Liquid-Phase Adsorption Behavior of ß-D-Glucooligosaccharides When Using Activated Carbon for Separation, and the Antioxidant Stress Activity of Purified Fractions.

The adsorption characteristics of ß-glucooligosaccharides on activated carbon and the purification were systematically investigated. The maximum adsorption capacity of activated carbon reached 0.419 g/g in the optimal conditions. The adsorption behavior was described to be monolayer, spontaneous, and exothermic based on several models' fitting results. Five fractions with different degrees of polymerization (DPs) and structures of ß-glucooligosaccharides were obtained by gradient ethanol elution. 10E mainly contained disaccharides with dp2a (G1→6G) and dp2b (G1→3G). 20E possessed trisaccharides with dp3a (G1→6G1→3G) and dp3b (G1→3G1→3G). 30E mainly consisted of dp3a and dp4a (G1→3G1→3(G1→6)G), dp4b (G1→6G1→3G1→3G), and dp4c (G1→3G1→3G1→3G). In addition to tetrasaccharides, 40E and 50E also contained pentasaccharides and hexasaccharides with ß-(1→3)-linked or ß-(1→6)-linked glucose residues. All fractions could inhibit the accumulation of intracellular reactive oxygen species (ROS) in H2O2-induced Caco-2 cells, and they could improve oxidative stress damage by increasing the activity of superoxide dismutase (SOD) and reduced glutathione (GSH), which were related to their DPs and structures. 50E with high DPs showed better anti-oxidative stress activity.

Relationship between low molecular weight heparin calcium therapy and prognosis in severe acute kidney injury in sepsis: Mendelian randomized analysis and retrospective study.

Background: Sepsis-associated acute kidney injury (SA-AKI) poses an independent risk for mortality due to the absence of highly sensitive biomarkers and a specific treatment plan. Objective: Investigate the association between low molecular weight heparin (LMWH) calcium therapy and prognosis in critically ill SA-AKI patients, and assess the causal relationship through Mendelian randomization (MR) analysis. Methods: A single-center, retrospective, cross-sectional study included 90 SA-AKI patients and 30 septic patients without acute kidney injury (AKI) from the intensive care unit (ICU) of the First Hospital of Lanzhou University. SA-AKI patients were categorized into control or LMWH groups based on LMWH calcium usage. Primary outcome was renal function recovery, with secondary outcomes including 28-day mortality, ICU stay length, number of renal replacement therapy (RRT) recipients, and 90-day survival. MR and related sensitivity analyses explored causal effects. Results: The combination of heparin-binding protein (HBP), heparanase (HPA), and neutrophil gelatinase-associated lipocalin (NGAL) demonstrated high diagnostic value for SA-AKI. MR analysis suggested a potential causal link between gene-predicted HBP and AKI (OR: 1.369, 95%CI: 1.040-1.801, p = 0.024). In the retrospective study, LMWH-treated patients exhibited improved renal function, reduced levels of HPA, HBP, Syndecan-1, and inflammation, along with enhanced immune function compared to controls. However, LMWH did not impact 28-day mortality, 90-day survival, or ICU stay length. Conclusion: LMWH could enhance renal function in SA-AKI patients. MR analysis supports this causal link, underscoring the need for further validation in randomized controlled trials.

Long Non-coding RNA PCED1B Antisense RNA 1 Promotes Cell Proliferation and Invasion in Hepatocellular Carcinoma by Regulating the MicroRNA-34a/CD44 Axis.

OBJECTIVE: This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1 (PCED1B-AS1) in the development of hepatocellular carcinoma (HCC). METHODS: A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients. The interactions of PCED1B-AS1 and microRNA-34a (miR-34a) were detected by dual luciferase activity assay and RNA pull-down assay. The RNA expression levels of PCED1B-AS1, miR-34a and CD44 were detected by RT-qPCR, and the protein expression level of CD44 was determined by Western blotting. The cell proliferation was detected by cell proliferation assay, and the cell invasion and migration by transwell invasion assay. The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study. RESULTS: PCED1B-AS1 was highly expressed in HCC tissues, which was associated with poor survival of HCC patients. Furthermore, PCED1B-AS1 interacted with miR-34a in HCC cells, but they did not regulate the expression of each other. Additionally, PCED1B-AS1 increased the expression level of CD44, which was targeted by miR-34a. The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro, while CD44 exhibited the opposite effects. Furthermore, PCED1B-AS1 suppressed the role of miR-34a. Moreover, the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo. CONCLUSION: PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.

