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Jing Yu,1 Yike Zhang,1 Zhixiong Ye,1 Kun Tang,1 Yiming Ma,1 Linlin Fu,1 Tongtong Cui,1 Hening Kang,2 Yadong Yuan,1 Wensen Pan1 1Second Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2College of Basic Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of ChinaCorrespondence: Wensen Pan, Email 27400010@hebmu.edu.cnBackground: Despite ongoing interventions, SARS-CoV-2 continues to cause significant global morbidity and mortality. Early diagnosis and intervention are crucial for effective clinical management. However, prognostic features based on transcriptional data have shown limited effectiveness, highlighting the need for more precise biomarkers to improve COVID-19 treatment outcomes.Methods: We retrospectively analyzed 149 clinical features from 189 COVID-19 patients, identifying prognostic features via univariate Cox regression. The cohort was split into training and validation sets, and 77 prognostic models were developed using seven machine learning algorithms. Among these, the least absolute shrinkage and selection operator (Lasso) method was employed to refine the selection of prognostic variables by ten-fold cross-validation strategy, which were then integrated with random survival forests (RSF) to build a robust COVID-19-related prognostic model (CRM). Model accuracy was evaluated across training, validation, and entire cohorts. The diagnostic relevance of interleukin-10 (IL-10) was confirmed in bulk transcriptional data and validated at the single-cell level, where we also examined changes in cellular communication between mononuclear cells with differing IL-10 expression and other immune cells.Results: Univariate Cox regression identified 43 prognostic features. Among the 77 machine learning models, the combination of Lasso and RSF produced the most robust CRM. This model consistently performed well across training, validation, and entire cohorts. IL-10 emerged as a key prognostic feature within the CRM, validated by single-cell transcriptional data. Transcriptome analysis confirmed the stable diagnostic value of IL-10, with mononuclear cells identified as the primary IL-10 source. Moreover, differential IL-10 expression in these cells was linked to altered cellular communication in the COVID-19 immune microenvironment.Conclusion: The CRM provides accurate prognostic predictions for COVID-19 patients. Additionally, the study underscores the importance of early IL-10 level testing upon hospital admission, which could inform therapeutic strategies.Keywords: SARS-CoV-2, machine learning, IL-10, therapeutic guidance, clinical decision making

Huiying Yan,1,* Wei Wang,2,* Tingting Cui,1 Yanxin Shao,3 Mingquan Li,1 Limei Fang,1 Lina Feng1 1Department of Neurology, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 2Department of Intensive Care Unit, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Limei Fang; Lina Feng, Department of Neurology, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Changchun, People’s Republic of China, Email fanglm008@163.com; Fenglina0001@126.comAbstract: Alzheimer’s disease (AD) is a fatal neurodegenerative disease with a subtle and progressive onset and is the most common type of dementia. However, its etiology and pathogenesis have not yet been fully elucidated. The common pathological manifestations of AD include extraneuronal β-amyloid deposition (Aβ), intraneuronal tau protein phosphorylation leading to the formation of ‘neurofibrillary tangles’ (NFTs), neuroinflammation, progressive loss of brain neurons/synapses, and glucose metabolism disorders. Current treatment approaches for AD primarily focus on the ‘Aβ cascade hypothesis and abnormal aggregation of hyperphosphorylation of tau proteins’, but have shown limited efficacy. Therefore, there is an ongoing need to identify more effective treatment targets for AD. The central nervous system (CNS) inflammatory response plays a key role in the occurrence and development of AD. Neuroinflammation is an immune response activated by glial cells in the CNS that usually occurs in response to stimuli such as nerve injury, infection and toxins or in response to autoimmunity. Neuroinflammation ranks as the third most prominent pathological feature in AD, following Aβ and NFTs. In recent years, the focus on the role of neuroinflammation and microglia in AD has increased due to the advancements in genome-wide association studies (GWAS) and sequencing technology. Furthermore, research has validated the pivotal role of microglia-mediated neuroinflammation in the progression of AD. Therefore, this article reviews the latest research progress on the role of neuroinflammation triggered by microglia in AD in recent years, aiming to provide a new theoretical basis for further exploring the role of neuroinflammation in the process of AD occurrence and development.Keywords: neuroinflammation, microglia, Alzheimer’s disease, review, Trem2

