摘要：
Sepsis-associated acute respiratory distress syndrome (ARDS) is a heterogeneous disease with high morbidity and mortality. Lactylation plays a crucial role in sepsis and sepsis-induced lung injury. This study aimed to identify distinct lactylation-based phenotypes in patients with sepsis-associated ARDS and determine relevant molecular biomarkers. We analyzed blood transcriptome and clinical data from patients with sepsis-associated ARDS and calculated the lactylation activity. KEGG pathway analysis, drug sensitivity prediction, and immune cell infiltration analysis were performed. Candidate molecular biomarkers were identified by intersecting the feature genes extracted from four machine learning models. Lactylation activity showed significant heterogeneity among patients with sepsis-associated ARDS, which enabled the classification into low- and high-lactylation activity phenotypes. Patients with high-lactylation experienced longer hospital stays and higher mortality rates, as well as distinct signaling pathways, drug responses, and circulating immune cell abundances. Six key markers (ALDOB, CCT5, EP300, PFKP, PPIA, and SIRT1) were identified to differentiate the two lactylation activity phenotypes, all significantly correlated with circulating immune cell populations. This study revealed significant heterogeneity in lactylation activity phenotypes among patients with sepsis-associated ARDS and identified potential biomarkers to facilitate the application of these phenotypes in clinical practice.
摘要：
Peptides exhibit various biological activities, including biorecognition, cell targeting, and tumor penetration, and can stimulate immune cells to elicit immune responses for tumor immunotherapy. Peptide self-assemblies and peptide-functionalized nanocarriers can reduce the effect of various biological barriers and the degradation by peptidases, enhancing the efficiency of peptide delivery and improving antitumor immune responses. To date, the design and development of peptides with various functionalities have been extensively reviewed for enhanced chemotherapy; however, peptide-mediated tumor immunotherapy using peptides acting on different immune cells, to the knowledge, has not yet been summarized. Thus, this work provides a review of this emerging subject of research, focusing on immunomodulatory anticancer peptides. This review introduces the role of peptides in the immunomodulation of innate and adaptive immune cells, followed by a link between peptides in the innate and adaptive immune systems. The peptides are discussed in detail, following a classification according to their effects on different innate and adaptive immune cells, as well as immune checkpoints. Subsequently, two delivery strategies for peptides as drugs are presented: peptide self-assemblies and peptide-functionalized nanocarriers. The concluding remarks regarding the challenges and potential solutions of peptides for tumor immunotherapy are presented. This work introduces the role of peptides in immune regulation of innate and adaptive immune cells, as well as immune checkpoints. Then this work introduces two strategies for delivering polypeptides: peptide self-assemblies, and peptide-functionalized nanocarriers. Finally, the challenges and prospects of peptides in tumor immunotherapy are summarized. image
通讯机构：
[Tan, XF; Yang, QL ; Chen, GD; Wu, GL] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Hepatopancreatobiliary Surg, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Sch Pharmaceut Sci, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, NHC Key Lab Birth Defect Res & Prevent, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.
摘要：
The advancement of mitochondria-targeted near-infrared-II (NIR-II) excitable phototheranostics constitutes a promising strategy for improving fluorescence-image-guided cancer phototherapy. However, developing phototheranostic agents that simultaneously combine high-contrast NIR-II fluorescence imaging with effective multimodal therapeutic techniques remains a substantial challenge. Herein, we reported a shielding-donor–acceptor–donor-shielding structured NIR-II phototheranostic (FCD-T) by a molecular engineering strategy, followed by self-assembly with glutathione-responsive copolymer to form FCD-T nanoparticles. The introduction of functional bithiophene endows FCD-T with significant electron-donating properties and reduces intermolecular π-π stacking interactions. The robust π-conjugation of fluorene with good rigidity would enhance the intramolecular charge transfer capability. Therefore, FCD-T NPs exhibited an NIR-II absorption peak at 1075 nm and an emission peak at 1280 nm. Upon NIR-II light excitation, such nanoparticles could generate excellent photothermal and photodynamic performances with good biocompatibility. Moreover, the NIR-II mitochondria-targeted phototherapy further facilitated mitochondrial apoptosis-related pathways, activating antitumor immunity and inhibiting tumor growth with single irradiation at low doses.
The advancement of mitochondria-targeted near-infrared-II (NIR-II) excitable phototheranostics constitutes a promising strategy for improving fluorescence-image-guided cancer phototherapy. However, developing phototheranostic agents that simultaneously combine high-contrast NIR-II fluorescence imaging with effective multimodal therapeutic techniques remains a substantial challenge. Herein, we reported a shielding-donor–acceptor–donor-shielding structured NIR-II phototheranostic (FCD-T) by a molecular engineering strategy, followed by self-assembly with glutathione-responsive copolymer to form FCD-T nanoparticles. The introduction of functional bithiophene endows FCD-T with significant electron-donating properties and reduces intermolecular π-π stacking interactions. The robust π-conjugation of fluorene with good rigidity would enhance the intramolecular charge transfer capability. Therefore, FCD-T NPs exhibited an NIR-II absorption peak at 1075 nm and an emission peak at 1280 nm. Upon NIR-II light excitation, such nanoparticles could generate excellent photothermal and photodynamic performances with good biocompatibility. Moreover, the NIR-II mitochondria-targeted phototherapy further facilitated mitochondrial apoptosis-related pathways, activating antitumor immunity and inhibiting tumor growth with single irradiation at low doses.
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通讯机构：
[Tan, XF; Yang, QL ; Wu, GL] U;Univ South China, Affiliated Hosp 1, Dept Hepatopancreatobiliary Surg, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Canc Res Inst, Ctr Mol Imaging Probe, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, NHC Key Lab Birth Defect Res & Prevent, Hengyang 421001, Hunan, Peoples R China.;Univ South China, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.
