摘要：
BACKGROUND: Neuronal senescence is a common pathological feature of various neurodegenerative diseases, with ferroptosis playing a significant role. This study aims to investigate the role of ErbB4 receptor activation in preventing D-Galactose (D-gal)-induced neuronal senescence. METHODS: Mice subjected to D-gal-induced aging were administered a small molecule ErbB4 receptor agonist (E4A), identified via virtual screening, melatonin, or a combination of both. Behavioral assessments were conducted to evaluate therapeutic efficacy in memory and cognitive functions. Immunofluorescence staining, western blot, and biochemical assays were primarily employed to assess changes in both senescence- and ferroptosis-related molecules in mouse hippocampal tissues in response to each treatment. Additionally, mouse hippocampal HT22 neuronal cell cultures were utilized to corroborate the in vivo findings. RESULTS: The targeted activation of ErbB4 receptor by E4A significantly ameliorated the behavioral deficits induced by D-gal in mice, demonstrating an effect comparable to that of melatonin, a natural inhibitor of in vivo senescence and ferroptosis. Both E4A and melatonin mitigated D-gal-induced aging in hippocampal neurons of mice. This was evidenced by the upregulation of Lamin B1 and the downregulation of P53, P21, P16, GFAP, and Iba-1 expression levels. Moreover, D-gal treatment markedly decreased the protein expression of the ferroptosis inhibitor Nrf2 while augmenting the expression of the ferroptosis promoter TFRC. These alterations were partially reversed by the individual administration of E4A and melatonin. In vitro studies further corroborated that D-gal treatment significantly and concurrently induced the expression of senescence markers and ferroptosis promoters. However, both E4A and melatonin were able to significantly reverse these changes. Additionally, E4A markedly ameliorated Erastin-induced ferroptosis in mouse hippocampal neuronal cells. CONLUSION: Our findings suggest that targeted activation of ErbB4 receptor may be a viable strategy for treating neuronal senescence by inhibiting ferroptosis, thereby offering a potential therapeutic avenue for senescence-associated neurodegenerative diseases.
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
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.
期刊：
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,2025年55(5) ISSN：1107-3756
作者机构：
[Zhou, Huijun] Department of Gastroenterology and Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan 410013, P.R. China;[Gong, Han] School of Life Sciences, Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha, Hunan 410011, P.R. China;[Zeng, Xiaohui] Department of Oncology, Hunan Institute of Schistosomiasis Control/The Third Hospital of Hunan Province, Yueyang, Hunan 414000, P.R. China;[Zeng, Chong] Department of Respiratory and Critical Care Medicine, The Seventh Affiliated Hospital, Hengyang Medical School, University of South China, Changsha, Hunan 410119, P.R. China;[Liu, Dian] Department of Lymphoma and Abdominal Radiotherapy, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan 410013, P.R. China
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.
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.
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.
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.
期刊：
EXPERIMENTAL AND THERAPEUTIC MEDICINE,2025年29(3):56 ISSN：1792-0981
通讯作者：
Tang, J
作者机构：
[Cao, Chuangjie] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pathol, Hengyang 421001, Hunan, Peoples R China.;[Xie, Haitao] Univ South China, Affiliated Hosp 1, Inst Microbiol & Infect Dis, Dept Clin Lab Med,Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Dou, Chengyun; Tang, Jian; Tang, J; Guo, Ruohan] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Infect Dis, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Tang, J ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Infect Dis, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
coronavirus disease 2019;distinction;eosinophil;influenza A;neutrophil-to-lymphocyte ratio
摘要：
Coronavirus disease 2019 (COVID-19) and influenza A outbreaks have spread rapidly in China. It is difficult to accurately differentiate these two different respiratory tract infections on the basis of their similar early-stage symptoms and lymphocytopenia. In the present study, the age, sex and white blood cell, neutrophil, lymphocyte, monocyte and eosinophil counts, as well as the neutrophil-to-lymphocyte ratio (NLR) of 201 outpatients with confirmed COVID-19 and 246 outpatients with influenza A were investigated and compared. A receiver operating characteristic curve was drawn to determine the thresholds in distinguishing COVID-19 from influenza A Our study found that the monocyte count and NLR were significantly elevated, while the eosinophil count/percentage was higher in outpatients with COVID-19 than in those with influenza A (0.06±0.07 vs. 0.04±0.09, P=0.002; 0.95±1.12 vs. 0.56±0.95, P<0.001, respectively). Logit(P)=-1.11 + 1.29 x eosinophil percentage -12.07 x eosinophil count +1.10 x monocyte count, deduced from the eosinophil count/percentage and monocyte count, had the largest area under the curve at 0.67, with high specificity (80.1%) and a sensitivity of 47.3%. The present study demonstrated that a higher eosinophil count/percentage may be a potential biomarker to significantly differentiate early COVID-19 from influenza A.
