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Abstract Background Stroke is a prevalent neurological disorder globally, often resulting in post-stroke depression (PSD). The cardiometabolic index (CMI) is a novel marker for assessing cardiovascular and metabolic health, but its association with PSD has not been adequately investigated. This study aims to explore the relationship between CMI and PSD, providing a basis for clinical prevention and treatment. Methods We utilized data from the 2007–2018 National Health and Nutrition Examination Survey (NHANES) in this cross-sectional analysis. Multivariable logistic regression and restricted cubic spline (RCS) models were applied to assess the independent and linear relationships between CMI and PSD. To minimize confounding, propensity score matching (PSM) was employed. Subgroup analyses and interaction tests were also conducted to further explore potential effect modifications. Results A total of 1082 participants were included, with 18.67% diagnosed with PSD. Higher CMI levels were positively associated with PSD in stroke patients. In the fully adjusted model, the association between CMI and PSD remained significant (OR = 1.06; 95% CI 1.01–1.12). RCS analysis indicated a linear relationship between CMI and PSD (nonlinearity P = 0.334). Subgroup analyses showed that this association persisted across different groups (all P for trend > 0.05). After covariate balance through PSM, the positive association between CMI and PSD was further supported. Conclusion This study demonstrates a positive association between CMI and PSD. CMI may serve as a useful tool for evaluating the risk of depressive symptom in stroke patients, potentially aiding in targeted clinical interventions.

Abstract Background Aspiration pneumonia (AP) is a type of lung inflammation caused by the aspiration of food, oropharyngeal secretions, or gastric contents. This condition is particularly common in older adults and individuals with impaired swallowing or consciousness. While the diagnosis of AP relies on clinical history, swallowing assessments, and imaging, these methods have significant limitations, often leading to underdiagnosis or misdiagnosis. Reliable biomarkers for AP diagnosis are lacking, making early detection and treatment challenging. Methods Nineteen patients diagnosed with pneumonia were included in this study, divided into two groups: AP (n = 10) and non-AP (n = 9). Biological fluid samples, including bronchoalveolar lavage fluid (BALF), saliva, serum, sputum, and urine, were analyzed using non-targeted liquid chromatography with tandem mass spectrometry (LC-MS/MS). Differential metabolites were identified using fold change analysis, statistical significance, and receiver operating characteristic (ROC) curve analysis to evaluate their diagnostic potential. Spearman correlation was used to examine the relationship between selected metabolites and clinical parameters. Results Significant metabolic differences were found between AP and non-AP patients, with many different metabolites identified across biological fluids. Dehydroepiandrosterone sulfate (DHEAS), Androstenediol-3-sulfate (ADIOLS), and beta-muricholic acid were identified as key biomarkers through fold change analysis and ROC curve analysis, showing consistent increasing or decreasing trends in BALF, sputum, and serum samples. DHEAS was found to be negatively correlated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) (r = − 0.619, p = 0.005) in BALF sample. The area under curve (AUC) values showed that these molecules could serve as effective biomarkers for AP. Conclusions This study identifies DHEAS, ADIOLS and beta-muricholic acid as promising biomarkers for AP, with the potential to improve early diagnosis and treatment. These findings underscore the clinical value of metabolomics in developing diagnostic tools for AP, facilitating better clinical management and patient outcomes. Further research is required to validate these biomarkers in larger cohorts and explore their mechanistic roles in AP pathophysiology.

Abstract Acute kidney injury (AKI) is associated with adverse hospitalization. Previous studies have reported that an elevated triglyceride glucose (TyG) index is significantly associated with the development of AKI in patients with cardiovascular disease, as well as in those undergoing surgery; however, the potential of the TyG index to predict AKI following neurotrauma remains unclear. Patients diagnosed with traumatic brain injury (TBI) in Chinese tertiary hospitals between January 2014 and December 2023 were included in this retrospective study. The outcome was the incidence of AKI. TyG was identified as an independent risk factor for AKI using logistic regression and propensity score matching (PSM). Finally, the association between TyG index and AKI was further assessed using multivariate logistic regression, restricted cubic spline (RCS) regression, and subgroup analysis. The present study enrolled 1,505 patients with TBI, of whom 66.45% were male, with an average age of 55.47 ± 17.32 years. The incidence of AKI was 9.4%. Multiple logistic regression analyses identified a relationship between the TyG levels and AKI risk. This relationship was retained after PSM. A significant positive correlation between TyG level and AKI was observed in all three models constructed using multivariate logistic regression. RCS regression analyses further indicated a linear increase in AKI risk with an increasing TyG index. In subgroup analyses, this correlation remained stable for the majority of the population but could be influenced by sex. TyG levels were positively correlated with the risk of AKI development in patients following TBI. As a predictive biomarker, the TyG index enables effective risk stratification and customization of management protocols to mitigate AKI in these patients, thus enhancing clinical outcomes.

Digestive system cancers are prevalent diseases with a high mortality rate, posing a significant threat to public health and economic burden. The diagnosis and treatment of digestive system cancer confront conventional cancer problems, such as tumor heterogeneity and drug resistance. Single-cell sequencing (SCS) emerged at times required and has developed from single-cell RNA-seq (scRNA-seq) to the single-cell multi-omics era represented by single-cell spatial transcriptomics (ST). This article comprehensively reviews the advances of single-cell omics technology in the study of digestive system tumors. While analyzing and summarizing the research cases, vital details on the sequencing platform, sample information, sampling method, and key findings are provided. Meanwhile, we summarize the commonly used SCS platforms and their features, as well as the advantages of multi-omics technologies in combination. Finally, the development trends and prospects of the application of single-cell multi-omics technology in digestive system cancer research are prospected.

