1.Ferrum@albumin assembled nanoclusters inhibit NF-κB signaling pathway for NIR enhanced acute lung injury immunotherapy.
Xiaoxuan GUAN ; Binbin ZOU ; Weiqian JIN ; Yan LIU ; Yongfeng LAN ; Jing QIAN ; Juan LUO ; Yanjun LEI ; Xuzhi LIANG ; Shiyu ZHANG ; Yuting XIAO ; Yan LONG ; Chen QIAN ; Chaoyu HUANG ; Weili TIAN ; Jiahao HUANG ; Yongrong LAI ; Ming GAO ; Lin LIAO
Acta Pharmaceutica Sinica B 2025;15(11):5891-5907
Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe3O4 loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4+/CD8+ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.
2.Effects of pharyngeal cavity and mentolingual muscle exercise on polysomnography,cardiac function and MACE in patients with mild OSAHS left after palatopharyngoplasty with diastolic cardiac dysfunction
Sheng LI ; Mang XIAO ; Xiaohua JIANG ; Qingye YANG ; Jinshan LAN ; Hongjian LIAO ; Hongwei ZHANG ; Yin FU
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(7):461-466
OBJECTIVE To investigate the effect of pharyngeal cavity and genoglossus muscle exercises in patients with mild obstructive sleep apnea syndrome(OSAHS)left over after palatopharyngoplasty with diastolic cardiac dysfunction.METHODS A total of 75 patients with mild OSAHS left after palatopharyngoplasty with diastolic cardiac dysfunction from January 2021 to August 2023 were selected for retrospective study.Among them,37 patients underwent pharyngeal cavity and mentoglossum muscle exercise(observation group),while 38 patients did not(control group).Using postoperative data as baseline value.mean blood oxygen saturation(MSpO2),lowest oxygen saturation(LSpO2),sleep efficiency,apnea index(AI),sleep latency,apnea hypopnea index(AHI),hypopnea index(HI),microarousal index(MAI),rapid eye movement latency,arterial blood pressure of carbon dioxide(PaCO2),pH,arterial partial oxygen pressure(PaO2),left ventricular end-systolic diameter(LVDs),blood lactic acid,left ventricular ejection fraction(LVEF),Tei index,left ventricular end-diastolic diameter(LVDd),daytime Epworth sleepiness scale(ESS)score,Pittsburgh sleep quality index(PSQI)score and incidence of adverse cardiovascular events(MACE)were compared at baseline and 3 months later.RESULTS After 3 months,AHI,HI and AI in observation group were lower than those in control group,and MSpO2 and LSpO2 were higher than those in control group(P<0.05);Sleep efficiency of observation group was higher than control group,daytime ESS score,PSQI score and MAI were lower than control group(P<0.05).There were no significant differences in PaCO2,LVDd,PaO2,blood lactic acid,sleep latency,pH,LVEF,rapid eye movement latency,LVDd,Tei index between the observation group and the control group(P>0.05).The incidence of MACE in the observation group was 5.41%(2/37),compared with 13.16%(5/38)in the control group,there was no significant difference(P>0.05).CONCLUSION In patients with mild OSAHS left after palatopharyngoplasty with diastolic cardiac dysfunction,the exercise of pharyngeal cavity and genoglossus can improve hypopnea,alleviate clinical symptoms and improve sleep quality,but it has limited effect on the improvement of cardiac function.
