polar cap patches are common phenomena in the polar ionosphere resulting from magnetosphere‐ionosphere coupling. A campaign was organized, with all‐sky imagers at Yellow River Station, the European Incoherent Scatter Svalbard Radar, and coordinated low‐altitude spacecraft observations. During periods of radial interplanetary magnetic field (IMF), observations showed that, as poleward moving throat auroras faded around the polar cap boundary, they linked to poleward moving ionization patches. The throat auroras were produced by soft‐electron precipitation associated with dayside magnetic reconnection. The red line emission intensity of throat auroras was correlated with dayside reconnection events. Dense plasma from lower latitudes was transported poleward via enhanced convection in the throat auroras to form patches. This is a potentially new formation mechanism for patches associated with throat auroras and magnetic reconnection for radial IMF. Moreover, the patches move anti‐sunward due to the E × B drift.

Abstract With rapid economic growth and changes at all levels (including environmental, social, individual), China is facing a cardiovascular disease (CVD) crisis. In China, more than 40% of deaths are attributable to CVDs, and the number of CVD deaths has almost doubled in the past decades, in contrast to a decline in high-income countries. The increasing prevalence of cardiometabolic risk factors underlies the rise of CVDs, and thus curbing the rising cardiometabolic pandemic is imperative. Few articles have addressed this topic and provided an updated review of the epidemiology of cardiometabolic risk factors in China. In this narrative review, we describe the temporal changes in the prevalence of cardiometabolic risk factors in the past decades and their management in China, including both the well-recognized risk factors (general obesity, central obesity, diabetes, prediabetes, dyslipidemia, hypertension) and the less recognized ones (hyperhomocysteinemia, hyperuricemia, and high C-reactive protein). We also summarize findings from landmark clinical trials regarding effective interventions and treatments for cardiometabolic risk factors. Finally, we propose strategies and approaches to tackle the rising pandemic of cardiometabolic risk factors in China. We hope that this review will raise awareness of cardiometabolic risk factors not only in Chinese population but also global visibility, which may help to prevent cardiovascular risk.

Abstract Background Currently, remnant cholesterol (RC), lipoprotein(a) [Lp(a)], and inflammation are considered the principal residual cardiovascular risk (RCVR) factors. This study sought to evaluate the combined impact of RC, Lp(a), and inflammation on prognosis of statin-treated patients with chronic coronary syndrome (CCS), which has not been investigated. Methods A total of 6839 patients with CCS were consecutively enrolled. Baseline RC, Lp(a), and high-sensitivity C-reactive protein (hsCRP) concentrations were measured and their medians were used for categorizations. All patients were followed for the major adverse cardiovascular events (MACEs), including cardiovascular death, non-fatal myocardial infarction, and stroke. The individual and combined effects of RC, Lp(a), and hsCRP on MACEs were examined and stratification analysis according to low-density lipoprotein cholesterol (LDL-C) was performed. Results Over an average of 54.93 ± 18.59 months follow-up, 462 MACEs were recorded. Multivariate Cox analysis showed that elevated RC and Lp(a) levels were significantly associated with an increased risk of MACEs, while high hsCRP levels were related to a slightly but non-significantly increased MACEs risk. Moreover, when participants were subgrouped according to RC, Lp(a), and hsCRP levels together, only High RC-High Lp(a)-High hsCRP group had significantly higher risk of MACEs [hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.15–3.47] compared with the reference group (Low RC-Low Lp(a)-Low hsCRP), especially in patients with LDL-C

Abstract The triglyceride-glucose (TyG) index has been identified as a reliable alternative biomarker of insulin resistance (IR). Recently, a considerable number of studies have provided robust statistical evidence suggesting that the TyG index is associated with the development and prognosis of cardiovascular disease (CVD). Nevertheless, the application of the TyG index as a marker of CVD has not systemically been evaluated, and even less information exists regarding the underlying mechanisms associated with CVD. To this end, in this review, we summarize the history of the use of the TyG index as a surrogate marker for IR. We aimed to highlight the application value of the TyG index for a variety of CVD types and to explore the potential limitations of using this index as a predictor for cardiovascular events to improve its application value for CVD and provide more extensive and precise supporting evidence.