Abstract This study explores the role and potential mechanisms of microRNA-125b-5p (miR-125b-5p) in pulmonary fibrosis (PF). PF is a typical outcome of many chronic lung diseases, with poor prognosis and the lack of appropriate medical treatment because PF’s molecular mechanisms remain poorly understood. In this study, using in vitro and in vivo analyses, we find that miR-125b-5p is likely a potent regulator of lung fibrosis. The findings reveal that, on the one hand, miR-125b-5p not only specifically decreases in the epithelial-mesenchymal transition (EMT) of lung epithelial cells, but also shows a downregulation trend in the lung tissues of mice with PF. On the other hand, overexpression of miR-125b-5p on the cellular and animal levels downregulates EMT and fibrotic phenotypes, respectively. To clarify the molecular mechanism of the “therapeutic” effect of miR-125b-5p, we use the target prediction tool combined with a dual luciferase assay and complete a rescue experiment by constructing the overexpression vector of the target gene Bcl-2 homologous antagonist/ killer (BAK1), thus confirming that miR-125b-5p can effectively inhibit EMT and fibrosis process by targeting BAK1 gene. MiR-125b-5p inhibits the EMT in lung epithelial cells by negatively regulating BAK1, while overexpression of miR-125b-5p can alleviate lung fibrosis. The findings suggest that MiR-125b-5p/BAK1 can serve as a potential treatment target for PF. Graphical abstract

Background and purposeIntracerebral hemorrhage remains a significant cause of death and disability worldwide, highlighting the urgent need for accurate prognostic assessments to optimize patient management. This study aimed to develop a practical nomogram for risk prediction of poor prognosis after 90 days in patients with intracerebral hemorrhage.MethodsA retrospective study was conducted on 638 patients with intracerebral hemorrhage in the Second Hospital of Fujian Medical University, China, who were divided into a training set (n = 446) and a test set (n = 192) by random splitting. Then the data on demographics, clinical symptoms, imaging characteristics, and laboratory findings were collected. In this study, adverse outcomes were defined as a Modified Rankin Scale (mRS) score of 3–6 at 90 days post-ICH onset, as assessed during follow-up. Later, least absolute shrinkage and selection operator (LASSO) regression and multifactorial logistic regression were used to screen the variables and construct a nomogram. Next, the evaluation was performed using the Receiver Operating Characteristic (ROC) curve, calibration curve, and decision curve analysis. Finally, the external validation was completed using the data of 496 patients with intracerebral hemorrhage from the Jinjiang Hospital of Traditional Chinese Medicine.ResultsIn the training and test sets of intracerebral hemorrhage, the incidence of poor prognosis was 60.53 and 61.46%, respectively. Through variable screening, this study identified age, Glasgow Coma Scale (GCS), blood glucose, uric acid, hemoglobin, and hematoma location as independent predictors of poor prognosis in intracerebral hemorrhage. The developed dynamic nomogram was easy to use and demonstrated strong predictive performance (training set AUC: 0.87; test set AUC: 0.839; external validation set AUC: 0.774), excellent calibration, and clinical applicability.ConclusionThe dynamic nomogram we developed using five independent risk factors serves as a practical tool for real-time risk assessment and can help facilitate early intervention and personalized patient management, thereby improving clinical outcomes in high-risk patients.

Abstract Background MutT homolog 1 (MTH1) sanitizes oxidized dNTP pools to promote the survival of cancer cells and its expression is frequently upregulated in cancers. Polyubiquitination stabilizes MTH1 to facilitate the proliferation of melanoma cells, suggesting the ubiquitin system controls the stability and function of MTH1. However, whether ubiquitination regulates MTH1 in gastric cancers has not been well defined. This study aims to investigate the interaction between MTH1 and a deubiquitinase, USP9X, in regulating the proliferation, survival, migration, and invasion of gastric cancer cells. Methods The interaction between USP9X and MTH1 was evaluated by co-immunoprecipitation (co-IP) in HGC-27 gastric cancer cells. siRNAs were used to interfere with USP9X expression in gastric cancer cell lines HGC-27 and MKN-45. MTT assays were carried out to examine the proliferation, propidium iodide (PI) and 7-AAD staining assays were performed to assess the cell cycle, Annexin V/PI staining assays were conducted to examine the apoptosis, and transwell assays were used to determine the migration and invasion of control, USP9X-deficient, and USP9X-deficient plus MTH1-overexpressing HGC-27 and MKN-45 gastric cancer cells. Results Co-IP data show that USP9X interacts with and deubiquitinates MTH1. Overexpression of USP9X elevates MTH1 protein level by downregulating its ubiquitination, while knockdown of USP9X has the opposite effect on MTH1. USP9X deficiency in HGC-27 and MKN-45 cells causes decreased proliferation, cell cycle arrest, extra apoptosis, and defective migration and invasion, which could be rescued by excessive MTH1. Conclusion USP9X interacts with and stabilizes MTH1 to promote the proliferation, survival, migration and invasion of gastric cancer cells.

