bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipidome is a valuable tool for the severity prediction of coronavirus disease 2019
Authors: Zhang Shan-Shan , Zhao Zhiling , Zhang Wan-Xue , Wu Rui , Li Fei , Yang Han , Zhang Qiang , Wei Ting-Ting , Xi Jingjing , Zhou Yiguo , Wang Tiehua , Du Juan , Huang Ninghua , Ge Qinggang , Lu Qing-Bin
Published: May 2024

Objective

To describe the lipid metabolic profile of different patients with coronavirus disease 2019 (COVID-19) and contribute new evidence on the progression and severity prediction of COVID-19.

Methods

This case–control study was conducted in Peking University Third Hospital, China. The laboratory-confirmed COVID-19 patients aged ≥18 years old and diagnosed as pneumonia from December 2022 to January 2023 were included. Serum lipids were detected. The discrimination ability was calculated with the area under the curve (AUC). A random forest (RF) model was conducted to determine the significance of different lipids.

Results

Totally, 44 COVID-19 patients were enrolled with 16 mild and 28 severe patients. The top 5 super classes were triacylglycerols (TAG, 55.9%), phosphatidylethanolamines (PE, 10.9%), phosphatidylcholines (PC, 6.8%), diacylglycerols (DAG, 5.9%) and free fatty acids (FFA, 3.6%) among the 778 detected lipids from the serum of COVID-19 patients. Certain lipids, especially lysophosphatidylcholines (LPCs), turned to have significant correlations with certain immune/cytokine indexes. Reduced level of LPC 20:0 was observed in severe patients particularly in acute stage. The AUC of LPC 20:0 reached 0.940 in discriminating mild and severe patients and 0.807 in discriminating acute and recovery stages in the severe patients. The results of RF models also suggested the significance of LPCs in predicting the severity and progression of COVID-19.

Conclusion

Lipids probably have the potential to differentiate and forecast the severity, progression, and clinical outcomes of COVID-19 patients, with implications for immune/inflammatory responses. LPC 20:0 might be a potential target in predicting the progression and outcome and the treatment of COVID-19.
Efficacy and safety of Chinese herbal medicine to prevent and treat COVID-19 household close contacts in Hong Kong: an open-label, randomized controlled trial
Authors: Du Peipei , Lam Wai Ching , Leung Choryin , Li Huijuan , Lyu Zipan , Yuen Chun Sum , Cheung Chun Hoi , Lam Tsz Fung , Bian Zhaoxiang , Zhong Linda
Published: May 2024

Objectives

To evaluate the efficacy and safety of CHM in the prevention of COVID-19 infection and treatment for COVID-19 related symptoms.

Design

Prospective open-label randomized controlled trial.

Setting

Participants’ home in Hong Kong.

Participants

Participants who had household close contact with COVID-19-infected family members.

Interventions

Close contacts were stratified into 4 groups (cohort A, B, C, D) based on symptoms and infection status and were randomized in 4:1 ratio to receive CHM granules (9g/sachet, two times daily) or blank control for 7 days with 2 weeks of follow-up.

Main outcome measures

The primary outcome measure was the rate of positive nucleic acid tests. Secondary outcomes were the proportion of developed COVID-19 related symptoms and adverse events during the whole 3-week study period. Subgroup analysis was used to evaluate demographic factors associated with positive infection rates.

Results

A total of 2163 contacts were enrolled and randomly assigned to the CHM group (1720 contacts) and blank control (443 contacts) group. During the 21 days, the rate of PCR-positive cases in cohort A was markedly lower in the CHM group (3.6%) compared to the control group (7.0%) (P=0.036). Overall, the rate of infection in the CHM group was significantly lower than that in the control group (10.69% vs. 6.03%; RR 0.56, 95% CI 0.39-0.82) after 7-day treatment. No serious adverse events were reported during the medication period.

Conclusion

The preliminary findings indicate that CHM may be effective and safe in preventing COVID-19. Future double-blind, randomized controlled trials and long-term follow-up are needed to fully evaluate the efficacy of CHM in a larger contact population.

Clinical trial registration

ClinicalTrials.gov, identifier NCT05269511
African swine fever virus MGF505–6R attenuates type I interferon production by targeting STING for degradation
Authors: Yao Manman , Cao Hua , Li Wentao , Hu Zihui , Rong Zhenxiang , Yin Mengge , Tian Linxing , Hu Dayue , Li Xiangmin , Qian Ping
Published: May 2024

African swine fever (ASF) is an acute hemorrhagic and devastating infectious disease affecting domestic pigs and wild boars. It is caused by the African swine fever virus (ASFV), which is characterized by genetic diversity and sophisticated immune evasion strategies. To facilitate infection, ASFV encodes multiple proteins to antagonize host innate immune responses, thereby contributing to viral virulence and pathogenicity. The molecular mechanisms employed by ASFV-encoded proteins to modulate host antiviral responses have not been comprehensively elucidated. In this study, it was observed that the ASFV MGF505–6R protein, a member of the multigene family 505 (MGF505), effectively suppressed the activation of the interferon-beta (IFN-β) promoter, leading to reduced mRNA levels of antiviral genes. Additional evidence has revealed that MGF505–6R antagonizes the cGAS-STING signaling pathway by interacting with the stimulator of interferon genes (STING) for degradation in the autophagy-lysosomal pathway. The domain mapping revealed that the N-terminal region (1–260aa) of MGF505–6R is the primary domain responsible for interacting with STING, while the CTT domain of STING is crucial for its interaction with MGF505–6R. Furthermore, MGF505–6R also inhibits the activation of STING by reducing the K63-linked polyubiquitination of STING, leading to the disruption of STING oligomerization and TANK binding kinase 1 (TBK1) recruitment, thereby impairing the phosphorylation and nuclear translocation of interferon regulatory factor 3 (IRF3). Collectively, our study elucidates a novel strategy developed by ASFV MGF505–6R to counteract host innate immune responses. This discovery may offer valuable insights for further exploration of ASFV immune evasion mechanisms and antiviral strategies.
Emerging role of immunogenic cell death in cancer immunotherapy
Authors: Arimoto Kei-ichiro , Miyauchi Sayuri , Liu Mengdan , Zhang Dong-Er
Published: May 2024