Abstract Background Familial hypercholesterolemia (FH) is a metabolic disease in which patients are prone to develop premature atherosclerosis (AS). Sorbin and SH3 Domain Containing 2 (SORBS2) is known to play a role in coronary heart disease (CHD). However, the mechanism underlying SORBS2 involvement in the development of hypercholesterolemia remains unknown. Here, we investigated the effects of SORBS2 on inflammation and foam cell formation and its underlying mechanisms. Methods Using Bioinformatics analysis, we established that SORBS2 is upregulated in patients with FH. Circulating concentrations of SORBS2 were measured using ELISA kit (n = 30). The association between circulating SORBS2 levels and inflammatory factors or lipid indexes were conducted using Spearman correlation analysis. We further conducted in vitro experiments that the expression of SORBS2 were analyzed, and SORBS2 siRNA were transfected into oxidized LDL (OxLDL)-induced macrophages, followed by western blot and immunofluorescence. Results Circulating SORBS2 levels were positively associated with inflammatory factors and lipid indexes. We also observed that high in vitro expression of SORBS2 in OxLDL-induced macrophages. After SORBS2 silencing, Nod like receptor family pyrin domain-containing 3 protein(NLRP3)-Caspase1 activation and NF-κB activation were attenuated, and secretion of pro-inflammatory cytokines (IL-1β and IL-18) was decreased. Moreover, SORBS2 silencing blocked reactive oxygen species (ROS) production and lipid accumulation, and promoted cholesterol efflux through ABCG1-PPARγ pathway. Conclusions SORBS2 regulates lipid-induced inflammation and foam cell formation, and is a potential therapeutic target for hypercholesterolemia.

Atherosclerosis, the key pathogenesis of cardiovascular disease, is a leading cause of death and disability worldwide. Statins are first-line lipid-lowering drugs, which have been demonstrated to be powerful agents for anti-atherosclerosis. Numerous studies have confirmed the cardiovascular benefits and long-term safety of statins in a wide range of patients. Statins play an indispensable and irreplaceable part in the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). In this article, we summarize the evolution of statins and their role in the treatment of cholesterol. The anti-atherosclerotic mechanism of statins, its efficacy, safety and clinical outcomes in secondary and primary prevention of ACSVD in different patient populations, the combination treatment effects, and guideline recommendations are also detailed. This paper highlights the profound significance of statins as the most successful anti-atherogenic drug in the cardiovascular field.

In previous studies, researchers have used singing to treat respiratory function in patients with spinal cord injury. However, few studies have examined the way in which vocal training affects respiratory neural plasticity in patients with spinal cord injury. Vocal respiratory training (VRT) is a type of vocal muscle-related treatment that is often a component of music therapy (MT) and focuses on strengthening respiratory muscles and improving lung function. In this randomized controlled study, we analyzed the therapeutic effects of VRT on respiratory dysfunction at 3 months after cervical spinal cord injury. Of an initial group of 37 patients, 26 completed the music therapy intervention, which comprised five 30-minute sessions per week for 12 weeks. The intervention group (n = 13) received VRT training delivered by professional certified music therapists. The control group (n = 13) received respiratory physical therapy delivered by professional physical therapists. Compared with the control group, we observed a substantial increase in respiratory function in the intervention group after the 12-week intervention. Further, the nerve fiber bundles in the respiratory center in the medulla exhibited a trend towards increased diversification, with an increased number, path length, thickness, and density of nerve fiber bundles. These findings provide strong evidence for the effect of music therapeutic VRT on neural plasticity. This study was approved by the Ethics Committee of China Rehabilitation Research Center (approval No. 2020-013-1) on April 1, 2020, and was registered with the Chinese Clinical Trial Registry (registration No. ChiCTR2000037871) on September 2, 2020.

Abstract Background The risk of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) can be easily evaluated by noninvasive scoring systems, of which the NAFLD fibrosis score (NFS) is the most commonly used. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a new predictor of cardiovascular events, has been reported to be associated with cardiovascular outcomes and NAFLD. However, the relationship of NFS with PCSK9 and their prognostic abilities in cardiovascular risks are unknown. Methods A total of 2008 hospitalized subjects who had chest pain without lipid-lowering therapy were consecutively included. Baseline clinical data were collected, and the NFS was calculated. The circulating PCSK9 concentration was determined by enzyme immunoassay. The major adverse cardiovascular event (MACE) occurrences were recorded in the follow-up period. Associations of PCSK9 concentration with NFS were examined. All of the participants were categorized into three groups according to NFS levels and were further stratified by PCSK9 tertiles to evaluate the MACEs. Results 158 (7.87%) MACEs were observed during a mean of 3.2 years of follow-up. NFS levels were independently related to higher PCSK9 levels according to multivariable linear regression analysis. Furthermore, elevated PCSK9 and NFS concentrations were respectively associated with increased MACE incidence in multivariable Cox regression models. When combining NFS status with PCSK9 tertiles as a stratifying factor, patients with intermediate-high NFS and high PCSK9 levels had higher risks of events than those with low NFS and low PCSK9 levels. Conclusions This study revealed for the first time that NFS is positively related to PCSK9 and that the combination of NFS and PCSK9 greatly increased the risk of MACEs in patients with chest pain, providing a potential link between NFS and PCSK9 for predicting cardiovascular events.