关键词：
NIR-II;Phototheranostics;Endoplasmic reticulum;Triple-negative breast cancer;Intermolecular π–π stacking interaction
摘要：
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by an extremely poor prognosis. Photoimmunotherapy has emerged as a promising strategy for the treatment of TNBC. This approach works by selectively destroying tumor cells, releasing tumor-associated antigens, activating the immune system, and effectively inhibiting tumor proliferation and metastasis. However, the majority of current phototheranostic approaches are hindered by limited tissue penetration in the first near-infrared (NIR-I) and ultraviolet-visible (UV-Vis) regions. Additionally, due to the lack of specific subcellular targets, it may be difficult to effectively treat deep-seated lesions with ambiguous and extensive boundaries caused by TNBC metastases. Consequently, the development of effective, deep-penetrating, organelle-targeted phototheranostics is essential for enhancing treatment outcomes in TNBC. This work proposes a novel molecular design strategy of NIR-II phototheranostics to realize planar rigid conjugation and alkyl chain functionalization. The di-hexaalkyl chains in a vertical configuration on the donor (4H-cyclopenta[2,1-b:3,4-b'] dithiophene) and shielding units (fluorene) are introduced to construct a S-D-A-D-S type NIR-II phototheranostics (IR-FCD). The planar and rigid structure of IR-FCD exhibits a robust intramolecular charge transfer capability, a lower band gap, enhanced photon absorption properties, and significant steric hindrance from vertically arranged alkyl chains to minimize non-radiative energy loss. By incorporating N-(but-3-yn-1-yl)-4-methylbenzenesulfonamide at the terminus of an elongated alkyl chain, followed by self-assembly into DSPE-S-S-PEG2000, NIR-II excitable phototheranostics (IR-FCD-Ts NPs) with endoplasmic reticulum (ER) targeting capability were successfully synthesized for imaging-guided photoimmunotherapy of TNBC. The IR-FCD-Ts NPs demonstrate exceptional optical characteristics, with maximum absorption at 1068nm (extending to 1300nm) and emission at 1273nm (extending to 1700nm), along with a high molar absorption coefficient of 2.76*10(4)L/mol·c at 1064nm in aqueous solution. Under exposure to 1064nm laser irradiation, IR-FCD-Ts NPs exhibit superior photothermal properties and have the potential for photodynamic therapy. By targeting ER, thereby inducing ER stress and significantly enhancing immunogenic cell death (ICD) in tumor cells, it triggers a strong antitumor immune response and inhibits the proliferation and metastasis of TNBC.
期刊：
Brain and Behavior,2025年15(1):e70245- ISSN：2162-3279
通讯作者：
Xiao, ZJ
作者机构：
[Deng, Limin; Lin, Shudong; Xie, Juan; Chen, Shuangxi; Liu, Guozhi; Xiao, Zijian; Wen, Xuanwei; Li, Sijing; Zhu, Guanghua; Wang, Feiyan; Xiao, ZJ] Univ South China, Affiliated Hosp 1, Multi Res Ctr Brain Disorders, Hengyang Med Sch,Dept Neurol, Hengyang, Hunan, Peoples R China.;[Deng, Limin; Lin, Shudong; Chen, Shuangxi; Liu, Guozhi; Xiao, Zijian; Wen, Xuanwei; Li, Sijing; Zhu, Guanghua; Wang, Feiyan; Xiao, ZJ] Univ South China, Clin Res Ctr Immune Related Encephalopathy Hunan P, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Xie, Juan] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Emergency, Hengyang, Hunan, Peoples R China.
通讯机构：
[Xiao, ZJ ] U;Univ South China, Affiliated Hosp 1, Multi Res Ctr Brain Disorders, Hengyang Med Sch,Dept Neurol, Hengyang, Hunan, Peoples R China.;Univ South China, Clin Res Ctr Immune Related Encephalopathy Hunan P, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.
关键词：
cerebral amyloid angiopathy (CAA);curcumin;learning and memory;necroptosis;neuroinflammation
摘要：
BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) is recognized as a major contributor to progressive cognitive decline and cerebral hemorrhages in the elderly population. Currently, there is a global shortage of safe and effective treatments for this condition. Bisdemethoxycurcumin (BDMC) has been demonstrated to exhibit pharmacological effects with anti-Aβ toxicity properties. Thus, the present study mainly focused on the potential therapeutic effects of BDMC on CAA. METHOD: The 30 male C57BL/6 mice were subjected to chronic treatment with five vascular risk factors (lipopolysaccharide, social stress, streptozotocin, high-cholesterol diet, and copper-containing drinking water) for 35 weeks to establish a CAA mouse model. Of these, 15 CAA mice received oral administration of BDMC (50mg/kg) for two consecutive weeks as an intervention, while the remaining 15 CAA mice received an equal volume of physiological saline by gavage. The study observed the levels of Aβ40 and proinflammatory factors in brain tissue and plasma, Aβ deposition in cerebral blood vessels, microbleeds in brain tissue, expression of proteins related to the cGAS/STING signaling pathway in brain tissue, as well as the contents of p-RIPK-1, p-RIPK-3, p-MLKL, neuronal morphology, and learning and memory abilities in mice. RESULT: The therapeutic administration of BDMC demonstrates a pronounced efficacy in alleviating Aβ burden and cerebral microbleeding in CAA mice, concurrently enhancing learning and memory capabilities. Interestingly, BDMC may inhibits neuroinflammatory responses by reducing the expression of cGAS/STING signaling pathway proteins and suppresses necroptosis. CONCLUSION: Our research findings demonstrate that BDMC exerts therapeutic effects in a mouse model of CAA established through chronic treatment involving five vascular risk factors.