期刊：
EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY,2025年 ISSN：0954-691X
作者机构：
[Pan, Linghui; Yan, Fangran] Department of Anesthesiology, Guangxi Medical University Cancer Hospital;[Yan, Fangran; Du, Xueke] Department of Anesthesiology;[Zhou, Zenghua] Departments of Pain, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region;[He, Sheng] Department of Anesthesiology, The First Affiliated Hospital of Southern China University, Hengyang, Hunan Province;[Pan, Linghui] Guangxi Clinical Research Center for Anesthesiology
摘要：
Acute kidney injury (AKI) is associated with poor prognosis. New biomarkers, like neutrophil gelatinase-associated lipocalin (NGAL), are helpful for early warning of AKI. This study aims to investigate the accuracy of NGAL in evaluating the perioperative AKI of liver transplantation. The four databases, PubMed, Web of Science, Embase, and Cochrane Library, were searched for relevant studies published from database inception to August 2023. Results were pooled using random-effects models, and heterogeneity was examined. A total of 16 case-control studies with 1271 patients were included. The results showed that both preoperative [standardized mean difference (SMD) = 0.53; 95% confidence interval (CI): 0.15, 0.91; P < 0.001] and postoperative NGAL levels (SMD = 0.63; 95% CI: 0.24, 1.03; P < 0.001) were higher in the AKI group compared with the non-AKI group. Subgroup analysis by continents showed higher preoperative NGAL levels in AKI patients in the European population (SMD = 1.63; 95% CI: 0.55, 0.27; P = 0.003), but no differences in Asian, African, North American, and South American. Subgroup analysis by continents revealed higher postoperative NGAL levels in the European (SMD = 1.63; 95% CI: 0.55, 0.27; P = 0.002) and Asian populations (SMD = 0.42; 95% CI: 0.04, 0.81; P = 0.039). Higher postoperative NGAL levels in plasma and urine were observed in AKI patients compared with non-AKI patients [plasma (SMD = 1.29; 95% CI: 0.21, 2.38; P = 0.011), urine (SMD = 0.88; 95% CI: 0.18, 1.59; P = 0.035)], while there was no difference in African, North American, South American, and serum NGAL. NGAL level may be an important biomarker for early detection of AKI in the perioperative period of liver transplantation.
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.
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.
作者：
Luo, Sihuan;Zhao, Xiaomei;Wang, Yijin;Jiang, Miao;Cao, Yi
期刊：
Food and Chemical Toxicology,2025年197:115304 ISSN：0278-6915
通讯作者：
Cao, Y
作者机构：
[Zhao, Xiaomei; Cao, Yi; Wang, Yijin; Luo, Sihuan] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.;[Jiang, Miao] Univ South China, Inst Cardiovasc Dis, Hengyang Med Coll, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, Hengyang 421001, Peoples R China.
通讯机构：
[Cao, Y ] U;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.
关键词：
Autophagy;In vivo toxicity;Lipid profiles;Nanoplastics;Oral exposure
摘要：
The wide uses of plastics lead to nanoplastic exposure in reality. Previous studies reported that micro- and nano-plastics (MNPs) disrupted metabolism, but few studies investigated lipid profile changes. Hereby, we exposed mice to vehicles (control), 0.05 or 0.5 mg/kg 20 or 100 nm nanoplastics via gavage, once a day, for 14 days. Albeit no obvious tissue damage, lipidomics data revealed 76 up-regulated and 29 down-regulated lipid molecules in mouse intestines. Further analysis revealed that a number of up-regulated lipid molecules belong to glycerophospholipid (GP). Among GP, we noticed an up-regulation of 9 phosphatidylserine (PS) molecules, and we further verified the presence of autophagosomes and co-localization of typical autophagic lipolysis proteins in intestinal sections, as well as decreased lysosomal associated protein 2 (LAMP2) and increased adipose triglyceride lipase (ATGL) in intestinal homogenates, indicating perturbed autophagic pathway. The exposure also up-regulated 9 phosphatidylinositol (PI) molecules, and we verified a significant decrease of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), indicating altered PI3K-signaling pathway. Besides GP, nanoplastics also significantly up-regulated some sphingolipids (SP), such as ceramide (Cer), and some sterol lipids, such as cholesterol derivatives. Combined, these results suggested that oral exposure to nanoplastics altered lipid profiles and related signaling pathway in mouse intestines.