Pengqi Zhang,1 Tianye Wang,1 Xiaoting Zhu,2 Lina Feng,1 Jiale Wang,1 Yunqiang Li,1 Xinyue Zhang,1 Tingting Cui,1 Mingquan Li2 1College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin Province, People’s Republic of China; 2Neurology Department, Third Affiliated Clinical Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Mingquan Li, Neurology Department, Third Affiliated Clinical Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130033, People’s Republic of China, Tel +86-15543120222, Email liminhquan0001@126.comObjective: The objective of this study was to explore the neuroprotective mechanism of JDYZF in treating AD from the perspective of inflammation and intestinal microflora.Methods: A total of 24 APP/PS1 mice were randomly divided into four groups: model (n = 6), JDYZF low-dose (n = 6), JDYZF high-dose (n = 6), and positive drug (n = 6), six C57 mice were used as the control group. The body weights and diets of all mice were examined daily. After 8 weeks of administration, the learning and memory of mice were evaluated by the Morris water maze test. The histopathological changes of hippocampus, liver and kidney in mice were observed by HE staining after being euthanized. The expression of p-tau in hippocampus tissue was detected by immunohistochemistry. After that, 16S rDNA sequencing was used to investigate the relationship between JDYZF and intestinal microbiota. Finally, a comparison of TLR4, p65, p-p65, iκB, p-iκB, and IL-1β protein expression in the hippocampus tissue of mice in each group was measured by Western blot.Results: The results showed that APP/PS1 mice taking JDYZF orally were generally in good condition. Compared with the control group, JDYZF significantly improved learning and memory ability in ethology. Histology showed that JDYZF improved the hippocampal structure of mice and inhibited the deposition of p-tau. JDYZF treatment could regulate the gut microbiota of APP/PS1 mice by increasing the richness of Lachnospiraceae, Ruminococcaceae, and Actinobacteria and reducing that of Alistipes and Muribaculaceae. It also significantly inhibited the activation of the TLR4/NF-κB signaling pathway in the brain. In addition, no obvious toxic reactions were found in the liver and kidney of APP/PS1 mice after taking JDYZF for 8 weeks.Conclusion: The findings revealed that JDYZF improved cognitive ability and alleviated the TLR4/NF-κB signaling pathway in APP/PS1 mice, and the modulating the gut microbiota presented here may help illuminate its activation mechanism.Keywords: Jiedu Yizhi Formula, Alzheimer’s disease, fecal microbial diversity, NF-κB, APP/PS1 mice

Tingting Cui, Jingshi Wang, Zhao Wang Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of ChinaCorrespondence: Zhao Wang, Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China, Tel +86-10-63138303, Email wangzhao@ccmu.edu.cnBackground: Hemophagocytic lymphohistiocytosis (HLH) is known as a life-threatening syndrome, and Leishmania is the most common protozoan that triggers infection-related HLH. It is thus important to find the root cause and treat it effectively.Case Report: This paper reports a 44-year-old man who developed antisynthetase antibody syndrome previously. The patient progressed rapidly to the extent of meeting the HLH-2004 diagnostic criteria, despite the unknown etiology. Although the patient was promptly treated in line with the HLH-1994 protocol to achieve remission, he still relapsed after glucocorticoid reduction. Afterwards, it was found out that HLH was secondary to Leishmania infection. The symptoms of HLH were alleviated quickly by the treatment with Ruxolitinib and Amphotericin B.Conclusion: Etiological screening plays a crucial role in leishmaniasis-related HLH. An experienced pathologist and real-time PCR are essential for treating Leishmania. The treatment of Ruxolitinib and Amphotericin B proved effective in alleviating the relapse of visceral leishmaniasis-related HLH.Keywords: hemophagocytic lymphohistiocytosis, visceral leishmaniasis, Amphotericin B, Ruxolitinib