Cancer immunotherapy, such as immune checkpoint blockade (ICB), has emerged as a groundbreaking approach for effective cancer treatment. Despite its considerable potential, clinical studies have indicated that the current response rate to cancer immunotherapy is suboptimal, primarily attributed to low immunogenicity in certain types of malignant tumors. Immunogenic cell death (ICD) represents a form of regulated cell death (RCD) capable of enhancing tumor immunogenicity and activating tumor-specific innate and adaptive immune responses in immunocompetent hosts. Therefore, gaining a deeper understanding of ICD and its evolution is crucial for developing more effective cancer therapeutic strategies. This review focuses exclusively on both historical and recent discoveries related to ICD modes and their mechanistic insights, particularly within the context of cancer immunotherapy. Our recent findings are also highlighted, revealing a mode of ICD induction facilitated by atypical interferon (IFN)-stimulated genes (ISGs), including polo-like kinase 2 (PLK2), during hyperactive type I IFN signaling. The review concludes by discussing the therapeutic potential of ICD, with special attention to its relevance in both preclinical and clinical settings within the field of cancer immunotherapy.
Association of the systemic immune-inflammation index with anemia: a population-based study
Authors: Chen Shuying , Xiao Jigang , Cai Wenyu , Lu Xulin , Liu Chenxi , Dong Yan , Zheng Yingchun , Song Ge , Sun Qi , Wang Huijun , Xiao Zhijian
Published: May 2024

Background

Inflammation has been reported to be related to anemia. As a novel inflammatory marker, Systemic immune-inflammation index (SII) has not been studied with Anemia. The aim of this study was to investigate the possible relationship between SII and anemia.

Methods

This retrospective cross-sectional survey was conducted using data from the 2005–2018 National Health and Nutrition Examination Survey (NHANES) population. In total, 19851 American adults aged ≥18 years were included. SII was calculated as the platelet count×neutrophil count/lymphocyte count. Anemia was defined as hemoglobin (Hgb) levels of < 13 g/dL in males and < 12 g/dL in females. Logistic regression analyses, subgroup analyses and sensitivity analyses were performed to investigate the relationship between SII and anemia.

Results

Our study included a total of 19851 patients, of which 1501 (7.6%) had anemia. After adjusting for all covariates, the multivariate logistic regression analysis showed that a higher SII (In-transform) level was associated with increased likelihood of anemia (OR=1.51, 95% CI: 1.36–1.68, P<0.001). The association between SII and anemia exhibited a nonlinear manner. The positive correlation between SII and anemia was related to the severity of anemia. Subgroup analysis showed that there was no significant dependence on age, family income, body mass index, hypertension, kidney disease and cancer except gender on this positive association. Furthermore, sensitivity analyses confirmed the robustness of our results.

Conclusion

Our study demonstrated that SII was positively associated with anemia especially among female participants. And this positive correlation was related to the severity of anemia. Further large-scale prospective studies are still needed to analyze the role of SII in anemia.
Spatial interaction and functional status of CD68+SHP2+ macrophages in tumor microenvironment correlate with overall survival of NSCLC
Authors: Liu Xu , Zhang Zengfu , Yuan Jupeng , Yu Jinming , Chen Dawei
Published: May 2024

Background

Tumor-associated macrophages (TAMs) constitute a plastic and heterogeneous cell population of the tumor microenvironment (TME) that can regulate tumor proliferation and support resistance to therapy, constituting promising targets for the development of novel anticancer agents. Our previous results suggest that SHP2 plays a crucial role in reprogramming the phenotype of TAMs. Thus, we hypothesized that SHP2+ TAM may predict the treatment efficacy of non-small cell lung cancer NSCLC patients as a biomarker.

Methods

We analyzed cancer tissue samples from 79 NSCLC patients using multiplex fluorescence (mIF) staining to visualize various SHP-2+ TAM subpopulations (CD68+SHP2+, CD68+CD86+, CD68 + 206+, CD68+ CD86+SHP2+, CD68+ CD206+SHP2+) and T cells (CD8+ Granzyme B +) of immune cells. The immune cells proportions were quantified in the tumor regions (Tumor) and stromal regions (Stroma), as well as in the overall tumor microenvironment (Tumor and Stroma, TME). The analysis endpoint was overall survival (OS), correlating them with levels of cell infiltration or effective density. Cox regression was used to evaluate the associations between immune cell subsets infiltration and OS. Correlations between different immune cell subsets were examined by Spearman’s tests.

Results

In NSCLC, the distribution of different macrophage subsets within the TME, tumor regions, and stroma regions exhibited inconsistency. The proportions of CD68+ SHP2+ TAMs (P < 0.05) were higher in tumor than in stroma. And the high infiltration of CD68+SHP2+ TAMs in tumor areas correlated with poor OS (P < 0.05). We found that the expression level of SHP2 was higher in M2-like macrophages than in M1-like macrophages. The CD68+SHP2+ subset proportion was positively correlated with the CD68+CD206+ subset within TME (P < 0.0001), tumor (P < 0.0001) and stroma (P < 0.0001).