The wide uses of plastics lead to nanoplastic exposure in reality. Previous studies reported that micro- and nano-plastics (MNPs) disrupted metabolism, but few studies investigated lipid profile changes. Hereby, we exposed mice to vehicles (control), 0.05 or 0.5 mg/kg 20 or 100 nm nanoplastics via gavage, once a day, for 14 days. Albeit no obvious tissue damage, lipidomics data revealed 76 up-regulated and 29 down-regulated lipid molecules in mouse intestines. Further analysis revealed that a number of up-regulated lipid molecules belong to glycerophospholipid (GP). Among GP, we noticed an up-regulation of 9 phosphatidylserine (PS) molecules, and we further verified the presence of autophagosomes and co-localization of typical autophagic lipolysis proteins in intestinal sections, as well as decreased lysosomal associated protein 2 (LAMP2) and increased adipose triglyceride lipase (ATGL) in intestinal homogenates, indicating perturbed autophagic pathway. The exposure also up-regulated 9 phosphatidylinositol (PI) molecules, and we verified a significant decrease of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), indicating altered PI3K-signaling pathway. Besides GP, nanoplastics also significantly up-regulated some sphingolipids (SP), such as ceramide (Cer), and some sterol lipids, such as cholesterol derivatives. Combined, these results suggested that oral exposure to nanoplastics altered lipid profiles and related signaling pathway in mouse intestines.
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.
作者机构：
[Kun Zhang] Department of Cardiology, The Seventh Affiliated Hospital of Sun Yat-Sen University, 628 Zhenyuan Road, Shenzhen 518107, China;[Chunlan Huang] Department of Neurology, The Second Affiliated Hospital, University of South China, 30 Jiefang Road, Hengyang 421001, China;[Junping Li] Department of Urology, Guangdong Second Provincial General Hospital, 466 Xingang Middle Road, Guangzhou 510120, China;[Peibiao Mai] Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences (Shenzhen Sun Yat-sen Cardiovascular Hospital), Shenzhen 518000, China;[Shuwan Xu] Department of Cardiology, Peking University Third Hospital, 49 Huayuan North Road, Haidian District, Beijing 100191, China
通讯机构：
[Huanji Zhang; Yang Liu; Weijing Feng] D;Department of Hematology, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025 Shennan Middle Road, Shenzhen 518033, China<&wdkj&>Department of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Lab of Cardiac Function and Microcirculation, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, 1838 Guangzhou North Road, Guangzhou 510515, China<&wdkj&>Department of Cardiology, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025 Shennan Middle Road, Shenzhen 518033, China
摘要：
Background The important effects of variability of some physiological/biological characteristics (such as LDL cholesterol, blood pressure) on cardiovascular outcomes have been elucidated, while the role of insulin variability is undefined.
The important effects of variability of some physiological/biological characteristics (such as LDL cholesterol, blood pressure) on cardiovascular outcomes have been elucidated, while the role of insulin variability is undefined.
Objectives To investigate the associations of long-term fasting insulin variability during young adulthood before the onset of diabetes with subsequent cardiovascular outcomes in middle age.
To investigate the associations of long-term fasting insulin variability during young adulthood before the onset of diabetes with subsequent cardiovascular outcomes in middle age.
Methods We included 3,983 CARDIA (Coronary Artery Risk Development Study in Young Adults) participants aged 18 to 30 years with at least three fasting insulin measurements. Intra-individual fasting insulin variability was defined by the average real variability (ARV) of insulin and standard deviation (SD) of insulin during 30-year follow-up. The presence and the degree of coronary artery calcification (CAC) were assessed by computed tomography at year 25. Incident cardiovascular disease (CVD) and all-cause mortality were adjudicated.
We included 3,983 CARDIA (Coronary Artery Risk Development Study in Young Adults) participants aged 18 to 30 years with at least three fasting insulin measurements. Intra-individual fasting insulin variability was defined by the average real variability (ARV) of insulin and standard deviation (SD) of insulin during 30-year follow-up. The presence and the degree of coronary artery calcification (CAC) were assessed by computed tomography at year 25. Incident cardiovascular disease (CVD) and all-cause mortality were adjudicated.