Jing Li, Wenjuan Wang, Xiaodan Zhang, Jinxing Liu, Haining Zhang, Tong Cui, Fangfang Wang, Guohong Zhou Department of Ophthalmology, Shanxi Eye Hospital Affiliated to Shanxi Medical University, Taiyuan, 030002, People’s Republic of ChinaCorrespondence: Guohong Zhou, Department of Ophthalmology, Shanxi Eye Hospital Affiliated to Shanxi Medical University, No. 100 Fudong St, Xinghualing District, Taiyuan, 030002, Shanxi, People’s Republic of China, Email guohongzhou2005@163.comPurpose: To evaluate the multifocal electroretinogram (mfERG) and optical coherence tomography (OCT) angiography features in patients with idiopathic macular hole (IMH) before and after vitrectomy.Patients and Methods: This prospective study was conducted at Shanxi Eye Hospital from January 2019 to December 2021. Twenty-five eyes of 25 patients with unilateral IMH, the unaffected fellow eyes, and 30 eyes of healthy patients were investigated. All unilateral IMH eyes underwent vitrectomy.Results: The IMH eyes had significantly delayed latency (rings 2– 5) of mfERG compared with the healthy control eyes, and the amplitude density of all rings of mfERG was reduced (P < 0.05). When comparing the mfERG components before surgery and at the follow-up, the amplitude density of IMH eyes (ring 1, 3, 4 and 5) was increased significantly (P < 0.05). The delayed implicit times of the second and fifth ring were significantly shortened compared with those of preoperative eyes (P < 0.05). The mean delayed implicit time of mfERG in six months after surgery was negatively correlated with visual acuity (r = − 0.890, P = 0.043). Significant differences of superficial retinal blood flow density (SRBFD, P < 0.001) and choroidal blood flow density (CBFD) (P < 0.05) got via OCTA were found between IMH before surgery and healthy control eyes. SRBFD of the fellow eyes were significantly different with the healthy control eyes (P = 0.038). Statistically significance of SRBFD and CBFD changes in IMH eyes were found before and after surgery (P < 0.05).Conclusion: IMH eyes had a decreased amplitude density and a delayed implicit time in some regions. Additionally, SRBFD and CBFD were both increased after vitrectomy, which suggests that the blood supply of the retina and choroid is partially restored after vitrectomy.Keywords: idiopathic macular hole, multifocal electroretinogram, OCT-angiography, pars plana vitrectomy

Yuan Yang,1,2 Ting Cui,1 Zuoxiao Li,2 Jinglun Li,2 Ting Duan,3 Zhengzhou Yuan,2 Changyi Wang,1 Jincheng Wan,1 Cao Li,4 Shujiang Zhang,2 Ling Li,2 Fayun Hu,1 Bo Wu1 1Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Radiology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Bo Wu; Fayun Hu, Center of Cerebrovascular Diseases, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China, Tel +86-18980602142 ; +86-15902861270, Email dr.bowu@hotmail.com; hufayun2006@163.comObjective: This study examined the functional outcomes and safety of endovascular treatment (EVT) in acute ischemic stroke (AIS) patients owing to large vessel occlusion of the anterior circulation, presented during a late-time window (6– 24 hours after last seen well (LSW)) in a real-world practice.Methods: This was a retrospective analysis from a bi-center prospective cohort. According to the stroke treatment, patients with continuous Alberta Stroke Plan Early Aspect score (ASPECTS) ≥ 6 on non-contrast CT (NCCT) and moderate to good collateral state on CT angiography (CTA) were divided into EVT group and standard medical treatment (SMT) group. The primary outcome was the rate of functional independence (90-day mRS ≤ 2). Safety outcomes were the occurrence of symptomatic intracranial hemorrhage (sICH) and the 90-day mortality.Results: Among the 288 enrolled patients (53.5% male, median age 64 years), there were 167 patients in the EVT group and 121 in the SMT group. After multivariable adjustments for potential confounders, EVT was associated with functional independence (adjusted OR: 3.052; 95% confidence interval (CI): 1.553– 5.997; p = 0.001). In the PSM cohort, 44.2% (42/95) of patients in the EVT group versus 18.9% (18/95) in the SMT group achieved functional independence (OR: 3.39, 95% CI: 1.763– 6.517), and there was a significant difference favoring EVT over the SMT in the overall distribution of mRS (OR: 2.170, 95% CI: 1.302– 3.618) at 90 days. The rate of sICH did not differ between the EVT and SMT groups (10.5% vs 8.4%, p = 0.804) nor did 90-day mortality (18.9% vs 22.1%, p = 0.719). No interaction was found in p-values with statistical significance in subgroup analysis.Conclusion: This real-world experience suggests that EVT for late-presenting stroke patients, based on small core on NCCT and moderate to good collaterals on CTA, is associated with better outcomes than SMT alone, with no increase in sICH and 90-day mortality rates.Keywords: endovascular treatment, late time window, propensity score matching, real-world study