摘要：
The Omicron BA.2.86 subvariants, JN.1, KP.2, and KP.3, have become predominant globally, raising concerns about their immune evasion from vaccines and monoclonal antibody (mAb) treatments. These variants harbor more receptor-binding domain (RBD) mutations than the XBB and EG.5 sub-lineages, which are already known to compromise vaccine and therapeutic efficacy. We evaluated sera from individuals vaccinated with inactivated vaccines, with or without breakthrough infections, as well as COVID-19 convalescents. Our results showed a substantial decrease in serum neutralizing activity against the JN.1, KP.2, XBB.1.5, and EG.5.1 variants compared to BA.2. Additionally, we developed 19 neutralizing antibodies from memory B cells, with some retaining efficacy against earlier Omicron variants. However, potency was notably diminished against newer subvariants like BF.7, BQ.1, XBB.1.5, and BA.2.86. Of mAbs, those isolated from COVID-19 convalescents, particularly SA-3, exhibited exceptional potency across ten variants from BA.2 to KP.2, with IC50 values ranging from 0.006 to 2.546 μg/mL. However, SA-3 had lost neutralizing activity against the KP.3 due to the Q493E mutation, but the KP.3 became susceptible to neutralization by the other mAb, SA-6. In contrast, SA-6 was unable to neutralize KP.2 because of the presence of R346T mutation. Our findings underscore the importance of continuous surveillance of viral evolution and the need for updated vaccines and therapeutics to combat the ongoing evolution of SARS-CoV-2, particularly in the context of emerging variants that escape both vaccine-induced immunity and monoclonal antibody treatments.
The Omicron BA.2.86 subvariants, JN.1, KP.2, and KP.3, have become predominant globally, raising concerns about their immune evasion from vaccines and monoclonal antibody (mAb) treatments. These variants harbor more receptor-binding domain (RBD) mutations than the XBB and EG.5 sub-lineages, which are already known to compromise vaccine and therapeutic efficacy. We evaluated sera from individuals vaccinated with inactivated vaccines, with or without breakthrough infections, as well as COVID-19 convalescents. Our results showed a substantial decrease in serum neutralizing activity against the JN.1, KP.2, XBB.1.5, and EG.5.1 variants compared to BA.2. Additionally, we developed 19 neutralizing antibodies from memory B cells, with some retaining efficacy against earlier Omicron variants. However, potency was notably diminished against newer subvariants like BF.7, BQ.1, XBB.1.5, and BA.2.86. Of mAbs, those isolated from COVID-19 convalescents, particularly SA-3, exhibited exceptional potency across ten variants from BA.2 to KP.2, with IC50 values ranging from 0.006 to 2.546 μg/mL. However, SA-3 had lost neutralizing activity against the KP.3 due to the Q493E mutation, but the KP.3 became susceptible to neutralization by the other mAb, SA-6. In contrast, SA-6 was unable to neutralize KP.2 because of the presence of R346T mutation. Our findings underscore the importance of continuous surveillance of viral evolution and the need for updated vaccines and therapeutics to combat the ongoing evolution of SARS-CoV-2, particularly in the context of emerging variants that escape both vaccine-induced immunity and monoclonal antibody treatments.
作者机构：
[Li, Shuihong; Zhang, Ru; Zuo, Yingying] Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, SH ] U;Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.
关键词：
M. pneumoniae;MAPK;NF-κB;RAW264.7;rMPN606
摘要：
Mycoplasma pneumoniae ( M. pneumoniae ) is one of the major pathogens causing community-acquired pneumonia (CAP), and its pathogenic mechanism is not fully understood. Inflammatory response is the most basic and common pathological phenomenon of CAP, but the specific mechanism needs further investigation. In this study, the inflammatory action of M. pneumoniae MPN606 protein was confirmed and its molecular mechanism was tentatively investigated. Compared with the control group treated with PBS, stimulation of RAW264.7 cells with rMPN606 can promote the release of NO, increase the expression level of TNF-α and IL⁃6 cytokines, and up-regulate the mRNA transcription levels of iNOS, IL-6 and TNF-α in RAW264.7 cells. In addition, rMPN606 also significantly induced the expression of iNOS protein in RAW264.7 cells, resulting in increased phosphorylation levels of p65, p38 and ERK proteins. The results of cellular immunofluorescence showed that NF-κB was transferred from cytoplasm to nucleus of RAW264.7 cells after stimulation with rMPN606, and nuclear translocation of NF-κB was significantly enhanced. These results indicate that Mycoplasma pneumoniae MPN606 induces M1-type activation of macrophages and secretes pro-inflammatory factors by activating NF-κB and MAPK pathways.
Mycoplasma pneumoniae ( M. pneumoniae ) is one of the major pathogens causing community-acquired pneumonia (CAP), and its pathogenic mechanism is not fully understood. Inflammatory response is the most basic and common pathological phenomenon of CAP, but the specific mechanism needs further investigation. In this study, the inflammatory action of M. pneumoniae MPN606 protein was confirmed and its molecular mechanism was tentatively investigated. Compared with the control group treated with PBS, stimulation of RAW264.7 cells with rMPN606 can promote the release of NO, increase the expression level of TNF-α and IL⁃6 cytokines, and up-regulate the mRNA transcription levels of iNOS, IL-6 and TNF-α in RAW264.7 cells. In addition, rMPN606 also significantly induced the expression of iNOS protein in RAW264.7 cells, resulting in increased phosphorylation levels of p65, p38 and ERK proteins. The results of cellular immunofluorescence showed that NF-κB was transferred from cytoplasm to nucleus of RAW264.7 cells after stimulation with rMPN606, and nuclear translocation of NF-κB was significantly enhanced. These results indicate that Mycoplasma pneumoniae MPN606 induces M1-type activation of macrophages and secretes pro-inflammatory factors by activating NF-κB and MAPK pathways.
作者机构：
[Zeng, Chenlu; Xie, Hailong; Li, Junru; Song, Ge; Liu, Jiajia; Xie, HL] Univ South China, Canc Res Inst Hengyang Med Coll, Key Lab Canc Cellular & Mol Pathol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Zhao, Juanxia] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Coll, Dept Pathol, Hengyang, Hunan, Peoples R China.;[Liu, Bin] Hunan Univ, Coll Biol, Changsha, Hunan, Peoples R China.;[Fan, Jialong; Fan, JL] Changsha Med Univ, Hunan Prov Key Lab Res & Dev Novel Pharmaceut Prep, Changsha 410219, Peoples R China.