Results After multivariable adjustment, comparing high versus low tertile of insulin ARV, the hazard of CVD increased by 65% (HR, 1.65; 95% CI, 1.13-2.39) and all-cause mortality by 97% (HR, 1.97; 95% CI, 1.38-2.82). Higher tertile of insulin ARV was associated with significantly worse degree of CAC (β =0.1; 95% CI, 0.03-0.18) but not with the presence of CAC ( P =0.197). Similar results were also observed in insulin SD.
After multivariable adjustment, comparing high versus low tertile of insulin ARV, the hazard of CVD increased by 65% (HR, 1.65; 95% CI, 1.13-2.39) and all-cause mortality by 97% (HR, 1.97; 95% CI, 1.38-2.82). Higher tertile of insulin ARV was associated with significantly worse degree of CAC (β =0.1; 95% CI, 0.03-0.18) but not with the presence of CAC ( P =0.197). Similar results were also observed in insulin SD.
Conclusion High long-term insulin variability in young adulthood before the onset of diabetes was associated with an increased risk of CVD and all-cause mortality in later life, independent of average FG, HOMA-IR and other established cardiovascular risk factors. Long-term insulin variability was associated with the degree but not the presence of CAC.
High long-term insulin variability in young adulthood before the onset of diabetes was associated with an increased risk of CVD and all-cause mortality in later life, independent of average FG, HOMA-IR and other established cardiovascular risk factors. Long-term insulin variability was associated with the degree but not the presence of CAC.
作者机构：
[Jia Huang; Wanting Zhang; Jia Zhou] Department of Ultrasound Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China;MOE Key Lab of Rare Pediatric Diseases, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421002, China;School of Basic Medical Science, Hengyang Medical School, University of South China, Hengyang 421001, China;Department of Gastroenterology, Clinical Research Institute, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China;[Jiayu Zeng; Longwei He] Department of Ultrasound Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China<&wdkj&>MOE Key Lab of Rare Pediatric Diseases, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421002, China<&wdkj&>School of Basic Medical Science, Hengyang Medical School, University of South China, Hengyang 421001, China
通讯机构：
[Longwei He; Jia Zhou] D;Department of Ultrasound Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China<&wdkj&>MOE Key Lab of Rare Pediatric Diseases, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421002, China<&wdkj&>School of Basic Medical Science, Hengyang Medical School, University of South China, Hengyang 421001, China<&wdkj&>Department of Ultrasound Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China
摘要：
Early recognition is key to improving the prognosis of ischemic stroke (IS), while available imaging methods tend to target events that have already undergone ischemia. A new method to detect early IS is urgently needed, as well as further study of its mechanisms. Viscosity and cysteine (Cys) levels of mitochondria have been associated with ferroptosis and IS. It is possible to identify IS and ferroptosis accurately and early by monitoring changes in mitochondrial Cys and viscosity simultaneously. In this work, a viscosity/Cys dual-responsive mitochondrial-targeted near-infrared (NIR) fluorescent probe ( NVCP ) was constructed for the precise tracking of IS using a two-dimensional design strategy. NVCP consists of a chromophore dyad containing diethylaminostyrene quinolinium rotor and chloro‑sulfonylbenzoxadiazole (SBD-Cl) derivative with two easily distinguished emission bands (λ em = 592 and 670 nm). NVCP performs the way of killing two birds with one stone, that is, the probe exhibits excellent selectivity and sensitivity for detecting viscosity and Cys in living cells with excellent biocompatibility and accurate mitochondrial targeting capability by dual channel imaging mode. In addition, NVCP recognized that the viscosity increases and Cys level decreases in cells when undergoing ferroptosis and oxygen-glucose deprivation (OGD) stress by confocal imaging, flow cytometry, and Western blot experiments. Treatment of ferroptosis inhibitors (ferrostatin-1 (Fer-1) and deferoxamine (DFO)) could reverse the variation tendency of viscosity and Cys. This is the first time that the relationship between ferroptosis and IS was identified through an analysis of Cys and viscosity. More importantly, the ischemic area was also instantly distinguished from normal tissues through fluorescence imaging of NVCP in vivo . The developed NIR dual-responsive probe NVCP toward viscosity and Cys could serve as a sensitive and reliable tool for tracking ferroptosis-related pathological processes during IS.