Ferroptosis is a recently discovered form of iron-dependent cell death, which occurs during the pathological process of various central nervous system diseases or injuries, including secondary spinal cord injury. Selenium has been shown to promote neurological function recovery after cerebral hemorrhage by inhibiting ferroptosis. However, whether selenium can promote neurological function recovery after spinal cord injury as well as the underlying mechanism remain poorly understood. In this study, we injected sodium selenite (3 µL, 2.5 µM) into the injury site of a rat model of T10 vertebral contusion injury 10 minutes after spinal cord injury modeling. We found that sodium selenite treatment greatly decreased iron concentration and levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal. Furthermore, sodium selenite increased the protein and mRNA expression of specificity protein 1 and glutathione peroxidase 4, promoted the survival of neurons and oligodendrocytes, inhibited the proliferation of astrocytes, and promoted the recovery of locomotive function of rats with spinal cord injury. These findings suggest that sodium selenite can improve the locomotive function of rats with spinal cord injury possibly through the inhibition of ferroptosis via the specificity protein 1/glutathione peroxidase 4 pathway.

Spinal cord injury leads to loss of innervation of skeletal muscle, decreased motor function, and significantly reduced load on skeletal muscle, resulting in atrophy. Factors such as braking, hormone level fluctuation, inflammation, and oxidative stress damage accelerate skeletal muscle atrophy. The atrophy process can result in skeletal muscle cell apoptosis, protein degradation, fat deposition, and other pathophysiological changes. Skeletal muscle atrophy not only hinders the recovery of motor function but is also closely related to many systemic dysfunctions, affecting the prognosis of patients with spinal cord injury. Extensive research on the mechanism of skeletal muscle atrophy and intervention at the molecular level has shown that inflammation and oxidative stress injury are the main mechanisms of skeletal muscle atrophy after spinal cord injury and that multiple pathways are involved. These may become targets of future clinical intervention. However, most of the experimental studies are still at the basic research stage and still have some limitations in clinical application, and most of the clinical treatments are focused on rehabilitation training, so how to develop more efficient interventions in clinical treatment still needs to be further explored. Therefore, this review focuses mainly on the mechanisms of skeletal muscle atrophy after spinal cord injury and summarizes the cytokines and signaling pathways associated with skeletal muscle atrophy in recent studies, hoping to provide new therapeutic ideas for future clinical work.

With the widespread application of low-dose computed tomography (LDCT) technology, pulmonary nodules have aroused more attention. Significant alteration in plasma metabolite levels, mainly amino acid and lipid, have been observed in patients of PNs. However, evidence on the association between central carbon metabolism and PNs are largely unknown. The aim of this study was to investigate the underlying association of PNs and plasma central carbon metabolites. We measured the levels of 16 plasma central carbon metabolites in 1954 participants who gained LDCT screening in MALSC cohort. The inverse probability weighting (IPW) technique was used to control for bias due to self-selection for LDCT in the assessed high-risk population. The least absolute shrinkage and selection operator (LASSO) penalized regression was used to deal with the problem of multicollinearity among metabolites and the combined association of central carbon metabolites with PNs was estimated by using quantile g-computation (QgC) models. A quartile increase in 3-hydroxybutyric acid, gluconic acid, succinic acid and hippuric acid was positively associated with the PNs risk, whereas a quartile increase in 2-oxadipic acid and fumaric acid was negatively associated with the risk of PNs in multiple-metabolite models. A positive but insignificant joint associations of the mixture of 16 metabolites with PNs was observed by using QgC models analyses. Further studies are warranted to clarify the association between circulating metabolites and PNs and the biological mechanisms.

ObjectiveTo evaluate the safety and efficacy of interventional therapy (iodine-125[125I] seed strand and portal vein stent [PVS] implantation plus transarterial chemoembolization [TACE]) combined with systemic therapy (lenvatinib plus anti-PD-1 antibody) as first-line treatment for hepatocellular carcinoma (HCC) patients with Vp4 portal vein tumor thrombus (PVTT).Patients and methodsFrom December 2018 to October 2021, 87 HCC patients with Vp4 PVTT were included in this single-center retrospective study. Forty-seven patients underwent interventional therapy combined with lenvatinib and anti-PD-1 antibody (group A), while 40 cases underwent interventional therapy combined with lenvatinib only (group B). Overall response rate (ORR), stent occlusion rates (SOR), median overall survival (OS), median progression-free survival (PFS) and median stent patency time (SPT) were compared between the 2 groups.ResultsThe mean intended dose (r = 10 mm; z = 0; 240 days) was 64.9 ± 1.0 Gy and 64.5 ± 1.1 Gy in group A and B, respectively (p = 0.133). ORR and SOR were significantly different between group A and B (ORR, 55.3% vs 17.5%, p < 0.001; SOR, 12.8% vs 35.0%, p = 0.014). In the propensity-score matching (PSM) cohort, the median OS, median PFS and median SPT were significantly longer in group A compared with group B (32 PSM pairs; OS, 17.7 ± 1.7 vs 12.0 ± 0.8 months, p = 0.010; PFS, 17.0 ± 4.3 vs 8.0 ± 0.7 months, p < 0.001; SPT, not-reached vs 12.5 ± 1.1 months, p = 0.028).ConclusionThis interventional therapy combined with lenvatinib and anti-PD-1 antibody is safe and effective for HCC patients with Vp4 PVTT.

