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Xiao-Yu Xu,1,* Yang Gao,2,* Chuang-Shi Yue,3,* Yu-Jia Tang,4,* Zhao-Jin Zhang,5 Feng-Jie Xie,6 Hong Zhang,6 Yu-Cheng Zhu,7 Yan Zhang,7 Qi-Qi Lai,4 Xin-Tong Wang,4 Jia-Xi Xu,4 Jia-Ning Zhang,4 Bo-Wen Liu,4 Jian-Nan Zhang,4 Kai Kang4 1Department of Critical Care Medicine, The Second People’s Hospital of Beihai, Beihai, People’s Republic of China; 2Department of Critical Care Medicine, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 3Department of Critical Care Medicine, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 4Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 5Department of Critical Care Medicine, The Yichun Central Hospital, Yichun, People’s Republic of China; 6Department of Critical Care Medicine, The Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 7Department of Critical Care Medicine, The Hongxinglong Hospital of Beidahuang Group, Shuangyashan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian-Nan Zhang; Kai Kang, Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang, 150001, People’s Republic of China, Tel +86-13836119816 ; +86-13904618016, Email zhangjiannan@hrbmu.edu.cn; janekk79@126.comPurpose: In this study, our objective was to investigate the potential utility of lymphocyte-C-reactive protein ratio (LCR) as a predictor of disease progression and a screening tool for intensive care unit (ICU) admission in adult patients with acute pancreatitis (AP).Methods: We included a total of 217 adult patients with AP who were admitted to the First Affiliated Hospital of Harbin Medical University between July 2019 and June 2022. These patients were categorized into three groups: mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP), based on the presence and duration of organ dysfunction. Various demographic and clinical data were collected and compared among different disease severity groups.Results: Height, diabetes, lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet count (PLT), D-Dimer, albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), glucose (GLU), calcium ion (Ca2+), C-reactive protein (CRP), procalcitonin (PCT), hospitalization duration, ICU admission, need for BP, LCR, sequential organ failure assessment (SOFA) score, bedside index for severity in AP (BISAP) score, and modified Marshall score showed significant differences across different disease severity groups upon hospitalization. Notably, there were significant differences in LCR between the MAP group and the MSAP and SAP combined group, and the MAP and MSAP combined group and the SAP group, and adult AP patients with ICU admission and those without ICU admission upon hospitalization.Conclusion: In summary, LCR upon hospitalization can be utilized as a simple and reliable predictor of disease progression and a screening tool for ICU admission in adult patients with AP.Keywords: lymphocyte-C-reactive protein ratio, acute pancreatitis, lymphocyte count, C-reaction protein, disease progression, ICU admission, screening tool

Zhe-Feng Zhao,1,* Bing-Bing Liu,1,* Jian-Nan Zhang,2,* Ni Shi,3,* Ping Zhang,1,* Gang-Zhi Yang,4 Yu-Fu Cao,4 Long-He Tian,4 Cheng-Cai Qiu,5 Yang Gao6,7 1Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 2Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 3Department of Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 4Department of Neurosurgery, People’s Hospital of Hegang City, Hegang, Heilongjiang, People’s Republic of China; 5Department of Neurosurgery, Traditional Chinese Medicine Hospital of Jixi City, Jixi, Heilongjiang, People’s Republic of China; 6Department of Critical Care Medicine, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 7Institute of Critical Care Medicine, The Sino Russian Medical Research Center of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhe-Feng Zhao, Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Email know810512@163.com Yang Gao, Department of Critical Care Medicine, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Email gaoyang0312@126.comObjective: In this study, we aimed to explore the demographic and clinical factors that could determine short- and long-term complete pain relief (CPR) in adult patients with primary trigeminal neuralgia (PTN) after microvascular decompression (MVD) to guide clinical practice.Methods: This single-center retrospective study included adult patients with PTN who underwent MVD as their initial neurosurgical procedure in the Department of Neurosurgery at the Second Affiliated Hospital of Harbin Medical University from January 2017 to December 2019 and completed a 3-year post-surgery follow-up. Demographic and clinical information was obtained from medical records. Pain relief of adult patients with PTN at various time points after sufficient decompression of trigeminal nerve (TN) during MVD was determined and classified by the patient’s subjective response and medications use. Pain relief of local patients was evaluated by outpatient follow-up at various time points, whereas that of local cases who could not return to outpatient or non-local cases was assessed through telephone or WeChat.Results: In univariate analysis, compression degree of TN and type of conflicting vessels constantly showed significant differences between the two groups at 3 months, 6 months, 1 year, 2 years, and 3 years after MVD. Compression degree of TN and type of conflicting vessels at various time points after MVD were always the related factors to CPR in logistic regression analysis, with the former having the greatest impact. The areas under the receiver operating characteristic (ROC) curve of CPR at various time points after MVD were 0.937, 0.874, 0.879, 0.864, and 0.869, respectively.Conclusion: In summary, compression degree of TN and type of conflicting vessels can determine short- and long-term CPR in adult patients with PTN after MVD.Keywords: compression degree of trigeminal nerve, type of conflicting vessels, microvascular decompression, sufficient decompression of trigeminal nerve, complete pain relief, primary trigeminal neuralgia

Jiang-Nan Zhang, Xi-Le Zhao Department of Endocrinology, The First Hospital of Fuzhou, Fuzhou, 350009, People’s Republic of ChinaCorrespondence: Jiang-Nan Zhang, Department of Endocrinology, The First Hospital of Fuzhou, No. 190 of DaDao Street, Taijiang District, Fuzhou, 350009, People’s Republic of China, Tel +86 13763892689, Email jiangnanzzhang@163.comObjective: To retrospectively analyze the changes of thyroid function and related factors in critical patients with non-thyroid illness, hoping to find some indicators for the further examination of the thyroid function in the intensive care unit situation.Methods: The clinical data of 52 patients admitted to the ICU of Fuzhou First Hospital in Fujian Province, China, from May 2018 to March 2019 were collected. Patients were allocated into the central hypothyroidism group (CH group, n = 21) and the low T3 syndrome group (LT3S group, n = 31) based on thyroid function. All related medical data were collected, and the correlations between variables were identified using Spearman’s or Pearson’s rank correlation coefficients.Results: The Acute Physiology and Chronic Health Evaluation (APACHE) II score in the CH group and the LT3S group were 20.6 ± 3.6 and 19.3 ± 3.6, respectively, measured within 24 hours following hospital admission. The mean value of thyroid-stimulating hormone (TSH) in the CH group (0.3 ± 0.3 IU/mL) was significantly lower than that in the LT3S group (1.7 ± 0.9 IU/mL), P < 0.001. Fasting plasma glucose (FPG) level in the CH group was significantly higher than that in the LT3S group (10.3 ± 5.0 mmol/L vs 6.8 ± 2.5 mmol/L, P = 0.002).Conclusion: Central hypothyroidism may exist in critically ill patients and may be associated with elevated fasting plasma glucose levels; accordingly, it should be included as part of patient assessment. When FPG is higher than 6.4mmol/L on admission, thyroid function should be actively examined.Keywords: central hypothyroidism, fasting blood glucose, critical illness, thyroid-stimulating hormone