Conclusions

The high infiltration of CD68+SHP2+ TAMs predict poor OS in NSCLC. Targeting SHP2 is a potentially effective strategy to inhibit M2-phenotype polarization. And it provides a new thought for SHP2 targeted cancer immunotherapy.
Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis
Authors: Tian Yu , Zhang Meng , Liu Li-xia , Wang Zi-chao , Liu Bin , Huang Youcai , Wang Xiaoling , Ling Yun-zhi , Wang Furong , Feng Xiaoqiang , Tu Yanyang
Published: May 2024

Hepatocellular carcinoma (HCC) is a significant contributor to cancer-related deaths in the world. The development and progression of HCC are closely correlated with the abnormal regulation of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Important biological pathways in cancer biology, such as cell proliferation, death, and metastasis, are impacted by these ncRNAs, which modulate gene expression. The abnormal expression of non-coding RNAs in HCC raises the possibility that they could be applied as new biomarkers for diagnosis, prognosis, and treatment targets. Furthermore, by controlling the expression of cancer-related genes, miRNAs can function as either tumor suppressors or oncogenes. On the other hand, lncRNAs play a role in the advancement of cancer by interacting with other molecules within the cell, which, in turn, affects processes such as chromatin remodeling, transcription, and post-transcriptional processes. The importance of ncRNA-driven regulatory systems in HCC is being highlighted by current research, which sheds light on tumor behavior and therapy response. This research highlights the great potential of ncRNAs to improve patient outcomes in this difficult disease landscape by augmenting the present methods of HCC care through the use of precision medicine approaches.
Reactive oxygen species-responsive supramolecular deucravacitinib self-assembly polymer micelles alleviate psoriatic skin inflammation by reducing mitochondrial oxidative stress
Authors: Yao Leiqing , Tian Faming , Meng Qinqin , Guo Lu , Ma Zhimiao , Hu Ting , Liang Qiongwen , Li Zhengxiao
Published: May 2024

Introduction

The new topical formula is urgent needed to meet clinical needs for majority mild patients with psoriasis. Deucravacitinib exerts outstanding anti-psoriatic capacity as an oral TYK2 inhibitor; however, single therapy is insufficient to target the complicated psoriatic skin, including excessive reactive oxygen species (ROS) and persistent inflammation. To address this need, engineered smart nano-therapeutics hold potential for the topical delivery of deucravacitinib.

Methods

hydrophobic Deucravacitinib was loaded into polyethylene glycol block-polypropylene sulphide (PEG-b-PPS) for transdermal delivery in the treatment of psoriasis. The oxidative stress model of HaCaT psoriasis was established by TNF-α and IL-17A in vitro. JC-1 assay, DCFH-DA staining and mtDNA copy number were utilized to assess mitochondrial function. 0.75% Carbopol®934 was incorporated into SPMs to produce hydrogels and Rhb was labeled to monitor penetration by Immunofluorescence. In vivo, we established IMQ-induced psoriatic model to evaluate therapeutic effect of Car@Deu@PEPS.

Results

Deu@PEPS exerted anti-psoriatic effects by restoring mitochondrial DNA copy number and mitochondrial membrane potential in HaCaT. In vivo, Car@Deu@PEPS supramolecular micelle hydrogels had longer retention time in the dermis in the IMQ-induced ROS microenvironment. Topical application of Car@Deu@PEPS significantly restored the normal epidermal architecture of psoriatic skin with abrogation of splenomegaly in the IMQ-induced psoriatic dermatitis model. Car@Deu@PEPS inhibited STAT3 signaling cascade with a corresponding decrease in the levels of the differentiation and proliferative markers Keratin 17 and Cyclin D1, respectively. Meanwhile, Car@Deu@PEPS alleviated IMQ-induced ROS generation and subsequent NLRP3 inflammasome-mediated pyroptosis.

Conclusion

Deu@PEPS exerts prominent anti-inflammatory and anti-oxidative effects, which may offers a more patient-acceptable therapy with fewer adverse effects compared with oral deucravacitinib.
Effects of salinity on the growth, physiological and biochemical components of microalga Euchlorocystis marina
Authors: Pan Yao , Amenorfenyo David Kwame , Dong Mingbiao , Zhang Ning , Huang Xianghu , Li Changling , Li Feng
Published: May 2024

Euchlorocystis marina, a new marine species of the genus Euchlorocystis discovered in 2022, has the potential to improve the water quality in mariculture ponds. However, the effects of salinity on the growth, physiology, and biochemical composition of these algae are not well understood. In this study, changes in physiological and biochemical indices such as cell density, photosynthetic pigment, polysaccharide, and lipid content of E. marina under different salinity treatments were analyzed. The results showed that the highest cell density was observed at a salinity of 15‰. The lowest photosynthetic pigment content was observed at a salinity of 60‰, and the highest polysaccharide and lipid content was observed at a salinity of 60‰. These results indicated that lower salinity was more conducive to E. marina reproduction and growth. E. marina can accumulate polysaccharides and lipids in high salinity environments. This study provides new information for understanding the salinity adaptation strategies of E. marina and has practical significance for its development and utilization.
CD4 expression on monocytes correlates with recovery from multiple organ dysfunction syndrome and mortality in patients with septic shock
Authors: Sun Yingqian , Lu Yan , Xing Rui , Zhang Yongjun , Zhang Longyi
Published: May 2024

Background

To date, the correlation between CD4 on the monocytes (mCD4) expression and the prognosis of patients with septic shock remains unclear. The purpose of this study was to analyze the expression of mCD4 in these patients and further evaluate whether mCD4 expression correlates with either the recovery from multiple organ dysfunction syndrome (MODS) or mortality.