通讯机构：
[Fan, JL ] C;[Xie, HL ] U;Univ South China, Canc Res Inst Hengyang Med Coll, Key Lab Canc Cellular & Mol Pathol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;Changsha Med Univ, Hunan Prov Key Lab Res & Dev Novel Pharmaceut Prep, Changsha 410219, Peoples R China.
关键词：
Exosomes;digestive system tumors;drug delivery;tumor therapy;exosome source
摘要：
Digestive system tumors constitute a major subset of malignancies, consistently ranking among the leading causes of mortality globally. Despite limitations inherent in current therapeutic modalities, recent advancements in targeted therapy and drug delivery systems have led to significant improvements in the efficacy of pharmacotherapy for digestive system tumors. In this context, exosomes - naturally occurring nanoscale vesicles - have emerged as promising drug delivery candidates due to their intrinsic molecular transport capabilities, superior biocompatibility, and targeted recognition of tumor cells. The integration of exosomes into cancer therapeutics represents a novel and potentially transformative approach for treating digestive system tumors, which may drive further progress in this field. This review comprehensively examines the sources, loading mechanisms, and therapeutic efficacy of exosomes in the context of digestive system tumor treatment. Furthermore, it discusses the opportunities and challenges associated with exosomes, offering insights into their future role within the therapeutic armamentarium against digestive tumors.
期刊：
JOURNAL OF GLOBAL HEALTH,2025年15:04001 ISSN：2047-2978
通讯作者：
Zhang, YP
作者机构：
[Zhuang, Xinqi; Lei, Xiaoyu; Zhang, Yin-Ping; Zhang, YP; Zhang, Dandan; Zhang, Jianzhong] Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Nursing, West Yanta Rd 76, Xian 710061, Shaanxi, Peoples R China.;[Zhang, Dandan] Univ South China, Affiliated Nanhua Hosp, Inst Clin Res, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Liu, Fen] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Gynecol & Obstet, Hengyang, Hunan, Peoples R China.;[Cui, Tianxin] Univ Edinburgh, Sch Hlth Social Sci, Edinburgh, Scotland.
通讯机构：
[Zhang, YP ] X;Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Nursing, West Yanta Rd 76, Xian 710061, Shaanxi, Peoples R China.
摘要：
BACKGROUND: As fertility rates decline and population ageing intensifies, the conflict between career and childbearing continues to impact clinicians, especially women. Exploring gender differences in the fertility intentions of male and female clinicians could help with identifying barriers to childbearing, developing effective policies to support work-life balance, and addressing the gap in research on gender disparities in this field. METHODS: We conducted a cross-sectional survey among health care personnel in Chinese public hospitals. Through cluster sampling from highly active WeChat groups, we gathered 698 responses from clinicians to the third fertility intention questionnaire online. We then used descriptive statistics and χ(2) tests for analysis. RESULTS: Men (28.28%) had higher intentions of having a third child than women (20.71%) (P = 0.013). In terms of reasons, female clinicians were more concerned than male clinicians about the impact on their career development (P = 0.002), difficulties in job hunting (P = 0.039), and physical injuries caused by multiple births (P < 0.001), and whether the elderly can help (P = 0.001). Conversely, men's apprehensions centred on economic factors such as real house costs (P < 0.001), policy support (P = 0.036), and wives' disagreement (P < 0.001). In discussing governmental interventions, men showed a higher level of interest in policies related to child care (P < 0.001), employment stability for women (P < 0.001), extended maternity leave (P < 0.001), and financial assistance than women (P < 0.001). CONCLUSIONS: Our findings show substantial gender-specific differences in third-child fertility intentions among clinicians. To address this, the government should consider divisions in family roles, future societal needs, and women's career development. Policies should focus on balancing work and family by offering affordable childcare, flexible parenting leave, financial incentives, and career support, ensuring childbirth does not negatively impact women's professional growth, and fostering gender equality in parenting.
摘要：
Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
关键词：
Drug reposition;Enrichment score;Immunoregulation;LINCS;Lenalidomide;Radioprotection
摘要：
Ionizing radiation induces DNA damage and impairs genomic integrity, leading to cell death and tissue injuries or carcinogenesis. Medical radiation protectors are essential and necessary. However, there are limited radioprotectors in clinics, which can't meet the growing demand for countering radiation emergencies. Traditional drug discovery approach has been proven expensive and risky. Computational drug repositioning provides an attractive strategy for radioprotector discovery. Here we constructed a systematic workflow to identify repositioning radioprotectors by comparison of biosimilarity between γ-ray and known medicines characterized by gene expression signatures from GEO and LINCS. Using enrichment scoring, medicines with negative scores were considered as candidates of revising or mitigating radiation injuries. Seven approved medicines were identified, and their targets enriched in steroid and estrogen metabolic, chemical carcinogenesis associated pathways. Lenalidomide, an approved medicine for multiple myeloma and anemia, was further verified as a promising potential radioprotector. It increases survival of mice after lethal doses of irradiation by alleviating bone marrow and intestinal injury in vivo, and inhibits apoptosis of cultured irradiated AHH- 1 and IEC- 6 cells in vitro. This study introduces rational drug repositioning to radiation medicine and provides viable candidates for radioprotective therapeutic regimens.