Ling Ma,1,* Wenjing Wang,2,* Jehane Michael Le Grange,2 Xiaorong Wang,3 Shuaixian Du,1 Chen Li,1 Jia Wei,4 Jin-Nong Zhang2 1Department of Clinical Laboratory, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China; 2Department of Emergency Medicine, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China; 4Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jin-Nong Zhang; Jia Wei Email zhangjnwhhb@163.com; jiawei@tjh.tjmu.edu.cnPurpose: To differentiate between respiratory infections caused by SARS-CoV-2 and other respiratory pathogens during the COVID-19 outbreak in Wuhan, we simultaneously tested for SARS-CoV-2 and pathogens associated with CAP to determine the incidence and impact of respiratory coinfections in COVID-19 patients.Patients and Methods: We included 250 patients who were diagnosed with COVID-19. RT-PCR was used to detect influenza A, influenza B and respiratory syncytial viruses. Chemiluminescence immunoassays were used to detect IgM antibodies for adenovirus, Chlamydia pneumoniae and Mycoplasma pneumoniae in the serum of patients. Based on these results, we divided the patients into two groups, the simple SARS-CoV-2-infected group and the coinfected SARS-COV-2 group. Coinfected patients were then further categorized as having a coinfection of viral pathogen (CoIV) or coinfection of atypical bacterial pathogen (CoIaB).Results: No statistically significant differences were found in age, gender, the time taken to return negative SARS-CoV-2 nucleic acid test results, length of hospital stays, and mortality between the simple SARS-CoV-2 infection group and the coinfection group. Of the 250 hospitalized COVID-19 patients, 39 (15.6%) tested positive for at least one respiratory pathogen in addition to SARS-CoV-2. A third of these pathogens were detected as early as the 1st week after symptom onset and another third were identified after more than three weeks. The most detected CAP pathogen was C. pneumoniae (5.2%), followed by the respiratory syncytial virus (4.8%), M. pneumoniae (4.4%) and adenovirus (2.8%). Patients coinfected with viral pathogens (CoIV) (n=18) had longer hospital stays when compared to patients coinfected with atypical bacterial pathogens (CoIaB) (n=21). Except for one fatality, the remaining 38 coinfected patients all recovered with favourable outcomes.Conclusion: Coinfections in COVID-19 patients are common. The coinfecting pathogens can be detected at variable intervals during COVID-19 disease course and remain an important consideration in targeted treatment strategies for COVID-19 patients.Keywords: SARS-CoV-2, COVID-19, viral coinfection, atypical bacterial coinfection

Abstract A facile, rapid, solution-phase method of detecting human cardiac troponin I for sensing myocardial damage has been described using gold nanorods-based biosensors. The sensing is demonstrated by the distinct change of the longitudinal surface plasmon resonance wavelength of the gold nanorods to specific antibody–antigen binding events. For a higher sensitivity, the aspect ratio of gold nanorods is increased up to ca 5.5 by simply adding small amount of HCl in seed-mediated growth solution. Experimental results show that the detecting limit of the present method is 10 ng/mL. Contrast tests reveal that these gold nanorods-based plasmonic biosensors hold much higher sensitivity than that of conventionally spherical gold nanoparticles.

LiCoO2 is a dominant cathode material for lithium-ion (Li-ion) batteries due to its high volumetric energy density, which could potentially be further improved by charging to high voltages. However, practical adoption of high-voltage charging is hindered by LiCoO2’s structural instability at the deeply delithiated state and the associated safety concerns. Here, we achieve stable cycling of LiCoO2 at 4.6 V (versus Li/Li+) through trace Ti–Mg–Al co-doping. Using state-of-the-art synchrotron X-ray imaging and spectroscopic techniques, we report the incorporation of Mg and Al into the LiCoO2 lattice, which inhibits the undesired phase transition at voltages above 4.5 V. We also show that, even in trace amounts, Ti segregates significantly at grain boundaries and on the surface, modifying the microstructure of the particles while stabilizing the surface oxygen at high voltages. These dopants contribute through different mechanisms and synergistically promote the cycle stability of LiCoO2 at 4.6 V.

Traumatic brain injury (TBI) is a major health and socioeconomic problem throughout the world. It is a complicated pathological process that consists of primary insults and a secondary insult characterized by a set of biochemical cascades. The imbalance between a higher energy demand for repair of cell damage and decreased energy production led by mitochondrial dysfunction aggravates cell damage. At the cellular level, the main cause of the secondary deleterious cascades is cell damage that is centred in the mitochondria. Excitotoxicity, Ca(2+) overload, reactive oxygen species (ROS), Bcl-2 family, caspases and apoptosis inducing factor (AIF) are the main participants in mitochondria-centred cell damage following TBI. Some preclinical and clinical results of mitochondria-targeted therapy show promise. Mitochondria- targeted multipotential therapeutic strategies offer new hope for the successful treatment of TBI and other acute brain injuries. [ABSTRACT FROM AUTHOR]

Purpose: The well-known excessive daytime sleepiness (EDS) assessment, Epworth Sleepiness Scale (ESS), is not consistently qualified for patients with diverse living habits. This study is aimed to build a modified ESS (mESS) and then to verify its feasibility in the assessment of EDS for patients with suspected sleep-disordered breathing (SDB) in central China.Methods: A Ten-item Sleepiness Questionnaire (10-ISQ) was built by adding two backup items to the original ESS. Then the 10-ISQ was administered to 122 patients in central China with suspected SDB [among them, 119 cases met the minimal diagnostic criteria for obstructive sleep apnea by sleep study, e.g., apnea and hypopnea index (AHI) ≥ 5 h(-1)] and 117 healthy central Chinese volunteers without SDB. Multivariate exploratory techniques were used for item validation. The unreliable item in the original ESS was replaced by the eligible backup item, thus a modified ESS (mESS) was built, and then verified.Results: Item 8 proved to be the only unreliable item in central Chinese patients, with the least factor loading on the main factor and the lowest item-total correlation both in the 10-ISQ and in the original ESS, deletion of it would increase the Cronbach's alpha (from 0.86 to 0.87 in the 10-ISQ; from 0.83 to 0.85 in the original ESS). The mESS was subsequently built by replacing item 8 in the original ESS with item 10 in the 10-ISQ. Verification with patients' responses revealed that the mESS was a single-factor questionnaire with good internal consistency (Cronbach's alpha = 0.86). The sum score of the mESS not only correlated with AHI (P < 0.01) but was also able to discriminate the severity of obstructive apnea (P < 0.01). Nasal CPAP treatment for severe OSA reduced the score significantly (P < 0.001). The performance of the mESS was poor in evaluating normal subjects.Conclusion: The mESS improves the validity of ESS for our patients. Therefore, it is justified to use it instead of the original one in assessment of EDS for patients with SDB in central China. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the local risk factors of traumatic brain injury (TBI) patients developing gastrointestinal (GI) bleeding during the early hospitalization in neurosurgery intensive care unit (NICU).Method: From September 2005 to February 2006, 41 patients admitted to NICU and 13 healthy volunteers were involved in our study. Blood samples at 24 hours, 2-3 days and 5-7 days were obtained from each patient via arterial line at 8 a.m. to measure the concentrations of serum adrenocorticotropic hormone (ACTH), total cortisol and gastrin. The collected serum was immersed in an ice bath and tested by the Immulite 1000 systems. Data were analyzed by SPSS 11.5.Results: Within 24 hours following TBI, the concentrations of total cortisol, ACTH and gastrin increased proportionally to the severity of injury, especially significant in the experimental group (P less than 0.05). The concentrations of ACTH and gastrin were higher in the GI bleeding positive group than in the GI bleeding negative group, (F equal to 1.413, P less than 0.253) for ACTH and (F equal to 9.371, P equal to 0.006) for gastrin. GI bleeding had a positive correlation with gastrin concentration (r equal to 0. 312, P less than 0.05) and a negative correlation with serum hemoglobin (Hb) (r equal to -0.420, P less than 0.01). The clinical incidence of GI bleeding was 24.39% (10/41) in the experimental group. Within 24 hours, GI bleeding had a strong correlation with gastrin concentration (OR equal to 26.643, P less than 0.05) and hematocrit (Hct) (OR equal to 5.385, P less than 0.05). High ACTH concentration ( larger than 100 pg/ml) increased the frequency of GI bleeding. For patients with severe TBI and treated with routine antacids, the incidence of GI bleeding was 40.91% (9/22) and the mortality rate was 20% (2/10).Conclusions: Low Glasgow coma scale scores, low Hb, high concentrations of gastrin and ACTH (larger than 100 pg/ml) are risk factors and can be predictive values for post-traumatic GI bleeding. Severe TBI patients have high risks of GI bleeding with high mortality. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a major cause of mortality and morbidity in the world. Recent clinical investigations and basic researches suggest that strategies to improve angiogenesis following TBI may provide promising opportunities to improve clinical outcomes and brain functional recovery. More and more evidences show that circulating endothelial progenitor cells (EPCs), which have been identified in the peripheral blood, may play an important role in the pathologic and physiological angiogenesis in adults. Moreover, impressive data demonstrate that EPCs are mobilized from bone marrow to blood circulation in response to traumatic or inflammatory stimulations. In this review, we discussed the role of EPCs in the repair of brain injury and the possible therapeutic implication for functional recovery of TBI in the future. [ABSTRACT FROM AUTHOR]