3.Multi-omics analysis for ferroptosis-related genes as prognostic factors in cutaneous melanoma
Meng WU ; Ke LI ; Yangying LIAO ; Lan LI ; Xiao XIAO ; Yongjian CHEN ; Junweichen GUO ; Feng HU ; Jing QU ; Zheng WANG ; Hao FENG
Journal of Central South University(Medical Sciences) 2024;49(2):159-174
Objective:Melanoma is highly malignant and heterogeneous.It is essential to develop a specific prognostic model for improving the patients'survival and treatment strategies.Recent studies have shown that ferroptosis results from the overproduction of lipid peroxidation and is an iron-dependent form of programmed cell death.Despite this,ferroptosis-related genes(FRGs)and their clinical significances remain unknown in malignant melanoma.This study aims to assess the role of FRGs in melanoma,with the goal of developing a novel prognostic model that provides new insights into personalized treatment and improvement of therapeutic outcomes for melanoma. Methods:We systematically characterized the genetic alterations and mRNA expression of 73 FRGs in The Cancer Genome Atlas(TCGA)-skin cutaneous melanoma(SKCM)dataset in this study.The results were validated with real-time RT-PCR and Western blotting.Subsequently,a multi-gene feature model was constructed using the TCGA-SKCM cohort.Melanoma patients were classified into a high-risk group and a low-risk group based on the feature model.As a final step,correlations between ferroptosis-related signatures and immune features,immunotherapy efficacy,or drug response were analyzed. Results:By analyzing melanoma samples from TCGA-SKCM dataset,FRGs exhibited a high frequency of genetic mutations and copy number variations(CNVs),significantly impacting gene expression.Additionally,compared with normal skin tissue,30 genes with significantly differential expression were identified in melanoma tissues.A prognostic model related to FRGs,constructed using the LASSO Cox regression method,identified 13 FRGs associated with overall survival prognosis in patients and was validated with external datasets.Finally,functional enrichment and immune response analysis further indicated significant differences in immune cell infiltration,mutation burden,and hypoxia status between the high-risk group and the low-risk group,and the model was effective in predicting responses to immunotherapy and drug sensitivity. Conclusion:This study develops a strong ferroptosis-related prognostic signature model which could put forward new insights into target therapy and immunotherapy for patients with melanoma.
4.Application of different transbronchoscopic biopsies in the diagnosis of senile central lung cancer
Pei ZHAN ; Yu ZHANG ; Fei-Yan LAN ; Wei YANG ; Xiao-Shuang LIAO ; Zhi-Qiang TIAN
Journal of Regional Anatomy and Operative Surgery 2024;33(12):1081-1084
Objective To study the application value of different transbronchial biopsies in the diagnosis of central lung cancer in elderly patients.Methods The clinical data of 97 elderly patients with central lung cancer diagnosed by pathology from June 2020 to June 2023 in the 923rd Hospital of Chinese People's Liberation Army Joint Logistic Support Force were retrospectively analyzed.According to the different initial transbronchial biopsy methods,the patients were divided into the endobronchial biopsy(EBB)group(n=51)and the conventional transbronchial needle aspiration(cTBNA)group(n=46).The histopathological results were statistically analyzed,and the first biopsy positive rates of EBB and cTBNA in the diagnosis of senile central lung cancer were calculated and compared.At the same time,the differences of biopsy tolerance and complications between the two groups were evaluated.Results The squamous cell carcinoma proportions in both groups were over 50%.There was no significant difference in the first biopsy positive rate between the two groups(P>0.05).The incidence of temporary retreat of the scope due to subjective tolerance in the EBB group was higher than that in the cTBNA group,and the difference was statistically significant(P<0.05).There was a statistically significant difference in the incidence of intraoperative complications of different grades between the two groups(P<0.001).Among them,the incidence of grade 2 and above complications during surgery in the EBB group was significantly higher than that in the cTBNA group(P<0.001).Conclusion For elderly patients with central lung cancer,the success rate of the first biopsy of EBB and cTBNA is roughly equivalent,but the incidence of postoperative complications of the latter is significantly lower than that of the former.cTBNA can be used as the first biopsy method for this population.