期刊：
Molecular and Cellular Biochemistry,2025年480(4):2143-2157 ISSN：0300-8177
通讯作者：
Jing Wang
作者机构：
[Tingting Jiang] Department of Clinical Laboratory, Hengyang Medical School, the Affiliated Nanhua Hospital, University of South China, Hengyang, 421000, China;[Qun Zeng] Department of Biochemistry and Molecular Biology, Hengyang Medical School, University of South China, Hengyang, 421000, China;[Jing Wang] Hunan Provincial Key Laboratory of the Traditional Chinese Medicine Agricultural Biogenomics, Changsha Medical University, Changsha, 410219, China. 805598382@qq.com;[Jing Wang] Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research On Functional Nucleic Acid, Changsha Medical University, Changsha, 410219, China. 805598382@qq.com;[Jing Wang] The First Clinical College, Changsha Medical University, Changsha, 410219, China. 805598382@qq.com
通讯机构：
[Jing Wang] H;Hunan Provincial Key Laboratory of the Traditional Chinese Medicine Agricultural Biogenomics, Changsha Medical University, Changsha, China<&wdkj&>Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research On Functional Nucleic Acid, Changsha Medical University, Changsha, China<&wdkj&>The First Clinical College, Changsha Medical University, Changsha, China
摘要：
FHL2 (Four-and-a-half LIM domain protein 2) is a crucial factor involved in cardiac morphogenesis, the process by which the heart develops its complex structure. It is expressed in various tissues during embryonic development, including the developing heart, and has been shown to play important roles in cell proliferation, differentiation, and migration. FHL2 interacts with multiple proteins to regulate cardiac development as a coactivator or a corepressor. It is involved in cardiac specification and determination of cell fate, cardiomyocyte growth, cardiac remodeling, myofibrillogenesis, and the regulation of HERG channels. Targeting FHL2 has therapeutic implications as it could improve cardiac function, control arrhythmias, alleviate heart failure, and maintain cardiac integrity in various pathological conditions. The identification of FHL2 as a signature gene in atrial fibrillation suggests its potential as a diagnostic marker and therapeutic target for this common arrhythmia.
作者机构：
[Liu, Ying; Deng, Min; Zhai, Zibo; He, Longwei; Wang, Peipei; Li, Songjiao; Cheng, Dan; He, LW] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang 421002, Peoples R China.;[Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang Med Sch,Dept Gastroenterol, Hengyang 421002, Peoples R China.;[He, LW; He, Longwei] Henan Normal Univ, Sch Chem & Chem Engn, Xinxiang 453007, Peoples R China.
通讯机构：
[He, LW ] H;[Li, SJ ; He, LW] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang 421002, Peoples R China.;Henan Normal Univ, Sch Chem & Chem Engn, Xinxiang 453007, Peoples R China.
摘要：
Revealing changes in the tumor microenvironment is crucial for understanding cancer and developing sensitive methods for precise cancer imaging and diagnosis. Intracellular hydrogen peroxide (H(2)O(2)) and microenvironmental factors (e.g., viscosity and polarity) are closely linked to various physiological and pathological processes, making them potential biomarkers for cancer. However, a triple-response theranostic probe for precise tumor imaging and therapy has not yet been achieved due to the lack of effective tools. Herein, we present a mitochondria-targeting near-infrared (NIR) fluorescent probe, VPH-5DF, capable of simultaneously monitoring H(2)O(2), viscosity, and polarity through dual NIR channels. The probe specifically detects H(2)O(2) via NIR emission (λ(em) = 650 nm) and shows high sensitivity to microenvironmental viscosity/polarity in the deep NIR channel (λ(em) ≈ 750 nm). Furthermore, the probe not only monitors mitochondrial polarity, viscosity, and fluctuations in endogenous/exogenous H(2)O(2) levels but also distinguishes cancer cells from normal cells through multiple parameters. Additionally, VPH-5DF can be employed to monitor alterations in H(2)O(2) levels, as well as changes in viscosity and polarity, during drug-induced pyroptosis in living cells. After treatment with VPH-5DF, chemotherapy-induced oxidative damage to the mitochondria in tumor cells activated the pyroptosis pathway, leading to a robust antitumor response, as evidenced in xenograft tumor models. Thus, this triple-response theranostic prodrug offers a new platform for precise in vivo cancer diagnosis and anticancer chemotherapy.
摘要：
Ferroptosis, a form of iron-dependent regulated cell death, has emerged as a critical mechanism in the pathogenesis of organ fibrosis. This review aims to provide an overview of the molecular mechanisms underlying ferroptosis and its contribution to fibrosis in various organs, including the liver, lung, heart, and kidneys. We explore how dysregulated iron metabolism, lipid peroxidation, and oxidative stress contribute to ferroptosis and subsequent tissue damage, promoting the progression of fibrosis. In addition, we highlight the complex interplay between ferroptosis and other cellular processes such as apoptosis, necrosis, and inflammation in the fibrotic microenvironment. Furthermore, this review discusses current therapeutic strategies targeting ferroptosis, including iron chelation, antioxidants, and modulators of lipid peroxidation. We also examine ongoing clinical and preclinical studies aimed at translating these findings into viable treatments for fibrotic diseases. Understanding the role of ferroptosis in organ fibrosis offers novel therapeutic opportunities, with the potential to mitigate disease progression and improve patient outcomes.
Ferroptosis, a form of iron-dependent regulated cell death, has emerged as a critical mechanism in the pathogenesis of organ fibrosis. This review aims to provide an overview of the molecular mechanisms underlying ferroptosis and its contribution to fibrosis in various organs, including the liver, lung, heart, and kidneys. We explore how dysregulated iron metabolism, lipid peroxidation, and oxidative stress contribute to ferroptosis and subsequent tissue damage, promoting the progression of fibrosis. In addition, we highlight the complex interplay between ferroptosis and other cellular processes such as apoptosis, necrosis, and inflammation in the fibrotic microenvironment. Furthermore, this review discusses current therapeutic strategies targeting ferroptosis, including iron chelation, antioxidants, and modulators of lipid peroxidation. We also examine ongoing clinical and preclinical studies aimed at translating these findings into viable treatments for fibrotic diseases. Understanding the role of ferroptosis in organ fibrosis offers novel therapeutic opportunities, with the potential to mitigate disease progression and improve patient outcomes.