Objectives: Rapid antigen test (RAT) and polymerase chain reaction (PCR) using nasopharyngeal (NP) or oropharyngeal (OP) swab specimens are the two main testing techniques used for laboratory diagnosis of influenza in clinical practice. However, performance variations have been observed not only between techniques, but also between different specimens. This study evaluated the differences in performance between specimens and testing techniques to identify the best combination in clinical practice. Methods: Both NP and OP samples from suspected influenza patients collected in the 2023/4–2023/5 Flu-season in Xiamen, China, were tested for RAT and quantitative PCR. The testing performance of the different specimens and testing techniques were recorded and evaluated. Results: Compared to PCR, RAT showed 58.9 % and 10.3 % sensitivity for NP and OP swabs, respectively. The Limit of Detection (LoD) was 28.71 the Median Tissue Culture Infectious Dose (TCID50)/mL. Compared with PCR using NP swabs, PCR with OP swabs showed 89.5 % sensitivity and 95.4 % specificity. Conclusions: There were no significant differences in performance between the specimens when PCR was used to test for influenza. However, a decrease in sensitivity was observed when the RAT was used, regardless of the specimen type. Therefore, to avoid false-negative results, PCR may be a better choice when OP swabs are used as specimens. In contrast, NP swabs should be the recommended specimens for RAT.

Abstract Objective To investigate the brain structural correlates of postoperative axial pain (PAP) in degenerative cervical myelopathy (DCM) following posterior cervical decompression surgery. Methods Structural images with high-resolution T1 weighting were collected from 62 patients with DCM and analyzed, in addition to 42 age/gender matched subjects who were healthy. Voxel-based morphometry (VBM) was analyzed, grey matter volume (GMV) was computed. One-way ANOVA was performed to reveal the GMV differences among DCM patients with PAP, patients without PAP and healthy controls (HC). Post-hoc analyses were conducted to identify the pair-wise GMV differences among these three groups. Analyses of correlations were conducted to uncover the link between clinical measurements and GMV variations. Last, support vector machine (SVM) was conducted to test the utility of GMV for classifying PAP and nPAP DCM patients. Results Three main findings were observed: [1] Compared to healthy controls, DCM patients showed a significantly lower GMV in the precuneus preoperatively. DCM patients with PAP also exhibited a lower GMV within precuneus than those without; [2] In DCM patients with PAP, the precuneus GMV was inversely related to the postoperative pain intensity; [3] Moreover, successful classification between PAP and nPAP were observed via SVM based on precuneus GMV as features. Conclusion In summary, our results indicate that precuneus GMV may be linked to PAP in DCM, and could be employed to forecast the emergence of PAP in DCM patients.

Abstract Background The purpose of this study was to explore the applicability of application effect of head-mounted mixed reality (MR) equipment combined with a three-dimensional (3D) printed model in neurosurgical ventricular and haematoma puncture training. Methods Digital Imaging and Communications in Medicine (DICOM) format image data of two patients with common neurosurgical diseases (hydrocephalus and basal ganglia haemorrhage) were imported into 3D Slicer software for 3D reconstruction, saved, and printed using 3D printing to produce a 1:1-sized head model with real person characteristics. The required model (brain ventricle, haematoma, puncture path, etc.) was constructed and imported into the head-mounted MR device, HoloLens, and a risk-free, visual, and repeatable system was designed for the training of junior physicians. A total of 16 junior physicians who studied under this specialty from September 2020 to March 2022 were selected as the research participants, and the applicability of the equipment and model during training was evaluated with assessment score sheets and questionnaires after training. Results According to results of the assessment and questionnaire, the doctors trained by this system are more familiar with the localization of the lateral anterior ventricle horn puncture and the common endoscopic surgery for basal ganglia haemorrhage, as well as more confident in the mastery of these two operations than the traditional training methods. Conclusions The use of head-mounted MR equipment combined with 3D printing models can provide an ideal platform for the operation training of young doctors. Through holographic images created from the combination of virtual and real images, operators can be better immersed in the operation process and deepen their understanding of the operation and related anatomical structures. The 3D printed model can be repeatedly reproduced so that doctors can master the technology, learn from mistakes, better achieve the purpose of teaching and training, and improve the effect of training.

BackgroundOver the past two decades, the field of radiation brain injury has attracted the attention of an increasing number of brain scientists, particularly in the areas of molecular pathology and therapeutic approaches. Characterizing global collaboration networks and mapping development trends over the past 20 years is essential.ObjectiveThe aim of this paper is to examine significant issues and future directions while shedding light on collaboration and research status in the field of radiation brain injury.MethodsBibliometric studies were performed using CiteSpaceR-bibliometrix and VOSviewer software on papers regarding radiation brain injury that were published before November 2023 in the Web of Science Core Collection.ResultsIn the final analysis, we found 4,913 records written in 1,219 publications by 21,529 authors from 5,007 institutions in 75 countries. There was a noticeable increase in publications in 2014 and 2021. The majority of records listed were produced by China, the United States, and other high-income countries. The largest nodes in each cluster of the collaboration network were Sun Yat-sen University, University of California–San Francisco, and the University of Toronto. Galldiks N, Barnett GH, Langen KJ and Kim JH are known to be core authors in the field. The top 3 keywords in that time frame are radiation, radiation necrosis, and radiation-therapy.ConclusionsThe objective and thorough bibliometric analysis also identifies current research hotspots and potential future paths, providing a retrospective perspective on RBI and offering useful advice to researchers choosing research topics. Future development directions include the integration of multi-omics methodologies and novel imaging techniques to improve RBI's diagnostic effectiveness and the search for new therapeutic targets.