5.Pathogenicity analysis of one isolate of avian infectious bronchitis virus from Hefei
Jianing LAN ; Xiyi BIAN ; Hao SHENG ; Peng XIAO ; Yan YAN ; Jiyong ZHOU ; Min LIAO
Chinese Journal of Veterinary Science 2024;44(9):1854-1864
To investigate the epidemiology of avian infectious bronchitis virus(IBV)and study the pathogenicity of IBV isolate,we isolated the IBV field strain from a clinical sample of chickens sus-pected to be infected with infectious bronchitis virus(IBV)from Hefei,Anhui Province,named HF210416.Sequencing analysis of the S1 gene showed that HF210416 belonged to the GI-22 geno-type,which was significantly differed from that of the reference GI-22-type strains,with homology ranging only from 84.5%to 87.8%.Recombinant analysis showed that HF210416 was a recombi-nant strain,with YX10(GI-19)as the major parent and YN(GI-19)as the minor parent.2-day-old SPF chicks infected with the HF210416 isolate showed clinical symptoms such as breathing with difficulty,depression and excreting watery droppings;the infected chicks had a rapid onset of dis-ease,with mortality occurring on the second day of inoculation,and mortality persisted until the fifth day,with 33.33%(5/15)mortality rate.The infected chicks recovered the 14th day after inoculation.RT-PCR detection of pharyngeal-anal swabs showed that the virus shedding by infected chicks could be continuously detected within 14 days of the test period;Enlarged and pale kidney as well as urate deposition in the kidney were observed in infected dead and undead chicks;and the HE staining of histopathological slices showed that the cilia of trachea were removed.Immunohis-tochemistry showed that obvious viral signals were observed in the trachea,lungs,and kidneys.The viral load of various tissues was detected by RT-qPCR and it showed that HF210416 had the high-est replication efficiency in kidney tissues,then in cecum tonsils and trachea.The results of serum neutralization test showed that HF210416 had a better neutralization effect on GI-22 homologous strains,but poorer neutralization effect on other genotypes strains,suggesting that HF210416 is not suitable for vaccine candidate.In conclusion,the GI-22 isolate HF210416 is highly pathogenic and nephrotropic to chicks,and its genomic genetic characteristics and immunogenicity are differ-ent from those of other strains.This study enriches the resources of IBV strains and provides refer-ence data for understanding of the prevalence and pathogenicity of GI-22 genotypes in China.
6.Genetic Mutation Profile and Risk Stratification of Cytogenetically Normal Acute Myeloid Leukemia with CEBPA-bZIP Mutations Based on Multi-Gene Sequencing
Lei-Ming CAO ; Ming-Yue LIAO ; Ya-Lan ZHOU ; Hao JIANG ; Qian JIANG ; Ying-Jun CHANG ; Lan-Ping XU ; Xiao-Hui ZHANG ; Xiao-Jun HUANG ; Guo-Rui RUAN
Journal of Experimental Hematology 2024;32(6):1631-1637
Objective:To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with CEBPA-bZIP mutation. Methods:Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with CEBPA-bZIP mutation. The nomogram model for leukemia-free survival (LFS) rate was generated by combining genetic abnormalities and clinical data. Risk stratification was conducted based on prognostic variables and the effect of risk-adjusted consolidation therapy was investigated by Kaplan-Meier method. Results:Four variables were finally included in our nomogram model after multivariate Cox analysis,and an equation for risk score calculation was obtained,risk score=1.3002×white blood cell (WBC) (≥18.77×109/L)+1.4065×CSF3R mutation positive+2.6489×KMT2A mutation positive+1.0128×DNA methylation-related genes mutation positive. According to the nomogram model,patients were further divided into low-risk group (score=0,n=46) and high-risk group (score>0,n=95). Prognostic analysis showed that the 5-year LFS rate,5-year overall survival (OS) rate,and 5-year cumulative incidence of relapse (CIR) of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the high-risk group were 93.5%,97.1%,and 3.5%,while those in patients who received maintenance chemotherapy were 32.9%,70.5%,and 63.4%,respectively. The differences were statistically significant (all P<0.05). Allo-HSCT could significantly improve the prognosis of patients in high-risk group. However,no corresponding benefit was observed in the low-risk group. Conclusion:Adult CN-AML with CEBPA-bZIP mutation has a complex co-mutation pattern. The nomogram model based on mutations of CFS3R,KMT2A and DNA methylation-related genes together with WBC count can further divide this subset of patients into a relatively low-risk group and a relatively high-risk group. For individuals in the high-risk group,allo-HSCT is proposed as post-remission therapy. The above data will benefit the prognosis estimation and treatment decision for adult CN-AML with CEBPA-bZIP mutation.