Background: Women comprise approximately two-thirds of Alzheimer's disease cases., Objective: This is the first known study to investigate the role of intersectionality between gender and other social determinants of health (SDOH) in the presentation of cognitive symptoms (i.e., being asymptomatic or symptomatic) among those with pathologically confirmed Alzheimer's disease., Methods: We studied 3107 individuals with Alzheimer's disease neuropathology (ADNP) confirmed at autopsy. Asymptomatic ADNP was defined as the absence of a clinical diagnosis of mild cognitive impairment (MCI) or dementia before death (versus symptomatic: diagnosis of MCI/dementia). SDOH included gender, education, ethnoracial group, living alone, and primary language. Multivariable logistic regression tested associations between SDOH and asymptomatic ADNP (versus symptomatic); models were also stratified by gender., Results: Women, Hispanics, those living alone, and more educated individuals were found to have higher odds of asymptomatic ADNP. Non-English speakers had lower odds of asymptomatic ADNP. Both women and men had higher odds of asymptomatic ADNP if Hispanic or living alone. In only women, non-English speakers had lower odds while in only men, more education was associated with higher odds of asymptomatic ADNP., Conclusions: Gender, education, ethnicity, primary language, and living alone, and intersectionality of gender with primary language, may differentially influence MCI and dementia diagnosis prior to death among those with underlying ADNP. These findings emphasize the need for future Alzheimer's disease research to prioritize social determinants of brain health including their intersectionality with gender and how to inform targeted interventions., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Besser, Dr O’Shea, and Dr Galvin are Editorial Board Member of this journal but were not involved in the peer-review process of this article nor had access to any information regarding its peer-review. The remaining authors have no conflict of interest to report.

Sepsis-induced myocardial dysfunction presents significant challenges in clinical management and is associated with increased mortality. Anisodamine (654-1/-2) has potentials in alleviating cardiac and endothelial impairments associated with sepsis. Exosomes, small vesicles secreted by cells, carry various bioactive molecules, such as nucleic acids, proteins, and lipids. These vesicles can travel to target cells to influence their function and modulating biological processes. In the context of endothelial-cardiac crosstalk, exosomes derived from endothelial cells can transfer signals that either exacerbate or mitigate myocardial injury, playing a crucial role in the progression of cardiovascular diseases. However, the precise role of endothelial-cardiac crosstalk, particularly through exosomes, in mediating the cardioprotective effects of anisodamine remains unclear. This study evaluated the effects of anisodamine on myocardial and endothelial injuries induced by LPS. Mechanisms were analyzed through network pharmacology, molecular docking, Western blotting, and RT-qPCR. The interaction between endothelial and cardiomyocyte inflammatory responses to anisodamine was assessed using a co-culture assay. Furthermore, both in vivo and in vitro assays were conducted to evaluate the effects of anisodamine-/LPS- treated HUVECs exosomes on A16 cell and myocardial function in mice. Anisodamine effectively mitigated apoptosis, inflammation, mitochondrial and myocardial injury, glycocalyx degradation, and oxidative stress by regulating the PI3K-AKT, NLRP-3/Caspase-1/ASC, TNF-α/PKCα/eNOs/NO, and NF-κB/iNOs/NO pathways in A16 cells and HUVECs. Moreover, in vivo and in vitro assays confirmed the protective effects of anisodamine against myocardial injuries mediated by exosomes derived from LPS-treated HUVECs. In summary, anisodamine ameliorated inflammation-induced endothelial and cardiomyocyte dysfunction. The in vitro and in vivo assays demonstrated that anisodamine could alleviate myocardial dysfunction through exosome-mediated mechanisms, offering new therapeutic avenues for treating myocardial injury and highlighting the potential of targeted exosome therapy in clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Catalytic conversion of lithium polysulfides (LiPSs) is a crucial approach to enhance the redox kinetics and suppress the shuttle effect in lithium-sulfur (Li-S) batteries. However, the roles of a typical heterogenous catalyst cannot be easily identified due to its structural complexity. Compared with the distinct sites of single atom catalysts (SACs), each active site of single site catalysts (SSCs) is identical and uniform in their spatial energy, binding mode, and coordination sphere, etc. Benefiting from the well-defined structure, iron phthalocyanine (FePc) is covalently clicked onto CuO nanosheet to prepare low spin-state Fe SSCs as the model catalyst for Li-S electrochemistry. The periodic polarizability evolution of Fe-N bonding is probed during sulfur redox reaction by in situ Raman spectra. Theoretical analysis shows the decreased d-band center gap of Fe (Δd) and delocalization of d xz /d yz after the axial click confinement. Consequently, Li-S batteries with Fe SSCs exhibit a capacity decay rate of 0.029% per cycle at 2 C. The universality of this methodological approach is demonstrated by a series of M SSCs (M = Mn, Co, and Ni) with similar variation of electronic configuration. This work provides guidance for the design of efficient electrocatalysis in Li-S batteries., (© 2024 Wiley‐VCH GmbH.)

This study aimed to determine the expression levels of the autophagy markers Beclin-1 and p62 in patients with diffuse large B-cell lymphoma (DLBCL) and explore the association between autophagy and disease prognosis. The expression of Beclin-1 and p62 was investigated in patients with DLBCL and patients with reactive lymphoproliferative disease (RLD) using immunohistochemistry. The association between the clinical characteristics of patients with DLBCL and autophagy status was further analyzed. Beclin-1 levels were increased in RLD patients compared with those with DLBCL, but the difference was not statistically significant (p > 0.05). p62 levels in DLBCL patients were significantly higher than those in RLD patients (p < 0.05). Beclin-1 expression was associated only with the Ann Arbor stage (p < 0.05), whereas p62 expression was associated with the Ann Arbor stage, IPI score, extranodal involvement, and Ki-67 index (p < 0.05). Beclin-1 and p62 levels were not associated with short-term treatment efficacy in DLBCL patients. Survival analysis showed that Beclin-1 expression had no significant effect on 2-year progression-free survival (PFS) or overall survival (OS) (p > 0.05). However, high p62 expression in DLBCL patients was associated with reduced 2-year PFS compared with that of patients with low p62 expression (p < 0.05); the 2-year OS was not affected (p > 0.05). Our results demonstrate that autophagic activity affects the prognosis of DLBCL patients; the lower the autophagic activity, the shorter the PFS. Targeted p62 knockout may be a novel therapeutic strategy for the treatment of DLBCL patients., Competing Interests: Conflict of Interest Disclosure The authors do not have any conflicts of interest to declare in relation to this work., (Copyright © 2024 International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)