ObjectiveThe aim of the present study was to examine the value of high-density lipoprotein (HDL) subfractions for predicting cardiovascular events (CVEs) in untreated type 2 diabetes mellitus (T2DM) patients with stable coronary artery disease (SCAD) using an age- and gender-matched case-control study.MethodsIn total, 185 SCAD patients and 185 T2DM patients with SCAD were enrolled and subjected to a clinical follow-up of CVEs. HDL subfractions were analyzed using the Quantimetrix Lipoprint System. The relationship between HDL subfractions and CVEs in T2DM patients with SCAD was evaluated by Kaplan–Meier analysis and Cox proportional hazard models.ResultsDuring a median 37.7-month follow-up, T2DM patients with SCAD had a higher percentage of CVEs compared to SCAD patients (p=0.039). The concentration of the combined intermediate and small HDL-C subfraction (defined as the mixed HDL subfraction) was related to the event incidence in T2DM patients with SCAD (p=0.004), and it was positively associated with increased CVEs even after adjustment in three models. Kaplan-Meier curve analysis indicated that T2DM patients with SCAD in the high mixed HDL subfraction group (>28 mg/dL) had lower event-free survival rates (p=0.008).ConclusionsElevated concentration of the mixed HDL subfraction predicts events in T2DM patients with SCAD.

Designated driving service provides new ideas for reducing drunk driving. As the core of designated driving industry, the health status of designated drivers is closely related to the safety of driving. Current researches are mainly about the utility evaluation of the designated driving service, and few about the designated drivers. This study summarizes the definition of designated drivers, the types, research methods and intervention measures of health risks, and provides references for exploring the health risk management measures for designated drivers.

An experiment system of tubes with one weakly covered end was established, and the outfield characteristics of fuel vapor explosions were studied through experiments. The results are as follows. After the rupture of the weakly covered end, three outfield overpressure peaks appeared due to the rupture of the weakly covered end (P1), the venting of the flame (P2), and external explosion (P3). The value of overpressure peaks showed a downward trend with an increase in distance, and the maximum overpressure was formed due to the external explosion. The value of overpressure peaks were related to the L/D ratio of the tube. With an increase in the L/D ratio, P1 and P3 in the near field showed an upward linear trend, while P2 and P3 in the far field showed a quadratic trend. In the case of the same L/D ratio, the maximum overpressure largely depended on the fuel volume fraction and external distance. The flame shape showed a changing process of jet flame - radial tension - mushroom cloud-shaped flame. The mushroom-shaped flame was formed mainly due to the Kelvin-Helmholtz instability and vortex effect, and the value of axial flame parameters were greater than those of radial ones. With an increase in the L/D ratio, the axial flame parameters showed an upward linear trend, the radial flame parameters showed a downward linear trend, and their ratio showed an upward linear trend.

Abstract Background Although the presence of physical signs [tendon xanthomas and/or corneal arcus (TX/CA)], are associated with the risk of coronary artery disease in patients with heterozygous familial hypercholesterolemia (HeFH), their relationship with genotypes and clinical characteristics has not been fully determined. This study aimed to examine the association of TX/CA with genetic mutation, lipid- and inflammation-related markers, the severity of coronary stenosis or calcification, and cardiovascular events (CVEs) in patients with HeFH. Methods LDLR, APOB, and PCSK9 genes were screened in 523 HeFH patients, and patients with TX/CA (n = 50) were 1:4 propensity score-matched to patients without TX/CA (n = 200) to adjust for age and sex. Laboratory markers (proprotein convertase subtilisin/kexin type 9 [PCSK9], lipoprotein(a) and high-sensitivity C-reactive protein [hsCRP]), computed tomography angiography, coronary angiography, and follow-up for CVEs were performed. Results Patients with physical signs had significantly higher low-density lipoprotein cholesterol levels; higher PCSK9 or hsCRP concentrations; more LDLR positive mutations; and higher prevalence of high tertiles of Gensini, SYNTAX and Jeopardy scores as well as coronary artery calcium scores than did those without. Over an average follow-up of 3.7 years, the incidence of CVEs was significantly higher in patients with TX/CA (log-rank p