Methods

The study participants were recruited from a tertiary general hospital in China (Affiliated Dongyang Hospital of Wenzhou Medical University). Sepsis and septic shock were diagnosed based on the diagnostic criteria of Sepsis-3. MODS was defined as a Sequential Organ Failure Assessment score of at least two organ systems ≥2. Persistent MODS was defined as the continual meeting of the MODS criteria when re-evaluated one week after admission (day 7). A logistic regression model was used to test whether mCD4 was an independent prognostic factor for mortality in patients with septic shock. A paired sample rank sum test was used to examine the correlation between mCD4 expression and MODS recovery.

Result

The study recruited 79 patients with septic shock as the study group, 74 patients with sepsis as the disease control group, and 56 volunteers as healthy controls. In the first 24 h after admission (day 1), mCD4 expression was significantly reduced in patients with septic shock compared to healthy controls and patients with sepsis. Moreover, mCD4 expression was an independent prognostic factor for in-hospital and 28 day mortality in patients with septic shock. mCD4 expression did not show significant differences in patients with persistent MODS on day 7 compared to day 1. However, mCD4 expression was significantly higher in patients without persistent MODS on day 7 than on day 1.

Conclusion

mCD4 expression is significantly reduced in patients with septic shock, which is an independent prognostic factor for mortality and closely related to recovery from MODS.
Translation and psychometric evaluation of the Chinese version of the Nursing Time Management Scale
Authors: Fu Zhaoquan , Wang Yaping , Zhang Limei , Tan Mingyang
Published: May 2024

Background

Reasonable and effective time allocation can promote the improvement of medical care service quality. This study aimed to translate, cross-culturally adapt and validate the Chinese Nursing Time Management Scale (NTMS).

Methods

Using a cross-sectional survey, 345 clinical nurses were selected from June to September 2023 for a general information questionnaire and Nursing Time Management Scale (NTMS) study. Item analysis, exploratory factor analysis and validation factor analysis were used to verify the reliability and validity of the Chinese version of Nursing Time Management Scale.

Results

The Chinese version of the Nurses’ Time Management Competency Scale includes 17 entries in 3 dimensions: planning activities and setting goals, coordinating activities and procedures, and organizing nursing activities. The Cronbach’s alpha coefficient for the total scale was 0.966. Exploratory factor analysis showed that the cumulative variance contribution of the three male factors was 97.44%.

Conclusion

The NTMS has acceptable validity and reliability and can be used to evaluate the nursing time management skills of Chinese clinical nurses.
Comparative genomic and transcriptome analyses of two Pectobacterium brasiliense strains revealed distinct virulence determinants and phenotypic features
Authors: Sun Yue , Utpal Handique , Wu Yajuan , Sun Qinghua , Feng Zhiwen , Shen Yue , Zhang Ruofang , Zhou Xiaofeng , Wu Jian
Published: May 2024

Potato soft rot caused by Pectobacterium spp. are devastating diseases of potato which cause severe economic losses worldwide. Pectobacterium brasiliense is considered as one of the most virulent species. However, the virulence mechanisms and pathogenicity factors of this strain have not been fully elucidated. Here, through pathogenicity screening, we identified two Pectobacterium brasiliense isolates, SM and DQ, with distinct pathogenicity levels. SM exhibits higher virulence compared to DQ in inducing aerial stem rot, blackleg and tuber soft rot. Our genomic and transcriptomic analyses revealed that SM encodes strain specific genes with regard to plant cell wall degradation and express higher level of genes associated with bacterial motility and secretion systems. Our plate assays verified higher pectinase, cellulase, and protease activities, as well as fast swimming and swarming motility in SM. Importantly, a unique endoglucanase S specific to SM was identified. Expression of this cellulase in DQ greatly enhances its virulence compared to wild type strain. Our study sheds light on possible determinants causing different pathogenicity of Pectobacterium brasiliense species with close evolutionary distance and provides new insight into the direction of genome evolution in response to host variation and environmental stimuli.
Functional connectivity alterations in the thalamus among patients with bronchial asthma
Authors: Wang Tao , Huang Xin , Dai Li-xue , Zhan Kang-min , Wang Jun
Published: May 2024

Objective

Bronchial Asthma (BA) is a common chronic respiratory disease worldwide. Earlier research has demonstrated abnormal functional connectivity (FC) in multiple cognition-related cortices in asthma patients. The thalamus (Thal) serves as a relay center for transmitting sensory signals, yet the modifications in the thalamic FC among individuals with asthma remain uncertain. This research employed the resting-state functional connectivity (rsFC) approach to explore alterations in thalamic functional connectivity among individuals with BA.

Patients and methods

After excluding participants who did not meet the criteria, this study finally included 31 patients with BA, with a gender distribution of 16 males and 15 females. Subsequently, we recruited 31 healthy control participants (HC) matched for age, gender, and educational background. All participants underwent the Montreal Cognitive Assessment (MoCA) and the Hamilton Depression Rating Scale (HAMD) assessment. Following this, both groups underwent head magnetic resonance imaging scans, and resting-state functional magnetic resonance imaging (rs-fMRI) data was collected. Based on the AAL (Automated Anatomical Labeling) template, the bilateral thalamic regions were used as seed points (ROI) for subsequent rsFC research. Pearson correlation analysis was used to explore the relationship between thalamic functional connectivity and neuropsychological scales in both groups. After controlling for potential confounding factors such as age, gender, intelligence, and emotional level, a two-sample t-test was further used to explore differences in thalamic functional connectivity between the two groups of participants.