摘要：
Malignant tumors have been a serious threat to human health with their increasing incidence. Difficulties with conventional treatments are toxicity, drug resistance, and recurrence. For this reason, non-invasive treatment modalities such as photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), and others have received much attention. Among them, Ferrocene (Fc)-based nanomedicines for enhanced Chemodynamic Therapy (ECDT) is a new therapeutic strategy based on the Fenton reaction. Based on ferrocene's good biocompatibility, potentiation in medicinal chemistry, and good stability of divalent iron ions, scientists are increasingly using it as a Fenton's iron donor for tumor therapy. Such ferrocene-based ECDT nanoplatforms have shown remarkable promise for clinical applications and have significantly increased the efficacy of CDT treatment. Ferrocene-based nanomedicines exhibit exceptional consistency owing to their low toxicity, high stability, enhanced bioavailability, and a multitude of advantages over conventional approaches to cancer treatment. As a consequence, a number of tactics have been investigated in recent years to raise the effectiveness of ferrocene-based ECDT. In this review, we detail the different forms and strategies used to enhance Ferrocene-based ECDT efficiency.
摘要：
One‑carbon metabolism plays an important role in cancer progression. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial enzyme in one‑carbon metabolism, is dysregulated in several cancer types. However, the precise role and mechanisms of MTHFD2 in esophageal squamous cell carcinoma (ESCC) remain unclear. The present study unravels the multifaceted mechanisms by which MTHFD2 contributes to ESCC pathogenesis. Bioinformatics analyses revealed significant upregulation of MTHFD2 in ESCC tumor tissues, which was associated with advanced disease stage and poor patient prognosis. Validating these findings in clinical samples, MTHFD2 overexpression was confirmed through immunohistochemistry, Reverse transcription‑quantitative PCR and western blotting. Knockdown of MTHFD2 inhibited ESCC cell viability, colony formation, invasion, and tumor growth in vivo, indicating its oncogenic potential. Mechanistically, the present study elucidated a novel regulatory axis involving N6‑methyladenosine modification and MTHFD2 mRNA stability. Specifically, methyltransferase‑like 3 (METTL3) and insulin‑like growth factor 2 mRNA binding protein 2 (IGF2BP2) were identified as key mediators of m6A‑dependent stabilization of MTHFD2 mRNA, contributing to its elevated expression in ESCC. Furthermore, MTHFD2 was found to activate PI3K/AKT and ERK signaling pathways by modulating interaction between phosphatidylethanolamine‑binding protein 1 (PEBP1) and raf‑1 proto‑oncogene (RAF1). This modulation was achieved through direct binding of MTHFD2 to PEBP1, disrupting the inhibitory effect of PEBP1 on RAF1 and promoting downstream pathway activation. The oncogenic functions of MTHFD2 were attenuated upon PEBP1 knockdown, underscoring the role of the MTHFD2‑PEBP1 axis in ESCC progression. In summary, the present study uncovers a novel regulatory mechanism involving m6A modification and the MTHFD2‑PEBP1 axis, unveiling potential therapeutic avenues for targeting MTHFD2 in ESCC.
摘要：
Biased µ-opioid receptor (MOR) agonists enhance pain relief by selectively activating G protein-coupled receptor signaling and minimizing β-arrestin-2 activation, resulting in fewer side effects. This multicenter Phase II/III trial evaluated the optimal dosage, efficacy, and safety of SHR8554, a biased MOR agonist, for postoperative pain management following orthopedic surgery. In Phase II, 121 patients were divided into four groups to receive varying patient-controlled analgesia (PCA) doses of SHR8554 or morphine. Phase III involved 320 patients with similar groupings, including a placebo group. The primary outcome was the resting summed pain intensity difference over 24 hours (rSPID 24 ). Secondary outcomes included rSPID and active-SPID (aSPID) at other time points, rescue analgesia received, cumulative dose of analgesics, and satisfaction scores. Safety endpoints included treatment-emergent adverse events (TEAEs) and AE of special interest (AESIs). In both phases, SHR8554 demonstrated significant analgesic efficacy. In Phase II, the least squares (LS) mean differences in rSPID 24 compared to morphine for the 0.05 mg,0.1 mg, and 0.2 mg SHR8554 groups were 16.8 (p = 0.01), 7.4 (p = 0.27), and 0.2 (p = 0.98), respectively. Phase III confirmed the efficacy of the 0.05 mg and 0.1 mg SHR8554 doses compared to placebo, with LS mean differences of 15.4 (p = 0.0001) and −19.8 (p < 0.0001), respectively. Trends in other secondary outcomes mirrored these findings. Safety analysis revealed that the 0.2 mg SHR8554 group had higher incidences of TEAEs (83.3 %) and AESIs (33.3 %) compared to other groups in Phase II. Similarly, in Phase III, the incidences of TEAEs were 81.0 %, 73.4 %, and 74.1 % in the 0.05 and 0.1 mg SHR8554 and morphine groups, respectively, compared with 61.3 % in the placebo group, while the AESIs were 29.1 %, 20.3 %, and 24.7 % compared with 12.5 % in the placebo group. In conclusion, SHR8554 exhibited efficacy compared to placebo and safety comparable to morphine for patients experiencing moderate-to-severe acute pain following unilateral total knee replacement or knee ligament reconstruction surgery.