Early recognition is key to improving the prognosis of ischemic stroke (IS), while available imaging methods tend to target events that have already undergone ischemia. A new method to detect early IS is urgently needed, as well as further study of its mechanisms. Viscosity and cysteine (Cys) levels of mitochondria have been associated with ferroptosis and IS. It is possible to identify IS and ferroptosis accurately and early by monitoring changes in mitochondrial Cys and viscosity simultaneously. In this work, a viscosity/Cys dual-responsive mitochondrial-targeted near-infrared (NIR) fluorescent probe ( NVCP ) was constructed for the precise tracking of IS using a two-dimensional design strategy. NVCP consists of a chromophore dyad containing diethylaminostyrene quinolinium rotor and chloro‑sulfonylbenzoxadiazole (SBD-Cl) derivative with two easily distinguished emission bands (λ em = 592 and 670 nm). NVCP performs the way of killing two birds with one stone, that is, the probe exhibits excellent selectivity and sensitivity for detecting viscosity and Cys in living cells with excellent biocompatibility and accurate mitochondrial targeting capability by dual channel imaging mode. In addition, NVCP recognized that the viscosity increases and Cys level decreases in cells when undergoing ferroptosis and oxygen-glucose deprivation (OGD) stress by confocal imaging, flow cytometry, and Western blot experiments. Treatment of ferroptosis inhibitors (ferrostatin-1 (Fer-1) and deferoxamine (DFO)) could reverse the variation tendency of viscosity and Cys. This is the first time that the relationship between ferroptosis and IS was identified through an analysis of Cys and viscosity. More importantly, the ischemic area was also instantly distinguished from normal tissues through fluorescence imaging of NVCP in vivo . The developed NIR dual-responsive probe NVCP toward viscosity and Cys could serve as a sensitive and reliable tool for tracking ferroptosis-related pathological processes during IS.
摘要：
Introduction Glucosylceramidase beta 1 (GBA1) mutations are a genetic risk factor for Parkinson's disease (PD), though most carriers do not develop the disease. This study aimed to identify exposure factors linked to PD in GBA1 carriers and assess clinical features and the probability of prodromal PD in non-manifesting carriers.
Glucosylceramidase beta 1 (GBA1) mutations are a genetic risk factor for Parkinson's disease (PD), though most carriers do not develop the disease. This study aimed to identify exposure factors linked to PD in GBA1 carriers and assess clinical features and the probability of prodromal PD in non-manifesting carriers.
Methods Data from the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China was used, including 59 GBA1 non-manifesting carriers, 62 controls, and 107 GBA1-associated PD, of whom 81 were in the early stage. Exposure factors included pesticide/solvent exposure, smoking, alcohol, and tea consumption. Logistic regression assessed the association between exposure factors and PD. Clinical characteristics were evaluated using multiple scales, relevant markers were collected based on the Movement Disorders Society criteria. A naive Bayesian classifier method determined the probability of prodromal PD in GBA1 non-manifesting carriers and controls.
Data from the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China was used, including 59 GBA1 non-manifesting carriers, 62 controls, and 107 GBA1-associated PD, of whom 81 were in the early stage. Exposure factors included pesticide/solvent exposure, smoking, alcohol, and tea consumption. Logistic regression assessed the association between exposure factors and PD. Clinical characteristics were evaluated using multiple scales, relevant markers were collected based on the Movement Disorders Society criteria. A naive Bayesian classifier method determined the probability of prodromal PD in GBA1 non-manifesting carriers and controls.
Results After adjusting for sociodemographic variables, pesticide/solvent exposure was positively associated with PD in GBA1 carriers (OR 8.40; 95 % CI 2.50–28.20), while smoking was inversely associated with PD (OR 0.18; 95 % CI 0.05–0.62). Rapid eye movement sleep behavior disorder, constipation, hyposmia, and cognitive deficits were more severe in early-stage GBA1-associated PD than in carriers and controls. Clinical symptoms and the probability of prodromal PD were similar between carriers and controls.
After adjusting for sociodemographic variables, pesticide/solvent exposure was positively associated with PD in GBA1 carriers (OR 8.40; 95 % CI 2.50–28.20), while smoking was inversely associated with PD (OR 0.18; 95 % CI 0.05–0.62). Rapid eye movement sleep behavior disorder, constipation, hyposmia, and cognitive deficits were more severe in early-stage GBA1-associated PD than in carriers and controls. Clinical symptoms and the probability of prodromal PD were similar between carriers and controls.
Conclusions PD in GBA1 carriers is closely linked to exposure factors. Early-stage GBA1-associated PD shows significant prodromal symptoms, which are not evident in carriers. The probability of prodromal PD in carriers is similar to that in controls.
PD in GBA1 carriers is closely linked to exposure factors. Early-stage GBA1-associated PD shows significant prodromal symptoms, which are not evident in carriers. The probability of prodromal PD in carriers is similar to that in controls.
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.