In this paper, we demonstrate a surface-enhanced Raman spectroscopy (SERS) biosensor based on the self-assembly of gold nanorods (AuNRs) for the specific detection of airway inflammatory factors in diluted sputum. The AuNR surface was modified with an antibody that was able to specifically recognize an airway inflammatory factor, interleukin-5 (IL-5), so that a end-to-end self-assembly system could be obtained, resulting in an order of magnitude amplification of the Raman signal and greatly improved sensitivity. Meanwhile, the outer layer of the biosensor was coated with silicon dioxide, which improved the stability of the system and facilitated its future applications. When the detected concentration was in the range of 0.1–50 pg/mL, the SERS signal generated by the sensor showed a good linear relationship with the IL-5 concentration. Moreover, it had satisfactory performance in diluted sputum and clinical subjects with asthma, which could achieve sensitive detection of the airway inflammatory factor IL-5. Overall, the developed biosensor based on the SERS effect exhibited the advantages of rapid and sensitive detecting performance, which is suitable for monitoring airway inflammatory factors in sputum.

ObjectiveRecent clinical studies have demonstrated that advanced age and low initial Glasgow Coma Scale (GCS) score were independent predictors of gastrointestinal bleeding (GIB) in patients with primary intracerebral hemorrhage (ICH). However, used singly, age and GCS score have their respective shortcomings in predicting the occurrence of GIB. This study aimed to investigate the association between the age-to-initial GCS score ratio (AGR) and the risk of GIB following ICH.MethodsWe conducted a single-center, retrospective observational study of consecutive patients presenting with spontaneous primary ICH at our hospital from January 2017 through January 2021. Patients who fulfilled the inclusion and exclusion criteria were categorized into GIB and non-GIB groups. Univariate and multivariate logistic regression analyses were implemented to identify the independent risk factors for the occurrence of GIB, and a multicollinearity test was performed. Furthermore, one-to-one matching was conducted to balance important patient characteristics by the groups' propensity score matching (PSM) analysis.ResultsA total of 786 consecutive patients fulfilled the inclusion/exclusion criteria for the study, and 64 (8.14%) patients experienced GIB after primary ICH. Univariate analysis revealed that patients with GIB were significantly older [64.0 (55.0–71.75) years vs. 57.0 (51.0–66.0) years, p = 0.001] and had a higher AGR [7.32 (5.24–8.96) vs. 5.40 (4.31–7.11), p < 0.001] and a lower initial GCS score [9.0 (7.0–11.0) vs. 11.0 (8.0–13.0), p < 0.001]. The multicollinearity test revealed that no multicollinearity was observed in the multivariable models. Multivariate analysis showed that the AGR was a significant independent predictor of GIB [odds ratio (OR) 1.155, 95% confidence interval (CI) 1.041–1.281, p = 0.007], as well as prior anticoagulation or antiplatelet therapy (OR 0.388, 95% CI 0.160–0.940, p = 0.036) and MV used >24 h (OR 0.462, 95% CI 0.252–0.848, p = 0.013). Receiver operating curve (ROC) analysis illustrated that the optimal cutoff value for the AGR as a predictor for GIB in patients with primary ICH was 6.759 [the area under the curve (AUC) was 0.713 with a corresponding sensitivity of 60.94% and specificity of 70.5%, 95% CI 0.680–0.745, p < 0.001]. After 1:1 PSM, the matched GIB group had significantly higher AGR levels compared with the matched non-GIB group [7.47(5.38–9.32) vs. 5.24(4.24–6.40), p

Silicosis is an uncurable occupational disease induced by crystalline silica. Increased prevalence of silicosis has resulted in the increased need for development of treatment options. Although macrophages respond first to silica, epithelial cells are also involved in silicosis. However, changes in protein and metabolite levels have not been reported simultaneously. We used mass spectrometry to profile changes in metabolites, proteins, and phosphorylation in silica-exposed BEAS-2B epithelial cells. Silica exposure increased TCA cycle, alanine, aspartate and glutamate metabolism, and aerobic glycolysis activity. In addition, protein levels in the endoplasmic reticulum were significantly altered, and phosphorylation of MAPK signaling proteins was increased. The results of this study increased understanding the role of epithelial cells in silicosis.

Human T-cell leukemia virus type 1 is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia-lymphoma (ATL). The HTLV-1 basic leucine zipper factor (HBZ) has been associated to the cancer-inducing properties of this virus, although the exact mechanism is unknown. In this study, we identified nucleophosmin (NPM1/B23) as a new interaction partner of HBZ. We show that sHBZ and the less abundant uHBZ isoform interact with nucleolar NPM1/B23 in infected cells and HTLV-1 positive patient cells, unlike equivalent antisense proteins of related non-leukemogenic HTLV-2, −3 and-4 viruses. We further demonstrate that sHBZ association to NPM1/B23 is sensitive to RNase. Interestingly, sHBZ was shown to interact with its own RNA. Through siRNA and overexpression experiments, we further provide evidence that NPM1/B23 acts negatively on viral gene expression with potential impact on cell transformation. Our results hence provide a new insight over HBZ-binding partners in relation to cellular localization and potential function on cell proliferation and should lead to a better understanding of the link between HBZ and ATL development.