Biased µ-opioid receptor (MOR) agonists enhance pain relief by selectively activating G protein-coupled receptor signaling and minimizing β-arrestin-2 activation, resulting in fewer side effects. This multicenter Phase II/III trial evaluated the optimal dosage, efficacy, and safety of SHR8554, a biased MOR agonist, for postoperative pain management following orthopedic surgery. In Phase II, 121 patients were divided into four groups to receive varying patient-controlled analgesia (PCA) doses of SHR8554 or morphine. Phase III involved 320 patients with similar groupings, including a placebo group. The primary outcome was the resting summed pain intensity difference over 24 hours (rSPID 24 ). Secondary outcomes included rSPID and active-SPID (aSPID) at other time points, rescue analgesia received, cumulative dose of analgesics, and satisfaction scores. Safety endpoints included treatment-emergent adverse events (TEAEs) and AE of special interest (AESIs). In both phases, SHR8554 demonstrated significant analgesic efficacy. In Phase II, the least squares (LS) mean differences in rSPID 24 compared to morphine for the 0.05 mg,0.1 mg, and 0.2 mg SHR8554 groups were 16.8 (p = 0.01), 7.4 (p = 0.27), and 0.2 (p = 0.98), respectively. Phase III confirmed the efficacy of the 0.05 mg and 0.1 mg SHR8554 doses compared to placebo, with LS mean differences of 15.4 (p = 0.0001) and −19.8 (p < 0.0001), respectively. Trends in other secondary outcomes mirrored these findings. Safety analysis revealed that the 0.2 mg SHR8554 group had higher incidences of TEAEs (83.3 %) and AESIs (33.3 %) compared to other groups in Phase II. Similarly, in Phase III, the incidences of TEAEs were 81.0 %, 73.4 %, and 74.1 % in the 0.05 and 0.1 mg SHR8554 and morphine groups, respectively, compared with 61.3 % in the placebo group, while the AESIs were 29.1 %, 20.3 %, and 24.7 % compared with 12.5 % in the placebo group. In conclusion, SHR8554 exhibited efficacy compared to placebo and safety comparable to morphine for patients experiencing moderate-to-severe acute pain following unilateral total knee replacement or knee ligament reconstruction surgery.
Trial Registration Trial Name: Study on the Efficacy and Safety of SHR8554 Injection for Postoperative Analgesia in Orthopedics: Multicenter, Randomized, Double Blind, Dose Exploration, Placebo/Positive Control, Phase II/III Clinical Trial Registered on: chinadrugtrials.org.cn Identifier: CTR20220639.
Trial Name: Study on the Efficacy and Safety of SHR8554 Injection for Postoperative Analgesia in Orthopedics: Multicenter, Randomized, Double Blind, Dose Exploration, Placebo/Positive Control, Phase II/III Clinical Trial Registered on: chinadrugtrials.org.cn Identifier: CTR20220639.
作者机构：
[Yao, Xiang-Rong; He, Jun-Yan] Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China;[Yao, Xiang-Rong; Xiao, Fang-Zhu] School of Public Health, University of South China, Hengyang, China;[Xiao, Wen-Tao] Department of Radiation Oncology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong University, Nantong, China;[Huang, Cui-Qin] Department of Pathology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
摘要：
Head and neck squamous cell carcinoma (HNSC) is a prevalent and aggressive malignancy with poor prognosis, underscoring the need for novel biomarkers and therapeutic strategies. This study investigates the role of C16orf74 as a potential diagnostic and prognostic biomarker in HNSC. Bioinformatics analyses revealed that C16orf74 is significantly overexpressed in HNSC and is associated with advanced disease stages, therapy resistance, and shorter overall and progression-free survival. A prognostic nomogram integrating C16orf74 expression with clinicopathological features demonstrated robust predictive performance. Functional enrichment and immune infiltration analyses suggest that high C16orf74 expression might contribute to an immunosuppressive tumor microenvironment by reducing key immune cell populations, such as B cells, T cells, and natural killer cells, which are critical for anti-tumor immunity. Moreover, C16orf74 expression was inversely associated with immune checkpoint expression and immunotherapy response, highlighting its potential as a predictive biomarker for immune checkpoint blockade (ICB) efficacy. Drug sensitivity analyses identified potential therapeutic agents, including arsenic trioxide, carmustine, vincristine, quercetin, and carboplatin for patients with high C16orf74 expression. These findings highlight the potential of C16orf74 as a biomarker and therapeutic target to improve HNSC management.
期刊：
International Immunopharmacology,2025年157:114777 ISSN：1567-5769
通讯作者：
Yi Yang
作者机构：
[He, Zhen-Biao; Liu, Kun; Xiao, Yuan; Yang, Xiu; Wang, De-Ming; Cheng, Yang; Zheng, Chuang-Xin; Guo, Ze-Yu; Yang, Yi] Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang 421001, PR China;[He, Zhen-Biao; Liu, Kun; Xiao, Yuan; Yang, Xiu; Wang, De-Ming; Cheng, Yang; Zheng, Chuang-Xin; Guo, Ze-Yu] Clinical Medical Research Center for Acute and Chronic Pain of Hunan Province (2023SK4014), Hengyang 421001, PR China;[Yang, Yi] Clinical Medical Research Center for Acute and Chronic Pain of Hunan Province (2023SK4014), Hengyang 421001, PR China. Electronic address: yangyi@usc.edu.cn
通讯机构：
[Yi Yang] D;Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang 421001, PR China<&wdkj&>Clinical Medical Research Center for Acute and Chronic Pain of Hunan Province (2023SK4014), Hengyang 421001, PR China
摘要：
Objectives Dysregulated inflammatory responses during sepsis often result in acute lung injury (ALI). Neutrophils activated at the primary site of injury can re-enter the circulation through reverse transendothelial migration (rTEM), subsequently infiltrating other organs and contributing to systemic inflammation and multi-organ damage. The specialized pro-resolving lipid mediator (SPM) maresin conjugate in tissue regeneration 1 (MCTR1) has been shown to mitigate organ injury in sepsis. This study investigated the role of neutrophil rTEM in ALI and examined whether MCTR1 can alleviate ALI by modulating neutrophil rTEM.
Dysregulated inflammatory responses during sepsis often result in acute lung injury (ALI). Neutrophils activated at the primary site of injury can re-enter the circulation through reverse transendothelial migration (rTEM), subsequently infiltrating other organs and contributing to systemic inflammation and multi-organ damage. The specialized pro-resolving lipid mediator (SPM) maresin conjugate in tissue regeneration 1 (MCTR1) has been shown to mitigate organ injury in sepsis. This study investigated the role of neutrophil rTEM in ALI and examined whether MCTR1 can alleviate ALI by modulating neutrophil rTEM.