Histology and transcriptomic analysis reveal the inflammation and affected pathways under 2-methylisoborneol (2-MIB) exposure on grass carp.

2-Methylisoborneol (2-MIB) is a common and widely distributed off-flavor compound in water. However, the toxic mechanisms of 2-MIB on aquatic organisms remain largely unexplored. In this study, grass carp larvae were exposed to different concentrations (0, 5, and 20 µg L-1) of 2-MIB for 96 h. The accumulation of 2-MIB in the dorsal muscle was measured. Histological analysis, ultrastructure observations, and transcriptomic sequencing were conducted on the liver tissues. The results showed that 2-MIB accumulated significantly in the fish muscle, with the accumulation increasing as the exposure concentration increased through gas chromatography-mass spectrometry (GC-MS) detection. Histological and ultrastructure observations indicated that 2-MIB caused concentration-dependent inflammatory infiltration and mitochondrial damage in the liver. Transcriptomic analysis revealed lipid metabolism disorders induced by exposure to 2-MIB in grass carp. Additionally, 5 µg L-1 2-MIB affected the neurodevelopment and cardiovascular system of grass carp larvae through extracellular matrix (ECM)-receptor interaction and focal adhesion pathway. Furthermore, several pathways related to the digestive system were significantly enriched, implying that 2-MIB may impact pancreatic secretion function, protein digestion and absorption processes. These findings provide new insights into the potential toxicological mechanisms of 2-MIB.

Comparing Sonazoid contrast-enhanced ultrasound to contrast-enhanced CT and MRI for differentially diagnosing renal lesions: a prospective multicenter study.

PURPOSE: To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. MATERIALS AND METHODS: 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7 days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2 year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. RESULTS: In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4 cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. CONCLUSIONS: SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.

The FAITHS2 Model Predicts Functional Disability in Patients With Acute Ischemic Stroke.

The present study aimed to develop a model to predict functional disability at 3 months in patients with acute ischemic stroke (AIS) (n = 5,406). The primary outcome was functional disability (modified Rankin Scale [mRS] >2) at 3 months. A prediction model including blood biomarkers was developed based on a multivariable logistic regression model, which was internally validated by the 100-time bootstrap method. A nomogram and a web-based calculator were developed for usage in clinical practice. At 3 months, 11% (638/5,406) of the patients had functional disability. Seven independent predictors of functional disability at 3 months were incorporated into the FAITHS2 model (fasting plasma glucose, age, interleukin-6, stroke history, National Institute of Health Stroke Scale [NIHSS] at admission, sex, and systolic blood pressure). The Area Under Curves (AUCs) were 0.814 (95% confidence interval [CI] 0.796-0.832) and 0.808 (95% CI 0.806-0.810), and the Brier scores were 0.088 ± 0.214 and 0.089 ± 0.003 for the derivation cohort and internal validation, respectively, showing optimal performance of the model. The FAITHS2 model has excellent potential to be a dependable application for individualized clinical decision making.

Moniezia benedeni infection increases IgE+ cells in sheep (Ovis aries) small intestine.