Result

Compared to the HC group, the BA group demonstrated heightened functional connectivity (FC) between the left thalamus and the left cerebellar posterior lobe (CPL), left postcentral gyrus (PCG), and right superior frontal gyrus (SFG). Concurrently, there was a decrease in FC with both the Lentiform Nucleus (LN) and the left corpus callosum (CC). Performing FC analysis with the right thalamus as the Region of Interest (ROI) revealed an increase in FC between the right thalamus and the right SFG as well as the left CPL. Conversely, a decrease in FC was observed between the right thalamus and the right LN as well as the left CC.

Conclusion

In our study, we have verified the presence of aberrant FC patterns in the thalamus of BA patients. When compared to HCs, BA patients exhibit aberrant alterations in FC between the thalamus and various brain areas connected to vision, hearing, emotional regulation, cognitive control, somatic sensations, and wakefulness. This provides further confirmation of the substantial role played by the thalamus in the advancement of BA.
MiR-122 overexpression alleviates oxygen–glucose deprivation-induced neuronal injury by targeting sPLA2-IIA
Authors: Yu Yuanfang , Li Pan , Chen Mengyuan , Zhan Wenfeng , Zhu Ting , Min Ling , Liu Hao , Lv Bo
Published: May 2024

Background

Ischemic stroke (IS) is a neurological disease with significant disability and mortality. MicroRNAs were proven to be associated with cerebral ischemia. Previous studies have demonstrated miR-122 downregulation in both animal models of IS and the blood of IS patients. Nonetheless, the role and mechanism of miR-122-5p in IS remain unclear.

Methods

We established primary human and mouse astrocytes, along with HT22 mouse hippocampal neuronal cells, through oxygen–glucose deprivation/reoxygenation (OGD/R) treatment. To assess the impact of miR-122, we employed CCK8 assays, flow cytometry, RT-qPCR, western blotting, and ELISA to evaluate cell viability, apoptosis, reactive oxygen species (ROS) generation, and cytokine expression. A dual-luciferase reporter gene assay was employed to investigate the interaction between miR-122 and sPLA2-IIA.

Results

Overexpression of miR-122 resulted in decreased apoptosis, reduced cleaved caspase-3 expression, and increased cell viability in astrocytes and HT22 cells subjected to OGD/R. RT-qPCR and ELISA analyses demonstrated a decrease in mRNA and cytokine levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in both astrocytes and HT22 cells following miR-122 overexpression. Moreover, miR-122 overexpression reversed OGD/R-induced ROS levels and 8-OHdG formation in astrocytes. Additionally, miR-122 overexpression decreased the mRNA and protein expression of inducible nitric oxide synthase (iNOS). Furthermore, we found that miR-122 attaches to the 3′-UTR of sPLA2-IIA, thereby downregulate its expression.

Conclusion

Our study demonstrates that miR-122-mediated inhibition of sPLA2-IIA attenuates OGD/R-induced neuronal injury by suppressing apoptosis, alleviating post-ischemic inflammation, and reducing ROS production. Thus, the miR-122/sPLA2-IIA axis may represent a promising target for IS treatment.
Akap5 links synaptic dysfunction to neuroinflammatory signaling in a mouse model of infantile neuronal ceroid lipofuscinosis
Authors: Koster Kevin P. , Fyke Zach , Nguyen Thu T. A. , Niqula Amanda , Noriega-González Lorena Y. , Woolfrey Kevin M. , Dell’Acqua Mark L. , Cologna Stephanie M. , Yoshii Akira
Published: May 2024

Palmitoylation and depalmitoylation represent dichotomic processes by which a labile posttranslational lipid modification regulates protein trafficking and degradation. The depalmitoylating enzyme, palmitoyl-protein thioesterase 1 (PPT1), is associated with the devastating pediatric neurodegenerative condition, infantile neuronal ceroid lipofuscinosis (CLN1). CLN1 is characterized by the accumulation of autofluorescent lysosomal storage material (AFSM) in neurons and robust neuroinflammation. Converging lines of evidence suggest that in addition to cellular waste accumulation, the symptomology of CLN1 corresponds with disruption of synaptic processes. Indeed, loss of Ppt1 function in cortical neurons dysregulates the synaptic incorporation of the GluA1 AMPA receptor (AMPAR) subunit during a type of synaptic plasticity called synaptic scaling. However, the mechanisms causing this aberration are unknown. Here, we used the Ppt1−/− mouse model (both sexes) to further investigate how Ppt1 regulates synaptic plasticity and how its disruption affects downstream signaling pathways. To this end, we performed a palmitoyl-proteomic screen, which provoked the discovery that Akap5 is excessively palmitoylated at Ppt1−/− synapses. Extending our previous data, in vivo induction of synaptic scaling, which is regulated by Akap5, caused an excessive upregulation of GluA1 in Ppt1−/− mice. This synaptic change was associated with exacerbated disease pathology. Furthermore, the Akap5- and inflammation-associated transcriptional regulator, nuclear factor of activated T cells (NFAT), was sensitized in Ppt1−/− cortical neurons. Suppressing the upstream regulator of NFAT activation, calcineurin, with the FDA-approved therapeutic FK506 (Tacrolimus) modestly improved neuroinflammation in Ppt1−/− mice. These findings indicate that the absence of depalmitoylation stifles synaptic protein trafficking and contributes to neuroinflammation via an Akap5-associated mechanism.
Folic acid protects against isoniazid-induced liver injury via the m6A RNA methylation of cytochrome P450 2E1 in mice
Authors: Jiang Lan , Ni Ya , Zhao Cong , Gao Dexin , Gai Xiaochun , Xiong Ke , Wang Jinyu
Published: May 2024

Background

Cytochrome P450 2E1 (CYP2E1) converts isoniazid (INH) to toxic metabolites and is critical in INH-induced liver injury. The aim is to investigate the effect of folic acid (FA) on CYP2E1 and INH-induced liver injury.