Spatial omics technologies have enabled the creation of intricate spatial maps that capture molecular features and tissue morphology, providing valuable insights into the spatial associations and functional organization of tissues. Accurate annotation of spot or domain types is essential for downstream spatial omics analyses, but this remains challenging. Therefore, this study aimed to develop a manually curated spatial omics database (SpatialRef, https://bio.liclab.net/spatialref/), to provide comprehensive and high-quality spatial omics data with known spot labels across multiple species. The current version of SpatialRef aggregates >9 million manually annotated spots across 17 Human, Mouse and Drosophila tissue types through extensive review and strict quality control, covering multiple spatial sequencing technologies and >400 spot/domain types from original studies. Furthermore, SpatialRef supports various spatial omics analyses about known spot types, including differentially expressed genes, spatially variable genes, Gene Ontology (GO)/KEGG annotation, spatial communication and spatial trajectories. With a user-friendly interface, SpatialRef facilitates querying, browsing and visualizing, thereby aiding in elucidating the functional relevance of spatial domains within the tissue and uncovering potential biological effects., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

This study investigates the role of S100A9 in sepsis-associated AKI (SA-AKI) through the lens of pyroptosis, a controlled form of cell death mediated by the gasdermin protein family. Using C57BL/6 mice and S100A9 knockout mice subjected to cecal ligation and puncture (CLP), RNA sequencing and bioinformatics analyses revealed differentially expressed genes (DEGs) related to inflammation and immune responses, with notable upregulation of S100A9. Functional enrichment analyses (GO and KEGG) indicated these DEGs are involved in interferon-beta response, immune processes, and cell adhesion. Protein-protein interaction (PPI) network analyses further emphasized S100A9's pivotal role in SA-AKI.Clinical validation measured S100A9 levels in serum and urine samples from SA-AKI patients and healthy volunteers, finding elevated S100A9 levels in the former. In vivo experiments showed that S100A9 knockout mice exhibited reduced kidney injury and inflammation, indicated by lower serum creatinine, urea nitrogen, and inflammatory markers (IL-1β and IL-18). Histopathological analyses and immunohistochemistry confirmed less renal damage and reduced expression of cleaved IL-1β and GSDMD-N in S100A9-deficient mice. Electron microscopy and Western blotting validated that S100A9 deficiency mitigates caspase-1-dependent pyroptosis.Cellular experiments with HK-2 cells demonstrated that S100A9 knockdown alleviated LPS-induced cell damage and reduced pyroptosis markers. These findings illuminate S100A9's involvement in NLRP3 inflammasome activation and pyroptosis, suggesting potential therapeutic targets for SA-AKI. Targeting S100A9 may offer new therapeutic avenues, improving outcomes for sepsis-related kidney injury patients. Future research should aim to validate these findings in larger clinical settings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Using big data and artificial intelligence to establish a multi-point monitoring, early warning, and disposal system to achieve early warning and intervention of infectious disease outbreaks is an important means of controlling the spread of the epidemic. Taking Xiaoshan district as an example, this study analyzes the monitoring contents, warning methods, and application effectiveness of the infectious disease monitoring, early warning and disposal system. Based on Xiaoshan's health big data resources, the system starts with syndrome, disease diagnosis and etiology. Through advanced technologies such as artificial intelligence and block chain, it realizes early identification of infectious disease outbreaks, data fusion, multi-cross collaboration, and closed-loop management. It has improved the sensitivity of clustered outbreaks monitoring and the effectiveness of epidemic disposal and provided a reference for grassroots disease prevention and control departments to establish an infectious disease monitoring and early warning system.

Magnolia bark is a traditional Chinese medicine used for hypoglycaemia. With the widespread use of Magnolia bark, its resources are facing a serious shortage. To address this issue, a strategy based on high-coverage mass spectrometry (HCMS) and multidimensional chemical-biological analysis (MCBA) was proposed for the comprehensive exploration of Magnolia officinalis which is the main source of Magnolia bark. The strategy is divided into three main steps. In the first step, the stem bark, stem xylem, root bark, root xylem, leaf and rootlet of Magnolia officinalis were comprehensively analyzed using high-coverage mass spectrometry. In the second step, multivariate statistical analysis was used to explore the heterogeneity of the six parts and detect differential chemical components. In the third step, a combination of experimental screening and molecular docking was used to explore α-glucosidase inhibitors from Magnolia officinalis. Multidimensional chemical-biological analysis (MCBA) of Magnolia officinalis was achieved by combining the last two steps. Finally, a total of 103 compounds were identified from the whole plant of Magnolia officinalis. Differential components of stem bark, stem xylem, leaf, root bark, root xylem and rootlet were systematically revealed. A pair of positional isomers, namely magnolol and honokiol, were found to be α-glucosidase inhibitors. The activity of their combination is superior to that of each single compound, indicating that magnolol and honokiol are in a synergistic relationship. This strategy contributes to comprehensive exploitation of functional plants and effective alleviation of resource shortage. This study also provides a research paradigm for other similar traditional Chinese medicinal plants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: To investigate the protective effects of anisodamine (654-1/654-2) against acute kidney injury (AKI) in LPS-induced septic shock rats and explore its molecular mechanisms., Methods: 56 rats were randomly divided into 8 groups: control, LPS, LPS + 654-1, and LPS + 654-2 (1.25, 2.5 and 5 mg/kg). The model was evaluated by monitoring MAP, HR, and plasma LD levels. ELISA and biochemical assay kits were used to measure the levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and kidney injury markers (BUN and CRE). Additionally, RNA-seq and bioinformatic analysis were performed to explore the mechanism of action of 654-1/654-2, and verification was conducted by western blotting and RT-PCR., Results: 654-1/654-2 significantly restored the levels of MAP, HR, and plasma LD in septic shock rats. Furthermore, 654-1/654-2 (5 mg/kg) effectively ameliorated LPS-induced kidney structural damage and exhibited a dose-dependent reduction in levels of inflammatory cytokines and kidney injury markers. In addition, RNA-seq, WB, and RT-PCR analyses revealed that 654-1/654-2 exerted its effects by inhibiting the expressions of the NF-κB and MAPK pathways and activating the Pi3K/Akt/Bcl-2 signaling pathway, thereby mitigating AKI., Discussion: This study suggested that 654-1/654-2 could alleviate AKI in septic shock rats by improving inflammation invasion and cell apoptosis. Notably, 654-1/654-2 collectively suppressed inflammation response through the p38/JNK/AP-1/NF-κB pathway. Additionally, 654-1 promotes survival signaling via the Pi3K/Akt/Bcl-2 pathway, whereas 654-2 reduces apoptosis through the P53/Bax pathway. These findings provided a theoretical basis for the clinical application of 654-1/654-2 in treating organ damage caused by septic shock., Competing Interests: Author FW was employed by Chengdu No. 1 Pharmaceutical Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Tang, Zhang, Wan, Xu, Zhang, Zhao, Ao and Peng.)

For the 2D metal-free carbon catalysts, the atomic coplanar architecture enables a large number of p z orbitals to overlap laterally, thus forming π-electron delocalization, and the delocalization degree of the central atom dominates the catalytic activity. Herein, designing sulfur-doped defect-rich graphitic carbon nitride (S-Nv-C 3 N 4 ) materials as a model, we propose a strategy to promote localized electron polarization by enhancing the ferromagnetism of ultra-thin 2D carbon nitride nanosheets. The introduction of sulfur (S) further promotes localized ferromagnetic coupling, thereby inducing long-range ferromagnetic ordering and accelerating the electron interface transport. Meanwhile, the hybridization of sulfur atoms breaks the symmetry and integrity of the unit structure, promotes electron enrichment and stimulating electron delocalization at the active site. This optimization enhances the *OOH desorption, providing a favorable kinetic pathway for the production of hydrogen peroxide (H 2 O 2 ). Consequently, S-Nv-C 3 N 4 exhibits high selectivity (>95 %) and achieves a superb H 2 O 2 production rate, approaching 4374.8 ppm during continuous electrolysis over 300 hour. According to theoretical calculation and in situ spectroscopy, the ortho-S configuration can provide ferromagnetic perturbation in carbon active centers, leading to the electron delocalization, which optimizes the OOH* adsorption during the catalytic process., (© 2024 Wiley-VCH GmbH.)