The concentration of immunoglobulin (Ig) E is the lowest among serum Igs, but it can induces type I hypersensitivity and plays an important role in anti-parasitic infection. The present study aimed to explore the residence characteristics of IgE+ cells in the sheep small intestine and the impact of Moniezia benedeni infection on them. The recombinant plasmids pET-28a-IgE were constructed and induced and expressed in Escherichia coli. BL21 (DE3). The rabbit anti-sheep IgE polyclonal antibody was prepared using the obtained recombinant protein as antigen. Finally, the levels of IgE+ cells in the small intestine of healthy (Control group) and naturally M. benedeni-infected (Infected group) sheep were detected analyzed. The results showed that the rabbit anti-sheep IgE polyclonal antibody with good immunogenicity (titer = 1: 128000) could specifically bind to the heavy chain of natural sheep IgE. In the Control group, the IgE+ cells were mainly distributed in lamina propria of the small intestine, and the densities were significantly decreased from duodenum to ileum (P<0.05), with respective values of (4.28 cells / 104 µm2, 1.80 cells / 104 µm2, and 1.44 cells / 104 µm2 in duodenum, jejunum, and ileum. In the Infected group, IgE+ cells density were 6.26 cells / 104 µm2, 3.01 cells / 104 µm2, and 2.09 cells / 104 µm2 in duodenum, jejunum and ileum respectively, which were significantly higher in all segments compared to the Control group (P<0.05), increasing by 46.26%, 67.22% and 45.14%, respectively. In addition, compared with the Control group, the IgE protein levels were significantly increased in all intestinal segments of the Infected group (P<0.01), however, there was no significant differences among the different intestinal segments within the same group (P>0.05). The results demonstrated that M. benedeni infection could significantly increase the content of IgE and the distribution density of its secreting cells in sheep small intestine. The intestinal mucosal immune system of sheep presented obvious specificity against M. benedeni infection. This lays a good foundation for further exploring molecular mechanisms of the intestinal mucosal immune system monitoring and responding to M. benedeni infection.

Inflammatory marker profiles and in-hospital neurological deterioration in patients with acute minor ischemic stroke.

AIM: The aim of the study was to analyze the association between inflammatory marker profiles and in-hospital neurological deterioration (ND) in acute ischemic stroke (AIS) patients. METHODS: Data from patients with minor AIS from the Third China National Stroke Registry were analyzed. Inflammatory cytokine levels within 24 h of admission were measured. The primary outcome was in-hospital ND (an increase in National Institutes of Health Stroke Scale score ≥4 from admission to discharge). Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from logistic regression models. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to evaluate incremental predictive values. RESULTS: A total of 4031 patients (1246 women, 30.9%) with a median age of 62 years were included. In-hospital ND occurred in 121 patients (3%). Each standard-deviation increase in interleukin (IL)-6 (OR, 1.17 [95% CI, 1.06-1.31]) and high-sensitivity C-reactive protein (hsCRP) (OR, 1.43 [95% CI, 1.24-1.66]) levels was associated with increased in-hospital ND risk. Incremental predictive values for adding IL-6 (IDI, 0.012; NRI, 0.329) but not hsCRP levels to the conventional risk factors were found. CONCLUSION: In minor AIS, hsCRP and IL-6 levels were associated with in-hospital ND, including IL-6 levels in prognostic models improved risk classification.

Factors associated with early-onset androgenetic alopecia: A scoping review.

BACKGROUND: Early-onset androgenetic alopecia (AGA) has been associated with various chronic conditions, including metabolic syndrome (MetS). Gaining a deep understanding of early-onset AGA may enable earlier intervention in individuals at high risks. This scoping review aims to explore the risk factors and etiology, associated conditions, and adverse effects on wellbeing in early-onset AGA. METHODS: Electronic literature searches were conducted in MEDLINE, EMBASE and CENTRIAL. Eligible studies included case-control, cohort, cross-sectional, and meta-analysis studies. Selected studies needed to clearly define early-onset AGA cases or include only cases starting before the age of 40 and compare them with appropriate controls. The exclusion criteria comprised editorials, commentaries, case series, and non-systematic reviews, among others. Data extraction involved collecting study characteristics, methodologies, main outcomes, and findings. Descriptive tables were used to summarize key information and relevant variables when necessary. RESULTS: Among the 65 eligible articles, 67.69% were case-control studies and 78.46% evaluated only male patients. "Early-onset" was defined as cases developing before the age of 30 years in 43.08% of the studies. The Hamilton-Norwood scale was the most frequently used method for evaluating the severity of alopecia in men (69.23%). Reported risk factors for early-onset AGA included a family history of AGA, cigarette smoking, unhealthy dietary habits, and a high body mass index. Early-onset AGA may also be associated with hormonal profiles, 5α-reductase enzyme activity, androgen receptor genes, and some susceptibility loci. Comorbidities investigated included MetS, cardiovascular disease, insulin resistance, dyslipidemia, and Parkinson's disease. Men with early-onset AGA may have reduced treatment efficacy with drug like rosuvastatin, metformin or lisinopril for dyslipidemia, prediabetes, or hypertension. Additionally, young men with AGA tended to suffer from psychological issues such as anxiety and low self-esteem compared to those without hair loss. CONCLUSION: Early-onset AGA is a complex condition with various risk factors and etiology, associated comorbidities, and potential implications for treatment response and psychological health.