7.Interactions Between Astrocytes and Oligodendroglia in Myelin Development and Related Brain Diseases.
Xuelian HU ; Guangdan YU ; Xiang LIAO ; Lan XIAO
Neuroscience Bulletin 2023;39(3):541-552
Astrocytes (ASTs) and oligodendroglial lineage cells (OLGs) are major macroglial cells in the central nervous system. ASTs communicate with each other through connexin (Cx) and Cx-based network structures, both of which allow for quick transport of nutrients and signals. Moreover, ASTs interact with OLGs through connexin (Cx)-mediated networks to modulate various physiological processes in the brain. In this article, following a brief description of the infrastructural basis of the glial networks and exocrine factors by which ASTs and OLGs may crosstalk, we focus on recapitulating how the interactions between these two types of glial cells modulate myelination, and how the AST-OLG interactions are involved in protecting the integrity of the blood-brain barrier (BBB) and regulating synaptogenesis and neural activity. Recent studies further suggest that AST-OLG interactions are associated with myelin-related diseases, such as multiple sclerosis. A better understanding of the regulatory mechanisms underlying AST-OLG interactions may inspire the development of novel therapeutic strategies for related brain diseases.
Humans
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Myelin Sheath
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Astrocytes
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Oligodendroglia
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Brain
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Brain Diseases
8.Expert consensus on clinical application of Lixuwang~® Xuesaitong Soft Capsules.
Min JIA ; Xiao LIANG ; Guo-Jing FU ; Xiang-Lan JIN ; Yan LU ; Xing LIAO ; Yun-Ling ZHANG
China Journal of Chinese Materia Medica 2023;48(20):5668-5674
Lixuwang~® Xuesaitong Soft Capsules(referred to as "Xuesaitong Soft Capsules") have the effects of promoting blood circulation, resolving blood stasis, and dredging meridians and collaterals. They are widely used in the prevention and treatment of cardiovascular and cerebrovascular diseases in clinical practice. Through years of clinical observation, they have shown significant efficacy in ischemic stroke, coronary heart disease, and other diseases, and have been recommended by multiple guidelines, consensus statements, and monographs. Based on the summary of clinical application experience by doctors and existing evidence-based research, following the Technical Specifications for Consensus Development of Chinese Patent Medicine by Clinical Experts issued by Standardization Office of the Chinese Association of Traditional Chinese Medicine, a nominal group method was used to reach 19 recommended opinions/consensus suggestions. This document proposes the timing of medication, syndrome differentiation for medication, therapeutic effects, dosage and administration, treatment duration, economic considerations, and safety considerations in the use of Xuesaitong Soft Capsules for the treatment of ischemic stroke and angina pectoris in coronary heart disease. It is intended for doctors in internal medicine, encephalopathy(neurology), cardiovascular medicine, geriatrics, emergency medicine, general practice, and traditional Chinese medicine departments of various medical institutions, as well as pharmacists in hospitals and pharmacies, as a medication reference when using Xuesaitong Soft Capsules. It is hoped that the widespread application of this consensus can improve the clinical efficacy of Xuesaitong Soft Capsules in the treatment of ischemic stroke and coronary heart disease, promote rational drug use, and reduce medication risks. This consensus has been reviewed and published by the China Association of Traditional Chinese Medicine, with the identification number GS/CACM 323-2023.