Eco-compensation is an important component of ecological civilization construction. Therefore, it is of great significance to elucidate the spatial and temporal pattern of eco-compensation performance and its internal coupling and coordinated features to promote ecological civilization construction. We proposed that eco-compensation performance consists of benefit and efficiency, and used the projection pursuit and super-efficiency SBM-DEA models to measure the eco-compensation benefit and efficiency of 101 cities in the Yangtze River Economic Belt from 2010 to 2021 and to analyze their spatial and temporal patterns. Finally, we used the coupling coordination degree model to reveal the coupling and coordinated features of eco-compensation performance. The results showed that the temporal trends of eco-compensation benefit and efficiency were "W" and "U" shaped. The eco-compensation benefit in eastern or mega-cities was the highest, whereas the eco-compensation efficiency in western or small/medium-sized cities was the highest. Coupling coordination degree of eco-compensation performance was in the coordinated development stage from 2010 to 2012, with a concentration of agglomeration effects in the central region. It was in the transition/adjustment stage from 2013 to 2020, with low-value areas concentrated and scattered high-value areas, and smaller regional differences. It was in the coordinated development stage in 2021, with a clear agglomeration effect in the eastern region. Cities in the Yangtze River Economic Belt should incorporate the eco-compensation performance coupling coordination mechanism into their optimized eco-compensation policy plans based on the stage of coordinated development, to achieve their environmental improvement goals.

Bioelectrochemical systems (BESs) have shown great potential in enhancing sulfamethoxazole (SMX) removal. However, electroactive biofilms (EBs) constructed with single potentials struggle due to limited biocatalytic activity, hindering deep SMX degradation. Here, we constructed a double-working potential BES (BES-D) to investigate its ability to eliminate SMX and reduce the levels of corresponding antibiotic resistance genes (ARGs). The preferable electrochemical activity of EB in BES-D was confirmed by electrochemical characterization, EPS analysis, physical structure, viability of the biofilm, and cytochrome content. BES-D exhibited a notably greater SMX removal efficiency (94.2 %) than did the single-working potential BES (BES-S) and the open-circuit group (OC). Degradation pathway analysis revealed that the cooperative EB could accelerate the in-depth removal of SMX. Moreover, EB interaction in BES-D decreased the relative abundance of ARGs in biofilms compared to that in BES-S, although the absolute number of ARG copies increased in BES-D effluents. Compared to those in BES-S and OC, more complex cross-niche microbial associations in the EB of BES-D were observed by network analysis of the bacterial community and ARG hosts, enhancing the degradation efficiency of SMX. In conclusion, BES-D has significant potential for SMX removal and the enhancement of EB activity. Nonetheless, the risk of ARG dissemination in effluent remains a concern., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Joint contracture is a common clinical problem affecting joint function. Capsule fibrosis plays a pivotal role in the progression of Joint contracture. Previous studies have reported that autophagy plays a regulatory role in visceral fibrosis., Objective: This study aimed to investigate whether extracorporeal shock wave therapy (ESWT) and melatonin alleviate joint capsule fibrosis in rats with extended knee joint contracture by regulating autophagy., Methods: A rat knee joint extension contracture model was made. Then, the rats were treated with ESWT, melatonin, ESWT + melatonin, or ESWT + melatonin + mTOR agonist for 4 weeks. The range of motion (ROM) of the knee joints was measured. Joint capsules were collected and observed for pathological changes by H&E and Masson staining. LC3B protein expression was evaluated by immunofluorescence staining. TGF-β1, MMP-1, Col-Ⅰ, Col-Ⅲ, LC3, ATG7, Beclin1, p-AMPK, p-mTOR and p-ULK1 protein expressions were measured by Western blot assay., Results: The intervention groups had significantly improved ROM of knee joint (P < 0.05), significantly improved pathological changes on HE and Masson staining, significantly decreased protein expressions of TGF-β1, MMP-1, Col-Ⅰ, Col-Ⅲ and pmTOR (P < 0.05), and significantly increased protein expressions of LC3B, LC3II/LC3I ratio, ATG7, Beclin1, p-AMPK, and p-ULK1 (P < 0.05). Among these groups, the effects demonstrated by the ESWT + melatonin group were the best. With the mTOR agonist supplement, the therapeutic effects of extracorporeal shock waves and melatonin were significantly reduced., Conclusion: ESWT plus melatonin alleviated knee joint capsule fibrosis in rats by regulating autophagy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Nonprecious metal catalysts, particularly M -N-C catalysts, are widely recognized as promising contenders for the oxygen reduction reaction (ORR). However, a notable performance gap persists between M -N-C catalysts and Pt-based catalysts under acidic conditions. In this study, hybrid catalysts comprising single Co atoms and ultralow concentrations of Pt 3 Co intermetallic nanoparticles (NPs) are introduced to enhance ORR performance. Under acidic conditions, these hybrid catalysts demonstrate ORR efficiency with a half-wave potential of 0.895 V, negligible decay even after 80 000 cycles, and a high maximum power density of 1.34 W cm -2 in fuel cells. This performance surpasses those of Co-N-C and Pt/Co-N-C catalysts. Both experimental findings and theoretical computations suggest that the heightened ORR activity stems from an increase in the spin density of Co sites induced by noble metal NPs, facilitating the activation of O-O bonds via side-on overlapping and enabling a transition in the reaction pathway from associative to dissociative processes. This research offers a promising avenue for the systematic design of M -N-C cathodes with an enhanced performance for acidic fuel cells.

Sepsis and septic shock are critical medical conditions characterized by a systemic inflammatory response to infection, significantly contributing to global mortality rates. The progression to multiple organ dysfunction syndrome (MODS) represents the most severe complication of sepsis and markedly increases clinical mortality. Central to the pathophysiology of sepsis, endothelial cells play a crucial role in regulating microcirculation and maintaining barrier integrity across various organs and tissues. Recent studies have underscored the pivotal role of endothelial function in the development of sepsis-induced MODS. This review aims to provide a comprehensive overview of the pathophysiology of sepsis-induced MODS, with a specific focus on endothelial dysfunction. It also compiles compelling evidence regarding potential small molecules that could attenuate sepsis and subsequent multi-organ damage by modulating endothelial function. Thus, this review serves as an essential resource for clinical practitioners involved in the diagnosing, managing, and providing intensive care for sepsis and associated multi-organ injuries, emphasizing the importance of targeting endothelial cells to enhance outcomes of the patients., Competing Interests: Declaration of Competing Interest These authors declared that there are no known conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients., Methods: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology., Results: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS., Conclusions: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.

The trail making test (TMT) is a commonly used tool for evaluating executive functions, and the activation of cerebral oxygenation in the prefrontal cortex (PFC) during the test can reflect the participation of executive function. This study aimed to compare the differences in cerebral oxygenation in the PFC between the computer- and paper-based versions of the TMT and provide a theoretical basis for the optimization and clinical application of the computer-based version. A total of 32 healthy adult participants completed the computer- and paper-based TMT Types A and B. Cerebral oxygenation changes in the PFC were monitored during the experiment using near-infrared spectroscopy. Moreover, average changes in oxyhemoglobin (Δoxy-Hb) levels at the baseline and during activation periods in different types of testing were compared and analyzed. The number of correct connections in the computer-based version Type B was less than that in the paper-based version Type B (p < .001). The task time of the computer-based version was longer than that of the paper-based version (p < .001). The B/A ratio of the number of correct connections in the computer-based version was lower than that in the paper-based version (p < .001). The Δoxy-Hb in the PFC of the paper-based version was higher than that of the computer-based version (p < .001). Significant differences in oxygenation in the PFC were observed between the paper- and computer-based versions of TMT. After further improvement and correction in the subsequent development of the computer-based TMT, and taking into account the psychological feelings and preferences of the participants when performing different versions of the TMTs, the computer-based TMT is expected to play a good auxiliary role in clinical evaluation., (© 2024. The Author(s).)