Double plasma molecular adsorption system for Stevens-Johnson syndrome/toxic epidermal necrolysis: A case report.

BACKGROUND: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are very serious skin allergies, with an etiology related to infections and medication. Since the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus-2 has also been considered to cause SJS/TEN. CASE SUMMARY: We report the case of a woman in her thirties who took acetaminophen after contracting COVID-19. After 3 d of fever relief, she experienced high fever and presented with SJS/TEN symptoms, accompanied by intrahepatic cholestasis. Three days of corticosteroid treatment did not alleviate the skin damage; therefore, double plasma molecular adsorption system (DPMAS) therapy was initiated, with treatment intervals of 48 h. Her skin symptoms improved gradually and were resolved after seven DPMAS treatments. CONCLUSION: DPMAS therapy is beneficial for abrogating SJS/TEN because plasma adsorption and perfusion techniques reduce the inflammatory mediators (e.g., tumor necrosis factor-alpha and interleukin-10 and-12) speculated to be involved in the pathology of the skin conditions.

Comprehensive mRNA and microRNA analysis revealed the effect and response strategy of freshwater fish, grass carp (Ctenopharyngodon idella) under geosmin exposure.

Geosmin is an environmental pollutant that causes off-flavor in water and aquatic products. The high occurrence of geosmin contamination in aquatic systems and aquaculture raises public awareness, however, few studies have investigated the response pathways of geosmin stress on freshwater fish. In this research, grass carp were exposed to 50 µg/L geosmin for 96 h, liver tissue was sequenced and validated using real-time qPCR. In total of 528 up-regulated genes and 488 down-regulated genes were observed, includes cytochrome P450 and uridine diphosphate (UDP)-glucuronosyltransferase related genes. KEGG analysis showed that chemical carcinogenesis-DNA adducts, metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450 pathway was enriched. Common genes from the target genes of microRNAs and differential expression genes are enriched in metabolism of xenobiotics cytochrome P450 pathway. Two miRNAs (dre-miR-146a and miR-212-3p) down regulated their target genes (LOC127510138 and adh5, respectively) which are enriched cytochrome P450 related pathway. The results present that geosmin is genetoxic to grass carp and indicate that cytochrome P450 system and UDP-glucuronosyltransferase play essential roles in biotransformation of geosmin. MicroRNAs regulate the biotransformation of geosmin by targeting specific genes, which contributes to the development of strategies to manage its negative impacts in both natural and artificial environments.

The silk gland proteome of Stenopsyche angustata provides insights into the underwater silk secretion.

Caddisworms (Trichoptera) spin adhesive silks to construct a variety of underwater composite structures. Many studies have focused on the fibroin heavy chain of caddisworm silk and found that it contains heavy phosphorylation to maintain a stable secondary structure. Besides fibroins, recent studies have also identified some new silk proteins within caddisworm silk. To better understand the silk composition and its secretion process, this study reports the silk gland proteome of a retreat-building caddisworm, Stenopsyche angustata Martynov (Trichoptera, Stenopsychidae). Using liquid chromatography tandem mass spectrometry (LC-MS/MS), 2389 proteins were identified in the silk gland of S. angustata, among which 192 were predicted as secreted silk proteins. Twenty-nine proteins were found to be enriched in the front silk gland, whereas 109 proteins were enriched in the caudal silk gland. The fibroin heavy chain and nine uncharacterized silk proteins were identified as phosphorylated proteins. By analysing the sequence of the fibroin heavy chain, we found that it contains 13 Gly/Thr/Pro-rich regions, 12 Val/Ser/Arg-rich regions and a Gly/Arg/Thr-rich region. Three uncharacterized proteins were identified as sericin-like proteins due to their larger molecular weights, signal peptides and repetitive motifs rich in serine. This study provides valuable information for further clarifying the secretion and adhesion of underwater caddisworm silk.