Abstract Baicalein is a biologically important flavonoid in extracted from the Scutellaria baicalensis Georgi, which can effectively inhibit the influenza virus. This study aimed to analyze the safety and pharmacokinetic (PK) characteristics of baicalein tablets in healthy Chinese subjects and provide more information for phase II clinical trials. In this multiple‐ascending‐dose placebo‐controlled trial, 36 healthy subjects were randomized to receive 200, 400, and 600 mg of baicalein tablet or placebo once daily on day 1 and day 10, 3 times daily on days 4–9. All groups were intended to produce safety and tolerability outcomes (lowest dose first). Blood and urine samples were collected from subjects in the 600 mg group for baicalein PK analysis. Our study had shown that Baicalein tablet was generally safe and well‐tolerated. All adverse events were mild and resolved without any intervention except one case of fever reported in the 600 mg group, which was considered as moderate but not related with baicalein as judged by the investigator. Oral baicalein tablets were rapidly absorbed with peak plasma levels being reached within 2 h after multiple administration. The highest urinary excretion of baicalein and its metabolites peaked in 2 h, followed by 12 h, with a double peak trend.

Traumatic brain injury (TBI) is a global health issue which causes millions of deaths and disabilities every year. The survivors of TBI may suffer from sensorimotor dysfunction, memory and cognitive disturbances, hearing and vision deficits, and various psychological problems. The primary insult may damage neurons, cerebral vessels and the blood-brain barrier, causing reactive astrogliosis and immune response with further damaging consequences. TBI lacks effective therapy. The currently available clinical treatment options include hyperbaric oxygenation, brain stimulation and rehabilitation. In recent years, the research on stem cell treatment of TBI has received extensive attention. Various types of stem cells, such as four types of mesenchymal stem cells, neural stem cells and olfactory ensheathing cells have been tried to treat TBI in clinical trials and preclinical models. This article reviews the research of autologous and non-autologous multipotent stem and progenitor cells for the treatment of TBI in both clinical and preclinical settings.

Introduction: Recent reports revealed that higher serum glucose-potassium ratio (GPR) levels at admission were significantly associated with poor outcomes at 3 months following aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to investigate the association between GPR and the risk of rebleeding following aSAH.Methods: This single-center retrospective study of patients with aSAH was conducted in our hospital between January 2008 and December 2020. Patients meeting the inclusion criteria were divided into the rebleed group and the non-rebleed group. Univariate and multivariate analyses were implemented to assess the association between risk factors of rebleeding and outcomes.Results: A total of 1,367 patients experiencing aSAH, 744 patients who met the entry criteria in the study [mean age (54.89 ± 11.30) years; 60.50% female patients], of whom 45 (6.05%) developed rebleeding. The patients in the rebleed group had significantly higher GPR levels than those of patients without rebleeding [2.13 (1.56–3.20) vs. 1.49 (1.23–1.87); p < 0.001]. Multivariable analysis revealed that higher mFisher grade and GPR were associated with rebleeding [mFisher grade, odds ratios (OR) 0.361, 95% CI 0.166–0.783, p = 0.01; GPR, OR 0.254, 95% CI 0.13–0.495, p < 0.001]. The receiver operating characteristics (ROCs) analysis described that the suitable cut-off value for GPR as a predictor for rebleeding in patients with aSAH was determined as 2.09 (the area under the curve [AUC] was 0.729, 95% CI 0.696–0.761, p < 0.0001; the sensitivity was 53.33%, and the specificity was 83.98%). Pearson correlation analysis showed a significant positive correlation between GPR and mFisher grade, between GPR and Hunt–Hess grade (mFisher grade r = 0.4271, OR 0.1824, 95% CI 0.3665–0.4842, p < 0.001; Hunt–Hess grade r = 0.4248, OR 0.1836, 95% CI 0.3697–0.4854, p < 0.001). The patients in the poor outcome had significantly higher GPR levels than those of patients in the good outcome [1.87 (1.53–2.42) vs. 1.45 (1.20–1.80); p < 0.001]. Multivariable analysis demonstrated that GPR was an independent predictor for poor prognosis. The AUC of GPR was 0.709 (95% CI 0.675–0.741; p < 0.0001) (sensitivity = 77.70%; specificity = 55.54%) for poor prognosis.Conclusion: Higher preoperative serum GPR level was associated with Hunt–Hess grade, mFisher grade, rebleeding, and unfunctional outcome, and that they predicted preoperative rebleeding and the 90-days outcome of non-diabetic patients with aSAH, who had potentially relevant clinical implications in patients with aSAH.

Background: Doxorubicin (Dox) is one of the most effective chemotherapy agents used in the treatment of solid tumors and hematological malignancies. However, it causes dose-related cardiotoxicity that may lead to heart failure in patients. Luteolin (Lut) is a common flavonoid that exists in many types of plants. It has been studied for treating various diseases such as hypertension, inflammatory disorders, and cancer. In this study, we evaluated the cardioprotective and anticancer effects of Lut on Dox-induced cardiomyopathy in vitro and in vivo to explore related mechanisms in alleviating dynamin-related protein (Drp1)-mediated mitochondrial apoptosis.Methods: MTT and LDH assay were used to determine the viability and toxicity of cardiomyocytes treated with Dox and Lut. Flow cytometry was used to examine ROS levels, and electron and confocal microscopy was employed to assess the mitochondrial morphology. The level of apoptosis was examined by Hoechst 33258 staining. The protein levels of myocardial fission protein and apoptosis-related protein were examined using Western blot. Transcriptome analysis of the protective effect of Lut against Dox-induced cardiac toxicity in myocardial cells was performed using RNA sequencing technology. The protective effects of Lut against cardiotoxicity mediated by Dox in zebrafish were quantified. The effect of Lut increase the antitumor activity of Dox in breast cancer both in vitro and in vivo were further employed.Results: Lut ameliorated Dox-induced toxicity in H9c2 and AC16 cells. The level of oxidative stress was downregulated by Lut after Dox treatment of myocardial cells. Lut effectively reduced the increased mitochondrial fission post Dox stimulation in cardiomyocytes. Apoptosis, fission protein Drp1, and Ser616 phosphorylation were also increased post Dox and reduced by Lut. In the zebrafish model, Lut significantly preserved the ventricular function of zebrafish after Dox treatment. Moreover, in the mouse model, Lut prevented Dox-induced cardiotoxicity and enhanced the cytotoxicity in triple-negative breast cancer by inhibiting proliferation and metastasis and inducing apoptosis.