Methods

Male Balb/c mice were used. The mice in the control group only received an AIN-93M diet. The AIN-93M diet was supplemented with 0.66 g INH/kg diet for the mice in the INH and FA groups. The mice in the FA group were treated with additional 0.01 g FA/kg diet. The one-carbon cycle metabolites, the expressions of CYP2E1 and the DNA and RNA methylation levels were detected to reveal the potential mechanism.

Results

FA treatment significantly reduced the alanine aminotransferase level and alleviated the liver necrosis. The mRNA and protein expressions of CYP2E1 were significantly lower in the FA group than those in the INH group. The N6-methyladenosine RNA methylation level of Cyp2e1 significantly increased in the FA group compared with the INH group, while the DNA methylation levels of Cyp2e1 were similar between groups. Additionally, the liver S-adenosyl methionine (SAM)/S-adenosyl homocysteine (SAH) was elevated in the FA group and tended to be positively correlated with the RNA methylation level of Cyp2e1.

Conclusion

FA alleviated INH-induced liver injury which was potentially attributed to its inhibitory effect on CYP2E1 expressions through enhancing liver SAM/SAH and RNA methylation.
Comparison of clinical characteristics and outcomes in primary neuroendocrine breast carcinoma versus invasive ductal carcinoma
Authors: Peng Li , Ma Mingwei , Zhao Dachun , Zhao Jialin , Sun Qiang , Mao Feng
Published: May 2024

Background

Neuroendocrine breast carcinoma (NECB) is a rare, special histologic type of breast cancer. There are some small sample studies on the clinical outcomes of NECB patients, which are worthy of further discussion.

Methods

We conducted a retrospective case-control study of clinical characteristics and outcomes among patients with primary NECB versus invasive carcinoma of no special type (NST) between November 2004 and November 2017 in the Peking Union Medical College Hospital, Beijing. NST patients were strictly matched 1:4 during the same period based on the TNM stage. Statistical comparisons were performed to determine the differences in survival between NST and NECB patients and to identify clinical factors that correlate with prognosis.

Results

A total of 121 participants affected by primary NECB were included in our analysis from November 2004 to November 2017. Elderly persons (>60 years of age) were more likely to have primary NECB than young persons (p=0.001). In addition, primary NECB patients had significantly higher odds of having tumors 2-5 cm (36.5%) and >5 cm (6.1%) in size than NST patients. Despite a significant difference in tumor size, the proportion of patients with lymph node metastases showed no difference between the two groups (p=0.021). In addition, the rate of patients with ER-negative tumors in the NECB group (4.2%) was significantly lower than that in the primary NST group (29.8%). Significant differences were noted in the PR-negative (13.3% versus 36.6%, P<0.001) and HER2-negative (90.5% versus 76.4%, P=0.001) expression statuses among these patients. Of 121 primary NECB patients, 11 (9.1%) experienced relapses during the follow-up period. We found that tumor size was an independent risk factor for relapse. For hormone receptors on tumor cells, ER-positive breast cancer patients had significantly lower odds of relapse than receptor-negative patients.

Conclusions

Our data demonstrate no significant difference in mortality and relapse between the primary NECB and NST groups. The tumor size in the primary NECB group was significantly larger than that in the NST group. In addition, the absence of ER independently increased the relapse rate for breast carcinoma patients.
Prognostic nomogram to predict cancer-specific survival with small-cell carcinoma of the prostate: a multi-institutional study
Authors: Di Yupeng , Song Jiazhao , Song Zhuo , Wang Yingjie , Meng Lingling
Published: May 2024

Objective

The aim of this study is to examine the predictive factors for cancer-specific survival (CSS) in patients diagnosed with Small-Cell Carcinoma of the Prostate (SCCP) and to construct a prognostic model.

Methods

Cases were selected using the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method was utilized to calculate survival rates, while Lasso and Cox regression were employed to analyze prognostic factors. An independent prognostic factor-based nomogram was created to forecast CSS at 12 and 24 months. The model’s predictive efficacy was assessed using the consistency index (C-index), calibration curve, and decision curve analysis (DCA) in separate tests.

Results

Following the analysis of Cox and Lasso regression, age, race, Summary stage, and chemotherapy were determined to be significant risk factors (P < 0.05). In the group of participants who received training, the rate of 12-month CSS was 44.6%, the rate of 24-month CSS was 25.5%, and the median time for CSS was 10.5 months. The C-index for the training cohort was 0.7688 ± 0.024. As for the validation cohort, it was 0.661 ± 0.041. According to the nomogram, CSS was accurately predicted and demonstrated consistent and satisfactory predictive performance at both 12 months (87.3% compared to 71.2%) and 24 months (80.4% compared to 71.7%). As shown in the external validation calibration plot, the AUC for 12- and 24-month is 64.6% vs. 56.9% and 87.0% vs. 70.7%, respectively. Based on the calibration plot of the CSS nomogram at both the 12-month and 24-month marks, it can be observed that both the actual values and the nomogram predictions indicate a predominantly stable CSS. When compared to the AJCC staging system, DCA demonstrated a higher level of accuracy in predicting CSS through the use of a nomogram.