Aims: The association of haemoglobin A1c (HbA1c) variability with the risk of adverse outcomes in patients with atrial fibrillation (AF) prescribed anticoagulants remains unclear. This study aimed to evaluate the association of HbA1c variability with the risk of ischaemic stroke (IS)/systemic embolism (SE) and all-cause mortality among patients with non-valvular AF prescribed anticoagulants., Methods and Results: Patients newly diagnosed with AF from 2013 to 2018 were included. Variability in HbA1c, indexed by the coefficient of variation (CV), was determined for those with at least three HbA1c measurements available from the time of study enrolment to the end of follow-up. To evaluate whether prevalent diabetes would modify the relationship between HbA1c variability and outcomes, participants were divided into diabetes and non-diabetes groups. The study included 8790 patients (mean age 72.7% and 48.5% female). Over a median follow-up of 5.5 years (interquartile range 5.2, 5.8), the incident rate was 3.74 per 100 person-years for IS/SE and 4.89 for all-cause mortality in the diabetes group. The corresponding incident rates in the non-diabetes group were 2.41 and 2.42 per 100 person-years. In the diabetes group, after adjusting for covariates including mean HbA1c, greater HbA1c variability was significantly associated with increased risk of IS/SE [hazard ratio (HR) = 1.65, 95% confidence interval (CI): 1.27-2.13) and all-cause mortality (HR = 1.24, 95% CI: 1.05-1.47) compared with the lowest CV tertile. A similar pattern was evident in the non-diabetes group (IS/SE: HR = 1.58, 95% CI: 1.23-2.02; all-cause mortality: HR = 1.35, 95% CI: 1.10-1.64)., Conclusion: Greater HbA1c variability was independently associated with increased risk of IS/SE and all-cause mortality among patients with AF, regardless of diabetic status., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Recently, the role of inorganic pyrophosphatase 2 (PPA2) has been remaining merely superficial in many tumors. Hence, the aim was to analyze the potential functions of PPA2 in pan-cancer, focusing on its role in breast cancer., Methods: A systematic pan-cancer analysis conducted primarily utilizing various open databases such as TCGA and GTEx. We explored the clinical value of PPA2 as well as various biological functions, including expression levels and subcellular localization, multi-dimensional immune-correlation analysis, co-expression networks, and gene heterogeneity. In addition, we not only verified the function of PPA2 through cell experiments but also analyzed PPA2 at the single-cell level and its drug sensitivity., Results: PPA2 is abnormally expressed in various tumors, and it is mainly distributed in mitochondria. Furthermore, the indicators (OS, DSS, DFI, and PFI) of analysis hint that PPA2 exhibits significant prognostic value. At the same time, the genomic heterogeneity (including TMB, MSI, MATH, and NEO) of PPA2 in pan-cancer was analyzed. Across multiple tumors, the results showed a close correlation between PPA2 expression levels and different immune signatures (such as immune cell infiltration). All of these indicate that PPA2 could potentially be applied in the guidance of immunotherapy. We also have demonstrated that PPA2 promoted the process of breast cancer. Finally, some potential therapeutic agents (such as Fulvestrant) targeting the abnormal expression of PPA2 are revealed., Conclusion: In conclusion, the results demonstrated the great value of PPA2 in pan-cancer research, as well as its potential as a therapeutic target for breast tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Yang, Li, Xu, Wang, Yi, Zhou and Liu.)

Zanthoxyli radix is a popular tea among the elderly, and it is believed to have a positive effect on Alzheimer's disease. In this study, a highly effective three-step strategy was proposed for comprehensive analysis of the active components and biological functions of Zanthoxylum nitidum (ZN), including high-resolution LC-Q-TOF mass spectrometry (HRMS), multivariate statistical analysis for heterogeneity (MSAH), and experimental and virtual screening for bioactivity analysis (EVBA). A total of 117 compounds were identified from the root, stem, and leaf of ZN through HRMS. Bioactivity assays showed that the order of acetylcholinesterase (AChE) inhibitory activity from strong to weak was root > stem > leaf. Nitidine, chelerythrine, and sanguinarine were found to be the main differential components of root, stem, and leaf by OPLS-DA. The IC 50 values of the three compounds are 0.81 ± 0.02, 0.14 ± 0.01, and 0.48 ± 0.01 μM respectively, indicating that they are potent and high-quality AChE inhibitors. Molecular docking showed that pi-pi T-shaped interactions and pi-lone pairs played important roles in AChE inhibition. This study not only explains the biological function of Zanthoxyli radix in alleviating Alzheimer's disease to some extent, but also lays the foundation for the development of stem and leaf of ZN.

Background: The common cause of sodium nitrite poisoning has shifted from previous accidental intoxication by exposure or ingestion of contaminated water and food to recent alarming intentional intoxication as an employed method of suicide/exit. The subsequent formation of methemoglobin (MetHb) restricts oxygen transport and utilization in the body, resulting in functional hypoxia at the tissue level. In clinical practice, a mismatch of cyanotic appearance and oxygen partial pressure usually contributes to the identification of methemoglobinemia. Prompt recognition of characteristic mismatch and accurate diagnosis of sodium nitrite poisoning are prerequisites for the implementation of standardized systemic interventions., Case Summary: A pregnant woman was admitted to the Department of Critical Care Medicine at the First Affiliated Hospital of Harbin Medical University due to consciousness disorders and drowsiness 2 h before admission. Subsequently, she developed vomiting and cyanotic skin. The woman underwent orotracheal intubation, invasive mechanical ventilation (IMV), and correction of internal environment disturbance in the ICU. Her premature infant was born with a higher-than-normal MetHb level of 3.3%, and received detoxification with methylene blue and vitamin C, supplemental vitamin K1, an infusion of fresh frozen plasma, as well as respiratory support via orotracheal intubation and IMV. On day 3 after admission, the puerpera regained consciousness, evacuated the IMV, and resumed enteral nutrition. She was then transferred to the maternity ward 24 h later. On day 7 after admission, the woman recovered and was discharged without any sequelae., Conclusion: MetHb can cross through the placental barrier. Level of MetHb both reflects severity of the sodium nitrite poisoning and serves as feedback on therapeutic effectiveness., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: This study investigated the long-term clinical and angiographic outcomes of encephaloduroarteriosynangiosis treatment for symptomatic intracranial atherosclerotic arterial steno-occlusive disease to further evaluate the potential therapeutic role of encephaloduroarteriosynangiosis in this population., Methods and Results: A total of 152 adult patients with symptomatic intracranial atherosclerotic arterial steno-occlusive disease who were treated with encephaloduroarteriosynangiosis and intensive medical management across 3 tertiary centers in China between January 2011 and September 2019 were retrospectively included. The primary outcomes were defined as postoperative cerebrovascular events, including ischemic and hemorrhagic stroke. The postoperative neovascularization was analyzed qualitatively and quantitatively by using angiography. Clinical, radiological, and long-term follow-up data were analyzed using Cox regression, logistic regression, and linear regression analyses. Primary outcome rates were 3.2% (5/152) within 30 days, 6.6% (10/152) within 2 years, 9.2% (14/152) within 5 years, and 11.1% (17/152) during a median 9.13 years follow-up. Initial infarction symptoms were positively associated with recurrent ischemic stroke. Additionally, posterior circulation involvement and coexisting cardiac disease indicated poorer neurological status, whereas encephaloduroarteriosynangiosis neovascularization efficacy was negatively associated with older age and vascular risk factors but positively associated with posterior circulation involvement., Conclusions: Encephaloduroarteriosynangiosis plus intensive medical management appears efficacious and safe for symptomatic intracranial atherosclerotic arterial steno-occlusive disease, with low perioperative risk and favorable long-term results. Further prospective trials are needed to verify its efficacy and determine the optimal patient selection criteria.