The role of peer relationships and flow experience in the relationship between physical exercise and social anxiety in middle school students.

The present study examined the relationship between physical exercise and social anxiety by testing a moderated mediation model that focused on how peer relationships mediate the relationship between physical exercise and social anxiety and how flow experience moderates this mediated relationship. A total of 1056 middle school students from six middle schools in Sichuan, China, volunteered to complete questionnaires comprising the Physical Activity Rating Scale, Student Peer Relationship Scale, Social Anxiety Subscale of the Self-Consciousness Scale, and Short (9-Item) Dispositional Flow Scales. Regression analysis indicated that physical exercise negatively influenced social anxiety through peer relationships (indirect effect = -0.04, 95% CI = [-0.067, -0.013]). In addition, a moderated regression analysis indicated that under high-flow experience, physical exercise suppresses social anxiety through positive effects on peer relationships (indirect effect = -0.04, 95% CI = [-0.087, -0.003]), and under low-flow experience, physical exercise exacerbates social anxiety through negative effects on peer relationships (indirect effect = 0.06, 95% CI = [0.016, 0.105]). Some practical implications have been discussed on the physical exercise intervention for suppressing social anxiety in middle school students.

Antibody preparation and age-dependent distribution of TLR8 in Bactrian camel spleens.

BACKGROUND: Toll-like receptor 8 (TLR8) can recognize specific pathogen-associated molecular patterns and exert multiple immunological functions through activation of signaling cascades. However, the precise distribution and age-related alterations of TLR8 in the spleens of Bactrian camels have not yet been investigated. This study aimed to prepare a rabbit anti-Bactrian camel TLR8 polyclonal antibody and elucidate the distribution of TLR8 in the spleens of Bactrian camels at different age groups. The methodology involved the construction of the pET-28a-TLR8 recombinant plasmid, followed by the expression of TLR8 recombinant protein via prokaryotic expression. Subsequently, rabbits were immunized with the purified protein to prepare the TLR8 polyclonal antibody. Finally, twelve Alashan Bactrian camels were categorized into four groups: young (1-2 years), pubertal (3-5 years), middle-aged (6-16 years) and old (17-20 years). These camels received intravenous sodium pentobarbital (20 mg/kg) anesthesia and were exsanguinated to collect spleen samples. Immunohistochemical techniques were employed to observe and analyze the distribution patterns and age-related changes of TLR8 in the spleen. RESULTS: The results showed that the TLR8 recombinant protein was expressed in the form of inclusion body with a molecular weight of 52 kDa, and the optimal induction condition involved 0.3 mmol/L IPTG induction for 8 h. The prepared antibody yielded a titer of 1:32 000, and the antibody demonstrated specific binding to TLR8 recombinant protein. TLR8 positive cells exhibited a consistent distribution pattern in the spleen across different age groups of Bactrian camels, primarily scattered within the periarterial lymphatic sheath of the white pulp, marginal zone, and red pulp. The predominant cell type expressing TLR8 was macrophages, with expression also observed in neutrophils and dendritic cells. Statistical analysis revealed that there were significant differences in the distribution density of TLR8 positive cells among different spleen regions at the same age, with the red pulp, marginal zone, and white pulp showing a descending order (P<0.05). Age-related changes indicated that the distribution density in the marginal zone and red pulp exhibited a similar trend of initially increasing and subsequently decreasing from young to old camels. As camels age, there was a significant decrease in the distribution density across all spleen regions (P<0.05). CONCLUSIONS: The results confirmed that this study successfully prepared a rabbit anti-Bactrian camel TLR8 polyclonal antibody with good specificity. TLR8 positive cells were predominantly located in the red pulp and marginal zone of the spleen, signifying their pivotal role in the innate immune response of the spleen. Aging was found to significantly reduce the density of TLR8 positive cells, while leaving their scattered distribution characteristics unaffected. These findings provide valuable support for further investigations into the immunomorphology and immunosenescence of the spleen in Bactrian camels.

Characterization of thyroid metastasis from clear cell renal cell carcinoma on ultrasonography: a report of three cases and literature review.