Conclusion

Clinical prognostic factors can be utilized with nomograms to forecast CSS in Small-Cell Carcinoma of the Prostate (SCCP).
Toripalimab plus cetuximab combined with radiotherapy in a locally advanced platinum-based chemotherapy-insensitive nasopharyngeal carcinoma patient: a case report
Authors: Piao Ying , Yang Yao , Wu Shihai , Han Ling
Published: May 2024

Background

Locoregionally advanced nasopharyngeal carcinoma (NPC) is an epithelial malignancy that primarily occurs in East and Southeast Asia, and it is associated with relatively poor overall survival (OS). Currently, there is no reliably effective standard treatment for NPC that progresses after first-line therapy with platinum-based chemotherapy.

Case report

A 55-year-old woman diagnosed with stage IVa NPC received two cycles of platinum-based chemotherapy but encountered an increase in the size of cervical lymph nodes and suffered from adverse events. The patient was then switched to toripalimab plus cetuximab combined with radical radiotherapy and had a complete clinical response within 2 months following the completion of radiotherapy without severe treatment-related adverse events.

Conclusion

This case report showed that toripalimab plus cetuximab combined with radiotherapy for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma may result in a fast and durable response with a manageable safety profile.
Treatment of renal leiomyosarcoma with right atrial tumor embolus without cardiopulmonary bypass: a case report
Authors: Duan Yuanpeng , Bi Chengwei , Zhang Guoying , Xing Yapeng , Qin Yang , Zhao Bin
Published: May 2024

Objective

To investigate the clinical manifestations, imaging and pathological features, treatment methods and prognosis of primary leiomyosarcoma of kidney, and the choice of treatment with tumor thrombus.

Methods

The clinical data of a patient with primary renal leiomyosarcoma complicated with inferior vena cava and right atrial tumor thrombus were retrospectively analyzed. Radical resection of right kidney without cardiopulmonary bypass and removal of inferior vena cava and right atrial tumor thrombus were performed. Adjuvant intravenous chemotherapy was given according to the results, and follow-up observation was made.

Results

Postoperative pathological findings were: leiomyosarcoma (right renal tumor), the size of the mass was about 12.1 cm, and no cancer was found at the incision end of the right ureter.

Conclusion

Primary leiomyosarcoma of kidney is rare in clinical practice, and complication of right atrial tumor embolus is even rarer. The disease has high malignant degree and poor prognosis. The clinical manifestations and imaging examinations were non-specific, and pathological diagnosis was the gold standard. Radical surgical resection is the main treatment method at present, and it provides experience for the treatment of grade IV tumor thrombus without cardiopulmonary bypass.
Case report: Long-term intracranial effect of zimberelimab monotherapy following surgical resection of high PD-L1-expressing brain metastases from NSCLC
Authors: Wu Weijia , Guo Jinyou , He Lianxiang , Deng Qi , Huang Xianping
Published: May 2024

Non-small cell lung cancer (NSCLC) accounted for the majority of lung cancer cases worldwide. Brain metastases (BM) frequently complicate NSCLC and portend a dismal prognosis. To control neurological symptoms, surgical resection is commonly followed by brain radiotherapy (RT). However, RT is often complicated by neurotoxicity. For patients with tumors that harbor positive driver genes, tyrosine kinase inhibitors are considered the standard of care. Nevertheless, treatment options for those without driver gene mutations are still debated. Programmed death receptor 1 (PD-1)/ligand 1 (PD-L1) inhibition has emerged as a novel therapeutic strategy for NSCLC patients with PD-L1-positive tumors, as well as for those with asymptomatic BM. However, the effect of anti-PD-1 antibodies on active BM within such specific populations is undetermined. Herein we present a case of a 65-year-old patient with NSCLC and high PD-L1-expressing BM. The patient underwent surgical resection of BM followed by first-line monotherapy with 31 cycles of zimberelimab, a novel anti-PD-1 antibody, and has already achieved 24 months of progression-free survival and intracranial recurrence-free survival. To our knowledge, this is the first report regarding the intracranial effect of zimberelimab on BM from primary lung cancer. This case report might facilitate an understanding of the intracranial effects of different anti-PD-1 antibodies for such populations.
Case report: a case report of excision of giant lipoma in the posterior neck
Authors: Du Aichao , Wang Hongyu , Dai Junqiang , Dong Qiang , Yuan Guoqiang , Pan Yawen
Published: May 2024

Lipomas, benign tumors originating from the anomalous proliferation of adipocytes, predominantly emerge in regions rich in adipose tissue. However, their presence in the head and neck areas remains rare, constituting approximately 13% of all diagnosed lipoma cases. This study presents a case involving a substantial subcutaneous lipoma located at the posterior neck, measuring about 20 cm × 19 cm × 10 cm. The patient presented with swelling and pain in the back of the neck. And the considerable dimensions of this lipoma significantly impacted the patient’s quality of life and aesthetic appearance. Concurrently, the patient exhibited symptoms indicative of degenerative cervical spine disease and cervical disc herniation. After admission, a comprehensive examination, including ultrasound, CT scan, and MRI, was conducted. Given the clinical complexity, the decision for surgical intervention was deemed essential. The surgical strategy entailed a meticulous total excision of the tumor through an incision made in the posterior cross-neck, coupled with the strategic removal of excess skin. To facilitate wound healing, postoperative management included the use of negative pressure drainage. Pathological examination conclusively identified the mass as a lipoma. Postoperative follow-ups indicated successful recovery, as evidenced by the restoration of the neck’s aesthetic contour and the complete resolution of the previously observed restrictions in sagittal neck movement.
Case report: A left forearm mass with eccentric intramedullary ulnar destruction diagnosed as alveolar rhabdomyosarcoma and treated by wide resection and free vascularized fibular graft
Authors: Yang Chenyu , Wang Xinjia , Lin Huaitai , Zhu Jinhao , Xu Zijian , Wang Weidong
Published: May 2024

Background

Alveolar Rhabdomyosarcoma is a profoundly malignant soft-tissue sarcoma that predominantly affects children and adolescents. However, the medical field lacks consensus regarding the optimal surgical approach to be undertaken in cases where this tumor causes local bone destruction in the upper limb.