Objective: To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes. Methods: A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results: Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ 2 =15.00, P <0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement ( RR =4.58,95% CI 1.96-10.70, P <0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group ( RR =0.90, 95% CI 0.57-1.41, P =0.517). Multivariate analysis further confirmed SNHL ( OR =11.58, 95% CI 2.10-63.93, P =0.005) and preterm birth ( OR =4.98, 95% CI 1.06-23.41, P =0.042) as independent risk factors for poor hearing outcomes. Conclusions: SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.

Background: Targeting DNA damage repair factors, such as DNA-dependent protein kinase catalytic subunit (DNA-PKcs), may offer an opportunity for effective treatment of multiple myeloma (MM). In combination with DNA damage-inducing agents, this strategy has been shown to improve chemotherapies partially via activation of cGAS-STING pathway by an elevated level of cytosolic DNA. However, as cGAS is primarily sequestered by chromatin in the nucleus, it remains unclear how cGAS is released from chromatin and translocated into the cytoplasm upon DNA damage, leading to cGAS-STING activation., Methods: We examined the role of DNA-PKcs inhibition on cGAS-STING-mediated MM chemosensitivity by performing mass spectrometry and mechanism study., Results: Here, we found DNA-PKcs inhibition potentiated DNA damage-inducing agent doxorubicin-induced anti-MM effect by activating cGAS-STING signaling. The cGAS-STING activation in MM cells caused cell death partly via IRF3-NOXA-BAK axis and induced M1 polarization of macrophages. Moreover, this activation was not caused by defective classical non-homologous end joining (c-NHEJ). Instead, upon DNA damage induced by doxorubicin, inhibition of DNA-PKcs promoted cGAS release from cytoplasmic chromatin fragments and increased the amount of cytosolic cGAS and DNA, activating cGAS-STING., Conclusions: Inhibition of DNA-PKcs could improve the efficacy of doxorubicin in treatment of MM by de-sequestrating cGAS in damaged chromatin., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

8p11 myeloproliferative syndrome (EMS) is a rare and aggressive hematological malignancy, characterized by myeloproliferative neoplasms, and associated with eosinophilia and T- or B-cell lineage lymphoblastic lymphoma. The pathogenesis is defined by the presence of chromosomal translocations associated with the fibroblast growth factor-1 ( FGFR1 ) gene, located in the 8p11-12.1 chromosomal locus. At present, only ~100 cases have been reported globally. At least 15 partner genes have been identified, including the most common, the zinc finger MYM-type containing 2 ( ZNF198)-FGFR1 fusion gene formed by t(8;13)(p11;q12). Different fusion genes determine the clinical manifestations and prognosis of the disease. Patients with EMS with t(8;13)(p11;q12) commonly present with lymphadenopathy and T-lymphoblastic lymphoma, which usually converts to acute myeloid leukemia (AML) with the progression of the disease. The present study describes the case of an elderly female patient with EMS with t(8;13)(p11;q12), presenting with myeloid/lymphoid syndrome (myeloproliferative neoplasms and T lymphoblastic lymphoma). The patient received the CHOPE regimen combined with tyrosine kinase inhibitor (dasatin) treatment and obtained short-term complete remission. However, 6 months later, the disease progressed from EMS to AML and the patient died due to ineffective induction therapy. The present study also reviews the relevant literature about this unusual entity to enhance the understanding of EMS., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Guo et al.)

Cardiac myosin-binding protein C (cMyBP-C) is a novel cardiac marker of acute myocardial infarction (AMI) and acute cardiac injuries (ACI). Construction of point-of-care testing techniques capable of sensing cMyBP-C with high sensitivity and precision is urgently needed. Herein, we synthesized an Au@NGQDs@Au/Ag multi-shell nanoUrchins (MSNUs), and then applied it in a colorimetric/SERS dual-mode immunoassay for detection of cMyBP-C. The MSNUs displayed superior stability, colorimetric brightness, and SERS enhancement ability with an enhanced factor of 5.4 × 10 9 , which were beneficial to improve the detection capability of test strips. The developed MSNU-based test strips can achieve an ultrasensitive immunochromatographic assay of cMyBP-C in both colorimetric and SERS modes with the limits of detection as low as 19.3 and 0.77 pg/mL, respectively. Strikingly, this strip was successfully applied to analyze actual plasma samples with significantly better sensitivity, negative predictive value, and accuracy than commercially available gold test strips. Notably, this method possessed a wide range of application scenarios via combining with a color recognizer application named Color Grab on the smartphone, which can meet various needs of different users. Overall, our MSNU-based test strip as a mobile health monitoring tool shows excellent sensitivity, reproducibility, and rapid detection of the cMyBP-C, which holds great potential for the early clinic diagnosis of AMI and ACI.

Osteoporosis (OP) constitutes a notable public health concern that significantly impacts the skeletal health of the global aging population. Its prevalence is steadily escalating, yet the intricacies of its diagnosis and treatment remain challenging. Recent investigations have illuminated a profound interlink between gut microbiota (GM) and bone metabolism, thereby opening new avenues for probing the causal relationship between GM and OP. Employing Mendelian randomization (MR) as the investigative tool, this study delves into the causal rapport between 211 varieties of GM and OP. The data are culled from genome-wide association studies (GWAS) conducted by the MiBioGen consortium, in tandem with OP genetic data gleaned from the UK Biobank, BioBank Japan Project, and the FinnGen database. A comprehensive repertoire of statistical methodologies, encompassing inverse-variance weighting, weighted median, Simple mode, Weighted mode, and MR-Egger regression techniques, was adroitly harnessed for meticulous analysis. The discernment emerged that the genus Coprococcus3 is inversely associated with OP, potentially serving as a deterrent against its onset. Additionally, 21 other gut microbial species exhibited a positive correlation with OP, potentially accentuating its proclivity and progression. Subsequent to rigorous scrutiny via heterogeneity and sensitivity analyses, these findings corroborate the causal nexus between GM and OP. Facilitated by MR, this study successfully elucidates the causal underpinning binding GM and OP, thereby endowing invaluable insights for deeper exploration into the pivotal role of GM in the pathogenesis of OP., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Having a gynecological tumor or undergoing treatment can be a traumatic experience for women, as it affects their self-image and sexual relationships and can lead to psychological reactions. Psychological adjustment following cancer occurrence remains a key issue among the survivors., Aim: To examine the current status of quality of life (QoL), anxiety, and depression in patients with gynecological cancer and to analyze the factors associated with it., Methods: Data for 160 patients with gynecological malignancies treated at Shanxi Bethune Hospital from June 2020 to June 2023 were collected and analyzed retrospectively. Patients' QoL was assessed using the European Organization for Research on Treatment of Cancer Quality of Life Questionnaire Core 30 and the Functional Assessment of Cancer Therapy-General Questionnaire. Their emotional status was evaluated using the Self-Rating Anxiety/Depression Scale. The associated factors of anxiety and depression were analyzed., Results: The overall QoL score of the patients 6 months after surgery was 76.39 ± 3.63 points. This included low levels of social and emotional function and severe fatigue and pain. The scores for physiological, functional, emotional, social, and family well-being exhibited an upward trend following surgery compared with those before surgery. One month after surgery, some patients experienced anxiety and depression, with an incidence of 18.75% and 18.13%, respectively. Logistic analysis revealed that good sleep was a protective factor against anxiety and depression in patients with gynecological tumors, whereas physical pain was a risk factor., Conclusion: Patients with gynecological malignancies often experience anxiety and depression. By analyzing the factors that affect patients' QoL, effective nursing measures can be administered., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: The purpose of this study is to summarize the design and methodology of a large-scale trial in northern China, the Beijing Angle Closure Progression Study (BAPS). This trial is designed to explore the 5-year incidence of primary angle-closure suspect (PACS) progressing to primary angle-closure (PAC) or primary angle-closure glaucoma (PACG) and to determine the possible risk factors of disease progression., Methods/design: The BAPS is a clinic-based, multicenter, noninterventional trial conducted on a sample of urban Chinese adults. Consecutive eligible patients who meet PACS diagnostic criteria will be recruited from eight participating centers, with the trial commencing on August 4, 2022. The target sample size is set at 825 subjects, with follow up planned for a minimum period of 5 years. Baseline examination will include presenting visual acuity, best corrected visual acuity, intraocular pressure (IOP), undilated slit-lamp biomicroscopy, stereoscopic evaluation of the optic disc, visual field test, optical coherence tomography evaluation of retinal nerve fiber layer, ultrasound biomicroscopy and IOLMaster. Questionnaires will also be used to collect detailed personal history. Patients are scheduled to visit the glaucoma clinic every 12 months and may visit the emergency room in case of acute attack of angle closure. Study endpoints include acute PAC episodes, elevated IOP, peripheral anterior synechiae, glaucomatous visual field defect, or glaucomatous abnormality of optic nerve., Discussion: The BAPS will provide data on the 5-year incidence of PACS progressing to PAC or PACG and determine the risk factors for disease progression. This study will also help redefine high-risk patients with PACS., Competing Interests: X-zS was employed by the company Ping An Healthcare Technology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liang, Yang, Lv, Ma, Sun, Liang, Yue, Qin, Zhao, Zhang, Yi, Sun and Wu.)