Mingcheng Huang,1,* Keping Wu,1,* Shan Zeng,2,* Wenfen Liu,1 Tianjiao Cui,1 Zhiqing Chen,1 Lian Lin,1 Dongying Chen,3 Hui Ouyang1 1Department of Nephrology, Kidney and Urology Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, ShenZhen, Guandong, People’s Republic of China; 2Department of Rheumatology, The First Affiliated Hospital of Jinan University, Guangzhou, Guandong, People’s Republic of China; 3Department of Rheumatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongying Chen; Hui Ouyang Email chendy3@mail.sysu.edu.cn; ouyh23@mail.sysu.edu.cnBackground: The aggressive phenotype of fibroblast-like synoviocytes (FLSs) is essential in the synovitis and bone destruction in rheumatoid arthritis (RA). Punicalagin is a natural polyphenol extracted in pomegranate juice, which possesses antioxidant, anti-inflammatory and anti-tumor properties suggesting it may be a potent drug for RA therapy. However, there is paucity of information on its effect in RA.Objective: To investigate the effects of punicalagin on synovial inflammation and bone destruction in RA.Methods: FLSs were isolated from synovial tissue of RA patients. The mRNA levels were evaluated by quantitative real-time PCR. Western blot was used for protein level measurements. The secretion of pro-inflammatory cytokines and metalloproteinases (MMPs) was detected by ELISA assays. Edu staining assays were carried out to investigate the proliferation of FLSs. Cell migration was assessed by Boyden chambers, wound scratch assays and F-actin staining in vitro. The intracellular translocation of nuclear factor kappa B (NF-κB) was investigated using immunofluorescence. The effects of punicalagin in vivo were measured by using collagen-induced arthritis (CIA) mice.Results: Punicalagin treatments significantly reduced the TNF-α induced expressions of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and IL-17A) and MMPs (MMP-1 and MMP-13) of RA FLSs. Punicalagin also suppressed the proliferation and migration of RA FLSs. Moreover, punicalagin (50mg/kg/d) alleviated arthritis severity and bone destruction, and decreased serum IL-6 and TNF-α in CIA mice. Further mechanism studies indicated that punicalagin blocked NF-κB activation via suppressing phosphorylation of IKK and IkBα, and preventing the translocation of 65.Conclusion: Our findings suggested that punicalagin might be one of natural therapeutic compounds for relieving RA progress via suppressing FLSs inflammation and migration through modulating NF-κB pathways.Keywords: rheumatoid arthritis, punicalagin, fibroblast-like synoviocytes, migration, pro-inflammatory cytokines

Yanjie Yang, Peisen Li, Yao Lin, Ziqi Li, Tianyi Cui, Zhenhua Song, Weixia Wu, Shuangyu Lv, Shaoping Ji Henan Provincial Engineering Centre for Tumor Molecular Medicine, Institute of Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng 475004, People’s Republic of ChinaCorrespondence: Shuangyu Lv; Shaoping JiSchool of Basic Medical Sciences, Henan University, Kaifeng 475004, People’s Republic of ChinaTel/Fax +86 371 2388 0585Email shuangyulv@henu.edu.cn; shaopingji@henu.edu.cnIntroduction: ZnO quantum dots (QDs) have drawn much attention recently as they are Cd-free, low-cost, and have excellent optical properties. With the expanded production and application of ZnO nanoparticles, concerns about their potential toxicity have also been raised.Materials and Methods: We used RNA sequencing (RNA-seq) to analyze the global gene expression of liver and lung tissues after ZnO QDs treatment. Differentially expressed genes (DEGs) were screened, with a fold change > 1.5 and padj < 0.05. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed, and padj < 0.05 was considered significantly enriched. The RNA-seq results were validated by quantitative real-time polymerase chain reaction (qRT-PCR).Results: A total of 47 and 218 genes were significantly differentially expressed in the liver and lung. Eight GO terms were enriched in the liver and lung, and retinol metabolism and the peroxisome proliferator-activated receptor (PPAR) signaling pathway were shared in different tissues.Discussion: According to DEGs and pathway enrichment analyses, inflammation might be induced in liver and lung tissues after intravenous injection of ZnO QDs. These findings will be helpful for future research and application of ZnO QDs.Keywords: ZnO QDs, transcriptome, differentially expressed genes