Case description

A 17-year-old male presented a mass in his left forearm and CT and MRI indicated that the mass had penetrated the ulnar cortex and infiltrating the medulla, resulting in the formation of an eccentric trans-ventricular tumor focus. The sizable tumor affected the volar muscles of the forearm as well as the ulnar bone marrow, exerting pressure on the ulnar artery and vein. It was confirmed by needle biopsy that the mass is alveolar rhabdomyosarcoma. Following two courses of neoadjuvant chemotherapy, the tumor was widely excised en bloc. Autologous fibula with a vascular pedicle was utilized for reconstruction during the procedure. In the postoperative follow-up, no local recurrence of the tumor was observed. Furthermore, the patient retained satisfactory wrist flexion and pronation function in the left forearm.

Conclusions

Alveolar rhabdomyosarcoma is an uncommon and highly aggressive form of soft tissue sarcoma. Scientific management necessitates a multidisciplinary approach, combining chemotherapy with surgery. In cases where the tumor invaded into compartment of the bone, careful consideration should be given to the boundaries of tumor resection, the extent of osteotomy, and the approach to musculoskeletal reconstruction when designing the surgical plan. Through reporting our own case and thoroughly reviewing previous clinical experiences, we aim to provide valuable insights for the treatment of this particular disease.
The safety and efficacy of the Stryker OptaBlate™ Bone Tumor Ablation system for vertebral body metastases
Authors: Evans Alexander R. , Harris Danielle M. , Gumerlock Mary K. , Shakir Hakeem J.
Published: May 2024

Background

Metastatic spinal lesions are a significant cause of morbidity and decreased quality of life in those with a high tumor burden. Despite treatment modalities such as medical therapy (e.g., chemotherapy, steroids), spinal augmentation procedures, and radiation therapy, many patients still experience refractory back pain due to neoplastic infiltration of the vertebral body and/or pathologic compression fractures. With the aim to address refractory pain in patients who have exhausted conventional treatment options, Stryker developed the OptablateTM Bone Tumor Ablation system (BTA; Stryker Corporation, Kalamazoo, MI), which delivers radiofrequency energy to pathologic vertebral body lesions. In this preliminary single-institution study, we characterize the use of the BTA system in 11 patients undergoing kyphoplasty for pathologic spinal lesions with the goal to demonstrate the impact of this novel technology on refractory pain in this challenging clinical setting.

Methods

A single-center retrospective chart review was performed on all patients identified as those receiving tumor ablation/kyphoplasty for spinal neoplasms using the OptablateTM BTA system performed by a single surgeon at the University of Oklahoma Medical Center. Sex, age, primary lesion type, presenting symptomatology, spinal level, time of follow-up, and outcome were obtained from the electronic medical record (EMR).

Results

Eleven patients (4 males, 7 females) with a mean age of 62 (range, 38–82) years had an average follow-up time of 6 months. Presenting symptoms attributed to spinal pathology included back pain (n = 11, 100%), pathologic fracture (n = 6, 55%), and lower extremity weakness (n = 3, 27%). A total of 20 lesions were ablated at 12 vertebral levels. Eight patients (73%) had improved pain. No complications were reported.

Conclusion

This preliminary study documents the safety of the BTA system, in addition to its diverse use across many levels. The majority of patients reported improvement in their pain. Further study is required to fully characterize the use of the BTA system in those with neoplastic spinal pathology.
Laparoscopic-assisted distal colon excision and proximal colon pull-through anorectoplasty for anorectal malformation
Authors: Li Siqi , Ye Shiru , Zhou Yan , Diao Mei , Li Long
Published: May 2024

Purpose

During the second stage surgery for anorectal malformations (ARM), patients whose distal intestine of the colostomy is particularly short underwent laparoscopic-assisted distal colon excision and proximal colon pull-through anorectoplasty (PCPARP). This study aimed to discuss the outcomes of PCPARP after colostomy in patients with ARM.

Methods

This is a single-center propensity score-matched (PSM) study which was retrospectively initiated patients with intermediate- or high-type ARM who underwent laparoscopic surgery from June 2007 to December 2018. These patients were divided into PCPARP group and conventional laparoscopic-assisted anorectoplasty (LAARP) group according to specific surgical methods. The general data, surgical data, postoperative complications, and functional results were evaluated.

Results

In total, 216 patients were included in this study: 190 (88.0%) undergoing LAARP approach and 26 (12.0%) undergoing PCPARP approach. After PSM, two well-balanced groups of 26 patients were analyzed and showed the postoperative complications (P = 0.126) and bowel function (P = 0.809) were similiar between the two groups.

Conclusions

The curative effect of PCPARP after colostomy is similar to that of classic LAARP surgery, which can be used for ARM patients with a very short and abnormal distal intestine of the stoma.