Disentangling the limitations of O-O bond activation and OH* site-blocking effects on Pt sites is key to improving the intrinsic activity and stability of low-Pt catalysts for the oxygen reduction reaction (ORR). Herein, we integrate of PtFe alloy nanocrystals on a single-atom Fe-N-C substrate (PtFe@Fe SAs -N-C) and further construct a ferromagnetic platform to investigate the regulation behavior of the spin occupancy state of the Pt d-orbital in the ORR. PtFe@Fe SAs -N-C delivers a mass activity of 0.75 A mg Pt -1 at 0.9 V and a peak power density of 1240 mW cm -2 in the fuel-cell, outperforming the commercial Pt/C catalyst, and a mass activity retention of 97%, with no noticeable current drop at 0.6 V for more than 220 h, is attained. Operando spectroelectrochemistry decodes the orbital interaction mechanism between the active center and reaction intermediates. The Pt dz 2 orbital occupation state is regulated to t 2g 6 e g 3 by spin-charge injection, suppressing the OH* site-blocking effect and effectively inhibiting H 2 O 2 production. This work provides valuable insights into designing high-performance and low-Pt catalysts via spintronics-level engineering., (© 2024. The Author(s).)

Triple-negative breast cancer (TNBC) is incurable and prone to widespread metastasis. Therefore, identification of key targets for TNBC progression is urgently needed. Our previous study revealed that isotoosendanin (ITSN) reduced TNBC metastasis by targeting TGFβR1. ITSN is currently used as an effective chemical probe to further discover the key molecules involved in TNBC metastasis downstream of TGFβR1. The results showed that GOT2 was the gene downstream of Smad2/3 and that ITSN decreased GOT2 expression by abrogating the activation of the TGF-β-Smad2/3 signaling pathway through directly binding to TGFβR1. GOT2 was highly expressed in TNBC, and its knockdown decreased TNBC metastasis. However, GOT2 overexpression reversed the inhibitory effect of ITSN on TNBC metastasis both in vitro and in vivo. GOT2 interacted with MYH9 and hindered its binding to the E3 ubiquitin ligase STUB1, thereby reducing MYH9 ubiquitination and degradation. Moreover, GOT2 also enhanced the translocation of MYH9 to mitochondria and thus induced DRP1 phosphorylation, thereby promoting mitochondrial fission and lamellipodia formation in TNBC cells. ITSN-mediated inhibition of mitochondrial fission and lamellipodia formation was associated with reduced GOT2 expression. In conclusion, ITSN prevented MYH9-regulated mitochondrial fission and lamellipodia formation in TNBC cells by enhancing MYH9 protein degradation through a reduction in GOT2 expression, thus contributing to its inhibition of TNBC metastasis., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: To explore the incidence of sudden deafness accompanied with tinnitus, the selection of examination protocols and treatment, and to provide reference for the establishment of new guidelines for sudden deafness. Methods: CiteSpace software was used for analysis and data mining to analyze and summarize the computer-retrieved articles on diagnostic examination and treatment of sudden deafness accompanied with tinnitus collected from CNIC, Wanfang and Web of Science databases from 2011 to 2021. Results: A total of 207 randomized controlled studies were retrieved in this study, including 121 in Chinese and 86 in English. Finally, 74 Chinese literatures and 16 English literatures were included. Among the 74 valid Chinese literatures, 64 (86.5%) were accompanied with tinnitus, 58 (78.4%) with dizziness/vertigo, 25 (33.8%) with aural fullness, 10 (13.5%) with headache, 4 (5.4%) with insomnia, 4 (5.4%) with a mixture of dizziness and tinnitus, and 2 (2.7%) with vomiting. Among the 16 English literatures, 15 (93.8%) were accompanied with tinnitus, 12 (75.0%) with vertigo, 1 (6.3%) with aural fullness, and 1 (6.3%) with a mixture of various symptoms. Among the 64 Chinese articles mentioning tinnitus, only 9 mentioned tinnitus matching tests, and 1 mentioned that the treatment for tinnitus accompanying symptoms was sound therapy and psychological counseling. The incidence rates of tinnitus accompanying four different types of sudden deafness, from low to high, are as follows: low-to-mid frequency, 82.4%; mid-to-high frequency, 90.7%; complete deafness, 92.4%; and flat type, 92.8%. Conclusion: Tinnitus is the most common accompanying symptom of sudden deafness, and tinnitus matching test is an effective evaluation method. When establishing a scientific, comprehensive, and systematic diagnosis and treatment system or guidelines for sudden deafness, attention should be paid to the diagnosis and treatment of tinnitus symptoms and their adverse psychological reactions, in order to reduce the incidence of tinnitus patients in the later stage of recovery from sudden deafness.

The orexin system is closely related to the pathogenesis of Alzheimer's disease (AD). Orexin-A aggravates cognitive dysfunction and increases amyloid β (Aβ) deposition in AD model mice, but studies of different dual orexin receptor (OXR) antagonists in AD have shown inconsistent results. Our previous study revealed that OX1R blockade aggravates cognitive deficits and pathological progression in 3xTg-AD mice, but the effects of OX2R and its potential mechanism in AD have not been reported. In the present study, OX2R was blocked by oral administration of the selective OX2R antagonist MK-1064, and the effects of OX2R blockade on cognitive dysfunction and neuropsychiatric symptoms in 3xTg-AD mice were evaluated via behavioral tests. Then, immunohistochemistry, western blotting, and ELISA were used to detect Aβ deposition, tau phosphorylation, and neuroinflammation, and electrophysiological and wheel-running activity recording were recorded to observe hippocampal synaptic plasticity and circadian rhythm. The results showed that OX2R blockade ameliorated cognitive dysfunction, improved LTP depression, increased the expression of PSD-95, alleviated anxiety- and depression-like behaviors and circadian rhythm disturbances in 3xTg-AD mice, and reduced Aβ pathology, tau phosphorylation, and neuroinflammation in the brains of 3xTg-AD mice. These results indicated that chronic OX2R blockade exerts neuroprotective effects in 3xTg-AD mice by reducing AD pathology at least partly through improving circadian rhythm disturbance and the sleep-wake cycle and that OX2R might be a potential target for the prevention and treatment of AD; however, the potential mechanism by which OX2R exerts neuroprotective effects on AD needs to be further investigated., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)