By directly altering microscopic interactions, pressure provides a powerful tuning knob for the exploration of condensed phases and geophysical phenomena1. The megabar regime represents an interesting frontier, in which recent discoveries include high-temperature superconductors, as well as structural and valence phase transitions2-6. However, at such high pressures, many conventional measurement techniques fail. Here we demonstrate the ability to perform local magnetometry inside a diamond anvil cell with sub-micron spatial resolution at megabar pressures. Our approach uses a shallow layer of nitrogen-vacancy colour centres implanted directly within the anvil7-9; crucially, we choose a crystal cut compatible with the intrinsic symmetries of the nitrogen-vacancy centre to enable functionality at megabar pressures. We apply our technique to characterize a recently discovered hydride superconductor, CeH9 (ref. 10). By performing simultaneous magnetometry and electrical transport measurements, we observe the dual signatures of superconductivity: diamagnetism characteristic of the Meissner effect and a sharp drop of the resistance to near zero. By locally mapping both the diamagnetic response and flux trapping, we directly image the geometry of superconducting regions, showing marked inhomogeneities at the micron scale. Our work brings quantum sensing to the megabar frontier and enables the closed-loop optimization of superhydride materials synthesis.

CdS, as an important photocatalytic degradation material, exhibits certain limitations. In our study, carbon nitride/cadmium sulfide (C3N5/CdS) nanocomposites were synthesized via an in-situ method, and the crystalline structure, composition, and morphology of the hybrid samples were evaluated using various techniques. The development of the Z-scheme heterojunction in the C3N5/CdS composite photocatalyst facilitated more effective separation of photogenerated charges, resulting in higher photocatalytic degradation efficiency. Under visible light irradiation at 425 nm, the composite with a 1:1 ratio exhibited the best degradation performance, achieving degradation rates of 93.8% for methyl orange solution and 96.8% for rhodamine B solution. Additionally, the introduction of C3N5 significantly reduced the photocorrosion of CdS. These experimental results were confirmed by fluorescence analysis, surface photovoltage (SPV) measurements, electrochemical tests, etc. [ABSTRACT FROM AUTHOR]

Air quality in subway systems is crucial as it affects the health of passengers and staff. Although most tests of PM2.5 concentrations in subway stations have taken place in public areas, PM2.5 is less understood in workplaces. Few studies have estimated the cumulative inhaled dose of passengers based on real-time changes in PM2.5 concentrations as they commute. To clarify the above issues, this study first measured PM2.5 concentrations in four subway stations in Changchun, China, where measuring points included five workrooms. Then, passengers' exposure to PM2.5 during the whole subway commute (20–30 min) was measured and segmented inhalation was calculated. The results showed that PM2.5 concentration in public places ranged from 50 to 180 μg/m3, and was strongly correlated with outdoors. While the PM2.5 average concentration in workplaces was 60 µg/m3, and it was less affected by outdoor PM2.5 concentration. Passenger's cumulative inhalations in single commuting were about 42 μg and 100 μg when the outdoor PM2.5 concentrations were 20–30 μg/m3 and 120–180 μg/m3, respectively. The PM2.5 inhalation in carriages accounted for the largest proportion of the entire commuting, about 25–40%, because of the longer exposure time and higher PM2.5 concentrations. It is recommended to improve the tightness of the carriage and filter the fresh air to improve the air quality inside. The average daily PM2.5 inhaled by staff was 513.53 μg, which was 5–12 times higher than that of passengers. Installing air purification devices in workplaces and reminding staff to take personal protection can positively protect their health. [ABSTRACT FROM AUTHOR]