Humans
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Consensus
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Drugs, Chinese Herbal/therapeutic use*
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Medicine, Chinese Traditional
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Coronary Disease/drug therapy*
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Ischemic Stroke/drug therapy*
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Capsules
9.Comparison of the myopia control effects of orthokeratology lens and peripheral defocus spectacles
Yan-Ling LI ; Wang-Ming SU ; Xiao-Hui HE ; Xiao-Lan LIAO ; Ping XIE
International Eye Science 2023;23(11):1887-1890
AIM: To investigate the effect of peripheral defocus spectacles and orthokeratology lenses on the control of axial length in children and adolescents with myopia.METHODS: Prospective study. A total of 71 cases(134 eyes)of children and adolescents with myopia who visited the Second Hospital of Longyan from June 2019 to June 2021 were selected. They were fitted with peripheral defocus spectacles for 12mo and then switched to orthokeratology lenses. The growth of axial length was observed at 3, 6, and 12mo after wearing peripheral defocus spectacles and orthokeratology lenses.RESULTS: The median axial length growth after wearing peripheral defocus spectacles and orthokeratology lenses for 12mo was 0.35 and 0.14mm, respectively. The axial growth at 3, 6, and 12mo after wearing orthokeratology lenses was lower than those after wearing peripheral defocus spectacles(P<0.001), and the growth rate of axial length was significantly reduced. The patients were divided into a rapid progression group(axial growth ≥0.4 mm, 29 cases, 54 eyes)and a non-rapid progression group(axial growth <0.4mm, 42 cases, 80 eyes)according to the axial growth of peripheral defocus spectacles for 12mo. The median axial growth after wearing peripheral defocus spectacles for 12mo in the two groups was 0.70 and 0.24mm, respectively, while the median axial growth after wearing orthokeratology lenses was 0.31 and 0.09mm, respectively. The growth rate was reduced by 56% and 63% respectively in the two groups after wearing orthokeratology lens. The axial growth of cases wearing orthokeratology lenses for 12mo in the non-rapid progression group was lower than that in the rapid progression group, and it did not change with age or diopter. There was no significant difference among different ages and different diopters in the rapid progression group(P>0.05). In the non-rapid progression group, axial growth of cases aged 7-12 years was higher than those aged 13-16 years(P<0.05), but there was no significant difference among different diopters(P>0.05).CONCLUSION: Orthokeratology lens is more effective than peripheral defocus spectacles in controlling axial growth in children and adolescents with myopia, and the control effect of orthokeratology lens on rapid-progressing myopia is remarkable.
10.Enrichment of Wee1/CDC2 and NF-κB Signaling Pathway Constituents Mutually Contributes to CDDP Resistance in Human Osteosarcoma
Zhengbo HU ; Lugen LI ; Wenxing LAN ; Xiao WEI ; Xiangyuan WEN ; Penghuan WU ; Xianliao ZHANG ; Xinhua XI ; Yufa LI ; Liqi WU ; Wenhu LI ; Xiaohong LIAO
Cancer Research and Treatment 2022;54(1):277-293
Purpose:
Osteosarcoma (OS) universally exhibits heterogeneity and cisplatin (CDDP) resistance. Although the Wee1/CDC2 and nuclear factor кB (NF-κB) pathways were reported to show abnormal activation in some tumor cells with CDDP resistance, whether there is any concrete connection is currently unclear. We explored it in human OS cells.
Materials and Methods:
Multiple OS cell lines were exposed to a Wee1 inhibitor (AZD1775) and CDDP to assess the half-maximal inhibitory concentration values. Western blot, coimmunoprecipitation, confocal immunofluorescence, cell cycle, and Cell Counting Kit-8assays were performed to explore the connection between the Wee1/CDC2 and NF-κB pathways and their subsequent physiological contribution to CDDP resistance. Finally, CDDP-resistant PDX-OS xenograft models were established to confirm that AZD1775 restores the antitumor effects of CDDP.
Results:
A sensitivity hierarchy of OS cells to CDDP and AZD1775 exists. In the highly CDDP-tolerant cell lines, Wee1 and RelA were physically crosslinked, which resulted in increased abundance of phosphorylated CDC2 (Y15) and RelA (S536) and consequent modulation of cell cycle progression, survival, and proliferation. Wee1 inhibition restored the effects of CDDP on these processes in CDDP-resistant OS cells. In addition, animal experiments with CDDP-resistant PDX-OS cells showed that AZD1775 combined with CDDP not only restored CDDP efficacy but also amplified AZD1775 in inhibiting tumor growth and prolonged the median survival of the mice.
Conclusion
Simultaneous enrichment of molecules in the Wee1/CDC2 and NF-κB pathways and their consequent coactivation is a new molecular mechanism of CDDP resistance in OS cells. OS with this molecular signature may respond well to Wee1 inhibition as an alternative treatment strategy.

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