Abstract Chronic lung diseases represent a largely global burden whose pathogenesis remains largely unknown. Research increasingly suggests that epigenetic modifications, especially DNA methylation, play a mechanistic role in chronic lung diseases. DNA methylation can affect gene expression and induce various diseases. Of the caveolae in plasma membrane of cell, caveolin‐1 (Cav‐1) is a crucial structural constituent involved in many important life activities. With the increasingly advanced progress of genome‐wide methylation sequencing technologies, the important impact of Cav‐1 DNA methylation has been discovered. The present review overviews the biological characters, functions, and structure of Cav‐1; epigenetic modifications of Cav‐1 in health and disease; expression and regulation of Cav‐1 DNA methylation in the respiratory system and its significance; as well as clinical potential as disease‐specific biomarker and targets for early diagnosis and therapy.

Abstract Background Citrullinemia type I (CTLN1) is a rare autosomal recessive disorder of the urea cycle caused by a deficiency in the argininosuccinate synthetase (ASS1) enzyme due to mutations in the ASS1 gene. Only a few Chinese patients with CTLN1 have been reported, and ASS1 gene mutations have been identified sporadically in China. Case presentation A Chinese family with one member affected with mild CTLN1 was enrolled. Targeted exome sequencing was performed on the proband, and Sanger sequencing was used to validate the detected mutation. We also reviewed the genetic and clinical characteristics of CTLN1 in Chinese patients that have been published to date. Newborn screening showed remarkably increased concentrations of citrulline with elevated ratios of citrulline/arginine and citrulline/phenylalanine, and the patient presented with a speech delay at age three. The urinary organic acid profiles were normal. A novel homozygous splicing variant c.773 + 4A > C in the ASS1 gene was identified in the proband, and it was predicted to affect splicing by in silico analysis. To date, only nine Chinese patients with CTLN1 have been reported, with a total of 15 ASS1 mutations identified and no high frequency or hot spot mutations found; the mutation spectrum of Chinese patients with CTLN1 was heterogeneous. Conclusions We described a mild Chinese CTLN1 case with a novel homozygous splicing variant c.773 + 4A > C and reviewed previous genotypes and phenotypes in Chinese patients with CTLN1. Thus, our findings contribute to understanding the molecular genetic background and clinical phenotype of CTLN1 in this population.

BackgroundIdiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome in adults involving multiple targets and factors. The effect of conservative nonimmunosuppressive or immunosuppressive therapies is unsatisfactory and with many side effects. Traditional Chinese medicine (TCM) can regulate immune function and improve kidney function.PurposeTo evaluate the total effective rate, curative rate, recurrence rate and adverse events of TCM alone or TCM as an adjunctive therapy for IMN.MethodsRandomized controlled trials (RCT) comparing either TCM alone or the combination of TCM to western medicine (WM) therapies for patients with IMN were retrieved by searching English and Chinese database. Risk of bias summary was used to assess the methodological quality of eligible studies. Dichotomous data were presented using odds ratios (OR). The primary outcome measure was the total effective rate. Secondary outcomes included curative rate, recurrence rate and adverse events.Results29 RCTs involving 1883 participants met the inclusion criteria. There was no statistically significant difference between the therapy of TCM alone and WM on the total effective rates (OR: 2.00; 95% CI: 0.80-4.98; P = 0.14) and curative rate (OR: 1.66; 95%CI: 0.66-4.22; p = 0.28). However, compared to basic treatment or immunosuppressive therapies alone, results showed that TCM as an adjunctive therapy had beneficial effects on the total effective rate (OR: 2.59; 95% CI: 1.38-4.86; P = 0.003 and OR: 3.01; 95% CI: 2.25-4.04; P < 0.00001) and curative rate (OR: 3.01; 95%CI: 1.24-7.28; p = 0.01 and OR: 1.73; 95%CI: 1.10-2.71; p = 0.02). In addition, the combination of TCM treatment could reduce the recurrence rate (OR: 0.28; 95% CI: 0.12-0.68; P = 0.004) and adverse reactions (OR: 0.38; 95% CI: 0.27-0.54; p < 0.00001).ConclusionThe results indicate that TCM is well-tolerated for the treatment of IMN. However, there remains a need for large-scale and high-quality trials.