Introduction: Thyroid metastasis from clear cell renal cell carcinoma (ccRCC) is relatively rare, so ultrasound doctors lack experience with the disease, which can easily lead to misdiagnosis. We describe three cases of thyroid metastasis from ccRCC detected 12, 8, and 7 years after nephrectomy. Case presentation: The first patient, a 78-year-old woman, was admitted to our institution for hoarseness and progressive dyspnea. Ultrasonography revealed bilateral thyroid nodules and abnormal cervical lymph nodes. Fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) of the thyroid was nondiagnostic. The other two patients, a 54-year-old man and a 65-year-old man, were admitted to our institution for a goiter pressing on the trachea. In each case, ultrasonography revealed a partially cystic nodule of the left lobe of the thyroid gland. Histological examination of three patients after thyroidectomy showed thyroid metastasis from ccRCC. Discussion/Conclusion: For patients with a history of ccRCC, long-term follow-up and routine thyroid ultrasonography should be performed. If a new thyroid nodule is found during the examination, metastases should be highly suspected. FNAB should be performed, even if benign ultrasound features seem to be in evidence. If the diagnosis of FNAB is incorrect and inconclusive, CNB should be performed.

Clinical characteristics, in-hospital management, and outcomes of patients with in-hospital vs. community-onset ischaemic stroke: a hospital-based cohort study.

Background: Lack of high-quality national-level data on in-hospital ischaemic stroke hinders the development of tailored strategies for this subgroup's identification, treatment, and management. Methods: We analyzed and compared clinical characteristics, in-hospital management measures, and outcomes, including death or discharge against medical advice (DAMA), major adverse cardiovascular events (MACEs), disability at discharge, and in-hospital complications between in-hospital and community-onset ischaemic stroke enrolled in the Chinese Stroke Center Association registry from August 2015 to December 2022. Findings: The cohort comprised 14,948 in-hospital and 1,366,898 community-onset ischaemic stroke patients. In-hospital ischaemic stroke exhibited greater stroke severity, higher prevalence of comorbidities, more pre-admission medications, and had suboptimal management measures, for example, the onset-to-needle time within 4.5 h (83.3% vs. 93.1%; difference, -9.8% [-11.4% to -8.3%]), and antithrombotics at discharge (78.6% vs. 90.0%; difference, -11.4% [95% CI, -12.1% to -10.7%]). After adjusting for covariates, in-hospital ischaemic stroke remains associated with higher risks of unfavorable outcomes, including in-hospital death/DAMA (13.9% vs. 8.6%; adjusted risk difference [aRD], 2.2% [95% CI, 1.8%-2.7%]; adjusted odds ratio [aOR], 1.35 [95% CI, 1.25-1.45]), MACE (12.6% vs. 6.5%; aRD, 4.1% [95% CI, 3.5%-4.7%]; aOR, 1.68 [95% CI, 1.52-1.85]), and complications (23.7% vs. 12.1%; aRD, 6.5% [95% CI, 5.1%-7.9%]; aOR, 1.72 [95% CI, 1.64-1.80]), except for disability at discharge (41.1% vs. 33.1%; aRD, 0.4% [95% CI, -1.7% to 2.5%]; aOR, 0.99 [95% CI, 0.88-1.11]). Interpretation: In-hospital ischaemic stroke demonstrated more severe strokes, worse vascular risk profiles, suboptimal management measures, and worse outcomes compared to community-onset ischaemic stroke. This emphasizes the urgent need for improved hospital systems of care and targeted quality improvement initiatives for better outcomes in in-hospital ischaemic stroke. Funding: National Key R&D Programme of China and Beijing Hospitals Authority.

Heparanase inhibition leads to improvement in patients with acute gastrointestinal injuries induced by sepsis.