Methods Lung injury was induced in mice by administrating lipopolysaccharide (LPS). Lung damage was assessed using H&E staining, lung wet-to-dry ratio, inflammatory mediator levels, and protein content in the bronchoalveolar lavage fluid. Neutrophil infiltration in lung tissue was evaluated by immunofluorescence, and flow cytometry was used to quantify rTEM neutrophils. Protein expression of neutrophil elastase (NE) and junctional adhesion molecule-C (JAM-C) was analyzed to assess rTEM activity. The role of CXCR4 in neutrophil rTEM was investigated using the CXCR4 inhibitor AMD3100. Additionally, bone marrow-derived neutrophils were isolated to evaluate the effects of MCTR1 on CXCR4 and GRK2 expression.
Lung injury was induced in mice by administrating lipopolysaccharide (LPS). Lung damage was assessed using H&E staining, lung wet-to-dry ratio, inflammatory mediator levels, and protein content in the bronchoalveolar lavage fluid. Neutrophil infiltration in lung tissue was evaluated by immunofluorescence, and flow cytometry was used to quantify rTEM neutrophils. Protein expression of neutrophil elastase (NE) and junctional adhesion molecule-C (JAM-C) was analyzed to assess rTEM activity. The role of CXCR4 in neutrophil rTEM was investigated using the CXCR4 inhibitor AMD3100. Additionally, bone marrow-derived neutrophils were isolated to evaluate the effects of MCTR1 on CXCR4 and GRK2 expression.
Results MCTR1 alleviated lung injury and inhibited neutrophils rTEM in LPS-induced lung injury. MCTR1 also decreased NE expression and increased JAM-C expression. The CXCR4 inhibitor AMD3100 effectively suppressed neutrophil rTEM and alleviated lung injury. Furthermore, MCTR1 inhibited CXCR4 expression and enhanced GRK2 expression.
MCTR1 alleviated lung injury and inhibited neutrophils rTEM in LPS-induced lung injury. MCTR1 also decreased NE expression and increased JAM-C expression. The CXCR4 inhibitor AMD3100 effectively suppressed neutrophil rTEM and alleviated lung injury. Furthermore, MCTR1 inhibited CXCR4 expression and enhanced GRK2 expression.
Conclusions MCTR1 reduces lung damage by upregulating GRK2 to inhibit CXCR4 expression, thereby suppressing neutrophil rTEM in LPS-induced lung injury.
MCTR1 reduces lung damage by upregulating GRK2 to inhibit CXCR4 expression, thereby suppressing neutrophil rTEM in LPS-induced lung injury.
期刊：
Brain and Behavior,2025年15(2):e70288- ISSN：2162-3279
通讯作者：
Tang, BS
作者机构：
[Tang, Beisha; Tang, BS; Wu, Heng; Li, Mingqiang; Wang, Yuzheng; Yi, Shanqing] Univ South China, Affiliated Hosp 1, Multi Res Ctr Brain Disorders, Hengyang Med Sch,Dept Neurol, Hengyang, Hunan, Peoples R China.;[Tang, Beisha; Tang, BS; Wu, Heng; Li, Mingqiang; Wang, Yuzheng; Yi, Shanqing] Univ South China, Affiliated Hosp 1, Clin Res Ctr Immune Related Encephalopathy Hunan P, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Tang, Beisha; Tang, BS; Xu, Qian; He, Runcheng; Guo, Jifeng; Zhou, Xun] Cent South Univ, Xiangya Hosp, Dept Neurol, Changsha, Hunan, Peoples R China.;[Sun, Qiying] Cent South Univ, Xiangya Hosp, Dept Geriatr Neurol, Changsha, Hunan, Peoples R China.;[Tang, Beisha; Xu, Qian; Guo, Jifeng; Sun, Qiying] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Hunan, Peoples R China.
通讯机构：
[Tang, BS ] U;Univ South China, Affiliated Hosp 1, Multi Res Ctr Brain Disorders, Hengyang Med Sch,Dept Neurol, Hengyang, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Clin Res Ctr Immune Related Encephalopathy Hunan P, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;Cent South Univ, Xiangya Hosp, Dept Neurol, Changsha, Hunan, Peoples R China.
摘要：
BACKGROUND: Distinguishing between essential tremor (ET) and tremor-dominant Parkinson's disease (PD-TD) can be challenging due to overlapping motor symptoms. This study aims to investigate the differences in nonmotor symptoms (NMS) between ET and PD-TD patients to provide additional evidence for differentiating these two conditions. METHODS: This retrospective study included 1656 participants, comprising 558 PD-TD patients, 584 ET patients, and 514 controls. ET patients were assessed using the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS), while PD-TD patients were evaluated based on the Unified Parkinson's Disease Rating Scale (UPDRS). All participants were assessed for NMS using the Nonmotor Symptoms Scale (NMSS). RESULTS: The composite NMSS score for the PD-TD group was significantly higher than that for the ET group and the control group (23.44 ± 20.20vs. 12.60 ± 14.89vs. 9.37 ± 12.44, p < 0.001). Compared to ET patients, PD-TD patients had an increased risk of all NMS, especially in hyposmia (OR = 7.70, 95% CI: 5.11-11.62). The NMSS score, urinary symptoms, and hyposmia may play a role in differentiating ET from PD-TD. The area under the curve (AUC) is 0.766 (95% CI: 0.739-0.793), with a sensitivity of 80.8% and specificity of 58.6%. When family history is included in the analysis, the AUC increases to 0.819 (95% CI: 0.795-0.843), with sensitivity improving to 82.4% and specificity to 68.2%. CONCLUSIONS: The study reveals significant differences in NMS between ET and PD-TD. Compared to patients with ET, those with PD-TD exhibit more frequent and severe NMS. NMS and family history are helpful in differentiating between ET and PD-TD.