Context: Huoxin formula is a Traditional Chinese Medicine for coronary heart disease (CHD) treatment. Objective: To explore the therapeutic mechanism of the Huoxin formula on arterial functions in CHD patients. Materials and methods: Fifty-eight CHD patients receiving cardiovascular drugs including β-receptor blocker, statins, and antiplatelet medications or others were randomized into intervention [additionally 13.5 g Huoxin formula granules dissolved in 150 mL warm water per time, twice a day (n = 30)] and control [only cardiovascular drugs (n = 28)] groups. Serum biomarkers (hs-CRP, IL-18, IL-17, TNF-α, MMP-9), and cardiovascular indicators of the common and internal carotid arteries (ICAs) were monitored before and after the treatments. Results: After 3 months of treatment, the increases of intima-media thicknesses (IMT) of the left and right common carotid arteries (CCAs) as well as of the left and right ICAs and the increases of the left and right cardio-ankle vascular index were all significantly (all p

Abstract Background Enhancing autophagy after traumatic brain injury (TBI) may decrease the expression of neuronal apoptosis-related molecules. Autophagy-mediated neuronal survival is regulated by the sirtuin family of proteins (SIRT). Omega-3 polyunsaturated fatty acids (ω-3 PUFA) are known to have antioxidative and anti-inflammatory effects. We previously demonstrated that ω-3 PUFA supplementation attenuated neuronal apoptosis by modulating the neuroinflammatory response through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway, leading to neuroprotective effects following experimental traumatic brain injury (TBI). However, no studies have elucidated if the neuroprotective effects of ω-3 PUFAs against TBI-induced neuronal apoptosis are modulated by SIRT1-mediated deacetylation of the autophagy pathway. Methods The Feeney DM TBI model was adopted to induce TBI rats. Modified neurological severity scores, the rotarod test, brain water content, and Nissl staining were employed to determine the neuroprotective effects of ω-3 PUFA supplementation. Immunofluorescent staining and western blot analysis were used to detect Beclin-1 nuclear translocation and autophagy pathway activation. The impact of SIRT1 deacetylase activity on Beclin-1 acetylation and the interaction between cytoplasmic Beclin-1 and Bcl-2 were assessed to evaluate the neuroprotective effects of ω-3 PUFAs and to determine if these effects were dependent on SIRT1-mediated deacetylation of the autophagy pathway in order to gain further insight into the mechanisms underlying the development of neuroprotection after TBI. Results ω-3 PUFA supplementation protected neurons against TBI-induced neuronal apoptosis via enhancement of the autophagy pathway. We also found that treatment with ω-3 PUFA significantly increased the NAD+/NADH ratio and SIRT1 activity following TBI. In addition, ω-3 PUFA supplementation increased Beclin-1 deacetylation and its nuclear export and induced direct interactions between cytoplasmic Beclin-1 and Bcl-2 by increasing SIRT1 activity following TBI. These events led to the inhibition of neuronal apoptosis and to neuroprotective effects through enhancing autophagy after TBI, possibly due to elevated SIRT1. Conclusions ω-3 PUFA supplementation attenuated TBI-induced neuronal apoptosis by inducing the autophagy pathway through the upregulation of SIRT1-mediated deacetylation of Beclin-1.

Abstract The airway smooth muscle (ASM) plays an indispensable role in airway structure and function. Dysfunction in ASM plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and contributes to alterations of contractility, inflammatory response, immunoreaction, phenotype, quantity, and size of airways. ASM makes a key contribution in COPD by various mechanisms including altered contractility and relaxation induce by [Ca2+]i, cell proliferation and hypertrophy, production and modulation of extracellular cytokines, and release of pro-and-anti-inflammatory mediators. Multiple dysfunctions of ASM contribute to modulating airway responses to stimuli, remodeling, and fibrosis, as well as influence the compliance of lungs. The present review highlights regulatory roles of multiple factors in the development of ASM dysfunction in COPD, aims to understand the regulatory mechanism by which ASM dysfunctions are initiated, and explores the clinical significance of ASM on alterations of airway structure and function in COPD and development of novel therapeutic strategies for COPD.

Abstract Elizabethkingia anophelis 12012‐2 PRCM was isolated from a patient with multiple organ dysfunction syndrome and lower respiratory tract infection in China. Minimum inhibitory concentration (MIC) analysis demonstrated that it was resistant to 20 antibiotics including trimethoprim/sulfamethoxazole and ciprofloxacin, which were effective for the elimination of other Elizabethkingia infections. To investigate multidrug resistance and pathogenicity mechanisms, we analyzed genome features of 12012‐2 PRCM and compared them to the other Elizabethkingia species. The draft genome size was 4.02 Mb with a GC content of 32%, comparable to that of other E. anophelis strains. Phylogenetic analysis showed that E. anophelis 12012‐2 PRCM formed a sister group with E. anophelis 502, distinct from clades formed by other clinical and environmental E. anophelis isolates. E. anophelis 12012‐2 PRCM contained multiple copies of β‐lactamase genes as well as genes predicted to function in antimicrobial efflux. It also contained 92 genes that were potentially involved in virulence, disease, and defense, and were associated with resistance and pathogenicity. Comparative genomic analysis showed high homology among three clinical and two environmental E. anophelis strains having a variety of similar antibiotic resistance and virulence factor genes, and similar genomic structure. Applications of this analysis will contribute to understanding the antibiotic resistance and pathogenic mechanisms of E. anophelis infections, which will assist in the management of infections as it increases in prevalence.