BACKGROUND: Patients with sepsis are at high risk for acute gastrointestinal injury (AGI), but the diagnosis and treatment of AGI due to sepsis are unsatisfactory. Heparanase (HPA) plays an important role in septic AGI (S-AGI), but its specific mechanism is not completely understood, and few clinical reports are available. AIM: To explore the effect and mechanism of HPA inhibition in S-AGI patients. METHODS: In our prospective clinical trial, 48 patients with S-AGI were randomly assigned to a control group to receive conventional treatment, whereas 47 patients were randomly assigned to an intervention group to receive conventional treatment combined with low molecular weight heparin. AGI grade, sequential organ failure assessment score, acute physiology and chronic health evaluation II score, D-dimer, activated partial thromboplastin time (APTT), anti-Xa factor, interleukin-6, tumour necrosis factor-α, HPA, syndecan-1 (SDC-1), LC3B (autophagy marker), intestinal fatty acid binding protein, D-lactate, motilin, gastrin, CD4/CD8, length of intensive care unit (ICU) stay, length of hospital stay and 28-d survival on the 1st, 3rd and 7th d after treatment were compared. Correlations between HPA and AGI grading as well as LC3B were compared. Receiver operator characteristic (ROC) curves were generated to evaluate the diagnostic value of HPA, intestinal fatty acid binding protein and D-lactate in S-AGI. RESULTS: Serum HPA and SCD-1 levels were significantly reduced in the intervention group compared with the control group (P < 0.05). In addition, intestinal fatty acid-binding protein, D-lactate, AGI grade, motilin, and gastrin levels and sequential organ failure assessment score were significantly decreased (P < 0.05) in the intervention group. However, LC3B, APTT, anti-Xa factor, and CD4/CD8 were significantly increased (P < 0.05) in the intervention group. No significant differences in interleukin-6, tumour necrosis factor-α, d-dimer, acute physiology and chronic health evaluation II score, length of ICU stay, length of hospital stay, or 28-d survival were noted between the two groups (P > 0.05). Correlation analysis revealed a significant negative correlation between HPA and LC3B and a significant positive correlation between HPA and AGI grade. ROC curve analysis showed that HPA had higher specificity and sensitivity in diagnosis of S-AGI. CONCLUSION: HPA has great potential as a diagnostic marker for S-AGI. Inhibition of HPA activity reduces SDC-1 shedding and alleviates S-AGI symptoms. The inhibitory effect of HPA in gastrointestinal protection may be achieved by enhanced autophagy.

Role of heparanase in pulmonary hypertension.

Pulmonary hypertension (PH) is a pathophysiological condition of increased pulmonary circulation vascular resistance due to various reasons, which mainly leads to right heart dysfunction and even death, especially in critically ill patients. Although drug interventions have shown some efficacy in improving the hemodynamics of PH patients, the mortality rate remains high. Hence, the identification of new targets and treatment strategies for PH is imperative. Heparanase (HPA) is an enzyme that specifically cleaves the heparan sulfate (HS) side chains in the extracellular matrix, playing critical roles in inflammation and tumorigenesis. Recent studies have indicated a close association between HPA and PH, suggesting HPA as a potential therapeutic target. This review examines the involvement of HPA in PH pathogenesis, including its effects on endothelial cells, inflammation, and coagulation. Furthermore, HPA may serve as a biomarker for diagnosing PH, and the development of HPA inhibitors holds promise as a targeted therapy for PH treatment.

Treatment of a patient with severe lactic acidosis and multiple organ failure due to mitochondrial myopathy: A case report.

BACKGROUND: Mitochondrial myopathy is a rare genetic disease with maternal inheritance that may involve multiple organ systems. Due to the lack of typical characteristics, its clinical diagnosis is difficult, and it is often misdiagnosed or even missed. CASE SUMMARY: The patient was a young college student. When he presented at the hospital, he had severe lactic acidosis, respiratory failure, and shock with multiple organ dysfunction syndrome (MODS). He was treated by mechanical ventilation, veno-arterial extracorporeal membrane oxygenation, and other organ support. However, his condition continued to worsen. After a thorough and detailed medical and family history was taken, a mitochondrial crisis was suspected. A muscle biopsy was taken. Further genetic testing confirmed a mitochondrial gene mutation (TRNL1 3243A>G). The final diagnosis of mitochondrial myopathy was made. Although there is no known specific treatment, intravenous methylprednisone and intravenous immunoglobulin were started. The patient's shock eventually improved. The further course was complicated by severe infection in multiple sites, severe muscle weakness, and recurrent MODS. After 2 mo of multidisciplinary management and intensive rehabilitation, the patient could walk with assistance 4 mo after admission and walk independently 6 mo after admission. CONCLUSION: More attention should be paid to mitochondrial myopathy to avoid missed diagnosis and misdiagnosis.