Malaria, a mosquito-borne infectious disease, is a severe health problem worldwide. As reported, some anti-malarial drugs with anti-parasitic properties also block mast cells (MCs) activities. It is hypothesized that MCs activity may be correlated with the pathogenesis of malaria. Thus, the role of MCs on malarial pathogenesis and the involved physiological action and pathways need to be further investigated. This study aimed to investigate the effect of MCs activation on malaria disease severity using KunMing mice with Plasmodium berghei ANKA (PbANKA) infection treated with MCs degranulator (compound 48/80, C48/80) or MCs stabilizer (disodium cromoglycate, DSCG). PbANKA infection caused a dramatic increase in MCs density and level of MCs degranulation in cervical lymph node (CLN) and skin. Compared with infected control, C48/80 treatment had shortened survival time, increased parasitemia, exacerbated liver inflammation and CLN hyperplasia, accompanied with increase in vascular leakage and leukocyte number. The infected mice with C48/80 treatment also elevated the release of CCL2, CXCL1, and MMP-9 from MCs in CLN and skin, and TNF-α, IFN-γ, CCR2, and CXCR2 mRNA expression in CLN and liver. In contrast, the infected mice treated with DSCG showed longer survival time, lower parasitemia, improved liver inflammation and CLN hyperplasia, followed by a decline of vascular leakage and leukocyte number. Decreased MCs-derived CCL2, CXCL1, and MMP-9 from CLN and skin, mRNA expression in CLN and liver (TNF-α, IFN-γ, CCR2, and CXCR2) were also observed in infected mice with DSCG treatment. Our data indicated that MCs activation may facilitate the pathogenesis of PbANKA infection.

Short/branched chain acyl-CoA dehydrogenase deficiency (SBCADD) is an autosomal recessive disorder of impaired isoleucine catabolism caused by mutations in the ACADSB gene. There are limited SBCADD cases worldwide and to date no Chinese patients with SBCADD have been reported. The aim of this study was to investigate the biochemical, clinical information, and genotypes of twelve patients with SBCADD in China for the first time. The estimated incidence of SBCADD was 1 in 30,379 in Quanzhou, China. The initial newborn screening (NBS) results revealed that all patients showed slightly or moderately elevated C5 concentrations with C5/C2 and C5/C3 ratios in the reference range, which has the highest risk of being missed. All patients who underwent urinary organic acid analysis showed elevation of 2-methylburtyrylglycine in urine. All patients were asymptomatic at diagnosis, and had normal growth and development during follow-up. Eight different variants in the ACADSB gene, including five previously unreported variants were identified, namely c.596A > G (p.Tyr199Cys), c.653T > C (p.Leu218Pro), c.746del (p.Pro249Leufs*15), c.886G > T (p.Gly296*) and c.923G > A (p.Cys308Tyr). The most common variant was c.1165A > G (33.3%), followed by c.275C > G (20.8%). All previously unreported variants may cause structural damage and dysfunction of SBCAD, as predicted by bioinformatics analysis. Thus, our findings indicate that SBCADD may be more frequent in the Chinese population than previously thought and newborn screening, combined with genetic testing is important for timely diagnosis. Although the clinical course of Chinese patients with SBCADD is likely benign, longitudinal follow-up may be helpful to better understand the natural history of SBCADD.

The Raman spectra of human blood serum can be used to identify cancer or other diseases; however, obtaining a reliable surface enhanced Raman scattering (SERS) signal of human blood serum is difficult. Two primary factors that affect SERS measurement of serum are photodegradation and sample composition, which are investigated in this research. In the end, this research proposes a promising set of measurement conditions that can both acquire reliable serum Raman signals and avoid photodegradation.

The case of a Chinese patient with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), who showed typical neurological symptoms of the disease, is reported here. Since the presence of anti-HTLV-1 antibody was not investigated, this patient’s diagnosis of HAM/TSP was delayed for 4 years. Magnetic resonance imaging revealed multiple spotty lesions in the cervical spinal cord, probably reflecting pathological changes known as perivascular lymphocytic infiltrations of the spinal cord. As this is the first case report of a HAM/TSP patient in China, it is suggested that serological testing for HTLV-1 should be considered in patients with spastic paraparesis even in areas that are non-endemic for HTLV-1. Keywords: HTLV-1, HAM/TSP, China, MRI, Multiple spotty lesions

Microglial activation and the inflammatory response in the central nervous system (CNS) play important roles in secondary damage after traumatic brain injury (TBI). Transcriptional activation of genes that limit secondary damage to the CNS are mediated by a cis-acting element called the antioxidant responsive element (ARE). ARE is known to associate with the transcription factor NF-E2-related factor 2 (Nrf2), a transcription factor that is associated with histone deacetylases (HDACs). This pathway, known as the Nrf2/ARE pathway, is a critical antioxidative factor pathway that regulates the balance of oxygen free radicals and the inflammatory response, and is also related to autophagic activities. Although valproic acid (VPA) is known to inhibit HDACs, it is unclear whether VPA plays a role in the microglia-mediated neuroinflammatory response after TBI via regulating oxidative stress and autophagy induced by the Nrf2/ARE signaling pathway. In this study, we demonstrate that microglial activation, oxidative stress, autophagy, and the Nrf2/ARE signaling pathway play essential roles in secondary injury following TBI. Treatment with VPA alleviated TBI-induced secondary brain injury, including neurological deficits, cerebral edema, and neuronal apoptosis. Moreover, VPA treatment upregulated the occurrence of autophagy and Nrf2/ARE pathway activity after TBI, and there was an increase in H3, H4 histone acetylation levels, accompanied by decreased transcriptional activity of the HDAC3 promoter in cortical lesions. These results suggest that VPA-mediated up-regulation of autophagy and antioxidative responses are likely due to increased activation of Nrf2/ARE pathway, through direct inhibition of HDAC3. This inhibition further reduces TBI-induced microglial activation and the subsequent inflammatory response, ultimately leading to neuroprotection.